Inositol 1, 4, 5-trisphosphate-dependent nuclear calcium signals regulate angiogenesis and cell motility in triple negative breast cancer.
Increases in nuclear calcium concentration generate specific biological outcomes that differ from those resulting from increased cytoplasmic calcium. Nuclear calcium effects on tumor cell proliferation are widely appreciated; nevertheless, its involvement in other steps of tumor progression is not well understood. Therefore, we evaluated whether nuclear calcium is essential in other additional stages of tumor progression, including key steps associated with the formation of the primary tumor or with the metastatic cascade. We found that nuclear calcium buffering impaired 4T1 triple negative breast cancer growth not just by decreasing tumor cell proliferation, but also by enhancing tumor necrosis. Moreover, nuclear calcium regulates tumor angiogenesis through a mechanism that involves the upregulation of the anti-angiogenic C-X-C motif chemokine 10 (CXCL10-IP10). In addition, nuclear calcium buffering regulates breast tumor cell motility, culminating in less cell invasion, likely due to enhanced vinculin expression, a focal adhesion structural protein. Together, our results show that nuclear calcium is essential for triple breast cancer angiogenesis and cell migration and can be considered as a promising strategic target for triple negative breast cancer therapy.


Mass spectrometry based proteomics in the diagnosis of kidney disease.
Laser microdissection (LMD) and mass spectrometry (MS) is a new technique that consists of dissection of glomeruli, tryptic digestion of dissected material, analysis by MS and generation of a protein profile using different algorithms. The review focuses on the use of this methodology as an ancillary technique in a clinical laboratory for the diagnosis of kidney diseases. LMD/MS is used in the diagnosis and typing of kidney diseases with organized deposits such as amyloidosis. Uncommon and familial forms of renal amyloidosis are diagnosed and typed on the basis of the presence of specific amyloidogenic proteins. LMD/MS is used to confirm and identify immunoglobulins and complement factors in immune complex mediated and complement-mediated proliferative glomerulonephritis, respectively. In particular, LMD/MS can detect monoclonal immunoglobulins in cases of equivocal immunofluorescence studies in monoclonal immunoglobulins-associated glomerulonephritis. LMD/MS can detect specific complement factors of the alternative pathway and terminal pathway in complement-mediated glomerulonephritis. LMD/MS is currently used for diagnosis and typing of amyloidosis. In addition, LMD/MS is useful in determining the type of immunoglobulins and complement factors in immune complex and complement-mediated glomerulonephritis, respectively.


Chemistry of rocks and soils at Meridiani Planum from the Alpha Particle X-ray Spectrometer.
The Alpha Particle X-ray Spectrometer on the Opportunity rover determined major and minor elements of soils and rocks in Meridiani Planum. Chemical compositions differentiate between basaltic rocks, evaporite-rich rocks, basaltic soils, and hematite-rich soils. Although soils are compositionally similar to those at previous landing sites, differences in iron and some minor element concentrations signify the addition of local components. Rocky outcrops are rich in sulfur and variably enriched in bromine relative to chlorine. The interaction with water in the past is indicated by the chemical features in rocks and soils at this site.


A model for personalized in vivo analysis of human immune responsiveness.
Studies of human immune diseases are generally limited to the analysis of peripheral blood lymphocytes of heterogeneous patient populations. Improved models are needed to allow analysis of fundamental immunologic abnormalities predisposing to disease and in which to assess immunotherapies. Immunodeficient mice receiving human fetal thymus grafts and fetal CD34(+) cells intravenously produce robust human immune systems, allowing analysis of human T cell development and function. However, to use humanized mice to study human immune-mediated disorders, immune systems must be generated from adult hematopoietic cells. Here, we demonstrated robust immune reconstitution in mice with hematopoietic stem cells (HSCs) aspirated from bone marrow of adults with type 1 diabetes (T1D) and healthy control volunteers. In these humanized mice, cryopreservation of human leukocyte antigen allele-matched fetal thymic tissue prevented allogeneic adult HSC rejection. Newly generated T cells, which included regulatory T cells (T(regs)), were functional and self-tolerant and had a diverse repertoire. The immune recognition of these mice mimicked that of the adult CD34(+) cell donor, but the T cell phenotypes were more predominantly "naïve" than those of the adult donors. HSCs from T1D and control donors generated similar numbers of natural T(regs) intrathymically; however, peripheral T cells from T1D subjects showed increased proportions of activated or memory cells compared to controls, suggesting possible HSC-intrinsic differences in T cell homeostasis that might underlie immune pathology in T1D. This "personalized immune" mouse provides a new model for individualized analysis of human immune responses that may provide new insights into not only T1D but also other forms of immune function and dysfunction as well.


Large-scale association analysis identifies new risk loci for coronary artery disease.
Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.


Leukocyte telomere length-related rs621559 and rs398652 genetic variants influence risk of HBV-related hepatocellular carcinoma.
Recent genome-wide association studies (GWAS) have identified eleven leukocyte telomere length (LTL)-related single nucleotide polymorphisms (SNPs). Since LTL has been associated with risk of many malignancies, LTL-related SNPs may contribute to cancer susceptibility. To test this hypothesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we genotyped these eleven LTL-related SNPs in a case-control set including 1186 HBV-related HCC cases, 508 chronic HBV carriers and 1308 healthy controls at the discovery stage. The associations of HCC risk with these SNPs were further confirmed in an independent case-control set. We found that 1p34.2 rs621559 and 14q21 rs398652 were significantly associated with HBV-related HCC risk (both P<0.005 after Bonferroni corrections). There was no significant difference of either rs621559 or rs398652 genotypes between chronic HBV carriers and healthy controls, demonstrating that the association was not due to predisposition to HBV infection. In the pooled analyses (1806 HBV-related HCC cases and 1954 controls), we observed a decreased HCC risk, 0.72-times, associated with the 1p34.2 rs621559 AA genotype compared to the GG genotype (P = 1.6×10(-6)). Additionally, there was an increased HCC risk, 1.27-fold, associated with the rs398652 GG genotype (P = 3.3×10(-6)). A statistical joint effect between the rs621559 GG and rs398652 GG genotypes may exist in elevating risk of HBV-related HCC. We show, for the first time, that rs398652 and rs621559 might be marker genetic variants for risk of HBV-related HCC in the Chinese population.


Characterization of 954 bovine full-CDS cDNA sequences.
Genome assemblies rely on the existence of transcript sequence to stitch together contigs, verify assembly of whole genome shotgun reads, and annotate genes. Functional genomics studies also rely on transcript sequence to create expression microarrays or interpret digital tag data produced by methods such as Serial Analysis of Gene Expression (SAGE). Transcript sequence can be predicted based on reconstruction from overlapping expressed sequence tags (EST) that are obtained by single-pass sequencing of random cDNA clones, but these reconstructions are prone to errors caused by alternative splice forms, transcripts from gene families with related sequences, and expressed pseudogenes. These errors confound genome assembly and annotation. The most useful transcript sequences are derived by complete insert sequencing of clones containing the entire length, or at least the full protein coding sequence (CDS) portion, of the source mRNA. While the bovine genome sequencing initiative is nearing completion, there is currently a paucity of bovine full-CDS mRNA and protein sequence data to support bovine genome assembly and functional genomics studies. Consequently, the production of high-quality bovine full-CDS cDNA sequences will enhance the bovine genome assembly and functional studies of bovine genes and gene products. The goal of this investigation was to identify and characterize the full-CDS sequences of bovine transcripts from clones identified in non-full-length enriched cDNA libraries. In contrast to several recent full-length cDNA investigations, these full-CDS cDNAs were selected, sequenced, and annotated without the benefit of the target organism's genomic sequence, by using comparison of bovine EST sequence to existing human mRNA to identify likely full-CDS clones for full-length insert cDNA (FLIC) sequencing. The predicted bovine protein lengths, 5' UTR lengths, and Kozak consensus sequences from 954 bovine FLIC sequences (bFLICs; average length 1713 nt, representing 762 distinct loci) are all consistent with previously sequenced mammalian full-length transcripts. In most cases, the bFLICs span the entire CDS of the genes, providing the basis for creating predicted bovine protein sequences to support proteomics and comparative evolutionary research as well as functional genomics and genome annotation. The results demonstrate the utility of the comparative approach in obtaining predicted protein sequences in other species.


The influence of excipients on the diffusion of ibuprofen and paracetamol in gastric mucus.
The aim of this study was to examine the diffusion of commonly administered analgesics, ibuprofen and paracetamol, through gastric mucus. As ibuprofen and paracetamol are often formulated with alkalising excipients, or are commonly co-administered with antacids that have been demonstrated to alter their absorption, diffusion was also studied in the presence of a range of soluble and insoluble antacids or buffering agents. The effect of pH, which has been demonstrated to modify the properties of mucus, was also studied. Mucus was a significant barrier to diffusion for both drugs, compared to an unstirred aqueous layer with diffusion rates significantly lower in the presence of a mucus barrier for both drugs; ibuprofen diffusion also demonstrated a significant increase in the lag time. Paracetamol diffusion was not significantly affected by addition of any antacid, whereas ibuprofen rates were affected and the diffusion lag time for ibuprofen was significantly reduced in all cases. Isolated increases in pH increased the rate and reduced the lag time for ibuprofen diffusion. It was shown that mucus acts as a passive barrier in the case of paracetamol diffusion, and an interactive barrier to ibuprofen diffusion. Changes in mucus viscosity at different pH values may be responsible for the observed changes in ibuprofen diffusion rate.


