title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Surgical needs of Nepal: pilot study of population based survey in Pokhara, Nepal. | The Surgeons OverSeas assessment of surgical need (SOSAS) tool, a population-based survey on surgical conditions in low- and middle-income countries (LMICs), was performed in Sierra Leone and Rwanda. This pilot study in Nepal is the initial implementation of the SOSAS survey in South Asia. A pilot study of SOSAS, modified for Nepal's needs and reprogrammed using mobile data collection software, was undertaken in Pokhara in January 2014. Cluster randomized sampling was utilized to interview 100 individuals in 50 households within two wards of Pokhara, one rural and one urban. The first portion of the survey retrieved demographic data, including household members and time to nearest health facilities. The second portion interviewed two randomly selected individuals from each household, inquiring about surgical conditions covering six anatomical regions. The pilot SOSAS in Nepal was easily completed over 3 days, including training of 18 Nepali interns over 2 days. The response rate was 100 %. A total of 13 respondents had a current surgical need (face 4, chest 1, back 1, abdomen 1, groin 3, extremity 3), although eight reported there was no need for surgical care. Five respondents (5 %) had a current unmet surgical need. The SOSAS pilot study in Nepal was successfully conducted, demonstrating the feasibility of performing SOSAS in South Asia. The estimated 5 % current unmet surgical need will be used for sample size calculation for the full country survey. Utilizing and improving on the SOSAS tool to measure the prevalence of surgical conditions in Nepal will help enumerate the global surgical burden of disease. | 25,189,447 | [
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Major post-operative complications predict long-term survival after esophagectomy in patients with adenocarcinoma of the esophagus. | Esophagectomy provides the best opportunity for a long-term cure despite its high post-operative morbidity. We reviewed our institutional records to evaluate the impact of major post-operative complications on the long-term survival of patients following esophagectomy after neoadjuvant treatment for locally advanced adenocarcinoma. We identified 241 patients who underwent esophagectomy as a curative procedure at our tertiary referral center. All consecutive patients with locally advanced adenocarcinoma of the esophagus who underwent neoadjuvant treatment followed by esophagectomy were analyzed. Complications were graded according to the Clavien scale. Patients were compared according to the complication grade (grades 0-1-2 vs. grades 3-4). Overall survival and disease-free survival were calculated using the Kaplan-Meier method, and survival curves were compared using log-rank tests. Factors predictive of survival were determined using multivariate analysis. A total of 116 patients underwent esophagectomy after neoadjuvant treatment for locally advanced adenocarcinoma of the esophagus. Fifty-four patients (46.5 %) developed post-operative complications. The post-operative mortality rate was 4.3 % (five patients). Patients with grade 3-4 complications had decreased overall survival and disease-free survival rates (p = 0.006 and 0.045). Grade 3-4 complications and positive nodes were found to be contributing factors to survival (p = 0.027 and 0.005). Our single-institution study found that major morbidity had a negative impact on long-term survival in patients who underwent esophagectomy after neoadjuvant treatment for locally advanced adenocarcinoma. | 25,189,448 | [
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Laparoscopic peritoneal dialysis catheter insertion using nitrous oxide under procedural sedation. | Laparoscopic peritoneal dialysis catheter (LPDC) implantation using nitrous oxide (N2O) pneumoperitoneum under procedural sedation is a technique that has many advantages over conventional insertion methods. The purpose of this study was to review the LPDC insertion results at our center. Data from 87 consecutive patients who underwent LPDC insertion was retrospectively reviewed. All procedures were attempted under procedural sedation. After patients received intravenous and local anesthesia, a N2O pneumoperitoneum was established. Peritoneal dialysis (PD) catheters were advanced using rectus sheath tunneling. The position of the catheter was confirmed by laparoscope, and adjunct procedures such as omentopexy and adhesiolysis were performed on select patients to prevent catheter flow problems. Nitrous oxide was well tolerated by 94 % of the patients. Only five patients required conversion to general anesthesia. After a mean follow-up of 18.2 months, mechanical complications included pericatheter/incision leakage (12.62 %), flow obstruction (4.60 %), incision/exit site hernia (3.45 %), hemoperitoneum (2.30 %), pleuroperitoneal fistula (1.15 %), scrotal leak (1.15 %), and migration (1.15 %). Infectious complications included exit site infection (1 episode per 312.95 patient-months) and peritonitis (1 episode per 31.93 patient-months). Revision-free catheter survival was 97.6 % after 1 year. Laparoscopic implantation of a PD catheter with N2O pneumoperitoneum and local anesthesia is safe and effective in patients with severe renal failure. N2O is an inert gas and better tolerated as an insufflation agent, enabling awake procedures. Our results show that catheter-related functional outcomes are comparable to those in the existing literature. This approach can be recommended as a good option for catheter implantation in patients needing dialysis. | 25,189,449 | [
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Risk factors and preventive measures for acute urinary retention after rectal cancer surgery. | Although several risk factors for acute urinary retention after rectal cancer surgery have been proposed, few studies have enrolled a homogeneous group of patients without preoperative urinary dysfunction. We aimed to identify risk factors and preventive measures for acute urinary retention after rectal cancer surgery. This study was a retrospective review of prospectively collected data from included patients who underwent rectal cancer surgery at a single center. Preoperative urinary function was evaluated using the International Prostate Symptom Score (IPSS). Clinical data were collected prospectively and analyzed to assess the risk factors for acute urinary retention, which was defined as the inability to self-void after removing the urinary catheter requiring catheterization or reinsertion of an indwelling catheter. Of 352 patients with mild preoperative IPSS (0-7), 48 (13.6 %) experienced acute urinary retention. Multivariate logistic regression analysis showed that male sex (odds ratio [OR] 2.240, p = 0.039), laparoscopic operation (OR 2.421, p = 0.024), intraoperative intravenous fluid ≥ 2,000 mL (OR 3.794, p < 0.001), and urinary catheter removal on postoperative day 1 or 2 (OR 3.650, p = 0.017) were independent risk factors for acute urinary retention after rectal cancer surgery. Patients with two risk factors had a significantly higher risk of acute urinary retention than patients with none or one risk factor. This study suggests the maintenance of a urinary catheter for a period longer than 2 days and intraoperative fluid restriction to prevent acute urinary retention after rectal cancer surgery. | 25,189,452 | [
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Long-term evolution of acute colonic diverticulitis after successful medical treatment. | The evidence is sparse concerning the natural history of acute diverticulitis after successful conservative management. This observational study aimed to evaluate the rate, severity, and need of surgery for recurrence after a first episode of acute diverticulitis successfully managed conservatively. All patients admitted for acute diverticulitis between 1994 and 2011 were considered for inclusion in the study. Severity of the first episode, demographic data, comorbidities, management, recurrence, and elective or emergency surgery during the follow-up period were prospectively recorded. The study included 560 patients. The mean follow-up period was of 67.2 ± 44.4 months. Severe diverticulitis was diagnosed in 22.3 % of the cases. Recurrence was observed in 14.8 % of the patients, and the rate of severe recurrence was 3.4 %. Most of the recurrences occurred during the first year of follow-up evaluation. Chronic corticoid therapy (P = 0.043) and the presence of more than one abscess (P < 0.001) were significantly related to recurrence. In the event of a mild recurrence, the first episode was either mild or severe (P = 0.172). In the case of severe recurrence, most patients presented with a previous severe diverticulitis (P < 0.001). During the follow-up period, 6.8 % of the patients needed an elective operation, and 1.4 % of them underwent emergency surgery. The rate of severe recurrence after successful nonoperative management of acute diverticulitis was low, and emergency surgery was rare. Prophylactic surgery, even in cases of recovered severe diverticulitis, should be considered on a case-by-case basis. Strict follow-up assessment during the first year is advised. | 25,189,456 | [
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Lung squamous cell carcinomas with basaloid histology represent a specific molecular entity. | The basaloid carcinoma (pure) and the (mixed) basaloid variant of lung squamous cell carcinoma (SCC) have a dismal prognosis but their underlying specific molecular characteristics remain obscure and no therapy has proven to be efficient. To assess their molecular specificity among other lung SCCs we analyzed DNA copy number aberrations and mRNA expression pangenomic profiles of 93 SCCs, including 42 basaloid samples (24 pure, 18 mixed). Supervised analyses reveal that pure basaloid tumors display a specific mRNA expression profile, encoding factors controlling the cell cycle, transcription, chromatin, and splicing, with prevalent expression in germline and stem cells, while genes related to squamous differentiation are underexpressed. From this signature, we derived a 2-genes (SOX4, IVL) immunohistochemistry-based predictor that discriminated basaloid tumors (pure and mixed) from non-basaloid tumors with 94% accuracy in an independent series. The pure basaloid tumors are also distinguished through unsupervised analyses. Using a centroid-based predictor, the corresponding molecular subtype was found in 8 independent public datasets (n = 58/533), and was shown to be associated with a very poor survival as compared with other SCCs (adjusted HR = 2.45; P = 0.000001). This study enlightens the heterogeneity of SCCs that can be subclassified in mRNA expression subtypes. This study demonstrates for the first time that basaloid SCCs constitute a distinct histomolecular entity, which justifies its recognition and distinction from non-basaloid SCCs. In addition, their characteristic molecular profile highlights their intrinsic resistance to cytotoxic chemotherapy and could serve as a guide for targeted therapies. | 25,189,482 | [
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Delay and inequality in treatment of the elderly with suspected acute coronary syndrome. | The aim of this study is to determine differences between elderly patients (≥80 years) and younger patients with suspected acute coronary syndrome (ACS) regarding delay times before diagnostic tests and treatments. All patients with chest pain who were admitted to a hospital in the Gothenburg area were included consecutively over a 3-month period. They were divided into an elderly group (≥80 years) and a reference group (<80 years). Previous medical history, ECG findings, treatments, diagnostic tests, and delay times were registered. Altogether, 2588 patients were included (478 elderly and 2110 reference). There were no significant differences in delay time to hospital ward admission, to first medical therapy with aspirin, or to investigation with coronary angiography (CA) between the two groups. The elderly patients had a significantly shorter median time from first medical contact to first ECG (12 vs. 14 min, p=0.002) but after adjustment for confounding factors, especially mode of transport, the opposite was found to be the case (p=0.002). Elderly hospitalized patients with ACS were less often investigated with CA (44% vs. 89%, p<0.0001) and received less medical treatment with P2Y12 antagonists and lipid lowering drugs. Elderly individuals with chest pain could not be shown to have a delay to hospital admission compared to their younger counterparts. Nevertheless, higher age was associated with a longer time to first ECG. The elderly patients received less active therapy, and fear of age-related side effects might explain this difference. | 25,189,499 | [
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Nomadic concepts in the history of biology. | The history of scientific concepts has firmly settled among the instruments of historical inquiry. In our section we approach concepts from the perspective of nomadic concepts (Isabelle Stengers). Instead of following the evolution of concepts within one disciplinary network, we see them as subject to constant reification and change while crossing and turning across disciplines and non-scientific domains. This introduction argues that understanding modern biology is not possible without taking into account the constant transfers and translations that affected concepts. We argue that this approach does not only engage with nomadism between disciplines and non-scientific domains, but reflects on and involves the metaphoric value of concepts as well. | 25,189,506 | [
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Strategic enhancement of algal biomass, nutrient uptake and lipid through statistical optimization of nutrient supplementation in coupling Scenedesmus obliquus-like microalgae cultivation and municipal wastewater treatment. | Supplementing proper nutrients could be a strategy for enhancing algal biomass, nutrients uptake and lipid accumulation in the coupling system of biodiesel production and municipal wastewater treatment. However, there is scant information reporting systematic studies on screening and optimization of key supplemented components in the coupling system. The main factors were scientifically screened and optimized using statistical methods. Plackett-Burman design (PBD) was used to explore the roles of added nutrient factors, whereas response surface methodology (RSM) was employed for optimization. Based on the statistic analysis, the optimum added TP and FeCl3·6H2O concentrations for Scenedesmus obliquus-like microalgae growth, nutrients uptake and lipid accumulation were 4.41 mg L(-1) and 6.48 mg L(-1), respectively. The corresponding biomass, lipid content and TN/TP removal efficiency were 1.46 g L(-1), 36.26% and >99%. The predicted value agreed well with the experimental value, as determined by validation experiments, which confirmed the availability and accuracy of the model. | 25,189,511 | [
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The effect of COD loading on the granule-based enhanced biological phosphorus removal system and the recoverability. | In this study, the effect of varied COD loading (200, 400, 500, 600 and 800 mg L(-1)) on stability and recoverability of granule-based enhanced biological phosphorus removal (EBPR) system was investigated during continuously 53-d operation. Results showed that COD loading higher than 500 mg L(-1) could obviously deteriorate the granular EBPR system and result in sludge bulking with filamentous bacteria. High COD loading also changed the transformation patterns of poly-β-hydroxyalkanoates (PHAs) and glycogen in metabolism process of polyphosphate-accumulating organisms (PAOs) and inhibited the EPS secretion, which completely destroyed the stability and integrality of granules. Results of FISH indicated that glycogen-accumulating organisms (GAOs) and other microorganisms had a competitive advantage over PAOs with higher COD loading. The community composition and EBPR performance were recovered irreversibly in long time operation when COD loading was higher than 500 mg L(-1). | 25,189,512 | [
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Preterm infants' orally directed behaviors and behavioral state responses to the integrated H-HOPE intervention. | Preterm infants are challenged by immature infant behavioral organization which may negatively influence their ability to oral feed. The purpose of this study was to determine whether the integrated H-HOPE (Hospital to Home: Optimizing the Infant's Environment) intervention would improve infant behavioral organization by increasing the frequency of orally directed behaviors and the proportion of time spent in an alert behavioral state when offered prior to oral feeding. Mother-infant dyads (n=198) were randomly assigned to the H-HOPE intervention or the Attention Control groups. Infants were born at 29-34 weeks gestation and were clinically stable. Mothers had at least two social environmental risk factors such as minority status or less than high school education. H-HOPE is an integrated intervention that included (1) twice-daily infant directed stimulation using the ATVV intervention (auditory, tactile, visual, and vestibular stimuli) and (2) maternal participatory guidance sessions by a nurse-community advocate team. Orally directed behaviors and behavioral states were assessed weekly prior to feeding during hospitalization when infants were able to feed orally. There were no differences between the groups at baseline (Day 0, prior to the initiation of the integrated H-HOPE intervention). We observed a pattern of increased frequency of orally directed behaviors in the H-HOPE intervention group when compared to the Attention Control group, however, the proportion of time spent in an alert behavioral state remained stable in both groups over the course of the study. On Day 7, the H-HOPE intervention group exhibited a significantly higher mean frequency of orally directed behaviors than the Attention Control group (12.6 vs. 7.1 pre-intervention, 51.8 vs. 33.2 during intervention, 4.3 vs. 3.2 immediately after intervention, and 8.9 vs. 5.3 immediately prior to feeding). On Day 7, the H-HOPE intervention group exhibited a significantly higher proportion of time spent in an alert behavioral state only during intervention (0.26 vs. 0.11) and immediately after intervention (0.28 vs. 0.06). These findings are suggestive that the integrated H-HOPE intervention facilitated infant behavioral organization for clinically stable infants born between 29 and 34 weeks gestation. The orally directed behaviors appear to be an important indicator of the infant's preparation for feeding, and when used in conjunction with assessment of behavioral states, are especially valuable to the clinician. Use of this combined assessment approach in practice would strengthen clinician assessment for initiation of (beginning the first oral feeding) and daily preparation for oral feeding in preterm infants. | 25,189,523 | [
