Optimization of heart FailUre medical Treatment after hospital discharge according to left ventricUlaR Ejection fraction: the FUTURE survey.
No clinical practice guidelines are available for the treatment of heart failure (HF) in patients with preserved left ventricular ejection fraction (LVEF). To determine how cardiologists manage medical treatment in HF patients after hospital discharge, according to LVEF. The FUTURE study was a cross-sectional survey conducted in HF outpatients by French private cardiologists between September 2007 and August 2008. Patients had to have been hospitalized within the previous 18 months with a diagnosis of HF. Clinical data and HF treatments (angiotensin-converting enzyme inhibitors [ACEIs], angiotensin receptor blockers [ARBs], beta-blockers, diuretics and aldosterone antagonists) were recorded retrospectively, with precise information on drug doses, at two successive time points (at hospital discharge and at the index consultation). HF treatment was compared in patients with reduced (less than or equal to 40%) versus preserved (more than 40%) LVEF. Completed data were available for 1137 HF patients enrolled by 424 cardiologists. Mean patient age was 72±11 years; LVEF was reduced in 56% and preserved in 44%. The therapeutic approach was similar in the two groups, both at hospital discharge and at the index consultation. At the index consultation, HF treatment was: beta-blocker (74%); ACEI/ARB (83%); loop diuretic (86%); aldosterone antagonist (31%). The majority of patients (62%) received a beta-blocker plus an ACEI or an ARB; 56% reached more than or equal to 50% of the target dose for each treatment. There were no major differences in treatments and dosages between the groups with low and preserved LVEF. In 15% of cases where the drug dose was not increased, fear of adverse events was reported as the reason. The FUTURE survey showed a similar approach to HF treatment irrespective of LVEF. Compared with previous studies, we saw an improvement in the use of recommended HF drugs, especially beta-blockers. However, achievement of target doses could be improved.


Prevalence of Batrachochytrium dendrobatidis in three species of wild frogs on Prince Edward Island, Canada.
Chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), has resulted in the decline or extinction of approximately 200 frog species worldwide. It has been reported throughout much of North America, but its presence on Prince Edward Island (PEI), on the eastern coast of Canada, was unknown. To determine the presence and prevalence of Bd on PEI, skin swabs were collected from 115 frogs from 18 separate sites across the province during the summer of 2009. The swabs were tested through single round end-point PCR for the presence of Bd DNA. Thirty-one frogs were positive, including 25/93 (27%) green frogs Lithobates (Rana) clamitans, 5/20 (25%) northern leopard frogs L. (R.) pipiens, and 1/2 (50%) wood frogs L. sylvaticus (formerly R. sylvatica); 12 of the 18 (67%) sites had at least 1 positive frog. The overall prevalence of Bd infection was estimated at 26.9% (7.2-46.7%, 95% CI). Prevalence amongst green frogs and leopard frogs was similar, but green frogs had a stronger PCR signal when compared to leopard frogs, regardless of age (p < 0.001) and body length (p = 0.476). Amongst green frogs, juveniles were more frequently positive than adults (p = 0.001). Green frogs may be the most reliable species to sample when looking for Bd in eastern North America. The 1 wood frog positive for Bd was found dead from chytridiomycosis; none of the other frogs that were positive for Bd by PCR showed any obvious signs of illness. Further monitoring will be required to determine what effect Bd infection has on amphibian population health on PEI.


Antibacterial, antifungal, and anticancer activities of volatile oils and extracts from stems, leaves, and flowers of Eucalyptus sideroxylon and Eucalyptus torquata.
Eucalyptus species leaves have been traditionally used to heal wounds and fungal infections. Essential oils and extracts of some Eucalyptus species possess antimicrobial and antitumor properties. We sought to determine antimicrobial and cytotoxic activities of oils and extracts of leaves, stems, and flowers of Eucalyptus sideroxylon and Eucalyptus torquata grown in Egypt. An agar diffusion method was used to analyze antimicrobial activities of essential oils and extracts of Eucalyptus against medically important gram-positive and gram-negative bacteria. A sulphorhodamine B assay was used to analyze the in vitro cytotoxic activities of oils and extracts against Human hepatocellular carcinoma cell line (HEPG2), and Human breast adenocarcinoma cell line (MCF7). Gram-positive bacteria were highly susceptible to oils and extracts of both Eucalyptus species. With the exception of Escherichia coli, gram-negative bacteria were resistant to extracts, but susceptible to the oil obtained from at least one organ of E sideroxylon and E torquata. Although Aspergillus flavus and Aspergillus niger were resistant to the extracts, essential oils of E sideroxylon and E torquata generally exhibited moderate to high antifungal activities against Candida albicans, A flavus and A niger. Oils of E torquata stems exhibited cytotoxic activities on MCF7 cells followed by oils of E torquata leaves and E sideroxylon leaves. However, oils from both species failed to exert cytotoxic effects on HEPG2 cells. This is the first report of antimicrobial and antitumor properties of E sideroxylon and E torquata. Results suggest a wider use of Eucalyptus species products in pharmaceutical, cosmetic, and food preparations.


Negative pressure characteristics of an evaporating meniscus at nanoscale.
This study aims at understanding the characteristics of negative liquid pressures at the nanoscale using molecular dynamics simulation. A nano-meniscus is formed by placing liquid argon on a platinum wall between two nano-channels filled with the same liquid. Evaporation is simulated in the meniscus by increasing the temperature of the platinum wall for two different cases. Non-evaporating films are obtained at the center of the meniscus. The liquid film in the non-evaporating and adjacent regions is found to be under high absolute negative pressures. Cavitation cannot occur in these regions as the capillary height is smaller than the critical cavitation radius. Factors which determine the critical film thickness for rupture are discussed. Thus, high negative liquid pressures can be stable at the nanoscale, and utilized to create passive pumping devices as well as significantly enhance heat transfer rates.


Laser mode hyper-combs.
Laser mode and frequency combs, as lasers, are commonly one-dimensional systems. Here we present a construction of multi-dimensional laser-mode lattices (mode hyper-combs) with unique properties. They are obtained from regular 1-dimensional combs by multi-frequency modulation in active mode-locking (AML). The hyper-comb, with near neighbor mode coupling and noise functioning as temperature, is mapped to interacting magnetic-spins lattices in the spherical-model which is one of the few statistical-mechanics systems soluble in all dimensions. The important result is that such systems have, in d>2 dimensions, a phase-transition to a global phase-ordered mode hyper-comb. It can therefore change the nature of AML lasers by capturing very broad coherent frequency bandwidths and obtaining ultimately short and robust pulses. Additionally, the hyper-combs can serve as a rare physical realization of the spherical-model in any dimension.


Anandamide alters the membrane properties, halts the cell division and prevents drug efflux in multidrug resistant Staphylococcus aureus.
Antibiotic resistance is a serious public health problem throughout the world. Overcoming methicillin and multidrug-resistant Staphylococcus aureus (MRSA/MDRSA) infections has become a challenge and there is an urgent need for new therapeutic approaches. We have previously demonstrated that the endocannabinoid Anandamide (AEA) can sensitize MRSA to antibiotics. Here we have studied the mechanism of action using a MDRSA clinical isolate that are sensitized by AEA to methicillin and norfloxacin. We found that AEA treatment halts the growth of both antibiotic-sensitive and antibiotic-resistant S. aureus. The AEA-treated bacteria become elongated and the membranes become ruffled with many protrusions. AEA treatment also leads to an increase in the percentage of bacteria having a complete septum, suggesting that the cell division is halted at this stage. The latter is supported by cell cycle analysis that shows an accumulation of bacteria in the G2/M phase after AEA treatment. We further observed that AEA causes a dose-dependent membrane depolarization that is partly relieved upon time. Nile red staining of the bacterial membranes indicates that AEA alters the membrane structures. Importantly, 4'-6-diamidino-2-phenylindole (DAPI) accumulation assay and ethidium bromide efflux (EtBr) assay unveiled that AEA leads to a dose-dependent drug accumulation by inhibiting drug efflux. In conclusion, our study demonstrates that AEA interferes with cell division, alters the membrane properties of MDRSA, and leads to increased intracellular drug retention, which can contribute to the sensitization of MDRSA to antibiotics.


Lifestyle advice to cancer survivors: a qualitative study on the perspectives of health professionals.
Adoption of healthy lifestyle behaviours has shown promising effectiveness in reducing the high morbidity burden of cancer survivors. Health professionals (HPs) are well suited to provide lifestyle advice but few survivors report receiving guidance from them. This study aimed to explore HPs' perspective of lifestyle advice (on healthy eating, physical activity, smoking, and alcohol) for cancer survivors. In-depth semistructured qualitative interviews were conducted by telephone or face to face. Data were analysed using qualitative content analysis. Twenty-one UK HPs working in secondary care with breast, prostate or colorectal cancer survivors were interviewed. The overarching theme was that HPs' desire to provide lifestyle advice was not necessarily matched by knowledge and action. Three main themes were identified: (1) survivorship-centred barriers to provision, (2) HP-centred barriers to provision, and (3) optimal delivery of lifestyle advice. Results suggested that HPs' perceptions of survivors' current status of practising health behaviours, their perceived socioeconomic barriers and ability to practise health behaviours, and HPs' fear for potential loss of connection with the patient influenced provision of lifestyle advice. Further factors included HPs' knowledge of healthy lifestyle guidelines, feeling that they were not the 'right person' to provide advice, and lack of time and resources. HPs stressed that the optimal delivery of lifestyle advice should (1) be tailored to the individual and delivered throughout the cancer journey, (2) be focused on small and achievable changes framed as part of their treatment regimen and (3) be cost-effective for wide-scale implementation. Incorporation of the identified barriers when developing HP training programmes and lifestyle interventions could increase the probability of successful behavioural change, and thus improve outcomes for cancer survivors.