Ethical issues in using the internet to engage participants in family and child research: A scoping review.
The internet is an increasingly popular tool in family and child research that is argued to pose new ethical challenges, yet few studies have systematically assessed the ethical issues of engaging parents and children in research online. This scoping review aims to identify and integrate evidence on the ethical issues reported when recruiting, retaining and tracing families and children in research online, and to identify ethical guidelines for internet research. Academic literature was searched using electronic academic databases (Scopus, PsycINFO, Embase, ERIC, CINAHL and Informit) and handsearching reference lists for articles published in English between January 2006 and February 2016. Grey literature was searched using Google to identify relevant ethical guidelines. Sixty-five academic articles were included after screening 3,537 titles and abstracts and 205 full-text articles. Most articles reported using the internet to recruit participants (88%) with few reporting online retention (12%) or tracing (10%). Forty percent commented on ethical issues; the majority did not discuss ethics beyond general consent or approval procedures. Some ethical concerns were specific to engaging minors online, including parental consent, age verification and children's vulnerability. Other concerns applied when engaging any research participant online, including privacy and confidentiality, informed consent and disparities in internet access. Five professional guidelines and 10 university guidelines on internet research ethics were identified. Few academic articles (5%) reported using these guidelines. Engaging families and children in research online introduces unique challenges requiring careful consideration. While researchers regarded themselves as responsible for ensuring research is conducted ethically, lack of use of available guidelines and limited academic literature suggests internet research is occurring without suitable guidance. We recommend broad dissemination of ethical guidelines and encourage researchers to report the methodological and ethical issues of using the internet to engage families and children in research.


Hookworm Infection: A Neglected Cause of Overt Obscure Gastrointestinal Bleeding.
Hookworm infections are widely prevalent in tropical and subtropical areas, especially in low income regions. In the body, hookworms parasitize the proximal small intestine, leading to chronic intestinal hemorrhage and iron deficiency anemia. Occasionally, hookworms can cause overt gastrointestinal bleeding, but this is often ignored in heavily burdened individuals from endemic infectious areas. A total of 424 patients with overt obscure gastrointestinal bleeding were diagnosed by numerous blood tests or stool examinations as well as esophagogastroduodenoscopy, colonoscopy, capsule endoscopy or double-balloon enteroscopy. All of the patients lived in hookworm endemic areas and were not screened for hookworm infection using sensitive tests before the final diagnosis. The patients recovered after albendazole treatment, blood transfusion, and iron replacement, and none of the patients experienced recurrent bleeding in the follow-up. All the 31 patients were diagnosed with hookworm infections without other concomitant bleeding lesions, a rate of 7.3% (31/424). Seventeen out of 227 patients were diagnosed with hookworm infections in the capsule endoscopy (CE), and 14 out of 197 patients were diagnosed with hookworm infections in the double balloon enteroscopy (DBE). Hookworm infections can cause overt gastrointestinal bleeding and should be screened in patients with overt obscure gastrointestinal bleeding (OGIB) in endemic infectious areas with sensitive methods. Specifically, the examination of stool specimens is clinically warranted for most patients, and the proper examination for stool eggs relies on staff's communication.


Scalp acupuncture effect on language development in children with autism: a pilot study.
Autism is a neurodevelopmental disorder that manifests in delays in social interaction, language used in social communication, and symbolic or imaginative play, with an onset prior to age 3 years. Language therapy (LT) for children with autism is the main form of rehabilitation, because it emphasizes its major presenting symptom (i.e., language impairment). Scalp acupuncture (scalp AP) is a modality based on the physiologic function of different brain areas, where different scalp zones are stimulated with needles so as to stimulate the reflexively related nervous tissue. This study aimed to evaluate the role of scalp AP as a complementary modality to LT in rehabilitation of children with autism. The study involved 20 children (divided into 2 equal groups: A and B), diagnosed as autistic according to DSM IV classification. Their ages ranged between 4 and 7 years old. All subjects underwent LT twice weekly, aiming at stimulation of cognitive and verbal abilities. Group B only was subjected to scalp AP sessions--twice weekly--as a rehabilitation complementary tool during the 9-month period of the study. The acupoints used were: Du 20, 26, GV17; three temple needles; and Yamamoto's New Scalp Acupuncture cerebrum and aphasia points (acupuncture needles 0.3 x 30 mm). A language test was performed before and after therapy to monitor cognition and expression (an Arabic test was included). Both groups, whose mean age range was 5.5 years+/-1.22 years, showed a significant improvement in cognitive and expressive language skills pre- and post-therapy, which was highly significant among group B children treated with scalp AP (attention 2.8+/-0.8 in group A versus 3.5+/-0.8 in group B; receptive semantics were 7+/-3.8 in group A versus 9.4+/-3.1 in group B). Expressive semantics significantly improved in both groups. Scalp AP is a safe complementary modality when combined with LT and has a significantly positive effect on language development in children with autism.


Statistical attribution analysis of the nonstationarity of the annual runoff series of the Weihe River.
Time-varying moments models based on Pearson Type III and normal distributions respectively are built under the generalized additive model in location, scale and shape (GAMLSS) framework to analyze the nonstationarity of the annual runoff series of the Weihe River, the largest tributary of the Yellow River. The detection of nonstationarities in hydrological time series (annual runoff, precipitation and temperature) from 1960 to 2009 is carried out using a GAMLSS model, and then the covariate analysis for the annual runoff series is implemented with GAMLSS. Finally, the attribution of each covariate to the nonstationarity of annual runoff is analyzed quantitatively. The results demonstrate that (1) obvious change-points exist in all three hydrological series, (2) precipitation, temperature and irrigated area are all significant covariates of the annual runoff series, and (3) temperature increase plays the main role in leading to the reduction of the annual runoff series in the study basin, followed by the decrease of precipitation and the increase of irrigated area.


Screening and risk assessment for coronary artery disease in HIV infection: an unmet need.
HIV infection is now considered a chronic, treatable disease, although treatment is associated with increased rates of coronary artery disease (CAD). Increased risk of CAD in HIV-infected patients has been associated with the inflammatory sequelae of the infection as well as the greater prevalence of cardiac risk factors in HIV-positive populations and the side effects of life-prolonging antiretroviral therapies. Patients with HIV infection now have a 1.5 to 2-fold greater risk of developing CAD compared with noninfected individuals, raising the independent risk of CAD in HIV infection to levels similar to those in diabetes. Despite this increased risk, screening and other adjuvant assessment tools are lacking. In this paper we explore the current climate of CAD in the contemporary HIV-infected population and look at the tools used in the assessment and management of patients as well as the limitations of these approaches for this at-risk population group.


Prediction of gestational diabetes based on nationwide electronic health records.
Gestational diabetes mellitus (GDM) poses increased risk of short- and long-term complications for mother and offspring1-4. GDM is typically diagnosed at 24-28 weeks of gestation, but earlier detection is desirable as this may prevent or considerably reduce the risk of adverse pregnancy outcomes5,6. Here we used a machine-learning approach to predict GDM on retrospective data of 588,622 pregnancies in Israel for which comprehensive electronic health records were available. Our models predict GDM with high accuracy even at pregnancy initiation (area under the receiver operating curve (auROC) = 0.85), substantially outperforming a baseline risk score (auROC = 0.68). We validated our results on both a future validation set and a geographical validation set from the most populated city in Israel, Jerusalem, thereby emulating real-world performance. Interrogating our model, we uncovered previously unreported risk factors, including results of previous pregnancy glucose challenge tests. Finally, we devised a simpler model based on just nine questions that a patient could answer, with only a modest reduction in accuracy (auROC = 0.80). Overall, our models may allow early-stage intervention in high-risk women, as well as a cost-effective screening approach that could avoid the need for glucose tolerance tests by identifying low-risk women. Future prospective studies and studies on additional populations are needed to assess the real-world clinical utility of the model.


Strategies for improving outcomes in NSCLC: a look to the future.
Advances in the management of non-small cell lung cancer (NSCLC) over the past 30 years have led to small increases in 5-year survival rates across Europe, though further improvements may require new treatment strategies. In order to improve efficiency and reduce the cost of development, future trials for new targeted agents in NSCLC should aim to recruit patients on the basis of tumour biology rather than clinical characteristics. However, identification of predictive biomarkers is required to maximise the benefits of new approaches and expedite the drug development process. Nevertheless, the NSCLC landscape is changing rapidly, and recent improvements in our understanding of the molecular biology of the disease will help in the identification of novel targeted agents as well as assisting in the development of personalised strategies for the numerous small subsets of defined NSCLC. Progress in imaging and treatment delivery is also likely to improve outcomes for patients with the disease. This article outlines recent progress in the treatment of NSCLC, identifies current challenges and describes proposals for improving the future management of the disease. It is hoped that implementation of some of these strategies will go some way to improving the outlook for patients with NSCLC.


An Economic Perspective on Personality Traits and Alcohol Misuse: Evidence from the Health and Retirement Study.
Recent economic work suggests a role for personality traits in determining socioeconomic outcomes. Much of this work has considered labor market outcomes, human capital accumulation, and, to some extent, health outcomes. No economic studies have explored the role of the Big Five taxonomy in alcohol use and misuse. Given defining characteristics of the Big Five, they are plausibly linked with these outcomes. Alcohol misuse is associated with large social costs through healthcare costs, traffic fatalities, violence, and reduced labor market productivity. Thus, understanding risk factors for such use is warranted. To investigate the associations between the Big Five, and measures of alcohol use and alcohol misuse. We obtain data on older adults 50 years and older from the Health and Retirement Study (HRS). Our outcomes include one measure of use (any use) and two measures of misuse (heavy drinking and binge drinking). Comparing across different measures of alcohol consumption can shed light on whether the Big Five are related to moderate alcohol use that need not impose social costs or alcohol misuse that may indeed impose such costs. A randomly selected sub-set of respondents completed a self-administered questionnaire developed for the Midlife Development Inventory in either the 2006 or 2008 round of the HRS. We use information collected in this instrument to generate our independent variables of primary interest: agreeableness, openness, extraversion, neuroticism, and conscientiousness traits. We find that the Big Five personality traits are linked with measures of both alcohol use and alcohol misuse. We observe substantial heterogeneity in the associations by personality traits. Specifically, agreeableness is associated with increased risk for alcohol use/misuse while extraversion and openness are negatively associated with risk for these patterns of alcohol consumption. We find no evidence that neuroticism or contentiousness predict alcohol use and misuse. We identify heterogeneity in the associations across demographic characteristics. We find associations between the Big Five and our measures of alcohol use and alcohol misuse. Our findings are subject to several data limitations, however. Although the Big Five personality taxonomy is well utilized, it has known limitations. Even in a survey as rich as the HRS, it is likely that we are unable to control for all important variables leading to omitted variable bias. Because we focus on a sample of older adults, the generalizability of our findings to other demographic groups is not clear. Agreeableness is significantly associated with alcohol use and misuse, which could lead to greater utilization of healthcare services and thus increased costs to the healthcare system. Healthcare providers should consider aspects of personality when developing and communicating treatment options. Moreover, psychology and economic work documents that interventions can alter aspects of personality even among older adults. Further research on and implementation of effective interventions may be warranted. Future studies should examine the implications of personality for a broader range of outcomes. Survey administrators could consider including validated measures of personality in surveys to facilitate such research.