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Targeting HIV latency: resting memory T cells, hematopoietic progenitor cells and future directions. | Current therapy for HIV effectively suppresses viral replication and prolongs life, but the infection persists due, at least in part, to latent infection of long-lived cells. One favored strategy toward a cure targets latent virus in resting memory CD4(+) T cells by stimulating viral production. However, the existence of an additional reservoir in bone marrow hematopoietic progenitor cells has been detected in some treated HIV-infected people. This review describes approaches investigators have used to reactivate latent proviral genomes in resting CD4(+) T cells and hematopoietic progenitor cells. In addition, the authors review approaches for clearance of these reservoirs along with other important topics related to HIV eradication. | 25,189,526 | [
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Synchronization in output-coupled temporal Boolean networks. | This paper presents an analytical study of synchronization in an array of output-coupled temporal Boolean networks. A temporal Boolean network (TBN) is a logical dynamic system developed to model Boolean networks with regulatory delays. Both state delay and output delay are considered, and these two delays are assumed to be different. By referring to the algebraic representations of logical dynamics and using the semi-tensor product of matrices, the output-coupled TBNs are firstly converted into a discrete-time algebraic evolution system, and then the relationship between the states of coupled TBNs and the initial state sequence is obtained. Then, some necessary and sufficient conditions are derived for the synchronization of an array of TBNs with an arbitrary given initial state sequence. Two numerical examples including one epigenetic model are finally given to illustrate the obtained results. | 25,189,531 | [
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Monensin inhibits epidermal growth factor receptor trafficking and activation: synergistic cytotoxicity in combination with EGFR inhibitors. | Targeting the EGFR, with inhibitors such as erlotinib, represents a promising therapeutic option in advanced head and neck squamous cell carcinomas (HNSCC). However, they lack significant efficacy as single agents. Recently, we identified the ability of statins to induce synergistic cytotoxicity in HNSCC cells through targeting the activation and trafficking of the EGFR. However, in a phase I trial of rosuvastatin and erlotinib, statin-induced muscle pathology limited the usefulness of this approach. To overcome these toxicity limitations, we sought to uncover other potential combinations using a 1,200 compound screen of FDA-approved drugs. We identified monensin, a coccidial antibiotic, as synergistically enhancing the cytotoxicity of erlotinib in two cell line models of HNSCC, SCC9 and SCC25. Monensin treatment mimicked the inhibitory effects of statins on EGFR activation and downstream signaling. RNA-seq analysis of monensin-treated SCC25 cells demonstrated a wide array of cholesterol and lipid synthesis genes upregulated by this treatment similar to statin treatment. However, this pattern was not recapitulated in SCC9 cells as monensin specifically induced the expression of activation of transcription factor (ATF) 3, a key regulator of statin-induced apoptosis. This differential response was also demonstrated in monensin-treated ex vivo surgical tissues in which HMG-CoA reductase expression and ATF3 were either not induced, induced singly, or both induced together in a cohort of 10 patient samples, including four HNSCC. These results suggest the potential clinical utility of combining monensin with erlotinib in patients with HNSCC. | 25,189,541 | [
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Impact of awareness drives and community-based active tuberculosis case finding in Odisha, India. | India's Revised National Tuberculosis Control programme employs passive case detection. The new sputum smear-positive case detection rate is less than 70% in Odisha State. During April-June 2012, active case finding (ACF) was conducted through awareness drives and field-based tuberculosis (TB) screening in select communities with the lowest case detection rates. During the campaign, 240 sputum smear-positive TB cases were detected. The number of smear-positive cases detected increased by 11% relative to April-June 2011 in intervention communities compared to an 0.8% increase in non-intervention communities. ACF brought TB services closer to the community and increased TB case detection. | 25,189,560 | [
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Homoarginine and cardiovascular outcome in the population-based Dallas Heart Study. | The nonproteinogenic amino acid homoarginine has been postulated to have antiatherosclerotic effects as a weak substrate of nitric oxide synthase. This investigation in the population-based Dallas Heart Study (DHS) aimed to evaluate the association of homoarginine with clinical and subclinical cardiovascular outcomes. Plasma homoarginine was measured in 3514 participants of the DHS using liquid chromatography-tandem mass spectrometry. Associations between homoarginine and major adverse cardiovascular events and all-cause mortality were analyzed using Cox proportional hazard models adjusting for cardiovascular risk factors. Linear regression was used to assess cross-sectional associations between homoarginine and subclinical cardiovascular disease, including coronary artery calcium measured by electron beam-computed tomography, and aortic plaque burden and aortic wall thickness by MRI. Median age was 43 (interquartile range, 36-52) years, with 56% women and 52% black participants. Median follow-up was 9.4 (9.0-9.8) years. Median plasma homoarginine was 2.80 (2.14-3.54) μmol/L. In multivariable models, higher homoarginine was associated with lower rate of major adverse cardiovascular events (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98) and lower all-cause mortality (hazard ratio, 0.82; 0.73-0.92; per 1 log SD increase in homoarginine). Homoarginine was inversely and independently associated with aortic wall thickness (β-estimate, -0.04; P<0.01) but not with aortic plaque burden and coronary artery calcium. Homoarginine is inversely associated with subclinical vascular disease and with risk for cardiovascular disease events. Additional studies are needed to evaluate whether the regulation of plasma homoarginine could emerge as a novel therapeutic option to improve outcomes in cardiovascular disease. | 25,189,571 | [
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Electrophoretic and field-effect graphene for all-electrical DNA array technology. | Field-effect transistor biomolecular sensors based on low-dimensional nanomaterials boast sensitivity, label-free operation and chip-scale construction. Chemical vapour deposition graphene is especially well suited for multiplexed electronic DNA array applications, since its large two-dimensional morphology readily lends itself to top-down fabrication of transistor arrays. Nonetheless, graphene field-effect transistor DNA sensors have been studied mainly at single-device level. Here we create, from chemical vapour deposition graphene, field-effect transistor arrays with two features representing steps towards multiplexed DNA arrays. First, a robust array yield--seven out of eight transistors--is achieved with a 100-fM sensitivity, on par with optical DNA microarrays and at least 10 times higher than prior chemical vapour deposition graphene transistor DNA sensors. Second, each graphene acts as an electrophoretic electrode for site-specific probe DNA immobilization, and performs subsequent site-specific detection of target DNA as a field-effect transistor. The use of graphene as both electrode and transistor suggests a path towards all-electrical multiplexed graphene DNA arrays. | 25,189,574 | [
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Draft Genome Sequences of Four Strains of Vibrio parahaemolyticus, Three of Which Cause Early Mortality Syndrome/Acute Hepatopancreatic Necrosis Disease in Shrimp in China and Thailand. | We sequenced four Vibrio parahaemolyticus strains, three of which caused serious acute hepatopancreatic necrosis disease. Sequence analysis of the virulent strains revealed not only genes related to cholera toxin and the type IV pilus/type IV secretion system but also a unique, previously unreported, large extrachromosomal plasmid that encodes a homolog to the insecticidal Photorhabdus insect-related binary toxin PirAB. | 25,189,578 | [
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Draft Genome Sequence of Pseudomonas sp. Strain JMM, a Sediment-Hosted Environmental Isolate. | Pseudomonas sp. strain JMM was isolated from the sediments of a natural water reservoir (pH, 6 to 7) located at Chambyal village in Samba district of Jammu and Kashmir, India. Here we report the annotated draft genome sequence of strain JMM having 52 contigs with 5,884 genes and an average G+C content of 66.5%. | 25,189,587 | [
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Mi-1.2, an R gene for aphid resistance in tomato, has direct negative effects on a zoophytophagous biocontrol agent, Orius insidiosus. | Mi-1.2 is a single dominant gene in tomato that confers race-specific resistance against certain phloem-feeding herbivores including aphids, whiteflies, psyllids, and root-knot nematodes. Few prior studies have considered the potential non-target effects of race-specific resistance genes (R genes), and this paper evaluates the compatibility of Mi-mediated resistance in tomato with a beneficial zoophytophagous predator, Orius insidiosus (Say). In addition to preying on aphids and other pests, this piercing-sucking insect also feeds from the xylem, epidermis, and/or mesophyll, and oviposits within plant tissues. Comparison of O. insidiosus confined to isogenic tomato plants with and without Mi-1.2 revealed that immatures of O. insidiosus had lower survival on resistant plants even when the immatures were provisioned with prey that did not feed on the host plant. Molecular gut content analysis confirmed that adults and immatures of O. insidiosus feed on both resistant (Mi-1.2+) and susceptible (Mi-1.2-) genotypes, and bioassays suggest that resistance does not affect oviposition rates, plant sampling, or prey acceptance by O. insidiosus adults. These results demonstrate a direct negative impact of R-gene-mediated host plant resistance on a non-target beneficial species, and reveal that Mi-mediated resistance can impact organisms that do not feed on phloem sap. Through laser capture microdissection and RT-PCR, Mi-1.2 transcripts were detected in the epidermis and mesophyll as well as the phloem of tomato plants, consistent with our observations that Mi-mediated resistance is active outside the phloem. These results suggest that the mode of action and potential ecological impacts of Mi-mediated resistance are broader than previously assumed. | 25,189,594 | [
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Coronary angioplasty in octogenarians with emergent coronary syndromes: study protocol for a randomized controlled trial. | Invasive treatment (coronary angiography and intervention if feasible) of patients with acute coronary syndrome (ACS) has been shown to lead to better outcomes than medical therapy alone, but the elderly have been under-represented in many of the studies. In the elderly, medical therapy is common in ACS. Fear of complications related to the procedure and unclear benefit in older patients are common reasons for invasive procedures being withheld. Our hypothesis is that invasive treatment of elderly patients with ACS will lead to a better outcome in terms of survival and quality of life than medical therapy alone, with acceptable risk. This multicenter, randomized controlled trial of patients 80 years of age and over has two parallel treatment arms, a medical group and an invasive group. In Swedish hospitals, 200 patients with non-ST elevation myocardial infarction or unstable angina will be randomized to medical or invasive treatment strategy. The primary outcome measure is the combined endpoint major adverse cardiac or cerebrovascular event (MACCE) within one year. Secondary outcome measures include quality of life, angina, and adverse events such as bleeding. Assessments will be conducted during hospitalization, at 1 month after allocation, and at 12 months. This study seeks to determine the efficacy and safety of invasive and medical treatment strategies in the elderly with ACS. The study is currently recruiting. ClinicalTrials.gov trial identifier: NCT02126202. Registered on 7 January 2014. | 25,189,626 | [
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In situ monitoring and optimization of room temperature ultra-fast sensitization for dye-sensitized solar cells. | We describe the fastest dyeing of TiO2 photo-electrodes for dye-sensitized solar cells reported to date (<2 min) at room temperature giving η = 7.5% for an N719-SQ1-CDCA mixture which is significantly higher than devices dyed for >12 h using the same dye mixture (η = 5.5%). Time-lapse photography has been used to monitor the ultra-fast co-sensitization. The data show significantly different dye uptake between passive and pump dyeing reflecting competitive sorption between a Ru complex (N719) and an organic dye (SQ1). | 25,189,646 | [
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Association of insulin-like growth factor-I receptor polymorphism with colorectal cancer development. | The insulin-like growth factor (IGF) system plays a prominent role in the cancer development. The IGF-1 receptor (IGF-1R) and its associated signalling pathway is an important growth regulatory pathway that has been implicated in colorectal carcinogenesis. This study was designed to compare +3179G/A IGF1R (rs 2229765) genotype distribution in 110 colorectal cancer (CRC) patients to a group of 143 healthy controls (HCs). We also investigated serum IGF-1 levels in CRC patients and HCs in an association to genotype. IGF-1 serum levels were measured by enzyme-linked immunosorbent assay and genotyping for the +3179G/A polymorphism was performed by restriction fragment length polymorphisms-polymerase chain reaction assay. Although the genotype frequencies were comparable in both groups, higher frequency of dominant genotypes [AA/AG; 71 vs. 62 %; odds ratio (OR) = 1.52] and lower frequency of GG genotype (29 vs. 38 %) was seen in cases versus controls. When CRC patient's group was divided into stages of disease by tumor-node-metastasis classification we observed the significantly highest frequency of AA genotype in III stage compared to controls: 22.5 versus 15 %; OR = 3.37, p = 0.026. There was a significant association between IGF-1R rs2229765 polymorphism and advanced CRC (AA/AG vs. GG: OR = 3.06, p = 0.004). The frequency of A-allele in advanced CRC was significantly higher then early CRC (52 vs. 37.7, OR = 1.78). According to genotype serum IGF-1 levels was significantly decreased in patients with GG genotype then patients with dominant genotypes. Our results showed a relationship between the +3179G>A polymorphism of the IGF-1R and serum IGF-1 with the progression of colorectal carcinoma. A dominant genetic model was established for IGF-1R rs2229765 polymorphism and CRC progression. | 25,189,651 | [
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Identifying child abuse and neglect risk among postpartum women in Japan using the Japanese version of the Kempe Family Stress Checklist. | The aims of this study were to determine the rate of women who are high-risk for child abuse and neglect in a perinatal unit in Japan, and to identify the factors associated with risk level. To assess the potential risk for child abuse and neglect the Japanese version of the Kempe Family Stress Checklist (FSC-J) was used to guide interviews with postpartum women. FSC-J uses a three-point scale to score 10 categories, categorizing responses as "no risk=0", "risk=5", and "high risk=10". The range of FSC-J is 0-100. Using an established cutoff point of 25, subjects were divided into high and low risk groups. For both groups, relationships between factors were analyzed. Of the 174 subjects who agreed to participate, 12 (6.9%) scored high-risk, and 162 (93.1%) scored low-risk. Adjusted odds ratio identified three associated factors as important for predicting risk level: past mental illness (OR=341.1), previous experience of intimate partner violence (OR=68.0), and having a partner who was unemployed (OR=14.5). Although this study was on a small sample of women in one hospital in Japan and a larger population would make this study much stronger, these results suggest that some 6.9% of postpartum women in Japan may be at high-risk for child abuse and neglect. It is critical, therefore, to develop a system for screening, intervention, and referral for such women and their children. | 25,189,711 | [
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It is time to change thrombosis risk assessment for PV and ET? | Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms to be diagnosed according to the WHO classification. Molecular profiling must include the analysis of JAK2 (looking for the V617F point-mutation in PV and ET, screening exon 12 for mutations only in V617F-negative PV), CALR and MPL mutations (both in V617F-negative ET). The current risk stratification to predict thrombosis requires two parameters: age over 60 years and prior history of thrombosis. On the basis of these two risk factors patients can be stratified in low-risk and high-risk and receive a proper treatment. However, a modern stratification of thrombotic risk might consider "new" low-risk patients: conventional low-risk plus absence of leukocytosis from diagnosis onwards and a hematocrit level below 45% during the course of disease for PV; conventional low-risk plus absence of leukocytosis from diagnosis onwards, JAK2 negativity, CALR positivity, and absence of cardiovascular risk factors for ET. | 25,189,723 | [
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Controversies and dilemmas in allogeneic transplantation for myelofibrosis. | JAK1/2 inhibitors have broadened the therapeutic options in myelofibrosis. Though not curative, they result in a meaningful clinical benefit with relatively fewer side effects. In contrast, allogeneic hematopoietic cell transplantation (HCT) is a potentially curative option, but is associated with significant morbidity and mortality. Hence, an important question is the optimal timing of HCT in the era of JAK inhibitors. Timing of HCT is a crucial decision, and need to be individualized based on the personal preferences and goals of therapy; in addition to patient, disease, and transplant related factors. Risk stratification by the currently established prognostic scoring systems need to be further refined by incorporation of prognostically significant mutations to guide the treatment choices better. Data on use of JAK inhibitors prior to HCT have just started to emerge. We discuss some of the current controversies and dilemmas in transplantation for myelofibrosis based on a few real life scenarios. | 25,189,727 | [
