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Who are the children using hospice care?
The purpose was to examine the characteristics of children who use hospice care. Using the Andersen Model of Health Services Use, California Medicaid administrative databases were analyzed to describe the characteristics of 76 children in hospice. The predisposing, enabling, and need characteristics of children were identified. Children who used hospice were a diverse group with community resources that enabled them to access care while presenting with serious health needs. Children enrolled in hospice were more likely older (15-20 years of age), resided nearer a pediatric hospice, and had a serious health condition such as neuromuscular disease with multiple comorbidities. With this knowledge, pediatric nurses can improve their clinical practice by targeting conversations with families and children most in need of hospice care.
25,131,751
[ -0.260186, -0.2930683, -0.01166902, -0.1655258, 0.1007514, 0.03627093, -0.03967549, -0.004834575, -0.1501563, 0.04610158, 0.1840563, 0.1670566, 0.0106054, -0.3685123, 0.03626194, -0.1173114, -0.2909732, 0.1139082, 0.04539243, -0.1686922, 0.2202695, 0.2541519, -0.1269526, ...
A heterogeneous hierarchy of co-regulatory receptors regulates exhaustion of HCV-specific CD8 T cells in patients with chronic hepatitis C.
The functionality of virus-specific T cells is regulated by a sophisticated network of an expanding repertoire of co-regulatory receptors, which could be harnessed for immunotherapeutic applications. However, targeting particular pathways during persistent virus infections has resulted in variable outcomes. The extent to which T cell exhaustion can be reversed, by targeting multiple co-regulatory pathways, still remains not fully investigated. We analysed the phenotype and in vitro functionality of HCV-specific CD8(+) T cells expressing PD-1, CTLA-4, TIM-3 or 2B4 either alone or in various combinations and compared expression levels to those of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) specific T cells in peripheral blood mononuclear cells (PBMCs) from the same cohort of patients with chronic hepatitis C (CHC) infection. Blockade and/or crosslinking of distinct co-regulatory pathways in exhausted HCV-specific CD8(+) T cells resulted in rather diverse and individualized T cell responses, irrespective of the type and number of receptors targeted. Overall, in vitro manipulations of these pathways yielded three response possibilities: (i) total non-response (ii) good single blockade response and (iii) good dual/multiple blockade response, with each comprising approximately one-third of the patients tested. The diversity of the in vitro responsiveness of HCV-specific T cells was reflected by an enormous ex vivo phenotypic heterogeneity. Despite this broad heterogeneity, HCV-specific CD8(+) T cells differed from EBV- and CMV-specific T cells in particular by TIM-3 expression, which also correlated with liver disease activity and viral load. HCV-specific CD8(+) T cell functionality, upon co-regulatory receptor manipulations, was characterized by an individual pattern of responses in patients with CHC, suggesting that treatment approaches, targeting these receptors, should consider inter-individual differences and be personalized.
25,131,771
[ -0.008275614, 0.1449796, -0.1001774, -0.08052799, 0.1066981, -0.4462611, -0.1785102, 0.3700018, -0.01792161, 0.2750686, -0.01356206, -0.07298525, 0.192601, 0.1081188, -0.4776539, -0.3294554, -0.2681623, 0.09390213, -0.01569423, 0.1697327, -0.05606842, 0.325642, -0.0476646...
Hepatic fungal infection in a young beagle with unrecognised hereditary cobalamin deficiency (Imerslund-Gräsbeck syndrome).
A 12-month-old beagle presented for anorexia, pyrexia and vomiting. The dog had been treated intermittently with antibiotics and corticosteroids for inappetence and lethargy since five months of age. Previous laboratory abnormalities included macrocytosis and neutropenia. At presentation, the dog was lethargic, febrile and thin. Laboratory examination findings included anaemia, a left shift, thrombocytopenia, hypoglycaemia and hyperbilirubinaemia. Multiple, small, hypoechoic, round hepatic lesions were observed on abdominal ultrasound. Cytological examination of hepatic fine needle aspirates revealed a fungal infection and associated pyogranulomatous inflammation. The dog's general condition deteriorated despite supportive measures and treatment with fluconazole, and owners opted for euthanasia before hypocobalaminaemia was identified. Subsequent genomic analysis revealed a CUBN:c.786delC mutation in a homozygous state, confirming hereditary cobalamin malabsorption (Imerslund-Gräsbeck syndrome). Similar to human infants, dogs with Imerslund-Gräsbeck syndrome may rarely be presented for infectious diseases, distracting focus from the underlying primary disorder.
25,131,805
[ -0.05672443, -0.03479696, 0.1583243, -0.537613, 0.4772802, -0.008942505, 0.1159386, -0.09898297, 0.1305999, -0.1308474, 0.2418518, -0.03764766, -0.2184224, 0.1895826, -0.1849036, 0.1572188, -0.5098225, -0.1647723, 0.1528554, 0.2406527, -0.03309487, 0.1207314, -0.06930006,...
Phylogenetic analysis of fowl adenoviruses isolated from chickens with gizzard erosion in Japan.
Thirty-four fowl adenoviruses (FAdVs) isolated from chickens with gizzard erosion (GE) from 1999 to 2010 were characterized phylogenetically together with foreign isolates. The phylogenetic analysis based on part of the hexon gene classified these 34 FAdV isolates into 3 groups: FAdV-1, -8a and 8b, thereby suggesting that FAdVs associated with GEs in chickens are diverse. All 30 FAdV-1 isolates were genetically identical, and they were also identical with FAdV-1 isolates from GEs in chickens in European countries (Germany, Poland, Austria, Hungary and Italy). Thus, the same type of FAdV-1 has been associated with outbreaks of GE in Japanese chickens for the past 10 years, which may have spread from a common ancestor, although the epidemiological relationship is unknown.
25,131,809
[ -0.09459912, -0.00004829965, -0.01460611, -0.1250275, 0.1275119, -0.05951431, 0.04975638, -0.1249164, -0.1622173, -0.1035107, 0.157407, -0.2373565, -0.1403116, -0.1041439, -0.4059435, -0.006051715, -0.1362476, 0.4606073, 0.05501651, 0.114263, 0.2077145, 0.3618704, -0.4215...
Effect of passive polarizing three-dimensional displays on surgical performance for experienced laparoscopic surgeons.
Although the potential benefits of stereoscopic laparoscopy have been recognized for years, the technology has not been adopted because of poor operator tolerance. Passive polarizing projection systems, which have revolutionized three-dimensional (3D) cinema, are now being trialled in surgery. This study was designed to see whether this technology resulted in significant performance benefits for skilled laparoscopists. Four validated laparoscopic skills tasks, each with ten repetitions, were performed by 20 experienced laparoscopic surgeons, in both two-dimensional (2D) and 3D conditions. The primary outcome measure was the performance error rate; secondary outcome measures were time for task completion, 3D motion tracking (path length, motion smoothness and grasping frequency) and workload dimension ratings of the National Aeronautics and Space Administration (NASA) Task Load Index. Surgeons demonstrated a 62 per cent reduction in the median number of errors and a 35 per cent reduction in median performance time when using the passive polarizing 3D display compared with the 2D display. There was a significant 15 per cent reduction in median instrument path length, an enhancement of median motion smoothness, and a 15 per cent decrease in grasper frequency with the 3D display. Participants reported significant reductions in subjective workload dimension ratings of the NASA Task Load Index following use of the 3D displays. Passive polarizing 3D displays improved both the performance of experienced surgeons in a simulated setting and surgeon perception of the operative field. Although it has been argued that the experience of skilled laparoscopic surgeons compensates fully for the loss of stereopsis, this study indicates that this is not the case. Surgical relevance The potential benefits of stereoscopic laparoscopy have been known for years, but the technology has not been adopted because of poor operator tolerance. The first laparoscopic operation was carried out using a prototype passive polarizing laparoscopic system in 2010. This is new three-dimensional (3D) technology offers a real option for 3D laparoscopic surgery where previous systems have failed. This study is the first to have been carried out using this technology. It is essential that new technologies are adopted only when there is robust evidence to support their use. Currently, there are concerns about the use of robotic technologies and whether advantages exist for patient care. If there are advantages, 3D must be playing a significant role. If so, perhaps the technology under investigation here offers potential to a greater spectrum of surgeons, as well as being a more affordable option.
25,131,843
[ -0.1173616, 0.1931905, -0.3114718, 0.1092966, -0.1997978, -0.2161208, 0.08478808, -0.2624285, 0.2464976, -0.03045536, 0.1852968, -0.4216935, -0.0009564778, -0.2696585, -0.3245833, -0.1192115, -0.5334906, 0.1214398, -0.156481, -0.4069884, -0.06957755, 0.3249801, -0.2511533...
Complete remission of VZV reactivation treated with valganciclovir in a patient with total lymphocyte depletion and acute kidney injury after allogeneic bone marrow transplantation.
Varicella zoster virus (VZV), a threat for hematopoietic stem cell transplantation (HSCT) recipients, is still one of the most common viral pathogens that affect these patients with a reported incidence ranging between 17% and 50% in the post transplantation period. Valganciclovir (V-GCV), a valine ester pro-drug of GCV orally administrable, has recently shown great activity against CMV infections, but there are no reports of its clinical efficacy against VZV. We here report a case history of a patient with positive serologic test for VZV, who underwent allogeneic HSCT and developed an atypical varicella-like illness. First-line therapy with foscarnet had to be discontinued due rapid development of renal impairment (creatinine: 2.60 mg/dL, urea: 130.6 mg/dL) and therefore was switched to V-GCV. The renal impairment and skin lesions of the patient fully recovered after few days of therapy, even though the patient had complete lymphocyte depletion. This is the first case of a patient with chickenpox-like illness treated successfully with V-GCV.
25,131,855
[ -0.1924162, -0.1302252, -0.3063846, -0.258325, 0.4181304, -0.1557647, -0.2842308, 0.1682913, -0.04700723, -0.0936176, 0.1314799, 0.3196269, 0.1247933, 0.5035725, -0.3259405, -0.1301662, -0.1342866, 0.2983597, 0.06008068, 0.1206802, -0.06941584, 0.2231717, -0.3336374, 0....
Expression, purification, and micelle reconstitution of antimicrobial piscidin 1 and piscidin 3 for NMR studies.
Piscidin 1 and piscidin 3, which were discovered in the mast cells of hybrid striped sea bass, are homologous antimicrobial peptides that are active against drug-resistant bacteria. Piscidin 1, the more antimicrobial and hemolytic peptide, also has anti-HIV-1 and anti-cancer properties. To understand the reasons underlying the different biological activities of the two peptides and identify principles to design antimicrobial drugs with improved efficacy and lower toxicity, their atomic-level structures must be obtained under physiologically-relevant conditions. High-resolution backbone structures of both piscidins exist in the presence of hydrated phospholipid bilayers but full structures that include the side chains are missing. Here, the piscidins 1 and 3 genes were cloned into the TrpLE vector. The corresponding TrpLE-piscidin fusion partners were expressed in Escherichiacoli and recovered from inclusion bodies. Following steps that included Ni-NTA chromatography, cyanogen bromide cleavage of the fusion proteins, and reverse-phase HPLC, purified piscidins 1 and 3 were recovered in very good yield and characterized by NMR. High quality (15)N-(1)H HSQC spectra of piscidins 1 and 3 bound to SDS micelles were collected, demonstrating the feasibility of producing and purifying the isotopically-labeled piscidin peptides required to determine their full structures by multidimensional NMR spectroscopy.
25,131,859
[ -0.1515496, -0.09717727, -0.312628, -0.06589814, -0.3080544, -0.1005889, -0.1527548, 0.1843498, 0.3337537, -0.04532612, -0.1006446, -0.1744664, -0.1323482, 0.3004388, -0.8113911, 0.07283475, -0.3190652, -0.04506482, 0.1256669, 0.3607936, 0.2191785, 0.03962344, 0.0715514, ...
Expression and biochemical characterization of recombinant human epididymis protein 4.
Whey acidic proteins (WAP) belong to a large gene family of antibacterial peptides that perform critical immune system functions. The function of human epididymis protein 4 (HE4), a 124-amino acid long polypeptide that has two whey acidic protein four-disulfide core (WFDC) domains, is not well studied. Here, a fusion gene encoding the HE4 protein fused to an IgG1 Fc domain was constructed. The recombinant HE4 protein was expressed as a secretory protein in Pichia pastoris and mammalian HEK293-F cells and was subsequently purified. Our data suggested that the HE4 protein produced by these two expression systems bound to both gram-negative and gram-positive bacteria, but demonstrated slightly inhibitory activity towards the growth of Staphylococcus aureus. Moreover, HE4 exhibited proteinase inhibitory activity towards trypsin, elastase, matrix metallopeptidase 9, and the secretory proteinases from Bacillus subtilis. The effects of glycosylation on the biochemical characterization of HE4 were also investigated. LC-ESI-MS glycosylation analysis showed that the high-mannose glycosylated form of HE4 expressed by P. pastoris has lower biological activity when compared to its complex-glycosylated form produced from HEK293-F cells. The implications of this are discussed, which may be provide theoretical basis for its important role in the development of cancer and innate immune system.
25,131,860
[ 0.2552697, -0.07399619, 0.04295109, 0.4129904, -0.00325057, -0.6010408, -0.1423737, 0.5601487, 0.05172975, 0.05288983, 0.06853777, 0.07339732, 0.03209345, -0.3447183, -0.5470115, -0.09369653, -0.3379782, -0.1354865, -0.1228062, -0.4710423, 0.2499531, 0.05951892, -0.384276...
[The efficacy and safety of FOLFIRI or combined FOLFIRI and bevacizumab treatment as second-line chemotherapy for metastatic colorectal cancer patients aged 75 years and older].
The safety and efficacy of FOLFIRI as second-line chemotherapy for metastatic colorectal cancer patients ≥ 75 years was retrospectively evaluated. We analyzed 106 patients, who received FOLFIRI or a combination of FOLFIRI and bevacizumab following oxaliplatin-based first-line chemotherapy. The clinical characteristics and outcome in elderly patients ≥75 years(elderly[EP]group; n=18)were compared with those in patients aged<75 years(control group; n=88). The number of patients treated by a combination of FOLFIRI and bevacizumab in the EP group was lower than that in the control group (27.8% vs 55.7%; p=0.03). The comparison revealed no significant differences in response rate, progression-free survival, overall survival, and the frequency of overall adverse events after the start of second-line chemotherapy, although the frequency of anemia(Bgrade 3, p=0.07)and alopecia(grade 1/2, p=0.054)tended to be higher in the EP group than in the control group. Although this study retrospectively analyzed a limited number of patients, our results indicate that the safety and efficacy of FOLFIRI as second-line chemotherapy for metastatic colorectal cancer are almost equal in patients ≥ 75 years and those aged<75 years.
25,131,872
[ -0.02224001, -0.02528259, -0.1974784, -0.152135, 0.254159, -0.3208181, 0.322706, -0.2153052, -0.2616567, -0.0330154, 0.004052357, 0.6222447, -0.005274407, 0.01563491, -0.2557894, -0.4075972, -0.309692, 0.3658569, 0.1749026, 0.3834234, 0.175679, 0.4838367, -0.1754923, 0....
[Successful treatment of advanced sigmoid colon cancer with liver metastases with cetuximab monotherapy as first-line treatment-a case report].
The prognosis for patients diagnosed with advanced colorectal cancer with liver metastases is poor. Chemotherapy should be administered with caution in such patients because of complications due to severe liver dysfunction. We report here the successful management of a case of advanced sigmoid colon cancer, with icterus due to severe liver metastases, treated with cetuximab as first-line therapy. A 72-year-old man presented at our institution with complaints of severe general fatigue, tarry stools, and abdominal distention. He was diagnosed with advanced sigmoid colon cancer with multiple liver metastases. Clinical examination revealed the presence of ascites. The patient had an Eastern Cooperative Oncology Group(ECOG) performance status(PS)score of 3. A biopsy specimen of the primary tumor showed well-moderately differentiated adenocarcinoma without KRAS mutation. He was diagnosed with advanced sigmoid colon cancer with multiple hepatic metastases. Cetuximab monotherapy was initiated as first-line treatment. After 4 courses of cetuximab monotherapy, results of laboratory tests showed an improvement, and a computed tomography(CT)scan revealed a regression in the size of the liver metastases. Because the results of liver function tests and the ECOG PS scores improved, we initiated combination chemotherapy with 5-fluorouracil, Leucovorin, oxaliplatin(FOLFOX), and cetuximab. This regimen was well tolerated up to 14 courses, during which the only adverse reaction reported was a rash of grade 2 toxicity. Thereafter, disease progression in the form of liver metastases resulted in a change in the combination therapy to irinotecan and S-1(IRIS)as second-line chemotherapy. Thereafter, irinotecan and panitumumab were administered as third-line therapy. The patient continued chemotherapy on an outpatient basis; however, he died due to disease progression 18 months after his first visit.
25,131,880
[ -0.02577694, 0.02430774, -0.04750336, -0.1348642, 0.03464466, -0.1835256, -0.2960458, -0.1248637, 0.02546004, 0.09219213, 0.2165785, 0.04295583, -0.09636258, 0.1854651, 0.09412133, -0.097026, -0.4681521, -0.03865462, 0.2542793, 0.1097471, -0.08233878, 0.1317814, -0.222305...
A cold-induced myo-inositol transporter-like gene confers tolerance to multiple abiotic stresses in transgenic tobacco plants.
A full length cDNA encoding a myo-inositol transporter-like protein, named as MfINT-like, was cloned from Medicago sativa subsp. falcata (herein falcata), a species with greater cold tolerance than alfalfa (M. sativa subsp. sativa). MfINT-like is located on plasma membranes. MfINT-like transcript was induced 2-4 h after exogenous myo-inositol treatment, 24-96 h with cold, and 96 h by salinity. Given that myo-inositol accumulates higher in falcata after 24 h of cold treatment, myo-inositol is proposed to be involved in cold-induced expression of MfINT-like. Higher levels of myo-inositol was observed in leaves of transgenic tobacco plants overexpressing MfINT-like than the wild-type but not in the roots of plants grown on myo-inositol containing medium, suggesting that transgenic plants had higher myo-inositol transport activity than the wild-type. Transgenic plants survived better to freezing temperature, and had lower ion leakage and higher maximal photochemical efficiency of photosystem II (Fv /Fm ) after chilling treatment. In addition, greater plant fresh weight was observed in transgenic plants as compared with the wild-type when plants were grown under drought or salinity stress. The results suggest that MfINT-like mediated transport of myo-inositol is associated with plant tolerance to abiotic stresses.
25,131,886
[ -0.2524439, -0.325495, -0.2864541, -0.169316, 0.124718, 0.0719442, -0.04203776, 0.08810219, 0.06444982, -0.3380433, 0.2011187, 0.2743537, 0.06718901, 0.07693406, -0.3158366, 0.1070245, -0.234413, -0.1889269, -0.08721087, 0.2272155, 0.2402786, 0.3550487, -0.162765, 0.018...
Geographical comparisons of information and support needs of Australian women following the primary treatment of breast cancer: a 10-year replication study.
In 2002, Raupach and Hiller examined the use of and satisfaction with information and support following treatment of breast cancer from a sample of participants in South Australia. In 2013 this study was replicated to include participants Australia wide and analyse comparisons based on geographical location. Statistical comparisons with the original study were also conducted. A 10 year replication study using a cross-sectional needs analysis survey. Women aged 18+ years diagnosed with breast cancer between 6 and 30 months ago were sourced from two national databases of women diagnosed with breast cancer. A total of 325 participants completed the survey. The Internet was the most commonly used source of information with 70% (n = 229 of 325) of women using the internet for information, a statistically significantly higher percentage compared with the 2002 study. The study found the top four information issues rated as moderately/extremely important by women in 2013 were identical in 2002. A comparison of sources of support used showed that women in outer regional, remote and very remote areas were statistically more likely to use the breast care nurse (BCN) for support (P = 0.044). The study provides useful, up-to-date data about information and support services used by Australian women with breast cancer. Comparisons with the earlier study show some of the needs of women have changed over time, but others have remained the same. Geographic comparisons overall, demonstrate many consistent findings regardless of location, however, the important work of the breast care nurse is an area in need of further research.
25,131,899
[ -0.05969017, -0.169235, -0.1587887, -0.3707074, -0.208561, -0.1533984, 0.0941162, -0.1373319, -0.03999892, 0.2933535, 0.1027724, -0.08889754, -0.15839, -0.3872942, -0.05861565, -0.4640132, -0.1260448, 0.07844714, 0.1282223, -0.4816971, -0.0758725, 0.3516455, -0.1413233, ...
Effects of salpingectomy and antituberculosis treatments on fertility results in patients with genital tuberculosis.
