Search

The Eating Disorders In weight-related Therapy (EDIT) Collaboration brings together data from randomised controlled trials of behavioural weight management interventions to identify individual participant risk factors and intervention strategies that contribute to eating disorder risk. We present a protocol for a systematic review and individual participant data (IPD) meta-analysis which aims to identify participants at risk of developing eating disorders, or related symptoms, during or after weight management interventions conducted in adolescents or adults with overweight or obesity. We systematically searched four databases up to March 2022 and clinical trials registries to May 2022 to identify randomised controlled trials of weight management interventions conducted in adolescents or adults with overweight or obesity that measured eating disorder risk at pre- and post-intervention or follow-up. Authors from eligible trials have been invited to share their deidentified IPD. Two IPD meta-analyses will be conducted. The first IPD meta-analysis aims to examine participant level factors associated with a change in eating disorder scores during and following a weight management intervention. To do this we will examine baseline variables that predict change in eating disorder risk within intervention arms. The second IPD meta-analysis aims to assess whether there are participant level factors that predict whether participation in an intervention is more or less likely than no intervention to lead to a change in eating disorder risk. To do this, we will examine if there are differences in predictors of eating disorder risk between intervention and no-treatment control arms. The primary outcome will be a standardised mean difference in global eating disorder score from baseline to immediately post-intervention and at 6- and 12- months follow-up. Identifying participant level risk factors predicting eating disorder risk will inform screening and monitoring protocols to allow early identification and intervention for those at risk.

ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or organ dysfunction after the acute phase of infection, termed Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are poorly understood. The objectives of the Researching COVID to Enhance Recovery (RECOVER) tissue pathology study (RECOVER-Pathology) are to: (1) characterize prevalence and types of organ injury/disease and pathology occurring with PASC; (2) characterize the association of pathologic findings with clinical and other characteristics; (3) define the pathophysiology and mechanisms of PASC, and possible mediation via viral persistence; and (4) establish a post-mortem tissue biobank and post-mortem brain imaging biorepository.MethodsRECOVER-Pathology is a cross-sectional study of decedents dying at least 15 days following initial SARS-CoV-2 infection. Eligible decedents must meet WHO criteria for suspected, probable, or confirmed infection and must be aged 18 years or more at the time of death. Enrollment occurs at 7 sites in four U.S. states and Washington, DC. Comprehensive autopsies are conducted according to a standardized protocol within 24 hours of death; tissue samples are sent to the PASC Biorepository for later analyses. Data on clinical history are collected from the medical records and/or next of kin. The primary study outcomes include an array of pathologic features organized by organ system. Causal inference methods will be employed to investigate associations between risk factors and pathologic outcomes.DiscussionRECOVER-Pathology is the largest autopsy study addressing PASC among US adults. Results of this study are intended to elucidate mechanisms of organ injury and disease and enhance our understanding of the pathophysiology of PASC.

BackgroundIntrapartum continuity of care to reduce maternal morbidity and mortality relies heavily on a functional and effective referral system between tiers of care. Capacity building of providers in managing intrapartum referrals is expected to improve the efficiency of the referral system, but this does not always work in practice. This study explored the experiences and perceptions of maternity healthcare providers on emergency intrapartum referrals in Dar es Salaam, Tanzania.MethodsAn exploratory qualitative study was conducted at Amana Regional Referral Hospital and Muhimbili National Hospital in Dar es Salaam. Maternity healthcare providers were purposively recruited based on cadre, working experience of more than three years in the maternity wards. An in-depth interview guide which involved questions and probes was used to conduct eleven interviews. Data was thematically analyzed.ResultsThree major themes emerged, namely: 1) causes of referrals are beyond medical indications; 2) limited maternity healthcare provider capability at referring facilities; and 3) limited communication between referring and receiving facilities. According to maternity healthcare professionals, referrals were seen as a way to minimize blame and a clinical management tool to prevent difficulties. They advocated for more understanding of the skill set among maternity healthcare providers, but some had negative perceptions towards performing their responsibilities.ConclusionsSkills gaps among maternity healthcare providers at referring hospitals influenced referral decision-making and service provision. There was hostility between referring and receiving hospitals. Capacity-strengthening strategies such as ongoing skills training and changes in attitudes toward referrals require improvements. The referring hospital should only consider referrals as a last resort after other case management has been completed.

Examining development is essential for a full understanding of behaviour, including how individuals acquire traits and how adaptive evolutionary forces shape these processes. The present study explores the development of cooperative behaviour among the Agta, a Filipino hunter-gatherer population. A simple resource allocation game assessing both levels of cooperation (how much children shared) and patterns of partner choice (who they shared with) was played with 179 children between the ages of 3 and 18. Children were given five resources (candies) and for each was asked whether to keep it for themselves or share with someone else, and if so, who this was. Between-camp variation in children’s cooperative behaviour was substantial, and the only strong predictor of children’s cooperation was the average level of cooperation among adults in camp; that is, children were more cooperative in camps where adults were more cooperative. Neither age, sex, relatedness or parental levels of cooperation were strongly associated with the amount children shared. Children preferentially shared with close kin (especially siblings), although older children increasingly shared with less-related individuals. Findings are discussed in terms of their implications for understanding cross-cultural patterns of children’s cooperation, and broader links with human cooperative childcare and life history evolution.

Background Syphilis has detrimental effects on the health of the mother and that of both fetuses and newborns exposed in utero or at delivery. Understanding its local epidemiology is essential for policies, planning, and implementation of targeted preventive interventions. Using data from the 2020 National Sentinel Surveillance of pregnant women attending antenatal clinics (ANCs) in Tanzania we determined the prevalence and determinants of syphilis among pregnant women in Tanzania mainland. Methodology The ANC surveillance was conducted in 159 ANC sites from all 26 regions of Tanzania’s mainland from September to December 2020. It included all pregnant women 15 years and above on their first ANC visit in the current pregnancy during the survey period. Counseling for syphilis was done using standard guidelines at the ANC and testing was done using rapid SD Bioline HIV/Syphilis Duo test kits. Analysis was done using both descriptive statistics to determine the prevalence and characteristics of syphilis, whereas, logistic regressions were used to examine the independent association between syphilis and dependent variables. Results A total of 38,783 women [median age (Interquartile range (IQR)) = 25 (21–30) years] participated in the surveillance. Of them, 582 (1.4%) tested positive for syphilis. A wide regional variation was observed with the highest burden in Kagera (4.5%) to the lowest burden in Kigoma (0.3%). The odds of syphilis infections were higher among older women and those with no formal education. Compared with primigravids, women with 1–2, those with 3–4 and those with more than four previous pregnancies had 1.8 (aOR = 1.8, 95% CI: 1.2–2.5), 2.1 (aOR = 2.1, 95% CI: 1.4–3.1) and 2.6 (aOR = 2.6, 95% CI: 1.7–3.9) higher odds of syphilis infection respectively. Conclusion Syphilis is still prevalent among pregnant women in Tanzania with a wide regional disparity. Efforts to prevent new infections, screen pregnant women, and treat those infected should be strategized to include all regions and renewed emphasis on regions with high burden, and importantly among women who are multipara, with a low level of education, and advanced age.

