Smoking Cessation and Quality of Life: Insights From Analysis of Longitudinal Australian Data, an Application for Economic Evaluations.
A number of studies have shown an association between smoking habit and quality of life, but these have mainly involved cross-sectional data. This study takes advantage of longitudinal panel data to estimate the effect of the transition from "smoker" to "ex-smoker" status (smoking cessation) on health-related quality of life (HRQoL), measured by SF-36, in an Australian general population sample. Panel data from 13 waves (2001-2013) of a nationally representative longitudinal survey of Household Income and Labour Dynamics of Australia (HILDA) were used; 1858 respondents (5% of total HILDA sample) who experienced only 1 cessation event in their HILDA life were selected. HRQoL trajectories elicited by SF-36 (0-100 scale, worst to best health) were modeled before and after cessation events using a piecewise (segmented) 2-way fixed-effect linear regression, adopted to capture within-person differences. This enabled measurement of changes of regression slopes and intercept while controlling time-invariant characteristics (eg, country of birth, gender) and time-varying changes in health status. Annual pre-post intervention improvements were estimated for the following dimensions: role physical 0.65 (95% CI 0.62-1.24), bodily pain 0.48 (95% CI 0.10-0.86), general health 0.55 (95% CI 0.2-0.9), and the physical component summary score 0.22 (95% CI 0.01-0.04). Immediate effects (discontinuity at the time of cessation) of smoking cessation existed for bodily pain -1.5 (95% CI -2.52 to -0.40) and general health 1.82 (95% CI 1.01-2.62). The effects for mental health domains were not significant. Adjusting for all unmeasured time-invariant confounders and controlling the effect of time, this study revealed the varied effects of smoking cessation on HRQoL; it has positive effect on physical and general health but nonsignificant effect on mental aspects. Preference-based utility measures based on SF-6D capture changes that can be measured in several of the domains of the SF-36.


Why do older workers with chronic health conditions prefer to retire early?
older workers experiencing chronic health conditions (CHCs) are more likely to retire early. The different pathways through which CHCs stimulate retirement preferences, however, remain largely unexplored. we present a more comprehensive model in which we test the different pathways through which four specific CHCs-arthritis, cardiovascular disease, sleep disorders and psychological disorders-influence early retirement preferences. We hypothesize that the association between CHCs and early retirement preferences is differentially mediated by subjective life expectancy (SLE), perceived health-related work limitations (HRWL) and vitality. we collected data from 5,696 wage-employed older workers (60 to 64 years) in the Netherlands in 2015. Regression models were estimated to examine the associations between CHCs and early retirement preferences. Mediation analysis with the Karlson, Holm and Breen method was used to examine potential mediation pathways. SLE, HRWL and vitality mediated the association between CHCs and older workers' early retirement preferences. The dominant mediator differed depending on the CHC. Severe HRWL predominantly guided the retirement preferences of older workers with arthritis and cardiovascular disease. Lower vitality mainly mediated retirement preferences of older workers with sleep and psychological disorders. Lower SLE was a significant mediation pathway for older workers with cardiovascular diseases. HRWL and vitality play a major role in determining retirement preferences of older workers experiencing CHCs. Since both mediators are modifiable, targeted interventions may not only extend older workers' working lives, but also improve the quality of their working lives.


E-selectin ligands mediate tumor necrosis factor-induced neutrophil sequestration and pulmonary edema in guinea pig lungs.
We have previously shown in perfused guinea pig lungs that tumor necrosis factor-alpha (TNF-alpha) pretreatment of lungs enhanced neutrophil sequestration as reflected by a 2.4-fold increase in lung myeloperoxidase (MPO) activity. Subsequent perfusion of phorbol 12-myristate 13-acetate (PMA) to activate the sequestered neutrophils produced an approximately threefold increase in the pulmonary capillary hydrostatic pressure and fulminant pulmonary edema. Using this ex vivo model of lung injury, we studied the role of three putative E-selectin ligands, sialyl-Lewis X, Lewis X, and dimeric sialyl-Lewis X, in mediating neutrophil sequestration and pulmonary edema. We pretreated neutrophils with monoclonal antibodies (mAbs) directed against these E-selectin ligands. Pretreatment of neutrophils with mAbs to sialyl-Lewis X and Lewis X reduced the neutrophil sequestration, as evidenced by 45% and 27% reductions in MPO activity from control levels, respectively. This occurred in parallel with inhibition of neutrophil adhesion to the TNF-alpha-activated endothelial cells in vitro. The mAbs to dimeric sialyl-Lewis X and an isotype-matched control mAb against lactosamines present on neutrophils had no effect on lung MPO activity and neutrophil adhesion. All mAbs to sialyl-Lewis X, Lewis X, and dimeric sialyl-Lewis X reduced the increases in the pulmonary capillary hydrostatic pressure after challenge of the sequestered neutrophils with PMA and also reduced lung weight gain by 71%, 45% and 38%, respectively. The control mAb to the lactosamines had no effect on the pulmonary capillary hydrostatic pressure and lung weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)


Levosimendan for Hemodynamic Support after Cardiac Surgery.
Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta-analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0.025 to 0.2 μg per kilogram of body weight per minute) or placebo, for up to 48 hours or until discharge from the intensive care unit (ICU), in addition to standard care. The primary outcome was 30-day mortality. The trial was stopped for futility after 506 patients were enrolled. A total of 248 patients were assigned to receive levosimendan and 258 to receive placebo. There was no significant difference in 30-day mortality between the levosimendan group and the placebo group (32 patients [12.9%] and 33 patients [12.8%], respectively; absolute risk difference, 0.1 percentage points; 95% confidence interval [CI], -5.7 to 5.9; P=0.97). There were no significant differences between the levosimendan group and the placebo group in the durations of mechanical ventilation (median, 19 hours and 21 hours, respectively; median difference, -2 hours; 95% CI, -5 to 1; P=0.48), ICU stay (median, 72 hours and 84 hours, respectively; median difference, -12 hours; 95% CI, -21 to 2; P=0.09), and hospital stay (median, 14 days and 14 days, respectively; median difference, 0 days; 95% CI, -1 to 2; P=0.39). There was no significant difference between the levosimendan group and the placebo group in rates of hypotension or cardiac arrhythmias. In patients who required perioperative hemodynamic support after cardiac surgery, low-dose levosimendan in addition to standard care did not result in lower 30-day mortality than placebo. (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825 .).


Neuronal Small RNAs Control Behavior Transgenerationally.
It is unknown whether the activity of the nervous system can be inherited. In Caenorhabditis elegans nematodes, parental responses can transmit heritable small RNAs that regulate gene expression transgenerationally. In this study, we show that a neuronal process can impact the next generations. Neurons-specific synthesis of RDE-4-dependent small RNAs regulates germline amplified endogenous small interfering RNAs (siRNAs) and germline gene expression for multiple generations. Further, the production of small RNAs in neurons controls the chemotaxis behavior of the progeny for at least three generations via the germline Argonaute HRDE-1. Among the targets of these small RNAs, we identified the conserved gene saeg-2, which is transgenerationally downregulated in the germline. Silencing of saeg-2 following neuronal small RNA biogenesis is required for chemotaxis under stress. Thus, we propose a small-RNA-based mechanism for communication of neuronal processes transgenerationally.


The concurrent recording of electroencephalography and impedance cardiography: effects on EEG.
Three experiments were performed testing the effects of a variety of impedance cardiograph electrode types and recording arrangements on recorded electroencephalography (EEG) using either a monopolar single-ear reference or a physically linked ears reference. EEG was recorded either alone or concurrently with an impedance cardiograph. When the cardiograph was recorded using a spot electrode for the top current-inducing electrode, there was an overall decrease in power density of the EEG, and this effect was dependent on the location of the recording electrode. This effect was diminished when the top cardiograph spot electrode was replaced by a mylar-coated neck band electrode and EEG was recorded using a monopolar, single-ear reference. However, there tended to be an overall increase in log power density of the EEG in each frequency band below 60 Hz when less technologically advanced EEG amplifiers were used. This effect was diminished if the EEG was recorded using a physically linked ears reference. Recommendations for the concurrent recording of EEG and impedance cardiography are discussed.


Lion (Panthera leo) populations are declining rapidly across Africa, except in intensively managed areas.
We compiled all credible repeated lion surveys and present time series data for 47 lion (Panthera leo) populations. We used a Bayesian state space model to estimate growth rate-λ for each population and summed these into three regional sets to provide conservation-relevant estimates of trends since 1990. We found a striking geographical pattern: African lion populations are declining everywhere, except in four southern countries (Botswana, Namibia, South Africa, and Zimbabwe). Population models indicate a 67% chance that lions in West and Central Africa decline by one-half, while estimating a 37% chance that lions in East Africa also decline by one-half over two decades. We recommend separate regional assessments of the lion in the World Conservation Union (IUCN) Red List of Threatened Species: already recognized as critically endangered in West Africa, our analysis supports listing as regionally endangered in Central and East Africa and least concern in southern Africa. Almost all lion populations that historically exceeded ∼ 500 individuals are declining, but lion conservation is successful in southern Africa, in part because of the proliferation of reintroduced lions in small, fenced, intensively managed, and funded reserves. If management budgets for wild lands cannot keep pace with mounting levels of threat, the species may rely increasingly on these southern African areas and may no longer be a flagship species of the once vast natural ecosystems across the rest of the continent.


Purification and characterization of the CheZ protein of bacterial chemotaxis.
The cheZ gene is the most distal of five genes that comprise the Meche operon of the Salmonella typhimurium chemotaxis system. We have determined the sequence of the cheZ gene along with an 800-nucleotide flanking region at its 3' end. The flanking sequence contains an open reading frame that probably corresponds to the 5' end of flaM. The cheZ coding sequence predicts an extremely acidic, hydrophilic protein with a molecular weight of 23,900. We have purified and characterized this protein. N-terminal analysis of pure CheZ yields an amino acid sequence identical to that predicted by the nucleotide sequence except that the amino-terminal methionine residue is modified by N methylation. The purified CheZ protein exhibits a native molecular weight of 115,000, but in cell extracts the majority of CheZ exists as a much larger aggregate (Mr greater than 500,000). Under these conditions, CheZ appears to be a homopolymer composed of at least 20 monomeric subunits.


