The Impact of Bisphenol A and Triclosan on Immune Parameters in the U.S. Population, NHANES 2003–2006

Background: Exposure to environmental toxicants is associated with numerous disease outcomes, many of which involve underlying immune and inflammatory dysfunction. Objectives: To address the gap between environmental exposures and immune dysfunction, we investigated the association of two endocrine-disrupting compounds (EDCs) with markers of immune function. Methods: Using data from the 2003–2006 National Health and Nutrition Examination Survey, we compared urinary bisphenol A (BPA) and triclosan levels with serum cytomegalovirus (CMV) antibody levels and diagnosis of allergies or hay fever in U.S. adults and children ≥ 6 years of age. We used multivariate ordinary least squares linear regression models to examine the association of BPA and triclosan with CMV antibody titers, and multivariate logistic regression models to investigate the association of these chemicals with allergy or hay fever diagnosis. Statistical models were stratified by age (\u3c 18 years and ≥ 18 years). Results: In analyses adjusted for age, sex, race, body mass index, creatinine levels, family income, and educational attainment, in the ≥ 18-year age group, higher urinary BPA levels were associated with higher CMV antibody titers (p \u3c 0.001). In the \u3c 18-year age group, lower levels of BPA were associated with higher CMV antibody titers (p \u3c 0.05). However, triclosan, but not BPA, showed a positive association with allergy or hay fever diagnosis. In the \u3c 18-year age group, higher levels of triclosan were associated with greater odds of having been diagnosed with allergies or hay fever (p \u3c 0.01). Conclusions: EDCs such as BPA and triclosan may negatively affect human immune function as measured by CMV antibody levels and allergy or hay fever diagnosis, respectively, with differential consequences based on age. Additional studies should be done to investigate these findings

Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations

Optogenetic stimulation of a hippocampal engram activates fear memory recall

A specific memory is thought to be encoded by a sparse population of neurons. These neurons can be tagged during learning for subsequent identification3 and manipulation. Moreover, their ablation or inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, the question of sufficiency remains: it is unclear whether it is possible to elicit the behavioural output of a specific memory by directly activating a population of neurons that was active during learning. Here we show in mice that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behaviour. We labelled a population of hippocampal dentate gyrus neurons activated during fear learning with channelrhodopsin-2 (ChR2) and later optically reactivated these neurons in a different context. The mice showed increased freezing only upon light stimulation, indicating light-induced fear memory recall. This freezing was not detected in non-fear-conditioned mice expressing ChR2 in a similar proportion of cells, nor in fear-conditioned mice with cells labelled by enhanced yellow fluorescent protein instead of ChR2. Finally, activation of cells labelled in a context not associated with fear did not evoke freezing in mice that were previously fear conditioned in a different context, suggesting that light-induced fear memory recall is context specific. Together, our findings indicate that activating a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Moreover, our experimental approach offers a general method of mapping cellular populations bearing memory engrams.RIKEN Brain Science InstituteNational Institutes of Health (U.S.) (Grant R01-MH078821)National Institutes of Health (U.S.) (Grant P50-MH58880

Sibling number and prevalence of allergic disorders in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study

<p>Abstract</p> <p>Background</p> <p>Although an inverse relationship between number of siblings and likelihood of allergic disorders has been shown in many epidemiological studies, the biological mechanism underlying this phenomenon has not yet been identified. There is no epidemiological research regarding the sibling effect on allergic disorders in Japanese adults. The current cross-sectional study examined the relationship between number of siblings and prevalence of allergic disorders among adult women in Japan.</p> <p>Methods</p> <p>Subjects were 1745 pregnant women. This study was based on questionnaire data. The definitions of wheeze and asthma were based on criteria from the European Community Respiratory Health Survey whereas those of eczema and rhinoconjunctivitis were based on criteria from the International Study of Asthma and Allergies in Childhood. Adjustment was made for age, region of residence, pack-years of smoking, secondhand smoke exposure at home and at work, family history of asthma, atopic eczema, and allergic rhinitis, household income, and education.</p> <p>Results</p> <p>The prevalence values of wheeze, asthma, eczema, and rhinoconjunctivitis in the past 12 months were 10.4%, 5.5%, 13.0%, and 25.9%, respectively. A significant inverse exposure-response relationship was observed between the number of older siblings and rhinoconjunctivitis, but not wheeze, asthma, or eczema (<it>P </it>for trend = 0.03); however, the adjusted odds ratio (OR) for having 2 or more older siblings was not significant although the adjusted OR for having 1 older sibling was statistically significant (adjusted OR = 0.71 [95% CI: 0.56-0.91]). Number of total siblings and number of younger siblings were not related to wheeze, asthma, eczema, or rhinoconjunctivitis.</p> <p>Conclusions</p> <p>This study found a significant inverse relationship between the number of older siblings and the prevalence of rhinoconjunctivitis among pregnant Japanese women. Our findings are likely to support the intrauterine programming hypothesis; however, we could not rule out the hygiene hypothesis.</p

