Associations of Meat and Fish Consumption With Conventional and Radiomics Cardiovascular Magnetic Resonance Phenotypes in the UK Biobank.
Background: Greater red and processed meat consumption has been linked to adverse cardiovascular outcomes. However, the impact of these exposures on cardiovascular magnetic resonance (CMR) phenotypes has not been adequately studied. Objective: We describe novel associations of meat intake with cardiovascular phenotypes and investigate underlying mechanisms through consideration of a range of covariates. Design: We studied 19,408 UK Biobank participants with CMR data available. Average daily red and processed meat consumption was determined through food frequency questionnaires and expressed as a continuous variable. Oily fish was studied as a comparator, previously associated with favourable cardiac outcomes. We considered associations with conventional CMR indices (ventricular volumes, ejection fraction, stroke volume, left ventricular mass), novel CMR radiomics features (shape, first-order, texture), and arterial compliance measures (arterial stiffness index, aortic distensibility). We used multivariable linear regression to investigate relationships between meat intake and cardiovascular phenotypes, adjusting for confounders (age, sex, deprivation, educational level, smoking, alcohol intake, exercise) and potential covariates on the causal pathway (hypertension, hypercholesterolaemia, diabetes, body mass index). Results: Greater red and processed meat consumption was associated with an unhealthy pattern of biventricular remodelling, worse cardiac function, and poorer arterial compliance. In contrast, greater oily fish consumption was associated with a healthier cardiovascular phenotype and better arterial compliance. There was partial attenuation of associations between red meat and conventional CMR indices with addition of covariates potentially on the causal pathway, indicating a possible mechanistic role for these cardiometabolic morbidities. However, other associations were not altered with inclusion of these covariates, suggesting importance of alternative biological mechanisms underlying these relationships. Radiomics analysis provided deeper phenotyping, demonstrating association of the different dietary habits with distinct ventricular geometry and left ventricular myocardial texture patterns. Conclusions: Greater red and processed meat consumption is associated with impaired cardiovascular health, both in terms of markers of arterial disease and of cardiac structure and function. Cardiometabolic morbidities appeared to have a mechanistic role in the associations of red meat with ventricular phenotypes, but less so for other associations suggesting importance of alternative mechanism for these relationships.


STAT5-glucocorticoid receptor interaction and MTF-1 regulate the expression of ZnT2 (Slc30a2) in pancreatic acinar cells.
The exocrine pancreas plays an important role in endogenous zinc loss by regulating excretion into the intestinal tract and hence influences the dietary zinc requirement. The present experiments show that the zinc transporter ZnT2 (Slc30a2) is localized to the zymogen granules and that dietary zinc restriction in mice decreased the zinc concentration of zymogen granules and ZnT2 expression. Excess zinc given orally increased ZnT2 expression and was associated with increased pancreatic zinc accumulation. Rat AR42J acinar cells when induced into a secretory phenotype, using the glucocorticoid analog dexamethasone (DEX), exhibited increased ZnT2 expression and labile zinc as measured with a fluorophore. DEX administrated to mice also induced ZnT2 expression that accompanied a reduction of the pancreatic zinc content. ZnT2 promoter analyses identified elements required for responsiveness to zinc and DEX. Zinc regulation was traced to a MRE located downstream from the ZnT2 transcription start site. Responsiveness to DEX is produced by two upstream STAT5 binding sites that require the glucocorticoid receptor for activation. ZnT2 knockdown in the AR42J cells using siRNA resulted in increased cytoplasmic zinc and decreased zymogen granule zinc that further demonstrated that ZnT2 may mediate the sequestration of zinc into zymogen granules. We conclude, based upon experiments with intact mice and pancreatic acinar cells in culture, that ZnT2 participates in zinc transport into pancreatic zymogen granules through a glucocorticoid pathway requiring glucocorticoid receptor and STAT5, and zinc-regulated signaling pathways requiring MTF-1. The ZnT2 transporter appears to function in a physiologically responsive manner involving entero-pancreatic zinc trafficking.


A High Serum Level of Taurocholic Acid Is Correlated With the Severity and Resolution of Drug-induced Liver Injury.
Alterations in the serum levels of bile acids are associated with drug-induced liver injury (DILI). We investigated the association between serum levels of bile acids and the severity and outcome of DILI, along with the potential role of variants in the ATP binding cassette subfamily B member 11 (ABCB11) gene and expression of its product, ABCB11 (also called BSEP). We performed this prospective study of 95 patients (median age, 53 years; 73.7% female) with DILI from August 2018 through August 2019. Patients were matched for age, gender, and body mass index with healthy individuals (n = 100; healthy controls) and patients with chronic hepatitis B (n = 105; CHB controls). We collected demographic and biochemical data at baseline and 1 week, 1 month, 3 months, and 6 months after DILI onset and at the time of biochemical recovery, liver failure or liver transplantation. Serum levels of bile acids were measured using high-performance liquid-chromatography tandem mass-spectrometry. All 27 exons of ABCB11 were sequenced and expression of BSEP was analyzed by immunohistochemistry in liver biopsy specimens. Levels of 30 of the 37 bile acids analyzed differed significantly between patients with DILI and healthy controls. Changes in levels of taurocholic acid (TCA), glycocholic acid, taurochenodeoxycholate, and glycochenodeoxycholate associated with the increased levels of bilirubin and greater severity of DILI, and were also associated with CHB. Cox regression analysis showed that only change in the levels of TCA independently associated with biochemical resolution of DILI. Combination of TCA level (≥ 1955.41 nmol/L), patient age, and DILI severity was associated with abnormal blood biochemistry at 6 months after DILI onset (area under the curve, 0.81; 95% confidence interval, 0.71-0.88; sensitivity, 0.69; specificity, 0.81). ABCB11 missense variants were not associated with differences in the serum bile acid profiles, DILI severity, or clinical resolution. However, lower levels of BSEP in bile canaliculi in liver biopsies were associated with altered serum levels of bile acids. In this prospective study performed in Chinese patients, we found that the serum levels of TCA were associated with the severity and clinical resolution of DILI. Reduced protein expression of BSEP in liver tissue, rather than variants of the ABCB11 gene were associated with altered serum levels of bile acids.


A Diffusion Tensor Imaging Study in Children With ADHD, Autism Spectrum Disorder, OCD, and Matched Controls: Distinct and Non-Distinct White Matter Disruption and Dimensional Brain-Behavior Relationships.
Neurodevelopmental disorders (NDDs) (attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) share genetic vulnerability and symptom domains. The authors present direct comparison of structural brain circuitry in children and adolescents with NDDs and control subjects and examine brain circuit-behavior relationships across NDDs using dimensional measures related to each disorder. Diffusion imaging and behavioral measures were acquired in 200 children and adolescents (ADHD: N=31; OCD: N=36; ASD: N=71; controls: N=62; mean age range: 10.3-12.6 years). Following Tract-Based Spatial Statistics, multigroup comparison of white matter indices was conducted, followed by pairwise comparisons. Relationships of fractional anisotropy with dimensional measures of inattention, social deficits, obsessive-compulsive symptoms, and general adaptive functioning were conducted across the NDD sample. Lower fractional anisotropy within the splenium of the corpus callosum was found in each NDD group, compared with the control group. Lower fractional anisotropy in additional white matter tracts was found in the ASD and ADHD groups, compared with the control group, but not in the OCD group. Fractional anisotropy was lower in the ASD and ADHD groups compared with the OCD group but was not different in ADHD participants compared with ASD participants. A positive relation between fractional anisotropy (across much of the brain) and general adaptive functioning across NDDs was shown. This study identified disruption in interhemispheric circuitry (i.e., fractional anisotropy alterations in the corpus callosum) as a shared feature of ASD, ADHD, and OCD. However, fractional anisotropy alterations may be more widespread and severe in ASD and ADHD than in OCD. Higher fractional anisotropy throughout the brain appears to be related to better adaptive function across NDDs.


AIDS-associated non-Hodgkin lymphoma.
Non-Hodgkin lymphoma is associated with HIV infection. We investigated the epidemiology and aetiology of AIDS-related non-Hodgkin lymphoma by analysing data from cases reported to the Centers for Disease Control, Atlanta, USA, up to June 30, 1989. During this period 97,258 AIDS cases were reported, of whom 2824 (2.9%) had non-Hodgkin lymphoma. The condition was about 60 times more common in AIDS patients than in the general US population. 1686 cases were immunoblastic lymphoma, 548 primary lymphoma of the brain, and 590 Burkitt's lymphoma, a condition which is not normally associated with immunosuppression. The proportion of AIDS patients with immunoblastic lymphoma increased from 0% in those under 1 year old to 3.5% in those aged 50 or more. Primary lymphoma of the brain was constant at 0.6% for all ages. The frequency of Burkitt's lymphoma increased from zero in infants to a peak at 10-19 years of age (1.8%). Each type of lymphoma was twice as common in whites as in blacks and in men as in women. Lymphoma was most common in patients with haemophilia or clotting disorders and least common in those born in the Caribbean or Africa who had acquired HIV by heterosexual contact. Epidemiological data suggested that whilst infectious agents (eg, Epstein-Barr virus) may be associated with development of non-Hodgkin lymphomas in AIDS patients there was probably no single cause for all the types of lymphoma. Perhaps the most puzzling question is why Burkitt's lymphoma is commonly associated with HIV infection but not with other types of immunosuppression.


The re-emerging burden of rickets: a decade of experience from Sydney.
To define the demographics and clinical characteristics of cases presenting with nutritional rickets to paediatric centres in Sydney, Australia. Retrospective descriptive study of 126 cases seen from 1993 to 2003 with a diagnosis of vitamin D deficiency and/or confirmed rickets defined by long bone x ray changes. A steady increase was seen in the number of cases per year, with a doubling of cases from 2002 to 2003. Median age of presentation was 15.1 months, with 25% presenting at less than 6 months of age. The most common presenting features were hypocalcaemic seizures (33%) and bowed legs (22%). Males presented at a younger age, with a lower weight SDS, and more often with seizures. The caseload was almost exclusively from recently immigrated children or first generation offspring of immigrant parents, with the region of origin predominantly the Indian subcontinent (37%), Africa (33%), and the Middle East (11%). Seventy nine per cent of the cases were born in Australia. Eleven cases (all aged <7 months) presented atypically with hyperphosphataemia. This large case series shows that a significant and increasing caseload of vitamin D deficiency remains, even in a developed country with high sunlight hours. Cases mirror recent immigration trends. Since birth or residence in Australia does not appear to be protective, screening of at risk immigrant families should be implemented through public health policies.