The Bee Microbiome: Impact on Bee Health and Model for Evolution and Ecology of Host-Microbe Interactions.
As pollinators, bees are cornerstones for terrestrial ecosystem stability and key components in agricultural productivity. All animals, including bees, are associated with a diverse community of microbes, commonly referred to as the microbiome. The bee microbiome is likely to be a crucial factor affecting host health. However, with the exception of a few pathogens, the impacts of most members of the bee microbiome on host health are poorly understood. Further, the evolutionary and ecological forces that shape and change the microbiome are unclear. Here, we discuss recent progress in our understanding of the bee microbiome, and we present challenges associated with its investigation. We conclude that global coordination of research efforts is needed to fully understand the complex and highly dynamic nature of the interplay between the bee microbiome, its host, and the environment. High-throughput sequencing technologies are ideal for exploring complex biological systems, including host-microbe interactions. To maximize their value and to improve assessment of the factors affecting bee health, sequence data should be archived, curated, and analyzed in ways that promote the synthesis of different studies. To this end, the BeeBiome consortium aims to develop an online database which would provide reference sequences, archive metadata, and host analytical resources. The goal would be to support applied and fundamental research on bees and their associated microbes and to provide a collaborative framework for sharing primary data from different research programs, thus furthering our understanding of the bee microbiome and its impact on pollinator health.


Signal processing in complex chemotaxis pathways.
Bacteria use chemotaxis to migrate towards environments that are better for growth. Chemoreceptors detect changes in attractant levels and signal through two-component systems to control swimming direction. This basic pathway is conserved across all chemotactic bacteria and archaea; however, recent work combining systems biology and genome sequencing has started to elucidate the additional complexity of the process in many bacterial species. This article focuses on one of the best understood complex networks, which is found in Rhodobacter sphaeroides and integrates sensory data about the external environment and the metabolic state of the cell to produce a balanced response at the flagellar motor.


Methane mitigation in ruminants: from microbe to the farm scale.
Decreasing enteric methane (CH4) emissions from ruminants without altering animal production is desirable both as a strategy to reduce global greenhouse gas (GHG) emissions and as a means of improving feed conversion efficiency. The aim of this paper is to provide an update on a selection of proved and potential strategies to mitigate enteric CH4 production by ruminants. Various biotechnologies are currently being explored with mixed results. Approaches to control methanogens through vaccination or the use of bacteriocins highlight the difficulty to modulate the rumen microbial ecosystem durably. The use of probiotics, i.e. acetogens and live yeasts, remains a potentially interesting approach, but results have been either unsatisfactory, not conclusive, or have yet to be confirmed in vivo. Elimination of the rumen protozoa to mitigate methanogenesis is promising, but this option should be carefully evaluated in terms of livestock performances. In addition, on-farm defaunation techniques are not available up to now. Several feed additives such as ionophores, organic acids and plant extracts have also been assayed. The potential use of plant extracts to reduce CH4 is receiving a renewed interest as they are seen as a natural alternative to chemical additives and are well perceived by consumers. The response to tannin- and saponin-containing plant extracts is highly variable and more research is needed to assess the effectiveness and eventual presence of undesirable residues in animal products. Nutritional strategies to mitigate CH4 emissions from ruminants are, without doubt, the most developed and ready to be applied in the field. Approaches presented in this paper involve interventions on the nature and amount of energy-based concentrates and forages, which constitute the main component of diets as well as the use of lipid supplements. The possible selection of animals based on low CH4 production and more likely on their high efficiency of digestive processes is also addressed. Whatever the approach proposed, however, before practical solutions are applied in the field, the sustainability of CH4 suppressing strategies is an important issue that has to be considered. The evaluation of different strategies, in terms of total GHG emissions for a given production system, is discussed.


Determination of the in vivo prebiotic potential of a maize-based whole grain breakfast cereal: a human feeding study.
Epidemiological studies have shown an inverse relationship between risk of CVD and intake of whole grain (WG)-rich food. Regular consumption of breakfast cereals can provide not only an increase in dietary WG but also improvements to cardiovascular health. Various mechanisms have been proposed, including prebiotic modulation of the colonic microbiota. In the present study, the prebiotic activity of a maize-derived WG cereal (WGM) was evaluated in a double-blind, placebo-controlled human feeding study (n 32). For a period of 21 d, healthy men and women, mean age 32 (sd 8) years and BMI 23·3 (sd 0·58) kg/m2, consumed either 48 g/d WG cereal (WGM) or 48 g placebo cereal (non-whole grain (NWG)) in a crossover fashion. Faecal samples were collected at five points during the study on days 0, 21, 42, 63 and 84 (representing at baseline, after both treatments and both wash-out periods). Faecal bacteriology was assessed using fluorescence in situ hybridisation with 16S rRNA oligonucleotide probes specific for Bacteroides spp., Bifidobacterium spp., Clostridium histolyticum/perfringens subgroup, Lactobacillus-Enterococcus subgroup and total bacteria. After 21 d consumption of WGM, mean group levels of faecal bifidobacteria increased significantly compared with the control cereal (P = 0·001). After a 3-week wash-out period, bifidobacterial levels returned to pre-intervention levels. No statistically significant changes were observed in serum lipids, glucose or measures of faecal output. In conclusion, this WG maize-enriched breakfast cereal mediated a bifidogenic modulation of the gut microbiota, indicating a possible prebiotic mode of action.


Long Noncoding RNAs and Cardiac Disease.
To maintain homeostasis, gene expression has to be tightly regulated by complex and multiple mechanisms occurring at the epigenetic, transcriptional, and post-transcriptional levels. One crucial regulatory component is represented by long noncoding RNAs (lncRNAs), nonprotein-coding RNA species implicated in all of these levels. Thus, lncRNAs have been associated with any given process or pathway of interest in a variety of systems, including the heart. Recent Advances: Mounting evidence implicates lncRNAs in cardiovascular diseases (CVD) and progression and their presence in the blood of heart disease patients indicates that they are attractive potential biomarkers. Our understanding of the regulation and molecular mechanisms of action of most lncRNAs remains rudimentary. A challenge is represented by their often low evolutionary sequence conservation that limits the use of animal models for preclinical studies. Nevertheless, a growing number of lncRNAs with an impact on heart function is rapidly accumulating. In this study, we will discuss (i) lncRNAs that control heart homeostasis and disease; (ii) concepts, approaches, and methodologies necessary to study lncRNAs in the heart; and (iii) challenges posed and opportunities presented by lncRNAs as potential therapeutic targets and biomarkers. A deeper knowledge of the molecular mechanisms underpinning CVDs is necessary to develop more effective treatments. Further studies are needed to clarify the regulation and function of lncRNAs in the heart before they can be considered as therapeutic targets and disease biomarkers. Antioxid. Redox Signal. 29, 880-901.


An incidental enterocolic lymphocytic phlebitis pattern is seen commonly in the rectal stump of patients with diversion colitis superimposed on inflammatory bowel disease.
Enterocolic lymphocytic phlebitis (ELP) is an uncommon cause of bowel pathology and most frequently results in ischaemia. It is characterised by an artery-sparing, venulocentric lymphoid infiltrate that causes a phlebitis and vascular compromise. Rare cases of ELP have been encountered with lymphocytic colitis in the absence of ischaemic bowel change. The present study examined the occurrence of ELP in the setting of diversion colitis and inflammatory bowel disease, as well as in random colectomy specimens. The study cohort comprised the following: 26 completion proctectomy specimens for ulcerative colitis with superimposed diversion colitis in the rectal stump; 3 colectomy specimens for Crohn disease with diversion colitis; 6 colectomy specimens for adenocarcinoma and/or diverticular disease with diversion colitis; 34 resection specimens with ulcerative colitis only; 19 with Crohn disease only; and 100 random colon resection specimens for adenocarcinoma, adenoma, diverticular disease and ischaemia. ELP was present in 18 of the 26 ulcerative colitis cases with diversion colitis, 3/3 Crohn disease cases with diversion colitis, 1/6 cases of diverticular disease with diversion colitis, 6/34 cases of ulcerative colitis without diversion, 2/19 Crohn disease cases without diversion colitis, and only 1 of 100 colectomy cases without inflammatory bowel disease or diversion colitis. ELP occurs most frequently in cases that have been diverted for inflammatory bowel disease. Fewer cases of ELP were noted in cases of inflammatory bowel disease in the absence of diversion colitis. It is postulated that altered bowel flora and immune dysregulation may be pivotal in the causation of this association.


"Every error counts": a web-based incident reporting and learning system for general practice.
Incident reporting systems have been established primarily in the inpatient setting. Their goal is the identification of safety risks in healthcare as a precondition for improvements in the overall quality of care. Knowledge about medical errors in general practice is sparse, as are reporting systems for patient safety in this setting. This article describes the development, structure and initial results of an incident reporting system for general practices in German-speaking countries. Jeder Fehler Zaehlt (JFZ; www.jeder-fehler-zaehlt.de) is a web-based reporting system that receives incident reports from anonymous German-speaking users. Reports are fed into a database, classified and analysed by a team of experts. Exemplary reports are published on the internet and in journals, and the reporting system provides the opportunity for users to comment on and learn from these incidents. The incident reporting system received 199 reports in the 17 months following its launch, of which 188 were classifiable. Of these, 72.9% were classified as process errors and 26.1% as knowledge/skills errors. The most frequently reported process errors were treatment errors (32.2%), communication errors (12.6%) and investigation errors (8.5%). Of the classified errors, 41.5% were associated with harm to the patient. More than 300 comments were made, mostly by anonymous users of the system. JFZ is a well-functioning and growing incident reporting system. Future efforts to improve the benefits of incident reporting will concentrate on increasing the utilisation of the system and broadening the spectrum of reported incidents.