Selenium-dependent biogenesis of formate dehydrogenase in Campylobacter jejuni is controlled by the fdhTU accessory genes.
The food-borne bacterial pathogen Campylobacter jejuni efficiently utilizes organic acids such as lactate and formate for energy production. Formate is rapidly metabolized via the activity of the multisubunit formate dehydrogenase (FDH) enzyme, of which the FdhA subunit is predicted to contain a selenocysteine (SeC) amino acid. In this study we investigated the function of the cj1500 and cj1501 genes of C. jejuni, demonstrate that they are involved in selenium-controlled production of FDH, and propose the names fdhT and fdhU, respectively. Insertional inactivation of fdhT or fdhU in C. jejuni resulted in the absence of FdhA and FdhB protein expression, reduced fdhABC RNA levels, the absence of FDH enzyme activity, and the lack of formate utilization, as assessed by (1)H nuclear magnetic resonance. The fdhABC genes are transcribed from a single promoter located two genes upstream of fdhA, and the decrease in fdhABC RNA levels in the fdhU mutant is mediated at the posttranscriptional level. FDH activity and the ability to utilize formate were restored by genetic complementation with fdhU and by supplementation of the growth media with selenium dioxide. Disruption of SeC synthesis by inactivation of the selA and selB genes also resulted in the absence of FDH activity, which could not be restored by selenium supplementation. Comparative genomic analysis suggests a link between the presence of selA and fdhTU orthologs and the predicted presence of SeC in FdhA. The fdhTU genes encode accessory proteins required for FDH expression and activity in C. jejuni, possibly by contributing to acquisition or utilization of selenium.


Calculating the power to examine treatment-covariate interactions when planning an individual participant data meta-analysis of randomized trials with a binary outcome.
Before embarking on an individual participant data meta-analysis (IPDMA) project, researchers and funders need assurance it is worth their time and cost. This should include consideration of how many studies are promising their IPD and, given the characteristics of these studies, the power of an IPDMA including them. Here, we show how to estimate the power of a planned IPDMA of randomized trials to examine treatment-covariate interactions at the participant level (ie, treatment effect modifiers). We focus on a binary outcome with binary or continuous covariates, and propose a three-step approach, which assumes the true interaction size is common to all trials. In step one, the user must specify a minimally important interaction size and, for each trial separately (eg, as obtained from trial publications), the following aggregate data: the number of participants and events in control and treatment groups, the mean and SD for each continuous covariate, and the proportion of participants in each category for each binary covariate. This allows the variance of the interaction estimate to be calculated for each trial, using an analytic solution for Fisher's information matrix from a logistic regression model. Step 2 calculates the variance of the summary interaction estimate from the planned IPDMA (equal to the inverse of the sum of the inverse trial variances from step 1), and step 3 calculates the corresponding power based on a two-sided Wald test. Stata and R code are provided, and two examples given for illustration. Extension to allow for between-study heterogeneity is also considered.


EXPERIMENTAL INVESTIGATION OF THE MECHANISMS AND PERFORMANCE OF ACTIVE AUXETIC AND SHEARING TEXTILES.
Anisotropic textiles are commonly used in wearable applications to achieve varied bi-axial stress-strain behavior around the body. Auxetic textiles, specifically those that exhibit a negative Poisson's ratio (v), likewise exhibit intriguing behavior such as volume increase in response to impact or variable air permeability. Active textiles are traditional textile structures that integrate smart materials, such as shape memory alloys, shape memory polymers, or carbon nanotubes, to enable spatial actuation behavior, such as contraction for on-body compression or corrugation for haptic feedback. This research is a first experimental investigation into active auxetic and shearing textile structures. These textile structures leverage the bending- and torsional-deformations of the fibers/filaments within traditional textile structures as well as the shape memory effect of shape memory alloys to achieve novel, spatial performance. Five textile structures were fabricated from shape memory alloy wire deformed into needle lace and weft knit textile structures. All active structures exhibited anisotropic behavior and four of the five structures exhibited auxetic behavior upon free recovery, contracting in both x- and y-axes upon actuation (v = -0.3 to -1.5). One structure exhibited novel shearing behavior, with a mean free angle recovery of 7°. Temperature-controlled biaxial tensile testing was conducted to experimentally investigate actuation behavior and anisotropy of the designed structures. The presented design and performance of these active auxetic, anisotropic, and shearing textiles inspire new capabilities for applications, such as smart wearables, soft robotics, reconfigurable aerospace structures, and medical devices.


Exercise and sleep in aging: emphasis on serotonin.
Reductions in central serotonin activity with aging might be involved in sleep-related disorders in later life. Although the beneficial effects of aerobic exercise on sleep are not new, sleep represents a complex recurring state of unconsciousness involving many lines of transmitters which remains only partly clear despite intense ongoing research. It is known that serotonin released into diencephalon and cerebrum might play a key inhibitory role to help promote sleep, likely through an active inhibition of supraspinal neural networks. Several lines of evidence support the stimulatory effects of exercise on higher serotonergic pathways. Hence, exercise has proved to elicit acute elevations in forebrain serotonin concentrations, an effect that waned upon cessation of exercise. While adequate exercise training might lead to adaptations in higher serotonergic networks (desensitization of forebrain receptors), excessive training has been linked to serious brain serotonergic maladaptations accompanied by insomnia. Dietary supplementation of tryptophan (the only serotonin precursor) is known to stimulate serotonergic activity and promote sleep, whereas acute tryptophan depletion causes deleterious effects on sleep. Regarding sleep-wake regulation, exercise has proved to accelerate resynchronization of the biological clock to new light-dark cycles following imposition of phase shifts in laboratory animals. Noteworthy, the effect of increased serotonergic transmission on wake state appears to be biphasic, i.e. promote wake and thereafter drowsiness. Therefore, it might be possible that acute aerobic exercise would act on sleep by increasing activity of ascending brain serotonergic projections, though additional work is warranted to better understand the implication of serotonin in the exercise-sleep axis.


Bone regeneration and collagen fiber orientation around calcium phosphate-coated implants with machined or rough surfaces: a short-term histomorphometric study in dog mandibles.
The aim of this study was to compare bone formation and tissue reactions around implants with a calcium phosphate (CaP)-coated machined surface (CPMS) and a CaP-coated rough surface (CPRS) at critical-sized circumferential ridge defects in dogs after 4 and 8 weeks. All mandibular premolars were extracted bilaterally from five male mongrel dogs. After 8 weeks, circumferential marginal defects (2 mm wide and 5 mm deep) were created unilaterally using a customized drill at sites of CPMS and CPRS implant insertion. Four weeks later, the contralateral side was prepared using the same protocol. The dogs were sacrificed 4 weeks later. Specimens were analyzed histologically and histomorphometrically. Both CPMS and CPRS implants showed successful osseointegration in the apical bone area (without defects) regardless of the observation period (4 or 8 weeks). All circumferential defects were incompletely filled and osseointegration was limited at the apical area of the defect. In the unfilled defect area, collagen fibers were arranged perpendicular or oblique to the exposed implant surfaces, especially on CPRS implants. Within the limits of this study, CPMS and CPRS implants showed no statistically significant differences in osseointegration and bone regeneration in circumferential defects, along with the unique feature of collagen fibers arranged perpendicular or oblique to the exposed implant surfaces.


Serum albumin level during intestinal exfoliative rejection: a potential predictor of graft recovery and patient outcome.
Exfoliative rejection is a severe complication after intestinal transplant. The assessment of mucosa histology is restricted to the area reached by endoscopy. We aim to evaluate the serum albumin (SA) value as a parameter of graft damage and clinical prognosis in intestinal exfoliative rejection (ExR). The present study is a retrospective analysis of 11 episodes of ExR occurred in a cohort of 26 patients. SA levels were measured 24 h after diagnosis and twice a week thereafter and then correlated with parameters of clinical and graft histological recovery (HR). During ExR, all patients had very low SA levels, reaching a minimum average of 1.9 ± 0.3 g/dL. According to the value of albumin levels at ExR diagnosis, the patients were grouped finding a correlation with their clinical evolution. Six ExR episodes presented with severe hipoalbuminemia (<2.2 g/dL; p < 0.05) that correlated with worse patient and graft outcome, ranging from graft loss and need for re-transplantation to delayed clinical and HR. SA at ExR diagnosis may be an indicator of the severity of the ExR process, and it could also be used as an early predictor of patient and graft outcome.


A Comparison of Methods for RNA-Seq Differential Expression Analysis and a New Empirical Bayes Approach.
Transcriptome-based biosensors are expected to have a large impact on the future of biotechnology. However, a central aspect of transcriptomics is differential expression analysis, where, currently, deep RNA sequencing (RNA-seq) has the potential to replace the microarray as the standard assay for RNA quantification. Our contributions here to RNA-seq differential expression analysis are two-fold. First, given the high cost of an RNA-seq run, biological replicates are rare, and therefore, information sharing across genes to obtain variance estimates is crucial. To handle such information sharing in a rigorous manner, we propose an hierarchical, empirical Bayes approach (R-EBSeq) that combines the Cufflinks model for generating relative transcript abundance measurements, known as FPKM (fragments per kilobase of transcript length per million mapped reads) with the EBArrays framework, which was previously developed for empirical Bayes analysis of microarray data. A desirable feature of R-EBSeq is easy-to-implement analysis of more than pairwise comparisons, as we illustrate with experimental data. Secondly, we develop the standard RNA-seq test data set, on the level of reads, where 79 transcripts are artificially differentially expressed and, therefore, explicitly known. This test data set allows us to compare the performance, in terms of the true discovery rate, of R-EBSeq to three other widely used RNAseq data analysis packages: Cuffdiff, DEseq and BaySeq. Our analysis indicates that DESeq identifies the first half of the differentially expressed transcripts well, but then is outperformed by Cuffdiff and R-EBSeq. Cuffdiff and R-EBSeq are the two top performers. Thus, R-EBSeq offers good performance, while allowing flexible and rigorous comparison of multiple biological conditions.