CDX-2 expression in malignant germ cell tumors of the testes, intratubular germ cell neoplasia, and normal seminiferous tubules.
CDX-2 is a caudal-type homeobox gene, encoding a transcription factor that plays an important role in proliferation and differentiation of intestinal epithelial cells. The utility of antibodies to CDX2 in the identification of adenocarcinomas of the gastrointestinal tract, particularly colorectal adenocarcinomas, in both primary and metastatic settings is well established. It is well-known that patients with testicular tumors may occasionally lack an obvious palpable mass. However, the expression of CDX2 in malignant germ cell tumors of the testes which have metastatic potential has not been previously studied in a large series. A tissue microarray was constructed from 52 malignant germ cell tumors of the testes including: 29 cases of classic seminoma, 8 cases of embryonal carcinoma, 8 cases of yolk sac tumor, 4 cases of malignant teratoma, 2 cases of choriocarcinoma, and 1 case of spermatocytic seminoma. Ten cases of intratubular germ cell neoplasia and seven cases of benign testicles with normal seminiferous tubules were also included in tissue microarray. Immunohistochemical stains for CDX2 was performed and analyzed. Only nuclear staining was considered positive. Positive expression of CDX2 was identified in 2/2 cases (100 %) of choriocarcinoma, 4/8 cases (50 %) of teratoma, 3/8 cases (38 %) of embryonal carcinoma, 3/8 cases (38 %) of yolk sac tumor, and 1/29 cases (3 %) of classic seminoma. CDX2 was negative in all cases of intratubular germ cell neoplasia, normal seminiferous tubules, and the only case of spermatocytic seminoma. The role of CDX-2 in the differentiation of intestinal/enteric epithelial cells may contribute to the formation of trophoblastic, glandular, villous, or cystic structures in germ cell tumors of the testes. This study suggests that the expression of CDX2 in a variety of malignant germ cell tumors of the testes may be a potential pitfall in metastatic tumors of unknown primary, which are thought to be of gastrointestinal/colorectal origin but are actually from a clinically occult testicular tumor.


Current use of equations for estimating glomerular filtration rate in Spanish laboratories.
In 2006 the Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC) and the Spanish Society of Nephrology (S.E.N.) developed a consensus document in order to facilitate the diagnosis and monitoring of chronic kidney disease with the incorporation of equations for estimating glomerular filtration rate (eGFR) into laboratory reports. The current national prevalence of eGFR reporting and the degree of adherence to these recommendations among clinical laboratories is unknown. We administered a national survey in 2010-11 to Spanish clinical laboratories. The survey was through e-mail or telephone to laboratories that participated in the SEQC's Programme for External Quality Assurance, included in the National Hospitals Catalogue 2010, including both primary care and private laboratories. A total of 281 laboratories answered to the survey. Of these, 88.2% reported on the eGFR, with 61.9% reporting on the MDRD equation and 31.6% using the MDRD-IDMS equation. A total of 42.5% of laboratories always reported serum creatinine values, and other variables only when specifically requested. Regarding the way results were presented, 46.2% of laboratories reported the exact numerical value only when the filtration rate was below 60mL/min/1.73m2, while 50.6% reported all values regardless. In 56.3% of the cases reporting eGFR, an interpretive commentary of it was enclosed. Although a high percentage of Spanish laboratories have added eGFR in their reports, this metric is not universally used. Moreover, some aspects, such as the equation used and the correct expression of eGFR results, should be improved.


Activity Limitation in Glaucoma: Objective Assessment by the Cambridge Glaucoma Visual Function Test.
We design and evaluate a computer-based objective simulation of activity limitation related to glaucoma. A cross-sectional study was performed involving 70 glaucoma patients and 14 controls. Mean age was 69.0 ± 10.2 years; 49 (58.3%) were male. The Cambridge Glaucoma Visual Function Test (CGVFT) was administered to all participants. Rasch analysis and criterion, convergent, and divergent validity tests assessed the psychometric properties of the CGVFT. Regression modeling was used to determine factors predictive of CGVFT person measures. Sociodemographic information, better and worse eye visual field parameters, visual acuity, contrast sensitivity, and the Rasch-analyzed Glaucoma Activity Limitation-9 (GAL-9) and Visual Function Questionnaire Utility Index (VFQUI) questionnaire responses were recorded. From 139 pilot CGVFT items, 59 had acceptable fit to the Rasch model, with acceptable precision (person separation index, 2.13) and targeting. Cambridge Glaucoma Visual Function Test person measure (logit) scores increased between controls (-0.20 ± 0.08) and patients with mild (-0.15 ± 0.08), moderate (-0.13 ± 0.10), and severe (-0.05 ± 0.10) glaucoma (P < 0.001, ANOVA) indicating good criterion validity. Correlation coefficients of 0.455 (P < 0.001) between CGVFT and GAL-9 person measures and 0.399 (P = 0.005) between CGVFT and VFQUI person measures demonstrated convergent validity. Divergent validity was suboptimal. On multivariable analysis, lower better eye mean deviation and greater age were associated with worsening CGVFT person measures (P ≤ 0.001). The CGVFT is a computerized visual challenge test administered to a cohort of glaucoma patients. It may benefit glaucoma patients, careers, health care providers, and policy makers, providing increased awareness of activity limitation due to glaucoma.


Mental representation: what can pitch tell us about the distance effect?
Reaction time (RT) profiles for comparing magnitudes (e.g., numbers, physical sizes) are similar - the larger the difference between the compared stimuli, the shorter the RT (distance effect). Nevertheless, it is unclear whether such correspondence is due to similar, two-dimensional, linear mental representations of magnitudes. In contrast, pitch perception has a more complex, two-dimensional, helical representation. This study examined whether comparisons of music pitches are similar to other magnitude response functions. Experiment 1 employed a comparison task, resulting in an RT profile identical to that obtained when comparing other magnitudes. In contrast, Experiment 2 employed a discrimination task, resulting in RTs that matched the helical representation and were dissociated from the classical distance effect. Experiment 3 replicated the results of Experiment 1 using a comparison task with different stimuli and intervals. These findings imply that the distance effect under comparison tasks might reflect a general sensorimotor transformation, rather than mental representation per se.


Randomized controlled trial of oral captopril, of oral isosorbide mononitrate and of intravenous magnesium sulphate started early in acute myocardial infarction: safety and haemodynamic effects. ISIS-4 (Fourth International Study of Infarct Survival) Pilot Study Investigators.
The purpose of this randomized controlled study was to assess the haemodynamic effects, safety and tolerability in acute myocardial infarction (AMI) of one month of oral captopril, one month of oral isosorbide mononitrate and 24 h of intravenous magnesium. It was carried out in four United Kingdom and six Polish hospitals in consecutive phases: oral captopril vs oral mononitrate vs placebo were compared among 400 patients in a 'three-way' study; and then oral captopril vs placebo and oral mononitrate vs placebo were compared among 474 patients in '2 x 2' and '2 x 2 x 2' factorial studies (with 208 patients in the latter study also randomized between intravenous magnesium and open control). The factorial studies differed from the three-way study in that one group of patients was allocated both oral captopril and oral mononitrate, a higher maintenance dose of captopril was used (following the same initial dose), and once daily controlled-release mononitrate was used. In the three-way study, the mean of the lowest systolic blood pressures recorded during the first 4 h after randomization were (mmHg +/- standard error): 104 +/- 2 captopril vs 105 +/- 1 mononitrate vs 112 +/- 2 placebo (P < 0.001 for captopril or for mononitrate vs placebo), and in the factorial studies were 105 +/- 1 captopril vs 110 +/- 1 placebo (P < 0.01) and 106 +/- 1 mononitrate vs 108 +/- 1 placebo (NS). There was an excess of hypotension recorded among patients allocated active treatment (captopril > mononitrate > placebo) and there was a small, but significant, excess of cardiogenic shock with captopril compared with control in the factorial study. However, in these studies, neither captopril nor mononitrate were associated with any overall increase in the incidence of hypotension considered severe enough to lead to treatment being stopped. No other serious complications were observed, and compliance with study tablets at hospital discharge was not significantly different between the active and placebo groups. Patients allocated magnesium in the 2 x 2 x 2 factorial study had a slightly lower mean systolic blood pressure just after the initial 15 min bolus injection (126 +/- 2 magnesium vs 134 +/- 3 control; P < 0.05) but there were no significant differences during the subsequent 24 h maintenance infusion period. Apart from some facial flushing, magnesium did not appear to be associated with any complications.(ABSTRACT TRUNCATED AT 400 WORDS)


Direct measurement of cutaneous pressures generated by pressure garments.
Pressure garments are the mainstay of burn scar management despite limited scientific evidence. This study demonstrates a simple method of directly measuring the cutaneous pressures generated by a pressure garment. The results show pressure garments generate an increase in subdermal pressures in the range 9-90 mmHg depending on the anatomical site. Garments over soft sites generate pressures ranging from 9 to 33 mmHg. Over bony prominences the pressures range from 47 to 90 mmHg. This method is believed to be more representative of the pressures generated than the interpositional techniques that measure garment-skin interface pressure, as it avoids garment distortion, the interference effect of the measurement device (size, conformation, area) and directly measures subdermal pressures. The method should be useful for larger research projects on pressure therapy and also for clinical management of pressure garments in the treatment of hypertrophic scar.