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Subjective perception of load heaviness. | This study examined human subjective perception of load heaviness. Forty-two (3 boxes × 14 weights) and 27 (3 boxes × 9 weights) experimental conditions were randomly presented to male and female participants, respectively. The results showed that the participants were not able to discriminate the effect of the box on perceived weight. The participants underestimated the weight for low weights and overestimated it for high weights. The females perceived a greater increase in weight than the males for the same increase in weight. The participants' linguistic term for perceived weight was positively correlated to the magnitude of weight. Approximately 50% of the males perceived a weight of 20 kg or over as risky, while ~60% of the females perceived a weight of 14 kg or over as risky. This study supposes that the gender difference in muscular capability is responsible for the effect of gender on the risk perception of weight. | 25,189,746 | [
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Hyperplasia and fibrosis in mice with conditional loss of the TSC2 tumor suppressor in Müllerian duct mesenchyme-derived myometria. | Uterine leiomyomata are the most common tumors found in the female reproductive tract. Despite the high prevalence and associated morbidities of these benign tumors, little is known about the molecular basis of uterine leiomyoma development and progression. Loss of the Tuberous Sclerosis 2 (TSC2) tumor suppressor has been proposed as a mechanism important for the etiology of uterine leiomyomata based on the Eker rat model. However, conflicting evidence showing increased TSC2 expression has been reported in human uterine leiomyomata, suggesting that TSC2 might not be involved in the pathogenesis of this disorder. We have produced mice with conditional deletion of the Tsc2 gene in the myometria to determine whether loss of TSC2 leads to leiomyoma development in murine uteri. Myometrial hyperplasia and increased collagen deposition was observed in Tsc2(cKO) mice compared with control mice, but no leiomyomata were detected by post-natal week 24. Increased signaling activity of mammalian target of rapamycin complex 1, which is normally repressed by TSC2, was also detected in the myometria of Tsc2(cKO) mice. Treatment of the mutant mice with rapamycin significantly inhibited myometrial expansion, but treatment with the progesterone receptor modulator, mifepristone, did not. The ovaries of the Tsc2(cKO) mice appeared normal, but half the mice were infertile and most of the other half became infertile after a single litter, which was likely due to oviductal blockage. Our study shows that although TSC2 loss alone does not lead to leiomyoma development, it does lead to myometrial hyperplasia and fibrosis. | 25,189,766 | [
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An investigation for population maintenance mechanism in a miniature garden: genetic connectivity or independence of small islet populations of the Ryukyu five-lined skink. | The Ryukyu five-lined skink (Plestiodon marginatus) is an island lizard that is even found in tiny islets with less than half a hectare of habitat area. We hypothesized that the island populations are maintained under frequent gene flow among the islands or independent of each other. To test our hypotheses, we investigated genetic structure of 21 populations from 11 land-bridge islands that were connected during the latest glacial age, and 4 isolated islands. Analyses using mitochondrial cytochrome b gene sequence (n = 67) and 10 microsatellite loci (n = 235) revealed moderate to high levels of genetic differentiation, existence of many private alleles/haplotypes in most islands, little contemporary migration, a positive correlation between genetic variability and island area, and a negative correlation between relatedness and island area. These evidences suggest a strong effect of independent genetic drift as opposed to gene flow, favoring the isolation hypothesis even in tiny islet populations. Isolation-by-distance effect was demonstrated and it became more prominent when the 4 isolated islands were excluded, suggesting that the pattern is a remnant of the land-bridge age. In a few island populations, however, the possibility of occasional overwater dispersals was partially supported and therefore could not be ruled out. | 25,189,776 | [
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Pure germinomas of the central nervous system: treatment strategies and outcomes. | To evaluate the role of chemotherapy and radiation therapy in the treatment of pure germinomas of the central nervous system (CNS). We reviewed a historical cohort of 79 patients between the ages of 3-35 years who received definitive treatment for newly diagnosed, pure CNS germinoma between 1985 and 2010 at the University of California, San Francisco (UCSF). Median age at diagnosis was 15 years (interquartile range, IQR 12-20 years) and 61 (77.2 %) patients were male. Median follow-up for the cohort was 111.1 months (IQR 45.7-185.1 months). Five-year PFS rate was 86.4 % (95 % CI 76.1-92.4) and 5 year OS rate was 93.0 % (95 % CI 84.1-97.1). Median PFS was 104.6 months (IQR 41.4-170.1 months). Fourteen patients progressed and 8 died of their disease. Patients who received focal irradiation (XRT) and chemotherapy had a significantly higher rate of progression compared to those who received whole brain irradiation (WBI) or whole ventricle irradiation (WVI). Three of 8 patients had a PR to chemotherapy and received focal XRT progressed whereas only 1 of 9 patients who had a CR to chemotherapy who went on to receive focal XRT progressed. Elevation of hCGβ > 50 mIU/ml was not significantly associated with disease progression (HR 5.64, 95 % CI 0.97-32.7, p = 0.054). Patients treated with WBI or WVI with or without chemotherapy achieve better disease control compared to patients treated with focal XRT + chemotherapy. | 25,189,788 | [
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Model development for naphthenic acids ozonation process. | Naphthenic acids (NAs) are toxic constituents of oil sands process-affected water (OSPW) which is generated during the extraction of bitumen from oil sands. NAs consist mainly of carboxylic acids which are generally biorefractory. For the treatment of OSPW, ozonation is a very beneficial method. It can significantly reduce the concentration of NAs and it can also convert NAs from biorefractory to biodegradable. In this study, a factorial design (2(4)) was used for the ozonation of OSPW to study the influences of the operating parameters (ozone concentration, oxygen/ozone flow rate, pH, and mixing) on the removal of a model NAs in a semi-batch reactor. It was found that ozone concentration had the most significant effect on the NAs concentration compared to other parameters. An empirical model was developed to correlate the concentration of NAs with ozone concentration, oxygen/ozone flow rate, and pH. In addition, a theoretical analysis was conducted to gain the insight into the relationship between the removal of NAs and the operating parameters. | 25,189,805 | [
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Dioscin inhibits adipogenesis through the AMPK/MAPK pathway in 3T3-L1 cells and modulates fat accumulation in obese mice. | Dioscin (DS) is a steroidal saponin present in a number of medicinal plants and has been shown to exert anticancer, antifungal and antiviral effects. The present study aimed to deternube the effects DS on the regulation of adipogenesis and to elucidate the underlying mechanisms. In vitro experiments were performed using differentiating 3T3-L1 cells treated with various concentrations (0-4 µM) of DS for 6 days. A cell viability assay was performed on differentiating cells following exposure to DS. Oil Red O staining and triglyceride content assay were performed to evaluate the lipid accumulation in the cells. We also carried out the following experiments: i) flow cytometry for cell cycle analysis, ii) quantitative reverse transcription polymerase chain reaction for measuring adipogenesis-related gene expression, and iii) western blot analysis to measure the expression of adipogenesis transcription factors and AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and mitogen-activated protein kinase (MAPK) phosphorylation. In vivo experiements were performed using mice with obesity induced by a high-fat diet (HFD) that were treated with or without DS for 7 weeks. DS suppressed lipid accumulation in the 3T3-L1 cells without affecting viability at a dose of up to 4 µM. It also delayed cell cycle progression 48 h after the initiation of adipogenesis. DS inhibited adipocyte differentiation by the downregulation of adipogenic transcription factors and attenuated the expression of adipogenesis-associated genes. In addition, it enhanced the phosphorylation of AMPK and its target molecule, ACC, during the differentiation of the cells. Moreover, the inhibition of adipogenesis by DS was mediated through the suppression of the phosphorylation of MAPKs, such as extracellular-regulated kinase 1/2 (ERK1/2) and p38, but not c-Jun-N-terminal kinase (JNK). DS significantly reduced weight gain in the mice with HFD-induced obesity; this was evident by the suppression of fat accumulation in the abdomen. the present study reveals an anti-adipogenic effect of DS in vitro and in vivo and highlights AMPK/MAPK signaling as targets for DS during adipogenesis. | 25,189,808 | [
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Masturbation and Pornography Use Among Coupled Heterosexual Men With Decreased Sexual Desire: How Many Roles of Masturbation? | The relation between masturbation and sexual desire has not been systematically studied. The present study assessed the association between masturbation and pornography use and the predictors and correlates of frequent masturbation (several times a week or more often) among coupled heterosexual men who reported decreased sexual desire. Analyses were carried out on a subset of 596 men with decreased sexual desire (mean age = 40.2 years) who were recruited as part of a large online study on male sexual health in 3 European countries. A majority of the participants (67%) reported masturbating at least once a week. Among men who masturbated frequently, 70% used pornography at least once a week. A multivariate assessment showed that sexual boredom, frequent pornography use, and low relationship intimacy significantly increased the odds of reporting frequent masturbation among coupled men with decreased sexual desire. These findings point to a pattern of pornography-related masturbation that can be dissociated from partnered sexual desire and can fulfill diverse purposes. Clinical implications include the importance of exploring specific patterns of masturbation and pornography use in the evaluation of coupled men with decreased sexual desire. | 25,189,834 | [
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Blast furnace residues for arsenic removal from mining-contaminated groundwater. | In this work, blast furnace (BF) residues were well characterized and then evaluated as an adsorbent material for arsenic removal from a mining-contaminated groundwater. The adsorption process was analysed using the theories of Freundlich and Langmuir. BF residues were found to be an effective sorbent for As (V) ions. The modelling of adsorption isotherms by empirical models shows that arsenate adsorption is fitted by the Langmuir model, suggesting a monolayer adsorption of arsenic onto adsorbents. Arsenate adsorption onto BF residue is explained by the charge density surface affinity and by the formation of Fe (II) and Fe (III) corrosion products onto BF residue particles. The results indicate that BF residues represent an attractive low-cost absorbent option for the removal of arsenic in wastewater treatment. | 25,189,836 | [
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Removal of naphthols and analogues by the combined use of an oxidoreductase polyphenol oxidase and a biopolymer chitosan from aqueous solutions. | In this study, the combined use of an amino group-containing polymer chitosan and an oxidoreductase polyphenol oxidase (PPO) was applied to the removal of naphthols and dihydroxynaphthalenes (DHNs) from aqueous solutions. The process parameters, such as the pH value, temperature and enzyme dose, were discussed for PPO-catalysed oxidation of 1-naphthol. The optimum conditions of enzymatic oxidation of 1-naphthol were determined to be pH 8.0 and 40 °C. Under the optimum conditions, PPO-catalysed oxidation of 1-naphthol increased with an increase in the enzyme dose. Quinone derivatives enzymatically generated were chemisorbed on chitosan beads and the initial velocity of PPO-catalysed oxidation increased with an increase in the amount of added chitosan beads. A specific initial velocity of 0.0675 μmol/U·min was obtained in the PPO concentration range below 200 U/cm³ and 1-naphthol was completely removed within 24 h by quinone adsorption on chitosan beads (0.20 cm³/cm³) at a PPO concentration of 100 U/cm³. The removal time was shortened by increasing the enzyme dose or the amount of added chitosan beads. 2-Naphthol was also completely removed at an initial concentration of 0.05 mM or less by prolonging the reaction time, since PPO-catalysed oxidation of 2-naphthol was much slower than that of 1-naphthol. In addition, this procedure was also applied to the removal of DHNs. These results revealed that the procedure constructed in this study was an effective technique to remove naphthols and DHNs from the aqueous medium. | 25,189,838 | [
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Biological treatment of acidic coal refuse using sulphate-reducing bacteria with chicken manure as carbon source. | The performance of using chicken manure as carbon source to promote sulphate-reducing bacteria (SRB) activity within acidic coal refuse to prevent the generation of acidic leachate was investigated in batch and column bioreactors. The bioreactors showed satisfactory performance in biological sulphate reduction, evidenced by the increase in effluent pH, high removal efficiencies of sulphate and metals, and the presence of large numbers of SRB. Scanning electron microscope-energy dispersive spectrometry (EDS) analysis of the formed precipitate indicated the formation of metal sulphides. Chicken manure was observed to play an important role in this treatment, which could not only provide carbon source but also reduce the adverse effect of strong acidity and metal toxicity on SRB activity. Metal removal could be mainly attributed to sulphides precipitation and sorption to chicken manure. This study indicated that SRB with chicken manure could be a novel alternative used for the prevention of acidic leachate from coal refuse. | 25,189,842 | [
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Contemporary challenges of catheter ablation for atrial fibrillation. | Catheter ablation of atrial fibrillation (AF) is now one of the most frequently performed ablation procedures, but there are currently 2 important challenges: achieving permanent/durable rather than transient pulmonary vein isolation (PVI) and improving the results of ablation for the wider patient population with persistent AF. Recent technical advances in the technique of ablation and the results of clinical trials aimed at achieving more permanent and durable PVI are reviewed. We also summarize recent advances in identifying atrial fibrosis and in understanding the pathophysiology of AF relevant to selecting patients for ablation of persistent AF. The use of contact force-sensing technology, adenosine testing after ablation, and pace capture-guided ablation all have the potential for achieving more durable ablation. Selection of patients suitable for ablation of persistent AF may be improved by assessing the extent of atrial fibrosis with delayed enhancement imaging with cardiac magnetic resonance or by assessing the pattern of atrial electrical activity with the use of complex atrial electrograms. Advances in treatment are likely to result from the recognition of localized rotors and focal sources as primary sustaining mechanisms for all types of human AF and in the use of noninvasive mapping for their identification. Linear ablation to supplement PVI may improve the results of AF ablation. Rapidly unfolding advances in the techniques of AF ablation and the understanding of mechanisms of AF hold promise for improving the durability of PVI and for extending the technique to carefully selected patients with persistent AF. | 25,189,853 | [
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Influence of body fatness distribution and total lean mass on aortic stiffness in nonobese individuals. | Subjects with normal body mass index but high body fat percentage have higher cardiovascular risk than subjects with normal weight and low fat mass. However, the association of fat distribution and lean mass with carotid-femoral pulse wave velocity (cfPWV) among nonobese apparently healthy individuals has never been assessed. In 136 nonobese volunteers (mean age = 45±9 years; 57% women) without manifest cardiovascular disease, cfPWV was measured by applanation tonometry. Fat and lean mass were measured by dual-energy x-ray absorptiometry. In univariate analysis, total fat (r = 0.17; P < 0.01), trunk fat (r = 0.27; P < 0.01), and trunk/total fat ratio (r = 0.32; P < 0.01) were correlated with cfPWV. After adjustment for age and mean arterial pressure, only central fat distribution (trunk/total fat ratio) was significantly associated with cfPWV. In the fully adjustment model, there was a significant interaction between fat distribution and lean mass. When the study sample was grouped by fat distribution and total lean mass medians, subjects with central fat distribution and low lean mass (group 4) had higher log-transformed cfPWV than the noncentral fat/low lean mass group (group 2) (0.89, 95% confidence interval (CI) = 0.86-0.92 vs. 0.85, 95% CI = 0.83-0.87; P < 0.01) or the noncentral fat/high lean mass group (group 1) (0.89, 95% CI = 0.86-0.92 vs. 0.84, 95% CI = 0.81-0.87; P < 0.01) after adjustments. Aortic stiffness increased from group 1 to group 4 (P for linear trend < 0.001). Among normal weight individuals without manifest cardiovascular disease, the combination of central fat distribution and low lean mass is associated with higher cfPWV. These factors are more closely related to cfPWV than total fat mass. | 25,189,869 | [
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Selected cyclic citrullinated peptides derived from the sequence of mutated and citrullinated vimentin (MCV) are targeted by different antibodies subclasses in patients with rheumatoid arthritis in Russian patients. | Antibodies against citrullinated antigens (ACPA) represent one rheumatoid arthritis (RA) classification criteria. Recently, mutated and citrullinated vimentin (MCV), containing approx. 45 potentially citrullinated sites, was characterised as another modified autoantigenic RA target. Therefore, we wanted to screen, select and validate predominant MCV autoantigenic epitopes (called here MCE) as possible new diagnostic targets. MCV-derived peptides with citrullinated sites were screened in healthy controls and patients. Based on this, twelve selected MCE were used for validation of ACPA isotypes (IgA/IgG/IgM) with ELISA in early RA (ERA, <12 months) and established RA (>12 months) Russian patients. Sensitivity of MCE reactivity was compared to commercially available ELISAs for anti-CCP IgG, anti-MCV IgG, and anti-RF IgA/IgM/IgG. Anti-MCE IgG/IgA//IgM antibodies were observed in 64.1%, 23.1%, and 15.4% ERA, and 63.9%, 26.7%, and 13.1% established RA patients, respectively. Anti-MCV IgG was present in 64.1% ERA and 55.0% RA patients. Furthermore, anti-CCP IgG and RF IgG/IgA/IgM were detectable in up to 76.9%, 71.8%, 71.8%, and 38.5% ERA, and 80.1%, 72.3%, 67.5%, and 43.0% RA patients. Anti-CCP IgG single positivity was observed in 7.7% ERA and 6.3% RA patients. Only one RA patient was anti-MCE single positive. MCV autoantigenic epitopes were emulated by cyclic citrullinated MCV-derived peptides and recognised by all autoantibody-Ig subclasses in RA. Tested MCE were recognized more frequently by IgG as the original MCV antigen. High antibody prevalence against CCP epitopes suggests a strong CCP-linkage to RA pathogenesis in the investigated Russian cohort. | 25,189,876 | [
