AHRQ series on complex intervention systematic reviews-paper 4: selecting analytic approaches.
Systematic reviews of complex interventions can vary widely in purpose, data availability and heterogeneity, and stakeholder expectations. This article addresses the uncertainty that systematic reviewers face in selecting methods for reviews of complex interventions. Specifically, it lays out parameters for systematic reviewers to consider when selecting analytic approaches that best answer the questions at hand and suggests analytic techniques that may be appropriate in different circumstances. Systematic reviews of complex interventions comprising multiple questions may use multiple analytic approaches. Parameters to consider when choosing analytic methods for complex interventions include nature and timing of the decision (clinical practice guideline, policy, or other); purpose of the review; extent of existing evidence; logistic factors such as the timeline, process, and resources for deciding the scope of the review; and value of information to be obtained from choosing specific systematic review methods. Reviewers may elect to revise their analytic approach based on new or changing considerations during the course of the review but should guard against bias through transparency of reporting.


Exogenous C3 protein enhances the adaptive immune response to polymicrobial sepsis through down-regulation of regulatory T cells.
The role of complement system in bridging innate and adaptive immunity has been confirmed in various invasive pathogens. It is still obscure how complement proteins promote T cell-mediated immune response during sepsis. The aim of this study is to investigate the role of exogenous C3 protein in the T-cell responses to sepsis. Sepsis was induced by colon ascendens stent peritonitis (CASP) in wild-type C57BL/6 mice, sham-operated mice for control. Human purified C3 protein (HuC3, 1 mg) was intraperitoneally injected at 6 h post-surgery, with 200 μl phosphate-buffered saline as control. The levels of C3 and cytokines, the expression of FOXP3 and NF-κB, and the percentages of CD4(+) T-cell subsets were compared among the groups at given time points. The polymicrobial sepsis produced considerable release of TNF-α and IL-10, and caused complement C3 exhaustion. Exogenous C3 administration markedly improved the 48 h survival rate, as compared with nontreatment (40% vs. 5%, P<0.01). The expression of FOXP3 protein was increased during sepsis, but can be suppressed by HuC3 administration. A single injection of HuC3 postponed the decline of differentiated Th1 cells, and depressed the activation of Th2/Th17 cells. Besides, the Th1-Th2 shift in late stage of sepsis can be controlled under C3 supplementation. The suppression of NF-κB pathway might be related to the appearance of immunocompromise. The study confirmed the important role of exogenous C3 in up-regulation of adaptive immune response to sepsis. The complement pathway would be a pivotal target for severe sepsis management.


Compost Soil Microbial Fuel Cell to Generate Power using Urea as Fuel.
The acute problem of eutrophication increasing in the environment is due to the increase of industrial wastewater, synthetic nitrogen, urine, and urea. This pollutes groundwater, soil and creates a danger to aquatic life. Therefore, it is advantageous to use these waste materials in the form of urea as fuel to generate power using Microbial Fuel Cell (MFC). In this work, we studied the compost soil MFC(CSMFC) unlike typical MFC with urea from the compost as fuel and graphite as a functional electrode. The electrochemical techniques such as Cyclic Voltammetry, Chronoamperometry are used to characterise CSMFC. It is observed that the CSMFC in which the compost consists of urea concertation of 0.5 g/ml produces maximum power. Moreover, IV measurement is carried out using polarization curves in order to study its sustainability and scalability. Bacterial studies were also playing a significant role in power generation. The sustainability study revealed that urea is consumed in CSMFC to generate power. This study confirmed that urea has a profound effect on the power generation from the CSMFC. Our focus is to get power from the soil processes in future by using waste like urine, industrial wastewater, which contains much amount of urea.


Quantitative measurements of receptive field changes during antagonism of GABAergic transmission in primary somatosensory cortex of cats.
In cortical area 3b of cats, responses of 76 single neurons to punctate indentations were recorded before and during iontophoretic administration of bicuculline methiodide (BMI), a GABAergic antagonist, at levels that did not affect spontaneous activity. Constant amplitude indentations were applied to selected sites along distal-proximal and radial-ulnar axes that intersected the most sensitive area in the receptive field. Profiles of response magnitudes were used to measure receptive field dimensions before and during antagonism of GABAergic inhibition. Blockade of GABAergic transmission caused receptive field dimensions of 48 rapidly-adapting neurons to increase an average 141%, or nearly 2.5 times their original size. Analysis of the spatial distribution of inhibition indicated that in-field inhibition was larger than surround inhibition. During BMI administration, response latency was significantly longer for response elicited from the expanded territory than for responses elicited from within the original receptive field, suggesting that receptive field expansion might be mediated by multisynaptic intracortical connections. The magnitude of receptive field expansion was independent of receptive field size or peripheral location. In a substantial number of neurons, however, BMI produced asymmetric expansions that extended only in the proximal direction. For 9 slowly-adapting neurons. BMI produced measurable increases in receptive field dimensions, but these changes were significantly smaller than the changes in rapidly-adapting neurons.


Attachment of cementum on different hydroxylapatite ceramic (HAC) substrata in vivo. A light and electron microscopic study.
The role of substrate surface characteristics for periodontal regeneration was studied in rats. Cementogenesis was initiated by dental follicle cells retained after dissecting out a molar tooth germ in 5-day-old rats. The tooth germ was substituted by a bone replacement material, namely HAC granules of porous consistency. Tissue blocks were removed after 24 weeks and processed for light and electron microscopic examination. On all HAC surfaces a new cementum-like tissue developed, similar to that of natural root surfaces. The results strongly indicate that the exposure of collagen fibers is not essential in order to achieve new periodontal attachment.


Of tacit knowledge, texts and thing-based learning (TBL).
Practical knowledge has two dimensions- a visible, codified component that resembles the tip of an iceberg. The larger but crucial tacit component which lies submerged consists of values, procedures and tricks of the trade and cannot be easily documented or codified. Undergraduate science students were given an opportunity to explore this component through an inquiry-based course.


[Community Health Agents' perceptions and practice in mental health].
The objectives of this study are to identity the perceptions of community health agents regarding health and mental disorders, and to verify the preparation these agents receive to work in this field. This qualitative study was performed using semi-structured interviews for data collection and utilizing content analysis to interpret the data. Interviews were performed with 45 community health agents working in the Family Health Strategy, who reported to 21 basic health units in the city of Maringá, PR. Results show the prejudice that these workers have regarding mental disorders. They recognize the importance of working with the patient and the family but do not feel prepared to provide adequate care. Because they share the same social context and have a close experience with the community dynamics, we see them as important facilitators of mental healthcare.


Assessment of biochemical methane potential of dairy wastewater with different co-substrates and evaluation of different kinetic models.
Dairy industry wastewater can be considered as an important source of pollution due to its high amounts and pollutant concentrations. Anaerobic treatment is seen as a suitable alternative over aerobic treatment which requires huge aeration systems. Biochemical methane potential (BMP) testing is a widely applied technique for estimating the performance of anaerobic digesters and still has no clear alternative. In the study, the biochemical methane potential change was investigated by mixing dairy wastewater with different co-substrates (cattle manure, chicken manure and slaughterhouse wastewater) at different rates. The highest biogas potential per gram of chemical oxygen demand added (CODadded) was determined as 574 mLbiogas in a mixture of 74% dairy wastewater + 2% chicken manure + 24% slaughterhouse wastewater inoculated with granular sludge. The highest methane potential was determined as 340 mLCH4 in the same co-substrate mixture inoculated with anaerobic sludge. In recent years, mathematical modeling offers an alternative to BMP tests and many different models are used for this purpose. In the study, six different mathematical models were used to simulate the BMP results, and the highest correlation coefficient in almost all mixtures ranged from 0.900 to 0.997 with the Modified Gompertz equation and Fitzhugh models.


Specific rhizosphere bacterial and fungal groups respond differently to elevated atmospheric CO(2).
Soil community responses to increased atmospheric CO(2) concentrations are expected to occur mostly through interactions with changing vegetation patterns and plant physiology. To gain insight into the effects of elevated atmospheric CO(2) on the composition and functioning of microbial communities in the rhizosphere, Carex arenaria (a non-mycorrhizal plant species) and Festuca rubra (a mycorrhizal plant species) were grown under defined atmospheric conditions with either ambient (350 p.p.m.) or elevated (700 p.p.m.) CO(2) concentrations. PCR-DGGE (PCR-denaturing gradient gel electrophoresis) and quantitative-PCR were carried out to analyze, respectively, the structure and abundance of the communities of actinomycetes, Fusarium spp., Trichoderma spp., Pseudomonas spp., Burkholderia spp. and Bacillus spp. Responses of specific functional groups, such as phloroglucinol, phenazine and pyrrolnitrin producers, were also examined by quantitative-PCR, and HPLC (high performance liquid chromatography) was employed to assess changes in exuded sugars in the rhizosphere. Multivariate analysis of group-specific community profiles showed disparate responses to elevated CO(2) for the different bacterial and fungal groups examined, and these responses were dependent on plant type and soil nutrient availability. Within the bacterial community, the genera Burkholderia and Pseudomonas, typically known as successful rhizosphere colonizers, were significantly influenced by elevated CO(2), whereas the genus Bacillus and actinomycetes, typically more dominant in bulk soil, were not. Total sugar concentrations in the rhizosphere also increased in both plants in response to elevated CO(2). The abundances of phloroglucinol-, phenazine- and pyrrolnitrin-producing bacterial communities were also influenced by elevated CO(2), as was the abundance of the fungal genera Fusarium and Trichoderma.


