title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Prevalence of triangular fibrocartilage complex abnormalities regardless of symptoms rise with age: systematic review and pooled analysis. | Triangular fibrocartilage complex abnormalities seem to be more common with age, but the degree to which this is so, and the degree to which the presence of an abnormality is associated with symptoms, are topics of controversy. We wished to perform a systematic review to determine the prevalence of triangular fibrocartilage complex abnormalities, and to determine if the prevalence of abnormalities are greater with increasing age. In addition, we stratified age groups based on symptoms. We searched MEDLINE, EMBASE, and the Cochrane Library through August 15, 2013. Studies that reported triangular fibrocartilage complex abnormalities by age were included. Fifteen studies including 977 wrists met our criteria and reported a total of 368 (38%) triangular fibrocartilage complex abnormalities. Eight studies included symptomatic patients; the remainder studied cadavers (six studies) or asymptomatic volunteers (one study). Patients were divided into four age groups (< 30, 30-49, 50-69, and 70 years and older) for pooled analysis, comparing the proportions of patients with and without abnormalities between groups using chi-square analysis. We also evaluated the proportions after stratifying each age group by symptoms. Overall, the prevalence of triangular fibrocartilage complex abnormalities increased with age, from 27% (80/301) in patients younger than 30 years to 49% (130/265) in patients 70 years and older (p < 0.001), odds ratio (OR), 2.7, 95% CI, 1.9-3.8 (p < 0.001). In asymptomatic patients, triangular fibrocartilage complex prevalence abnormality increased from 15% (24/159) to 49% (129/263) in the same age groups (p < 0.001), OR, 5.4, 95% CI, 3.3-8.9 (p < 0.001). For symptomatic patients prevalence ranged from 39% (56/142) to 70% (14/20) in patients between 50 and 69 years old (p < 0.034), OR, 3.6, 95% CI, 1.3-9.9 (p < 0.014). Triangular fibrocartilage complex abnormalities are common in symptomatic and asymptomatic wrists, and they are increasingly common with age. As in all situations where abnormalities are so common that they may be incidental, we need (1) a reliable and accurate method for determining whether these abnormalities are the cause of symptoms; and (2) evidence that treatment of these abnormalities improves symptoms better than placebo. Level III, prognostic study. See the Instructions for Authors for a complete description of levels of evidence. | 25,091,224 | [
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Risk-adapted single or fractionated stereotactic high-precision radiotherapy in a pooled series of nonfunctioning pituitary adenomas: high local control and low toxicity. | The purpose of this work was to evaluate a prospectively initiated two-center protocol of risk-adapted single-fraction (SRS) or fractionated radiotherapy (SRT) in patients with nonsecretory pituitary adenomas (NSA). A total of 73 NSA patients (39 men/34 women) with a median age of 62 years were prospectively included in a treatment protocol of SRS [planning target volume (PTV) < 4 ccm, > 2 mm to optic pathways = low risk] or SRT (PTV ≥ 4 ccm, ≤ 2 mm to optic pathways = high risk) in two Novalis® centers. Mean tumor volume was 7.02 ccm (range 0.58-57.29 ccm). Based on the protocol guidelines, 5 patients were treated with SRS and 68 patients with SRT. Median follow-up (FU) reached 5 years with 5-year overall survival (OS) of 90.4 % (CI 80.2-95 %) and 5-year local control and progression-free survival rates of 100 % (CI 93.3-100 %) and 90.4 % (CI 80.2-95 %), respectively. A post-SRS/SRT new visual disorder occurred in 2 patients (2.7 %), a new oculomotor nerve palsy in one pre-irradiated patient, in 3 patients (4.1 %) a pre-existing visual disorder improved. New complete hypopituitarism occurred in 4 patients (13.8 %) and in 3 patients (25 %) with pre-existing partial hypopituitarism. Pituitary function in 26 % of patients retained normal. Patients with tumor shrinkage (65.75 %) had a significantly longer FU (p = 0.0093). Multivariate analysis confirmed correlation of new hypopituitarism with duration of FU (p = 0.008) and correlation of new hypopituitarism and tumor volume (p = 0.023). No significant influence factors for occurrence of visual disorders were found. Our SRS/SRT protocol proved to be safe and successful in terms of tumor control and protection of the visual system, especially for large tumors located close to optic pathways. | 25,091,268 | [
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A role for the TIM-3/GAL-9/BAT3 pathway in determining the clinical phenotype of multiple sclerosis. | T-cell immunoglobulin and mucin domain 3 (Tim-3) ligates galectin-9 (Gal-9); this process, resulting in the inhibition of Th1 responses and in the apoptosis of antigen-specific cells, is hampered by binding of the molecular adaptor human leukocyte antigen B (HLA-B)-associated transcript 3 (Bat3) to the intracellular tail of Tim-3. Apoptosis of myelin basic protein (MBP)-specific T lymphocytes correlates with reduced rates of disease progression in multiple sclerosis (MS). We extensively analyzed the Tim-3/Gal-9/Bat3 pathway in 87 patients with a diagnosis of stable relapsing-remitting MS (RRMS), primary progressive MS (PPMS), or benign MS (BEMS), as well as in 40 healthy control (HC) subjects. Results showed that MBP-specific CD4(+)Tim-3(+), CD4(+)/Gal-9(+), and CD4(+)/Tim-3(+)/AV(+) (apoptotic) T lymphocytes were augmented in the BEMS group, whereas CD4(+)/Bat3(+) and CD8(+)/Bat3(+) T lymphocytes were increased and CD4(+)/Tim-3(+)/AV(+) T cells were reduced in the PPMS group (>2 fold and P<0.05 in all cases). Blocking the Tim-3/Gal-9 interaction with specific mAb reduced T-lymphocyte apoptosis and augmented production of IFNγ and IL-17 in the BEMS, RRMS, and HC groups, but not in the PPMS group. The Tim-3/Gal-9 interaction favors apoptosis of MBP-specific T lymphocytes in BEMS; this process is reduced in PPMS by the up-regulation of Bat3. Therapeutic interventions aimed at silencing Bat3 could be beneficial in MS. | 25,091,272 | [
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The reliability of an adolescent dietary pattern identified using reduced-rank regression: comparison of a FFQ and 3 d food record. | Despite the increasing use of dietary patterns (DP) to study diet and health outcomes, relatively few studies have examined the reliability of DP using different dietary assessment methods. Reduced-rank regression (RRR) is an emerging statistical method that incorporates a priori information to characterise DP related to specific outcomes of interest. The aim of the present study was to compare DP identified using the RRR method in a FFQ with those in a 3 d food record (FR). Participants were 783 adolescents from the Western Australian Pregnancy (Raine) Cohort Study who completed both a FFQ and FR at 14 years of age. A similar 'energy-dense, high-fat and low-fibre' DP was identified in the FFQ and FR that was characterised by high intakes of processed meat and sugar-sweetened beverages, and low intakes of vegetables and fresh fruit. Nutrient profiles for this DP were consistent in the FFQ and FR. Pearson's correlation coefficient between participants' z-scores for the DP identified in the FFQ and FR was 0·35 for girls and 0·49 for boys (P< 0·05). The mean difference between DP z-scores derived from the FFQ and FR was -0·08 (95 % CI -0·21, 0·04) for girls and -0·05 (95 % CI -0·17, 0·07) for boys. The 95 % limits of agreement were -2·55 to 2·39 for girls and -2·52 to 2·41 for boys. These findings suggest that very similar DP may be identified and their z-scores show modest agreement when applying the RRR method to dietary intake data collected from adolescents using a FFQ or FR. | 25,091,285 | [
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A novel treatment in X-linked agammaglobulinaemia - hyperbaric oxygen therapy in refractory chronic wounds. | Chronic wounds are a rare complication of X-linked agammaglobulinaemia (XLA). Fastidious organisms such as helicobacter bills have been reported in XLA with chronic wounds but sterile chronic wounds also occur. Hyperbaric Oxygen Therapy has been used in chronic wounds but has not previously been reported in primary antibody deficiencies. We present a case of a chronic wound in a patient with XLA refractory to antimicrobial therapy that made a remarkable recovery following Hyperbaric Oxygen Therapy. | 25,091,287 | [
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Effect of prolonged administration of pegylated interferon/ribavirin therapy in genotypes 2a and 2b: propensity score-matched analysis. | Chronic hepatitis C genotype 2 patients show high susceptibility to pegylated interferon plus ribavirin therapy (PEG/RBV). However, the differences in response to therapy between genotypes 2a and 2b, and the efficacy of prolonged therapy for refractory patients have not been evaluated. We investigated the differences in response to PEG/RBV between each genotype and examined the efficacy of prolonged therapy. A total of 343 chronic hepatitis patients infected with hepatitis C virus (HCV) genotype 2 (2a: n = 195; 2b: n = 148) were enrolled in this study. All patients received PEG/RBV for 24 (24 week group, n = 242) or more weeks (prolonged group, n = 101). We analyzed the differences in virological response between genotypes 2a and 2b. Clinical and virological factors of patients in the 24-week group and the prolonged treatment group were matched using propensity score analysis, and the efficacy of prolonged therapy established by comparing time of serum HCV disappearance for each genotype. Virological response tended to be higher for genotype 2a compared with genotype 2b; however, there was no significant difference in sustained virological response rates between genotypes (2a: 78.3%; 2b: 70.2%; P = 0.19). After propensity score matching, the adjusted P-value for sustained virological response rate was significantly different for genotype 2b patients with undetectable HCV-RNA between weeks 5 and 8, and for genotype 2a patients with detectable HCV-RNA at week 8. Prolonged therapy with PEG/RBV may be effective when serum HCV-RNA is detectable at week 4 and week 8 for genotype 2b and 2a patients, respectively. | 25,091,289 | [
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Clinical assessment of potential drug interactions of faldaprevir, a hepatitis C virus protease inhibitor, with darunavir/ritonavir, efavirenz, and tenofovir. | Faldaprevir is a potent, once-daily hepatitis C virus (HCV) NS3/4A protease inhibitor. Studies were performed to investigate potential drug interactions between faldaprevir and the commonly used antiretrovirals darunavir/ritonavir, efavirenz, and tenofovir to guide the coadministration of faldaprevir with these agents in human immunodeficiency virus/HCV-coinfected patients. In 3 open-label, phase 1 pharmacokinetic (PK) studies, healthy adult volunteers received (1) darunavir/ritonavir (800 mg/100 mg once daily) with and without faldaprevir (240 mg once daily); (2) faldaprevir (240 mg twice daily) with and without efavirenz (600 mg once daily); or (3) faldaprevir (240 mg twice daily) or tenofovir (300 mg once daily) alone and in combination. To assess potential drug interactions, geometric mean ratios and 90% confidence intervals for PK parameters were calculated. Safety was evaluated. Efavirenz decreased faldaprevir area under the concentration-time curve (AUC) by 35%, Cmax by 28%, and Cmin by 46%, consistent with induction of CYP3A by efavirenz. Tenofovir decreased faldaprevir AUC by 22%, which was not considered to be clinically relevant. Faldaprevir had no clinically relevant effects on darunavir or tenofovir PK (15% and 22% AUC increase, respectively). Adverse events were consistent with the known safety profiles of faldaprevir and the antiretrovirals being examined. No clinically significant interactions were observed between faldaprevir and darunavir/ritonavir or tenofovir. A potentially clinically relevant decrease in faldaprevir exposure was observed when coadministered with efavirenz; this decrease can be managed using the higher of the 2 faldaprevir doses tested in phase 3 trials (240 mg once daily as opposed to 120 mg once daily). | 25,091,302 | [
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Effects of ribavirin monotherapy on the viral population in patients with chronic hepatitis C genotype 1: direct sequencing and pyrosequencing of the HCV regions. | Ribavirin remains essential to chronic hepatitis C treatment. This paper investigates the influence of ribavirin priming to steady state before combined pegylated-interferon/ribavirin treatment on viral kinetics, ribavirin trough concentrations, genetic variability within HCV-core, -NS5B and -NS5A, and response to antiviral therapy. A prospective cohort study was made of 27 chronic hepatitis C genotype 1 naïve patients who received four weeks of ribavirin followed by pegIFN-α-2a/ribavirin for 48 weeks (Group A). The results obtained were compared with those for a control/historical group (Group B). In addition, direct sequencing and pyrosequencing were applied to determine ribavirin monotherapy-induced sequence changes. The rapid, early, and sustained virological response values obtained were 48%, 89%, and 52%, respectively, in Group A, and 52%, 90%, and 52% in Group B (P > 0.05). In the four-week combined treatment, the Group A patients showed a greater decrease in HCV-RNA (2.3 log10 IU/ml vs. 1.2 log10 IU/ml; P = 0.04), lower alanine aminotransferase levels (23.5 ± 1.33 U/L vs. 60.11 ± 18 U/L; P < 0.001) and higher mean ribavirin trough concentrations (3.28 ± 1.26 mg/L vs. 1.74 ± 0.7 mg/L; P = 0.001). No general increase in rates of nucleotide substitutions in the ribavirin monotherapy-treated patients was observed in NS5B, ISDR, or PKRbd, but there was a decrease in silent mutations in the HCV core (P = 0.04). This result was confirmed by pyrosequencing in the NS5A region. It is concluded that the ribavirin priming combined treatment with pegIFN-α-2a does not improve sustained virological response rates in HCV genotype 1 naïve infected patients. However, the greater reductions in viral load and alanine aminotransferase levels, together with the higher ribavirin trough concentration values obtained, could reflect the greater effectiveness of the treatment. Ribavirin does not have a mutagenic effect on the virus in patients with chronic hepatitis C. | 25,091,333 | [
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Geriatric assessment in surgical oncology: a systematic review. | The comprehensive geriatric assessment (CGA) has developed as an important prognostic tool to risk stratify older adults and has recently been applied to the surgical field. In this systematic review, we examined the utility of CGA components as predictors of adverse outcomes among geriatric patients undergoing major oncologic surgery. MEDLINE, Embase, and the Cochrane Library were searched for prospective studies examining the association of components of the CGA with specific outcomes among geriatric patients undergoing elective oncologic surgery. Outcome parameters included 30-d postoperative complications (POC), mortality, and discharge to a nonhome institution. The initial search identified 178 potentially relevant articles, with six studies meeting inclusion criteria. Deficiencies in instrumental activities of daily living, activities of daily living, fatigue, cognition, frailty, and cognitive impairment were associated with increased POC. No CGA predictors were identified for postoperative mortality whereas frailty, deficiencies in instrumental activities of daily living, and depression predicted discharge to a nonhome institution. Across a variety of surgical oncologic populations and cancer types, components of the CGA appear to be predictive of POC and discharge to a nonhome institution. These results argue for inclusion of focused geriatric assessments as part of routine preoperative care in the geriatric surgical oncology population. | 25,091,339 | [
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Behavioural support of a proposed neurocognitive connection between physical activity and improved eating behaviour in obese women. | An explanation of the association between physical activity and improved eating behaviours has recently been posited via the effect of physical activity on executive functions of the brain resulting in a reduction in the hedonic drive to overeat. Decomposition and clarification of embedded relationship through a behavioural/psychological framework was sought. Changes in theory-based psychosocial factors over 26 weeks were tested with 134 severely obese women (age 41.7±10.4 years) initiating a physical activity support treatment. Mediation and reciprocal effects analyses incorporating these changes were then computed. Significant improvements in mood, self-regulation for eating, and self-efficacy for controlled eating were found. Emanating from mood change, a reciprocal relationship between changes in the self-regulation and self-efficacy measures was found. Thus, each factor reinforced the other's change. Findings suggest a convergence of neurocognitively and behaviourally based explanations of the relations of physical activity and controlled eating. Implications for behavioural weight-loss theory and treatments were suggested. | 25,091,353 | [
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Association of body mass index and prostate cancer mortality. | Inconsistent evidence exists on whether obesity is associated with an increased risk of prostate cancer death post-radical prostatectomy. We examined data from three large health plans to evaluate if an increased body mass index (BMI) at prostate cancer diagnosis is related to prostate cancer mortality This population-based case-control study included 751 men with prostate cancer who underwent radical prostatectomy. Cases were men who died due to prostate cancer (N=323) and matched controls (N=428). We used multivariable logistic regression models to assess the association between BMI at diagnosis and prostate cancer mortality, adjusted for Gleason score, PSA, tumour characteristics, and matching factors. Study subjects were classified into the following BMI (kg/m2) categories: healthy (18.5-24.9), overweight (25-29.9) and obese (≥30). Nearly 43% of the participants had a BMI ≥25 at diagnosis. A higher fraction of cases (30%) were obese compared to controls (22%). Overall, obese men had more than a 50% increase in prostate cancer mortality (adjusted odds ratio=1.50 [95% CI, 1.03-2.19]) when compared to men with healthy BMI. After stratifying by Gleason score, the odds of mortality generally rose with increasing BMI. The strongest effect was observed in the Gleason score 8+ category (2.37, 95% CI: 1.11-5.09). These associations persisted after adjusting for PSA at diagnosis and other tumour characteristics. These results suggest that BMI at diagnosis is strongly correlated with prostate cancer mortality, and that men with aggressive disease have a markedly greater odds of death if they are overweight or obese. | 25,091,359 | [