Is association of preterm birth with cognitive-neurophysiological impairments and ADHD symptoms consistent with a causal inference or due to familial confounds?
Preterm birth is associated with an increased risk for cognitive-neurophysiological impairments and attention-deficit/hyperactivity disorder (ADHD). Whether the associations are due to the preterm birth insult per se, or due to other risk factors that characterise families with preterm-born children, is largely unknown. We employed a within-sibling comparison design, using cognitive-performance and event-related potential (ERP) measures from 104 preterm-born adolescents and 104 of their term-born siblings. Analyses focused on ADHD symptoms and cognitive and ERP measures from a cued continuous performance test, an arrow flanker task and a reaction time task. Within-sibling analyses showed that preterm birth was significantly associated with increased ADHD symptoms (β = 0.32, p = 0.01, 95% CI 0.05 to 0.58) and specific cognitive-ERP impairments, such as IQ (β = -0.20, p = 0.02, 95% CI -0.40 to -0.01), preparation-vigilance measures and measures of error processing (ranging from β = 0.71, -0.35). There was a negligible within-sibling association between preterm birth with executive control measures of inhibition (NoGo-P3, β = -0.07, p = 0.45, 95% CI -0.33 to 0.15) or verbal working memory (digit span backward, β = -0.05, p = 0.63, 95% CI -0.30 to 0.18). Our results suggest that the relationship between preterm birth with ADHD symptoms and specific cognitive-neurophysiological impairments (IQ, preparation-vigilance and error processing) is independent of family-level risk and consistent with a causal inference. In contrast, our results suggest that previously observed associations between preterm birth with executive control processes of inhibition and working memory are instead linked to background characteristics of families with a preterm-born child rather than preterm birth insult per se. These findings suggest that interventions need to target both preterm-birth specific and family-level risk factors.


Implicit learning of a motor skill after mild and moderate stroke.
To determine if adults in the subacute phase post moderate or mild stroke could learn a motor task under implicit practice conditions. Non-randomized, between-group design. Subjects' homes. Sample of convenience of 15 adults with moderate stroke, 22 adults with mild stroke, and 32 age-matched controls. Stroke severity was determined using the Orpington Prognostic Scale. Practice of movements to target switches in two conditions, a repeated series and a random series. Practice was organized into a single session of six blocks of 80 trials such that blocks 1 and 2 were the random series, blocks 3 and 4 the repeated series, block 5 the random series, and block 6 the repeated series. Explicit knowledge of the two conditions was not provided. The mean response time and the coefficient of variation were calculated for each block for each group. Regardless of group, participants had a slower response time when practice was unexpectedly switched from the repeated to random condition. The response time and coefficient of variation for those with moderate stroke were persistently greater than those with mild stroke and controls, who were not different from each other. Implicit motor learning is preserved in adults with moderate stroke and may be a viable strategy for teaching motor skills in rehabilitation. The clinician should be aware that subjects with moderate stroke, even when performing with the less affected upper extremity, have significantly slower and more variable movements than those with mild stroke and controls.


Delayed sleep phase disorder in youth.
For over 30 years, delayed sleep phase disorder (DSPD) has been defined as a debilitating sleep condition. Recently, there is more awareness of DSPD in young people, yet considerable information is needed to understand its cause and treatment. This review describes the latest research findings describing the clinical features, cause, and treatment of DSPD. The prevalence of DSPD in adolescents and young adults ranges from 1 to 16%. The impact on the individuals is significant, particularly in the domains of school/work performance and mental health. We describe various contributing factors including reduced homeostatic sleep pressure, a lengthened and delayed circadian rhythm, insensitivity to clock-resetting morning light, and heightened cognitive activity. Evening melatonin administration as a sole treatment appears promising, as is a combination of cognitive-behavior therapy and morning bright light. Recent findings suggest clinicians to be aware of the clinical features (i.e., significant daytime sleepiness, anxiety and depression symptoms, potential for school dropout) of DSPD, as several biological features underpinning this disorder are unseen in clinical settings. We advise clinicians to become familiar with exogenous evening melatonin administration, and cognitive and behavioral techniques to simultaneously treat the delayed circadian rhythm and associated sleep-onset insomnia.


Randomized comparison of minimally invasive direct coronary artery bypass surgery versus sirolimus-eluting stenting in isolated proximal left anterior descending coronary artery stenosis.
The purpose of this randomized study was to compare sirolimus-eluting stenting (SES) with minimally invasive direct coronary artery bypass (MIDCAB) surgery for patients with isolated proximal left anterior descending (LAD) coronary artery disease. Bare-metal stenting is inferior to MIDCAB surgery in patients with isolated proximal LAD lesions due to a higher reintervention rate with similar results for mortality and reinfarction. SES are effective in restenosis reduction. A total of 130 patients with significant proximal LAD coronary artery disease were randomized to either SES (n = 65) or MIDCAB surgery (n = 65). The primary clinical end point was noninferiority in freedom from major adverse cardiac events (MACE), such as cardiac death, myocardial infarction, and the need for target vessel revascularization within 12 months. Follow-up was completed for all patients. MACE occurred in 7.7% of patients after stenting, as compared with 7.7% after surgery (p = 0.03 for noninferiority). The individual components of the combined end point revealed mixed results. Although noninferiority was revealed for the difference in death and myocardial infarction (1.5% vs. 7.7%, noninferiority p < 0.001), noninferiority was not established for the difference in target vessel revascularization (6.2% vs. 0%, noninferiority p = 0.21). Clinical symptoms improved significantly in both treatment groups in comparison with baseline, and the percentage of patients free from angina after 12 months was 81% versus 74% (p = 0.49). In isolated proximal LAD disease, SES is noninferior to MIDCAB surgery at 12-month follow-up with respect to MACE at a similar relief in clinical symptoms.


Distinct roles of GABAergic interneurons in the regulation of striatal output pathways.
Striatal GABAergic microcircuits are critical for motor function, yet their properties remain enigmatic due to difficulties in targeting striatal interneurons for electrophysiological analysis. Here, we use Lhx6-GFP transgenic mice to identify GABAergic interneurons and investigate their regulation of striatal direct- and indirect-pathway medium spiny neurons (MSNs). We find that the two major interneuron populations, persistent low-threshold spiking (PLTS) and fast spiking (FS) interneurons, differ substantially in their excitatory inputs and inhibitory outputs. Excitatory synaptic currents recorded from PLTS interneurons are characterized by a small, nonrectifying AMPA receptor-mediated component and a NMDA receptor-mediated component. In contrast, glutamatergic synaptic currents in FS interneurons have a large, strongly rectifying AMPA receptor-mediated component, but no detectable NMDA receptor-mediated responses. Consistent with their axonal morphology, the output of individual PLTS interneurons is relatively weak and sparse, whereas FS interneurons are robustly connected to MSNs and other FS interneurons and appear to mediate the bulk of feedforward inhibition. Synaptic depression of FS outputs is relatively insensitive to firing frequency, and dynamic-clamp experiments reveal that these short-term dynamics enable feedforward inhibition to remain efficacious across a broad frequency range. Surprisingly, we find that FS interneurons preferentially target direct-pathway MSNs over indirect-pathway MSNs, suggesting a potential mechanism for rapid pathway-specific regulation of striatal output pathways.


Natriuretic peptides in cardiovascular diseases: current use and perspectives.
The natriuretic peptides (NPs) family, including atrial, B-type, and C-type NPs, is a group of hormones possessing relevant haemodynamic and anti-remodelling actions in the cardiovascular (CV) system. Due to their diuretic, natriuretic, vasorelaxant, anti-proliferative, and anti-hypertrophic effects, they are involved in the pathogenic mechanisms leading to major CV diseases, such as heart failure (HF), coronary artery disease, hypertension and left ventricular hypertrophy, and cerebrovascular accidents. Blood levels of NPs have established predictive value in the diagnosis of HF, as well as for its prognostic stratification. In addition, they provide useful clinical information in hypertension and in both stable and unstable coronary artery disease. Structural abnormalities of atrial natriuretic peptide gene (NPPA), as well as genetically induced changes in circulating levels of NPs, have a pathogenic causal link with CV diseases and represent emerging markers of CV risk. Novel NP-based therapeutic strategies are currently under advanced clinical development, as they are expected to contribute to the future management of hypertension and HF. The present review provides a current appraisal of NPs' clinical implications and a critical perspective of the potential therapeutic impact of pharmacological manipulation of this class of CV hormones.


Relationship between Sonographic Placental Thickness and Gestational Age in Normal Singleton Fetuses in Enugu, Southeast Nigeria.
The accuracy of common ultrasound parameters for the estimation of gestational age (GA) decreases as pregnancy advances in age. Hence, there is need to explore other parameters that may complement the established fetal biometric parameters in predicting GA in late pregnancy. The aim of this study is to determine the relationship between the sonographic placental thickness (PT) and GA in the second and third trimesters. A cross-sectional study of 627 normal pregnant women with GA between 14 and 40 weeks was conducted at the University of Nigeria Teaching Hospital Ituku-Ozalla, Enugu from May 2013 to February 2014 by sonography. Anteroposterior diameter of the placenta was measured at the level of the umbilical cord insertion. The last menstrual period of the women, femur length, biparietal diameter, head circumference, and abdominal circumference of the fetus were measured for GA estimation. Descriptive statistics, regression analysis, and independent sample t-test were used in statistical analysis. Mean PT was 23.2 (2.8) mm in the second trimester and 36.1 (3.6) mm in the third trimester. There was a significant difference between the values in the present study and values from similar studies in other populations (P < 0.04). There was a strong relationship between GA and PT and the following mathematical relationships for the second and third trimesters were obtained in the GA = 0.982 (PT) + 3.614 and GA = 0.977 (PT) + 3.354, respectively. Population-specific charts for PT may be used to estimate GA in the second and third trimesters.


Sex-Specific Association between Longitudinal Changes in Adiposity, FTO rs9939609 Polymorphism, and Leukocyte Telomere Length.
A longitudinal study was conducted to examine sex-specific associations between changes in adiposity over a 10-year period, the FTO rs9939609 polymorphism, and leukocyte telomere length (LTL). A population-based cohort including 2128 middle-aged and older Korean men (n = 1087) and women (n = 1041) participated in a prospective study. Anthropometric measurements of weight, height, and waist and hip circumference were taken at baseline (from 2001 to 2003) and at the 10-year follow-up period (from 2011 to 2012). The FTO rs9939609 polymorphism was genotyped using DNA samples collected at baseline and LTL was assessed at the 10-year follow-up period. Multiple linear regression analysis was used with adjustments for age, baseline body mass index, and other potential confounders. Presence of the FTO rs9939609 polymorphism risk allele was inversely associated with LTL (p < 0.01) in all participants, with a significant association seen only in women when the genders were modeled separately. Conversely, a significant inverse association between changes in waist circumference and LTL was found in men (p < 0.001) but not in women. No significant interaction between adiposity measures and the FTO polymorphism in association with LTL was identified for either sex. These data suggest that biological aging in men may be accelerated by increasing waist circumference, whereas in women, aging may be affected by genetic variations in FTO regardless of adiposity changes over time.


