Analysis of the cystic fibrosis lung microbiota via serial Illumina sequencing of bacterial 16S rRNA hypervariable regions.
The characterization of bacterial communities using DNA sequencing has revolutionized our ability to study microbes in nature and discover the ways in which microbial communities affect ecosystem functioning and human health. Here we describe Serial Illumina Sequencing (SI-Seq): a method for deep sequencing of the bacterial 16S rRNA gene using next-generation sequencing technology. SI-Seq serially sequences portions of the V5, V6 and V7 hypervariable regions from barcoded 16S rRNA amplicons using an Illumina short-read genome analyzer. SI-Seq obtains taxonomic resolution similar to 454 pyrosequencing for a fraction of the cost, and can produce hundreds of thousands of reads per sample even with very high multiplexing. We validated SI-Seq using single species and mock community controls, and via a comparison to cystic fibrosis lung microbiota sequenced using 454 FLX Titanium. Our control runs show that SI-Seq has a dynamic range of at least five orders of magnitude, can classify >96% of sequences to the genus level, and performs just as well as 454 and paired-end Illumina methods in estimation of standard microbial ecology diversity measurements. We illustrate the utility of SI-Seq in a pilot sample of central airway secretion samples from cystic fibrosis patients.


HLPI-Ensemble: Prediction of human lncRNA-protein interactions based on ensemble strategy.
LncRNA plays an important role in many biological and disease progression by binding to related proteins. However, the experimental methods for studying lncRNA-protein interactions are time-consuming and expensive. Although there are a few models designed to predict the interactions of ncRNA-protein, they all have some common drawbacks that limit their predictive performance. In this study, we present a model called HLPI-Ensemble designed specifically for human lncRNA-protein interactions. HLPI-Ensemble adopts the ensemble strategy based on three mainstream machine learning algorithms of Support Vector Machines (SVM), Random Forests (RF) and Extreme Gradient Boosting (XGB) to generate HLPI-SVM Ensemble, HLPI-RF Ensemble and HLPI-XGB Ensemble, respectively. The results of 10-fold cross-validation show that HLPI-SVM Ensemble, HLPI-RF Ensemble and HLPI-XGB Ensemble achieved AUCs of 0.95, 0.96 and 0.96, respectively, in the test dataset. Furthermore, we compared the performance of the HLPI-Ensemble models with the previous models through external validation dataset. The results show that the false positives (FPs) of HLPI-Ensemble models are much lower than that of the previous models, and other evaluation indicators of HLPI-Ensemble models are also higher than those of the previous models. It is further showed that HLPI-Ensemble models are superior in predicting human lncRNA-protein interaction compared with previous models. The HLPI-Ensemble is publicly available at: http://ccsipb.lnu.edu.cn/hlpiensemble/ .


Contribution of primary care to health systems and health.
Evidence of the health-promoting influence of primary care has been accumulating ever since researchers have been able to distinguish primary care from other aspects of the health services delivery system. This evidence shows that primary care helps prevent illness and death, regardless of whether the care is characterized by supply of primary care physicians, a relationship with a source of primary care, or the receipt of important features of primary care. The evidence also shows that primary care (in contrast to specialty care) is associated with a more equitable distribution of health in populations, a finding that holds in both cross-national and within-national studies. The means by which primary care improves health have been identified, thus suggesting ways to improve overall health and reduce differences in health across major population subgroups.


Gene Therapy Applications of Non-Human Lentiviral Vectors.
Recent commercialization of lentiviral vector (LV)-based cell therapies and successful reports of clinical studies have demonstrated the untapped potential of LVs to treat diseases and benefit patients. LVs hold notable and inherent advantages over other gene transfer agents based on their ability to transduce non-dividing cells, permanently transform target cell genome, and allow stable, long-term transgene expression. LV systems based on non-human lentiviruses are attractive alternatives to conventional HIV-1-based LVs due to their lack of pathogenicity in humans. This article reviews non-human lentiviruses and highlights their unique characteristics regarding virology and molecular biology. The LV systems developed based on these lentiviruses, as well as their successes and shortcomings, are also discussed. As the field of gene therapy is advancing rapidly, the use of LVs uncovers further challenges and possibilities. Advances in virology and an improved understanding of lentiviral biology will aid in the creation of recombinant viral vector variants suitable for translational applications from a variety of lentiviruses.


Hierarchical anatomical brain networks for MCI prediction: revisiting volumetric measures.
Owning to its clinical accessibility, T1-weighted MRI (Magnetic Resonance Imaging) has been extensively studied in the past decades for prediction of Alzheimer's disease (AD) and mild cognitive impairment (MCI). The volumes of gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) are the most commonly used measurements, resulting in many successful applications. It has been widely observed that disease-induced structural changes may not occur at isolated spots, but in several inter-related regions. Therefore, for better characterization of brain pathology, we propose in this paper a means to extract inter-regional correlation based features from local volumetric measurements. Specifically, our approach involves constructing an anatomical brain network for each subject, with each node representing a Region of Interest (ROI) and each edge representing Pearson correlation of tissue volumetric measurements between ROI pairs. As second order volumetric measurements, network features are more descriptive but also more sensitive to noise. To overcome this limitation, a hierarchy of ROIs is used to suppress noise at different scales. Pairwise interactions are considered not only for ROIs with the same scale in the same layer of the hierarchy, but also for ROIs across different scales in different layers. To address the high dimensionality problem resulting from the large number of network features, a supervised dimensionality reduction method is further employed to embed a selected subset of features into a low dimensional feature space, while at the same time preserving discriminative information. We demonstrate with experimental results the efficacy of this embedding strategy in comparison with some other commonly used approaches. In addition, although the proposed method can be easily generalized to incorporate other metrics of regional similarities, the benefits of using Pearson correlation in our application are reinforced by the experimental results. Without requiring new sources of information, our proposed approach improves the accuracy of MCI prediction from 80.83% (of conventional volumetric features) to 84.35% (of hierarchical network features), evaluated using data sets randomly drawn from the ADNI (Alzheimer's Disease Neuroimaging Initiative) dataset.


Leukocyte telomere length in relation to the risk of Barrett's esophagus and esophageal adenocarcinoma.
Chronic inflammation and oxidative damage caused by obesity, cigarette smoking, and chronic gastroesophageal reflux disease (GERD) are major risk factors associated with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). EAC has been increasing the past few decades, and early discovery and treatment are crucial for survival. Telomere shortening due to cell division and oxidative damage may reflect the impact of chronic inflammation and could possibly be used as predictor for disease development. We examined the prevalence of shorter leukocyte telomere length (LTL) among individuals with GERD, BE, or EAC using a pooled analysis of studies from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). Telomere length was measured in leukocyte DNA samples by Q-PCR. Participants included 1173 patients (386 with GERD, 384 with EAC, 403 with BE) and 736 population-based controls. The association of LTL (in tertiles) along the continuum of disease progression from GERD to BE to EAC was calculated using study-specific odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models adjusted for potential confounders. Shorter LTL were less prevalent among GERD patients (OR 0.57; 95% CI: 0.35-0.93), compared to population-based controls. No statistically significant increased prevalence of short/long LTL among individuals with BE or EAC was observed. In contrast to some earlier reports, our findings add to the evidence that leukocyte telomere length is not a biomarker of risk related to the etiology of EAC. The findings do not suggest a relationship between LTL and BE or EAC.


Evaluation of antimicrobial regimens for treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis.
The most appropriate therapy for meningitis caused by Streptococcus pneumoniae strains resistant to the extended-spectrum cephalosporins is unknown. We evaluated ceftriaxone, vancomycin, and rifampin alone and in different combinations and meropenem, cefpirome, and clinafloxacin alone in the rabbit meningitis model. Meningitis was induced in rabbits by intracisternal inoculation of one of two pneumococcal strains isolated from infants with meningitis (ceftriaxone MICs, 4 and 1 microgram/ml, respectively). Two doses, 5 h apart, of each antibiotic were given intravenously (except that ceftriaxone was given as one dose). Cerebrospinal fluid bacterial concentrations were measured at 0, 5, 10, and 24 h after therapy was started. Clinafloxacin was the most active single agent against both strains. Against the more resistant strain, ceftriaxone or meropenem alone was ineffective. The combination of vancomycin and ceftriaxone was synergistic, suggesting that this combination might be effective for initial empiric therapy of pneumococcal meningitis until results of susceptibility studies are available.


Comparison of twin and autologous transplants for multiple myeloma.
Relapse is the overwhelming cause of treatment failure after autologous transplantation for multiple myeloma (MM). For patients with a syngeneic donor, twin transplants provide a healthy graft that is free of myeloma. The relative impact of the graft on posttransplant relapse can be estimated by comparing risk of relapse after hematopoietic cell transplantation from genetically identical twins versus autotransplants because confounding differences in minor or major histocompatibility antigens are absent in the syngeneic transplant setting. Outcomes of 43 subjects who received twin transplants for MM were compared to 170 matched autotransplant recipients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Multivariate analysis was performed by fitting a Cox model stratified on matched pairs. The matched transplant patients studied were similar with respect to subject-, disease-, and transplant-related characteristics. Cumulative incidence of relapse/progression was significantly lower, and progression-free survival (PFS) was significantly higher following twin transplants. In multivariate analysis, the probability of relapse/progression was lower in twins (relative risk [RR] = 0.49, 95% confidence interval [CI] 0.28-0.86, P = .011). Twin transplants have a significantly lower relapse risk than autotransplants in MM, suggesting that graft composition may impact outcomes following high-dose chemotherapy.