Analytical study of pulse amplification in silicon Raman amplifiers.
The nonlinear process of stimulated Raman scattering is important for silicon photonics as it enables optical amplification and lasing. To understand the dynamics of silicon Raman amplifiers (SRAs), a numerical approach is generally employed, even though it provides little insight into the contribution of different SRA parameters to the signal amplification process. In this paper, we solve the coupled pump-signal equations analytically under realistic conditions, and derive an exact formula for the envelope of a signal pulse when picosecond optical pulses are amplified inside a SRA pumped by a continuous-wave laser beam. Our solution is valid for an arbitrary pulse shape and fully accounts for the Raman gain-dispersion effects, including temporal broadening and group-velocity reduction (a slow-light effect). It can be applied to any pumping scenario and leads to a simple analytic expression for the maximum optical delay produced by the Raman dispersion in a unidirectionally pumped SRA. We employ our analytical formulation to study the evolution of optical pulses with Gaussian, exponential, and Lorentzian shapes. The ability of a Gaussian pulse to maintain its shape through the amplifier makes it possible to realize soliton-like propagation of chirped Gaussian pulses in SRAs. We obtain analytical expressions for the required linear chirp and temporal width of a soliton-like pulse in terms of the net signal gain and the Raman-dispersion parameter. Our results are useful for optimizing the performance of SRAs and for engineering controllable signal delays.


Microbial Functional Capacity Is Preserved Within Engineered Soil Formulations Used In Mine Site Restoration.
Mining of mineral resources produces substantial volumes of crushed rock based wastes that are characterised by poor physical structure and hydrology, unstable geochemistry and potentially toxic chemical conditions. Recycling of these substrates is desirable and can be achieved by blending waste with native soil to form a 'novel substrate' which may be used in future landscape restoration. However, these post-mining substrate based 'soils' are likely to contain significant abiotic constraints for both plant and microbial growth. Effective use of these novel substrates for ecosystem restoration will depend on the efficacy of stored topsoil as a potential microbial inoculum as well as the subsequent generation of key microbial soil functions originally apparent in local pristine sites. Here, using both marker gene and shotgun metagenome sequencing, we show that topsoil storage and the blending of soil and waste substrates to form planting substrates gives rise to variable bacterial and archaeal phylogenetic composition but a high degree of metabolic conservation at the community metagenome level. Our data indicates that whilst low phylogenetic conservation is apparent across substrate blends we observe high functional redundancy in relation to key soil microbial pathways, allowing the potential for functional recovery of key belowground pathways under targeted management.


N-acetylcysteine for the management of anemia and oxidative stress in hemodialysis patients.
To explore the efficacy of oral N-acetylcysteine (NAC) supplementation for anemia and oxidative stress in hemodialysis (HD) patients. Of the eligible patients (n = 325) in an outpatient HD unit, 49 received NAC 200 mg orally thrice a day during the first 3 months, while the other 276 patients not receiving NAC were observed. During the 4-month study, 11 patients receiving NAC withdrew but had no severe adverse effects, while 49 patients not receiving NAC had negative confounding events. Thus only the data of the remaining patients, 38 taking NAC and 227 not taking NAC, were analyzed for efficacy. The demographic and laboratory data of both groups were similar at baseline. When the erythropoietin dosage was stable throughout, only the NAC group had a significant increase in hematocrit, accompanied with a decrease in plasma levels of 8-isoprostane and oxidized low-density lipoprotein. Analyzed as a nested case-control study, NAC supplementation was also found to be a significant predictor of positive outcomes in uremic anemia. Oral NAC supplementation may be a promising therapy for uremic anemia and oxidative stress in HD patients.


Displacement in new economy labor markets: Post-displacement wage loss in high tech versus low tech cities.
While scholars and politicians tout education as the salve to employment disruptions, we argue that the geography of the new economy, and the social closure mechanisms that geography creates, may be just as important as individuals' characteristics for predicting post-displacement wage loss (or gain). We use data from the 2012 Displaced Workers ement of the Current Population Survey and from the 2010 United States Census to test hypotheses linking local labor markets in different industrial contexts to post-displacement wage loss. Our results point to age as a closure mechanism, and to the partially protective effect of education in high-tech versus low-tech economic sectors. This study is the first to use national level data to examine how employment in high-tech cities influences post-displacement wages. These findings are relevant both for theorizing about the new economy and for public policy.


Platelet-rich plasma for articular cartilage repair.
Platelet concentrates have been gaining popularity for a number of applications in orthopedic surgery as a way to enhance both healing of various tissues and reduce pain. One major area of focus has been the effect of platelet-rich plasma (PRP) on stem cells and chondrocytes and the potential for PRP to enhance cartilage regeneration as well as reduce catabolic factors that lead to cartilage degradation. This article provides an up-to-date review of the current literature regarding the effect of PRP on articular cartilage and its use in the treatment of osteoarthritis. Basic science, animal, and human clinical investigations are presented. In general, PRP has been shown to promote chondrogenic differentiation in vitro and lead to enhanced cartilage repair during animal investigations. Human trials, mostly conducted in the form of injection into knees with osteoarthritis, have shown promise in a number of investigations for achieving symptomatic relief of pain and improving function.


Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease characterized by intense and debilitating fatigue not due to physical activity that has persisted for at least 6 months, post-exertional malaise, unrefreshing sleep, and accompanied by a number of secondary symptoms, including sore throat, memory and concentration impairment, headache, and muscle/joint pain. In patients with post-exertional malaise, significant worsening of symptoms occurs following physical exertion and exercise challenge serves as a useful method for identifying biomarkers for exertion intolerance. Evidence suggests that intestinal dysbiosis and systemic responses to gut microorganisms may play a role in the symptomology of ME/CFS. As such, we hypothesized that post-exertion worsening of ME/CFS symptoms could be due to increased bacterial translocation from the intestine into the systemic circulation. To test this hypothesis, we collected symptom reports and blood and stool samples from ten clinically characterized ME/CFS patients and ten matched healthy controls before and 15 minutes, 48 hours, and 72 hours after a maximal exercise challenge. Microbiomes of blood and stool samples were examined. Stool sample microbiomes differed between ME/CFS patients and healthy controls in the abundance of several major bacterial phyla. Following maximal exercise challenge, there was an increase in relative abundance of 6 of the 9 major bacterial phyla/genera in ME/CFS patients from baseline to 72 hours post-exercise compared to only 2 of the 9 phyla/genera in controls (p = 0.005). There was also a significant difference in clearance of specific bacterial phyla from blood following exercise with high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS patients versus clearance in the controls. These results provide evidence for a systemic effect of an altered gut microbiome in ME/CFS patients compared to controls. Upon exercise challenge, there were significant changes in the abundance of major bacterial phyla in the gut in ME/CFS patients not observed in healthy controls. In addition, compared to controls clearance of bacteria from the blood was delayed in ME/CFS patients following exercise. These findings suggest a role for an altered gut microbiome and increased bacterial translocation following exercise in ME/CFS patients that may account for the profound post-exertional malaise experienced by ME/CFS patients.


On the stability and dynamics of stochastic spiking neuron models: Nonlinear Hawkes process and point process GLMs.
Point process generalized linear models (PP-GLMs) provide an important statistical framework for modeling spiking activity in single-neurons and neuronal networks. Stochastic stability is essential when sampling from these models, as done in computational neuroscience to analyze statistical properties of neuronal dynamics and in neuro-engineering to implement closed-loop applications. Here we show, however, that despite passing common goodness-of-fit tests, PP-GLMs estimated from data are often unstable, leading to divergent firing rates. The inclusion of absolute refractory periods is not a satisfactory solution since the activity then typically settles into unphysiological rates. To address these issues, we derive a framework for determining the existence and stability of fixed points of the expected conditional intensity function (CIF) for general PP-GLMs. Specifically, in nonlinear Hawkes PP-GLMs, the CIF is expressed as a function of the previous spike history and exogenous inputs. We use a mean-field quasi-renewal (QR) approximation that decomposes spike history effects into the contribution of the last spike and an average of the CIF over all spike histories prior to the last spike. Fixed points for stationary rates are derived as self-consistent solutions of integral equations. Bifurcation analysis and the number of fixed points predict that the original models can show stable, divergent, and metastable (fragile) dynamics. For fragile models, fluctuations of the single-neuron dynamics predict expected divergence times after which rates approach unphysiologically high values. This metric can be used to estimate the probability of rates to remain physiological for given time periods, e.g., for simulation purposes. We demonstrate the use of the stability framework using simulated single-neuron examples and neurophysiological recordings. Finally, we show how to adapt PP-GLM estimation procedures to guarantee model stability. Overall, our results provide a stability framework for data-driven PP-GLMs and shed new light on the stochastic dynamics of state-of-the-art statistical models of neuronal spiking activity.


Inflammatory bowel disease associated with immune thrombocytopenic purpura in children.
Previous reports suggest an association between inflammatory bowel disease (IBD) and immune thrombocytopenic purpura (ITP) in adults. To date, only five children with both diseases have been described. The aim of the study was to describe the characteristics of children with IBD and ITP. Cases were obtained from the pediatric gastroenterology community by means of the pediatric gastroenterology internet bulletin board in June 1999. Eight cases were submitted from seven medical centers. Medical records were reviewed by two pediatric gastroenterologists and a pediatric hematologist. The age range of the patients was 2.1 to 16.5 years, with a mean age of 9.6 +/- 5.2 years. Four children had ulcerative colitis, three had Crohn disease, and one had indeterminate colitis. All had colonic involvement of IBD. Of eight patients, three had IBD first, three had ITP first, and two had both simultaneously. At ITP diagnosis, platelet count was less than 10,000/mL in five children, 17,000/mL in one child, and 50,000 to 60,000/mL in two children. Of the three children diagnosed with ITP first, two initially had rectal bleeding at the time of ITP diagnosis. Bone marrow evaluations, performed in six of eight children, were consistent with ITP. Six of the eight children had chronic ITP, including three children who were 5 years of age or younger. Therapy for ITP included steroids (n = 6), intravenous immunoglobulin (n = 6), Rh o (D) intravenous immunoglobulin (n = 2), and splenectomy (n = 1). The authors describe the largest pediatric case series of children with IBD and ITP. More than 50% of the children had the chronic form of ITP. Most patients responded to conventional therapy for ITP and IBD.


