title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Corneal resistance factor and corneal hysteresis in a 6- to 18-year-old population. | To determine the distribution and normal range of the corneal resistance factor (CRF) and corneal hysteresis (CH) in the 6- to 18-year age range and their relationship with biometric components. Dezful, Iran. Cross-sectional study. This study of Dezful school children used a multistage, stratified, cluster approach sampling. All students had examinations for biometry, noncycloplegic refraction, and corneal biomechanical properties; the examinations were performed in the same order in all cases. Of the 864 selected students, 683 participated in the study. The mean CRF and CH was 11.74 mm Hg±1.77 (SD) (95% confidence interval [CI], 11.58-11.89) and 11.49±1.91 mm Hg (95% CI, 11.33-11.65), respectively. In a linear multiple regression model, the CRF significantly correlated with female sex (β coefficient=0.488, P=.013), central corneal thickness (CCT) (β coefficient=.034, P=.001), and keratometry (β-coefficient=0.157, P=.003) and CH significantly correlated with CCT (β coefficient=0.025, P<.001), axial length (β coefficient=-0.303, P=.011), and keratometry (β coefficient=0.11, P=.043). Each year increase in age was associated with a 42-unit decrease in the peak 1 area (P=.003). The distribution of CRF and CH in an Iranian population was symmetrical and bell shaped. However, the CRF did not have a normal distribution. The mean CRF and CH were higher than those reported in almost all previous studies. No author has a financial or proprietary interest in any material or method mentioned. | 25,135,536 | [
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Mode of delivery and the probability of subsequent childbearing: a population-based register study. | To investigate the relationship between mode of first delivery and probability of subsequent childbearing. Population-based study. Nationwide study in Sweden. A cohort of 771 690 women who delivered their first singleton infant in Sweden between 1992 and 2010. Using Cox's proportional-hazards regression models, risks of subsequent childbearing were compared across four modes of delivery. Hazard ratios (HRs) were calculated, using 95% confidence intervals (95% CIs). Probability of having a second and third child; interpregnancy interval. Compared with women who had a spontaneous vaginal first delivery, women who delivered by vacuum extraction were less likely to have a second pregnancy (HR 0.96, 95% CI 0.95-0.97), and the probabilities of a second childbirth were substantially lower among women with a previous emergency caesarean section (HR 0.85, 95% CI 0.84-0.86) or an elective caesarean section (HR 0.82, 95% CI 0.80-0.83). There were no clinically important differences in the median time between first and second pregnancy by mode of first delivery. Compared with women younger than 30 years of age, older women were more negatively affected by a vacuum extraction with respect to the probability of having a second child. A primary vacuum extraction decreased the probability of having a third child by 4%, but having two consecutive vacuum extraction deliveries did not further alter the probability. A first delivery by vacuum extraction does not reduce the probability of subsequent childbearing to the same extent as a first delivery by emergency or elective caesarean section. | 25,135,574 | [
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Meeting report: consensus recommendations for a research agenda in exercise in solid organ transplantation. | With improved survival rates in solid organ transplantation there has been an increased focus on long-term outcomes following transplant, including physical function, health-related quality-of-life and cardiovascular mortality. Exercise training has the potential to affect these outcomes, however, research on the optimal timing, type, dose of exercise, mode of delivery and relevant outcomes is limited. This article provides a summary of a 2-day meeting held in April 2013 (Toronto, Canada) in which a multi-disciplinary group of clinicians, researchers, administrators and patient representatives engaged in knowledge exchange and discussion of key issues in exercise in solid organ transplant (SOT). The outcomes from the meeting were the development of top research priorities and a research agenda for exercise in SOT, which included the need for larger scale, multi-center intervention studies, development of standardized outcomes for physical function and surrogate measures for clinical trials, examining novel modes of exercise delivery and novel outcomes from exercise training studies such as immunity, infection, cognition and economic outcomes. The development and dissemination of "expert consensus guidelines," synthesizing both the best available evidence and expert opinion was prioritized as a key step toward improving program delivery. | 25,135,579 | [
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The role of patient-mode high-resolution peripheral quantitative computed tomography indices in the prediction of failure strength of the elderly women's thoracic vertebral body. | The correlations between the failure load of 20 T12 vertebral bodies, their patient-mode high-resolution peripheral quantitative computed tomography (HR-pQCT) indices, and the L1 areal bone mineral density (aBMD) were investigated. For the prediction of the T12 vertebral failure load, the T12 HR-pQCT microarchitectural parameters added significant information to that of L1 aBMD and to that of cortical BMD, but not to that of T12 vertebral BMD and not to that of T12 trabecular BMD. HR-pQCT is a new in vivo imaging technique for assessing the three-dimensional microarchitecture of cortical and trabecular bone at the distal radius and tibia. But little is known about this technique in the direct measurement of vertebral body. Twenty female donors with the mean age of 80.1 (7.6) years were included in the study. Dual X-ray absorptiometry of the lumbar spine and femur was performed. The spinal specimens (T11/T12/L1) were dissected, scanned using HR-pQCT scanner, and mechanically tested under 4° wedge compression. The L1 aBMD, T12 patient-mode HR-pQCT indices, and T12 vertebral failure loads were analyzed. For the prediction of vertebral failure load, the inclusion of BV/TV into L1 aBMD was the best model (R (2) = 0.52), Tb.N and Tb.Sp added significant information to the L1 aBMD and to the cortical BMD, but none of the vertebral microarchitectural parameters yielded additional significant information to the trabecular BMD (or BV/TV) and to the vertebral BMD. Vertebral microarchitectural parameters obtained from the patient-mode HR-pQCT analysis provide significant information on bone strength complementary to that of aBMD and to that of cortical BMD, but not to that of vertebral BMD and not to that of trabecular BMD. | 25,135,580 | [
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Increased prevalence of gastrointestinal viruses and diminished secretory immunoglobulin a levels in antibody deficiencies. | Gastrointestinal disease occurs frequently in antibody deficiencies. This study aims to explore the relation between gastrointestinal infections and mucosal homeostasis in patients with antibody deficiencies. We performed an observational study including 54 pediatric antibody deficient patients (48 % CVID, 41 % CVID-like, 11 % XLA) and 66 healthy controls. Clinical symptom scores and stool samples were collected prospectively. Stool samples were evaluated for bacteria, parasites, viruses, secretory IgA- and for calprotectin levels. Results were compared between patients and controls. 24 % of antibody deficient patients versus 9 % of healthy controls tested positive for gastrointestinal viruses (p = 0.028). Fecal calprotectin levels were significantly higher in virus positive patients compared to virus negative patients (p = 0.002). However, in controls, fecal calprotectin levels were similar between virus positive and virus negative controls. Moreover, gastrointestinal virus positive patients had low serum IgA levels in 13/14 cases (94 %) versus 40/62 (62 %) patients in the virus negative patient group (p = 0.04). The virus positive patient group also displayed significantly lower secretory IgA levels in stool (median 13 ug/ml) than patients without gastrointestinal viruses detected or healthy controls (median 155 ug/ml) (p = 0.046). We here report an increased prevalence of gastrointestinal viruses and gastrointestinal complaints in antibody deficient patients. Patients that tested positive for gastrointestinal viruses showed diminished serum- and secretory IgA levels, and only in patients, virus positivity was associated with signs of mucosal inflammation. These findings suggest that particularly patients with low IgA are at risk for longstanding replication of gastrointestinal viruses, which may eventually result in CVID-related enteropathy. | 25,135,597 | [
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Long-term use of 5α-reductase inhibitors and the risk of male breast cancer. | The 5α-reductase inhibitors (5-ARI) finasteride and dutasteride are indicated for the treatment of lower urinary tract symptoms caused by benign prostatic hyperplasia. Case reports have suggested that 5-ARIs increase the risk for male breast cancer, with no conclusive evidence. The objective of this study was to quantify the association between use of 5-ARIs and the risk for male breast cancer. A case-control study was conducted with data from the United Kingdom Clinical Practice Research Datalink database among all men aged 45 years and older in the period 1 January 1992 to 31 December 2011. Cases of men diagnosed with breast cancer were matched to up 10 controls on age and general practice. Crude and adjusted odds ratios were estimated for the risk of breast cancer associated with the use of 5-ARIs. Three hundred and ninety-eight cases were identified and matched to 3,930 controls. Ever use of 5-ARIs was associated with an adjusted odds ratio for breast cancer of 1.08 (95 % CI 0.62-1.87) compared to non-users. Increasing cumulative duration of treatment showed no increasing risks: adjusted odds ratios for use for less than 280, for 280 to 1,036 and for more than 1,036 days were 1.21 (95 % CI 0.47-3.10), 0.94 (95 % CI 0.36-2.41) and 1.29 (95 % CI 0.54-3.08), respectively. In this study, there was no evidence of an association between short- or long-term treatment with 5-ARIs and the risk for breast cancer in older men. | 25,135,615 | [
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Can vitamin D status be assessed by serum 25OHD in children? | To examine the relationship of serum 25-hydroxyvitamin D (25OHD) concentrations with serum parathyroid hormone (PTH) levels, body mass index (BMI), and environmental factors in a population of Caucasian children living at latitude 43°N. Cross-sectional study on 288 children aged 1 month to 13 years who presented to a pediatric emergency unit during a 21-month period. Mean (SD) serum 25OHD concentrations were 40.6 (17.6), 30.9 (12.0), and 26.4 (9.9) ng/ml (1 ng/ml = 2.5 nmol/l), in children aged 0-1, 2-5, and ≥ 6 years, respectively. Serum PTH levels were 26.6 (13.6), 24.3 (11.9), and 32.7 (12.1) pg/ml in the same groups. Infants had 25OHD concentrations significantly higher. PTH levels were significantly higher in children aged ≥ 6 years. There was no significant correlation between serum 25OHD and PTH concentrations. Totals of 15.6 % and 2.1 % of children had 25OHD values less than 20 and 10 ng/ml, respectively, but none had elevated serum PTH or clinical manifestations related with vitamin D deficiency. Age (inverse correlation) and season (higher values in summer), but not BMI, sex, and time spent outdoors, influenced serum 25OHD concentrations. Our results raise doubt on the assumption of only a serum 25OHD threshold as indicative of vitamin D deficiency in children. | 25,135,619 | [
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Clinical challenges in targeting anaplastic lymphoma kinase in advanced non-small cell lung cancer. | The revolution in individualized therapy for patients with advanced non-small cell lung cancer (NSCLC) has seen the emergence of a number of molecularly targeted therapies for distinct patient molecular subgroups. Activating anaplastic lymphoma kinase (ALK)-gene rearrangement has been detected in 3-7 % of NSCLC cases, and the ALK inhibitor crizotinib is now an approved treatment for patients with tumors harboring this event. However, resistance to ALK-targeted therapies is a ubiquitous problem in the management of advanced ALK-positive NSCLC and can be mediated by secondary kinase mutations or the activation of compensatory alternative oncogenic drivers. New, more potent ALK inhibitors such as ceritinib (LDK378), alectinib (CH5424802), and AP26113 are now emerging, together with an increased knowledge of the molecular basis of resistance. There is a need to evaluate the optimal clinical application of these new agents, either as sequential therapies or in combination with other targeted agents, to combat resistance and prolong survival in patients with ALK-positive NSCLC. The remarkable clinical activity of ALK inhibitors also emphasizes the importance of optimal diagnostic testing algorithms, to ensure that all eligible patients receive these breakthrough therapies. | 25,135,623 | [
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Benzoic and sorbic acid in soft drink, milk, ketchup sauce and bread by dispersive liquid-liquid microextraction coupled with HPLC. | Benzoic acid and sorbic acid are widely used for food preservation. These preservatives are generally recognised as safe. The aim of this study was to determine the level of benzoic and sorbic acid in food samples that are usually consumed in Iran. Therefore, 54 samples, including 15 soft drinks, 15 ultra-high-temperature milk, 15 ketchup sauces and 9 bread samples, were analysed by high-performance liquid chromatography with UV detection. Benzoic acid was detected in 50 (92.5%) of the samples ranging from 3.5 to 1520 µg mL⁻¹, while sorbic acid was detected in 29 (50.3%) samples in a range of 0.8 and 2305 µg mL⁻¹. Limits of detection and limits of quantification for benzoate were found to be 0.1 and 0.5 µg mL⁻¹, respectively, and for sorbate 0.08 and 0.3 µg mL⁻¹, respectively. The results showed that benzoic acid and sorbic acid widely occur in food products in Iran. | 25,135,626 | [
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Dendritic cell subsets require cis-activation for cytotoxic CD8 T-cell induction. | Dendritic cells (DCs) are required for the induction of cytotoxic T cells (CTL). In most tissues, including the lung, the resident DCs fall into two types expressing the integrin markers CD103 and CD11b. The current supposition is that DC function is predetermined by lineage, designating the CD103(+) DC as the major cross-presenting DC able to induce CTL. Here we show that Poly I:C (TLR3 agonist) or R848 (TLR7 agonist) do not activate all endogenous DCs. CD11b(+) DCs can orchestrate a CTL response in vivo in the presence of a TLR7 agonist but not a TLR3 agonist, whereas CD103(+) DCs require ligation of TLR3 for this purpose. This selectivity does not extend to antigen cross-presentation for T-cell proliferation but is required for induction of cytotoxicity. Thus, we demonstrate that the ability of DCs to induce functional CTLs is specific to the nature of the pathogen-associated molecular pattern (PAMP) encountered by endogenous DC. | 25,135,627 | [
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Low-risk transfusion-related acute lung injury donor strategies and the impact on the onset of transfusion-related acute lung injury: a meta-analysis. | Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. In the past decade blood banks have implemented low-risk TRALI donor strategies, including a male-only donor policy for plasma-containing blood products to prevent onset of TRALI. We performed a meta-analysis to determine whether use of low-risk TRALI donor strategies for plasma indeed reduces onset of TRALI. We searched MEDLINE and Cochrane Central Register of Controlled Trials from January 1995 up to January 2013. Two reviewers independently extracted data on study characteristics, methods, and outcomes. Primary endpoint was onset of TRALI. Subgroup analyses were performed for patient populations prone to develop TRALI and general patient populations. Ten articles were included. Meta-analysis using a random-effects model taking into account all transfused products showed a significant reduction for the risk of TRALI after implementation of low-risk TRALI donor strategies (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.42-0.88). Data from patient populations prone to develop TRALI showed a significant reduction of TRALI risk (OR, 0.51; 95% CI, 0.29-0.90), while data from general patient populations showed a similar nonsignificant trend (OR, 0.66; 95% CI, 0.40-1.09). Results were similar when taking only plasma products into account (OR, 0.62; 95% CI, 0.42-0.92). The introduction of low-risk TRALI donor strategies for plasma-containing products results in a reduction of TRALI. | 25,135,630 | [
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Frequent cough in unsatisfactory controlled asthma--results from the population-based West Sweden Asthma study. | Asthma is a complex disease presenting with variable symptoms which are sometimes hard to control. The purpose of the study was to describe the prevalence of asthma symptoms, use of asthma medications and allergic sensitization in subjects with asthma. We also related those indices to the level of asthma control, lung function and in particular, cough. An extensive questionnaire was sent to randomly selected adults from the West Sweden region. Clinical examinations and interview were performed in a subset. Of the participants, 744 were defined as having an ongoing asthma - reported ever having asthma or physician diagnosed asthma and one of the following - use of asthma medications, recurrent wheeze or attacks of shortness of breath with or without wheeze in the last 12 months. A respiratory disease-free control group of 847 subjects was also described. According to GINA guidelines, 40.6% of the asthmatics had partly controlled and 17.8% had uncontrolled asthma. Asthmatic subjects reported significantly more symptoms in the last 12 months than the control group - wheezing (79.4 vs 9.2%), shortness of breath (36.1 vs 2.5%), wheezing with shortness of breath (58.7 vs 1.3%). Important complaints were morning cough (42.5 vs 15.5%), cough with sputum production (36.1 vs 6.8%) and longstanding cough (32.5 vs 11.1%), which bothered two thirds of the uncontrolled and one third of partly controlled subjects. Asthma medications were used by 87.5% of the asthmatics, although around 30% of them who had insufficiently controlled disease used only short-acting beta-agonists. Asthmatics also had lower lung function, reacted to lower doses of methacholine that the controls and 13.6% of them had a FEV1/FVC ratio below 0.7. Allergic rhinitis was reported by 73.8% of the asthmatics and they were more frequently sensitized to several common allergens. Approximately 60% of asthmatics from this population-based study had insufficiently controlled asthma and persistent complaints, despite a high use of asthma medications. These self-reported symptoms were supported by clinical examination data. Increased cough frequency is an indicator of a more severe and difficult to control disease and should be considered when asthma is characterized. | 25,135,646 | [