The aim of this study was to demonstrate the effects of tubal surgery and antituberculosis treatments in patients with genital tuberculosis. A total of 38 infertile women who had been diagnosed with pelvic tuberculosis and who had had laparoscopy and hysteroscopy were recruited into the study. All women with female genital tuberculosis were divided into two groups: group 1 (salpingectomized, n=21) and group 2 (not salpingectomized, n=15). Both of the groups were treated with antitubercular therapy for 6-12 months. There was no significant difference in level of gonadotrophins used, estradiol levels on human chorionic gonadotrophin day, mean and mature oocytes retrieved, mean embryos transferred, or cancellation and fertilization rates. Only the number of days of stimulation was statistically significantly higher in group 1 compared to group 2 (10.4±2.3 vs 9.2±1.8; P=0.048). Although it did not reach the statistically significant level, clinical pregnancy rate was higher in group 1 (37.5%, 12/32 vs 23.8%, 5/21; P=0.306). Although not statistically significant, number of ongoing pregnancies per embryo transfer, spontaneous abortion rates before 20 weeks of gestation and take-home baby rates were higher in group 1 compared to group 2 (15.5%, 12/77 vs 6.6%, 3/45; P=0.150; 28.1%, 9 vs 23.8%, 5; P=0.600; 9%, 3 vs 0; P=0.160, respectively). Salpingectomy is an option for treatment in patients diagnosed with pelvic tuberculosis and infertility to improve both clinical pregnancy rates and take-home baby rates in patients treated with antituberculosis therapy for 12 months.
25,131,900
[ 0.1972792, 0.03871951, -0.2583086, 0.08782046, -0.1405011, -0.4657719, -0.3115994, -0.05662778, 0.02125586, -0.218008, 0.05682841, 0.04160663, 0.06814164, 0.005272086, 0.04002206, -0.3555436, -0.1729076, -0.09148728, 0.002316353, 0.07799532, 0.1631519, 0.2982611, -0.14186...
Appetite predicts mortality in free-living older adults in association with dietary diversity. A NAHSIT cohort study.
This study aimed to assess the predictive ability of appetite for mortality among representative free-living Taiwanese older adults. A total of 1856 participants aged 65 years or over from the Elderly Nutrition and Health Survey during 1999-2000 completed an appetite question in a larger questionnaire. Personal information was obtained by face-to-face interview at baseline, together with a 24-hour dietary recall and simplified food frequency questionnaire which provided a dietary diversity score and food intake frequency. Survivorship was ascertained from the Death Registry until December 31, 2008. Participants with a poor appetite had lower dietary diversity scores (DDS) and intake frequencies of meat, fish and sea food, egg, vegetable and fruit intake, along with lower energy, protein, vitamin B-1, niacin, iron and phosphate intakes. Those who had fair and poor appetites had a higher risk of all-cause mortality compared to those with good appetite, with hazard ratios (HR) (95% confidence interval, CI) of 1.28 (1.03-1.58) and 2.27 (1.71-3.02), respectively. After adjustment for confounders, the HRs (95% CI) were 1.05 (0.83-1.33) and 1.50 (1.03-2.18), respectively. With further adjustment for DDS or general health these HRs became non-significant. The joint HR (95% CI) for "DDS ≤ 4 and poor appetite" was 1.77 (1.04-3.00) compared to "DDS > 4 and good appetite" as referent. Poor appetite is associated with lower food and nutrient intakes and an independent risk for mortality in older Taiwanese. In conclusion, appetite is separate, mediated by general health and modulated by dietary quality in its predictive capacity for mortality.
25,131,903
[ -0.02439846, -0.2939338, -0.1567677, -0.0863688, 0.009929719, -0.6359453, 0.4209319, 0.09797458, -0.1904705, -0.6342536, 0.1527602, 0.0698045, 0.08346093, -0.1433251, -0.3764507, -0.3368694, -0.1242798, 0.2983728, 0.1626541, -0.2780796, 0.02950667, 0.2726482, -0.4192, 0...
PTX3: a modulator of human coronary plaque vulnerability acting by macrophages type 2.
Acute myocardial infarction (AMI), is related to a diffuse active inflammation of the coronary tree associated with rupture of one of the multiple vulnerable plaques. The presence of soluble mediators of inflammation with their synergic or antagonistic actions coordinates the physiological response determining the plaque fate and the fatal event. The present study focus on the cytokines network operating in human coronary plaques of patients died from AMI and controls, pointing out that coronaries of AMI patients produce PTX3 protein twice as that of controls and express high level of PTX3 mRNA. The presence of CX3CR1 polymorphisms is significantly correlated with the incidence and the outcome of acute myocardial infarction inducing in the whole coronary tree a strong recruitment of Th1 polarized inflammation that is directly correlated to PTX3 expression. Moreover we found a positive correlation between the expression of PTX3 in the plaque and the content of macrophage cells showing a M2 polarization indicating the possible role of this chemokine as mediator of immune response that would orchestrate plaque evolution and inflammatory cell type activation.
25,131,923
[ 0.03410518, 0.07244891, -0.2092032, -0.01575656, -0.06759657, -0.2637178, -0.167228, 0.05801383, 0.05696199, -0.05690356, -0.0735252, -0.3504517, -0.1499904, -0.06903803, -0.2014314, -0.4113907, -0.4590783, -0.2619677, -0.03045183, 0.04125828, 0.1704882, 0.06403235, -0.15...
Severe autonomic failure as a predictor of mortality in aortic valve stenosis.
Identification of new risk markers in aortic valve stenosis (AS) is of great interest. Here, we hypothesized that the presence of severe autonomic failure (SAF) is an important prognostic marker in both, symptomatic patients undergoing invasive treatment for severe AS, and in asymptomatic patients with severe AS who were primarily treated conservatively. We prospectively enrolled 300 patients with severe AS (aortic valve area<1.0 cm2 or mean aortic gradient>40 mmHg) in sinus rhythm. All patients underwent a 24-h Holter recording for assessment of heart rate turbulence (HRT) and deceleration capacity (DC). Patients with both, abnormal DC and HRT were considered to suffer from SAF. The first hypothesis was tested in 216 symptomatic patients who underwent successful aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI). During follow-up of 2 years, 29 of these patients died. SAF was the strongest independent predictor of mortality (hazard ratio 5.6, 95% confidence interval 2.6-12.0; p<0.001) with 2-year mortality rates of 50.0% and 10.7% in SAF-positive and SAF-negative patients, respectively (p<0.001). The second hypothesis was tested in 71 patients, who were asymptomatic at study entry and for whom a primarily conservative treatment strategy was proposed. During follow-up, 10 of these patients died. SAF also predicted death in asymptomatic patients with 2-year mortality rates of 52.4% and 8.7% in SAF-positive and SAF-negative patients, respectively (p=0.010). SAF is a strong and independent predictor of mortality in symptomatic and asymptomatic patients with severe AS.
25,131,928
[ 0.06922826, 0.08378423, -0.09690465, -0.07144668, 0.004807463, -0.6878806, 0.04846458, -0.1486943, 0.08661263, -0.292902, -0.07968055, 0.2115361, 0.1046873, -0.109405, 0.2873308, -0.0435539, -0.3557858, -0.1106243, -0.003091235, 0.07892267, 0.04359628, 0.2686665, -0.15527...
Protective effect of the herbal preparation, STW 5, against intestinal damage induced by gamma radiation in rats.
STW 5 (marketed as Iberogast(®), Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany) is a herbal preparation reported to possess anti-inflammatory properties and antioxidant activity. We investigated the effect of STW 5 against intestinal injury induced after whole body exposure to ionizing radiation (IR). Intestinal mucositis was induced in rats by irradiation at a level of 6 Gy. STW 5 (5 ml/kg) was delivered orally for 5 days before irradiation and 2 days after. Rats were sacrificed, jejunum homogenates were tested to assess biochemical parameters indicating intestinal injury and jejunum segments were exposed to semi-quantitative histological examination. IR led to an increase in overall damage severity (ODS) score associated with a significant rise in tumor necrosis factor (TNF-α) and thiobarbituric acid reactive substances (TBARS) by 46% and 50% (p ≤ 0.05), respectively, whereas the reduced glutathione (GSH), sucrase and alkaline phosphatase enzyme activities were significantly decreased by 68%, 76% and 25% (p ≤ 0.05), respectively, in intestinal homogenates. IR led to a reduction of plasma citrulline. Pre-treatment with STW 5 guarded against the changes in ODS score and in all parameters measured. Pre-treatment with STW 5 has the potential to decrease the severity of radiation-induced mucositis.
25,131,937
[ -0.1144446, -0.3960066, -0.02528129, -0.0493649, 0.1452673, -0.2364267, -0.05485165, -0.2501665, 0.4054964, 0.2327428, -0.04144844, -0.3270905, 0.05187255, -0.07606393, -0.7542729, 0.2687717, -0.7972126, -0.09100693, -0.0961796, 0.8627183, -0.02210019, 0.4230649, -0.06036...
Transcript elongation factors: shaping transcriptomes after transcript initiation.
Elongation is a dynamic and highly regulated step of eukaryotic gene transcription. A variety of transcript elongation factors (TEFs), including modulators of RNA polymerase II (RNAPII) activity, histone chaperones, and histone modifiers, have been characterized from plants. These factors control the efficiency of transcript elongation of subsets of genes in the chromatin context and thus contribute to tuning gene expression programs. We review here how genetic and biochemical analyses, primarily in Arabidopsis thaliana, have advanced our understanding of how TEFs adjust plant gene transcription. These studies have revealed that TEFs regulate plant growth and development by modulating diverse processes including hormone signaling, circadian clock, pathogen defense, responses to light, and developmental transitions.
25,131,948
[ 0.2984736, 0.1362747, -0.1181017, -0.281446, -0.1248314, -0.3051586, 0.384829, 0.1897096, 0.1024049, -0.04729311, -0.01308473, 0.09477703, -0.183855, -0.04453568, -0.06627667, -0.0612841, -0.1619123, 0.06037596, 0.03099106, -0.1427782, 0.335731, 0.2343568, -0.4275424, -...
Imatinib mesylate plus hydroxyurea chemotherapy for cerebellar meningioma in a Belgian Malinois dog.
An 8-year-old intact male Belgian Malinois, weighing 37.2 kg, was referred for evaluation due to right side facial paresis, ataxia and a 2-month history of decreased cognitive ability. Physical and neurological examinations revealed mild depression, left-sided head tilt, right-sided facial paresis and ataxia. A well-demarcated, broad-based cerebellar mass and hyperostosis were found on CT imaging of the brain. Based on these CT findings, a cerebellar meningioma was strongly suspected. Hydroxyurea and prednisolone were administered; after 4 weeks, there was reduction in mass size as compared to initial CT results. However, the mass size was found to have grown 6 weeks after hydroxyurea treatment. We then prescribed a combination of imatinib mesylate and hydroxyurea. Two weeks following combination treatment, the mass size had reduced significantly. The mass continuously decreased in size until the patient died during anesthesia. Cerebellar transitional meningioma was confirmed by histopathologic examination. To the author's knowledge, this is the first reported case of imatinib mesylate plus hydroxyurea therapy for the treatment of meningioma in veterinary medicine.
25,131,949
[ -0.3009126, 0.1922246, 0.3021131, -0.6358863, 0.04842006, -0.3950758, 0.2110949, -0.03370647, -0.1117373, 0.1105559, 0.1491662, 0.2365163, -0.06602748, -0.08214229, -0.4900308, 0.3656957, -0.08632004, 0.2218459, -0.1209768, 0.1216635, -0.3333411, -0.0552698, 0.01695876, ...
Triglycerides and cardiovascular disease.
After the introduction of statins, clinical emphasis first focussed on LDL cholesterol-lowering, then on the potential for raising HDL cholesterol, with less focus on lowering triglycerides. However, the understanding from genetic studies and negative results from randomised trials that low HDL cholesterol might not cause cardiovascular disease as originally thought has now generated renewed interest in raised concentrations of triglycerides. This renewed interest has also been driven by epidemiological and genetic evidence supporting raised triglycerides, remnant cholesterol, or triglyceride-rich lipoproteins as an additional cause of cardiovascular disease and all-cause mortality. Triglycerides can be measured in the non-fasting or fasting states, with concentrations of 2-10 mmol/L conferring increased risk of cardiovascular disease, and concentrations greater than 10 mmol/L conferring increased risk of acute pancreatitis and possibly cardiovascular disease. Although randomised trials showing cardiovascular benefit of triglyceride reduction are scarce, new triglyceride-lowering drugs are being developed, and large-scale trials have been initiated that will hopefully provide conclusive evidence as to whether lowering triglycerides reduces the risk of cardiovascular disease.
25,131,982
[ -0.1377055, 0.07376134, -0.1404368, -0.2702, -0.04424464, -0.1127732, 0.2240419, 0.3286331, 0.08578952, -0.1811344, 0.1422863, 0.3485237, 0.03242653, -0.08402607, -0.2690136, -0.3411441, -0.2807899, 0.08070276, 0.1249355, 0.4183412, -0.3442927, 0.2203666, -0.232369, -0....
Gallic acid regulates skin photoaging in UVB-exposed fibroblast and hairless mice.
Ultraviolet (UV) radiation is the primary factor in skin photoaging, which is characterized by wrinkle formation, dryness, and thickening. The mechanisms underlying skin photoaging are closely associated with degradation of collagen via upregulation of matrix metalloproteinase (MMP) activity, which is induced by reactive oxygen species (ROS) production. Gallic acid (GA), a phenolic compound, possesses a variety of biological activities including antioxidant and antiinflammatory activities. We investigated the protective effects of GA against photoaging caused by UVB irradiation using normal human dermal fibroblasts (NHDFs) in vitro and hairless mice in vivo. The production levels of ROS, interlukin-6, and MMP-1 were significantly suppressed, and type I procollagen expression was stimulated in UVB-irradiated and GA-treated NHDFs. GA treatment inhibited the activity of transcription factor activation protein 1. The effects of GA following topical application and dietary administration were examined by measuring wrinkle formation, histological modification, protein expression, and physiological changes such as stratum corneum hydration, transepidermal water loss, and erythema index. We found that GA decreased dryness, skin thickness, and wrinkle formation via negative modulation of MMP-1 secretion and positive regulation of elastin, type I procollagen, and transforming growth factor-β1. Our data indicate that GA is a potential candidate for the prevention of UVB-induced premature skin aging.
25,131,997
[ -0.08644482, -0.4538081, -0.1401162, 0.1094443, 0.3067063, 0.02594625, 0.263776, -0.1790848, 0.1392241, -0.07887383, -0.005994146, 0.1049502, -0.06011574, -0.1219238, -0.3166707, 0.2602032, -0.08264205, 0.466303, -0.404028, 0.0715116, 0.003230981, 0.3179112, -0.3494671, ...
Clinical and molecular characteristics of community-acquired methicillin-resistant Staphylococcus aureus infections in Chinese neonates.
This study aims to characterize the clinical features of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in Chinese neonates, as well as the molecular characteristics and expression of key virulence genes of isolates. Clinical information and molecular characteristics of 130 cases were analyzed. Up to 83.8% patients were affected with late-onset infection. Cesarean delivery was the main delivery route, accounting for 74.6% of the total deliveries. Pneumonia (69, 53.1%) was the most common infection. A total of 38 patients (29.2%) suffered from complications. Moreover, 35 cases (26.9%) were invasive infections, among which 88.6% involved multiple organs and 45.7% suffered from complications. Cesarean section and premature birth were the risk factors for invasive CA-MRSA infection. ST59-MRSA-SCCmecIVa-t437 (54, 41.5%) was the most predominant CA-MRSA clone. The hla expression in the ST59 isolates was higher than that in ST910 (p = 0.02) and the hla expression in ST59-SCCmecV-t437 was higher than that in ST59-SCCmecIVa-t437. Approximately, 46.4% (13/28) of the infections caused by ST59-SCCmecV were invasive. This value is higher than that of ST59-SCCmecVa caused infections (14/59, 23.7%) (p = 0.03). This study showed that neonatal CA-MRSA infections in China readily become invasive, involve multiple organs, and are often accompanied by complications. The SCCmec V clone may be more pathogenic than the SCCmecVIa clone.
25,132,016
[ 0.1916585, -0.2054581, 0.03633427, -0.008694985, -0.01088357, 0.07569639, -0.3008562, 0.110693, 0.04296098, 0.4318952, 0.1844943, 0.4344415, 0.06636769, -0.1144883, 0.3320582, -0.1682645, -0.2835442, -0.1616409, 0.06307696, -0.03085618, 0.08048698, 0.4042852, 0.007204053,...
Heritability of head motion during resting state functional MRI in 462 healthy twins.
Head motion (HM) is a critical confounding factor in functional MRI. Here we investigate whether HM during resting state functional MRI (RS-fMRI) is influenced by genetic factors in a sample of 462 twins (65% female; 101 MZ (monozygotic) and 130 DZ (dizygotic) twin pairs; mean age: 21 (SD = 3.16), range 16-29). Heritability estimates for three HM components-mean translation (MT), maximum translation (MAXT) and mean rotation (MR)-ranged from 37 to 51%. We detected a significant common genetic influence on HM variability, with about two-thirds (genetic correlations range 0.76-1.00) of the variance shared between MR, MT and MAXT. A composite metric (HM-PC1), which aggregated these three, was also moderately heritable (h(2) = 42%). Using a sub-sample (N = 35) of the twins we confirmed that mean and maximum translational and rotational motions were consistent "traits" over repeated scans (r = 0.53-0.59); reliability was even higher for the composite metric (r = 0.66). In addition, phenotypic and cross-trait cross-twin correlations between HM and resting state functional connectivities (RS-FCs) with Brodmann areas (BA) 44 and 45, in which RS-FCs were found to be moderately heritable (BA44: h(2) = 0.23 (sd = 0.041), BA45: h(2) = 0.26 (sd = 0.061)), indicated that HM might not represent a major bias in genetic studies using FCs. Even so, the HM effect on FC was not completely eliminated after regression. HM may be a valuable endophenotype whose relationship with brain disorders remains to be elucidated.
25,132,021
[ -0.03793006, 0.1910642, 0.2622745, -0.02322475, 0.1875448, -0.3493819, -0.008948585, 0.02641701, -0.08657914, 0.2033454, 0.0531396, -0.1702856, -0.1585369, -0.4558851, -0.3339556, -0.3750986, -0.007832968, 0.186055, -0.204528, -0.149181, -0.1685141, 0.06506191, -0.2130716...
[Maintenance therapy for advanced non-small-cell lung cancer].
Maintenance therapy is a new treatment strategy for advanced non-small-cell lung cancer(NSCLC), and it consists of switch maintenance and continuation maintenance.Switch maintenance is the introduction of a different drug, not included as part of the induction therapy, immediately after completion of 4 cycles of first-line platinum-based chemotherapy.Continuation maintenance is a continuation of at least one of the drugs used in the induction therapy in the absence of disease progression.Several phase III trials have reported survival benefits with continuation maintenance of pemetrexed and switch maintenance of pemetrexed or erlotinib.Therefore, maintenance therapy has become a part of the standard first-line treatment for advanced NSCLC.However, further research is needed to elucidate the selection criteria of patients who may benefit the most from maintenance therapy.
25,132,023
[ -0.2473212, 0.03629678, 0.04639902, -0.4769544, 0.09798352, -0.2736724, -0.02635046, -0.08133188, -0.08777173, 0.03466294, -0.04041084, 0.1493067, -0.1022833, 0.05047408, -0.5394393, -0.3143122, -0.178531, 0.1988947, -0.2464638, 0.1716065, 0.07872833, -0.07829048, -0.0147...
[Gallbladder cancer with elevated serum α-fetoprotein, α-fetoprotein-L3, and human chorionic gonadotropin levels].
A 61-year-old woman presented with fever and was diagnosed with choledocholithiasis, which was removed endoscopically. Incidentally, a markedly elevated serum α-fetoprotein(AFP)level was detected(1,951 ng/mL), but computed tomography( CT)showed only diffuse gallbladder wall thickening. Subsequently, markedly elevated serum AFP-L3 and human chorionic gonadotropin(HCG)levels were detected(99.6%and 2,867mIU/mL, respectively). Fluorodeoxyglucose(FDG)- positron emission tomography/CT demonstrated high FDG uptake only in the gallbladder. Gallbladder cancer was suspected and the patient was scheduled for a cholecystectomy. However, CT just prior to surgery revealed multiple liver metastases. Percutaneous gallbladder biopsy revealed a moderately differentiated adenocarcinoma positive for AFP but not HCG. The patient underwent chemotherapy consisting of gemcitabine and cisplatin. A CT scan obtained 12 weeks later showed disease progression and AFP and HCG levels were found to have increased to 4,021 ng/mL and 66,000mIU/mL, respectively. Although immunohistochemistry of biopsy specimen did not demonstrate HCG production, increased serum HCG level on disease progression definitely suggested HCG production of gallbladder cancer. We believe the biopsy specimen was very small and therefore did not prove HCG production. Gallbladder cancer with simultaneous production of AFP and HCG is rare, and we therefore report this case together with a review of the literature.