Histone deacetylase inhibition in the treatment of acute myeloid leukemia: the effects of valproic acid on leukemic cells, and the clinical and experimental evidence for combining valproic acid with other antileukemic agents.
Several new therapeutic strategies are now considered for acute myeloid leukemia (AML) patients unfit for intensive chemotherapy, including modulation of protein lysine acetylation through inhibition of histone deacetylases (HDACs). These enzymes alter the acetylation of several proteins, including histones and transcription factors, as well as several other proteins directly involved in the regulation of cell proliferation, differentiation and apoptosis. Valproic acid (VPA) is a HDAC inhibitor that has been investigated in several clinical AML studies, usually in combination with all-trans retinoic acid (ATRA) for treatment of patients unfit for intensive chemotherapy, for example older patients, and many of these patients have relapsed or primary resistant leukemia. The toxicity of VPA in these patients is low and complete hematological remission lasting for several months has been reported for a few patients (<5% of included patients), but increased peripheral blood platelet counts are seen for 30 to 40% of patients and may last for up to 1 to 2 years. We review the biological effects of VPA on human AML cells, the results from clinical studies of VPA in the treatment of AML and the evidence for combining VPA with new targeted therapy. However, it should be emphasized that VPA has not been investigated in randomized clinical studies. Despite this lack of randomized studies, we conclude that disease-stabilizing treatment including VPA should be considered especially in unfit patients, because the possibility of improving normal blood values has been documented in several studies and the risk of clinically relevant toxicity is minimal.


Clinical Utility of a Bronchial Genomic Classifier in Patients With Suspected Lung Cancer.
Bronchoscopy is often the initial diagnostic procedure performed in patients with pulmonary lesions suggestive of lung cancer. A bronchial genomic classifier was previously validated to identify patients at low risk for lung cancer after an inconclusive bronchoscopy. In this study, we evaluated the potential of the classifier to reduce invasive procedure utilization in patients with suspected lung cancer. In two multicenter trials of patients undergoing bronchoscopy for suspected lung cancer, the classifier was measured in normal-appearing bronchial epithelial cells from a mainstem bronchus. Among patients with low and intermediate pretest probability of cancer (n = 222), subsequent invasive procedures after an inconclusive bronchoscopy were identified. Estimates of the ability of the classifier to reduce unnecessary procedures were calculated. Of the 222 patients, 188 (85%) had an inconclusive bronchoscopy and follow-up procedure data available for analysis. Seventy-seven (41%) patients underwent an additional 99 invasive procedures, which included surgical lung biopsy in 40 (52%) patients. Benign and malignant diseases were ultimately diagnosed in 62 (81%) and 15 (19%) patients, respectively. Among those undergoing surgical biopsy, 20 (50%) were performed in patients with benign disease. If the classifier had been used to guide decision making, procedures could have been avoided in 50% (21 of 42) of patients undergoing further invasive testing. Further, among 35 patients with an inconclusive index bronchoscopy who were diagnosed with lung cancer, the sensitivity of the classifier was 89%, with 4 (11%) patients having a false-negative classifier result. Invasive procedures after an inconclusive bronchoscopy occur frequently, and most are performed in patients ultimately diagnosed with benign disease. Using the genomic classifier as an adjunct to bronchoscopy may reduce the frequency and associated morbidity of these invasive procedures. ClinicalTrials.gov; Nos. NCT01309087 and NCT00746759; URL: www.clinicaltrials.gov.


IRE1α/XBP-1 promotes β-catenin signaling activation of airway epithelium in lipopolysaccharide-induced acute lung injury.
Acute lung injury (ALI), along with the more severe condition--acute respiratory distress syndrome (ARDS), is a major cause of respiratory failure in critically ill patients with high morbidity and mortality. Inositol-requiring protein 1α (IRE1α)/X box protein-1 (XBP1) pathway was proved to regulate lipopolysaccharide (LPS)-induced lung injury and inflammation. Yet, its role on epithelial β-catenin in LPS-induced ALI remains to be elucidated. LPS-induced models were generated in mice (5 mg/kg) and Beas-2B cells (200 μg/mL). Two selective antagonists of IRE1α (4μ8c and STF-083010) were respectively given to LPS-exposed mice and cultured cells. Up-regulated expression of endoplasmic reticulum (ER) stress markers immunoglobulin-binding protein (BIP) and spliced X box protein-1(XBP-1s) was detected after LPS exposure. Besides, LPS also led to a down-regulated total β-catenin level in the lung and Beas-2B cells, with decreased membrane distribution as well as increased cytoplasmic and nuclear accumulation, paralleled by extensively up-regulated downstream targets of the Wnt/β-catenin signaling. Treatment with either 4μ8c or STF-083010 not only significantly attenuated LPS-induced lung injury and inflammation, but also recovered β-catenin expression in airway epithelia, preserving the adhesive function of β-catenin while blunting its signaling activity. These results illustrated that IRE1α/XBP1 pathway promoted the activation of airway epithelial β-catenin signaling in LPS-induced ALI.


Metal-organic extended 2D structures: Fe-PTCDA on Au(111).
In this work we combine organic molecules of 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA) with iron atoms on an Au (111) substrate in ultra-high vacuum conditions at different temperatures. By means of scanning tunnelling microscopy (STM) we study the formation of stable 2D metal-organic structures. We show that at certain growth conditions (temperature, time and coverage) stable 'ladder-like' nanostructures are obtained. These are the result of connecting together two metal-organic chains through PTCDA molecules placed perpendicularly, as rungs of a ladder. These structures, stable up to 450 K, can be extended in a 2D layer covering the entire surface and presenting different rotation domains. STM images at both polarities show a contrast reversal between the two molecules at the unit cell. By means of density functional theory (DFT) calculations, we confirm the stability of these structures and that their molecular orbitals are placed separately at the different molecules.


Findings from the Hispanic Community Health Study/Study of Latinos on the Importance of Sociocultural Environmental Interactors: Polygenic Risk Score-by-Immigration and Dietary Interactions.
Introduction: Hispanic/Latinos experience a disproportionate burden of obesity. Acculturation to US obesogenic diet and practices may lead to an exacerbation of innate genetic susceptibility. We examined the role of gene-environment interactions to better characterize the sociocultural environmental determinants and their genome-scale interactions, which may contribute to missing heritability of obesity. We utilized polygenic risk scores (PRSs) for body mass index (BMI) to perform analyses of PRS-by-acculturation and other environmental interactors among self-identified Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods: PRSs were derived using genome-wide association study (GWAS) weights from a publicly available, large meta-analysis of European ancestry samples. Generalized linear models were run using a set of a priori acculturation-related and environmental factors measured at visit 1 (2008-2011) and visit 2 (2014-2016) in an analytic subsample of 8,109 unrelated individuals with genotypic, phenotypic, and complete case data at both visits. We evaluated continuous measures of BMI and waist-to-hip ratio. All models were weighted for complex sampling design, combined, and sex-stratified. Results: Overall, we observed a consistent increase of BMI with greater PRS across both visits. We found the best-fitting model adjusted for top five principal components of ancestry, sex, age, study site, Hispanic/Latino background genetic ancestry group, sociocultural factors and PRS interactions with age at immigration, years since first arrival to the United States (p < 0.0104), and healthy diet (p < 0.0036) and explained 16% of the variation in BMI. For every 1-SD increase in PRS, there was a corresponding 1.10 kg/m2 increase in BMI (p < 0.001). When these results were stratified by sex, we observed that this 1-SD effect of PRS on BMI was greater for women than men (1.45 vs. 0.79 kg/m2, p < 0.001). Discussion: We observe that age at immigration and the adoption of certain dietary patterns may play a significant role in modifying the effect of genetic risk on obesity. Careful consideration of sociocultural and immigration-related factors should be evaluated. The role of nongenetic factors, including the social environment, should not be overlooked when describing the performance of PRS or for promoting population health in understudied populations in genomics.


Neurologic Complications of Conventional Chemotherapy and Radiation Therapy.
Neurologic complications are among the most common and feared outcomes of cancer treatments. This review discusses the signs and symptoms, mechanisms, and management of the most common peripheral and central neurologic complications of chemotherapy, radiation therapy, and antiangiogenic therapy during cancer treatment and in survivors. The landscape of cancer treatments is evolving to include more targeted and biologic therapies, in addition to more traditional cytotoxic therapies and radiation therapy. With increasingly complex regimens and longer survival for patients with cancer, the early recognition and management of neurologic complications is key to improving the morbidity and mortality of patients living with cancer. Neurologists should be familiar with acute central and peripheral toxicities that can occur during cancer treatment and delayed toxicities that can occur years after exposure. Neurologists should be familiar with the clinical and radiologic presentations of these complications and strategies for management.


Parkinsonian Tremor Detection with Compact Convolutional Transformer from Bispectrum Representation of tri-Axial Accelerometer Signals.
After the breakthroughs of Transformer networks in Natural Language Processing (NLP) tasks, they have led to exciting progress in visual tasks as well. Nonetheless, there has been a parallel growth in the number of parameters and the amount of training data, which led to the conclusion that Transformers are not suited for small datasets. This paper is the first to convey the feasibility of Compact Convolutional Transformers (CCT) for the prediction of Parkinsonian postural tremor based on the Bispectrum (BS) representation of IMU accelerometer time series. The dataset includes tri-axial accelerometer signals collected unobtrusively in-the-wild while subjects are on a phone call, and labelled by neurologists and signal processing experts. The BS is a noise-immune, higher-order representation that reflects a signal's deviation from Gaussianity and measures quadratic phase coupling. We performed comparative classification experiments using the CCT, pre-trained CNNs such as VGG-16 and ResNet-50, and the conventional Vision Transformer (ViT). Our model achieves competitive prediction accuracy and F1 score of 96% with only 1.016 M trainable parameters, compared to the ViT with 21.659 M trainable parameters, in a five-fold cross-validation scheme. Our model also outperforms pre-trained CNNs such as VGG-16 and ResNet-50. Furthermore, we show that the performance gains are maintained when training on a larger dataset of BS images. Our effort here is motivated by the hypothesis that data-efficient transformers outperform transfer learning using pre-trained CNNs, paving the way for promising deep learning architecture for small-scale, novel and noisy medical imaging datasets.Clinical relevance- Novel deep learning model for unobtrusive prediction of Parkinsonian Postural Tremor from Bispectrum image representation of tri-axial accelerometer signals collected in-the-wild.