BackgroundFor successful HIV response, updated information on the burden and progress toward HIV elimination targets are required to guide programmatic interventions. We used data from the 2020 HIV sentinel surveillance to update on the burden and factors associated with HIV infection, HIV status awareness, and ART coverage among pregnant women in Tanzania mainland.MethodologyWe conducted the surveillance in 159 antenatal clinics (ANC) from all 26 regions of Tanzania's mainland from September to December 2020. This cross-sectional study included all pregnant women (≥15 years) on their first ANC visit in the current pregnancy during the survey period. Routine HIV counselling and testing were done at the facility. A multivariable logistic regression model accounting for the survey design was used to examine factors associated with HIV infections.Results38,783 pregnant women were enrolled (median age (IQR) = 25 (21-30) years). HIV prevalence was 5.9% (95%CI: 5.3% - 6.6%), ranging from 1.9% in the Manyara region to 16.4% in the Njombe region. Older age, lower and no education, not being in a marital union, and living in urban or semi-urban areas were associated with higher odds of HIV infection. HIV status awareness among women who tested positive was 70.9% (95% CI: 67.5%- 74.0%). ART coverage among those aware of their status was 91.6% (86.5%- 94.9%). Overall, 66.6% (95% CI: 62.4%- 70.6%) of all pregnant women who tested positive for HIV knew their HIV status and were on ART.ConclusionHIV is increasingly prevalent among pregnant women in Tanzania mainland especially among older, those with lower or no formal education, those outside marital union, and pregnant women living in urban and semi-urban areas. Behind the global fast-target to end HIV/ AIDS, about a third of pregnant women living with HIV initiating ANC were not on ART. Interventions to increase HIV testing and linkage to care among women of reproductive age should be intensified.

The Eating Disorders In weight-related Therapy (EDIT) Collaboration brings together data from randomised controlled trials of behavioural weight management interventions to identify individual participant risk factors and intervention strategies that contribute to eating disorder risk. We present a protocol for a systematic review and individual participant data (IPD) meta-analysis which aims to identify participants at risk of developing eating disorders, or related symptoms, during or after weight management interventions conducted in adolescents or adults with overweight or obesity. We systematically searched four databases up to March 2022 and clinical trials registries to May 2022 to identify randomised controlled trials of weight management interventions conducted in adolescents or adults with overweight or obesity that measured eating disorder risk at pre- and post-intervention or follow-up. Authors from eligible trials have been invited to share their deidentified IPD. Two IPD meta-analyses will be conducted. The first IPD meta-analysis aims to examine participant level factors associated with a change in eating disorder scores during and following a weight management intervention. To do this we will examine baseline variables that predict change in eating disorder risk within intervention arms. The second IPD meta-analysis aims to assess whether there are participant level factors that predict whether participation in an intervention is more or less likely than no intervention to lead to a change in eating disorder risk. To do this, we will examine if there are differences in predictors of eating disorder risk between intervention and no-treatment control arms. The primary outcome will be a standardised mean difference in global eating disorder score from baseline to immediately post-intervention and at 6- and 12- months follow-up. Identifying participant level risk factors predicting eating disorder risk will inform screening and monitoring protocols to allow early identification and intervention for those at risk.

BackgroundHyperhidrosis (excessive sweating, OMIM %114110) is a complex disorder with multifactorial causes. Emotional strains and social stress increase symptoms and lead to a vicious circle. Previously, we showed significantly higher depression scores, and normal cortisol awakening responses in patients with primary focal hyperhidrosis (PFH). Stress reactivity in response to a (virtual) Trier Social Stress Test (TSST-VR) has not been studied so far. Therefore, we measured sweat secretion, salivary cortisol and alpha amylase (sAA) concentrations, and subjective stress ratings in affected and non-affected subjects in response to a TSST-VR.MethodIn this pilot study, we conducted TSST-VRs and performed general linear models with repeated measurements for salivary cortisol and sAA levels, heart rate, axillary sweat and subjective stress ratings for two groups (diagnosed PFH (n = 11), healthy controls (n = 16)).ResultsPFH patients showed significantly heightened sweat secretion over time compared to controls (p = 0.006), with highest quantities during the TSST-VR. In both groups, sweating (p < 0.001), maximum cortisol levels (p = 0.002), feelings of stress (p < 0.001), and heart rate (p < 0.001) but not sAA (p = 0.068) increased significantly in response to the TSST-VR. However, no differences were detected in subjective ratings, cortisol concentrations and heart rate between PFH patients and controls (pall > 0.131).ConclusionPatients with diagnosed PFH showed stress-induced higher sweat secretion compared to healthy controls but did not differ in the stress reactivity with regard to endocrine or subjective markers. This pilot study is in need of replication to elucidate the role of the sympathetic nervous system as a potential pathway involved in the stress-induced emotional sweating of PFH patients.

Torquetenovirus (TTV) is present in biological fluids from healthy individuals and measurement of its titer is used to assess immune status in individuals with chronic infections and after transplants. We assessed if the titer of TTV in saliva varied with the presence of SARS-CoV-2 in the nasopharynx and could be a marker of COVID-19 status. Saliva from 91 individuals positive for SARS-CoV-2 in nasal-oropharyngeal samples, and from 126 individuals who were SARS-CoV-2-negative, all with mild respiratory symptoms, were analyzed. Both groups were similar in age, gender, symptom duration and time after symptom initiation when saliva was collected. Titers of TTV and SARS-CoV-2 were assessed by gene amplification. Loss of smell (p = 0.0001) and fever (p = 0.0186) were more prevalent in SARS-CoV-2-positive individuals, while sore throat (p = 0.0001), fatigue (p = 0.0037) and diarrhea (p = 0.0475) were more frequent in the SARS-CoV-2 negative group. The saliva TTV and nasal-oropharyngeal SARS-CoV-2 titers were correlated (p = 0.0085). The TTV level decreased as symptoms resolved in the SARS-CoV-2 infected group (p = 0.0285) but remained unchanged in the SARS-CoV-2 negative controls. In SARS-CoV-2 positive subjects who provided 2-4 saliva samples and in which TTV was initially present, the TTV titer always decreased over time as symptoms resolved. We propose that sequential TTV measurement in saliva is potentially useful to assess the likelihood of symptom resolution in SARS-CoV-2-positive individuals and to predict prognosis.

Comprehensive characterizations of bladder cancer (BCa) have established molecular phenotype classes with distinct alterations and survival trends. Extending these studies within the tyrosine kinase (TK) family to identify disease drivers could improve our use of TK inhibitors to treat specific patient groups or individuals. We examined the expression distribution of TKs as a class (n = 89) in The Cancer Genome Atlas (TCGA) muscle invasive BCa data set (n >400). Patient profiles of potentially oncogenic alterations (overexpression and/or amplification) clustered TKs into 3 groups; alterations of group 1 and 3 TKs were associated with significantly worse patient survival relative to those without alterations. Many TK pathways induce epithelial-to-mesenchymal transition (EMT), which promotes tumor invasiveness and metastasis. Overexpression and/or amplification among 9 EMT transcriptional activators occurred in 43% of TCGA cases. Co-occurring alterations of TKs and EMT transcriptional activators involved most group 1 TKs; 24% of these events were associated with significantly worse patient survival. Co-occurring alterations of receptor TKs and their cognate ligands occurred in 16% of TCGA cases and several BCa-derived cell lines. Suppression of GAS6, MST1 or CSF1, or their respective receptors (AXL, MST1R and CSF1R), in BCa cell lines was associated with decreased receptor activation, cell migration, cell proliferation and anchorage independent cell growth. These studies reveal the patterns and prevalence of potentially oncogenic TK pathway-related alterations in BCa and identify specific alterations associated with reduced BCa patient survival. Detection of these features in BCa patients could better inform TK inhibitor use and improve clinical outcomes.