The impact of health insurance on maternal health care utilization: evidence from Ghana, Indonesia and Rwanda.
While research has assessed the impact of health insurance on health care utilization, few studies have focused on the effects of health insurance on use of maternal health care. Analyzing nationally representative data from the Demographic and Health Surveys (DHS), this study estimates the impact of health insurance status on the use of maternal health services in three countries with relatively high levels of health insurance coverage-Ghana, Indonesia and Rwanda. The analysis uses propensity score matching to adjust for selection bias in health insurance uptake and to assess the effect of health insurance on four measurements of maternal health care utilization: making at least one antenatal care visit; making four or more antenatal care visits; initiating antenatal care within the first trimester and giving birth in a health facility. Although health insurance schemes in these three countries are mostly designed to focus on the poor, coverage has been highly skewed toward the rich, especially in Ghana and Rwanda. Indonesia shows less variation in coverage by wealth status. The analysis found significant positive effects of health insurance coverage on at least two of the four measures of maternal health care utilization in each of the three countries. Indonesia stands out for the most systematic effect of health insurance across all four measures. The positive impact of health insurance appears more consistent on use of facility-based delivery than use of antenatal care. The analysis suggests that broadening health insurance to include income-sensitive premiums or exemptions for the poor and low or no copayments can increase use of maternal health care.


Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis): a case-control study protocol and GWAS in Ethiopia, Kenya, South Africa and Uganda.
Schizophrenia and bipolar disorder account for a large proportion of the global burden of disease. Despite their enormous impact, little is known about their pathophysiology. Given the high heritability of schizophrenia and bipolar disorder, unbiased genetic studies offer the opportunity to gain insight into their neurobiology. However, advances in understanding the genetic architecture of schizophrenia and bipolar disorder have been based almost exclusively on subjects of Northern European ancestry. The Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis) project aims to expand our understanding of the causes of schizophrenia and bipolar disorder through large-scale sample collection and analyses in understudied African populations. NeuroGAP-Psychosis is a case-control study of 34 000 participants recruited across multiple sites within Ethiopia, Kenya, South Africa and Uganda. Participants will include individuals who are at least 18 years old with a clinical diagnosis of schizophrenia or bipolar disorder ('psychosis') or those with no history of psychosis. Research assistants will collect phenotype data and saliva for DNA extraction. Data on mental disorders, history of physical health problems, substance use and history of past traumatic events will be collected from all participants.DNA extraction will take place in-country, with genotyping performed at the Broad Institute. The primary analyses will include identifying major groups of participants with similar ancestry using the computation-efficient programme single nucleotide polymorphisms (SNP) weights. This will be followed by a GWAS within and across ancestry groups. All participants will be assessed for capacity to consent using the University of California, San Diego Brief Assessment of Capacity to Consent. Those demonstrating capacity to consent will be required to provide informed consent. Ethical clearances to conduct this study have been obtained from all participating sites. Findings from this study will be disseminated in publications and shared with controlled access public databases, such as the database of Genotypes and Phenotypes, dbGaP.


Age-Related Changes in Pharyngeal Lumen Size: A Retrospective MRI Analysis.
Age-related loss of muscle bulk and strength (sarcopenia) is often cited as a potential mechanism underlying age-related changes in swallowing. Our goal was to explore this phenomenon in the pharynx, specifically, by measuring pharyngeal wall thickness and pharyngeal lumen area in a sample of young versus older women. MRI scans of the neck were retrospectively reviewed from 60 women equally stratified into three age groups (20s, 60s, 70+). Four de-identified slices were extracted per scan for randomized, blinded analysis: one mid-sagittal and three axial slices were selected at the anterior inferior border of C2 and C3, and at the pit of the vallecula. Pixel-based measures of pharyngeal wall thickness and pharyngeal lumen area were completed using ImageJ and then converted to metric units. Measures of pharyngeal wall thickness and pharyngeal lumen area were compared between age groups with one-way ANOVAs using Sidak adjustments for post-hoc pairwise comparisons. A significant main effect for age was observed across all variables whereby pharyngeal wall thickness decreased and pharyngeal lumen area increased with advancing age. Pairwise comparisons revealed significant differences between 20s versus 70+ for all variables and 20s versus 60s for all variables except those measured at C2. Effect sizes ranged from 0.54 to 1.34. Consistent with existing sacropenia literature, the pharyngeal muscles appear to atrophy with age and consequently, the size of the pharyngeal lumen increases.


Prediction scores do not correlate with clinically adjudicated categories of pulmonary embolism in critically ill patients.
Prediction scores for pretest probability of pulmonary embolism (PE) validated in outpatient settings are occasionally used in the intensive care unit (ICU). To evaluate the correlation of Geneva and Wells scores with adjudicated categories of PE in ICU patients. In a randomized trial of thromboprophylaxis, patients with suspected PE were adjudicated as possible, probable or definite PE. Data were then retrospectively abstracted for the Geneva Diagnostic PE score, Wells, Modified Wells and Simplified Wells Diagnostic scores. The chance-corrected agreement between adjudicated categories and each score was calculated. ANOVA was used to compare values across the three adjudicated PE categories. Among 70 patients with suspected PE, agreement was poor between adjudicated categories and Geneva pretest probabilities (kappa=0.01 [95% CI -0.0643 to 0.0941]) or Wells pretest probabilities (kappa=-0.03 [95% CI -0.1462 to 0.0914]). Among four possible, 16 probable and 50 definite PEs, there were no significant differences in Geneva scores (possible = 4.0, probable = 4.7, definite = 4.5; P=0.90), Wells scores (possible = 2.8, probable = 4.9, definite = 4.1; P=0.37), Modified Wells (possible = 2.0, probable = 3.4, definite = 2.9; P=0.34) or Simplified Wells (possible = 1.8, probable = 2.8, definite = 2.4; P=0.30). Pretest probability scores developed outside the ICU do not correlate with adjudicated PE categories in critically ill patients. Research is needed to develop prediction scores for this population.


Circulating and dietary magnesium and risk of cardiovascular disease: a systematic review and meta-analysis of prospective studies.
Clinical hypomagnesemia and experimental restriction of dietary magnesium increase cardiac arrhythmias. However, whether or not circulating or dietary magnesium at usual concentrations or intakes influences the risk of cardiovascular disease (CVD), including fatal ischemic heart disease (IHD), is unclear. We performed a systematic review and meta-analysis to investigate prospective associations of circulating and dietary magnesium with incidence of CVD, IHD, and fatal IHD. Multiple literature databases were systematically searched without language restriction through May 2012. Inclusion decisions and data extraction were performed in duplicate. Linear dose-response associations were assessed by using random-effects meta-regression. Potential nonlinear associations were evaluated by using restricted cubic splines. Of 2303 articles, 16 studies met the eligibility criteria; these studies comprised 313,041 individuals and 11,995 CVD, 7534 IHD, and 2686 fatal IHD events. Circulating magnesium (per 0.2 mmol/L increment) was associated with a 30% lower risk of CVD (RR: 0.70; 95% CI: 0.56, 0.88 per 0.2 mmol/L) and trends toward lower risks of IHD (RR: 0.83; 95% CI: 0.75, 1.05) and fatal IHD (RR: 0.61; 95% CI: 0.37, 1.00). Dietary magnesium (per 200-mg/d increment) was not significantly associated with CVD (RR: 0.89; 95% CI: 0.75, 1.05) but was associated with a 22% lower risk of IHD (RR: 0.78; 95% CI: 0.67, 0.92). The association of dietary magnesium with fatal IHD was nonlinear (P < 0.001), with an inverse association observed up to a threshold of ∼250 mg/d (RR: 0.73; 95% CI: 0.62, 0.86), compared with lower intakes. Circulating and dietary magnesium are inversely associated with CVD risk, which supports the need for clinical trials to evaluate the potential role of magnesium in the prevention of CVD and IHD.


Bromide-bridged palladium(III) chain complexes showing charge bistability near room temperature.
We synthesized and characterized bromide-bridged Pd(III) chain complexes, [Pd(en)2Br](MalCn-Y)2·H2O (en = ethylenediamine; MalCn-Y = dialkyl sulfomalonate; n: the number of carbon atoms) (n = 7 and 12). The compound with n = 7 showed charge-bistability near room temperature. In addition, it is shown that the Pd(III) state is maintained in the thin film state.


Stress and cognition.
Stress can affect cognition in many ways, with the outcome (i.e., facilitating or impairing) depending on a combination of factors related to both stress and the cognitive function under study. Among the factors identified as particularly relevant to define the cognitive effects of stress are the intensity or magnitude of stress, its origin (i.e., whether triggered by the task or externally), and its duration (i.e., whether acute or chronically delivered). At the cognitive end, the specific cognitive operation (e.g., implicit or explicit memory, long-term or working memory, goal-directed or habit learning) and information processing phases (e.g., learning, consolidation, and retrieval) are essential as well to define stress effects. The emerging view is that mild stress tends to facilitate cognitive function, particularly in implicit memory or simple declarative tasks or when the cognitive load is not excessive. Exposure to high or very high stress acutely (whether elicited by the cognitive task or experienced before being trained or tested in the task) or chronically impairs the formation of explicit memories and, more generally, of those that require complex, flexible reasoning (as typically observed for hippocampus- and prefrontal cortex-related functions) while improving performance of implicit memory and well-rehearsed tasks (as reported for amygdala-dependent conditioning tasks and for striatum-related processes). In addition to these general principles, there are important individual differences in the cognitive impact of stress, with gender and age being particularly influencing factors. WIREs Cogn Sci 2013, 4:245-261. doi: 10.1002/wcs.1222 For further resources related to this article, please visit the WIREs website.