Redefining the Economics of Geriatric Orthopedics.
The heath care system in the United States is in the midst of a transition, in large part to help accommodate an older and more medically complex population. Central to the current evolution is the reassessment of value based on the cost utility of a particular procedure compared to alternatives. The existing contribution of geriatric orthopedics to the societal burden of disease is substantial, and literature focusing on the economic value of treating elderly populations with musculoskeletal injuries is growing. A literature review of peer-reviewed publications and abstracts related to the cost-effectiveness of treating geriatric patients with orthopedic injuries was carried out. In our review, we demonstrate that while cost-utility studies generally demonstrate net society savings for most orthopedic procedures, geriatric populations often contribute to negative net society savings due to decreased working years and lower salaries while in the workforce. However, the incremental cost-effective ratio for operative intervention has been shown to be below the financial willingness to treat threshold for common procedures including joint replacement surgery of the knee (ICER US$8551), hip (ICER US$17 115), and shoulder (CE US$957) as well as for spinal procedures and repair of torn rotator cuffs (ICER US$12 024). We also discuss the current trends directed toward improving institutional value and highlight important complementary next steps to help overcome the growing demands of an older, more active society. The geriatric population places a significant burden on the health care system. However, studies have shown that treating this demographic for orthopedic-related injuries is cost effective and profitable for providers under certain scenarios.


Testing the perfectionism model of binge eating in mother-daughter dyads: a mixed longitudinal and daily diary study.
The perfectionism model of binge eating is an integrative model explaining why perfectionism is tied to binge eating. This study extended and tested this emerging model by proposing daughters' socially prescribed perfectionism (i.e., perceiving one's mother is harshly demanding perfection of oneself) and mothers' psychological control (i.e., a negative parenting style involving control and demandingness) contribute indirectly to daughters' binge eating by generating situations or experiences that trigger binge eating. These binge triggers include discrepancies (i.e., viewing oneself as falling short of one's mother's expectations), depressive affect (i.e., feeling miserable and sad), and dietary restraint (i.e., behaviors aimed at reduced caloric intake). This model was tested in 218 mother-daughter dyads studied using a mixed longitudinal and daily diary design. Daughters were undergraduate students. Results largely supported hypotheses, with bootstrapped tests of mediation suggesting daughters' socially prescribed perfectionism and mothers' psychological control contribute to binge eating through binge triggers. For undergraduate women who believe their mothers rigidly require them to be perfect and whose mothers are demanding and controlling, binge eating may provide a means of coping with or escaping from an unhealthy, unsatisfying mother-daughter relationship.


To Be or Not To Be…Toxic-Is RNA Association With TDP-43 Complexes Deleterious or Protective in Neurodegeneration?
TAR DNA binding protein (TDP-43) is a nucleic acid binding protein associated with insoluble cytoplasmic aggregates in several neurodegenerative disorders, including 97% of the ALS cases. In healthy individuals, TDP-43 is primarily localized to the nucleus; it can shuttle between the nucleus and the cytoplasm, and is involved in several aspects of RNA processing including transcription, splicing, RNA stability, transport, localization, stress granule (SG) formation, and translation. Upon stress, TDP-43 aggregates in the cytoplasm and associates with several types of RNA and protein assemblies, resulting in nuclear depletion of TDP-43. Under conditions of prolonged stress, cytoplasmic TDP-43 undergoes liquid-liquid phase separation (LLPS) and becomes less mobile. Evidence exists to support a scenario in which insoluble TDP-43 complexes sequester RNA and/or proteins causing disturbances in both ribostasis and proteostasis, which in turn contribute to neurodegeneration. However, the relationship between RNA binding and TDP-43 toxicity remains unclear. Recent studies provide conflicting views on the role of RNA in TDP-43 toxicity, with some finding RNA as a toxic factor whereby RNA binding contributes to TDP-43 toxicity, while others find RNA to be a protective factor that inhibits TDP-43 aggregation. Here we review and discuss these recent reports, which ultimately highlight the importance of understanding the heterogeneity of TDP-43 assemblies and collectively point to solubilizing TDP-43 as a potential therapeutic strategy.


Suicides and deaths of undetermined intent among veterinary professionals from 2003 through 2014.
To analyze data for death of veterinary professionals and veterinary students, with manner of death characterized as suicide or undetermined intent from 2003 through 2014. Death records for 202 veterinary professionals and veterinary students. Decedents employed as veterinarians, veterinary technicians or technologists, or veterinary assistants or laboratory animal caretakers and veterinary students who died by suicide or of undetermined intent were identified through retrospective review of National Violent Death Reporting System records. Standardized mortality ratios (SMRs) and 95% confidence intervals were calculated, and mechanisms and circumstances of death were compared among veterinary occupational groups. 197 veterinary professionals and 5 veterinary students had deaths by suicide or of undetermined intent. Among decedents employed at the time of death, SMRs for suicide of male and female veterinarians (1.6 and 2.4, respectively) and male and female veterinary technicians or technologists (5.0 and 2.3, respectively) were significantly greater than those for the general US population, whereas SMRs for suicide of male and female veterinary assistants or laboratory animal caretakers were not. Poisoning was the most common mechanism of death among veterinarians; the drug most commonly used was pentobarbital. For most (13/18) veterinarians who died of pentobarbital poisoning, the death-related injury occurred at home. When decedents with pentobarbital poisoning were excluded from analyses, SMRs for suicide of male and female veterinarians, but not veterinary technicians or technologists, did not differ significantly from results for the general population. Results suggested higher SMRs for suicide among veterinarians might be attributable to pentobarbital access. Improving administrative controls for pentobarbital might be a promising suicide prevention strategy among veterinarians; however, different strategies are likely needed for veterinary technicians or technologists.


Acute health impacts of airborne particles estimated from satellite remote sensing.
Satellite-based remote sensing provides a unique opportunity to monitor air quality from space at global, continental, national and regional scales. Most current research focused on developing empirical models using ground measurements of the ambient particulate. However, the application of satellite-based exposure assessment in environmental health is still limited, especially for acute effects, because the development of satellite PM(2.5) model depends on the availability of ground measurements. We tested the hypothesis that MODIS AOD (aerosol optical depth) exposure estimates, obtained from NASA satellites, are directly associated with daily health outcomes. Three independent healthcare databases were used: unscheduled outpatient visits, hospital admissions, and mortality collected in Beijing metropolitan area, China during 2006. We use generalized linear models to compare the short-term effects of air pollution assessed by ground monitoring (PM(10)) with adjustment of absolute humidity (AH) and AH-calibrated AOD. Across all databases we found that both AH-calibrated AOD and PM(10) (adjusted by AH) were consistently associated with elevated daily events on the current day and/or lag days for cardiovascular diseases, ischemic heart diseases, and COPD. The relative risks estimated by AH-calibrated AOD and PM(10) (adjusted by AH) were similar. Additionally, compared to ground PM(10), we found that AH-calibrated AOD had narrower confidence intervals for all models and was more robust in estimating the current day and lag day effects. Our preliminary findings suggested that, with proper adjustment of meteorological factors, satellite AOD can be used directly to estimate the acute health impacts of ambient particles without prior calibrating to the sparse ground monitoring networks.


The color of the surface of venus.
Multispectral images of the basaltic surface of Venus obtained by Venera 13 were processed to remove the effects of orange-colored incident radiation resulting from interactions with the thick Venusian atmosphere. At visible wavelengths the surface of Venus appears dark and without significant color. High-temperature laboratory reflectance spectra of basaltic materials indicate that these results are consistent with mineral assemblages bearing either ferric or ferrous iron. A high reflectance in the near-infrared region observed at neighboring Venera 9 and 10 sites, however, suggests that the basaltic surface material contains ferric minerals and thus may be relatively oxidized.


Adiabatic TOCSY MAS in liquids.
The effect of magic angle spinning (MAS) of liquids upon the performance of various isotropic mixing sequences is investigated. Although the mathematical formalism for isotropic mixing under MAS conditions is similar for both liquids and solids, the mechanism through which the coherence transfer is disturbed is different. In liquids, the use of sample spinning in the presence of both RF and magnetic-field inhomogeneities introduces a modulation of the effective field, which compromises the performance of the conventional mixing sequences. This effect is further amplified by supercycles, which normally improve the performance of the mixing and decoupling experiments. It is demonstrated that adiabatic mixing sequences are less susceptible to such modulations and perform considerably better in TOCSY MAS experiments. The best performance of TOCSY MAS is observed under the rotational resonance condition when the sample appears static in the nutation reference frame.


Autonomic nervous function during haemodialysis assessed by spectral analysis of heart-rate variability.
1. Short-term autonomic response to haemodialysis-induced hypovolaemia was studied in 30 patients undergoing chronic haemodialysis by analysing power spectra of heart-period variability. Patients were classified as haemodynamically stable (15 patients) and unstable (15 patients) according to their past history of cardiovascular collapse during the treatment. Blood volume, systolic arterial pressure and heart period were measured during sessions that ended without the occurrence of collapse. 2. No significant differences were observed when comparing blood volume, heart rate and arterial pressure of stable and unstable patients during the dialysis, and the two groups could not be distinguished merely on the basis of these haemodynamic parameters. Conversely, spectral analysis of beat-to-beat heart-period variability showed markedly different power patterns: in stable patients power was mainly in the low-frequency (LF) band (0.06-0.15 Hz), whereas in unstable patients it was mainly in the high-frequency (HF) band (0.15-0.4 Hz). 3. The efficiency of the autonomic response to hypovolaemia was evaluated by the ratio between the powers in the LF and HF bands. Stable patients exhibited an LF/HF power ratio systematically greater than unstable patients during the entire dialysis, and on the basis of this index the two groups were clearly separated. 4. Results obtained with spectral analysis lead us to conclude that reduced efficiency in the autonomic control of cardiovascular functions could be the main cause of the haemodynamic instability of patients prone to collapse.