Background Ageing populations and rising prevalence of non-communicable diseases (NCDs) increasingly contribute to the growing cost burden facing European healthcare systems. Few studies have attempted to quantify the future magnitude of this burden at the European level, and none of them consider the impact of potential changes in risk factor trajectories on future health expenditures. Methods The new microsimulation model forecasts the impact of behavioural and metabolic risk factors on NCDs, longevity and direct healthcare costs, and shows how changes in epidemiological trends can modify those impacts. Economic burden of NCDs is modelled under three scenarios based on assumed future risk factors trends: business as usual (BAU); best case and worst case predictions (BCP and WCP). Findings The direct costs of NCDs in the EU 27 countries and the UK (in constant 2014 prices) will grow under all scenarios. Between 2014 and 2050, the overall healthcare spending is expected to increase by 0.8% annually under BAU. In the all the countries, 605 billion Euros can be saved by 2050 if BCP is realized compared to the BAU, while excess spending under the WCP is forecast to be around 350 billion. Interpretation: Although the savings realised under the BCP can be substantial, population ageing is a stronger driver of rising total healthcare expenditures in Europe compared to scenario-based changes in risk factor prevalence.

The huge power for social influence of digital media may come with the risk of intensifying common societal biases, such as gender and age stereotypes. Speaker's gender and age also behaviorally manifest in language use, and language may be a powerful tool to shape impact. The present study took the example of TED, a highly successful knowledge dissemination platform, to study online influence. Our goal was to investigate how gender- and age-linked language styles-beyond chronological age and identified gender-link to talk impact and whether this reflects gender and age stereotypes. In a pre-registered study, we collected transcripts of TED Talks along with their impact measures, i.e., views and ratios of positive and negative talk ratings, from the TED website. We scored TED Speakers' (N = 1,095) language with gender- and age-morphed language metrics to obtain measures of female versus male, and younger versus more senior language styles. Contrary to our expectations and to the literature on gender stereotypes, more female language was linked to higher impact in terms of quantity, i.e., more talk views, and this was particularly the case among talks with a lot of views. Regarding quality of impact, language signatures of gender and age predicted different types of positive and negative ratings above and beyond main effects of speaker's gender and age. The differences in ratings seem to reflect common stereotype contents of warmth (e.g., "beautiful" for female, "courageous" for female and senior language) versus competence (e.g., "ingenious", "informative" for male language). The results shed light on how verbal behavior may contribute to stereotypical evaluations. They also illuminate how, within new digital social contexts, female language might be uniquely rewarded and, thereby, an underappreciated but highly effective tool for social influence. WC = 286 (max. 300 words).

Primary focal hyperhidrosis (PFH, OMIM %144110) is a genetically influenced condition characterised by excessive sweating. Prevalence varies between 1.0-6.1% in the general population, dependent on ethnicity. The aetiology of PFH remains unclear but an autosomal dominant mode of inheritance, incomplete penetrance and variable phenotypes have been reported. In our study, nine pedigrees (50 affected, 53 non-affected individuals) were included. Clinical characterisation was performed at the German Hyperhidrosis Centre, Munich, by using physiological and psychological questionnaires. Genome-wide parametric linkage analysis with GeneHunter was performed based on the Illumina genome-wide SNP arrays. Haplotypes were constructed using easyLINKAGE and visualised via HaploPainter. Whole-exome sequencing (WES) with 100x coverage in 31 selected members (24 affected, 7 non-affected) from our pedigrees was achieved by next generation sequencing. We identified four genome-wide significant loci, 1q41-1q42.3, 2p14-2p13.3, 2q21.2-2q23.3 and 15q26.3-15q26.3 for PFH. Three pedigrees map to a shared locus at 2q21.2-2q23.3, with a genome-wide significant LOD score of 3.45. The chromosomal region identified here overlaps with a locus at chromosome 2q22.1-2q31.1 reported previously. Three families support 1q41-1q42.3 (LOD = 3.69), two families share a region identical by descent at 2p14-2p13.3 (LOD = 3.15) and another two families at 15q26.3 (LOD = 3.01). Thus, our results point to considerable genetic heterogeneity. WES did not reveal any causative variants, suggesting that variants or mutations located outside the coding regions might be involved in the molecular pathogenesis of PFH. We suggest a strategy based on whole-genome or targeted next generation sequencing to identify causative genes or variants for PFH.

Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or organ dysfunction after the acute phase of infection, termed Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are poorly understood. The objectives of the Researching COVID to Enhance Recovery (RECOVER) tissue pathology study (RECOVER-Pathology) are to: (1) characterize prevalence and types of organ injury/disease and pathology occurring with PASC; (2) characterize the association of pathologic findings with clinical and other characteristics; (3) define the pathophysiology and mechanisms of PASC, and possible mediation via viral persistence; and (4) establish a post-mortem tissue biobank and post-mortem brain imaging biorepository. Methods: RECOVER-Pathology is a cross-sectional study of decedents dying at least 15 days following initial SARS-CoV-2 infection. Eligible decedents must meet WHO criteria for suspected, probable, or confirmed infection and must be aged 18 years or more at the time of death. Enrollment occurs at 7 sites in four U.S. states and Washington, DC. Comprehensive autopsies are conducted according to a standardized protocol within 24 hours of death; tissue samples are sent to the PASC Biorepository for later analyses. Data on clinical history are collected from the medical records and/or next of kin. The primary study outcomes include an array of pathologic features organized by organ system. Causal inference methods will be employed to investigate associations between risk factors and pathologic outcomes. Discussion: RECOVER-Pathology is the largest autopsy study addressing PASC among US adults. Results of this study are intended to elucidate mechanisms of organ injury and disease and enhance our understanding of the pathophysiology of PASC. [ABSTRACT FROM AUTHOR]

IntroductionNon-communicable diseases (NCDs) like cancer, cardiovascular disease, and diabetes have spread at a remarkable pace in European countries over the past decades. Overweight/obesity and alcohol use are two leading risk factors contributing to both economic and epidemiological burden associated with NCDs. In OECD countries, the impact of indirect costs of obesity varies between 0.20% and 1.21% of GDP. Indirect costs of alcohol use range from 0.19% (Portugal) to 1.6% (Estonia) of GDP.AimTo assess the longitudinal impact of alcohol use and high body-mass index (BMI) on labour market outcomes in the European region by modeling the direct effect of high BMI and alcohol use, and the effect via associated diseases.MethodsThe impact of BMI, alcohol use, and associated diseases on employment likelihood, intent to retire early, days of absenteeism, and hours of work per week, were modelled via lagged Poisson and Zero-inflated Poisson regressions, adjusting for missingness via inverse probability weighting, as appropriate, using European SHARE data.ResultsControlling for other chronic conditions, being overweight increases employment likelihood among men, but not among women. Obesity decreased female, but not male, employment chances. All chronic conditions linked with high BMI negatively affected employment likelihood, and increased the intention to retire early significantly. Alcohol use positively affects employment likelihood in women at all drinking levels relative to lifetime abstainers, but only in moderate (not heavy) male drinkers. There is super-additionality of impact of NCDs on absenteeism and hours worked, presenting a key economic argument to tackle NCD prevention and compression of morbidity.ImplicationsNCD prevention is not just important for employment and hours worked, but also for employee morale, especially given increasing retirement age in Europe and globally.