Exploiting the antiviral potential of intermetallic nanoparticles.
Viral pandemic outbreaks cause a significant burden on global health as well as healthcare expenditure. The use of antiviral agents not only reduces the spread of viral pathogens but also diminishes the likelihood of them causing infection. The antiviral properties of novel copper-silver and copper-zinc intermetallic nanoparticles against Escherichia coli bacteriophage MS2 (RNA virus) and Escherichia coli bacteriophage T4 (DNA virus) are presented. The intermetallic nanoparticles were spherical in shape and were between 90 and 120 nm. Antiviral activity was assessed at concentrations ranging from 0.05 to 2.0 wt/v% for 3 and 24 h using DNA and RNA virus model organisms. Both types of nanoparticles demonstrated strong potency towards RNA viruses (> 89% viral reduction), whilst copper-silver nanoparticles were slightly more toxic towards DNA viruses when compared to copper-zinc nanoparticles. Both nanoparticles were then incorporated into polymeric fibres (carrier) to investigate their antiviral effectiveness when composited into polymeric matrices. Fibres containing copper-silver nanoparticles exhibited favourable antiviral properties, with a viral reduction of 75% after 3 h of exposure. The excellent antiviral properties of the intermetallic nanoparticles reported in this study against both types of viruses together with their unique material properties can make them significant alternatives to conventional antiviral therapies and decontamination agents.


The forces of ankle joint structures during ergometer cycling.
The ankle joint moment, joint compressive force, and Achilles tendon force obtained during ergometer cycling were calculated by using a quartz force-measuring transducer mounted on the pedal. Six healthy subjects rode in 11 different ways at different workloads, pedalling rates, saddle heights, and pedal foot positions. The mean maximum dorsiflexing load moment about the ankle joint during standardized ergometer cycling was calculated to 30.9 nm. The mean ankle joint compressive force and mean Achilles tendon force measured 1008 N (1.4 times body weight) and 762 N (1.1 times body weight), respectively. The ankle joint moment was significantly changed by a change of workload or pedal foot position.


Which fatigue scale should I use? A Rasch analysis of two fatigue scales in inflammatory conditions.
This study aimed to assess the psychometric properties of two widely used fatigue scales in a sample of patients with inflammatory conditions. Rasch analysis was used to examine scale reliability, item bias, unidimensionality and overall fit to the Rasch model. Sub-test methodology was utilised to attempt to improve model fit for the CFQ and BRAF-MDQ. Initial analysis displayed strong reliability (PSI=0.89 0.96), alongside a lack of item bias in both scales. However, evidence for unidimensionality was not found for either scale. Overall fit to the Rasch model was marginal for the CFQ, and misfitting for the BRAF-MDQ. Local dependency was observed, as well as significant item misfit for both scales. Sub-test modifications resulted in the best model fit for the BRAF-MDQ (χ2(16)=15.77, p=0.469) and the CFQ (χ2(25)=15.49, p=0.929). Modifications resulted in improved fit, reductions in measurement error, and the production of ordinal-to-interval conversion tables for both scales. Conversion tables apply the benefits of enhanced measurement accuracy, valid comparison of BRAF-MDQ and CFQ scores to other interval-level data, appropriate use in parametric statistics, and enhanced precision in clinical cut-off scores-without the need to change administration format. The BRAF-MDQ and CFQ are valid, reliable tools for fatigue assessment. Psychometric indices and content factors suggest the CFQ is suited to measuring general fatigue, particularly when response burden is a concern, while the BRAF-MDQ should be used in clinical presentations where other symptoms are severe and the impact of fatigue on daily living, emotional, and social well-being is of interest.


Design and evaluation of a robotic system for transcranial magnetic stimulation.
Transcranial magnetic stimulation is a noninvasive brain stimulation technique. It is based on current induction in the brain with a stimulation coil emitting a strong varying magnetic field. Its development is currently limited by the lack of accuracy and repeatability of manual coil positioning. A dedicated robotic system is proposed in this paper. Contrary to previous approaches in the field, a custom design is introduced to maximize the safety of the subject. Furthermore, the control of the force applied by the coil on the subject's head is implemented. The architecture is original and its experimental evaluation demonstrates its interest: the compensation of the head motion is combined with the force control to ensure accuracy and safety during the stimulation.


The role of spinal fusion in the treatment of cervical synovial cysts: a series of 17 cases and meta-analysis.
This study was undertaken to compare surgical outcomes between patients with atlantoaxial versus subaxial cervical synovial cysts (CSCs) and to compare outcomes between patients who underwent decompression alone versus decompression and fusion for the treatment of CSCs. The authors present a series of 17 cases involving patients treated at their institution and report the surgical outcomes. Due to the rarity of CSCs, a meta-analysis was conducted, and results of the literature search were combined with the case series to enhance the power of the study. Seventeen patients underwent surgical treatment for CSCs at our institution: 3 patients (17.6%) had atlantoaxial cysts and 14 (82.3%) had subaxial cysts. Of the 17 patients, 16 underwent a decompression and fusion; most patients experienced symptom resolution at last follow-up, and there were no cyst recurrences. A total of 54 articles (including the current series) and 101 patients were included in the meta-analysis. The mean age at presentation was 64 ± 13.9 years, and the most common symptoms were motor and sensory deficits. Forty-one patients (40.6%) presented with atlantoaxial cysts, and 60 (59.4%) with subaxial cysts. There were no significant differences between groups in terms of presenting symptoms, Nurick scores, surgical treatment, or surgical outcomes. Fifty-two patients (51.4%) underwent surgical decompression without fusion, while 49 patients (48.6%) underwent fusion. The preoperative Nurick scores were significantly lower in the fused group (p = 0.001), with an average score of 1.32 compared with 2.75 in the nonfused group. After a mean follow-up of 16.5 months, a difference of means analysis between final and preoperative Nurick scores revealed that patients who received a decompression alone improved on average 1.66 points (95% CI 1.03-2.29) compared with 0.8 points (95% CI 0.23-1.39) in the fused group (p = 0.004). However, there was no statistically significant difference in symptom resolution between the groups, and the rate of cyst recurrence was found to be 0%. In this study, patients with CSCs had similar outcomes regardless of cyst location and regardless of whether they underwent decompression only or fusion. In the authors' institutional experience, 16 of 17 patients underwent fusion due to underlying spinal instability. While there were no reports of cyst recurrence in their series or in the literature in patients who only received decompression, this is likely due to the limited follow-up time available for the study population. Longer follow-up and prospective and biomechanical studies are needed to corroborate these findings.


Synthesis, characterization and biological activity of organometallic derivatives of the antimalarial drug mefloquine as new antischistosomal drug candidates.
We present the design, synthesis, characterization and biological evaluation of new ferrocenyl and ruthenocenyl derivatives of the organic antimalarial mefloquine, a drug also known for its antischistosomal activity. The two metallocenyl derivatives prepared (3 and 4) demonstrated comparable activity to mefloquine against adult-stage Schistosoma mansoni in vitro. Importantly, both compounds were found to have lower toxicity in all cell lines than mefloquine itself. Administration of a 200 mg kg-1 oral dose of 3 and 4 to S. mansoni-infected mice did not significantly reduce worm burden, contrary to mefloquine.


Histidine-rich glycoprotein as a prognostic biomarker for sepsis.
Various biomarkers have been proposed for sepsis; however, only a few become the standard. We previously reported that plasma histidine-rich glycoprotein (HRG) levels decreased in septic mice, and supplemental infusion of HRG improved survival in mice model of sepsis. Moreover, our previous clinical study demonstrated that HRG levels in septic patients were lower than those in noninfective systemic inflammatory response syndrome patients, and it could be a biomarker for sepsis. In this study, we focused on septic patients and assessed the differences in HRG levels between the non-survivors and survivors. We studied ICU patients newly diagnosed with sepsis. Blood samples were collected within 24 h of ICU admission, and HRG levels were determined using an enzyme-linked immunosorbent assay. Ninety-nine septic patients from 11 institutes in Japan were included. HRG levels were significantly lower in non-survivors (n = 16) than in survivors (n = 83) (median, 15.1 [interquartile ranges, 12.7-16.6] vs. 30.6 [22.1-39.6] µg/ml; p < 0.01). Survival analysis revealed that HRG levels were associated with mortality (hazard ratio 0.79, p < 0.01), and the Harrell C-index (predictive power) for HRG was 0.90. These results suggested that HRG could be a novel prognostic biomarker for sepsis.


Menstrual blood-derived stem cells exosomal miR-let-7 to ameliorate pulmonary fibrosis through inhibiting ferroptosis by Sp3/HDAC2/Nrf2 signaling pathway.
Idiopathic pulmonary fibrosis (IPF) is a serious, lifelong lung disease with high morbidity and high mortality. Menstrual blood-derived stem cells (MenSCs) derived exosomes (MenSCs-Exo) emerge as an attractive tool for the treatment of acute lung injury and fibrosis-related diseases. However, more comprehensive mechanism over how MenSCs derived exosomes exhibits anti-pulmonary fibrosis needs to be elucidated. In this study, TGF-β was used to construct cell fibrosis model, and bleomycin (BLM) was applied to induce lung tissue fibrosis mice model. BLM- and TGF-β1-induced cellular reactive oxygen species (ROS), mitochondrial DNA (mtDNA) damage, and lung epithelial cell apoptosis were alleviated by MenSCs-Exo treatment in vivo and in vitro. Besides, it was found that MenSCs-Exo delivered miR-let-7 into MLE-12 cells/lung epithelial cell and the reduction of miR-let-7 blocked the improvement produced by MenSCs-Exo. Mechanistically, miR-let-7 directly bound to Sp3 and negatively regulated its expression. Sp3 elevation promoted the expression of ferroptosis-related protein and mitochondrial DNA (mtDNA) damage markers via recruiting HDAC2, thereby inactivating keap1/Nrf2 signal cascade, which were confirmed in BLM-induced pulmonary fibrosis mice model under the combination therapy of the MenSCs-Exo and let-7 inhibitor. Collectively, MenSCs derived exosomes could transmit miR-let-7 into MLE-12 cells to inhibit the expression of Sp3, thereby weakening the recruitment effect of Sp3 on HDAC2, lifting the deacetylation restriction of HDAC2 on Nrf2, and enhancing the Nrf2 pathway. These changes further declined ferroptosis and delayed the pathological process of oxidative damage and lung epithelial cell apoptosis in PF.