Raman profiles of the stratum corneum define 3 filaggrin genotype-determined atopic dermatitis endophenotypes.
Filaggrin (FLG) has a central role in the pathogenesis of atopic dermatitis (AD). FLG is a complex repetitive gene; highly population-specific mutations and multiple rare mutations make routine genotyping complex. Furthermore, the mechanistic pathways through which mutations in FLG predispose to AD are unclear. We sought to determine whether specific Raman microspectroscopic natural moisturizing factor (NMF) signatures of the stratum corneum could be used as markers of FLG genotype in patients with moderate-to-severe AD. The composition and function of the stratum corneum in 132 well-characterized patients with moderate-to-severe AD were assessed by means of confocal Raman microspectroscopy and measurement of transepidermal water loss (TEWL). These parameters were compared with FLG genotype and clinical assessment. Three subpopulations closely corresponding with FLG genotype were identified by using Raman spectroscopy. The Raman signature of NMF discriminated between FLG-associated AD and non-FLG-associated AD (area under the curve, 0.94; 95% CI, 0.91-0.99). In addition, within the subset of FLG-associated AD, NMF distinguished between patients with 1 versus 2 mutations. Five novel FLG mutations were found on rescreening outlying patients with Raman signatures suggestive of undetected mutations (R3418X, G1138X, S1040X, 10085delC, and L2933X). TEWL did not associate with FLG genotype subgroups. Raman spectroscopy permits rapid and highly accurate stratification of FLG-associated AD. FLG mutations do not influence TEWL within established moderate-to-severe AD.


In situ analysis of sulfate-reducing bacteria related to Desulfocapsa thiozymogenes in the chemocline of meromictic Lake Cadagno (Switzerland).
Comparative sequence analysis of a 16S rRNA gene clone library from the chemocline of the meromictic Lake Cadagno (Switzerland) retrieved two clusters of sequences resembling sulfate-reducing bacteria within the family Desulfovibrionaceae. In situ hybridization showed that, similar to sulfate-reducing bacteria of the family Desulfobacteriaceae, bacteria of one cluster with similarity values to the closest cultured relatives of between 92.6 and 93.1% resembled free cells or cells loosely attached to other cells or debris. Bacteria of the second cluster closely related to Desulfocapsa thiozymogenes DSM7269 with similarity values between 97. 9 and 98.4% were generally associated with aggregates of different small-celled phototrophic sulfur bacteria, suggesting a potential interaction between the two groups of bacteria.


Colonization of Ireland: revisiting 'the pygmy shrew syndrome' using mitochondrial, Y chromosomal and microsatellite markers.
There is great uncertainty about how Ireland attained its current fauna and flora. Long-distance human-mediated colonization from southwestern Europe has been seen as a possible way that Ireland obtained many of its species; however, Britain has (surprisingly) been neglected as a source area for Ireland. The pygmy shrew has long been considered an illustrative model species, such that the uncertainty of the Irish colonization process has been dubbed 'the pygmy shrew syndrome'. Here, we used new genetic data consisting of 218 cytochrome (cyt) b sequences, 153 control region sequences, 17 Y-intron sequences and 335 microsatellite multilocus genotypes to distinguish between four possible hypotheses for the colonization of the British Isles, formulated in the context of previously published data. Cyt b sequences from western Europe were basal to those found in Ireland, but also to those found in the periphery of Britain and several offshore islands. Although the central cyt b haplotype in Ireland was found in northern Spain, we argue that it most likely occurred in Britain also, from where the pygmy shrew colonized Ireland as a human introduction during the Holocene. Y-intron and microsatellite data are consistent with this hypothesis, and the biological traits and distributional data of pygmy shrews argue against long-distance colonization from Spain. The compact starburst of the Irish cyt b expansion and the low genetic diversity across all markers strongly suggests a recent colonization. This detailed molecular study of the pygmy shrew provides a new perspective on an old colonization question.


High-speed optical DQPSK and FSK modulation using integrated Mach-Zehnder interferometers.
We investigated an integrated optical modulator consisting of two Mach-Zehnder interferometers. The modulator can generate optical signals in various types of modulation formats, which have advantages for long-haul transmission, optical labeling, etc. By using a fabricated versatile optical modulator having traveling-wave electrodes designed for high-speed signals, we demonstrated generation of optical 40Gb/s frequency-shift-keying signals, which can be demodulated by an optical filter. 80Gb/s optical differential quadrature-shift-keying modulation was also demonstrated, where 40Gb/s in-phase and quadrature data were, simultaneously, fed to the modulator.


Clinical and genetic study of hereditary spastic paraplegia in Canada.
To describe the clinical, genetic, and epidemiologic features of hereditary spastic paraplegia (HSP) in Canada and to determine which clinical, radiologic, and genetic factors determine functional outcomes for patients with HSP. We conducted a multicenter observational study of patients who met clinical criteria for the diagnosis of HSP in the provinces of Alberta, Ontario, and Quebec from 2012 to 2015. Characteristics of the participants were analyzed using descriptive statistics. The main outcome measure for a subset of the cohort (n = 48) was the Spastic Paraplegia Rating Scale. We also used the SPATAX-EUROSPA disability stage (disability score) to assess disability (n = 65). A total of 526 patients were identified with HSP across the country, and 150 patients had a confirmed genetic diagnosis. Mutations were identified in 15 different genes; the most common were SPAST (SPG4, 48%), ATL1 (SPG3A, 16%), SPG11 (8%), SPG7 (7%), and KIAA0196 (SPG8, 5%). The diagnosis of SPG4 was associated with older age at symptom onset (p = 0.0017). SPG4 and SPG3A were less associated with learning disabilities compared to other subtypes of HSP, and SPG11 was strongly associated with progressive cognitive deficits (odds ratio 87.75, 95% confidence interval 14.04-548.24, p < 0.0001). SPG3A was associated with better functional outcomes compared to other HSP subtypes (p = 0.04) on multivariate analysis. The strongest predictor of significant disability was abnormal brain MRI (p = 0.014). The most important predictors of disability in our HSP cohort were SPG11 mutations and abnormal brain MRI. Accurate molecular characterization of well-phenotyped cohorts and international collaboration are essential to establish the natural history of these rare neurodegenerative disorders.


[Ethical advice on the prevention of suicide in mental health care].
Professional carers are regularly confronted with clients who want to commit suicide. To develop ethical advice on the question how professional carers can provide ethically justified care that will prevent suicide. The research method combines ethical discussion with a review of the literature. results According to the ethical advice, suicide is a manifestation of an existential crisis and is determined partly by the client's pathology. Three values are at stake in the prevention of suicide: the inviolability of life, the autonomy of the client and the care relationship between carers and their client. In order to integrate these values it is advisable to give attention to the following points. The best prevention consists of good care and a good care relationship involving intensive counselling of the client with regard to existential questions. In this way carers can increase the client's freedom and responsibility. Sometimes, however, carers need to come to protective agreements with the client or impose coercive measures in order to restrict the client's freedom. Such preventive measures must be accompanied by care for the carers themselves and the client's next of kin. By means of the integrating value of the care relationship carers should try to achieve a reasonable balance between the inviolability of life and the autonomy of the client.


Relational pathways between socioeconomic position and cardiovascular risk in a multiethnic urban sample: complexities and their implications for improving health in economically disadvantaged populations.
The study was designed to provide evidence of a cascade effect linking socioeconomic position to anthropometric indicators of cardiovascular disease (CVD) risk through effects on psychosocial stress, psychological distress and health-related behaviours, and consider implications for disease prevention and health promotion. A cross-sectional stratified two-stage probability sample of occupied housing units in three areas of Detroit, Michigan, was used in the study. 919 adults aged > or =25 years completed the survey (mean age 46.3; 53% annual household income <$20 000; 57% non-Hispanic black, 22% Latino, 19% non-Hispanic white). Variables included self-report (eg, psychosocial stress, depressive symptoms, health behaviours) and anthropometric measurements (eg, waist circumference, height, weight). The main outcome variables were depressive symptoms, smoking status, physical activity, body mass index and waist circumference. Income was inversely associated with depressive symptoms, likelihood of current smoking, physical inactivity and waist circumference. These relationships were partly or fully mediated by psychosocial stress. A suppressor effect of current smoking on the relationship between depressive symptoms and waist circumference was found. Independent effects of psychosocial stress and psychological distress on current smoking and waist circumference were found, above and beyond the mediated pathways. The results suggest that relatively modest improvements in the income of economically disadvantaged people can set in motion a cascade of effects, simultaneously reducing exposure to stressful life conditions, improving mental well-being, increasing health-promoting behaviours and reducing anthropometric risks associated with CVD. Such interventions offer important opportunities to improve population health and reduce health disparities.


Acute cocoa flavanol improves cerebral oxygenation without enhancing executive function at rest or after exercise.
Acute exercise-induced improvements in cognitive function are accompanied by increased (cerebral) blood flow and increased brain-derived neurotrophic factor (BDNF) levels. Acute cocoa flavanol (CF) intake may improve cognitive function, cerebral blood flow (in humans), and BNDF levels (in animals). This study investigated (i) the effect of CF intake in combination with exercise on cognitive function and (ii) cerebral hemodynamics and BDNF in response to CF intake and exercise. Twelve healthy men participated in this randomized, double-blind, crossover study. Participants performed a cognitive task (CT) at 100 min after acute 903-mg CF or placebo (PL) intake, followed by a 30-min time-trial. Immediately after this exercise, the same CT was performed. Prefrontal near-infrared spectroscopy was applied during CT and exercise to measure changes in oxygenated (ΔHbO2), deoxygenated (ΔHHb), and total haemoglobin (ΔHbtot) and blood samples were drawn and analyzed for BDNF. Reaction time was faster postexercise, but was not influenced by CF. ΔHbO2 during the resting CT was increased by CF, compared with PL. ΔHbO2, ΔHHb, and ΔHbtot increased in response to exercise without any effect of CF. During the postexercise cognitive task, there were no hemodynamic differences between CF or PL. Serum BDNF was increased by exercise, but was not influenced by CF. In conclusion, at rest, CF intake increased cerebral oxygenation, but not BDNF concentrations, and no impact on executive function was detected. This beneficial effect of CF on cerebral oxygenation at rest was overruled by the strong exercise-induced increases in cerebral perfusion and oxygenation.