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Severe and refractory solar urticaria treated with intravenous immunoglobulins: a phase II multicenter study. | Retrospective data have suggested the effectiveness of intravenous immunoglobulins (IVIG) for solar urticaria (SU). We sought to prospectively assess the efficacy of IVIG for SU. We conducted a multicentric phase II study to test the efficacy of a single course of IVIG (2 g/kg) in patients with severe and refractory SU. The primary outcome was remission of SU on phototesting at 12 weeks after IVIG treatment. Secondary objectives included clinical remission, improved quality of life, and 50% improvement in disease intensity as measured on a visual analog scale. Of the 9 patients who received IVIG injection, 2 showed remission of SU on phototesting, corresponding to a response rate of 22.2% (95% confidence interval 2.8%-60.0%). In all, 6 patients (67%) showed at least 1 response criterion after 4 weeks and 5 (56%) after 12 weeks. Response was maintained after 24 weeks for 2 patients and after 48 weeks for 1 patient. About half of the patients (56%) had moderate to severe headache. Lack of control arm and small number of patients are limitations. A single course of IVIG appears insufficient to obtain prolonged significant control of SU; future evaluation of different schedules of IVIG administration is warranted. | 25,135,650 | [
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The development and application of a quantitative peptide microarray based approach to protein interaction domain specificity space. | Protein interaction domain (PID) linear peptide motif interactions direct diverse cellular processes in a specific and coordinated fashion. PID specificity, or the interaction selectivity derived from affinity preferences between possible PID-peptide pairs is the basis of this ability. Here, we develop an integrated experimental and computational cellulose peptide conjugate microarray (CPCMA) based approach for the high throughput analysis of PID specificity that provides unprecedented quantitative resolution and reproducibility. As a test system, we quantify the specificity preferences of four Src Homology 2 domains and 124 physiological phosphopeptides to produce a novel quantitative interactome. The quantitative data set covers a broad affinity range, is highly precise, and agrees well with orthogonal biophysical validation, in vivo interactions, and peptide library trained algorithm predictions. In contrast to preceding approaches, the CPCMAs proved capable of confidently assigning interactions into affinity categories, resolving the subtle affinity contributions of residue correlations, and yielded predictive peptide motif affinity matrices. Unique CPCMA enabled modes of systems level analysis reveal a physiological interactome with expected node degree value decreasing as a function of affinity, resulting in minimal high affinity binding overlap between domains; uncover that Src Homology 2 domains bind ligands with a similar average affinity yet strikingly different levels of promiscuity and binding dynamic range; and parse with unprecedented quantitative resolution contextual factors directing specificity. The CPCMA platform promises broad application within the fields of PID specificity, synthetic biology, specificity focused drug design, and network biology. | 25,135,669 | [
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Screening methodologies for the development of spray-dried amorphous solid dispersions. | To present a new screening methodology intended to be used in the early development of spray-dried amorphous solid dispersions. A model that combines thermodynamic, kinetic and manufacturing considerations was implemented to obtain estimates of the miscibility and phase behavior of different itraconazole-based solid dispersions. Additionally, a small-scale solvent casting protocol was developed to enable a fast assessment on the amorphous stability of the different drug-polymer systems. Then, solid dispersions at predefined drug loads were produced in a lab-scale spray dryer for powder characterization and comparison of the results generated by the model and solvent cast samples. The results obtained with the model enabled the ranking of the polymers from a miscibility standpoint. Such ranking was consistent with the experimental data obtained by solvent casting and spray drying. Moreover, the range of optimal drug load determined by the model was as well consistent with the experimental results. The screening methodology presented in this work showed that a set of amorphous formulation candidates can be assessed in a computer model, enabling not only the determination of the most suitable polymers, but also of the optimal drug load range to be tested in laboratory experiments. The set of formulation candidates can then be further fine-tuned with solvent casting experiments using a small amount of API, which will then provide the decision for the final candidate formulations to be assessed in spray drying experiments. | 25,135,702 | [
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Correlation between low tube voltage in dual source CT coronary artery imaging with image quality and radiation dose. | The influence of low tube voltage in dual source CT (DSCT) coronary artery imaging on image quality and radiation dose and its application value in clinical practice were investigated. Totally, 300 cases of chest pain with low body mass index (BMI <18.5 kg/m(2)) subjected to DSCT coronary artery imaging were prospectively enrolled. The heart rate in all patients were greater than 65/min. The retrospective ECG gated scanning mode and simple random sampling method were used to assign the patients into groups A, B and C (n=100 each). The patients in groups A, B and C experienced 120-, 100-, and 80-kV tube voltage imaging respectively, and the image quality was evaluated. The CT volume dose index (CTDIvol) and dose length product (DLP) were recorded, and the effective dose (ED) was calculated in each group. The image quality scores and radiation doses in groups were compared, and the influence of tube voltage on image quality and radiation dose was analyzed. The results showed that the excellent rate of image quality in groups A, B and C was 95.69%, 94.72% and 96.33% respectively with the difference being not statistically significant among the three groups (P>0.05). The CTDIvol values in groups A, B and C were 51.35±12.21, 21.28±7.13 and 6.34±3.34 mGy, respectively, with the difference being statistically significant (P<0.05). The ED values in groups A, B and C were 9.27±1.63, 4.56±2.29 and 2.29±1.69 mSv, respectively, with the difference being statistically significant (P<0.05). It was suggested that for the patients with low BMI, the application of DSCT coronary artery imaging with low tube voltage can obtain satisfactory image quality, and simultaneously, significantly reduce the radiation dose. | 25,135,738 | [
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Molecular analysis of different classes of RNA molecules from formalin-fixed paraffin-embedded autoptic tissues: a pilot study. | For a long time, it has been thought that fresh and frozen tissues are the only possible source of biological material useful to extract nucleic acids suitable for downstream molecular analysis. Recently, for forensic purpose such as personal identification, also fixed tissues have been used to recover DNA molecules, whereas RNA extracted from such material is still considered too degraded for gene expression studies. In the present pilot study, we evaluated the possibility to use forensic formalin-fixed paraffin-embedded (FFPE) samples, collected at autopsy at different postmortem intervals (PMI) from four individuals, to perform advanced molecular analyses. In particular, we performed qualitative and quantitative analyses of total RNAs extracted from different FFPE tissues and put expression profiles in relation with the organ type and the duration of PMI. Different classes of RNA molecular targets were studied by real-time quantitative RT-PCR. We report molecular evidence that small RNAs are the only RNA molecules still detectable in all the FFPE autoptic tissues. In particular, microRNAs (miRNAs) represent a consistent, stable, and well-preserved molecular target detectable even from tissue sources displaying signs of ongoing putrefaction at autopsy. In this pilot study, we show that miRNAs could represent a highly sensitive and potentially useful forensic marker. Amplification of specific miRNAs using paraffin-embedded blocks could facilitate retrospective molecular analysis using specific forensic-archived tissues chosen as most suitable according to PMI, and this approach would address molecular evidence in forensic cases in which fresh or frozen material is no longer available. | 25,135,750 | [
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Projection radiography of the clavicle: still recommendable for forensic age diagnostics in living individuals? | As superimposition effects often impede the evaluation of the ossification status of the medial clavicular epiphysis in standard posterior-anterior (PA) radiographs, additional oblique images (right anterior oblique, RAO, and left anterior oblique, LAO) are currently recommended to allow for reliable stage assessments. The present study examines the influence of the radiographic projection type on stage determination. To this end, 836 sternoclavicular joints were prospectively obtained during forensic autopsies of bodies aged between 15 and 30 years. Subsequently, three different radiographs (PA, RAO, and LAO) were taken from each specimen and separately evaluated as to the developmental stage of the medial clavicular epiphysis. A forensically established five-stage classification system was used. In 25 % of the cases, the medial clavicular epiphysis depicted in an oblique projection showed a different ossification stage than in the PA projection. In at least 10 % of the cases, a higher ossification stage was observed which would have significant disadvantages in criminal proceedings (ethically unacceptable error). In conclusion, the usage of the current radiographic reference data, which rely upon chest radiographs taken as PA projections, appears to be inadmissible for oblique projections. Projection radiography of the clavicle can therefore no longer be recommended for forensic age estimation practice. As to the question of whether an individual has achieved the age of 18 or 21, computed tomography of the clavicle must be regarded as the exclusive method of choice. | 25,135,751 | [
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Clinical utility and diagnostic accuracy of faecal calprotectin for IBD at first presentation to gastroenterology services in adults aged 16-50 years. | Distinguishing inflammatory bowel disease (IBD) from functional gastrointestinal (GI) disease remains an important issue for gastroenterologists and primary care physicians, and may be difficult on the basis of symptoms alone. Faecal calprotectin (FC) is a surrogate marker for intestinal inflammation but not cancer. This large retrospective study aimed to determine the most effective use of FC in patients aged 16-50 presenting with GI symptoms. FC results were obtained for patients presenting to the GI clinics in Edinburgh between 2005 and 2009 from the Edinburgh Faecal Calprotectin Registry containing FCs from >16,000 patients. Case notes were interrogated to identify demographics, subsequent investigations and diagnoses. 895 patients were included in the main analysis, 65% female and with a median age of 33 years. 10.2% were diagnosed with IBD, 7.3% with another GI condition associated with an abnormal GI tract and 63.2% had functional GI disease. Median FC in these three groups were 1251, 50 and 20 μg/g (p < 0.0001). On ROC analysis, the AUC for FC as a predictor of IBD vs. functional disease was 0.97. Using a threshold of ≥ 50 μg/g for IBD vs. functional disease yielded a sensitivity of 0.97, specificity of 0.74, positive predictive value of 0.37 and negative predictive value of 0.99. Combined with alarm symptoms, the sensitivity was 1.00. Implementation of FC in the initial diagnostic workup of young patients with GI symptoms, particularly those without alarm symptoms, is highly accurate in the exclusion of IBD, and can provide reassurance to patients and physicians. | 25,135,754 | [
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The significance of mixed states in depression and mania. | The DSM-5 definition of mixed features "specifier" of manic, hypomanic and major depressive episodes captures sub-syndromal non-overlapping symptoms of the opposite pole, experienced in bipolar (I, II, and not otherwise specified) and major depressive disorders. This combinatory model seems to be more appropriate for less severe forms of mixed state, in which mood symptoms are prominent and clearly identifiable. Sub-syndromal depressive symptoms have been frequently reported to co-occur during mania. Similarly, manic or hypomanic symptoms during depression resulted common, dimensionally distributed, and recurrent. The presence of mixed features has been associated with a worse clinical course and high rates of comorbidities including anxiety, personality, alcohol and substance use disorders and head trauma or other neurological problems. Finally, mixed states represent a major therapeutic challenge, especially when you consider that these forms tend to have a less favorable response to drug treatments and require a more complex approach than non-mixed forms. | 25,135,783 | [
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Metamemory monitoring and control following retrieval practice for text. | Test-taking is assumed to help learners diagnose what they do and do not know, and by so doing improve the effectiveness of their subsequent study. Previous work has examined metamemory monitoring (e.g., predictions of future performance) and control (e.g., restudy decisions) following testing or retrieval practice with relatively simple materials (e.g., word pairs). There is reason to believe, however, that such monitoring and control decisions might be more difficult with text materials, even after retrieval practice, owing perhaps to difficulty in accurately assessing one's performance on the retrieval-practice test. In two experiments, participants read texts about world regions, then engaged in retrieval practice or rereading of the information in those texts, made estimates about future performance, and then received an opportunity to restudy the texts before taking a final recall test, with self-paced restudy enabling an examination of control processes. Memory predictions were more accurate in the retrieval-practice than in the rereading condition, and learners in both conditions allocated restudy time on the basis of their predictions. Additionally, restudy provided a greater benefit following retrieval practice than following rereading. The present study has implications for how students can use retrieval practice with text to foster subsequent learning. | 25,135,813 | [
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Glioblastoma multiforme from diagnosis to death: a prospective, hospital-based, cohort, pilot feasibility study of patient reported symptoms and needs. | Glioblastoma (GBM) patients have many palliative care (PC) issues. To date, there are no studies examining the prospective usage of validated PC assessment tools as patient reported outcome measures for GBM patients. GBM patients' PC issues were assessed from diagnosis to death or for at least 12 months every 7 weeks (±8 days) using semi-structured interviews and the Hospice and Palliative Care Evaluation (HOPE, including Eastern Cooperative Oncology Group (ECOG) performance status, 17 items) and the Palliative Outcome Scale (POS, 11 items). Data from patients who died within 12 months of the last patient's enrollment were evaluated using summarizing content analysis, visual graphical analysis (VGA), and linear mixed models for repeated measures. Nineteen of 33 patients screened were enrolled; two dropped out and four were still alive at the end of the study. The remaining 13 were assessed at 59 points until death (time range 4-68 weeks; 1-10 contacts per patient; assessment: self, 33; joint, 8; external, 18). VGA of the HOPE and POS data, including all 1,652 assessed item data, showed consistent trajectory profiles for 14 of 28 items: 10 were increasing (meaning symptom worsening) and comprised predominantly psychosocial issues and care dependency. Type of assessment partly interacted with time, however, not qualitatively so. Analysis of semi-structured interviews revealed delayed interactions with PC/hospice services and numerous neuropsychiatric problems not detected by HOPE and POS. Prospective self-assessment of GBM patients' PC issues is feasible. However, disease progression may necessitate further, external assessment. Modification of existing PC assessment tools is needed to detect GBM-specific issues. | 25,135,840 | [
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PegIFNα/ribavirin/protease inhibitor combination in severe hepatitis C virus-associated mixed cryoglobulinemia vasculitis. | The aim of this study was to analyse the safety and efficacy of the PegIFNα/ribavirin/protease inhibitor combination in severe and/or refractory hepatitis C virus (HCV)-mixed cryoglobulinemia (MC) vasculitis. This prospective cohort study included 30 patients (median age 59 years [53-66] and 57% of women) with HCV-MC vasculitis. PegIFNα/ribavirin (for 48 weeks) was associated with telaprevir (375 mg three times daily, for 12 weeks, [n = 17]) or boceprevir (800 mg three times daily, for 44 weeks, (n = 13]). Twenty three patients (76.7%) were non-responders to previous antiviral therapy. At week 72, twenty patients (66.7%) were complete clinical and sustained virological responders. The cryoglobulin level decreased from 0.45 to 0 g/L (p<0.0001) and the C4 level increased from 0.09 to 0.14 g/L (p = 0.017). Complete clinical responders had a higher frequency of purpura (16/20 [80%] vs. 4/10 [40%], p = 0.045), and a trend towards lower frequency of neuropathy (9/20 (45%) vs. 8/10 [80%], p = 0.12) compared with partial responders. Serious adverse events occurred in 14 patients (46.6%) during the 72 weeks of follow-up. Twenty eight patients (93.3%) received erythropoietin, 14 (46.6%) had red blood cell transfusion and 2 (6.6%) received granulocyte stimulating agent. The baseline factors associated with serious adverse events included liver fibrosis (p = 0.045) and a low platelet count (p = 0.021). The PegIFNα/ribavirin/protease inhibitor combination is highly effective in severe and/or refractory HCV-MC at the cost of frequent side effects. Baseline platelet count and liver fibrosis are useful in guiding treatment decisions. | 25,135,864 | [