Extreme rainfall events alter the trophic structure in bromeliad tanks across the Neotropics

Changes in global and regional precipitation regimes are among the most pervasive components of climate change. Intensification of rainfall cycles, ranging from frequent downpours to severe droughts, could cause widespread, but largely unknown, alterations to trophic structure and ecosystem function. We conducted multi-site coordinated experiments to show how variation in the quantity and evenness of rainfall modulates trophic structure in 210 natural freshwater microcosms (tank bromeliads) across Central and South America (18°N to 29°S). The biomass of smaller organisms (detritivores) was higher under more stable hydrological conditions. Conversely, the biomass of predators was highest when rainfall was uneven, resulting in top-heavy biomass pyramids. These results illustrate how extremes of precipitation, resulting in localized droughts or flooding, can erode the base of freshwater food webs, with negative implications for the stability of trophic dynamics

The GOLMePsA study protocol: an investigator-initiated, double-blind, parallel-group, randomised, controlled trial of GOLimumab and methotrexate versus methotrexate in early diagnosed psoriatic arthritis using clinical and whole body MRI outcomes

Background: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis which impacts significantly on the quality of life and work capacity of affected individuals. Recent evidence has shown that early control of inflammation in PsA leads to improved long-term outcomes. It is postulated that prompt intervention after diagnosis using a remission-induction treatment strategy will lead to improved outcomes and optimal disease control of PsA. The aim of the present study was to compare the clinical efficacy of a treatment strategy in newly diagnosed, treatment naïve PsA subjects, using the combination of golimumab (GOL), methotrexate (MTX) and steroids versus standard care (MTX monotherapy plus steroids). Methods/design: GOLMePsA is an investigator initiated, phase IIIb, single-centre, randomised, double-blind, placebo-controlled, two-armed, parallel-group, imaging-supplemented study. Eighty-eight PsA patients, diagnosed within 24 months prior to screening and treatment naïve, will be randomised at baseline to receive: (arm 1) the combination of intramuscular/intra-articular prednisolone, MTX and GOL or (arm 2) the combination of intramuscular/intra-articular prednisolone, MTX and placebo for 24 weeks (interventional period). Primary outcome measure is clinical improvement (at least 1 unit difference) in the Psoriatic ArthritiS Disease Activity Score (PASDAS) composite index. Reflecting a “step down” therapeutic approach, all participants successfully completing the interventional period will be followed up for a further 28 weeks. During this observational period, stable maintenance MTX monotherapy will continue for both arms, unless in case of intolerance or PsA relapse. In the latter case, additional treatment will be provided. Overall, the GOLMePsA study length is planned to be 52 weeks. Discussion: The hypothesis underlining this study is that very early treatment with first-line GOL reduces disease activity in PsA, in comparison to conventional therapy. Trial registration: EudraCT 2013–004122-28. 24/09/2013

Effectiveness and cost-effectiveness of a group-based pain self-management intervention for patients undergoing total hip replacement: Feasibility study for a randomized controlled trial

Background: Total hip replacement (THR) is a common elective surgical procedure and can be effective for reducing chronic pain. However, waiting times can be considerable. A pain self-management intervention may provide patients with skills to more effectively manage their pain and its impact during their wait for surgery. This study aimed to evaluate the feasibility of conducting a randomized controlled trial to assess the effectiveness and cost-effectiveness of a group-based pain self-management course for patients undergoing THR.Methods: Patients listed for a THR at one orthopedic center were posted a study invitation pack. Participants were randomized to attend a pain self-management course plus standard care or standard care only. The lay-led course was delivered by Arthritis Care and consisted of two half-day sessions prior to surgery and one full-day session after surgery. Participants provided outcome and resource-use data using a diary and postal questionnaires prior to surgery and one month, three months and six months after surgery. Brief telephone interviews were conducted with non-participants to explore barriers to participation.Results: Invitations were sent to 385 eligible patients and 88 patients (23%) consented to participate. Interviews with 57 non-participants revealed the most common reasons for non-participation were views about the course and transport difficulties. Of the 43 patients randomized to the intervention group, 28 attended the pre-operative pain self-management sessions and 11 attended the post-operative sessions. Participant satisfaction with the course was high, and feedback highlighted that patients enjoyed the group format. Retention of participants was acceptable (83% of recruited patients completed follow-up) and questionnaire return rates were high (72% to 93%), with the exception of the pre-operative resource-use diary (35% return rate). Resource-use completion rates allowed for an economic evaluation from the health and social care payer perspective.Conclusions: This study highlights the importance of feasibility work prior to a randomized controlled trial to assess recruitment methods and rates, barriers to participation, logistics of scheduling group-based interventions, acceptability of the intervention and piloting resource use questionnaires to improve data available for economic evaluations. This information is of value to researchers and funders in the design and commissioning of future research.Trial registration: Current Controlled Trials ISRCTN52305381. © 2014 Wylde et al.; licensee BioMed Central Ltd

