Miracle-dz/UniFAR-FTUs huggingface dataset:
Prolonged lipopolysaccharide exposure induces transient immunosuppression in BV2 microglia

Continuous pre‐exposure of immune cells to low level of inflammatory stimuli makes them hyporesponsive to subsequent exposure. This pathophysiological adaptation; known as endotoxin tolerance is a general paradigm behind several disease pathogenesis. Current study deals with this immunosuppression with respect to BV2 microglia. We attempted to investigate their immune response under prolonged endotoxin exposure and monitor the same upon withdrawal of the stimuli. BV2 microglia cells were maintained under continual exposure of lipopolysaccharide (LPS) for weeks with regular passage after 72 hr (prolonged LPS exposed cells [PLECs]). PLECs were found to be immunosuppressed with diminished expression of proinflammatory cytokines (IL6, IL1β, TNF‐α, and iNOS) and production of nitric oxide, as compared to once LPS exposed cells. Upon remaintenance of cells in normal media without LPS exposure (LPS withdrawal cells [LWCs]), the induced immunosuppression reversed and cells started responding to inflammatory stimuli; revealed by significant expression of proinflammatory cytokines. LWCs showed functional similarities to never LPS exposed cells (NLECs) in phagocytosis activity and their response to anti‐inflammatory agents like dexamethasone. Despite their immunoresponsiveness, PLECs were inflamed and showed higher autophagy rate than NLECs. Additionally, we investigated the role of inhibitor of apoptotic proteins (IAPs) in PLECs to understand whether IAPs aids in the survival of microglial cells under stress conditions. Our results revealed that cIAP1 and cIAP2 are induced in PLECs which might play a role in retaining the viability. Furthermore, antagonism of IAPs has significantly induced cell death in PLECs suggesting the role of IAPs in microglial survival under stress condition. Conclusively, our data suggest that continuous exposure of BV2 microglia cells to LPS results in transient immunosuppression and indicates the involvement of IAPs in retaining their viability under inflammatory stress.
Quantifying the Nature and Extent of Children’s Real-time Exposure to Alcohol Marketing in Their Everyday Lives Using Wearable Cameras: Children’s Exposure via a Range of Media in a Range of Key Places

Aims Children's exposure to alcohol marketing is typically measured using self-report data, television viewing data or street marketing audits, which are subject to bias and often do not provide quantifiable measures of daily exposure. This article describes an innovative methodology to capture the world in which children live using wearable cameras. Short summary Children wearing wearable cameras were exposed 4.5 times per day to alcohol marketing in multiple places and via a range of marketing media. The results reinforce calls for legislative restrictions and a global response to alcohol marketing in order to protect children and reduce alcohol-related harm. Methods Children aged 11-13 years (n = 167) wore cameras that automatically captured images approximately every 7 s for a 4-day period between June 2014 and July 2015. Content analysis of images (n = 700,000) was manually undertaken to assess children's exposure to alcohol marketing. Results On average, children were exposed to alcohol marketing 4.5 (95% CI: 3.3, 6.0) times per day, excluding within off-licence retailers, on screens and product packaging. Children were exposed at home (47%), on-licence alcohol retailers (19%), off-licence shop fronts (16%) and sporting venues (12%), and via sports sponsorship (31%) and shop front signage (31%) and merchandise (25%). The highest exposure rates were found among Māori (5.4 times higher than New Zealand European) and Pacific (3.0 times higher than New Zealand European), and boys (2.0 times higher than girls). Conclusions These findings highlight the urgent need to implement strict legislative restrictions on all forms of alcohol marketing to fulfil the World Health Organization Global Alcohol Strategy.
Recommendations for participation in leisure time or competitive sports in athletes-patients with coronary artery disease: a position statement from the Sports Cardiology Section of the European Association of Preventive Cardiology (EAPC).