Fentanyl Pharmacokinetics in Pregnant Sheep after Intravenous and Transdermal Administration to the Ewe.
Fentanyl is used for pain treatment during pregnancy in human beings and animals. However, fentanyl pharmacokinetics during pregnancy has not been fully established. The aim of this study was to characterize fentanyl pharmacokinetics in pregnant sheep after intravenous and transdermal dosing during surgical procedure performed to ewe and foetus. Pharmacokinetic parameters reported for non-pregnant sheep and nominal transdermal dose rate were utilized for a priori calculation to achieve analgesic fentanyl concentration (0.5-2 ng/ml) in maternal plasma. A total of 20 Aland landrace ewes at 118-127 gestational days were used. In the first protocol, 1 week before surgery, 10 animals received 2 μg/kg fentanyl intravenous bolus, and on the operation day, transdermal fentanyl patches at nominal dose rate of 2 μg/kg/hr were applied to antebrachium, and ewes were then given a 2 μg/kg intravenous bolus followed by an intra-operative 2.5 μg/kg/hr infusion. In the second protocol, 10 animals received fentanyl only as transdermal patches on the operation day and oxycodone for rescue analgesia. The data were analysed with population pharmacokinetic modelling. Intra- and post-operative fentanyl concentrations were similar and slightly lower than the a priori predictions, and elimination and distribution clearances appeared slower during than before or after the surgery. Transdermal patches provided sustained fentanyl absorption for up to 5 days, but the absorption rate was slower than the nominal dose rate and showed a high interindividual variability. Further research is warranted to evaluate the clinical relevance of the observations made in sheep.


Image-based face recognition under illumination and pose variations.
We present an image-based method for face recognition across different illuminations and poses, where the term image-based means that no explicit prior three-dimensional models are needed. As face recognition under illumination and pose variations involves three factors, namely, identity, illumination, and pose, generalizations in all these three factors are desired. We present a recognition approach that is able to generalize in the identity and illumination dimensions and handle a given set of poses. Specifically, the proposed approach derives an identity signature that is illumination- and pose-invariant, where the identity is tackled by means of subspace encoding, the illumination is characterized with a Lambertian reflectance model, and the given set of poses is treated as a whole. Experimental results using the Pose, Illumination, and Expression (PIE) database demonstrate the effectiveness of the proposed approach.


Mortality from scleroderma in England and Wales 1968-1985.
Mortality data for scleroderma derived from death certificates from England and Wales for the years 1968-1985 were analysed. The overall crude mortalities were 0.9 and 3.8 per million per year in men and women respectively, which are similar to comparable data from the United States. There has been a small but statistically significant increase in mortality of 3% a year over this period, possibly reflecting an underlying increasing trend in incidence. Such analyses are subject to the limitation of the accuracy of death certificates, but in a disease as rare as scleroderma the death rates provide useful data on the trends in occurrence and death from this disease.


Congenital Zika syndrome is associated with maternal protein malnutrition.
Zika virus (ZIKV) infection during pregnancy is associated with a spectrum of developmental impairments known as congenital Zika syndrome (CZS). The prevalence of this syndrome varies across ZIKV endemic regions, suggesting that its occurrence could depend on cofactors. Here, we evaluate the relevance of protein malnutrition for the emergence of CZS. Epidemiological data from the ZIKV outbreak in the Americas suggest a relationship between undernutrition and cases of microcephaly. To experimentally examine this relationship, we use immunocompetent pregnant mice, which were subjected to protein malnutrition and infected with a Brazilian ZIKV strain. We found that the combination of protein restriction and ZIKV infection leads to severe alterations of placental structure and embryonic body growth, with offspring displaying a reduction in neurogenesis and postnatal brain size. RNA-seq analysis reveals gene expression deregulation required for brain development in infected low-protein progeny. These results suggest that maternal protein malnutrition increases susceptibility to CZS.


Earthworm genomes, genes and proteins: the (re)discovery of Darwin's worms.
Small incremental biological change, winnowed by natural selection over geological time scales to produce large consequences, was Darwin's singular insight that revolutionized the life sciences. His publications after 1859, including the 'earthworm book', were all written to amplify and support the evolutionary theory presented in the Origin. Darwin was unable to provide a physical basis for the inheritance of favoured traits because of the absence of genetic knowledge that much later led to the 'modern synthesis'. Mistaken though he was in advocating systemic 'gemmules' as agents of inheritance, Darwin was perceptive in seeking to underpin his core vision with concrete factors that both determine the nature of a trait in one generation and convey it to subsequent generations. This brief review evaluates the molecular genetic literature on earthworms published during the last decade, and casts light on the specific aspects of earthworm evolutionary biology that more or less engaged Darwin: (i) biogeography, (ii) species diversity, (iii) local adaptations and (iv) sensitivity. We predict that the current understanding will deepen with the announcement of a draft earthworm genome in Darwin's bicentenary year, 2009. Subsequently, the earthworm may be elevated from the status of a soil sentinel to that elusive entity, an ecologically relevant genetic model organism.


Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies.
To estimate the incidence of serious and fatal adverse drug reactions (ADR) in hospital patients. Four electronic databases were searched from 1966 to 1996. Of 153, we selected 39 prospective studies from US hospitals. Data extracted independently by 2 investigators were analyzed by a random-effects model. To obtain the overall incidence of ADRs in hospitalized patients, we combined the incidence of ADRs occurring while in the hospital plus the incidence of ADRs causing admission to hospital. We excluded errors in drug administration, noncompliance, overdose, drug abuse, therapeutic failures, and possible ADRs. Serious ADRs were defined as those that required hospitalization, were permanently disabling, or resulted in death. The overall incidence of serious ADRs was 6.7% (95% confidence interval [CI], 5.2%-8.2%) and of fatal ADRs was 0.32% (95% CI, 0.23%-0.41%) of hospitalized patients. We estimated that in 1994 overall 2216000 (1721000-2711000) hospitalized patients had serious ADRs and 106000 (76000-137000) had fatal ADRs, making these reactions between the fourth and sixth leading cause of death. The incidence of serious and fatal ADRs in US hospitals was found to be extremely high. While our results must be viewed with circumspection because of heterogeneity among studies and small biases in the samples, these data nevertheless suggest that ADRs represent an important clinical issue.


Postmortem evidence of structural brain changes in schizophrenia. Differences in brain weight, temporal horn area, and parahippocampal gyrus compared with affective disorder.
The brains of 232 patients with a case-note diagnosis of schizophrenia or affective disorder who died in one mental hospital over a period of 22 years were weighed, and were assessed in a coronal section at the level of the interventricular foramina. From this sample were eliminated the brains of patients whose illnesses did not meet the Washington University criteria for a diagnosis of definite schizophrenia or primary affective disorder and those brains that showed significant histopathologic evidence of Alzheimer's-type change or cerebrovascular disease. This left a sample of 41 patients with schizophrenia and 29 patients with affective disorder. With age, sex, and year of birth controlled for, the brains of the patients with schizophrenia were 6% lighter, had lateral ventricles that were larger in the anterior (by 19%), and particularly in the temporal, (by 97%) horn cross section, and had significantly thinner parahippocampal cortices (by 11%). The findings provide postmortem confirmation of reports of ventricular enlargement in radiological studies and suggest that such enlargement is associated with tissue loss in the temporal lobe. The changes in schizophrenia were of a lesser degree than those seen in a sample of brains of patients with Alzheimer's-type dementia and Huntington's chorea.


Heritable variation in heat shock gene expression: a potential mechanism for adaptation to thermal stress in embryos of sea turtles.
The capacity of species to respond adaptively to warming temperatures will be key to their survival in the Anthropocene. The embryos of egg-laying species such as sea turtles have limited behavioural means for avoiding high nest temperatures, and responses at the physiological level may be critical to coping with predicted global temperature increases. Using the loggerhead sea turtle (Caretta caretta) as a model, we used quantitative PCR to characterise variation in the expression response of heat-shock genes (hsp60, hsp70 and hsp90; molecular chaperones involved in cellular stress response) to an acute non-lethal heat shock. We show significant variation in gene expression at the clutch and population levels for some, but not all hsp genes. Using pedigree information, we estimated heritabilities of the expression response of hsp genes to heat shock and demonstrated both maternal and additive genetic effects. This is the first evidence that the heat-shock response is heritable in sea turtles and operates at the embryonic stage in any reptile. The presence of heritable variation in the expression of key thermotolerance genes is necessary for sea turtles to adapt at a molecular level to warming incubation environments.


Oxidative stress, molecular inflammation and sarcopenia.
Sarcopenia is the decline of muscle mass and strength with age. Evidence suggests that oxidative stress and molecular inflammation play important roles in age-related muscle atrophy. The two factors may interfere with the balance between protein synthesis and breakdown, cause mitochondrial dysfunction, and induce apoptosis. The purpose of this review is to discuss some of the major signaling pathways that are activated or inactivated during the oxidative stress and molecular inflammation seen in aged skeletal muscle. Combined interventions that may be required to reverse sarcopenia, such as exercise, caloric restriction, and nutrition, will also be discussed.


