Bifidobacterium breve with α-linolenic acid and linoleic acid alters fatty acid metabolism in the maternal separation model of irritable bowel syndrome.
The aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15) were orally gavaged with either B. breve DPC6330 (10(9) microorganisms/day) alone or in combination with 0.5% (w/w) linoleic acid & 0.5% (w/w) α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11) in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (p<0.05). Administration of B. breve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11) in adipose tissue and palmitoleic acid in the prefrontal cortex (p<0.05), whereas feeding B. breve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (p<0.05) compared with the NS un-supplemented controls. Administration of B. breve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (p<0.01) and α-linolenic acid in adipose tissue (p<0.001), whereas feeding B. breve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (p<0.05), and α-linolenic acid in adipose tissue (p<0.001). B. breve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated rats significantly modified the palmitoleic acid, arachidonic acid and docosahexaenoic acid contents in tissues. The effect was not observed in non-separated animals.


Prediction of food protein allergenicity: a bioinformatic learning systems approach.
Food hypersensitivity is constantly increasing in Western societies with a prevalence of about 1-2% in Europe and in the USA. Among children, the incidence is even higher. Because of the introduction of foods derived from genetically modified crops on the marketplace, the scientific community, regulatory bodies and international associations have intensified discussions on risk assessment procedures to identify potential food allergenicity of the newly introduced proteins. In this work, we present a novel biocomputational methodology for the classification of amino acid sequences with regard to food allergenicity and non-allergenicity. This method relies on a computerised learning system trained using selected excerpts of amino acid sequences. One example of such a successful learning system is presented which consists of feature extraction from sequence alignments performed with the FASTA3 algorithm (employing the BLOSUM50 substitution matrix) combined with the k-Nearest-Neighbour (kNN) classification algorithm. Briefly, the two features extracted are the alignment score and the alignment length and the kNN algorithm assigns the pair of extracted features from an unknown sequence to the prevalent class among its k nearest neighbours in the training (prototype) set available. 91 food allergens from several specialised public repositories of food allergy and the SWALL database were identified, pre-processed, and stored, yielding one of the most extensively characterised repositories of allergenic sequences known today. All allergenic sequences were classified using a standard one-leave-out cross validation procedure yielding about 81% correctly classified allergens and the classification of 367 non-allergens in an independent test set resulted in about 98% correct classifications. The biocomputational approach presented should be regarded as a significant extension and refinement of earlier attempts suggested for in silico food safety assessment. Our results show that the framework described here is powerful enough to become useful as part of a multiple-procedure test scheme that also depicts other evaluation approaches such as solid phase immunoassay and tests for stability to digestions.


Characteristics of proximal early gastric cancer differentiating distal early gastric cancer.
Previous studies reported substantial differences between proximal and distal gastric cancer, however, most of the cases included in these studies were advanced gastric cancers (AGCs). The aim of this study was to investigate the unique characteristics of proximal early gastric cancer (EGC) by comparing with distal EGC. From March 2007 to March 2016, proximal and distal EGC patients who underwent endoscopic or surgical resection at our institution were matched 1:3 according to age and sex. We retrospectively analyzed the clinical and histopathological information. A total of 368 patients were enrolled including 92 (25%) in the proximal and 276 (75%) in the distal group. The proportion of patients who underwent surgery (56.5 vs. 20.3%, p<0.001), undifferentiated type (38.0 vs. 19.6%, p<0.001), tumor size (29.5 ±19.4 vs. 20.3 ±16.8 mm, p<0.001) and submucosal (SM) invasion (60.9 vs. 25.7%, p<0.001) were significantly higher in the proximal group than in the distal group. In multivariate analysis, the proximal location of EGC was a significant risk factor for SM invasion in the total population (odds ratio [OR], 3.541; 95% confidence interval [CI], 2.053-6.110; p<0.001), and in subgroup with EGC < 30mm (n = 279) (OR, 5.940; 95% CI, 2.974-11.862; p<0.001). In conclusion, careful therapeutic decision of proximal EGC is essential due to the different histopathological characteristics such as large tumor size and higher potential for SM invasion.


Genetic variation of oxidative phosphorylation genes in stroke and Alzheimer's disease.
Previous research implicates alterations in oxidative phosphorylation (OXPHOS) in the development of Alzheimer's disease (AD). We sought to test whether genetic variants within OXPHOS genes increase the risk of AD. We first used gene-set enrichment analysis to identify associations, and then applied a previously replicated stroke genetic risk score to determine if OXPHOS genetic overlap exists between stroke and AD. Gene-set enrichment analysis identified associations between variation in OXPHOS genes and AD versus control status (p = 0.012). Conversion from cognitively normal controls to mild cognitive impairment was also associated with the OXPHOS gene-set (p = 0.045). Subset analyses demonstrated association for complex I genes (p < 0.05), but not for complexes II-V. Among neuroimaging measures, hippocampal volume and entorhinal cortex thickness were associated with OXPHOS genes (all p < 0.025). The stroke genetic risk score demonstrated association with clinical status, baseline and longitudinal imaging measures (p < 0.05). OXPHOS genetic variation influences clinical status and neuroimaging intermediates of AD. OXPHOS genetic variants associated with stroke are also linked to AD progression. Further studies are needed to explore functional consequences of these OXPHOS variants.


C16orf57, a gene mutated in poikiloderma with neutropenia, encodes a putative phosphodiesterase responsible for the U6 snRNA 3' end modification.
C16orf57 encodes a human protein of unknown function, and mutations in the gene occur in poikiloderma with neutropenia (PN), which is a rare, autosomal recessive disease. Interestingly, mutations in C16orf57 were also observed among patients diagnosed with Rothmund-Thomson syndrome (RTS) and dyskeratosis congenita (DC), which are caused by mutations in genes involved in DNA repair and telomere maintenance. A genetic screen in Saccharomyces cerevisiae revealed that the yeast ortholog of C16orf57, USB1 (YLR132C), is essential for U6 small nuclear RNA (snRNA) biogenesis and cell viability. Usb1 depletion destabilized U6 snRNA, leading to splicing defects and cell growth defects, which was suppressed by the presence of multiple copies of the U6 snRNA gene SNR6. Moreover, Usb1 is essential for the generation of a unique feature of U6 snRNA; namely, the 3'-terminal phosphate. RNAi experiments in human cells followed by biochemical and functional analyses confirmed that, similar to yeast, C16orf57 encodes a protein involved in the 2',3'-cyclic phosphate formation at the 3' end of U6 snRNA. Advanced bioinformatics predicted that C16orf57 encodes a phosphodiesterase whose putative catalytic activity is essential for its function in vivo. Our results predict an unexpected molecular basis for PN, DC, and RTS and provide insight into U6 snRNA 3' end formation.


Risk assessment in professional football: an examination of accidents and incidents in the 1994 World Cup finals.
To assess the risks to footballers' health and safety during competitive international matches, with identification of the most common causes of injury. Videos of 44 of the 52 matches played during the 1994 World Cup finals staged in the USA were analysed. During each match, several relevant variables were recorded, including the number of fouls, injuries, treatments, times of incidents, identity of players treated or injured, and the injury mechanism. Additional information on players' injuries was obtained from the extensive media coverage of the event. Only 29% of injuries resulted from foul play, whereas 71% of injuries to players occurred where no foul play was adjudged by the referee to have taken place (P < 0.01). Defenders were found to be proportionately subjected to a greater risk of injury than other players (P < 0.05). Fifteen per cent of all injuries were judged to be at least moderate, resulting in the player missing at least one match. Frequency of moderate injury was 1026 injuries per 100,000 hours played. The major causes of injuries during international football matches were not found to be associated with foul play, as judged by the referees. However, in those cases where injuries occurred without a foul being committed, almost 50% involved player to player contact. This gives some cause for concern and is worth further investigation.


The motor phenotype of Parkinson's disease in relation to age at onset.
Parkinson's disease (PD) is heterogeneous and age at onset may define variation in clinical phenotype. Most previous studies have used various age cut-offs and have been based on clinical case series. We have studied the association between clinical features and age of onset in 358 community-based and regional patients with PD. Tremor at presentation is twice as common in those with onset over 64 years as compared to those with onset under 45 (early onset PD - EOPD) and becomes more common with increasing age at onset (p values for trend ≤ 0.004). Dystonia affects 60% of those with EOPD, shows a curvilinear relationship with age at onset (cubic versus linear p=0.01) with highest risk in patients whose disease began before 48 years. In this study age at onset was a strong predictor of the development of dyskinesias, with younger age associated with a higher risk of dyskinesias. Following multivariable analysis, allowing for possibly confounding factors (disease duration, L-DOPA dosage, L-DOPA treatment duration) younger age at onset, (less than 55 years) predicted the development of L-DOPA induced dyskinesia (odds ratio <45 years 2.1, 95% CI 1.0, 4.8; odds ratio < 55 years 3.8, 95% CI 1.8, 8.0). Only 2/70 (2.9%) EOPD patients carried pathogenic parkin or PINK1 mutations and the clinical differences between early and late onset disease were not explained by the presence of mutations in these genes. This study highlights the clinical differences between early and late onset PD, which have important implications for diagnosis and management.


Optimization of primer design for the detection of variable genomic lesions in cancer.
Primer approximation multiplex PCR (PAMP) is a new experimental protocol for efficiently assaying structural variation in genomes. PAMP is particularly suited to cancer genomes where the precise breakpoints of alterations such as deletions or translocations vary between patients. The design of PCR primer sets for PAMP is challenging because a large number of primer pairs are required to detect alterations in the hundreds of kilobases range that can occur in cancer. These sets of primers must achieve high coverage of the region of interest, while avoiding primer dimers and satisfying the physico-chemical constraints of good PCR primers. We describe a natural formulation of these constraints as a combinatorial optimization problem. We show that the PAMP primer design problem is NP-hard, and design algorithms based on simulated annealing and integer programming, that provide good solutions to this problem in practice. The algorithms are applied to a test region around the known CDKN2A deletion, which show excellent results even in a 1:49 mixture of mutated:wild-type cells. We use these test results to help set design parameters for larger problems. We can achieve near-optimal designs for regions close to 1 Mb.