This paper presents a brief summary of the recommendations from the Sports Cardiology section of the European Association of Preventive Cardiology (EAPC) on sports-participation in patients with coronary artery disease, coronary artery anomalies or spontaneous dissection of the coronary arteries, all entities being associated with myocardial ischaemia.1 Given the wealth of evidence supporting the benefits of exercise for primary and secondary prevention of coronary artery disease, individuals should be restricted from competitive sport only when a substantial risk of adverse event or disease progression is present. These recommendations aim to encourage regular physical activity including participation in sports and, with reasonable precaution, ensure a high level of safety for all individuals with coronary artery disease. The present document is based on available current evidence, but in most instances because of lack of evidence, also on clinical experience and expert opinion.
Peripheral Blood Monocytes With an Antiinflammatory Phenotype Display Limited Phagocytosis and Oxidative Burst in Patients With Visceral Leishmaniasis

Background Monocytes are important effector cells during Leishmania infection, and changes in their functions may impact development of immunity. However, functional characteristics of monocytes in patients with visceral leishmaniasis (VL) remains poorly understood. Methods Peripheral blood monocytes from patients with VL and healthy endemic controls from Muzaffarpur, India, were isolated and compared in an ex vivo setting, using cell-culture techniques, flow cytometry, and reverse transcription quantitative polymerase chain reaction analysis. Results A blood monocyte population with a gene signature comprising upregulated expression of TGM2, CTLRs, VDR, PKM, SOCS1, and CAMP1 and downregulated expression of NOS2 and HIF1A was observed in patients with VL but not in controls. Monocytes from patients with VL also had impaired expression of chemokine receptors and adhesion molecules and decreased frequencies of interleukin 1β- and interleukin 6-producing cells. Importantly, monocytes from patients with VL had a markedly reduced capacity for phagocytosis of amastigotes, p47phox and p67phox expression, and reactive oxygen species production. Conclusions Monocytes from patients with VL express antiinflammatory molecules and lack a classically activated phenotype. They have reduced expression of molecules related to activation and antiparasitic effector functions, indicating that monocytes are skewed toward an antiinflammatory phenotype. These findings provide insights into the functional status of monocytes during VL and advise that therapeutic manipulation of this important cell population may result in favorable patient outcomes.
Similarities and Differences in Tobacco Control Research Findings From Convenience and Probability Samples.

BACKGROUND Online convenience samples are a quick and low-cost way to study health behavior, but the comparability to findings from probability samples is not yet well understood. PURPOSE We sought to compare convenience and probability samples' findings for experiments, correlates, and prevalence in the context of tobacco control research. METHODS Participants were a probability sample of 5,014 U.S. adults recruited by phone from September 2014 through May 2015 (cost ~U.S.$620,000) and an online convenience sample of 4,137 U.S. adults recruited through Amazon Mechanical Turk (MTurk) in December 2014 (cost ~U.S.$17,000). Participants completed a survey with experiments, measures of tobacco product use and demographic characteristics. RESULTS MTurk convenience and probability samples showed the same pattern of statistical significance and direction in almost all experiments (21 of 24 analyses did not differ) and observational studies (19 of 25 associations did not differ). Demographic characteristics of the samples differed substantially (1 of 17 estimates did not differ), with the convenience sample being younger, having more years of education, and including more Whites and Asians. Tobacco product use also differed substantially (1 of 22 prevalence estimates did not differ), with the convenience sample reporting more cigarette and e-cigarette use (median error 19%). CONCLUSIONS Using MTurk convenience samples can yield generalizable findings for experiments and observational studies. Prevalence estimates from MTurk convenience samples are likely to be over- or underestimates.
Cytoskeletal mechanisms of axonal contractility