Supplementation with undenatured whey protein during diabetes mellitus improves the healing and closure of diabetic wounds through the rescue of functional long-lived wound macrophages.
Long and persistent uncontrolled diabetes tends to degenerate the immune system and increase the incidence of infections in diabetic patients. A serious complication of diabetes is impaired healing, which diminishes physical activity and, in some cases, leads to chronic wounds and limb amputation. Whey proteins (WPs) enhance immunity during early development and have a protective role in some immune disorders. The effect of camel WPs on wound healing in a streptozotocin-induced type 1 diabetic mice model was investigated. Sixty male mice were equally distributed into 3 experimental groups: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice that were orally supplemented with undenatured WP (100 mg/kg body weight/day for 1 month through oral gavage). We observed that the diabetic mice exhibited delayed wound closure characterized by a significant reduction in collagen deposition, prolonged elevation in inflammatory cytokines, aberrant activation of STAT3 and reduction in the activation of Akt and NF-κB when compared with the control mice. Moreover, in the diabetic mice, the wound-resident macrophages were dysfunctional and demonstrated increased apoptosis, a significant reduction in their phagocytotic ability, aberrant activation of STAT3 and a marked reduction in the activation of Akt. Interestingly, the supplementation of diabetic mice with WP significantly enhanced the collagen deposition, limited the inflammatory stimuli, restored the activation of STAT3, Akt and NF-κB and greatly improved the closure of diabetic wounds compared with the control mice. Most important, the supplementation of diabetic mice with WP rescued functional, long-lived wound-resident macrophages. Our data reveal the benefits of WP supplementation in improving the healing and closure of diabetic wounds.


Familiality of neural preparation and response control in childhood attention deficit-hyperactivity disorder.
Patients with attention deficit-hyperactivity disorder (ADHD) exhibit difficulties in multiple attentional functions. Although high heritability rates suggest a strong genetic impact, aetiological pathways from genes and environmental factors to the ADHD phenotype are not well understood. Tracking the time course of deviant task processing using event-related electrophysiological brain activity should characterize the impact of familiality on the sequence of cognitive functions from preparation to response control in ADHD. Method Preparation and response control were assessed using behavioural and electrophysiological parameters of two versions of a cued continuous performance test with varying attentional load in boys with ADHD combined type (n = 97), their non-affected siblings (n = 27) and control children without a family history of ADHD (n = 43). Children with ADHD and non-affected siblings showed more variable performance and made more omission errors than controls. The preparatory Cue-P3 and contingent negative variation (CNV) following cues were reduced in both ADHD children and their non-affected siblings compared with controls. The NoGo-P3 was diminished in ADHD compared with controls whilst non-affected siblings were located intermediate but did not differ from both other groups. No clear familiality effects were found for the Go-P3. Better task performance was further associated with higher CNV and P3 amplitudes. Impairments in performance and electrophysiological parameters reflecting preparatory processes and to some extend also for inhibitory response control, especially under high attentional load, appeared to be familially driven in ADHD and may thus constitute functionally relevant endophenotypes for the disorder.


Evaluation of Inhibitory Effects of Caffeine on Human Carcinoma Cells.
One of the world's most consumed medications is caffeine which is available in the vast majority of beverages. Previously, some effects of caffeine have been evaluated including its inhibitory effect on cancer cells. But, the influence of caffeine on esophagus carcinoma squamous cells (CSC) and head and neck carcinoma cells still has not well understood. Herein, the relation between different amounts of caffeine with the proliferation rate of human esophagus carcinoma squamous cell line KYSE-30 as well as human head and neck carcinoma cell line HN5 was evaluated. Furthermore, concentrations of caffeine were adjusted and their effect on cells were studied. The inhibitory effects of caffeine on cells were measured using the conventional colorimetric MTT assay after 3 and 7 day of incubation. Our findings are suggested that caffeine has a significant inhibitory effect on both cell lines at the concentrations of 20, 50, and 70 milli-mol (mmol). The result shows that caffeine can prevent the proliferation of carcinoma cells and it is a perfect candidate for therapeutic applications.


Sex ratios at birth in African populations: a review of survey data.
This study analyzes the distribution of sex ratio at birth in African populations using data collected in birth histories in sample demographic surveys (Demographic and Health Surveys and World Fertility Surveys). The average sex ratio from 56 surveys, totaling 1.130 million births, was 1.033 (95% CI, 1.029-1.037), significantly different from the world average of 1.055. The distribution of sex ratios across surveys was found to be heterogeneous, and different from what could have been expected from random fluctuations due to sample size. Three subsets were identified: a subset with lower sex ratios, primarily in countries of eastern and southern Africa of Bantu populations (1.010), a subset with average sex ratios (1.035), and a subset of countries with higher sex ratios, in particular Nigeria and Ethiopia (1.070). Further analysis revealed that African populations are as diverse as other populations, with sex ratios ranging from low values (below 1.00) to high values (above 1.08). Results are discussed in light of independent data sources and in comparison with other human populations.


Selectively erasable multilayer thin film by photoinduced disassembly.
A multilayer film consisting of poly(acrylic acid) (PAA) and an azobenzene-containing surfactant (AzoTEA) was fabricated via a layer-by-layer assembly technique. The micellar structure favored by AzoTEA while in solution results in a bilayer structure when deposited on a substrate surface. This aggregation conversion behavior favors the deposition of AzoTEA and PAA in an alternating pattern to form a photoresponsive multilayer film. The molecular amphiphilicity of AzoTEA can be tuned by photoisomerization of the azobenzene moiety, which affects the aggregation behavior of AzoTEA in both films and solutions. The disassembly of AzoTEA aggregates caused by photoirradiation can induce the disassembly of the whole multilayer film. The AzoTEA-PAA multilayer films were found to be stable in pH 4 acetic acid (AcOH) solution, unless treated with UV radiation. On the basis of the different stability of multilayers with or without photoirradiation, when the multilayer films are selectively irradiated with UV light, the regions exposed to UV radiation disassembled after being immersed in pH 4 AcOH solution for 10 min but the regions not exposed to photoradiation are maintained on the substrate. Moreover, the plausible mechanism for the assembly and disassembly of these multilayer films and the confirmation of erasable films by atomic force microscopy are discussed.


Cost of epilepsy care in a Nigerian tertiary hospital.
The economic impact of epilepsy is enormous in terms of use of health care resources and loss of productivity. There is presently scanty data on economic impact of epilepsy in Nigeria,which necessitated this study. This cross-sectional study is on epilepsy patients age e"16 years who attended Neurology clinic at UITH Ilorin. Data collected included clinical characteristics, utilisation of resources and cost of care. Direct medical costs included recurring costs like consultation, hospitalisation, medication and investigation fees. Indirect costs were number of days lost due to seizure attack and travelling to clinic by patients and relatives. Sixty-five patients (32 males, 33 females) participated in the study with age range of 16 to 74 years and mean (SD) of 35±17 years. Total clinic attendance was 314 days and 53 days were spent on admission. Close to 25% of patients resided outside Ilorin metropolis and distance traveled to attend clinic varied from 4 to 200 km (mean=47±30.6 km). The total annual cost per patient was 41, 878 ($279.2 USD). It consisted of direct cost [DC] of 33,616 (80%) and indirect cost [IC] of 8262 (20%). The three leading consumptive items in DC were: antiepileptic drugs (AEDs)-24,138, investigations-5373 and transportation-2387. Majority (76.9%) of the patients were on carbamazepine. Self-estimated monthly family income varies from 3000 to 200,000 (median of 25,000). Only 23 patients (35.4%) bore the cost of care themselves. Of the IC, lost earnings due to absenteeism from work amounted to 6177. Equivalent of 1 USD was 150 at time of study. AEDs accounted for a significant proportion of TC. Increase in availability of generic drugs could help bring down the cost of care within affordable reach of indigent patients.


Sudden death and ventricular preexcitation: is it necessary to treat the asymptomatic patients?
Currently, asymptomatic ventricular preexcitation, which has been put at rest for many decades, remains a clinical challenge as there are no predictors of sudden death, which can be the first clinical presentation of the syndrome. Identification of risk factors for sudden death is important, considering the availability of a definitive treatment. Now, as radiofrequency catheter ablation of accessory pathways has reported success rates approaching 100 percent without major complications in many centers worldwide, it becomes unacceptable that even one asymptomatic individual with WPW will die or will experience life-threatening arrhythmic events. In our extensive experience a short anterograde refractory period of accessory pathways, inducibility of sustained tachyarrhythmias and the presence of multiple accessory pathways are the strongest predictors of life-threatening arrhythmias and sudden death. Therefore, it is not yet justified that, after an incidental diagnosis of WPW syndrome has been made, no risk stratification by invasive testing is done. Subjects at high risk, particularly if young or adolescent, should be identified and then ablated in the same session as they can develop lethal arrhythmic events within a few years and this is our current practice. Recently, we sent a questionnaire to investigate clinical practices over a large number of centers around the world about asymptomatic ventricular preexcitation. A total of 100 replies were received and the results demonstrate that there is worldwide agreement in performing invasive electrophysiologic testing and prophylactic ablation in selected subjects. These findings provide strong evidence to revisit current guidelines, which appropriately in the absence of evidence had been conservative.


Prospective investigation of body mass index, colorectal adenoma, and colorectal cancer in the prostate, lung, colorectal, and ovarian cancer screening trial.
Obesity has consistently been linked to an increased risk of colorectal cancer, particularly among men. Whether body mass index (BMI) differentially influences the risk across the stages of colorectal cancer development remains unclear. We evaluated the associations of BMI with colorectal adenoma incidence, adenoma recurrence, and cancer in the context of a large screening trial, in which cases and controls had an equal chance for disease detection. We prospectively evaluated the association between baseline BMI and the risk of incident distal adenoma (1,213 cases), recurrent adenoma (752 cases), and incident colorectal cancer (966 cases) among men and women, ages 55 to 74 years, randomly assigned to receive flexible sigmoidoscopy screening as part of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We calculated odds ratios (ORs) and 95% CIs for adenoma incidence and recurrence, and hazard ratios (HRs) and 95% CIs for colorectal cancer incidence, using multivariable-adjusted models. Compared with normal-weight men (18.5 to 24.9 kg/m(2)), obese men (≥ 30 kg/m(2)) had significantly higher risk of incident adenoma (OR, 1.32; 95% CI, 1.06 to 1.65) and colorectal cancer (HR, 1.48; 95% CI, 1.16 to 1.89) and a borderline increased risk of recurrent adenoma (OR, 1.50; 95% CI, 0.98 to 2.30). No associations were observed for either adenoma or cancer in women. Data from this large prospective study suggest that obesity is important throughout the natural history of colorectal cancer, at least in men, and colorectal cancer prevention efforts should encourage the achievement and maintenance of a healthy body weight in addition to regular screenings.