Determination of minimum clinically important difference in pain, disability, and quality of life after extension of fusion for adjacent-segment disease.
Spinal surgical outcome studies rely on patient-reported outcome (PRO) measurements to assess treatment effect. A shortcoming of these questionnaires is that the extent of improvement in their numerical scores lack a direct clinical meaning. As a result, the concept of minimum clinical important difference (MCID) has been used to measure the critical threshold needed to achieve clinically relevant treatment effectiveness. As utilization of spinal fusion has increased over the past decade, so has the incidence of adjacent-segment degeneration following index lumbar fusion, which commonly requires revision laminectomy and extension of fusion. The MCID remains uninvestigated for any PROs in the setting of revision lumbar surgery for adjacent-segment disease (ASD). In 50 consecutive patients undergoing revision surgery for ASD-associated back and leg pain, PRO measures of back and leg pain on a visual analog scale (BP-VAS and LP-VAS, respectively), Oswestry Disability Index (ODI), 12-Item Short Form Health Survey Physical and Mental Component Summaries (SF-12 PCS and MCS, respectively), and EuroQol-5D health survey (EQ-5D) were assessed preoperatively and 2 years postoperatively. The following 4 well-established anchor-based MCID calculation methods were used to calculate MCID: average change; minimum detectable change (MDC); change difference; and receiver operating characteristic curve (ROC) analysis for the following 2 separate anchors: health transition item (HTI) of the SF-36 and satisfaction index. All patients were available for 2-year PRO assessment. Two years after surgery, a statistically significant improvement was observed for all PROs (mean changes: BP-VAS score [4.80 ± 3.25], LP-VAS score [3.28 ± 3.25], ODI [10.24 ± 13.49], SF-12 PCS [8.69 ± 12.55] and MCS [8.49 ± 11.45] scores, and EQ-5D [0.38 ± 0.45]; all p < 0.001). The 4 MCID calculation methods generated a range of MCID values for each of the PROs (BP-VAS score, 2.3-6.5; LP-VAS score, 1.7-4.3; ODI, 6.8-16.9; SF-12 PCS, 6.1-12.6; SF-12 MCS, 2.4-10.8; and EQ-5D, 0.27-0.54). The area under the ROC curve was consistently greater for the HTI anchor than the satisfaction anchor, suggesting this as a more accurate anchor for MCID. Adjacent-segment disease revision surgery-specific MCID is highly variable based on calculation technique. The MDC approach with HTI anchor appears to be most appropriate for calculation of MCID after revision lumbar fusion for ASD because it provided a threshold above the 95% CI of the unimproved cohort (greater than the measurement error), was closest to the mean change score reported by improved and satisfied patients, and was not significantly affected by choice of anchor. Based on this method, MCID following ASD revision lumbar surgery is 3.8 points for BP-VAS score, 2.4 points for LP-VAS score, 6.8 points for ODI, 8.8 points for SF-12 PCS, 9.3 points for SF-12 MCS, and 0.35 quality-adjusted life-years for EQ-5D.


Irinotecan-induced diarrhea: functional significance of the polymorphic ABCC2 transporter protein.
Interindividual pharmacokinetic variability of the anticancer agent irinotecan is high. Life-threatening diarrhea is observed in up to 25% of patients receiving irinotecan and has been related with irinotecan pharmacokinetics and UGT1A1 genotype status. Here, we explore the association of ABCC2 (MRP2) polymorphisms and haplotypes with irinotecan disposition and diarrhea. A cohort of 167 Caucasian cancer patients who were previously assessed for irinotecan pharmacokinetics (90-min infusion given every 21 days), toxicity, and UGT1A1*28 genotype were genotyped for polymorphisms in ABCC2 using Pyrosequencing. Fifteen ABCC2 haplotypes were identified in the studied patients. The haplotype ABCC2*2 was associated with lower irinotecan clearance (28.3 versus 31.6 l/h; P=0.020). In patients who did not carry a UGT1A1*28 allele, a significant reduction of severe diarrhea was noted in patients with the ABCC2*2 haplotype (10 versus 44%; odds ratio, 0.15; 95% confidence interval, 0.04-0.61; P=0.005). This effect was not observed in patients with at least one UGT1A1*28 allele (32 versus 20%; odds ratio, 1.87; 95% confidence interval, 0.49-7.05; P=0.354). This study suggests that the presence of the ABCC2*2 haplotype is associated with less irinotecan-related diarrhea, maybe as a consequence of reduced hepatobiliary secretion of irinotecan. As the association was seen in patients not genetically predisposed at risk for diarrhea due to UGT1A1*28, confirmatory studies of the relationships of ABCC2 genotypes and irinotecan disposition and toxicity are warranted.


The oxidative environment and protein damage.
Proteins are a major target for oxidants as a result of their abundance in biological systems, and their high rate constants for reaction. Kinetic data for a number of radicals and non-radical oxidants (e.g. singlet oxygen and hypochlorous acid) are consistent with proteins consuming the majority of these species generated within cells. Oxidation can occur at both the protein backbone and on the amino acid side-chains, with the ratio of attack dependent on a number of factors. With some oxidants, damage is limited and specific to certain residues, whereas other species, such as the hydroxyl radical, give rise to widespread, relatively non-specific damage. Some of the major oxidation pathways, and products formed, are reviewed. The latter include reactive species, such as peroxides, which can induce further oxidation and chain reactions (within proteins, and via damage transfer to other molecules) and stable products. Particular emphasis is given to the oxidation of methionine residues, as this species is readily oxidised by a wide range of oxidants. Some side-chain oxidation products, including methionine sulfoxide, can be employed as sensitive, specific, markers of oxidative damage. The product profile can, in some cases, provide valuable information on the species involved; selected examples of this approach are discussed. Most protein damage is non-repairable, and has deleterious consequences on protein structure and function; methionine sulfoxide formation can however be reversed in some circumstances. The major fate of oxidised proteins is catabolism by proteosomal and lysosomal pathways, but some materials appear to be poorly degraded and accumulate within cells. The accumulation of such damaged material may contribute to a range of human pathologies.


Developmental changes during childhood in single-letter acuity and its crowding by surrounding contours.
Crowding refers to impaired target recognition caused by surrounding contours. We investigated the development of crowding in central vision by comparing single-letter and crowding thresholds in groups of 5-year-olds, 8-year-olds, 11-year-olds, and adults. The task was to discriminate the orientation of a Sloan letter E. Single-letter thresholds, defined as the stroke width forming the smallest discriminable E, were worse than those of adults (0.83 arcmin) at 5 years of age (1.05 arcmin) but not at older ages (8-year-olds: 0.81 arcmin; 11-year-olds: 0.78 arcmin). The maximum distances over which crowding occurred, as measured in multiples of threshold stroke width, were smaller in adults (2.83) than in the three groups of children, who did not differ from each other (5-year-olds: 7.03; 8-year-olds: 7.84; 11-year-olds: 7.13). Thus, even 11-year-olds are more affected than adults by surrounding contours despite having single-letter acuity that has been mature for several years. The stronger influence of crowding in children may be caused by immaturities in the brain areas beyond the primary visual cortex (V1) where early visual inputs are combined and may contribute to their slower reading speed.


Cognitive biases toward Internet game-related pictures and executive deficits in individuals with an Internet game addiction.
The cue-related go/no-go switching task provides an experimental approach to study individual's flexibility in changing situations. Because Internet addiction disorder (IAD) belongs to the compulsive-impulsive spectrum of disorders, it should present cognitive bias and executive functioning deficit characteristics of some of these types of disorders. Until now, no studies have been reported on cognitive bias and executive function involving mental flexibility and response inhibition in IAD. A total of 46 subjects who met the criteria of the modified Young's Diagnostic Questionnaire for Internet addiction (YDQ) were recruited as an Internet game addiction (IGA) group, along with 46 healthy control individuals. All participants performed the Internet game-shifting task. Using hit rate, RT, d' and C as the dependent measures, a three-way ANOVA (group × target × condition) was performed. For hit rate, a significant effect of group, type of target and condition were found. The group-target interaction effect was significant. For RT, significant effects were revealed for group and type of target. The group-target interaction effect was significant. Comparisons of the means revealed that the slowing down of IGA relative to NIA was more pronounced when the target stimuli were neutral as opposed to Internet game-related pictures. In addition, the group-condition interaction effect was significant. For d', significant effects of group, type of target and condition were found. The group-target interaction effect was significant. For C, the type of target produced a significant effect. There was a positive correlation between the length of the addiction (number of years) and the severity of the cognitive bias. IGA present cognitive biases towards information related to Internet gaming. These biases, as well as poor executive functioning skills (lower mental flexibility and response inhibition), might be responsible for Internet game addiction. The assessment of cognitive biases in IGA might provide a methodology for evaluation of therapeutic effects.


Glucose Self-monitoring in Non-Insulin-Treated Patients With Type 2 Diabetes in Primary Care Settings: A Randomized Trial.
The value of self-monitoring of blood glucose (SMBG) levels in patients with non-insulin-treated type 2 diabetes has been debated. To compare 3 approaches of SMBG for effects on hemoglobin A1c levels and health-related quality of life (HRQOL) among people with non-insulin-treated type 2 diabetes in primary care practice. The Monitor Trial study was a pragmatic, open-label randomized trial conducted in 15 primary care practices in central North Carolina. Participants were randomized between January 2014 and July 2015. Eligible patients with type 2 non-insulin-treated diabetes were: older than 30 years, established with a primary care physician at a participating practice, had glycemic control (hemoglobin A1c) levels higher than 6.5% but lower than 9.5% within the 6 months preceding screening, as obtained from the electronic medical record, and willing to comply with the results of random assignment into a study group. Of the 1032 assessed for eligibility, 450 were randomized. No SMBG, once-daily SMBG, and once-daily SMBG with enhanced patient feedback including automatic tailored messages delivered via the meter. Coprimary outcomes included hemoglobin A1c levels and HRQOL at 52 weeks. A total of 450 patients were randomized and 418 (92.9%) completed the final visit. There were no significant differences in hemoglobin A1c levels across all 3 groups (P = .74; estimated adjusted mean hemoglobin A1c difference, SMBG with messaging vs no SMBG, -0.09%; 95% CI, -0.31% to 0.14%; SMBG vs no SMBG, -0.05%; 95% CI, -0.27% to 0.17%). There were also no significant differences found in HRQOL. There were no notable differences in key adverse events including hypoglycemia frequency, health care utilization, or insulin initiation. In patients with non-insulin-treated type 2 diabetes, we observed no clinically or statistically significant differences at 1 year in glycemic control or HRQOL between patients who performed SMBG compared with those who did not perform SMBG. The addition of this type of tailored feedback provided through messaging via a meter did not provide any advantage in glycemic control. clinicaltrials.gov Identifier: NCT02033499.