Emergent properties of HIV risk among injection drug users in Tallinn, Estonia: synthesis of individual and neighbourhood-level factors.
HIV/AIDS risk is embodied within multiple levels including structural and social levels. The aim of this study was to assess the effects of neighbourhood characteristics on HIV prevalence among injection drug users (IDU) residing in the area of Tallinn, Estonia in 2007. A cross-sectional, multilevel design collecting individual-level data--a behaviour survey including data on self-reported residency and HIV antibody testing among 350 IDU and neighbourhood-level data--aggregate measures on socio-demo-economic residential characteristics from the 2000 Estonian census. Geocoding and multilevel modelling analysis was employed. Among the 350 IDU recruited, earlier age at first injection, fentanyl as the main injection drug, receptive syringe sharing, main income source other than legal employment and ever attended a syringe exchange programme remained significantly associated with increased odds of anti-HIV positivity in the multivariable analysis involving individual effects with no predictors at the neighbourhood level. In the multilevel model, individual (earlier at IDU initiation AOR 1.86, 95% CI 1.01 to 3.44; injecting opioids AOR 4.43, 95% CI 2.74 to 7.18; receptive syringe sharing AOR 2.51, 95% CI 1.86 to 3.37; main income source other than work AOR 2.04, 95% CI 1.32 to 3.14; ever attended a syringe exchange programme AOR 2.58, 95% CI 1.83 to 3.61) and neighbourhood level (higher unemployment rate AOR 5.95, 95% CI 2.47 to 14.31; greater residential change AOR 1.89, 95% CI 1.09 to 3.26) emerged as significant predictors of individual HIV-positive status. Our results indicate that both individual-level and emergent neighbourhood-level factors contribute to HIV risk among IDU and are amenable for preventive interventions.


Five new cases of breast cancer in transsexual persons.
Cross-sex hormone treatment of transsexual people may be associated with the induction and growth stimulation of hormone-related malignancies. We report here five cases of breast cancer, three in female-to-male (FtoM) transsexual subjects and two in male-to-female (MtoF) transsexual subjects. In the general population the incidence of breast cancer increases with age and with duration of exposure to sex hormones. This pattern was not recognised in these five transsexual subjects. Tumours occurred at a relatively young age (respectively, 48, 41, 41, 52 and 46 years old) and mostly after a relatively short span of time of cross-sex hormone treatment (9, 9-10 but in one after 30 years). Occurrence of breast cancer was rare. As has been reported earlier, breast tumours may occur in residual mammary tissue after breast ablation in FtoM transsexual people. For adequate treatment and decisions on further cross-sex hormone treatment it is important to have information on the staging and histology of the breast tumour (type, grade and receptor status), with an upcoming role for the androgen receptor status, especially in FtoM transsexual subjects with breast cancer who receive testosterone administration. This information should be taken into account when considering further cross-sex hormone treatment.


Endogenous axoplasmic proteins and proteins containing nuclear localization signal sequences use the retrograde axonal transport/nuclear import pathway in Aplysia neurons.
When the nuclear localization signal peptide (sp) of the SV 40 large T antigen was coupled to human serum albumin (HSA), rhodaminated (r), and microinjected into axons of Aplysia neurons in vitro, the rHSA-sp was conveyed through the axon to the cell body and then into the nucleus (Ambron et al., 1992). But since rHSA-sp is an artificial construct, we needed to determine whether naturally occurring nuclear proteins use this pathway. We therefore injected calf thymus histone H-1 and Xenopus oocyte nucleoplasmin into axons. By 3 hr both were retrogradely transported and targeted into the nucleus, though histone H-1 less efficiently than rHSA-sp or nucleoplasmin. In contrast, neither rHSA, nor rHSA conjugated to a peptide with a random distribution of basic amino acids, was transported or imported. To see if proteins that use the pathway remain intact, we coupled sp to HRP. When injected into varicosities, the HRP-sp was transported/imported to the nucleus, where it was enzymatically active. A key issue was to determine whether endogenous proteins use this pathway. Consequently, axoplasm was extruded from Aplysia nerves and the proteins were fractionated by size. SDS-PAGE and Western blots showed that two fractions contained proteins that were recognized by an affinity-purified antibody to sp: fraction 3 included sp83, and fraction 4 contained sp75. In addition, these two proteins were found in nuclei isolated from neurons. To assess transport, the total proteins in the fractions were rhodaminated and injected into varicosities. Fraction 3, but not fraction 4, contained protein that was transported through the axon to the nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)


Rye kernel breakfast increases satiety in the afternoon - an effect of food structure.
The structure of whole grain cereals is maintained to varying degrees during processing and preparation of foods. Food structure can influence metabolism, including perceived hunger and satiety. A diet that enhances satiety per calorie may help to prevent excessive calorie intake. The objective of this work was to compare subjective appetite ratings after consumption of intact and milled rye kernels. Two studies were performed using a randomized, cross-over design. Ratings for appetite (hunger, satiety and desire to eat) were registered during an 8-h period after consumption of whole and milled rye kernels prepared as breads (study 1, n = 24) and porridges (study 2, n = 20). Sifted wheat bread was used as reference in both study parts and the products were eaten in iso-caloric portions with standardized additional breakfast foods. Breads and porridges were analyzed to determine whether structure (whole vs. milled kernels) effected dietary fibre content and composition after preparation of the products. Statistical evaluation of the appetite ratings after intake of the different breakfasts was done by paired t-tests for morning and afternoon ratings separately, with subjects as random effect and type of breakfast and time points as fixed effects. All rye breakfasts resulted in higher satiety ratings in the morning and afternoon compared with the iso-caloric reference breakfast with sifted wheat bread. Rye bread with milled or whole kernels affected appetite equally, so no effect of structure was observed. In contrast, after consumption of the rye kernel breakfast, satiety was increased and hunger suppressed in the afternoon compared with the milled rye kernel porridge breakfast. This effect could be related to structural differences alone, because the products were equal in nutritional content including dietary fibre content and composition. The study demonstrates that small changes in diet composition such as cereal grain structure have the potential to effect feelings of hunger and satiety. This trial was registered at clinicaltrials.gov as NCT01042418.


Into the realm of social capital for adolescents: A latent profile analysis.
Recent reports of increasing prevalence of frequent health complaints and mental health problems among adolescents call for directing more attention on determinants of adolescent health. The relationship between health and social capital has gained increased attention since the early 2000's and research at review level confirms the importance of social capital for health outcomes, despite methodological heterogeneity. The aim of this study was to identify distinct profiles of family, school and peer social capital in a nationally representative sample of adolescents and to explore health outcomes in those profiles. Cross-sectional data from the Swedish Health Behaviour of School-aged Children 2013/14 was used for this study. The analytical sample consisted of 7,804 adolescents aged 11-, 13- and 15-years. Items representing sense of belonging and emotional support were assessed in three contexts; family, school and among peers. Latent profile analyses (LPA) were run to determine social capital profiles. Health outcomes included frequent health complaints and life satisfaction, while socioeconomic status and genders were included as predictors. The results show that five distinct profiles best represent the data for 11- and 15-year olds, while a four-profile model was optimal for 13-year olds. Some profiles were recurrent between age groups but unique profiles were also found. Health outcomes were significantly different between profiles depending on levels of social capital in the different contexts. This study provides novel insight into how social capital co-occurs among adolescents within the contexts of family, school and peers and how this translates into differences in health outcomes. The national representativeness of the sample increases the implications of the results and contributes to meaningful insights that help explain the interactions of social capital in multiple contexts, complementing what is previously known about the relationship with adolescent health.


Mortality in patients with non-functioning pituitary adenoma is increased: systematic analysis of 546 cases with long follow-up.
Non-functioning pituitary adenomas (NFAs) have a prevalence of 7-22/100,000 people. A significant number of patients suffer from morbidities related to the tumor, possible recurrence(s), and treatments utilized. Our aim was to assess mortality of patients with macroNFA and predictive factors. Retrospective cohort study in a tertiary referral center in the UK. A total of 546 patients operated for a macroNFA between 1963 and 2011 were studied. Mortality data were retrieved through the National Health Service Central Register and hospital records and recorded as standardized mortality ratio (SMR). Mortality was estimated for the total and various subgroups with clinical follow-up data. Median follow-up was 8 years (range: 1 month-48.5 years). SMR was 3.6 (95% CI, 2.9-4.5), for those operated before 1990, 4.7 (95% CI, 2.7-7.6) and for those after 1990, 3.5 (95% CI, 2.8-4.4). Main causes of death were cardio/cerebrovascular (33.7%), infections (30.1%), and malignancy (28.9%). Cox regression analysis demonstrated that only age at diagnosis remained an independent predictor of mortality (hazard ratio 1.10; 95% CI, 1.07-1.13, P<0.001), whereas sex, presentation with acute apoplexy, extent of tumor removal, radiotherapy, recurrence, untreated GH deficiency, FSH/LH deficiency, ACTH deficiency, TSH deficiency, and treatment with desmopressin had no impact. Despite the improvement of treatments over the last three decades, the mortality of patients with NFAs in our series remains high. Apart from age, factors related with the management/outcome of the tumor are not independent predictors, and pituitary hormone deficits managed with the currently-used substitution protocols do not adversely affect mortality.


IgG antibodies from dourine infected horses identify a distinctive Trypanosoma equiperdum antigenic pattern of low molecular weight molecules.
Diagnosis and control of dourine is strongly based on serological evidence, but knowledge of the humoral response of horses during infection is limited. In this study we developed a chemiluminescent immunoblotting (cIB) assay to characterise the Trypanosoma equiperdum antigen pattern recognised by IgGs from naturally or experimentally dourine-infected horses and analyse the kinetics of IgG humoral response following the infection. One compounding factor is that sera from uninfected animals often cross-react with T. equiperdum antigens. Development of the cIB assay was based on the hypothesis that serum IgGs from healthy and infected animals recognise different T. equiperdum antigen patterns. We used sera from 8 naturally infected horses which had recovered from Italian outbreaks and 2 experimentally infected mares. In addition, sera from 10 healthy control animals, eight of which were CFT positive but IFA negative for dourine, were collected from disease free regions. Sera were compared by the complement fixation test (CFT), indirect immune fluorescence (IFA) and the cIB assay. cIB analysis revealed that IgGs from infected horses, in contrast to IgGs from healthy horses, specifically recognise a T. equiperdum antigenic profile with low molecular weight bands ranging between 16 and 35 kDa. A time course experiment indicated that IgGs specific for the 16-35 kDa parasite protein fraction appear 17 days post-infection. The cIB assay confirmed all ten infected animals as positive and all controls as negative. This study demonstrated that analysis of IgGs by cIB can provide clear confirmation of trypanosome infection in horses, suggesting that this technique can be applied as a confirmatory serological test for dourine infection.