Elevated serum nitric oxide and superoxide dismutase in euthymic bipolar patients: impact of past episodes.
Nitric oxide (NO) has been implicated to play a role in the pathogenesis of many neuropsychiatric disorders. NO level was found high in acute manic inpatients. In this study, we aimed to assess NO level and activity of the antioxidant enzyme, superoxide dismutase (SOD), in euthymic bipolar patients. Twenty-seven patients with bipolar disorder (BD) in euthymic phase, and 20 healthy volunteers were included in this study. A semi-structured form was used to note social, demographic and clinical parameters of the patients. NO level and SOD activity were studied in the serum samples obtained from the patients and controls. The mean serum NO level in BD was significantly higher than in controls. Mean serum SOD activity was found to be elevated in patients with BD compared to controls. Total number of the manic episodes correlated with NO levels, but not with SOD activity. In conclusion, the number of manic episodes is positively associated with NO levels. NO and SOD appear to have a pathophysiological role in BD, especially in Type I euthymic phase, and may be considered an available trait marker for BD.


No rainbow for grey bamboo sharks: evidence for the absence of colour vision in sharks from behavioural discrimination experiments.
Despite convincing data collected by microspectrophotometry and molecular biology, rendering sharks colourblind cone monochromats, the question of whether sharks can perceive colour had not been finally resolved in the absence of any behavioural experiments compensating for the confounding factor of brightness. The present study tested the ability of juvenile grey bamboo sharks to perceive colour in an experimental design based on a paradigm established by Karl von Frisch using colours in combination with grey distractor stimuli of equal brightness. Results showed that contrasts but no colours could be discriminated. Blue and yellow stimuli were not distinguished from a grey distractor stimulus of equal brightness but could be distinguished from distractor stimuli of varying brightness. In addition, different grey stimuli were distinguished significantly above chance level from one another. In conclusion, the behavioural results support the previously collected physiological data on bamboo sharks, which mutually show that the grey bamboo shark, like several marine mammals, is a cone monochromate and colourblind.


Salmonella enteritidis induced myocarditis in a 16-year-old girl.
Myocarditis typically presents with non-specific clinical symptoms, and can easily be missed in the absence of a high index of clinical suspicion. Myocarditis caused by bacterial pathogens is rare in immunocompetent individuals, more commonly seen following viral infection. Although more classically associated with typhoid fever and gastroenteritis, Salmonella species are a rare cause of myocarditis. We report a case of Salmonella enteritidis-induced myocarditis after gastrointestinal infection in a 16 year-old girl, and discuss the diagnostic tools currently utilised to ascertain the diagnosis.


Life cycle assessment and grid electricity: what do we know and what can we know?
The generation and distribution of electricity comprises nearly 40% of U.S. CO(2), emissions, as well as large shares of SO(2), NO(x), small particulates, and other toxins. Thus, correctly accounting for these electricity-related environmental releases is of great importance in life cycle assessment of products and processes. Unfortunately, there is no agreed-upon protocol for accounting for the environmental emissions associated with electricity, as well as significant uncertainty in the estimates. Here, we explore the limits of current knowledge about grid electricity in LCA and carbon footprinting for the U.S. electrical grid, and show that differences in standards, protocols, and reporting organizations can lead to important differences in estimates of CO(2) SO(2), and NO(x) emissions factors. We find a considerable divergence in published values for grid emissions factor in the U.S. We discuss the implications of this divergence and list recommendations for a standardized approach to accounting for air pollution emissions in life cycle assessment and policy analyses in a world with incomplete and uncertain information.


Climatic changes lead to declining winter chill for fruit and nut trees in California during 1950-2099.
Winter chill is one of the defining characteristics of a location's suitability for the production of many tree crops. We mapped and investigated observed historic and projected future changes in winter chill in California, quantified with two different chilling models (Chilling Hours, Dynamic Model). Based on hourly and daily temperature records, winter chill was modeled for two past temperature scenarios (1950 and 2000), and 18 future scenarios (average conditions during 2041-2060 and 2080-2099 under each of the B1, A1B and A2 IPCC greenhouse gas emissions scenarios, for the CSIRO-MK3, HadCM3 and MIROC climate models). For each scenario, 100 replications of the yearly temperature record were produced, using a stochastic weather generator. We then introduced and mapped a novel climatic statistic, "safe winter chill", the 10% quantile of the resulting chilling distributions. This metric can be interpreted as the amount of chilling that growers can safely expect under each scenario. Winter chill declined substantially for all emissions scenarios, with the area of safe winter chill for many tree species or cultivars decreasing 50-75% by mid-21st century, and 90-100% by late century. Both chilling models consistently projected climatic conditions by the middle to end of the 21st century that will no longer support some of the main tree crops currently grown in California, with the Chilling Hours Model projecting greater changes than the Dynamic Model. The tree crop industry in California will likely need to develop agricultural adaptation measures (e.g. low-chill varieties and dormancy-breaking chemicals) to cope with these projected changes. For some crops, production might no longer be possible.


Structure of rabbit muscle phosphoglucomutase refined at 2.4 A resolution.
Data between 6.0 and 2.4 A resolution, collected at 253 K, wer used to refine a revised atomic model of muscle phosphoglucomutase: final crystallographic R factor = 16.3% (Rfree = 19.1%); final r.m.s. deviations from ideal bond lengths and angles = 0.018 A and 3.2 degrees, respectively. Features of the protein that were recognized only in the revised model include: the disposition of water molecules within domain-domain interfaces; two ion pairs buried in domain-domain interfaces, one of which is a structural arginine around which the active-site phosphoserine loop is wound; the basic architecture of the active-site 'crevice', which is a groove in a 1(1/3)-turn helix, open at both ends, that is produced by the interfacing of the four domains; the distorted hexacoordinate ligand sphere of the active-site Mg2+, where the enzymic phosphate group acts as a bidentate ligand; a pair of arginine residues in domain IV that form part of the enzymic phosphate-binding site (distal subsite) whose disposition in the two monomers of the asymmetric unit is affected unequally by distant crystallographic contacts; structural differences throughout domain IV, produced by these differing contacts, that may mimic solution differences induced by substrate binding; large differences in individually refined Debye-Waller thermal factors for corresponding main-chain atoms in monomers (1) and (2), suggesting a dynamic disorder within the crystal that may involve domain-size groups of residues; and a 'nucleophilic elbow' in the active site that resides in a topological environment differing from previous descriptions of this type of structure in other proteins.


Jones matrix analysis for a polarization-sensitive optical coherence tomography system using fiber-optic components.
We present an analysis for polarization-sensitive optical coherence tomography that facilitates the unrestricted use of fiber and fiber-optic components throughout an interferometer and yields sample birefringence, diattenuation, and relative optic axis orientation. We use a novel Jones matrix approach that compares the polarization states of light reflected from the sample surface with those reflected from within a biological sample for pairs of depth scans. The incident polarization alternated between two states that are perpendicular in a Poincaré sphere representation to ensure proper detection of tissue birefringence regardless of optical fiber contributions. The method was validated by comparing the calculated diattenuation of a polarizing sheet, chicken tendon, and muscle with that obtained by independent measurement. The relative importance of diattenuation versus birefringence to angular displacement of Stokes vectors on a Poincaré sphere was quantified.


Nosocomial infection and its molecular mechanisms of antibiotic resistance.
Nosocomial infection is a kind of infection, which is spread in various hospital environments, and leads to many serious diseases (e.g. pneumonia, urinary tract infection, gastroenteritis, and puerperal fever), and causes higher mortality than community-acquired infection. Bacteria are predominant among all the nosocomial infection-associated pathogens, thus a large number of antibiotics, such as aminoglycosides, penicillins, cephalosporins, and carbapenems, are adopted in clinical treatment. However, in recent years antibiotic resistance quickly spreads worldwide and causes a critical threat to public health. The predominant bacteria include Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii. In these bacteria, resistance emerged from antibiotic resistant genes and many of those can be exchanged between bacteria. With technical advances, molecular mechanisms of resistance have been gradually unveiled. In this review, recent advances in knowledge about mechanisms by which (i) bacteria hydrolyze antibiotics (e.g. extended spectrum β-lactamases, (ii) AmpC β-lactamases, carbapenemases), (iii) avoid antibiotic targeting (e.g. mutated vanA and mecA genes), (iv) prevent antibiotic permeation (e.g. porin deficiency), or (v) excrete intracellular antibiotics (e.g. active efflux pump) are summarized.


Addressing existential disruption in traumatic spinal cord injury: a new approach to human temporality in inpatient rehabilitation.
This article uses Heidegger's notion of humanp temporality to illuminate the meaning of the temporal disruption that can occur after traumatic spinal cord injury (TSCI). Though time is seen as important in rehabilitation practice, especially in occupational theory, it is often conceptualised in linear terms thus missing its existential structure. Our goal in this article is to enhance researchers' and rehabilitation clinicians' ways of doing and thinking about rehabilitation by revealing and articulating the role of human temporality in recovery and re-habilitation in the case of TSCI. Data come from ethnographic observations and field notes from one rehabilitation facility, interviews with former and current patients of spinal units and interviews with allied health staff who work with adults with TSCI. We discuss research and practice implications of this work for allied health staff in identifying ways of bringing this new approach to temporality into practice.


Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification.
Melanomas harbor aberrations in the c-Kit gene. We tested the efficiency of the tyrosine kinase inhibitor imatinib in selected patients with metastatic melanoma harboring c-Kit mutations or amplifications. Forty-three patients with metastatic melanoma harboring c-Kit aberrations were enrolled on this phase II trial. Each patient received a continuous dose of imatinib 400 mg/d unless intolerable toxicities or disease progression occurred. Fifteen patients who experienced progression of disease were allowed to escalate the dose to 800 mg/d. Forty-three patients were eligible for evaluation, and the median follow-up time was 12.0 months. The median progression-free survival (PFS) was 3.5 months, and the 6-month PFS rate was 36.6%. Rate of total disease control was 53.5%: 10 patients (23.3%; 95% CI, 10.2% to 36.4%) and 13 patients (30.2%; 95% CI, 16.0% to 44.4%) achieved partial response (PR) and stable disease (SD), respectively. Eighteen patients (41.9%) demonstrated regression of tumor mass. Notably, nine of the 10 PRs were observed in patients with mutations in exons 11 or 13. The 1-year overall survival (OS) rate was 51.0%. The median PFS and OS times for patients who had PR or SD versus disease progression were 9.0 months versus 1.5 months (P < .001) and 15.0 months versus 9.0 months (P = .036), respectively. Imatinib 400 mg/d was well tolerated, and only one of the 15 patients who received dose escalation to 800 mg/d achieved SD. Imatinib demonstrated significant activity in patients with metastatic melanoma harboring genetic c-Kit aberrations, with an overall response rate of 23.3%. Escalation to 800 mg/d could not restore disease control.


Plumbing in the embryo: developmental defects of the urinary tracts.
Kidney and urinary tract malformations are among the most frequent developmental defects identified in newborns. Ranging from asymptomatic to neonatal lethal, these malformations represent an important clinical challenge. Recent progress in understanding the developmental origin of urinary tract defects in the mouse and other animal models suggests a new framework for the interpretation of these defects in humans. Gene inactivation studies in mice provided invaluable information on the formation of the Wolffian duct, a central component of embryonic renal development, on ureter and kidney induction as well as on distal ureter maturation. All three developmental processes are crucial for normal urinary tract morphogenesis. A failure to complete these developmental steps is responsible for a spectrum of kidney and urinary tract malformations including renal agenesis, renal dysplasia, vesicoureteral reflux, hydroureter, hydronephrosis and ureterocele. Surprisingly, distal ureter maturation, the process by which the ureter is displaced from the Wolffian duct to its final position within the bladder wall, has only recently been characterized at the morphological level. Anomalies in this process are emerging as a major source of urinary tract developmental defects. This review is aimed at bridging the current knowledge on the morphological and molecular events identified in the mouse, together with clinical observations of urinary tract malformation in humans.


Care-seeking and management of common childhood illnesses in Tanzania--results from the 2010 Demographic and Health Survey.
Malaria, pneumonia and diarrhoea continue to kill millions of children in Africa despite the available and effective treatments. Correct diagnosis and prompt treatment with effective drugs at the first option consulted for child care is crucial for preventing severe disease and death from these illnesses. Using the 2010 Demographic and Health Survey data, the present study aims to assess care-seeking and management of suspected malaria, pneumonia and diarrhoea at various health care facilities in Tanzania. We analyzed data for 8176 children born within a 5 years period preceding the survey.The information was collected by interviewing 5519 women aged 15-49 years in 10,300 households selected from 475 sample points throughout Tanzania. The most common first option for child care was PHC facilities (54.8%), followed by private pharmacies (23.4%). These were more commonly utilized in rural compared to urban areas: 61.2% versus 34.5% for PHC facilities, and 26.5% versus 17.7% for pharmacies. Women in urban areas and those with higher level of education more commonly utilized higher level hospitals and private facilities as their first option for child care. Only one in four children with fever had received a blood test during the illness with lowest proportion being reported among children solely attended at PHC facilities. Use of abandoned antimalarial drugs for the treatment of suspected malaria was also observed in public health facilities and antibiotics use for diarrhoea treatment was high (49.0%). PHC facilities and pharmacies most commonly provided sub-optimal care. These facilities were more commonly utilized as the first option for child care in rural areas and among the poor and non-educated families. These are groups with the highest child mortality, which calls for interventions' targeting improvement of care at these facilities to further reduce child mortality from treatable illnesses in Tanzania.


Thermal monitoring during photothermia: hybrid probes for simultaneous plasmonic heating and near-infrared optical nanothermometry.
The control of temperature during photothermal therapy is key to preventing unwanted damage in surrounding tissue or post-treatment inflammatory responses. Lack of accurate thermal control is indeed one of the main limitations that hyperthermia techniques present to allow their translation into therapeutic applications. We developed a nanoprobe that allows controlled local heating, combined with in situ nanothermometry. The design of the probe follows a practical rationale that aims at simplifying experimental requirements and exploits exclusively optical wavelengths matching the first and second biological windows in the near-infrared. Methods: Hybrid nanostructures were chemically synthesized, and combine gold nanostars (photothermal agents) with CaF2:Nd3+,Y3+ nanoparticles (luminescent nanothermometers). Both components were simultaneously excited in the near-infrared range, at 808 nm. Following the goal of simplifying the thermal monitoring technique, the luminescent signal was recorded with a portable near-infrared detector. The performance of the probes was tested in 3D tumor spheroids from a human glioblastoma (U87MG) cell line. The location of the beads within the spheroids was determined measuring Nd3+ emission in a commercial Lightsheet microscope, modified in-house to be able to select the required near-infrared wavelengths. The temperature achieved inside the tumor spheroids was deduced from the luminescence of Nd3+, following a protocol that we developed to provide reliable thermal readings. Results: The choice of materials was shown to work as an optically excited hybrid probe. Depending on the illumination parameters, temperature can be controlled in a range between 37 ºC and 100 ºC. The near-infrared emission of nanothermometers also allows microscopic tracking of the hybrid nanostructures, confirming that the probes can penetrate deeper into the spheroid mass. We observed that, application of optical thermometry in biological environments requires often neglected considerations, since the optical signal changes along the optical path. Accordingly, we developed data analysis protocols that guarantee reliable thermal readings. Conclusions: The prepared hybrid probes are internalized in 3D tumor spheroids and can be used to induce cell death through photothermal effects, while simultaneously measuring the local temperature in situ. We show that luminescent thermometry in biomedical applications requires the development of protocols that guarantee accurate readings. Regarding photothermal treatments, we observe a sharp thermal threshold at around 55 ºC (for 10 min treatments) that separates high survival ratio from complete cell death.


A Community's Awareness and Perceptions of Genomic Medicine.
Focus groups were conducted in a mid-sized community to explore community members' awareness and perceptions of genomic medicine and identify effective methods to educate the public about this topic. Thirteen focus groups were conducted with a demographically representative pool of 121 participants using a semi-structured interview guide. Transcripts were analyzed through a computer assisted approach with Atlas TI consisting of coding, categorizing, comparing, and contrasting relevant data. Identified categories were organized into 6 main themes, which were similar across the groups and included: a lack of awareness, perceived benefits, concerns about genomic medicine, reasons for poor health related behavior, the potential impact of genetic information on health behavior, and the best ways to educate the community. Common concerns included lack of affordability, unanticipated physical harm, mistrust of the government and researchers, downstream effects like overpopulation, playing God/disturbing the natural order, lack of regulations, loss of privacy, genetic discrimination, and moral dilemmas posed by genetic engineering, cloning, choosing traits, and abortions resulting from genetic information. Participants also discussed ways to educate the community. While individuals recognized that diseases run in families, personal experience was a driving factor in participants' level of knowledge. Many expressed optimism about genomic medicine. However, the lack of depth in responses and their misconceptions reflect a deficiency of knowledge, which along with their personal, moral, and global concerns could impede acceptance and utilization of genomic medicine. Many community members are receptive to learning more about genomic medicine, and many of their concerns and misconceptions can be addressed through a well designed education strategy.


Comparative ocular microbial communities in humans with and without blepharitis.
The aims of our study were to compare the ocular microbial communities of humans with and without blepharitis in an attempt to elucidate which microorganisms may cause blepharitis. Bacterial 16S rRNA genes of eyelash and tear samples from seven blepharitis patients and four healthy controls were sequenced using a pyrosequencing method, and their bacterial community structures were compared bioinformatically. Phylotypic analysis demonstrated that eyelash and tear samples had highly diverse bacterial communities with many previously undescribed bacteria. Bacterial communities in eyelash samples from subjects with blepharitis were less diverse than those from healthy controls, while the bacterial communities of tear subjects with blepharitis were more diverse than those of healthy subjects. Statistical analyses using UniFrac and a principle coordinate analysis showed that the bacterial communities of tear samples from subjects with blepharitis were well clustered, regardless of individual, while the bacterial communities of all eyelash samples and healthy tear samples were not well clustered due to high interpersonal variability. Bioinformatic analysis revealed that Propionibacterium, Staphylococcus, Streptophyta, Corynebacterium, and Enhydrobacter were the common ocular bacteria. An increase of Staphylococcus, Streptophyta, Corynebacterium, and Enhydrobacter, and a decrease of Propionibacterium were observed from blepharitis subjects, in terms of the relative abundances. Higher abundances of Streptophyta, Corynebacterium, and Enhydrobacter in blepharitis subjects suggested that human blepharitis might be induced by the infestations of pollens, dusts, and soil particles. These results will provide valuable information for the prevention and treatment of human blepharitis based on ocular microbial flora.


Effect of chemotherapeutic stress on induction of vascular endothelial growth factor family members and receptors in human colorectal cancer cells.
Vascular endothelial growth factor (VEGF) is induced by stress. We determined whether chemotherapy (genotoxic stress) could induce expression of VEGF and VEGF receptors (VEGFR) in human colorectal cancer cells. The colorectal cancer cell lines HT29, RKO, and HCT116 were acutely exposed to increasing doses of oxaliplatin or 5-fluorouracil for 2, 6, and 24 h in vitro. Expression of VEGF ligand family members, VEGFRs, and signaling intermediates was determined by reverse transcription-PCR and Northern and Western blotting. The effect of oxaliplatin on VEGF-A transcriptional activity was determined by promoter assays. Acute exposure of human colorectal cancer cells to oxaliplatin led to a marked induction of VEGF-A mRNA and protein, whereas 5-fluorouracil alone or when added to oxaliplatin did not cause a further increase in VEGF levels. VEGF-A promoter activity was induced by oxaliplatin exposure. Expression of VEGF-C, placental growth factor, VEGFR-1, and neuropilin-1 levels were also increased when cells were treated with oxaliplatin. Oxaliplatin led to an increase in Akt and Src activation in HT29 cells. In contrast, Akt activation did not change in RKO cells whereas phospho-Src and phospho-p44/42 mitogen-activated protein kinase was dramatic increased by oxaliplatin. Inhibition of Akt or Src activation with wortmannin or PP2 blocked induction of VEGF-A by oxaliplatin in HT29 or RKO cells, respectively. VEGFRs may reflect the adaptive stress responses by which tumor cells attempt to protect themselves from genotoxic stress. Neutralization of prosurvival responses with anti-VEGF therapy might explain, in part, some of the beneficial effects of anti-VEGF therapy when added to chemotherapy.