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The effects of replacement of whole-plant corn with oat and common vetch on the fermentation quality, chemical composition and aerobic stability of total mixed ration silage in Tibet. | The objective of this experiment was to evaluate the effects of replacement of whole-plant corn with oat and common vetch on the fermentation quality, chemical composition and aerobic stability of total mixed ration (TMR) silage in Tibet. Four TMR that varied in the forage sources on dry matter basis were used: (i) 52% whole-plant corn (Control); (ii) 43% oat + 12% common vetch (OC3.6); (iii) 38% oat + 18% common vetch (OC2.2); and (iv) 33% oat + 23% common vetch (OC1.5). Silos were opened on day 45 and then subjected to an aerobic stability test for 12 days. The results showed that all silages were well preserved with low pH and NH3 -N, and high lactic acid and V-scores. With the increasing proportion of common vetch, crude protein, ether extract increased (P < 0.05), and neutral detergent fiber and acid detergent fiber decreased (P < 0.05). Under aerobic conditions, treated silages were more stable than the control silage as indicated by lower (P < 0.05) pH and yeast population. It was concluded that replacement of whole-plant corn with oat and common vetch had no unfavorable effects on the fermentation quality and improved crude protein content and aerobic stability of TMR silage. OC2.2 silage was the best among three treated TMR silages. | 25,091,371 | [
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Surgical and endovascular treatment of hepatic arterial complications following liver transplant. | Vascular complications after liver transplantation increase post-operative morbidity and contribute to the incidence of retransplantation. Vascular complications comprise arterial, caval, and portal venous pathology, with the majority of complications being arterial in etiology, including anastomotic stricture, pseudoaneurysm, and thrombosis. There are two major therapeutic options for the treatment of these arterial complications: endovascular intervention and surgery. The former includes intra-arterial thrombolysis, embolization, percutaneous transluminal angioplasty, and stent placement. The latter includes thrombectomy, reanastomosis, and retransplantation. Although surgical treatment has been considered the first choice for management in the past, advances in endovascular intervention have increased and make it a viable therapeutic option following orthotopic liver transplantation. This review focuses on the role of surgical and endovascular therapy in the management of hepatic arterial complications after liver transplantation. | 25,091,402 | [
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Highly sensitive beam steering with plasmonic antenna. | In this work, we design and study a highly sensitive beam steering device that integrates a spiral plasmonic antenna with a subwavelength metallic waveguide. The short effective wavelength of the surface plasmon polaritons (SPPs) mode supported by the metallic waveguide is exploited to dramatically miniaturize the device and improve the sensitivity of the beam steering. Through introducing a tiny displacement of feed point with respect to the geometrical center of the spiral plasmonic antenna, the direction of the radiation can be steered at considerably high angles. Simulation results show that steering angles of 8°, 17° and 34° are obtainable for a displacement of 50 nm, 100 nm and 200 nm, respectively. Benefiting from the reduced device size and the shorter SPP wavelength, the beam steering sensitivity of the beam steering is improved by 10-fold compared with the case reported previously. This miniature plasmonic beam steering device may find many potential applications in quantum optical information processing and integrated photonic circuits. | 25,091,405 | [
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What can funders do to better link science with decisions? Case studies of coastal communities and climate change. | Many reports and studies have noted that a significant portion of problem-oriented coastal science does not actually link to decisions. Here, three competitively funded project case studies are studied to determine what funders can and should do to better link science with decisions. The qualitative analysis used for this study indicates that the studied program was seen as being unusually attentive to the issue of linking science to decisions, as opposed to simply generating new knowledge. Nevertheless, much of the data indicate that funders can and should do more. Three ideas figured most prominently in the qualitative data: (1) funders should do more to ensure that the problem itself is defined more thoroughly with people who are envisioned as potential users of the science; (2) funders need to allocate more resources and attention to communicating effectively (with users) throughout the project; and (3) funders need to demand more engagement of users throughout the project. These findings have important implications for how funders review and support science, especially when competitive processes are used. Most importantly, funders should adjust what kind of science they ask for. Secondly, funders need to change who is involved in the review process. Currently, review processes focus on knowledge generation, which means that the reviewers themselves have expertise in that area. Instead, review panels should be balanced between those who focus on knowledge generation and those who focus on linking knowledge to decisions; this is a separate but critical discipline currently left out of the review process. | 25,091,428 | [
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In vivo assessment of white matter damage in neuromyelitis optica: a diffusion tensor and diffusion kurtosis MR imaging study. | In patients with neuromyelitis optica (NMO), damage to extensive regions of normal-appearing WM has been observed. To investigate the possibility that microstructural alterations are present in these WM tracts, DTI and diffusion kurtosis imaging (DKI) techniques were applied and compared. Thirteen patients with NMO and 13 demographically and gender-matched controls underwent MRI using a 3T MR scanner, with DTI/DKI sequence acquired jointly fitted. Parametric fractional anisotropy maps were derived from diffusion tensor (FADTI) values using b-values of 0s/mm(2) and 1000s/mm(2). Parametric fractional anisotropy maps derived from diffusion kurtosis tensor (FADKI) values were also acquired using b-values of 0, 1000, and 2000s/mm(2). Mean FADTI and FADKI values were also calculated. A ROI analysis of the genu and splenium of the corpus callosum (CC), cerebral peduncle (CP), and optic radiation (OR) was also performed. Student's t-test and corrections for multiple comparisons were used to evaluate the data obtained. A significant decrease in the FADTI values obtained for NMO patients versus controls was observed for the splenium of the CC and the left OR (p<0.05). However, just a positive trend was observed for the FADKI values associated with the same WM tracts. To our knowledge, this is the first study to analyze WM tracts of NMO patients using DTI and DKI. These data indicate that DKI could have limitations in evaluating the WM integrity in NMO patients. Furthermore, the results obtained are consistent with the hypothesis that diffuse brain involvement characterizes NMO. | 25,091,453 | [
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Increased expression of MUC1 and sialyl Lewis antigens in different areas of clear renal cell carcinoma. | Changes in expression patterns of the sialyl Lewis antigens and MUC1 mucin can be considered as markers for the diagnosis of various cancers. However, there are no reports which have been devoted to analysis of differences in the sialyl Lewis antigens and MUC1 expression patterns as potential discrimination markers among different areas of clear cell renal cell carcinoma (ccRCC). The aim of this study was to determine the level of MUC1 and specific Lewis antigens on glycoproteins in three different areas: tumor (cancer tissue), intermediate zone (adjacent to tumor tissue) and normal renal cortex/medulla (uninvolved by tumor). Study was performed on renal tissues taken from 30 patients with clear cell renal cell carcinoma. Relative amounts of sugar structures bound with proteins were determined by ELISA-like test with biotinylated lectins or monoclonal antibodies: anti-MUC1 and anti-sialyl Lewis(a/x). The study presented here provides novel information about relationship between MUC1 and sialyl Lewis antigens in the tumor, intermediate zone and noninvolved areas of normal renal tissue distant of tumor. We have found statistically significant increase of MUC1 and sialic acid linked by α-2,3 bond with galactose in cancer tissue and in intermediate zone comparing to normal renal tissue distant of tumor. Moreover, we observed statistically significant increase of sialic acid linked by α-2,6 bond with Gal/GalNAc and sialyl Lewis(a/x) antigens in cancer tissues only, comparing to normal ones. MUC1 and sialylated antigens can be involved in renal tumor development and can be considered as potential markers distinguishing normal renal tissue from intermediate zone and from cancer renal cells during ccRCC development. | 25,091,456 | [
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Text2Floss: the feasibility and acceptability of a text messaging intervention to improve oral health behavior and knowledge. | Text messaging is useful for promoting numerous health-related behaviors. The Text2Floss Study examines the feasibility and utility of a 7-day text messaging intervention to improve oral health knowledge and behavior in mothers of young children. Mothers were recruited from a private practice and a community clinic. Of 156 mothers enrolled, 129 randomized into text (n = 60) and control groups (n = 69) completed the trial. Participants in the text group received text messages for 7 days, asking about flossing and presenting oral health information. Oral health behaviors and knowledge were surveyed pre- and post-intervention. At baseline, there were no differences between text and control group mothers in knowledge and behaviors (P > 0.10). Post-intervention, text group mothers flossed more (P = 0.01), had higher total (P = 0.0006) and specific (P < 0.05) knowledge, and tried to improve their child's oral health behaviors (P = 0.03) and decrease their soda and sugary snacks (P = 0.05) more than control mothers. Text messages were accepted and perceived as useful. Mothers receiving text messages improved their own oral health behaviors and knowledge as well as their behaviors regarding their children's oral health. Text messaging represents a viable method to improve oral health behaviors and knowledge. Its high acceptance may make it useful for preventing oral disease. | 25,091,471 | [
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DNA analysis using an integrated microchip for multiplex PCR amplification and electrophoresis for reference samples. | A system that automatically performs the PCR amplification and microchip electrophoretic (ME) separation for rapid forensic short tandem repeat (STR) forensic profiling in a single disposable plastic chip is demonstrated. The microchip subassays were optimized to deliver results comparable to conventional benchtop methods. The microchip process was accomplished in sub-90 min compared with >2.5 h for the conventional approach. An infrared laser with a noncontact temperature sensing system was optimized for a 45 min PCR compared with the conventional 90 min amplification time. The separation conditions were optimized using LPA-co-dihexylacrylamide block copolymers specifically designed for microchip separations to achieve accurate DNA size calling in an effective length of 7 cm in a plastic microchip. This effective separation length is less than half of other reports for integrated STR analysis and allows a compact, inexpensive microchip design. This separation quality was maintained when integrated with microchip PCR. Thirty samples were analyzed conventionally and then compared with data generated by the microfluidic chip system. The microfluidic system allele calling was 100% concordant with the conventional process. This study also investigated allelic ladder consistency over time. The PCR-ME genetic profiles were analyzed using binning palettes generated from two sets of allelic ladders run three and six months apart. Using these binning palettes, no allele calling errors were detected in the 30 samples demonstrating that a microfluidic platform can be highly consistent over long periods of time. | 25,091,472 | [
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Molecular imaging insights into neurodegeneration: focus on α-synuclein radiotracers. | Neurodegenerative diseases characterized by the presence of α-synuclein-a hallmark of pathologic inclusions termed Lewy bodies-include Parkinson's disease, dementia with Lewy bodies, and multiple-system atrophy. Although motor symptoms are related to the altered presynaptic dopaminergic function in these diseases, the appearance of α-synuclein inclusions precedes the involvement of the nigrostriatal dopaminergic pathway. Hence, the most accurate and earliest definition of premotor Parkinson's disease ought to rely on imaging α-synuclein rather than dopaminergic changes. Moreover, dopaminergic imaging has been controversial in monitoring the effects of investigational disease-modifying drugs. For these clinical trials, intense interest in longitudinally imaging α-synuclein as the primary pathologic process has led to efforts toward developing a suitable radiotracer for this key protein. An overview of the present α-synuclein radiotracer development scenario is presented here. | 25,091,474 | [
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p32, a novel binding partner of Mcl-1, positively regulates mitochondrial Ca(2+) uptake and apoptosis. | Mcl-1 is a major anti-apoptotic Bcl-2 family protein. It is well known that Mcl-1 can interact with certain pro-apoptotic Bcl-2 family proteins in normal cells to neutralize their pro-apoptotic functions, thus prevent apoptosis. In addition, it was recently found that Mcl-1 can also inhibit mitochondrial calcium uptake. The detailed mechanism, however, is still not clear. Based on Yeast Two-Hybrid screening and co-immunoprecipitation, we identified a mitochondrial protein p32 (C1qbp) as a novel binding partner of Mcl-1. We found that p32 had a number of interesting properties: (1) p32 can positively regulate UV-induced apoptosis in HeLa cells. (2) Over-expressing p32 could significantly promote mitochondrial calcium uptake, while silencing p32 by siRNA suppressed it. (3) In p32 knockdown cells, Ruthenium Red treatment (an inhibitor of mitochondrial calcium uniporter) showed no further suppressive effect on mitochondrial calcium uptake. In addition, in Ruthenium Red treated cells, Mcl-1 also failed to suppress mitochondrial calcium uptake. Taken together, our findings suggest that p32 is part of the putative mitochondrial uniporter that facilitates mitochondrial calcium uptake. By binding to p32, Mcl-1 can interfere with the uniporter function, thus inhibit the mitochondrial Ca(2+) uploading. This may provide a novel mechanism to explain the anti-apoptotic function of Mcl-1. | 25,091,479 | [
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Trends in antibiotic prescribing in primary care for clinical syndromes subject to national recommendations to reduce antibiotic resistance, UK 1995-2011: analysis of a large database of primary care consultations. | To measure trends in antibiotic prescribing in UK primary care in relation to nationally recommended best practice. A descriptive study linking individual patient data on diagnosis and prescription in a large primary care database, covering 537 UK general practices during 1995-2011. The proportion of cough/cold episodes for which antibiotics were prescribed decreased from 47% in 1995 to 36% in 1999, before increasing to 51% in 2011. There was marked variation by primary care practice in 2011 [10th-90th percentile range (TNPR) 32%-65%]. Antibiotic prescribing for sore throats fell from 77% in 1995 to 62% in 1999 and then stayed broadly stable (TNPR 45%-78%). Where antibiotics were prescribed for sore throat, recommended antibiotics were used in 69% of cases in 2011 (64% in 1995). The use of recommended short-course trimethoprim for urinary tract infection (UTI) in women aged 16-74 years increased from 8% in 1995 to 50% in 2011; however, a quarter of practices prescribed short courses in ≤16% of episodes in 2011. For otitis media, 85% of prescriptions were for recommended antibiotics in 2011, increasing from 77% in 1995. All these changes in annual prescribing were highly statistically significant (P < 0.001). The implementation of national guidelines in UK primary care has had mixed success, with prescribing for coughs/colds, both in total and as a proportion of consultations, now being greater than before recommendations were made to reduce it. Extensive variation by practice suggests that there is significant scope to improve prescribing, particularly for coughs/colds and for UTIs. | 25,091,508 | [
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Sleep disturbances in preschool age children with cerebral palsy: a questionnaire study. | The study aimed to analyze (i) the prevalence of sleep disorders in pre-school children with cerebral palsy (CP) using the Sleep Disturbance Scale for Children (SDSC), (ii) the possible association with motor, cognitive and behavioral problems, and (iii) the possible differences with typically developing children matched for age and gender. One-hundred children with CP (age range: 3-5 years, mean: 3.8 years) were assessed using the SDSC, the Gross Motor Function Classification System (GMFCS), the Wechsler Preschool and Primary Scale of Intelligence, and the Child Behaviour Check List (CBCL) to assess sleep, motor, cognitive, and behavioral problems, respectively. Further 100 healthy children matched for age and sex were assessed using the SDSC. An abnormal total sleep score was found in 13% of children with CP while 35% had an abnormal score on at least one SDSC factor. SDSC total score was significantly associated with pathological internalizing scores on CBCL and active epilepsy on multivariate analysis. CP group reported higher significant median scores on SDSC total, parasomnias, and difficulty in initiating and maintaining sleep factors. In pre-school children sleep disorders are more common in children with CP than in healthy control group and are often associated with epilepsy and behavioral problems. | 25,091,533 | [
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A new species of Scytalidium causing slippery scar on cultivated Auricularia polytricha in China. | Slippery scar is one of the most destructive diseases encountered in the cultivation of Auricularia polytricha (hairy wood ear); however, the identity of the pathogenic agent has remained uncertain. This study was designed to identify the causative pathogen of slippery scar in A. polytricha and to investigate the taxonomic classification of the pathogen by morphological observations, in vivo pathogenicity tests, and molecular evidences of ITS and RPB2 sequences. The results showed that the pathogen was a new Scytalidium species, here named Scytalidium auriculariicola. Scytalidium auriculariicola was characterized by its rapid growth rate, the catenate conidia of variable size, and the pale brown to brown chlamydoconidia. Phylogenetic analyses based on internal transcribed spacer regions and RPB2 sequences on the pathogen isolated and related species supported that S. auriculariicola was a true Scytalidium species. It was congeneric with and close to Scytalidium lignicola, the type species of Scytalidium. However, it differed from the latter species in the size of conidia, 33 different nucleotide bases in ITS sequences and 30 different nucleotide bases in RPB2 sequences. | 25,091,557 | [
