Can an aversive, extinction-resistant memory trigger impairments in walking adaptability? An experimental study using adult rats

Cognitive demands can influence the adaptation of walking, a crucial skill to maintain body stability and prevent falls. Whilst previous research has shown emotional load tunes goal-directed movements, little attention has been given to this finding. This study sought to assess the effects of suffering an extinction-resistant memory on skilled walking performance in adult rats, as an indicator of walking adaptability. Thus, 36 Wistar rats were divided in a two-part experiment. In the first part (n = 16), the aversive, extinction-resistance memory paradigm was established using a fear-conditioning chamber. In the second, rats (n = 20) were assessed in a neutral room using the ladder rung walking test before and tree days after inducing an extinction-resistance memory. In addition, the elevated plus-maze test was used to control the influence of the anxiety-like status on gait adaptability. Our results revealed the shock group exhibited worse walking adaptability (lower skilled walking score), when compared to the sham group. Moreover, the immobility time in the ladder rung walking test was similar to the controls, suggesting that gait adaptability performance was not a consequence of the fear generalization. No anxiety-like behavior was observed in the plus maze test. Finally, correlation coefficients also showed the skilled walking performance score was positively correlated with the number of gait cycles and trial time in the ladder rung walking test and the total crossings in the plus maze. Overall, these preliminary findings provide evidence to hypothesize an aversive, extinction-resistant experience might change the emotional load, affecting the ability to adapt walking

Interviewer-driven Variability in Social Network Reporting: Results from Health and Aging in Africa: a Longitudinal Study of an INDEPTH community (HAALSI) in South Africa

Social network analysis depends on how social ties to others are elicited during interviews, a process easily affected by respondent and interviewer behaviors. We investigate how the number of self-reported important social contacts varied within a single data collection round. Our data come from Health and Aging in Africa: a Longitudinal Study of an INDEPTH community (HAALSI), a comprehensive population-based survey of individuals aged 40 years and older conducted over 13 months at the Agincourt health and demographic surveillance site in rural South Africa. As part of HAALSI, interviewers elicited detailed egocentric network data. The average number of contacts reported by the 5,059 respondents both varied significantly across interviewers and fell over time as the data collection progressed, even after adjusting for respondent, interviewer, and respondent–interviewer dyad characteristics. Contact numbers rose substantially after a targeted interviewer intervention. We conclude that checking (and adjusting) for interviewer effects, even within one data collection round, is critical to valid and reliable social network analysis. Measurements of social networks depend on the number and type of social ties to others (Berkman et al. 2000; Smith and Christakis 2008). These ties are typically elicited through interviews, a process easily affected by respondent or interviewer characteristics and behaviors. Understanding social network structure and composition requires substantial amounts of information from respondents (“egos”) about the people (“alters”) they have relationships with (Marsden 1990). Notably, the survey burden associated with network data collection depends heavily on the number of alters elicited through “name generator” questions: Each alter named leads to the repetition of all follow-up questions characterizing the ego–alter relationship (“name interpreters”; Burt 1984). Interviewers have been identified as a key source of variation in survey responses, particularly for questions that are attitudinal, ambiguous, or have complex skip patterns (West and Blom 2016). Several studies have previously identified interviewer effects on network size (Brüderl et al. 2013; Josten and Trappmann 2016; Marsden 2003; Paik and Sanchagrin 2013; van Tilburg 1998). These interviewer effects may arise from differential understanding of survey questions, and therefore how questions are presented to respondents. Interviewers can also affect which alters are elicited due to their own characteristics (e.g., sex, race, age, or experience), or the nature of the interviewer–respondent dyad (e.g., gender, race, or age homophily), leading to different lines of enquiry, levels of probing, or expectations of social acceptability (Collins 1980; Hox 1994; Marsden 2003; Phung et al. 2015). Furthermore, if respondents or interviewers are aware that naming more alters substantially increases survey length, then either group may consciously or unconsciously seek to minimize the number of alters named (Eagle and Proeschold-Bell 2015; van der Zouwen and van Tilburg 2001). In cross-sectional surveys, the opportunities for respondents to learn are limited, but those for interviewers will increase as the survey period progresses. Interviewers may try to reduce survey burden, either for themselves or for respondents, by favoring language or probes that decrease the number of alters elicited. Indeed, past studies in Europe have found evidence of interviewers intentionally filtering out questions by entering fewer responses that would trigger more questions. Such filtering behavior has been seen in Europe for interviewers who are being compensated by the interview rather than by the hour (Josten and Trappmann 2016; Kosyakova et al. 2014), for interviewers with prior experience using the relevant screening tool (Matschinger et al. 2005), and where interviewers are under substantial pressure to complete more interviews (Schnell and Kreuter 2000). We aim to extend this literature by assessing how the number of alters elicited systematically changed over the course of a cross-sectional social network survey of older adults in rural South Africa. We show a substantial drop in alter numbers over time, and a swift reversal following retraining, providing substantial evidence for interviewer effects