Mechanotransduction is likely to be an important mechanism of signalling in thin, elongated cells like neurons. Maintenance of pre-stress or rest tension may facilitate mechanotransduction in these cells. In recent years, functional roles for mechanical tension in neuronal development and physiology are beginning to emerge but the cellular mechanisms regulating neurite tension remain poorly understood. Active contraction of neurites is a potential mechanism of tension regulation. In this study, we have explored cytoskeletal mechanisms mediating active contractility of neuronal axons. We have developed a simple assay where we evaluate contraction of curved axons upon trypsin-mediated detachment. We show that curved axons undergo contraction and straighten upon de-adhesion. Axonal straightening was found to be actively driven by actomyosin contractility, while microtubules may subserve a secondary role. We find that while axons show a monotonous decrease in length upon contraction, subcellularly, the cytoskeleton shows a heterogeneous contractile response. Further, using an assay for spontaneous development of tension without trypsin-induced de-adhesion, we show that axons are intrinsically contractile. These experiments, using novel experimental approaches, implicate the axonal cytoskeleton in tension homeostasis. Our data suggest that while globally the axon behaves as a mechanical continuum, locally the cytoskeleton is remodelled heterogeneously.
Clinical efficacy of virtual reality for acute procedural pain management: A systematic review and meta-analysis

Background Acutely painful procedures are commonplace. Current approaches to pain most often involve pharmacotherapy, however, there is interest in virtual reality (VR) as a non-pharmacological alternative. A methodologically rigorous systematic review and meta-analysis is lacking. Methods Following PRISMA guidelines, we searched the Cochrane Library, Ovid MEDLINE, Embase, CINAHL, ERIC, NIHR Centre for Review and Dissemination, Proquest, the System for Information on Grey Literature in Europe and the WHO International Clinical Trials Registry Platform from inception to 5 November 2017. Included studies were randomised with an experimental trial design, included a non-VR control group and examined the efficacy of VR with regards to an acutely painful clinical intervention. Bias was assessed along Cochrane guidelines, with performance bias not assessed due to the non-blindable nature of VR. We extracted summary data for maximal pain score and used standard mean difference DerSimonian-Laird random-effects meta-analysis (RevMan 5.3). This review was prospectively registered (PROSPERO CRD42017058204). Findings Of the 12,450 studies identified, 20 studies were eligible for the systematic review. No trials reported in sufficient detail to judge their risk of bias, and 10 studies were at high risk of bias in at least one domain. 16 studies (9 randomised controlled trials, 7 crossover studies) examining 656 individuals were included in quantitative synthesis. Pain scales were heterogenous, but mostly employed 100-point scales. Across all trials, meta-analysis was suggestive of a -0.49 (95%CI -0.83 to -0.41, p = 0.006) standardised mean difference reduction in pain score with VR. However there was a high degree of statistical heterogeneity (χ2 p<0.001, I2 81%, 95%CI for I2 70–88%), driven by randomised studies, with substantial clinical heterogeneity. Conclusion These data suggest that VR may have a role in acutely painful procedures, however included studies were clinically and statistically heterogenous. Further research is required to validate findings, establish cost efficacy and optimal clinical settings for usage. Future trials should report in accordance with established guidelines.
The cascade of care following community-based detection of HIV in sub-Saharan Africa – A systematic review with 90-90-90 targets in sight

Introduction We aimed to establish how effective community-based HIV testing services (HTS), including home and community location based (non-health facility) HIV testing services (HB-/CLB-HTS), are in improving care in sub-Saharan Africa (SSA), with a view to achieving the 90-90-90 targets. Methods We conducted a systematic review of published literature from 2007–17 which reported on the proportion of individuals who link-to-care and/or initiate ART after detection with HIV through community-based testing. A meta-analysis was deemed inappropriate due to heterogeneity in reporting. Results and discussion Twenty-five care cascades from 6 SSA countries were examined in the final review– 15 HB-HTS, 8 CLB-HTS, 2 combined HB-/CLB-HTS. Proportions linked-to-care over 1–12 months ranged from 14–96% for HB-HTS and 10–79% for CLB-HTS, with most studies reporting outcomes over short periods (3 months). Fewer studies reported ART-related outcomes following community-based testing and most of these studies included <50 HIV-positive individuals. Proportions initiating ART ranged from 23–93%. One study reported retention on ART (76% 6 months after initiation). Viral suppression 3–12 months following ART initiation was 77–85% in three studies which reported this. There was variability in definitions of outcomes, numerators/denominators and observation periods. Outcomes varied between studies even for similar time-points since HTS. The methodological inconsistencies hamper comparisons. Previously diagnosed individuals appear more likely to link-to-care than those who reported being newly-diagnosed. It appears that individuals diagnosed in the community need time before they are ready to link-to-care/initiate ART. Point-of-care (POC) CD4-counts at the time of HTS did not achieve higher proportions linking-to-care or initiating ART. Similarly, follow-up visits to HIV-positive individuals did not appear to enhance linkage to care overall. Conclusion This systematic review summarises the available data on linkage to care/ART initiation following community-based detection of HIV, to help researchers and policy makers evaluate findings. The available evidence suggests that different approaches to community-based HTS including HB-HTS and CLB-HTS, are equally effective in achieving linkage to care and ART initiation among those detected. Engagement and support for newly diagnosed individuals may be key to achieving all three UNAIDS 90-90-90 targets. We also recommend that standardised measures of reporting of steps on the cascade of care are needed, to measure progress against targets and compare across settings.
Resistance Training Alone or Combined With N-3 PUFA-Rich Diet in Older Women: Effects on Muscle Fiber Hypertrophy