Stochastic distribution of small soil eukaryotes resulting from high dispersal and drift in a local environment.
A central challenge in ecology is to understand the relative importance of processes that shape diversity patterns. Compared with aboveground biota, little is known about spatial patterns and processes in soil organisms. Here we examine the spatial structure of communities of small soil eukaryotes to elucidate the underlying stochastic and deterministic processes in the absence of environmental gradients at a local scale. Specifically, we focus on the fine-scale spatial autocorrelation of prominent taxonomic and functional groups of eukaryotic microbes. We collected 123 soil samples in a nested design at distances ranging from 0.01 to 64 m from three boreal forest sites and used 454 pyrosequencing analysis of Internal Transcribed Spacer for detecting Operational Taxonomic Units of major eukaryotic groups simultaneously. Among the main taxonomic groups, we found significant but weak spatial variability only in the communities of Fungi and Rhizaria. Within Fungi, ectomycorrhizas and pathogens exhibited stronger spatial structure compared with saprotrophs and corresponded to vegetation. For the groups with significant spatial structure, autocorrelation occurred at a very fine scale (<2 m). Both dispersal limitation and environmental selection had a weak effect on communities as reflected in negative or null deviation of communities, which was also supported by multivariate analysis, that is, environment, spatial processes and their shared effects explained on average <10% of variance. Taken together, these results indicate a random distribution of soil eukaryotes with respect to space and environment in the absence of environmental gradients at the local scale, reflecting the dominant role of drift and homogenizing dispersal.


Acute central effects of L-glutamate in pentobarbital-anesthetized dogs.
Microinjections of L-glutamate (10(-10) to 2 X 10(-8) mol/kg) into the nucleus of tractus solitarii produced a dose-dependent increase in mean arterial pressure and a decrease in heart rate. L-Glutamate-induced hypertension was prevented by spinal transection and pretreatment with atropine (1 mg/kg iv) reversed the bradycardia. L-Glutamate also produced a dose-dependent increase in mean arterial pressure when injected intravenously and into the cisterna magna, but the dose-effect curves were shifted to the right. Finally, pretreatment with hexamethonium (30 mg/kg iv) abolished the hypertension resulting from intravenous injections of L-glutamate. These data demonstrate that the nucleus of tractus solitarii may play a determinant role in the central pressor effects of L-glutamate. In addition, we demonstrated that this hypertension was due to a central sympathetic stimulation and that the autonomic nervous system also mediated the pressor effects of intravenous L-glutamate.


Asymptomatic corneal staining associated with the use of balafilcon silicone-hydrogel contact lenses disinfected with a polyaminopropyl biguanide-preserved care regimen.
To compare subjective symptoms and signs in a group of individuals who wear silicone-hydrogel lenses on a daily wear basis while they sequentially used two differing care regimens. Fifty adapted soft-lens wearers were fitted with a silicone-hydrogel lens material (PureVision, Bausch & Lomb). The lenses were worn on a daily wear basis for two consecutive 1-month periods, during which the subjects used either a Polyquad (polyquaternium-1) -based system or a polyaminopropyl biguanide (PHMB) -based system, using a double-masked, randomized, crossover experimental design. Significant levels of relatively asymptomatic corneal staining were observed when subjects used the PHMB-based system, with 37% of subjects demonstrating a level of staining consistent with a classical solution-based toxicity reaction. Only 2% of the subjects exhibited such staining when using the Polyquad-based system. These results were significantly different (p < 0.001). Significant symptoms were not correlated with the degree of staining, with no differences in lens comfort or overall preference being reported between the regimens (p = NS). The only statistically significant difference in symptoms related to minor differences in stinging after lens insertion being reported, with the Polyquad-based system demonstrating less stinging (p < 0.008). Practitioners who fit silicone-hydrogel contact lenses on a daily wear basis should be wary of the potential for certain PHMB-containing multipurpose care systems to invoke corneal staining. Switching to non-PHMB based regimens will eliminate this complication in most instances.


Understanding people's experience of vitreo-retinal day surgery: a Gadamerian-guided study.
This paper is a report of a study that aimed to understand the individual's experience of day surgery for repair of vitreo-retinal pathology. Day surgery evolved as a global phenomenon in response to tensions existing between community demand for health-care services and fiscal limitations. Since then vitreo-retinal surgery has been routinely performed as day surgery. Whilst studies have reported on patients' experience's following inpatient surgery, there has been limited investigation of vitreo-retinal day surgery from the patient's perspective. In-depth unstructured interviews with 18 people were conducted between July 2006 and December 2007. Data analysis using philosophical hermeneutic techniques enabled a co-constructed understanding, where, the 'conditions of understanding' as described by Gadamer were established. Guided by a Gadamerian approach to analysis, four constitutive themes were identified: 'the physical Self', 'the psychological Self', 'the historically located Self' and 'the Self located in the community'. Within each theme the participant's positive and negative experiences were understood in the context of human need, and gaps in nursing care became illuminated. These experiences included: pain, nausea, problematic self-care and psychological angst. Insights into the experience of vitreo-retinal day surgery, gained from this study can be used to inform nurses planning care for people with vitreo-retinal pathology. Nursing care must address broader patient needs that span multiple human domains, particularly when vision has been threatened by complex pathology.


How do United Kingdom (UK) medical schools identify and support undergraduate medical students who 'fail' communication assessments? A national survey.
The doctor's ability to communicate effectively (with patients, relatives, advocates and healthcare colleagues) relates directly to health outcomes, and so is core to clinical practice. The remediation of medical students' clinical communication ability is rarely addressed in medical education literature. There is nothing in the current literature reporting a contemporary national picture of how communication difficulties are managed, and the level of consequence (progression implications) for students of performing poorly. This survey aimed to consolidate practices for identifying and processes for managing students who 'fail' communication assessments across all UK medical schools. Data were collected via an email survey to all leads for clinical communication in all UK Medical Schools for the UK Council for Clinical Communication in Undergraduate Medical Education. All but two participating Schools reported some means of support and/or remediation in communication. There was diversity of approach, and variance in the level of systemisation adopted. Variables such as individuality of curricula, resourcing issues, student cohort size and methodological preferences were implicated as explaining diversity. Support is relatively ad hoc, and often in the hands of a particular dedicated individual or team with an interest in communication delivery with few Schools reporting robust, centralised, school level processes. This survey has demonstrated that few Medical Schools have no identifiable system of managing their students' clinical communication difficulties. However, some Schools reported ad hoc approaches and only a small number had a centralised programme. There is scope for discussion and benchmarking of best practice across all Schools with allocation of appropriate resources to support this.


Potassium channel opening: a subtle two-step.
Voltage-gated K(+) channels undergo a voltage-dependent conductance change that plays a key role in modulating cellular excitability. While the Open state is captured in crystal structures of Kv1.2 and a chimeric Kv1.2/Kv2.1 channel, the Close state and the mechanism of this transition are still a subject of debate. Here, we propose a model based on mutagenesis combined with measurements of both ionic and gating currents which is consistent with the idea that the Open state is the default state, the energy of the electric field being used to keep the channel closed. Our model incorporates an 'Activated state' where the bulk of sensor movement is completed without channel opening. The model accounts for the well characterized electrophysiology of the 'V2' and 'ILT' mutations in Shaker, where sensor movement and channel opening occur over distinct voltage ranges. Moreover, the model proposes relatively small protein rearrangements in going from the Activated to the Open state, consistent with the rapid transitions observed in single channel records of Shaker type channels at zero millivolts.


When civil registration is inadequate: interim methods for generating vital statistics.
Comprehensive guidelines and tools to help countries rapidly improve their vital statistics systems, based on international best practice are now available. For many countries, however, attainment of timely, accurate statistics on births and deaths and causes of death will require years of strategic and prioritized investment, with technical assistance from WHO, the United Nations, and academia. In the meantime, however, countries will need accurate and unbiased data in order to measure progress with their health programs and broader development goals, such as the MDGs and the growing crisis of non-communicable diseases. This article has introduced some interim strategies that can yield adequate vital statistics and cause of death data as countries work to strengthen their civil registration systems. These methods mirror the skills, practices and advantages of complete and functioning civil registration and vital statistics systems, but for a sample of the population. They are based on the principle of rigorous and continuous data collection for a defined and manageable part of the population. Doing "smaller, representative" populations well rather than "larger populations poorly" will reduce the biases that would otherwise occur from missing data, incorrect application of data management procedures, poor data quality checking and lack of medical certification of causes of death. A critical component of this strategy is to routinely apply verbal autopsy methods to collect essential cause of death data. When properly applied, VA can yield population-based cause of death data of comparable quality to what is typically collected in hospitals in developing countries. Moreover, with the availability of automated methods to diagnose causes of death, it is now possible to obtain accurate cause of death data routinely, cheaply and quickly in resource-poor settings. The long-term goal of strengthening civil registration and vital statistics systems is to ensure that every birth and death is properly registered, and that causes of death are accurately certified. Stakeholders wishing to establish sentinel surveillance or sample registration should work in collaboration with national and local authorities responsible for civil registration and should support and promote the formal registration of births and deaths whenever possible. In addition, sentinel or sample registration systems should help strengthen the capacity of the health system to correctly certify the causes of death for each decedent.


Characteristics of suicidality among adolescents.
The identification of high-risk adolescent suicide attempters in a population of depressed and suicidal adolescents is of crucial importance. This retrospective study examined characteristics of suicidality (recent and lifetime, active and passive) and psychopathology (depression, aggression, impulsivity, stressful life events, SCL-90 dimensions) among four groups of depressed adolescent outpatients: (1) suicide attempters who required medical treatment (n = 84), (2) suicide attempters who did not require medical treatment (n = 57), (3) suicidal ideators who had never made a suicide attempt (n = 40), and (4) nonsuicidal patients (n = 44). Results indicate that the nonsuicidal group could be differentiated from the three suicidal groups on the basis of suicidality and psychopathology, and that the three suicidal groups could be differentiated from one another on the basis of suicidality but not psychopathology. These findings are discussed in terms of the usefulness of certain self-report measures of suicidality for identifying suicidal adolescents and for differentiating among them. Furthermore, the findings suggest that psychopathological factors do not determine which suicidal adolescents make a medically dangerous suicide attempt and which do not.