Post-Operative Outcome of Traumatic Extradural Haematoma in HOSHAS

Introduction: Traumatic extradural haematoma (EDH) is a common surgical emergency with huge socio-economic impact. Prompt diagnosis and management are key for patient survival and good outcome. Considering that neurosurgical units are mostly only available in tertiary centres, it is a challenge for non-neurosurgical centres to transport patient to the nearest neurosurgical unit for emergency surgery, which may be of significant distance away, hence, a delay in surgery. General surgery units are more widely available and general surgeons are trained to competently manage patients with EDH. Referring to the nearest general surgery unit for emergency surgery for EDH can be life-saving and avoid delay in surgery. There is a lack of study regarding outcome of patients with EDH operated by general surgeons, hence the aim of this study to investigate in this regard. To determine the post-operative functional outcome of patients with extradural haematoma in a nonneurosurgical centre, and compare the outcome with other centres. Materials and Methods: This study was a retrospective review of records of all post-operative patients operated in HOSHAS for traumatic EDH in year 2017. Sample were obtained from 2017 General Surgery Department operative census in HOSHAS. Data were obtained from patient admission records using a proforma. Documented patient post-operative functional status was classified as per Glasgow Outcome Scale (GOS). Data were analysed using SPSS version 22. Results: A total of 11 patient data were collected. Mean age of the study population is 27. All samples were male patients. Road traffic accident was the main mode of injury (82%). Seven patients had GCS on arrival of 9 to 12 (64%), while 4 patients had severe brain injury on arrival (36%). All except 1 patient with moderate brain injury (GCS on arrival 9-12) recovered well post-operatively. As for patients with severe brain injury on arrival (GCS 3-8), only half of the patients had complete recovery post operatively. Most of the patients (73%) had good post-operative recovery (GOS 4-5). One patient died (GOS 1) and another ended up in vegetative state (GOS 2). The post-operative outcome in this study is comparable to other studies done in neurosurgical unit. Conclusion: The functional outcomes of traumatic EDH patients operated by general surgeons in HOSHAS are similar to those in neurosurgical centre

Cd36 Is Expressed In A Defined Subpopulation Of Neurons In The Olfactory Epithelium

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The sensory neurons in the olfactory epithelium (OSNs) are equipped with a large repertoire of olfactory receptors and the associated signal transduction machinery. In addition to the canonical OSNs, which express odorant receptors (ORs), the epithelium contains specialized subpopulations of sensory neurons that can detect specific information from environmental cues and relay it to relevant neuronal circuitries. Here we describe a subpopulation of mature OSNs in the main olfactory epithelium (MOE) which expresses CD36, a multifunctional receptor involved in a series of biological processes, including sensory perception of lipid ligands. The Cd36 expressing neurons coexpress markers of mature OSNs and are dispersed throughout the MOE. Unlike several ORs analyzed in our study, we found frequent coexpression of the OR Olfr287 in these neurons, suggesting that only a specific set of ORs may be coexpressed with CD36 in OSNs. We also show that CD36 is expressed in the cilia of OSNs, indicating a possible role in odorant detection. CD36-deficient mice display no signs of gross changes in the organization of the olfactory epithelium, but show impaired preference for a lipid mixture odor. Our results show that CD36-expressing neurons represent a distinct population of OSNs, which may have specific functions in olfaction.6Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [FAPESP: 2007/53732-8]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [CNPq 484869/2012-4]FAPESP [FAPESP11/51604-8]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