25,132,038
[ -0.1869194, -0.04850129, -0.3768534, -0.09091693, 0.02061234, -0.3681571, -0.3657267, 0.000405863, 0.1396966, 0.2397847, 0.1273261, 0.06339669, 0.05609405, 0.0871427, 0.08071312, -0.3242375, -0.5905158, 0.1420579, 0.110696, -0.05747087, 0.05492388, -0.3434579, -0.4201332,...
The development of a classification schema for arts-based approaches to knowledge translation.
Arts-based approaches to knowledge translation are emerging as powerful interprofessional strategies with potential to facilitate evidence uptake, communication, knowledge, attitude, and behavior change across healthcare provider and consumer groups. These strategies are in the early stages of development. To date, no classification system for arts-based knowledge translation exists, which limits development and understandings of effectiveness in evidence syntheses. We developed a classification schema of arts-based knowledge translation strategies based on two mechanisms by which these approaches function: (a) the degree of precision in key message delivery, and (b) the degree of end-user participation. We demonstrate how this classification is necessary to explore how context, time, and location shape arts-based knowledge translation strategies. Classifying arts-based knowledge translation strategies according to their core attributes extends understandings of the appropriateness of these approaches for various healthcare settings and provider groups. The classification schema developed may enhance understanding of how, where, and for whom arts-based knowledge translation approaches are effective, and enable theorizing of essential knowledge translation constructs, such as the influence of context, time, and location on utilization strategies. The classification schema developed may encourage systematic inquiry into the effectiveness of these approaches in diverse interprofessional contexts.
25,132,050
[ -0.176443, 0.3323064, -0.03310446, 0.09665837, 0.3873957, -0.1299652, 0.2888995, 0.0383784, 0.3721298, 0.1997202, -0.126092, -0.2287666, 0.1501829, -0.1608352, 0.05094132, 0.006787054, -0.3989164, -0.1791097, -0.2341701, -0.3229019, 0.2239334, 0.3774736, -0.06919868, 0....
Effect of lithium chloride on the production and sialylation of Fc-fusion protein in Chinese hamster ovary cell culture.
Lithium chloride (LiCl), which is a specific inhibitor of glycogen synthase kinase-3β, is known to induce cell cycle arrest at the G2/M phase and to regulate apoptosis. To determine the potential of LiCl as a chemical additive to enhance specific productivity (q p) of recombinant Chinese hamster ovary (rCHO) cells through cell cycle arrest at G2/M phase, rCHO cells producing Fc-fusion protein were cultivated in serum-free media with LiCl concentrations ranging from 0 to 20 mM. The addition of LiCl induced cell cycle arrest at G2/M phase and thereby decreased the specific cell growth rate. However, LiCl increased q p in a dose-dependent manner. The beneficial effect of LiCl on q p outweighed its detrimental effect on μ, resulting in improved maximum Fc-fusion protein concentration (MFPC) at 10 mM LiCl. The q p and MFPC in the bioreactor culture with 10 mM LiCl were 5.0 and 2.1 times higher than those without LiCl, respectively. In addition, the presence of LiCl at 10 mM did not significantly affect either intracellular α2,3-ST or extracellular sialidase activity. LiCl also inhibited apoptosis of cells in the decline phase of growth by increasing Bcl-2 expression. Taken together, the results obtained in this study demonstrate the potential of LiCl as a q p-enhancing additive in CHO cell culture for improved recombinant protein production.
25,132,065
[ -0.1770719, -0.08610006, 0.0228917, 0.0711939, -0.1058391, -0.2910355, -0.06858263, 0.1246873, -0.006847206, 0.1262931, -0.1137787, 0.3306234, -0.3646955, 0.2512929, 0.02734326, -0.2952734, -0.1703497, -0.1487167, 0.1464492, 0.2255676, 0.5837139, 0.2698933, -0.3802208, ...
Efficacy of catheter ablation for persistent atrial fibrillation: a systematic review and meta-analysis of evidence from randomized and nonrandomized controlled trials.
Catheter ablation (CA) is commonly performed for persistent atrial fibrillation, but few high-quality randomized controlled trials (RCTs) exist, leading to funding restrictions being proposed in several countries. We performed a random-effects meta-analysis of RCTs and non-RCTs to assess the efficacy of CA for persistent atrial fibrillation. We systematically searched PubMed, EMBASE, CENTRAL, OpenGrey, and clinicaltrials.gov for RCTs and non-RCTs reporting clinical outcomes after CA for persistent atrial fibrillation. Forty-six eligible studies were identified containing 3819 patients. After a single procedure, CA significantly reduced the risk of recurrent atrial fibrillation compared with medical therapy (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.20-0.53; P<0.001). Outcomes were better if the pulmonary veins were encircled (OR, 0.26; 95% CI, 0.09-0.74; P=0.01), and electrical isolation reduced AF recurrence compared with purely anatomic encirclement (OR, 0.33; 95% CI, 0.13-0.86; P=0.02). Linear ablation within the left atrium (OR, 0.22; 95% CI, 0.10-0.49; P<0.001), but not complex fractionated atrial electrogram ablation (OR, 0.64; 95% CI, 0.35-1.18; P=0.15), significantly reduced AF recurrence. Results were not improved by performing more extensive linear lesion sets (OR, 0.77; 95% CI, 0.41-1.43; P=0.40) or from biatrial ablation (OR, 0.62; 95% CI, 0.31-1.24; P=0.17). Where data were available, the relative benefits seen held true both after a single or multiple procedure(s). Sensitivity analyses showed that inclusion of non-RCTs increased statistical power without biasing the calculated effect sizes. For patients with persistent atrial fibrillation, CA achieves significantly greater freedom from recurrent atrial fibrillation compared with medical therapy. The most efficacious strategy is likely to combine isolation of the pulmonary veins with limited linear ablation within the left atrium.
25,132,078
[ 0.1137285, 0.2783068, -0.3003135, -0.1125663, 0.05992329, -0.3766629, -0.3003936, -0.2731849, 0.00900664, -0.141742, 0.05984814, 0.2478687, -0.05259681, -0.06462147, 0.350111, -0.5682824, -0.3724784, 0.3201069, 0.08851337, -0.2556816, -0.2043719, 0.004161289, -0.2654575, ...
Mitochondrial macro-haplogroup JT may play a protective role in ovarian ageing.
This study of 200 Caucasian women shows that the distribution of the mtDNA macro-haplogroups in patients with diminished ovarian reserve (DOR) differed significantly from that of patients with normal ovarian reserve (NOR) (p=0.02). The JT macro-haplogroup was significantly under-represented in DOR patients compared with NOR patients (p=0.006) and compared with the estimated frequency of 18.8% in the general French population (p=0.0012). Our findings suggest that the risk of a prematurely depleted ovarian reserve would be three times lower for patients carrying the JT macro-haplogroup than for patients with any of the other mtDNA haplogroups (odds ratio: 0.3; 95% CI: 0.13-0.74). If these preliminary results are confirmed in larger independent studies, they should lead to the better management of infertility.
25,132,080
[ 0.1321204, 0.06750836, 0.1170798, 0.09432447, 0.02380081, -0.2334307, 0.4388663, 0.1225987, 0.04599376, 0.2754463, -0.1231191, 0.2858539, 0.251945, 0.1957124, -0.4359419, -0.5177779, -0.2276171, 0.1028287, 0.347951, -0.2583198, 0.2260693, 0.08605731, -0.1518455, 0.17763...
Structural mapping of divergent regions in the type 1 ryanodine receptor using fluorescence resonance energy transfer.
Ryanodine receptors (RyRs) release Ca(2+) to initiate striated muscle contraction. Three highly divergent regions (DRs) in the RyR protein sequence (DR1, DR2, and DR3) may confer isoform-specific functional properties to the RyRs. We used cell-based fluorescence resonance energy transfer (FRET) measurements to localize these DRs to the cryoelectron microscopic (cryo-EM) map of the skeletal muscle RyR isoform (RyR1). FRET donors were targeted to RyR1 using five different FKBP12.6 variants labeled with Alexa Fluor 488. FRET was then measured to the FRET acceptors, Cy3NTA or Cy5NTA, targeted to decahistidine tags introduced within the DRs. DR2 and DR3 were localized to separate positions within the "clamp" region of the RyR1 cryo-EM map, which is presumed to interface with Cav1.1. DR1 was localized to the "handle" region, near the regulatory calmodulin-binding site on the RyR. These localizations provide insights into the roles of DRs in RyR allosteric regulation during excitation contraction coupling.
25,132,084
[ -0.3411798, -0.01087225, -0.4234337, 0.1944756, 0.01139093, 0.1455718, -0.001690995, 0.1879818, 0.270314, 0.1784274, 0.1857792, -0.08547857, 0.2206175, 0.002213509, -0.5670892, -0.1740819, -0.5834121, -0.1031807, 0.2316328, -0.1022663, 0.1423382, 0.324281, -0.2716888, 0...
Crystal structures of designed armadillo repeat proteins: implications of construct design and crystallization conditions on overall structure.
Designed armadillo repeat proteins (dArmRP) are promising modular proteins for the engineering of binding molecules that recognize extended polypeptide chains. We determined the structure of a dArmRP containing five internal repeats and 3rd generation capping repeats in three different states by X-ray crystallography: without N-terminal His6 -tag and in the presence of calcium (YM5 A/Ca(2+) ), without N-terminal His6 -tag and in the absence of calcium (YM5 A), and with N-terminal His6 -tag and in the presence of calcium (His-YM5 A/Ca(2+)). All structures show different quaternary structures and superhelical parameters. His-YM5 A/Ca(2+) forms a crystallographic dimer, which is bridged by the His6 -tag, YM5 A/Ca(2+) forms a domain-swapped tetramer, and only in the absence of calcium and the His6 -tag, YM5 A forms a monomer. The changes of superhelical parameters are a consequence of calcium binding, because calcium ions interact with negatively charged residues, which can also participate in the modulation of helix dipole moments between adjacent repeats. These observations are important for further optimizations of dArmRPs and provide a general illustration of how construct design and crystallization conditions can influence the exact structure of the investigated protein.
25,132,085
[ 0.02811759, 0.09626627, -0.1327245, 0.1176849, -0.5118524, -0.2286879, -0.22747, 0.6129848, 0.3769367, 0.2535817, 0.03380284, 0.08913767, 0.02457769, -0.1885861, -0.9600137, 0.152172, -0.09952275, 0.03744151, -0.3182853, 0.05880251, 0.5029573, 0.2098597, -0.02099799, 0....
Efficacy of concurrent cetuximab vs. 5-fluorouracil/carboplatin or high-dose cisplatin with intensity-modulated radiation therapy (IMRT) for locally-advanced head and neck cancer (LAHNSCC).
We previously reported inferior outcomes for locally-advanced head and neck squamous cell carcinoma (LAHNSCC) patients treated with concurrent cetuximab vs. high-dose cisplatin with intensity-modulated radiation therapy (IMRT). Prior to FDA approval of cetuximab for LAHNSCC, non-cisplatin eligible patients at our institution received 5-fluorouracil (5FU)/carboplatin. We sought to compare concurrent cetuximab vs. 5FU/carboplatin vs. high-dose cisplatin with IMRT for LAHNSCC. Retrospective review was performed for LAHNSCC patients treated at Memorial Sloan-Kettering Cancer Center from 11/02 to 04/08 with concurrent cetuximab (n=49), 5FU/carboplatin (n=52), or cisplatin (n=259) and IMRT. Overall survival (OS), locoregional failure (LRF), distant metastasis-free survival, and late toxicity were analyzed using univariate and multivariate analyses. OS analysis was confirmed by propensity score adjustment. Treatment groups were similar with regard to primary tumor site, overall stage, and alcohol and tobacco history. Cetuximab and 5FU/carboplatin patients were older, with lower performance status, more comorbidities, higher T classification, and worse renal function. On multivariate analysis, compared with cisplatin and 5FU/carboplatin, cetuximab was associated with inferior 4-year OS (86.9% vs. 70.2% vs. 40.9%; P<.0001) and 4-year LRF (6.3% vs. 9.7% vs. 40.2%; P<.0001). Late toxicity was highest with 5FU/carboplatin (25.0%) vs. cisplatin (8.0%) vs. cetuximab (7.7%). Although 5FU/carboplatin patients were sicker and experienced greater toxicity than cisplatin patients, no significant difference was found in all endpoints. In contrast, despite similar pretreatment characteristics, outcomes for cetuximab vs. 5FU/carboplatin were significantly worse. We feel that caution should be used with routine use of cetuximab in the management of LAHNSCC.
25,132,089
[ 0.1433475, -0.1158228, -0.337017, 0.1748562, 0.2912985, -0.4565599, 0.07800406, 0.179144, -0.1359861, 0.1643584, -0.01210295, 0.2293142, -0.03208273, -0.395613, 0.1990162, -0.5169685, 0.03611834, 0.155666, 0.304088, 0.05075314, -0.09898549, 0.2932951, -0.3081764, -0.034...
FrxA is an S-nitrosoglutathione reductase enzyme that contributes to Helicobacter pylori pathogenicity.
Helicobacter pylori is a pathogen that infects the gastric mucosa of a large percentage of the human population worldwide, and predisposes to peptic ulceration and gastric cancer. Persistent colonization of humans by H. pylori triggers an inflammatory response that leads to the production of reactive nitrogen species. However, the mechanisms of H. pylori defence against nitrosative stress remain largely unknown. In this study, we show that the NADH-flavin oxidoreductase FrxA of H. pylori, besides metabolizing nitrofurans and metronidazole, has S-nitrosoglutathione reductase activity. In agreement with this, inactivation of the FrxA-encoding gene resulted in a strain that was more sensitive to S-nitrosoglutathione. FrxA was also shown to contribute to the proliferation of H. pylori in macrophages, which are key phagocytic cells of the mammalian innate immune system. Moreover, FrxA was shown to support the virulence of the pathogen upon mouse infection. Altogether, we provide evidence for a new function of FrxA that contributes to the successful chronic colonization ability that characterizes H. pylori.
25,132,107
[ -0.03964781, -0.4886411, 0.07800828, 0.1284815, 0.2445118, -0.1483452, 0.3118774, 0.09793843, -0.1064304, -0.03581722, 0.1667268, -0.3470536, -0.04415515, 0.02516692, -0.5216316, -0.2132962, -0.3263337, -0.1036884, -0.194785, 0.1680855, -0.02683826, 0.1126658, -0.255323, ...
Efficient solar cells sensitized by porphyrins with an extended conjugation framework and a carbazole donor: from molecular design to cosensitization.
Porphyrin dyes containing the carbazole electron donor have been designed and optimized by wrapping the porphyrin framework, introducing an additional ethynylene bridge to extend the wavelength range of light absorption, and further suppression of the dye aggregation by introducing additional alkoxy chains. Application of a cosensitization approach results in improved current density (Jsc) and open-circuit voltage (Voc) values, thus achieving the highest cell efficiency of 10.45%. This work provides an effective combined strategy of molecular design and cosensitization for developing efficient dye-sensitized solar cells (DSSCs). In addition, carbazole has been demonstrated to be a promising donor for porphyrin sensitizers.
25,132,108
[ -0.037166, -0.1171066, 0.0517491, -0.08147869, 0.2593239, -0.1162214, -0.3187395, 0.07999661, 0.2954861, 0.003623602, -0.04939263, -0.2593316, -0.2062732, 0.3607516, -0.5270801, -0.2621925, -0.860965, 0.3770459, -0.03855707, 0.3231042, 0.1223192, 0.1897399, -0.05276469, ...
Quantification of the statistical effects of spatiotemporal processing of nontask FMRI data.
Nontask functional magnetic resonance imaging (fMRI) has become one of the most popular noninvasive areas of brain mapping research for neuroscientists. In nontask fMRI, various sources of "noise" corrupt the measured blood oxygenation level-dependent signal. Many studies have aimed to attenuate the noise in reconstructed voxel measurements through spatial and temporal processing operations. While these solutions make the data more "appealing," many commonly used processing operations induce artificial correlations in the acquired data. As such, it becomes increasingly more difficult to derive the true underlying covariance structure once the data have been processed. As the goal of nontask fMRI studies is to determine, utilize, and analyze the true covariance structure of acquired data, such processing can lead to inaccurate and misleading conclusions drawn from the data if they are unaccounted for in the final connectivity analysis. In this article, we develop a framework that represents the spatiotemporal processing and reconstruction operations as linear operators, providing a means of precisely quantifying the correlations induced or modified by such processing rather than by performing lengthy Monte Carlo simulations. A framework of this kind allows one to appropriately model the statistical properties of the processed data, optimize the data processing pipeline, characterize excessive processing, and draw more accurate functional connectivity conclusions.
25,132,113
[ -0.09703285, 0.4449506, -0.2159939, 0.2841781, -0.01757135, -0.3156226, -0.02359078, 0.1191689, 0.09129804, -0.1252139, -0.0744366, -0.114502, 0.01163602, -0.1309442, -0.4223554, 0.03904307, -0.2372209, 0.09438145, 0.01726794, 0.1062463, 0.02784766, 0.3343398, -0.04940936...
Snacks, beverages, vending machines, and school stores: a comparison of alternative and regular schools in Minnesota, 2002 to 2008.
In US secondary schools, vending machines and school stores are a common source of low-nutrient, energy-dense snacks and beverages, including sugar-sweetened beverages, high-fat salty snacks, and candy. However, little is known about the prevalence of these food practices in alternative schools, which are educational settings for students at risk of academic failure due to truancy, school expulsion, and behavior problems. Nationwide, more than 5,000 alternative schools enroll about one-half million students who are disproportionately minority and low-income youth. Principal survey data from a cross-sectional sample of alternative (n=104) and regular (n=339) schools collected biennially from 2002-2008 as part of the Centers for Disease Control and Prevention Minnesota School Health Profiles were used to assess and compare food practice prevalence over time. Generalized estimating equation models were used to estimate prevalence, adjusting for school demographics. Over time, food practice prevalence decreased significantly for both alternative and regular schools, although declines were mostly modest. However, the decrease in high-fat, salty snacks was significantly less for alternative than regular schools (-22.9% vs -42.2%; P<0.0001). Efforts to improve access to healthy food choices at school should reach all schools, including alternative schools. Study findings suggest high-fat salty snacks are more common in vending machines and school stores in alternative schools than regular schools, which may contribute to increased snacking behavior among students and extra consumption of salt, fat, and sugar. Study findings support the need to include alternative schools in future efforts that aim to reform the school food environment.
25,132,120
[ -0.2169068, 0.3816999, -0.4555289, 0.1911107, 0.2397742, -0.2846096, -0.1707681, 0.2575825, 0.1278986, -0.04867494, 0.2207257, -0.09033023, -0.1745016, 0.01888622, -0.2406474, -0.1711838, 0.0107345, -0.1265715, -0.03872331, -0.2609267, -0.1216514, 0.3162147, -0.03245182, ...
Recent advances in germination of Clostridium spores.
Members of Clostridium genus are a diverse group of anaerobic spore-formers that includes several pathogenic species. Their anaerobic requirement enhances the importance of the dormant spore morphotype during infection, persistence and transmission. Bacterial spores are metabolically inactive and may survive for long times in the environment and germinate in presence of nutrients termed germinants. Recent progress with spores of several Clostridium species has identified the germinant receptors (GRs) involved in nutrient germinant recognition and initiation of spore germination. Signal transduction from GRs to the downstream effectors remains poorly understood but involves the release of dipicolinic acid. Two mechanistically different cortex hydrolytic machineries are present in Clostridium spores. Recent studies have also shed light into novel biological events that occur during spore formation (accumulation of transcriptional units) and transcription during early spore outgrowth. In summary, this review will cover all of the recent advances in Clostridium spore germination.
25,132,133
[ 0.1294406, -0.2017588, -0.08152496, -0.2574867, -0.0008976058, -0.3142959, -0.08070228, 0.04191827, -0.05108912, 0.04455478, -0.01033193, 0.06176998, -0.0889748, 0.1397568, -0.7758977, 0.02412175, -0.4229103, 0.05385613, 0.3921746, -0.1487173, 0.3429866, 0.3542595, -0.273...
Life history responses of Daphnia similoides simultaneously exposed to microcystin-LR and ammonia and their postexposure recovery.