[Agglutinating and immobilizing activity of an ethanol extract of Bursera fagaroides on human and other mammalian spermatozoa].
Human spermatozoa and those obtained from mouse epididymis incubated in ethanolic from mouse epididymis incubated in ethanolic extracts of the cortex of Bursera fagaroides became agglutinated and immobilized in 100% with 30% of viability decrease. This double effect occurred in 50% of pig'ssperm and 50% of rabbit sperm when the concentration was increased tenfold. The pattern of progressive motility was affected 80% of rat's spermatocytes without agglutination. The values remained the same when the extracts were partially purified with salts of Zn++ and Ba++ or by filtration in a sephadex g-10 column. Analysis with thin layer chromatography of both purified extracts produced 3 compounds in comparison with the ethanolic unpurified extract. The extract of the plant Bursera fagaroides contains 3 compounds, which apparently are glycosides with a potent activity upon agglutination -immobilization and a low effect upon spermatocytes viability, which might be used as contraceptives .


Physiological responses of Holstein calves to heat stress and dietary supplementation with a postbiotic from Aspergillus oryzae.
Increased ambient temperature causes heat stress in mammals, which affects physiological and molecular functions. We have recently reported that the dietary administration of a postbiotic from Aspergillus oryzae (AO) improves tolerance to heat stress in fruit flies and cattle. Furthermore, heat-induced gut dysfunction and systemic inflammation have been ameliorated in part by nutritional interventions. The objective of this study was to characterize the phenotypic response of growing calves to heat stress compared to thermoneutral ad libitum fed and thermoneutral feed-restricted counterparts and examining the physiologic alterations associated with the administration of the AO postbiotic to heat-stressed calves with emphasis on intestinal permeability. In this report, we expand previous work by first demonstrating that heat stress reduced partial energetic efficiency of growth in control (45%) but not in AO-fed calves (62%) compared to thermoneutral animals (66%). While heat stress increased 20% the permeability of the intestine, AO postbiotic and thermoneutral treatments did not affect this variable. In addition, AO postbiotic reduced fecal water content relative to thermoneutral and heat stress treatments. Heat stress increased plasma concentrations of serum amyloid A, haptoglobin and lipocalin-2, and administration of AO postbiotic did not ameliorate this effect. In summary, our findings indicated that heat stress led to reduced nutrient-use efficiency and increased systemic inflammation. Results suggest that the AO postbiotic improved energy-use efficiency, water absorption, and the intestinal permeability in heat stress-mediated increase in gut permeability but did not reduce heat stress-mediated rise in markers of systemic inflammation.


The relationship between COMT genotype and the clinical effectiveness of tolcapone, a COMT inhibitor, in patients with Parkinson's disease.
Patients with Parkinson's Disease (PD) have a variable response to tolcapone, a catechol-O-methyltransferase (COMT) inhibitor. In addition, a subset of patients develop severe diarrhea as a side effect. Two codominant alleles for the COMT gene exist, coding for low and high activity, resulting in low-, medium-, and high-activity genotypes. This study investigates the relationship between this variation in genotype and clinical effects in patients with PD taking tolcapone. To investigate the relationship between COMT polymorphism and clinical response, 24 patients who completed tolcapone clinical trials provided blood samples for COMT genotype analysis. Change in levodopa dose and United Parkinson Disease Rating Scale (UPDRS) Part III (motor subscale) were analyzed at baseline, at 1-2 weeks, and 6 months after initiation of tolcapone. Genotype analysis was performed on seven patients who had diarrhea as a side effect. There was no significant correlation between genotype and improvement in UPDRS score (p = 0.29) according to a linear models approach that adjusted for the subject's severity of PD, tolcapone dose (either 100 or 200 mg three times daily) and initial differences in baseline scores. No significant difference was seen in change in daily levodopa intake and genotype. There was also no relation between diarrhea and COMT genotype. These results indicate that, in the treatment of Parkinson's disease, COMT genotype is not a major contributor to the clinical response to tolcapone.


Differential Effects of Long Term FTY720 Treatment on Endothelial versus Smooth Muscle Cell Signaling to S1P in Rat Mesenteric Arteries.
The sphingosine-1-phosphate (S1P) analog FTY720 exerts pleiotropic effects on the cardiovascular system and causes down-regulation of S1P receptors. Myogenic constriction is an important mechanism regulating resistance vessel function and is known to be modulated by S1P. Here we investigated myogenic constriction and vascular function of mesenteric arteries of rats chronically treated with FTY720. Wistar rats received FTY720 1mg/kg/daily for six weeks. At termination, blood pressure was recorded and small mesenteric arteries collected for vascular studies in a perfusion set up. Myogenic constriction to increased intraluminal pressure was low, but a sub-threshold dose of S1P profoundly augmented myogenic constriction in arteries of both controls and animals chronically treated with FTY720. Interestingly, endothelial denudation blocked the response to S1P in arteries of FTY720-treated animals, but not in control rats. In acute experiments, presence of FTY720 significantly augmented the contractile response to S1P, an effect that was partially abolished after the inhibition of cyclooxygenase (COX-)-derived prostaglandins. FTY720 down regulated S1P1 but not S1P2 in renal resistance arteries and in cultured human endothelial cells. This study therefore demonstrates the endothelium is able to compensate for the complete loss of responsiveness of the smooth muscle layer to S1P after long term FTY720 treatment through a mechanism that most likely involves enhanced production of contractile prostaglandins by the endothelium.


POLYAN: a computer program for polyparametric analysis of cardio-respiratory variability signals.
A polyparametric approach to the study of cardiovascular and respiratory systems, with the analysis of several simultaneously recorded signals and of their mutual relationships, is essential for the assessment of autonomic regulation. A computer program which implements all the procedures used in this investigative context and also makes the approach easy for researchers without an engineering background is described. Spectral techniques (univariate and bivariate), time domain techniques and non invasive baroreflex sensitivity assessment are available and integrated in the same package. In order to allow the flexibility and easy expandability required in a research tool, POLYAN was written in Matlab. POLYAN is currently used in our Hospital by several research groups and is a fundamental research tool for the interdisciplinary assessment of the autonomic nervous system. Establishing a common analysis framework, POLYAN has made sharing new findings and co-operating in research work much easier.


Modulation of the mRNA-binding protein HuR as a novel reversal mechanism of epirubicin-triggered multidrug resistance in colorectal cancer cells.
HuR (ELAVL1), a RNA-binding protein, plays a key role in posttranscriptional regulation of multidrug resistance (MDR)-related genes. Among various HuR-regulated oncogenic transcripts, the activation of galectin-3/β-catenin survival pathway is critical to induce transcription of cyclin D1, P-glycoprotein (P-gp) and/or multidrug resistance-associated proteins (MRPs). In this study, we aim to elucidate the HuR-regulating pathways related to epirubicin-mediated resistance in human colorectal carcinoma cells. The effects and mechanisms of epirubicin treatment on the expressions of upstream survival signals (e.g., β-catenin) and downstream MDR transporters (e.g., P-gp) and anti-apoptotic pathways (e.g., Bcl-2) were assessed with or without HuR knockdown (siHuR) or overexpression (overHuR; ectopic HuR or pcDNA3/HA-HuR). Our results showed that siHuR decreased transcriptional expressions of galectin-3, β-catenin, cyclin D1, Bcl-2, P-gp, MRP1, and MRP2 in epirubicin-treated colon cancer cells. Consistently, the co-treatment of epirubicin and siHuR diminished the expressions of galectin-3, ß-catenin, c-Myc, P-gp and MRP1. HuR silencing enhanced the intracellular accumulation of epirubicin in colon cancer cells. On the other hand, overHuR abolished such effects. Furthermore, siHuR significantly intensified epirubicin-mediated apoptosis via increasing reactive oxygen species and thus promoted the cytotoxic effect of epirubicin. The combined treatments of siHuR and epirubicin significantly reduced the expression of Bcl-2, but increased the expression of Bax, as well as activity and expression levels of caspase-3 and -9. In contrast, overHuR abrogated these effects. Our findings provide insight into the mechanisms by which siHuR potentiated epirubicin-induced cytotoxicity via inhibiting galectin-3/β-catenin signaling, suppressing MDR transporters and provoking apoptosis. To our best knowledge, this is an innovative investigation linking the post-transcriptional control by HuR silencing to survival signaling repression, efflux transporter reversal and apoptosis induction. Our study thus provides a powerful regimen for circumventing MDR in colon cancer cells.


There is a mismatch between the medicare benefit package and the preferences of patients with cancer and their caregivers.
To identify insured services that are most important to Medicare beneficiaries with cancer and their family caregivers when coverage is limited. A total of 440 participants (patients, n = 246; caregivers, n = 194) were enrolled onto the CHAT (Choosing Health Plans All Together) study from August 2010 to March 2013. The exercise elicited preferences about what benefits Medicare should cover for patients with cancer in their last 6 months of life. Facilitated sessions lasted 2.5 hours, included 8 to 10 participants, and focused on choices about Medicare health benefits within the context of a resource-constrained environment. Six of 15 benefit categories were selected by > 80% of participants: cancer care, prescription drugs, primary care, home care, palliative care, and nursing home coverage. Only 12% of participants chose the maximum level of cancer benefits, a level of care commonly financed in the Medicare program. Between 40% and 50% of participants chose benefits not currently covered by Medicare: unrestricted cash, concurrent palliative care, and home-based long-term care. Nearly one in five participants picked some level of each of these three benefit categories and allocated on average 30% of their resources toward them. The mismatch between covered benefits and participant preferences shows that addressing quality of life and the financial burden of care is a priority for a substantial subset of patients with cancer in the Medicare program. Patient and caregiver preferences can be elicited, and the choices they express could suggest potential for Medicare benefit package reform and flexibility.