The Patient Experience: Informing Practice through Identification of Meaningful Communication from the Patient's Perspective.
(1) Background: There is limited empirical knowledge concerning aspects of healthcare that contribute to a good patient experience from the patient's perspective and how patient feedback informs service development. (2) Aim: To examine the issues that influence the effectiveness of communication on patient satisfaction, experience and engagement, in an acute National Health Service (NHS) setting, through identification of the patient's requirements and expectations. (3) Method: Data was gathered from a large teaching hospital using a Friends and Family Test (FFT) and a communication specific survey. Both surveys captured patient narrative to identify predominant influences to explain the quantitative responses. (4) Results: The key priorities for patients are involvement in their care and receiving the right amount of information to support this. However, the delivery of compassionate care was identified as having the most influence on the likelihood of patients to recommend an acute NHS Trust. (5) Conclusion: The findings support a broader understanding of the constituents of an all-encompassing patient experience from the patient's perspective. (6) Implications: healthcare organizations need to focus their resources on how to improve patient/provider communication to support patients to be true partners in their care.


Sulfite determination by a biosensor based on bay leaf tissue homogenate: very simple and economical method.
Of all the food additives for which the FDA has received adverse reaction reports, the ones that most closely resemble true allergens are sulfur-based preservatives. Sulfites are used primarily as antioxidants to prevent or reduce discoloration of light-colored fruits and vegetables, such as dried apples and potatoes, and to inhibit the growth of microorganisms in fermented foods such as wine. This work aims to prepare an electrochemical biosensor based on bay leaf tissue homogenate that contains polyphenol oxidase enzyme abundantly for sulfite detection in foods. The principle of the biosensor is based on the inhibition effect of sulfites on polyphenol oxidase in the bioactive layer. Optimum conditions for the biosensor, such as temperature and pH, were investigated. Some stability parameters of the biosensor were also identified. The biosensor showed a linear calibration graph in the range of 25-100 microM sulfite. The biosensor presents a very simple, economical, reliable, and feasible method for sulfite detection in foods.


EUS-guided fine needle aspiration of the liver: indications, yield, and safety based on an international survey of 167 cases.
The liver is a common site of metastases for various malignancies. EUS-guided fine needle aspiration (EUS-FNA) of liver masses has only been reported in small series from single centers. A retrospective questionnaire was sent by e-mail to 130 EUS-FNA centers around the world regarding indications, complications, and findings of EUS-FNA of the liver. Twenty-one centers reported 167 cases of EUS-FNA of the liver. A complication was reported in 6 (4%) of 167 cases including the following: death in 1 patient with an occluding biliary stent and biliary sepsis, bleeding (1), fever (2), and pain (2). EUS-FNA diagnosed malignancy in 23 of 26 (89%) cases after nondiagnostic fine needle aspiration under transabdominal US guidance. EUS localized an unrecognized primary tumor in 17 of 33 (52%) cases in which CT had demonstrated only liver metastases. EUS image characteristics were not predictive of malignant versus benign lesions. EUS-guided FNA of the liver appears to be a safe procedure with a major complication rate of approximately 1%. EUS-FNA should be considered when a liver lesion is poorly accessible to US-, or CT-guided FNA should be considered when US- or CT-guided FNA fail to make a diagnosis, when a liver lesion(s) is detected (de novo) by EUS, and for investigation of possible upper GI primary tumors in the setting of liver metastases.


5-Hydroxytryptamine (serotonin) 2A receptor gene polymorphism is associated with schizophrenia.
Schizophrenia, the debilitating neuropsychiatric disorder, is known to be heritable, involving complex genetic mechanisms. Several chromosomal regions associated with schizophrenia have been identified during the past; putative gene (s) in question, to be called the global signature for the pathophysiology of the disease, however, seems to evade us. The results obtained from the several population-wise association-non association studies have been diverse. w0 e therefore, undertook the present study on Tamil speaking population in south India to examine the association between the single nucleotide polymorphisms (SNPs) at the serotonin receptor gene (5HT2A) and the occurrence of the disease. Blood samples collected from 266 cases and 272 controls were subjected to genotyping (PCR amplification of candidate SNPs, RFLP and sequencing). The data on the SNPs were subjected to statistical analysis for assessing the gene frequencies in both the cases and the controls. The study revealed significant association between the genotypic frequencies of the serotonin receptor polymorphism and schizophrenia. SNP analysis revealed that the frequencies of GG (30%, rs6311) and CC genotypes (32%, rs6313), were higher in patients (P<0.05) than in controls. The study also showed presence of G and C alleles in patients. s0 ignificant levels of linkage disequilibrium (LD) were found to exist between the genotype frequencies of rs6311 and rs6313. This study indicated an association between the SNPs (rs6311 and rs6313) of the serotonin receptor 5HT2A and schizophrenia. HapMap analysis revealed that in its genotype distribution, the Tamil speaking population was different from several other populations across the world, signifying the importance of such ethnicity-based studies to improve our understanding of this complex disease.


The prevalence and severity of low back pain and associated symptoms in 3,009 old men.
The aim of this study is to evaluate the prevalence and severity of low back pain (LBP) and the influence of sciatica and neurological deficits in old men. Mister osteoporosis Sweden includes 3,014 community-dwelling men aged 69-81 years. At study start 3,009 participants answered questions on LBP, low back pain and sciatica (LBP + SCI) or low back pain and sciatica with associated neurological deficits (LBP + SCI + NEU) during the preceding 12 months. Data are presented as proportions or medians with mid-quartile ranges. Differences between groups were tested by χ(2) test and Kruskall-Wallis test. 24% had experienced LBP without SCI, 8% LBP + SCI and 14% LBP + SCI + NEU. 10% of the men with LBP, 22% of those with LBP + SCI, and 36% of those with LBP + SCI + NEU rated the pain as severe (p < 0.001). 23% of the men with LBP, 31% of those with LBP + SCI and 50% of those with LBP + SCI + NEU reported limitation in activity of daily living (ADL) (p < 0.001). Men with only LBP had to restrict their activities for 7 days (3-14), those with LBP + SCI 6 days (2-14) and those with LBP + SCI + NEU 10 days (3-30) (p < 0.05). The 1-year prevalence of LBP in community living men aged 69-81 years was close to 50% but for individuals with LBP or LBP + SCI the morbidity was low with more than two-thirds having no limitations in ADL. In men with LBP + SCI + NEU more than one-third rated the pain as severe and close to half had limitations in ADL.


Genome-wide analysis of mRNAs regulated by the THO complex in Drosophila melanogaster.
In yeast cells, the THO complex has been implicated in mitotic recombination, transcription elongation and mRNA nuclear export. The stable core of THO consists of Tho2p, Hpr1p, Mft1p and Thp2p. Whether a complex with similar functions assembles in metazoa has not yet been established. Here we report that Drosophila melanogaster THO consists of THO2, HPR1 and three proteins, THOC5-THOC7, which have no orthologs in budding yeast. Gene expression profiling in cells depleted of THO components revealed that <20% of the transcriptome was regulated by THO. Nonetheless, export of heat-shock mRNAs under heat stress was strictly dependent on THO function. Notably, 8% of upregulated genes encode proteins involved in DNA repair. Thus, although THO function seems to be conserved, the vast majority of mRNAs are transcribed and exported independently of THO in D. melanogaster.


The attentional role of the left parietal cortex: the distinct lateralization and localization of motor attention in the human brain.
It is widely agreed that visuospatial orienting attention depends on a network of frontal and parietal areas in the right hemisphere. It is thought that the visuospatial orienting role of the right parietal lobe is related to its role in the production of overt eye movements. The experiments reported here test the possibility that other parietal regions may be important for directing attention in relation to response modalities other than eye movement. Specifically, we used positron emission tomography (PET) to test the hypothesis that a 'left' parietal area, the supramarginal gyrus, is important for attention in relation to limb movements (Rushworth et al., 1997; Rushworth, Ellison, & Walsh, in press). We have referred to this process as 'motor attention' to distinguish it from orienting attention. In one condition subjects spent most of the scanning period covertly attending to 'left' hand movements that they were about to make. Activity in this first condition was compared with a second condition with identical stimuli and movement responses but lacking motor attention periods. Comparison of the conditions revealed that motor attention-related activity was almost exclusively restricted to the 'left' hemisphere despite the fact that subjects only ever made ipsilateral, left-hand responses. Left parietal activity was prominent in this comparison, within the parietal lobe the critical region for motor attention was the supramarginal gyrus and the adjacent anterior intraparietal sulcus (AIP), a region anterior to the posterior parietal cortex identified with orienting attention. In a second part of the experiment we compared a condition in which subjects covertly rehearsed verbal responses with a condition in which they made verbal responses immediately without rehearsal. A comparison of the two conditions revealed verbal rehearsal-related activity in several anterior left hemisphere areas including Broca's area. The lack of verbal rehearsal-related activity in the left supra-marginal gyrus confirms that this area plays a direct role in motor attention that cannot be attributed to any strategy of verbal mediation. The results also provide evidence concerning the importance of ventral premotor (PMv) and Broca's area in motor attention and language processes.


Microbial polysaccharides template assembly of nanocrystal fibers.
Biological systems can produce extraordinary inorganic structures and morphologies. The mechanisms of synthesis are poorly understood but are of great interest for engineering novel materials. We use spectromicroscopy to show that microbially generated submicrometer-diameter iron oxyhydroxide (FeOOH) filaments contain polysaccharides, providing an explanation for the formation of akaganeite pseudo-single crystals with aspect ratios of approximately 1000:1. We infer that the cells extrude the polysaccharide strands to localize FeOOH precipitation in proximity to the cell membrane to harness the proton gradient for energy generation. Characterization of organic compounds with high spatial resolution, correlated with mineralogical information, should improve our understanding of biomineralization mechanisms.


An integrated approach to identifying cis-regulatory modules in the human genome.
In eukaryotic genomes, it is challenging to accurately determine target sites of transcription factors (TFs) by only using sequence information. Previous efforts were made to tackle this task by considering the fact that TF binding sites tend to be more conserved than other functional sites and the binding sites of several TFs are often clustered. Recently, ChIP-chip and ChIP-sequencing experiments have been accumulated to identify TF binding sites as well as survey the chromatin modification patterns at the regulatory elements such as promoters and enhancers. We propose here a hidden Markov model (HMM) to incorporate sequence motif information, TF-DNA interaction data and chromatin modification patterns to precisely identify cis-regulatory modules (CRMs). We conducted ChIP-chip experiments on four TFs, CREB, E2F1, MAX, and YY1 in 1% of the human genome. We then trained a hidden Markov model (HMM) to identify the labels of the CRMs by incorporating the sequence motifs recognized by these TFs and the ChIP-chip ratio. Chromatin modification data was used to predict the functional sites and to further remove false positives. Cross-validation showed that our integrated HMM had a performance superior to other existing methods on predicting CRMs. Incorporating histone signature information successfully penalized false prediction and improved the whole performance. The dataset we used and the software are available at http://nash.ucsd.edu/CIS/.