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Ubiquitin-hepatitis B core antigen-cytoplasmic transduction peptide enhances HBV-specific humoral and CTL immune responses in vivo. | Therapeutic strategies based on an enhanced hepatitis B virus (HBV)-specific cytotoxic T lymphocyte (CTL) activity may eradicate HBV. We previously verified that a fusion protein ubiquitin (Ub)-hepatitis B core antigen (HBcAg)-cytoplasmic transduction peptide (CTP) can enter the cytoplasm of dendritic cells and enhance T cell response to generate HBV-specific CTLs efficiently in vitro. Ub, a marker of protein degradation, may promote the generation of peptides appropriate for major histocompatibility complex class I presentation. In the present study, the specific immune responses of the fusion protein Ub-HBcAg-CTP in BALB/c mice were evaluated and the underlying mechanisms were investigated. Results showed that Ub-HBcAg-CTP increased the anti-HBcAg titer and produced the cytokines IFN-γ and IL-2. This fusion protein also induced higher percentages of IFN-γ(+)CD8(+) cells and specific CTL responses. Ub-HBcAg-CTP could also upregulate the expressions of Jak2, Tyk2, STAT1, and STAT4 in T lymphocytes. In conclusion, Ub-HBcAg-CTP enhanced cellular and humoral immune responses and induced robust HBV-specific CTL activities in BALB/c mice. | 25,135,878 | [
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Factors associated with the use of prenatal corticosteroids in the management of preterm delivery in Chinese hospitals. | To assess the prevalence of the use of prenatal corticosteroids (PCS) in the management of preterm delivery and the factors associated with PCS administration. A secondary analysis was performed of a cross-sectional study conducted in 21 Chinese healthcare facilities between November 2010 and January 2011. The medical records of women who delivered preterm were reviewed. Associations between PCS administration and individual and organizational-level factors were determined. The study population comprised 659 women who delivered at 20 facilities. PCS were given to 158 (68.1%) of 232 women delivering after 27-34 weeks of pregnancy and 119 (27.9%) of 427 delivering after 35-36 weeks. Teenaged girls were less likely to receive PCS after 27-34 weeks than were women aged 20-35 years (odds ratio [OR] 0.22; 95% confidence interval [CI] 0.07-0.70). Among women who delivered after 35-36 weeks, the odds of receiving PCS were lower in urban hospitals than in periurban or rural hospitals (OR 0.04; 95% CI 0.00-0.44), and there was significant hospital-level variance with regard to the administration of PCS (P<0.05). Generally, PCS were underprescribed to women at risk of preterm delivery and many women received the treatment after 35-36 weeks of pregnancy, when it might not have been effective. | 25,135,881 | [
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Adventitious agents in viral vaccines: lessons learned from 4 case studies. | Since the earliest days of biological product manufacture, there have been a number of instances where laboratory studies provided evidence for the presence of adventitious agents in a marketed product. Lessons learned from such events can be used to strengthen regulatory preparedness for the future. We have therefore selected four instances where an adventitious agent, or a signal suggesting the presence of an agent, was found in a viral vaccine, and have developed a case study for each. The four cases are: a) SV40 in polio vaccines; b) bacteriophage in measles and polio vaccines; c) reverse transcriptase in measles and mumps vaccines; and d) porcine circovirus and porcine circovirus DNA sequences in rotavirus vaccines. The lessons learned from each event are discussed. Based in part on those experiences, certain scientific principles have been identified by WHO that should be considered in regulatory risk evaluation if an adventitious agent is found in a marketed vaccine in the future. | 25,135,887 | [
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Independent birth of a novel TRIMCyp in Tupaia belangeri with a divergent function from its paralog TRIM5. | The origin of novel genes and their evolutionary fates are long-standing questions in evolutionary biology. These questions become more complicated for genes conserved across various lineages, such as TRIM5, an antiretroviral restriction factor and a retrovirus capsid sensor in immune signaling. TRIM5 has been subjected to numerous pathogenic challenges and undergone dynamic evolution, making it an excellent example for studying gene diversification. Previous studies among several species showed that TRIM5 gained genetic and functional novelty in a lineage-specific manner, either through gene duplication or a cyclophilin A retrotransposing into the TRIM5 locus, creating the gene fusion known as TRIM5-Cyclophilin A (TRIMCyp). To date, the general pattern of TRIM5 across the mammalian lineage remains elusive. In this study, we surveyed 36 mammalian genomes to verify a potentially novel TRIM5 pattern that uniquely seems to have occurred in tree shrews (Tupaia belangeri), and found that both gene duplication and retrotransposition worked jointly to form a specific TRIM5/TRIMCyp cluster not found among other mammals. Evolutionary analyses showed that tree shrew TRIMCyp (tsTRIMCyp) originated independently in comparison with previously reported TRIMCyps and underwent strong positive selection, whereas no signal of positive selection was detected for other tree shrew TRIM5 (tsTRIM5) genes. Functional assay results suggest a functional divergence between tsTRIMCyp and its closest paralog TRIM5-4, likely reflecting different fates under diverse evolutionary forces. These findings present a rare example of novel gene origination resulting from a combination of gene duplication, retrotransposition, and exon shuffling processes, providing a new paradigm to study genetic innovations and evolutionary fates of duplicated genes. | 25,135,944 | [
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The RNA-centred view of the synapse: non-coding RNAs and synaptic plasticity. | If mRNAs were the only RNAs made by a neuron, there would be a simple mapping of mRNAs to proteins. However, microRNAs and other non-coding RNAs (ncRNAs; endo-siRNAs, piRNAs, BC1, BC200, antisense and long ncRNAs, repeat-related transcripts, etc.) regulate mRNAs via effects on protein translation as well as transcriptional and epigenetic mechanisms. Not only are genes ON or OFF, but their ability to be translated can be turned ON or OFF at the level of synapses, supporting an enormous increase in information capacity. Here, I review evidence that ncRNAs are expressed pervasively within dendrites in mammalian brain; that some are activity-dependent and highly enriched near synapses; and that synaptic ncRNAs participate in plasticity responses including learning and memory. Ultimately, ncRNAs can be viewed as the post-it notes of the neuron. They have no literal meaning of their own, but derive their functions from where (and to what) they are stuck. This may explain, in part, why ncRNAs differ so dramatically from protein-coding genes, both in terms of the usual indicators of functionality and in terms of evolutionary constraints. ncRNAs do not appear to be direct mediators of synaptic transmission in the manner of neurotransmitters or receptors, yet they orchestrate synaptic plasticity-and may drive species-specific changes in cognition. | 25,135,965 | [
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Enhancing the objectivity of the Japanese classification of peritoneal metastases from colorectal cancer. | The Japanese classification of peritoneal metastases from colorectal cancer is easy to use for general surgeons in routine clinical practice. However, the objectivity of this classification has not been determined. This study aimed to clarify the objectivity of the Japanese classification of peritoneal metastases from colorectal cancer. The data of patients with Stage IV colorectal cancer between 1991 and 2007 in 16 hospitals, who were members of the Japanese Society for Cancer of the Colon and Rectum, were investigated. The size, number and extent (nine areas) of peritoneal metastases according to the Japanese classification (P1, P2 and P3) were investigated using Akaike's information criterion. Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 had hematogenous metastases. The minimum Akaike's information criterion was obtained with the cutoff value of one area for P1 metastasis and two or more areas for P2 metastasis (P < 0.0001). When P2 metastasis was compared with P3 metastasis, the cutoff value of the number of peritoneal metastases was 10. The present study proposes a revision that would give objectivity to the present Japanese classification as follows: P1 is defined as peritoneal metastases 20 mm or smaller confined to one area; P2 is defined as 10 or fewer peritoneal metastases disseminated in two or more areas, or peritoneal metastases confined to one area but the size is >20 mm and P3 is defined as >10 peritoneal metastases disseminated in two or more areas. | 25,135,985 | [
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Molecular characterization of Streptococcus agalactiae isolates harboring small erm(T)-carrying plasmids. | Among 1,827 group B Streptococcus (GBS) strains collected between 2006 and 2013 by the French National Reference Center for Streptococci, 490 (26.8%) strains were erythromycin resistant. The erm(T) resistance gene was found in six strains belonging to capsular polysaccharides Ia, III, and V and was carried by the same mobilizable plasmid, which could be efficiently transferred by mobilization to GBS and Enterococcus faecalis recipients, thus promoting a broad dissemination of erm(T). | 25,136,004 | [
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In vitro combination of isavuconazole with micafungin or amphotericin B deoxycholate against medically important molds. | Whether isavuconazole, an extended-spectrum triazole, possesses synergistic activity in combination therapy with echinocandins or amphotericin B for the treatment of invasive molds infections has not been studied. Our in vitro combination studies showed that isavuconazole and micafungin are synergistically active against Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, and Cunninghamella bertholletiae. These results suggest that isavuconazole, in combination with micafungin, may have a role in the treatment of invasive aspergillosis and warrants further investigation. | 25,136,021 | [
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Distinct signaling mechanisms in multiple developmental pathways by the SCRAMBLED receptor of Arabidopsis. | SCRAMBLED (SCM), a leucine-rich repeat receptor-like kinase in Arabidopsis (Arabidopsis thaliana), is required for positional signaling in the root epidermis and for tissue/organ development in the shoot. To further understand SCM action, we generated a series of kinase domain variants and analyzed their ability to complement scm mutant defects. We found that the SCM kinase domain, but not kinase activity, is required for its role in root epidermal patterning, supporting the view that SCM is an atypical receptor kinase. We also describe a previously uncharacterized role for SCM in fruit dehiscence, because mature siliques from scm mutants fail to open properly. Interestingly, the kinase domain of SCM appears to be dispensable for this developmental process. Furthermore, we found that most of the SCM kinase domain mutations dramatically inhibit inflorescence development. Because this process is not affected in scm null mutants, it is likely that SCM acts redundantly to regulate inflorescence size. The importance of distinct kinase residues for these three developmental processes provides an explanation for the maintenance of the conserved kinase domain in the SCM protein, and it may generally explain its conservation in other atypical kinases. Furthermore, these results indicate that individual leucine-rich repeat receptor-like kinases may participate in multiple pathways using distinct signaling mechanisms to mediate diverse cellular communication events. | 25,136,062 | [
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Efficacy of electronic cigarettes for smoking cessation. | To review data demonstrating effective smoking cessation with electronic cigarettes (e-cigarettes). A literature search of MEDLINE/PubMed (1946-March 2014) was performed using the search terms e-cigarettes, electronic cigarettes, and smoking cessation. Additional references were identified from a review of literature citations. All English-language clinical studies assessing efficacy of e-cigarettes compared with baseline, placebo, or other pharmacological methods to aid in withdrawal symptoms, smoking reduction, or cessation were evaluated. A total of 6 clinical studies were included in the review. In small studies, e-cigarettes significantly decreased desire to smoke, number of cigarettes smoked per day, and exhaled carbon monoxide levels. Symptoms of nicotine withdrawal and adverse effects were variable. The most common adverse effects were nausea, headache, cough, and mouth/throat irritation. Compared with nicotine patches, e-cigarettes were associated with fewer adverse effects and higher adherence. Most studies showed a significant decrease in cigarette use acutely; however, long-term cessation was not sustained at 6 months. There is limited evidence for the effectiveness of e-cigarettes in smoking cessation; however, there may be a place in therapy to help modify smoking habits or reduce the number of cigarettes smoked. Studies available provided different administration patterns such as use while smoking, instead of smoking, or as needed. Short-term studies reviewed were small and did not necessarily evaluate cessation with a focus on parameters associated with cessation withdrawal symptoms. Though long-term safety is unknown, concerns regarding increased poisoning exposures among adults in comparison with cigarettes are alarming. | 25,136,064 | [
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PRMT7 induces epithelial-to-mesenchymal transition and promotes metastasis in breast cancer. | Epithelial-to-mesenchymal transition (EMT) enables metastasis. E-cadherin loss is a hallmark of EMT, but there remains an incomplete understanding of the epigenetics of this process. The protein arginine methyltransferase PRMT7 functions in various physiologic processes, including mRNA splicing, DNA repair, and neural differentiation, but its possible roles in cancer and metastasis have not been explored. In this report, we show that PRMT7 is expressed at higher levels in breast carcinoma cells and that elevated PRMT7 mediates EMT and metastasis. PRMT7 could inhibit the expression of E-cadherin by binding to its proximal promoter in a manner associated with altered histone methylation, specifically with elevated H4R3me2s and reduced H3K4me3, H3Ac, and H4Ac, which occurred at the E-cadherin promoter upon EMT induction. Moreover, PRMT7 interacted with YY1 and HDAC3 and was essential to link these proteins to the E-cadherin promoter. Silencing PRMT7 restored E-cadherin expression by repressing H4R3me2s and by increasing H3K4me3 and H4Ac, attenuating cell migration and invasion in MDA-MB-231 breast cancer cells. Overall, our results define PRMT7 as an inducer of breast cancer metastasis and present the opportunity for applying PRMT7-targeted therapeutics to treat highly invasive breast cancers. | 25,136,067 | [
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Mortality reduction in relation to implantable cardioverter defibrillator programming in the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT). | The benefit of novel implantable cardioverter defibrillator (ICD) programming in reducing inappropriate ICD therapy and mortality was demonstrated in Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT). However, the cause of mortality reduction remains incompletely evaluated. We aimed to identify factors associated with mortality, with focus on ICD therapy and programming in the MADIT-RIT population. In MADIT-RIT, 1500 patients with a primary prophylactic indication for ICD or cardiac resynchronization therapy with defibrillator were randomized to 1 of 3 different ICD programming arms: conventional programming (ventricular tachycardia zone ≥170 beats per minute), high-rate programming (ventricular tachycardia zone ≥200 beats per minute), and delayed programming (60-second delay before therapy ≥170 beats per minute). Multivariate Cox models were used to assess the influence of time-dependent appropriate and inappropriate ICD therapy (shock and antitachycardia pacing) and randomized programming arm on all-cause mortality. During an average follow-up of 1.4±0.6 years, 71 of 1500 (5%) patients died: cardiac in 40 patients (56.3%), noncardiac in 23 patients (32.4%), and unknown in 8 patients (11.3%). Appropriate shocks (hazard ratio, 6.32; 95% confidence interval, 3.13-12.75; P<0.001) and inappropriate therapy (hazard ratio, 2.61; 95% confidence interval, 1.28-5.31; P=0.01) were significantly associated with an increased mortality risk. There was no evidence of increased mortality risk in patients who experienced appropriate antitachycardia pacing only (hazard ratio, 1.02; 95% confidence interval, 0.36-2.88; P=0.98). Randomization to conventional programming was identified as an independent predictor of death when compared with patients randomized to high-rate programming (hazard ratio, 2.0; 95% confidence interval, 1.06-3.71; P=0.03). In MADIT-RIT, appropriate shocks, inappropriate ICD therapy, and randomization to conventional ICD programming were independently associated with an increased mortality risk. Appropriate antitachycardia pacing was not related to an adverse outcome. clinicaltrials.gov Unique identifier: NCT00947310. | 25,136,077 | [
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Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction. | Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration. | 25,136,093 | [