Aquatic organisms often suffer episodic stress from cyanobacterial bloom-derived concomitants and sometimes interactive stressors, and they may recover when stressors terminate. To assess whether exposed Daphnia can quickly recover from combined toxicity of bloom-derived stressors, Daphnia similoides were exposed to mixtures of ammonia (0 mg L(-1) , 0.37 mg L(-1) , and 0.58 mg L(-1) ) and dissolved microcystin-LR (0 µg L(-1) , 10 µg L(-1) , 30 µg L(-1) , and 100 µg L(-1) ) in a full factorial design for 14 d and subsequently allowed to recover for 7 d. During the exposure, the mixtures of ammonia and microcystin-LR showed different effects on the selected variables. Ammonia delayed the time to maturation, but microcystin-LR was not negative to the development of the tested daphnids. Furthermore, microcystin-LR reduced the prolonged developmental time to first eggs and first clutch caused by high ammonia. The total reproduction of D. similoides was dramatically reduced by 64% to 79% by both toxicants and their combinations, but there were no interactive effects. After the recovery period, organisms under most treatments did not recover completely from the combined stress but showed positive signs of recovery, based on the size of the last clutch and the mean number of clutches during recovery; thus the affected D. similoides have the potential to quickly recover from the combined toxic stressors.
25,132,136
[ -0.2479966, -0.06058028, -0.07633191, 0.1515747, 0.2013027, -0.1458389, 0.01732188, 0.3248002, 0.007643329, 0.01464358, -0.1304113, 0.3485931, -0.3048447, -0.07722413, -0.01785894, -0.1730275, -0.5094478, 0.4278426, 0.4699959, 0.2253183, 0.3707353, 0.01804349, -0.03680779...
The kinematic relationship between sitting and standing posture and pelvic inclination and its significance to cup positioning in total hip arthroplasty.
The aim of this study is to describe the influence of sitting and standing posture on sagittal pelvic inclination in total hip replacement patients to assist with correct acetabular component positioning. Lateral radiographs of the pelvis and lumbar spine in sitting and standing positions were extracted. Pelvic tilt was measured using the vertical inclination of a line from the anterior superior iliac spine (ASIS) to pubic tubercle. Sacral inclination, Cobb angle of the lumbar spine and hip flexion were recorded. Sixty patients were identified with a mean age of 63. Men were more likely to flex the lumbar spine in sitting (p = 0.004); 80° of hip flexion is required for seated posture. Stiff hips required compensatory pelvic flexion and lumbar flexion in sitting. There is a linear relationship between hip flexion and pelvic tilt, hip flexion and lumbar lordosis. Pelvic orientation is determined by lumbar and hip stiffness. This impacts on acetabular version.
25,132,150
[ 0.1944743, 0.1227944, -0.0827651, 0.06700857, -0.02126733, -0.2786998, -0.02861193, 0.2867345, -0.3861969, 0.1271635, 0.1143092, -0.2479345, -0.2379947, -0.4154212, -0.08071904, -0.1155352, -0.4364862, 0.1513749, -0.3760917, -0.05363534, 0.1155489, -0.08152846, -0.1319025...
Reproductive factors and non-Hodgkin lymphoma: a systematic review.
Considerable efforts have been made to elucidate non-Hodgkin lymphoma's (NHL) etiology during the last decades. Some evidence points to an association with reproductive factors, as incidence rates for most NHL subtypes are usually higher in men than in women, and several subtypes express hormonal receptors. Although the evidence is not compelling, some studies show an inverse association with gravidity. Associations with postmenopausal hormone therapy are usually derived from unopposed estrogen use, rather than for the combination of estrogen with progestin, but these findings vary by study design. Inconsistencies in the results are likely due to the complex relationship between reproductive, biological, and sociodemographic factors, as well as to study limitations. Elucidating the role of hormonal factors should provide clues for therapeutic options and public health decisions. We provide an overview of the available evidence on reproductive factors in NHL etiology, underscoring potential sources of discrepancies and bias.
25,132,165
[ -0.2314005, -0.05395322, 0.3441117, -0.1606413, 0.02663814, -0.1360804, 0.03384322, -0.112129, -0.001668539, 0.4788935, 0.0430012, 0.1549294, 0.165339, 0.1092392, -0.3108336, -0.1091961, 0.05738854, 0.1289687, -0.1921354, -0.2081121, 0.1309727, 0.2090416, -0.1496039, 0....
Hi-C analysis in Arabidopsis identifies the KNOT, a structure with similarities to the flamenco locus of Drosophila.
Chromosomes are folded, spatially organized, and regulated by epigenetic marks. How chromosomal architecture is connected to the epigenome is not well understood. We show that chromosomal architecture of Arabidopsis is tightly linked to the epigenetic state. Furthermore, we show how physical constraints, such as nuclear size, correlate with the folding principles of chromatin. We also describe a nuclear structure, termed KNOT, in which genomic regions of all five Arabidopsis chromosomes interact. These KNOT ENGAGED ELEMENT (KEE) regions represent heterochromatic islands within euchromatin. Similar to PIWI-interacting RNA clusters, such as flamenco in Drosophila, KEEs represent preferred landing sites for transposable elements, which may be part of a transposon defense mechanism in the Arabidopsis nucleus.
25,132,176
[ 0.4772941, 0.3994293, 0.1298773, -0.06909794, 0.2888072, 0.1065559, 0.1490131, -0.09274863, 0.3070427, 0.2017852, 0.09413038, 0.03029552, -0.139212, -0.1820201, -0.4494917, -0.1152714, -0.2210799, 0.3713161, 0.03015775, -0.0564014, 0.3428818, 0.1527656, -0.1273502, -0.2...
Theoretical study on molecular structure and vibrational analysis included FT-IR, FT-Raman and UV techniques of 2,4,5-trimethylbenzoic acid (monomer and dimer structures).
Theoretical study on the structural and vibrational analysis of monomer and dimer structures of 2,4,5-trimethylbenzoic acid (2,4,5-TMBA, C₁₀H₁₂O₂) were presented. The geometry of the molecule was fully optimized. The Fourier transform infrared (FT-IR) and the Fourier transform Raman (FT-Raman) spectra of the title molecule in solid phase were recorded in the region 4000-400 cm(-1) and 4000-50 cm(-1), respectively. The geometrical parameters and energies were investigated with the help of Density Functional Theory (DFT) employing B3LYP method and 6-311++G(d,p) basis set. The spectroscopic data of the molecule in the ground state were calculated by using DFT/B3LYP method with the 6-311++G(d,p) basis set. The vibrational spectra were calculated and fundamental vibrations were assigned on the basis of the potential energy distribution (PED) of the vibrational modes. The geometric parameters were compared with experimental data of the title molecule. The UV absorption spectrum of the studied compound was computed and recorded in the range of 190-400 nm dissolved in water and ethanol. Besides, charge transfer occurring in the molecule between HOMO and LUMO energies, frontier energy gap, molecular electrostatic potential (MEP) were calculated and presented. In addition these, thermodynamic properties and Mulliken atomic charges were performed.
25,132,184
[ -0.2476098, -0.2340863, 0.002928745, -0.08964943, -0.002594699, -0.04083865, 0.02371466, -0.2450094, 0.1393626, 0.04282669, 0.09306207, 0.08673162, -0.00435405, 0.2185142, -0.5722722, 0.4890811, -0.4875236, 0.203874, -0.06121554, 0.3857142, 0.1332135, 0.2610639, -0.058353...
A novel treatment for propagated crown fractures.
A major complication after endodontic treatment is persistent pain on biting or chewing. Although unsuccessful endodontic treatment can account for such pain, pain to chewing and biting can also be a result of an unsupported or propagated crown fracture. Crown fractures that extend apically result in deterioration of the localized periodontium and ultimate loss of the tooth. To date, no predictable treatment for apically extending crown fractures exists. Three cases of nonsurgical excision of a propagated crown fracture and the repair of the subsequent iatrogenic perforation are presented. This case report series describes a novel treatment for apically progressive crown fractures that results in patient comfort and maintenance as well as improved periodontal status of the tooth.
25,132,190
[ -0.3573474, 0.4647714, -0.2776511, -0.208324, -0.1796094, -0.2443319, -0.08109901, -0.03205828, 0.3835036, -0.0553569, 0.09351335, -0.0025876, -0.07535975, -0.0648463, -0.1172798, -0.1546287, -0.3972268, -0.08785087, -0.1911189, -0.1191045, -0.05428332, 0.1150623, 0.00098...
Simultaneous determination of phenolic compounds in Equisetum palustre L. by ultra high performance liquid chromatography with tandem mass spectrometry combined with matrix solid-phase dispersion extraction.
A method based on matrix solid-phase dispersion extraction followed by ultra high performance liquid chromatography with tandem mass spectrometry is presented for the extraction and determination of phenolic compounds in Equisetum palustre. This method combines the high efficiency of matrix solid-phase dispersion extraction and the rapidity, sensitivity, and accuracy of ultra high performance liquid chromatography with tandem mass spectrometry. The influential parameters of the matrix solid-phase dispersion extraction were investigated and optimized. The optimized conditions were as follows: silica gel was selected as dispersing sorbent, the ratio of silica gel to sample was selected to be 2:1 (400/200 mg), and 8 mL of 80% methanol was used as elution solvent. Furthermore, a fast and sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was developed for the determination of nine phenolic compounds in E. palustre. This method was carried out within <6 min, and exhibited satisfactory linearity, precision, and recovery. Compared with ultrasound-assisted extraction, the proposed matrix solid-phase dispersion procedure possessed higher extraction efficiency, and was more convenient and time saving with reduced requirements on sample and solvent amounts. All these results suggest that the developed method represents an excellent alternative for the extraction and determination of active components in plant matrices.
25,132,205
[ 0.02475967, 0.5625229, 0.2677426, 0.05980677, 0.2071988, -0.1561679, -0.02298443, 0.04873585, 0.553502, -0.01377904, -0.1744353, -0.007171186, -0.07976763, -0.03850721, -0.3560365, 0.03808935, -0.5332098, 0.2910924, -0.09444796, 0.2307498, 0.04438217, 0.2372223, -0.268030...
Does dexmedetomidine have a cardiac protective effect during non-cardiac surgery? A randomised controlled trial.
This study was designed to determine the effects of dexmedetomidine on perioperative myocardial injury by observing peripheral circulatory changes in response to tracheal intubation and extubation, myocardial enzyme levels, myocardial ischaemia improvements, cardiovascular adverse events and cytokines in patients with coronary heart disease (CHD) undergoing non-cardiac surgery. This study was a prospective, randomized, double-blind trial. Eighty patients having CHD were scheduled for elective hip-replacement surgery and randomly allocated to receive a loading dose of 1 μg/kg dexmedetomidine followed by a 0.2 μg/kg per h infusion (Dex group; n = 40) or normal saline (control group; n = 40). Systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, rate-pressure product and changes in ST-T segment on the electrocardiogram were recorded every 5 min during surgery. Serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), glycogen phosphorylase BB (GP-BB), interleukin (IL)-6 and tumour necrosis factor (TNF)-α protein levels were determined preoperatively, at the end of surgery and 12 and 24 h after surgery. The improvement rate of myocardial ischaemia was higher in the Dex than control group (87.5% vs 32.5%, respectively; P < 0.05). In addition, the Dex group had lower serum CK-MB, IL-6, cTnI and GP-BB concentrations than the control group (P < 0.05). There was no significance difference in TNF-α between the two groups (P > 0.05). Dexmedetomidine can reduce myocardial injury and cytokine levels in patients with CHD undergoing non-cardiac surgery.
25,132,247
[ -0.3799735, -0.2642173, -0.3676314, -0.1655231, -0.2587932, -0.8362517, -0.05467151, 0.06440569, -0.442658, -0.177523, 0.05244149, 0.4689185, -0.03080947, -0.06099485, 0.09420932, -0.03535037, -0.7347267, 0.02252629, -0.07126588, 0.3689756, -0.1943796, 0.08846858, -0.2065...
Identification of a Plasmodium falciparum inhibitor-2 motif involved in the binding and regulation activity of protein phosphatase type 1.
The regulation of Plasmodium falciparum protein phosphatase type 1 (PfPP1) activity remains to be deciphered. Data from homologous eukaryotic type 1 protein phosphatases (PP1) suggest that several protein regulators should be involved in this essential process. One such regulator, named PfI2 based on its primary sequence homology with eukaryotic inhibitor 2 (I2), was recently shown to be able to interact with PfPP1 and to inhibit its phosphatase activity, mainly through the canonical 'RVxF' binding motif. The details of the structural and functional characteristics of this interaction are investigated here. Using NMR spectroscopy, a second site of interaction is suggested to reside between residues D94 and T117 and contains the 'FxxR/KxR/K' binding motif present in other I2 proteins. This site seems to play in concert/synergy with the 'RVxF' motif to bind PP1, because only mutations in both motifs were able to abolish this interaction completely. However, regarding the structure/function relationship, mutation of either the 'RVxF' or 'FxxR/KxR/K' motif is more drastic, because each mutation prevents the capacity of PfI2 to trigger germinal vesicle breakdown in microinjected Xenopus oocytes. This indicates that the tight association of the PfI2 regulator to PP1, mediated by a two-site interaction, is necessary to exert its function. Based on these results, the use of a peptide derived from the 'FxxR/KxR/K' PfI2 motif was investigated for its potential effect on Plasmodium growth. This peptide, fused at its N-terminus to a penetrating sequence, was shown to accumulate specifically in infected erythrocytes and to have an antiplasmodial effect.
25,132,288
[ -0.01701353, -0.01879002, -0.1586288, -0.08572212, 0.03094464, -0.05113629, 0.3508818, 0.2784046, 0.1073048, -0.02049283, 0.1187363, 0.1795729, -0.3950927, -0.1658009, -0.4852775, -0.2025796, -0.4425424, -0.1104209, 0.4141365, 0.0158486, 0.464905, 0.3050954, -0.1417049, ...
Fragmentation of negative ions from N-linked carbohydrates: part 6. Glycans containing one N-acetylglucosamine in the core.
Negative ion collision-induced dissociation (CID) spectra of N-glycans contain many diagnostic ions that provide more structural information than positive ion spectra. EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. However, their negative ion CID spectra do not appear to have been studied in detail. This paper examines the CID and ion mobility properties of these endoH-released glycans to determine if the missing GlcNAc influences the production of diagnostic fragment ions. N-Glycans were released from ribonuclease B, ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from IgG with endoS to produce biantennary complex glycans, all missing the reducing-terminal GlcNAc residue. Negative ion CID and travelling wave ion mobility spectra were recorded with a Waters Synapt G2 mass spectrometer using nanospray sample introduction. The majority of glycans yielded CID spectra exhibiting the same diagnostic fragments, which were equivalently informative, as the fully released structures. However, the ability of ion mobility to separate isomers was generally found to be inferior to its use with the full glycans despite the smaller nature of the compounds. The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. The results show that the CID spectra of endoH- and endoS-released glycans are as useful as the corresponding spectra of the intact glycans (as released by PNGase F) in providing structural information on N-glycans.
25,132,301
[ -0.1449372, 0.07100248, -0.1298762, 0.1784188, -0.2026242, -0.253796, -0.188443, 0.1568253, 0.2817622, 0.1608224, -0.004086724, -0.1829782, 0.2068031, -0.1250315, 0.1429251, -0.005676448, -0.4172522, -0.01130877, 0.100244, -0.1655636, 0.02168997, 0.09405137, -0.2029592, ...
Synaptic plasticity under learning challenge.
Memory formation requires changes in neuronal networks connectivity based on modifications in strength and number of synapses. The mechanisms driving these changes have been intensively studied, but mostly under naive conditions, i.e. in animals that have not been cognitively challenged. Better characterization of synaptic requirements supporting memory formation can emerge from studies focusing on synaptic changes in memory-encoding structures while or after the animal model is cognitively challenged. Here, with this concept in mind, we review the literature describing structural, functional and molecular alterations developing in the hippocampus when animals are asked to form memories. We also briefly discuss the interest of this approach for disclosing pathological mechanisms in memory disorders, which might otherwise not be observed in naive conditions.
25,132,316
[ -0.04611492, -0.01892677, 0.1912848, -0.3709766, 0.0533129, -0.367591, -0.1612969, -0.2264736, 0.08379259, 0.2627684, 0.03657518, 0.002156885, 0.03861122, -0.129572, -0.6518032, 0.04424571, -0.3414155, 0.1548173, 0.004068331, 0.1663326, -0.1449087, 0.0008183385, -0.029284...
Avian influenza H9N2 subtype in Poland--characterization of the isolates and evidence of concomitant infections.
In April/May 2013, four outbreaks of avian influenza virus (AIV) infections caused by H9N2 subtype were diagnosed in Poland in fattening turkey flocks exhibiting a drop in feed and water intake, depression, respiratory signs and mortality. The subsequent serological survey carried out on samples collected between June 2012 and September 2013 from 92 poultry flocks detected positive sera in two additional meat turkey flocks located in the same province. The analysis of amino acids in the haemagglutinin and neuraminidase glycoproteins revealed that the detected H9N2 viruses possessed molecular profiles suggestive of low pathogenicity, avian-like SAα2,3 receptor specificity and adaptation to domestic poultry. Phylogenetic studies showed that these H9N2 AIVs grouped within the Eurasian clade of wild bird-origin AIVs and had no relationship with H9N2 AIV circulating in poultry in the Middle East and Far East Asia over the past decade. Experimentally infected SPF chickens with the index-case H9N2 virus remained healthy throughout the experiment. On the other hand, ten 3-week-old commercial turkeys infected via the oculonasal route showed respiratory signs and mortality (2/10 birds). Additional diagnostic tests demonstrated the consistent presence of DNA/RNA of Ornithobacterium rhinotracheale, Bordetella avium and, less frequently, of astro-, rota-, reo-, parvo- and adenoviruses in turkeys both from field outbreaks and laboratory experiment. Although no microbiological culture was performed, we speculate that these secondary pathogens could play a role in the pathogenicity of the current H9N2 infections.
25,132,323
[ -0.1690441, -0.5182878, -0.1082503, -0.1501951, -0.1249723, -0.5121461, -0.1594125, 0.3200014, -0.04746213, -0.05926748, 0.05412661, 0.06570271, 0.08669491, -0.2049593, -0.02252368, -0.1602166, -0.3769374, 0.2032202, -0.17885, 0.2207472, -0.07592016, 0.2869075, -0.3141361...
Melatonin treatment further improves adipose-derived mesenchymal stem cell therapy for acute interstitial cystitis in rat.
This study tests the hypothesis that combined melatonin and adipose-derived mesenchymal stem cell (ADMSC, 1.2 × 10(6) given intravenously) treatment offer superior protection against cyclophosphamide (CYP 150 mg/kg)-induced acute interstitial cystitis (AIC) in rats. Male adult Sprague-Dawley rats were treated as follows: sham controls, AIC alone, AIC + melatonin, AIC + ADMSC, and AIC + melatonin +ADMSC. When melatonin was used, it was given as follows: 20 mg/kg at 30 min after CYP and 50 mg/kg at 6 and 18 hr after CYP. Twenty-four-hour urine volume, urine albumin level, and severity of hematuria were highest in AIC rats and lowest in the controls; likewise urine volume was higher in AIC + melatonin rats than in AIC + ADMSC and AIC + melatonin + ADMSC treated rats; in all cases, P < 0.001. The numbers of CD14+, CD74+, CD68+, MIP+, Cox-2+, substance P+, cells and protein expression of IL-6, IL-12, RANTES, TNF-α, NF-κB, MMP-9, iNOS (i.e. inflammatory biomarkers), glycosaminoglycan level, expression of oxidized protein, and protein expression of reactive oxygen species (NOX-1, NOX-2, NOX-4) in the bladder tissue exhibited an identical pattern compared with that of hematuria among the five groups (all P < 0.0001). The integrity of epithelial layer and area of collagen deposition displayed an opposite pattern compared to that of hematuria among all groups (P < 0.0001). The cellular expressions of antioxidants (GR, GPx, HO-1, NQO 1) showed a significant progressive increase form controls to AIC + melatonin + ADMSC (all P < 0.0001). Combined regimen of melatonin and ADMSC was superior to either alone in protecting against CYP-induced AIC.
25,132,326
[ -0.02673368, -0.01853652, -0.4114789, -0.1500394, 0.156483, -0.2340938, -0.329845, 0.1783744, 0.02856307, -0.03807028, 0.1536046, -0.05623083, 0.2088866, 0.09379298, -0.46355, 0.1628042, -0.2157122, -0.112888, 0.01029946, -0.05389617, -0.1656142, -0.2524402, -0.3488718, ...
Protective properties of a fusion pneumococcal surface protein A (PspA) vaccine against pneumococcal challenge by five different PspA clades in mice.