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Influence of static magnetic fields combined with human insulin-like growth factor 1 on human satellite cell cultures. | Tissue engineering represents a promising research field, targeting the creation of new functional muscle tissue in vitro. The aim of the present study was to show the influence of static magnetic fields (SMF) and insulin-like growth factor-1 (IGF1), as enhancing stimuli on human satellite cell cultures, which are preferred sources of stem cells in engineering skeletal muscle tissue. To detect effects on myogenic maturation and proliferation, AlamarBlue® proliferation, assay and semi-quantitative reverse transcription-polymerase chain reaction of following markers was performed: desmin (DES), myogenic factor-5 (MYF5), myogenic differentiation antigen-1 (MYOD1), myogenin (MYOG), myosin heavy chain (MYH) and α1 actin (ACTA1). As a distinct marker of differentiation, immunohistochemical staining and fusion index determination was performed on satellite cell cultures stimulated with IGF1 and IGF1-plus-SMF with an intensity of 80 mT. Proliferation was increased by additional SMF application to IGF1-stimulated cell cultures on the first day of myogenesis. Relative gene expression of measured markers was increased by IGF1 application in the first days of myogenesis except for ACTA1. Additional SMF application enhanced this effect. Nevertheless we were unable to demonstrate the formation of contractile muscle tissue. Immunhistochemical staining verified muscle origin and all markers were displayed. | 25,189,891 | [
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Synergistic effect of sorafenib with ionizing radiation on human oral cancer cells. | Although anticancer effects of sorafenib on renal, liver and colon carcinomas are well-known, its combination effect with ionizing radiation on oral squamous cell carcinoma (OSCC) is unclear. Herein human SAS cells, an OSCC cell line, were used in order to elucidate this combination effect. Both SAS and SAS/nuclear factor kappa-B-luciferase (SAS/NF-κB-luc2) cell lines were used in the study. Cell viability, NF-κB activation, and protein expression of NF-κB downstream effectors were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, NF-κB-luc2 reporter gene system, NF-κB/DNA binding activity and western blotting. Sorafenib significantly increased radiation-induced cytotoxicity and apoptosis via both mitochondrial-dependent and independent pathways. In addition, NF-κB activity and downstream effector protein expression induced by radiation was suppressed by sorafenib in SAS/NF-κB-luc2 cells. Combination of sorafenib with radiation for the treatment of human OSCC shows a synergistic effect via suppression of radiation-induced NF-κB activity and its regulated downstream effector proteins. | 25,189,909 | [
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Progressive multifocal leukoencephalopathy--a case report and review of the literature. | Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system which affects the white matter and is caused by reactivation of the JC polyomavirus. We report the case of a 63-year-old man with chronic lymphocytic leukemia who was treated with fludarabine; rituximab and fludarabine; fludarabine, cyclophsphamide and rituximab; and lenalidomide. While he underwent chemotherapy, the patient was diagnosed with PML. After stabilization of PML, the patient underwent non-myeloablative allogeneic bone marrow transplantation as a treatment for chronic lymphocytic leukemia. Unfortunately, after several opportunistic infections, the patient died. The patient underwent allogeneic bone marrow transplantation with the expectation that donor-derived competent immunological cells would migrate into the cerebral lesions, maintaining immunological response. The effect of bone marrow transplantation in patients with PML requires investigation in larger patient series. | 25,189,911 | [
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Leptin levels in women with polycystic ovaries undergoing ovarian stimulation: relation to lipoprotein profiles. | To investigate serum and follicular fluid (FF) leptin levels in normally-ovulating women and subjects with polycystic ovary syndrome (PCOS) undergoing controlled ovarian stimulation and correlate them with their lipid lipoprotein profile. We included 70 PCOS women (35 lean and 35 overweight or obese) and 76 age- and weight-matched non-PCOS controls (39 lean and 37 overweight or obese). Serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein B, lipoprotein(a) and homocysteine in women with PCOS were significantly higher compared to control groups while levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A1 were significantly lower. Serum leptin levels did not differ between groups and were lower than FF levels. Serum and FF leptin levels were positively correlated and were significantly decreased when apolipoprotein B levels increased. PCOS women exhibit lipid metabolism abnormalities putting them at increased risk of developing early atherosclerosis. | 25,189,919 | [
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Postsurgical pain related to breast implant: reduction with lipofilling procedure. | After a review of clinical cases of the Unit of Plastic Surgery of the University of Siena, Italy, we found that 22 patients undergoing lipofilling for breast recontruction needed less pain drugs compared to 18 patients which did not undergo lipofilling. In this work, the postoperative pain was analyzed in two groups of patients: a cohort treated with prosthesis and a cohort treated with prosthesis implant together with a lipofilling procedure. During the immediate postoperative period, a visual analog scale for pain was submitted to every patient every eight hours until they were discharged, then every day for a week, every two days during the second week and once a week in the first three months. The administration of analgesics was also registered. Pain intensity was lower in the group treated with prosthesis and lipofilling. Fat transplant is a procedure well-tolerated by patients, resulting in a lower rate of pain. | 25,189,920 | [
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Executive deficit in spinocerebellar ataxia type 2 is related to expanded CAG repeats: evidence from antisaccadic eye movements. | Although antisaccadic task is a sensitive research tool in psychopathology, it has not been systematically studied in patients with spinocerebellar ataxia type 2 (SCA2). To identify putative biomarkers of executive dysfunction in SCA2 we assessed the antisaccade performance in 41 SCA2 patients and their sex-and-age matched controls using an electronystagmography device. We studied the relationship between findings in the antisaccade task and CAG repeat length and motor function as assessed using the Scale for the Assessment and Rating of Ataxia (SARA), Nine-Hole Pegboard Test and a validated battery for executive dysfunctions. SCA2 patients showed a significant increase of inhibition and omission antisaccadic error rates, decrease of corrected antisaccadic errors and prolongation of antisaccadic latency and antisaccadic correction latency. Multiple regression predictions identified the expanded CAG repeat as a significant contributing factor on inhibition antisaccadic error rate and percentage of corrected antisaccadic errors. Impaired antisaccadic performance was associated to higher Stroop interference task and verbal fluency test deficits. In conclusion, antisaccadic eye movement abnormalities are a newly recognized association with the genetic abnormality in SCA2 and correlate with executive dysfunction in SCA2. Antisaccade parameters are a promising source of cognitive biomarkers for exploring the disease pathophysiology, and assessing the efficacy of therapeutic options. | 25,189,938 | [
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Application of immunosuppressant facilitates the therapy of optic neuritis combined with Sjögren's syndrome. | Optic neuritis (ON) is often the first symptom of multiple sclerosis (MS) and neuromyelitis optica (NMO) while there has been very little research reported on ON combined with Sjögren's syndrome (SS). The aim of this study is to provide different treatments and services for and NMO patients combined with SS. Twenty-seven patients with ON combined SS were divided into two groups: corticosteroid group (C group, methylprednisolone sodium succinate, 14 patients) and corticosteroid+ immunosuppressant group (C+I group, leflunomide, 13 patients). ON relapse times in 1 year after treatment, number of patients who relapsed to NMO/MS in 1 years, visual acuity and retina nerve fiber layer (RNFL) thickness were measured. Mann Whitney-Wilcoxon test was used to compare continuous variables and Chi-square test or Fisher's exact test was to compare proportions. ON combined with SS patients had higher incidence rates in middle-aged women who have binocular damage and heavier visual function damage or when there is an easy relapse, and the patients are often hormone dependent. The patients are more likely anti-aquaporin-4 IgG seropositive (70.4%). They are liable to form a centrocecal scotoma and tubular vision. The times of relapse decreased in patients who used immunosuppressant, and a significant difference was found between immunosuppressant and non-immunosuppressant groups in visual acuity recovery during 6-month follow-up period (P < 0.05); however, the RNFL thickness at the four quadrants was not significantly different. The effect of immunosuppressant plus corticosteroid on the early onset of ON combined with SS was to provide ON remedy and to prevent recurrence in clinics. This study provides a significant reference for the prevention and treatment of ON on the basis of immunosuppressant and corticosteroid. | 25,189,952 | [
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[Differential effects of diabetes education programs by levels of HbA1c and the presence of chronic complications in patients with type 1 diabetes]. | Diabetes Education Programs (DEP) that improve metabolic control are applied to a wide variety of patient types. The aim is to test whether DEPs work differently depending on the patient profile. Thirty-six type 1 diabetics participated. They were divided into four groups according to their haemoglobin levels (range: 7-13 %) and into two groups according to the presence or absence of complications. The ECODI scale for assessing diabetes knowledge and the Frequency of Self-Care scale were completed by all patients. The results showed that HbA1c decreased after the DEP, with some areas of self-care also improving. There were no changes, however, to diet or exercise. DEP appear to work better in patients with worse control and with complications, suggesting that they have a certain role to play in prevention. Their lack of impact on diet or exercise, would suggest that the DEPs require improvement to include psychological strategies that motivate lasting lifestyle changes. | 25,189,981 | [
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Magnetic actuator for the control and mixing of magnetic bead-based reactions on-chip. | While magnetic bead (MB)-based bioassays have been implemented in integrated devices, their handling on-chip is normally either not optimal--i.e. only trapping is achieved, with aggregation of the beads--or requires complex actuator systems. Herein, we describe a simple and low-cost magnetic actuator to trap and move MBs within a microfluidic chamber in order to enhance the mixing of a MB-based reaction. The magnetic actuator consists of a CD-shaped plastic unit with an arrangement of embedded magnets which, when rotating, generate the mixing. The magnetic actuator has been used to enhance the amplification reaction of an enzyme-linked fluorescence immunoassay to detect Escherichia coli O157:H7 whole cells, an enterohemorrhagic strain, which have caused several outbreaks in food and water samples. A 2.7-fold sensitivity enhancement was attained with a detection limit of 603 colony-forming units (CFU) /mL, when employing the magnetic actuator. | 25,190,010 | [
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Promoter polymorphisms of miR-34b/c are associated with risk of gastric cancer in a Chinese population. | More and more evidence reveals that noncoding RNA miR-34b/c and tumor suppressor gene TP-53 independently, and/or jointly, play crucial roles in carcinogenesis. The purpose of the present hospital-based case-control study was to investigate the association between the miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms and the risk of gastric cancer. Two polymorphisms were genotyped in 419 gastric cancer patients and 402 age- and sex-matched cancer-free controls using polymerase chain reaction-restriction fragment length polymorphism analysis. The CC genotype and C allele of the miR-34b/c rs4938723 were associated with a significantly decreased risk of gastric cancer compared with the TT genotype and T allele (CC vs. TT: P = 0.006, adjusted odds ratio (OR) = 0.53, 95 % confidence interval (95 % CI) = 0.34-0.83; C vs. T: P = 0.005, adjusted OR = 0.75, 95 % CI = 0.61-0.92). Compared with individuals with the wild-type TT genotype, subjects with the variant genotypes (CT + CC) had a significantly decreased risk of gastric cancer (P = 0.047, adjusted OR = 0.75, 95 % CI = 0.57-0.99). Stratified analysis showed that the association between the risk of gastric cancer and the variant genotypes of miR-34b/c was more profound among men. However, no overall association was found between the TP53 Arg72Pro polymorphism and gastric cancer risk. In the combined analysis, no effects of the interaction of miR-34b/c rs4938723 and TP53Arg72Pro on gastric cancer risk were observed. Our findings indicate that the miR-34b/c rs4938723 CT/CC genotypes may be associated with a decreased risk of gastric cancer and the C allele may be a protective factor in gastric cancer. | 25,190,020 | [
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Corneal biomechanical properties in 3 corneal transplantation techniques with a dynamic Scheimpflug analyzer. | To compare the corneal biomechanical properties of eyes that have undergone penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), and Descemet stripping automated endothelial keratoplasty (DSAEK). This case-control study comprised 20 post-PK eyes, 14 post-DALK eyes, 15 post-DSAEK eyes, and 50 normal control eyes. A dynamic Scheimpflug analyzer (the Corvis ST) was used to evaluate the corneal biomechanical properties including deformation amplitude (DA) and radius at the highest concavity (R hc). In post-PK eyes, the mean DA was 1.20 ± 0.13 mm, which was significantly higher than those of the control eyes (1.07 ± 0.09) and the post-DSAEK eyes (1.08 ± 0.12). The DA (1.18 ± 0.18) in the post-DALK eyes was significantly higher than in the control eyes. The R hc in the post-PK (6.34 ± 0.37 mm), -DALK (6.04 ± 1.22), and -DSAEK (6.44 ± 0.58) eyes was significantly smaller than in the control eyes (7.57 ± 0.78). The dynamic Scheimpflug analyzer provides a method to obtain new biomechanical information on the cornea such as the DA and R hc, and these parameters differed among eyes that had undergone 3 different types of corneal surgery. Abnormalities in these parameters after the different corneal transplantation techniques may indicate larger deviations in the stress-strain reaction of the cornea and more uncertainty in the intraocular pressure measurements than in normal eyes. | 25,190,024 | [
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Barriers in asthma care for pediatric patients in primary care. | There are many barriers to treating children with asthma. Barriers limit access with subsequent disturbances in quality outcomes. This study explored the difference in quality outcomes, utilization outcomes, parental knowledge, and barriers to care between children who had controlled versus uncontrolled asthma. Data were analyzed between two intact groups of caregivers of children with asthma. Caregivers in both groups completed the Asthma Knowledge Test and the Asthma Barrier Questionnaire. Caregivers (n = 62) were primarily mothers (85.5%). Children with uncontrolled asthma missed 33.3% more days of school. The caregivers of the children with controlled asthma answered more questions on the Asthma Knowledge Test correctly and had a lower score on the Asthma Barrier Questionnaire. Asthma control is essential. By identifying barriers to care, health care providers can build an action care plan to individualize each patient's needs. | 25,190,036 | [
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Phosphoproteome and proteome analyses reveal low-phosphate mediated plasticity of root developmental and metabolic regulation in maize (Zea mays L.). | Phosphate (Pi) deficiency has become a significant challenge to worldwide agriculture due to the depletion of accessible rock phosphate that is the major source of cheap Pi fertilizers. Previous research has identified a number of diverse adaptive responses to Pi starvation in the roots of higher plants. In this study, we found that accelerated axile root elongation of Pi-deprived maize plants resulted from enhanced cell proliferation. Comparative phosphoproteome and proteome profiles of maize axile roots were conducted in four stages in response to Pi deficiency by multiplex staining of high-resolution two dimensional gel separated proteins. Pro-Q DPS stained gels revealed that 6% of phosphoprotein spots displayed changes in phosphorylation state following low-Pi treatment. These proteins were involved in a large number of metabolic and cellular pathways including carbon metabolism and signal transduction. Changes in protein abundance of a number of enzymes indicated that low-Pi induced a number of carbon flux modifications in metabolic processes including sucrose breakdown and other downstream sugar metabolic pathways. A few key metabolic enzymes, including sucrose synthase (EC 2.4.1.13) and malate dehydrogenase (EC 1.1.1.37), and several signaling components involved in protein kinase or phosphatase cascades, auxin signaling and 14-3-3 proteins displayed low-Pi responsive changes in phosphorylation state or protein abundance. A variety of key enzymes and signaling components identified as potential targets for phosphorylation provide novel clues for comprehensive understanding of Pi regulation in plants. Protein phosphorylation, coordinating with changes in protein abundance, is required for maize root metabolic regulation and developmental acclimation to Pi starvation. | 25,190,054 | [