Use of grating theories in integrated optics.
Recently [Opt. Lett. 25, 1092 (2000)], two of the present authors proposed extending the domain of applicability of grating theories to aperiodic structures, especially the diffraction structures that are encountered in integrated optics. This extension was achieved by introduction of virtual periodicity and incorporation of artificial absorbers at the boundaries of the elementary cells of periodic structures. Refinements and extensions of that previous research are presented. Included is a thorough discussion of the effect of the absorber quality on the accuracy of the computational results, with highly accurate computational results being achieved with perfectly matched layer absorbers. The extensions are concerned with the diversity of diffraction waveguide problems to which the method is applied. These problems include two-dimensional classical problems such as those involving Bragg mirrors and grating couplers that may be difficult to model because of the length of the components and three-dimensional problems such as those involving integrated diffraction gratings, photonic crystal waveguides, and waveguide airbridge microcavities. Rigorous coupled-wave analysis (also called the Fourier modal method) is used to support the analysis, but we believe that the approach is applicable to other grating theories. The method is tested both against available numerical data obtained with finite-difference techniques and against experimental data. Excellent agreement is obtained. A comparison in terms of convergence speed with the finite-difference modal method that is widely used in waveguide theory confirms the relevancy of the approach. Consequently, a simple, efficient, and stable method that may also be applied to waveguide and grating diffraction problems is proposed.


Determining the microbiological cause of a chest infection.
Over recent years non-culture techniques such as specific viral and bacterial nucleic acid amplification, serology and antigen detection have considerably developed and been applied within research studies to clinical samples, significantly increasing pathogen detection in pneumonia. There are promising signs of improved diagnostic yields for pneumococcal pneumonia when using molecular techniques to detect pneumococcal gene sequences in blood or by combining serum biomarkers with rapid pneumococcal urinary antigen testing. Pathogens have traditionally been difficult to detect in pneumonia and treatment is usually successful with empiric antibiotics. However, directed antibiotic treatment has significant benefits in terms of antibiotic stewardship and these new technologies make this goal a possibility, though not yet a reality.


Genetic and physiologic dissection of the vertebrate cardiac conduction system.
Vertebrate hearts depend on highly specialized cardiomyocytes that form the cardiac conduction system (CCS) to coordinate chamber contraction and drive blood efficiently and unidirectionally throughout the organism. Defects in this specialized wiring system can lead to syncope and sudden cardiac death. Thus, a greater understanding of cardiac conduction development may help to prevent these devastating clinical outcomes. Utilizing a cardiac-specific fluorescent calcium indicator zebrafish transgenic line, Tg(cmlc2:gCaMP)(s878), that allows for in vivo optical mapping analysis in intact animals, we identified and analyzed four distinct stages of cardiac conduction development that correspond to cellular and anatomical changes of the developing heart. Additionally, we observed that epigenetic factors, such as hemodynamic flow and contraction, regulate the fast conduction network of this specialized electrical system. To identify novel regulators of the CCS, we designed and performed a new, physiology-based, forward genetic screen and identified for the first time, to our knowledge, 17 conduction-specific mutations. Positional cloning of hobgoblin(s634) revealed that tcf2, a homeobox transcription factor gene involved in mature onset diabetes of the young and familial glomerulocystic kidney disease, also regulates conduction between the atrium and the ventricle. The combination of the Tg(cmlc2:gCaMP)(s878) line/in vivo optical mapping technique and characterization of cardiac conduction mutants provides a novel multidisciplinary approach to further understand the molecular determinants of the vertebrate CCS.


C-Terminal Binding Protein 1 Modulates Cellular Redox via Feedback Regulation of MPC1 and MPC2 in Melanoma Cells.
BACKGROUND Recent studies have illustrated that the transcription co-repressor, C-terminal binding protein 1 (CtBP1), links the metabolic alterations to transcription controls in proliferation, EMT, genome stability, metabolism, and lifespan, but whether CtBP1 affects the cellular redox homeostasis is unexplored. This study was designed to investigate the mechanism of CtBP1-mediated transcription repression that contributes to the metabolic reprogramming. MATERIAL AND METHODS Knockdown of CtBP1 in both mouse MEF cells and human melanoma cells changed cell redox homeostasis. Further, chromatin immunoprecipitation (ChIP) and luciferase reporter assay were performed for identification of CtBP1 downstream targets, pyruvate carrier 1 and 2 genes (MPC1 and MPC2), which contribute to redox homeostasis and are transcriptionally regulated by CtBP1. Moreover, blockage of the cellular NADH level with the glycolysis inhibitor 2-Deoxy-D-Glucose (2-DG) rescued MPC1 and MPC2 expression. MTT assay and scratch assay were performed to investigate the effect of MPC1 and MPC2 expression on malignant properties of melanoma cells. RESULTS The data demonstrated that CtBP1 directly bound to the promoters of MPC1 and MPC2 and transcriptionally repressed them, leading to increased levels of free NADH in the cytosol and nucleus, thus positively feeding back CtBP1's functions. Consequently, restoring MPC1 and MPC2 in human tumor cells decreases free NADH and inhibits melanoma cell proliferation and migration. CONCLUSIONS Our data indicate that MPC1 and MPC2 are principal mediators that link CtBP1-mediated transcription regulation to NADH production. The discovery of CtBP1 as an NADH regulator in addition to being an NADH sensor shows that CtBP1 is at the center of tumor metabolism and transcription control.


Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds.
Individuals with a family history of pancreatic cancer have an increased risk of developing pancreatic cancer. Quantification of this risk provides a rational basis for cancer risk counseling and for screening for early pancreatic cancer. In a prospective registry-based study, we estimated the risk of pancreatic cancer in individuals with a family history of pancreatic cancer. Standardized incidence ratios were calculated by comparing the number of incident pancreatic cancers observed with those expected using Surveillance, Epidemiology and End Results (SEER) rates. Familial pancreatic cancer (FPC) kindreds were defined as kindreds having at least one pair of first-degree relatives with pancreatic cancer, and sporadic pancreatic cancer (SPC) kindreds as families without such an affected pair. Nineteen incident pancreatic cancers developed among 5,179 individuals from 838 kindreds (at baseline, 370 FPC kindreds and 468 SPC kindreds). Of these 5,179 individuals, 3,957 had at least one first-degree relative with pancreatic cancer and contributed 10,538 person-years of follow-up. In this group, the observed-to-expected rate of pancreatic cancer was significantly elevated in members of FPC kindreds [9.0; 95% confidence interval (CI), 4.5-16.1], but not in the SPC kindreds (1.8; 95% CI., 0.22-6.4). This risk in FPC kindreds was elevated in individuals with three (32.0; 95% CI, 10.2-74.7), two (6.4; CI, 1.8-16.4), or one (4.6; CI, 0.5-16.4) first-degree relative(s) with pancreatic cancer. Risk was not increased among 369 spouses and other genetically unrelated relatives. Risk was higher in smokers than in nonsmokers. Individuals with a strong family history of pancreatic cancer have a significantly increased risk of developing pancreatic cancer.


Ptc6 is required for proper rapamycin-induced down-regulation of the genes coding for ribosomal and rRNA processing proteins in S. cerevisiae.
Ptc6 is one of the seven components (Ptc1-Ptc7) of the protein phosphatase 2C family in the yeast Saccharomyces cerevisiae. In contrast to other type 2C phosphatases, the cellular role of this isoform is poorly understood. We present here a comprehensive characterization of this gene product. Cells lacking Ptc6 are sensitive to zinc ions, and somewhat tolerant to cell-wall damaging agents and to Li(+). Ptc6 mutants are sensitive to rapamycin, albeit to lesser extent than ptc1 cells. This phenotype is not rescued by overexpression of PTC1 and mutation of ptc6 does not reproduce the characteristic genetic interactions of the ptc1 mutation with components of the TOR pathway, thus suggesting different cellular roles for both isoforms. We show here that the rapamycin-sensitive phenotype of ptc6 cells is unrelated to the reported role of Pt6 in controlling pyruvate dehydrogenase activity. Lack of Ptc6 results in substantial attenuation of the transcriptional response to rapamycin, particularly in the subset of repressed genes encoding ribosomal proteins or involved in rRNA processing. In contrast, repressed genes involved in translation are Ptc6-independent. These effects cannot be attributed to the regulation of the Sch9 kinase, but they could involve modulation of the binding of the Ifh1 co-activator to specific gene promoters.


Associations among Listeria monocytogenes genotypes and distinct clinical manifestations of listeriosis in cattle.
To determine whether specific strains of Listeria monocytogenes, as determined by genetic characteristics and virulence phenotypes, were associated with distinct clinical manifestations of listeriosis in cattle and thus may potentially have tissue specificity. 32 cattle. DNA sequence data for the virulence genes actAand inlAwere used to infer the phylogeny of L. monocytogenes and to test for positive selection. Isolates were screened for the presence or absence of internalin genes and assigned an internalin profile. Plaquing assays were performed to determine the relative cytopathogenicity of each isolate. Categorical data analyses were performed to describe associations among L. monocytogenes genotypes, virulence phenotypes, and clinical manifestations of listeriosis. Results confirmed that L. monocytogenes represents 2 deeply separated evolutionary lineages. Genes actA and inlA contained amino acid sites under positive selection, and specific residues at some sites were associated with lineage and manifestation of listeriosis. Whereas lineage I was clonal and predominantly composed of isolates from cases of encephalitis, lineage II was more genetically diverse and equally represented by isolates from cases of encephalitis versus septicemia and fetal infection. Lineage I isolates also had greater cytopathogenicity in vitro, compared with lineage II isolates. Results indicated that L. monocytogenes virulence genes underwent positive selection that is consistent with the diversification of 2 evolutionary lineages: lineage I is clonal and associated with encephalitis, and lineage II is more genetically diverse and equally likely to cause both major forms of listeriosis in cattle.