Case management for depression by health care assistants in small primary care practices: a cluster randomized trial.
Case management by health care assistants in small primary care practices provides unclear benefit for improving depression symptoms. To determine whether case management provided by health care assistants in small primary care practices is more effective than usual care in improving depression symptoms and process of care for patients with major depression. Cluster randomized, controlled trial. A central automated system generated the randomization scheme, which was stratified by urban and rural practices; allocation sequence was concealed until groups were assigned. 74 small primary care practices in Germany from April 2005 to September 2007. 626 patients age 18 to 80 years with major depression. Structured telephone interview to monitor depression symptoms and support for adherence to medication, with feedback to the family physician. Depression symptoms at 12 months, as measured by the Patient Health Questionnaire-9 (PHQ-9); secondary outcomes were patient assessment of chronic illness care, adherence to medication, and quality of life. A total of 310 patients were randomly assigned to case management and 316 to usual care. At 12 months, 249 intervention recipients and 278 control patients were assessed; 555 patients were included in a modified intention-to-treat-analysis (267 intervention recipients vs. 288 control patients). Compared with control patients, intervention recipients had lower mean PHQ-9 values in depression symptoms (-1.41 [95% CI, -2.49 to -0.33]; P = 0.014), more favorable assessments of care (3.41 vs. 3.11; P = 0.011), and increased treatment adherence (2.70 vs. 2.53; P = 0.042). Quality-of-life scores did not differ between groups. Patients, health care assistants, family physicians, and researchers were not blinded to group assignment, and 12-month follow-up of patients was incomplete. Case management provided by primary care practice-based health care assistants may reduce depression symptoms and improve process of care for patients with major depression more than usual care. German Ministry of Education and Research.


Psy2 targets the PP4 family phosphatase Pph3 to dephosphorylate Mth1 and repress glucose transporter gene expression.
The reversible nature of protein phosphorylation dictates that any protein kinase activity must be counteracted by protein phosphatase activity. How phosphatases target specific phosphoprotein substrates and reverse the action of kinases, however, is poorly understood in a biological context. We address this question by elucidating a novel function of the conserved PP4 family phosphatase Pph3-Psy2, the yeast counterpart of the mammalian PP4c-R3 complex, in the glucose-signaling pathway. Our studies show that Pph3-Psy2 specifically targets the glucose signal transducer protein Mth1 via direct binding of the EVH1 domain of the Psy2 regulatory subunit to the polyproline motif of Mth1. This activity is required for the timely dephosphorylation of the downstream transcriptional repressor Rgt1 upon glucose withdrawal, a critical event in the repression of HXT genes, which encode glucose transporters. Pph3-Psy2 dephosphorylates Mth1, an Rgt1 associated corepressor, but does not dephosphorylate Rgt1 at sites associated with inactivation, in vitro. We show that Pph3-Psy2 phosphatase antagonizes Mth1 phosphorylation by protein kinase A (PKA), the major protein kinase activated in response to glucose, in vitro and regulates Mth1 function via putative PKA phosphorylation sites in vivo. We conclude that the Pph3-Psy2 phosphatase modulates Mth1 activity to facilitate precise regulation of HXT gene expression by glucose.


Population Structure and Diversity in European Honey Bees (Apismellifera L.)-An Empirical Comparison of Pool and Individual Whole-Genome Sequencing.
Whole-genome sequencing has become routine for population genetic studies. Sequencing of individuals provides maximal data but is rather expensive and fewer samples can be studied. In contrast, sequencing a pool of samples (pool-seq) can provide sufficient data, while presenting less of an economic challenge. Few studies have compared the two approaches to infer population genetic structure and diversity in real datasets. Here, we apply individual sequencing (ind-seq) and pool-seq to the study of Western honey bees (Apis mellifera). We collected honey bee workers that belonged to 14 populations, including 13 subspecies, totaling 1347 colonies, who were individually (139 individuals) and pool-sequenced (14 pools). We compared allele frequencies, genetic diversity estimates, and population structure as inferred by the two approaches. Pool-seq and ind-seq revealed near identical population structure and genetic diversities, albeit at different costs. While pool-seq provides genome-wide polymorphism data at considerably lower costs, ind-seq can provide additional information, including the identification of population substructures, hybridization, or individual outliers. If costs are not the limiting factor, we recommend using ind-seq, as population genetic structure can be inferred similarly well, with the advantage gained from individual genetic information. Not least, it also significantly reduces the effort required for the collection of numerous samples and their further processing in the laboratory.


DNA copy number aberrations in small-cell lung cancer reveal activation of the focal adhesion pathway.
Small-cell lung cancer (SCLC) is the most aggressive subtype of lung cancer in its clinical behavior, with a 5-year overall survival as low as 5%. Despite years of research in the field, molecular determinants of SCLC behavior are still poorly understood, and this deficiency has translated into an absence of specific diagnostics and targeted therapeutics. We hypothesized that tumor DNA copy number alterations would allow the identification of molecular pathways involved in SCLC progression. Array comparative genomic hybridization was performed on DNA extracted from 46 formalin-fixed paraffin-embedded SCLC tissue specimens. Genomic profiling of tumor and sex-matched control DNA allowed the identification of 70 regions of copy number gain and 55 regions of copy number loss. Using molecular pathway analysis, we found a strong enrichment in these regions of copy number alterations for 11 genes associated with the focal adhesion pathway. We verified these findings at the genomic, gene expression and protein level. Focal Adhesion Kinase (FAK), one of the central genes represented in this pathway, was commonly expressed in SCLC tumors and constitutively phosphorylated in SCLC cell lines. Those were poorly adherent to most substrates but not to laminin-322. Inhibition of FAK phosphorylation at Tyr(397) by a small-molecule inhibitor, PF-573,228, induced a dose-dependent decrease of adhesion and an increase of spreading in SCLC cell lines on laminin-322. Cells that tended to spread also showed a decrease in focal adhesions, as demonstrated by a decreased vinculin expression. These results support the concept that pathway analysis of genes in regions of copy number alterations may uncover molecular mechanisms of disease progression and demonstrate a new role of FAK and associated adhesion pathways in SCLC. Further investigations of FAK at the functional level may lead to a better understanding of SCLC progression and may have therapeutic implications.


Narrative citizenship, resilience and inclusion with dementia: On the inside or on the outside of physical and social places.
There has been little research that addresses the importance of place in enabling resilience and citizenship - most to date focussing on these as a characteristic of the individual. This paper reports on findings from a qualitative study that aimed to explore the everyday experiences of living with dementia within rural and semi-urban communities. Data collection included a sequence of four research diaries and interviews with 13 families living at home with dementia and interviews with service providers and commissioners (a total of 57 diaries, 69 interviews with people living with dementia and 6 interviews with service providers and commissioners). Key themes identified included: Others Knowing and Responding; Socially Withdrawing and Feeling Excluded; Sustaining and Changing Activities; Belonging and Estrangement from Place; Engaging Services and Supports. The study found that familiarity with people and place can be supportive, and these factors support a narrative citizenship in which people can tell a story of inclusion and feeling on the inside. However, this familiarity with place may also create a social barrier and a sense of estrangement, or being on the outside. Narrative citizenship allows us to explore how people with dementia position themselves in relation to others and in so doing, negotiate their own and other's understandings of dementia. It also allows for people to tell stories about themselves in relation to their sense of belonging in a social and physical place, which augment the personal and political approaches to citizenship and thus offers an approach that enhances individualised yet collective understandings of living with dementia.


The Possible Importance of β3 Integrins for Leukemogenesis and Chemoresistance in Acute Myeloid Leukemia.
Acute myeloid leukemia (AML) is an aggressive bone marrow malignancy where the immature leukemia cells communicate with neighboring cells through constitutive cytokine release and through their cell surface adhesion molecules. The primary AML cells express various integrins. These heterodimeric molecules containing an α and a β chain are cell surface molecules that bind extracellular matrix molecules, cell surface molecules and soluble mediators. The β3 integrin (ITGB3) chain can form heterodimers only with the two α chains αIIb and αV. These integrins are among the most promiscuous and bind to a large number of ligands, including extracellular matrix molecules, cell surface molecules and soluble mediators. Recent studies suggest that the two β3 integrins are important for leukemogenesis and chemosensitivity in human AML. Firstly, αIIb and β3 are both important for adhesion of AML cells to vitronectin and fibronectin. Secondly, β3 is important for the development of murine AML and also for the homing and maintenance of the proliferation for xenografted primary human AML cells, and for maintaining a stem cell transcriptional program. These last effects seem to be mediated through Syk kinase. The β3 expression seems to be regulated by HomeboxA9 (HoxA9) and HoxA10, and the increased β3 expression then activates spleen tyrosine kinase (Syk) and thereby contributes to cytokine hypersensitivity and activation of β2 integrins. Finally, high integrin αV/β3 expression is associated with an adverse prognosis in AML and decreased sensitivity to the kinase inhibitor sorafenib; this integrin can also be essential for osteopontin-induced sorafenib resistance in AML. In the present article, we review the experimental and clinical evidence for a role of β3 integrins for leukemogenesis and chemosensitivity in AML.