An increase in the appearance of nonvaccine serotypes in both children and adults with invasive pneumococcal disease (IPD) after introduction of pneumococcal conjugate vaccine represents a limitation of this vaccine. In this study, we generated three recombinant pneumococcal surface protein A (PspA) proteins comprising PspA families 1 and 2, and we examined the reactivity of antisera raised in mice immunized with a PspA fusion protein in combination with CpG oligonucleotides plus aluminum hydroxide gel. The protective effects of immunization with PspA fusion proteins against pneumococcal challenge by strains with five different PspA clades were also examined in mice. Flow cytometry demonstrated that PspA3+2-induced antiserum showed the greatest binding of PspA-specific IgG to all five challenge strains with different clades. PspA2+4- or PspA2+5-induced antiserum showed the lowest binding of PspA-specific IgG to clade 3. Immunization with PspA3+2 afforded significant protection against pneumococcal challenge by five strains with different clades in mice, but immunization with PspA2+4 or PspA2+5 failed to protect mice from pneumococcal challenge by strains with clades 1 and 3. The binding of PspA-specific IgG in antisera raised by three PspA fusion proteins was examined in 68 clinical isolates from adult patients with IPD. Immunization of mice with PspA3+2-induced antiserum with a high binding capacity for clinical isolates expressing clades 1-4, but not clade 5. Our results suggest that the PspA3+2 vaccine has an advantage over the PspA2+4 or PspA2+5 vaccine in terms of a broad range of cross-reactivity with clinical isolates and cross-protection against pneumococcal challenge in mice.
25,132,335
[ 0.03621894, 0.007297031, 0.1555422, -0.2326576, -0.1712964, -0.1055922, -0.1329962, 0.02016331, 0.1586592, 0.05213759, -0.09446152, 0.06605071, -0.06807459, -0.3384098, -0.4351537, -0.1316486, 0.05806439, 0.006773691, -0.05958075, 0.1279416, 0.5539398, 0.1255081, -0.16883...
Curcumin attenuates cardiac fibrosis in spontaneously hypertensive rats through PPAR-γ activation.
To investigate the effects of curcumin (Cur) on cardiac fibrosis in spontaneously hypertensive rats (SHRs) and the mechanisms underlying the anti-fibrotic effect of Cur in rat cardiac fibroblasts (CFs) in vitro. SHRs were orally treated with Cur (100 mg·kg(-1)·d(-1)) or Cur (100 mg·kg(-1)·d(-1)) plus the PPAR-γ antagonist GW9662 (1 mg·kg(-1)·d(-1)) for 12 weeks. Cultured CFs were treated with angiotensin II (Ang II, 0.1 μmol/L) in vitro. The expression of relevant proteins and mRNAs was analyzed using Western blotting and real-time PCR, respectively. The expression and activity of peroxisome proliferator-activated receptor-γ (PPAR-γ) were detected using Western blotting and a DNA-binding assay, respectively. Treatment of SHRs with Cur significantly decreased systolic blood pressure, blood Ang II concentration, heart weight/body weight ratio and left ventricle weight/body weight ratio, with concurrently decreased expression of connective tissue growth factor (CTGF), plasminogen activator inhibitor (PAI)-1, collagen III (Col III) and fibronectin (FN), and increased expression and activity of PPAR-γ in the left ventricle. Co-treatment with GW9662 partially abrogated the anti-fibrotic effects of Cur in SHRs. Pretreatment of CFs with Cur (5, 10, 20 μmol/L) dose-dependently inhibited Ang II-induced expression of CTGF, PAI-1, Col III and FN, and increased the expression and binding activity of PPAR-γ. Pretreatment with GW9662 partially reversed anti-fibrotic effects of Cur in vitro. Furthermore, pretreatment of CFs with Cur inhibited Ang II-induced expression of transforming growth factor-β1 (TGF-β1) and phosphorylation of Smad2/3, which were reversed by GW9662. Cur attenuates cardiac fibrosis in SHRs and inhibits Ang II-induced production of CTGF, PAI-1 and ECM in CFs in vitro. The crosstalk between PPAR-γ and TGF-β1/Smad2/3 signaling is involved in the anti-fibrotic and anti-proliferative effects of Cur.
25,132,338
[ -0.05769614, -0.002287184, -0.2231733, -0.09430871, 0.2111031, 0.01570682, -0.1104204, 0.2599091, 0.268182, 0.07007392, -0.06751195, 0.5886238, 0.08420291, 0.1744135, -0.161856, 0.303604, -0.3652143, 0.04582616, -0.08520132, 0.30512, -0.3904612, 0.164459, -0.6580371, 0....
Animal models of social anxiety disorder and their validity criteria.
Anxiety disorders pose one of the largest threats to global mental health, and they predominantly emerge early in life. Social anxiety disorder, also known as social phobia, is the most common of all anxiety disorders. Moreover, it has severe consequences and is a disabling disorder that can cause an individual to be unable to perform the tasks of daily life. Social anxiety disorder is associated with the subsequent development of major depression and other mental diseases, as well as increased substance abuse. Although some neurobiological alterations have been found to be associated with social anxiety disorder, little is known about this disorder. Animal models are useful tools for the investigation of this disorder, as well as for finding new pharmacological targets for treatment. Thus, this review will highlight the main animal models of anxiety associated with social phobia.
25,132,362
[ -0.4188097, -0.1303426, -0.03738409, -0.06993566, 0.06657468, -0.3541013, -0.276056, -0.07306538, -0.1816704, -0.3267339, 0.1550574, 0.0818968, -0.02171534, -0.2810575, -0.07656385, -0.1670071, -0.2686097, 0.3026081, 0.05649998, 0.08842943, -0.129513, 0.2657626, -0.101125...
In-office bleaching gel with 35% hydrogen peroxide enhanced biofilm formation of early colonizing streptococci on human enamel.
To compare the effects of 25% and 35% hydrogen peroxide in-office bleaching systems on surface roughness and streptococcal biofilm formation on human enamel. Enamel specimens (3mm×3mm×2mm, n=162) from human permanent teeth were randomly divided into 3 treatment groups (n=54 each): (1) control, (2) bleached with 25% hydrogen peroxide (Zoom2™), and (3) bleached with 35% hydrogen peroxide (Beyond™). The enamel surface roughness was measured by a profilometer before and after treatments. Subsequently, the treated enamel specimens were randomly placed into 3 subgroups (n=18 each) and incubated with: (1) trypticase soy broth control, (2) Streptococcus mutans culture and (3) Streptococcus sanguinis culture for 24h. Biofilm formation was quantified by crystal violet staining. The biofilm structure on three specimens from each group was visualized by scanning electron microscopy. Data were analyzed by Kruskal-Wallis and Mann-Whitney U tests with Bonferroni corrections. Significance level was set at p<0.05. Both bleaching systems significantly reduced enamel surface roughness comparing to the control group (p<0.001), but there was no difference between the two treatment groups. Remarkably, S. sanguinis biofilm formation was significantly higher on enamel specimens bleached with 35% hydrogen peroxide than other treatments (p<0.001), but was lower on those bleached with 25% hydrogen peroxide (p<0.001). In contrast, no difference in S. mutans biofilm formation was observed among the three treatment groups. Both 25% and 35% hydrogen peroxide caused similar degrees of reduction in enamel surface roughness. Nevertheless, bleaching with 35% hydrogen peroxide appeared to markedly promote S. sanguinis biofilm formation. The increase of early colonizer biofilm raised concerns over adverse effects of in-office bleaching on plaque formation. This should be further investigated in vivo and efficient plaque control should be emphasized after bleaching with high concentrations of hydrogen peroxide.
25,132,364
[ 0.3812155, 0.2741136, -0.2466557, 0.366879, -0.2847714, -0.2742252, -0.08892503, 0.1051801, 0.07556142, -0.5507002, 0.08116936, 0.08406905, 0.009273715, -0.1585677, -0.09252042, -0.248883, -0.1090202, -0.00547821, 0.05381322, -0.3905451, 0.1798109, 0.6699698, -0.1442349, ...
Percutaneous carbon dioxide treatment using a gas mist generator enhances the collateral blood flow in the ischemic hindlimb.
Highly concentrated carbon dioxide (CO2) is thought to be useful for ischemic diseases. We investigated whether treatment with a few micrometers of CO2 molecules atomized via two fluidnozzles (CO2 mist) exerts an angiogenic effect in a mouse ischemic hindlimb model. Mice with unilateral hindlimb ischemia were divided into untreated (UT), 100% CO2 gas alone-treated (CG), mixed air (O2; 20%, N2; 80%) mist-treated (AM) and 100% CO2 mist-treated (CM) groups. The lower body of the mice was encased in a polyethylene bag filled with each gaseous agent using a gas mist generator for 10 minutes daily. According to a laser Doppler analysis, the ischemic hindlimb blood flow was persistently higher after the seventh day of induction of ischemia in the CM group than in the UT group. The capillary density was also greater in the CM group on day 28 compared with that observed in the UT group. In addition, the parameters in the AM and CG groups were similar to those obtained in the UT group. The observed effects were abolished by the administration of an inhibitor of nitric oxide synthase (NOS). The vascular endothelial growth factor mRNA expression and protein levels and the phosphorylated endothelial NOS level were increased in the CM group compared with that observed in the UT group. A proteomic analysis using liquid chromatography-tandem mass spectrometry identified novel protein candidates regulated by CO2 mist. Percutaneous CO2 mist therapy may be useful for treating ischemia-induced angiogenesis.
25,132,376
[ -0.2523036, 0.5388288, -0.05048082, -0.05394124, 0.03541334, -0.1048209, -0.1680181, -0.252924, 0.3513703, -0.08508348, -0.1372583, 0.2337273, -0.05448563, -0.1877372, -0.194661, 0.2059693, 0.05977817, -0.07906539, 0.03488562, 0.1774316, 0.09572732, -0.02132245, -0.103269...
Closed suction drainage for treatment of septic peritonitis of confirmed gastrointestinal origin in 20 dogs.
To determine survival rate in dogs with septic peritonitis of confirmed gastrointestinal origin treated with closed suction drainage. Retrospective case series. Dogs (n = 20) with septic peritonitis. Medical records (2007-2010) of dogs with septic peritonitis of confirmed gastrointestinal origin treated by closed suction drainage were reviewed. Information on signalment, clinicopathologic abnormalities, underlying cause, surgical procedure performed, postoperative management, complications, and outcome was obtained. Dehiscence of a previous anastomosis was the most common source of contamination (80%). Drains remained in place, collecting fluid produced within the abdomen, for a median of 6 days (range, 2-11 days). Eighteen dogs received nutritional support, and 14 received plasma transfusions. Seventeen dogs (85%) survived to discharge. Closed suction drainage together with resolution of the underlying cause of peritonitis and appropriate postoperative management is an effective technique for treatment of septic peritonitis of confirmed gastrointestinal origin in dogs.
25,132,380
[ -0.2563293, 0.03209149, 0.1472148, -0.3032928, -0.08680263, -0.1544298, -0.1041379, -0.3263656, -0.09074829, -0.1052334, 0.181578, -0.4032228, -0.4199007, -0.07845113, 0.1350457, -0.02284498, 0.01224358, -0.04772812, 0.250257, -0.3769997, -0.3068556, 0.3090359, -0.0158397...
Successful management of chronic postsurgical pain following total knee replacement.
We report reversal of chronic postsurgical pain (CPSP) along with functional restoration after total knee replacement (TKR) in two patients, using a combination therapy that included ultrasonography-guided pulsed radiofrequency (PRF) of nerves supplying the knee to provide pain relief, along with dry needling (DN) to relax myofascial triggers/bands that caused painful stiffness and restricted movement of muscles acting across the knee. Both patients showed demonstrable pain relief, as evidenced by changes in pain as assessed on the Numeric Rating Scale (patient 1: 4-9/10 [pre-treatment] to 0-3/10 [6 months post-treatment]; patient 2: 5-9/10 to 0-4/10), Oxford Knee Score (patient 1: 17 to 40; patient 2: 12 to 39), Self-Administered Leeds Assessment of Neuropathic Symptoms and Signs score (patient 1: 16 to 0; patient 2: 18 to 0), and Patient Health Questionnaire-9 score (patient 1: 17 to 2; patient 2: 20 to 2). The selection of the PRF-and-DN combination for treating post-TKR CPSP was based on a new idea that CPSP is a neuromyopathic phenomenon involving both sensory and motor neuropathy. It has evolved from our experience of 8 years. Physiotherapy worked synergistically with DN, optimizing muscle performance and pain relief.
25,132,412
[ 0.1403782, -0.1080988, 0.08204168, -0.1646488, -0.2273812, -0.2674855, -0.1620341, 0.1235718, 0.1619764, -0.291509, 0.00826704, -0.06123442, -0.03728173, -0.0781422, -0.2778358, -0.1531292, -0.359866, -0.1941004, -0.2166769, -0.1399728, -0.4201727, -0.08551984, 0.06107946...
Beyond the use of modifiers in selective alkyne hydrogenation: silver and gold nanocatalysts in flow mode for sustainable alkene production.
We report on the excellent stereo and chemoselectivity of nanosized silver and gold catalysts in the three-phase hydrogenation of acetylenic compounds under flow chemistry conditions. The materials featuring metal nanoparticles in the range of 2-21 nm were prepared by spray deposition or incipient wetness impregnation of silver nitrate and sol immobilisation of gold chloride on different carriers (Al2O3, SiO2, TiO2, and carbon), followed by activation in various atmospheres. The samples were characterised by ICP-OES, N2 sorption, XPS, HAADF-STEM, and HRTEM, and evaluated in a continuous-flow flooded-bed micro-reactor. Both metals display optimal activities for particles below 5 nm, enabling stable operation at T = 373 K and P = 10 bar. While the performance of the silver catalysts is less influenced by the support, the gold nanoparticles exhibit significant activity only when deposited on TiO2, likely due to the strong metal-support interaction. Hydrogenations of functionalised alkynes reveal that silver and gold match, and in some cases exceed, the selectivity of benchmark palladium-based catalysts. Furthermore, in contrast to Pd, the Ag and Au samples require no modifiers, which brings fundamental and practical simplifications for their understanding and large scale manufacture. Therefore, these materials could be advantageously used for the continuous production of olefinic intermediates in the fine chemical and pharmaceutical industries.
25,132,414
[ -0.1007103, 0.08049005, 0.3113035, -0.008789615, -0.06913698, -0.004413369, -0.1955674, -0.05108491, -0.01627831, 0.19407, -0.1936442, -0.2765764, -0.01305334, -0.1694407, -0.2509778, -0.08883757, -0.258075, 0.1561758, 0.01212832, -0.05888578, 0.1262255, 0.05763522, -0.11...
An analysis of genetic factors related to risk of inflammatory bowel disease and colon cancer.
Patients with inflammatory bowel disease (IBD) have a higher risk of developing colorectal cancer than the general population. Genome-wide association studies have identified and replicated several loci associated with risk of IBD; however, it is currently unknown whether these loci are also associated with colon cancer risk. We selected 15 validated SNPs associated with risk of either Crohn's disease, ulcerative colitis, or both in previous GWAS and tested whether these loci were also associated with colon cancer risk in a two-stage study design. We found that rs744166 in STAT3 was associated with colon cancer risk in two studies; however, the direction of the observation was reversed in TP53 mutant tumors possibly due to a nullification of the effect by mutant p53. The SNP, which lies within intron 1 of the STAT3 gene, was associated with lower expression of STAT3 mRNA in TP53 wild-type, but not mutant, tumors. These data suggest that the STAT3 locus is associated with both IBD and cancer. Further understanding the function of this variant in relation to TP53 could possibly explain the role of this gene in autoimmunity and cancer. Furthermore, an analysis of this locus, specifically in a population with IBD, could help to resolve the relationship between this SNP and cancer.
25,132,422
[ -0.06531398, -0.3119542, 0.08598504, -0.3612294, 0.05487828, -0.1493618, 0.01278661, 0.2060157, 0.1069236, 0.1075365, -0.02905465, 0.03714619, -0.04777429, -0.3266488, 0.006066394, -0.1312484, -0.02522113, -0.3036728, 0.1894981, -0.02590814, 0.1854095, 0.2036769, -0.04508...
[A painful occipital mass revealing a posterior encephalocele].
Encephalocele is a congenital malformation caused by a neural tube defect during embryonic development. We report a case of posterior encephalocele in a 7-month-old infant with a painful occipital mass known since birth. Pathological examination of the mass showed different mature tissues derived from the brain and its coverings (e.g., neuroglia, ependymal canals and clusters of meningothelial cells). A diagnosis of encephalocele was made. The different forms of neural tube defect will be briefly discussed, especially the "aborted" forms (e.g., non-specific midline mass lesion or angioma) that the pathologist may encounter in his/her daily practice.
25,132,445
[ -0.2601095, 0.2748906, -0.1627368, -0.09392966, 0.08724966, -0.3666488, -0.1772823, -0.1858859, 0.1905633, -0.07809102, 0.06249281, 0.1565098, 0.04172653, -0.1592126, -0.4859363, -0.03280921, -0.4501334, 0.2365826, -0.04660523, -0.08564327, 0.3547101, 0.1995353, 0.0727051...
Identification of putative kdr mutations in the tropical bed bug, Cimex hemipterus (Hemiptera: Cimicidae).
Bed bugs [both Cimex hemipterus (F.) and Cimex lectularius L.] are highly resistant to pyrethroids worldwide. An important resistance mechanism known as 'knockdown resistance' (kdr) is caused by genetic point mutations on the voltage-gated sodium channel (VGSC) gene. Previous studies have identified two point mutations (V419L and L925I) on the VGSC gene in C. lectularius that are responsible for kdr-type resistance. However, the kdr mutations in C. hemipterus have not been investigated. Four novel mutations, L899V (leucine to valine), M918I (methionine to isoleucine), D953G (aspartic acid to glycine) and L1014F (leucine to phenylalanine), were identified in the domain II region of the C. hemipterus VGSC gene. This region has been widely investigated for the study of kdr-type resistance to pyrethroids in other insect pests. The V419L and L925I kdr mutations as previously identified in C. lectularius were not detected in C. hemipterus. M918I and L1014F are considered to be probable kdr mutations and may play essential roles in kdr-type resistance to pyrethroids in C. hemipterus. Further studies are under way in the authors' laboratory to determine the non-kdr-type resistance mechanisms in C. hemipterus.
25,132,449
[ 0.1285533, 0.1884043, 0.1207974, -0.4151289, -0.06965268, -0.07621794, -0.04141345, -0.2265032, 0.2363429, 0.1535901, 0.2126223, 0.2361292, -0.3287995, -0.01500434, -0.6564951, -0.09833188, -0.1408793, 0.2825122, 0.008621912, 0.03651503, -0.2122277, 0.2481882, 0.03908764,...
Development of a fluoride chronic effects benchmark for aquatic life in freshwater.
Canada has an interim water-quality guideline for fluoride for protection of freshwater aquatic life that dates from 2002, and 1 Canadian province has a different interim water-quality guideline for fluoride that dates to 1995. The United States does not have a national benchmark for fluoride in freshwater, and only 1 US state has such a benchmark. There are no other national or regional benchmarks for fluoride chronic toxicity in freshwater. In the present study, available data on the acute and chronic toxicity of fluoride to freshwater aquatic life were compiled and reviewed. Acute toxicity was reported to occur at concentrations ranging from 11.5 to >800 mg/L fluoride (F(-) ). The majority of chronic effects occur at concentrations between 1.8 mg/L and 195 mg/L. A total of 10 chronic studies representing 16 species (5 fish, 7 invertebrates, and 4 algae/aquatic plants) were used to derive a chronic effects benchmark of 1.94 mg/L F(-) , applying the species sensitivity distribution approach.
25,132,451
[ -0.5808415, -0.14752, -0.03350705, -0.0749722, 0.06581917, -0.06330704, -0.2328564, 0.05772237, 0.2003662, -0.09132, -0.07768908, 0.08915841, -0.0366661, 0.08607638, -0.01085598, -0.5442979, 0.09674751, 0.3937905, -0.3021289, 0.06353569, -0.1709681, 0.4812079, -0.02057516...
The immunology of human cytomegalovirus latency: could latent infection be cleared by novel immunotherapeutic strategies?
While the host immune response following primary human cytomegalovirus (HCMV) infection is generally effective at stopping virus replication and dissemination, virus is never cleared by the host and like all herpesviruses, persists for life. At least in part, this persistence is known to be facilitated by the ability of HCMV to establish latency in myeloid cells in which infection is essentially silent with, importantly, a total lack of new virus production. However, although the viral transcription programme during latency is much suppressed, a number of viral genes are expressed during latent infection at the protein level and many of these have been shown to have profound effects on the latent cell and its environment. Intriguingly, many of these latency-associated genes are also expressed during lytic infection. Therefore, why the same potent host immune responses generated during lytic infection to these viral gene products are not recognized during latency, thereby allowing clearance of latently infected cells, is far from clear. Reactivation from latency is also a major cause of HCMV-mediated disease, particularly in the immune compromised and immune naive, and is also likely to be a major source of virus in chronic subclinical HCMV infection which has been suggested to be associated with long-term diseases such as atherosclerosis and some neoplasias. Consequently, understanding latency and why latently infected cells appear to be immunoprivileged is crucial for an understanding of the pathogenesis of HCMV and may help to design strategies to eliminate latent virus reservoirs, at least in certain clinical settings.