BackgroundHospitalisation is associated with adverse health outcomes including loss of muscle strength, muscle mass and functional decline, which might be further aggravated by acute inflammation. This study aimed to determine whether acute inflammation, as denoted by C-reactive protein (CRP), is associated with muscle strength, muscle mass and functional dependency in hospitalised older patients.MethodsThe observational, prospective EMPOWER study included 378 hospitalised patients aged 70 years and older. As part of the hospital assessment, 191 patients (50.5%) had CRP measured. Muscle strength and mass were measured using handheld dynamometry and bioelectrical impedance analysis respectively. Activities of Daily Living (ADL) were assessed using Katz score and Instrumental ADL (IADL) by Lawton and Brody score. Linear regression analyses and logistic regression analyses were performed stratified by sex and adjusted for age and comorbidities.ResultsMean age was 79.7 years (SD 6.4) and 50.8% were males. On admission and discharge, males with elevated CRP had significantly lower handgrip strength and lower absolute muscle mass compared with males with normal CRP and those with no CRP measured. At three months post-discharge, males with elevated CRP were more likely to be ADL dependent than those with normal CRP and with no CRP measured. In females, no associations were found between CRP and muscle strength, muscle mass, ADL or IADL.ConclusionsHospitalised older male patients with acute inflammation had lower muscle strength at admission and discharge and lower absolute muscle mass at admission and higher ADL dependency at three months post-discharge.

ObjectiveTo examine the test performance of careHPV, Hybrid Capture2 (HC2) and visual inspection with acetic acid (VIA) for detection of cytologically diagnosed high-grade cervical lesions or cancer (HSIL+).DesignCross-sectional study.SettingOcean Road Cancer Institute (ORCI) and Kilimanjaro Christian Medical Center (KCMC), Tanzania.PopulationWomen attending routine cervical cancer screening.MethodWe enrolled 4080 women (25-60 years) in the study. The women were interviewed on lifestyle habits, and tested for HIV. A cervical specimen for careHPV testing (performed at ORCI and KCMC), and a liquid-based cytology sample for HPV DNA detection using HC2 (performed at Tuebingen University Hospital, Germany) and for cytology assessment (performed at Vejle Hospital, Denmark) were obtained at a gynecological examination. Subsequently, VIA was performed. With cytology as gold standard, the sensitivity and specificity of careHPV, HC2, and VIA for detection of HSIL+ were calculated.ResultsAltogether, 23.6% had a positive careHPV test, 19.1% had positive HC2 test, and 6.3% had a positive VIA test. The sensitivity/specificity was 88.9%/78.9% for careHPV and 91.1%/83.7%, for HC2. VIA showed a low sensitivity of 31.1% but a high specificity (94.6%) for detection of HSIL+. The sensitivity of careHPV, HC2 and VIA was higher among younger women, and among HIV positive women. VIA triage of careHPV positive women improved specificity, but sensitivity dropped to 27%.ConclusionOur results confirm the low sensitivity of VIA for detection of HSIL+ and further document that careHPV test is promising as a primary screening method for cervical-cancer prevention in low-resource regions. A suitable triage test has to be identified.

OBJECTIVES:The metabolic syndrome has been associated with a variety of individual variables, including demographics, lifestyle, clinical measures and physical performance. We aimed to identify independent predictors of the prevalence and incidence of metabolic syndrome in a large cohort of older adults. METHODS:The Longitudinal Aging Study Amsterdam is a prospective cohort including community-dwelling adults aged 55-85 years. Metabolic syndrome was defined according to criteria of the National Cholesterol Education Program Adult Treatment Panel III. The incidence of metabolic syndrome was calculated over a period of three years. Stepwise backward logistic regression analyses were used to identify predictors, including variables for demographics, lifestyle, clinical measures and physical performance, both in a cross-sectional cohort (n = 1292) and a longitudinal sub-cohort (n = 218). RESULTS:Prevalence and incidence of metabolic syndrome were 37% (n = 479) and 30% (n = 66), respectively. Cross-sectionally, heart disease (OR: 1.91, 95% CI: 1.37-2.65), peripheral artery disease (OR: 2.13, 95% CI: 1.32-3.42), diabetes (OR: 4.74, 95% CI: 2.65-8.48), cerebrovascular accident (OR: 1.92, 95% CI: 1.09-3.37), and a higher Body Mass Index (OR: 1.32, 95% CI: 1.26-1.38) were significant independent predictors of metabolic syndrome. Longitudinally, Body Mass Index (OR: 1.16, 95% CI: 1.05-1.27) was an independent predictor of metabolic syndrome. CONCLUSION:Four age related diseases and a higher Body Mass Index were the only predictors of metabolic syndrome in the cross-sectional cohort, despite the large variety of variables included in the multivariable analysis. In the longitudinal sub-cohort, a higher Body Mass Index was predictive of developing metabolic syndrome.

BACKGROUND:Physical activity is associated with a lower risk of disease recurrence among colon cancer patients. Circulating tumor cells (CTC) are prognostic of disease recurrence among stage I-III colon cancer patients. The pathways through which physical activity may alter disease outcomes are unknown, but may be mediated by changes in CTCs. METHODS:Participants included 23 stage I-III colon cancer patients randomized into one of three groups: usual-care control, 150 min∙wk-1 of aerobic exercise (low-dose), and 300 min∙wk-1 of aerobic exercise (high-dose) for six months. CTCs from venous blood were quantified in a blinded fashion using an established microfluidic antibody-mediated capture device. Poisson regression models estimated the logarithmic counts of CTCs. RESULTS:At baseline, 78% (18/23) of patients had ≥1 CTC. At baseline, older age (-0.12±0.06; P = 0.04), lymphovascular invasion (0.63±0.25; P = 0.012), moderate/poor histology (1.09±0.34; P = 0.001), body mass index (0.07±0.02; P = 0.001), visceral adipose tissue (0.08±0.04; P = 0.036), insulin (0.06±0.02; P = 0.011), sICAM-1 (0.04±0.02; P = 0.037), and sVCAM-1 (0.06±0.03; P = 0.045) were associated with CTCs. Over six months, significant decreases in CTCs were observed in the low-dose (-1.34±0.34; P