Current Treatment Patterns Among Postmenopausal Women with HR+/HER2- Metastatic Breast Cancer in US Community Oncology Practices: An Observational Study.
Recent approval of novel agents has changed the treatment landscape for post menopausal women with hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) metastatic breast cancer (mBC). The objective of this study was to describe contemporary treatment patterns among postmenopausal women with HR+/HER2- mBC in the real-world setting. Data were collected from 64 community oncologists in the US between February and June 2017 using an online medical records extraction tool. Physicians reviewed medical records and provided information on patient demographics and disease characteristics, and treatment regimens. Treatment patterns were described overall and separately by line of therapy and type of treatment received. Discontinuation rates were estimated using Kaplan-Meier analyses to account for censoring. Data were collected on 401 patients. Mean age at the time of mBC diagnosis was 67 years. In the first-line setting, 52.4% of patients received a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor-based regimen, most commonly with an aromatase inhibitor (AI) (39.2%) or fulvestrant (10.0%); 30.2% received endocrine therapy, most commonly an AI (21.4%) or fulvestrant (5.2%) in monotherapy, while 12.7% received a chemotherapy-based regimen. In the second-line setting, 42.9% of patients received a CDK4/6 inhibitor-based regimen, 18.4% received endocrine therapy, and 22.4% received a chemotherapy-based regimen. The 18-month discontinuation rate was 34.5% for patients receiving a CDK4/6 inhibitor-based regimen and 45.8% for patients receiving endocrine monotherapy. CDK4/6 inhibitor-based regimens were the most commonly prescribed treatment in both first- and second-line settings. A wide variety of treatment sequences were observed which suggests an absence of a standard of care for postmenopausal women with HR+/HER2- mBC in real-world practice.


Qualitative outcomes of progressive resistance exercise for people with COPD.
The outcomes of quantitative investigations examining the effectiveness of exercise interventions for people with COPD are limited by the small number of measurement tools that can be included. In contrast, qualitative inquiry allows broader exploration of the perceived outcomes of an intervention. The purpose of this investigation is to explore the qualitative outcomes of a progressive resistance exercise (PRE) program for people with COPD. People with COPD, enrolled in a randomized controlled trial of PRE, were invited to participate in two semi-structured interviews conducted at the end (12 weeks) and 12 weeks after the training intervention (24 weeks). Interviews were audiotaped, transcribed and then coded independently by two researchers. Themes relating to training outcomes were then developed and described. Twenty-two participants were interviewed at 12 weeks, and 19 participants at 24 weeks. After PRE, participants reported a range of physical gains, particularly with regard to improved strength and reduced breathlessness during daily activities. Improved control and confidence during activities of daily living were important psychological benefits perceived by people with COPD, as was the social support experienced during group training sessions. At 24 weeks, confidence persisted despite a perceived plateau or dissipation of physical gains. People with COPD reported physical, psychological and social benefits after PRE, which had a positive effect on activity performance. Although the perceived physical benefits of training were not prominent at 24 weeks, feelings of increased confidence and control persisted.


Partitioning of the molecular density matrix over atoms and bonds.
A double-index atomic partitioning of the molecular first-order density matrix is proposed. Contributions diagonal in the atomic indices correspond to atomic density matrices, whereas off-diagonal contributions carry information about the bonds. The resulting matrices have good localization properties, in contrast to single-index atomic partitioning schemes of the molecular density matrix. It is shown that the electron density assigned to individual atoms, when derived from the density matrix partitioning, can be made consistent with well-known partitions of the electron density over atom in the molecule basins, either with sharp or with fuzzy boundaries. The method is applied to a test set of about 50 molecules, representative for various types of chemical binding. A close correlation is observed between the trace of the bond matrices and the shared electron density index.


WRKY2/34-VQ20 Modules in Arabidopsis thaliana Negatively Regulate Expression of a Trio of Related MYB Transcription Factors During Pollen Development.
Male gametogenesis in plants is tightly controlled and involves the complex and precise regulation of transcriptional reprogramming. Interactions between WRKY proteins and VQ motif-containing proteins are required to control these complicated transcriptional networks. However, our understanding of the mechanisms by which these complexes affect downstream gene expression is quite limited. In this study, we found that WRKY2 and WKRY34 repress MYB97, MYB101, and MYB120 expression during male gametogenesis. MYB expression was up-regulated in the wrky2-1 wrky34-1 vq20-1 triple mutant during male gametogenesis. The expression levels of six potential targets of the three MYBs increased the most in the wrky2-1 wrky34-1 vq20-1 triple mutant, followed by the wrky2-1 wrky34-1 double mutant, compared with in wild-type. Yeast one-hybrid and dual luciferase reporter assays indicated that WRKY2 and WRKY34 recognized the MYB97 promoter by binding to its W-boxes. MYB97 overexpression caused defects in pollen germination and pollen tube length, which impacted male fertility. Thus, WRKY2/34-VQ20 complexes appear to negatively regulate the expression of certain MYBs during plant male gametogenesis.


Facile synthesis of highly efficient one-dimensional plasmonic photocatalysts through Ag@Cu₂O core-shell heteronanowires.
A novel class of one-dimensional (1D) plasmonic Ag@Cu2O core-shell heteronanowires have been synthesized at room temperature for photocatalysis application. The morphology, size, crystal structure and composition of the products were investigated by XRD, SEM, TEM, XPS, and UV-vis instruments. It was found the reaction time and the amount of Ag nanowires play crucial roles in the formation of well-defined 1D Ag@Cu2O core-shell heteronanowires. The resultant 1D Ag@Cu2O NWs exhibit much higher photocatalytic activity toward degradation of organic contaminants than Ag@Cu2O core-shell nanoparticles or pure Cu2O nanospheres under solar light irradiation. The drastic enhancement in photocatalytic activity could be attributed to the surface plasmon resonance and the electron sink effect of the Ag NW cores, and the unique 1D core-shell nanostructure.


Relationship between 24-hour urinary-free cortisol excretion and salivary cortisol levels sampled from awakening to bedtime in healthy subjects.
The utility of repeated salivary cortisol sampling as a substitute for 24-hour urinary-free cortisol (UFC) assessment was examined. Forty-four participants completed both 24-hour collections and 6 salivary collections at wake-up, 08:00, 12:00, 16:00, 20:00 and bedtime, during the same 24-hour period. The results demonstrated that mean, maximum, and amplitude (maximum minus minimum) for salivary cortisol all correlated positively with urinary cortisol, but the associations of these variables with urinary-free cortisol excretion were relatively small. Furthermore, a single salivary sample taken at wake-up was as good an indicator of overall cortisol production as the measures derived from multiple salivary samples. An examination of subject compliance indicated that many subjects failed to collect the timed salivary collections as instructed. The authors conclude that diurnal salivary cortisol sampling versus 24-hour urinary cortisol collections are likely to provide different information about ambient hypothalamic-pituitary-adrenal productivity, and therefore these measures should not be used interchangeably. In addition, subject compliance is a serious consideration in designing studies that employ home salivary collections.


Association of crossed renal ectopia and aortic aneurism. Case report.
Renal malformations are rare entities and rarely have clinical consequences. Crossed renal ectopia has an incidence of 1/2.000 autopsies. The association with aortic aneurysm is even more exceptional. We present our case and perform a bibliographic review. To date and in our knowledge, seven cases of crossed renal ectopia associated with aortic aneurysm were described on the literature. This malformation makes the treatment of the aneurysm more complex. The possibility of renal function decrease caused by injuries to the renal arteries during the surgical procedure is always present. Because of this risk of injury of the kidney during surgery preoperative evaluation of the vascularization must include image technologies as the MRI, CT-angiography or conventional arteriography. During the aortic intervention vascular conservation must be performed and it is necessary to minimize the time of renal ischemia. The association of crossed renal ectopia and aortic aneurysm is a rare event. The surgical intervention of the aorta does not have to necessarily originate a loss of renal function. Anyway the worsening of the renal clearance must be foreseen.


Induction of human cytochrome P450 3A enzymes in cultured placental cells by thalidomide and relevance to bioactivation and toxicity.
Evidence has been presented for auto-induced human cytochrome P450 3A enzyme involvement in the teratogenicity and clinical outcome of thalidomide due to oxidation to 5-hydroxythalidomide and subsequent metabolic activation in livers. In this study, more relevant human placenta preparations and placental BeWo cells showed low but detectable P450 3A4/5 mRNA expression and drug oxidation activities. Human placental microsomal fractions from three subjects showed detectable midazolam 1´- and 4-hydroxylation and thalidomide 5-hydroxylation activities. Human placental BeWo cells, cultured in the recommended media, also indicated detectable midazolam 1´- and 4-hydroxylation and thalidomide 5-hydroxylation activities. To reduce any masking effects by endogenous hormones used in the recommended media, induction of P450 3A4/5 mRNA and oxidation activities were measured in placental BeWo cells cultured with a modified medium containing 5% charcoal-stripped fetal bovine serum. Thalidomide significantly induced P450 3A4/5, 2B6, and pregnane X receptor (PXR) mRNA levels 2 to 3-fold, but rifampicin only enhanced P450 3A5 and PXR mRNA under the modified media conditions. Under these modified conditions, thalidomide also significantly induced midazolam 1´-hydroxylation and thalidomide 5-hydroxylaion activities 3-fold but not bupropion hydroxylation activity. Taken together, activation of thalidomide to 5-hydroxythalidomide with autoinduction of P450 3A enzymes in human placentas, as well as livers, is suggested in vivo.