25,132,454
[ -0.1672651, -0.01514747, -0.1475997, -0.1388776, 0.07942607, -0.2842799, -0.1474999, 0.1374773, 0.09955633, 0.2098109, 0.03928426, 0.04097592, 0.157544, -0.05971228, -0.4078831, -0.04562565, -0.4412045, -0.07286954, 0.09441128, 0.2464161, 0.02867514, 0.2158621, -0.0097065...
Practical knowledge of experienced nurses in critical care: a qualitative study of their narratives.
Scholars of nursing practices have claimed practical knowledge is source of knowledge in its own right, nevertheless we know little about this knowledge associated with day-to-day practice. The purpose of this study is to describe knowledge that the more experienced nurses the in ICU make use of and discover the components of care it includes. Understanding this knowledge can contribute to improving the working practices of nurses with less experience. We used a phenomenologic and hermeneutic approach to conduct a qualitative study. Open in-depth dialogue interviews were conducted with 13 experienced ICU nurses selected by intentional sampling. Data was compiled on significant stories of their practice. The data analysis enabled units of meaning to be categorised and grouped into topics regarding everyday practical knowledge. Knowledge related to everyday practice was evaluated and grouped into seven topics corresponding to how the ICU nurses understand their patient care: 1) Connecting with, calming and situating patients who cannot communicate; 2) Situating and providing relief to patients in transitions of mechanical respiration and non-invasive ventilation; 3) Providing reassurance and guaranteeing the safety of immobilised patients; 4) The "connection" with patients in comas; 5) Taking care of the body; 6) The transition from saving life to palliative care; and 7) How to protect and defend the patient from errors. The components of caretaking that guarantee success include: the calm, care and affection with which they do things; the time devoted to understanding, situating and comforting patients and families; and the commitment they take on with new staff and doctors for the benefit of the patient. These results show that stories of experiences describe a contextual practical knowledge that the more experienced nurses develop as a natural and spontaneous response. In critical patients the application of everyday practical knowledge greatly influences their well-being. In those cases in which the nurses describe how they have protected the patients from error, this practical knowledge can mean the difference between life and death. The study highlights the need to manage practical knowledge and undertake further research. The study is useful in keeping clinical practice up-to-date.
25,132,455
[ -0.2183915, 0.006576658, 0.06088087, 0.06467167, 0.3490451, 0.1457652, 0.2163826, -0.2602672, -0.05689797, -0.1963906, -0.01954271, -0.1710697, -0.3279056, -0.2673839, -0.03537099, 0.06887767, -0.3016316, 0.03092664, -0.03672468, 0.01016427, 0.03766146, 0.101864, -0.12596...
Desiccation enhances phosphorylation of PSII and affects the distribution of protein complexes in the thylakoid membrane.
Desiccation has significant effects on photosynthetic processes in intertidal macro-algae. We studied an intertidal macro-alga, Ulva sp., which can tolerate desiccation, to investigate changes in photosynthetic performance and the components and structure of thylakoid membrane proteins in response to desiccation. Our results demonstrate that photosystem II (PSII) is more sensitive to desiccation than photosystem I (PSI) in Ulva sp. Comparative proteomics of the thylakoid membrane proteins at different levels of desiccation suggested that there were few changes in the content of proteins involved in photosynthesis during desiccation. Interestingly, we found that both the PSII subunit, PsbS (Photosystem II S subunit) (a four-helix protein in the LHC superfamily), and light-harvesting complex stress-related (LHCSR) proteins, which are required for non-photochemical quenching in land plants and algae, respectively, were present under both normal and desiccation conditions and both increased slightly during desiccation. In addition, the results of immunoblot analysis suggested that the phosphorylation of PSII and LHCII increases during desiccation. To investigate further, we separated out a supercomplex formed during desiccation by blue native-polyacrylamide gel electrophoresis and identified the components by mass spectrometry analysis. Our results show that phosphorylation of the complex increases slightly with decreased water content. All the results suggest that during the course of desiccation, few changes occur in the content of thylakoid membrane proteins, but a rearrangement of the protein complex occurs in the intertidal macro-alga Ulva sp.
25,132,456
[ 0.05510184, 0.05392195, 0.01888816, -0.1404626, 0.1002811, -0.3256831, -0.2310348, 0.1147462, 0.4424275, 0.233188, 0.08998682, 0.0118734, -0.4999787, 0.3021975, 0.03583955, -0.2730856, -0.1053165, 0.07815681, -0.1210723, -0.4342756, 0.1034134, 0.3543431, -0.07478615, -0...
Lactate dehydrogenase and caspase activity in nasopharyngeal secretions are predictors of bronchiolitis severity.
Bronchiolitis is the leading cause of hospitalization in infants. Biomarkers of disease severity might help in clinical management. To determine the clinical predictiveness of NW-LDH, NW-caspase 3/7, and NW-LDH/NW-caspase 3/7 ratio in bronchiolitis. Previously healthy children less than 24 months of age with bronchiolitis were recruited from the Texas Children's emergency room and intensive care unit from October 2010 to April 2011. Demographic, clinical information, and NW samples were obtained at enrollment. NW samples were analyzed for respiratory viruses, caspase 3/7, and LDH. A viral pathogen was detected in 91·6% of 131 children, with the most common being respiratory syncytial virus and human rhinovirus. A single infection was found in 61·8% of subjects and co-infection in 29·8%. Children admitted to ICU had significantly higher NW-LDH than children sent home from the ER or admitted to the general floor (P = 0·02). Children infected with RSV had the highest NW-LDH concentration (P = 0·03) compared with other viral infections. NW-LDH and NW-caspase were significantly correlated (r = 0·77, P < 0·0001). The univariate models showed NW-LDH and NW-LDH/NW- caspase 3/7 ratio were directly associated with hospitalization. Mutivariate regression analyses suggested a complex interaction between the biomarkers, demographics, and disposition. NW-LDH, NW-caspase 3/7 and NW-LDH/NW-caspase 3/7 ratio and their interactions with demographic factors are predictive of bronchiolitis severity and can help distinguish children requiring ICU-level care from those admitted to the general floor, or discharged home from the emergency center.
25,132,512
[ -0.2569038, -0.3785766, -0.21437, -0.05244876, -0.02139349, -0.4424287, 0.04439363, -0.3235377, -0.06844701, -0.07725327, -0.03851365, 0.3439517, -0.200078, 0.04296347, 0.09946017, -0.03916465, -0.2449474, 0.2308311, 0.08996352, 0.007681873, 0.1057752, 0.01302848, -0.0517...
Magnetic ring anastomosis of suprahepatic vena cava: novel technique for liver transplantation in rat.
To improve the technique of suprahepatic vena cava (SHVC) reconstruction in rat OLT, novel magnetic rings were designed and manufactured to facilitate reconstruction of SHVC and shorten the anhepatic time. One-hundred and twenty adult male Wistar rats were randomly divided into two groups: rings group (n = 30), using magnetic rings for SHVC reconstruction; suture group (n = 30), 7/0 prolene suture was used for SHVC running anastomosis as control. Cuff techniques were used for portal vein and infrahepatic vena cava reconstruction as Kamada and Calne described. The bile duct was reconnected with a stent. The hepatic re-arterialization was omitted. In the rings group, the SHVC reconstruction took 0.91 ± 0.24 (mean ± SD) min; the anhepatic phase and the recipient operation time were 5.63 ± 0.65 min and 36.02 ± 8.02 min, respectively. In suture group, the anastomotic time of SHVC was 10.40 ± 2.11 min; the anhepatic phase and the recipient operation time were 17.76 ± 2.51 and 49.38 ± 12.06 min, respectively, and there was statistically significant difference between the two groups. The ALT levels reached peak at 24 h post-OLT (186.2 ± 32.5 IU/l) and restored to normal level at 96 h gradually. In the rings group, 29 of 30 rats survived at day 7 and 28 of 30 rats survived at day 30. In contrast, only 25 of 30 recipients in suture group remained alive at day 7 and 22 of 30 remained alive at day 30 (P < 0.05). Better anastomotic healing was founded in rings group by pathology and scanning electron microscope. The magnetic rings technique provides a novel, simple method for SHVC reconstruction of OLT in rat. It significantly shortens anhepatic phase, while the success rate of the operation is satisfactory.
25,132,515
[ 0.1526454, 0.05717033, -0.2191265, 0.05059379, 0.1666058, -0.02837395, -0.1604241, -0.2123315, 0.2726589, 0.1352435, 0.2036913, -0.1140643, 0.163577, 0.3181322, -0.7617067, -0.3934289, -0.1624654, 0.1037088, 0.1040734, 0.3538067, 0.0782254, 0.5279698, 0.1021276, 0.29029...
Ranolazine attenuates mechanical allodynia associated with demyelination injury.
The aim of this study was to determine whether ranolazine, a new medication that targets sodium channels to improve cardiac ischemia and angina, could be an effective analgesic agent for pain associated with demyelination injury. Many agents have been used to treat neuropathic pain but not all neuropathic conditions respond similarly to treatment. We have demonstrated that ranolazine, an agent that blocks voltage-gated sodium channels Nav 1.4, 1.5, 1.7, and 1.8, is effective in attenuating mechanical hyperalgesia in both complete Freund's adjuvant and spared nerve injury preclinical models of inflammatory and neuropathic pain, respectively. Here we test the efficacy of this drug in a newly validated model of demyelination injury that responds uniquely to a number of treatment options. After determination of baseline nerve conduction velocities (NCVs) and withdrawal responses from heat and mechanical stimulation in male Sprague-Dawley rats (300-350 g), 1 μg/30 μL of doxorubicin was injected into one sciatic nerve. The contralateral nerve provided a sham-injected control. Two weeks after doxorubicin injection, NCV and sensitivity to heat and mechanical stimulation were reassessed before and after treatment with ranolazine (10, 30, 50 mg/kg) administered intraperitoneally using an experimenter-blinded, randomized design. Doxorubicin injection produced a significant hyperalgesic effect in response to mechanical but not heat stimulation. Conduction velocities in the injected limbs were reduced when compared with controls. Ranolazine reduced mechanical allodynia with peak efficacy at 30 mg/kg. Fifty milligram/kilogram ranolazine restored NCVs by approximately 50%, but had no effect in the uninjected limb. Ranolazine exerts broad-spectrum actions to reduce mechanical allodynia that is associated with peripheral demyelination injury.
25,132,522
[ -0.1371219, 0.1111642, -0.2584484, -0.106627, -0.1150952, -0.2645541, -0.1650227, 0.261176, 0.1383851, -0.2567141, 0.09508582, -0.01757087, 0.0584252, -0.1300265, 0.1950169, -0.3529958, -0.626826, -0.176571, -0.2479957, 0.1445574, -0.1701513, 0.1128967, -0.08549089, 0.4...
Hallucigenia's onychophoran-like claws and the case for Tactopoda.
The Palaeozoic form-taxon Lobopodia encompasses a diverse range of soft-bodied 'legged worms' known from exceptional fossil deposits. Although lobopodians occupy a deep phylogenetic position within Panarthropoda, a shortage of derived characters obscures their evolutionary relationships with extant phyla (Onychophora, Tardigrada and Euarthropoda). Here we describe a complex feature in the terminal claws of the mid-Cambrian lobopodian Hallucigenia sparsa--their construction from a stack of constituent elements--and demonstrate that equivalent elements make up the jaws and claws of extant Onychophora. A cladistic analysis, informed by developmental data on panarthropod head segmentation, indicates that the stacked sclerite components in these two taxa are homologous-resolving hallucigeniid lobopodians as stem-group onychophorans. The results indicate a sister-group relationship between Tardigrada and Euarthropoda, adding palaeontological support to the neurological and musculoskeletal evidence uniting these disparate clades. These findings elucidate the evolutionary transformations that gave rise to the panarthropod phyla, and expound the lobopodian-like morphology of the ancestral panarthropod.
25,132,546
[ 0.09316985, 0.09928291, 0.2225558, 0.09245741, -0.08341858, -0.162884, -0.3345704, 0.02278442, 0.3143257, -0.2089136, -0.02799791, -0.1540188, 0.0955696, -0.2346013, -0.354165, 0.05319054, -0.4005527, 0.02846927, 0.03657072, -0.0115655, 0.1335003, 0.1954067, -0.07803403, ...
Transcriptional interference by antisense RNA is required for circadian clock function.
Eukaryotic circadian oscillators consist of negative feedback loops that generate endogenous rhythmicities. Natural antisense RNAs are found in a wide range of eukaryotic organisms. Nevertheless, the physiological importance and mode of action of most antisense RNAs are not clear. frequency (frq) encodes a component of the Neurospora core circadian negative feedback loop, which was thought to generate sustained rhythmicity. Transcription of qrf, the long non-coding frq antisense RNA, is induced by light, and its level oscillates in antiphase to frq sense RNA. Here we show that qrf transcription is regulated by both light-dependent and light-independent mechanisms. Light-dependent qrf transcription represses frq expression and regulates clock resetting. Light-independent qrf expression, on the other hand, is required for circadian rhythmicity. frq transcription also inhibits qrf expression and drives the antiphasic rhythm of qrf transcripts. The mutual inhibition of frq and qrf transcription thus forms a double negative feedback loop that is interlocked with the core feedback loop. Genetic and mathematical modelling analyses indicate that such an arrangement is required for robust and sustained circadian rhythmicity. Moreover, our results suggest that antisense transcription inhibits sense expression by mediating chromatin modifications and premature termination of transcription. Taken together, our results establish antisense transcription as an essential feature in a circadian system and shed light on the importance and mechanism of antisense action.
25,132,551
[ 0.1216974, 0.2319383, -0.301385, -0.05313188, 0.06073423, 0.03362029, 0.1024883, 0.203288, 0.3070305, -0.161677, 0.1138121, 0.2559525, -0.03116448, -0.04144081, -0.08511469, -0.0913744, -0.4572809, -0.1321332, -0.2182226, -0.3535321, 0.2676376, 0.06608476, -0.2516971, -...
An albumin-based theranostic nano-agent for dual-modal imaging guided photothermal therapy to inhibit lymphatic metastasis of cancer post surgery.
A large variety of cancers are associated with a high incidence of lymph node metastasis, which leads to a high risk of cancer death. Herein, we demonstrate that multimodal imaging guided photothermal therapy can inhibit tumor metastasis after surgery by burning the sentinel lymph nodes (SLNs) with metastatic tumor cells. A near-infrared dye, IR825, is absorbed onto human serum albumin (HSA), which is covalently linked with diethylenetriamine pentaacetic acid (DTPA) molecules to chelate gadolinium. The formed HSA-Gd-IR825 nanocomplex exhibits strong fluorescence together with high near-infrared (NIR) absorbance, and in the mean time could serve as a T1 contrast agent in magnetic resonance (MR) imaging. In vivo bi-modal fluorescence and MR imaging uncovers that HSA-Gd-IR825 after being injected into the primary tumor would quickly migrate into tumor-associated SLNs through lymphatic circulation. Utilizing the strong NIR absorbance of HSA-Gd-IR825, SLNs with metastatic cancer cells can be effectively ablated under exposure to a NIR laser. Such treatment when combined with surgery to remove the primary tumor offers remarkable therapeutic outcomes in greatly inhibiting further metastatic spread of cancer cells and prolonging animal survival. Our work presents an albumin-based theranostic nano-probe with functions of multimodal imaging and photothermal therapy, together with a 'photothermal ablation assisted surgery' strategy, promising for future clinical cancer treatment.
25,132,606
[ -0.09795735, -0.3217065, -0.4920283, 0.04439809, -0.1015402, 0.07925382, 0.2190203, 0.02760973, 0.1065435, 0.1806419, -0.2186726, 0.1568235, 0.1295574, -0.6164259, -0.2952817, -0.03856893, -0.1903953, 0.03203237, -0.08686893, 0.1031493, -0.01356414, 0.5286806, -0.04555866...
In vivo 1H MRS of human gallbladder bile at 3 T in one and two dimensions: detection and quantification of major biliary lipids.
In vitro (1)H MRS of human bile has shown potential in the diagnosis of various hepatopancreatobiliary (HPB) diseases. Previously, in vivo (1)H MRS of human bile in gallbladder using a 1.5 T scanner demonstrated the possibility of quantification of choline-containing phospholipids (chol-PLs). However, other lipid components such as bile acids play an important role in the pathophysiology of the HPB system. We have employed a higher magnetic field strength (3 T), and a custom-built receive array coil, to improve the quality of in vivo (1)H MRS of human bile in the gallbladder. We obtained significant improvement in the quality of 1D spectra (17 healthy volunteers) using a respiratory-gated PRESS sequence with well distinguished signals for total bile acids (TBAs) plus cholesterol resonating at 0.66 ppm, taurine-conjugated bile acids (TCBAs) at 3.08 ppm, chol-PLs at 3.22 ppm, glycine-conjugated bile acids (GCBAs) at 3.74 ppm, and the amide proton (-NH) arising from GCBAs and TCBAs in the region 7.76-8.05 ppm. The peak areas of these signals were measured by deconvolution, and subsequently the molar concentrations of metabolites were estimated with good accuracy, except for that of TBAs plus cholesterol. The concentration of TBAs plus cholesterol was overestimated in some cases, which could be due to lipid contamination. In addition, we report the first 2D L-COSY spectra of human gallbladder bile in vivo (obtained in 15 healthy volunteers). 2D L-COSY spectra will be helpful in differentiating various biliary chol-PLs in pathological conditions of the HPB system.
25,132,620
[ 0.2558255, -0.03291576, -0.2647308, 0.2411327, -0.3116551, 0.1001817, 0.006815226, -0.107556, -0.1256095, -0.2506165, 0.1018794, 0.1400354, -0.05878805, 0.05627467, -0.7859998, -0.1118593, -0.3457879, 0.01381326, -0.06541249, 0.1523392, 0.177009, 0.415141, 0.05924769, 0...
Management of the pediatric spontaneous pneumothorax: is primary surgery the treatment of choice?
Surgery as the primary management strategy for pediatric primary spontaneous pneumothorax is controversial. This study aims to evaluate the outcomes and effectiveness of management approaches for pediatric spontaneous pneumothorax. Outcomes of pediatric patients undergoing initial nonoperative treatment versus video-assisted thoracoscopic surgery with blebectomy and mechanical pleurodesis were compared via a retrospective review. We identified 96 patients with 108 pneumothoraces. Of 98 pneumothoraces with initial nonoperative management, 37% had surgery during their initial hospitalization for persistent air leak. Of those discharged home without video-assisted thoracoscopic surgery, 40% recurred. Initial nonoperative management resulted in more total hospital days (median: 11 vs 5 days, P < .001). No significant predictors of recurrence were identified on multivariate analysis. Sixty-three percent of all patients ultimately required surgery. Fewer than 40% of primary spontaneous pneumothorax patients are definitively treated with nonoperative management. A prospective study is needed to determine whether primary surgery with blebectomy/mechanical pleurodesis is a more effective treatment strategy.
25,132,627
[ 0.0732171, 0.09165456, -0.1918303, -0.3630944, -0.1528276, -0.2136692, -0.5493085, -0.4031117, -0.1302554, -0.04073593, 0.2881353, 0.0151872, -0.5340564, -0.4401764, 0.002319637, -0.2570772, -0.151695, 0.02882316, 0.1431136, -0.564312, -0.009775145, -0.1772469, -0.2520084...
Infant perceptual development for faces and spoken words: an integrated approach.
There are obvious differences between recognizing faces and recognizing spoken words or phonemes that might suggest development of each capability requires different skills. Recognizing faces and perceiving spoken language, however, are in key senses extremely similar endeavors. Both perceptual processes are based on richly variable, yet highly structured input from which the perceiver needs to extract categorically meaningful information. This similarity could be reflected in the perceptual narrowing that occurs within the first year of life in both domains. We take the position that the perceptual and neurocognitive processes by which face and speech recognition develop are based on a set of common principles. One common principle is the importance of systematic variability in the input as a source of information rather than noise. Experience of this variability leads to perceptual tuning to the critical properties that define individual faces or spoken words versus their membership in larger groupings of people and their language communities. We argue that parallels can be drawn directly between the principles responsible for the development of face and spoken language perception.