Sarcopenia is an emerging clinical challenge in an ageing population and is associated with serious negative health outcomes. This study aimed to assess the current state of the art regarding the knowledge about the concept of sarcopenia and practice of the diagnostic strategy and management of sarcopenia in a cohort of Dutch healthcare professionals (physicians, physiotherapists, dietitians and others) attending a lecture cycle on sarcopenia.This longitudinal study included Dutch healthcare professionals (n = 223) who were asked to complete a questionnaire before, directly after and five months after (n = 80) attending a lecture cycle on the pathophysiology of sarcopenia, diagnostic strategy and management of sarcopenia, i.e. interventions and collaboration.Before attendance, 69.7% of healthcare professionals stated to know the concept of sarcopenia, 21.4% indicated to know how to diagnose sarcopenia and 82.6% had treated patients with suspected sarcopenia. 47.5% used their clinical view as diagnostic strategy. Handgrip strength was the most frequently used objective diagnostic measure (33.9%). Five months after attendance, reported use of diagnostic tests was increased, i.e. handgrip strength up to 67.4%, gait speed up to 72.1% and muscle mass up to 20.9%. Bottlenecks during implementation of the diagnostic strategy were experienced by 67.1%; lack of awareness among other healthcare professionals, acquisition of equipment and time constraints to perform the diagnostic measures were reported most often. Before attendance, 36.4% stated not to consult a physiotherapists or exercise therapists (PT/ET) or dietitian for sarcopenia interventions, 10.5% consulted a PT/ET, 32.7% a dietitian and 20.5% both a PT/ET and dietitian. Five months after attendance, these percentages were 28.3%, 21.7%, 30.0% and 20.0% respectively.The concept of sarcopenia is familiar to most Dutch healthcare professionals but application in practice is hampered, mostly by lack of knowledge, availability of equipment, time constraints and lack of collaboration.

Increasing evidence suggests that brain signal variability is an important measure of brain function reflecting information processing capacity and functional integrity. In this study, we examined how maturation from childhood to adulthood affects the magnitude and spatial extent of state-to-state transitions in brain signal variability, and how this relates to cognitive performance. We looked at variability changes between resting-state and task (a symbol-matching task with three levels of difficulty), and within trial (fixation, post-stimulus, and post-response). We calculated variability with multiscale entropy (MSE), and additionally examined spectral power density (SPD) from electroencephalography (EEG) in children aged 8-14, and in adults aged 18-33. Our results suggest that maturation is characterized by increased local information processing (higher MSE at fine temporal scales) and decreased long-range interactions with other neural populations (lower MSE at coarse temporal scales). Children show MSE changes that are similar in magnitude, but greater in spatial extent when transitioning between internally- and externally-driven brain states. Additionally, we found that in children, greater changes in task difficulty were associated with greater magnitude of modulation in MSE. Our results suggest that the interplay between maturational and state-to-state changes in brain signal variability manifest across different spatial and temporal scales, and influence information processing capacity in the brain.

One of the major complications related to delivery is labor dystocia, or an arrested labor progress. Many dystocic deliveries end vaginally after administration of oxytocin, but a large numbers of women with labor dystocia will undergo a long and unsafe parturition. As a result of the exertion required in labor, the uterus produces lactate. The uterine production of lactate is mirrored by the level of lactate in amniotic fluid (AFL).To evaluate whether the level of AFL, analysed in a sample of amniotic fluid collected vaginally at arrested labor when oxytocin was needed, could predict labor outcome in nulliparous deliveries.A prospective multicentre study including 3000 healthy primiparous women all with a singleton pregnancy, gestational age 37 to 42 weeks and no maternal /fetal chronic and/or pregnancy-related conditions. A spontaneous onset of labor, regular contractions and cervical dilation ≥ 3 cm were required before the women were invited to take part in the study.AFL, analysed within 30 minutes before augmentation, provides information about delivery outcome. Sensitivity for an acute cesarean section according to high (≥10.1mmol/l) or low (< 10.1mmol/l) AFL values was 39.0% (95% CI; 27-50), specificity 90.3% (95% CI; 87-93) PPV 37.3% (95% CI; 27-48) and NPV was 91.0% (95% CI; 88-93). The overall percentage of correct predictions of delivery outcome when the AFL level was used was 83.7%. Deliveries with a high AFL-level correlated with delivery time >12h (p = 0.04), post-partum fever (>38°C, p = 0.01) and post-partum haemorrhage >1.5L (p = 0.04).The AFL is a good predictor of delivery outcome in arrested nulliparous deliveries. Low levels of AFL may support the decision to continue a prolonged vaginal labor by augmentation with oxytocin. A high level of AFL correlates with operative interventions and post-partum complications.

BACKGROUND:The consumption of sugar-sweetened beverages (SSBs), which can lead to weight gain, is rising in middle-income countries (MICs). Taxing SSBs may help address this challenge. Systematic reviews focused on high-income countries indicate that taxing SSBs may reduce SSB consumption. Responsiveness to price changes may differ in MICs, where governments are considering the tax. To help inform their policy decisions, this review compiles evidence from MICs, assessing post-tax price increases (objective 1), changes in demand for SSBs and other products, overall and by socio-economic groups (objective 2), and effects on overweight and obesity prevalence (objective 3). METHODS AND FINDINGS:We conducted a systematic review on the effectiveness of SSB taxation in MICs (1990-2016) and identified nine studies from Brazil, Ecuador, India, Mexico, Peru, and South Africa. Estimates for own-price elasticity ranged from -0.6 to -1.2, and decreases in SSB consumption ranged from 5 to 39 kilojoules per person per day given a 10% increase in SSB prices. The review found that milk is a likely substitute, and foods prepared away from home, snacks, and candy are likely complements to SSBs. A quasi-experimental study and two modeling studies also found a negative relationship between SSB prices and obesity outcomes after accounting for substitution effects. Estimates are consistent despite variation in baseline obesity prevalence and per person per day consumption of SSBs across countries studied. CONCLUSIONS:The review indicates that taxing SSBs will increase the prices of SSBs, especially sugary soda, in markets with few producers. Taxing SSBs will also reduce net energy intake by enough to prevent further growth in obesity prevalence, but not to reduce population weight permanently. Additional research using better survey data and stronger study designs is needed to ascertain the long-term effectiveness of an SSB tax on obesity prevalence in MICs.