Carotid sparing intensity modulated radiotherapy on early glottic cancer: preliminary study.
To compare the dose distribution between carotid sparing intensity modulated radiotherapy (IMRT) and opposed lateral field technique (LAFT), and to determine the effects of carotid sparing IMRT in early glottic cancer patients who have risk factors for atherosclerosis. Ten early glottic cancer patients were treated with carotid sparing IMRT. For each patient, the conventional LAFT plan was developed for comparison. IMRT and LAFT plans were compared in terms of planning target volume (PTV) coverage, conformity index, homogeneity index, and the doses to planning organ at risk volume (PRV) for carotid arteries, spinal cord and pharyngeal constrictor muscle. Recurrence was not observed in any patients during the follow-up period. V95% for PTV showed no significant difference between IMRT and LAFT plans, while V100% was significantly higher in the IMRT plan (95.5% vs. 94.6%, p = 0.005). The homogeneity index (11.6%) and conformity index (1.4) in the IMRT plan were significantly better than those in the LAFT plans (8.5% and 5.1, respectively) (p = 0.005). The median V5Gy (90.0%), V25Gy (13.5%), and V50Gy (0%) for carotid artery PRV in the IMRT plan were significantly lower than those in the LAFT plan (99.1%, 89.0%, and 77.3%, respectively) (p = 0.005). Our study suggests that carotid sparing IMRT can significantly decrease the dose to carotid arteries compared to LAFT, and it would be considered for early glottic cancer patient with high risk of atherosclerosis.


The relationship among asymmetric dimethylarginine (ADMA) levels, residual renal function, and left ventricular hypertrophy in continuous ambulatory peritoneal dialysis patients.
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial-based nitric oxide synthase. Its level is increased by end stage renal disease. However, most studies showing an increase in ADMA in dialysis patients have focused on hemodialysis. Results with peritoneal dialysis patients have been more inconclusive. Recent studies suggest that ADMA may be a new cardiovascular risk factor. The aim of the present study was to evaluate the relationship between ADMA levels, residual renal function, and left ventricular hypertrophy in peritoneal dialysis patients. Serum ADMA measurements and echocardiographic evaluations were performed in 54 peritoneal dialysis patients and 26 healthy volunteers. Residual renal function was measured in peritoneal dialysis patients by urea clearance from a urine collection. Thirty-two of the 54 peritoneal dialysis patients had residual renal function. ADMA levels of the peritoneal dialysis group were found to be significantly higher than those of healthy individuals (p = 0.03). Within the peritoneal dialysis group, ADMA levels of patients with residual renal function were significantly lower than those without residual renal function (p = 0.01), though they were still higher than the ADMA levels of the control group (p = 0.04). Serum levels of ADMA were positively correlated with left ventricular mass index (r = 0.29, p = 0.01) and negatively correlated with early mitral inflow velocity (Em) (r = -0.28, p = 0.01), Em/Late mitral inflow velocity (Am) (r = -0,32, p = 0.00), and isovolumetric relaxation time (r = -0.30, p = 0.01). In conclusion, increased ADMA levels seem to be associated with left ventricular hypertrophy in peritoneal dialysis patients, and residual renal function may lead to a reduction of serum ADMA levels.


Genome-wide SNPs and re-sequencing of growth habit and inflorescence genes in barley: implications for association mapping in germplasm arrays varying in size and structure.
Considerations in applying association mapping (AM) to plant breeding are population structure and size: not accounting for structure and/or using small populations can lead to elevated false-positive rates. The principal determinants of population structure in cultivated barley are growth habit and inflorescence type. Both are under complex genetic control: growth habit is controlled by the epistatic interactions of several genes. For inflorescence type, multiple loss-of-function alleles in one gene lead to the same phenotype. We used these two traits as models for assessing the effectiveness of AM. This research was initiated using the CAP Core germplasm array (n = 102) assembled at the start of the Barley Coordinated Agricultural Project (CAP). This array was genotyped with 4,608 SNPs and we re-sequenced genes involved in morphology, growth and development. Larger arrays of breeding germplasm were subsequently genotyped and phenotyped under the auspices of the CAP project. This provided sets of 247 accessions phenotyped for growth habit and 2,473 accessions phenotyped for inflorescence type. Each of the larger populations was genotyped with 3,072 SNPs derived from the original set of 4,608. Significant associations with SNPs located in the vicinity of the loci involved in growth habit and inflorescence type were found in the CAP Core. Differentiation of true and spurious associations was not possible without a priori knowledge of the candidate genes, based on re-sequencing. The re-sequencing data were used to define allele types of the determinant genes based on functional polymorphisms. In a second round of association mapping, these synthetic markers based on allele types gave the most significant associations. When the synthetic markers were used as anchor points for analysis of interactions, we detected other known-function genes and candidate loci involved in the control of growth habit and inflorescence type. We then conducted association analyses--with SNP data only--in the larger germplasm arrays. For both vernalization sensitivity and inflorescence type, the most significant associations in the larger data sets were found with SNPs coincident with the synthetic markers used in the CAP Core and with SNPs detected via interaction analysis in the CAP Core. Small and highly structured collections of germplasm, such as the CAP Core, are cost-effectively phenotyped and genotyped with high-throughput markers. They are also useful for characterizing allelic diversity at loci in germplasm of interest. Our results suggest that discovery-oriented exercises in AM in such small arrays may generate a large number of false-positives. However, if haplotypes in candidate genes are available, they may be used as anchors in an analysis of interactions to identify other candidate regions harboring genes determining target traits. Using larger germplasm arrays, genome regions where the principal genes determining vernalization sensitivity and row type are located were identified.


Role of immune system in development and progress of combined arterial hypertension and gout.
Introduction: Multiple data available indicate high prevalence of comorbid abnormalities in gouty arthritis patients, namely, high incidence of arterial hypertension, coronary artery disease, stroke, atherosclerosis of carotid arteries, vascular dementia. For instance, hypertension is found in 36-41% gout patients, and combined with metabolic syndrome it may reach 80%. The aim: Studying features of clinical course, lipid profile and immune status in patients with combined hypertension and gout. Materials and methods: The study involved examination of 137 male patients with stage II hypertension, average age 56.9±3.4. All patients underwent echocardiography with estimation of the left ventricular mass index to verify hypertension stage, blood chemistry test with estimation of uric acid level, as well as lipid profile and immune status. Results: We have found significant disorders in the lipid profile of blood serum in patients with combined hypertension and gout. Positively higher percentage of activated T-cells was found in patients with combined hypertension and gout, both with early (CD3+CD25+) and late (CD3+HLA-DR+) activation marker, as well as those expressing FAS receptor, and ready to enter into apoptosis. Conclusion: We have identified abnormalities in adhesion and cooperation of immune competent cells, resulting in more intense activation of the same, effector functions and migration to the area of inflammation in the vessel wall.


Factors influencing the transmission of western equine encephalomyelitis virus between its vertebrate maintenance hosts and from them to humans.
A simple model is used to explore the extent to which the uniquely comprehensive studies of western equine encephalomyelitis in Kern County, California, by Reeves and his colleagues over many years, explain the dynamics and epidemiology of the infection. It is concluded that not only does this series of integrated field and laboratory studies successfully account for these phenomena, to an extent which is unlikely to be substantially improved upon, not least because of the inherent difficulties in measuring the key factors with greater precision; but it also provides a unique model of the dedication and ingenuity required if comparable levels of understanding of the ecology and epidemiology of other arbovirus infections are to be achieved.


Attitude of Thai Dental Practitioners towards the Use of Botulinum Toxin in Dentistry.
This study aims to investigate the attitude of Thai dentists towards the use of botulinum toxin (BTX) in dentistry and the associated factors. An online survey was conducted using a semi-structured questionnaire consisting of four parts: demographic data, background knowledge, attitude, and an open-ended question for further suggestions related to BTX usage in dental patients. Multivariate logistic regression was used to analyze factors that affect the decision to use BTX in dentistry, and a content analysis approach was used to describe open-ended suggestion data. We received 444 responses from currently practicing dentists throughout Thailand. Roughly 80% of the participants agreed to the use of BTX in their patients. Most participants were aware that BTX could be used for facial esthetic repairs and bruxism treatment but unaware of other therapeutic benefits. Despite impressively positive attitudes towards BTX use, only 5.9% of the participants had the experience of using BTX in their dental patients. The limit on BTX use is mainly due to the lack of knowledge of related laws and educational resources. In summary, official training courses should be established to promote the safe and legal use of BTX in dentistry in Thailand.


A practice-based model to guide nursing science and improve the health and well-being of patients and caregivers.
The purpose of this paper is to describe a model to guide nursing science in a clinical practice-based setting. Exemplars are provided to highlight the application of this nursing research model, which can be applied to other clinical settings that aim to fill evidence gaps in the literature. Nurse scientists are well positioned to develop new knowledge aimed at identifying global health solutions to multiple disparities. The generation and application of this knowledge are essential to inform and guide professional nursing practice. While a number of evidence-based practice models exist to guide the integration of literature findings and other sources of evidence into practice, there is a need for additional models that serve as a guide and focus for the conduct of research in distinct scientific areas in practice-based settings. Model development and description. Mayo Clinic is a large, comprehensive healthcare system with a mission to address unmet patient needs through practice, research and education. PhD-prepared nurse scientists engage in practice-based research as an integral component of Mayo Clinic's mission. A practice-based nursing research model was developed with the intent to advance nursing research in a clinical setting. The components of the Mayo Clinic Nursing Research model include symptom science, self-management science and caregiving science. The generation of nursing science is focused on addressing needs of patients with complex health conditions, inclusive of caregivers. While clinical settings provide rich opportunities for the conduct of research, priorities need to be established in which to focus scientific endeavours. The Mayo Clinic Nursing Research model may be applicable to nurses around the globe who are engaged in the generation of knowledge to guide practice. The Mayo Clinic Nursing Research model can be used by nurse scientists embedded in healthcare settings to address clinically relevant questions, advance the generation of new nursing knowledge and ultimately improve the health and well-being of patients and caregivers.


Coping styles as correlates of health in high school students.
To study a large, population-based sample of adolescents with the goal of expanding our knowledge base about the relationship of coping and health outcomes. We examined 1769 nonclinical, high school students (48% girls, mean age 16 years, predominantly white) using one class period to establish a link between coping styles, health problems, and health risk behaviors. Instruments employed included the Coping Response Inventory - Youth form (abbreviated version) and the Juvenile Wellness and Health Survey. ANCOVAs were used to test the main effects of coping typology, gender, and their interaction on the five health domains. Findings were consistent with previous research and showed that approach coping correlated negatively with indicators of health problems and health risk behaviors, while avoidance coping correlated positively with these domains. The presence of both forms of coping mitigated the negative effects of avoidance coping. As early as mid-adolescence, habitual coping styles appear to be associated with significant health outcomes. In screening nonclinical samples the clinician can rely on habitual coping styles as indicators of potential health problems.