Factors affecting influential discussions among physicians: a social network analysis of a primary care practice.
Physicians often rely on colleagues for new information and advice about the care of their patients. Evaluate the network of influential discussions among primary care physicians in a hospital-based academic practice. Survey of physicians about influential discussions with their colleagues regarding women's health issues. We used social network analysis to describe the network of discussions and examined factors predictive of a physician's location in the network. All 38 primary care physicians in a hospital-based academic practice. Location of physician within the influential discussion network and relationship with other physicians in the network. Of 33 responding physicians (response rate = 87%), the 5 reporting expertise in women's health were more likely than others to be cited as sources of influential information (odds ratio [OR] 6.81, 95% Bayesian confidence interval [CI] 2.25-23.81). Physicians caring for more women were also more often cited (OR 1.03, 95% CI 1.01-1.05 for a 1 percentage-point increase in the proportion of women patients). Influential discussions were more frequent among physicians practicing in the same clinic within the practice than among those in different clinics (OR 5.03, 95% CI 3.10-8.33) and with physicians having more weekly clinical sessions (OR 1.33, 95% CI 1.15 to 1.54 for each additional session). In the primary care practice studied, physicians obtained information from colleagues with greater expertise and experience as well as colleagues who were accessible based on location and schedule. It may be possible to organize practices to promote more rapid dissemination of high-quality evidence-based medicine.


Preliminary observations on rinderpest in pregnant cattle.
A Kabete 'O' strain of rinderpest virus enhanced in virulence was inoculated subcutaneously into four cows which were between six and eight months pregnant. All the cows developed clinical signs of rinderpest from the third day after inoculation and shed high titres of virus in their ocular and vaginal secretions during the course of the clinical disease. Three of the cows died of rinderpest on the third day after the onset of fever but no virus was isolated from their fetuses which were examined post mortem. The fourth cow showed complete clinical and virological recovery by the eighth day after the onset of fever and aborted an eight-and-a-half-month-old fetus on the 12th day after it recovered. Rinderpest virus was demonstrated in a wide range of the aborted fetal tissues. Virus was also detected in the maternal vaginal discharges up to 24 hours after abortion. The only gross pathological change observed was a severe necrotising placentitis.


Fostering Inclusion through an Interinstitutional, Community-Engaged, Course-Based Undergraduate Research Experience.
Creation of an inclusive environment requires a culture of equity, justice, value and respect for diverse backgrounds, and opportunities for students to engage with communities while addressing issues in science and society. These tasks are particularly challenging for institutions lacking a diverse population. Here, we demonstrate evidence of a successful model for creating an inclusive environment in an interinstitutional course between a large, public, historically black institution and a small, private, primarily white institution. Because many individuals from underrepresented minority groups tend to value communal goals of working together and helping their communities, we incorporated two high-impact practices of community-engaged learning and course-based undergraduate research experiences (CUREs) focused on health disparities research in neighboring communities. Although the research projects varied each semester, they were linked by their impact on and engagement with the community. Students practiced cultural competency skills in both small group projects within the class and engagement activities in the community. We measured the efficacy of CURE components (novel authentic research, scientific process skills, iteration, collaboration, and broader impact) through a combination of direct and indirect assessments, quantitative and qualitative analysis. More than simply scientific skills, students from both institutions developed lasting interest in working with diverse populations as well as respecting and valuing different backgrounds. This inclusive environment, combined with increased interest in research, suggests that this course could potentially serve as a model for interinstitutional collaborations in creating inclusive environments that support the future success of diverse students, eventually changing the STEM research culture.


New Insights into the Complex Relationship between Weight and Maturity of Burgundy Truffles (Tuber aestivum).
Despite an increasing demand for Burgundy truffles (Tuber aestivum), gaps remain in our understanding of the fungus' overall lifecycle and ecology. Here, we compile evidence from three independent surveys in Hungary and Switzerland. First, we measured the weight and maturity of 2,656 T. aestivum fruit bodies from a three-day harvest in August 2014 in a highly productive orchard in Hungary. All specimens ranging between 2 and 755 g were almost evenly distributed through five maturation classes. Then, we measured the weight and maturity of another 4,795 T. aestivum fruit bodies harvested on four occasions between June and October 2015 in the same truffière. Again, different maturation stages occurred at varying fruit body size and during the entire fruiting season. Finally, the predominantly unrelated weight and maturity of 81 T. aestivum fruit bodies from four fruiting seasons between 2010 and 2013 in Switzerland confirmed the Hungarian results. The spatiotemporal coexistence of 7,532 small-ripe and large-unripe T. aestivum, which accumulate to ~182 kg, differs from species-specific associations between the size and ripeness that have been reported for other mushrooms. Although size-independent truffle maturation stages may possibly relate to the perpetual belowground environment, the role of mycelial connectivity, soil property, microclimatology, as well as other abiotic factors and a combination thereof, is still unclear. Despite its massive sample size and proof of concept, this study, together with existing literature, suggests consideration of a wider ecological and biogeographical range, as well as the complex symbiotic fungus-host interaction, to further illuminate the hidden development of belowground truffle fruit bodies.


Marine Metazoan Modern Mass Extinction: Improving Predictions by Integrating Fossil, Modern, and Physiological Data.
Evolution, extinction, and dispersion are fundamental processes affecting marine biodiversity. Until recently, studies of extant marine systems focused mainly on evolution and dispersion, with extinction receiving less attention. Past extinction events have, however, helped shape the evolutionary history of marine ecosystems, with ecological and evolutionary legacies still evident in modern seas. Current anthropogenic global changes increase extinction risk and pose a significant threat to marine ecosystems, which are critical for human use and sustenance. The evaluation of these threats and the likely responses of marine ecosystems requires a better understanding of evolutionary processes that affect marine ecosystems under global change. Here, we discuss how knowledge of ( a) changes in biodiversity of ancient marine ecosystems to past extinctions events, ( b) the patterns of sensitivity and biodiversity loss in modern marine taxa, and ( c) the physiological mechanisms underpinning species' sensitivity to global change can be exploited and integrated to advance our critical thinking in this area.


Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer.
Inflammation has been hypothesized to increase the risk of cancer development as an initiator or promoter, yet no large-scale study of inherited variation across cancer sites has been conducted. We conducted a cross-cancer genomic analysis for the inflammation pathway based on 48 genome-wide association studies within the National Cancer Institute GAME-ON Network across five common cancer sites, with a total of 64 591 cancer patients and 74 467 control patients. Subset-based meta-analysis was used to account for possible disease heterogeneity, and hierarchical modeling was employed to estimate the effect of the subcomponents within the inflammation pathway. The network was visualized by enrichment map. All statistical tests were two-sided. We identified three pleiotropic loci within the inflammation pathway, including one novel locus in Ch12q24 encoding SH2B3 (rs3184504), which reached GWAS significance with a P value of 1.78 x 10(-8), and it showed an association with lung cancer (P = 2.01 x 10(-6)), colorectal cancer (GECCO P = 6.72x10(-6); CORECT P = 3.32x10(-5)), and breast cancer (P = .009). We also identified five key subpathway components with genetic variants that are relevant for the risk of these five cancer sites: inflammatory response for colorectal cancer (P = .006), inflammation related cell cycle gene for lung cancer (P = 1.35x10(-6)), and activation of immune response for ovarian cancer (P = .009). In addition, sequence variations in immune system development played a role in breast cancer etiology (P = .001) and innate immune response was involved in the risk of both colorectal (P = .022) and ovarian cancer (P = .003). Genetic variations in inflammation and its related subpathway components are keys to the development of lung, colorectal, ovary, and breast cancer, including SH2B3, which is associated with lung, colorectal, and breast cancer.


Dietary patterns of Korean adults and the prevalence of metabolic syndrome: a cross-sectional study.
The prevalence of metabolic syndrome has been increasing in Korea and has been associated with dietary habits. The aim of our study was to identify the relationship between dietary patterns and the prevalence of metabolic syndrome. Using a validated food frequency questionnaire, we employed a cross-sectional design to assess the dietary intake of 1257 Korean adults aged 31 to 70 years. To determine the participants' dietary patterns, we considered 37 predefined food groups in principal components analysis. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III. The abdominal obesity criterion was modified using Asian guidelines. Prevalence ratios and 95% confidence intervals for the metabolic syndrome were calculated across the quartiles of dietary pattern scores using log binomial regression models. The covariates used in the model were age, sex, total energy intake, tobacco intake, alcohol consumption, and physical activity. The prevalence of metabolic syndrome was 19.8% in men and 14.1% in women. The PCA identified three distinct dietary patterns: the 'traditional' pattern, the 'meat' pattern, and the 'snack' pattern. There was an association of increasing waist circumference and body mass index with increasing score in the meat dietary pattern. The multivariate-adjusted prevalence ratio of metabolic syndrome for the highest quartile of the meat pattern in comparison with the lowest quartile was 1.47 (95% CI: 1.00-2.15, p for trend = 0.016). A positive association between the prevalence of metabolic syndrome and the dietary pattern score was found only for men with the meat dietary pattern (2.15, 95% CI: 1.10-4.21, p for trend = 0.005). The traditional pattern and the snack pattern were not associated with an increased prevalence of metabolic syndrome. The meat dietary pattern was associated with a higher prevalence of metabolic syndrome in Korean male adults.