Relationships between Causes of Fever of Unknown Origin and Inflammatory Markers: A Multicenter Collaborative Retrospective Study.
Although inflammatory markers, such as the white blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) and procalcitonin, are widely used to differentiate causes of fever of unknown origin (FUO), little is known about the usefulness of this approach. We evaluated relationships between the causes of classical FUO and the levels of inflammatory markers. A nationwide retrospective study including 17 hospitals affiliated with the Japanese Society of Hospital General Medicine was conducted. This study included 121 patients ≥18 years old diagnosed with "classical FUO" (axillary temperature ≥38.0°C at least twice over a ≥3-week period without elucidation of the cause on three outpatient visits or during three days of hospitalization) between January and December 2011. The causative disease was infectious diseases in 28 patients (23.1%), non-infectious inflammatory disease (NIID) in 37 patients (30.6%), malignancy in 13 patients (10.7%), other in 15 patients (12.4%) and unknown in 28 patients (23.1%). The rate of malignancy was significantly higher for a WBC count of <4,000/μL than for a WBC count of 4,000-8,000/μL (p=0.015). Among the patients with a higher WBC count, the rate of FUO due to NIID tended to be higher and the number of unknown cases tended to be lower. All FUO patients with malignancy showed an ESR of >40 mm/h. A normal ESR appeared to constitute powerful evidence for excluding a diagnosis of malignancy. In contrast, the concentrations of both serum CRP and procalcitonin appeared to be unrelated to the causative disease. The present study identified inflammatory markers that should be considered in the differential diagnosis of classical FUO, providing useful information for future diagnosis.


Bone loss in Great Britain and Japan: a comparative longitudinal study.
Hip fracture incidence is lower in Japan than in the West. Although differences have been found in peak bone mass and hip geometry between white and Japanese populations, these do not fully explain the difference in hip fracture rates. Variation in the rates of involutional bone loss may be an additional contributing factor. We address this issue in a prospective epidemiological study comparing bone loss rate among elderly people in Britain and Japan. Two population-based studies of bone loss rate in a British and a Japanese cohort were performed. Annual bone loss rates were obtained for 172 Hertfordshire men and 143 Hertfordshire women of mean age 66 years, and a questionnaire administered to obtain information on known confounding lifestyle factors. Eighty-six Japanese men and 90 Japanese women of mean age 69 years completed a similar study in Taiji, Japan. British men and women were heavier than Japanese men and women. Differences in lifestyle were also evident; the British men were less likely to smoke and the women more likely to consume alcohol than their Japanese counterparts. The British population also spent more time walking outdoors. Statistically significant differences between the two populations were apparent in baseline bone mineral density at lumbar spine (p < 0.05) and trochanter (p < 0.001) in men and women with Japanese subjects having lower values. There were also significant differences in bone density at the femoral neck (p < 0.001) between British and Japanese males. Men gained bone at the lumbar spine over the follow-up period in both populations. Bone loss rates were generally greater in the British female population than in Japanese women: the difference was statistically significant at the femoral neck (p < 0.05) and femoral trochanter (p < 0.001). These differences all remained significant after adjustment for differences in age between the two populations. Japanese subjects appear to have lower peak bone mass, but slower bone loss rates in later life than their European counterparts. These differences in bone loss rate help to explain the relatively low hip fracture rates found in Japan.


A biomechanical analysis of the squat between competitive collegiate, competitive high school, and novice powerlifters.
The purpose of this study was to measure and analyze kinematic differences between competitive collegiate (CLG, n = 9) powerlifters, competitive high school (HS, n = 9) powerlifters, and novice (NV, n = 11) powerlifters during a maximal squat to determine the effect of skill level on performance. All powerlifters performed 3 squats, with the final squat being their 1 repetition maximum. Kinematic data (descent, ascent, total lift times, knee angle magnitude, knee angular velocity, and knee angular acceleration) was measured using 2-dimensional motion analysis equipment. Differences in mean peak kinematic values between the 3 groups were analyzed using a 1-way multivariate analysis of variance, p <or= 0.05. Differences were found between the NV and HS in the time to ascent, the total lift time, the normalized time to peak (NTTP) in knee angular velocity from the "sticking point" to the "lockout," and the NTTP in knee angular acceleration during the ascent. A difference was found between the CLG and HS in the peak knee angular velocity between the bottom of the lift and the sticking point. Differences were also found in the rate of acceleration upward after coming out of "the hole" between the CLG and NV and CLG and HS. A difference was found in the rate of peak deceleration upward to the sticking point between the CLG and NV. To avoid injury and to achieve optimum results in powerlifting, lifting technique must be optimized. The HS and NV accumulated several significant differences in NTTP during the ascending phase. However, the major finding between the 3 groups was in the rate of acceleration upward after coming out of the hole. Coaches should focus their training programs on increasing strength in unskilled powerlifters for the purpose of increasing acceleration from the bottom of the lift.


Decreased Hip, Lower Leg, and Humeral Fractures but Increased Forearm Fractures in Highly Active Individuals.
It is not known how physical exercise affects the risk of different types of fractures, especially in highly active individuals. To investigate this association, we studied a cohort of 118,204 men and 71,757 women who from 1991 to 2009 participated in Vasaloppet, a long-distance cross-country skiing race in Sweden, and 505,194 nonparticipants frequency-matched on sex, age, and county of residence from the Swedish population. Participants ranged from recreational exercisers to world-class skiers. Race participation, distance of race run, number of races participated in, and finishing time were used as proxies for physical exercise. Incident fractures from 1991 to 2010 were obtained from national Swedish registers. Over a median follow-up of 8.9 years, 53,175 fractures of any type, 2929 hip, 3107 proximal humerus, 11,875 lower leg, 11,733 forearm, and 2391 vertebral fractures occurred. In a Cox proportional hazard regression analysis using time-updated exposure and covariate information, participation in the race was associated with an increased risk of any type of fracture (hazard ratio [HR], 1.02; 95% CI, 1.00 to 1.05); forearm fractures had an HR, 1.11 with a 95% CI, 1.06 to 1.15. There was a lower risk of hip (HR, 0.75; 95% CI, 0.67 to 0.83), proximal humerus (HR, 0.90; 95% CI, 0.82 to 0.98), and lower leg fractures (HR, 0.93; 95% CI, 0.89 to 0.97), whereas the HR of vertebral fracture was 0.97 with a 95% CI, 0.88 to 1.07. Among participants, the risk of fracture was similar irrespective of race distance and number of races run. Participants close to the median finishing time had a lower risk of fracture compared with faster and slower participants. In summary, high levels of physical exercise were associated with a slightly higher risk of fractures of any type, including forearm fractures, but a lower risk of hip, proximal humerus, and lower leg fractures. © 2018 American Society for Bone and Mineral Research.


Canine leishmaniasis. Immunophenotypic profile of leukocytes in different compartments of symptomatic, asymptomatic and treated dogs.
Canine visceral leishmaniasis (CanL) is an emerging disease, expanding in various parts of the world. The infection caused by Leishmania, an intracellular protozoan parasite, can show different clinical manifestations, from asymptomatic or subclinical to symptomatic dogs, in which a wide spectrum of clinical signs is evident. The fact that the parasite replicates in different organs raises the hypothesis that each organ may have a specific immune response. The local immune responses should be evaluated and taken into consideration when developing prophylactic tools. Therefore, phenotypic characterization of peripheral blood, lymph node and bone marrow lymphocyte populations and the expression of class II molecules of major histocompatibility complex (MHCII) were performed in asymptomatic and symptomatic dogs and in dogs that had been diagnosed and treated for leishmaniasis. Our findings showed that blood and bone marrow lymphocytes from symptomatic dogs were highly activated. In bone marrow of asymptomatic and treated dogs, a high frequency of MHCII(+) lymphocytes was observed, as well as MHCII(+) monocytes in the treated group. These results show increased expression of MHCII molecules giving evidence for antigenic presentation mainly by lymphocytes. The symptomatic and treated dogs showed an expansion of CD4(+) T cells subpopulations in lymph nodes, revealing an important contribution of these cells in controlling local parasite replication. This study also underlines the eventual importance of CD3(+)CD4(-)CD8(-) (double negative) and CD3(+)CD4(+)CD8(+) (double positive) T cell subsets in sensing and controlling latent infections and their possible function in the immune dynamics during CanL. The specific cellular immune responses raised in different compartments where the parasite replicates seem to have variable effects on local parasite control, highlighting the complexity of the cellular immune response developed by the dog infected by Leishmania infantum.


[Sodium levels in the Dalmatian water resources in 2003].
The objective of this paper was to analyse the sodium levels in the spring water, surface and groundwater in Dalmatia during 2003. The sodium concentrations were computed from the difference between coefficient K1 (the ratio between the chlorides and sulfates sum and the carbonate hardness) and K2 (the ratio between non-carbonate and carbonate hardness) and carbonate hardness. The average sodium concentrations have been expressed by a median and they ranged from 1.8 mg/L Na to 17.6 mg/L Na in the spring water, in the surface water they ranged from 1.0 to 502 mg/L Na and in the groundwater they ranged from 11.1 mg/L Na to 124.3 mg/L Na. In the spring water the sodium concentrations varied from 32% to 217%, in the surface water from 40% to 159% and in the groundwater from 77.3% to 180%. According to the corrosiveness coefficient K1, 83% of the spring waters are classified as non-corrosive and 17% as water with a low degree of corrosiveness; 84% of the surface waters are classified as non-corrosive water and 16% as very corrosive; all groundwater is classified as very corrosive water. Out of the total of 60 analyzed water resources 64% are classified as hypotensive, 20% as normotensive and 17% as hypertensive water. The drinking water has been defined as hypotensive (<10 mg/L Na), normotensive (from 11 to 20 mg/L Na) and hypertensive (>20 mg/L Na) by relating the sodium concentration projectively with the notion of arterial pressure knowing that an increased sodium concentration in blood increases the blood pressure. From the informatics standpoint the data related to health should be classified into data bases which can serve as a methodological starting point for studying the influence of sodium upon human health. Consequently, epidemiological studies should relate various sodium levels in drinking water to other factors which affect human health.