Complex decisions for first-line and maintenance treatment of advanced wild-type non-small cell lung cancer.
Until recently, the first-line treatment of advanced non-small cell lung cancer (NSCLC) required minimal clinical decision making. Patients who were eligible for chemotherapy received a platinum-based doublet, and 5-year survival rates were poor. With the advent of molecularly targeted agents and better tolerated chemotherapies--namely, bevacizumab, erlotinib, and pemetrexed--new therapeutic opportunities have emerged. Some of the strategies that have proven to be successful for the treatment of patients with NSCLC are targeting of the vascular endothelial growth factor, use of maintenance chemotherapy for patients without progression of disease after initial therapy, and tailoring of cytotoxic agents specific to the histology of an individual patient's cancer. Each approach has been independently shown to improve overall survival, but integrating the data from a number of complicated trials into the "best" approach for patients remains challenging. This review attempts to address three fundamental questions clinicians face in choosing first-line and maintenance treatment for advanced NSCLC, particularly nonsquamous histology: Is pemetrexed or a taxane agent better for combination with platinum therapy? Should bevacizumab be used, and is it beneficial when added to pemetrexed chemotherapy? When is maintenance therapy indicated, and which agent is best?


Weissella kimchii sp. nov., a novel lactic acid bacterium from kimchi.
A gram-positive, catalase-negative, non-sporulating, facultatively anaerobic, short rod-shaped bacterium, with cells measuring 0.3-0.5 x 1-2 microm and designated strain CHJ3T, was isolated from partially fermented kimchi, a traditional Korean fermented vegetable food. The strain produced CO2 gas, D-lactate from glucose and dextran from sucrose and hydrolysed aesculin and arginine. It also fermented N-acetylglucosamine, amygdalin, arbutin, cellobiose, D-fructose, galactose, beta-gentiobiose, gluconate, D-glucose, maltose, D-mannose, salicin, sucrose and D-xylose. The G+C content of the DNA was 48.2 mol%. Phylogenetic analysis of 16S rRNA showed that strain CHJ3T is a member of the genus Weissella. The nearest phylogenetic relative of strain CHJ3T was Weissella confusa, with 16S rRNA similarity of 98.3%. However, strain CHJ3T could be differentiated from W. confusa on the basis of some phenotypic characteristics, analysis of whole-cell protein patterns and DNA-DNA hybridization data. These data suggest that strain CHJ3T be classified in the genus Weissella as a novel species, Weissella kimchii sp. nov. The type strain is CHJ3T (= KCCM 41287T = DSM 14295T = KCTC 3746T).


Small fiber neuropathy in women with fibromyalgia. An in vivo assessment using corneal confocal bio-microscopy.
A consistent line of investigation suggests that fibromyalgia is a neuropathic pain syndrome. This outlook has been recently reinforced by several controlled studies that describe decreased small nerve fiber density in skin biopsies of patients with fibromyalgia. The cornea receives the densest small fiber innervation of the body. Corneal confocal bio-microscopy is a new noninvasive method to evaluate small nerve fiber morphology. Our objective was to assess corneal small nerve fiber morphology in patients with fibromyalgia, and to associate corneal nerve microscopic features with neuropathic pain descriptors and other fibromyalgia symptoms. We studied 17 female patients with fibromyalgia and 17 age-matched healthy control subjects. All the participants completed different questionnaires regarding the symptoms of fibromyalgia, including a neuropathic pain survey. A central corneal thickness scan was obtained with a confocal microscope. Nerve measurements were made by a single ophthalmologist without knowledge of the clinical diagnosis. Stromal nerve thickness was defined as the mean value between the widest and the narrowest portion of each analyzed stromal nerve. Corneal sub-basal plexus nerve density was also assessed. Patients with fibromyalgia had stromal nerve thickness of 5.0 ± 1.0 µm (mean ± standard deviation) significantly different from that of control's values (6.1 ± 1.3) p = 0.01. Patients also had decreased sub-basal plexus nerve density per square millimeter (85 ± 29) vs. 107 ± 26 of controls p = 0.02. When controls and patients were grouped together, there was an association between stromal nerve slenderness and neuropathic pain descriptors (Fisher's exact test p = 0.007). Women suffering from fibromyalgia have thinner corneal stromal nerves and diminished sub-basal plexus nerve density when compared to healthy controls. Nerve scarcity is associated with neuropathic pain descriptors. Small fiber neuropathy may play a role in the pathogenesis of fibromyalgia pain. Corneal confocal microscopy could become a useful test in the study of patients with fibromyalgia.


[An experimental study on electrophysiological and histopathological changes in 2,5-hexanedione-intoxicated rats].
An experimental study of neuropathy due to 2,5-hexanedione (2,5-HDione) was performed in rats by using simultaneously both electrophysiological and histopathological methods. Seven rats were given subcutaneously five days a week 200 mg/kg of 2,5-HDione for first 3 weeks and then 300 mg/kg for the next 5 weeks. Nerve conduction velocities in the tail were measured every week and after the respective measurement times one animals was sacrificed for histological study. At the 2nd week of the experiment, 2,5-HDione-treated rat showed a slight morphological changes with swollen axons in the posterior spinal root fiber and tail nerve. A slowing of motor and sensory conduction velocity (MCV and SCV) in the tail was observed in the treated group at the 4th week. Weakness of hindlimbs was apparently seen at the 5th week. At the 6th and 7th week, histological changes including giant axonal swelling, fiber loss, thinning of myelin and demyelination, were prominent in the various regions of the peripheral nervous system. Additionally, degenerative changes of the spermatogenic cells, especially the formation of multinucleated giant spermatids, were markedly observed in the treated rats at the 6th and 7th week.


Junctional and compound pigmented nevi induced by 9, 10-dimethyl-1,2-benzanthracene in skin of albino guinea pigs.
Seventy albino guinea pigs were used in the experiment to investigate the influence of 9,10-dimethyl-1,2-benzanthracene on amelanotic melanocytes. A field 5 sq cm was marked on the flank of each animal. Hairs from these fields were clipped twice a week and painted for 20 consecutive weeks with 0.3 ml of 1% 9,10-dimethyl-1,2-benzanthracene in acetone. During the 1-year observation period, pigmented sports appeared in 40 animals. Biopsies were taken under local anesthesia, and sections were prepared for light and electron microscopic observations. Melanin formation of unknown mechanism took place in the epidermal melanocytes and in the melanocytes from the outer root sheath. These melanocytes also formed junctional and compound nevi; serial sections revealed various stages of pigmented nevi development. Schwann cells did not participate in the formation of nevi. Evidence is presented that 9,10-dimethyl-1,2-benzanthracene can convert amelanotic melanocytes into melanin-producing cells in the albino guinea pig skin. In addition, this system produces an animal model for the development of junctional and compound nevi.


Youth Suicide Attempt Nomenclature Used in Two Central Texas Hospitals.
Surveillance systems capturing instances of self-directed violence (SDV) continue to lack uniform nomenclature and classification methodology. To apply and compare two retrospective surveillance approaches to youth experiencing SDV presenting to two urban hospitals with Level I Trauma Centers. Two suicide attempt surveillance methods where retrospectively applied to our SDV cohort: (a) a rigorous method facilitated by medical record review and application of standardized classification; and (b) a common surveillance method conducted by systematic queries of suicide attempt key terms and diagnosis codes among hospital databases. Rigorous surveillance identified 249 patients attempting suicide. The common method's querying suicide attempt in the chief complaint field had a high positive predictive value and specificity; however, sensitivity was low. Authors were unable to determine whether all SDV encounters during the study timeframe were identified for initial screening owing to the hospital's lack of a uniform nomenclature or classification system. Results showed underreporting of suicide attempt cases, inadequate sensitivity and specificity in common surveillance methods, and skewed demographic representation compared with the rigorous surveillance method. This study elucidates the negative impact of inconsistent SDV nomenclature including impeding effective patient identification, treatment, surveillance, and generalizable research.


Emotion matters: The influence of valence on episodic future thinking in young and older adults.
In young adults, valence not only alters the degree to which future events are imagined in rich episodic detail, but also how memorable these events are later on. For older adults, how valence influences episodic detail generation while imagining future events, or recalling these details at another time, remains unclear. We investigated the effect of valence on the specificity and memorability of episodic future thinking (EFT) in young and older adults. Among young and older adults, negative EFT was accompanied by less episodic detail generation relative to positive and neutral EFT. A similar reduction in episodic specificity for negative EFT was found two days later when participants recalled their previously imagined events. Notably, while older adults generated less episodically specific future thoughts relative to young adults, age did not influence the effect of valence on episodic detail generation at imagination or recollection.


Growth differentiation factor-15 levels and the risk of contrast induced acute kidney injury in acute myocardial infarction patients treated invasively: A propensity-score match analysis.
Growth differentiation factor-15 (GDF-15) is an emerging biomarker for risk stratification in cardiovascular disease. Contrast-induced acute kidney injury (AKI) is an important complication in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). In this retrospectively observational study, we aimed to determine the role of GDF-15 and the risk of AKI in acute myocardial infarction (AMI) patients. The medical records of 1195 patients with AMI were reviewed. After exclusion criteria, a total of 751 eligible patients who underwent CAG or PCI were studied. Preoperative clinical parameters including GDF-15 levels were recorded. Multivariate logistic regression analysis was used to identify the risk factors of AKI. Subsequently, to reduce a potential selection bias and to balance differences between the two groups, a propensity score-matched analysis was performed. We recorded the 30-day all-cause mortality of the total study population. Kaplan-Meier analysis was performed to identify the association between short term survival in AMI patients and GDF-15 level. Among 751 enrolled patients, 106 patients (14.1%) developed AKI. Patients were divided into two groups: AKI group (n = 106) and non-AKI group (n = 645). GDF-15 levels were significantly higher in AKI group compared to non-AKI group (1328.2 ± 349.7 ng/L vs. 1113.0 ± 371.3 ng/L, P <0.001). Multivariate logistic regression analyses showed GDF-15 was an independent risk factor of AKI (per 1000 ng/L increase of GDF-15, OR: 3.740, 95% CI: 1.940-7.207, P < 0.001). According to GDF-15 tertiles, patients were divided into three groups. Patients in middle (OR 2.93, 95% CI: 1.46-5.89, P = 0.003) and highest GDF-15 tertile (OR 3.72, 95% CI: 1.87-7.39, P <0.001) had higher risk of AKI compared to patients in the lowest GDF-15 tertile. The propensity score-matched group set comprised of 212 patients. Multivariate logistic regression revealed that GDF-15 is still an independent risk factor for AKI after matching (per 1000 ng/L increase of GDF-15, OR: 2.395, 95% CI: 1.020-5.626, P = 0.045). Based on the Kaplan-Meier analysis, the risk of 30-day all-cause mortality increased in higher GDF-15 tertiles log rank chi-square: 29.895, P <0.001). This suggests that preoperative plasma GDF-15 is an independent risk factor of AKI in AMI patients underwent CAG or PCI. GDF-15 and AKI are associated with poor short term survival of AMI patients.