BACKGROUND:High BMI and blood pressure are leading chronic disease risk factors in South Africa. Longterm effects of HIV and ART on adiposity and blood pressure are poorly understood, and direct comparisons of risk factor trajectories in HIV- versus HIV+ populations are rare. METHODS:In 2003 and 2010, height, weight, and blood pressure were recorded in a study population (n = 505) in KwaZulu-Natal, South Africa (30% adult HIV prevalence). We modeled change in BMI and BP longitudinally in HIV- individuals (n = 315), seroconverters (n = 32), HIV+ patients not on ART (HIV+ART-; n = 52), HIV+ patients on ART for 0-

The ability to rise from sitting to standing is critical to an individual's quality of life, as it is a prerequisite for functional independence. The purpose of the current study was to examine the hypothesis that test durations as assessed with the instrumented repeated Sit-To-Stand (STS) show stronger associations with health status, functional status and daily physical activity of older adults than manually recorded test durations.In 63 older participants (mean age 83 ±6.9 years, 51 female), health status was assessed using the European Quality of Life questionnaire and functional status was assessed using the physical function index of the of the RAND-36. Physical performance was measured using a wearable sensor-based STS test. From this test, durations, sub-durations and kinematics of the STS movements were estimated and analysed. In addition, physical activity was measured for one week using an activity monitor and episodes of lying, sitting, standing and locomotion were identified. Associations between STS parameters with health status, functional status and daily physical activity were assessed.The manually recorded STS times were not significantly associated with health status (p = 0.457) and functional status (p = 0.055), whereas the instrumented STS times were (both p = 0.009). The manually recorded STS durations showed a significant association to daily physical activity for mean sitting durations (p = 0.042), but not for mean standing durations (p = 0.230) and mean number of locomotion periods (p = 0.218). Furthermore, durations of the dynamic sit-to-stand phase of the instrumented STS showed more significant associations with health status, functional status and daily physical activity (all p = 0.001) than the static phases standing and sitting (p = 0.043-0.422).As hypothesized, instrumented STS durations were more strongly associated with participant health status, functional status and physical activity than manually recorded STS durations in older adults. Furthermore, instrumented STS allowed assessment of the dynamic phases of the test, which were likely more informative than the static sitting and standing phases.

OBJECTIVES:System identification techniques have the potential to assess the contribution of the underlying systems involved in standing balance by applying well-known disturbances. We investigated the reliability of standing balance parameters obtained with multivariate closed loop system identification techniques. METHODS:In twelve healthy elderly balance tests were performed twice a day during three days. Body sway was measured during two minutes of standing with eyes closed and the Balance test Room (BalRoom) was used to apply four disturbances simultaneously: two sensory disturbances, to the proprioceptive and the visual system, and two mechanical disturbances applied at the leg and trunk segment. Using system identification techniques, sensitivity functions of the sensory disturbances and the neuromuscular controller were estimated. Based on the generalizability theory (G theory), systematic errors and sources of variability were assessed using linear mixed models and reliability was assessed by computing indexes of dependability (ID), standard error of measurement (SEM) and minimal detectable change (MDC). RESULTS:A systematic error was found between the first and second trial in the sensitivity functions. No systematic error was found in the neuromuscular controller and body sway. The reliability of 15 of 25 parameters and body sway were moderate to excellent when the results of two trials on three days were averaged. To reach an excellent reliability on one day in 7 out of 25 parameters, it was predicted that at least seven trials must be averaged. CONCLUSION:This study shows that system identification techniques are a promising method to assess the underlying systems involved in standing balance in elderly. However, most of the parameters do not appear to be reliable unless a large number of trials are collected across multiple days. To reach an excellent reliability in one third of the parameters, a training session for participants is needed and at least seven trials of two minutes must be performed on one day.

Pseudomonas aeruginosa infections of wounds in clinical settings are major complications whose outcomes are influenced by host responses that are not completely understood. Herein we evaluated transcriptomic changes of wounds as they counter P. aeruginosa infection-first active infection, and then chronic biofilm infection. We used the dermal full-thickness, rabbit ear excisional wound model. We studied the wound response: towards acute infection at 2, 6, and 24 hrs after inoculating 106 bacteria into day-3 wounds; and, towards more chronic biofilm infection of wounds similarly infected for 24 hrs but then treated with topical antibiotic to coerce biofilm growth and evaluated at day 5 and 9 post-infection. The wounds were analyzed for bacterial counts, expression of P. aeruginosa virulence and biofilm-synthesis genes, biofilm morphology, infiltrating immune cells, re-epithelialization, and genome-wide gene expression (RNA-Seq transcriptome). This analysis revealed that 2 hrs after bacterial inoculation into day-3 wounds, the down-regulated genes (infected vs. non-infected) of the wound edge were nearly all non-coding RNAs (ncRNAs), comprised of snoRNA, miRNA, and RNU6 pseudogenes, and their down-regulation preceded a general down-regulation of skin-enriched coding gene expression. As the active infection intensified, ncRNAs remained overrepresented among down-regulated genes; however, at 6 and 24 hrs they changed to a different set, which overlapped between these times, and excluded RNU6 pseudogenes but included snRNA components of the major and minor spliceosomes. Additionally, the raw counts of multiple types of differentially-expressed ncRNAs increased on post-wounding day 3 in control wounds, but infection suppressed this increase. After 5 and 9 days, these ncRNA counts in control wounds decreased, whereas they increased in the infected, healing-impaired wounds. These data suggest a sequential and coordinated change in the levels of transcripts of multiple major classes of ncRNAs in wound cells transitioning from inflammation to the proliferation phase of healing.

Diabetic nephropathy is the leading cause of end stage renal disease in the world. Although tremendous efforts have been made, scientists have yet to identify an ideal animal model that can reproduce the characteristics of human diabetic nephropathy. In this study, we hypothesize that taurine insufficiency is a critical risk factor for development of diabetic nephropathy associated with diabetes mellitus. This hypothesis was tested in vivo in TauT heterozygous (TauT+/-) and homozygous (TauT-/-) knockout in C57BL/6 background mice. We have shown that alteration of the TauT gene (also known as SLC6A6) has a substantial effect on the susceptibility to development of extensive diabetic kidney disease in both TauT+/- and TauT-/-mouse models of diabetes. These animals developed histological changes characteristic of human diabetic nephropathy that included glomerulosclerosis, nodular lesions, arteriosclerosis, arteriolar dilation, and tubulointerstitial fibrosis. Immunohistochemical staining of molecular markers of smooth muscle actin, CD34, Ki67 and collagen IV further confirmed these observations. Our results demonstrated that both homozygous and heterozygous TauT gene deletion predispose C57BL/6 mice to develop end-stage diabetic kidney disease, which closely replicates the pathological features of diabetic nephropathy in human diabetic patients.

ObjectivesDiagnostic criteria for sarcopenia include measures of muscle mass, muscle strength and physical performance. Consensus on the definition of sarcopenia has not been reached yet. To improve insight into the most clinically valid definition of sarcopenia, this study aimed to compare the association between parameters of malnutrition, as a risk factor in sarcopenia, and diagnostic measures of sarcopenia in geriatric outpatients.Material and methodsThis study is based on data from a cross-sectional study conducted in a geriatric outpatient clinic including 185 geriatric outpatients (mean age 82 years). Parameters of malnutrition included risk of malnutrition (assessed by the Short Nutritional Assessment Questionnaire), loss of appetite, unintentional weight loss and underweight (body mass index ResultsNone of the parameters of malnutrition was consistently associated with diagnostic measures of sarcopenia. The strongest associations were found for both relative and absolute muscle mass; less stronger associations were found for muscle strength and physical performance. Underweight (p = ConclusionParameters of malnutrition relate differently to diagnostic measures of sarcopenia in geriatric outpatients. The association between parameters of malnutrition and diagnostic measures of sarcopenia was strongest for both relative and absolute muscle mass, while less strong associations were found with muscle strength and physical performance.