Transplanted hematopoietic stem cells demonstrate impaired sarcoglycan expression after engraftment into cardiac and skeletal muscle.
Pluripotent bone marrow-derived side population (BM-SP) stem cells have been shown to repopulate the hematopoietic system and to contribute to skeletal and cardiac muscle regeneration after transplantation. We tested BM-SP cells for their ability to regenerate heart and skeletal muscle using a model of cardiomyopathy and muscular dystrophy that lacks delta-sarcoglycan. The absence of delta-sarcoglycan produces microinfarcts in heart and skeletal muscle that should recruit regenerative stem cells. Additionally, sarcoglycan expression after transplantation should mark successful stem cell maturation into cardiac and skeletal muscle lineages. BM-SP cells from normal male mice were transplanted into female delta-sarcoglycan-null mice. We detected engraftment of donor-derived stem cells into skeletal muscle, with the majority of donor-derived cells incorporated within myofibers. In the heart, donor-derived nuclei were detected inside cardiomyocytes. Skeletal muscle myofibers containing donor-derived nuclei generally failed to express sarcoglycan, with only 2 sarcoglycan-positive fibers detected in the quadriceps muscle from all 14 mice analyzed. Moreover, all cardiomyocytes with donor-derived nuclei were sarcoglycan-negative. The absence of sarcoglycan expression in cardiomyocytes and skeletal myofibers after transplantation indicates impaired differentiation and/or maturation of bone marrow-derived stem cells. The inability of BM-SP cells to express this protein severely limits their utility for cardiac and skeletal muscle regeneration.


Arabidopsis mitogen-activated protein kinase kinases MKK1 and MKK2 have overlapping functions in defense signaling mediated by MEKK1, MPK4, and MKS1.
The Arabidopsis (Arabidopsis thaliana) MKK1 and MKK2 mitogen-activated protein kinase kinases have been implicated in biotic and abiotic stress responses as part of a signaling cascade including MEKK1 and MPK4. Here, the double loss-of-function mutant (mkk1/2) of MKK1 and MKK2 is shown to have marked phenotypes in development and disease resistance similar to those of the single mekk1 and mpk4 mutants. Because mkk1 or mkk2 single mutants appear wild type, basal levels of MPK4 activity are not impaired in them, and MKK1 and MKK2 are in part functionally redundant in unchallenged plants. These findings are confirmed and extended by biochemical and molecular analyses implicating the kinases in jasmonate- and salicylate-dependent defense responses, mediated in part via the MPK4 substrate MKS1. In addition, transcriptome analyses delineate overlapping and specific effects of the kinases on global gene expression patterns demonstrating both redundant and unique functions for MKK1 and MKK2.


Prevention and management of catheter-related infection in hemodialysis patients.
Central venous catheter-related infections have been associated with high morbidity, mortality, and costs. Catheter use in chronic hemodialysis patients has been recognized as distinct from other patient populations who require central venous access, leading to recent adaptations in guidelines-recommended diagnosis for catheter-related bacteremia (CRB). This review will discuss the epidemiology and pathogenesis of hemodialysis CRB, in addition to a focus on interventions that have favorably affected CRB outcomes. These include: (1) the use of prophylactic topical antimicrobial ointments at the catheter exit site, (2) the use of prophylactic catheter locking solutions for the prevention of CRB, (3) strategies for management of the catheter in CRB, and (4) the use of vascular access managers and quality initiative programs.


Dynamic control of chromatin-associated m6A methylation regulates nascent RNA synthesis.
N6-methyladenosine (m6A) methylation is co-transcriptionally deposited on mRNA, but a possible role of m6A on transcription remains poorly understood. Here, we demonstrate that the METTL3/METTL14/WTAP m6A methyltransferase complex (MTC) is localized to many promoters and enhancers and deposits the m6A modification on nascent transcripts, including pre-mRNAs, promoter upstream transcripts (PROMPTs), and enhancer RNAs. PRO-seq analyses demonstrate that nascent RNAs originating from both promoters and enhancers are significantly decreased in the METTL3-depleted cells. Furthermore, genes targeted by the Integrator complex for premature termination are depleted of METTL3, suggesting a potential antagonistic relationship between METTL3 and Integrator. Consistently, we found the Integrator complex component INTS11 elevated at promoters and enhancers upon loss of MTC or nuclear m6A binders. Taken together, our findings suggest that MTC-mediated m6A modification protects nascent RNAs from Integrator-mediated termination and promotes productive transcription, thus unraveling an unexpected layer of gene regulation imposed by RNA m6A modification.


A zebrafish model for Waardenburg syndrome type IV reveals diverse roles for Sox10 in the otic vesicle.
In humans, mutations in the SOX10 gene are a cause of the auditory-pigmentary disorder Waardenburg syndrome type IV (WS4) and related variants. SOX10 encodes an Sry-related HMG box protein essential for the development of the neural crest; deafness in WS4 and other Waardenburg syndromes is usually attributed to loss of neural-crest-derived melanocytes in the stria vascularis of the cochlea. However, SOX10 is strongly expressed in the developing otic vesicle and so direct roles for SOX10 in the otic epithelium might also be important. Here, we examine the otic phenotype of zebrafish sox10 mutants, a model for WS4. As a cochlea is not present in the fish ear, the severe otic phenotype in these mutants cannot be attributed to effects on this tissue. In zebrafish sox10 mutants, we see abnormalities in all otic placodal derivatives. Gene expression studies indicate deregulated expression of several otic genes, including fgf8, in sox10 mutants. Using a combination of mutant and morphant data, we show that the three sox genes belonging to group E (sox9a, sox9b and sox10) provide a link between otic induction pathways and subsequent otic patterning: they act redundantly to maintain sox10 expression throughout otic tissue and to restrict fgf8 expression to anterior macula regions. Single-cell labelling experiments indicate a small and transient neural crest contribution to the zebrafish ear during normal development, but this is unlikely to account for the strong defects seen in the sox10 mutant. We discuss the implication that the deafness in WS4 patients with SOX10 mutations might reflect a haploinsufficiency for SOX10 in the otic epithelium, resulting in patterning and functional abnormalities in the inner ear.


Adolescent gambling: relationships with parent gambling and parenting practices.
This study explored the possible links between family risk factors (i.e., parent gambling and parenting practices) and adolescent gambling. A community sample of 938 adolescents (496 females and 442 males) completed the South Oaks Gambling Screen Revised for Adolescents (SOGS-RA; K. C. Winters, R. Stinchfield, & J. Fulkerson, 1993b) along with a questionnaire assessing parenting practices. Both parents completed the SOGS (H. R. Lesieur & S. B. Blume, 1987). Results showed that adolescent gambling frequency was related to both parents' gambling frequency and problems. However, adolescent gambling problems were linked only to fathers' severity of gambling problems. Low levels of parental monitoring enhanced adolescents' risk of getting involved in gambling activities and developing related problems. A higher level of inadequate disciplinary practices was also related to greater gambling problems in youth. These links were significant after controlling for socioeconomic status, gender, and impulsivity-hyperactivity problems.


A pathway from midcingulate cortex to posterior insula gates nociceptive hypersensitivity.
The identity of cortical circuits mediating nociception and pain is largely unclear. The cingulate cortex is consistently activated during pain, but the functional specificity of cingulate divisions, the roles at distinct temporal phases of central plasticity and the underlying circuitry are unknown. Here we show in mice that the midcingulate division of the cingulate cortex (MCC) does not mediate acute pain sensation and pain affect, but gates sensory hypersensitivity by acting in a wide cortical and subcortical network. Within this complex network, we identified an afferent MCC-posterior insula pathway that can induce and maintain nociceptive hypersensitivity in the absence of conditioned peripheral noxious drive. This facilitation of nociception is brought about by recruitment of descending serotonergic facilitatory projections to the spinal cord. These results have implications for our understanding of neuronal mechanisms facilitating the transition from acute to long-lasting pain.


Effect of meditation on psychological distress and brain functioning: A randomized controlled study.
Psychological stability and brain integration are important factors related to physical and mental health and organization effectiveness. This study tested whether a mind-body technique, the Transcendental Meditation (TM) program could increase EEG brain integration and positive affect, and decrease psychological distress in government employees. Ninety-six central office administrators and staff at the San Francisco Unified School District were randomly assigned to either immediate start of the TM program or to a wait-list control group. At baseline and four-month posttest, participants completed an online version of the Profile of Mood States questionnaire (POMS). In addition, a subset of this population (N = 79) had their EEG recorded at baseline and at four-month posttest to calculate Brain Integration Scale (BIS) scores. At posttest, TM participants significantly decreased on the POMS Total Mood Disturbance and anxiety, anger, depression, fatigue, and confusion subscales, and significantly increased in the POMS vigor subscale. TM participants in the EEG-subgroup also significantly increased in BIS scores. Compliance with meditation practice was high (93%). Findings indicate the feasibility and effectiveness of implementing the TM program to improve brain integration and positive affect and reduce psychological distress in government administrators and staff.


Demographics, clinical disease characteristics, and quality of life in a large cohort of psoriasis patients with and without psoriatic arthritis.
What is already known about the topic: psoriasis (PsO) is a common skin disease with major impact on quality of life (QoL). Patient-reported data on QoL from large number of PsO patients with and without psoriatic arthritis (PsA) are limited. In a large cohort referred to a university psoriasis center, patients with PsO and concomitant PsA (~30% in this group) had greater degrees of skin and nail involvement and experienced greater negative impacts on QoL. Despite large numbers of patients with moderate-to-severe disease, use of systemic therapy by community practitioners was uncommon. PsO and PsA are common diseases that have marked adverse impacts on QoL. The disease features and patient-reported QoL data comparing PsO and PsA patients are limited. To identify and compare demographics, clinical disease characteristics, and QoL scores in a large cohort of PsO patients with and without PsA. All PsO patients seen in a psoriasis specialty clinic, named the Center of Excellence for Psoriasis and Psoriatic Arthritis, were enrolled in an observational cohort. Demographic, QoL, and clinical data were collected from patient-reported questionnaires and from physical examinations performed by Center of Excellence for Psoriasis and Psoriatic Arthritis dermatologists and a rheumatologists. Cross sectional descriptive data were collected and comparisons between patients with PsO alone and those with concomitant PsA are presented. A total of 568 patients were enrolled in the database. Mean age of PsO onset was 28 years and mean disease duration was 18 years. Those with family history had an earlier onset of PsO by ~7 years. Mean body surface area involvement with PsO was 14%. Mean body mass index was 30.7. Prevalence of PsA was 29.8%. PsA patients had a higher mean body surface area compared to patients with PsO alone (16.7% vs 13.4%, P<0.05), higher prevalence of psoriatic nail changes (54.4% vs 36%, P<0.0002), and worse QoL scores as assessed by the Short Form-12 (67 vs 52, P<0.00001), Psoriasis Quality of Life-12 questionnaire (62 vs 71, P<0.01), and Routine Assessment of Patient Index Data 3 (2.3 vs 4.7, P<0.01). Strikingly, 49% of patients with PsO had never received any systemic therapy. These data highlight that PsO has marked negative impacts on QoL, while those patients with concomitant PsA are affected to a much greater degree. Despite large numbers of patients presenting with moderate-to-severe disease, use of systemic therapy for both PsO and PsA was uncommon.