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Early myocardial and skeletal muscle interstitial remodelling in systemic sclerosis: insights from extracellular volume quantification using cardiovascular magnetic resonance. | Systemic sclerosis (SSc) may induce cardiac fibrosis and systo-diastolic dysfunction. Cardiovascular magnetic resonance (CMR) can detect replacement myocardial fibrosis with late gadolinium enhancement (LGE) and interstitial myocardial fibrosis with T1 mapping techniques. The aim of the study was to detect subclinical cardiac involvement with CMR in paucisymptomatic SSc patients with no previous history of myocardial disease, comparing it with skeletal muscle remodelling. Thirty consecutive SSc patients (mean age: 51 ± 12 years, all women) and 10 healthy controls (mean age: 48 ± 15 years, all women) underwent clinical, biohumoral assessment, and CMR. Extracellular volume fraction (ECV) was calculated from pre- and post-contrast T1 values in the myocardium and skeletal muscle. Seventeen patients (57%) were asymptomatic, 13 (43%) paucisymptomatic (effort dyspnoea). All patients had normal biventricular volumes and systolic function, while LGE was present in seven patients (23%). Myocardial ECV was significantly increased in patients with SSc (30 ± 4%) than controls (28 ± 4%, P = 0.03), as was skeletal muscle ECV (23 ± 6% vs. 18 ± 4%, P < 0.01). Myocardial ECV did not differ between patients with and without LGE (P = NS) and showed no significant correlations with clinical data, biventricular volumes, systolic, or diastolic function. Overall, myocardial ECV showed a significant correlation with skeletal muscle ECV (R = 0.58, P < 0.001). SSc is associated not only with myocardial replacement fibrosis, as detected by LGE, but also with interstitial remodelling of the myocardium and skeletal muscles, as detected by an increased ECV also in patients with normal biventricular function, with potential diagnostic, prognostic, and therapeutic clinical implications. | 25,190,071 | [
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Fluorescent gold nanoclusters based photoelectrochemical sensors for detection of H2O2 and glucose. | In this work, low-toxicity fluorescent gold nanoclusters (AuNCs) based photoelectrochemical sensors were developed for H2O2 and glucose detection. Herein, the processes used to fabricate the sensors and the photoelectrochemical performances of the sensors under different conditions were presented. Based on the energy band levels of the AuNCs and electron tunneling processes, a detailed photoelectrochemical sensing model was given. The designed sensors were then used for H2O2 and glucose detection without any extra modification of the AuNCs or complex enzyme immobilization. The results demonstrate that the AuNCs allow for H2O2 sensing based on their capacity for both fluorescence and catalysis. Indeed, it was observed that H2O2 was catalyzed by the AuNCs and reduced by photoinduced electrons derived from excited AuNCs. Furthermore, an enhancement in photocurrent amplitude followed the increase in the concentrations of H2O2 and glucose. The effects of the types of ligands surrounding the AuNCs and the applied potential on the output photocurrent were well studied to optimize the measurement conditions. The sensitivity and LOD of MUA-AuNCs at -500 mV were 4.33 nA/mM and 35 μM, respectively. All experimental results indicated that AuNCs could not only serve as a promising photoelectrical material for building the photoelectrochemical biosensors but as catalysts for H2O2 sensing. | 25,190,086 | [
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Molecular pathophysiology of metabolic effects of antipsychotic medications. | Antipsychotic medications are associated with major metabolic changes that contribute to medical morbidity and a significantly shortened life span. The mechanisms for these changes provide us with a broader understanding of central nervous and peripheral organ-mediated metabolic regulation. This paper reviews an extensive literature regarding putative mechanisms for effects of antipsychotic medications on weight regulation and glucose homeostasis as well as potential inherent metabolic risks of schizophrenia itself. We present a model suggesting that peripheral antipsychotic targets play a critical role in drug-induced weight gain and diabetes. We propose that a better understanding of these mechanisms will be crucial to developing improved treatments for serious mental illnesses as well as providing potentially novel therapeutic targets of metabolic disorders including diabetes. | 25,190,097 | [
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Nuclear ING2 expression is reduced in osteosarcoma. | Osteosarcoma is a high-grade malignant bone tumor. Loss of inhibitor of growth 2 (ING2) expression has been demonstrated in numerous types of cancers. However, no study has shown the relationship between ING2 expression and osteosarcoma. In the present study, we confirmed that the levels of ING2 mRNA and protein were lower in cancer tissues than these levels in normal tissues. Loss of nuclear ING2 protein was significantly associated with a decreased survival time of patients. Osteosarcoma cells were transfected with ING2 protein without a nuclear localization signal or intact ING2 protein to examine the effects of exogenous expression of ING2 in vitro. Compared to the control cells, intact ING2-expressing cells exhibited increased apoptosis, G1 phase arrest and senescence. Taken together, these results suggest that ING2 acts as a tumor suppressor in osteosarcoma. | 25,190,103 | [
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[A family with two children diagnosed with aspartylglucosaminuria-case report and literature review]. | The authors sought to investigate the clinical features and characteristics of genetic mutation in patients with aspartylglucosaminuria. Clinical data of two pediatric siblings in a family were analyzed retrospectively and relative literature was reviewed in order to study the clinical features, imaging and enzymatic characteristics and genetic mutations. Case 1, the proband, male, he was hospitalized at 20 months of age because of fever and hepatosplenomegaly for nine days. This child was of moderate nutritional status and normal development. Blood tests showed hemoglobin 78.0 g/L, RBC3.18 × 10¹²/L, WBC 4.06 × 10⁹/L, neutrophils 0.236, lymphocytes 0.631, platelets 34 × 10⁹/L, C-reactive protein 17 mg/L. Blood biochemistry showed alanine aminotransferase 67.1 U/L, aspartate aminotransferase 74.1 U/L, serum albumin 32.8 g/L, direct bilirubin 10.5 µmol/L, lactate dehydrogenase 301.7 U/L. Bone marrow cytology showed reactive morphological changes in bone marrow cells. Atypical lymphocytes could be seen in both peripheral blood and bone marrow smears. Cranial MRI showed poor myelination. Aspartylglucosaminidase activity in peripheral leucocytes of the proband 5.7 nmol/(g × min) vs. normal control>26.6 nmol/(g × min). On his AGA gene and that of his parents, a heterozygous mutation site located in exon 3, c.392C>T (p.S131L), was identified as a novel mutation inherited from his father. The mutation from his mother has not been detected. The proband was not responsive to the anti-infectious medication, nutritional intervention and symptomatic treatment.He died one month after diagnosis.His elder brother, Case 2, showed fever, recurrent respiratory tract infection and progressive psychomotor regression with hepatosplenomegaly from the age of four years. Cranial MRI revealed extensive symmetrical leukodystrophy in bilateral cerebra, cerebellum and brainstem.He died at the age of six years.Related literature was summarized, and no Chinese AGU cases had been reported; 221 foreign cases were collected. The clinical and imaging characteristics were summarized. Delay in language development was one of the clinical symptoms that the majority of parents of AGU children first noted. Patients with aspartylglucosaminuria lack of specific symptoms.For children with unexplained delayed speech and progressive mental retardation, the possibility of AGU should be considered, and efforts be made for enzymatic and genetic diagnosis. c.392C> T (p.S131L) was identified as a novel mutation of AGA gene. | 25,190,167 | [
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[Cardiac catheterization and pulmonary vasoreactivity testing in children with idiopathic pulmonary arterial hypertension]. | As an important method of hemodynamic assessment in idiopathic pulmonary arterial hypertension (IPAH), cardiac catheterization combined with pulmonary vasoreactivity testing remains with limited experience in children, and the acute pulmonary vasodilator agents as well as response criteria for vasoreactivity testing remain controversial. The aim of this study was to investigate the clinical importance, agent selection, and responder definition of cardiac catheterization combined with pulmonary vasoreactivity testing in pediatric IPAH. The patients admitted to Department of Pediatric Cardiology of Beijing Anzhen Hospital between April 2009 and September 2013 with suspected IPAH, under 18 years of age, with WHO functional class II or III, were enrolled. All the patients were arranged to receive left and right heart catheterization and pulmonary vasoreactivity testing with inhalation of pure oxygen and iloprost (PGI2) respectively. Hemodynamic changes were analyzed, and two criteria, the European Society of Cardiology recommendation criteria (Sitbon criteria) and traditional application criteria (Barst criteria), were used to evaluate the test results. Thirty-nine cases of children with suspected IPAH underwent cardiac catheterization. In 4 patients IPAH was excluded; 4 patients developed pulmonary hypertension crisis. The other 31 patients received standard cardiac catheterization and pulmonary vasoreactivity testing. Baseline mean pulmonary artery pressure (mPAP) was (66 ± 16) mmHg (1 mmHg = 0.133 kPa), and pulmonary vascular resistance index (PVRI) (17 ± 8) Wood U · m². After inhalation of pure oxygen, mPAP fell to (59 ± 16) mmHg, and PVRI to (14 ± 8) Wood U · m² (t = 4.88 and 4.56, both P < 0.001) . After inhalation of PGI2, mPAP fell to (49 ± 21) mmHg, and PVRI to (12 ± 9) Wood U · m² (t = 7.04 and 6.33, both P < 0.001). According to the Sitbon criteria, the proportion of pure oxygen responders was 6.5% (3/31) , while PGI2 responders was 35.5%, and the difference was significant (P = 0.004). According to the Barst criteria, the proportion of pure oxygen responders was 16.1% (5/31), while PGI2 responders was 51.6% (16/31), and the difference was significant (χ² = 0.09, P = 0.001). For children with IPAH, cardiac catheterization combined with pulmonary vasoreactivity testing has important value in differential diagnosis, severity estimation, and treatment (including the emergency treatment) choices. Pulmonary hypertension crisis is an important complication of cardiac catheterization in pediatric IPAH. Younger age, general anesthesia, crisis history, and poor heart function are important risk factors for pulmonary hypertension crisis. PGI2 is a relatively ideal agent for vasoreactivity testing in children with IPAH, which has more responders than traditionally used pure oxygen. of responders are not completely consistent using different criteria, and comprehensive evaluation should be done according to the goals of treatment in clinical practice. | 25,190,170 | [
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Pharmacovigilance: empowering healthcare professionals and patients. | The European Union has thoroughly reformed its pharmacovigilance legislation in July 2012. Despite the changes, underreporting of adverse drug reactions remains a concern. This underreporting seems to be partially associated with incorrect customs and beliefs by healthcare professionals. Therefore, strengthening teaching and training in drug safety monitoring and reporting are essential. Sustained campaigns and education on pharmacovigilance are key elements to enhance its performance and effectiveness. In general, all healthcare professionals as well as patients should be more sensitized and empowered to contribute to pharmacovigilance programmes in order to improve drug safety. | 25,190,178 | [
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Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes. | The objectives of this study were to: (1) determine the amniotic fluid (AF) microbiology of patients with preterm prelabor rupture of membranes (PROM); and (2) examine the relationship between intra-amniotic inflammation with and without microorganisms (sterile inflammation) and adverse pregnancy outcomes in patients with preterm PROM. AF samples obtained from 59 women with preterm PROM were analyzed using cultivation techniques (for aerobic and anaerobic bacteria as well as genital mycoplasmas) and with broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). AF concentration of interleukin-6 (IL-6) was determined using ELISA. Results of both tests were correlated with AF IL-6 concentrations and the occurrence of adverse obstetrical/perinatal outcomes. (1) PCR/ESI-MS, AF culture, and the combination of these two tests each identified microorganisms in 36% (21/59), 24% (14/59) and 41% (24/59) of women with preterm PROM, respectively; (2) the most frequent microorganisms found in the amniotic cavity were Sneathia species and Ureaplasma urealyticum; (3) the frequency of microbial-associated and sterile intra-amniotic inflammation was overall similar [ 29% (17/59)]: however, the prevalence of each differed according to the gestational age when PROM occurred; (4) the earlier the gestational age at preterm PROM, the higher the frequency of both microbial-associated and sterile intra-amniotic inflammation; (5) the intensity of the intra-amniotic inflammatory response against microorganisms is stronger when preterm PROM occurs early in pregnancy; and (6) the frequency of acute placental inflammation (histologic chorioamnionitis and/or funisitis) was significantly higher in patients with microbial-associated intra-amniotic inflammation than in those without intra-amniotic inflammation [93.3% (14/15) versus 38% (6/16); p = 0.001]. (1) The frequency of microorganisms in preterm PROM is 40% using both cultivation techniques and PCR/ESI-MS; (2) PCR/ESI-MS identified microorganisms in the AF of 50% more women with preterm PROM than AF culture; and (3) sterile intra-amniotic inflammation was present in 29% of these patients, and it was as or more common than microbial-associated intra-amniotic inflammation among those presenting after, but not before, 24 weeks of gestation. | 25,190,175 | [
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Nanosecond electric pulses: a mini-review of the present state of the art. | Nanosecond electric pulses (nsEPs) are defined as very short high intensity electric pulses which present great potential for the destabilization of intracellular structures. Their theoretical descriptions first suggested specific effects on organelles that have been confirmed by various observations both in vitro and in vivo. However, due to their concomitant effects on the plasma membrane, nsEPs can also affect cell functions. In this mini-review, nsEP effects on cells are described following three topics: effects at the plasma membrane level, intracellular effects, and the impact on cell survival. Eventually, a short description of the major results obtained in vivo will be presented. This study shows that the use of nsEPs has evolved during the last decade to focus on low voltage for practical applications. | 25,190,180 | [
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Association between disease activity and risk of serious infections in subjects with rheumatoid arthritis treated with etanercept or disease-modifying anti-rheumatic drugs. | To determine the risk of serious infection in patients with rheumatoid arthritis (RA) receiving etanercept (ETN) or disease-modifying anti-rheumatic drugs (DMARDs) and to identify factors that predict a higher risk. Five-year data from the British Society of Rheumatology Biologics Register (BSRBR), a prospective observational study of patients with active RA treated with ETN, were used. These data were compared with a cohort of patients receiving DMARDs with active RA. Total follow-up was 19,964 patient-years (py; ETN, 14,381 py; DMARDs, 5583 py). Over the study period, 651 first-recorded serious infections were reported (ETN, 469 [39.9 per 1000 py]; DMARDs, 182 [35.0 per 1000 py]). Overall the risk of serious infection was similar for the 2 treatments; however, in the first 6 months of treatment the hazard ratio (HR) was higher in the ETN than the DMARD group (1.979; p=0.015). A linear association was observed between the serious infection rate and disease-activity score in 28 joints (DAS28) in patients from each treatment group and overall (DAS28 <4, 27.1 per 1000 py; DAS28 ≥8, 64.4 per 1000 py; 7.5% increase in serious infection for each unit increase of DAS28 score at baseline). In a time-dependent analysis, a DAS28 change of 1 unit during follow-up predicted a 27% increase in serious infection rates. No significant increase in the risk of serious infection was observed with ETN versus DMARDs over the 5-year study; a linear relationship existed between the serious infection rate and disease activity, as measured by DAS28. | 25,190,189 | [
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Stabilization of a recombinant human epidermal growth factor parenteral formulation through freeze-drying. | Development studies were performed to design a pharmaceutical composition that allows the stabilization of a parenteral rhEGF formulation in a lyophilized dosage form. Unannealed and annealed drying protocols were tested for excipients screening. Freeze-dry microscopy was used as criterion for excipients and formulation selection; as well as to define freeze-drying parameters. Excipients screening were evaluated through their effect on freeze-drying recovery and dried product stability at 50 °C by using a comprehensive set of analytical techniques assessing the chemical stability, protein conformation and bioactivity. The highest stability of rhEGF during freeze-drying was achieved by the addition of sucrose or trehalose. After storing the dried product at 50 °C, the highest stability was achieved by the addition of dextran, sucrose, trehalose or raffinose. The selected formulation mixture of sucrose and dextran could prevent protein degradation during the freeze-drying and delivery processes. The degradation rate assessed by RP-HPLC could decrease 100 times at 37 °C and 70 times at 50 °C in dried with respect to aqueous formulation. These results indicate that the freeze-dried formulation represents an appropriate technical solution for stabilizing rhEGF. | 25,190,208 | [
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Sleep disorders increase the risk of burning mouth syndrome: a retrospective population-based cohort study. | Sleep disorders (SD), including apnea and nonapnea, and burning mouth syndrome (BMS) have been mutually associated with systemic diseases. Based on our research, the association between BMS and SD has not been elucidated. We determined whether SD patients have an increased risk of BMS. We used information from health insurance claims obtained from the Taiwanese National Health Insurance (NHI) program. We identified patients newly diagnosed with sleep apnea syndrome between 1998 and 2001 as the apnea SD cohort, and newly diagnosed patients with nonapnea SD as the nonapnea SD cohort. The non-SD cohort was 1:2 frequency matched the case group according to sex, age, and index year. We analyzed the risks of BMS by using Cox proportional hazards regression models. Compared with the non-SD cohort, both of the apnea SD (adjusted HR = 2.56, 95% CI = 1.30-5.05) and nonapnea SD (adjusted HR = 2.89, 95% CI = 2.51-3.34) were associated with a significantly higher risk of BMS. The hazard ratio (HR) increased with increased age in the apnea SD cohort and in the nonapnea SD cohort compared with patients younger than 40 years of age. Female apnea SD patients (IRR = 4.63, 95% CI = 3.82-5.61) had a higher risk of developing BMS than did male patients (IRR = 1.76, 95% CI = 1.39-2.24). Based on our research, SD might increase the risk of BMS. | 25,190,261 | [