The role of community-based health insurance within the health care financing system: a framework for analysis.
There is increasing advocacy for community-based health insurance (CBHI) schemes as part of a broader solution to health care financing problems in low-income countries, but to date there is very limited understanding of how CBHI schemes interact with other elements of a health care financing system. This paper aims to set out a preliminary conceptual framework for understanding such interactions, and highlights the kind of research questions raised by such a framework. A basic conceptual map of a CBHI scheme is developed, and extensions added to this map that incorporate (1). effects upon non-members of schemes, (2). government subsidies to providers, (3). government subsidies to schemes, and (4). issues raised by the existence of multiple risk-pooling schemes in a particular context. The utility of a broader approach to analyzing/assessing CBHI schemes is illustrated through examination of two policy issues, namely (1). coordination of CBHI risk pools and government risk pools, and (2). equity implications of CBHI schemes and the role of government subsidies in such schemes. It is concluded that there is a strong need for empirical work to explore how CBHI schemes and the broader health care financing system interact, and that even if individual schemes achieve their own objectives (in terms of equity, efficiency etc.), this does not necessarily imply that such objectives will be achieved at the system level.


"Brain drain" of health professionals: from rhetoric to responsible action.
The question of the "brain drain" of health professionals has re-emerged since last exposed in 1970s. This paper is based on exploratory studies in Ghana, South Africa and the UK, a literature review and subsequent tracking of contemporary events. It reviews what is currently known about professional migration in the health sector and its impact on health services in poorer countries. The relevant responsibilities at the global level and source and recipient country levels are then reviewed. It is concluded that that the situation is more complex than portrayed by some of the rhetoric and that meaningful dialogue and consideration of responsibilities is needed. In addition, better information is needed to monitor migration flows; source countries need to improve staff attraction and retention strategies; and recipient countries need to ensure that they do not become a permanent drain on health professionals from the developing countries.


Double-pass rotary mirror array for fast scanning optical delay line.
We have developed a fast scanning optical delay line based on a rotary mirror array. A double-pass configuration is adopted to optimize the fiber-optical coupling and thus minimize the amplitude modulation in the reflected light. The achieved scanning range is extended to over 3 mm. An additional Michelson interferometer is incorporated into the reference arm to achieve high delay repeatability. Such a device is ideal for real-time optical coherence tomography, optical Doppler tomography, and spectroscopic optical coherence tomography.


Breast cancer "tailored follow-up" in Italian oncology units: a web-based survey.
Breast cancer follow-up procedures after primary treatment are still a controversial issue. Aim of this study was to investigate, through a web-based survey, surveillance methodologies selected by Italian oncologists in everyday clinical practice. Referents of Italian medical oncology units were invited to participate to the study via e-mail through the SurveyMonkey website. Participants were asked how, in their institution, exams of disease staging and follow-up are planned in asymptomatic women and if surveillance continues beyond the 5th year. Between February and May 2013, 125 out of 233 (53.6%) invited referents of Italian medical oncology units agreed to participate in the survey. Ninety-seven (77.6%) referents state that modalities of breast cancer follow-up are planned according to the risk of disease progression at diagnosis and only 12 (9.6%) oncology units apply the minimal follow-up procedures according to international guidelines. Minimal follow-up is never applied in high risk asymptomatic women. Ninety-eight (78.4%) oncology units continue follow-up in all patients beyond 5 years. Our survey shows that 90.4% of participating Italian oncology units declare they do not apply the minimal breast cancer follow-up procedures after primary treatment in asymptomatic women, as suggested by national and international guidelines. Interestingly, about 80.0% of interviewed referents performs the so called "tailored follow-up", high intensity for high risk, low intensity for low risk patients. There is an urgent need of randomized clinical trials able to determine the effectiveness of risk-based follow-up modalities, their ideal frequency and persistence in time.


Prefrontal cortex and impulsive decision making.
Impulsivity refers to a set of heterogeneous behaviors that are tuned suboptimally along certain temporal dimensions. Impulsive intertemporal choice refers to the tendency to forego a large but delayed reward and to seek an inferior but more immediate reward, whereas impulsive motor responses also result when the subjects fail to suppress inappropriate automatic behaviors. In addition, impulsive actions can be produced when too much emphasis is placed on speed rather than accuracy in a wide range of behaviors, including perceptual decision making. Despite this heterogeneous nature, the prefrontal cortex and its connected areas, such as the basal ganglia, play an important role in gating impulsive actions in a variety of behavioral tasks. Here, we describe key features of computations necessary for optimal decision making and how their failures can lead to impulsive behaviors. We also review the recent findings from neuroimaging and single-neuron recording studies on the neural mechanisms related to impulsive behaviors. Converging approaches in economics, psychology, and neuroscience provide a unique vista for better understanding the nature of behavioral impairments associated with impulsivity.


Inactivation of YME1, a member of the ftsH-SEC18-PAS1-CDC48 family of putative ATPase-encoding genes, causes increased escape of DNA from mitochondria in Saccharomyces cerevisiae.
The yeast nuclear gene YME1 was one of six genes recently identified in a screen for mutations that elevate the rate at which DNA escapes from mitochondria and migrates to the nucleus. yme1 mutations, including a deletion, cause four known recessive phenotypes: an elevation in the rate at which copies of TRP1 and ARS1, integrated into the mitochondrial genome, escape to the nucleus; a heat-sensitive respiratory-growth defect; a cold-sensitive growth defect on rich glucose medium; and synthetic lethality in rho- (cytoplasmic petite) cells. The cloned YME1 gene complements all of these phenotypes. The gene product, Yme1p, is immunologically detectable as an 82-kDa protein present in mitochondria. Yme1p is a member of a family of homologous putative ATPases, including Sec18p, Pas1p, Cdc48p, TBP-1, and the FtsH protein. Yme1p is most similar to the Escherichia coli FtsH protein, an essential protein involved in septum formation during cell division. This observation suggests the hypothesis that Yme1p may play a role in mitochondrial fusion and/or division.


Emotion specific neural activation for the production and perception of facial expressions.
The distinction between different facial emotions is crucial for interpersonal communication. Shared neural circuits for facial emotion production and perception are considered to facilitate the ability to understand other's emotional state via mirror neuron mechanisms. Little is known about how diverse emotions differentially activate the Mirror Neuron System (MNS) during facial expression processing. In a functional magnetic resonance imaging (fMRI) task, 178 healthy subjects perceived and produced emotional (happy vs angry) and non-emotional (lip-protrusion vs no movement) facial expressions. Dynamic facial expressions were displayed as 5 sec video clips. We identified three overlapping networks of neural activation for happy, angry, and non-emotional (lip-protrusion) facial expression production and perception. Importantly, this overlap was largely due to the common motor component of facial expressions. However, for happy facial expressions, we found specific MNS activation in the right temporal pole. For angry facial expressions we found such activation in the left inferior frontal gyrus, pars orbitalis, and the cerebellum (lobules VII and VIII). We extend knowledge on mirror neuron mechanisms as our results provide evidence for emotion specific shared neural activation for the production and perception of facial emotions. This emotion specific representation of other's emotion in one's own neural production system might facilitate understanding of other's mental or emotional states.


'ASIA' - autoimmune/inflammatory syndrome induced by adjuvants.
The role of various environmental factors in the pathogenesis of immune mediated diseases is well established. Of which, factors entailing an immune adjuvant activity such as infectious agents, silicone, aluminium salts and others were associated with defined and non-defined immune mediated diseases both in animal models and in humans. In recent years, four conditions: siliconosis, the Gulf war syndrome (GWS), the macrophagic myofasciitis syndrome (MMF) and post-vaccination phenomena were linked with previous exposure to an adjuvant. Furthermore, these four diseases share a similar complex of signs and symptoms which further support a common denominator.Thus, we review herein the current data regarding the role of adjuvants in the pathogenesis of immune mediated diseases as well as the amassed data regarding each of these four conditions. Relating to the current knowledge we would like to suggest to include these comparable conditions under a common syndrome entitled ASIA, "Autoimmune (Auto-inflammatory) Syndrome Induced by Adjuvants".


Twelve-month training-induced changes in elite international volleyball players.
The purpose of this investigation was to examine the strength, power, and anthropometric contributors to vertical jump performances that are considered specific to volleyball success, including countermovement vertical jump (CMVJ) and spike jump (SPJ), by examining changes across 12 months in elite volleyball players. Anthropometry (height, mass, summation Sigma 7 skinfolds), vertical jump ability (CMVJ, SPJ, and depth jumps from 35 cm), kinetic and kinematic data from an unloaded and loaded (body mass + 50%) jump squat were assessed before and after 12 months of training in 20 elite male volleyball players. To examine the association between the change in each of the strength, power, and anthropometric variables with the changes in CMVJ and SPJ, a correlation analysis of the percent change of each variable with the percent change in CMVJ and SPJ was performed. A significant correlation (r = 0.47; p = 0.04) was observed between changes in CMVJ and SPJ. Significant (p = 0.006-0.02) improvements in CMVJ were associated with increased peak force in the unloaded (r = 0.61) and loaded jump squat (r = 0.59) and greater relative power and peak velocity in the loaded jump squat (r = 0.49 and 0.51, respectively). The significant increase in CMVJ was strongly associated (r = 0.865; p < 0.001) with an improved depth-jump ability. Significant (p = 0.003-0.03) increases in SPJ were related to increases in relative power (r = 0.64), peak force (r = 0.46), and peak velocity (r = 0.49) in the loaded jump and improved depth-jumping ability (r = 0.591). This study demonstrates that, in an elite population of volleyball players, stretch-shortening cycle performance and the ability to tolerate high stretch loads, as in the depth jump, are critical to improving jumping performance.