Design and implementation of the AIRWAYS-2 trial: A multi-centre cluster randomised controlled trial of the clinical and cost effectiveness of the i-gel supraglottic airway device versus tracheal intubation in the initial airway management of out of hospital cardiac arrest.
Health outcomes after out of hospital cardiac arrest (OHCA) are extremely poor, with only 7-9% of patients in the United Kingdom (UK) surviving to hospital discharge. Currently emergency medical services (EMS) use either tracheal intubation or newer supraglottic airway devices (SGAs) to provide advanced airway management during OHCA. Equipoise between the two techniques has led to calls for a well-designed randomised controlled trial. The primary objective of the AIRWAYS-2 trial is to assess whether the clinical effectiveness of the i-gel, a second-generation SGA, is superior to tracheal intubation in the initial airway management of OHCA patients in the UK. Paramedics recruited to the AIRWAYS-2 trial are randomised to use either tracheal intubation or i-gel as their first advanced airway intervention. Adults who have had a non-traumatic OHCA and are attended by an AIRWAYS-2 paramedic are retrospectively assessed against eligibility criteria for inclusion. The primary outcome is the modified Rankin Scale score at hospital discharge. Secondary objectives are to: (i) estimate differences between groups in outcome measures relating to airway management, hospital stay and recovery at 3 and 6 months; (ii) estimate the cost effectiveness of the i-gel compared to tracheal intubation. Because OHCA patient needs immediate treatment there are several unusual features and challenges to the design and implementation of this trial; these include level of randomisation, the automatic enrolment model, enrolment of patients that lack capacity and minimisation of bias. Patient enrolment began in June 2015. The trial will enrol 9070 patients over two years. The results are expected to influence future resuscitation guidelines. Trial Registration ISRCTN: 08256118.


Gender and grade differences in objectively measured physical activity and sedentary behavior patterns among Japanese children and adolescents: a cross-sectional study.
Physical activity levels in childhood have decreased, making the promotion of children's physical activity an important issue. The present study examined gender and grade differences in objectively measured sedentary behavior, physical activity, and physical activity guideline attainment among Japanese children and adolescents. In total, 329 boys and 362 girls age 3-15 years completed the survey. School grade, gender, height, and weight were collected by questionnaires and physical activity objectively measured using an accelerometer (Lifecorder Suzuken Co.). Physical activity level (in MET) was classified as sedentary (<1.5), light (≥1.5 to <3), moderate (≥3 to <6), or vigorous (≥6). Continuous zero accelerometer counts for ≥20 min were censored and a valid accelerometry study required at least 3 days (2 weekdays and 1 weekend day) with > 600 min/day total wear time. Two-way analysis of covariance and logistic regression analyses, adjusted for weight status and accelerometer wear time, were used to examine gender and grade differences in physical activity variables and the likelihood of physical activity guideline attainment by gender and grade level. Participants were sedentary 441.4 (SD, 140.1) min/day or 53.7 % of the average daily accelerometer wear time of 811.2 (118.7) min, engaged in light physical activity 307.1 (70.0) min or 38.4 % of wear time, moderate physical activity 34.6 (14.8) min (4.3 %), vigorous physical activity 28.3 (19.1) min (3.6 %), and took 12462.6 (4452.5) steps/day. Boys were more physically active and took more steps/day than girls. Students in higher grades were less active than those in lower grades. Boys were significantly more likely to meet physical activity guidelines than girls (OR: 2.07, 95 % CI: 1.45-2.96). Preschoolers (6.66, 4.01-11.06), lower-grade elementary school students (17.11, 8.80-33.27), and higher-grade elementary school students (7.49, 4.71-11.92) were more likely to meet guidelines than junior high school students. Boys and lower-grade students engaged in more physical activity and were more likely to attain guidelines than girls and higher-grade students. These findings highlight the need for effective and sustainable strategies to promote physical activity in Japanese school children.


Statistical approach to segmentation of single-channel cerebral MR images.
A statistical model is presented that represents the distributions of major tissue classes in single-channel magnetic resonance (MR) cerebral images. Using the model, cerebral images are segmented into gray matter, white matter, and cerebrospinal fluid (CSF). The model accounts for random noise, magnetic field inhomogeneities, and biological variations of the tissues. Intensity measurements are modeled by a finite Gaussian mixture. Smoothness and piecewise contiguous nature of the tissue regions are modeled by a three-dimensional (3-D) Markov random field (MRF). A segmentation algorithm, based on the statistical model, approximately finds the maximum a posteriori (MAP) estimation of the segmentation and estimates the model parameters from the image data. The proposed scheme for segmentation is based on the iterative conditional modes (ICM) algorithm in which measurement model parameters are estimated using local information at each site, and the prior model parameters are estimated using the segmentation after each cycle of iterations. Application of the algorithm to a sample of clinical MR brain scans, comparisons of the algorithm with other statistical methods, and a validation study with a phantom are presented. The algorithm constitutes a significant step toward a complete data driven unsupervised approach to segmentation of MR images in the presence of the random noise and intensity inhomogeneities.


The Relationship Between Ocular Itch, Ocular Pain, and Dry Eye Symptoms (An American Ophthalmological Society Thesis).
To evaluate associations between sensations of ocular itch and dry eye (DE) symptoms, including ocular pain, and DE signs. A cross-sectional study of 324 patients seen in the Miami Veterans Affairs eye clinic was performed. The evaluation consisted of questionnaires regarding ocular itch, DE symptoms, descriptors of neuropathic-like ocular pain (NOP), and evoked pain sensitivity testing on the forehead and forearm, followed by a comprehensive ocular surface examination including corneal mechanical sensitivity testing. Analyses were performed to examine for differences between those with and without subjective complaints of ocular itch. The mean age was 62 years with 92% being male. Symptoms of DE and NOP were more frequent in patients with moderate-severe ocular itch compared to those with no or mild ocular itch symptoms. With the exception of ocular surface inflammation (abnormal matrix metalloproteinase 9 testing) which was less common in those with moderate-severe ocular itch symptoms, DE signs were not related to ocular itch. Individuals with moderate-severe ocular itch also demonstrated greater sensitivity to evoked pain on the forearm and had higher non-ocular pain, depression, and post-traumatic stress disorders scores, compared to those with no or mild itch symptoms. Subjects with moderate-severe ocular itch symptoms have more severe symptoms of DE, NOP, non-ocular pain and demonstrate abnormal somatosensory testing in the form of increased sensitivity to evoked pain at a site remote from the eye, consistent with generalized hypersensitivity.


The autonomic control and functional significance of the changes in heart rate associated with air breathing in the jeju, Hoplerythrinus unitaeniatus.
The jeju is a teleost fish with bimodal respiration that utilizes a modified swim bladder as an air-breathing organ (ABO). Like all air-breathing fish studied to date, jeju exhibit pronounced changes in heart rate (fH) during air-breathing events, and it is believed that these may facilitate oxygen uptake (MO2) from the ABO. The current study employed power spectral analysis (PSA) of fH patterns, coupled with instantaneous respirometry, to investigate the autonomic control of these phenomena and their functional significance for the efficacy of air breathing. The jeju obtained less than 5% of total MO2 (MtO2) from air breathing in normoxia at 26 degrees C, and PSA of beat-to-beat variability in fH revealed a pattern similar to that of unimodal water-breathing fish. In deep aquatic hypoxia (water PO2)=1 kPa) the jeju increased the frequency of air breathing (fAB) tenfold and maintained MtO2 unchanged from normoxia. This was associated with a significant increase in heart rate variability (HRV), each air breath (AB) being preceded by a brief bradycardia and then followed by a brief tachycardia. These fH changes are qualitatively similar to those associated with breathing in unimodal air-breathing vertebrates. Within 20 heartbeats after the AB, however, a beat-to-beat variability in fH typical of water-breathing fish was re-established. Pharmacological blockade revealed that both adrenergic and cholinergic tone increased simultaneously prior to each AB, and then decreased after it. However, modulation of inhibitory cholinergic tone was responsible for the major proportion of HRV, including the precise beat-to-beat modulation of fH around each AB. Pharmacological blockade of all variations in fH associated with air breathing in deep hypoxia did not, however, have a significant effect upon fAB or the regulation of MtO2. Thus, the functional significance of the profound HRV during air breathing remains a mystery.


Statistics of the disorder-induced losses of high-Q photonic crystal cavities.
We analyze and compare the effect of fabrication disorder on the quality factor of six well-known high-index photonic crystal cavity designs. The theoretical quality factors for the different nominal structures span more than three orders of magnitude, ranging from 5.4 × 10(4) to 7.5 × 10(7), and the defect responsible for confining light is introduced in a different way for each structure. Nevertheless, among the different designs we observe similar behavior of the statistics of the disorder-induced light losses. In particular, we show that for high enough disorder, such that the quality factor is mainly determined by the disorder-induced losses, the measured quality factors differ marginally - not only on average as commonly acknowledged, but also in their full statistical distributions. This notably shows that optimizing the theoretical quality factor brings little practical improvement if its value is already much larger than what is typically measured, and if this is the case, there is no way to choose an alternative design more robust to disorder.


Septic polyarthritis caused by Erysipelothrix rhusiopathiae in a dog.
A 14-month-old, male German Shepherd dog was admitted with a six-week history of lameness and swelling of the right hindlimb. Clinical examination revealed polyarthritis, fever, petechiae and ecchymoses of the abdominal skin and prepuce. The haematology and blood chemistry were indicative of sepsis. Mediolateral radiographic views of both of the stifle joints revealed signs of bilateral articular capsule swelling. The radiographical, bacteriological and necropsy findings confirmed a diagnosis of septic polyarthritis due to infection with Erysipelothrix rhusiopathiae.