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Melanoma differentiation-associated gene-7/interleukin-24 as a potential prognostic biomarker and second primary malignancy indicator in head and neck squamous cell carcinoma patients. | The significance of melanoma differentiation-associated gene-7/interleukin-24 (MDA-7/IL-24) expression in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study was designed to investigate and evaluate the clinical significance of MDA-7/IL-24 expression in HNSCC by detecting expression by immunostaining in 131 HNSCC specimens. The function of MDA-7/IL-24 was investigated by real-time polymerase chain reaction (PCR) and Western blot in Ad5.mda-7-infected HNSCC cell lines. Our results showed that MDA-7/IL-24 was mainly expressed in the cytoplasm of HNSCC cells. MDA-7/IL-24 high patients presented with a favorable postoperative prognosis compared with MDA-7/IL-24 low patients, and high expression of MDA-7/IL-24 was significantly correlated with a lower incidence of second primary malignancies (SPMs) in the head and neck regions. In vitro assays showed that high expression of MDA-7/IL-24 could upregulate the expression of the epithelial terminal differentiation markers cytokeratin (KRT) 1, KRT4, KRT13, phosphorylated endoplasmic reticulum stress protein (p)-EIF2a, and the apoptosis-related protein cleaved caspase-3. It also downregulated the epithelial proliferative markers KRT5, KRT14, Integrin β4, and anti-apoptosis protein Bcl-2, which might be partially involved in the underlying mechanisms of Ad.mda-7-mediated HNSCC differentiation and apoptosis. Our results indicate that MDA-7/IL-24 can be a prognostic biomarker and an indicator of second primary malignancies (SPM) in HNSCC. | 25,091,574 | [
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Multi-spectral imaging with infrared sensitive organic light emitting diode. | Commercially available near-infrared (IR) imagers are fabricated by integrating expensive epitaxial grown III-V compound semiconductor sensors with Si-based readout integrated circuits (ROIC) by indium bump bonding which significantly increases the fabrication costs of these image sensors. Furthermore, these typical III-V compound semiconductors are not sensitive to the visible region and thus cannot be used for multi-spectral (visible to near-IR) sensing. Here, a low cost infrared (IR) imaging camera is demonstrated with a commercially available digital single-lens reflex (DSLR) camera and an IR sensitive organic light emitting diode (IR-OLED). With an IR-OLED, IR images at a wavelength of 1.2 µm are directly converted to visible images which are then recorded in a Si-CMOS DSLR camera. This multi-spectral imaging system is capable of capturing images at wavelengths in the near-infrared as well as visible regions. | 25,091,589 | [
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Team collaboration: the use of behavior principles for serving students with ASD. | Speech-language pathologists (SLPs) and behavior analysts are key members of school-based teams that serve children with autism spectrum disorders (ASD). Behavior analysts approach assessment and intervention through the lens of applied behavior analysis (ABA). ABA-based interventions have been found effective for targeting skills across multiple domains for children with ASD. However, some SLPs may be unfamiliar with the breadth of ABA-based interventions. The intent of this tutorial is to briefly introduce key ABA principles, provide examples of ABA-based interventions used within schools, and identify strategies for successful collaboration between behavior analysts and SLPs. This tutorial draws from empirical studies of ABA-based interventions for children with ASD within school settings, as well as discussions in the extant literature about the use of behavior principles by SLPs and strategies for interdisciplinary collaboration. Given the prevalence of ASD at 1 in 68 children (Centers for Disease Control and Prevention, 2014) and the high cost of serving these children within schools (an average cost of 286% over regular education; Chambers, Shkolnik, & Perez, 2003), the need for effective, comprehensive service provision and efficiency within interdisciplinary teams is paramount. Communication, mutual understanding, and recognition of common ground between SLPs and behavior analysts can lead to successful collaboration. | 25,091,620 | [
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Determinants of fruit and vegetable intake in low-income children and adolescents. | Although low-income youth are likely to have low or less frequent fruit and vegetable intake, current understanding of the influences on intake in youth is limited. A systematic review of quantitative research on determinants of fruit and vegetable intake among low-income youth (i.e., persons aged <20 years) was conducted. The aims were to identify which determinants have been studied and which are consistently associated with intake. Fifty-eight papers published between 2003 and August 2013 were included. Across studies, 85 unique determinants were identified. Those best supported by evidence were race/ethnicity (with intake consistently higher among Hispanic as compared with African American and white youth), fruit and vegetable preferences, and maternal fruit and vegetable intake. For many potential determinants, the consistency of evidence could not be examined because of a lack of studies. Findings highlight racial/ethnic differences in fruit and vegetable intake and influences on intake that should be considered when designing dietary interventions for low-income youth. Further research on intake determinants in this at-risk population is needed to establish an evidence base to guide interventions. | 25,091,630 | [
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Both gene deletion and promoter hyper-methylation contribute to the down-regulation of ZAC/PLAGL1 gene in gastric adenocarcinomas: a case control study. | Pleiomorphic adenoma gene-like 1 (PLAGL1, also known as LOT1 and ZAC) is a zinc-finger nuclear transcription factor, which possesses antiproliferative effects and is frequently epigenetically silenced during tumorigenesis. PLAGL1 gene is located on 6q24-25, a chromosomal region that is frequently deleted in various kinds of cancers. Both promoter hyper-methylation and loss of heterozygosity may lead to the down-regulation of PLAGL1 in human somatic cancers. Here we aimed to investigate the abnormalities of PLAGL1 in gastric cancers. We collected 153 case-matched gastric adenocarcinoma (GAC) cases. Quantitative real-time PCR method was applied to evaluate the expression levels as well as gene copy numbers of PLAGL1 in the collected samples. Methylation-specific PCR (MSP) assay was performed to analyze the methylation status of PLAGL1 P1 promoter. Decreased expression of PLAGL1 mRNA was observed in GAC tissues, especially in advanced GACs. Copy number decrease of PLAGL1 gene in GACs was observed in 9.15% (19 out of 153) of the GAC samples and was closely correlated with gene expression. Methylation status of PLAGL1 promoter in GAC tissues was higher than in normal controls, which was inversely correlated with the expression levels of PLAGL1 mRNA. DNA deletion and promoter hyper-methylation both contribute to the down-regulation of PLAGL1 in GACs. | 25,091,631 | [
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The effects of human keratinocyte coculture on human adipose-derived stem cells. | The potential for adipose-derived stem cells to differentiate into keratinocyte-like cells has recently been receiving attention, stemming from the hypothesis that a bioengineered skin may be manufactured from these readily available mesenchymal stem cells. This study was conducted to evaluate the influence of human keratinocyte non-contact coculture on hADSCs. Human epidermal keratinocytes and hADSCs obtained by lipoaspiration were cultured in keratinogenic growth media, which were divided into the following groups: human adipose-derived stem cell (hADSC) monoculture, non-contact coculture of hADSCs and human keratinocytes and keratinocyte monoculture. Cell proliferation was assessed, and keratogenicity was analysed through immunocytochemistry and polymerase chain reaction of early, intermediate and late keratogenic markers. hADSCs cocultured with keratinocytes displayed enhanced proliferation compared with the monoculture group. After a 7-day coculture period, immunohistochemistry and polymerase chain reaction findings revealed the presence of specific keratinocyte markers in the coculture group. This study demonstrates that hADSCs cocultured with keratinocytes have the capacity to transdifferentiate into keratinocyte lineage cells, and suggests that adipose tissue may be a source of keratinocytes that may further be used in structuring the bioengineered skin. | 25,091,634 | [
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Diagnosis-specific readmission risk prediction using electronic health data: a retrospective cohort study. | Readmissions after hospital discharge are a common occurrence and are costly for both hospitals and patients. Previous attempts to create universal risk prediction models for readmission have not met with success. In this study we leveraged a comprehensive electronic health record to create readmission-risk models that were institution- and patient- specific in an attempt to improve our ability to predict readmission. This is a retrospective cohort study performed at a large midwestern tertiary care medical center. All patients with a primary discharge diagnosis of congestive heart failure, acute myocardial infarction or pneumonia over a two-year time period were included in the analysis.The main outcome was 30-day readmission. Demographic, comorbidity, laboratory, and medication data were collected on all patients from a comprehensive information warehouse. Using multivariable analysis with stepwise removal we created three risk disease-specific risk prediction models and a combined model. These models were then validated on separate cohorts. 3572 patients were included in the derivation cohort. Overall there was a 16.2% readmission rate. The acute myocardial infarction and pneumonia readmission-risk models performed well on a random sample validation cohort (AUC range 0.73 to 0.76) but less well on a historical validation cohort (AUC 0.66 for both). The congestive heart failure model performed poorly on both validation cohorts (AUC 0.63 and 0.64). The readmission-risk models for acute myocardial infarction and pneumonia validated well on a contemporary cohort, but not as well on a historical cohort, suggesting that models such as these need to be continuously trained and adjusted to respond to local trends. The poor performance of the congestive heart failure model may suggest that for chronic disease conditions social and behavioral variables are of greater importance and improved documentation of these variables within the electronic health record should be encouraged. | 25,091,637 | [
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[Breast surgeon role in the management of high-risk breast lesions]. | Diagnostics of high-risk breast lesions have increased these last years with the augmentation of breast percutaneous biopsies. They are lesions that confer an enlarged risk of breast cancer, either because of an increased probability of finding cancer after open surgery, a possible evolution toward in situ or invasive cancer, or because of an increased probability of developing breast cancer over the long term. Much progress has been made these last years in their histological diagnostic, classification and pathogenesis. Nevertheless, no consensus exists to date on the management of these "high-risk" lesions. In particular, surgical indications and follow-up modalities remain controversial for each histological type. In this review, the principal factors that could impact surgical decision and long-term follow-up are discussed with areas of controversy highlighted. | 25,091,655 | [
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[Breast cancer: radiotherapy and estrogen signaling]. | Hormone receptors are expressed in more than 75% of breast cancer. Therefore, two prescription modalities of endocrine therapy could be proposed: either sequential or concomitant to breast cancer irradiation. If combined to radiotherapy, is endocrine therapy a radiosensitizer? Does endocrine therapy enhance the risk factor of radio-induced toxicity? Here, we will distinguish the interaction of ionizing radiation combined with therapies targeting oestrogen receptor (REα) from the interaction of ionizing radiation with oestrogen. This review aims at making clear all these items. | 25,091,654 | [
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[Carcinosarcomas in female genital tracts: general review]. | Carcinosarcoma, also known as mixed mesodermal tumor or malignant mixed Mullerian tumor (MMMT) is a pathological entity combining a sarcomatous and a carcinomatous component. Found in thoracic, digestive, genitourinary, liver or skin locations, the most common location is the female genital tract. In gynecological tumors, carcinosarcoma accounts for about 2-5% of endometrial cancers, and 1% of ovarian cancers. To date, there is no consensus on the therapeutic strategy. It relies mostly on maximum cytoreductive surgery. Adjuvant therapy remains controversial, and few prospective studies investigating its interest. Retrospective studies show the benefits of adjuvant chemotherapy based on platinum in most cases. Radiation therapy has a place in the adjuvant situations of endometrial and cervical carcinosarcoma. A more detailed pathological knowledge, and the use of targeted therapies may be promising in this histological subtype whose prognosis remains very poor. The objective of this study is to present the main principles of carcinosarcoma management in female genital tracts, describing pathological and prognostic features at the same time. | 25,091,658 | [
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[Pertuzumab (Perjeta®) approval in HER2-positive metastatic breast cancers]. | Fifteen to 20% of breast cancers display HER2 amplification. Many therapeutic successes have been obtained for this subtype in the last decade since trastuzumab approval for metastatic and localized diseases. Pertuzumab, a new anti-HER2 antibody, has been approved in 2013 by the European Medicine Agency. This drug can be used in combination with trastuzumab and docetaxel for the first line treatment of metastatic or locally recurrent non resecable HER2-positive breast cancers not previously treated by chemotherapy or HER2-inhibitors in the metastatic setting. This approval has been done after the CLEOPATRA trial results. This was a randomized, double-blind, multicentre, phase III trial evaluating the standard treatment (trastuzumab plus docetaxel) associated to pertuzumab or placebo. The authors have reported a statistically significant and clinically relevant benefit for the pertuzumab-based treatment. Median progression-free survival was 18.4 for the pertuzumab arm versus 12.5 months for the control group (p<0.001). They also observed benefits concerning the secondary endpoints: overall response rate and overall survival. Patients receiving pertuzumab presented more frequent diarrhea and febrile neutropenia but no increase in cardiac events. This drug has already been evaluated in the neoadjuvant setting with a FDA approval recently obtained. Its use in the adjuvant setting is under evaluation. | 25,091,659 | [
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Bovine rotavirus pentavalent vaccine development in India. | A bovine rotavirus pentavalent vaccine (BRV-PV) containing rotavirus human-bovine (UK) reassortant strains of serotype G1, G2, G3, G4 and G9 has been developed by the Serum Institute of India Ltd, in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), USA. The vaccine underwent animal toxicity studies and Phase I and II studies in adults, toddlers and infants. It has been found safe and immunogenic and will undergo a large Phase III study to assess efficacy against severe rotavirus gastroenteritis. | 25,091,665 | [
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Soluble biglycan as a biomarker of inflammatory renal diseases. | Chronic renal inflammation is often associated with a progressive accumulation of various extracellular matrix constituents, including several members of the small leucine-rich proteoglycan (SLRP) gene family. It is becoming increasingly evident that the matrix-unbound SLRPs strongly regulate the progression of inflammation and fibrosis. Soluble SLRPs are generated either via partial proteolytic processing of collagenous matrices or by de novo synthesis evoked by stress or injury. Liberated SLRPs can then bind to and activate Toll-like receptors, thus modulating downstream inflammatory signaling. Preclinical animal models and human studies have recently identified soluble biglycan as a key initiator and regulator of various inflammatory renal diseases. Biglycan, generated by activated macrophages, can enter the circulation and its elevated levels in plasma and renal parenchyma correlate with unfavorable renal function and outcome. In this review, we will focus on the critical role of soluble biglycan in inflammatory signaling in various renal disorders. Moreover, we will provide new data implicating proinflammatory effects of soluble decorin in unilateral ureteral obstruction. Finally, we will critically evaluate the potential application of soluble biglycan vis-à-vis other SLRPs (decorin, lumican and fibromodulin) as a promising target and novel biomarker of inflammatory renal diseases. | 25,091,702 | [
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Solubility and some crystallization properties of conglomerate forming chiral drug guaifenesin in water. | The solubility of 3-(2-methoxyphenoxy)-propane-1,2-diol, the well-known chiral drug guaifenesin 1, in water has been investigated by means of polythermal and isothermal approaches. It was found that the solubilities of racemic and enantiomeric diols rac- and (R)-1 depend strongly on temperature. The ternary phase diagram of the guaifenesin enantiomers in water in the temperature range between 10°C and 40°C was constructed. Clear evidence was obtained that rac-1 crystallizes as a stable conglomerate. The Meyerhoffer coefficient for the guaifenesin-water system is more than two and strongly depends on temperature. Neither crystalline hydrates nor polymorphs were detected within the range of conditions covered. Metastable zone width data with regard to primary nucleation were also collected for rac-1 and (R)-1. On the basis of the knowledge acquired, the resolution of racemic guaifenesin by preferential crystallization from solution could be realized successfully. | 25,091,705 | [