Does cytomegalovirus play a causative role in the development of various inflammatory diseases and cancer?
Human cytomegalovirus (HCMV) is a herpes virus that infects and is carried by 70-100% of the world's population. During its evolution, this virus has developed mechanisms that allow it to survive in an immunocompetent host. For many years, HCMV was not considered to be a major human pathogen, as it appeared to cause only rare cases of HCMV inclusion disease in neonates. However, HCMV is poorly adapted for survival in the immunosuppressed host and has emerged as an important human pathogen in AIDS patients and in patients undergoing immunosuppressive therapy following organ or bone marrow transplantation. HCMV-mediated disease in such patients has highlighted the possible role of this virus in the development of other diseases, in particular inflammatory diseases such as vascular diseases, autoimmune diseases and, more recently, with certain forms of cancers. Current research is focused on determining whether HCMV plays a causative role in these diseases or is merely an epiphenomenon of inflammation. Inflammation plays a central role in the pathogenesis of HCMV. This virus has developed a number of mechanisms that enable it to hide from the cells of the immune system and, at the same time, reactivation of a latent infection requires immune activation. Numerous products of the HCMV genome are devoted to control central functions of the innate and adaptive immune responses. By influencing the regulation of various cellular processes including the cell cycle, apoptosis and migration as well as tumour invasiveness and angiogenesis, HCMV may participate in disease development. Thus, the various drugs now available for treatment of HCMV disease (e.g. ganciclovir, acyclovir and foscarnet), may also prove to be useful in the treatment of other, more widespread diseases.


Neighborhood environment and physical activity among older adults: do the relationships differ by driving status?
Some attributes of neighborhood environments are associated with physical activity among older adults. This study examined whether the associations were moderated by driving status. Older adults from neighborhoods differing in walkability and income completed written surveys and wore accelerometers (N = 880, mean age = 75 years, 56% women). Neighborhood environments were measured by geographic information systems and validated questionnaires. Driving status was defined on the basis of a driver's license, car ownership, and feeling comfortable to drive. Outcome variables included accelerometer-based physical activity and self-reported transport and leisure walking. Multilevel generalized linear regression was used. There was no significant Neighborhood Attribute × Driving Status interaction with objective physical activity or reported transport walking. For leisure walking, almost all environmental attributes were positive and significant among driving older adults but not among nondriving older adults (five significant interactions at p < .05). The findings suggest that driving status is likely to moderate the association between neighborhood environments and older adults' leisure walking.


Determination of myoglobin concentration in blood-perfused tissue.
The standard method for determining the myoglobin (Mb) concentration in blood-perfused tissue often relies on a simple but clever differencing algorithm of the optical spectra, as proposed by Reynafarje. However, the underlying assumptions of the differencing algorithm do not always lead to an accurate assessment of Mb concentration in blood-perfused tissue. Consequently, the erroneous data becloud the understanding of Mb function and oxygen transport in the cell. The present study has examined the Mb concentration in buffer and blood-perfused mouse heart. In buffer-perfused heart containing no hemoglobin (Hb), the optical differencing method yields a tissue Mb concentration of 0.26 mM. In blood-perfused tissue, the method leads to an overestimation of Mb. However, using the distinct (1)H NMR signals of MbCO and HbCO yields a Mb concentration of 0.26 mM in both buffer- and blood-perfused myocardium. Given the NMR and optical data, a computer simulation analysis has identified some error sources in the optical differencing algorithm and has suggested a simple modification that can improve the Mb determination. Even though the present study has determined a higher Mb concentration than previously reported, it does not alter significantly the equipoise PO(2), the PO(2) where Mb and O(2) contribute equally to the O(2) flux. It also suggests that any Mb increase with exercise training does not necessarily enhance the intracellular O(2) delivery.


Dietary flaxseed administered post thoracic radiation treatment improves survival and mitigates radiation-induced pneumonopathy in mice.
Flaxseed (FS) is a dietary supplement known for its antioxidant and anti-inflammatory properties. Radiation exposure of lung tissues occurs either when given therapeutically to treat intrathoracic malignancies or incidentally, such as in the case of exposure from inhaled radioisotopes released after the detonation of a radiological dispersion devise (RDD). Such exposure is associated with pulmonary inflammation, oxidative tissue damage and irreversible lung fibrosis. We previously reported that dietary FS prevents pneumonopathy in a rodent model of thoracic X-ray radiation therapy (XRT). However, flaxseed's therapeutic usefulness in mitigating radiation effects post-exposure has never been evaluated. We evaluated the effects of a 10%FS or isocaloric control diet given to mice (C57/BL6) in 2 separate experiments (n = 15-25 mice/group) on 0, 2, 4, 6 weeks post a single dose 13.5 Gy thoracic XRT and compared it to an established radiation-protective diet given preventively, starting at 3 weeks prior to XRT. Lungs were evaluated four months post-XRT for blood oxygenation levels, inflammation and fibrosis. Irradiated mice fed a 0%FS diet had a 4-month survival rate of 40% as compared to 70-88% survival in irradiated FS-fed mouse groups. Additionally, all irradiated FS-fed mice had decreased fibrosis compared to those fed 0%FS. Lung OH-Proline content ranged from 96.5 ± 7.1 to 110.2 ± 7.7 μg/ml (Mean ± SEM) in all irradiated FS-fed mouse groups, as compared to 138 ± 10.8 μg/ml for mice on 0%FS. Concomitantly, bronchoalveolar lavage (BAL) protein and weight loss associated with radiation cachexia was significantly decreased in all FS-fed groups. Inflammatory cell influx to lungs also decreased significantly except when FS diet was delayed by 4 and 6 weeks post XRT. All FS-fed mice (irradiated or not), maintained a higher blood oxygenation level as compared to mice on 0%FS. Similarly, multiplex cytokine analysis in the BAL fluid revealed a significant decrease of specific inflammatory cytokines in FS-fed mice. Dietary FS given post-XRT mitigates radiation effects by decreasing pulmonary fibrosis, inflammation, cytokine secretion and lung damage while enhancing mouse survival. Dietary supplementation of FS may be a useful adjuvant treatment mitigating adverse effects of radiation in individuals exposed to inhaled radioisotopes or incidental radiation.


Early-Life Telomere Dynamics Differ between the Sexes and Predict Growth in the Barn Swallow (Hirundo rustica).
Telomeres are conserved DNA-protein structures at the termini of eukaryotic chromosomes which contribute to maintenance of genome integrity, and their shortening leads to cell senescence, with negative consequences for organismal functions. Because telomere erosion is influenced by extrinsic and endogenous factors, telomere dynamics may provide a mechanistic basis for evolutionary and physiological trade-offs. Yet, knowledge of fundamental aspects of telomere biology under natural selection regimes, including sex- and context-dependent variation in early-life, and the covariation between telomere dynamics and growth, is scant. In this study of barn swallows (Hirundo rustica) we investigated the sex-dependent telomere erosion during nestling period, and the covariation between relative telomere length and body and plumage growth. Finally, we tested whether any covariation between growth traits and relative telomere length depends on the social environment, as influenced by sibling sex ratio. Relative telomere length declined on average over the period of nestling maximal growth rate (between 7 and 16 days of age) and differently covaried with initial relative telomere length in either sex. The frequency distribution of changes in relative telomere length was bimodal, with most nestlings decreasing and some increasing relative telomere length, but none of the offspring traits predicted the a posteriori identified group to which individual nestlings belonged. Tail and wing length increased with relative telomere length, but more steeply in males than females, and this relationship held both at the within- and among-broods levels. Moreover, the increase in plumage phenotypic values was steeper when the sex ratio of an individual's siblings was female-biased. Our study provides evidence for telomere shortening during early life according to subtly different dynamics in either sex. Furthermore, it shows that the positive covariation between growth and relative telomere length depends on sex as well as social environment, in terms of sibling sex ratio.


Cell growth and protein expression of Shewanella oneidensis in biofilms and hydrogel-entrapped cultures.
The performance of biofilm-based bioprocesses is difficult to predict and control because of the intrinsic heterogeneous and dynamic properties of microbial biofilms. Biofilm mimics, such as microbial cells entrapped in polymeric scaffolds that are permeable for nutrients, have been proposed to replace real biofilms to achieve long-term robust performance in engineering applications. However, the physiological differences between cells that are physically entrapped in a synthetic polymeric matrix and biofilm cells that are encased in a self-produced polymeric matrix remain unknown. In this study, using Shewanella oneidensis as a model organism and alginate hydrogel as a model synthetic matrix, we compared the cell growth and protein expression in entrapped cultures and biofilms. The hydrogel-entrapped cultures were found to exhibit a growth rate comparable with biofilms. There was no substantial difference in cell viability, surface charge, as well as hydrophobicity between the cells grown in alginate hydrogel and those grown in biofilms. However, the gel-entrapped cultures were found to be physiologically different from biofilms. The gel-entrapped cultures had a higher demand for metabolic energy. The siderophore-mediated iron uptake was repressed in the gel-entrapped cells. The presence of the hydrogel matrix decreased the expression of proteins involved in biofilm formation, while inducing the production of extracellular DNA (eDNA) in the gel-entrapped cultures. These results advance the fundamental understanding of the physiology of hydrogel-entrapped cells, which can lead to more efficient biofilm mimic-based applications.


[Cannabis for medical purposes and its prescription].
Since 10 March 2017, physicians have been allowed to prescribe cannabis to patients with serious illnesses and in the absence of alternative therapies. Patients can obtain it as dried flowers or extracts in standardised pharmaceutical quality by prescription (narcotic prescription, except for cannabidiol) in pharmacies. When prescribing, physicians have to take a few things into account. The first step is to decide which therapeutic effects are to be achieved and which is the most suitable cannabis product.Cannabis for medical use must meet the requirements for pharmaceutical quality. An identity check must be carried out in the pharmacy on the basis of the monographs of the German Pharmacopoeia (DAB) or the German Pharmaceutical Codex/New Prescription Form (DAC/NRF). For the production of prescription drugs, e.g. capsules, drops or inhalates, there are also corresponding monographs for the preparation of prescription drugs. These standardised, quality-assured prescription formulas should be given preference in the case of a medical prescription.When prescribing an oral or inhalative form of application, it should be noted that the onset and duration of action are very different. Also, due to the complex pharmacology of cannabinoids, interindividual genetic differences in the metabolisation of ∆9-tetrahydrocannabinol (THC), the individual structure and function of the cannabinoid receptors, as well as differences in receptor density and distribution, the dosage and frequency of application must be individually determined. Last but not least, the dosage also depends on the type of disease and individual susceptibility to side effects. When prescribed for the first time, a creeping dosage with a very low initial dose is recommended.