Preterm Prelabor Rupture of Membranes: Outcomes with Expectant Management until 34 versus 35 Weeks.
To evaluate outcomes with expectant management of preterm prelabor rupture of membranes (PROM) until 35 weeks versus immediate delivery at ≥34 weeks. This was a multicenter retrospective cohort study of singletons with preterm PROM at >20 weeks from 2011 through 2017. Groups were defined as expectant management until 35 weeks versus immediate delivery at ≥34 weeks. Primary outcome was composite neonatal morbidity: need for respiratory support, culture positive neonatal sepsis, or antibiotic administration for >72 hours. Univariate and general estimating equation models were used with p < 0.05 considered significant. A total of 280 mother-infant dyads were included. There was no difference in composite neonatal outcome in pregnancies managed with expectant management compared with immediate delivery (43.4 vs. 37.5%; p = 0.32). Those with expectant management had shorter length of neonatal intensive care unit (NICU) admission but higher rates of neonatal antibiotics for > 72 hours, endometritis, and histological chorioamnionitis. There were no cases of fetal demise, neonatal death, or maternal sepsis, and only three cases of neonatal sepsis. There is no difference in composite neonatal morbidity in pregnancies with preterm PROM managed with expectant management until 35 weeks as compared with immediate delivery at 34 weeks. Expectant management is associated with a decreased length of NICU admission but increased short-term infectious morbidity.


Prevalence and incidence of vertebral deformities.
There is a need to identify vertebral fractures from radiographs taken at a single point in time, but considerable controversy surrounds the methods to be used. We extended a data set to comprise baseline radiographs of the thoracic and lumbar spine on an age-stratified random sample of 762 Rochester, Minnesota, women and used revised methods to define vertebral deformities morphometrically. Changes in the method of measuring vertebral heights, changes in the source of normal values for vertebral measurements and changes in the criteria for assessing vertebral deformity had little impact on estimated prevalence and incidence in this population. The prevalence of any vertebral deformity was estimated at 25.3 per 100 Rochester women aged 50 years and over (95% CI, 22.3-28.2), while the incidence of a new deformity in this group was estimated at 17.8 per 1000 person-years (95% CI, 16.0-19.7). Projected nationally, these data suggest that over 500,000 white women in the United States develop vertebral deformities for the first time each year and that over 7 million white women aged 50 years and over might be affected at any given time. These estimates are limited by the absence of a reliable 'gold standard' with which to determine false positive and false negative rates associated with this or any other morphometric method. Information on the health consequences of vertebral deformities of various sorts would be most helpful in choosing between alternative approaches to defining them.


Plexin-B2 and Plexin-D1 in dendritic cells: expression and IL-12/IL-23p40 production.
Plexins are a family of genes (A,B,C, and D) that are expressed in many organ systems. Plexins expressed in the immune system have been implicated in cell movement and cell-cell interaction during the course of an immune response. In this study, the expression pattern of Plexin-B2 and Plexin-D1 in dendritic cells (DCs), which are central in immune activation, was investigated. Plexin-B2 and Plexin-D1 are reciprocally expressed in myeloid and plasmacytoid DC populations. Plasmacytoid DCs have high Plexin-B2 but low Plexin-D1, while the opposite is true of myeloid DCs. Expression of Plexin-B2 and Plexin-D1 is modulated upon activation of DCs by TLR ligands, TNFα, and anti-CD40, again in a reciprocal fashion. Semaphorin3E, a ligand for Plexin-D1 and Plexin-B2, is expressed by T cells, and interestingly, is dramatically higher on Th2 cells and on DCs. The expression of Plexins and their ligands on DCs and T cells suggest functional relevance. To explore this, we utilized chimeric mice lacking Plxnb2 or Plxnd1. Absence of Plexin-B2 and Plexin-D1 on DCs did not affect the ability of these cells to upregulate costimulatory molecules or the ability of these cells to activate antigen specific T cells. Additionally, Plexin-B2 and Plexin-D1 were dispensable for chemokine-directed in-vitro migration of DCs towards key DC chemokines, CXCL12 and CCL19. However, the absence of either Plexin-B2 or Plexin-D1 on DCs leads to constitutive expression of IL-12/IL-23p40. This is the first report to show an association between Plexin-B2 and Plexin-D1 with the negative regulation of IL-12/IL-23p40 in DCs. This work also shows the presence of Plexin-B2 and Plexin-D1 on mouse DC subpopulations, and indicates that these two proteins play a role in IL-12/IL-23p40 production that is likely to impact the immune response.


Hereditary and familial colon cancer.
Between 2% to 5% of all colon cancers arise in the setting of well-defined inherited syndromes, including Lynch syndrome, familial adenomatous polyposis, MUTYH-associated polyposis, and certain hamartomatous polyposis conditions. Each is associated with a high risk of colon cancer. In addition to the syndromes, up to one-third of colon cancers exhibit increased familial risk, likely related to inheritance. A number of less penetrant, but possibly more frequent susceptibility genes have been identified for this level of inheritance. Clarification of predisposing genes allows for accurate risk assessment and more precise screening approaches. This review examines the colon cancer syndromes, their genetics and management, and also the common familial colon cancers with current genetic advances and screening guidelines.


Management options for dental extraction in hemophiliacs: a study of 55 extractions (2000-2002).
Dental extraction in hemophiliacs is associated with a high risk of bleeding. It requires a multidisciplinary approach and stringent protocol. The current trend is to simplify these protocols. In this study we review the efficacy of a protocol using systemic treatment--factors/dihydro-D-arginine vasopressin (DDAVP)--and simplified local hemostatic measures to control bleeding, to limit patient discomfort, and to minimize hospital length of stay. This retrospective study of 55 dental extractions was performed during 19 interventions in 16 patients with hemophilia A or B to assess the efficacy of a protocol combining general management via the injection of factor concentrates or DDAVP and local hemostasis using biological glue and gelatin packing. Compressive, hemostatic splints, which have been in use by some for many years, are replaced by intermittent tranexamic acid compression during the first 3 days after surgery. We recorded 6 instances of postsurgical bleeding, 4 of which occurred after the compression period. In 2 cases repetition of the local hemostasic measures was required along with the injection of an antihemophilic factor concentrate. In the other 4 cases, the patients' condition reverted to normal following injection of the factor concentrate and the reapplication of the compression. The adopted protocol produced a reliable outcome, limiting the duration of the hospital stay to 24 hours in most cases, and improving postsurgical comfort thanks to a combination of systemic treatment and local hemostasic measures including intermittent tranexamic acid compression.


Anteroposterior patterning in the limb and digit specification: contribution of mouse genetics.
The limb has been a privileged object of investigation and reflection for scientists over the past two centuries and continues to provide a heuristic framework to analyze vertebrate development. Recently, accumulation of new data has significantly changed our view on the mechanisms of limb patterning, in particular along the anterior-posterior axis. These data have led us to revisit the mode of action of the zone of polarizing activity. They shed light on the molecular and cellular mechanisms of patterning linked to the Shh-Gli3 signaling pathway and give insights into the mechanism of activation of these cardinal factors, as well as the consequences of their activity. These new data are in good part the result of systematic Application of tools used in contemporary mouse molecular genetics. These have extended the power of mouse genetics by introducing mutational strategies that allow fine-tuned modulation of gene expression, interchromosomal deletions and duplication. They have even made the mouse embryo amenable to cell lineage analysis that used to be the realm of chick embryos. In this review, we focus on the data acquired over the last five years from the analysis of mouse limb development and discuss new perspectives opened by these results.


The effect of unrestricted milk feeding on the growth and health of Jersey calves.
This study was conducted to determine the effect of feeding high milk volumes on the growth rate, health and cross-sucking behaviour in group-fed Jersey calves. Three-day-old heifers (n = 120) in a seasonal calving dairy herd were randomly assigned to one of 6 treatment groups. Three groups received high milk volumes (HMV), consisting of ad libitum milk or milk replacer feeding twice a day, while 3 groups received restricted milk volumes (RMV), consisting of 2 l twice daily, during the pre-weaning period. After a pre-weaning period during which feeding was reduced to once daily, all calves were weaned at 42 days and monitored until 60 days of age. Adjusting for birth mass, birth date, dam parity and sire, average daily mass gain (ADG), both pre-weaning (days 0-42) and overall (days 0-60), was higher in HMV than in RMV calves (P < 0.001). After weaning, growth rates showed no differences and at 60 days of age the HMV calves maintained a 6.74 kg advantage in mean body mass (P < 0.001). The mean intake of dry starter feed was higher in RMV than in HMV calves. Overall feed conversion rate of HMV calves was 9.6 % better than RMV calves. However, the variable cost per kg mass gain was 12 % higher for HMV calves. In the RMV groups 75 % of calves showed cross-sucking behaviour pre-weaning and 18 % post-weaning, whereas in HMV calves the proportions were 2 % and 7 %, respectively. There was no significant effect of milk volume on the incidence of diarrhoea. We conclude that the feeding of high volumes of milk to Jersey calves has a positive effect on growth rate, without compromising health or reducing solid feed intake after weaning. However, the higher cost of such a feeding system may limit its implementation.


Imaging granulomatous lesions with optical coherence tomography.
To investigate and compare the presentation of granulomatous lesions in optical coherence tomography (OCT) images and compare this to previous studies of nonmelanoma skin tumors. Two patients with granulomas, tophi and granuloma annulare (GA), respectively, were photographed digitally, OCT-scanned and biopsied in the said order. Normal skin was OCT-scanned for comparison, but not biopsied. The OCT images from each lesion were compared with their histologic images as well as with OCT images with similar characteristics obtained from nonmelanoma skin tumors. The OCT images of the tophi showed hyperreflective, rounded cloud-like structures in dermis, their upper part sharply delineated by a hyporeflective fringe. The deeper areas appeared blurred. The crystalline structures were delineated by a hyporeflective fringe. OCT images of GA showed two different structures in dermis: a hyporeflective rounded one, and one that was lobulated and wing-like. Granulomatous tissue surrounding urate deposits appeared as a clear hyporeflective fringe surrounding a light, hyperreflective area. The urate crystals appeared as hyperreflective areas, shielding the deeper part of dermis, meaning OCT could only visualize the upper part of the lesions. The lobulated, wing-like structure in GA may resemble diffuse GA or a dense lymphocytic infiltrate as seen on histology. The rounded structure in GA may represent an actual granuloma or either diffuse GA or a dense lymphocytic infiltrate as described above. This case suggests that OCT images granulomatous tissue as absorbent, hyporeflective areas, and urate crystals appear as reflective areas, obscuring the underlying tissue. In GA a new image shape looking like a wing has been found. The frequency, specificity and sensitivity of this new pattern in OCT imaging will require further studies.