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UV damage-induced RNA polymerase II stalling stimulates H2B deubiquitylation. | Histone H2B monoubiquitylation plays an important role in RNA polymerase II (RNAPII) elongation. Whether this modification responds to RNAPII stalling is not yet known. We report that both yeast and human cells undergo a rapid and significant H2B deubiquitylation after exposure to UV irradiation. This deubiquitylation occurs concurrently with UV-induced transcription arrest and is significantly reduced in a DNA damage-bypassing RNAPII yeast mutant. Consistent with these results, yeast deubiquitylases Ubp8 and Ubp10 are associated with the RNAPII complex. Moreover, simultaneous deletion of Ubp8 and Ubp10 leads to a lack of H2B deubiquitylation after UV exposure. Consequently, nucleotide excision repair at an actively transcribed gene locus is decreased, whereas UV-induced RNAPII degradation is increased in ubp8Δubp10Δ mutant cells. These results indicate that eukaryotic cells respond to RNAPII arrest by deubiquitylating H2B to coordinate DNA repair and RNAPII degradation. | 25,136,098 | [
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Gyrification from constrained cortical expansion. | The exterior of the mammalian brain--the cerebral cortex--has a conserved layered structure whose thickness varies little across species. However, selection pressures over evolutionary time scales have led to cortices that have a large surface area to volume ratio in some organisms, with the result that the brain is strongly convoluted into sulci and gyri. Here we show that the gyrification can arise as a nonlinear consequence of a simple mechanical instability driven by tangential expansion of the gray matter constrained by the white matter. A physical mimic of the process using a layered swelling gel captures the essence of the mechanism, and numerical simulations of the brain treated as a soft solid lead to the formation of cusped sulci and smooth gyri similar to those in the brain. The resulting gyrification patterns are a function of relative cortical expansion and relative thickness (compared with brain size), and are consistent with observations of a wide range of brains, ranging from smooth to highly convoluted. Furthermore, this dependence on two simple geometric parameters that characterize the brain also allows us to qualitatively explain how variations in these parameters lead to anatomical anomalies in such situations as polymicrogyria, pachygyria, and lissencephalia. | 25,136,099 | [
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Robustness against serum neutralization of a poliovirus type 1 from a lethal epidemic of poliomyelitis in the Republic of Congo in 2010. | In 2010, a large outbreak of poliomyelitis with unusual 47% lethality occurred in Pointe Noire, Republic of Congo. Vaccine-mediated immunity against the outbreak virus was never investigated. A wild poliovirus 1 (WPV1) isolated from a fatal case (termed PV1-RC2010) showed a previously unknown combination of amino acid exchanges in critical antigenic site 2 (AgS2, VP1 capsid protein positions 221SAAL → 221PADL). These exchanges were also detected in an additional 11 WPV1 strains from fatal cases. PV1-RC2010 escaped neutralization by three different mAbs relevant for AgS2. Virus neutralization was tested in sera from fatal cases, who died before supplementary immunization (n = 24), Gabonese recipients of recent oral polio vaccination (n = 12), routinely vaccinated German medical students (n = 34), and German outpatients tested for antipoliovirus immunity (n = 17) on Vero, human rhabdomyosarcoma, and human epidermoid carcinoma 2 cells. Fatal poliomyelitis cases gave laboratory evidence of previous trivalent vaccination. Neutralizing antibody titers against PV1-RC2010 were significantly lower than those against the vaccine strain Sabin-1, two genetically distinct WPV1s isolated in 1965 and 2010 and two genetically distinct vaccine-derived PV strains. Of German vaccinees tested according to World Health Organization protocols, 15-29% were unprotected according to their neutralization titers (<1:8 serum dilution), even though all were protected against Sabin-1. Phylogenetic analysis of the WPV1 outbreak strains suggested a recent introduction of virus progenitors from Asia with formation of separate Angolan and Congolese lineages. Only the latter carried both critical AgS2 mutations. Antigenetically variant PVs may become relevant during the final phase of poliomyelitis eradication in populations with predominantly vaccine-derived immunity. Sustained vaccination coverage and clinical and environmental surveillance will be necessary. | 25,136,105 | [
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Formation and structures of GroEL:GroES2 chaperonin footballs, the protein-folding functional form. | The GroE chaperonins assist substrate protein (SP) folding by cycling through several conformational states. With each cycle the SP is, in turn, captured, unfolded, briefly encapsulated (t1/2 ∼ 1 s), and released by the chaperonin complex. The protein-folding functional form is the US-football-shaped GroEL:GroES2 complex. We report structures of two such "football" complexes to ∼ 3.7-Å resolution; one is empty whereas the other contains encapsulated SP in both chambers. Although encapsulated SP is not visible on the electron density map, using calibrated FRET and order-of-addition experiments we show that owing to SP-catalyzed ADP/ATP exchange both chambers of the football complex encapsulate SP efficiently only if the binding of SP precedes that of ATP. The two rings of GroEL thus behave as a parallel processing machine, rather than functioning alternately. Compared with the bullet-shaped GroEL:GroES1 complex, the GroEL:GroES2 football complex differs conformationally at the GroEL-GroES interface and also at the interface between the two GroEL rings. We propose that the electrostatic interactions between the ε-NH(3+) of K105 of helix D in one ring with the negatively charged carboxyl oxygen of A109 at the carboxyl end of helix D of the other ring provide the structural basis for negative inter-ring cooperativity. | 25,136,110 | [
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Immune evasion mediated by tumor-derived lactate dehydrogenase induction of NKG2D ligands on myeloid cells in glioblastoma patients. | Myeloid cells are key regulators of the tumor microenvironment, governing local immune responses. Here we report that tumor-infiltrating myeloid cells and circulating monocytes in patients with glioblastoma multiforme (GBM) express ligands for activating the Natural killer group 2, member D (NKG2D) receptor, which cause down-regulation of NKG2D on natural killer (NK) cells. Tumor-infiltrating NK cells isolated from GBM patients fail to lyse NKG2D ligand-expressing tumor cells. We demonstrate that lactate dehydrogenase (LDH) isoform 5 secreted by glioblastoma cells induces NKG2D ligands on monocytes isolated from healthy individuals. Furthermore, sera from GBM patients contain elevated amounts of LDH, which correlate with expression of NKG2D ligands on their autologous circulating monocytes. NKG2D ligands also are present on circulating monocytes isolated from patients with breast, prostate, and hepatitis C virus-induced hepatocellular carcinomas. Together, these findings reveal a previously unidentified immune evasion strategy whereby tumors produce soluble factors that induce NKG2D ligands on myeloid cells, subverting antitumor immune responses. | 25,136,121 | [
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A wave-mechanical model of incoherent quasielastic scattering in complex systems. | Quasielastic incoherent neutron scattering (QENS) is an important tool for the exploration of the dynamics of complex systems such as biomolecules, liquids, and glasses. The dynamics is reflected in the energy spectra of the scattered neutrons. Conventionally these spectra are decomposed into a narrow elastic line and a broad quasielastic band. The band is interpreted as being caused by Doppler broadening due to spatial motion of the target molecules. We propose a quantum-mechanical model in which there is no separate elastic line. The quasielastic band is composed of sharp lines with twice the natural line width, shifted from the center by a random walk of the protein in the free-energy landscape of the target molecule. The walk is driven by vibrations and by external fluctuations. We first explore the model with the Mössbauer effect. In the subsequent application to QENS we treat the incoming neutron as a de Broglie wave packet. While the wave packet passes the protons in the protein and the hydration shell it exchanges energy with the protein during the passage time of about 100 ns. The energy exchange broadens the ensemble spectrum. Because the exchange involves the free-energy landscape of the protein, the QENS not only provides insight into the protein dynamics, but it may also illuminate the free-energy landscape of the protein-solvent system. | 25,136,125 | [
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A sharp T-cell antigen receptor signaling threshold for T-cell proliferation. | T-cell antigen receptor (TCR) signaling is essential for activation, proliferation, and effector function of T cells. Modulation of both intensity and duration of TCR signaling can regulate these events. However, it remains unclear how individual T cells integrate such signals over time to make critical cell-fate decisions. We have previously developed an engineered mutant allele of the critical T-cell kinase zeta-chain-associated protein kinase 70 kDa (Zap70) that is catalytically inhibited by a small molecule inhibitor, thereby blocking TCR signaling specifically and efficiently. We have also characterized a fluorescent reporter Nur77-eGFP transgenic mouse line in which T cells up-regulate GFP uniquely in response to TCR stimulation. The combination of these technologies unmasked a sharp TCR signaling threshold for commitment to cell division both in vitro and in vivo. Further, we demonstrate that this threshold is independent of both the magnitude of the TCR stimulus and Interleukin 2. Similarly, we identify a temporal threshold of TCR signaling that is required for commitment to proliferation, after which T cells are able to proliferate in a Zap70 kinase-independent manner. Taken together, our studies reveal a sharp threshold for the magnitude and duration of TCR signaling required for commitment of T cells to proliferation. These results have important implications for understanding T-cell responses to infection and optimizing strategies for immunomodulatory drug delivery. | 25,136,127 | [
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Local anesthetic and antiepileptic drug access and binding to a bacterial voltage-gated sodium channel. | Voltage-gated sodium (Nav) channels are important targets in the treatment of a range of pathologies. Bacterial channels, for which crystal structures have been solved, exhibit modulation by local anesthetic and anti-epileptic agents, allowing molecular-level investigations into sodium channel-drug interactions. These structures reveal no basis for the "hinged lid"-based fast inactivation, seen in eukaryotic Nav channels. Thus, they enable examination of potential mechanisms of use- or state-dependent drug action based on activation gating, or slower pore-based inactivation processes. Multimicrosecond simulations of NavAb reveal high-affinity binding of benzocaine to F203 that is a surrogate for FS6, conserved in helix S6 of Domain IV of mammalian sodium channels, as well as low-affinity sites suggested to stabilize different states of the channel. Phenytoin exhibits a different binding distribution owing to preferential interactions at the membrane and water-protein interfaces. Two drug-access pathways into the pore are observed: via lateral fenestrations connecting to the membrane lipid phase, as well as via an aqueous pathway through the intracellular activation gate, despite being closed. These observations provide insight into drug modulation that will guide further developments of Nav inhibitors. | 25,136,136 | [
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Management of infantile hemangiomas: current trends. | Infantile hemangiomas (IH) are common vascular tumours. IH have a characteristic natural course. They proliferate rapidly during the early infantile period followed by a period of gradual regression over several years. Most of the uncomplicated IH undergo spontaneous involution, with a small proportion of cases requiring intervention. These are children with IH in life-threatening locations, local complications like haemorrhage, ulceration and necrosis and functional or cosmetic disfigurements. Systemic corticosteroids have been the first line of treatment for many years. Recently, non-selective beta-blockers, such as oral propranalol and topical timolol, have emerged as promising and safer therapies. Other treatment options include interferon α and vincristine which are reserved for life-threatening haemangiomas that are unresponsive to conventional therapy. This review mainly focuses on the current trends and evidence-based approach in the management of IH. | 25,136,206 | [
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Ancient schwannoma of the orbit. | The ancient schwannoma is a rare variant of a neurilemoma with a course typical of a slow-growing benign neoplasm. Histologically, it can be confused with a malignant mesenchymal tumor because of increased cellularity, nuclear pleomorphism, and hyperchromatism. Despite the degree of nuclear atypia, mitotic figures are absent. We describe the clinical and histopathologic features of an ancient schwannoma of the orbit. A need for early removal of such tumors is recommended to prevent complications. | 25,136,229 | [
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Cornelia de Lange syndrome with optic disk pit: Novel association and review of literature. | Cornelia de Lange syndrome (CdLS), also called Brachmann-de Lange syndrome, is a multiple congenital anomaly syndrome characterized by a distinctive facial appearance, ophthalmological abnormalities, prenatal and postnatal growth deficiency, psychomotor delay, behavioral problems, and malformations of the upper extremities. Most common and consistent ophthalmic features reported are nasolacrimal duct obstruction, long and curly eyelashes, blepharitis, ptosis, synophrys, telecanthus, hypertelorism, microcornea, peripapillary pigment ring, and myopia. In this report we report a case of a 5-year old boy who presented to our institution with complaint of blurring of vision in the right eye since birth. A diagnosis of Cornelia de Lange syndrome was arrived at based on the characteristic external and ophthalmic examination. He was found to have a rare association of optic nerve head coloboma in the right eye and a novel finding of an optic disk pit in the left eye. The association of optic disk pit with CdLS has never been reported earlier. We aim to provide a thorough review of literature of this not so uncommon syndrome. | 25,136,230 | [
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Optical coherence tomography demonstrating macular retinal nerve fiber thinning in advanced optic disc drusen. | Optic disc drusen (ODD) are extracellular proteinaceous excrescences in the optic nerve head. They enlarge over time and can cause damage to nerve fibers with resulting loss of visual field. The authors report a case of advanced ODD in which macular optical coherence tomography demonstrated retinal nerve fiber thinning. A single case report of a 42-year-old woman with known ODD presented to the eye clinic with worsening field of vision which was impacting on her daily life. The patient was subject to full ophthalmic examination as well as Goldmann visual field testing, optic disc photography and optical coherence tomography (OCT) of both her optic discs and maculae. ODD although rare, can be visually devastating. No treatment is currently available however patients should be counseled about progressive nature of ODD and the potential for visual loss. OCT imaging of the maculae as well as optic discs may serve a role in monitoring the damage disc drusen cause to the eye. | 25,136,235 | [
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Research progress on vertebrobasilar dolichoectasia. | Vertebrobasilar dolichoectasia (VBD) is a rare disease characterized by significant expansion, elongation, and tortuosity of the vertebrobasilar arteries. Current data regarding VBD are very limited. Here we systematically review VBD incidence, etiology, characteristics, clinical manifestations, treatment strategies, and prognosis. The exact incidence rate of VBD remains unclear, but is estimated to be 1.3% of the population. The occurrence of VBD is thought to be due to the cooperation of multiple factors, including congenital factors, infections and immune status, and degenerative diseases. The VBD clinical manifestations are complex with ischemic stroke as the most common, followed by progressive compression of cranial nerves and the brain stem, cerebral hemorrhage, and hydrocephalus. Treatment of VBD remains difficult. Currently, there are no precise and effective treatments, and available treatments mainly target the complications of VBD. With the development of stent technology, however, it may become an effective treatment for VBD. | 25,136,259 | [
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Bone morphogenetic protein-9 induces PDLSCs osteogenic differentiation through the ERK and p38 signal pathways. | Periodontal ligament stem cells (PDLSCs) with bone morphogenic ability are used to treat diseases such as periodontitis. Their treatment potential is increased when used in combination with proteins that induce osteogenic differentiation. For example, bone morphogenetic protein-9 (BMP9) has been found to have potent osteogenic activity. In the present study, PDLSCs were isolated from human periodontal membrane and infected with recombinant adenoviruses expressing BMP9 (Ad-BMP9). Levels of osteogenic markers such as runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN) as well as mineralization ability were measured. The results showed that BMP9 promoted bone formation of PDLSCs. In other experiments, SB203580 and PD98059, which are inhibitors of p38 and ERK1/2, respectively, were used to determine if these kinases are involved in the osteogenic differentiation process. The resulting protein expression profiles and osteogenic markers of PDLSCs revealed that the mitogen-activated protein kinase (MAPK) signaling pathway might play an important role in the process of BMP9-induced osteogenic differentiation of PDLSCs. | 25,136,261 | [