Association between atrial fibrillation and <i>Helicobacter pylori</i>

The connection between atrial fibrillation (AF) and H. pylori (HP) infection is still matter of debate. We performed a systematic review and metanalysis of studies reporting the association between AF and HF. A systematic review of all available reports in literature of the incidence of HP infection in AF and comparing this incidence with subjects without AF were analysed. Risk ratio and 95% confidence interval (CI) and risk difference with standard error (SE) were the main statistics indexes. Six retrospective studies including a total of 2921 were included at the end of the selection process. Nine hundred-fifty-six patients (32.7%) were in AF, whereas 1965 (67.3%) were in normal sinus rhythm (NSR). Overall, 335 of 956 patients with AF were HP positive (35%), whereas 621 were HP negative (65%). In addition, 643 of 1965 NSR patients (32.7%) were HP positive while 1,322 were negative (67.3%; Chi-square 2.15, p = 0.21). The Cumulative Risk Ratio for AF patients for developing an HP infection was 1.19 (95% CI 1.08–1.41). In addition, a small difference risk towards AF was found (0.11 [SE = 0.04]). Moreover, neither RR nor risk difference were influenced by the geographic area at meta-regression analysis. Finally, there was a weak correlation between AF and HP (coefficient = 0.04 [95% CI −0.01–0.08]). We failed to find any significant correlation between H. pylori infection and AF and, based on our data, it seems unlikely than HP can be considered a risk factor for AF. Further larger research is warranted

The use of electric fields for edible coatings and films development and production: A review

Edible films and coatings can provide additional protection for food, while being a fully biodegradable, environmentally friendly packaging system. A diversity of raw materials used to produce edible coatings and films are extracted from marine and agricultural sources, including animals and plants. Electric fields processing holds advantage in producing safe, wholesome and nutritious food. Recently, the presence of a moderate electric field during the preparation of edible coatings and films was shown to influence their main properties, demonstrating its usefulness to tailor edible films and coatings for specific applications. This manuscript reviews the main aspects of the use of electric fields in the production of edible films and coatings, including the effect in their transport and mechanical properties, solubility and microstructure.Fundação para a Ciência e a Tecnologia (FCT), Portugal.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brasil

Digital IAPT: the effectiveness & cost-effectiveness of internet-delivered interventions for depression and anxiety disorders in the Improving Access to Psychological Therapies programme: study protocol for a randomised control trial

BACKGROUND: Depression and anxiety are common mental health disorders worldwide. The UK's Improving Access to Psychological Therapies (IAPT) programme is part of the National Health Service (NHS) designed to provide a stepped care approach to treating people with anxiety and depressive disorders. Cognitive Behavioural Therapy (CBT) is widely used, with computerised and internet-delivered cognitive behavioural therapy (cCBT and iCBT, respectively) being a suitable IAPT approved treatment alternative for step 2, low- intensity treatment. iCBT has accumulated a large empirical base for treating depression and anxiety disorders. However, the cost-effectiveness and impact of these interventions in the longer-term is not routinely assessed by IAPT services. The current study aims to evaluate the clinical and cost-effectiveness of internet-delivered interventions for symptoms of depression and anxiety disorders in IAPT. METHODS: The study is a parallel-groups, randomised controlled trial examining the effectiveness and cost-effectiveness of iCBT interventions for depression and anxiety disorders, against a waitlist control group. The iCBT treatments are of 8 weeks duration and will be supported by regular post-session feedback by Psychological Wellbeing Practitioners. Assessments will be conducted at baseline, during, and at the end of the 8-week treatment and at 3, 6, 9, and 12-month follow-up. A diagnostic interview will be employed at baseline and 3-month follow-up. Participants in the waitlist control group will complete measures at baseline and week 8, at which point they will receive access to the treatment. All adult users of the Berkshire NHS Trust IAPT Talking Therapies Step 2 services will be approached to participate and measured against set eligibility criteria. Primary outcome measures will assess anxiety and depressive symptoms using the GAD-7 and PHQ-9, respectively. Secondary outcome measures will allow for the evaluation of long-term outcomes, mediators and moderators of outcome, and cost-effectiveness of treatment. Analysis will be conducted on a per protocol and intention-to-treat basis. DISCUSSION: This study seeks to evaluate the immediate and longer-term impact, as well as the cost effectiveness of internet-delivered interventions for depression and anxiety. This study will contribute to the already established literature on internet-delivered interventions worldwide. The study has the potential to show how iCBT can enhance service provision, and the findings will likely be generalisable to other health services. TRIAL REGISTRATION: Current Controlled Trials ISRCTN ISRCTN91967124. DOI: https://doi.org/10.1186/ISRCTN91967124 . Web: http://www.isrctn.com/ISRCTN91967124 . Clinicaltrials.gov : NCT03188575. Trial registration date: June 8, 2017 (prospectively registered)