Genomic Characterization of Fluoroquinolone-Resistant Thermophilic Campylobacter Strains Isolated from Layer Chicken Feces in Gangneung, South Korea by Whole-Genome Sequencing.
Thermophilic Campylobacter species of poultry origin have been associated with up to 80% of human campylobacteriosis cases. Layer chickens have received less attention as possible reservoirs of Campylobacter species. Initially, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of two archived Campylobacter isolates (Campylobacter jejuni strain 200605 and Campylobacter coli strain 200606) from layer chickens to five antimicrobials (ciprofloxacin, nalidixic acid, erythromycin, tetracycline, and gentamicin) were determined using broth microdilution while the presence of selected antimicrobial resistance genes was performed by polymerase chain reaction (PCR) using specific primers. Whole-genome sequencing (WGS) was performed by the Illumina HiSeq X platform. The analysis involved antimicrobial resistance genes, virulome, multilocus sequence typing (MLST), and phylogeny. Both isolates were phenotypically resistant to ciprofloxacin (MIC: 32 vs. 32 µg/mL), nalidixic acid (MIC: 128 vs. 64 µg/mL), and tetracycline (MIC: 64 vs. 64 µg/mL), but sensitive to erythromycin (MIC: 1 vs. 2 µg/mL) and gentamicin (MIC: 0.25 vs. 1 µg/mL) for C. jejuni strain 200605 and C. coli strain 200606, respectively. WGS confirmed C257T mutation in the gyrA gene and the presence of cmeABC complex conferring resistance to FQs in both strains. Both strains also exhibited tet(O) genes associated with tetracycline resistance. Various virulence genes associated with motility, chemotaxis, and capsule formation were found in both isolates. However, the analysis of virulence genes showed that C. jejuni strain 200605 is more virulent than C. coli strain 200606. The MLST showed that C. jejuni strain 200605 belongs to sequence type ST-5229 while C. coli strain 200606 belongs to ST-5935, and both STs are less common. The phylogenetic analysis clustered C. jejuni strain 200605 along with other strains reported in Korea (CP028933 from chicken and CP014344 from human) while C. coli strain 200606 formed a separate cluster with C. coli (CP007181) from turkey. The WGS confirmed FQ-resistance in both strains and showed potential virulence of both strains. Further studies are recommended to understand the reasons behind the regional distribution (Korea, China, and Vietnam) of such rare STs.


The Value of the "Lab-Score" Method in Identifying Febrile Infants at Risk for Serious Bacterial Infections.
Most children with fever without source will have a self limited viral infection though a small percent will develop a serious bacterial infection (SBI) like urinary tract infection, pneumonia, bacteraemia, meningitis or sepsis. The challenge facing practitioners is to distinguish between these two groups and currently biomarkers, like C-reactive protein (CRP) and Procalcitonin (PCT), are available for this purpose.The aim of the current study was to identify SBI in infants with fever without an identifiable cause using the recently introduced "Lab-score" combining C-reactive protein, procalcitonin and urine dipstick results. This survey is part of an observational study aimed at identifying children with fever without source at risk of SBI. Patients were recruited from the Emergency Department of Tîrgu Mures Emergency Clinical County Hospital, Romania, during 2013. SBI diagnosis was based on urine, blood and cerebrospinal fluid cultures and chest radiographs. For infants, aged 7 days to 12 months, CRP and PCT were determined and the "Lab-score" was calculated. Positive and negative likelihood ratios and post test probabilities were calculated for each parameter and score. Of the ninety infants included in the study, SBI was diagnosed in nineteen (21.11%). Ten had a urinary tract infection, seven had pneumonia, one had a urinary tract infection and bacteraemia, and one had sepsis. Positive and negative likelihood ratios for CRP (≥40.0 mg/L) and PCT (≥0.5 ng/mL) were 10.27/0.45 and 7.07/0.24 and post-test probabilities 73%/65%. For a "Lab-score" (≥3), positive and negative likelihood ratios were 10.43/0.28, and the posttest probability was 73%. In our survey the "Lab-score" proved a strong predictor for the identification of febrile infants at risk of SBI, but showed no significant difference compared with CRP and PCT which both proved equally good predictors for SBI.


Posttraumatic stress symptomatology is associated with unexplained illness attributed to Persian Gulf War military service.
Controversy exists concerning unexplained illness in Persian Gulf War veterans, especially regarding the contribution of psychological trauma. We sought to determine if war zone trauma or posttraumatic stress symptomatology (PTSS) are associated with illnesses reported by Gulf War veterans that were documented by medical examination but not attributable to a medical diagnosis. A total of 1119 (55% response rate) of 2022 randomly sampled veterans of the United States Persian Gulf War were screened and 237 cases and 113 controls were identified by medical examination for a case-control study comparing Persian Gulf War military veterans with or without medically documented, but unexplained, symptoms. Multivariate logistic regression and cross-validation analyses examined self-report measures of demographics, subjective physical symptoms and functioning, psychiatric symptoms, stressors, war zone trauma, and PTSS, to identify correlates of case-control status. Posttraumatic stress symptomatology and somatic complaints were independently associated with case status, as were (although less consistently) war zone trauma and depression. Age, education, and self-reported health, stress-related somatization, pain, energy/fatigue, illness-related functional impairment, recent stressors, and anxiety were univariate (but not multivariate) correlates of case status. PTSS related to war zone trauma warrants additional prospective research study and attention in clinical screening and assessment as a potential contributor to the often debilitating physical health problems experienced by Persian Gulf War veterans.


Temporal analysis of the relationship between dengue and meteorological variables in the city of Rio de Janeiro, Brazil, 2001-2009.
Dengue, a reemerging disease, is one of the most important viral diseases transmitted by mosquitoes. Climate is considered an important factor in the temporal and spatial distribution of vector-transmitted diseases. This study examined the effect of seasonal factors and the relationship between climatic variables and dengue risk in the city of Rio de Janeiro, Brazil, from 2001 to 2009. Generalized linear models were used, with Poisson and negative binomial distributions. The best fitted model was the one with "minimum temperature" and "precipitation", both lagged by one month, controlled for "year". In that model, a 1°C increase in a month's minimum temperature led to a 45% increase in dengue cases in the following month, while a 10-millimeter rise in precipitation led to a 6% increase in dengue cases in the following month. Dengue transmission involves many factors: although still not fully understood, climate is a critical factor, since it facilitates analysis of the risk of epidemics.


The perception of self-produced sensory stimuli in patients with auditory hallucinations and passivity experiences: evidence for a breakdown in self-monitoring.
To test the hypothesis that certain psychotic symptomatology is due to a defect in self-monitoring, we investigated the ability of groups of psychiatric patients to differentiate perceptually between self-produced and externally produced tactile stimuli. Responses to tactile stimulation were assessed in three groups of subjects: schizophrenic patients; patients with bipolar affective disorder or depression; and normal control subjects. Within the psychiatric groups subjects were divided on the basis of the presence or absence of auditory hallucinations and/or passivity experiences. The subjects were asked to rate the perception of a tactile sensation on the palm of their left hand. The tactile stimulation was either self-produced by movement of the subject's right hand or externally produced by the experimenter. Normal control subjects and those psychiatric patients with neither auditory hallucinations nor passivity phenomena experienced self-produced stimuli as less intense, tickly and pleasant than identical, externally produced tactile stimuli. In contrast, psychiatric patients with these symptoms did not show a decrease in their perceptual ratings for tactile stimuli produced by themselves as compared with those produced by the experimenter. This failure to show a difference in perception between self-produced and externally produced stimuli appears to relate to the presence of auditory hallucinations and/or passivity experiences rather than to the diagnosis of schizophrenia. We propose that auditory hallucinations and passivity experiences are associated with an abnormality in the self-monitoring mechanism that normally allows us to distinguish self-produced from externally produced sensations.


Ertapenem-induced acute reversible peripheral neuropathy in chronic kidney disease: 3 case reports.
Ertapenem is a broad-spectrum and long-acting carbapenem which is predominantly eliminated by the kidneys, and it requires dose adjustment in renal failure. Although it is known that excessive doses of ertapenem can cause neurotoxicity, there are very few case reports of ertapenem-induced reversible peripheral neuropathy in the literature when used with renal adjusted doses. We report 3 patients with a history of stage 4 or 5 chronic kidney disease (CKD) who developed acute reversible peripheral neuropathy proven with electroencephalography (EEG) and electromyography (EMG). All patients received renal adjusted doses of ertapenem for complicated urinary tract infection (UTI). We also discuss the incidence of carbapenem-related neurotoxicity, mechanisms, and risk factors with a review of the literature. All patients developed acute peripheral, and additionally one acute central nervous system, neuropathy within 1 week of treatment with ertapenem, which was confirmed by EMG. Complete clinical recovery was obtained in all patients within 2 weeks of cessation of ertapenem treatment, and electromyography was confirmatory in all patients. Ertapenem is potentially neurotoxic in patients with CKD even when it is given with renal adjusted doses according to recommendations. Although carbapenem-related neurotoxicity most commonly manifests as seizures, our series indicates that acute and reversible peripheral neuropathy can also develop. Clinicians administering ertapenem for patients with a GFR of < 30 mL/min/1.73 m2 should be cautious.


Examining risk and resilience factors for depression: The role of self-criticism and self-compassion.
Whereas self-criticism has been proposed as an important risk factor for major depressive disorder (MDD), self-compassion has been suggested as a resilience factor that protects against the development and maintenance of depressive episodes. This study aimed to test the hypothesis that frequent self-criticism and low habitual self-compassion are related to concurrent depression and to vulnerability to depression by comparing groups of currently, remitted and never depressed individuals. As expected, both currently and remitted depressed individuals reported higher levels of self-criticism and lower self-compassion than never depressed controls. Individual differences in self-criticism and self-compassion were related to depression status above and beyond additional potential correlates of MDD (i.e., perfectionistic beliefs and cognitions, rumination and overall adaptive emotion regulation). The findings provide support for the idea that increased self-criticism and decreased self-compassion place certain individuals at increased risk for experiencing depression repeatedly or chronically over the course of their lives.