Perspective rectification of integral images produced using arrays of circular lenses.
There are many different three-dimensional (3D) techniques to capture and deliver autostereoscopic 3D content. A promising technique that provides two-dimensional parallax as well as high-quality, full-color 3D content is integral imaging (InI). Misalignments between the lens arrays (LAs) and the camera charged coupled device, however, introduce geometric distortions in the acquired image that propagate through the different image processing stages and deteriorate the 3D effect. Here, we propose a method to accurately rectify the perspective distortion of integral images (InIms) generated using circular lenses. Using an edge-linking approach, we extracted elliptically shaped contours of elemental images in the perspectively distorted InIm. To calculate the rectification matrix, we used the images of the circular points. Subsequently, we applied a triangulation scheme followed by a statistical approach to accurately estimate the grid structure of the LA. Finally, we provided experimental results over a wide range of InIms to evaluate the robustness and accuracy of the proposed method using objective metrics.


Perioperative risk factors related to lumbar spine fusion surgery in korean geriatric patients.
Life expectancy for humans has increased dramatically and with this there has been a considerable increase in the number of patients suffering from lumbar spine disease. Symptomatic lumbar spinal disease should be treated, even in the elderly, and surgical procedures such as fusion surgery are needed for moderate to severe lumbar spinal disease. However, various perioperative complications are associated with fusion surgery. The aim of this study was to examine perioperative complications and assess risk factors associated with lumbar spinal fusion, focusing on geriatric patients at least 70 years of age in the Republic of Korea. We retrospectively investigated 489 patients with various lumbar spinal diseases who underwent lumbar spinal fusion surgery between 2003 and 2007 at our institution. Three fusion procedures and the number of fused segments were analyzed in this study. Chronic diseases were also evaluated. Risk factors for complications and their association with age were analyzed. In this study, 74 patients experienced complications (15%). The rate of perioperative complications was significantly higher in patients 70 years of age or older than in other age groups (univariate analysis, p=0.001; multivariate analysis, p=0.004). However, perioperative complications were not significantly associated with the other factors tested (sex, comorbidities, operation procedures, fusion segments involved). Increasing age was an important risk factor for perioperative complications in patients undergoing lumbar spinal fusion surgery whereas other factors were not significant. We recommend good clinical judgment and careful selection of geriatric patients undergoing lumbar spinal fusion surgery.


CSF-1-dependant donor-derived macrophages mediate chronic graft-versus-host disease.
Chronic GVHD (cGVHD) is the major cause of late, nonrelapse death following stem cell transplantation and characteristically develops in organs such as skin and lung. Here, we used multiple murine models of cGVHD to investigate the contribution of macrophage populations in the development of cGVHD. Using an established IL-17-dependent sclerodermatous cGVHD model, we confirmed that macrophages infiltrating the skin are derived from donor bone marrow (F4/80+CSF-1R+CD206+iNOS-). Cutaneous cGVHD developed in a CSF-1/CSF-1R-dependent manner, as treatment of recipients after transplantation with CSF-1 exacerbated macrophage infiltration and cutaneous pathology. Additionally, recipients of grafts from Csf1r-/- mice had substantially less macrophage infiltration and cutaneous pathology as compared with those receiving wild-type grafts. Neither CCL2/CCR2 nor GM-CSF/GM-CSFR signaling pathways were required for macrophage infiltration or development of cGVHD. In a different cGVHD model, in which bronchiolitis obliterans is a prominent manifestation, F4/80+ macrophage infiltration was similarly noted in the lungs of recipients after transplantation, and lung cGVHD was also IL-17 and CSF-1/CSF-1R dependent. Importantly, depletion of macrophages using an anti-CSF-1R mAb markedly reduced cutaneous and pulmonary cGVHD. Taken together, these data indicate that donor macrophages mediate the development of cGVHD and suggest that targeting CSF-1 signaling after transplantation may prevent and treat cGVHD.


Comparison of EPI gradient-echo contrast changes in cat brain caused by respiratory challenges with direct simultaneous evaluation of cerebral oxygenation via a cranial window.
A gradient-echo echo planar imaging (EPI) sequence has been used to generate images of cat brain during respiratory challenges. Direct spectrophotometric measurements have been made simultaneously in order to correlate the changes in oxygen saturation as measured by spectrophotometry with the image intensity changes seen in the gradient-echo images. When blood volume remains approximately constant, as derived from the spectrophotometry data, good correlation is seen between calculated plots made of changes in the transverse relaxation rate, delta R2*, and the oxygen saturation as measured by spectrophotometry for much of the time course of the respiratory challenges of anoxia, apnea and hypercapnia. In some cases, the correlation is poorer during the recovery periods of the apnea and anoxia challenges. Those lower correlations can often be accounted for by changes in blood volume, which also affects the NMR relaxation rate. These results contribute to the understanding of the image intensity changes seen during functional brain imaging studies in humans.


Fatty acid uptake in normal human myocardium.
Fatty acid binding protein has been found in rat aortic endothelial cell membrane. It has been identified to be a 40-kDa protein that corresponds to a 40-kDa fatty acid binding protein with high affinity for a variety of long chain fatty acids isolated from rat heart myocytes. It is proposed that this endothelial membrane fatty acid binding protein might mediate the myocardial uptake of fatty acids. For evaluation of this hypothesis in vivo, influx kinetics of tracer-labeled fatty acids was examined in 15 normal subjects by scintigraphic techniques. Variation of the plasma fatty acid concentration and plasma perfusion rate has been achieved by modulation of nutrition state and exercise conditions. The clinical results suggest that the myocardial fatty acid influx rate is saturable by increasing fatty acid plasma concentration as well as by increasing plasma flow. For analysis of these data, functional relations describing fatty acid transport from plasma into myocardial tissue in the presence and absence of an "unstirred layer" were developed. The fitting of these relations to experimental data indicate that the free fatty acid influx into myocardial tissue reveals the criteria of a reaction on a capillary surface in the vicinity of flowing plasma but not of a reaction in extravascular space or in an unstirred layer and that the fatty acid influx into normal myocardium is a saturable process that is characterized by the quantity corresponding to the Michaelis-Menten constant, Km, and the maximal velocity, Vmax, 0.24 +/- 0.024 mumol/g and 0.37 +/- 0.013 mumol/g(g.min), respectively. These data are compatible with a nondiffusional uptake process mediated by the initial interaction of fatty acids with the 40-kDa membrane fatty acid binding protein of cardiac endothelial cells.


Effect of Estradiol valerate plus dienogest on body composition of healthy women in the menopausal transition: a prospective one-year evaluation.
In the menopausal transition (MT), combined oral contraceptive (COC) should be chosen accordingly to its neutrality on liver metabolism and to its ability to counter the increase of fat mass (FM) that occurs in this reproductive period of life. This prospective multi-centric observational study was conducted on 36 women in their MT at the Universities of Cagliari, Modena and Naples. The body weight (BW), the Body Mass Index (BMI), the waist to hip ratio (WHR), the measurement of body composition (BC) with the Multi-frequency Bioelectrical Impedance (MF-BIA) were performed before, at the 6th and at the 12th month of the study in which a group of women (control group; N.18) did not assume COC, whereas the other 18 women assumed the four-phasic COC containing estradiol valerate (EV) associated with dienogest (EV/DNG group). In comparison to controls in the EV/DNG group, a significant decrease (p < 0.05) of BW (58.8 ± 7.6 to 57.3 ± 7.0), BMI (24.1 ± 2.7 to 23.5 ± 2.8), WHR (0.82 ± 0.052 to 0.79 ± 0.048) and FM (17.7 ± 5.4 to 16.4 ± 5.6) was observed. In controls, FM significantly increased (17.0 ± 11 to 17.7 ± 2.7; p < 0.05). In conclusion, these results suggest that the anti-androgenic and progestinic activities of DNG associated with a weak estrogenic activity of EV, is a contraceptive method capable of counteracting the negative changes of BC occurring in the MT.


The Relationship between the Blood Level of Persistent Organic Pollutants and Common Gastrointestinal Symptoms.
Persistent organic pollutants (POPs) are toxic materials that cannot be broken down naturally and that easily accumulate in the body. Although several studies have attempted to reveal the effects of POPs on the endocrine and nervous system and on cancer, few studies focus on the relationship between low-dose POPs and public health. We attempted to find a relationship between the level of POPs and common gastrointestinal symptoms, including abdominal discomfort, diarrhea, and constipation. We recruited 121 subjects who visited Kyungpook National University Hospital for a health screening. Plasma concentrations were evaluated for 40 kinds of POPs including 17 types of polychlorinated biphenyls and 23 types of organochlorine pesticides. Furthermore, the Korean version of the Rome III criteria was used to identify gastrointestinal symptoms. Our results showed that abdominal discomfort had an inverse relationship with several polychlorinated biphenyls. Moreover, an inverted U-shaped relationship was observed between abdominal discomfort and several other organochlorine pesticides including p,p'-dichlorodiphenyldichloroethane and p,p'-dichlorodiphenyltrichloroethane, and the effects of these pesticides on abdominal discomfort were similar to that of organochlorine pesticides on obesity and metabolic syndrome. Our results suggest that mild and unspecified gastrointestinal symptoms with no clear cause could be related to POPs levels.