25,132,626
[ -0.1403436, 0.03246327, -0.1600267, -0.2653774, 0.3886277, -0.1517092, -0.3915649, -0.05609524, 0.2729883, 0.07809492, 0.02163097, -0.3870818, -0.1595271, -0.3489482, 0.009638956, 0.05248357, -0.409741, 0.1740612, -0.01091402, 0.01506343, 0.319187, 0.256336, -0.1664826, ...
Cross-sectional evidence for a decrease in cognitive function with age in children with autism spectrum disorders?
Autism spectrum disorders (ASD) are associated with early disturbances in brain maturation processes and these interferences presumably have their consequences for the progressive emergence of cognitive deficits later in life, as expressed in intelligence profiles. In this study, we addressed the impact of age on cognitive functioning of 6- to 15-year-old children and adolescents with ASD. Intelligence profiles were measured by the Wechsler Intelligence Scale for Children and compared among four consecutive age cohorts (children aged 6.17-8.03 years, 8.04-9.61 years, and 9.68-11.50 years and adolescents aged 11.54-15.85 years) of 237 high-functioning boys with ASD. The results clearly demonstrated that the global intelligence level was lower in children aged 8 years and older, when compared with 6- and 7-year-old children with ASD. This is mostly due to the Freedom From Distractibility factor, suggesting that older children were less able to sustain their attention, they were more distractible, or had more graph motor difficulties. Moreover, an effect of age was also found with respect to the relatively poor performance on the subtest Comprehension when compared with other verbal comprehension subtests, indicating that specifically the impairments in verbal comprehension and social reasoning abilities were more profound in older children when compared with 6- and 7-year-old children with ASD. Findings of this cross-sectional study showed that it is relevant to take age into account when evaluating the impact of cognitive impairments on intelligence in children with ASD, because the impact of these developmental disorders might be different at different ages.
25,132,666
[ -0.1306508, 0.1738917, -0.04933678, -0.2793584, 0.1996276, -0.1730289, -0.1605463, -0.02935799, -0.4215601, -0.259655, 0.05743545, 0.1092004, -0.2518182, -0.4083595, -0.5546124, -0.1518531, -0.3312113, 0.2565304, -0.1182929, -0.2441986, 0.4087414, 0.3092468, -0.2473651, ...
Modeling Oral Reading Fluency Development in Latino Students: A Longitudinal Study Across Second and Third Grade.
This study examines growth in oral reading fluency across 2nd and 3rd grade for Latino students grouped in 3 English proficiency levels: students receiving English as a second language (ESL) services (<in</i = 2,182), students exited from ESL services (<in</i = 965), and students never designated as needing services (<in</i = 1,857). An important focus was to learn whether, within these 3 groups, proficiency levels and growth were reliably related to special education status. Using hierarchical linear modeling, the authors compared proficiency levels and growth in oral reading fluency in English between and within groups and then to state reading benchmarks. Findings indicate that oral reading fluency scores reliably distinguished between students with learning disabilities and typically developing students within each group (effect sizes ranging from 0.96 to 1.51). The growth trajectory included a significant quadratic trend (generally slowing over time). These findings support the effectiveness of using oral reading fluency in English to screen and monitor reading progress under Response to Intervention models, but also suggest caution in interpreting oral reading fluency data as part of the process in identifying students with learning disabilities.
25,132,688
[ -0.07428411, -0.03008047, 0.05574144, -0.3731558, 0.1177126, -0.08977602, 0.05215207, -0.02325978, 0.1035134, -0.1012703, 0.1351313, 0.2362793, -0.4492719, -0.2705458, -0.1566902, -0.06489032, -0.1343835, -0.1126499, -0.1617428, -0.3958136, 0.2503752, 0.2291266, -0.085711...
Variable Selection in Generalized Functional Linear Models.
Modern research data, where a large number of functional predictors is collected on few subjects are becoming increasingly common. In this paper we propose a variable selection technique, when the predictors are functional and the response is scalar. Our approach is based on adopting a generalized functional linear model framework and using a penalized likelihood method that simultaneously controls the sparsity of the model and the smoothness of the corresponding coefficient functions by adequate penalization. The methodology is characterized by high predictive accuracy, and yields interpretable models, while retaining computational efficiency. The proposed method is investigated numerically in finite samples, and applied to a diffusion tensor imaging tractography data set and a chemometric data set.
25,132,690
[ 0.156954, -0.009622993, -0.1069486, 0.2081314, 0.02866344, -0.314706, -0.1210924, 0.1803496, -0.1160657, 0.0387982, -0.02866009, -0.04733625, 0.1287699, 0.1965258, 0.01560332, 0.002428388, -0.1860507, 0.1272375, -0.3095127, 0.2264262, -0.09998658, 0.01462314, -0.1792796, ...
Medical universities educational and research online services: benchmarking universities' website towards e-government.
Websites as one of the initial steps towards an e-government adoption do facilitate delivery of online and customer-oriented services. In this study we intended to investigate the role of the websites of medical universities in providing educational and research services following the E-government maturity model in the Iranian universities. This descriptive and cross- sectional study was conducted through content analysis and benchmarking the websites in 2012. The research population included the entire medical university website (37). Delivery of educational and research services through these university websites including information, interaction, transaction, and Integration were investigated using a checklist. The data were then analyzed by means of descriptive statistics and using SPSS software. Level of educational and research services by websites of the medical universities type I and II was evaluated medium as 1.99 and 1.89, respectively. All the universities gained a mean score of 1 out of 3 in terms of integration of educational and research services. Results of the study indicated that Iranian universities have passed information and interaction stages, but they have not made much progress in transaction and integration stages. Failure to adapt to e-government in Iranian medical universities in which limiting factors such as users' e-literacy, access to the internet and ICT infrastructure are not so crucial as in other organizations, suggest that e-government realization goes beyond technical challenges.
25,132,713
[ -0.08225698, 0.1921221, 0.1299185, -0.2613529, 0.4103243, -0.2349788, -0.06093736, 0.1106801, 0.03225696, 0.1744624, 0.110591, -0.08106211, -0.1458033, 0.05408106, -0.4615836, 0.09130635, 0.132335, -0.05536662, -0.2729183, -0.1923131, 0.1201928, 0.09144568, -0.1267704, ...
Changes in the Muscle Strength of the Elbow Flexors Following a Six-week Experimental Procedure in Adolescents Monitored Through Isokinetic and Motor Tests.
A group of 7 subjects underwent an experimental procedure which studied the potential changes in the maximal strength of the non-dominant arm elbow flexors. The programme duration was limited to 6 weeks during which the subjects practiced exercises 3 times a week, 3 series, on a Scott bench. Individual approach was applied to the external load and it was designed so that the weight being lifted would increase if the number of lifts in one series would exceed 3. The subjects were monitored through the one-repetition maximum 1 RM motor test and the isokinetic tests performed on biodex system, tested in 3 time periods (at the beginning, after 3 weeks, and after the 6th week). Of the 6 isokinetic tests, only the test for the maximum torque and the time for achieving the maximum torque have shown statistically important changes in terms of reduction in values, which was not expected. The one-repetition maximum test, unlike the isokinetic tests, has shown statistically important increase of the maximal muscle strength of 32.1% after the third week of exercising, and 46.8% after the six weeks of exercising. The statistical test for the correlation between the two variables has shown low correlation between these two tests. The values of the data of the two test types have not shown any correspondence among the subjects possibly due to the type of performance of the maximal muscle load during exercises, performed in conditions identical to the one-repetition maximum test, with similar and yet different conditions in the case of isokinetic tests. Most probably, due to the conditions in which the exercises and the tests took place, there is difference in the obtained results.
25,132,716
[ -0.3296865, 0.333536, -0.137257, -0.2414502, 0.0005131387, -0.4395703, -0.397578, -0.4531932, -0.1601875, -0.1409044, 0.03206743, -0.2372047, -0.02848666, -0.07240563, -0.3236592, -0.2279923, -0.09433961, 0.159969, -0.4111492, -0.02277152, 0.1414273, -0.200989, 0.07671462...
YKL-40 as a novel factor associated with inflammation and catabolic mechanisms in osteoarthritic joints.
YKL-40 is associated with tissue injury and inflammation, and consequently to diseases in which these mechanisms lead to tissue degradation, for example, asthma and rheumatoid arthritis. The purpose of the present study was to investigate if YKL-40 is also a significant factor in osteoarthritis (OA) by assessing associations of YKL-40 with mediators related to the pathogenesis of OA: cartilage destructing matrix metalloproteinases (MMPs) and proinflammatory cytokines interleukin-6 (IL-6) and interleukin-17 (IL-17). Cartilage, synovial fluid (SF), and plasma samples were obtained from 100 OA patients undergoing total knee replacement surgery. SF levels of YKL-40 (1027.9 ± 78.3 ng/mL) were considerably higher than plasma levels (67.2 ± 4.5 ng/mL) and correlated with YKL-40 released from cartilage samples obtained from the same patients (r = 0.37, P = 0.010), indicating that YKL-40 is produced by OA cartilage. Interestingly, YKL-40 concentrations in OA SF correlated positively with MMP-1 (r = 0.36, P = 0.014), MMP-3 (r = 0.46, P = 0.001), IL-6 (r = 0.57, P &lt; 0.001), and IL-17 (r = 0.52, P = 0.010) levels. Moreover, IL-6 and IL-17 enhanced YKL-40 production in human primary chondrocyte cultures. The present study introduces YKL-40 as a cartilage-derived factor associated with mediators of inflammation and cartilage destruction involved in the pathogenesis of OA.
25,132,728
[ -0.09936163, -0.1596894, -0.0459667, -0.2319641, -0.2729363, -0.227332, -0.03672414, 0.3031346, -0.1830773, -0.01084109, 0.2605458, -0.003688891, -0.1012061, -0.2701285, -0.011437, 0.2380812, 0.04194392, 0.294988, -0.1054155, 0.2750435, 0.2532229, 0.03613259, -0.071699, ...
Oral administration of herbal mixture extract inhibits 2,4-dinitrochlorobenzene-induced atopic dermatitis in BALB/c mice.
CP001 is four traditional herbal medicine mixtures with anti-inflammatory properties. In this study, we investigated the effect of oral administration of CP001 ethanol extract on the 2,4-dinitrochlorobenzene- (DNCB-) induced AD mouse models. For that purpose, we observed the effects of oral administration of CP001 on skin inflammatory cell infiltration, skin mast cells, production of serum IgE, and expression of Th2 cytokine mRNA in the AD skin lesions of DNCB treated BALB/c mice. Histological analyses demonstrated that CP001 decreased dermis and epidermis thickening as well as dermal infiltration induced by inflammatory cells. In addition, CP001 decreased mast cell infiltration in count as well as dermal infiltration induced by inflammatory cells. In the skin lesions, mRNA expression of interleukin- (IL-) 4 and IL-13 was inhibited by CP001. CP001 also reduced the production of IgE level in mouse plasma. In addition, we investigated the effect of CP001 on the inflammatory allergic reaction using human mast cells (HMC-1). In HMC-1, cytokine production and mRNA levels of IL-4, IL-13, IL-6, and IL-8 were suppressed by CP001. Taken together, our results showed that oral administration of CP001 exerts beneficial effects in AD symptoms, suggesting that CP001 might be a useful candidate for the treatment of AD.
25,132,731
[ -0.2721867, -0.1512042, 0.2156319, -0.2173403, 0.2419605, 0.2273654, -0.2319265, 0.1044611, 0.2680903, -0.05021687, -0.2174945, 0.1095434, 0.04344261, 0.06423395, -0.3090592, 0.2277555, -0.1636082, 0.476397, -0.2420285, 0.05418048, -0.1157567, 0.2705984, -0.04987024, -0...
Hepatitis B virus, HBx mutants and their role in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the leading causes of death induced by cancer in the modern world and majority of the cases are related to chronic hepatitis B virus (HBV) infection. HBV-encoded X protein (HBx) is known to play a pivotal role in the pathogenesis of viral induced HCC. HBx is a multifunctional protein of 17 kDa which modulates several cellular processes by direct or indirect interaction with a repertoire of host factors resulting in HCC. HBX might interfere with several cellular processes such as oxidative stress, DNA repair, signal transduction, transcription, protein degradation, cell cycle progression and apoptosis. A number of reports have indicated that HBx is one of the most common viral ORFs that is often integrated into the host genome and its sequence variants play a crucial role in HCC. By mutational or deletion analysis it was shown that carboxy terminal of HBx has a likely role in protein-protein interactions, transcriptional transactivation, DNA repair, cell, signaling and pathogenesis of HCC. The accumulated evidence thus far suggests that it is difficult to understand the mechanistic nature of HBx associated HCC, and HBx mediated transcriptional transactivation and signaling pathways may be a major determinant. This article addresses the role of HBx in the development of HCC with particular emphasis on HBx mutants and their putative targets.
25,132,741
[ -0.2383543, -0.2983029, 0.09970207, 0.0379512, 0.006653492, -0.1997464, 0.07623389, 0.06787599, 0.1425405, 0.2218969, 0.06656057, 0.09452148, -0.3506735, 0.1549902, -0.3591606, -0.2617301, -0.1442798, 0.1138938, 0.04304859, -0.1267157, 0.1647843, 0.2303512, -0.1139414, ...
Natural history of chronic hepatitis B: phases in a complex relationship.
Chronic hepatitis B (CHB) is a condition of global prevalence and its sequelae include cirrhosis and hepatocellular carcinoma. The natural history of CHB is a complex interplay of virological, environmental and host factors. The dynamic relationship between the virus and host evolves over the duration of the infection and different phases of the disease have been observed and described. These have been conceptualized in terms of the state of balance between the host immune system and the hepatitis B virus and have been given the labels immune tolerant, immune clearance, immune control and immune escape although other nomenclature is also used. Host factors, such as age at infection, determine progression to chronicity. Virological factors including hepatitis B viral load, mutations and genotype also have an impact on the adverse outcomes of the infection, as do hepatotoxic cofactors such as alcohol. Our understanding of the natural history of CHB has evolved significantly over the past few decades and characterizing the phase of disease of CHB remains an integral part of managing this virus in the clinic.
25,132,755
[ -0.1160449, -0.1182223, -0.2504382, 0.1763237, -0.04819653, -0.3669659, 0.05287581, 0.2329991, 0.006297078, 0.3259603, -0.1209157, -0.2959979, -0.04242597, 0.3005271, -0.4173684, -0.3342348, -0.004383427, 0.1675272, 0.3058096, 0.02276595, -0.190785, 0.1796583, -0.2663013,...
Proton pump inhibitor responsive esophageal eosinophilia, a distinct disease entity?
Recent studies have suggested the existence of a patient population with esophageal eosinophilia that responds to proton pump inhibitor therapy. These patients are being referred to as having proton pump inhibitor responsive esophageal eosinophilia (PPI-REE), which is currently classified as a distinct and separate disease entity from both gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE). The therapeutic effect of proton pump inhibitor (PPI) on PPI-REE is thought to act directly at the level of the esophageal mucosa with an anti-inflammatory capacity, and completely independent of gastric acid suppression. The purpose of this manuscript is to review the mechanistic data of the proposed immune modulation/anti-inflammatory role of the PPI at the esophageal mucosa, and the existence of PPI-REE as a distinct disease entity from GERD and EoE.
25,132,757
[ -0.1498016, -0.1842867, 0.1278007, -0.1159945, -0.05114335, -0.03976901, 0.3113138, 0.08182095, 0.02318864, 0.2025273, -0.09351495, -0.01531259, 0.06179044, -0.267518, -0.4568461, 0.05960173, -0.4011405, 0.371741, 0.1051801, 0.04803861, -0.1513475, 0.04722305, -0.1844022,...
Clinical epidemiology of gastric cancer in Hehuang valley of China: a 10-year epidemiological study of gastric cancer.
To investigate the clinical epidemiological characteristics of gastric cancer in the Hehuang valley, China, to provide a reference for treatment and prevention of regional gastric cancer. Between February 2003 and February 2013, the records of 2419 patients with gastric cancer were included in this study. The patient's characteristics, histological and pathological features, as well as the dietary habits of the patients, were investigated. The clinical data showed that adenocarcinoma was the leading histological type of gastric cancer in this area. Characteristics of gastric cancer in different ethnic groups and age showed that the 60.55-65.50 years group showed the high incidence of gastric cancer in all ethnic groups. There were more male gastric cancer patients than female. Intestinal was the most common type of gastric cancer in the Hehuang valley. There was no significant difference in the proportion of sex in terms of Helicobacter pylori infection. The impact of dietary habits on gastric cancer showed that regular consumption of fried or grilled food, consumption of high-salt, high-fat and spicy food and drinking strong Boiled brick-tea were three important factors associated with gastric cancer in males and females. Differences existed in race, sex, and age of patients according to the epidemiology of gastric cancer in the Hehuang valley. Moreover, dietary habits was also an important factor contributing to gastric cancer.
25,132,766
[ 0.3351065, -0.111443, -0.2799824, 0.08557729, 0.007975157, 0.03160424, 0.1727123, 0.1436571, -0.05025391, 0.2602776, 0.1792056, -0.03434128, -0.04484064, -0.1205264, 0.1335754, -0.4107792, 0.01753233, 0.1810501, 0.01532884, 0.2071043, 0.1424617, 0.5258187, -0.145077, 0....
Comparative analysis of ERCP, IDUS, EUS and CT in predicting malignant bile duct strictures.
To compare endoscopic retrograde cholangio-pancreatography (ERCP), intraductal ultrasound (IDUS), endosonography (EUS), endoscopic transpapillary forceps biopsies (ETP) and computed tomography (CT) with respect to diagnosing malignant bile duct strictures. A patient cohort with bile duct strictures of unknown etiology was examined by ERCP and IDUS, ETP, EUS, and CT. The sensitivity, specificity, and accuracy rates of the diagnostic procedures were calculated based on the definite diagnoses proved by histopathology or long-term follow-up in those patients who did not undergo surgery. For each of the diagnostic measures, the sensitivity, specificity, and accuracy rates were calculated. In all cases, the gold standard was the histopathologic staging of specimens or long-term follow-up of at least 12 mo. A comparison of the accuracy rates between the localization of strictures was performed by using the Mann-Whitney U-test and the χ(2) test as appropriate. A comparison of the accuracy rates between the diagnostic procedures was performed by using the McNemar's test. Differences were considered statistically significant if P &lt; 0.05. A total of 234 patients (127 males, 107 females, median age 64, range 20-90 years) with indeterminate bile duct strictures were included. A total of 161 patients underwent operative exploration; thus, a surgical histopathological correlation was available for those patients. A total of 113 patients had malignant disease proven by surgery; in 48 patients, benign disease was surgically found. In these patients, the decision for surgical exploration was made due to the suspicion of malignant disease in multimodal diagnostics (ERCP, CT, or EUS). Fifty patients had a benign diagnosis and were followed by a surveillance protocol with a follow-up of at least 12 mo; the median follow-up was 34 mo. Twenty-three patients had extended malignant disease, and thus were considered palliative. A comparison of the different diagnostic tools for detecting bile duct malignancy resulted in accuracy rates of 91% (ERCP/IDUS), 59% (ETP), 92% (IDUS + ETP), 74% (EUS), and 73% (CT), respectively. In the subgroup analysis, the accuracy rates (%, ERCP + IDUS/ETP/IDUS + ETP; EUS; CT) for each tumor entity were as follows: cholangiocellular carcinoma: 92%/74%/92%/70%/79%; pancreatic carcinoma: 90%/68%/90%/81%/76%; and ampullary carcinoma: 88%/90%/90%/76%/76%. The detection rate of malignancy by ERCP/IDUS was superior to ETP (91% vs 59%, P &lt; 0.0001), EUS (91% vs 74%, P &lt; 0.0001) and CT (91% vs 73%, P &lt; 0.0001); EUS was comparable to CT (74% vs 73%, P = 0.649). When analyzing accuracy rates with regard to localization of the bile duct stenosis, the accuracy rate of EUS for proximal vs distal stenosis was significantly higher for distal stenosis (79% vs 57%, P &lt; 0.0001). ERCP/IDUS is superior to EUS and CT in providing accurate diagnoses of bile duct strictures of uncertain etiology. Multimodal diagnostics is recommended.
25,132,767
[ 0.04738486, -0.1682079, -0.06083494, -0.1293773, -0.08637863, -0.5259891, -0.04537764, 0.06059112, 0.2535043, 0.3004695, -0.0643387, 0.0945937, -0.2646592, -0.09745004, -0.2109359, -0.6395839, -0.387968, 0.420637, -0.008211488, 0.06240469, 0.005537562, -0.1048986, -0.0310...
Separating Octadecyltrimethoxysilane Hydrolysis and Condensation at the Air/Water Interface through Addition of Methyl Stearate.