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Older persons with dementia at risk for institutionalization in eight European countries: a cross-sectional study on the perceptions of informal caregivers and healthcare professionals. | To explore the perceptions of informal caregivers and healthcare professionals regarding potential reasons for the institutionalization of older persons with dementia in eight European countries. Healthcare professionals may have an important role in facilitating informal caregivers' decision-making regarding institutionalization. Little is known about the perceptions of informal caregivers and healthcare professionals prior to institutionalization. Cross-sectional survey in eight European countries (November 2010-January 2012). Healthcare professionals reported why they clinically judged persons with dementia at risk for institutionalization. Informal caregivers reported potential reasons from their perspectives. Answers were openly coded and categorized. Variation between informal caregivers and healthcare professionals was investigated (agreement on at least one potential reason per case/proportion of maximum attainable kappa). Judgements of healthcare professionals and informal caregivers on 1160 persons with dementia were included. A total of 22 categories emerged. Approximately 90% of informal caregivers reported potential reasons. In 41% of the cases, informal caregivers and healthcare professionals agreed on at least one reason. Discrepancy was high for potential reasons related to caregiver burden. For the most frequent categories (caregiver burden, caregiver unable to provide care, neuropsychiatric symptoms, overall deterioration, care dependency), 24-41% of the attainable kappa was achieved. Differences between countries emerged indicating more favourable agreement in Finland, Sweden and Estonia and lowest agreement in England and Spain. Agreement between healthcare professionals and informal caregivers on potential reasons for institutionalization was low-to-moderate. Healthcare professionals are challenged to develop a detailed understanding of the perspectives and perceived burden of informal caregivers. | 25,091,706 | [
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Patient perceptions of asthma-related financial burden: public vs. private health insurance in the United States. | Given the complexity of the health insurance market in the United States and the confusion that often stems from these complexities, patient perception about the value of health insurance in managing chronic disease is important to understand. To examine differences between public and private health insurance in perceptions of financial burden with managing asthma, outcomes, and factors that explain these perceptions. Secondary analysis was performed using baseline data from a randomized clinical trial that were collected through telephone interviews with 219 African American women seeking services for asthma and reporting perceptions of financial burden with asthma management. Path analysis with multigroup models and multiple variable regression analyses were used to examine associations. For public (P < .001) and private (P < .01) coverage, being married and more educated were indirectly associated with greater perceptions of financial burden through different explanatory pathways. When adjusted for multiple morbidities, asthma control, income, and out-of-pocket expenses, those with private insurance used fewer inpatient (P < .05) and emergency department (P < .001) services compared with those with public insurance. When also adjusted for health insurance, greater financial burden was associated with more urgent office visits (P < .001) and lower quality of life (P < .001). African American women who perceive asthma as a financial burden regardless of health insurance report more urgent health care visits and lower quality of life. Burden may be present despite having and being able to generate economic resources and health insurance. Further policy efforts are indicated and special attention should focus on type of coverage. | 25,091,716 | [
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Low birth weight is associated with adiposity, impaired skeletal muscle energetics and weight loss resistance in mice. | In utero undernutrition is associated with obesity and insulin resistance, although its effects on skeletal muscle remain poorly defined. Therefore, in the current study we explored the effects of in utero food restriction on muscle energy metabolism in mice. We used an experimental mouse model system of maternal undernutrition during late pregnancy to examine offspring from undernourished dams (U) and control offspring from ad libitum-fed dams (C). Weight loss of 10-week-old offspring on a 4-week 40% calorie-restricted diet was also followed. Experimental approaches included bioenergetic analyses in isolated mitochondria, intact (permeabilized) muscle and at the whole body level. U have increased adiposity and decreased glucose tolerance compared to C. Strikingly, when U are put on a 40% calorie-restricted diet they lose half as much weight as calorie-restricted controls. Mitochondria from muscle overall from U had decreased coupled (state 3) and uncoupled (state 4) respiration and increased maximal respiration compared to C. Mitochondrial yield was lower in U than C. In permeabilized fiber preparations from mixed fiber-type muscle, U had decreased mitochondrial content and decreased adenylate-free leak respiration, fatty acid oxidative capacity and state 3 respiratory capacity through complex I. Fiber maximal oxidative phosphorylation capacity did not differ between U and C but was decreased with calorie restriction. Our results reveal that in utero undernutrition alters metabolic physiology through a profound effect on skeletal muscle energetics and blunts response to a hypocaloric diet in adulthood. We propose that mitochondrial dysfunction links undernutrition in utero with metabolic disease in adulthood. | 25,091,727 | [
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DSDs: genetics, underlying pathologies and psychosexual differentiation. | Mammalian sex determination is the unique process whereby a single organ, the bipotential gonad, undergoes a developmental switch that promotes its differentiation into either a testis or an ovary. Disruptions of this complex genetic process during human development can manifest as disorders of sex development (DSDs). Sex development can be divided into two distinct processes: sex determination, in which the bipotential gonads form either testes or ovaries, and sex differentiation, in which the fully formed testes or ovaries secrete local and hormonal factors to drive differentiation of internal and external genitals, as well as extragonadal tissues such as the brain. DSDs can arise from a number of genetic lesions, which manifest as a spectrum of gonadal (gonadal dysgenesis to ovotestis) and genital (mild hypospadias or clitoromegaly to ambiguous genitalia) phenotypes. The physical attributes and medical implications associated with DSDs confront families of affected newborns with decisions, such as gender of rearing or genital surgery, and additional concerns, such as uncertainty over the child's psychosexual development and personal wishes later in life. In this Review, we discuss the underlying genetics of human sex determination and focus on emerging data, genetic classification of DSDs and other considerations that surround gender development and identity in individuals with DSDs. | 25,091,731 | [
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Development of extrahepatic bile duct excluding gall bladder in human fetuses: histological, histochemical, and immunohistochemical analysis. | The fetal development of extrahepatic bile ducts (EBD) is unkown. Development of EBD was examined by immunohistochemistry in 16 fetuses of 7-40 gestational week (GW). Gall bladder (GB) was not investigated. At seven GW, a hepato-pancreatic bud (HPB) was seen near the hepatic hilus. At eight GW, embryonic EBD, GB and pacreas developed from HPB. Portal veins (PV) and hepatic arteries (HAs) were present in EBD at eight GW. Liver parenchyma was already present in seven GW. At eight GW, EBD at porta hepatis (PH) was already established; PH EBD was derived from ductal plate (DP). The distal and middle EBD gradually develeped and took shape of EBD at nine GW. In PH, cystic and hepatic ducts developed from DP at eight GW. EBD developed further, accompanying many nerve fibers (NF) at PH and distal and middle EBD. Apparent PV and HA were seen around 12 GW. Around 20 GW, HA and capillaries proliferated, giving rise to peribiliary capillary plexus (PCP) in all parts of EBD. EBD grew gradually further, and around 30 GW extrahepatic peribiliary glands (EPG) emerged from EBD but not from cystic duct. Around 36 GW, exocrine pancreatic acinar cells emerged from remodeled DP at PH. At term (40 GW), EBD was established but was as yet immature. Numerous NF were present around EBD. Histochemically, EBD epithelium had no mucins at 7-12 GW but contained neutral and acidic mucins at 23-40 GW. EPG had abundant neutral and acidic mucins. Immunohistochemically, alpha-fetoprotein (AFP) was consistently positive in the epithelial and mesenychyma. The NF and muscles of HPB present at seven GW were positive for neural cell adhesion molecule (NCAM), neuron-specific enolase (NSE), platelet-derived growth factor receptor-α (PDGFRA), and KIT, but they disappeared in nine GW. Expressions of cytokeratin (CK) seven and CK19 in EBD and EPG were slight or none, while expression of CK8 was moderate, and that of CK18 was strong. NF were positive for NCAM, NSE, synaptophysin, and chromogranin, and PDGFRA. MUC1 and MUC6 apomucins were noted in EBD and EPG. EPG contained numerous endocrine cells positive for chromogranin, synaptophysin, NCAM and NSE. A few endocrine cells positive for these antigens were seen in EBD. Numeous KIT-positive stem cells (SC) were seen in PH, EBD, PV, HA, PCP, and EPG. NCAM-positive and bcl-2-positive SC were also located in these structures. Epithelial cells of EBD and EPG showed expressions of MET, PDGFRA, CA19-9, MUC1, MUC2, MUC6, KIT, bcl-2, and ErbB2. No expressions of HepPar1, carcinoembryonic antigen (CEA), and epithelial membrane antigen (EMA) were noted. Although the findings have limitatios because this study of humans are descriptive one, the present data suggest that the processes of the development and differentiation of EBD system may be associated with EBD SC, CK prolifes, SFC/KIT signaling, HGF/MET signaling, PDGRa/PDGFRA signaling, fibroblast growth factor/ErbB2 signaling, neuroendocrine lineage, NF differentiation, pancreatic aninar cell differentiation, PCP differentiation, MUC apomucins differentiation, and expressions of AFP and CA19-9. HepPar1, EMA and CEA were not involved in them. | 25,091,784 | [
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3,4,5-Trihydroxycinnamic acid increases heme-oxygenase-1 (HO-1) and decreases macrophage infiltration in LPS-induced septic kidney. | We previously demonstrated that 3,4,5-trihydorxycinnamic acid (THC), a derivative of hydroxycinnamic acids, possesses protective effect in lipopolysaccharide (LPS)-induced endotoxemia models. However, the effects of THC in LPS-induced septic kidney are still unclear. Therefore, the present study was carried out to examine the effects of THC in LPS-challenged septic kidney using mesangial cell line and Balb/c mice. THC pretreatment effectively inhibited LPS-induced macrophage infiltration and the secretion of pro-inflammatory cytokines in the kidney of LPS-challenged animals. Pretreatment of rat mesangial cells with THC significantly attenuated LPS-induced PGE2 production and COX-2 expression. THC also significantly suppressed LPS-induced expression of MCP-1 in LPS-activated septic kidney and rat mesangial cells. In addition, THC significantly attenuated LPS-induced degradation of IκB-α in LPS-induced rat mesangial cells. THC also increased the expression of heme oxygenase-1 (HO-1) in LPS-challenged septic kidney and mesangial cells. Multiple signaling pathways including p38 and AKT have been observed to be involved in the THC-induced activation of HO-1 expression. The present data clearly demonstrate that THC protects LPS-challenged septic kidney by decreasing macrophage infiltration and increasing HO-1 expression, suggesting that THC might be a valuable therapeutic agent for compromised kidney in sepsis. | 25,091,807 | [
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Carbon nanotube facilitation of myocardial ablation with radiofrequency energy. | The use of carbon nanotubes (CNTs) in oncology has been proposed for the purpose of sensitizing tumors to radiofrequency (RF) ablation. We hypothesize that myocardial tissue infiltrated with CNTs will improve thermal conductivity of RF heating and lead to altered ablation lesion characteristics. An ex vivo model consisting of viable bovine myocardium, a circulating saline bath at 37 °C, a submersible load cell, and a deflectable sheath was assembled. A 4-mm nonirrigated ablation catheter was positioned with 10 gm of force over bovine myocardium infiltrated with CNTs, 0.9% saline, or sham injections. A series of ablation lesions were delivered at 20 and 50 W, and lesion volumes were acquired by analyzing tissue sections with a digital micrometer. Tissue temperature analyses at 3 and 5 mm depths were also performed. Myocardial tissue treated with CNTs resulted in significantly larger lesions at both low and high power settings. The electrical impedance was increased in CNT treated tissue with a greater impedance change observed in the CNT infiltrated myocardium. The thermal conductivity of heat generated by application of RF in the tissue was altered by the presence of CNTs, resulting in higher temperatures at 3 and 5 mm depths for both 20 and 50 W. Myocardial tissue treated with CNTs resulted in significantly larger lesions at both low and high power settings. The electrical and thermal conductivity of heat generated by application of RF in myocardial tissue was altered by the presence of CNTs. Further research is needed to assess the in vivo applicability for this concept of facilitated ablation with CNTs. | 25,091,811 | [
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High-throughput fabrication of anti-counterfeiting colloid-based photoluminescent microtags using electrical nanoimprint lithography. | This work demonstrates the excellent capability of the recently developed electrical nanoimprint lithography (e-NIL) technique for quick, high-throughput production of well-defined colloid assemblies on surfaces. This is shown by fabricating micron-sized photoluminescent quick response (QR) codes based on the electrostatic directed trapping (so called nanoxerography process) of 28 nm colloidal lanthanide-doped upconverting NaYF4 nanocrystals. Influencing experimental parameters have been optimized and the contribution of triboelectrification in e-NIL was evidenced. Under the chosen conditions, more than 300 000 nanocrystal-based QR codes were fabricated on a 4 inch silicon wafer, in less than 15 min. These microtags were then transferred to transparent flexible films, to be easily integrated onto desired products. Invisible to the naked eye, they can be decoded and authenticated using an optical microscopy image of their specific photoluminescence mapping. Beyond this very promising application for product tracking and the anti-counterfeiting strategies, e-NIL nanoxerography, potentially applicable to any types of charged and/or polarizable colloids and pattern geometries opens up tremendous opportunities for industrial scale production of various other kinds of colloid-based devices and sensors. | 25,091,823 | [
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The detergent fraction is effective in the detection of IgG anti-Strongyloides stercoralis in serum samples from immunocompromised individuals. | Human strongyloidiasis is an intestinal helminthiasis that can be fatal particularly in cases of immunosuppression. The aim of this study is to assess the diagnostic accuracy of the detergent fraction (D), purified from total saline extract (SE) of Strongyloides venezuelensis, in the detection of anti-Strongyloides stercoralis IgG antibodies in serum samples from individuals coming from endemic areas for strongyloidiasis and presenting immunocompromised conditions: human immunodeficiency virus (HIV(+)), diabetes mellitus type 2, cancer, tuberculosis and alcoholism. Serum samples from 93 individuals were analyzed by ELISA, as follows: Group 1: 30 immunocompromised individuals with strongyloidiasis; Group 2: 33 immunocompromised individuals without strongyloidiasis and Group 3: 30 healthy individuals. The total saline extract (SE) and detergent fraction (D) showed a sensitivity of 73.33 and 83.33%, and specificity of 82.15 and 86.36%, respectively. The detergent fraction was effective to detect anti-S. stercoralis IgG antibodies in immunocompromised individuals with strongyloidiasis and may be applied as an important tool in the immunodiagnosis of human strongyloidiasis related to immunosuppression. | 25,091,831 | [
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Lymph node ratio improves TNM and Astler-Coller's assessment of colorectal cancer prognosis: an analysis of 761 node positive cases. | Prognosis assessment of node-positive colorectal cancer patients by Astler-Coller (AC) and TNM classifications is suboptimal. Recently, several versions of lymph node ratio (LNR; ratio metastatic/examined nodes) have been proposed but are still mostly unused. The prognostic value of several criteria, including LNR (two classes-LNR1 and LNR2-identified by a 15% cut-off) was studied in 761 consecutive patients, from 2000 through 2010. The relationships between total examined nodes, N, T and LNR were also analysed. LNR1 and LNR2 patients' survival was analysed within AC and TNM subgroups, and then coupled with them. Age, tumour location and LNR are independent factors predicting survival. The relationships between LNR, N stage and T stage with examined nodes suggest confusing factors. LNR allows for identification of subgroups with different survival within AC and TNM classifications (p < 0.0001). Patients with LNR class discordant from AC stage (LNR1-C2 and LNR2-C1) have a similar 5-year survival (54 and 57%, respectively). LNR2 and TNM stage IIIC define a poor 5-year prognosis (33%). LNR is a powerful prognosis predictor, easily integrated with TNM and AC classifications to improve prognosis assessment and facilitate clinical use. Possible confusing factors should be considered in future studies. | 25,091,835 | [
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Predictors of negative intraoperative findings at emergent laparotomy in patients with cirrhosis. | Emergent surgery in the setting of decompensated cirrhosis is highly morbid. We sought to determine the clinical factors associated with negative intraoperative findings at emergent laparotomy. We performed a retrospective cohort study of consecutive inpatients with a diagnosis of cirrhosis (ICD-9 571) admitted to the Beth Israel Deaconess Medical Center (Boston, MA) who underwent emergent, nonhepatic, abdominal surgery between May 6, 2005 and September 3, 2012. Eighty-six patients with cirrhosis were included with a mean model for end-stage liver disease score of 21.3 ± 7.95 and a 90-day mortality rate of 39.5%. Twelve (16.2%) patients had negative laparotomies. Negative intraoperative findings were independently associated with (1) paracentesis prior to a preoperative diagnosis of perforated viscus (P = 0.006), (2) development of an indication for emergent surgery after 24 h into hospital admission for another reason (P = 0.020), and (3) a preoperative diagnosis of bowel ischemia (P = 0.005), with odds ratios of 10.1 (CI 1.92-66.83), 5.80 (CI 1.32-33.39), and 11.1 (CI 2.08-77.4), respectively. Free air on computed tomography (CT) imaging was found in 64.3% (9/14) of patients who had a paracentesis within the preceding 48 h compared to 10.1% (7/72) among patients who did not undergo a paracentesis (P < 0.001). Only 45% of patients with free air following a paracentesis had positive findings at laparotomy compared to 100% in those without a preceding paracentesis (P = 0.038). Negative laparotomy was independently predictive of in-hospital mortality (OR 4.7; P = 0.034). The possibility of a negative laparotomy is suggested by preoperative clinical factors. In particular, free air following a paracentesis does not necessarily indicate that operative intervention is required. Consideration of close observation before laparotomy in these patients is reasonable. | 25,091,839 | [