Comparison of a high-resolution melting assay to next-generation sequencing for analysis of HIV diversity.
Next-generation sequencing (NGS) has recently been used for analysis of HIV diversity, but this method is labor-intensive, costly, and requires complex protocols for data analysis. We compared diversity measures obtained using NGS data to those obtained using a diversity assay based on high-resolution melting (HRM) of DNA duplexes. The HRM diversity assay provides a single numeric score that reflects the level of diversity in the region analyzed. HIV gag and env from individuals in Rakai, Uganda, were analyzed in a previous study using NGS (n = 220 samples from 110 individuals). Three sequence-based diversity measures were calculated from the NGS sequence data (percent diversity, percent complexity, and Shannon entropy). The amplicon pools used for NGS were analyzed with the HRM diversity assay. HRM scores were significantly associated with sequence-based measures of HIV diversity for both gag and env (P < 0.001 for all measures). The level of diversity measured by the HRM diversity assay and NGS increased over time in both regions analyzed (P < 0.001 for all measures except for percent complexity in gag), and similar amounts of diversification were observed with both methods (P < 0.001 for all measures except for percent complexity in gag). Diversity measures obtained using the HRM diversity assay were significantly associated with those from NGS, and similar increases in diversity over time were detected by both methods. The HRM diversity assay is faster and less expensive than NGS, facilitating rapid analysis of large studies of HIV diversity and evolution.


Identification and characterization of hemoangiogenic progenitors during cynomolgus monkey embryonic stem cell differentiation.
We identified intermediate-stage progenitor cells that have the potential to differentiate into hematopoietic and endothelial lineages from nonhuman primate embryonic stem (ES) cells. Sequential fluorescence-activated cell sorting and immunostaining analyses showed that when ES cells were cultured in an OP9 coculture system, both lineages developed after the emergence of two hemoangiogenic progenitor-bearing cell fractions, namely, vascular endothelial growth factor receptor (VEGFR)-2(high) CD34(-) and VEGFR-2(high) CD34(+) cells. Exogenous vascular endothelial growth factor increased the proportion of VEGFR-2(high) cells, particularly that of VEGFR-2(high) CD34(+) cells, in a dose-dependent manner. Although either population of VEGFR-2(high) cells could differentiate into primitive and definitive hematopoietic cells (HCs), as well as endothelial cells (ECs), the VEGFR-2(high) CD34(+) cells had greater hemoangiogenic potential. Both lineages developed from VEGFR-2(high) CD34(-)or VEGFR-2(high) CD34(+) precursor at the single-cell level, which strongly supports the existence of hemangioblasts in these cell fractions. Thus, this culture system allows differentiation into the HC and EC lineages to be defined by surface markers. These observations should facilitate further studies both on early developmental processes and on regeneration therapies in human.


Concomitant atrial fibrillation ablation in patients undergoing coronary artery bypass and cardiac valve surgery.
Surgical ablation of atrial fibrillation (AF) in conjunction with other cardiac surgery is now a class I guideline recommendation. Multiple studies have demonstrated that the concomitant surgical ablation of AF can be performed safely and effectively during valve and coronary artery bypass grafting (CABG) resulting in a return to sinus rhythm postoperatively and improved long-term results. However, the surgical ablation of AF at the time of other cardiac surgery is performed less often than it should be, especially in patients undergoing CABG and aortic valve surgery. Randomized-controlled trials designed to determine the effect of treating AF concomitantly with other cardiac surgical procedures have lacked long-term follow up, but multiple, large observational studies have demonstrated an improved quality of life, a decrease in long-term strokes, and improved late survival in patients who undergo AF ablation. However, the potential survival benefit of concomitant AF ablation was not addressed by either the Society of Thoracic Surgery or American Association for Thoracic Surgery guideline committees. Left atrial appendage closure is an important part of the surgical ablation of AF as it significantly reduces the long-term risk of stroke following cardiac surgery and improves the success of AF treatment. In this study, we update the electrophysiology and surgical community on the recommended surgical techniques for AF ablation and its effect on perioperative morbidity, perioperative mortality, as well as its long-term effects on stroke, quality of life, and survival.


The ABRF Proteomics Research Group studies: educational exercises for qualitative and quantitative proteomic analyses.
Resource (core) facilities have played an ever-increasing role in furnishing the scientific community with specialized instrumentation and expertise for proteomics experiments in a cost-effective manner. The Proteomics Research Group (PRG) of the Association of Biomolecular Resource Facilities (ABRF) has sponsored a number of research studies designed to enable participants to try new techniques and assess their capabilities relative to other laboratories analyzing the same samples. Presented here are results from three PRG studies representing different samples that are typically analyzed in a core facility, ranging from simple protein identification to targeted analyses, and include intentional challenges to reflect realistic studies. The PRG2008 study compares different strategies for the qualitative characterization of proteins, particularly the utility of complementary methods for characterizing truncated protein forms. The use of different approaches for determining quantitative differences for several target proteins in human plasma was the focus of the PRG2009 study. The PRG2010 study explored different methods for determining specific constituents while identifying unforeseen problems that could account for unanticipated results associated with the different samples, and included (15) N-labeled proteins as an additional challenge. These studies provide a valuable educational resource to research laboratories and core facilities, as well as a mechanism for establishing good laboratory practices.


Adrenoceptor α2A signalling countervails the taming effects of synchronous cyclic nucleotide-elevation on thrombin-induced human platelet activation and aggregation.
The healthy vascular endothelium constantly releases autacoids which cause an increase of intracellular cyclic nucleotides to tame platelets from inappropriate activation. Elevating cGMP and cAMP, in line with previous reports, cooperated in the inhibition of isolated human platelet intracellular calcium-mobilization, dense granules secretion, and aggregation provoked by thrombin. Further, platelet alpha granules secretion and, most relevant, integrin αIIaβ3 activation in response to thrombin are shown to be prominently affected by the combined elevation of cGMP and cAMP. Since stress-related sympathetic nervous activity is associated with an increase in thrombotic events, we investigated the impact of epinephrine in this setting. We found that the assessed signalling events and functional consequences were to various extents restored by epinephrine, resulting in full and sustained aggregation of isolated platelets. The restoring effects of epinephrine were abolished by either interfering with intracellular calcium-elevation or with PI3-K signalling. Finally, we show that in our experimental setting epinephrine likewise reconstitutes platelet aggregation in heparinized whole blood, which may indicate that this mechanism could also apply in vivo.


Catechol-O-methyltransferase polymorphism modulates cognitive control in children with chromosome 22q11.2 deletion syndrome.
Dopamine plays a critical role in regulating neural activity in prefrontal cortex (PFC) and modulates cognition via a hypothesized inverse U function. We investigated PFC function in children with chromosome 22q11.2 deletion syndrome (22q11.2DS) in which one copy of catechol-O-methyltransferase (COMT) is deleted, thereby shifting them toward the lower end of dopamine turnover on the nonlinear function. A common polymorphism with valine to methionine substitution alters COMT activity that results in higher enzyme activity in the valine variant. Twenty-seven children with 22q11.2DS between 7 and 14 years old, and 21 age-matched typically developing children, performed a modified version of the Attention Network Test. Children with a single valine allele showed a reduction in response times when trials with incongruent flankers were repeated, whereas those who were hemizygous for the methionine allele did not show the same context-based response facilitation. Our results support that a single gene, COMT, could modulate PFC-dependent cognition.


The marginal zone and its contribution to the hypoblast and primitive streak of the chick embryo.
The marginal zone of the chick embryo has been shown to play an important role in the formation of the hypoblast and of the primitive streak. In this study, time-lapse filming, fate mapping, ablation and transplantation experiments were combined to study its contribution to these structures. It was found that the deep (endodermal) portion of the posterior marginal zone contributes to the hypoblast and to the junctional endoblast, while the epiblast portion of the same region contributes to the epiblast of the primitive streak and to the definitive (gut) endoderm derived from it. Within the deep part of the posterior marginal zone, a subpopulation of HNK-1-positive cells contributes to the hypoblast. Removal of the deep part of the marginal zone prevents regeneration of the hypoblast but not the formation of a primitive streak. Removal of both layers of the marginal zone leads to a primitive streak of abnormal morphology but mesendodermal cells nevertheless differentiate. These results show that the two main properties of the posterior marginal zone (contributing to the hypoblast and controlling the site of primitive streak formation) are separable, and reside in different germ layers. This conclusion does not support the idea that the influence of the posterior marginal zone on the development of axial structures is due to it being the source of secondary hypoblast cells.


Vascular endothelial growth factor expression in pig latissimus dorsi myocutaneous flaps after ischemia reperfusion injury.
Exogenous administration of vascular endothelial growth factor (VEGF) improves long-term viability of myocutaneous flaps. However, endogenous expression of this substance in flaps following ischemia-reperfusion injury has not been reported previously. Endogenous production of VEGF was measured in myocutaneous pig latissimus dorsi flaps after ischemia-reperfusion injury. Latissimus dorsi myocutaneous flaps (15 x 10 cm) were simultaneously elevated bilaterally in six Yorkshire-type male pigs (25 kg). Before elevation, three flap zones (5 x 10 cm) were marked according to their distance from the vascular pedicle. After isolation of the vascular pedicle, ischemia-reperfusion injury was induced in one flap by occlusion of the thoracodorsal artery and vein for 4 hours, followed by 2 hours of reperfusion. The contralateral flap served as a control. Perfusion in each zone was monitored by laser Doppler flowmetry at baseline, during ischemia, and during reperfusion. At the end of the protocol, skin and muscle biopsies of each flap zone and adjacent tissues were obtained for later determination of VEGF protein levels. VEGF concentrations were quantified using the Quantikine human VEGF immunoassay. Skin perfusion was similar among all flap zones before surgery. Flow fell in all flaps immediately after flap elevation. After 4 hours of ischemia, blood flow in the ischemic flaps was significantly decreased (p < 0.05) compared with nonischemic control flaps. After 2 hours of reperfusion, flow in ischemic flap skin recovered to levels similar to those in control flaps. VEGF protein concentrations in muscle tissue exceeded concentrations in skin and decreased from zones 2 to 3 in control and ischemic flaps. No significant differences in VEGF concentrations between ischemic and control muscle zones were observed. However, the concentration of VEGF in all muscle zones was significantly higher (p < 0.05) than muscle adjacent to the flap. Concentrations in skin zones 1 and 2 were significantly higher (p < 0.05) in ischemic flaps than in control flaps, but levels in zone 3 (most ischemic flaps) showed no significant difference.