Response of canine soft tissue sarcomas to radiation or radiation plus hyperthermia: a randomized phase II study.
Sixty-four dogs with spontaneous soft tissue sarcomas without evidence of metastases were stratified by tumour volume and randomized to receive graded doses of radiotherapy (XRT) alone or radiotherapy plus hyperthermia (HT). An improvement in duration of local control was achieved with the addition of hyperthermia as compared with XRT alone (Wilcoxon, p = 0.040; log rank, p = 0.064). Overall frequency of late complications was not different for the two treatment arms when comparing across equivalent XRT dose groups. Frequency of distant metastases after therapy completion was not significantly different for the two treatment arms at 1 year (7.4% for XRT versus 20% for HT plus XRT) or 2 years (11.5% for XRT versus 25% for HT plus XRT) post therapy. These results suggest that a therapeutic gain was achieved for this group of tumour-bearing animals. Uni- and multivariate analyses were performed to examine the potential for various factors to influence treatment outcome. Patient related variables included tumour stage, histologic subtype and grade and tumour site. Treatment related variables included total radiation dose and 15 descriptors of temperature distributions achieved during hyperthermia. When considering patient related factors, tumour histology, grade and location were important predictors of time to minimum volume, but only tumour location influenced time to tumour regrowth. When considering treatment related factors, radiation dose was not significantly correlated with time to minimum volume or time to local regrowth, but it was correlated with probability for late normal tissue damage in the XRT alone group (p = 0.005). For the hyperthermia treatments, 13 of 15 tumour temperature distribution descriptors were correlated with time to minimum volume, but none were correlated with time to local regrowth. These results suggest that caution should be used in interpreting the value of temperature distribution descriptors in predicting for long-term local control after hyperthermia and radiotherapy, based on analysis of short-term responses.


Impact of International Monetary Fund programs on child health.
Parental education is located at the center of global efforts to improve child health. In a developing-country context, the International Monetary Fund (IMF) plays a crucial role in determining how governments allocate scarce resources to education and public health interventions. Under reforms mandated by IMF structural adjustment programs, it may become harder for parents to reap the benefits of their education due to wage contraction, welfare retrenchment, and generalized social insecurity. This study assesses how the protective effect of education changes under IMF programs, and thus how parents' ability to guard their children's health is affected by structural adjustment. We combine cross-sectional stratified data (countries, 67; children, 1,941,734) from the Demographic and Health Surveys and the Multiple Indicator Cluster Surveys. The sample represents ∼2.8 billion (about 50%) of the world's population in year 2000. Based on multilevel models, our findings reveal that programs reduce the protective effect of parental education on child health, especially in rural areas. For instance, in the absence of IMF programs, living in an household with educated parents reduces the odds of child malnourishment by 38% [odds ratio (OR), 0.62; 95% CI, 0.66-0.58]; in the presence of programs, this drops to 21% (OR, 0.79; 95% CI, 0.86-0.74). In other words, the presence of IMF conditionality decreases the protective effect of parents' education on child malnourishment by no less than 17%. We observe similar adverse effects in sanitation, shelter, and health care access (including immunization), but a beneficial effect in countering water deprivation.


Lateral ligament injuries of the knee.
Between 1982 and 1994 28 patients were treated for acute lateral knee ligament injuries; 25 patients, with a median age of 25.5 (range 16-75) years at injury, appeared for follow-up. Seven patients had isolated injury of the lateral collateral ligament/capsular structures, the remaining 19 patients had concomitant ligament injuries in the knee. Eight patients were treated conservatively, 1 with plaster immobilization and 7 with early mobilization. Eighteen patients underwent surgery, 17 of these within 3 weeks of injury. Repair/reconstruction of the cruciate ligaments was done at the same time as the lateral collateral ligament repair in 10 patients. At follow-up after a median of 7.5 years (range 6 months to 13 years), 11 had no varus instability, 7 had 1+, 5 had 2+, and 2 patients had 3+ varus instability. All patients with a final result of 2+ or 3+ had combined ligament injuries. The surgically treated lateral collateral ligament injuries all had a primary instability of 2+ or more. These patients showed an improvement in varus instability from a mean of 2.83+ preoperatively to a mean of 1.17+ postoperatively. Two-thirds of the surgically treated patients were stable or had a 1+ instability at follow-up. One conservatively treated patient with a 2+ varus instability and 1 with 1+ showed no improvement. Five conservatively treated patients with initial varus instability of 1+ were stable at follow-up. One patient with a 1+ varus instability had anterior cruciate ligament (ACL) rupture. He had a primary ACL reconstruction without lateral repair. He had no varus instability at follow-up. Our study supports the notion that operation performed at an early stage in fresh injuries with a varus instability of 2+ or more gives improved stability as a final result. Conservative treatment may not be expected to give an improved stability, but is sufficient in mild varus instability (1+) without additional cruciate ligament injuries.


The Bellagio Report: Cardiovascular risks of spaceflight: implications for the future of space travel.
Long-duration space missions, as well as emerging civilian tourist space travel activities, prompted review and assessment of data available to date focusing on cardiovascular risk and available risk mitigation strategies. The goal was the creation of tools for risk priority assessments taking into account the probability of the occurrence of an adverse cardiovascular event and available and published literature from spaceflight data as well as available risk mitigation strategies. An international group of scientists convened in Bellagio, Italy, in 2004 under the auspices of the Aerospace Medical Association to review available literature for cardiac risks identified in the Bioastronautics Critical Path Roadmap (versions 2000, 2004). This effort led to the creation of a priority assessment framework to allow for an objective assessment of the hazard, probability of its occurrence, mission impact, and available risk mitigation measures. Spaceflight data are presented regarding evidence/ no evidence of cardiac dysrhythmias, cardiovascular disease, and cardiac function as well as orthostatic intolerance, exercise capacity, and peripheral resistance in presyncopal astronauts compared to non-presyncopal astronauts. Assessment of the priority of different countermeasures was achieved with a tabular framework with focus on probability of occurrence, mission impact, compliance, practicality, and effectiveness of countermeasures. Special operational settings and circumstances related to sensitive portions of any mission and the impact of environmental influences on mission effectiveness are addressed. The need for development of diagnostic tools, techniques, and countermeasure devices, food preparation, preservation technologies and medication, as well as an infrastructure to support these operations are stressed. Selected countermeasure options, including artificial gravity and pharmacological countermeasures need to be systematically evaluated and validated in flight, especially after long-duration exposures. Data need to be collected regarding the emerging field of suborbital and orbital civilian space travel, to allow for sound risk assessment.


Multiplex sequencing of 1.5 Mb of the Mycobacterium leprae genome.
The nucleotide sequence of 1.5 Mb of genomic DNA from Mycobacterium leprae was determined using computer-assisted multiplex sequencing technology. This brings the 2.8-Mb M. leprae genome sequence to approximately 66% completion. The sequences, derived from 43 recombinant cosmids, contain 1046 putative protein-coding genes, 44 repetitive regions, 3 tRNAs, and 15 tRNAs. The gene density of one per 1.4 kb is slightly lower than that of Mycoplasma (1.2 kb). Of the protein coding genes, 44% have significant matches to genes with well-defined functions. Comparison of 1157 M. leprae and 1564 Mycobacterium tuberculosis proteins shows a complex mosaic of homologous genomic blocks with up to 22 adjacent proteins in conserved map order. Matches to known enzymatic, antigenic, membrane, cell wall, cell division, multidrug resistance, and virulence proteins suggest therapeutic and vaccine targets. Unusual features of the M. leprae genome include large polyketide synthase (pks) operons, inteins, and highly fragmented pseudogenes.


Viral and atypical bacterial etiology of acute respiratory infections in children under 5 years old living in a rural tropical area of Madagascar.
In Madagascar, very little is known about the etiology and prevalence of acute respiratory infections (ARIs) in a rural tropical area. Recent data are needed to determine the viral and atypical bacterial etiologies in children with defined clinical manifestations of ARIs. During one year, we conducted a prospective study on ARIs in children between 2 to 59 months in the community hospital of Ampasimanjeva, located in the south-east of Madagascar. Respiratory samples were analyzed by multiplex real-time RT-PCR, including 18 viruses and 2 atypical bacteria. The various episodes of ARI were grouped into four clinical manifestations with well-documented diagnosis: "Community Acquired Pneumonia"(CAP, group I), "Other acute lower respiratory infections (Other ALRIs, group II)", "Upper respiratory tract infections with cough (URTIs with cough, group III)"and "Upper respiratory tract infections without cough (URTIs without cough, group IV)". 295 children were included in the study between February 2010 and February 2011. Viruses and/or atypical bacteria respiratory pathogens were detected in 74.6% of samples, the rate of co-infection was 27.3%. Human rhinovirus (HRV; 20.5%), metapneumovirus (HMPV A/B, 13.8%), coronaviruses (HCoV, 12.5%), parainfluenza virus (HPIV, 11.8%) and respiratory syncytial virus A and B (RSV A/B, 11.8%) were the most detected. HRV was predominantly single detected (23.8%) in all the clinical groups while HMPV A/B (23.9%) was mainly related to CAP (group I), HPIV (17.3%) to the "Other ALRIs" (group II), RSV A/B (19.5%) predominated in the group "URTIs with cough" (group III) and Adenovirus (HAdV, 17.8%) was mainly detected in the "without cough" (group IV). This study describes for the first time the etiology of respiratory infections in febrile children under 5 years in a malaria rural area of Madagascar and highlights the role of respiratory viruses in a well clinically defined population of ARIs.


Enhanced energy metabolism contributes to the extended life span of calorie-restricted Caenorhabditis elegans.
Caloric restriction (CR) markedly extends life span and improves the health of a broad number of species. Energy metabolism fundamentally contributes to the beneficial effects of CR, but the underlying mechanisms that are responsible for this effect remain enigmatic. A multidisciplinary approach that involves quantitative proteomics, immunochemistry, metabolic quantification, and life span analysis was used to determine how CR, which occurs in the Caenorhabditis elegans eat-2 mutants, modifies energy metabolism of the worm, and whether the observed modifications contribute to the CR-mediated physiological responses. A switch to fatty acid metabolism as an energy source and an enhanced rate of energy metabolism by eat-2 mutant nematodes were detected. Life span analyses validated the important role of these previously unknown alterations of energy metabolism in the CR-mediated longevity of nematodes. As observed in mice, the overexpression of the gene for the nematode analog of the cytosolic form of phosphoenolpyruvate carboxykinase caused a marked extension of the life span in C. elegans, presumably by enhancing energy metabolism via an altered rate of cataplerosis of tricarboxylic acid cycle anions. We conclude that an increase, not a decrease in fuel consumption, via an accelerated oxidation of fuels in the TCA cycle is involved in life span regulation; this mechanism may be conserved across phylogeny.