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Association between alcohol consumption and risk of cardiovascular disease and all-cause mortality in patients with hypertension: a meta-analysis of prospective cohort studies. | To conduct a meta-analysis summarizing the risk of cardiovascular disease (CVD) and all-cause mortality (ACM) in relation to alcohol consumption in patients with hypertension, focusing on clarifying dose-response associations. PubMed and EMBASE were searched for eligible prospective cohort studies from December 3, 1949, through January 18, 2014. The semi-parameter method and dose-response analysis were used. Nine studies (11 cohorts) were included in the meta-analysis. Compared with the lowest alcohol level (abstainers/occasional drinkers), the pooled relative risk (RR) was 0.72 (95% CI, 0.68-0.77) for the third highest category (median, 10 g/d), 0.81 (95% CI, 0.71-0.93) for the second highest category (median, 20 g/d), and 0.60 (95% CI, 0.54-0.67) for the highest category (median, 30 g/d). A J-shaped relationship between alcohol use and ACM was observed, and the nadir (RR, 0.82; 95% CI, 0.76-0.88) was found to be at a dose of 8 to 10 g of alcohol consumption per day. Findings of this meta-analysis suggest that low-to-moderate alcohol consumption was inversely significantly associated with the risk of CVD and ACM in patients with hypertension. | 25,091,872 | [
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Smokers' physical activity and weight gain one year after a successful versus unsuccessful quit attempt. | To examine whether smokers' physical activity is related to weight change following a quit attempt. Data were analyzed for participants (n=683) of a randomized controlled trial comparing the efficacy of different smoking cessation pharmacotherapies (Wisconsin, 2005-2008). Activity (assessed via pedometry) and body weight were measured in the days surrounding the quit day and again one year later, at which time 7-day point-prevalence abstinence from smoking was assessed. We examined the effects of quitting, physical activity, and their interaction, on a one-year weight change with relevant covariate adjustment. Participants were predominantly female (57%), 46 ± 11 years of age (mean ± SD), and took 7544 ± 3606 steps/day at baseline. Of those who quit, 87% gained weight. A main effect was found for quitting (p<0.001), but not physical activity (p=0.06). When pattern of activity was examined across the 1-year study period, quitters who decreased their physical activity had significantly greater weight gain than quitters who increased their physical activity (p<0.01) or maintained a high level of activity (p=0.02). Physical activity is associated with an attenuation of the weight gain that often occurs after quitting smoking. | 25,091,879 | [
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Immunosuppressant dose reduction and long-term rejection risk in renal transplant recipients with severe bacterial pneumonia. | Due to lifelong immunosuppression, renal transplant recipients (RTRs) are at risk of infectious complications such as pneumonia. Severe pneumonia results in respiratory failure and is life‑threatening. We aimed to examine the influence of immunosuppressant dose reduction on RTRs with bacterial pneumonia and respiratory failure. From January 2001 to January 2011, 33 of 1,146 RTRs at a single centre developed bacterial pneumonia with respiratory failure. All patients were treated using mechanical ventilation and aggressive therapies in the intensive care unit. Average time from kidney transplantation to pneumonia with respiratory failure was 6.8 years. In-hospital mortality rate was 45.5% despite intensive care and aggressive therapies. Logistic regression analysis indicated that a high serum creatinine level at the time of admission to the intensive care unit (odds ratio 1.77 per mg/dL, 95% confidence interval 1.01-3.09; p = 0.045) was a mortality determinant. Out of the 33 patients, immunosuppressive agents were reduced in 17 (51.5%). We found that although immunosuppressant dose reduction tended to improve in-hospital mortality, this was not statistically significant. Nevertheless, during a mean follow-up period of two years, none of the survivors (n = 18) developed acute rejection or allograft necrosis. In RTRs with bacterial pneumonia and respiratory failure, higher serum creatinine levels were a mortality determinant. Although temporary immunosuppressant dose reduction might not reduce mortality, it was associated with a minimal risk of acute rejection during the two-year follow-up. Our results suggest that early immunosuppressant reduction in RTRs with severe pneumonia of indeterminate microbiology may be safe even when pathogens are bacterial in nature. | 25,091,886 | [
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Production of a polyclonal antibody against osteogenic protein-1, and its role in the diagnosis of osteoarthritis. | Osteoarthritis (OA) is a progressive degenerative disorder of the articular cartilage. Available diagnostic radiography has been poorly associated with the progress and severity of this clinical disease. As osteogenic protein-1 (OP-1) has been identified as a bone morphogenetic protein with a major role in cartilage repair, we aimed to evaluate its potential role in the diagnosis of OA. This was an experimental study conducted at the Department of Biochemistry, Sikkim Manipal Institute of Medical Sciences, India. Polyclonal antibodies (i.e. anti-OP-1[f]) were raised against OP-1 in mice, and subsequently used in a sandwich enzyme-linked immunosorbent assay (ELISA) to detect the presence of OP-1 in the synovial fluids of 75 osteoarthritic patients. For the purpose of correlation, the radiographic assessments of the knees of the 75 patients were graded using the Kellgren-Lawrence scoring system. The polyclonal antibody (i.e. anti-OP-1[f]) raised against OP-1 was able to detect the presence of OP-1 in the synovial fluids of all the osteoarthritic patients via sandwich ELISA. The level of the OP-1 was found to be much higher than the reference range and correlated positively with the severity of OA (r = 0.24; p = 0.04). Our study shows that the polyclonal antibody, anti OP-1(f), could be used for the immunodiagnosis of osteoarthritis via sandwich ELISA. | 25,091,889 | [
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Small bowel obstruction due to an unconjugated ursodeoxycholic acid enterolith following living donor liver transplantation: Report of a case. | We report an unusual case of small bowel obstruction due to an ursodeoxycholic acid (UDCA) enterolith that occurred 7 years after liver transplantation. A 70-year-old man had undergone multiple operations, including a living donor liver transplantation (LDLT) and hepaticojejunostomy. Four years after the LDLT, cholestasis developed, for which oral UDCA was administrated. Seven years after the LDLT, he was admitted to our hospital because of pneumonia; intestinal obstruction occurred following its resolution. A radiographic contrast study and computed tomographic scan indicated a movable mass as the cause of the ileus, suggesting a giant stone. We were unable to observe or remove the stone by double balloon enteroscopy owing to the presence of severe adhesion; thus, we surgically removed the mass. The patient's postoperative course was uneventful. He was discharged 20 days after the operation. An infrared spectrophotometric analysis revealed that the stone was a true enterolith, primarily composed of unconjugated UDCA. An ileus caused by a true enterolith is a rare clinical complication of LDLT. Nevertheless, it must be considered in the differential diagnosis of intestinal obstructions in liver transplant recipients with Roux-en-Y hepaticojejunostomies and/or bowel stasis. | 25,091,893 | [
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Amphibian declines in the twenty-first century: why we need assisted reproductive technologies. | Each amphibian species is evolutionarily distinct, having developed highly specialized and diverse reproductive strategies in both terrestrial and aquatic environments. These unique reproductive patterns and mechanisms, key to species propagation, have only been explored in a limited number of laboratory models. Although the development of applied reproductive technologies for amphibians has proven useful for a few threatened species, the real benefit of this technology has been new insights into the reproductive adaptations, behavior, endocrinology, and physiological mechanisms that have evolved over millions of years. As the basic fundamental database on amphibian reproductive physiology has grown, so has the applied benefit for species conservation. In particular, technologies such as non-invasive fecal and urinary hormone assays, hormone treatments for induced breeding or gamete collection, in vitro fertilization, and the ability to establish genome resource banks have all played important roles in monitoring or managing small populations of captive species. Amphibians have the ability to produce a large excess of germplasm (up to 10,000 ovulated eggs in a single reproductive event) that if not collected and preserved, would represent a wasted valuable resource. We discuss the current state of knowledge in assisted reproductive technologies for amphibians and why their extinction crisis means these available tools can no longer be implemented as small-scale, last-ditch efforts. The reproductive technologies must be established early as a key component of large-scale species recovery. | 25,091,914 | [
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Conclusions: environmental change, wildlife conservation and reproduction. | Our intention when planning this book was to explore the diverse ways that reproductive science is inextricably tied to many aspects of biodiversity conservation, using the opportunity to present a vast amount of specialised information in a way that forms a coherent and important body of work. Some of the chapters were therefore concerned with understanding how taxonomic groups and species are being affected by globally important environmental changes, mostly caused through anthropogenic influences. Others were more focused on monitoring and understanding the physiology of wild species, with the aim of better understanding mechanisms underlying responses to captive conditions and environmental change, in both wild and captive animals. We also wanted to review advances in technological measures that are being actively developed to support the breeding and management of wildlife. In a few cases we have presented specific case studies that highlight the amount of effort required for the successful development of assisted reproductive technologies for wild species. Viewed overall, the outcome is spectacular; the last decade has seen enormous progress in many aspects of the sciences and technologies relevant to the topic. It is also clear that the boundaries between different scientific disciplines are becoming ever more blurred, and it is no longer easy or even possible to remain focused on a highly specialized topic in reproduction or conservation, without having at least some understanding of allied subjects. Here we present a few concluding comments about what we have learnt, and how the various topics interact with each other. We also emphasize that, as far as we know, no similarly comprehensive consideration of the contribution of reproductive science to wildlife conservation has been published within the last decade. | 25,091,922 | [
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Synthesis of {[5-(adenin-9-yl)-2-furyl]methoxy}methyl phosphonic acid and evaluations against human adenylate kinases. | AMP mimics constitute an important class of therapeutic derivatives to treat diseases where the pool of ATP is involved. A new phosphonate derivative of 9-(5-hydroxymethylfuran-2-yl)adenine was synthesized in a multi-step sequence from commercially available adenosine. Its ability to behave as a substrate of human adenylate kinases 1 and 2 was assessed. The phosphonate was shown to be a moderate but selective substrate of the mitochondrial human AK2, better than well-known antiviral acyclic phosphonates 9-(2-phosphonomethoxyethyl)adenine (PMEA, Adefovir) and (R)-9-(2-phosphonomethoxypropyl)adenine (PMPA, Tenofovir). Putative binding mode within adenylate kinase NMP site revealed by molecular docking in comparison to AMP native substrate allowed to illustrate this selective behavior. | 25,091,927 | [
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Calcium scoring and cardiac computed tomography in 2014. | Although recent advances in noninvasive imaging technologies have potentially improved diagnostic efficiency and clinical outcomes of patients with acute chest pain, controversy remains regarding much of the accumulated evidence. This article reviews the role of coronary computed tomography (CT) angiography in the assessment of coronary risk, and its usefulness in the emergency department in facilitating appropriate disposition decisions. Also discussed is coronary artery calcification incidentally found on CT scans when done for indications such as evaluation of pulmonary embolism or lung cancer. The evidence base and clinical applications for both techniques are described, together with cost-effectiveness and radiation exposure considerations. | 25,091,967 | [
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Predictors of workplace violence among female sex workers in Tijuana, Mexico. | For sex workers, differences in rates of exposure to workplace violence are likely influenced by a variety of risk factors, including where one works and under what circumstances. Economic stressors, such as housing insecurity, may also increase the likelihood of exposure. Bivariate analyses demonstrate statistically significant associations between workplace violence and selected predictor variables, including age, drug use, exchanging sex for goods, soliciting clients outdoors, and experiencing housing insecurity. Multivariate regression analysis shows that after controlling for each of these variables in one model, only soliciting clients outdoors and housing insecurity emerge as statistically significant predictors for workplace violence. | 25,091,980 | [
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The role of professional societies in limiting indication creep. | New technology is a major driver of health care inflation. One contributor to this inflation is indication creep, the diffusion of interventions that have been proven beneficial in specific patient populations into untested broader populations who may be less likely to benefit. Professional societies sometimes promote indication creep, as we illustrate with the case of therapeutic hypothermia after cardiac arrest. Professional societies are in a unique position to limit indication creep. We propose that, at a minimum, professional societies should refrain from recommending new diagnostic and therapeutic technologies in their guidelines until they have been proven beneficial in the targeted populations. In some circumstances, professional societies could be more active in combatting indication creep, either recommending against expanded use of clinical interventions when evidence is lacking, or coordinating efforts to collect data in these broader populations. | 25,092,014 | [
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Mutational analysis of the mycobacteriophage BPs promoter PR reveals context-dependent sequences for mycobacterial gene expression. | The PR promoter of mycobacteriophage BPs directs early lytic gene expression and is under the control of the BPs repressor, gp33. Reporter gene fusions showed that PR has modest activity in an extrachromosomal context but has activity that is barely detectable in an integrated context, even in the absence of its repressor. Mutational dissection of PR showed that it uses a canonical -10 hexamer recognized by SigA, and mutants with mutations to the sequence 5'-TATAMT had the greatest activities. It does not contain a 5'-TGN-extended -10 sequence, although mutants with mutations creating an extended -10 sequence had substantially increased promoter activity. Mutations in the -35 hexamer also influenced promoter activity but were strongly context dependent, and similar substitutions in the -35 hexamer differentially affected promoter activity, depending on the -10 and extended -10 motifs. This warrants caution in the construction of synthetic promoters or the bioinformatic prediction of promoter activity. Combinations of mutations throughout PR generated a calibrated series of promoters for expression of stably integrated recombinant genes in both Mycobacterium smegmatis and M. tuberculosis, with maximal promoter activity being more than 2-fold that of the strong hsp60 promoter. | 25,092,027 | [
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Fabrication of a novel naltrexone biosensor based on a computationally engineered nanobiocomposite. | A computationally engineered impedimetric naltrexone (NLT) biosensor based on immobilization of bovine serum albumin (BSA) onto fullerene-C60/glassy carbon electrode (FLR/GCE) has been developed using initial characterization by computational methods and complementing them by experimental ones. Computational results showed that BSA hydrophobically binds to FLR which is energetically favorable and leads to the spontaneous formation of the stable nanobiocomposite and also showed that interaction of NLT with BSA is mainly driven by hydrogen bonding and hydrophobic interactions. Besides complementing the computational studies, experimental results showed that addition of FLR to the surface of the electrode facilitated electron transfer reactions, and also showed that the presence of BSA inhibits the interfacial electron transfer in some extent due to the non-conductive properties of BSA. The presence of NLT may form a negatively charged electroactive complex with BSA which repels the negatively charged redox probe and decelerates interfacial electron transfer leading to obvious faradaic impedance change. The faradaic impedance responses were linearly related to naltrexone concentration between 0.1 nM and 80 nM and limit of detection (LOD) was calculated to be 0.01 nM 3Sb/b. Finally, the proposed biosensor was successfully applied to determination of NLT in urine samples of both healthy and addict volunteers. | 25,092,049 | [