We aimed to examine cellular and molecular changes in skeletal muscle of recreationally active older women in response to 24 weeks of combined resistance training and N-3 PUFA-rich healthy diet. Sixty-three women (65-70 years) were randomized into resistance training and healthy diet rich in N-3PUFAs (RT-HD), resistance training only (RT) and controls (CON). Fiber type-specific morphological characteristics and gene expression of inflammatory biomarkers and regulators of muscle mass were analyzed in m. vastus lateralis biopsies obtained before the intervention and 4 days after the last training session. Gene expression of the proinflammatory cytokine IL-1β was downregulated (p < .05) and that of the regulator of cellular growth mTOR (p < 0.05) was upregulated in skeletal muscle of RT-HD only. There was also a significant hypertrophy of fast type IIA muscle fibers in RT-HD only (+23%, p < .05). In conclusion, resistance training combined to an N-3 PUFA-rich healthy diet but not alone triggers local anti-inflammatory and growth responses, favoring skeletal muscle hypertrophy in already recreationally active older women.
Killing with proficiency: Integrated post-translational regulation of an offensive Type VI secretion system

The Type VI secretion system (T6SS) is widely used by bacterial pathogens as an effective weapon against bacterial competitors and is also deployed against host eukaryotic cells in some cases. It is a contractile nanomachine which delivers toxic effector proteins directly into target cells by dynamic cycles of assembly and firing. Bacterial cells adopt distinct post-translational regulatory strategies for deployment of the T6SS. ‘Defensive’ T6SSs assemble and fire in response to incoming attacks from aggressive neighbouring cells, and can utilise the Threonine Protein Phosphorylation (TPP) regulatory pathway to achieve this control. However, many T6SSs are ‘offensive’, firing at all-comers without the need for incoming attack or other cell contact-dependent signal. Post-translational control of the offensive mode has been less well defined but can utilise components of the same TPP pathway. Here, we used the anti-bacterial T6SS of Serratia marcescens to elucidate post-translational regulation of offensive T6SS deployment, using single-cell microscopy and genetic analyses. We show that the integration of the TPP pathway with the negative regulator TagF to control core T6SS machine assembly is conserved between offensive and defensive T6SSs. Signal-dependent PpkA-mediated phosphorylation of Fha is required to overcome inhibition of membrane complex assembly by TagF, whilst PppA-mediated dephosphorylation promotes spatial reorientation and efficient killing. In contrast, the upstream input of the TPP pathway defines regulatory strategy, with a new periplasmic regulator, RtkS, shown to interact with the PpkA kinase in S. marcescens. We propose a model whereby the opposing actions of the TPP pathway and TagF impose a delay on T6SS re-assembly after firing, providing an opportunity for spatial re-orientation of the T6SS in order to maximise the efficiency of competitor cell targeting. Our findings provide a better understanding of how bacterial cells deploy competitive weapons effectively, with implications for the structure and dynamics of varied polymicrobial communities.
Validity and Reliability of Global Positioning System Units (STATSports Viper) for Measuring Distance and Peak Speed in Sports