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Drug Resistance Mutations Alter Dynamics of Inhibitor-Bound HIV-1 Protease. | Under the selective pressure of therapy, HIV-1 protease mutants resistant to inhibitors evolve to confer drug resistance. Such mutations can impact both the dynamics and structures of the bound and unbound forms of the enzyme. Flap+ is a multidrug-resistant variant of HIV-1 protease with a combination of primary and secondary resistance mutations (L10I, G48V, I54V, V82A) and a strikingly altered thermodynamic profile for darunavir (DRV) binding relative to the wild-type protease. We elucidated the impact of these mutations on protein dynamics in the DRV-bound state using molecular dynamics simulations and NMR relaxation experiments. Both methods concur in that the conformational ensemble and dynamics of protease are impacted by the drug resistance mutations in Flap+ variant. Surprisingly this change in ensemble dynamics is different from that observed in the unliganded form of the same variant (Cai, Y. et al. <iJ. Chem. Theory Comput.</i<b2012</b, <i8</i, 3452-3462). Our comparative analysis of both inhibitor-free and bound states presents a comprehensive picture of the altered dynamics in drug-resistant mutant HIV-1 protease and underlies the importance of incorporating dynamic analysis of the whole system, including the unliganded state, into revealing drug resistance mechanisms. | 25,136,270 | [
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Pyrolysis and co-pyrolysis of Laminaria japonica and polypropylene over mesoporous Al-SBA-15 catalyst. | The catalytic co-pyrolysis of a seaweed biomass, Laminaria japonica, and a typical polymer material, polypropylene, was studied for the first time. A mesoporous material Al-SBA-15 was used as a catalyst. Pyrolysis experiments were conducted using a fixed-bed reactor and pyrolysis gas chromatography/mass spectrometry (Py-GC/MS). BET surface area, N2 adsorption-desorption isotherms, and NH3 temperature programmed desorption were measured to examine the catalyst characteristics. When only L. japonica was pyrolyzed, catalytic reforming slightly increased the gas yield and decreased the oil yield. The H2O content in bio-oil was increased by catalytic reforming from 42.03 to 50.32 wt% due to the dehydration reaction occurring on the acid sites inside the large pores of Al-SBA-15. Acids, oxygenates, mono-aromatics, poly aromatic hydrocarbons, and phenolics were the main components of the bio-oil obtained from the pyrolysis of L. japonica. Upon catalytic reforming over Al-SBA-15, the main oxygenate species 1,4-anhydro-d-galactitol and 1,5-anhydro-d-manitol were completely removed. When L. japonica was co-pyrolyzed with polypropylene, the H2O content in bio-oil was decreased dramatically (8.93 wt% in the case of catalytic co-pyrolysis), contributing to the improvement of the oil quality. A huge increase in the content of gasoline-range and diesel-range hydrocarbons in bio-oil was the most remarkable change that resulted from the co-pyrolysis with polypropylene, suggesting its potential as a transport fuel. The content of mono-aromatics with high economic value was also increased significantly by catalytic co-pyrolysis. | 25,136,282 | [
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Improving the performance of dye-sensitized solar cells with TiO2/graphene/TiO2 sandwich structure. | This study investigates the extent to which the TiO2/graphene/TiO2 sandwich structure improves the performance of dye-sensitized solar cells (DSSCs) over that of DSSCs with the traditional structure. Studies have demonstrated that the TiO2/graphene/TiO2 sandwich structure effectively enhances the open circuit voltage (V oc), short-circuit current density (J sc), and photoelectrical conversion efficiency (η) of DSSCs. The enhanced performance of DSSCs with the sandwich structure can be attributed to an increase in electron transport efficiency and in the absorption of light in the visible range. The DSSC with the sandwich structure in this study exhibited a V oc of 0.6 V, a high J sc of 11.22 mA cm(-2), a fill factor (FF) of 0.58, and a calculated η of 3.93%, which is 60% higher than that of a DSSC with the traditional structure. | 25,136,284 | [
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How may the basal ganglia contribute to auditory categorization and speech perception? | Listeners must accomplish two complementary perceptual feats in extracting a message from speech. They must discriminate linguistically-relevant acoustic variability and generalize across irrelevant variability. Said another way, they must categorize speech. Since the mapping of acoustic variability is language-specific, these categories must be learned from experience. Thus, understanding how, in general, the auditory system acquires and represents categories can inform us about the toolbox of mechanisms available to speech perception. This perspective invites consideration of findings from cognitive neuroscience literatures outside of the speech domain as a means of constraining models of speech perception. Although neurobiological models of speech perception have mainly focused on cerebral cortex, research outside the speech domain is consistent with the possibility of significant subcortical contributions in category learning. Here, we review the functional role of one such structure, the basal ganglia. We examine research from animal electrophysiology, human neuroimaging, and behavior to consider characteristics of basal ganglia processing that may be advantageous for speech category learning. We also present emerging evidence for a direct role for basal ganglia in learning auditory categories in a complex, naturalistic task intended to model the incidental manner in which speech categories are acquired. To conclude, we highlight new research questions that arise in incorporating the broader neuroscience research literature in modeling speech perception, and suggest how understanding contributions of the basal ganglia can inform attempts to optimize training protocols for learning non-native speech categories in adulthood. | 25,136,291 | [
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Executive function and endocrinological responses to acute resistance exercise. | First, to explore the effects of acute resistance exercise (RE, i.e., using exercise machines to contract and stretch muscles) on behavioral and electrophysiological performance when performing a cognitive task involving executive functioning in young male adults; Second, to investigate the potential biochemical mechanisms of such facilitative effects using two neurotrophic factors [i.e., growth hormone (GH) and insulin-like growth factor-1 (IGF-1)] and the cortisol levels elicited by such an exercise intervention mode with two different exercise intensities. Sixty young male adults were recruited and randomly assigned to a high-intensity (HI) exercise group, moderate-intensity (MI) exercise group, and non-exercise-intervention (NEI) group. Blood samples were taken, and the behavioral and electrophysiological indices were simultaneously measured when individuals performed a Go/No-Go task combined with the Erikson Flanker paradigm at baseline and after either an acute bout of 30 min of moderate- or high-intensity RE or a control period. The results showed that the acute RE could not only benefit the subjects' behavioral (i.e., RTs and accuracy) performance, as found in previous studies, but also increase the P3 amplitude. Although the serum GH and IGF-1 levels were significantly increased via moderate or high intensity RE in both the MI and HI groups, the increased serum levels of neurotrophic factors were significantly decreased about 20 min after exercise. In addition, such changes were not correlated with the changes in cognitive (i.e., behavioral and electrophysiological) performance. In contrast, the serum levels of cortisol in the HI and MI groups were significantly lower after acute RE, and the changes in cortisol levels were significantly associated with the changes in electrophysiological (i.e., P3 amplitude) performance. The findings suggest the beneficial effects of acute RE on executive functioning could be due to changes in arousal, possibly modulated by the serum cortisol levels. | 25,136,300 | [
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Microtubule networks for plant cell division. | During cytokinesis the cytoplasm of a cell is divided to form two daughter cells. In animal cells, the existing plasma membrane is first constricted and then abscised to generate two individual plasma membranes. Plant cells on the other hand divide by forming an interior dividing wall, the so-called cell plate, which is constructed by localized deposition of membrane and cell wall material. Construction starts in the centre of the cell at the locus of the mitotic spindle and continues radially towards the existing plasma membrane. Finally the membrane of the cell plate and plasma membrane fuse to form two individual plasma membranes. Two microtubule-based cytoskeletal networks, the phragmoplast and the pre-prophase band (PPB), jointly control cytokinesis in plants. The bipolar microtubule array of the phragmoplast regulates cell plate deposition towards a cortical position that is templated by the ring-shaped microtubule array of the PPB. In contrast to most animal cells, plants do not use centrosomes as foci of microtubule growth initiation. Instead, plant microtubule networks are striking examples of self-organizing systems that emerge from physically constrained interactions of dispersed microtubules. Here we will discuss how microtubule-based activities including growth, shrinkage, severing, sliding, nucleation and bundling interrelate to jointly generate the required ordered structures. Evidence mounts that adapter proteins sense the local geometry of microtubules to locally modulate the activity of proteins involved in microtubule growth regulation and severing. Many of the proteins and mechanisms involved have roles in other microtubule assemblies as well, bestowing broader relevance to insights gained from plants. | 25,136,380 | [
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Knowledge and reported use of antibiotics amongst school-teachers in New Zealand. | Gaps in public knowledge about antibiotics have led to calls for public education campaigns about antibiotics, including education of school children. This study investigates New Zealand primary school teachers' current level of knowledge about antibiotics, to assess whether this is adequate for providing accurate education for children. Two hundred and sixty-six primary school teachers from 39 schools in four cities were interviewed about their knowledge and understandings of antibiotics, using a questionnaire. Teachers reported having little current involvement with antibiotics. There were gaps in the understanding of antibiotics amongst many of the teachers. Only about 60% knew that antibiotics were useful only in bacterial infections, many believed antibiotics were useful for colds and flu, and many did not know about antibiotic resistance. On the other hand, teachers largely reported appropriate patterns of antibiotic use. If teachers are to educate children about antibiotics, basic education about antibiotics and resistance will be required for school teachers. | 25,136,399 | [
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Parotid gland solitary fibrous tumor with mandibular bone destruction and aggressive behavior. | Solitary fibrous tumor is associated with serosal surfaces. Location in the salivary glands is extremely unusual. Extrathoracic tumors have an excellent prognosis associated with their benign clinical behavior. We report an aggressive and recurrent case of this tumor. We review the clinical presentation, inmunohistochemical profiles and therapeutic approaches. A 73-years-old woman presented a mass in her right parotid gland. She had a past history of right superficial parotidectomy due to a neurilemoma. FNAB and magnetic resonance were non-specific. After a tumor resection, microscopic findings were spindled tumor cells with reactivity to CD34, bcl-2 and CD99 and the tumor was diagnosed as Solitary Fibrous Tumor. The patient suffered two recurrences and the tumor had a histological aggressive behavior and a destruction of the cortical bone of the mandible adjacent to the mass. A marginal mandibulectomy with an alveolar inferior nerve lateralization was performed. Solitary fibrous tumor is a very rare tumor. Usually, they are benign, but occasionally they can be aggressive. Complete resection is the most important prognostic factor and no evidence supports the efficacy of any therapy different to surgery. Due to the unknown prognosis and to the small number of cases reported, a long-term follow-up is guaranteed. Key words:Solitary fibrous tumor, parotid mass, parotid gland, salivary gland, rare tumors. | 25,136,435 | [
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Latency after preterm prelabor rupture of the membranes: increased risk for periventricular leukomalacia. | To identify the risk factors for cystic periventricular leukomalacia (cPVL) and their implications for deciding between immediate delivery and conservative management of preterm prelabor rupture of the membranes (pPROM). The following risk factors were compared between cPVL infants and 6440 controls: chorioamnionitis, sex, gestational age (GA), birth weight, pPROM, and pPROM-delivery interval. Factor impact on cPVL risk and clinical decision-making was determined by multivariate logistic regression. Overall cPVL prevalence (n = 32) was 0.99/1000 births. All cPVL infants but one were born <34 weeks of gestation and were <2500 g; 56% had histological chorioamnionitis versus 1.1% of controls (OR 35.9; 95%-CI 12.6-102.7). Because chorioamnionitis is a postnatal diagnosis, logistic regression was performed with prenatally available factors: pPROM-delivery interval >48 hours (OR 9.0; 95%-CI 4.1-20.0), male gender (OR 3.2; 95%-CI 1.4-7.3). GA was not a risk factor if birth weight was included. Risk decreased with increasing fetal weight despite a prolonged pPROM-delivery interval. pPROM-delivery interval is the single most important prenatally available risk factor for the development of cPVL. Immediate delivery favors babies with chorioamnionitis but disfavors those with non infectious pPROM. In the absence of clinical chorioamnionitis fetal weight gain may offset the inflammatory risk of cPVL caused by a prolonged pPROM-delivery interval. | 25,136,457 | [
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Management of humeral and glenoid bone loss in recurrent glenohumeral instability. | Recurrent shoulder instability and resultant glenoid and humeral head bone loss are not infrequently encountered in the population today, specifically in young, athletic patients. This review on the management of bone loss in recurrent glenohumeral instability discusses the relevant shoulder anatomy that provides stability to the shoulder joint, relevant history and physical examination findings pertinent to recurrent shoulder instability, and the proper radiological imaging choices in its workup. Operative treatments that can be used to treat both glenoid and humeral head bone loss are outlined. These include coracoid transfer procedures and allograft/autograft reconstruction at the glenoid, as well as humeral head disimpaction/humeroplasty, remplissage, humeral osseous allograft reconstruction, rotational osteotomy, partial humeral head arthroplasty, and hemiarthroplasty on the humeral side. Clinical outcomes studies reporting general results of these techniques are highlighted. | 25,136,461 | [
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Speckle contrast optical spectroscopy, a non-invasive, diffuse optical method for measuring microvascular blood flow in tissue. | We introduce a new, non-invasive, diffuse optical technique, speckle contrast optical spectroscopy (SCOS), for probing deep tissue blood flow using the statistical properties of laser speckle contrast and the photon diffusion model for a point source. The feasibility of the method is tested using liquid phantoms which demonstrate that SCOS is capable of measuring the dynamic properties of turbid media non-invasively. We further present an in vivo measurement in a human forearm muscle using SCOS in two modalities: one with the dependence of the speckle contrast on the source-detector separation and another on the exposure time. In doing so, we also introduce crucial corrections to the speckle contrast that account for the variance of the shot and sensor dark noises. | 25,136,500 | [
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Palliative low dose fortnightly methotrexate in oral cancers: Experience at a rural cancer centre from India. | Palliative fortnightly chemotherapy in oral cancers. We present our experience with a regimen employing fortnightly (once in 2 weeks) injectable methotrexate (MTX) (40 mg/m(2) ) in a predominantly elderly cohort of patients with carcinoma of oral cavity and oropharynx. Retrospective chart review conducted at a rural cancer center in India. All patients with oral cavity and oropharyngeal cancers started on treatment with fortnightly injectable MTX (40 mg/m(2) ) between 01/01/2011 and 31/12/2011. The factors analyzed included the duration of disease control, pain control, overall survival and progression free survival which were evaluated using the Kaplan Meier method. A total of 60 patients with a median age of 66.5 years were analyzed. Majority of the patients had poor nutritional status, performance status or co-morbidities. MTX was given for recurrent disease in 19 patients and after initial palliative radiotherapy in 41 patients. The median number of cycles delivered was nine. Grade 3/4 toxicities were seen in 2 patients only. Disease control rate at the end of treatment was seen in 33 (55%) patients. Median overall survival was 34 weeks (interquartile range: 17-50 weeks). The fortnightly regimen of MTX was well-tolerated and showed a good clinical activity in this elderly cohort of patients with advanced oral cavity and oropharyngeal cancers. | 25,136,524 | [
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Medical Nutrition Therapy based on Nutrition Intervention for a Patient with Chronic Obstructive Pulmonary Disease. | Chronic obstructive pulmonary disease (COPD) is a major cause of disability, and according to statistics from the World Health Organization, COPD is the fourth leading cause of death overall in the face of decades, and expected to be increased. In 2005, the reported prevalence of COPD in Korea was 17.2% of adults over the age of 45. Malnutrition is a common problem in papatients with COPD. And several nutritional intervention studies showed a significant improvement in physical and functional outcomes. According to the results of previous studies, the nutritional support is important. This is a case report of a patient with COPD who was introduced to a proper diet through nutrition education based on the medical nutrition therapy protocol for COPD. | 25,136,543 | [