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Toxicological outcomes in rats exposed to inhaled ethanol during gestation. | Recent legislation has encouraged replacing petroleum-based fuels with renewable alternatives including ethanol, which is typically blended with gasoline in the United States at concentrations up to 10%, with allowances for concentrations up to 85% for some vehicles. Efforts to increase the amount of ethanol in gasoline have prompted concerns about the potential toxicity of inhaled ethanol vapors from these fuels. The well-known sensitivity of the developing nervous and immune systems to ingested ethanol, and the lack of information about its toxicity by inhalation prompted the present work on its potential developmental effects in a rat model. Pregnant Long-Evans rats were exposed for 6.5h/day on days 9-20 of gestation to clean air or ethanol vapor at concentrations of 5000, 10,000, or 21,000 ppm, which resulted in estimated peak blood ethanol concentrations (BECs) of 2.3, 6.7, and 192 mg/dL, respectively. No overt toxicity in the dams was observed. Ethanol did not affect litter size or weight, or postnatal weight gain in the pups. Motor activity was normal in offspring through postnatal day (PND) 29. On PND 62, the 5000 and 21,000 ppm groups were more active than controls. On PND 29 and 62, offspring were tested with a functional observational battery, which revealed small changes in the neuromuscular and sensorimotor domains that were not systematically related to dose. Cell-mediated and humoral immunity were not affected by ethanol exposure in 6-week-old offspring. Systolic blood pressure was increased by 10,000 ppm ethanol in males at PND 90 but not at PND 180. No differences in lipoprotein profile, liver function, or kidney function were observed. In summary, prenatal exposure to inhaled ethanol caused some mild changes in physiological and behavioral development in offspring that were not clearly related to inhaled concentration or BEC, and did not produce detectable changes in immune function. This low toxicity of inhaled ethanol may result from the slow rise in BEC by the inhalation route. | 25,092,052 | [
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Maternal and pregnancy characteristics and risk of infantile hypertrophic pyloric stenosis. | The incidence of infantile hypertrophic pyloric stenosis (IHPS) in Sweden decreased dramatically during the 1990s. The aim of the study was to examine IHPS risk factors and the possible change in them as the incidence declined. This is a case-control study including 3608 surgically treated IHPS cases and 17588 matched controls during 1973-2008. Cases were identified in the Swedish National Patient Register and data on possible risk factors were collected from the Swedish Medical Birth Register. The association between study variables and IHPS was analyzed using conditional logistic regression for the whole study period and separately for periods with high and low IHPS incidences. Prematurity (OR, 2.54; 95% CI, 2.06-3.14), caesarean delivery (OR, 1.67; 95% CI, 1.51-1.86), maternal smoking (OR, 1.82; 95% CI, 1.53-2.16), and young maternal age (< 20yrs) (OR, 1.42; 95% CI, 1.17-1.73) were associated with an increased IHPS risk. Birth order 2 (OR, 0.78; 95% CI, 0.71-0.85) or more was associated with a lower IHPS risk. ORs for smoking increased at low incidence rate. We report caesarean section, prematurity, primiparity, young maternal age, and smoking as significant IHPS risk factors. The impact of smoking was higher during periods with a low incidence. | 25,092,081 | [
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Experience with FiberWire for pectus bar attachment. | Minimally invasive repair of pectus excavatum has become an established method for repair of pectus excavatum. Bar displacement or rotation remains the most common complication of this repair requiring return to the operating room. Retrospective review of all patients at a single institution who underwent repair of pectus excavatum using FiberWire for bar stabilization between December 2009 and March 2013 was undertaken. 93 patients underwent minimally invasive pectus repair using FiberWire during the study period. The patients included 73 males and 20 females, with an average age of 14.6years (range 7-21years). Mean operative time was 102minutes (range 56-198minutes). No patients developed wound complications, two patients developed pain because of bar migration and required return to the OR, and no patients had recurrence of their pectus defect because of bar migration during the study period. Median length of follow-up was 17months (range 3-36months). Stabilization of pectus bars using circumferential rib fixation with FiberWire at multiple points on both sides of the bar appears to be effective in preventing bar rotation and displacement, and requires minimal change to the operation as it has been previously described. Early experience shows a low rate of complications. | 25,092,086 | [
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Neuroblastoma: outcome over a 14 year period from a tertiary care referral centre in India. | To evaluate the outcome of children with neuroblastoma (NB) from a tertiary care referral centre in India. All children with NB registered from October 1996 through July 2009 were included in the study. INSS was used for staging. All children included in the study received chemotherapy and radiation therapy appropriate for stage. Tumor resection was done when feasible. The final outcome was overall survival and it was categorized as Complete Response (CR), Partial Response (PR); No Response (NR) and Progressive Disease (PD). Analysis of three-year overall survival was done using Kaplan Meier method and Log Rank test of significance. Multivariate analysis for significance of age, site and stage was performed. 144 children in the age range of 1-132months (median 36) were enrolled. Only 38 (26.4%) children were below 12months. 112 (77.8%) of the tumors were abdominal and 32 (22.2%) were extra-abdominal. Stage distribution was 1+2 in 6 (4.2%); 3 in 58 (40.3%); 4 in 68 (47.2%); 4s in 12 (8.3%). 83 (57.6%) underwent gross complete resection. At the time of last follow-up, 100 (69.4%) were alive [60 CR (41.7%); 33 PR; 7 PD/NR] and 44 (30.6%) were dead [1CR; 11PR; 32 PD/NR]. The three-year OS was 60.7% [95 CI 50.4-69.5]. The OS was 69.7% for those<12months of age [95 CI 51.8-82.0] and CR was achieved in 57.9%, while for those >12months the OS was 55.3% [95 CI 42.2-66.6] and CR was achieved in 35.8% (p=0.73). All 6 (100%) patients with Stage 1 and Stage 2 disease were alive and disease free. The OS was 71.5% for Stage 3[95 CI 55.3-82.7] and CR was achieved in 56.9%, while for Stage 4 the OS was 35.7%[95 CI 19.3-52.4] and CR was achieved in 17.6% (p=0.001). The OS was 83.3% for 4s [95 CI 48.2-95.6] and CR was achieved in 75%. All the six children with Stage 1 & 2 achieved CR and were alive, while 57% of Stage 3 could achieve CR and had an OS of 71.5%. The OS (35.7%) and CR (17.6%) for Stage 4 were significantly less (p=0.001). | 25,092,090 | [
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Caudal anesthesia with sedation for inguinal hernia repair in high risk neonates. | The use of caudal anesthesia with sedation (CAS) has theoretical benefits over general anesthesia (GA) in high risk neonates undergoing inguinal hernia repair. This benefit has not been established in clinical studies. We compare outcomes of these two approaches at a single institution. A retrospective review was performed of all neonates and preterm infants undergoing inguinal hernia over an 8year period. Of 71 infants meeting inclusion criteria, 50 underwent repair with caudal block and systemic sedation, and 21 with general anesthesia. Minor incidents of respiratory depression requiring non invasive interventions were common in the first 24h post operatively (24% for CAS, 14% with GA), 4% of patients receiving CAS had a respiratory complication which prolonged their hospital stay beyond 24h post operation. Both required conversion to general anesthesia. Statistically significant differences between the two groups were lacking in terms of preoperative risk and post operative outcome. CAS is a safe, effective anesthetic option for high risk neonates undergoing inguinal hernia repair. Patients requiring conversion to GA from CAS may be at increased risk for complications. Large, randomized trials are needed to determine any benefit over GA. | 25,092,095 | [
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Accessory hemi diaphragm. | Accessory hemi diaphragm (AHD) is an uncommon condition. Its clinical features, diagnosis and management have not been clearly defined. We reviewed the world literature and added a case of our own. There are 40 proven cases in the literature. The lesion occurs almost exclusively in the right hemithorax. Twenty seven cases presented with cardiovascular and/or respiratory symptoms while 3 had symptoms pertaining to other systems. In the remaining 10 patients the diagnosis was either made accidentally or information pertaining to their presentation is missing. Abnormalities of pulmonary and systemic blood vessels often accompany the abnormality. The diagnosis is usually suspected because of an abnormal chest radiograph and confirmed by a variety of tests. If the AHD prevents proper aeration of the lung it should be excised. If vascular abnormalities coexist they should be treated along with the AHD. Asymptomatic patients may be observed after confirming the diagnosis. | 25,092,100 | [
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Structural transformation of carbon-supported Pt₃Cr nanoparticles from a disordered to an ordered phase as a durable oxygen reduction electrocatalyst. | The sluggish oxygen reduction kinetics and insufficient durability of cathode catalysts restrict the practical application of proton exchange membrane fuel cells. This study focuses on the structural transformation of carbon-supported Pt₃Cr from a disordered to an ordered phase and on the effect of such structural transformation on oxygen reduction reaction (ORR) activity and durability. X-ray diffraction and transmission electron microscopy results confirm the formation of carbon-supported Pt₃Cr intermetallic nanoparticles with a mean particle size of ca. 7.2 nm. Line scanning EDX reveals that the practical Pt-Cr atomic ratio is approximately 3 : 1. X-ray photoelectron spectroscopy results indicate that the proportion of metallic Pt increases while the binding energy of Pt 4f decreases with such structural transformation. The Pt₃Cr/C intermetallic nanoparticles exhibit enhanced mass and specific activities toward the ORR compared with commercial Pt/C but slightly lower mass activity than the disordered Pt₃Cr/C alloy nanoparticles. After the accelerated durability test for 5000 cycles, the Pt₃Cr intermetallic nanoparticles displayed negligible decay in ORR mass activity; however the ORR mass activity on the isordered Pt₃Cr alloy decreases to ca. 50%. Much enhanced durability of the Pt₃Cr/C intermetallic nanoparticles toward the ORR is definitely caused by the much higher structural and compositional stabilities of the Pt₃Cr/C intermetallic nanoparticles than that of the disordered Pt3Cr/C alloy nanoparticles, suggesting that the Pt₃Cr intermetallic nanoparticles may serve as highly active and durable ORR electrocatalysts for practical application. | 25,092,107 | [
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HINT1 peptide/Hsp70 complex induces NK-cell-dependent immunoregulation in a model of autoimmune demyelination. | Heat shock proteins (Hsps) interact with the immune system and have been shown to contribute to immunoregulation. As efficient chaperones, Hsps bind many peptides and these complexes have many yet-to-be-clarified functions. We have shown that Hsp70 is complexed within the mouse CNS with peptide CLAFHDISPQAPTHFLVIPK derived from histidine triad nucleotide-binding protein-1 (HINT1₃₈₋₅₇/Hsp70). Only this complex, in contrast to other peptides complexed with Hsp70, was able to prevent experimental autoimmune encephalomyelitis (EAE) by induction of immunoregulatory mechanisms dependent on NK cells. Pretreatment of proteolipid protein peptide ₁₃₉₋₁₅₁(PLP₁₃₉₋₁₅₁) sensitized SJL/J mice with HINT1₃₈₋₅₇/Hsp70 prevented the development of EAE, suppressed PLP₁₃₉₋₁₅₁-induced T-cell proliferation, and blocked secretion of IL-17. HINT1₃₈₋₅₇ /Hsp70 stimulation of NK cells depended on synergistic activation of two NK-cell receptors, CD94 and NKG2D. NK cells with depleted CD94 or with blocked NKG2D did not inhibit PLP₁₃₉₋₁₅₁-induced spleen cell (SC) proliferation. The HINT1₃₈₋₅₇/Hsp70 complex enhanced surface expression of the NKG2D ligand-H60. Downstream signaling of CD94 and NKG2D converged at the adaptor proteins DAP10 and DAP12, and in response to HINT1₃₈₋₅₇ /Hsp70 stimulation, expression of DAP10 and DAP12 was significantly increased in NK cells. Thus, we have shown that the HINT1₃₈₋₅₇ /Hsp70 complex affects NK-cell function by enhancing NK-cell-dependent immunoregulation in the EAE model of autoimmune demyelination. | 25,092,109 | [
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Fetal syringomyelia. | We explored the prevalence of syringomyelia in a series of 113 cases of fetal dysraphism and hindbrain crowding, of gestational age ranging from 17.5 to 34 weeks with the vast majority less than 26 weeks gestational age. We found syringomyelia in 13 cases of Chiari II malformations, 5 cases of Omphalocele/Exostrophy/Imperforate anus/Spinal abnormality (OEIS), 2 cases of Meckel Gruber syndrome and in a single pair of pyopagus conjoined twins. Secondary injury was not uncommon, with vernicomyelia in Chiari malformations, infarct like histology, or old hemorrhage in 8 cases of syringomyelia. Vernicomyelia did not occur in the absence of syrinx formation. The syringes extended from the sites of dysraphism, in ascending or descending patterns. The syringes were usually in a major proportion anatomically distinct from a dilated or denuded central canal and tended to be dorsal and paramedian or median. We suggest that fetal syringomyelia in Chiari II malformation and other dysraphic states is often established prior to midgestation, has contributions from the primary malformation as well as from secondary in utero injury and is anatomically and pathophysiologically distinct from post natal syringomyelia secondary to hindbrain crowding. | 25,092,126 | [
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Advances in epigenome-wide association studies for common diseases. | Epigenome-wide association studies (EWASs) provide a systematic approach to uncovering epigenetic variants underlying common diseases. Discoveries have shed light on novel molecular mechanisms of disease and enabled the application of epigenetic variants as biomarkers. Here, we highlight the recent advances in this emerging line of research and discuss key challenges for current and future studies. | 25,092,140 | [
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Lymph node metastases do not impact survival in follicular variant papillary thyroid cancer. | Follicular variant of papillary thyroid cancer (FVPTC) is the most common and fastest growing subtype of papillary thyroid cancer (PTC) with features of both PTC and follicular thyroid cancer (FTC). The purpose of this study was to determine the patient and tumor features associated with lymph node metastases (LNM) in FVPTC. This was a retrospective review of adult (≥18) patients with histologically confirmed diagnoses of FVPTC within the SEER database between 1988 and 2009. LNM were defined by at least two lymph nodes with metastatic disease. To determine factors associated with LNM, we constructed a multivariate logistic regression model from significant variables (p < 0.05) identified on univariate analysis. Similarly, we used a Cox proportional hazards model to understand the relative importance of LNM in determining disease-specific mortality (DSM). Of the 20,357 cases of FVPTC with lymph node data available, 1,761 (8.7%) had LNM; 61.1% of these LNM were located in the central neck and 38.9% were in the lateral neck. Extrathyroidal extension (odds ratio [OR] 2.6, 95% confidence interval [CI] 2.2-3.0, p < 0.01) and multifocality (OR 3.0, 95% CI 2.5-3.6, p < 0.01) were the strongest predictors of LNM. Importantly, LNM did not independently predict DSM (p = 0.52). Tumor size >4 cm (hazards ratio [HR] 5.3, 95% CI 2.2-12.8, p < 0.01) and extrathyroidal extension (HR 8.2, 95% CI 3.0-22.0, p < 0.01) were the strongest predictors of DSM. LNM occur in less than 10% of patients with FVPTC but do not impact DSM. Instead, DSM in FVPTC is related to size and local invasion. | 25,092,163 | [
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Blunt chest trauma as a cause of acute myocardial infarction. | Chest pain after thoracic trauma may be a symptom of cardiac injury or myocardial infarction. A 63-year-old healthy man had chest pain after blunt chest trauma in a motor vehicle accident. Chest computed tomography scan showed a displaced sternal fracture, lung contusion in the left upper lobe, atelectasis and consolidation in both lower lobes, and bilateral haemothorax. Electrocardiography showed ST elevation (2 mm) in leads II, III, and aVF and ST depression (2 mm) in leads I and aVL, consistent with acute inferior myocardial infarction. Urgent coronary angiography showed ostial occlusion of the right coronary artery. After the right coronary occlusion was passed with a guide wire, dissection of the right coronary artery was observed and treated with a balloon and stent to reestablish normal flow. This case emphasizes the importance of a high index of suspicion for coronary artery injury and myocardial infarction after blunt chest trauma. | 25,092,198 | [
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Implications for observant Jewish families in the provision of mother's own and donor milk for their very low birth weight infant. | Jewish law recognizes the importance of breast milk, and breastfeeding rates are high among religious mothers. Infants born at very low birth weight are medically fragile, and breast milk is of critical importance for their health protection and optimal growth and development. For observant Jewish infants and their families, there may be scenarios for special consideration in their health care. This report reviews briefly the relevant Jewish laws related to breast milk provision, both mother's own milk and donor milk, in the neonatal intensive care unit with background information for counseling such families. | 25,092,199 | [
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A novel cardiac ryanodine receptor gene (RyR2) mutation in an athlete with aborted sudden cardiac death: a case of adult-onset catecholaminergic polymorphic ventricular tachycardia. | Sudden cardiac death (SCD) in athletes <35 years of age are mostly due to congenital or acquired cardiac malformations or hypertrophic cardiomyopathy. However, ion channelopathies such as catecholaminergic polymorphic ventricular tachycardia (CPVT) or long-QT syndromes, which are less frequently observed, are also potential pathogenesis of SCD in young athletes. CPVT is an inherited arrhythmia that is induced by physical or emotional stress and may lead to ventricular fibrillation syncope or SCD. Here, we report a case of athlete woman with adult-onset CPVT and aborted SCD who has a novel missense mutation (K4392R) in the cardiac RyR2 gene. | 25,092,222 | [