Rheumatology Workforce Planning in Western Countries: A Systematic Literature Review.
To compare health care planning models forecasting rheumatology workforce requirements in western countries. A systematic literature review was conducted through medical databases (Ovid MEDLINE, Embase, CINAHL, and Cochrane Library) and the grey literature. All articles reporting a rheumatology workforce model were included. The search yielded 6,508 articles, and 14 publications (on 12 studies) were included. Workforce models were available for the US (n = 3), Canada (n = 3), the US plus Canada (n = 1), Germany (n = 2), Spain (n = 1), and the UK (n = 2). The number of rheumatologists required to serve a population of 100,000 people was calculated, with a range of 0.7 (UK, calculated for 1988) to 3.5 (Spain, calculated for 2021). Most models used a needs-based approach (n = 6); 3 studies each applied a supply- or demand-based method. The following variables were considered by ≥1 model: disease prevalence, patients' referral to rheumatologists, clinical visits/patient/year, population development, factors influencing performance of rheumatologists, patient flow/care sharing, and medical technologies/infrastructure development. Heterogeneity in methods used, the period or calendar years for which the estimates were projected, and heterogeneity of variables evaluated led to disparate estimates, with results ranging from 0.7 to 3.5 rheumatologists per 100,000 population. An international initiative is needed to agree upon a common approach for a reliable estimation of manpower requirements in rheumatology.


Exopolysaccharide Produced by Lactobacillus paracasei IJH-SONE68 Prevents and Improves the Picryl Chloride-Induced Contact Dermatitis.
Allergic disease is one of the most important and common health problems worldwide. We have previously demonstrated that a fig leaf-derived lactic acid bacterium Lactobacillus (Lb.) paracasei IJH-SONE68 produces a novel exopolysaccharide (EPS). Furthermore, we have shown that the EPS inhibits the catalytic activity of hyaluronidase (EC 126.96.36.199) promoting inflammatory reactions. To evaluate the anti-allergy and anti-inflammatory effects of the EPS, in the present study, we employed the picryl-chloride-induced delayed-type (type IV) allergy model mice, which is used to evaluate the contact dermatitis. Oral administration of the EPS was observed to reduce the ear swelling in the model mice. We also observed that the overexpression of ear interleukin-4 (T helper (Th) 2 cytokine) mRNA and the increase in serum immunoglobulin E (IgE) are repressed. However, the expression of interferon-γ (Th1 cytokine) was not accelerated in all of the allergen-challenged model mice. The improvement may be responsible for the Th2 downregulation rather than the Th1 upregulation. In addition, the symptom of immediate-type (type I) allergy model mice was improved by oral administration of the IJH-SONE68 cell (data not shown). We can conclude that the IJH-SONE68-derived EPS is useful to improve the type I and IV allergies including atopic dermatitis.


Progressive formation of DNA lesions in cultured Ehrlich ascites tumor cells treated with hydroxyurea.
We have previously demonstrated an accumulation of strand breaks in mature DNA of cultured Ehrlich ascites tumor cells treated with methotrexate. We postulated that the strand breaks arose from unrepaired spontaneous DNA lesions. The present study describes a progressive accumulation of strand breaks in mature DNA of Ehrlich ascites cells treated with hydroxyurea (HU). Strand breaks were determined by alkaline elution. Accumulation of strand breaks was dependent on the length of incubation (0-16 h) and on HU concentration (0-10 mM). About 70% of strand breaks were repaired when cells were incubated without HU. About 67% of strand breaks were prevented by 0.4 mM deoxyadenosine, deoxyguanosine, and deoxycytidine, with or without thymidine. Prevention was less effective by deoxyadenosine and deoxyguanosine and ineffective by deoxycytidine. Free radical scavengers did not prevent strand breaks. S-phase cells accumulated about twice the number of strand breaks as non-S-phase cells. Cell survival decreased in proportion to the increase in HU concentration (0-10 mM). The results demonstrate that lack of purine, as well as of pyrimidine, nucleotides results in strand breaks in mature DNA, suggest that HU cytotoxicity is due to fragmentation of mature DNA, and caution against the use of HU in DNA repair studies.


Proteasome inhibitors, including curcumin, improve pancreatic β-cell function and insulin sensitivity in diabetic mice.
Type 2 diabetes stems from obesity-associated insulin resistance, and in the genetically susceptible, concomitant pancreatic β-cell failure can occur, which further exacerbates hyperglycemia. Recent work by our group and others has shown that the natural polyphenol curcumin attenuates the development of insulin resistance and hyperglycemia in mouse models of hyperinsulinemic or compensated type 2 diabetes. Although several potential downstream molecular targets of curcumin exist, it is now recognized to be a direct inhibitor of proteasome activity. We now show that curcumin also prevents β-cell failure in a mouse model of uncompensated obesity-related insulin resistance (Lepr(db/db) on the Kaliss background). In this instance, dietary supplementation with curcumin prevented hyperglycemia, increased insulin production and lean body mass, and prolonged lifespan. In addition, we show that short-term in vivo treatment with low dosages of two molecularly distinct proteasome inhibitors celastrol and epoxomicin reverse hyperglycemia in mice with β-cell failure by increasing insulin production and insulin sensitivity. These studies suggest that proteasome inhibitors may prove useful for patients with diabetes by improving both β-cell function and relieving insulin resistance.


Younger and Older Users' Recognition of Virtual Agent Facial Expressions.
As technology advances, robots and virtual agents will be introduced into the home and healthcare settings to assist individuals, both young and old, with everyday living tasks. Understanding how users recognize an agent's social cues is therefore imperative, especially in social interactions. Facial expression, in particular, is one of the most common non-verbal cues used to display and communicate emotion in on-screen agents (Cassell, Sullivan, Prevost, & Churchill, 2000). Age is important to consider because age-related differences in emotion recognition of human facial expression have been supported (Ruffman et al., 2008), with older adults showing a deficit for recognition of negative facial expressions. Previous work has shown that younger adults can effectively recognize facial emotions displayed by agents (Bartneck & Reichenbach, 2005; Courgeon et al. 2009; 2011; Breazeal, 2003); however, little research has compared in-depth younger and older adults' ability to label a virtual agent's facial emotions, an import consideration because social agents will be required to interact with users of varying ages. If such age-related differences exist for recognition of virtual agent facial expressions, we aim to understand if those age-related differences are influenced by the intensity of the emotion, dynamic formation of emotion (i.e., a neutral expression developing into an expression of emotion through motion), or the type of virtual character differing by human-likeness. Study 1 investigated the relationship between age-related differences, the implication of dynamic formation of emotion, and the role of emotion intensity in emotion recognition of the facial expressions of a virtual agent (iCat). Study 2 examined age-related differences in recognition expressed by three types of virtual characters differing by human-likeness (non-humanoid iCat, synthetic human, and human). Study 2 also investigated the role of configural and featural processing as a possible explanation for age-related differences in emotion recognition. First, our findings show age-related differences in the recognition of emotions expressed by a virtual agent, with older adults showing lower recognition for the emotions of anger, disgust, fear, happiness, sadness, and neutral. These age-related difference might be explained by older adults having difficulty discriminating similarity in configural arrangement of facial features for certain emotions; for example, older adults often mislabeled the similar emotions of fear as surprise. Second, our results did not provide evidence for the dynamic formation improving emotion recognition; but, in general, the intensity of the emotion improved recognition. Lastly, we learned that emotion recognition, for older and younger adults, differed by character type, from best to worst: human, synthetic human, and then iCat. Our findings provide guidance for design, as well as the development of a framework of age-related differences in emotion recognition.


Semidirect Restorations in Multidisciplinary Treatment: Viable Option for Children and Teenagers.
Due to the esthetic necessity required nowadays, the multidisciplinary treatment became a fundamental step in the restoration success. When the patient exhibits dental agenesis of one or more elements, he can show difficulty in social interactions. The age of the patient is a limiting factor to esthetic procedures, however, it should be evaluated as a real indicative with each case. The utilization of semi-direct restorations is a viable option due the cost, esthetic and improvement of physical and mechanical properties. The purpose of this paper is to present a case detailing the confection and cementation of anterior semi-direct restorations aimed at an anatomic reestablishment associated with integrated treatment with periodontics and orthodontics.


Two-dimensional membrane protein patterns of acute myeloid leukemia cells and mature myeloid cells after various ectolabeling procedures.
Surface exposed membrane proteins of malignant cells may offer important clues about the differentiation stage of the cell or may contain proteins specific for the malignant state. We have studied the surface exposed membrane proteins of human acute myeloid leukemia cells employing the lactoperoxidase, periodate, or the neuraminidase/galactose oxidase ectolabeling procedures. One-dimensional membrane protein patterns were prepared from 20 patients, and from 19 patients, two-dimensional patterns were prepared according to O'Farrell. No consistent differences in membrane proteins could be found between patients classified as M1, M2, M4, or M5 (FAB classification). A diagram of membrane proteins from acute myeloid leukemia cells subjected to two-dimensional electrophoresis could be composed from the results obtained. About 25 different membrane proteins can be indicated. Two-dimensional patterns, after the various ectolabeling procedures, were also prepared from mature myeloid cells, visualizing about 18 different membrane proteins. Comparison of these and the undifferentiated myeloid leukemia cell pattern reveals some maturation-linked or leukemia-associated differences. The most relevant proteins will be discussed, along with their association with a recently described "malignancy marker" with a molecular weight of 68,000 daltons.