Association of the LINGO2-related SNP rs10968576 with body mass in a cohort of elderly Swedes.
Genome-wide association studies (GWAS) have identified common genetic factors influencing body mass as well as body adiposity. The functional implications of these loci are currently under investigation. Intense scrutiny of the body mass-associated FTO locus revealed age-specific effects, or a weakened effect in elderly populations. In this study, we aimed to determine the effects of single nucleotide polymorphisms (SNPs) representing 35 GWAS-identified body mass- and adiposity-associated genetic loci. In our analysis, 949 participants of the Prospective Investigation of the Vasculature in Uppsala Seniors cohort were included. All participants were born between 1920 and 1924. Data were available for 474 male and 475 female participants at age 70 and 380 male and 390 female participants at age 75. Genetic associations with BMI and change in BMI from age 70 to 75 were analyzed. In our analysis, rs10968576, an intronic SNP within the LINGO2 (LERN3, LRRN6C) gene, was associated with body mass in a cross section of elderly Swedes at age 70. This is the first study to replicate the association of a LINGO2-related genetic variant with body mass in an independent cohort of elderly citizens.


Impact of the Nordic hamstring and hip extension exercises on hamstring architecture and morphology: implications for injury prevention.
The architectural and morphological adaptations of the hamstrings in response to training with different exercises have not been explored. To evaluate changes in biceps femoris long head (BFLH) fascicle length and hamstring muscle size following 10-weeks of Nordic hamstring exercise (NHE) or hip extension (HE) training. 30 recreationally active male athletes (age, 22.0±3.6 years; height, 180.4±7 cm; weight, 80.8±11.1 kg) were allocated to 1 of 3 groups: (1) HE training (n=10), NHE training (n=10), or no training (control, CON) (n=10). BFLH fascicle length was assessed before, during (Week 5) and after the intervention with a two-dimensional ultrasound. Hamstring muscle size was determined before and after training via MRI. Compared with baseline, BFLH fascicles were lengthened in the NHE and HE groups at mid-training (d=1.12-1.39, p<0.001) and post-training (d=1.77-2.17, p<0.001) and these changes did not differ significantly between exercises (d=0.49-0.80, p=0.279-0.976). BFLH volume increased more for the HE than the NHE (d=1.03, p=0.037) and CON (d=2.24, p<0.001) groups. Compared with the CON group, both exercises induced significant increases in semitendinosus volume (d=2.16-2.50, ≤0.002) and these increases were not significantly different (d=0.69, p=0.239). NHE and HE training both stimulate significant increases in BFLH fascicle length; however, HE training may be more effective for promoting hypertrophy in the BFLH.


Five-year follow-up of patients with type 1 diabetes transplanted with allogeneic islets: the UIC experience.
This report summarizes a 5-year phase 1/2 allogeneic islet transplantation clinical trial conducted at the University of Illinois at Chicago (UIC). Ten patients were enrolled in this single center, open label, and prospective trial in which patients received 1-3 transplants. The first four subjects underwent islet transplantation with the Edmonton immunosuppressive regimen and the remaining six subjects received the UIC immunosuppressive protocol (Edmonton plus etanercept and exenatide). All 10 patients achieved insulin independence after 1-3 transplants. At 5 years of follow-up, 6 of the initial 10 patients were free of exogenous insulin. During the follow-up period, 7 of the 10 patients maintained positive C-peptide levels and a composite hypoglycemic score of 0. Most patients maintained HbA1c levels <6.0 % (42.1 mmol/mol) and a significantly improved β-score. In conclusion, this study demonstrated long-term islet graft function without using T cell depleting induction, with an encouraging outcome that includes 60 % of patients remaining insulin independent after 5 years of initial transplantation.


Oxidative Stress during the Progression of β-Amyloid Pathology in the Neocortex of the Tg2576 Mouse Model of Alzheimer's Disease.
Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive neurodegeneration. Pathogenetic mechanisms, triggered by β-amyloid (Aβ) accumulation, include oxidative stress, derived from energy homeostasis deregulation and involving mitochondria and peroxisomes. We here addressed the oxidative stress status and the elicited cellular response at the onset and during the progression of Aβ pathology, studying the neocortex of Tg2576 model of AD. Age-dependent changes of oxidative damage markers, antioxidant enzymes, and related transcription factors were analysed in relation to the distribution of Aβ peptide and oligomers, by a combined molecular/morphological approach. Nucleic acid oxidative damage, accompanied by defective antioxidant defences, and decreased PGC1α expression are already detected in 3-month-old Tg2576 neurons. Conversely, PPARα is increased in these cells, with its cytoplasmic localization suggesting nongenomic, anti-inflammatory actions. At 6 months, when intracellular Aβ accumulates, PMP70 is downregulated, indicating impairment of fatty acids peroxisomal translocation and their consequent harmful accumulation. In 9-month-old Tg2576 neocortex, Aβ oligomers and acrolein deposition correlate with GFAP, GPX1, and PMP70 increases, supporting a compensatory response, involving astroglial peroxisomes. At severe pathological stages, when senile plaques disrupt cortical cytoarchitecture, antioxidant capacity is gradually lost. Overall, our data suggest early therapeutic intervention in AD, also targeting peroxisomes.


Cognitive, emotional, and social processes in psychosis: refining cognitive behavioral therapy for persistent positive symptoms.
Psychosis used to be thought of as essentially a biological condition unamenable to psychological interventions. However, more recent research has shown that positive symptoms such as delusions and hallucinations are on a continuum with normality and therefore might also be susceptible to adaptations of the cognitive behavioral therapies found useful for anxiety and depression. In the context of a model of cognitive, emotional, and social processes in psychosis, the latest evidence for the putative psychological mechanisms that elicit and maintain symptoms is reviewed. There is now good support for emotional processes in psychosis, for the role of cognitive processes including reasoning biases, for the central role of appraisal, and for the effects of the social environment, including stress and trauma. We have also used virtual environments to test our hypotheses. These developments have improved our understanding of symptom dimensions such as distress and conviction and also provide a rationale for interventions, which have some evidence of efficacy. Therapeutic approaches are described as follows: a collaborative therapeutic relationship, managing dysphoria, helping service users reappraise their beliefs to reduce distress, working on negative schemas, managing and reducing stressful environments if possible, compensating for reasoning biases by using disconfirmation strategies, and considering the full range of evidence in order to reduce high conviction. Theoretical ideas supported by experimental evidence can inform the development of cognitive behavior therapy for persistent positive symptoms of psychosis.


Percutaneous plating of distal tibial fractures in children and adolescents.
Fractures of the tibia and fibula are among the most common injuries involving the lower extremities in children and adolescents. Although most can be treated nonoperatively, with satisfactory long-term results, some fractures require surgical stabilization. The increasing experience in adults with minimally invasive plate osteosynthesis for the treatment of complex fractures of the lower extremity has supported the treatment of selected distal tibia fractures in older children and adolescents. This article details the surgical technique for plating of the distal tibia using the percutaneous approach and assesses the results and complications in a pediatric series. We retrospectively reviewed 11 consecutive patients with open physes who had undergone percutaneous plating of a distal tibial fracture between January 2008 and January 2012. All patients were monitored clinically and radiographically until fracture union. Complications related to treatment, such as malunion, delayed union, nonunion, infection, and the need for subsequent surgical treatment, were recorded. Eleven patients (11 tibial fractures) were treated with minimally invasive plate osteosynthesis. The average follow-up period was 22 months (range, 12-48 months). Fractures healed with an average time to union of 9.4 weeks (range, 8-16 weeks). There were no cases of delayed union or nonunion. No clinically evident neurovascular complications were observed. One patient had a superficial infection, treated successfully by oral antibiotics. There were no cases of rotational deformity or leg-length discrepancy at the final follow-up. Because of its biologic advantages and stable fixation that allows early mobilization, percutaneous plating seems a reasonable treatment option for selected distal tibial fractures in children and adolescents. Level IV therapeutic study - Case series.


Prevalence of work-related musculoskeletal complaints among dentists in India: a national cross-sectional survey.
Work-related musculoskeletal disorders (WRMSD) had been previously reported to have a high prevalence among dentists in different parts of the world. The study aimed to assess the prevalence of self-reported WRMSD among dental professionals in India. A cross-sectional survey of 646 dentists (response rate of 82.97%) was done using self-administered questionnaire which consisted of 27 items based on Nordic questionnaire for screening WRMSDs. Additional items of the questionnaire were added after preliminary content validation from six experienced dentists. Participant socio-demographic characteristics, work-related physical load characteristics, musculoskeletal symptom characteristics were evaluated. All data were analyzed descriptively using percentiles and association between work-related physical load and WRMSD prevalence was done using Chi-square test. All 536 dentists had at least one work-related musculoskeletal symptom in the previous year with an overall period prevalence rate of 100%. The type of symptoms present were pain (99.06%), stiffness (3.35%), fatigue (8.39%), discomfort (12.87%), clicks/sounds (4.1%), and other neurogenic (20.14%). The regions of symptoms were neck (75.74%), wrist/hand (73.13%), lower back (72.01%), shoulder (69.4%), hip (29.85%), upper back (18.65%), ankle (12.31%), and elbow (7.46%). Number of regions affected were two (82.83%), three (51.86%), four, or more (15.11%). Recurrent symptoms were present in 76.11%. Strong association was noted between sustained work postures and symptom regions for pain in WRMSD. The study found an overall one-year period prevalence rate of 100% for WRMSDs among Indian dentists. Measures for improving education and ergonomic evaluations are indicated on a large scale to prevent decline in work performance and incidence of WRMSDs among Indian dentists.