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Corosolic acid content and SSR markers in Lagerstroemia speciosa (L.) Pers.: a comparative analysis among populations across the Southern Western Ghats of India. | Lagerstroemia speciosa commonly known as 'Banaba' is native of south-east Asia which exhibits both horticultural and therapeutic value. The anti-diabetic and anti-obese property of the tree is attributed to corosolic acid (CRA)-a pentacyclic triterpene seen predominantly in the mature leaves. Although there are studies on either chemical or genetic variation in L. speciosa from different regions, none have dealt with their association to discuss the formation of chemical diversity. For the first time, we have analyzed CRA content in 12 natural populations corresponding to 42 samples seen in the Southern Western Ghats (SWG) using chromatography techniques and genetic variation estimated using SSR markers. Significant variation in percentage distribution of CRA ranging from 0.005% to 0.868% dr.wt. was recorded wherein populations from the north SWG contain relatively more active principle (mean=0.321%) than their counterparts in the south (mean=0.064%). Similarly, SSR data showing relatively high rate of gene flow (Nm=2.72) and low genetic differentiation (FST=0.14) is indicative that populations from north are genetically more diverse than those in the south (Nm=0.48; FST=0.38). The scatter plot derived by Principle Component Analysis (PCA) of chemical and genetic data shows similar pattern of clustering that reveals strong association between the two sets of data. It is concluded that the observed variation in CRA content in natural populations of the species depends more on the genetic background and less on edaphic factors. | 25,092,227 | [
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Age-related sperm DNA methylation changes are transmitted to offspring and associated with abnormal behavior and dysregulated gene expression. | Advanced paternal age (APA) has been shown to be a significant risk factor in the offspring for neurodevelopmental psychiatric disorders, such as schizophrenia and autism spectrum disorders. During aging, de novo mutations accumulate in the male germline and are frequently transmitted to the offspring with deleterious effects. In addition, DNA methylation during spermatogenesis is an active process, which is susceptible to errors that can be propagated to subsequent generations. Here we test the hypothesis that the integrity of germline DNA methylation is compromised during the aging process. A genome-wide DNA methylation screen comparing sperm from young and old mice revealed a significant loss of methylation in the older mice in regions associated with transcriptional regulation. The offspring of older fathers had reduced exploratory and startle behaviors and exhibited similar brain DNA methylation abnormalities as observed in the paternal sperm. Offspring from old fathers also had transcriptional dysregulation of developmental genes implicated in autism and schizophrenia. Our findings demonstrate that DNA methylation abnormalities arising in the sperm of old fathers are a plausible mechanism to explain some of the risks that APA poses to resulting offspring. | 25,092,244 | [
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Characterization of urinary CD4⁺ and CD8⁺ T cells in kidney transplantation patients with polyomavirus BK infection and allograft rejection. | The objective of this study was to characterize CD4(+) and CD8(+) T-cell populations in blood and urine of renal transplant patients with BK virus (BKV) infection or allograft rejection. Percentages and absolute numbers of CD4(+) and CD8(+) effector memory T-cell subtype (TEM ) and terminal differentiated T cells (TTD ) in renal transplant patients with BKV infection (n = 14), with an episode of allograft rejection (n = 9), and in uncomplicated renal transplant patients with a stable kidney function (n = 12) were measured and compared using 4-color fluorescence-activated cell sorting. Results were correlated with the number of CD4(+) and CD8(+) T cells in renal biopsies. In patients with allograft rejection, the number of urinary CD4(+) TEM and CD8(+) TEM cells was significantly increased compared to patients with BKV infection or patients without complications. Positive correlation was found between the number of CD4(+) and CD8(+) cells in the renal biopsies and the number of CD4(+) and CD8(+) cells in urine. In patients with rejection, after 2 months of immunosuppressive therapy, a reduction in urinary CD8(+) TEM cells was found. CD4(+) TEM and CD8(+) TEM cells in urine could be a marker to distinguish allograft rejection from BKV-associated nephropathy and to monitor therapy effectiveness in renal transplant patients with allograft rejection. | 25,092,256 | [
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Positional isomerization of a non-cleavable combi-molecule dramatically altered tumor cell response profile. | To potentiate the quinazoline-based inhibitor of the epidermal growth factor receptor (EGFR), a chloroethyl alkylating moiety was appended to its 6-position. This led to molecules with extremely strong EGFR inhibitory potency and anomalously strong DNA-damaging potential. To assess the role of the chloroethyl group on potency, we designed a molecule in which it is shifted to the 7-position where it would be less reactive and away from the cys773 of the EGFR ATP site. The results showed that (i) ZR2009 was 10-fold less potent than its positional isomer ZR2003 in EGFR tyrosine kinase inhibition, (ii) it consistently exhibited significantly weaker antiproliferative potency than ZR2003, (iii) in reversibility assays, while ZR2003 induced sustained inhibition of EGFR phosphorylation, ZR2009 inhibitory activity was partially reversed, and (iv) likewise, ZR2009 significantly lost its activity in short exposure growth inhibitory assays and induced lower levels of DNA damage than ZR2003. Molecular modeling suggested that while the chloroethylamino group in ZR2003 was at 3.5 Å away from Cys773, that of ZR2009 was at 6.3 Å. The results in toto suggest that, while the chloroethyl is a strong alkylating group, its appendage to the 6-position is optimal for DNA damage, sustained EGFR, and growth inhibition. | 25,092,264 | [
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Perceptions of hospital manual handling policy and impact on nursing team involvement in promoting patients' mobility. | To report the findings gained from interviews with hospital nurses and care assistants, regarding the impact of hospital manual handling policies on their role in maintaining and promoting patients' mobility. Older hospitalised adults often experience deteriorations in mobility, which are often partially caused by protective or custodial care practice and environments that promote patient dependency. Hospital-induced mobility loss may be conceptualised as a problematic source of iatrogenic patient harm, worthy of attention from a patient safety standpoint. Preventative rehabilitation nursing interventions have the potential to prevent mobility loss. Grounded theory study. Data were collected in three clinical settings: general rehabilitation, spinal injuries and stroke rehabilitation. Semi-structured interviews with 39 rehabilitation staff were completed. Perceptions of hospital manual handling policy were described via four subcategories: policy as stimulus to improved practice; policy as divorced from reality; policy as threat; and policy as hindrance to rehabilitation. Hospital manual handling policy was perceived negatively by some nursing team members both as a threat and as a barrier to patients' rehabilitation. Risk aversion, divided teamwork practices and overuse of patient handling equipment were matters of concern. Perceptions of hospital manual handling policy should be openly discussed by nursing managers and direct care providers. It is important to recognise that beliefs about and perceptions of policy will often impact later on staff practices and behaviours. Unintended consequences arising from dominant interpretations of manual handling policy must be acknowledged and risks identified. It is important that practitioners balance risk assessment and prevention of falls with patients' needs for mobilisation. | 25,092,267 | [
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miR-15b/16-2 regulates factors that promote p53 phosphorylation and augments the DNA damage response following radiation in the lung. | MicroRNAs (miRNAs) are regulatory RNAs frequently dysregulated in disease and following cellular stress. Investigators have described changes in miR-15b expression following exposure to several stress-inducing anticancer agents, including ionizing radiation (IR), etoposide, and hydrogen peroxide. However, the role for miR-15b as a mediator of cellular injury in organs such as the lung has yet to be explored. In this study, we examined miR-15b expression patterns as well as its potential role in DNA damage and repair in the setting of IR exposure. We showed that miR-15b is up-regulated in a dose- and time-dependent manner in human bronchial epithelial cells following IR. miR-15b expression was highest after 2 h of IR and decreased gradually. Survival rates following IR were also higher in miR-15b/16-2-overexpressing cells. Cell cycle arrest in G2/M phase and an increased DNA repair response were observed in IR-exposed miR-15b/16-2 stable cells. We observed an up-regulation of components of the ataxia telangiectasia mutated (ATM)/Chek1/p53 pathway in miR-15b/16-2-overexpressing cells after IR. Moreover, a pathway-based PCR expression array of genes demonstrated that miR-15b/16-2 overexpression significantly induced the expression of genes involved in ATM/ataxia telangiectasia and Rad-3-related (ATR) signaling, apoptosis, the cell cycle, and DNA repair pathways. Here we demonstrated a novel biological link between miR-15b and DNA damage and cellular protection in lung cells. We identified Wip1 (PPM1D) as a functional target for miR-15b and determined that miR-15b induction of the DNA damage response is partially dependent upon suppression of Wip1. Our study suggests that miR-15b/Wip1 could be a potential therapeutic target in radiation-induced lung disease. | 25,092,292 | [
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Modeling host interactions with hepatitis B virus using primary and induced pluripotent stem cell-derived hepatocellular systems. | Hepatitis B virus (HBV) chronically infects 400 million people worldwide and is a leading driver of end-stage liver disease and liver cancer. Research into the biology and treatment of HBV requires an in vitro cell-culture system that supports the infection of human hepatocytes, and accurately recapitulates virus-host interactions. Here, we report that micropatterned cocultures of primary human hepatocytes with stromal cells (MPCCs) reliably support productive HBV infection, and infection can be enhanced by blocking elements of the hepatocyte innate immune response associated with the induction of IFN-stimulated genes. MPCCs maintain prolonged, productive infection and represent a facile platform for studying virus-host interactions and for developing antiviral interventions. Hepatocytes obtained from different human donors vary dramatically in their permissiveness to HBV infection, suggesting that factors--such as divergence in genetic susceptibility to infection--may influence infection in vitro. To establish a complementary, renewable system on an isogenic background in which candidate genetics can be interrogated, we show that inducible pluripotent stem cells differentiated into hepatocyte-like cells (iHeps) support HBV infection that can also be enhanced by blocking interferon-stimulated gene induction. Notably, the emergence of the capacity to support HBV transcriptional activity and initial permissiveness for infection are marked by distinct stages of iHep differentiation, suggesting that infection of iHeps can be used both to study HBV, and conversely to assess the degree of iHep differentiation. Our work demonstrates the utility of these infectious systems for studying HBV biology and the virus' interactions with host hepatocyte genetics and physiology. | 25,092,305 | [
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Rare events in earth history include the LB1 human skeleton from Flores, Indonesia, as a developmental singularity, not a unique taxon. | The original centrally defining features of "Homo floresiensis" are based on bones represented only in the single specimen LB1. Initial published values of 380-mL endocranial volume and 1.06-m stature are markedly lower than later attempts to confirm them, and facial asymmetry originally unreported, then denied, has been established by our group and later confirmed independently. Of nearly 200 syndromes in which microcephaly is one sign, more than half include asymmetry as another sign and more than one-fourth also explicitly include short stature. The original diagnosis of the putative new species noted and dismissed just three developmental abnormalities. Subsequent independent attempts at diagnosis (Laron Syndrome, Majewski osteodysplastic primordial dwarfism type II, cretinism) have been hampered a priori by selectively restricted access to specimens, and disparaged a posteriori using data previously unpublished, without acknowledging that all of the independent diagnoses corroborate the patent abnormal singularity of LB1. In this report we establish in detail that even in the absence of a particular syndromic diagnosis, the originally defining features of LB1 do not establish either the uniqueness or normality necessary to meet the formal criteria for a type specimen of a new species. In a companion paper we present a new syndromic diagnosis for LB1. | 25,092,307 | [
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A computational and neural model of momentary subjective well-being. | The subjective well-being or happiness of individuals is an important metric for societies. Although happiness is influenced by life circumstances and population demographics such as wealth, we know little about how the cumulative influence of daily life events are aggregated into subjective feelings. Using computational modeling, we show that emotional reactivity in the form of momentary happiness in response to outcomes of a probabilistic reward task is explained not by current task earnings, but by the combined influence of recent reward expectations and prediction errors arising from those expectations. The robustness of this account was evident in a large-scale replication involving 18,420 participants. Using functional MRI, we show that the very same influences account for task-dependent striatal activity in a manner akin to the influences underpinning changes in happiness. | 25,092,308 | [
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Sequential combination therapy of ovarian cancer with degradable N-(2-hydroxypropyl)methacrylamide copolymer paclitaxel and gemcitabine conjugates. | For rapid and effective clinical translation, polymer-based anticancer therapeutics need long circulating conjugates that produce a sustained concentration gradient between the vasculature and solid tumor. To this end, we designed second-generation backbone-degradable diblock N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer carriers and evaluated sequential combination therapy of HPMA copolymer-paclitaxel and HPMA copolymer-gemcitabine conjugates against A2780 human ovarian carcinoma xenografts. First, extensive in vitro assessment of administration sequence impact on cell cycle, viability, apoptosis, migration, and invasion revealed that treatment with paclitaxel conjugate followed by gemcitabine conjugate was the most effective scheduling strategy. Second, in an in vivo comparison with first-generation (nondegradable, molecular weight below the renal threshold) conjugates and free drugs, the second-generation degradable high-molecular weight conjugates showed distinct advantages, such as favorable pharmacokinetics (three- to five-times half-life compared with the first generation), dramatically enhanced inhibition of tumor growth (complete tumor regression) by paclitaxel and gemcitabine conjugate combination, and absence of adverse effects. In addition, multimodality imaging studies of dual-labeled model conjugates confirmed the efficacy of second-generation conjugates by visualizing more than five-times enhanced tumor accumulation, rapid conjugate internalization, and effective intracellular release of payload. Taken together, the results indicate that the second-generation degradable HPMA copolymer carrier can provide an ideal platform for the delivery of a range of antitumor compounds, which makes it one of the most attractive candidates for potential clinical application. | 25,092,316 | [
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Temperate origins of long-distance seasonal migration in New World songbirds. | Migratory species exhibit seasonal variation in their geographic ranges, often inhabiting geographically and ecologically distinct breeding and nonbreeding areas. The complicated geography of seasonal migration has long posed a challenge for inferring the geographic origins of migratory species as well as evolutionary sequences of change in migratory behavior. To address this challenge, we developed a phylogenetic model of the joint evolution of breeding and nonbreeding (winter) ranges and applied it to the inference of biogeographic history in the emberizoid passerine birds. We found that seasonal migration between breeding ranges in North America and winter ranges in the Neotropics evolved primarily via shifts of winter ranges toward the tropics from ancestral ranges in North America. This result contrasts with a dominant paradigm that hypothesized migration evolving out of the tropics via shifts of the breeding ranges. We also show that major lineages of tropical, sedentary emberizoids are derived from northern, migratory ancestors. In these lineages, the winter ranges served as a biogeographic conduit for temperate-to-tropical colonization: winter-range shifts toward the tropics during the evolution of long-distance migration often preceded southward shifts of breeding ranges, the loss of migration, and in situ tropical diversification. Meanwhile, the evolution of long-distance migration enabled the persistence of old lineages in North America. These results illuminate how the evolution of seasonal migration has contributed to greater niche conservatism among tropical members of this diverse avian radiation. | 25,092,321 | [
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Competition between recently potentiated synaptic inputs reveals a winner-take-all phase of synaptic tagging and capture. | Canonical models suggest that mechanisms of long-term memory consist of a synapse-specific, protein synthesis-independent induction phase (changes in synaptic weights/temporary tagging of such synapses) and, within adjacent dendritic compartments, a protein synthesis-dependent distribution phase that may accompany or immediately precede induction and whose protein products enable consolidation through synaptic capture. We now report that this distribution phase is competitive in a "winner-take-all" fashion when synapses potentiated at induction compete with each other for plasticity-related proteins. This finding highlights the importance of synaptic competition in creating stable long-lasting memory in neural networks without disruption. | 25,092,326 | [