Modeling of IK1 mutations in human left ventricular myocytes and tissue.
Elucidation of the cellular basis of arrhythmias in ion channelopathy disorders is complicated by the inherent difficulties in studying human cardiac tissue. Thus we used a computer modeling approach to study the mechanisms of cellular dysfunction induced by mutations in inward rectifier potassium channel (K(ir))2.1 that cause Andersen-Tawil syndrome (ATS). ATS is an autosomal dominant disorder associated with ventricular arrhythmias that uncommonly degenerate into the lethal arrhythmia torsade de pointes. We simulated the cellular and tissue effects of a potent disease-causing mutation D71V K(ir)2.1 with mathematical models of human ventricular myocytes and a bidomain model of transmural conduction. The D71V K(ir)2.1 mutation caused significant action potential duration prolongation in subendocardial, midmyocardial, and subepicardial myocytes but did not significantly increase transmural dispersion of repolarization. Simulations of the D71V mutation at shorter cycle lengths induced stable action potential alternans in midmyocardial, but not subendocardial or subepicardial cells. The action potential alternans was manifested as an abbreviated QRS complex in the transmural ECG, the result of action potential propagation failure in the midmyocardial tissue. In addition, our simulations of D71V mutation recapitulate several key ECG features of ATS, including QT prolongation, T-wave flattening, and QRS widening. Thus our modeling approach faithfully recapitulates several features of ATS and provides a mechanistic explanation for the low frequency of torsade de pointes arrhythmia in ATS.


Interventional treatment for symptomatic acute-subacute portal and superior mesenteric vein thrombosis.
To summarize our methods and experience with interventional treatment for symptomatic acute-subacute portal vein and superior mesenteric vein thrombosis (PV-SMV) thrombosis. Forty-six patients (30 males, 16 females, aged 17-68 years) with symptomatic acute-subacute portal and superior mesenteric vein thrombosis were accurately diagnosed with Doppler ultrasound scans, computed tomography and magnetic resonance imaging. They were treated with interventional therapy, including direct thrombolysis (26 cases through a transjugular intrahepatic portosystemic shunt; 6 through percutaneous transhepatic portal vein cannulation) and indirect thrombolysis (10 through the femoral artery to superior mesenteric artery catheterization; 4 through the radial artery to superior mesenteric artery catheterization). The blood reperfusion of PV-SMV was achieved completely or partially in 34 patients 3-13 d after thrombolysis. In 11 patients there was no PV-SMV blood reperfusion but the number of collateral vessels increased significantly. Symptoms in these 45 patients were improved dramatically without severe operational complications. In 1 patient, the thrombi did not respond to the interventional treatment and resulted in intestinal necrosis, which required surgical treatment. In 3 patients with interventional treatment, thrombi re-formed 1, 3 and 4 mo after treatment. In these 3 patients, indirect PV-SMV thrombolysis was performed again and was successful. Interventional treatment, including direct or indirect PV-SMV thrombolysis, is a safe and effective method for patients with symptomatic acute-subacute PV-SMV thrombosis.


Neuroanatomical differences in toddler boys with fragile x syndrome and idiopathic autism.
Autism is an etiologically heterogeneous neurodevelopmental disorder for which there is no known unifying etiology or pathogenesis. Many conditions of atypical development can lead to autism, including fragile X syndrome (FXS), which is presently the most common known single-gene cause of autism. To examine whole-brain morphometric patterns that discriminate young boys with FXS from those with idiopathic autism (iAUT) as well as control participants. Cross-sectional, in vivo neuroimaging study. Academic medical centers. Young boys (n = 165; aged 1.57-4.15 years) diagnosed as having FXS or iAUT as well as typically developing and idiopathic developmentally delayed controls. Univariate voxel-based morphometric analyses, voxel-based morphometric multivariate pattern classification (linear support vector machine), and clustering analyses (self-organizing map). We found that frontal and temporal gray and white matter regions often implicated in social cognition, including the medial prefrontal cortex, orbitofrontal cortex, superior temporal region, temporal pole, amygdala, insula, and dorsal cingulum, were aberrant in FXS and iAUT as compared with controls. However, these differences were in opposite directions for FXS and iAUT relative to controls; in general, greater volume was seen in iAUT compared with controls, who in turn had greater volume than FXS. Multivariate analysis showed that the overall pattern of brain structure in iAUT generally resembled that of the controls more than FXS, both with and without AUT. Our findings demonstrate that FXS and iAUT are associated with distinct neuroanatomical patterns, further underscoring the neurobiological heterogeneity of iAUT.


Cardiac MRI improves cardiovascular risk stratification in hazardous occupations.
The benefit of cardiovascular magnetic resonance Imaging (CMR) in assessing occupational risk is unknown. Pilots undergo frequent medical assessment for occult disease, which threatens incapacitation or distraction during flight. ECG and examination anomalies often lead to lengthy restriction, pending full investigation. CMR provides a sensitive, specific assessment of cardiac anatomy, tissue characterisation, perfusion defects and myocardial viability. We sought to determine if CMR, when added to standard care, would alter occupational outcome. A retrospective review was conducted of all personnel attending the RAF Aviation Medicine Consultation Service (AMCS) for assessment of a cardiac anomaly, over a 2-year period. Those undergoing standard of care (history, examination, exercise ECG, 24 h-Holter and transthoracic echocardiography), and those undergoing a CMR in addition, were identified. The influence of CMR upon the final decision regarding flying restriction was determined by comparing the diagnosis reached with standard of care plus CMR vs. standard of care alone. Of the ~ 8000 UK military aircrew, 558 personnel were seen for cardiovascular assessment. Fifty-two underwent CMR. A normal TTE did not reliably exclude abnormalities subsequently detected by CMR. Addition of CMR resulted in an upgraded occupational status in 62% of those investigated, with 37% returning to unrestricted duties. Only 8% of referrals were undiagnosed following CMR. All these were cases of borderline chamber dilatation and reduction in systolic function in whom diagnostic uncertainty remained between physiological exercise adaptation and early cardiomyopathy. CMR increases the likelihood of a definitive diagnosis and of return to flying. This study supports early use of CMR in occupational assessment for high-hazard occupations.


Intermittent screening and treatment versus intermittent preventive treatment of malaria in pregnancy: user acceptability.
Malaria in pregnancy is associated with increased risks of maternal and foetal complications. Currently, intermittent preventive treatment (IPT) of malaria during pregnancy with sulphadoxine-pyrimethamine (SP) is recommended by the WHO as part of a package of interventions also including insecticide-treated nets and effective case management. However, with increasing resistance to SP, the effectiveness of SP-IPT has been questioned. A randomized controlled trial (RCT) to investigate the relative efficacy of an alternative strategy of intermittent screening and treatment (IST), which involves a rapid diagnostic test for malaria at scheduled ANC visits and treatment of women only if positive, versus SP-IPT has been conducted in Ashanti region, Ghana. This paper reports on a complementary study investigating the acceptability of the different strategies to women enrolled in the trial. Data were collected through twelve focus group discussions with women selected at random from the different arms of the RCT, exploring their experiences and perceptions about antenatal care and their involvement in the trial. Content analysis was used to identify relevant themes to structure the results. Five main themes emerged from participants' experiences of ANC and the RCT that would influence their acceptability of malaria prevention strategies during pregnancy: health benefits; drugs received; tests received; other services received; and health worker attitude. Their own health and that of their baby were strong motivations for attending ANC, and reported favourably as an outcome of being in the RCT. Women were not always clear on the biomedical function of drugs or blood tests but generally accepted them due to strong trust in the health staff. Home visits by staff and free ITNs as part of the trial were appreciated. Politeness and patience of health staff was a very strong positive factor. Overall, both intermittent screening and treatment and intermittent preventive treatment appeared equally acceptable to pregnant women as strategies for the control of malaria in pregnancy. The women were more concerned about quality of services received, in particular the polite and patient attitude of health staff, and positive health implications for themselves and their babies than about the nature of the intervention.


Differential expression of arid5b isoforms in Xenopus laevis pronephros.
Arid5b belongs to the ARID family of transcription factors characterised by a helix-turn-helix motif- based DNA-binding domain called ARID (A-T Rich Interaction Domain). In human, alternative splicing leads to long and short isoforms (isoform1 and 2, respectively) which differ in their N-terminal part. In this study, we report the cloning and expression pattern of Xenopus laevis arid5b. We have isolated a full length cDNA that shows homology with the human arid5b isoform1. Furthermore, 5'RACE experiments revealed the presence of a shorter isoform equivalent to the human isoform2. Temporal expression analysis by RT-qPCR indicated that X. laevis arid5b isoform1 and isoform2 are differentially expressed during development. Isoform1 is strongly expressed maternally, while isoform2 expression is essentially restricted to tailbud stages. Spatial expression analysis by whole mount in situ showed that arid5b is predominantly expressed in the developing pronephros. Arid5b mRNAs are detected in the antero-dorsal part of the pronephros anlage at the early tailbud stage and later on, in the proximal part of the pronephric tubule. RT-qPCR analyses with primers that allow to discriminate isoform1 from isoform2 showed that the latter is enriched in the pronephros anlage. In agreement with a specific pronephric signature of the isoform2, we also observed that isoform2 but not isoform1 is upregulated in animal caps induced to form pronephric tissue in response to activin A and retinoic acid. These results indicate that the two arid5b isoforms are differentially expressed and likely play different roles during early Xenopus development.


Decreased visual attention further from the perceived direction of gaze for equidistant retinal targets.
The oculomotor and spatial attention systems are interconnected. Whereas a link between motor commands and spatial shifts in visual attention is demonstrated, it is still unknown whether the recently discovered proprioceptive signal in somatosensory cortex impacts on visual attention, too. This study investigated whether visual targets near the perceived direction of gaze are detected more accurately than targets further away, despite the equal eccentricity of their retinal projections. We dissociated real and perceived eye position using left somatosensory repetitive transcranial magnetic stimulation (rTMS), which decreases cortical processing of eye muscle proprioceptive inflow and produces an underestimation of the rotation of the right eye. Participants detected near-threshold visual targets presented in the left or right visual hemifield at equal distance from fixation. We have previously shown that when the right eye is rotated to the left of the parasagittal plane, TMS produces an underestimation of this rotation, shifting perceived eye position to the right. Here we found that, in this condition, TMS also decreased target detection in the left visual hemifield and increased it in the right. This effect depended on the direction of rotation of the right eye. When the right eye was rotated rightward and TMS, we assume, shifted perceived gaze direction in opposite direction, leftward, visual accuracy decreased now in the right hemifield. We suggest that the proprioceptive eye position signal modulates the spatial distribution of visual processing resources, producing "pseudo-neglect" for objects located far relative to near the perceived direction of gaze.