Versatile gene-specific sequence tags for Arabidopsis functional genomics: transcript profiling and reverse genetics applications.
Microarray transcript profiling and RNA interference are two new technologies crucial for large-scale gene function studies in multicellular eukaryotes. Both rely on sequence-specific hybridization between complementary nucleic acid strands, inciting us to create a collection of gene-specific sequence tags (GSTs) representing at least 21,500 Arabidopsis genes and which are compatible with both approaches. The GSTs were carefully selected to ensure that each of them shared no significant similarity with any other region in the Arabidopsis genome. They were synthesized by PCR amplification from genomic DNA. Spotted microarrays fabricated from the GSTs show good dynamic range, specificity, and sensitivity in transcript profiling experiments. The GSTs have also been transferred to bacterial plasmid vectors via recombinational cloning protocols. These cloned GSTs constitute the ideal starting point for a variety of functional approaches, including reverse genetics. We have subcloned GSTs on a large scale into vectors designed for gene silencing in plant cells. We show that in planta expression of GST hairpin RNA results in the expected phenotypes in silenced Arabidopsis lines. These versatile GST resources provide novel and powerful tools for functional genomics.


Complete annotated genome sequence of Mycobacterium tuberculosis (Zopf) Lehmann and Neumann (ATCC35812) (Kurono).
We report the completely annotated genome sequence of Mycobacterium tuberculosis (Zopf) Lehmann and Neumann (ATCC35812) (Kurono), which is a used for virulence and/or immunization studies. The complete genome sequence of M. tuberculosis Kurono was determined with a length of 4,415,078 bp and a G+C content of 65.60%. The chromosome was shown to contain a total of 4,340 protein-coding genes, 53 tRNA genes, one transfer messenger RNA for all amino acids, and 1 rrn operon. Lineage analysis based on large sequence polymorphisms indicated that M. tuberculosis Kurono belongs to the Euro-American lineage (lineage 4). Phylogenetic analysis using whole genome sequences of M. tuberculosis Kurono in addition to 22 M. tuberculosis complex strains indicated that H37Rv is the closest relative of Kurono based on the results of phylogenetic analysis. These findings provide a basis for research using M. tuberculosis Kurono, especially in animal models.


Fetuin/alpha2-HS glycoprotein enhances phagocytosis of apoptotic cells and macropinocytosis by human macrophages.
Inflammatory diseases are associated with reduced serum concentrations of alpha(2)-HS glycoprotein (the human homologue of bovine fetuin), but the role of fetuin in inflammation is poorly understood. We hypothesized that fetuin may influence the resolution of inflammation by modulating the phagocytosis of apoptotic cells by macrophages. Using an in vitro flow cytometry-based phagocytosis assay, we investigated the role of fetuin in apoptotic cell clearance. Bovine fetuin and human alpha(2)-HS glycoprotein significantly augmented the phagocytosis of apoptotic cells by human peripheral blood monocyte-derived macrophages, whereas the control proteins BSA, sialylated BSA and asialofetuin were ineffective. The enhancement of phagocytosis was concentration-dependent, and required the presence of intact fetuin at the time of interaction between macrophages and apoptotic cells. Fetuin also substantially increased the uptake of labelled dextran 70000 by macrophages, which occurs by macropinocytosis, suggesting that this may be one of the mechanisms utilized for apoptotic cell uptake.


Prevalence and correlates of active syphilis and HIV co-Infection among sexually active persons aged 15-59 years in Zambia: Results from the Zambia Population-based HIV Impact Assessment (ZAMPHIA) 2016.
The main objectives of the study are to estimate HIV prevalence, active syphilis prevalence, and correlates of co-infection with HIV in Zambia, among recently sexually active individuals aged 15 to 59 years old. We used data from the 2016 Zambia Population-based HIV Impact Assessment (ZAMPHIA), a national household survey that included biomarker testing for HIV and syphilis. Chembio DPP® Syphilis Screen and Confirm Assay was used to distinguish between active and older syphilis infections. This is the first time Chembio DPP® has been used in a national survey. Log-binominal modelling was utilized to understand the risk of acquiring HIV/active syphilis co-infection using select socio-demographic and sexual behavior variables. Multivariable analysis compared those with co-infection and those with no infection. All reported results account for the complex survey design and are weighted. A total of 19,114 individuals aged 15-59 years responded to the individual interview and had a valid syphilis and/or HIV test. The prevalence for those sexually active in the 12 months preceding ZAMPHIA 2016 was 3.5% and 13% for active syphilis and HIV, respectively. The prevalence of HIV/active syphilis co-infection was 1.5%. Factors associated with higher prevalence of co-infection versus no infection among females included, but were not limited to, those living in urban areas (adjusted prevalence ratio (aPR) = 3.0, 95% CI = 1.8, 4.8), those had sexual intercourse before age 15 years (aPR = 1.8, 95% CI = 1.1, 2.9), and those who had two or more sexual partners in the 12 months preceding the survey (aPR = 2.7, 95% CI = 1.6, 4.7). These findings show high prevalence for both mono-infection with HIV and syphilis, as well as co-infection with HIV/active syphilis in Zambia. There is a need for better screening and partner services, particularly among those engaging in high-risk sexual behaviors (e.g., engaging in transactional sex).


Estrogen and bone--a reproductive and locomotive perspective.
The primary function of the skeleton is locomotion, and the primary function of estrogen is reproduction. When the skeleton is considered within this locomotive context, the onset of estrogen secretion at puberty leads to packing of mechanically excess mineral into female bones for reproductive needs. Accordingly, the unpacking of this reproductive safety deposit at menopause denotes the origin of type I osteoporosis. According to the prevailing unitary model of involutional osteoporosis, female postmenopausal bone loss can be described as having an initial accelerated, transient phase (type I), followed by a gradual continuous phase (type II). Estrogen withdrawal is generally accepted as the primary cause of the type I osteoporosis. Thus, the quest to uncover the origin of type I osteoporosis has focused on the estrogen withdrawal-related skeletal changes at and around the menopause. However, considering that the cyclical secretion of estrogen normally begins in early adolescence and continues over the entire fertile period, one could argue that focusing on perimenopause alone may be too narrow. This is not a systematic review of the literature on the skeletal function of estrogen(s), but rather, an introduction of a novel structure- and locomotion-oriented perspective to this particular issue through pertinent experimental and clinical studies. When considering locomotion as the primary function of the skeleton and integrating the classic findings of the pubertal effects of estrogen on female bones and the more recent hypothesis-driven experimental and clinical studies on estrogen and mechanical loading on bone within this context, a novel evolution-based explanation for the role of estrogen in controlling female bone mass can be outlined: the onset of estrogen secretion at puberty induces packing of mechanically excess bone into female skeleton for needs of reproduction (pregnancy and lactation). Accordingly, the unpacking of this reproductive safety deposit of calcium at menopause denotes the accelerated phase of bone loss and thus the origin of type I osteoporosis.


Multidrug-resistant chronic osteomyelitis complicating war injury in Iraqi civilians.
War-related orthopedic injury is frequently complicated by environmental contamination and delays in management, placing victims at increased risk for long-term infectious complications. We describe, among Iraqi civilians with war-related chronic osteomyelitis, the bacteriology of infection at the time of admission. In the Médecins Sans Frontières Reconstructive Surgery Project in Amman, Jordan, we retrospectively reviewed baseline demographics and results of initial intraoperative surgical cultures among Iraqi civilians with suspected osteomyelitis. One hundred thirty-seven patients (90% male; median age, 35 years [interquartile range {IQR}, 28-46]; median time since initial injury, 19 months [IQR, 10-35]) were admitted with suspected chronic osteomyelitis after war-related injury. One hundred seven patients had a positive intraoperative culture. Before arrival, patients had undergone a median of 4 (IQR, 2-6) surgical procedures in Iraq. Fifty-nine (55%) of 107 patients with confirmed osteomyelitis had a multidrug-resistant (MDR) organism isolated at admission: cefepime-resistant Enterobacteriaceae (n = 40), methicillin-resistant Staphylococcus aureus (n = 16), and MDR Acinetobacter baumannii (n = 3). An association of borderline significance existed between a history of more than two prior surgical procedures in Iraq and an MDR isolate at program entry (multivariate: odds ratio, 5.3; 95% confidence interval, 0.9-30.6; p = 0.064). Health care actors, including Iraqi health facilities and humanitarian medical organizations, must be aware of the link between chronic war injury and antimicrobial drug resistance in this region and should be prepared for the management challenges involved with the treatment of chronic drug-resistant osteomyelitis.


Disrupted mechanobiology links the molecular and cellular phenotypes in familial dilated cardiomyopathy.
Familial dilated cardiomyopathy (DCM) is a leading cause of sudden cardiac death and a major indicator for heart transplant. The disease is frequently caused by mutations of sarcomeric proteins; however, it is not well understood how these molecular mutations lead to alterations in cellular organization and contractility. To address this critical gap in our knowledge, we studied the molecular and cellular consequences of a DCM mutation in troponin-T, ΔK210. We determined the molecular mechanism of ΔK210 and used computational modeling to predict that the mutation should reduce the force per sarcomere. In mutant cardiomyocytes, we found that ΔK210 not only reduces contractility but also causes cellular hypertrophy and impairs cardiomyocytes' ability to adapt to changes in substrate stiffness (e.g., heart tissue fibrosis that occurs with aging and disease). These results help link the molecular and cellular phenotypes and implicate alterations in mechanosensing as an important factor in the development of DCM.