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A validated high-performance liquid chromatography method for determination of tannin-related marker constituents gallic acid, corilagin, chebulagic acid, ellagic acid and chebulinic Acid in four Terminalia species from India. | A validated rapid HPLC-PDA method was developed for identification and quantification of five tannin-related constituents gallic acid (GA), corilagin (CL), chebulagic acid (CB), ellagic acid (EA) and chebulinic acid (CN) in the extracts prepared from the bark and fruits of four Terminalia species available in India. The separation of the five analytes was achieved on an RP-18 column (4.6 × 250 mm, 5 µm) at 25°C using a solvent mixture comprising of acetonitrile and (0.05%) trifluoroacetic acid-water in a gradient elution mode. Limit of detection was 1.0, 0.5, 1.0, 0.5 and 1.0 μg/mL for GA, CL, CB, EA and CN, respectively. Similarly, limit of quantification was 2.5, 1.0, 2.5, 1.0 and 2.5 μg/mL for GA, CL, CB, EA and CN, respectively. Good linearity (r(2) > 0.992) was observed for all the five compounds in wide concentration range. Using the developed HPLC method, the five analytes were identified and quantified in bark and fruit extracts of Terminalia chebula, Terminalia bellirica, Terminalia arjuna and Terminalia catappa. This is the first report of identification and quantification of the five tannin-related marker constituents in the bark and fruit extracts of T. chebula, T. bellirica, T. arjuna and T. catappa. | 25,190,275 | [
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Larvicidal efficacy of Cryptomeria japonica leaf essential oils against Anopheles gambiae. | Alternative insecticidal compounds with mortality effect against mosquito life cycle stages are currently needed. The compounds should be biodegradable and nontoxic to non-targeted insects. Plant based larvicides provide effective control of vector populations. This study explored Cryptomeria japonica leaf essential oil larvicidal potency against Anopheles gambiae sensu stricto. Essential oils (12.5 to 200 μg/mL) extracted from C. japonica leaves were evaluated against An. gambiae s.s. larvae in both the laboratory and semi field in 6 replicates for each dose. Larval mortality readings were taken at 12, 24, 48, and 72 h post treatment. C. japonica leaf essential oil yield was 17.06 ± 0.56 mL/kg and 1.60 ± 0.33% (w/w). GC-FID and GC-MS analyses revealed 22 constituents. Essential oil was more effective against An. gambiae s.s. larvae in the laboratory than in semi field trials. Mortality increased with increasing dosages (12.5 to 200 μg/mL) in the laboratory (31.75 to 100%) and semi field trials (17.75 to 99.5%), respectively. The LC50 value ranged from 5.55 to 63.92 μg/mL in the laboratory, and 8.22 to 134.84 μg/mL in semi field conditions, LC90 value ranged from 41.34 to 205.93 μg/mL in the laboratory and 50.92 to 213.11 μg/mL in semi field conditions. This study has demonstrated the potential of C. japonica leaf essential oil to cause mortality effects to An. gambiae s. s. larval populations, however, further studies need to be conducted under field conditions and also with individual active compounds of C. japonica essential oil. | 25,190,294 | [
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[Review and expert opinion in age related macular degeneration. Focus on the pathophysiology, angiogenesis and pharmacological and clinical data]. | Age related macular degeneration (AMD) is a pathological aging of the macula, brought about by the interaction of genetic and environmental factors. It induces geographic atrophy of the retina and/or choroidal neovascularization. In the latter, abnormal vessels develop from the choriocapillaris, with the involvement of VEGF (vascular endothelial growth factor). The VEGF family includes several factors, including VEGF-A, B, C, D, F and PlGF (placental growth factor). Their biological properties and their affinities to the VEGFR1, VEGFR2 and VEGFR3 receptors found on endothelial cells differ. Exudative AMD involves mainly VEGF-A and VEGF-R2. Anti-VEGF agents used in ophthalmology (ranibizumab, bevacizumab and aflibercept) are designed to primarily target this pathway. In vitro, all have sufficient affinity to their ligands. Their therapeutic efficacy must therefore be judged based on clinical criteria. In clinical practice, the minimum number of injections required for a satisfactory result appears to be comparable with all the three. The few available studies on therapeutic substitutions of anti-VEGF compounds suggest that some patients may benefit from substituting the anti-VEGF in cases of an unsatisfactory response to an initial molecule. Although local side effects, including increased risk of geographic atrophy, and systemic effects, including vascular accidents, have been suggested, these risks remain low, specially compared to the benefits of the treatment. Differences in safety between anti-VEGF are theoretically possible but unproven. | 25,190,312 | [
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XAV939 promotes apoptosis in a neuroblastoma cell line via telomere shortening. | Telomeres, telomerase and tankyrase (TNKS) have an extremely important and special association with human cell aging and cancer. Telomerase activity is abnormally high in cancer cells and is accompanied by the overexpression of tankyrase 1 (TNKS1). TNKS1 is a positive regulator of telomerase activation and telomere extension in the human body, indicating that TNKS1 may be a possible therapeutic target for cancer. XAV939 is a small-molecule inhibitor of TNKS1. The objective of the present study was to investigate the apoptotic effect of XAV939 on the neuroblastoma (NB) SH-SY5Y cell line, as well as the change in telomere length and telomerase activity and elucidate the mechanism from this perspective. In the present study, we initially treated SH-SY5Y cells with XAV939 and RNA interference (RNAi)-TNKS1, and subsequently chose the optimal sequence for RNAi-TNKS1. We then measured the telomere length using quantitative real-time polymerase chain reaction (qPCR) assay, detected the telomerase activity using the ELISA kit, observed apoptotic morphology by transmission electron microscopy, and detected the percentages of apoptotic cells using flow cytometry and Hoechst 33342 staining. We also determined the invasive ability by a cell invasion assay. The results showed that short hairpin RNA-2 (shRNA-2) was the optimal sequence for RNAi-TNKS1. Treatment with both XAV939 and RNAi-TNKS1 shortened the telomere length, promoted apoptosis and reduced the invasive ability of the SH-SY5Y cells, yet had no effect on telomerase activity. XAV939 promoted apoptosis and reduced the invasiveness of SH-SY5Y cells dependent on telomere shortening, and further research should be conducted to clarify the exact mechanisms. This research may contribute to the cure of malignant NB using multi-targeted therapy with small-molecule agents. | 25,190,315 | [
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The cued recognition task: dissociating the abrupt onset effect from the social and arrow cueing effect. | In a standard center cueing paradigm, participants are asked to identify a target object presented either to the left or the right of a center cue (e.g., eye gaze, head-turn, arrow, etc.). When the center cue is non-predictive (e.g., the arrow points to the correct location of the target only 50 % of the time), the target can still be identified faster at the validly cued location than at the invalidly cued location. However, the abrupt onset of an object can elicit reflexive attention orientation. It is important to investigate whether this abrupt onset effect interferes with the cueing effect elicited by center cues because this interference effect, if it exists, should be controlled for in order to improve the test validity of the center cueing task. In an attentional cueing paradigm, we examined how the abrupt appearance of an exogenous target object mitigates the influence of center cues involving either a head turn (Experiment 1) or an arrow (Experiment 2). In Experiment 1, a non-predictive head-turn cue was followed by a target object (circle or square) presented in the left or right visual field. In the non-distractor condition, the target object was presented by itself. In this case, it is assumed that the sudden appearance of the target provides an orienting cue to the observer. To equalize the cueing effect of the target object, we presented a competing distractor object (triangle) in the opposite visual field to the target object. The participant's task was to categorize the target object as either a circle or square while ignoring the non-target triangle object in the opposite visual field. In Experiment 2, the arrow version of the cued recognition task was used, in which a single-headed arrow pointed to the object. The results from both experiments showed that both the non-predictive head-turn and arrow cues produced a reliable cueing effect in the distractor and non-distractor conditions. However, the magnitude of the cueing effect was greater in the distractor condition than in the non-distractor condition, suggesting that the abrupt onset of the target object acts like an exogenous signal, thereby reducing the impact of the internal head turn and arrow cues. | 25,190,323 | [
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Trends in preterm birth in singleton deliveries in a Hong Kong population. | To examine trends in preterm birth and its relationship with perinatal mortality in Hong Kong. In a retrospective cohort study, data were reviewed from singletons delivered between 1995 and 2011 at a university teaching hospital. Trends in preterm birth (between 24 and 36 weeks of pregnancy), perinatal mortality, and subtypes of preterm birth (spontaneous, iatrogenic, and following preterm premature rupture of membranes [PPROM]) were examined via linear regression. There were 103 364 singleton deliveries, of which 6722 (6.5%) occurred preterm, including 1835 (1.8%) early preterm births (24-33 weeks) and 4887 (4.7%) late preterm births (34-36 weeks). Frequency of preterm birth remained fairly consistent over the study period, but that of spontaneous preterm birth decreased by 25% (β=-0.83; P<0.001), from 4.5% to 3.8%. Frequency of preterm birth following PPROM increased by 135% (β=0.82; P<0.001), from 0.7% to 1.7%. The perinatal mortality rate decreased from 56.7 to 37.0 deaths per 1000 deliveries before 37 weeks (β=-0.16; P=0.54). Early preterm birth contributed to 16.0% of all deaths. Although the overall rate of preterm birth in Hong Kong has remained constant, the frequencies of its subtypes have changed. Overall perinatal mortality is gradually decreasing, but early preterm birth remains a major contributor. | 25,190,352 | [
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MiR-152 suppresses the proliferation and invasion of NSCLC cells by inhibiting FGF2. | MicroRNAs (miRNAs) regulate the proliferation and metastasis of cancer cells. Here, we showed that miR-152 was downregulated in non-small-cell lung cancer (NSCLC) tissues and cell lines. Overexpression of miR-152 suppressed cell proliferation and colony formation and also limited migration and invasion. Fibroblast growth factor 2 (FGF2) was confirmed as a direct target of miR-152. FGF2 knockdown suppressed cell proliferation, colony formation, migration and invasion, whereas FGF2 overexpression partially reversed the suppressive effect of miR-152. Furthermore, the presence of miR-152 was inversely correlated with FGF2 in NSCLC tissues. Overall, this study demonstrated that miR-152 suppressed the proliferation and invasion of NSCLC cells by downregulating FGF2. These findings provide novel insights with potential therapeutic applications for the treatment of NSCLC. | 25,190,353 | [
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Growth, cadmium uptake and accumulation of maize (Zea mays L.) under the effects of arbuscular mycorrhizal fungi. | The effects of three arbuscular mycorrhizal fungi isolates on Cd uptake and accumulation by maize (Zea mays L.) were investigated in a planted pot experiment. Plants were inoculated with Glomus intraradices, Glomus constrictum and Glomus mosseae at three different Cd concentrations. The results showed that root colonization increased with Cd addition during a 6-week growth period, however, the fungal density on roots decreased after 9-week growth in the treatments with G. constrictum and G. mosseae isolates. The percentage of mycorrhizal colonization by the three arbuscular mycorrhizal fungi isolates ranged from 22.7 to 72.3%. Arbuscular mycorrhizal fungi inoculations decreased maize biomass especially during the first 6-week growth before Cd addition, and this inhibitory effect was less significant with Cd addition and growth time. Cd concentrations and uptake in maize plants increased with arbuscular mycorrhizal fungi colonization at low Cd concentration (0.02 mM): nonetheless, it decreased at high Cd concentration (0.20 mM) after 6-week growth period. Inoculation with G. constrictum isolates enhanced the root Cd concentrations and uptake, but G. mosseae isolates showed the opposite results at high Cd concentration level after 9 week growth period, as compared to non-mycorrhizal plants. In conclusion, maize plants inoculated with arbuscular mycorrhizal fungi were less sensitive to Cd stress than uninoculated plants. G. constrictum isolates enhanced Cd phytostabilization and G. mosseae isolates reduced Cd uptake in maize (Z. mays L.). | 25,190,357 | [
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The Opposites Attract Study of viral load, HIV treatment and HIV transmission in serodiscordant homosexual male couples: design and methods. | Studies in heterosexual HIV serodiscordant couples have provided critical evidence on the role of HIV treatments and undetectable viral load in reducing the risk of HIV transmission. There is very limited data on the risk of transmission from anal sex in homosexual male serodiscordant couples. The Opposites Attract Study is an observational prospective longitudinal cohort study of male homosexual serodiscordant partnerships running from 2012 to 2015 and conducted in clinics throughout Australia, Brazil and Thailand. Couples attend two or more clinic visits per year. The HIV-positive partner's viral load is tested and the HIV-negative partner is tested for HIV antibodies at every clinic visit. Results from any tests for sexually transmitted infections are also collected. Detailed behavioural questionnaires are completed by both partners at the time of each visit. The primary research question is whether HIV incidence is lower in those couples where the HIV-positive partner is receiving HIV treatment compared to couples where he is not receiving treatment. A voluntary semen sub-study will examine semen plasma viral load in a subsample of HIV-positive partners in Sydney, Rio de Janeiro and Bangkok. In cases of seroconversion of the initially HIV-negative partner, phylogenetic analysis will be conducted at the end of the study on virus from stored blood samples from both partners to determine if the infection came from the HIV-positive study partner. Men in new serodiscordant relationships will specifically be targeted for recruitment. This study will provide critical data on the reduction in HIV transmission risk associated with being on HIV treatment in homosexual male serodiscordant couples in different regions of the world. Data from men in new relationships will be particularly valuable given that the highest transmission risk is in the first year of serodiscordant relationships. Furthermore, the detailed behavioural and attitudinal data from the participant questionnaires will allow exploration of many contextual factors associated with HIV risk, condom use and the negotiation of sexual practice within couples. | 25,190,360 | [
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Optimal shaping of acoustic resonators for the generation of high-amplitude standing waves. | Within this paper, optimal shaping of acoustic resonators for the generation of high-amplitude standing waves through the use of evolutionary algorithms is discussed. The resonator shapes are described using sets of control points interconnected with cubic-splines. Positions of the control points are calculated by means of an evolutionary algorithm in order to maximize acoustic pressure amplitude at a given point of the resonator cavity. As an objective function for the optimization procedure, numerical solution of one-dimensional linear wave equation taking into account boundary-layer dissipation is used. Resonator shapes maximizing acoustic pressure amplitude are found in case of a piston, shaker, or loudspeaker driving. It is shown that the optimum resonator shapes depend on the method of driving. In all the cases, acoustic field attains higher amplitude in the optimized resonators than in simple-shaped non-optimized resonators of similar dimensions. Theoretical results are compared with experimental data in the case of a loudspeaker driving, good agreement of which is achieved. | 25,190,376 | [
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Potential-based methodology for active sound control in three dimensional settings. | This paper extends a potential-based approach to active noise shielding with preservation of wanted sound in three-dimensional settings. The approach, which was described in a previous publication [Lim et al., J. Acoust. Soc. Am. 129(2), 717-725 (2011)], provides several significant advantages over conventional noise control methods. Most significantly, the methodology does not require any information including the characterization of sources, impedance boundary conditions and surrounding medium, and that the methodology automatically differentiates between the wanted and unwanted sound components. The previous publication proved the concept in one-dimensional conditions. In this paper, the approach for more realistic conditions is studied by numerical simulation and experimental validation in three-dimensional cases. The results provide a guideline to the implementation of the active shielding method with practical three-dimensional conditions. Through numerical simulation it is demonstrated that while leaving the wanted sound unchanged, the developed approach offers selective volumetric noise cancellation within a targeted domain. In addition, the method is implemented in a three-dimensional experiment with a white noise source in a semi-anechoic chamber. The experimental study identifies practical difficulties and limitations in the use of the approach for real applications. | 25,190,385 | [