Effects of dietary cellobiose on the intestinal microbiota and excretion of nitrogen metabolites in healthy adult dogs.
In order to evaluate the potential prebiotic effects of cellobiose, 10 healthy adult research beagle dogs received a complete diet containing 0, 0.5 and 1 g cellobiose/kg bodyweight (BW)/day. At the end of each feeding period, faeces, urine and blood of the dogs were collected. The results demonstrated a significant increase of faecal lactate concentrations, indicating a bacterial fermentation of cellobiose in the canine intestine. Along with this, a dose-dependent linear increase of the relative abundance of Lactobacillaceae in the faeces of the dogs was observed (p = 0.014). In addition, a dose-dependent increase (p < 0.05) of Alloprevotella, Bacteroides and Prevotella, and a linear decrease for unidentified Lachnospiraceae (p = 0.011) was observed when cellobiose was added to the diet, although the relative abundance of these genera was low (<1%) among all groups. The faecal pH was not affected by dietary cellobiose. Cellobiose seemed to modulate the excretion of nitrogen metabolites, as lower concentrations of phenol (p = 0.034) and 4-ethylphenol (p = 0.002) in the plasma of the dogs were measured during the supplementation periods. Urinary phenols and indoles, however, were not affected by the dietary supplementation of cellobiose. In conclusion, cellobiose seems to be fermented by the intestinal microbiota of dogs. Although no effect on the faecal pH was detected, the observed increase of microbial lactate production might lower the pH in the large intestine and consecutively modulate the intestinal absorption of nitrogen metabolites. Also, the observed changes of some bacterial genera might have been mediated by increased intestinal lactate concentrations or a higher relative abundance of lactobacilli. Whether these results could be considered as a prebiotic effect and used as a dietetic strategy in diseased animals to improve gut function or hepatic and renal nitrogen metabolism should be evaluated in future studies.


Computationally generated cardiac biomarkers for risk stratification after acute coronary syndrome.
The existing tools for estimating the risk of death in patients after they experience acute coronary syndrome are commonly based on echocardiography and clinical risk scores (for example, the TIMI risk score). These identify a small group of high-risk patients who account for only a minority of the deaths that occur in patients after acute coronary syndrome. Here, we investigated the use of three computationally generated cardiac biomarkers for risk stratification in this population: morphologic variability (MV), symbolic mismatch (SM), and heart rate motifs (HRM). We derived these biomarkers from time-series analyses of continuous electrocardiographic data collected from patients in the TIMI-DISPERSE2 clinical trial through machine learning and data mining methods designed to extract information that is difficult to visualize directly in these data. We evaluated these biomarkers in a blinded, prespecified, and fully automated study on more than 4500 patients in the MERLIN-TIMI36 (Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 36) clinical trial. Our results showed a strong association between all three computationally generated cardiac biomarkers and cardiovascular death in the MERLIN-TIMI36 trial over a 2-year period after acute coronary syndrome. Moreover, the information in each of these biomarkers was independent of the information in the others and independent of the information provided by existing clinical risk scores, electrocardiographic metrics, and echocardiography. The addition of MV, SM, and HRM to existing metrics significantly improved model discrimination, as well as the precision and recall of prediction rules based on left ventricular ejection fraction. These biomarkers can be extracted from data that are routinely captured from patients with acute coronary syndrome and will allow for more accurate risk stratification and potentially for better patient treatment.


Does knee alignment influence gait in patients with severe knee osteoarthritis?
Patients with knee osteoarthritis present an altered gait pattern. Amongst many factors, the lower limb alignment (varus, valgus) has been identified as an important risk factor for the progression of knee osteoarthritis. Among the large number of studies on knee osteoarthritis gait, only a few have included patients with a valgus deformity. The aims of this study were to determine how knee alignment influences full-body gait in patients with knee osteoarthritis and if knee malalignment is associated with pain and functional capacity. Sixty patients with severe knee osteoarthritis scheduled for a total knee arthroplasty were included in this study. Twenty-six subjects were recruited as the control group. The spatio-temporal parameters, three-dimensional full-body kinematics, and lower body kinetics were evaluated during a comfortable gait and compared between the groups. Pain and function were assessed with the WOMAC questionnaire. The full-body gait analysis demonstrated substantially different gait patterns and compensation mechanisms between the three groups. Patients with varus knee alignment significantly augmented their trunk movements in sagittal and frontal planes compared to patients with a valgus knee. In addition, patients with a valgus knee reported lower pain and lower functional deficits compared to patients with a varus knee. We found that gait compensations were significantly influenced by lower limb alignment. These new insights related to different knee osteoarthritis gait patterns might help in the understanding of gait compensation behaviours prior to total knee arthroplasty and better manage the strategies of rehabilitation following surgery.


Quantification of amyloid PET for future clinical use: a state-of-the-art review.
Amyloid-β (Aβ) pathology is one of the earliest detectable brain changes in Alzheimer's disease (AD) pathogenesis. The overall load and spatial distribution of brain Aβ can be determined in vivo using positron emission tomography (PET), for which three fluorine-18 labelled radiotracers have been approved for clinical use. In clinical practice, trained readers will categorise scans as either Aβ positive or negative, based on visual inspection. Diagnostic decisions are often based on these reads and patient selection for clinical trials is increasingly guided by amyloid status. However, tracer deposition in the grey matter as a function of amyloid load is an inherently continuous process, which is not sufficiently appreciated through binary cut-offs alone. State-of-the-art methods for amyloid PET quantification can generate tracer-independent measures of Aβ burden. Recent research has shown the ability of these quantitative measures to highlight pathological changes at the earliest stages of the AD continuum and generate more sensitive thresholds, as well as improving diagnostic confidence around established binary cut-offs. With the recent FDA approval of aducanumab and more candidate drugs on the horizon, early identification of amyloid burden using quantitative measures is critical for enrolling appropriate subjects to help establish the optimal window for therapeutic intervention and secondary prevention. In addition, quantitative amyloid measurements are used for treatment response monitoring in clinical trials. In clinical settings, large multi-centre studies have shown that amyloid PET results change both diagnosis and patient management and that quantification can accurately predict rates of cognitive decline. Whether these changes in management reflect an improvement in clinical outcomes is yet to be determined and further validation work is required to establish the utility of quantification for supporting treatment endpoint decisions. In this state-of-the-art review, several tools and measures available for amyloid PET quantification are summarised and discussed. Use of these methods is growing both clinically and in the research domain. Concurrently, there is a duty of care to the wider dementia community to increase visibility and understanding of these methods.


Casein kinase 1 regulates human hypoxia-inducible factor HIF-1.
Hypoxia-inducible factor 1 (HIF-1), a transcriptional activator that mediates cellular response to hypoxia and a promising target of anticancer therapy, is essential for adaptation to low oxygen conditions, embryogenesis and tumor progression. HIF-1 is a heterodimer of HIF-1alpha, expression of which is controlled by oxygen levels as well as by various oxygen-independent mechanisms, and HIF-1beta (or ARNT), which is constitutively expressed. In this work, we investigate the phosphorylation of the N-terminal heterodimerization (PAS) domain of HIF-1alpha and identify Ser247 as a major site of in vitro modification by casein kinase 1delta (CK1delta). Mutation of this site to alanine, surprisingly, enhanced the transcriptional activity of HIF-1alpha, a result phenocopied by inhibition or small interfering RNA (siRNA)-mediated silencing of CK1delta under hypoxic conditions. Conversely, overexpression of CK1delta or phosphomimetic mutation of Ser247 to aspartate inhibited HIF-1alpha activity without affecting its stability or nuclear accumulation. Immunoprecipitation and in vitro binding experiments suggest that CK1-dependent phosphorylation of HIF-1alpha at Ser247 impairs its association with ARNT, a notion also supported by modeling the structure of the complex between HIF-1alpha and ARNT PAS-B domains. We suggest that modification of HIF-1alpha by CK1 represents a novel mechanism that controls the activity of HIF-1 during hypoxia by regulating the interaction between its two subunits.


FOXL2 and SOX9 as parameters of female and male gonadal differentiation in patients with various forms of disorders of sex development (DSD).
The transcription factors SOX9 and FOXL2 are required for male and female mammalian gonadal development. We have used specific antibodies to investigate the role of these key proteins in disorders of sex development (DSD), specifically inter-sex states. In normal gonads, SOX9 was found to be restricted to the presence of (pre-)Sertoli cells, while FOXL2 was found in granulosa cells, and in stromal cells interpreted as early ovarian stroma. Both proteins were found within a single patient, when testicular and ovarian development was present; and within the same gonad, when both differentiation lineages were identified, as in ovotesticular DSD (ie hermaphrodite). Especially SOX9 was informative to support the presence of early testicular development (ie seminiferous tubules), expected based on morphological criteria only. In a limited number of DSD cases, FOXL2 was found within reasonably well-developed seminiferous tubules, but double staining demonstrated that it was never strongly co-expressed with SOX9 in the same cell. All seminiferous tubules containing carcinoma in situ (CIS), the malignant counterpart of a primordial germ cell, ie the precursor of type II germ cell tumours of the testis, seminomas and non-seminomas, showed the presence of SOX9 and not FOXL2. In contrast, gonadoblastomas (GBs), the precursor of the same type of cancer, in a dysgenetic gonad, showed expression of FOXL2 and no, or only very low, SOX9 expression. These findings indicate that gonadal differentiation, ie testicular or ovarian, determines the morphology of the precursor of type II germ cell tumours, CIS or GB, respectively. We show that in DSD patients, the formation of either ovarian or/and testicular development can be visualized using FOXL2 and SOX9 expression, respectively. In addition, it initiates a novel way to study the role of the supportive cells in the development of either CIS or GB.