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Estimates of the number of people living with HIV in Italy. | Objective. To estimate the HIV prevalence and the number of people living with HIV (PLHIV) in Italy with a projection for 2020. Methods. Two methods elaborated by Joint United Nations Programme on HIV/AIDS (UNAIDS) were used: Estimate and Projection Package and Spectrum. Results. A total of 123,000 (115,000-145,000) individuals aged 15 or more were estimated to be living with HIV in Italy at the end of 2012 and the estimated HIV prevalence was 0.28 (0.24-0.32) per 100 residents aged 15 or more. In 2012, the estimated number of new HIV infections among adults was 3,000 (2,700-4,000), and the number of adults in need for ART was 93,000 (80,000-110,000). The projection estimates that 130,000 (110,000-150,000) adults will live with HIV/AIDS in 2020 in Italy. Conclusion. Estimates of PLHIV in Italy stress the high number of PLHIV in need of care and treatment, as well as the need for more information and prevention campaigns. | 25,136,562 | [
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Effects of crude extracts from medicinal herbs Rhazya stricta and Zingiber officinale on growth and proliferation of human brain cancer cell line in vitro. | Hitherto, limited clinical impact has been achieved in the treatment of glioblastoma (GBMs). Although phytochemicals found in medicinal herbs can provide mankind with new therapeutic remedies, single agent intervention has failed to bring the expected outcome in clinical trials. Therefore, combinations of several agents at once are gaining increasing attractiveness. In the present study, we investigated the effects of crude alkaloid (CAERS) and flavonoid (CFEZO) extracts prepared from medicinal herbs, Rhazya stricta and Zingiber officinale, respectively, on the growth of human GBM cell line, U251. R. stricta and Z. officinale are traditionally used in folkloric medicine and have antioxidant, anticarcinogenic, and free radical scavenging properties. Combination of CAERS and CFEZO treatments synergistically suppressed proliferation and colony formation and effectively induced morphological and biochemical features of apoptosis in U251 cells. Apoptosis induction was mediated by release of mitochondrial cytochrome c, increased Bax : Bcl-2 ratio, enhanced activities of caspase-3 and -9, and PARP-1 cleavage. CAERS and CFEZO treatments decreased expression levels of nuclear NF-κBp65, survivin, XIAP, and cyclin D1 and increased expression level of p53, p21, and Noxa. These results suggest that combination of CAERS and CFEZO provides a useful foundation for studying and developing novel chemotherapeutic agents for the treatment of GBM. | 25,136,570 | [
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Recognition of 27-class protein folds by adding the interaction of segments and motif information. | The recognition of protein folds is an important step for the prediction of protein structure and function. After the recognition of 27-class protein folds in 2001 by Ding and Dubchak, prediction algorithms, prediction parameters, and new datasets for the prediction of protein folds have been improved. However, the influences of interactions from predicted secondary structure segments and motif information on protein folding have not been considered. Therefore, the recognition of 27-class protein folds with the interaction of segments and motif information is very important. Based on the 27-class folds dataset built by Liu et al., amino acid composition, the interactions of secondary structure segments, motif frequency, and predicted secondary structure information were extracted. Using the Random Forest algorithm and the ensemble classification strategy, 27-class protein folds and corresponding structural classification were identified by independent test. The overall accuracy of the testing set and structural classification measured up to 78.38% and 92.55%, respectively. When the training set and testing set were combined, the overall accuracy by 5-fold cross validation was 81.16%. In order to compare with the results of previous researchers, the method above was tested on Ding and Dubchak's dataset which has been widely used by many previous researchers, and an improved overall accuracy 70.24% was obtained. | 25,136,571 | [
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Monte Carlo simulation of protein adsorption on energetically heterogeneous surfaces. | The modified triangular-well potential model was applied to incorporate the effect of surface energy on the adsorption of particles or proteins on energetically heterogeneous surfaces. The method is convenient in simulating the adsorption on heterogeneous surface of which different region possesses different free energy. Spherical particles with attractive forces were added on the surface and underwent surface diffusion before they were quenched in place. It was seen that the ratio of surface energies of two regions had to be greater than 10 in order to simulate the adsorption in which the particles were selectively adsorbed on a favorable area. At a fixed ratio of surface energies, the obtained structures were similar. If the ratio was less than 10, the probability of adsorption on any site on the surface was not much different so the adsorption would be homogeneous adsorption. The method, thus, could be applied widely to simulate the adsorption of various conditions. | 25,136,574 | [
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Proton-based stereotactic ablative radiotherapy in early-stage non-small-cell lung cancer. | Stereotactic ablative radiotherapy (SABR), a recent implementation in the practice of radiation oncology, has been shown to confer high rates of local control in the treatment of early stage non-small-cell lung cancer (NSCLC). This technique, which involves limited invasive procedures and reduced treatment intervals, offers definitive treatment for patients unable or unwilling to undergo an operation. The use of protons in SABR delivery confers the added physical advantage of normal tissue sparing due to the absence of collateral radiation dose delivered to regions distal to the target. This may translate into clinical benefit and a decreased risk of clinical toxicity in patients with nearby critical structures or limited pulmonary reserve. In this review, we present the rationale for proton-based SABR, principles relating to the delivery and planning of this modality, and a summary of published clinical studies. | 25,136,582 | [
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Diversity and enzymatic profiling of halotolerant micromycetes from Sebkha El Melah, a Saharan salt flat in southern Tunisia. | Twenty-one moderately halotolerant fungi have been isolated from sample ashes collected from Sebkha El Melah, a Saharan salt flat located in southern Tunisia. Based on morphology and sequence inference from the internal transcribed spacer regions, 28S rRNA gene and other specific genes such as β-tubulin, actin, calmodulin, and glyceraldehyde-3-phosphate dehydrogenase, the isolates were found to be distributed over 15 taxa belonging to 6 genera of Ascomycetes: Cladosporium (n = 3), Alternaria (n = 4), Aspergillus (n = 3), Penicillium (n = 5), Ulocladium (n = 2), and Engyodontium (n = 2). Their tolerance to different concentrations of salt in solid and liquid media was examined. Excepting Cladosporium cladosporioides JA18, all isolates were considered as alkali-halotolerant since they were able to grow in media containing 10% of salt with an initial pH 10. All isolates were resistant to oxidative stresses and low temperature whereas 5 strains belonging to Alternaria, Ulocladium, and Aspergillus genera were able to grow at 45°C. The screening of fungal strains for sets of enzyme production, namely, cellulase (CMCase), amylase, protease, lipase, and laccase, in presence of 10% NaCl, showed a variety of extracellular hydrolytic and oxidative profiles. Protease was the most abundant enzyme produced whereas laccase producers were members of the genus Cladosporium. | 25,136,587 | [
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Inference of SNP-gene regulatory networks by integrating gene expressions and genetic perturbations. | In order to elucidate the overall relationships between gene expressions and genetic perturbations, we propose a network inference method to infer gene regulatory network where single nucleotide polymorphism (SNP) is involved as a regulator of genes. In the most of the network inferences named as SNP-gene regulatory network (SGRN) inference, pairs of SNP-gene are given by separately performing expression quantitative trait loci (eQTL) mappings. In this paper, we propose a SGRN inference method without predefined eQTL information assuming a gene is regulated by a single SNP at most. To evaluate the performance, the proposed method was applied to random data generated from synthetic networks and parameters. There are three main contributions. First, the proposed method provides both the gene regulatory inference and the eQTL identification. Second, the experimental results demonstrated that integration of multiple methods can produce competitive performances. Lastly, the proposed method was also applied to psychiatric disorder data in order to explore how the method works with real data. | 25,136,606 | [
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Clinical applications of end-to-side neurorrhaphy: an update. | End-to-side neurorrhaphy constitutes an interesting option to regain nerve function after damage in selected cases, in which conventional techniques are not feasible. In the last twenty years, many experimental and clinical studies have been conducted in order to understand the biological mechanisms and to test the effectiveness of this technique, with contrasting results. In this updated review, we consider the state of the art about end-to-side coaptation, focusing on all the current clinical applications, such as sensory and mixed nerve repair, treatment of facial palsy, and brachial plexus injuries and painful neuromas management. | 25,136,607 | [
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Intensive insulin therapy for septic patients: a meta-analysis of randomized controlled trials. | Background. Studies on the effect of intensive insulin therapy (IIT) in septic patients with hyperglycemia have given inconsistent results. The primary purpose of this meta-analysis was to evaluate whether it is effective in reducing mortality. Methods. We searched PubMed, Embase, the Cochrane Library, clinicaltrials.gov, and relevant reference lists up to September 2013 and including randomized controlled trials that compared IIT with conventional glucose management in septic patients. Study quality was assessed using the Cochrane Risk of Bias Tool. And our primary outcome measure was pooled in the random effects model. Results. We identified twelve randomized controlled trials involving 4100 patients. Meta-analysis showed that IIT did not reduce any of the outcomes: overall mortality (risk ratio [RR] = 0.98, 95% CI [0.85, 1.15], P = 0.84), 28-day mortality (RR = 0.66, 95% CI [0.40, 1.10], P = 0.11), 90-day mortality (RR = 1.10, 95% CI [0.97, 1.26], P = 0.13), ICU mortality (RR = 0.94, 95% CI [0.77, 1.14], P = 0.52), hospital mortality (RR = 0.98, 95% CI [0.86, 1.11], P = 0.71), severity of illness, and length of ICU stay. Conversely, the incidence of hypoglycemia was markedly higher in the IIT (RR = 2.93, 95% CI [1.69, 5.06], P = 0.0001). Conclusions. For patients with sepsis, IIT and conservative glucose management show similar efficacy, but ITT is associated with a higher incidence of hypoglycemia. | 25,136,614 | [
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Modified titanium implant as a gateway to the human body: the implant mediated drug delivery system. | The aim of this study was to investigate the efficacy of a proposed new implant mediated drug delivery system (IMDDS) in rabbits. The drug delivery system is applied through a modified titanium implant that is configured to be implanted into bone. The implant is hollow and has multiple microholes that can continuously deliver therapeutic agents into the systematic body. To examine the efficacy and feasibility of the IMDDS, we investigated the pharmacokinetic behavior of dexamethasone in plasma after a single dose was delivered via the modified implant placed in the rabbit tibia. After measuring the plasma concentration, the areas under the curve showed that the IMDDS provided a sustained release for a relatively long period. The result suggests that the IMDDS can deliver a sustained release of certain drug components with a high bioavailability. Accordingly, the IMDDS may provide the basis for a novel approach to treating patients with chronic diseases. | 25,136,624 | [
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Magnetic resonance imaging for the normal mesostenium and involvement of the mesostenium in acute pancreatitis. | The main point of this paper is to study MRI findings of the normal mesostenium and the involvement of the mesostenium in acute pancreatitis and to discuss the relationship between the involvement of the mesostenium and the severity of acute pancreatitis. In clinical practice, the mesenterical involvement in acute pancreatitis was often observed on MRI in daily works, which was little recorded in the reported studies. We conducted the current study to assess the mesenterical involvement in acute pancreatitis with MRI. We found that the mesenterical involvement of acute pancreatitis patients is common on MRI. The mesenterical involvement has a positive correlation with the MR severity index and the Acute Physiology and Chronic Healthy Evaluation II scoring system. It has been shown that MR can be used to visualize mesenterical involvement, which is a supplementary indicator in evaluating the severity of acute pancreatitis and local and systemic complications. | 25,136,639 | [
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Real life cancer comorbidity in Greek patients with diabetes mellitus followed up at a single diabetes center: an unappreciated new diabetes complication. | We determined cancer comorbidity in patients with diabetes followed up at a single Greek academic clinic and investigated the potential related factors. Cancer comorbidity was prospectively recorded for all patients with type 2 (T2DM, n = 759) or type 1 (T1DM, n = 134) diabetes of at least 10-year duration examined during one year. Patient characteristics, diabetes age of onset, duration, treatment, control, and complication rates were compared between subjects with and without cancer. Moreover, a retrospective collection of data from similar patients examined for the first time during the last 25 years, but lost to follow-up, after at least one-year's regular visits, was performed. In regularly followed-up T2DM patients cancer comorbidity was 12.6%. Patients with cancer were older and more frequently smokers. Prostate cancer was the most frequent (24.0%) type. In T1DM cancer comorbidity was 3.0%. Similar rates of comorbidity and types of cancer were observed in lost to follow-up patients. In conclusion, our patients with T2DM of at least 10-year' duration show high cancer comorbidity. No specific characteristics discriminate patients with cancer. Therefore presymptomatic cancer detection and prevention strategies may have to be incorporated into the annual systematic evaluation of our patients. | 25,136,643 | [
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Effects of pristane alone or combined with chloroquine on macrophage activation, oxidative stress, and TH1/TH2 skewness. | We investigated the protective role of chloroquine against pristane-induced macrophage activation, oxidative stress, and Th1/Th2 skewness in C57BL/6J mice. Those mice were treated with pristane alone or combined with chloroquine. Hematological and biochemical parameters, macrophage phagocytic function, the oxidant/antioxidant index, cytokine for IFN-γ, TNF-α, IL-4, and IL-6, and the isotypes of IgG2a and IgG1 were determined. And the expression of T-bet/GATA-3 and IL-12/IL-10 mRNA in spleen were analyzed by real-time PCR. We found that pristane treatment for a period of 12 or 24 weeks triggered macrophage activation syndrome, characterized by hemophagocytosis in spleen and peripheral blood, enhanced lipid phagocytosis by peritoneal macrophages in vitro, erythropenia and leucopenia, increased anti-Smith, lactic dehydrogenase, triglyceride, and ferritin, as well as hypercytokinemia of IFN-γ, TNF-α, IL-4, and IL-6. In parallel, a significant increase in lipid peroxidation and a decrease in superoxide dismutase, glutathione, and catalase activity, as well as a skewed Th1/Th2 balance in spleen, were observed. However, chloroquine supplementation showed a remarkable amelioration of these abnormalities. Our data indicate that pristane administration induces macrophage activation, oxidative stress, and Th1/Th2 skewness, which can be attenuated by chloroquine. | 25,136,646 | [
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Determination of the sediment carrying capacity based on perturbed theory. | According to the previous studies of sediment carrying capacity, a new method of sediment carrying capacity on perturbed theory was proposed. By taking into account the average water depth, average flow velocity, settling velocity, and other influencing factors and introducing the median grain size as one main influencing factor in deriving the new formula, we established a new sediment carrying capacity formula. The coefficients were determined by the principle of dimensional analysis, multiple linear regression method, and the least square method. After that, the new formula was verified through measuring data of natural rivers and flume tests and comparing the verified results calculated by Cao Formula, Zhang Formula, Li Formula, Engelung-Hansen Formula, Ackers-White Formula, and Yang Formula. According to the compared results, it can be seen that the new method is of high accuracy. It could be a useful reference for the determination of sediment carrying capacity. | 25,136,652 | [
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Inducing effect of dihydroartemisinic acid in the biosynthesis of artemisinins with cultured cells of Artemisia annua by enhancing the expression of genes. | Artemisinin has been used in the production of "artemisinin combination therapies" for the treatment of malaria. Feeding of precursors has been proven to be one of the most effective methods to enhance artemisinin production in plant cultured cells. At the current paper, the biosynthesis of artemisinin (ART) and its four analogs from dihydroartemisinic acid (DHAA) in suspension-cultured cells of Artemisia annua were investigated. ARTs were detected by HPLC/GC-MS and isolated by various chromatography methods. The structures of four DHAA metabolites, namely, dihydro-epi-deoxyarteannuin B, arteannuin I, arteannuin K, and 3-β-hydroxy-dihydro-epi-deoxyarteannuin B, were elucidated by physicochemical and spectroscopic analyses. The correlation between gene expression and ART content was investigated. The results of RT-PCR showed that DHAA could up-regulate expression of amorpha-4,11-diene synthase gene (ADS), amorpha-4,11-diene C-12 oxidase gene (CYP71AV1), and farnesyl diphosphate synthase gene (FPS) (3.19-, 7.21-, and 2.04-fold higher than those of control group, resp.), which indicated that biosynthesis processes from DHAA to ART were enzyme-mediated. | 25,136,654 | [