BackgroundMen's involvement in reproductive health is recommended. Their involvement in antenatal care service is identified as important in maternal health. Awareness of obstetric danger signs facilitates men in making a joint decision with their partners regarding accessing antenatal and delivery care. This study aims to assess the level of knowledge of obstetric complications among men in a rural community in Tanzania, and to determine their involvement in birth preparedness and complication readiness.MethodsA cross-sectional survey was conducted where 756 recent fathers were invited through a two-stage cluster sampling procedure. A structured questionnaire was used to collect socio-demographic characteristics, knowledge of danger signs and steps taken on birth preparedness and complication readiness. Data were analyzed using bivariate and multivariable logistic regression to determine factors associated with being prepared, with statistically significant level at pResultsAmong the invited men, 95.9% agreed to participate in the community survey. Fifty-three percent could mention at least one danger sign during pregnancy, 43.9% during delivery and 34.6% during the postpartum period. Regarding birth preparedness and complication readiness, 54.3% had bought birth kit, 47.2% saved money, 10.2% identified transport, 0.8% identified skilled attendant. In general, only 12% of men were prepared. Birth preparedness was associated with knowledge of danger signs during pregnancy (AOR = 1.4, 95% CI: 1.8-2.6). It was less likely for men living in the rural area to be prepared (AOR=0.6, 95% CI; 0.5-0.8).ConclusionThere was a low level of knowledge of obstetric danger signs among men in a rural district in Tanzania. A very small proportion of men had prepared for childbirth and complication readiness. There was no effect of knowledge of danger signs during childbirth and postpartum period on being prepared. Innovative strategies that increase awareness of danger signs as well as birth preparedness and complication readiness among men are required. Strengthening counseling during antenatal care services that involve men together with partners is recommended.

The correct wiring of neuronal circuits is of crucial importance for precise neuromuscular functionality. Therefore, guidance cues provide tight spatiotemporal control of axon growth and guidance. Mice lacking the guidance cue Semaphorin 3F (Sema3F) display very specific axon wiring deficits of motor neurons in the medial aspect of the lateral motor column (LMCm). While these deficits have been investigated extensively during embryonic development, it remained unclear how Sema3F mutant mice cope with these errors postnatally. We therefore investigated whether these animals provide a suitable model for the exploration of adaptive plasticity in a system of miswired neuronal circuitry. We show that the embryonically developed wiring deficits in Sema3F mutants persist until adulthood. As a consequence, these mutants display impairments in motor coordination that improve during normal postnatal development, but never reach wildtype levels. These improvements in motor coordination were boosted to wildtype levels by housing the animals in an enriched environment starting at birth. In contrast, a delayed start of enriched environment housing, at 4 weeks after birth, did not similarly affect motor performance of Sema3F mutants. These results, which are corroborated by neuroanatomical analyses, suggest a critical period for adaptive plasticity in neuromuscular circuitry. Interestingly, the formation of perineuronal nets, which are known to close the critical period for plastic changes in other systems, was not altered between the different housing groups. However, we found significant changes in the number of excitatory synapses on limb innervating motor neurons. Thus, we propose that during the early postnatal phase, when perineuronal nets have not yet been formed around spinal motor neurons, housing in enriched environment conditions induces adaptive plasticity in the motor system by the formation of additional synaptic contacts, in order to compensate for coordination deficits.

Engrailed-1 (En1) is expressed in the ventral ectoderm of the developing limb where it plays an instructive role in the dorsal-ventral patterning of the forelimb. Besides its well-described role as a transcription factor in regulating gene expression through its DNA-binding domain, En1 may also be secreted to form an extracellular gradient, and directly impact on the formation of the retinotectal map. We show here that absence of En1 causes mispatterning of the forelimb and thus defects in the dorsal-ventral pathfinding choice of motor axons in vivo. In addition, En1 but not En2 also has a direct and specific repulsive effect on motor axons of the lateral aspect of the lateral motor column (LMC) but not on medial LMC projections. Moreover, an ectopic dorsal source of En1 pushes lateral LMC axons to the ventral limb in vivo. Thus, En1 controls the establishment of limb innervation through two distinct molecular mechanisms.

ObjectivesAssessment of the association of blood pressure measurements in supine and standing position after a postural change, as a proxy for blood pressure regulation, with standing balance in a clinically relevant cohort of elderly, is of special interest as blood pressure may be important to identify patients at risk of having impaired standing balance in routine geriatric assessment.Materials and methodsIn a cross-sectional cohort study, 197 community-dwelling elderly referred to a geriatric outpatient clinic of a middle-sized teaching hospital were included. Blood pressure was measured intermittently (n = 197) and continuously (subsample, n = 58) before and after a controlled postural change from supine to standing position. The ability to maintain standing balance was assessed during ten seconds of side-by-side, semi-tandem and tandem stance, with both eyes open and eyes closed. Self-reported impaired standing balance and history of falls were recorded by questionnaires. Logistic regression analyses were used to examine the association between blood pressure and 1) the ability to maintain standing balance; 2) self-reported impaired standing balance; and 3) history of falls, adjusted for age and sex.ResultsBlood pressure decrease after postural change, measured continuously, was associated with reduced ability to maintain standing balance in semi-tandem stance with eyes closed and with increased self-reported impaired standing balance and falls. Presence of orthostatic hypotension was associated with reduced ability to maintain standing balance in semi-tandem stance with eyes closed for both intermittent and continuous measurements and with increased self-reported impaired standing balance for continuous measurements.ConclusionContinuous blood pressure measurements are of additional value to identify patients at risk of having impaired standing balance and may therefore be useful in routine geriatric care.

Nonsense-mediated mRNA decay (NMD), which is best known for degrading mRNAs with premature termination codons (PTCs), is thought to be triggered by aberrant translation termination at stop codons located in an environment of the mRNP that is devoid of signals necessary for proper termination. In mammals, the cytoplasmic poly(A)-binding protein 1 (PABPC1) has been reported to promote correct termination and therewith antagonize NMD by interacting with the eukaryotic release factors 1 (eRF1) and 3 (eRF3). Using tethering assays in which proteins of interest are recruited as MS2 fusions to a NMD reporter transcript, we show that the three N-terminal RNA recognition motifs (RRMs) of PABPC1 are sufficient to antagonize NMD, while the eRF3-interacting C-terminal domain is dispensable. The RRM1-3 portion of PABPC1 interacts with eukaryotic initiation factor 4G (eIF4G) and tethering of eIF4G to the NMD reporter also suppresses NMD. We identified the interactions of the eIF4G N-terminus with PABPC1 and the eIF4G core domain with eIF3 as two genetically separable features that independently enable tethered eIF4G to inhibit NMD. Collectively, our results reveal a function of PABPC1, eIF4G and eIF3 in translation termination and NMD suppression, and they provide additional evidence for a tight coupling between translation termination and initiation.