Knowledge of Chlamydia trachomatis infection in genitourinary medicine clinic attenders.
To determine the level of awareness of genital chlamydial infection, and level of knowledge related to this infection, in genitourinary medicine (GUM) clinic attenders. 500 consecutive patients attending a GUM clinic for the first time during a 3 month study period were invited to complete an anonymous self administered questionnaire on aspects of chlamydial infection. 482 (96.4%) questionnaires were available for analysis (57% female). 289 (60%) respondents had heard of Chlamydia trachomatis compared with 472 (98%) for thrush, 467 (97%) for HIV/AIDS, and 434 (90%) for gonorrhoea. Subjective knowledge of chlamydia, relative to the other infections, was poor. Overall, the mean chlamydial knowledge score was 0.38 (range 0.0-1.0). Females scored significantly higher than males (0.45 v 0.26; p < 0.00001) and younger females scored significantly higher than older females (p = 0.001). More females had experienced genital chlamydial infection than males (22.4% v 12.1%, p = 0.004). Those with prior exposure to C trachomatis had higher mean knowledge scores than those without (males 0.55 v 0.25, p < 0.00001; females 0.68 v 0.37, p < 0.00001). Even for a population considered as "high risk" by their attendance at a GUM clinic, there was poor awareness of genital chlamydial infection, and mean knowledge scores were low. Whether increased knowledge was due to successful health education at the time of diagnosis in those with previous infection remains to be determined. In the future, one would hope for increased knowledge scores in those at risk before the acquisition of infection, which may be achieved by national health education programmes for C trachomatis.


Kinetic Detection of Orthogonal Protein and Chemical Coordinates in Enzyme Catalysis: Double Mutants of Soybean Lipoxygenase.
Soybean lipoxygenase-1 (SLO-1) is a paradigmatic enzyme system for studying the contribution of hydrogen tunneling to enzymatic proton-coupled electron transfer processes. In this study, the impact of pairs of double mutants on the properties of SLO-1 is presented. Steady-state rates and their deuterium kinetic isotope effects (KIEs) have been measured for the bimolecular reaction of enzyme with free substrate (kcat/Km) and compared to the unimolecular rate constant, kcat. A key kinetic finding is that the competitive KIEs on the second-order rate constant (kcat/Km) are all reduced from (D)kcat and, despite large changes in rate and activation parameters, remain essentially unaltered under a variety of conditions. These data implicate a protein reaction coordinate that is orthogonal to the chemical reaction coordinate and controls the concentration of the active enzyme. This study introduces a new means to interrogate the alteration of conformational landscapes that can occur following site-specific mutagenesis.


Comparison of transfusion efficacy of amotosalen-based pathogen-reduced platelet components and gamma-irradiated platelet components.
Trials of transfusions of platelets (PLTs) treated with amotosalen-based pathogen reduction (PR) showed lower corrected count increments (CCIs) compared to conventional PLT components (PCs). However, PR-PLTs and conventional PCs often differed in various factors besides PR. We compared transfusion efficacy of single-donor apheresis PCs treated with PR or gamma irradiation. Hematologic patients were assigned to receive PR-PLTs or gamma-irradiated conventional PCs, both prepared in PLT additive solution (PAS). One-hour CCI (primary endpoint), 24-hour CCI, time to next PLT transfusion, and transfusion requirement of red blood cells and plasma were analyzed. Forty-four patients assigned to PR-PLTs received 220 PR-PLTs and 136 conventional PCs; 72 controls received 517 conventional PCs. No differences between patient groups were observed for mean (±standard deviation [SD]) 1-hour CCI (11.4 [±4.9] for PR-PLT vs. 11.0 [±4.9] for controls), mean (±SD) 24-hour CCI (6.1 [±4.4] for PR-PLTs vs. 6.2 [±4.8] for controls), and for the other evaluated outcomes. No differences between PC types were observed for mean (±SD) 1-hour CCI (10.6 [±6.7] for PR-PLTs vs. 9.9 [±6.2] for conventional PCs) and mean 24 hour-CCI (3.3 [±3.9] for PR-PLTs vs. 4.2 [±5] for conventional PCs). Thirty-five percent of PR-PLTs and 38% of conventional PCs (p = 0.63) were associated with 1-hour CCIs of less than 7.5. Inadequate 24-hour CCIs were observed for 72% of PR-PLTs and 64% of conventional PCs (p = 0.002). Transfusion efficacy of single-donor apheresis PCs in PAS treated with amotosalen PR versus gamma irradiation is comparable.


Using honey to heal a chronic wound in a patient with epidermolysis bullosa.
This case study details the healing of a chronic wound (20 years' duration) in a patient with dystrophic epidermolysis bullosa (EB). Many different dressings and creams had been used, and on occasions the wound began to heal but never progressed to closure. A honey impregnated dressing was used and the wound healed in 15 weeks. A brief overview of the dystrophic form of EB is given and some evidence for the efficacy of honey is presented.


Self-reported perceptions and knowledge of telemedicine in medical students and professionals who enrolled in an online course in Peru.
Telemedicine has become more relevant during the COVID-19 pandemic. However, medical students and professionals do not acquire competences in telemedicine during their training. Our objective was to describe the self-reported perception and baseline knowledge of telemedicine among medical students and professionals enrolled in a virtual course. Cross-sectional study that included physicians or medical students aged 18 years or older who were interested in a free virtual telemedicine course and who completed the data collection questionnaire. We used a Likert scale to assess the self-reported perceptions of four domains related to telemedicine. The participants were grouped into three levels for each domain: low, medium and high. We also objectively assessed telemedicine knowledge by means of 10 questions, with a cut-off point of 50% of correct answers. The Fisher's exact test, the Chi-square test, and the Mann-Whitney U test were used for the comparison of categorical data. A p-value < 0.05 was considered statistically significant. We included 161 participants: 118 medical students and 43 physicians. We observed no significant differences between medical students and physicians in self-reported perceptions of knowledge, security, or utility of telemedicine. However, students had a high self-reported perception of the disadvantages of telemedicine especially related to patient security (p = 0.018), efficiency of care (p = 0.040), and the possibility of medical malpractice (p = 0.010) compared to physicians. Nearly half of the students (n = 53,44.9%) and physicians (n = 22,51.7%) answered 50% or more of the questions related to telemedicine knowledge correctly. Among the physicians and medical students enrolled in the course, the students perceived the disadvantages of telemedicine more frequently. Although physicians and students have limited knowledge of telemedicine, there appears to be no influence of experience and prior training in telemedicine.


Equity in access to total joint replacement of the hip and knee in England: cross sectional study.
To explore geographical and sociodemographic factors associated with variation in equity in access to total hip and knee replacement surgery. Combining small area estimates of need and provision to explore equity in access to care. English census wards. Patients throughout England who needed total hip or knee replacement and numbers who received surgery. Predicted rates of need (derived from the Somerset and Avon Survey of Health and English Longitudinal Study of Ageing) and provision (derived from the hospital episode statistics database). Equity rate ratios comparing rates of provision relative to need by sociodemographic, hospital, and distance variables. For both operations there was an "n" shaped curve by age. Compared with people aged 50-59, those aged 60-84 got more provision relative to need, while those aged >or=85 received less total hip replacement (adjusted rate ratio 0.68, 95% confidence interval 0.65 to 0.72) and less total knee replacement (0.87, 0.82 to 0.93). Compared with women, men received more provision relative to need for total hip replacement (1.08, 1.05 to 1.10) and total knee replacement (1.31, 1.28 to 1.34). Compared with the least deprived, residents in the most deprived areas got less provision relative to need for total hip replacement (0.31, 0.30 to 0.33) and total knee replacement (0.33, 0.31 to 0.34). For total knee replacement, those in urban areas got higher provision relative to need, but for total hip replacement it was highest in villages/isolated areas. For total knee replacement, patients living in non-white areas received more provision relative to need (1.04, 1.00 to 1.07) than those in predominantly white areas, but for total hip replacement there was no effect. Adjustment for hospital characteristics did not attenuate the effects. There is evidence of inequity in access to total hip and total knee replacement surgery by age, sex, deprivation, rurality, and ethnicity. Adjustment for hospital and distance did not attenuate these effects. Policy makers should examine factors at the level of patients or primary care to understand the determinants of inequitable provision.


Cough Frequency During Treatment Associated With Baseline Cavitary Volume and Proximity to the Airway in Pulmonary TB.
Cough frequency, and its duration, is a biomarker that can be used in low-resource settings without the need of laboratory culture and has been associated with transmission and treatment response. Radiologic characteristics associated with increased cough frequency may be important in understanding transmission. The relationship between cough frequency and cavitary lung disease has not been studied. We analyzed data in 41 adults who were HIV negative and had culture-confirmed, drug-susceptible pulmonary TB throughout treatment. Cough recordings were based on the Cayetano Cough Monitor, and sputum samples were evaluated using microscopic observation drug susceptibility broth culture; among culture-positive samples, bacillary burden was assessed by means of time to positivity. CT scans were analyzed by a US-board-certified radiologist and a computer-automated algorithm. The algorithm evaluated cavity volume and cavitary proximity to the airway. CT scans were obtained within 1 month of treatment initiation. We compared small cavities (≤ 7 mL) and large cavities (> 7 mL) and cavities located closer to (≤ 10 mm) and farther from (> 10 mm) the airway to cough frequency and cough cessation until treatment day 60. Cough frequency during treatment was twofold higher in participants with large cavity volumes (rate ratio [RR], 1.98; P = .01) and cavities located closer to the airway (RR, 2.44; P = .001). Comparably, cough ceased three times faster in participants with smaller cavities (adjusted hazard ratio [HR], 2.89; P = .06) and those farther from the airway (adjusted HR, 3.61;, P = .02). Similar results were found for bacillary burden and culture conversion during treatment. Cough frequency during treatment is greater and lasts longer in patients with larger cavities, especially those closer to the airway.


Gastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia.
Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.