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Cylindrical acoustical holography applied to full-scale jet noise. | Near-field acoustical holography methods are used to predict sound radiation from an engine installed on a high-performance military fighter aircraft. Cylindrical holography techniques are an efficient approach to measure the large and complex sound fields produced by full-scale jets. It is shown that a ground-based, one-dimensional array of microphones can be used in conjunction with a cylindrical wave function field representation to provide a holographic reconstruction of the radiated sound field at low frequencies. In the current work, partial field decomposition methods and numerical extrapolation of data beyond the boundaries of the hologram aperture are required prior to holographic projection. Predicted jet noise source distributions and directionality are shown for four frequencies between 63 and 250 Hz. It is shown that the source distribution narrows and moves upstream, and that radiation directionality shifts toward the forward direction, with increasing frequency. A double-lobe feature of full-scale jet radiation is also demonstrated. | 25,190,387 | [
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Perception and automatic detection of wind-induced microphone noise. | Wind can induce noise on microphones, causing problems for users of hearing aids and for those making recordings outdoors. Perceptual tests in the laboratory and via the Internet were carried out to understand what features of wind noise are important to the perceived audio quality of speech recordings. The average A-weighted sound pressure level of the wind noise was found to dominate the perceived degradation of quality, while gustiness was mostly unimportant. Large degradations in quality were observed when the signal to noise ratio was lower than about 15 dB. A model to allow an estimation of wind noise level was developed using an ensemble of decision trees. The model was designed to work with a single microphone in the presence of a variety of foreground sounds. The model outputted four classes of wind noise: none, low, medium, and high. Wind free examples were accurately identified in 79% of cases. For the three classes with noise present, on average 93% of samples were correctly assigned. A second ensemble of decision trees was used to estimate the signal to noise ratio and thereby infer the perceived degradation caused by wind noise. | 25,190,392 | [
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A finite element model to predict the sound attenuation of earplugs in an acoustical test fixture. | Acoustical test fixtures (ATFs) are currently used to measure the attenuation of the earplugs. Several authors pointed out that the presence of an artificial skin layer inside the cylindrical ear canal of the ATFs strongly influenced the attenuation measurements. In this paper, this role is investigated via a 2D axisymmetric finite element model of a silicon earplug coupled to an artificial skin. The model is solved using COMSOL Multiphysics (COMSOL(®), Sweden) and validated experimentally. The model is exploited thereafter to better understand the role of each part of the earplug/ear canal system and how the energy circulates within the domains. This is investigated by calculating power balances and by representing the mechanical and acoustical fluxes in the system. The important dissipative role of the artificial skin is underlined and its contribution as a sound transmission pathway is quantified. In addition, the influence of both the earplug and the artificial skin parameters is assessed via sensitivities analyses performed on the model. | 25,190,400 | [
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Optimizing pulse-spreading harmonic complexes to minimize intrinsic modulations after auditory filtering. | All signals, except sine waves, exhibit intrinsic modulations that affect perceptual masking. Reducing the physical intrinsic modulations of a broadband signal does not necessarily have a perceptual impact: auditory filtering can reintroduce modulations. Broadband signals with low intrinsic modulations after auditory filtering have proved difficult to design. To that end, this paper introduces a class of signals termed pulse-spreading harmonic complexes (PSHCs). PSHCs are generated by summing harmonically related components with such a phase that the resulting waveform exhibits pulses equally-spaced within a repetition period. The order of a PSHC determines its pulse rate. Simulations with a gamma-tone filterbank suggest an optimal pulse rate at which, after auditory filtering, the PSHC's intrinsic modulations are lowest. These intrinsic modulations appear to be less than those for broadband pseudo-random (PR) or low-noise (LN) noise. This hypothesis was tested in a modulation-detection experiment involving five modulation rates ranging from 8 to 128 Hz and both broadband and narrowband carriers using PSHCs, PR, and LN noise. PSHC showed the lowest thresholds of all broadband signals. Results imply that optimized PSHCs exhibit less intrinsic modulations after auditory filtering than any other broadband signal previously considered. | 25,190,401 | [
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The role of creaky voice in Cantonese tonal perception. | There are few studies on the role of phonation cues in the perception of lexical tones in tonal languages where pitch is the primary dimension of contrast. This study shows that listeners are sensitive to creaky phonation in native tonal perception in Cantonese, a language in which the low falling tone, Tone 4, has anecdotally been reported to be sometimes creaky. First, in a multi-speaker corpus of lab speech, it is documented that creak occurs systematically more often on Tone 4 than other tones. Second, for stimuli drawn from this corpus, listeners identified Tone 4 with 20% higher accuracy when it was realized with creak than when it was not. Third, in a two-alternative forced choice task of identifying stimuli as Tone 4 or Tone 6 (the low level tone) isolating creak from any concomitant pitch cues, listeners had a higher proportion of Tone 4 responses for creaky stimuli. Finally, listeners had more Tone 4 responses for creaky stimuli with longer durations of nonmodal phonation. These results underscore that differences in voice quality contribute to human perception of tone alongside f0. Automatic tonal recognition and clinical applications for tone would benefit from attention to voice quality beyond f0 and pitch. | 25,190,405 | [
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A three-dimensional, longitudinally-invariant finite element model for acoustic propagation in shallow water waveguides. | A three-dimensional, longitudinally-invariant finite element (FE) model for shallow water acoustic propagation is constructed through a cosine transform of a series of two-dimensional FE models at different values of the out-of-plane wavenumber. An innovative wavenumber sampling method is developed that efficiently captures the essential components of the integral as the out-of-plane wave number approaches the water wavenumber. The method is validated by comparison with benchmark solutions of two shallow water waveguide environments: a flat range independent case and a benchmark wedge. | 25,190,422 | [
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Preliminary evaluation of a two-interval, two-alternative infant behavioral testing procedure. | The purpose of this study was to evaluate the feasibility and efficiency of an observer-based, two-interval forced-choice infant psychophysical testing procedure. Ten of 11 infants (7-9 months of age) achieved a criterion of 80%-correct detection of a 50-dB sound pressure level noise band in a single testing session. Fewer trials were needed to reach criterion using the two-interval procedure than previously reported for the single-interval observer-based psychophysical procedure [Olsho, Koch, Halpin, and Carter (1987). Devel. Psychol. 23, 627-640]. These results provide preliminary evidence that the two-interval procedure is feasible and efficient while controlling for observer and listener response bias. | 25,190,427 | [
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Validity of hospital discharge diagnosis codes for stroke: the Atherosclerosis Risk in Communities Study. | Characterizing International Classification of Disease 9th Revision, Clinical Modification (ICD-9-CM) code validity is essential given widespread use of hospital discharge databases in research. Using the Atherosclerosis Risk in Communities (ARIC) Study, we estimated the accuracy of ICD-9-CM stroke codes. Hospitalizations with ICD-9-CM codes 430 to 438 or stroke keywords in the discharge summary were abstracted for ARIC cohort members (1987-2010). A computer algorithm and physician reviewer classified definite and probable ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Using ARIC classification as a gold standard, we calculated the positive predictive value (PPV) and sensitivity of ICD-9-CM codes grouped according to the American Heart Association/American Stroke Association (AHA/ASA) 2013 categories and an alternative code grouping for comparison. Thirty-three percent of 4260 hospitalizations were validated as strokes (1251 ischemic, 120 intracerebral hemorrhage, 46 subarachnoid hemorrhage). The AHA/ASA code groups had PPV 76% and 68% sensitivity compared with PPV 72% and 83% sensitivity for the alternative code groups. The PPV of the AHA/ASA code group for ischemic stroke was slightly higher among blacks, individuals <65 years, and at teaching hospitals. Sensitivity was higher among older individuals and increased over time. The PPV of the AHA/ASA code group for intracerebral hemorrhage was higher among blacks, women, and younger individuals. PPV and sensitivity varied across study sites. A new AHA/ASA discharge code grouping to identify stroke had similar PPV and lower sensitivity compared with an alternative code grouping. Accuracy varied by patient characteristics and study sites. | 25,190,443 | [
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Synthesis and protein kinase C (PKC)-C1 domain binding properties of diacyltetrol based anionic lipids. | The protein kinase C (PKC) family of lipid-activated kinases plays a significant role in the regulation of diverse cellular functions including tumor promotion, apoptosis, differentiation, and others. The lipophilic second messenger diacylglycerols (DAGs) act as endogenous ligands for the PKCs in the presence of anionic phospholipids. To develop effective PKC regulators and understand the importance of anionic phospholipids in DAG binding of PKC isoforms, we conveniently synthesized octanoic acid containing diacyltetrol (DAT) based hybrid lipids with both DAG and anionic phospholipid headgroups within the same molecule. We also used palmitic and oleic acid containing hybrid lipids for additional understanding of the PKC-C1 domain binding mechanism. Biophysical studies showed that hydrophobic side chains, DAG and anionic phospholipids headgroups are necessary for their interaction with the C1-domain of PKC isoforms. The hybrid lipids DAT-PS and DAT-PA specifically interact with the PKCδ-C1b and PKCθ-C1b subdomains and showed 5- and 2.5-fold stronger binding affinity compared with DAG, respectively. Whereas, the PKCα-C1a subdomain interacts with the hybrid lipids, without any significant specificity. The present results show that hybrid lipids bind to the PKC C1b/a subdomains and can be further studied to decipher their binding mechanism and biological activities. This study proposes a new concept of developing PKC activators by using tetrol-based anionic hybrid lipids having both phospholipids and diacylglycerol headgroups within the same molecule. This study also supplies useful information for the binding potencies of hybrid lipids with PKC-C1 domains. | 25,190,464 | [
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Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice. | The gut-brain-microbiota axis is increasingly recognized as an important regulator of intestinal physiology. Exposure to psychological stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis and causes altered intestinal barrier function, intestinal dysbiosis, and behavioral changes. The primary aim of this study was to determine whether the effects of psychological stress on intestinal physiology and behavior, including anxiety and memory, are mediated by the adaptive immune system. Furthermore, we wanted to determine whether treatment with probiotics would normalize these effects. Here we demonstrate that B and T cell-deficient Rag1(-/-) mice displayed altered baseline behaviors, including memory and anxiety, accompanied by an overactive HPA axis, increased intestinal secretory state, dysbiosis, and decreased hippocampal c-Fos expression. Both local (intestinal physiology and microbiota) and central (behavioral and hippocampal c-Fos) changes were normalized by pretreatment with probiotics, indicating an overall benefit on health conferred by changes in the microbiota, independent of lymphocytes. Taken together, these findings indicate a role for adaptive immune cells in maintaining normal intestinal and brain health in mice and show that probiotics can overcome this immune-mediated deficit in the gut-brain-microbiota axis. | 25,190,473 | [
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Sequestration of latent TGF-β binding protein 1 into CADASIL-related Notch3-ECD deposits. | Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) represents the most common hereditary form of cerebral small vessel disease characterized by early-onset stroke and premature dementia. It is caused by mutations in the transmembrane receptor Notch3, which promote the aggregation and accumulation of the Notch3 extracellular domain (Notch3-ECD) within blood vessel walls. This process is believed to mediate the abnormal recruitment and dysregulation of additional factors including extracellular matrix (ECM) proteins resulting in brain vessel dysfunction. Based on recent evidence indicating a role for the transforming growth factor-β (TGF-β) pathway in sporadic and familial small vessel disease we studied fibronectin, fibrillin-1 and latent TGF-β binding protein 1 (LTBP-1), three ECM constituents involved in the regulation of TGF-β bioavailability, in post-mortem brain tissue from CADASIL patients and control subjects. Fibronectin and fibrillin-1 were found to be enriched in CADASIL vessels without co-localizing with Notch3-ECD deposits, likely as a result of fibrotic processes secondary to aggregate formation. In contrast, LTBP-1 showed both an accumulation and a striking co-localization with Notch3-ECD deposits suggesting specific recruitment into aggregates. We also detected increased levels of the TGF-β prodomain (also known as latency-associated peptide, LAP) indicating dysregulation of the TGF-β pathway in CADASIL development. In vitro analyses revealed a direct interaction between LTBP-1 and Notch3-ECD and demonstrated a specific co-aggregation of LTBP-1 with mutant Notch3. We propose LTBP-1 as a novel component of Notch3-ECD deposits and suggest its involvement in pathological processes triggered by Notch3-ECD aggregation. | 25,190,493 | [
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The role of orbital ultrasonography in distinguishing papilledema from pseudopapilledema. | To determine the sensitivity and specificity of orbital ultrasonography in distinguishing papilledema from pseudopapilledema in adult patients. The records of all adult patients referred to the neuro-ophthalmology service who underwent orbital ultrasonography for the evaluation of suspected papilledema were reviewed. The details of history, ophthalmologic examination, and results of ancillary testing including orbital ultrasonography, MRI, and lumbar puncture were recorded. Results of orbital ultrasonography were correlated with the final diagnosis of papilledema or pseudopapilledema on the basis of the clinical impression of the neuro-ophthalmologist. Ultrasound was considered positive when the optic nerve sheath diameter was ≥3.3 mm along with a positive 30° test. The sensitivity of orbital ultrasonography for detection of papilledema was 90% (CI: 80.2-99.3%) and the specificity in detecting pseudopapilledema was 79% (CI: 67.7-90.7%). Orbital ultrasonography is a rapid and noninvasive test that is highly sensitive, but less specific in differentiating papilledema from pseudopapilledema in adult patients, and can be useful in guiding further management of patients in whom the diagnosis is initially uncertain. | 25,190,532 | [
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Structural clues to UO₂²⁺/VO₂⁺ competition in seawater extraction using amidoxime-based extractants. | Here we present the first structural comparison of amidoxime complexes of UO2(2+) and VO2(+) (the main competitor in the extraction of uranium from seawater using amidoxime-based sorbents) using a 4,5-di(amidoxime)-functionalized imidazole ligand. The amidoxime groups resist tautomerization in both cases and quite different coordination modes (chelating vs. bridging) are observed. | 25,190,568 | [
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[Protein O-GlcNAcylation and regulation of cell signalling: involvement in pathophysiology]. | O-GlcNAcylation corresponds to the addition of N-acetyl glucosamine (GlcNAc) on serine or threonine residues of cytosolic and nuclear proteins. This reversible post-translational modification regulates protein phosphorylation, sub-cellular localisation, stability and activity. Only two enzymes, OGT (O-linked N-acetyl-glucosaminyltransferase) and OGA (O-linked N-acetyl-β-D glucosaminidase), control the addition and removal of GlcNAc from more than a thousand of proteins. Alternative splicing generates different isoforms of OGT and OGA, and address these enzymes to different sub-cellular compartments (mitochondria, cytosol...), restraining their action to specific subsets of substrates. Moreover, interaction with adaptor proteins may also help address these enzymes to specific substrates. Alterations in protein O-GlcNAcylation have been observed in a number of important human diseases, such as Alzheimer, cancer and diabetes. A reciprocal relationship between Tau protein phosphorylation and O-GlcNAcylation has been observed, and decreased O-GlcNAcylation in the brain of patients with Alzheimer diseases may favour Tau aggregation, destabilisation of microtubules and neuronal alterations. Alterations in OGT/OGA expression levels, and in protein O-GlcNAcylation, have been described in different types of cancer, and much evidence indicates that O-GlcNAcylation may participate in abnormal proliferation and migration of cancer cells. O-GlcNAcylation of transcription factors and signalling effectors may also participate in defects observed in diabetes. Indeed, in situation of chronic hyperglycaemia, abnormal O-GlcNAcylation may have deleterious effect on insulin secretion and action, resulting in further impairment of glucose homeostasis. Therefore, O-GlcNAcylation appears to be a major regulator of cellular activities and may play an important part in different human diseases. However, because of the large spectrum of OGT and OGA substrates, targeting O-GlcNAc for treatment of these diseases will be a highly challenging task. | 25,190,571 | [