Symmetry in running.
Symmetry plays a key role in simplifying the control of legged robots and in giving them the ability to run and balance. The symmetries studied describe motion of the body and legs in terms of even and odd functions of time. A legged system running with these symmetries travels with a fixed forward speed and a stable upright posture. The symmetries used for controlling legged robots may help in elucidating the legged behavior of animals. Measurements of running in the cat and human show that the feet and body sometimes move as predicted by the even and odd symmetry functions.


Ursodeoxycholic acid stimulates cholangiocyte fluid secretion in mice via CFTR-dependent ATP secretion.
Cholangiopathies are characterized by impaired cholangiocyte secretion. Ursodeoxycholic acid (UDCA) is widely used for cholangiopathy treatment, but its effects on cholangiocyte secretory functions remain unclear and are the subject of this study. Polarized mouse cholangiocytes in tubular (isolated bile-duct units [IBDU]) or monolayer configuration were obtained from wild-type (WT) and B6-129-Cftr(tm1Kth) and Cftr(tm1Unc) mice that are defective in CFTR, an adenosine 3',5'-cyclic monophosphate (cAMP)-stimulated Cl(-) channel expressed in cholangiocytes. Fluid secretion was assessed by video-optical planimetry, Cl(-) and Ca(2+) efflux by microfluorimetry (6-methoxy-N-ethylquinolinium chloride, fura-2, and fluo-4), adenosine triphosphate (ATP) secretion by luciferin-luciferase assay, and protein kinase C (PKC) by Western blot. UDCA stimulated fluid secretion and Cl(-) efflux in WT-IBDU but not in CFTR-KO-IBDU or in WT-IBDU exposed to CFTR inhibitors. UDCA did not affect intracellular cAMP levels but increased [Ca(2+)]i in WT and not in CFTR-KO cholangiocytes. UDCA stimulated apical ATP secretion in WT but not in CFTR-KO cholangiocytes. UDCA-stimulated [Ca(2+)]i increase was inhibited by suramin, a purinergic 2Y-receptor inhibitor. UDCA stimulated the translocation of PKC-alpha and PKC-epsilon to the plasma membrane. UDCA-stimulated secretion was inhibited by 2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid and by phospholipase C and PKC inhibitors. UDCA increased ATP output in isolated perfused livers from WT but not from CFTR-KO mice. Our data indicate that UDCA stimulates a CFTR-dependent apical ATP release in cholangiocytes. Secreted ATP activates purinergic 2Y receptors, and, through [Ca(2+)]i increase and PKC activation stimulates Cl(-) efflux and fluid secretion. These data support the concept that CFTR plays a role in modulating purinergic signaling in secretory epithelia and suggest a novel mechanism explaining the choleretic effect of UDCA.


The assessment of patients with long-term psychotic disorders: application of the WHO Disability Assessment Schedule II.
To evaluate the use of the World Health Organization Disability Assessment Schedule II (WHODAS II), a patient questionnaire measuring disability, in patients treated for long-term psychotic disorders. The study was conducted at St. Vincent's Mental Health Service, Melbourne, Australia. Twenty patients with long-term psychotic disorders under the care of either the residential Community Care Unit or the outpatient Mobile Support and Treatment Service were selected. For all 20 patients a clinician assessment of disability and functional status was recorded using the International Classification of Impairments, Disabilities and Handicaps-2 (ICIDH-2), Life Skills Profile (LSP) and Health of the Nation Outcome Scale (HoNOS). The WHODAS II survey was then administered to each patient. The WHODAS II was re-administered by a second rater within 5 days of the initial assessment for the purpose of test-retest reliability analysis. Each patient also completed the WHO Quality of Life instrument (brief version) (WHQOL-BREF), a self-report questionnaire on quality of life. The WHODAS II was experienced as relatively complex and at times difficult to administer with full co-operation in this clinical context. Overall, test-retest reliability was fair. The information it yielded gave valuable insights into patients' experiences. Most of the participants reported fewer impairments in mental functions and fewer activity limitations than reported by clinicians. However, patients reported significant restrictions in participation in social activities and limitations due to environmental barriers. The WHOQOL-BREF highlighted difficulties experienced by patients in their participation in society, through exploring difficulties and satisfaction with various aspects of life experience and this instrument was well accepted. The self-reported experience of patients is needed alongside clinician-rated measures to assess outcomes in people with long-term psychotic disorders. The WHODAS II records and measures patients' own experiences of disability. It may be used together with the WHOQOL-BREF, a distinct and complementary self-report assessment of quality of life.


Socioeconomic differentials in mortality risk among men screened for the Multiple Risk Factor Intervention Trial: II. Black men.
This study examined socioeconomic differentials in risk of death from a number of causes in a large cohort of Black men in the United States. For 20 224 Black men screened for the Multiple Risk Factor Intervention Trial between 1973 and 1975, data were collected on median family income of Black households in zip code of residence, age, cigarette smoking, blood pressure, serum cholesterol, previous heart attack, and drug treatment for diabetes. The 2937 deaths that occurred over the 16-year follow-up period were grouped into specific causes and related to median Black family income. There was an inverse association between age-adjusted all-cause mortality and median family income. There was no attenuation of this association over the follow-up period, and the association was similar for the 22 clinical centers carrying out the screening. The gradient was seen for most of the specific causes of death, although the strength of the association varied. Median income was markedly lower for the Black men screened than for the White men, but the relationship between income and all-cause mortality was similar. Socioeconomic position is an important determinant of mortality risk for Black men. Even though Blacks lived in areas with substantially lower median family income than Whites, the association of income with mortality was similar for Blacks and Whites.


Hearing Norton Sound: community involvement in the design of a mixed methods community randomized trial in 15 Alaska Native communities.
Community involvement is important in good research practice. We led a community-based study to improve early detection and treatment of childhood hearing loss in rural Alaska. This study evaluated a cell phone-based hearing screening process and compared a new telemedicine specialty referral pathway to the standard primary care referral pathway. The study included community involvement, engagement, and participation from the very beginning to inform how to best design the trial. We obtained insight and feedback from community members through involvement of a core stakeholder team and through community engagement and participation in focus groups and community events. Feedback received through community involvement and participation influenced the design of the trial at key decision points. Community member guidance shaped the research question, the outcomes to be measured, and the procedures for completing the project, such as participant recruitment. This study offers an example of community involvement, engagement and participation that could be mirrored in future research to maintain the interests of participating communities. Background Effective systems for early identification and treatment of childhood hearing loss are essential in rural Alaska, where data indicate a high prevalence of childhood ear infections and hearing loss. However, loss to follow-up from school hearing screening programs is pervasive. The Hearing Norton Sound study was a mixed methods community randomized controlled trial that was developed to address this gap. The study engaged community members and participants in the design of the trial, including involvement of stakeholders as collaborators. Methods Community engagement and participation in research design occurred through focus groups and through the integration of stakeholders into the study team. Representation was cross-sectoral, involving individuals from multiple levels of the school and health system, as well as community members from each of the 15 communities. Feedback obtained between April 2017 and August 2017 informed the final design of the randomized trial, which began enrollment of children in October 2017 and concluded in March 2019. Results Stakeholder involvement and community participation shaped the design of specific trial elements (research question; comparators; outcomes and measures; telemedicine protocols; and recruitment and retention). Community involvement was strengthened by the use of multiple modalities of involvement and by the positionality of lead stakeholders on the study team. Conclusions This study highlights the effectiveness of multifaceted stakeholder involvement and participation in the design of health research conducted within Alaska Native communities. It offers an example of involvement and reporting that could be mirrored in future research in order to protect and further the interests of the participating community. Trial registration ClinicalTrials.gov, NCT03309553 , First registered 10/9/2017.


REC protein family expansion by the emergence of a new signaling pathway.
We explore when and why large classes of proteins expand into new sequence space. We used an unsupervised machine learning approach to observe the sequence landscape of REC domains of bacterial response regulator proteins. We find that within-gene recombination can switch effector domains and, consequently, change the regulatory context of the duplicated protein.


Effect of growth rate and substrate limitation on the composition and structure of the cell wall of Saccharomyces cerevisiae.
1. A study was made of the composition and structure of walls isolated from yeast grown in continuous culture at different rates, under three conditions of glucose limitation in which the concentrations of glucose and ammonium sulphate in the medium and the oxygen-transfer rate in the culture were varied, and one condition of NH(4) (+) limitation. 2. The contents of total glucan and total mannan in the walls were relatively little affected by the growth rate under any of the four sets of conditions. The phosphorus and protein contents of walls from yeast grown under each of the four conditions increased as the growth rate was decreased. Walls from yeast grown under NH(4) (+) limitation contained only half as much protein as walls from cells grown under glucose limitation. The proportion of lipid was greatest in walls from yeast grown under NH(4) (+) limitation. 3. A procedure was devised for fractionating isolated walls, based on the ease with which the glucan and mannan were extracted with water and with hot and cold 6% (w/v) potassium hydroxide solution. The percentage of glucan, mannan, protein and phosphorus in each of the fractions was affected by the rate of growth and by the nature of the substrate limitation. 4. The beta-fructofuranosidase activities of yeast grown under glucose limitation increased as the growth rate was lowered, but decreased at very low growth rates. The effects at low growth rates were probably due to repression of enzyme synthesis by residual glucose in the culture filtrate. The beta-fructofuranosidase activities of yeast grown under NH(4) (+) limitation were much lower than those from yeast grown under any of the conditions of glucose limitation. 5. Yeast cells grown at any of the rates under NH(4) (+) limitation were longer and thinner than those grown at the same rate under any of the conditions of glucose limitation. Mean cell volumes were dependent on growth rate but not on the nature of the substrate limitation. 6. Electron micrographs of thin sections of isolated walls showed that cells grown under NH(4) (+) limitation had a more porous structure than those from cells grown under any of the conditions of glucose limitation.