Factors associated with pastoral community knowledge and occurrence of mycobacterial infections in human-animal interface areas of Nakasongola and Mubende districts, Uganda.
Nontuberculous mycobacteria (NTM) are emerging opportunistic pathogens whose role in human and animal disease is increasingly being recognized. Major concerns are their role as opportunistic pathogens in HIV/AIDS infections. The role of open natural water sources as source and livestock/wildlife as reservoirs of infections to man are well documented. This presents a health challenge to the pastoral systems in Africa that rely mostly on open natural water sources to meet livestock and human needs. Recent study in the pastoral areas of Uganda showed infections with same genotypes of NTM in pastoralists and their livestock. The aim of this study was to determine the environmental, animal husbandry and socio-demographic factors associated with occurrence and the pastoral community knowledge of mycobacterial infections at the human-environment-livestock/wildlife interface (HELI) areas in pastoral ecosystems of Uganda. Two hundred and fifty three (253) individuals were subjected to a questionnaire survey across the study districts of Nakasongola and Mubende. Data were analyzed using descriptive statistics and multivariable logistic regression analysis. Humans sharing of the water sources with wild animals from the forest compared to savannah ecosystem (OR = 3.3), the tribe of herding pastoral community (OR = 7.9), number of rooms present in household (3-5 vs. 1-2 rooms) (OR = 3.3) were the socio-demographic factors that influenced the level of knowledge on mycobacterial infections among the pastoral communities. Tribe (OR = 6.4), use of spring vs. stream water for domestic use (OR = 4.5), presence of sediments in household water receptacle (OR = 2.32), non separation of water containers for drinking and domestic use (OR = 2.46), sharing of drinking water sources with wild animals (OR = 2.1), duration of involvement of >5 yrs in cattle keeping (OR = 3.7) and distance of household to animal night shelters (>20 meters) (OR = 3.8) were significant socio-demographic factors associated with the risk of occurrence of mycobacterioses among the pastoral communities in Uganda. The socio-demographic, environmental and household related factors influence the risk of occurrence as well as pastoralists' knowledge of mycobacterial infections in the pastoral households at the human-environment-livestock/wildlife pastoral interface areas of Uganda.


Deriving trends in life expectancy by the National Statistics Socioeconomic Classification using the ONS Longitudinal Study.
Health inequalities among socio-economic groups are well documented. One of the measures used to track inequalities over time is the series 'Trends in life expectancy by social class, 1972-2005', on the Office for National Statistics website. In 2001 the National Statistics Socio-economic Classification (NS-SEC), replaced Registrar General's social class (RGSC) for the purposes of official statistics. This paper describes the challenges involved in producing an analogous series of trends in life expectancy by NS-SEC to that by RGSC, the approach adopted, and publishes the first results of the new series. NS-SEC was devised in the 1990s and introduced in 2001. Like RGSC, it is an occupation-based measure. In order to produce a series of trends over more than 20 years based on NS-SEC, it is necessary to classify people according to NS-SEC based on their occupation at the 1981 and 1991 Censuses and then to measure subsequent mortality rates for different classes. The 1981 Census preceded the construction of the NS-SEC classification system by nearly 20 years, and there was no recognised way of classifying 1981 Census respondents by NS-SEC. This paper describes how an approximation to allow such a classification was derived. The ONS Longitudinal Study was used to provide the data from which mortality and survival rates by NS-SEC class could then be estimated. The results are presented in terms of life expectancy at birth and at age 65 by five-year calendar periods, from 1982-86 to 2002-06. A social gradient was found using NS-SEC, similar to the one found using RGSC. For most classes for all periods studied, life expectancy improved for both males and females but inequalities persisted between classes. There was a difference of around six years for males between the most and least advantaged classes in expectation of life at birth and about four years for females in the period 2002-06. The estimates suggested a widening of inequalities over the study period for men, which appeared to end after 2001. For women, no overall trend could be detected, but there were no signs of any narrowing of the gap in the most recent period. NS-SEC can be used to provide medium-term trends in life expectancy by occupation based class, which will be capable of extension over time, although certain approximations are necessary. It is important that work should continue on investigating other means of classification, particularly for women, for example based on educational attainment and on household rather than individual-based measures.List of Tables, 12.


Markers of anthropogenic contamination: A validated method for quantification of pharmaceuticals, illicit drug metabolites, perfluorinated compounds, and plasticisers in sewage treatment effluent and rain runoff.
An effective, specific and accurate method is presented for the quantification of 13 markers of anthropogenic contaminants in water using solid phase extraction (SPE) followed by high performance liquid chromatography (HPLC) tandem mass spectrometry (MS/MS). Validation was conducted according to the International Conference on Harmonisation (ICH) guidelines. Method recoveries ranged from 77 to 114% and limits of quantification between 0.75 and 4.91 ng/L. A study was undertaken to quantify the concentrations and loadings of the selected contaminants in 6 sewage treatment works (STW) effluent discharges as well as concentrations in 5 rain-driven street runoffs and field drainages. Detection frequencies in STW effluent ranged from 25% (ethinylestradiol) to 100% (benzoylecgonine, bisphenol-A (BPA), bisphenol-S (BPS) and diclofenac). Average concentrations of detected compounds in STW effluents ranged from 3.62 ng/L (ethinylestradiol) to 210 ng/L (BPA). Levels of perfluorinated compounds (PFCs) perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) as well as the plasticiser BPA were found in street runoff at maximum levels of 1160 ng/L, 647 ng/L and 2405 ng/L respectively (8.52, 3.09 and 2.7 times more concentrated than maximum levels in STW effluents respectively). Rain-driven street runoff may have an effect on levels of PFCs and plasticisers in receiving rivers and should be further investigated. Together, this method with the 13 selected contaminants enables the quantification of various markers of anthropogenic pollutants: inter alia pharmaceuticals, illicit drugs and their metabolites from humans and improper disposal of drugs, while the plasticisers and perfluorinated compounds may also indicate contamination from industrial and transport activity (street runoff).


Liver-specific deletion of insulin receptor substrate 2 does not impair hepatic glucose and lipid metabolism in mice.
Hepatic insulin resistance is thought to be a critical component in the pathogenesis of type 2 diabetes but the role of intrinsic insulin signalling pathways in the regulation of hepatic metabolism remains controversial. Global gene targeting in mice and in vitro studies have suggested that IRS2 mediates the physiological effects of insulin in the liver. Reduced hepatic production of IRS2 is found in many cases of insulin resistance. To investigate the role of IRS2 in regulating liver function in vivo, we generated mice that specifically lack Irs2 in the liver (LivIrs2KO). Hepatic insulin signalling events were examined in LivIrs2KO mice by western blotting. Glucose homeostasis and insulin sensitivity were assessed by glucose tolerance tests and hyperinsulinaemic-euglycaemic clamp studies. The effects of high-fat feeding upon glucose homeostasis were also determined. Liver function tests were performed and expression of key metabolic genes in the liver was determined by RT-PCR. Proximal insulin signalling events and forkhead box O1 and A2 function were normal in the liver of LivIrs2KO mice, which displayed minimal abnormalities in glucose and lipid homeostasis, hepatic gene expression and liver function. In addition, hepatic lipid homeostasis and the metabolic response to a high-fat diet did not differ between LivIrs2KO and control mice. Our findings suggest that liver IRS2 signalling, surprisingly, is not required for the long-term maintenance of glucose and lipid homeostasis, and that extra-hepatic IRS2-dependent mechanisms are involved in the regulation of these processes.


Illness representation, coping and outcome in irritable bowel syndrome (IBS).
OBJECTIVE: Irritable bowel syndrome has no observable symptom markers and there is little that the medical profession can do to help sufferers. Psychotherapy, antidepressants and drugs aimed at the most problematic symptoms have been shown to have limited efficacy. In an attempt to help understand the illness better, and to suggest alternative forms of intervention, the study tested whether outcome might be influenced by patients' representation of their illness and by their coping strategies. METHOD: All members of the IBS Network (an independent charitable support network based in the UK) were invited to participate via their quarterly newsletter, and 209 completed questionnaires were returned. Participants completed the Illness Perception Questionnaire (IPQ), the COPE, and the Hospital Anxiety and Depression Scale (HADS), and rated their quality of life and their satisfaction with their health. RESULTS: The reporting of serious consequences was associated with lower quality of life and lower satisfaction with health, and with higher scores for anxiety and depression (p <.001). Weaker control beliefs were related to lower quality of life, lower satisfaction with health, and higher depression scores (p <.01). Lower illness scores were associated with more satisfaction with health (p <.01), but not with quality of life (p >.05). Psychological causal attribution of IBS was positively correlated with anxiety (p <.001) and depression (p <.01). Path analyses based on multiple linear regression demonstrated that (1) the reporting of serious consequences was a strong independent predictor of outcome; (2) coping mediated the link between representation and outcome; and (3) when predicting depression, coping strategies predicted coping independently of representation dimensions. CONCLUSIONS: The findings indicate that the illness representations of IBS sufferers can have significant implications for outcome. Therapeutic interventions based on illness representations may prove useful for treatment.