The hydrolysis and condensation of octadecyltrimethoxysilane (OTMS) at the air/water interface were monitored through molecular area changes at a constant surface pressure of 10 mN/m. The onset of condensation was delayed through the addition of methyl stearate (SME) acting as an inert filler molecule. In the absence of SME, complete gelation of OTMS required 30 h, during which time OTMS condensation occurred concomitantly with hydrolysis. In the presence of SME, the OTMS monolayer gelation rate increased in proportion to the amount of SME present. A 1:6 OTMS:SME molar ratio resulted in monolayer gelation within 30 min, suggesting completion of monomer hydrolysis prior to condensation. These findings indicate that lability of OTMS to hydrolysis at the air/water interface is governed by steric and conformational constraints at the silicon atom site, with monomeric OTMS being much more reactive than oligomeric OTMS. Fluorescence microscope images demonstrated that the OTMS condensed domain size also decreased with increasing SME concentrations, further implicating SME's role as an inert filler.
25,132,807
[ -0.2943718, 0.2538975, 0.149349, -0.3373835, -0.2048985, -0.1340813, -0.06797922, -0.2314731, 0.3973904, -0.1307378, -0.1643754, -0.1958108, -0.2823364, -0.0972686, -0.3322207, 0.2076009, -0.1811062, 0.1435854, 0.3567295, 0.1675545, 0.4861764, 0.2695782, -0.0514937, 0.0...
On the Existence and Uniqueness of the Scientific Method.
The ultimate utility of science is widely agreed upon: the comprehension of reality. But there is much controversy about what scientific understanding actually means, and how we should proceed in order to gain new scientific understanding. Is there a method for acquiring new scientific knowledge? Is this method unique and universal? There has been no shortage of proposals, but neither has there been a shortage of skeptics about these proposals. This article proffers for discussion a potential scientific method that aspires to be unique and universal and is rooted in the recent and ancient history of scientific thinking. Curiously, conclusions can be inferred from this scientific method that also concern education and the transmission of science to others.
25,132,810
[ -0.09437592, -0.1088192, -0.03867879, -0.146653, 0.2285199, -0.1616332, -0.1446972, 0.08131365, 0.1345439, -0.03791356, -0.03723422, 0.1063196, 0.1090743, 0.06155135, -0.5305746, -0.04864401, -0.01113906, -0.0858008, -0.3313603, 0.1074905, 0.1340587, 0.009733965, -0.08173...
Quantification of a secondary task-specific tremor in a violinist after a temporal lobectomy.
Task-specific tremors (TSTs) occur mainly during certain tasks and may be highly disabling. In this case study, we report on a 66-year-old violinist who developed a TST of the right arm only while playing the violin 4 weeks after a temporal lobectomy, which had been performed as a result of his temporal lobe epilepsy. Since a similar case, to our knowledge, has not been reported so far, our aim was to quantitatively assess and describe the tremor by measuring (a) the electromyography (EMG) activity of the wrist flexor and extensor as well as (b) an accelerometer signal of the hand. We found a tremor-related frequency of about 7 Hz. Furthermore, at a similar frequency of about 7 Hz, there was coherence between the tremor acceleration and EMG-activity of the wrist flexor and extensor as well as between the tremor acceleration and coactivation. The tremorgenesis remains unclear, and possible explanations can only be speculative.
25,132,815
[ 0.001552354, 0.2776168, -0.2936536, -0.278156, -0.008452268, -0.2899925, -0.03227679, -0.2603272, 0.1399797, 0.1440742, 0.08210389, -0.03023238, -0.04517129, -0.3621203, -0.125917, -0.06134911, -0.0536021, 0.4274171, -0.05275078, 0.0766217, 0.2578562, 0.1842281, -0.013426...
Inhibiting lung lining fluid glutathione metabolism with GGsTop as a novel treatment for asthma.
Asthma is characterized by airway inflammation. Inflammation is associated with oxidant stress. Airway epithelial cells are shielded from this stress by a thin layer of lung lining fluid (LLF) which contains an abundance of the antioxidant glutathione. LLF glutathione metabolism is regulated by γ-glutamyl transferase (GGT). Loss of LLF GGT activity in the mutant GGT(enu1) mouse causes an increase in baseline LLF glutathione content which is magnified in an IL-13 model of allergic airway inflammation and protective against asthma. Normal mice are susceptible to asthma in this model but can be protected with acivicin, a GGT inhibitor. GGT is a target to treat asthma but acivicin toxicity limits clinical use. GGsTop is a novel GGT inhibitor. GGsTop inhibits LLF GGT activity only when delivered through the airway. In the IL-13 model, mice treated with IL-13 and GGsTop exhibit a lung inflammatory response similar to that of mice treated with IL-13 alone. But mice treated with IL-13 and GGsTop show attenuation of methacholine-stimulated airway hyper-reactivity, inhibition of Muc5ac and Muc5b gene induction, decreased airway epithelial cell mucous accumulation and a fourfold increase in LLF glutathione content compared to mice treated with IL-13 alone. Mice treated with GGsTop alone are no different from that of mice treated with saline alone, and show no signs of toxicity. GGsTop could represent a valuable pharmacological tool to inhibit LLF GGT activity in pulmonary disease models. The associated increase in LLF glutathione can protect lung airway epithelial cells against oxidant injury associated with inflammation in asthma.
25,132,819
[ 0.02413353, -0.2498083, -0.232042, -0.2187974, 0.1042067, 0.1054696, 0.4993671, -0.1502997, 0.4501696, -0.05631387, 0.08097368, -0.02173301, -0.0188986, -0.1036359, 0.2134846, 0.1057874, -0.3271283, 0.2143589, -0.0794443, 0.1440402, -0.1901096, -0.3621171, -0.2714145, -...
Contrasting group analysis of Brazilian students with dyslexia and good readers using the computerized reading and writing assessment battery "BALE".
The analysis of cognitive processes underpinning reading and writing skills may help to distinguish different reading ability profiles. The present study used a Brazilian reading and writing battery to compare performance of students with dyslexia with two individually matched control groups: one contrasting on reading competence but not age and the other group contrasting on age but not reading competence. Participants were 28 individuals with dyslexia (19 boys) with a mean age of 9.82 (SD ± 1.44) drawn from public and private schools. These were matched to: (1) an age control group (AC) of 26 good readers with a mean age of 9.77 (SD ± 1.44) matched by age, sex, years of schooling, and type of school; (2) reading control group (RC) of 28 younger controls with a mean age of 7.82 (SD ± 1.06) matched by sex, type of school, and reading level. All groups were tested on four tasks from the Brazilian Reading and Writing Assessment battery ("BALE"): Written Sentence Comprehension Test (WSCT); Spoken Sentence Comprehension Test (OSCT); Picture-Print Writing Test (PPWT 1.1-Writing); and the Reading Competence Test (RCT). These tasks evaluate reading and listening comprehension for sentences, spelling, and reading isolated words and pseudowords (non-words). The dyslexia group scored lower and took longer to complete tasks than the AC group. Compared with the RC group, there were no differences in total scores on reading or oral comprehension tasks. However, dyslexics presented slower reading speeds, longer completion times, and lower scores on spelling tasks, even compared with younger controls. Analysis of types of errors on word and pseudoword reading items showed students with dyslexia scoring lower for pseudoword reading than the other two groups. These findings suggest that the dyslexics overall scores were similar to those of younger readers. However, specific phonological and visual decoding deficits showed that the two groups differ in terms of underpinning reading strategies.
25,132,829
[ -0.1519181, 0.33181, 0.07389744, -0.2130515, 0.2905001, -0.5818265, 0.06232768, -0.4139309, 0.1407394, -0.2700901, 0.1846934, 0.2338625, -0.2757681, -0.1442068, -0.6423056, -0.1493461, -0.005556494, 0.2001818, -0.1221927, -0.04730608, -0.02220513, 0.5285557, -0.1313584, ...
The incidence and risk factors for lower limb skin graft failure.
Lower limb skin grafts are thought to have higher failure rates than skin grafts in other sites of the body. Currently, there is a paucity of literature on specific factors associated with lower limb skin graft failure. We present a series of 70 lower limb skin grafts in 50 patients with outcomes at 6 weeks. One-third of lower limb skin grafts went on to fail with increased BMI, peripheral vascular disease, and immunosuppressant medication use identified as significant risk factors.
25,132,847
[ 0.07742994, -0.2485423, -0.3798897, -0.2786838, 0.2906338, 0.04614377, 0.006762053, -0.0515773, -0.08940206, -0.3724525, 0.256514, -0.182559, 0.2682565, -0.05003874, -0.04039268, -0.02693055, 0.006871395, 0.0896282, -0.1540432, 0.267876, -0.1935952, 0.2575874, -0.1421629,...
MTNR1B Genetic Variability Is Associated with Gestational Diabetes in Czech Women.
The gene MTNR1B encodes a receptor for melatonin. Melatonin receptors are expressed in human β-cells, which implies that genetic variants might affect glucose tolerance. Meta-analysis confirmed that the rs10830963 shows the most robust association. The aim of the study was to assess the rs10830963 in Czech GDM patients and controls and to study relations between the SNP and biochemical as well as anthropometric characteristics. Our cohort consisted of 880 women; 458 were diagnosed with GDM, and 422 were normoglycemic controls without history of GDM. Despite similar BMI, the GDM group showed higher WHR, waist circumference, abdominal circumference, and total body fat content. The risk allele G was more frequent in the GDM group (38.3 versus 29.4% in controls, OR 1.49 CI95% [1.22; 1.82]; P OR = 0.0001). In spite of higher frequency, the G allele in the GDM group was not associated with any markers of glucose metabolism. In contrast, controls showed significant association of the allele G with FPG and with postchallenge glycemia during the oGTT. Frequency analysis indicates that rs10830963 is involved in gestational diabetes in Czech women. However, the association of the SNP with glucose metabolism, which is obvious in controls, is covert in women who have experienced GDM.
25,132,852
[ 0.3751574, -0.4293647, -0.2701755, -0.0735378, 0.031043, -0.3979259, -0.4490993, 0.05475545, 0.2863941, 0.1881422, 0.1768575, -0.1107072, -0.0784467, 0.1641364, -0.09283091, -0.09239143, -0.3522798, 0.2623412, -0.05995217, 0.1689657, 0.1670935, 0.3647116, -0.03380547, -...
Heat Stress Increases Long-term Human Migration in Rural Pakistan.
Human migration attributable to climate events has recently received significant attention from the academic and policy communities (1-2). Quantitative evidence on the relationship between individual, permanent migration and natural disasters is limited (3-9). A 21-year longitudinal survey conducted in rural Pakistan (1991-2012) provides a unique opportunity to understand the relationship between weather and long-term migration. We link individual-level information from this survey to satellite-derived measures of climate variability and control for potential confounders using a multivariate approach. We find that flooding-a climate shock associated with large relief efforts-has modest to insignificant impacts on migration. Heat stress, however-which has attracted relatively little relief-consistently increases the long-term migration of men, driven by a negative effect on farm and non-farm income. Addressing weather-related displacement will require policies that both enhance resilience to climate shocks and lower barriers to welfare-enhancing population movements.
25,132,865
[ -0.2200925, 0.1163189, 0.1292769, -0.09535679, -0.1394423, -0.2243424, -0.1065052, 0.002969997, 0.1481348, -0.05695608, 0.04036028, -0.2137867, 0.007777719, 0.003111994, 0.0319448, -0.1318098, 0.001584228, 0.1020234, -0.2573895, -0.09741563, -0.1371217, -0.03016101, -0.16...
Comparison of prescribing and dispensing processes between veterinarians and pharmacists in New Zealand: Are there opportunities for cooperation?
Prescribing and dispensing of medicines are fundamental processes in providing healthcare for both human and animal patients. There has been recent discussion in the literature to advocate for increased co-operation between pharmacists and veterinarians, however there is little data available about veterinary prescribing and dispensing processes. The aims of this study were to gain information on veterinary prescribing and dispensing processes for companion animals in the Dunedin region of New Zealand. Open interviews were conducted with a selection of five veterinarians at practices in Dunedin. All interviews were transcribed verbatim. In New Zealand almost all dispensing of medicines for animals is carried out by veterinarians or their staff. There is a lack of standard treatment guidelines and a lack of regulation around the treatment period for which medicines can be dispensed at one time (i.e. period of supply). Medicines for animals are sometimes dispensed by community pharmacies, where clients are experiencing financial difficulties or when particular medicines are not held by veterinary practices. Record keeping requirements and practices for veterinarians are similar to those for community pharmacies. Processes undertaken by veterinarians in terms of prescribing and dispensing were similar to pharmacists' practices for human patients and so there is opportunity for collaboration between the two professions. Pharmacists also have complementary knowledge about dosing and formulating medicines that can assist in delivering optimal healthcare to animal patients.
25,132,886
[ -0.3532907, 0.4522582, 0.04244765, 0.0931071, 0.0839762, -0.4175382, 0.1087505, -0.1238846, 0.03166214, -0.04294134, 0.2601023, -0.09700476, -0.0009707587, -0.1050316, -0.09895817, -0.02299583, -0.3100594, 0.04187712, -0.3258854, -0.0177061, -0.1801155, 0.1716936, 0.07152...
Hyperlipidemia medication management in patients admitted for a myocardial infarction.
The purpose of this study is to determine the percentage of patients admitted for acute myocardial infarction currently prescribed a statin, with low-density lipoprotein (LDL) &lt;100 mg/dL, and high-density lipoprotein (HDL) &lt;50 mg/dL for men and &lt;55 mg/dL for women and evaluate their medication management with a focus on niacin initiation. This was a retrospective study from 12/07 to 12/09, conducted at a private, community hospital. Inclusion criteria required patients to have an acute myocaridal infarction (AMI) ICD-9 code, troponin ≥0.2 ng/dL and lipid panel performed within 96 hours of troponin. Patients with a triglyceride level &gt; 400 mg/dL were excluded. The residual risk population consisted of patients currently taking a statin with LDL &lt;100 mg/dL and HDL &lt;50/55 mg/dL. Patients were excluded from the residual risk population if they were on niacin, had an allergy to or previously failed niacin therapy, or expired within 72 hours. A total of 553 patients experiencing an AMI had lipid panels available for evaluation. The mean LDL was 97.3 ± 36.0 mg/dL, mean HDL was 33.5 ± 11.1 mg/dL, and mean triglycerides were 133.1 ± 71.3 mg/dL. The majority of patients (n=521, 94.2%) had an HDL &lt; 50 or 55 mg/dL respective of gender. Ninety-two (80.0%) residual risk patients had no change in their home lipid medications post AMI. Fifteen (13.0%) residual risk patients had their dose of statin medication increased. Seven (6.1%) residual risk patients were initiated on niacin. The study results confirm an existence of a residual risk population with nearly 25% of AMI patients meeting the criteria. The results also confirm a low incidence of medication intervention in the residual risk population post AMI (20.0%) regarding lipid therapy, including the initiation of niacin in only 6.1% of patients.
25,132,887
[ -0.1872089, 0.3225367, -0.2065474, -0.4381268, 0.1111887, -0.1868159, -0.1831193, 0.1501556, 0.02282633, -0.3849257, 0.2138237, 0.08527957, 0.1988529, -0.0110709, -0.1662818, 0.07460093, -0.121163, -0.07440886, 0.1551434, 0.03736748, -0.2491483, 0.05394646, -0.2647313, ...
High-grade microscopic hematuria in adult men can predict urothelial malignancy.
Microscopic hematuria in men younger than 40 is a confusing issue to urologists, especially when these men have normal radiological findings. We report our experience in looking for urologic malignancy in this group of patients. We conducted a prospective study for men with vague urological symptoms. We included men under 40 years old, men with microscopic hematuria greater than 25 red blood cells/high power field in 2 properly collected mid-stream urine samples, and men with free urine culture and normal multiphasic computed tomography abdomen and pelvis studies. All patients underwent diagnostic cystoscurethroscopy. If there were no lesions, multiple random biopsies were taken. In cases of apparently normal cystoscopic findings and associated renal colic, uretroscopy was done to the suspected side. Only 20 patients fulfilled our inclusion criteria. The mean age of the patients were 34; 2 patients presented with pain. The other 18 patients were presenting with mild recurrent lower urinary tract symptoms. Cystoscopy showed small papillary low-grade tumour in 3 patients. All random biopsies were free of malignancy. Unilateral uretroscopy for the 2 cases presented with pain detected carcinoma in situ in one of them. Cystoscopy is highly recommended for young adult men, with significant levels of microscopic hematuria, due to the 20% incidence rate of associated urological malignancy. Random bladder biopsies, in the absence of suspicious lesions, have no diagnostic role, and should not be done. Uretroscopy is advised for patients with microscopic hematuria and loin pain, even in the absence of suspicious radiological findings.
25,132,893
[ 0.2453146, 0.02994102, -0.2791636, -0.1344173, 0.08370107, -0.2817967, -0.5535557, -0.03479934, -0.1251971, -0.3378808, 0.1978517, 0.1507697, 0.09680451, 0.1863991, -0.2487391, -0.2885076, -0.09759119, 0.08274395, 0.2692404, -0.4263375, 0.257387, 0.1404494, -0.2377048, ...
A surgical challenge: Idiopathic scrotal elephantiasis.
Scrotal elephantiasis is a condition rarely encountered in developed nations. It is endemic in tropical regions due to the presence of filariasis (Wucheria bancrofti). We report 2 cases of idiopathic scrotal elephantiasis in Canadian citizens with no history of travel to endemic filariasis regions, malignancy, surgery or radiation. Both patients underwent complete excision of the involved tissue with reconstruction. We found that for advanced cases of scrotal lymphedema, surgery is currently the only solution. In our cases of advanced idiopathic disease, surgical treatment combining the expertise of a plastic surgeon and a urologist provided a successful functional and cosmetic result.
25,132,898
[ -0.0187007, -0.2430581, 0.07566585, -0.1353494, 0.006042422, -0.3221421, -0.3240596, 0.022209, 0.04877658, 0.09323869, 0.5446274, -0.1563125, -0.08473164, -0.1687005, -0.1563263, -0.3065634, -0.156641, -0.3044194, -0.04434543, -0.2231516, -0.1303139, 0.129717, -0.3795286,...
Entertainment Venue Visiting and Commercial Sex in China.
Entertainment venues in China play an important role in the sexually transmitted disease (STD)/HIV epidemic. Most previous studies have focused on sex workers working in entertainment venues, but little is known about their clients. This study investigated the perceptions and behavior of the patrons visiting entertainment venues. Qualitative in-depth interviews were conducted with 30 male market vendors who visited entertainment venues at least once in the past 3 months in an eastern city in China. Information about their risky behavior, attitude toward commercial sex, and STD/HIV prevention approaches was collected. Saunas, karaoke bars, and massage centers are the most frequently visited entertainment venues. Seventy-three percent of study participants reported purchasing commercial sex at these entertainment venues. Participants expressed a very liberal attitude toward commercial sex. Seeking commercial sex was perceived as a characteristic of a male's nature. The perceived risks of STD/HIV infection do not deter participants from engaging in commercial sex. Commercial sex clients reported irregular condom use and a number of other misperceptions and improper practices toward preventing STD/HIV infection. Venue-based intervention is urgently needed to target the population. The sex workers themselves could potentially serve as "health educators" to communicate prevention information to their clients and encourage safer sex behavior.
25,132,901
[ -0.1800585, 0.3822693, 0.138692, 0.2813273, 0.2982085, -0.009018372, 0.1190833, -0.05083111, -0.03049872, -0.3017898, 0.3400455, -0.3603082, 0.04608729, 0.363483, 0.3281516, -0.09657936, -0.8100287, -0.1987313, -0.1312537, -0.3528071, 0.06108252, 0.4834539, 0.07354808, ...
Linking the Ohio Cancer Incidence Surveillance System with Medicare, Medicaid, and Clinical Data from Home Health Care and Long Term Care Assessment Instruments: Paving the Way for New Research Endeavors in Geriatric Oncology.
This study describes the Ohio Cancer-Aging Linked Database, which mirrors in structure the linked Surveillance, Epidemiology, and End-Results (SEER)-Medicare files, but also incorporates data from Medicaid enrollment and claims files, the home health care (HHC) Outcome Assessment Information Set (OASIS), and the long term care (LTC) Minimum Data Set (MDS). This article also discusses the potential uses of this database, particularly in addressing new research questions emerging from the nascent and rapidly developing field of geriatric oncology.
25,132,914
[ 0.1765559, -0.2964739, 0.1363818, -0.2805351, -0.1128719, -0.09391162, 0.1124718, 0.2692761, -0.2292459, -0.04420311, -0.08577425, 0.19793, 0.01035799, -0.1659195, -0.2190764, -0.153262, 0.3221751, 0.2860745, 0.6069059, -0.1581171, 0.3363932, 0.1512023, -0.3032905, 0.25...