Short-term clinical outcomes and long-term survival of minimally invasive direct coronary artery bypass grafting.
Minimally invasive direct coronary artery bypass (MIDCAB) grafting is regarded as an alternative to conventional coronary artery bypass grafting (CABG) through full sternotomy, particularly for patients with isolated proximal left anterior descending (LAD) artery stenosis deemed unsuitable for percutaneous coronary intervention. However, the technically demanding nature of the procedure and lack of long-term published outcomes have precluded its universal adoption. We report the comparative short-term outcomes and long-term survival of MIDCAB and conventional CABG through full sternotomy for grafting of isolated LAD. From February 1996 to October 2017, a total of 668 patients underwent MIDCAB (n=508) and full sternotomy (n=160) CABG for isolated proximal LAD stenosis. Their data were prospectively entered into the institutional cardiac surgery database (Patients Analysis & Tracking System; Dendrite Clinical Systems, Ltd, Oxford, England, United Kingdom) and analyzed retrospectively. Information on patient deaths was obtained from the institutional database and the National General Register Office for all patients. The two groups were comparable with respect to preoperative demographics and risk profile. MIDCAB was associated with longer operative time (177±32 versus 141±12 min; P=0.003). The two groups did not significantly differ with regard to other complications including operative mortality. At a mean follow-up of 12.95±0.47 years, survival was also similar. This large single centre study with longest follow-up validates the status of MIDCAB as an effective strategy for grafting of LAD. However, it fails to show superiority of the minimally invasive approach compared to conventional CABG through full sternotomy.


Lumbar spine stability for subjects with and without low back pain during one-leg standing test.
An experimental design comparing kinematic changes in the lumbar spine axis in subjects with and without low back pain (LBP) while standing on one leg with and without visual feedback. The purpose of this study was to evaluate the lumbar stability index, which includes relative holding time (RHT) and relative standstill time (RST), in subjects with and without LBP. Even though a number of studies have evaluated postural adjustments based on kinematic changes in subjects with LBP, lumbar spine stability has not been examined for abnormal postural responses with visual feedback. All participants were asked to maintain the stork test position (standing on one leg with the contra lateral hip flexed 90 degrees) for 25 seconds. The outcome measures included RHT and RST for the axes of the core spine and lumbar spine. Independent t tests were used to compare the differences between groups. Two-way repeated measure analysis of variance was used to compare the differences for both axes. The age variable was used as a covariate to control confounding effects for the data analyses. The RHT was longer for the lumbar spine axis in subjects without LBP than those with LBP, especially without visual feedback. There was also significant interaction in RST between subjects with and without LBP (F = 7.18, P = 0.01). For the core axis of the trunk, significant differences existed based on the main effect of side (F = 9.07, P = 0.004), trunk rotation (F = 24.30, P = 0.001), and both of these interactions (F = 8.93, P = 0.004). However, there was a lack of significant interaction with age for the lumbar and core spine axes (F = 0.06, P = 0.81). Although the control group included slightly younger volunteers compared with the LBP group, the stability index of the core spine significantly decreased in RHT and RST, especially when visual feedback was blocked for subjects with LBP. The interaction between visual feedback and trunk rotation indicated that core spine stability is critical in coordinating balance control. A trunk muscle imbalance may contribute to unbalanced postural activity, which could prompt a decreased, uncoordinated bracing effect in subjects with LBP. As a result, core spine training could be used in the prevention of postural instability in such subjects.


Measurement of the t-channel single top quark production cross section in pp collisions at √s=7 TeV.
Electroweak production of the top quark is measured for the first time in pp collisions at √=7 TeV, using a data set collected with the CMS detector at the LHC and corresponding to an integrated luminosity of 36 pb⁻¹. With an event selection optimized for t-channel production, two complementary analyses are performed. The first one exploits the special angular properties of the signal, together with background estimates from the data. The second approach uses a multivariate analysis technique to probe the compatibility with signal topology expected from electroweak top-quark production. The combined measurement of the cross section is 83.6±29.8(stat+syst)±3.3(lumi) pb, consistent with the standard model expectation.


Physiologic Specialization of Puccinia triticina on Wheat in the United States in 2011.
Collections of Puccinia triticina were obtained from rust-infected leaves provided by cooperators throughout the United States and from wheat fields and breeding plots by USDA-ARS personnel and cooperators in the Great Plains, Ohio River Valley, southeastern states, Oregon, and Washington State in order to determine the virulence of the wheat leaf rust population in 2011. Single uredinial isolates (440 total) were derived from the collections and tested for virulence phenotype on 18 lines of Thatcher wheat and a winter wheat line that are near-isogenic for 19 leaf rust resistance genes. In 2011, 87 virulence phenotypes were described in the United States. Virulence phenotypes TBBGJ, MLDSD, and TCRKG were the three most common phenotypes. Phenotype TBBGJ is virulent to Lr39/41 and was widely distributed throughout the hard red winter wheat region of the Great Plains. Phenotype MLDSD is virulent to Lr17 and Lr39/41 and was widely distributed throughout the United States. Phenotype TCRKG is virulent to Lr11, Lr18, and Lr26 and was found mostly in the soft red winter wheat region in the eastern United States. Isolates with virulence to Lr39/41 and avirulence to Lr9 were prevalent in the Great Plains region for the first time. Virulence to Lr21 was present in five virulence phenotypes mostly from the spring wheat region of the northern Great Plains.


Crossing diagnostic borders: herpes encephalitis complicated by cultural and language barriers.
The patient who complains of vague mental status changes requires extra vigilance in that the underlying condition might itself affect the patient's ability to communicate well and relate a medical history. The differential diagnosis of delirium is broad, ranging from the benign to the potentially fatal. The diagnostic uncertainty inherent in primary care is compounded when language and cultural differences interfere with physician-patient communication. We undertook a MEDLINE-assisted review of the medical literature concerning herpes simplex encephalitis. Additionally, we performed an Internet search of several government Web sites to find current legal and federal guidelines concerning the use of medical interpreters. We recount the case of a young Eastern European immigrant who complained initially of vague mental status changes and was found to have herpes simplex encephalitis. Diagnosis could have been made sooner had the physician been familiar with the patient's baseline mental status or had cultural and language barriers not stood between the physician and the patient and his mother. Herpes simplex encephalitis is a rare, but specific, cause of delirium for which prompt diagnosis and treatment with intravenous acyclovir can prevent death or serious sequelae.


Physicochemical, antioxidant, calcium binding, and angiotensin converting enzyme inhibitory properties of hydrolyzed tomato seed proteins.
The objective of this was to determine the impact of enzymatic hydrolysis on the multifunctionality of tomato seed protein hydrolysates (TSPH) and their physicochemical properties. The enzymatic hydrolysis was performed using alcalase and two factors response surface methodology. The best conditions were 131.4 min and 3% enzyme/substrate (E/S) for antioxidant activity; 174.5 min and 2.93% E/S for angiotensin-converting enzyme (ACE) inhibition; and 66.79 min and 2.27% E/S for the calcium binding. Antioxidant and ACE hydrolysates were characterized by higher solubility, zeta potential, and thermal stability while properties of the calcium binding hydrolysate were only minimally affected by the enzymatic hydrolysis. Gel electrophoresis showed that molecular weights of polypeptides in the calcium binding TSPH were higher compared to those in ACE and antioxidant TSPHs. This was due to the low degree of hydrolysis of the calcium binding hydrolysate. PRACTICAL APPLICATIONS: Nowadays, different protein sources are used to produce protein hydrolysates containing bioactive peptides that can help alleviate oxidation of foods, oxidative stress, and chronic conditions (e.g., hypertension, diabetes, cardiovascular disorder). Hydrolyzed proteins also have the potential to increase mineral absorption through the formation of mineral-binding complexes. Biological activities of proteins and peptides from tomato processing byproduct (i.e., pomace) have received until now little attention. The determination of physicochemical properties and biological activities of the hydrolyzed proteins has application in the formulation of value-added food products for the reduction of oxidative stress and risks of developing chronic diseases. In addition, there will be a reduction of pomace waste generated by the tomato processing industry.


Variable-region-identical antibodies differing in isotype demonstrate differences in fine specificity and idiotype.
A central tenet of the current understanding of the relationship between Ab structure and function is that the variable region domain is solely responsible for Ag specificity. However, this view was recently challenged by the observation that families of mouse-human chimeric Abs with identical V regions demonstrate differences in fine specificity and by reports of changes in Ab Id structure with isotype switching. Here we revisited this question by evaluating the reactivity of two families of murine IgG switch variants that differed in V region usage for Cryptococcus neoformans glucuronoxylomannan, glucuronoxylomannan peptide mimetics, and anti-Id mAbs. The results reveal isotype-related differences in fine specificities and Id for two mAb isotype switched families, thus establishing the validity of this observation with sets of homologous Abs. The results suggest that the C region affects V region protein conformation, leading to differences in fine specificity and Id. The finding that isotype can affect fine specificity has major implications for current concepts of the generation of secondary responses, idiotypic network regulation, and isotype function. Given that isotype class switching and Ig gene somatic hypermutation share molecular mechanisms, these observations unify these processes in the sense that both can alter specificity and affinity.


Vitamin C supplementation reduces the odds of developing a common cold in Republic of Korea Army recruits: randomised controlled trial.
The Republic of Korea (ROK) military has a high incidence of respiratory diseases at training centres. Vitamin C has been reported to reduce the incidence of colds. For the purpose of preventing soldiers' respiratory diseases, this study aimed to investigate whether vitamin C intake can prevent common colds in the ROK Army soldiers. This was a randomised, placebo-controlled, and double-blind trial of soldiers who enlisted in the Korea Army Training Centre for 30 days from 12 February to 13 March 2018. The study participants were divided into groups (vitamin C vs placebo). The military medical records were searched to determine whether the participants had a common cold. Multiple logistic regression analysis was performed to identify the association between vitamin C intake and diagnosis of common colds. In addition, subgroup analysis on the relationship between vitamin C intake and common cold according to smoking status, training camp and physical rank was conducted. A total of 1444 participants were included in our study. Of these participants, 695 received vitamin C (6000 mg/day, vitamin C group), while 749 participants received placebo (0 mg/day, placebo group). The vitamin C group had a 0.80-fold lower risk of getting a common cold than did the placebo group. Subgroup analyses showed that this effect was stronger among subjects in camp A, among never smokers and among those in physical rank 3. Vitamin C intake provides evidence to suggest that reducing the common colds in Korean Army soldiers. Our results may serve as a basis for introducing military healthcare policies that can provide vitamin C supplementation for military personnel in basic military training.