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Induced effects of transcranial magnetic stimulation on the autonomic nervous system and the cardiac rhythm. | Several standard protocols based on repetitive transcranial magnetic stimulation (rTMS) have been employed for treatment of a variety of neurological disorders. Despite their advantages in patients that are retractable to medication, there is a lack of knowledge about the effects of rTMS on the autonomic nervous system that controls the cardiovascular system. Current understanding suggests that the shape of the so-called QRS complex together with the size of the different segments and intervals between the PQRST deflections of the heart could predict the nature of the different arrhythmias and ailments affecting the heart. This preliminary study involving 10 normal subjects from 20 to 30 years of age demonstrated that rTMS can induce changes in the heart rhythm. The autonomic activity that controls the cardiac rhythm was indeed altered by an rTMS session targeting the motor cortex using intensity below the subject's motor threshold and lasting no more than 5 minutes. The rTMS activation resulted in a reduction of the RR intervals (cardioacceleration) in most cases. Most of these cases also showed significant changes in the Poincare plot descriptor SD2 (long-term variability), the area under the low frequency (LF) power spectrum density curve, and the low frequency to high frequency (LF/HF) ratio. The RR intervals changed significantly in specific instants of time during rTMS activation showing either heart rate acceleration or heart rate deceleration. | 25,136,660 | [
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Carbon dioxide absorption and release properties of pyrolysis products of dolomite calcined in vacuum atmosphere. | The decomposition of dolomite into CaO and MgO was performed at 1073 K in vacuum and at 1273 K in an Ar atmosphere. The dolomite calcined in vacuum was found to have a higher specific surface area and a higher micropore volume when compared to the dolomite calcined in the Ar atmosphere. These pyrolysis products of dolomite were reacted with CO2 at 673 K for 21.6 ks. On the absorption of CO2, the formation of CaCO3 was observed. The degree of absorption of the dolomite calcined in vacuum was determined to be above 50%, which was higher than the degree of absorption of the dolomite calcined in the Ar atmosphere. The CO2 absorption and release procedures were repeated three times for the dolomite calcined in vacuum. The specific surface area and micropore volume of calcined dolomite decreased with successive repetitions of the CO2 absorption and release cycles leading to a decrease in the degree of absorption of CO2. | 25,136,696 | [
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Blocked inverted indices for exact clustering of large chemical spaces. | The calculation of pairwise compound similarities based on fingerprints is one of the fundamental tasks in chemoinformatics. Methods for efficient calculation of compound similarities are of the utmost importance for various applications like similarity searching or library clustering. With the increasing size of public compound databases, exact clustering of these databases is desirable, but often computationally prohibitively expensive. We present an optimized inverted index algorithm for the calculation of all pairwise similarities on 2D fingerprints of a given data set. In contrast to other algorithms, it neither requires GPU computing nor yields a stochastic approximation of the clustering. The algorithm has been designed to work well with multicore architectures and shows excellent parallel speedup. As an application example of this algorithm, we implemented a deterministic clustering application, which has been designed to decompose virtual libraries comprising tens of millions of compounds in a short time on current hardware. Our results show that our implementation achieves more than 400 million Tanimoto similarity calculations per second on a common desktop CPU. Deterministic clustering of the available chemical space thus can be done on modern multicore machines within a few days. | 25,136,755 | [
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Teen pregnancy: an update. | To provide clinicians with a review of recent research and clinically applicable tools regarding teen pregnancy. Teen pregnancy rates have declined but still remain a significant problem in the USA. Teen pregnancy prevention was identified by Centers for Disease Control and Prevention as one of its top six priorities, which is increasing research and intervention data. Long-acting contraceptive methods are acceptable to teens and have been shown to reduce teen birth rates. Pregnant teens need special attention to counseling on pregnancy options and reducing risk during pregnancy with regular prenatal care. Postpartum teens should be encouraged and supported to breastfeed, monitored for depression, and have access to reliable contraception to avoid repeat undesired pregnancy. This review highlights important issues for all providers caring for female adolescents and those who may encounter teen pregnancy. Foremost prevention of teen pregnancy by comprehensive sexual education and access to contraception is the priority. Educating patients and healthcare providers about safety and efficacy of long-acting reversible contraception is a good step to reducing undesired teen pregnancies. Rates of postpartum depression are greater in adolescents than in adults, and adolescent mothers need to be screened and monitored for depression. Strategies to avoid another undesired pregnancy shortly after delivery should be implemented. | 25,136,760 | [
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Patient perspective in health technology assessment of pharmaceuticals in Finland. | The need to consider the patient perspective in health technology assessments (HTA) has been widely recognized. In July 2012, the Finnish Medicines Agency (Fimea) published a national recommendation for integrating the patient perspective into the HTAs of pharmaceuticals. The aim of this study is to describe the development of the recommendation for integrating the patient perspective into the HTA process of pharmaceuticals in Finland. The development of the recommendation was based on a review of international recommendations and experiences of patient and public involvement in HTA. The draft recommendation was tested in two focus group discussions (n = 7 patients) and three individual interviews among diabetes patients (type 1 or 2) using long-acting insulin treatment. The recommendation was open for public consultation in April 2012 and revised according to the comments received. Patients will be involved in multiple stages of Fimea's HTA process. The recommendation includes step-by-step instructions on how to assess the patient perspective. The main focus is on qualitative interviews, which will be conducted at the beginning of the assessments to gain information, particularly on patient preferences and values, including positive and negative outcomes important to patients and ethical and social aspects of the medicine's use. The recommendation will act as a tool to integrate patients' experiences, needs and preferences into Fimea's HTAs of pharmaceuticals. | 25,136,762 | [
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Macrophage-derived chemokine (CCL22) is a novel mediator of lung inflammation following hemorrhage and resuscitation. | Resuscitation of patients after hemorrhage often results in pulmonary inflammation and places them at risk for the development of acute respiratory distress syndrome. Our previous data indicate that macrophage-derived chemokine (MDC/CCL22) is elevated after resuscitation, but its direct role in this inflammatory response is unknown. Macrophage-derived chemokine signaling through the C-C chemokine receptor type 4 (CCR4) is implicated in other pulmonary proinflammatory conditions, leading us to hypothesize that MDC may also play a role in the pathogenesis of lung inflammation following hemorrhage and resuscitation. To test this, C57BL/6 mice underwent pressure-controlled hemorrhage followed by resuscitation with lactated Ringer's solution. Pulmonary inflammation and inflammatory cell recruitment were analyzed with histological staining, and serum- and tissue-level cytokines were measured by enzyme-linked immunosorbent assay. Pulmonary inflammation and cell recruitment following hemorrhage and resuscitation were associated with systemic MDC levels. Inhibition of MDC via injection of a specific neutralizing antibody prior to hemorrhage and resuscitation significantly reduced pulmonary levels of the chemotactic cytokines keratinocyte-derived chemokine and macrophage inflammatory proteins 2 and 1α, as well as inflammatory cell recruitment to the lungs. Intravenous administration of recombinant MDC prior to resuscitation augmented pulmonary inflammation and cell recruitment. Histological evaluation revealed the expression of CCR4 within the bronchial epithelium, and in vitro treatment of activated bronchial epithelial cells with MDC resulted in production and secretion of neutrophil chemokines. The present study identifies MDC as a novel mediator of lung inflammation after hemorrhage and resuscitation. Macrophage-derived chemokine neutralization may provide a therapeutic strategy to mitigate this inflammatory response. | 25,136,780 | [
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L. monocytogenes in a cheese processing facility: Learning from contamination scenarios over three years of sampling. | The aim of this study was to analyze the changing patterns of Listeria monocytogenes contamination in a cheese processing facility manufacturing a wide range of ready-to-eat products. Characterization of L. monocytogenes isolates included genotyping by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Disinfectant-susceptibility tests and the assessment of L. monocytogenes survival in fresh cheese were also conducted. During the sampling period between 2010 and 2013, a total of 1284 environmental samples were investigated. Overall occurrence rates of Listeria spp. and L. monocytogenes were 21.9% and 19.5%, respectively. Identical L. monocytogenes genotypes were found in the food processing environment (FPE), raw materials and in products. Interventions after the sampling events changed contamination scenarios substantially. The high diversity of globally, widely distributed L. monocytogenes genotypes was reduced by identifying the major sources of contamination. Although susceptible to a broad range of disinfectants and cleaners, one dominant L. monocytogenes sequence type (ST) 5 could not be eradicated from drains and floors. Significantly, intense humidity and steam could be observed in all rooms and water residues were visible on floors due to increased cleaning strategies. This could explain the high L. monocytogenes contamination of the FPE (drains, shoes and floors) throughout the study (15.8%). The outcome of a challenge experiment in fresh cheese showed that L. monocytogenes could survive after 14days of storage at insufficient cooling temperatures (8 and 16°C). All efforts to reduce L. monocytogenes environmental contamination eventually led to a transition from dynamic to stable contamination scenarios. Consequently, implementation of systematic environmental monitoring via in-house systems should either aim for total avoidance of FPE colonization, or emphasize a first reduction of L. monocytogenes to sites where contamination of the processed product is unlikely. Drying of surfaces after cleaning is highly recommended to facilitate the L. monocytogenes eradication. | 25,136,788 | [
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[Arthrogenic muscle inhibition after trauma - is there an age dependency of the intensity of arthrogenic muscle inhibition?]. | Backround: Knee trauma with arthrogenic muscle inhibition (AMI) lead to muscle weakness. The aim of this study was to analyse the intensity of AMI after meniscus and cartilage injuries and to investigate the association between age, BMI and severity of cartilage leasions with AMI. 48 patients with meniscus or cartilage injury were preoperatively interviewed and examined for isometric maximum force values of the extension muscles of the knee joints. We analysed AMI as comparison of maximum isometric force values between healthy and injured leg by use of Wilcoxon matched pairs test. Moreover a regression analysis was done to assess the association between age, BMI and severity of cartilage lesion with AMI. Trauma of the knee joint with meniscus or cartilage injuries led to a 23.6 % reduction of maximum force values of injured in comparison to healthy leg (460.1 ± 223.6 N vs. 601.9 ± 224.6 N, P < 0,000001) in mean. Regression analysis did not show associations between age (β -2.645, P = 0.345), BMI (β 2.268, P = 0.792) or severity of cartilage damage (β -13.527, P = 0.670) with AMI. Trauma of the knee joint with meniscus or cartilage damage cause an AMI with 23.6 % force reduction. We could not identify an association between age and AMI. | 25,136,807 | [
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The response of human thermal sensation and its prediction to temperature step-change (cool-neutral-cool). | This paper reports on studies of the effect of temperature step-change (between a cool and a neutral environment) on human thermal sensation and skin temperature. Experiments with three temperature conditions were carried out in a climate chamber during the period in winter. Twelve subjects participated in the experiments simulating moving inside and outside of rooms or cabins with air conditioning. Skin temperatures and thermal sensation were recorded. Results showed overshoot and asymmetry of TSV due to the step-change. Skin temperature changed immediately when subjects entered a new environment. When moving into a neutral environment from cool, dynamic thermal sensation was in the thermal comfort zone and overshoot was not obvious. Air-conditioning in a transitional area should be considered to limit temperature difference to not more than 5°C to decrease the unacceptability of temperature step-change. The linear relationship between thermal sensation and skin temperature or gradient of skin temperature does not apply in a step-change environment. There is a significant linear correlation between TSV and Qloss in the transient environment. Heat loss from the human skin surface can be used to predict dynamic thermal sensation instead of the heat transfer of the whole human body. | 25,136,808 | [
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Stress hyperglycaemia in hospitalised patients and their 3-year risk of diabetes: a Scottish retrospective cohort study. | Hyperglycaemia during hospital admission is common in patients who are not known to have diabetes and is associated with adverse outcomes. The risk of subsequently developing type 2 diabetes, however, is not known. We linked a national database of hospital admissions with a national register of diabetes to describe the association between admission glucose and the risk of subsequently developing type 2 diabetes. In a retrospective cohort study, patients aged 30 years or older with an emergency admission to hospital between 2004 and 2008 were included. Prevalent and incident diabetes were identified through the Scottish Care Information (SCI)-Diabetes Collaboration national registry. Patients diagnosed prior to or up to 30 days after hospitalisation were defined as prevalent diabetes and were excluded. The predicted risk of developing incident type 2 diabetes during the 3 years following hospital discharge by admission glucose, age, and sex was obtained from logistic regression models. We performed separate analyses for patients aged 40 and older, and patients aged 30 to 39 years. Glucose was measured in 86,634 (71.0%) patients aged 40 and older on admission to hospital. The 3-year risk of developing type 2 diabetes was 2.3% (1,952/86,512) overall, was <1% for a glucose ≤ 5 mmol/l, and increased to approximately 15% at 15 mmol/l. The risks at 7 mmol/l and 11.1 mmol/l were 2.6% (95% CI 2.5-2.7) and 9.9% (95% CI 9.2-10.6), respectively, with one in four (21,828/86,512) and one in 40 (1,798/86,512) patients having glucose levels above each of these cut-points. For patients aged 30-39, the risks at 7 mmol/l and 11.1 mmol/l were 1.0% (95% CI 0.8-1.3) and 7.8% (95% CI 5.7-10.7), respectively, with one in eight (1,588/11,875) and one in 100 (120/11,875) having glucose levels above each of these cut-points. The risk of diabetes was also associated with age, sex, and socio-economic deprivation, but not with specialty (medical versus surgical), raised white cell count, or co-morbidity. Similar results were obtained for pre-specified sub-groups admitted with myocardial infarction, chronic obstructive pulmonary disease, and stroke. There were 25,193 deaths (85.8 per 1,000 person-years) over 297,122 person-years, of which 2,406 (8.1 per 1,000 person-years) were attributed to vascular disease. Patients with glucose levels of 11.1 to 15 mmol/l and >15 mmol/l had higher mortality than patients with a glucose of <6.1 mmol/l (hazard ratio 1.54; 95% CI 1.42-1.68 and 2.50; 95% CI 2.14-2.95, respectively) in models adjusting for age and sex. Limitations of our study include that we did not have data on ethnicity or body mass index, which may have improved prediction and the results have not been validated in non-white populations or populations outside of Scotland. Plasma glucose measured during an emergency hospital admission predicts subsequent risk of developing type 2 diabetes. Mortality was also 1.5-fold higher in patients with elevated glucose levels. Our findings can be used to inform patients of their long-term risk of type 2 diabetes, and to target lifestyle advice to those patients at highest risk. Please see later in the article for the Editors' Summary. | 25,136,809 | [
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Gene-specific function prediction for non-synonymous mutations in monogenic diabetes genes. | The rapid progress of genomic technologies has been providing new opportunities to address the need of maturity-onset diabetes of the young (MODY) molecular diagnosis. However, whether a new mutation causes MODY can be questionable. A number of in silico methods have been developed to predict functional effects of rare human mutations. The purpose of this study is to compare the performance of different bioinformatics methods in the functional prediction of nonsynonymous mutations in each MODY gene, and provides reference matrices to assist the molecular diagnosis of MODY. Our study showed that the prediction scores by different methods of the diabetes mutations were highly correlated, but were more complimentary than replacement to each other. The available in silico methods for the prediction of diabetes mutations had varied performances across different genes. Applying gene-specific thresholds defined by this study may be able to increase the performance of in silico prediction of disease-causing mutations. | 25,136,813 | [