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The use of a portable breath analysis device in monitoring type 1 diabetes patients in a hypoglycaemic clamp: validation with SIFT-MS data. | Monitoring blood glucose concentrations is a necessary but tedious task for people suffering from diabetes. It has been noted that breath in people suffering with diabetes has a different odour and thus it may be possible to use breath analysis to monitor the blood glucose concentration. Here, we evaluate the analysis of breath using a portable device containing a single mixed metal oxide sensor during hypoglycaemic glucose clamps and compare that with the use of SIFT-MS described in previously published work on the same set of patients. Outputs from both devices have been correlated with the concentration of blood glucose in eight volunteers suffering from type 1 diabetes mellitus. The results demonstrate that acetone as measured by SIFT-MS and the sensor output from the breath sensing device both correlate linearly with blood glucose; however, the sensor response and acetone concentrations differ greatly between patients with the same blood glucose. It is therefore unlikely that breath analysis can entirely replace blood glucose testing. | 25,190,582 | [
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Perpetual conservation easements and landowners: evaluating easement knowledge, satisfaction and partner organization relationships. | Conservation easements are being more widely used to facilitate permanent land conservation. While landowners who initially place a conservation easement on their land are generally highly motivated to protect the conservation values of their land, changes in landownership may hinder long-term active landowner support for these easements. Maintaining such support is critical for ensuring their effectiveness as a conservation tool. Our research reports on results from a mail survey sent to landowners in Texas who own property encumbered with perpetual conservation easements. They were asked about their level of satisfaction concerning their conservation easement and the relationship with their easement holder. Additionally, landowners were asked how well they remembered and understood the terms of their conservation easement. We also examined institutional aspects of easement holding organizations and variables associated with landownership that affected these attitudes. Among institutional factors, frequency of contact between landowners and easement holders and the category of agency (federal, state and local or non-governmental agency) were significant in determining level of satisfaction with the easement and perceived relationship with the easement holder. Landowner factors affecting these same issues included easement grantor or successive generation landowner, gender and motivations driving landownership. We did not find any significant variables related to landowners' knowledge about their easement. Management implications from this study suggest that easement holders should increase staff capacity capable of providing targeted landowner technical assistance and outreach beyond compliance monitoring. Additionally, landownership motivations should be considered by easement holders when deciding whether to accept an easement. Finally, expressed dissatisfaction with federal governmental easement holding institutions should be explored further. | 25,190,596 | [
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Update on obinutuzumab in the treatment of B-cell malignancies. | The anti-CD20 mAb rituximab has revolutionized the treatment of B-cell malignancies, improving outcome for patients. Despite these improvements, the majority of patients still relapse and become refractory to rituximab. Further efforts to improve anti-CD20 mAb efficacy have recently focused on obinutuzumab /GA101, a novel anti-CD20 mAb glycoengineered to display enhanced Fc-mediated effector mechanisms and induce direct cell death. We provide an overview of the current insights into the mechanisms of action of obinutuzumab focusing on how structural modifications and differences to rituximab led to designation of obinutuzumab as a type II antibody. We summarize data from preclinical studies and recent clinical trials including the Phase III trial in chronic lymphocytic leukemia (CLL), which led to FDA approval in November 2013. Clinical data are now emerging confirming the promise of the initial preclinical data that demonstrated superior efficacy of obinutuzumab over rituximab at similar dosing. The emerging randomized Phase III data from older comorbid patients with previously untreated CLL demonstrated significant improvements in molecular remission rates and median progression-free survival of obinutuzumab plus chlorambucil versus rituximab plus chlorambucil. This emerging data provide reasons to be optimistic that outcomes for patients with B-cell malignancies can be further improved with obinutuzumab. | 25,190,612 | [
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Metformin treatment alters memory function in a mouse model of Alzheimer's disease. | Metabolic dysfunction exacerbates Alzheimer's disease (AD) incidence and progression. Here we report that activation of the AMPK pathway, a common target in the management of diabetes, results in gender-divergent cognitive effects in a murine model of the disease. Specifically, our results show that activation of AMPK increases memory dysfunction in males but is protective in females, suggesting that gender considerations may constitute an important factor in medical intervention of diabetes as well as AD. | 25,190,626 | [
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Regional cingulum disruption, not gray matter atrophy, detects cognitive changes in amnestic mild cognitive impairment subtypes. | Amnestic mild cognitive impairment (aMCI), which has a high risk of progression to Alzheimer's disease (AD), can be classified into single domain (S-aMCI) and multiple domain (M-aMCI) subtypes. We investigated the integrity of regional gray matter and segments of the cingulum bundle with diffusion spectrum imaging tract-specific analysis, and their relationships to neuropsychological functioning, in 46 individuals with aMCI (S-aMCI n = 24; M-aMCI n = 22) and 36 healthy controls (HC). Results demonstrated that although both aMCI groups were impaired on all memory measures relative to HCs, the M-aMCI group demonstrated worse performance on paired association memory and on selective executive function relative to the S-aMCI group. The two aMCI groups did not show significant atrophy in regional gray matter indices as compared to the HC group, but the M-aMCI group showed significant disruption in white matter of the left anterior and inferior cingulum bundles relative to the S-aMCI and HC groups. Furthermore, disruption in the inferior cingulum bundles was significantly associated with executive function and attention/processing speed in all aMCI participants above and beyond the contribution of bilateral hippocampal volumes. Overall, these results indicate that the degeneration of cingulum fibers did not appear to arise from degeneration of the corresponding cerebral cortex. It also suggests relatively greater sensitivity of a white matter biomarker and comprehensive neuropsychological evaluation over gray matter biomarkers in early detection of AD. | 25,190,630 | [
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0.1534684,
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Linguistic and content validation of a German-language PRO-CTCAE-based patient-reported outcomes instrument to evaluate the late effect symptom experience after allogeneic hematopoietic stem cell transplantation. | The aim of this sequential mixed methods study was to develop a PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events)-based measure of the symptom experience of late effects in German speaking long-term survivors of allogeneic stem cell transplantation (SCT), and to examine its content validity. The US National Cancer Institute's PRO-CTAE item library was translated into German and linguistically validated. PRO-CTCAE symptoms prevalent in ≥50% of survivors (n = 15) and recognized in its importance by SCT experts (n = 9) were identified. Additional concepts relevant to the symptom experience and its consequences were elicited. Content validity of the PROVIVO (Patient-Reported Outcomes of long-term survivors after allogeneic SCT) instrument was assessed through an additional round of cognitive debriefing in 15 patients, and item and scale content validity indices by 9 experts. PROVIVO is comprised of a total of 49 items capturing the experience of physical, emotional and cognitive symptoms. To improve the instrument's utility for clinical decision-making, questions soliciting limitations in activities of daily living, frequent infections, and overall well-being were added. Cognitive debriefings demonstrated that items were well understood and relevant to the SCT survivor experience. Scale Content Validity Index (CVI) (0.94) and item CVI (median = 1; range 0.75-1) were very high. Qualitative and quantitative data provide preliminary evidence supporting the content validity of PROVIVO and identify a PRO-CTCAE item bundle for use in SCT survivors. A study to evaluate the measurement properties of PROVIVO and to examine its capacity to improve survivorship care planning is underway. | 25,190,633 | [
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0.09040777,
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0.2737905,
0.2734514,
0.2663913,
0.4769181,
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0... |
Characterization of circulating endothelial microparticles and endothelial progenitor cells in primary Sjögren's syndrome: new markers of chronic endothelial damage? | Chronic autoimmune diseases are associated with increased risk of cardiovascular death. Endothelial dysfunction represents the first stage of subclinical atherosclerosis and multiple factors contribute to endothelial injury. Among these, an altered balance between endothelial microparticle (EMP) release and endothelial progenitor cell (EPC) generation promotes endothelial dysfunction. The role of EMPs and EPCs in promoting endothelial damage in primary SS (pSS) has never been investigated. Our aim was to evaluate the role of EMPs and EPCs as markers of endothelial damage in pSS and their correlation with disease clinical and immunological features. Circulating EMPs (CD31(+)/CD42(-)), true EPCs (CD34(+)/KDR(+)/CD133(+)) and mature EPCs (CD34(+)/KDR(+)/CD133(-)) were quantified by FACS analysis in 34 pSS patients and 18 age- and sex-matched controls. Correlation between EMP and EPC levels and parameters of disease activity and damage, clinical features and markers of immunological dysfunction was performed. Patients displayed higher EMP numbers with respect to healthy controls [HCs; mean 450 n/μl (S.D. 155) vs 231 (110), P < 0.0001]. EPC and mature EPC levels were higher in patients compared with HCs [mean 226 n/ml (S.D. 181) vs 69 (53), P < 0.001 and 166 (161) vs 36 (32), P < 0.0001, respectively). EMP levels directly correlated with disease duration from symptoms and diagnosis (ρ = 0.5, P < 0.01). Early EPCs inversely correlated with disease duration from symptoms (ρ = -0.5, P < 0.01) and diagnosis (ρ = -0.4, P < 0.05). This is the first demonstration of chronic endothelial fragmentation characterizing pSS. The reparative potentiality of the endothelial layer appears to be preserved in the earliest stages of disease. During the course of the disease, progressive exhaustion of the precursor endothelial pool may be hypothesized, leading to defective vascular layer restoration and endothelial dysfunction. | 25,190,637 | [
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0.3865596,
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0.5993353,
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0.0660618,
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0.07762192,
0.1590212,
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-0.... |
Restoring conjunctival tolerance by topical nuclear factor-κB inhibitors reduces preservative-facilitated allergic conjunctivitis in mice. | To evaluate the role of nuclear factor-κB (NF-κB) activation in eye drop preservative toxicity and the effect of topical NF-κB inhibitors on preservative-facilitated allergic conjunctivitis. Balb/c mice were instilled ovalbumin (OVA) combined with benzalkonium chloride (BAK) and/or NF-κB inhibitors in both eyes. After immunization, T-cell responses and antigen-induced ocular inflammation were evaluated. Nuclear factor-κB activation and associated inflammatory changes also were assessed in murine eyes and in an epithelial cell line after BAK exposure. Benzalkonium chloride promoted allergic inflammation and leukocyte infiltration of the conjunctiva. Topical NF-κB inhibitors blocked the disruptive effect of BAK on conjunctival immunological tolerance and ameliorated subsequent ocular allergic reactions. In line with these findings, BAK induced NF-κB activation and the secretion of IL-6 and granulocyte-monocyte colony-stimulating factor in an epithelial cell line and in the conjunctiva of instilled mice. In addition, BAK favored major histocompatibility complex (MHC) II expression in cultured epithelial cells in an NF-κB-dependent fashion after interaction with T cells. Benzalkonium chloride triggers conjunctival epithelial NF-κB activation, which seems to mediate some of its immune side effects, such as proinflammatory cytokine release and increased MHC II expression. Breakdown of conjunctival tolerance by BAK favors allergic inflammation, and this effect can be prevented in mice by topical NF-κB inhibitors. These results suggest a new pharmacological target for preservative toxicity and highlight the importance of conjunctival tolerance in ocular surface homeostasis. | 25,190,648 | [
-0.1339554,
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0.2040142,
0.0962313,
0.07622381,
0.04317961,
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0.1337319,
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0.2078255,
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0.433436,
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0.2022878,
0.1383272,... |
Hepatic epithelioid hemangioendothelioma in a patient with hemochromatosis. | Hepatic epithelioid hemangioendothelioma (HEHE) is a rare hepatic vascular tumor that represents a diagnostic challenge. The rarity of this neoplasm precludes establishment of a standard-of-care treatment. Risk factors for HEHE are not well-known. Liver transplant remains the most common therapeutic modality for nonmetastatic disease. This article describes a patient who presented with abdominal pain, fatigue, poor appetite, and weight loss. Genetic testing showed that the patient was homozygous for C282Y consistent with hereditary hemochromatosis, and liver biopsy was consistent with malignant epithelioid hemangioendothelioma. The patient was referred for a liver transplant but was deemed inappropriate for transplant secondary to peritoneal studding, with frozen-section analysis showing metastatic disease at the time of surgery. | 25,190,690 | [
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0.1624216,
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0.4340227,
-0.3485903,... |
Teicoplanin therapy for MRSA bacteraemia: a retrospective study emphasizing the importance of maintenance dosing in improving clinical outcomes. | To study the relationship between teicoplanin maintenance dosing and clinical outcomes in adults with MRSA bacteraemia. MRSA bacteraemic patients who received three teicoplanin loading doses (6 mg/kg/12 h) followed by maintenance doses of 6 mg/kg/24 h (Group 1) or 6 mg/kg/12 h (Group 2) were retrospectively analysed. Evaluated on day 7, an unfavourable early clinical response referred to the presence of septic shock, persistent fever, persistent leucocytosis and/or persistent bacteraemia. Assessed at completion of teicoplanin therapy, an unfavourable final clinical response referred to clinical treatment failure. Compared with those in Group 1 (n = 122), patients in Group 2 (n = 82) had significantly higher rates of favourable early clinical response (P = 0.040) and final clinical response (P < 0.001) and a lower bloodstream-infection-related mortality rate (P = 0.018). Based on estimated ORs for favourable final clinical response in multivariate analysis, endocarditis (P < 0.001; OR 0.109, 95% CI 0.032-0.368), pneumonia (P < 0.001; OR 0.172, 95% CI 0.069-0.433), ICU admission (P < 0.001; OR 0.132, 95% CI 0.054-0.325) and high Pittsburgh bacteraemia score (P = 0.042; OR 0.187, 95% CI 0.021-0.457) were each a risk factor for an unfavourable final clinical response. Higher teicoplanin maintenance dosing contributed to a favourable final clinical response (P < 0.001; OR 8.800, 95% CI 3.602-21.502). Significantly higher favourable final clinical response rates were also found in patients with endocarditis (P = 0.007) and pneumonia (P < 0.001) in Group 2 compared with their counterparts in Group 1. These data highlight the importance of higher teicoplanin maintenance dosing, especially for severe infections due to MRSA. | 25,190,719 | [
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0.2112506,
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0.3161633,
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0.01467189,
0.0368374... |
Concurrent speed endurance and resistance training improves performance, running economy, and muscle NHE1 in moderately trained runners. | The purpose of this study was to examine whether speed endurance training (SET, repeated 30-s sprints) and heavy resistance training (HRT, 80-90% of 1 repetition maximum) performed in succession are compatible and lead to performance improvements in moderately trained endurance runners. For an 8-wk intervention period (INT) 23 male runners [maximum oxygen uptake (V̇O(2max)) 59 ± 1 ml·min(-1)·kg(-1); values are means ± SE] either maintained their training (CON, n = 11) or performed high-intensity concurrent training (HICT, n = 12) consisting of two weekly sessions of SET followed by HRT and two weekly sessions of aerobic training with an average reduction in running distance of 42%. After 4 wk of HICT, performance was improved (P < 0.05) in a 10-km run (42:30 ± 1:07 vs. 44:11 ± 1:08 min:s) with no further improvement during the last 4 wk. Performance in a 1,500-m run (5:10 ± 0:05 vs. 5:27 ± 0:08 min:s) and in the Yo-Yo IR2 test (706 ± 97 vs. 491 ± 65 m) improved (P < 0.001) only following 8 wk of INT. In HICT, running economy (189 ± 4 vs. 195 ± 4 ml·kg(-1)·km(-1)), muscle content of NHE1 (35%) and dynamic muscle strength was augmented (P < 0.01) after compared with before INT, whereas V̇O(2max), muscle morphology, capillarization, content of muscle Na(+)/K(+) pump subunits, and MCT4 were unaltered. No changes were observed in CON. The present study demonstrates that SET and HRT, when performed in succession, lead to improvements in both short- and long-term running performance together with improved running economy as well as increased dynamic muscle strength and capacity for muscular H(+) transport in moderately trained endurance runners. | 25,190,744 | [
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-0.05029485,
-0.1298159,
0.1151621,
0.002187884,
-0.1176... |
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