Abstract Beato, M, Devereux, G, and Stiff, A. Validity and reliability of global positioning system units (STATSports Viper) for measuring distance and peak speed in sports. J Strength Cond Res 32(10): 2831–2837, 2018—Previous evidence has proven that large variability exists in the accuracy of different brands of global positioning systems (GPS). Therefore, any GPS model should be validated independently, and the results of a specific brand cannot be extended to others. The aim of this study is to assess the validity and reliability of GPS units (STATSports Viper) for measuring distance and peak speed in sports. Twenty participants were enrolled (age 21 ± 2 years [range 18 to 24 years], body mass 73 ± 5 kg, and height 1.78 ± 0.04 m). Global positioning system validity was evaluated by comparing the instantaneous values of speed (peak speed) determined by GPS (10 Hz, Viper Units; STATSports, Newry, Ireland) with those determined by a radar gun during a 20-m sprint. Data were analyzed using the Stalker (34.7 GHz, USA) ATS Version 5.0. 3.0 software as gold standard. Distance recorded by GPS was also compared with a known circuit distance (400-m running, 128.5-m sports-specific circuit, and 20-m linear running). The distance bias in the 400-m trial, 128.5-m circuit, and 20-m trial was 1.99 ± 1.81%, 2.7 ± 1.2%, and 1.26 ± 1.04%, respectively. Peak speed measured by the GPS was 26.3 ± 2.4 km·h−1, and criterion was 26.1 ± 2.6 km·h−1, with a bias of 1.80 ± 1.93%. The major finding of this study was that GPS did not underestimate the criterion distance during a 400-m trial, 128.5-m circuit, and 20-m trial, as well as peak speed. Small errors (<5%, good) were found for peak speed and distances. This study supported the validity and reliability of this GPS model.
Nosip functions during vertebrate eye and cranial cartilage development

Background: The nitric oxide synthase interacting protein (Nosip) has been associated with diverse human diseases including psychological disorders. In line, early neurogenesis of mouse and Xenopus is impaired upon Nosip deficiency. Nosip knockout mice show craniofacial defects and the down‐regulation of Nosip in the mouse and Xenopus leads to microcephaly. Until now, the exact underlying molecular mechanisms of these malformations were still unknown. Results: Here, we show that nosip is expressed in the developing ocular system as well as the anterior neural crest cells of Xenopus laevis. Furthermore, Nosip inhibition causes severe defects in eye formation in the mouse and Xenopus. Retinal lamination as well as dorso–ventral patterning of the retina were affected in Nosip‐depleted Xenopus embryos. Marker gene analysis using rax, pax6 and otx2 reveals an interference with the eye field induction and differentiation. A closer look on Nosip‐deficient Xenopus embryos furthermore reveals disrupted cranial cartilage structures and an inhibition of anterior neural crest cell induction and migration shown by twist, snai2, and egr2. Moreover, foxc1 as downstream factor of retinoic acid signalling is affected upon Nosip deficiency. Conclusions: Nosip is a crucial factor for the development of anterior neural tissue such the eyes and neural crest cells. Developmental Dynamics 247:1070‐1082, 2018. © 2018 Wiley Periodicals, Inc.
Sicuophora (Syn. Wichtermania) multigranularis from Quasipaa spinosa (Anura): morphological and molecular study, with emphasis on validity of Sicuophora (Armophorea, Clevelandellida)

Morphological studies of Sicuophora (Syn. Wichtermania) multigranularis Xiao et al., 2002, from the rectum of the frog, Quasipaa spinosa, performed using silver impregnation and scanning electron microscopy, confirmed the following newly recognized features: (1) only one apical suture on the right surface; (2) two naked regions at the posterior end of both the left and the right side of the body. Phylogenetic analysis based on the SSU-rRNA gene showed that S. multigranularis is a sister to a clade comprising all other Clevelandellida, strongly supporting the validity of the genus Sicuophora. This is also the first molecular data obtained for the genus Sicuophora. Because of the lack of molecular data, it will be necessary to obtain more genetic data from the family Sicuophoridae to discuss the question of the taxonomic status of the genus Sicuophora.