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Short sequences can efficiently recruit histone H3 lysine 27 trimethylation in the absence of enhancer activity and DNA methylation. | Trimethylation of histone H3 at lysine 27 (H3K27me3) is a chromatin mark associated with Polycomb-mediated gene repression. Despite its critical role in development, it remains largely unclear how this mark is targeted to defined loci in mammalian cells. Here, we use iterative genome editing to identify small DNA sequences capable of autonomously recruiting Polycomb. We inserted 28 DNA elements at a defined chromosomal position in mouse embryonic stem cells and assessed their ability to promote H3K27me3 deposition. Combined with deletion analysis, we identified DNA elements as short as 220 nucleotides that correctly recapitulate endogenous H3K27me3 patterns. Functional Polycomb recruiter sequences are invariably CpG-rich but require protection against DNA methylation. Alternatively, their activity can be blocked by placement of an active promoter-enhancer pair in cis. Taken together, these data support the model whereby PRC2 recruitment at specific targets in mammals is positively regulated by local CpG density yet obstructed by transcriptional activity or DNA methylation. | 25,092,339 | [
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IL-17 drives psoriatic inflammation via distinct, target cell-specific mechanisms. | Psoriasis is a chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation and differentiation and by an influx of inflammatory cells. The mechanisms underlying psoriasis in humans and in mouse models are poorly understood, although evidence strongly points to crucial contributions of IL-17 cytokines, which signal via the obligatory adaptor CIKS/Act1. Here we identify critical roles of CIKS/Act1-mediated signaling in imiquimod-induced psoriatic inflammation, a mouse model that shares features with the human disease. We found that IL-17 cytokines/CIKS-mediated signaling into keratinocytes is essential for neutrophilic microabscess formation and contributes to hyperproliferation and markedly attenuated differentiation of keratinocytes, at least in part via direct effects. In contrast, IL-17 cytokines/CIKS-mediated signaling into nonkeratinocytes, particularly into dermal fibroblasts, promotes cellular infiltration and, importantly, leads to enhanced the accumulation of IL-17-producing γδT cells in skin, comprising a positive feed-forward mechanism. Thus, CIKS-mediated signaling is central in the development of both dermal and epidermal hallmarks of psoriasis, inducing distinct pathologies via target cell-specific effects. CIKS-mediated signaling represents a potential therapeutic target in psoriasis. | 25,092,341 | [
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The future of spectroscopic life detection on exoplanets. | The discovery and characterization of exoplanets have the potential to offer the world one of the most impactful findings ever in the history of astronomy--the identification of life beyond Earth. Life can be inferred by the presence of atmospheric biosignature gases--gases produced by life that can accumulate to detectable levels in an exoplanet atmosphere. Detection will be made by remote sensing by sophisticated space telescopes. The conviction that biosignature gases will actually be detected in the future is moderated by lessons learned from the dozens of exoplanet atmospheres studied in last decade, namely the difficulty in robustly identifying molecules, the possible interference of clouds, and the permanent limitations from a spectrum of spatially unresolved and globally mixed gases without direct surface observations. The vision for the path to assess the presence of life beyond Earth is being established. | 25,092,345 | [
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Epilepsy: Asia versus Africa. | Is epilepsy truly an "African ailment"? We aimed to determine this, since international health agencies often refer to epilepsy as an African disease and the scientific literature has spoken the same tone. Various published materials, mainly reports, articles, were used to gather Asian and African evidence on various aspects of epilepsy and many of its risk and associated factors. Our results suggest that in no way can epilepsy be considered as an African ailment and such characterization is most likely based on popular beliefs rather than scientific evidence. In comparison to Africa, Asia has a 5.0% greater burden from all diseases, and is 17.0% more affected from neuropsychiatric disorders (that include epilepsy). Given that more countries in Asia are transitioning, there may be large demographic and lifestyle changes in the near future. However these changes are nowhere close to those expected in Africa. Moreover, 23 million Asians have epilepsy in comparison to 3.3 million Africans and 1.2 million sub-Saharan Africans. In comparison to Africa, Asia has more untreated patients, 55.0% more additional epilepsy cases every year, because of its larger population, with greater treatment cost and possibly higher premature mortality. Of several associated factors discussed herein, many have more importance for Asia than Africa. The current state of epilepsy in Asia is far less than ideal and there is an urgent need to recognize and accept the importance of epilepsy in Asia. In no way can epilepsy be considered as an African ailment. This is most likely based on popular beliefs rather than scientific evidence. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. | 25,092,379 | [
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Representation of health conditions on Facebook: content analysis and evaluation of user engagement. | A sizable majority of adult Internet users report looking for health information online. Social networking sites (SNS) like Facebook represent a common place to seek information, but very little is known about the representation and use of health content on SNS. Our goal in this study was to understand the role of SNS in health information seeking. More specifically, we aimed to describe how health conditions are represented on Facebook Pages and how users interact with these different conditions. We used Google Insights to identify the 20 most searched for health conditions on Google and then searched each of the resulting terms on Facebook. We compiled a list of the first 50 Facebook "Pages" results for each health condition. After filtering results to identify pages relevant to our research, we categorized pages into one of seven categories based on the page's primary purpose. We then measured user engagement by evaluating the number of "Likes" for different conditions and types of pages. The search returned 50 pages for 18 of the health conditions, but only 48 pages were found for "anemia" and 5 pages were found for "flu symptoms", yielding a total of 953 pages. A large number of pages (29.4%, 280/953) were irrelevant to the health condition searched. Of the 673 relevant pages, 151 were not in English or originated outside the United States, leaving 522 pages to be coded for content. The most common type of page was marketing/promotion (32.2%, 168/522) followed by information/awareness (20.7%, 108/522), Wikipedia-type pages (15.5%, 81/522), patient support (9.4%, 49/522), and general support (3.6%, 19/522). Health conditions varied greatly by the primary page type. All health conditions had some marketing/promotion pages and this made up 76% (29/38) of pages on acquired immunodeficiency syndrome (AIDS). The largest percentage of general support pages were cancer (19%, 6/32) and stomach (16%, 4/25). For patient support, stroke (67%, 4/6), lupus (33%, 10/30), breast cancer (19%, 6/31), arthritis (16%, 6/36), and diabetes (16%, 6/37) ranked the highest. Six health conditions were not represented by any type of support pages (ie, human papillomavirus, diarrhea, flu symptoms, pneumonia, spine, human immunodeficiency virus). Marketing/promotion pages accounted for 46.73% (10,371,169/22,191,633) of all Likes, followed by support pages (40.66%, 9,023,234/22,191,633). Cancer and breast cancer accounted for 86.90% (19,284,066/22,191,633) of all page Likes. This research represents the first attempts to comprehensively describe publicly available health content and user engagement with health conditions on Facebook pages. Public health interventions using Facebook will need to be designed to ensure relevant information is easy to find and with an understanding that stigma associated with some health conditions may limit the users' engagement with Facebook pages. This line of research merits further investigation as Facebook and other SNS continue to evolve over the coming years. | 25,092,386 | [
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Accessory lower limb associated with spina bifida: case report. | Heterotopic redundancies, such as an accessory limb associated with spina bifida, are extremely rare anomalies. There are 12 cases of accessory limb associated with spinal bifida in literature. This report aims a detailed description of the additional case and an analysis of the findings in light. A male baby was born at 40 weeks of gestation and was referred to the neurosurgery clinic with a diagnosis of accessory lower limb. On physical examination, the dorsal meningocele was located at the lumbosacral region and there was accessory lower limb on it. There was no open neural placode. The accessory limb was excised on postnatal day 3. Dysraphic appendages are rare and complicated anomalies. They should be investigated carefully, and all of the lesions must be repaired for babies' quality of life. | 25,092,402 | [
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The capsaicin receptor TRPV1 as a novel modulator of neural precursor cell proliferation. | The capsaicin receptor (TRPV1, transient receptor potential vanilloid type 1) was first discovered in the peripheral nervous system as a detector of noxious chemical and thermal stimuli including the irritant chili pepper. Recently, there has been increasing evidence of TRPV1 expression in the central nervous system. Here, we show that TRPV1 is expressed in neural precursor cells (NPCs) during postnatal development, but not in the adult. However, expression of TRPV1 is induced in the adult in paradigms linked to an increase in neurogenesis, such as spatial learning in the Morris water maze or voluntary exercise. Loss of TRPV1 expression in knockout mice leads to an increase in NPC proliferation. Functional TRPV1 expression has been confirmed in cultured NPCs. Our results indicate that TRPV1 expression influences both postnatal and activity-induced neurogenesis in adulthood. | 25,092,424 | [
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Prevalence of depression in patients with type 2 diabetes attending an outpatient clinic in India. | Clinical studies have suggested that depression is common among patients with type 2 diabetes (T2D). Depression is an important factor which affects the management and complications of diabetes. However, the available data regarding its prevalence in India are limited. To estimate the prevalence of depression in patients in India with T2D and to compare it with a non-diabetic group; and to determine the association of depression with glycaemic control and complications of diabetes in patients with T2D. This case-control study was carried out over 5 months from May to September 2012 at a tertiary care hospital in India. Cases were patients with T2D and controls were individuals without diabetes. Depression was assessed using the Patient Health Questionnaire (PHQ)-9. The sociodemographic profile, duration of diabetes, presence of complications and other medical variables were also analysed. 260 subjects of Indian origin (162 men and 98 women; 130 with known T2D and 130 controls without T2D) were evaluated. The prevalence of depression in subjects with T2D was almost twice that in control subjects (46/130 (35.38%) vs 26/130 (20%); p=0.006). A statistically significant difference was found in the fasting blood glucose levels of subjects with depression and those without depression among the patients with T2D (145.70±53.92 vs 130.61±42.39; p=0.022), but depression was not found to be associated with any of the diabetic complications and glycaemic control. Our findings demonstrate that there is a higher prevalence of depression in Indian patients with T2D, which is almost twice that in those without T2D. Since patients with T2D are at higher risk of developing depression, assessment of depression should be performed as part of the routine practice in India. CTRI/2012/06/002747. | 25,092,455 | [
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Interobserver reliability of echocardiography for prognostication of normotensive patients with pulmonary embolism. | To evaluate the interobserver reliability of echocardiographic findings of right ventricle (RV) dysfunction for prognosticating normotensive patients with pulmonary embolism (PE). A central panel of cardiologists evaluated echocardiographic studies of 75 patients included in the PROTECT study for the following signs: RV diameter, RV/left ventricular (LV) diameter ratio, hypokinesis of the RV free wall, and tricuspid plane systolic excursion (TAPSE). Investigators used intraclass correlation to assess agreement between the measurements of the central panel and each of the local cardiologists. Investigators used the single weighted kappa statistic to test for agreement between readers of interpretation of RV enlargement and RV hypokinesis. The two observers had fair agreement (k = 0.45) for RV enlargement assessed by the RV diameter, and good agreement (k = 0.65) for RV enlargement assessed by the RV/LV diameter ratio. The interobserver reliability of the assessment whether hypokinesis of the RV free wall is present was good (к = 0.70), and whether RV dysfunction (assessed by TAPSE measurement) is present was very good (k = 0.86). The intraclass correlation for the RV/LV diameter ratio was fair (0.55; 95% confidence interval [CI], 0.37-0.69), for the RV diameter was good (0.70; 95% CI, 0.56-0.80), and for the TAPSE measurement was very good (0.85; 95% CI, 0.77-0.90). On Bland-Altman analysis, the mean differences for RV diameter, RV/LV diameter ratio and TAPSE measurement were 2.33 (±5.38), 0.06 (±0.23) and 0.08 (±2.20), respectively. TAPSE measurement is the least user dependent and most reproducible echocardiographic finding of RV dysfunction in normotensive patients with PE. | 25,092,465 | [
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Whole-genome duplication in teleost fishes and its evolutionary consequences. | Whole-genome duplication (WGD) events have shaped the history of many evolutionary lineages. One such duplication has been implicated in the evolution of teleost fishes, by far the most species-rich vertebrate clade. After initial controversy, there is now solid evidence that such event took place in the common ancestor of all extant teleosts. It is termed teleost-specific (TS) WGD. After WGD, duplicate genes have different fates. The most likely outcome is non-functionalization of one duplicate gene due to the lack of selective constraint on preserving both. Mechanisms that act on preservation of duplicates are subfunctionalization (partitioning of ancestral gene functions on the duplicates), neofunctionalization (assigning a novel function to one of the duplicates) and dosage selection (preserving genes to maintain dosage balance between interconnected components). Since the frequency of these mechanisms is influenced by the genes' properties, there are over-retained classes of genes, such as highly expressed ones and genes involved in neural function. The consequences of the TS-WGD, especially its impact on the massive radiation of teleosts, have been matter of controversial debate. It is evident that gene duplications are crucial for generating complexity and that WGDs provide large amounts of raw material for evolutionary adaptation and innovation. However, it is less clear whether the TS-WGD is directly linked to the evolutionary success of teleosts and their radiation. Recent studies let us conclude that TS-WGD has been important in generating teleost complexity, but that more recent ecological adaptations only marginally related to TS-WGD might have even contributed more to diversification. It is likely, however, that TS-WGD provided teleosts with diversification potential that can become effective much later, such as during phases of environmental change. | 25,092,473 | [
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Expression pattern and tissue localization of the class B scavenger receptor BmSCRBQ4 in Bombyx mori. | Class B scavenger receptors (SR-Bs) are cell surface glycoproteins involved in various physiological processes in vivo, including the transport and metabolism of lipids, binding and phagocytosis of xenobiotics, and signaling. But little information is available about silkworm SR-Bs; it is necessary to study these SR-Bs for revealing their function. In this study, we cloned the full-length coding sequence of BmSCRBQ4, a SR-B gene from the silkworm Bombyx mori L. We found that the BmSCRBQ4 gene consists of nine exons and eight introns, with an open reading frame of 1371 bp encoding 456 amino acids. Gene expression studies determined that BmSCRBQ4 messenger RNA (mRNA) was expressed in unfertilized eggs, during embryonic development and throughout the majority of the larval period. Expression of mRNA was detected in the mid gut, middle silk gland, posterior silk gland, head, integumentum, fat body, testes and the ovaries of the larval B. mori Dazao strain, as well as in the silkworm cell lines BmN and BmE. Protein expression studies found BmSCRBQ4 protein was expressed only in the testes, fat body and middle silk gland of larvae, as well as in the silkworm cell lines BmN and BmE. The BmSCRBQ4 protein showed variability in banding patterns in different tissues and cells when analyzed by Western blotting. Immunohistochemical staining showed that the BmSCRBQ4 protein localizes to the constitutive membranes or cellular membranes of these tissues. These results indicated that BmSCRBQ4 gene may play some physiologically relevant roles at the cell surface in each tissue. | 25,092,485 | [
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SCOPRISM: a new algorithm for automatic sleep scoring in mice. | Scoring of wake-sleep states by trained investigators is a time-consuming task in many sleep experiments. We aimed to validate SCOPRISM, a new open-source algorithm for sleep scoring based on automatic graphical clustering of epoch distribution. We recorded sleep and blood pressure signals of 36 orexin-deficient, 7 leptin knock-out, and 43 wild-type control mice in the PRISM laboratory. Additional groups of mice (n=14) and rats (n=6) recorded in independent labs were used to validate the algorithm across laboratories. The overall accuracy, specificity and sensitivity values of SCOPRISM (97%, 95%, and 94%, respectively) on PRISM lab data were similar to those calculated between human scorers (98%, 98%, and 94%, respectively). Using SCOPRISM, we replicated the main sleep and sleep-dependent cardiovascular findings of our previous studies. Finally, the cross-laboratory analyses showed that the SCOPRISM algorithm performed well on mouse and rat data. SCOPRISM performed similarly or even better than recently reported algorithms. SCOPRISM is a very simple algorithm, extensively (cross)validated and with the possibility to evaluate its efficacy following a quick and easy visual flow chart. We validated SCOPRISM, a new, automated and open-source algorithm for sleep scoring on a large population of mice, including different mutant strains and on subgroups of mice and rats recorded by independent labs. This algorithm should help accelerate basic research on sleep and integrative physiology in rodents. | 25,092,499 | [
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