Primary hyperhidrosis is defined as excessive sweating of certain body areas without physiological reasons. Hyperhidrotic individuals report a high psychological strain and an impairment of their quality of life. Thus, the aim of the study is to investigate the relation between hyperhidrosis and different psychological as well as physiological aspects of chronic stress as a co-factor for the etiology of depression. In this study, forty hyperhidrotic subjects were compared to forty age- and sex-matched healthy control subjects. The Trier Inventory of Chronic Stress ('Trierer Inventar zum chronischen Stress': TICS), the Beck Depression Inventory (BDI-II) and the Screening for Somatoform Disorders (SOMS-2) were used to examine the correlation between primary hyperhidrosis and stress as well as accompanying depressive and somatic symptoms. The cortisol awakening response of each subject was analyzed as a physiological stress correlate. In hyperhidrotics, we found a significant lack of social recognition as well as significantly more depressive symptoms compared to the control subjects. A subgroup of patients with axillary hyperhidrosis had the highest impact on these increased issues of chronic stress, pointing to a higher embarrassment in these subjects. Especially in social situations, hyperhidrotics showed higher stress levels, whereby a vicious circle of stress and sweating is triggered. However, the cortisol awakening response did not significantly differ between hyperhidrotics and controls. Moreover, affected persons suffer from more depressive symptoms, which may be caused by feelings of shame and a lack of self-confidence. This initial study provides an impetus for further investigation to reveal a causative relationship between hyperhidrosis and its psychological concomitants.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically significant viral diseases facing the global swine industry. Viremia profiles of PRRS virus challenged pigs reflect the severity and progression of infection within the host and provide crucial information for subsequent control measures. In this study we analyse the largest longitudinal PRRS viremia dataset from an in-vivo experiment. The primary objective was to provide a suitable mathematical description of all viremia profiles with biologically meaningful parameters for quantitative analysis of profile characteristics. The Wood's function, a gamma-type function, and a biphasic extended Wood's function were fit to the individual profiles using Bayesian inference with a likelihood framework. Using maximum likelihood inference and numerous fit criteria, we established that the broad spectrum of viremia trends could be adequately represented by either uni- or biphasic Wood's functions. Three viremic categories emerged: cleared (uni-modal and below detection within 42 days post infection(dpi)), persistent (transient experimental persistence over 42 dpi) and rebound (biphasic within 42 dpi). The convenient biological interpretation of the model parameters estimates, allowed us not only to quantify inter-host variation, but also to establish common viremia curve characteristics and their predictability. Statistical analysis of the profile characteristics revealed that persistent profiles were distinguishable already within the first 21 dpi, whereas it is not possible to predict the onset of viremia rebound. Analysis of the neutralizing antibody(nAb) data indicated that there was a ubiquitous strong response to the homologous PRRSV challenge, but high variability in the range of cross-protection of the nAbs. Persistent pigs were found to have a significantly higher nAb cross-protectivity than pigs that either cleared viremia or experienced rebound within 42 dpi. Our study provides novel insights into the nature and degree of variation of hosts' responses to infection as well as new informative traits for subsequent genomic and modelling studies.

Non-invasive tubulointerstitial damage markers may allow better titration and monitoring of renoprotective therapy. We investigated the value of urinary vitamin D binding protein excretion (uVDBP) as a tubulointerstitial inflammation and fibrosis marker in adriamycin rats, and tested whether uVDBP parallels renal damage and responds to therapy intensification in humans. In adriamycin (ADR) rats, uVDBP was strongly elevated vs controls (CON) already 6 wks after nephrosis induction (ADR: 727±674 [mean±SD] vs CON: 9±12 µg/d, p100-fold increased during maximal therapy vs normoalbuminurics (p

Protein N-glycosylation patterns are known to show vast genetic as well as physiological and pathological variation and represent a large pool of potential biomarkers. Large-scale studies are needed for the identification and validation of biomarkers, and the analytical techniques required have recently been developed. Such methods have up to now mainly been applied to complex mixtures of glycoproteins in biofluids (e.g. plasma). Here, we analyzed N-glycosylation profiles of alpha1-antitrypsin (AAT) and immunoglobulin A (IgA) enriched fractions by 96-well microtitration plate based high-throughput immuno-affinity capturing and N-glycan analysis using multiplexed capillary gel electrophoresis with laser-induced fluorescence detection (CGE-LIF). Human plasma samples were from the Leiden Longevity Study comprising 2415 participants of different chronological and biological ages. Glycosylation patterns of AAT enriched fractions were found to be associated with chronological (calendar) age and they differed between females and males. Moreover, several glycans in the AAT enriched fraction were associated with physiological parameters marking cardiovascular and metabolic diseases. Pronounced differences were found between males and females in the glycosylation profiles of IgA enriched fractions. Our results demonstrate that large-scale immuno-affinity capturing of proteins from human plasma using a bead-based method combined with high-throughput N-glycan analysis is a powerful tool for the discovery of glycosylation-based biomarker candidates.

BackgroundDecline in cognitive performance is a highly prevalent health condition in elderly. We studied whether offspring of nonagenarian siblings with a familial history of longevity, perform better on cognitive tests compared to their partners as controls. This is relevant since it could provide insights into determinants underlying decline in cognitive performance.MethodsCross-sectional analysis within the longitudinal cohort of the Leiden Longevity Study consisting of middle-aged offspring of nonagenarian siblings together with their partners (n = 500, mean age (SD) 66.3 (6.1) and 65.7 (7.2) years, respectively) as controls. Memory function, attention and processing speed were tested using the 15-Picture Learning Test, Stroop test and Digit Symbol Substitution Test. Data were analyzed with regression adjusted for age, gender, years of education and additionally for diabetes mellitus, cardiovascular diseases, alcohol use, smoking, inflammatory markers and apolipoprotein E genotype. Robust standard errors were used to account for familial relationships among the offspring.ResultsCognitive performance was worse at higher calendar age (pConclusionsOffspring of nonagenarian siblings with a familial history of longevity have better cognitive performance compared to the group of their partners of comparable age. This effect is independent of age-related diseases and known possible confounders. Possible explanations might be differences in subclinical vascular pathology between both groups.

Human aging is associated with a progressive loss of muscle mass and strength and a concomitant fat accumulation in form of inter-muscular adipose tissue, causing skeletal muscle function decline and immobilization. Fat accumulation can also occur as intra-muscular triglycerides (IMTG) deposition in lipid droplets, which are associated with perilipin proteins, such as Perilipin2 (Plin2). It is not known whether Plin2 expression changes with age and if this has consequences on muscle mass and strength. We studied the expression of Plin2 in the vastus lateralis (VL) muscle of both healthy subjects and patients affected by lower limb mobility limitation of different age. We found that Plin2 expression increases with age, this phenomenon being particularly evident in patients. Moreover, Plin2 expression is inversely correlated with quadriceps strength and VL thickness. To investigate the molecular mechanisms underpinning this phenomenon, we focused on IGF-1/p53 network/signalling pathway, involved in muscle physiology. We found that Plin2 expression strongly correlates with increased p53 activation and reduced IGF-1 expression. To confirm these observations made on humans, we studied mice overexpressing muscle-specific IGF-1, which are protected from sarcopenia. These mice resulted almost negative for the expression of Plin2 and p53 at two years of age. We conclude that fat deposition within skeletal muscle in form of Plin2-coated lipid droplets increases with age and is associated with decreased muscle strength and thickness, likely through an IGF-1- and p53-dependent mechanism. The data also suggest that excessive intramuscular fat accumulation could be the initial trigger for p53 activation and consequent loss of muscle mass and strength.