The number of prehospital defibrillation shocks and 1-month survival in patients with out-of-hospital cardiac arrest.
The relationship between the number of pre-hospital defibrillation shocks and treatment outcome in patients with out-of-hospital cardiac arrest (OHCA) presenting with ventricular fibrillation (VF) is unknown currently. We examined the association between the number of pre-hospitalization defibrillation shocks and 1-month survival in OHCA patients. We conducted a prospective observational study using national registry data obtained from patients with OHCA between January 1, 2009 and December 31, 2012 in Japan. The study subjects were ≥ 18-110 years of age, had suffered from an OHCA before arrival of EMS personnel, had a witnessed collapse, had an initial rhythm that was shockable [VF/ventricular tachycardia (pulseless VT)], were not delivered a shock using a public automated external defibrillator (AED), received one or more shocks using a biphasic defibrillator by EMS personnel, and were transported to a medical institution between January 1, 2009 and December 31, 2012. There were 20,851 OHCA cases which met the inclusion criteria during the study period. Signal detection analysis was used to identify the cutoff point in the number of prehospital defibrillation shocks most closely related to one-month survival. Variables related to the number of defibrillations or one-month survival in OHCA were identified using multiple logistic regression analysis. A cutoff point in the number of pre-hospital defibrillation shocks most closely associated with 1-month OHCA survival was between two and three (χ(2) = 209.61, p < 0.0001). Among those patients who received two shocks or less, 34.48% survived for at least 1 month, compared with 24.75% of those who received three shocks or more. The number of defibrillations (odds ratio [OR] = 1.19, 95% CI: 1.03, 1.38), OHCA origin (OR = 2.81, 95% CI: 2.26, 3.49), use of ALS devices (OR = 0.68, 95% CI: 0.59, 0.79), use of epinephrine (OR = 0.33, 95% C: 0.28, 0.39), interval between first defibrillation and first ROSC (OR = 1.45, 95% CI: 1.18, 1.78), and chest compression (OR = 1.21, 95% CI: 1.06, 1.38) were associated significantly with 1-month OCHA survival. The cutoff point in the number of defibrillations of patients with OHCA most closely related to one-month survival was between 2 and 3, and the likelihood of non-survival 1 month after an OHCA was increased when ≥3 shocks were needed. Further studies are needed to verify this finding.


Does patient self-management education of primary care professionals improve patient outcomes: a systematic review.
Patient self-management support is recognised as a key component of chronic care. Education and training for health professionals has been shown in the literature to be associated with better uptake, implementation and effectiveness of self-management programs, however, there is no clear evidence regarding whether this training results in improved health outcomes for patients with chronic conditions. A systematic review was undertaken using the PRISMA guidelines using the Cochrane Library, PubMEd, ERIC, EMBASE, CINAHL, PsycINFO, Web searches, Hand searches and Bibliographies. Articles published from inception to September 1st, 2013 were included. Systematic reviews, Meta-analysis, Randomized controlled trials (RCTs), Controlled clinical trials, Interrupted time series and Controlled before and after studies, which reported on primary care health professionals' continuing education or evidence-based medicine/education on patient self-management for any chronic condition, were included. A minimum of two reviewers participated independently at each stage of review. From 7533 abstracts found, only two papers provided evidence on the effectiveness of self-management education for primary healthcare professionals in terms of measured outcomes in patients. These two articles show improvement in patient outcomes for chronic back pain and diabetes based on RCTs. The educational interventions with health professionals spanned a range of techniques and modalities but both RCTs included a motivational interviewing component. Before and up to 2 years after the incorporation of patient empowerment for self-management into the WONCA Europe definition of general practice, there was a scarcity of high quality evidence showing improved outcomes for patients as a result of educating health professionals in patient self-management of chronic conditions.


Effects of Post Ischemia-Reperfusion Treatment with Trimetazidine on Renal Injury in Rats: Insights on Delayed Renal Fibrosis Progression.
Even after recovery from acute kidney injury, glomeruli remain vulnerable to further injury by way of interstitial fibrosis. This study is aimed at elucidating the effects of post ischemia-reperfusion (I/R) treatment with trimetazidine on the progression to renal fibrosis as well as short- and intermediate-term aspects. Trimetazidine 3 mg/kg or 0.9% saline was given intraperitoneally once upon reperfusion or daily thereafter for 5 d or 8 w. Renal histologic changes and related signaling proteins were assessed. After 24 h, post I/R treatment with trimetazidine significantly reduced serum blood urea nitrogen and creatinine levels and tubular injury accompanied with upregulation of hypoxia-inducible factor- (HIF-) 1α, vascular endothelial growth factor (VEGF), and Bcl-2 expression. After 5 d, post I/R treatment with trimetazidine reduced renal tubular cell necrosis and apoptosis with upregulation of HIF-1α-VEGF and tissue inhibitors of metalloproteinase activities, attenuation of matrix metalloproteinase activities, and alteration of the ratio of Bax to Bcl-2 levels. After 8 w, however, post I/R treatment with trimetazidine did not modify the progression of renal fibrosis. In conclusion, post I/R treatment with trimetazidine allows ischemic kidneys to regain renal function and structure more rapidly compared to nontreated kidneys, but not enough to resolute renal fibrosis in long-term aspect.


Reablement in community-dwelling adults: study protocol for a randomised controlled trial.
As a result of the ageing population, there is an urgent need for innovation in community health-care in order to achieve sustainability. Reablement is implemented in primary care in some Western countries to help meet these challenges. However, evidence to support the use of such home-based rehabilitation is limited. Reablement focuses on early, time-intensive, multidisciplinary, multi-component and individualised home-based rehabilitation for older adults with functional decline. The aim of this study is to investigate the effectiveness of reablement in home-dwelling adults compared with standard treatment in relation to daily activities, physical functioning, health-related quality of life, use of health-care services, and costs. The study will be a 1:1 parallel-group randomised controlled superiority trial conducted in a rural municipality in Norway. The experimental group will be offered reablement and the control group offered standard treatment. A computer-generated permuted block randomisation sequence, with randomly selected block sizes, will be used for allocation. Neither participants nor health-care providers will be blinded, however all research assistants and researchers will be blinded. The sample size will consist of 60 participants. People will be eligible if they are home-dwelling, over 18 years of age, understand Norwegian and have functional decline. The exclusion criteria will be people in need of institution-based rehabilitation or nursing home placement, and people who are terminally ill or cognitively reduced. The primary outcome will be self-perceived performance, and satisfaction with performance of daily activities, assessed with the Canadian Occupational Performance Measure. In addition, physical capacity, health-related quality of life, use of health-care services, and cost data will be collected at baseline, and after 3 and 9 months in both groups, and again after 15 months in the intervention group. Data will be analysed on an intention-to-treat basis using a linear mixed model for repeated measures. The findings will make an important contribution to evaluating cost-effective and evidence-based rehabilitation approaches for community-dwelling adults. The trial was registered in ClinicalTrials.gov November 20, 2012, identifier: NCT02043262.


A double blind, placebo-controlled, randomized clinical trial that breast milk derived-Lactobacillus gasseri BNR17 mitigated diarrhea-dominant irritable bowel syndrome.
The exact pathogenesis of diarrhea-dominant irritable bowel syndrome (IBS) is not known, but the abnormal microbiota of the gastrointestinal tract is considered to be one of the important contributing factors as in other gastrointestinal diseases such as inflammatory bowel disease, antibiotic-associated diarrhea, and colorectal cancer as well as systemic diseases. Though diverse trials of probiotics had been continued in the treatment of diarrhea-IBS, only a few proved by randomized clinical trial. To prove the efficacy of Lactobacillus gasseri BNR17 isolated from breast milk in patients with diarrhea-IBS, prospective, randomized, placebo controlled clinical trial was done including health related-quality of life analysis, colon transit time, and the changes of fecal microbiota. BNR17 significantly improved the symptoms of diarrhea compared to control group. Health related-QOL analysis showed significant improvement of abdominal pain, distension, disturbed daily life, and mean defecation frequency with BNR17. On comparative CTT before and after BNR17, 6 out of 24 subjects showed significant correction of rapid colon transit pattern, while only 2 out of 24 in placebo (p<0.01). Upon fecal microbiota analysis, BNR17 significantly increased B. fecalis, E. rectale, C. aerofaciens, F. prausnitzil and B. steroris. Conclusively, Lactobacillus gasseri BNR17 can be a potential probiotics to ameliorate diarrhea-IBS.


Learning to learn causal models.
Learning to understand a single causal system can be an achievement, but humans must learn about multiple causal systems over the course of a lifetime. We present a hierarchical Bayesian framework that helps to explain how learning about several causal systems can accelerate learning about systems that are subsequently encountered. Given experience with a set of objects, our framework learns a causal model for each object and a causal schema that captures commonalities among these causal models. The schema organizes the objects into categories and specifies the causal powers and characteristic features of these categories and the characteristic causal interactions between categories. A schema of this kind allows causal models for subsequent objects to be rapidly learned, and we explore this accelerated learning in four experiments. Our results confirm that humans learn rapidly about the causal powers of novel objects, and we show that our framework accounts better for our data than alternative models of causal learning.


Accurate and simultaneous measurement of thickness and refractive index of thermally evaporated thin organic films by surface plasmon resonance spectroscopy.
We demonstrate that Surface Plasmon Resonance spectroscopy can be used for the accurate and simultaneous determination of the thickness and refractive index of transparent thin thermally deposited organic films. The experimental approach is based on a two-metal deposition or a two-thickness method. These methods have been applied to an encapsulated sample containing a thin film of commercial tris(8-hydroxyquinoline) (Alq3). The accuracy of the measurement depends on the control of the film deposition process and suggests the use of SPR spectroscopy as inexpensive and valuable metrology tool for small molecule organic thin films.


The relationship between self-reports of imagery and spatial ability.
A puzzling question arising from imagery research is why no relationship has been found between self-reports of imagery and performance on spatial tests thought to require the use of imagery. To investigate this, spatial ability, measured by performance on two spatial tests, was compared with performance on the Vividness of Visual Imagery Questionnaire (VVIQ; Marks, 1973) and a newly constructed imagery questionnaire. The choice of items and ratings for the new questionnaire was based on Kosslyn's (1980, 1994) theories of the imagery system. Ratings on the new questionnaire consistently correlated significantly with performance on the spatial tests, whereas ratings from the VVIQ did not. The new ratings captured more of the imagery process than ratings of vividness alone, but the largest change depended upon the type of item imagined. Ratings of items of the same type as used on the spatial tests predicted performance on the spatial tests, whereas vividness ratings of items recalled or constructed from long-term memory did not. Participants can successfully introspect on several different properties of their images, and their ratings do predict performance on tasks thought to require imagery. The large effect of item type raises questions about the predictive value of existing models of the imagery system especially in relation to the role of phenomenological properties of our images.