The triggering receptor expressed on myeloid cells (TREM) in inflammatory bowel disease pathogenesis

The Triggering Receptors Expressed on Myeloid cells (TREM) are a family of cell-surface molecules that control inflammation, bone homeostasis, neurological development and blood coagulation. TREM-1 and TREM-2, the best-characterized receptors so far, play divergent roles in several infectious diseases. In the intestine, TREM-1 is highly expressed by macrophages, contributing to inflammatory bowel disease (IBD) pathogenesis. Contrary to current understanding, TREM-2 also promotes inflammation in IBD by fueling dendritic cell functions. This review will focus specifically on recent insights into the role of TREM proteins in IBD development, and discuss opportunities for novel treatment approaches

A barrier to homologous recombination between sympatric strains of the cooperative soil bacterium Myxococcus xanthus

The bacterium Myxococcus xanthus glides through soil in search of prey microbes, but when food sources run out, cells cooperatively construct and sporulate within multicellular fruiting bodies. M. xanthus strains isolated from a 16 × 16-cm-scale patch of soil were previously shown to have diversified into many distinct compatibility types that are distinguished by the failure of swarming colonies to merge upon encounter. We sequenced the genomes of 22 isolates from this population belonging to the two most frequently occurring multilocus sequence type (MLST) clades to trace patterns of incipient genomic divergence, specifically related to social divergence. Although homologous recombination occurs frequently within the two MLST clades, we find an almost complete absence of recombination events between them. As the two clades are very closely related and live in sympatry, either ecological or genetic barriers must reduce genetic exchange between them. We find that the rate of change in the accessory genome is greater than the rate of amino-acid substitution in the core genome. We identify a large genomic tract that consistently differs between isolates that do not freely merge and therefore is a candidate region for harbouring gene(s) responsible for self/non-self discrimination

Operation and performance of the ATLAS Tile Calorimeter in Run 1

The Tile Calorimeter is the hadron calorimeter covering the central region of the ATLAS experiment at the Large Hadron Collider. Approximately 10,000 photomultipliers collect light from scintillating tiles acting as the active material sandwiched between slabs of steel absorber. This paper gives an overview of the calorimeter’s performance during the years 2008–2012 using cosmic-ray muon events and proton–proton collision data at centre-of-mass energies of 7 and 8TeV with a total integrated luminosity of nearly 30 fb−1. The signal reconstruction methods, calibration systems as well as the detector operation status are presented. The energy and time calibration methods performed excellently, resulting in good stability of the calorimeter response under varying conditions during the LHC Run 1. Finally, the Tile Calorimeter response to isolated muons and hadrons as well as to jets from proton–proton collisions is presented. The results demonstrate excellent performance in accord with specifications mentioned in the Technical Design Report

Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

Background Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. Methods We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. Findings Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. Interpretation Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: a comparative risk assessment

Background High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods We used data for exposure to risk factors by country, age group, and sex from pooled analyses of populationbased health surveys. We obtained relative risks for the eff ects of risk factors on cause-specifi c mortality from metaanalyses of large prospective studies. We calculated the population attributable fractions for- each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the eff ects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specifi c population attributable fractions by the number of disease-specifi c deaths. We obtained cause-specifi c mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the fi nal estimates. Findings In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10\ub78 million deaths, 95% CI 10\ub71\u201311\ub75) of deaths from these diseases in 2010 were attributable to the combined eff ect of these four metabolic risk factors, compared with 67% (7\ub71 million deaths, 6\ub76\u20137\ub76) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined eff ects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing eff ect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the globalresponse to non-communicable diseases