The MTHFR 677C>T polymorphism is associated with unmetabolized folic acid in breast milk in a cohort of Canadian women.
Maternal nutrition and genetics are determinants of breast-milk nutrient composition and, as such, are determinants of the nutritional exposure of breastfed infants. The aim of this study was to determine whether common maternal single nucleotide polymorphisms (SNPs) in folate-dependent enzymes are associated with breast-milk folate content in a cohort of mothers enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) study. The MIREC study is a Canadian prospective pregnancy cohort study that recruited 2001 participants between 2008 and 2011. Five folate-related SNPs-MTHFR 677C>T (rs1801133), MTHFR 1298A>C (rs1801131), MTHFR 1793G>A (rs2274976), MTR 2756A>G (rs1805087), and MTRR 66A>G (rs1801394)-were genotyped. Breast milk was sampled ∼1 mo postpartum, and tetrahydrofolate (THF), 5-methyl-THF, 5-formyl-THF, 5,10-methenyl-THF, and unmetabolized folic acid (UMFA) were measured using liquid chromatography-tandem mass spectrometry in a subset of participants (n = 551). Associations were assessed using Wald's test. Associations were considered significant if P ≤ 0.01 (Bonferroni correction for multiple testing). None of the SNPs were associated with total breast-milk folate. However, the MTHFR 677C>T SNP was associated with breast-milk UMFA (R2 = 0.01; unadjusted P = 0.004), explaining a small portion of total variance; this association remained significant when adjusted for other covariates, including supplemental folic acid consumption. The MTHFR 1793G>A and MTRR 66A>G SNPs tended to be associated with 5-methyl-THF (R2 = 0.008, P = 0.04) and reduced folates (THF + 5-methyl-THF + 5-formyl-THF + 5,10-methenyl-THF; R2 = 0.01, P = 0.02), respectively. We found that total breast-milk folate content was not associated with any of the folate-related SNPs examined. The association between the MTHFR 677C>T SNP and breast-milk UMFA, albeit modest, highlights the need to better understand the determinants of breast-milk folate and the impact they might have on milk folate bioavailability.


Weathering the storm: parental effort and experimental manipulation of stress hormones predict brood survival.
Unpredictable and inclement weather is increasing in strength and frequency, challenging organisms to respond adaptively. One way in which animals respond to environmental challenges is through the secretion of glucocorticoid stress hormones. These hormones mobilize energy stores and suppress non-essential physiological and behavioral processes until the challenge passes. To investigate the effects of glucocorticoids on reproductive decisions, we experimentally increased corticosterone levels (the primary glucocorticoid in birds) in free-living female tree swallows, Tachycineta bicolor, during the chick-rearing stage. Due to an unprecedented cold and wet breeding season, 90 % of the nests in our study population failed, which created a unique opportunity to test how challenging environmental conditions interact with the physiological mechanisms underlying life-history trade-offs. We found that exogenous corticosterone influenced the regulation of parental decisions in a context-dependent manner. Control and corticosterone-treated females had similar brood failure rates under unfavorable conditions (cold and rainy weather), but corticosterone treatment hastened brood mortality under more favorable conditions. Higher female nest provisioning rates prior to implantation were associated with increased probability of brood survival for treatment and control groups. However, higher pre-treatment male provisioning rates were associated with increased survival probability in the control group, but not the corticosterone-treated group. These findings reveal complex interactions between weather, female physiological state, and partner parental investment. Our results also demonstrate a causal relationship between corticosterone concentrations and individual reproductive behaviors, and point to a mechanism for why naturally disturbed populations, which experience multiple stressors, could be more susceptible and unable to respond adaptively to changing environmental conditions.


Role of the central cations in the mechanical unfolding of DNA and RNA G-quadruplexes.
Cations are known to mediate diverse interactions in nucleic acids duplexes but they are critical in the arrangement of four-stranded structures. Here, we use all-atom molecular dynamics simulations with explicit solvent to analyse the mechanical unfolding of representative intramolecular G-quadruplex structures: a parallel, a hybrid and an antiparallel DNA and a parallel RNA, in the presence of stabilising cations. We confirm the stability of these conformations in the presence of [Formula: see text] central ions and observe distortions from the tetrad topology in their absence. Force-induced unfolding dynamics is then investigated. We show that the unfolding events in the force-extension curves are concomitant to the loss of coordination between the central ions and the guanines of the G-quadruplex. We found lower ruptures forces for the parallel configuration with respect to the antiparallel one, while the behaviour of the force pattern of the parallel RNA appears similar to the parallel DNA. We anticipate that our results will be essential to interpret the fine structure rupture profiles in stretching assays at high resolution and will shed light on the mechanochemical activity of G-quadruplex-binding machinery.


The experiences of underrepresented minority faculty in schools of medicine.
Faculty of color in schools of medicine play an essential role in addressing health disparities, increasing diversity in healthcare, and improving health professions education. Yet inadequate progress has been made in increasing the numbers of faculty of color in medical schools. The reasons for this gap, and ways to address it, are poorly understood. We conducted a grounded theory study of 25 of faculty from groups historically underrepresented in academic medicine at 17 schools in the United States. Faculty were interviewed in person (n=4, 16%) and by telephone (n=21, 84%). We identified two processes that contribute to a greater understanding of the experiences of faculty of color: patterns of exclusion and control, and surviving and thriving. We also identified one outcome - faculty of color having influence. Strong support from leaders, mentors, and peers to nurture and protect faculty of color in schools of medicine is needed to counteract the negative effects of racism and to promote the positive effects this group has on diversity and excellence in medical education. Specific strategies for survival and success are described.


Biogenesis of membrane-bound and secreted immunoglobulins. I. Two distinct translation products of human mu-chain, with identical N-termini and different C-termini.
Structural differences between the heavy chain of membrane-bound IgM (mu m) and the heavy chain of secreted IgM (mu s) were investigated. The primary translation products of the mu-chain, free of posttranslational modifications, were synthesized in a wheat-germ cell-free system, programmed with messenger RNA derived from human lymphoblastoid cell lines positive for both membrane-bound and secreted IgM. Encoded in this sytem were two mu-chains, which shared N-terminal signal peptides and which differed both in molecular weight and in C-terminal amino acid sequence. In vivo pulse labeling of cells confirmed that, as intermediates in the rough endoplasmic reticulum, these two forms expressed the same idiotype and maintained their difference in molecular weight and in C-terminal sequence. By correlation with pulse-chase kinetics and with immunofluorescence, one form of mu-chain represents mu m, and the other, mu s. Because the molecular weight difference between the two is manifest at the level of their primary translation products, these studies demonstrate that mu m is distinguished from mu s by a difference in primary structure, at least in part at the C-terminus.


Testosterone and dihydrotestosterone differentially improve cognition in aged female mice.
Compared with age-matched male mice, female mice experience a more severe age-related cognitive decline (ACD). Since androgens are less abundant in aged female mice compared with aged male mice, androgen supplementation may enhance cognition in aged female mice. To test this, we assessed behavioral performance on a variety of tasks in 22- to 24-mo-old gonadally intact female mice treated for 6 wk with silastic capsules containing either testosterone (T) or dihydrotestosterone (DHT) or empty capsules (placebo). Compared with placebo-treated mice, spatial memory retention in the water maze was enhanced by testosterone treatment, but not DHT treatment. In contrast, DHT treatment improved passive avoidance (PA) retention, while T treatment only did so marginally. These data support that androgen supplementation in old female mice improves cognitive performance differentially depending upon the type of hormone treatment and cognitive task.


Improved clinical management but not patient outcome in women with postpartum haemorrhage-An observational study of practical obstetric team training.
Postpartum haemorrhage (PPH) is the most common obstetric emergency. A well-established postpartum haemorrhage protocol in the labour ward is crucial for effective treatment. The aim of the study was to investigate if practical obstetric team training improves the patient outcome and clinical management of PPH. The practical obstetric team training (PROBE) at Linköping University Hospital, Sweden, with approximate 3000 deliveries annually, was studied between the years of 2004-2011. Each team consisted of one or two midwives, one obstetrician or one junior doctor and one nurse assistant. Emergency obstetrics cases were trained in a simulation setting. PROBE was scheduled during work hours at an interval of 1.5 years. Pre-PROBE women (N = 419 were defined as all women with vaginal birth between the years of 2004-2007 with an estimated blood loss of ≥1000 ml within the first 24 hours of delivery. Post-PROBE women (N = 483) were defined as all women with vaginal birth between the years of 2008-2011 with an estimated blood loss of ≥1000 ml within the first 24 hours of delivery. The two groups were compared regarding blood loss parameters and management variables using retrospective data from medical records. No difference was observed in estimated blood loss, haemoglobin level, blood transfusions or the incidence of postpartum haemorrhage between the two groups. Post-PROBE women had more often secured venous access (p<0.001), monitoring of vital signs (p<0.001) and received fluid resuscitation (p<0.001) compared to pre-PROBE women. The use of uterine massage was also more common among the post-PROBE women compared with the pre-PROBE women (p<0.001). PROBE improved clinical management but not patient outcome in women with postpartum haemorrhage in the labour ward. These new findings may have clinical implications since they confirm that training was effective concerning the management of postpartum haemorrhage. However, there is still no clear evidence that simulation training improve patient outcome in women with PPH.


[Increased infections by herpes simplex virus type 1 and polymicrobials of the genital tract, in the general population of a Spanish middle city].
Infections by genitopathogens are a frequent reason for consultation in Primary Health Care and in the specialties of Infectious Diseases, Urology, Gynecology, and Dermatology. The most common causes are opportunistic microorganisms and responsible for sexually transmitted infections associated with unprotected sex. The objective is to determine the microorganisms that cause these infections in patients treated at the Hospital Universitario Virgen de las Nieves in Granada and Neisseria gonorrhoeae susceptibility to antibiotics. A transversal-descriptive and retrospective study was carried out, which included the results issued, between January 2018 and December 2019, in the Microbiology Laboratory from all the episodes studied using standardized working procedures. The most frequently detected microorganisms were Gardnerella vaginalis (23.81%) followed by Candida spp. (20.9%), especially in females, and N. gonorrhoeae (11.36%) and Ureaplasma urealyticum (11.99%), in males. Many times, they were presented in combination. Regarding herpes simplex viruses, infection by both species had a similar prevalence (50%) in males, while type 1 was more prevalent (76.52%) in females. The most active antibiotics against N. gonorrhoeae were cefotaxime (98%) and cefixime (100%). Tetracycline (39.02%) a poorly active antibiotic. The most frequent pathogens corresponded to those that usually caused infections in females, although N. gonorrhoeae was the most frequent in males and mixed infections are not an accidental finding. HSV-1 infections were more frequent than HSV-2, confirming the trend of a change in the epidemiology of genital herpes.