Selective targeting of neuroblastoma tumour-initiating cells by compounds identified in stem cell-based small molecule screens.
Neuroblastoma (NB) is the most deadly extra-cranial solid tumour in children necessitating an urgent need for effective and less toxic treatments. One reason for the lack of efficacious treatments may be the inability of existing drugs to target the tumour-initiating or cancer stem cell population responsible for sustaining tumour growth, metastases and relapse. Here, we describe a strategy to identify compounds that selectively target patient-derived cancer stem cell-like tumour-initiating cells (TICs) while sparing normal paediatric stem cells (skin-derived precursors, SKPs) and characterize two therapeutic candidates. DECA-14 and rapamycin were identified as NB TIC-selective agents. Both compounds induced TIC death at nanomolar concentrations in vitro, significantly reduced NB xenograft tumour weight in vivo, and dramatically decreased self-renewal or tumour-initiation capacity in treated tumours. These results demonstrate that differential drug sensitivities between TICs and normal paediatric stem cells can be exploited to identify novel, patient-specific and potentially less toxic therapies.


Effects of individual and combined toxicity of bisphenol A, dibutyl phthalate and cadmium on oxidative stress and genotoxicity in HepG 2 cells.
Bisphenol A, dibutyl phthalate and cadmium can be found in environment simultaneously. Several studies suggested that they had genotoxic effect. In this study, mono-exposure and co-exposure treatments, designed by 3 × 3 full factorial, were established to determine the individual toxicity and binary mixtures' combined effects on the oxidative stress and genotoxicity in HepG 2 cells. The highest oxidative damage was observed in the Cd treatments groups. Compared with control groups, the maximum level of reactive oxygen species and malondialdehyde were ∼1.4 fold and ∼2.22 fold respectively. And a minimum level of superoxide dismutase activity was found with the decrease of 43%. The mechanism that excessive oxidative stress led to the DNA damage was inferred. However, cells treated with BPA showed the worst DNA damage rather than Cd, which may because Cd mainly damages DNA repairing mechanism. For the joint effect, different interactions can be found in different biological endpoints for different combinations since different mechanisms have been clarified in mixture toxicity studies. It is sure that the co-exposure groups enhanced cytotoxicity, oxidative stress and genotoxicity compared to the mono-exposures. Synergistic and additive interactions were considered, which means greater threat to organisms when exposed to multiple estrogenic endocrine disruptors.


No Role of Herpes Simplex Virus Type 2 (HSV-2) Infection on HIV Progression in Naïve HIV Patients
Herpes simplex virus type 2 (HSV-2) is a common infection in human immunodeficiency virus (HIV) patients and may accelerate HIV progression by rising HIV viral load and decreasing CD4 count. However, the available data regarding the influence of HSV-2 seropositivity on HIV progression in HIV individuals are inconclusive. Therefore, we aimed to determine HSV-2 seroprevalence in naïve HIV patients and normal controls and also investigate the relation of HIV viral load and CD4 count with HSV-2 seropositivity. Subsequently, we investigated the association of HSV-2 serostatus with changing in CD4 count and HIV viral load in our subjects, after one year follow-up. In this study, 116 naïve HIV patients and 85 healthy controls from Tehran, Iran were enrolled. HSV-2 IgG antibody was detected by ELISA. CD4 count was determined by flowcytometry, and serum HIV RNA copy numbers were determined using real-time PCR. The prevalence of HSV-2 IgG was 18.1% in naïve HIV patients and 0% in the control group (P=0.000). HSV-2 seroconversion was observed in 2.43% of HIV patients after one year. There was no significant difference regarding HSV-2 serostatus with CD4 count and HIV RNA viral load in our study cohort at baseline and after one year. Our results revealed that the prevalence and incidence of HSV-2 infection are low in our HIV cases, and it is negligible in control group. However, it seems that HIV/HSV2 co-infection has no role on HIV infection acceleration.


Multimarker risk model containing troponin-T, interleukin 10, myeloperoxidase and placental growth factor predicts long-term cardiovascular risk after non-ST-segment elevation acute coronary syndrome.
To evaluate the predictive value of seven biomarkers, which individually have been shown to be independent predictors, for use in a combined multimarker model for long-term cardiovascular outcome after non-ST-segment elevation acute coronary syndrome (NSTEACS). Levels of high-sensitivity C-reactive protein (hsCRP), myeloperoxidase, pregnancy-associated plasma protein A, placental growth factor (PlGF), soluble CD40 ligand (sCD40L), interleukin 10 (IL-10) and troponin-T (TnT) were determined in patients enrolled in the CAPTURE trial. Cox proportional hazard regression analyses were applied to evaluate the relation between biomarkers and the occurrence of all-cause mortality or non-fatal myocardial infarction (MI). 1090 patients with NSTEACS. All-cause mortality and non-fatal MI during a median follow-up of 4 years. The composite endpoint was reached by 15.3% of patients. Admission levels of TnT >0.01 μg/l (adjusted HR 1.8), IL-10 <3.5 ng/l (1.7), myeloperoxidase >350 μg/l (1.5) and PlGF >27 ng/l (1.9) remained significant predictors for the incidence of all-cause mortality or non-fatal MI after multivariable adjustment for other biomarkers and clinical characteristics, whereas hsCRP, pregnancy-associated plasma protein A and sCD40L were only associated with the endpoint in univariate analysis. A multimarker model consisting of TnT, IL-10, myeloperoxidase and PlGF predicted 4-year event rates that varied between 6.0% (all markers normal) and 35.8% (three or more biomarkers abnormal). In patients with NSTEACS, biomarkers characterising distinct aspects of the underlying atherosclerotic process and myocardial damage of the initial cardiac event can assist in predicting long-term adverse cardiac outcomes. The use of combinations of selected biomarkers adds incremental predictive value to further risk stratification in an otherwise seemingly homogeneous NSTEACS population.


Trends in gestational age at time of surgical abortion for fetal aneuploidy and structural abnormalities.
Screening for fetal aneuploidy has evolved over the past 2 decades. Whether these advances impact gestational age at abortion has received little study. We sought to describe trends in the gestational age at the time of abortion by fetal diagnosis over an 11-year study period. We hypothesized that gestational age at time of abortion would decrease for fetal aneuploidy but remain unchanged for structural abnormalities. We conducted a retrospective case series of all women undergoing surgical abortion for fetal aneuploidy or structural abnormalities up to 24 weeks' gestation from 2004 through 2014 in a hospital operating room setting at a single, urban medical center. We excluded labor induction abortions (<1% of abortions at our medical center) and suction aspirations performed in the office practice. We performed suction aspiration up to 14 weeks and dilation and evacuation after that gestational age. We describe the median gestational age at abortion by fetal indication and year. For women undergoing abortion for fetal aneuploidy (n = 392), the median gestational age at time of abortion decreased from 19.0 weeks (interquartile range 18.0-21.0) in 2004 to 14.0 weeks (interquartile range 13.0-17.0) in 2014 (Kruskal-Wallis P < .0001). For women undergoing abortion for fetal structural abnormalities (n = 586), the median gestational age was ≥20 weeks for each year during the study interval (P = .1). As gestational age decreased in the fetal aneuploidy group, fewer women underwent dilation and evacuation and more became eligible for suction aspiration (<14 weeks). In 2004, >90% of women underwent dilation and evacuation for either indication. By 2014, 31% of women with fetal aneuploidy were eligible for suction aspiration compared to 11% of those with structural anomalies. Gestational age at the time of abortion for fetal aneuploidy decreased substantially from 2004 through 2014; earlier abortion is safer for women. In contrast, women seeking abortion for fetal structural abnormalities did not experience a change in timing. Legislation restricting gestational age at the time of abortion could disproportionately affect women with fetal structural abnormalities.


Vitamin K2 improves proliferation and migration of bovine skeletal muscle cells in vitro.
Skeletal muscle function is highly dependent on the ability to regenerate, however, during ageing or disease, the proliferative capacity is reduced, leading to loss of muscle function. We have previously demonstrated the presence of vitamin K2 in bovine skeletal muscles, but whether vitamin K has a role in muscle regulation and function is unknown. In this study, we used primary bovine skeletal muscle cells, cultured in monolayers in vitro, to assess a potential effect of vitamin K2 (MK-4) during myogenesis of muscle cells. Cell viability experiments demonstrate that the amount of ATP produced by the cells was unchanged when MK-4 was added, indicating viable cells. Cytotoxicity analysis show that MK-4 reduced the lactate dehydrogenase (LDH) released into the media, suggesting that MK-4 was beneficial to the muscle cells. Cell migration, proliferation and differentiation was characterised after MK-4 incubation using wound scratch analysis, immunocytochemistry and real-time PCR analysis. Adding MK-4 to the cells led to an increased muscle proliferation, increased gene expression of the myogenic transcription factor myod as well as increased cell migration. In addition, we observed a reduction in the fusion index and relative gene expression of muscle differentiation markers, with fewer complex myotubes formed in MK-4 stimulated cells compared to control cells, indicating that the MK-4 plays a significant role during the early phases of muscle proliferation. Likewise, we see the same pattern for the relative gene expression of collagen 1A, showing increased gene expression in proliferating cells, and reduced expression in differentiating cells. Our results also suggest that MK-4 incubation affect low density lipoprotein receptor-related protein 1 (LRP1) and the low-density lipoprotein receptor (LDLR) with a peak in gene expression after 45 min of MK-4 incubation. Altogether, our experiments show that MK-4 has a positive effect on muscle cell migration and proliferation, which are two important steps during early myogenesis.


Functional brain imaging predicts public health campaign success.
Mass media can powerfully affect health decision-making. Pre-testing through focus groups or surveys is a standard, though inconsistent, predictor of effectiveness. Converging evidence demonstrates that activity within brain systems associated with self-related processing can predict individual behavior in response to health messages. Preliminary evidence also suggests that neural activity in small groups can forecast population-level campaign outcomes. Less is known about the psychological processes that link neural activity and population-level outcomes, or how these predictions are affected by message content. We exposed 50 smokers to antismoking messages and used their aggregated neural activity within a 'self-localizer' defined region of medial prefrontal cortex to predict the success of the same campaign messages at the population level (n = 400,000 emails). Results demonstrate that: (i) independently localized neural activity during health message exposure complements existing self-report data in predicting population-level campaign responses (model combined R(2) up to 0.65) and (ii) this relationship depends on message content-self-related neural processing predicts outcomes in response to strong negative arguments against smoking and not in response to compositionally similar neutral images. These data advance understanding of the psychological link between brain and large-scale behavior and may aid the construction of more effective media health campaigns.