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Instability of trinucleotidic repeats during chromatin remodeling in spermatids. | Transient DNA breaks and evidence of DNA damage response have recently been reported during the chromatin remodeling process in haploid spermatids, creating a potential window of enhanced genetic instability. We used flow cytometry to achieve separation of differentiating spermatids into four highly purified populations using transgenic mice harboring 160 CAG repeats within exon 1 of the human Huntington disease gene (HTT). Trinucleotic repeat expansion was found to occur immediately following the chromatin remodeling steps, confirming the genetic instability of the process and pointing to the origin of paternal anticipation observed in some trinucleotidic repeats diseases. | 25,136,821 | [
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The transient receptor potential vanilloid 2 cation channel is abundant in macrophages accumulating at the peri-infarct zone and may enhance their migration capacity towards injured cardiomyocytes following myocardial infarction. | A novel family of transient receptor potential (TRP) channels, that may hold a role in calcium homeostasis, has recently been described. By employing a GeneChip array analysis we have demonstrated a clear and specific upregulation of the TRP vanilloid 2 (TRPV2) mRNA in the left ventricles (LV) 3-5 days post-acute myocardial infarction (MI) compared to sham-operated controls, both in rats and in mice. We sought to characterize the cardiac cellular subpopulations in which TRPV2 is overexpressed upon acute MI. Lewis rats underwent an acute MI by ligation of the left anterior descending artery or chest opening only (sham). The animals were terminated at various time points and an immunohistochemical (IHC) and immunofluorescent (IFC) staining of the LV sections as well as a flow cytometry analysis of LV-derived cells were carried out, using anti-TRPV2 and anti-monocyte/macrophage antibodies. Rat alveolar macrophage cells, NR8383, transiently transfected with TRPV2 siRNA were allowed to migrate towards hypoxic conditioned media of the rat cardiac myoblast line H9C2 using a trans-well migration assay. The macrophage cells migrating to the bottom side of the inserts were counted. The IHC and IFC staining as well as the flow cytometry data demonstrated a substantial expression of TRPV2 in infiltrating macrophages in the peri-infarct region 3-5 days post-acute MI. The in vitro migration assay data demonstrated that following inhibition of the TRPV2 channel, the number of migrating macrophages towards conditioned medium of hypoxic cardiomyocytes was significantly reduced. TRPV2 is highly expressed on the peri-infarct infiltrating macrophages and may play an important role in post-MI phagocytosis. Better characterization of this channel may pave the way for identifying a new target for modulating the dramatic post-MI immune reactions. | 25,136,832 | [
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In vitro inflammation inhibition model based on semi-continuous toll-like receptor biosensing. | A chemical inhibition model of inflammation is proposed by semi-continuous monitoring the density of toll-like receptor 1 (TLR1) expressed on mammalian cells following bacterial infection to investigate an in vivo-mimicked drug screening system. The inflammation was induced by adding bacterial lysate (e.g., Pseudomonas aeruginosa) to a mammalian cell culture (e.g., A549 cell line). The TLR1 density on the same cells was immunochemically monitored up to three cycles under optimized cyclic bacterial stimulation-and-restoration conditions. The assay was carried out by adopting a cell-compatible immunoanalytical procedure and signal generation method. Signal intensity relative to the background control obtained without stimulation was employed to plot the standard curve for inflammation. To suppress the inflammatory response, sodium salicylate, which inhibits nuclear factor-κB activity, was used to prepare the standard curve for anti-inflammation. Such measurement of differential TLR densities was used as a biosensing approach discriminating the anti-inflammatory substance from the non-effector, which was simulated by using caffeic acid phenethyl ester and acetaminophen as the two components, respectively. As the same cells exposed to repetitive bacterial stimulation were semi-continuously monitored, the efficacy and toxicity of the inhibitors may further be determined regarding persistency against time. Therefore, this semi-continuous biosensing model could be appropriate as a substitute for animal-based experimentation during drug screening prior to pre-clinical tests. | 25,136,864 | [
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Arthroscopic anterior shoulder stabilization with percutaneous assistance and posteroinferior capsular plication. | To study the technique and clinical outcomes of arthroscopic shoulder stabilization with anterior labral repair and percutaneous posteroinferior capsular plication, we retrospectively reviewed 20 cases. Mean (SD) final postoperative follow-up was 3.4 (0.6) years (range, 2.7-5.1 years). A mean (SD) of 4.9 (0.9) suture anchors (range, 4-7) was used during surgery, with 1.6 (0.7) (range, 1-3) devoted to the posteroinferior plication. There were statistically significant improvements in forward elevation (P = .016) and internal rotation (P = .018) from before surgery to final postoperative follow-up; external rotation did not change (P = .336). Significant improvements (P < .001) were also seen in visual analog scale pain ratings, American Shoulder and Elbow Surgeons survey scores, and Simple Shoulder Test scores. Mean (SD) Rowe instability score at final follow-up was 81.1 (28.9). Eighty-five percent of the patients returned to sport at or above preinjury level, and 70% returned to a degree of athletic physical contact at or above preinjury level. Two cases (10%) were categorized as treatment failures (redislocation). Percutaneously assisted arthroscopic anterior stabilization with posteroinferior capsular plication produces acceptable results, with functional outcomes and redislocation rates comparable to those reported in the literature. | 25,136,869 | [
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Effects of corticosteroid injection on nerve conduction testing for the diagnosis of carpal tunnel syndrome. | We conducted a study to determine the change in nerve conduction testing after steroid injection in patients with carpal tunnel syndrome (CTS). One hundred forty-five patients with suspected CTS were targeted for this study. Twenty-seven patients underwent testing before and after injection. Repeat studies were performed 4 to 6 weeks after injection. All data from the electrodiagnostic studies were entered into a database and used for comparison. Before injection, mean (SD) distal motor latency (DML) was 5.01 (0.9) ms, and mean (SD) peak sensory latency (PSL) was 5.01 (0.88) ms. After injection, mean (SD) DML was 4.82 (0.7) ms, and mean (SD) PSL was 4.69 (0.66) ms. Mean (SD) difference between preinjection and postinjection DML was 0.187 (0.45) ms, and mean difference between preinjection and postinjection PSL was 0.319 (0.48) ms. Both differences were statistically significant (paired t test). Our study results showed a statistical difference between testing done before and after steroid injection. These results indicate that injections given before electrodiagnostic testing alter results and may affect patient management. | 25,136,873 | [
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Three-year clinical outcome in the Primary Stenting of Totally Occluded Native Coronary Arteries III (PRISON III) trial: a randomised comparison between sirolimus-eluting stent implantation and zotarolimus-eluting stent implantation for the treatment of total coronary occlusions. | Sirolimus-eluting stents (SES) have been shown to be superior to Endeavor zotarolimus-eluting stents (ZES) and comparable to Resolute ZES at eight-month angiography in patients treated for total coronary occlusions (TCO). This study investigated clinical outcome at three-year follow-up. The PRISON III trial investigated the efficacy and safety of SES against ZES (Endeavor and Resolute) in two study phases. In the first phase, 51 patients were randomised to receive SES and 46 to Endeavor ZES. In the second phase, 103 and 104 patients were randomised to SES or Resolute ZES, respectively. Between one and three years there were only a few additional clinical events in all groups. As a result, the rates of target lesion revascularisation 12.2% vs. 19.6%, p=0.49, target vessel failure 14.3% vs. 19.6%, p=0.68, and definite or probable stent thrombosis 4.1% vs. 2.2% were comparable between SES and Endeavor ZES at three years. In the second study phase, the rates of target lesion revascularisation 10% vs. 5.9%, p=0.42, target vessel failure 10% vs. 7.9%, p=0.79 and definite or probable stent thrombosis 1.0% vs. 0% were similar between SES and Resolute ZES. The present study demonstrated a low incidence of clinical events between one- and three-year follow-up with either SES compared to Endeavor ZES or SES versus Resolute ZES in patients treated for total coronary occlusions. | 25,136,884 | [
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Effect of cleansing methods on saliva-contaminated zirconia--an evaluation of resin bond durability. | The aims of this study were to investigate 1) the influence of cleansing methods after saliva contamination and 2) aging conditions (thermocycling and water storage) on zirconia shear bond strength (SBS) with a resin cement. One hundred and eighty zirconia specimens were sandblasted with 50 μm aluminum oxide particles, immersed in saliva for one minute (with the exception of the control group, [C]), and divided into groups according to the cleansing method, as follows: water rinse (W); 37% phosphoric acid gel (PA); cleaning paste (ie, Ivoclean®) containing mainly zirconium oxide (IC); and 70% isopropanol (AL). Scanning electron microscopy was done to qualitatively evaluate the zirconia surface after each cleansing method. For the SBS test, resin cement buttons were bonded to the specimens using a dedicated jig. SBS was evaluated according to standard protocols after 24 hours, 5000 thermal cycles (TC), or 150 days of water storage. Statistical analysis was performed using two-way analysis of variance and Tukey test (p<0.05). Data showed a significant effect for the 150 days of water storage, TC, and 24 hours of water storage (150 days < TC < 24 hours). Group comparisons showed that PA < AL and W < IC and C. SBS ranged from 10.4 to 21.9 MPa (24 hours), from 6.4 to 14.8 MPa (TC), and from 2.9 to 7.0 MPa (150 days). Failure analysis revealed a greater percentage of mixed failures for the majority of the specimens and a smaller percentage of adhesive failures at the ceramic-resin cement interface. Our findings suggest that Ivoclean® was able to maintain adequate SBS values after TC and 150 days of storage, comparable to the uncontaminated zirconia. | 25,136,900 | [
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0.1371668,
0.2483705,
0.4145238,
0.3012525,
0.09800024,
-0.... |
Analysis of lymph node metastasis correlation with prognosis in patients with T2 gastric cancer. | To investigate the correlated factors for lymph node metastasis and prognosis for patients with T2 gastric cancer. A total of 442 patients with T2 gastric cancer who underwent gastrectomy from January 1996 to December 2009 were evaluated. The clinicopathological parameters were analyzed for lymph node metastasis and prognosis, including gender, age, tumor size, tumor location, histological type, depth of invasion, vascular tumor emboli, nervous invasion, resection type, and pathological stage. The rate of lymph node metastasis was 45.9%. Univariate analysis showed that depth of invasion, tumor size, and vascular tumor emboli were associated with lymph node metastasis. Logistic regression demonstrated that depth of invasion, tumor size, and vascular tumor emboli were independently predictive factors for lymph node metastasis. The 5-year survival rate was 64.0%. Multivariate analysis showed that tumor size, tumor location, resection type, and pathological stage were independent prognostic factors. Based on tumor size, there were significant differences of 5-year survival between small size tumor (<6 cm) and large size tumor (≥ 6 cm) according to stage IIA (P = 0.006). Based on tumor location, there were significant differences of 5-year survival among different tumor location according to stage IB. Based on resection type, there were significant differences of overall 5-year survival between curative surgery and palliative surgery according to stage IIB (P = 0.015) and IIIA (P = 0.001). Depth of invasion, tumor size, and vascular tumor emboli were independently predictive factors for lymph node metastasis. Tumor size, tumor location, resection type, and pathological stage were independent prognostic factors. | 25,136,920 | [
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0.35... |
Metamorphosis alters contaminants and chemical tracers in insects: implications for food webs. | Insects are integral to most freshwater and terrestrial food webs, but due to their accumulation of environmental pollutants they are also contaminant vectors that threaten reproduction, development, and survival of consumers. Metamorphosis from larvae to adult can cause large chemical changes in insects, altering contaminant concentrations and fractionation of chemical tracers used to establish contaminant biomagnification in food webs, but no framework exists for predicting and managing these effects. We analyzed data from 39 studies of 68 analytes (stable isotopes and contaminants), and found that metamorphosis effects varied greatly. δ(15)N, widely used to estimate relative trophic position in biomagnification studies, was enriched by ∼ 1‰ during metamorphosis, while δ(13)C used to estimate diet, was similar in larvae and adults. Metals and polycyclic aromatic hydrocarbons (PAHs) were predominantly lost during metamorphosis leading to ∼ 2 to 125-fold higher larval concentrations and higher exposure risks for predators of larvae compared to predators of adults. In contrast, manufactured organic contaminants (such as polychlorinated biphenyls) were retained and concentrated in adults, causing up to ∼ 3-fold higher adult concentrations and higher exposure risks to predators of adult insects. Both food web studies and contaminant management and mitigation strategies need to consider how metamorphosis affects the movement of materials between habitats and ecosystems, with special regard for aquatic-terrestrial linkages. | 25,136,925 | [
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... |
Nitrite and hydroxylamine as nitrogenase substrates: mechanistic implications for the pathway of N₂ reduction. | Investigations of reduction of nitrite (NO2(-)) to ammonia (NH3) by nitrogenase indicate a limiting stoichiometry, NO2(-) + 6e(-) + 12ATP + 7H(+) → NH3 + 2H2O + 12ADP + 12Pi. Two intermediates freeze-trapped during NO2(-) turnover by nitrogenase variants and investigated by Q-band ENDOR/ESEEM are identical to states, denoted H and I, formed on the pathway of N2 reduction. The proposed NO2(-) reduction intermediate hydroxylamine (NH2OH) is a nitrogenase substrate for which the H and I reduction intermediates also can be trapped. Viewing N2 and NO2(-) reductions in light of their common reduction intermediates and of NO2(-) reduction by multiheme cytochrome c nitrite reductase (ccNIR) leads us to propose that NO2(-) reduction by nitrogenase begins with the generation of NO2H bound to a state in which the active-site FeMo-co (M) has accumulated two [e(-)/H(+)] (E2), stored as a (bridging) hydride and proton. Proton transfer to NO2H and H2O loss leaves M-[NO(+)]; transfer of the E2 hydride to the [NO(+)] directly to form HNO bound to FeMo-co is one of two alternative means for avoiding formation of a terminal M-[NO] thermodynamic "sink". The N2 and NO2(-) reduction pathways converge upon reduction of NH2NH2 and NH2OH bound states to form state H with [-NH2] bound to M. Final reduction converts H to I, with NH3 bound to M. The results presented here, combined with the parallels with ccNIR, support a N2 fixation mechanism in which liberation of the first NH3 occurs upon delivery of five [e(-)/H(+)] to N2, but a total of seven [e(-)/H(+)] to FeMo-co when obligate H2 evolution is considered, and not earlier in the reduction process. | 25,136,926 | [
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... |
Serum sphingolipids reflect the severity of chronic HBV infection and predict the mortality of HBV-acute-on-chronic liver failure. | Patients with HBV-acute-on-chronic liver failure (HBV-ACLF) have high mortality and frequently require liver transplantation; few reliable prognostic markers are available. As a class of functional lipids, sphingolipids are extensively involved in the process of HBV infection. However, their role in chronic HBV infection remains unknown. The aim of this study was to determine the serum sphingolipid profile in a population of patients with chronic HBV infection, paying special attention to exploring novel prognostic markers in HBV-ACLF. High performance liquid chromatography tandem mass spectrometry was used to examine the levels of 41 sphingolipids in 156 serum samples prospectively collected from two independent cohorts. The training and validation cohorts comprised 20 and 28 healthy controls (CTRL), 29 and 23 patients with chronic hepatitis B (CHB), and 30 and 26 patients with HBV-ACLF, respectively. Biometric analysis was used to evaluate the association between sphingolipid levels and disease stages. Multivariate analysis revealed difference of sphingolipid profiles between CHB and HBV-ACLF was more drastic than that between CTRL and CHB, which indicated that serum sphingolipid levels were more likely to associate with the progression HBV-ACLF rather than CHB. Furthermore, a 3-month mortality evaluation of HBV-ACLF patients showed that dhCer(d18 : 0/24 : 0) was significantly higher in survivors than in non-survivors (including deceased patients and those undergoing liver transplantation, p < 0.05), and showed a prognostic performance similar to that of the MELD score. The serum sphingolipid composition varies between CTRL and chronic HBV infection patients. In addition, dhCer(d18 : 0/24 : 0) may be a useful prognostic indicator for the early prediction of HBV-ACLF. | 25,136,927 | [
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0.2345759,
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0.3418086,
-0.3471783,... |
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