Effect of starter feeding program on growth performance and gains of body components from weaning to market weight in swine.
Three experiments were conducted to test the hypothesis that different starter feeding programs (High, high quality; Low, low quality) will affect growth performance and body composition of pigs from weaning to market weight and that this effect may be influenced by gender (barrows or gilts) and breed (F, Yorkshire-Duroc x Hampshire; P, PIC Camborough 15 x PIC line 405). In Exp. 1, 21 +/- 4-d-weaned F pigs (n = 90) were used in a 2 (High or Low) x 2 (barrows or gilts) factorial design. In Exp. 2, 21 +/- 3-d-weaned pigs (n = 184) were used in a 2 (F or P) x 2 (High or Low) x 2 (barrows or gilts) factorial design. In Exp. 3, 21 F pigs from each gender and feeding program treatment were killed at d 0, 3, 7, 14, 42, 82, or 152 postweaning for evaluating body composition. Two starter feeding programs (High or Low) were applied to pigs for 6 wk postweaning. Pigs from both High and Low treatments were provided the same corn-soybean meal-based diets for the growing and finishing periods. Although the ADG of all pigs receiving the High treatment during the early starter period were higher (P < .01) than those of the Low, the terminal BW of F barrows were similar between High and Low (Exp. 1 and 2) and those of gilts were similar between High and Low (Exp. 2) (P > .80). However, the BW of P pigs receiving the High treatment, regardless of gender, tended to be heavier than those receiving the Low (Exp. 2) and F barrows receiving the High treatment tended to be heavier than those receiving the Low (Exp. 1). For the first 7 d postweaning, the High-fed pigs gained more protein (P < .05) and lost less fat (P < .05) than Low-fed pigs. During the growing-finishing period, the Low-fed pigs exhibited compensatory protein gain and achieved a body protein content similar (P < .60) to High-fed pigs by termination. Protein gains from weaning to termination between High- and Low-fed pigs were not different in Exp. 2 and 3. The protein gain of gilts was higher (P < .05) than that of barrows. Similarly, fat gain within genders was not affected by starter feeding program. Fat gain of gilts, however, was lower (P < .08) than that of barrows in Exp. 3. In conclusion, the nutritional quality of the starter feeding program affected growth performance immediately after weaning but did not affect protein gain over the entire production period.


The Planet's Stressed River Basins: Too Much Pressure or Too Little Adaptive Capacity?
Freshwater is one of the most critical elements for sustainable development of ecosystems and societies. River basins, concomitant with administrative zones, form a common unit for freshwater management. So far, no comprehensive, global analysis exists that would link the ecological challenges of the planet's river basins to the capacity of the societies to cope with them. We address this gap by performing a geospatial resilience analysis for a global set of 541 river basins. We use the social-ecological systems approach by relating three ecological vulnerability factors (human footprint, natural hazards, and water scarcity) with three adaptive capacity factors (governance, economy, and human development), based on temporal trajectories from 1990 to 2015. Additionally, we examine resilience by subtracting ecological vulnerability from adaptive capacity. The most striking result is the fundamentally different patterns of controlling factors of the resilience in different developing regions, particularly those of Africa and Asia. Their root causes are particularly low adaptive capacity in Africa and high ecological vulnerability in Asia. Alarmingly, the difference between those continents grew within the study period. Finally, this study highlights the rapid dynamics of adaptive capacity in comparison to ecological vulnerability, the latter having more inertia. Their fragile balance is of our interest; they can either support or counteract each other depending on the geographic location.


Demographic and Occupational Risk Factors Associated With Suicide-Related Aeromedical Evacuation Among Deployed U.S. Military Service Members.
Suicide is a significant problem in the U.S. military, with rates surpassing the U.S. general population as of 2008. Although there have been significant advances regarding suicide risk factors among U.S. military service members and veterans, there is little research about risk factors associated with suicide that could be potentially identified in theater. One salient study group consists of service members who receive a psychiatric aeromedical evacuation out of theater. The primary aims of this study were as follows: (1) determine the incidence of suicide-related aeromedical evacuation in deployed service members, (2) identify demographic and military characteristics associated with suicide-related aeromedical evacuation, and (3) evaluate the relationship between suicide-related aeromedical evacuation from a deployed setting and military separation. This was an archival analysis of U.S. Transportation Command Regulating and Command and Control Evacuation System and Defense Manpower Data Center electronic records of U.S. military service members (N = 7023) who were deployed to Iraq or Afghanistan and received a psychiatric aeromedical evacuation out of theater between 2001 and 2013. χ2 tests of independence and standardized residuals were used to identify cells with observed frequencies and proportions, respectively, that significantly differed from what would be expected by chance. In addition, odds ratios were calculated to provide context about the nature of any significant relationships. For every 1000 psychiatric aeromedical evacuations that occurred between 2001 and 2013, 34.4 were suicide related. Gender, ethnicity, branch of service, occupation classification, and deployment theater were associated with suicide-related aeromedical evacuation (odds ratios ranged from 1.37 to 3.02). Overall, 53% of all service members who received an aeromedical evacuation for any psychiatric condition had been separated from the military for a variety of reasons (both voluntary and involuntary) upon record review in 2015. Suicide-related aeromedical evacuation was associated with a 37% increased risk of military separation compared to evacuation for another psychiatric condition (P < 0.02). Findings provide novel information on risk factors associated with suicide-related aeromedical evacuation as well as military separation following a suicide-related aeromedical evacuation. In many cases, the psychiatric aeromedical evacuation of a service member for suicidal ideations and their subsequent separation from active duty is in the best interest of the individual and the military. However, the evacuation and eventual military separation can be costly for the military and the service member. Consequently, the military should focus on indicated prevention interventions for individuals who show sufficient early signs of crisis and functional problems so that specialized interventions can be used in theater to prevent evacuation. Indicated prevention interventions should start with leaders' awareness and mitigation of risk and, when feasible, evidence-based interventions for suicide risk provided by behavioral health (eg, brief cognitive behavioral therapy for suicide). Future research should evaluate the feasibility, safety, and efficacy of delivering suicide-related interventions in theater.


The Effects of Limiting Instructions about Emotional Evidence Depend on Need for Cognition.
Although limiting instructions are provided for specific evidence that may have a negative impact on jurors' decision-making, there may be individual differences in the effectiveness of the instructions. The individual predisposition towards the enjoyment of cognitive activity is called need for cognition (NFC), and individuals high in NFC tend to seek out and engage in cognitive activity spontaneously. The present study examined the influence of NFC and limiting instructions about emotional evidence on mock jurors' legal decision-making. The results showed that mock jurors who were lower in NFC were more likely to render a guilty decision than those higher in NFC, and that the tendency was more salient when the limiting instructions were presented compared with when they were not presented. Similar results were found in regard to sentencing decisions and arousal of anger. A partial mediation effect of anger was found between NFC and verdict decisions. The influence of NFC on the limiting instructions and legal decision-making as well as the effect of anger on the decision is discussed in relation to these results.


Polarization-independent dual-band perfect absorber utilizing multiple magnetic resonances.
We propose a dual-band metamaterial perfect absorber at microwave frequencies. Using a planar metamaterial, which consists of periodic metallic donut-shape meta-atoms at the front separated from the metallic plane at the back by a dielectric layer, we demonstrate the multi-plasmonic high-frequency perfect absorptions induced by the third-harmonic as well as the fundamental magnetic resonances. The origin of the induced multi-plasmonic perfect absorption was elucidated. It was also found that the perfect absorptions at dual peaks are persistent with varying polarization.


Nanoporous molybdenum carbide wires as an active electrocatalyst towards the oxygen reduction reaction.
A non-precious metal electrocatalyst has been developed for the oxygen reduction reaction based on nanoporous molybdenum carbide (nano-Mo2C) wires through a facile calcination of sub-nanometer periodic organic-inorganic hybrid nanowires. The highly dispersed Mo2C wires were composed of 10-15 nm nanocrystals with a mesopore size of 3.3 nm. The properties of nano-Mo2C wires were characterized using scanning electron microscopy, transmission electron microscopy, X-ray diffraction and N2 adsorption/desorption porosimetry. The highly active surface area and enriched nanoporosity for nano-Mo2C wires are unique features that make them a high-performance electrocatalyst for oxygen reduction in an alkaline medium. The electrocatalysis and reaction kinetics results show that nano-Mo2C-based materials can be developed as new catalysts with high activity at low cost for electrochemical energy conversion applications.


Comparison of Platelet Rich Plasma and Prolotherapy in the Management of Osteochondral Lesions of the Talus: A Retrospective Cohort Study.
BACKGROUND Osteochondral lesions of talus (OLT) are among the most common ankle problems. Platelet-rich plasma (PRP) and prolotherapy (PrT) are 2 successful injection-based techniques for treatment of chronic musculoskeletal problems. The aim of the present study was to compare PRP and PrT injections for the management of OLT. MATERIAL AND METHODS This was a retrospective cohort study of 49 patients with OLT symptoms of more than 6 months who had been refractory to 3 months of treatment using conservative methods. The patients were divided into 2 groups: PrT injections (PrT group, n=27) or PRP injections (PRP group, n=22). The patients were given 3 injections of 4 mL solution into periarticular and intra-articular ankle joint spaces. After treatment, patients were evaluated via Visual Analogue Scale (VAS), American Orthopedic Foot and Ankle Society Score (AOFAS), and Ankle Osteoarthritis Scale (AOS) at baseline and 21-, 90-, 180-, and 360-day follow-up periods. RESULTS Both PRP and PrT treatments resulted in greater improvement in pain and ankle functions at follow-up periods extending to 1 year (P<0.001) and there was no difference between the groups for the outcomes at follow-up periods (P>0.05). Excellent or good outcomes were reported by 88.8% of the patients in PrT group and 90.9% of the patients in PRP group. CONCLUSIONS Both PRP and PrT are efficient and safe methods in treatment of OLT. PrT offers advantages of less cost and minimal invasiveness.