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Pig Liver organ Esterases Hydrolyze Endocannabinoids and also Promote Inflammatory Reaction.
AIMS/HYPOTHESIS The association between pubertal timing and type 2 diabetes, independent of prepubertal BMI, is not fully understood. The aim of the present study was to evaluate the association between pubertal timing and risk of adult type 2 diabetes, independent of prepubertal BMI, in Swedish men. METHODS We included 30,697 men who had data for BMI at age 8 and 20 years and age at Peak Height Velocity (PHV), an objective assessment of pubertal timing, available from the BMI Epidemiology Study Gothenburg (BEST Gothenburg), Sweden. Information on type 2 diabetes (n = 1851) was retrieved from the Swedish National Patient Register. HRs and 95% CIs were estimated by Cox regression analysis. We observed violations of the assumption of proportional hazards for the association between age at PHV and the risk of type 2 diabetes and therefore split the follow-up period at the median age of type 2 diabetes diagnosis (57.2 years of age) to define early (≤57.2 years) and late (>57.2 years) type 2 diabetes diagnosis. RESULTS Age at PHV was inversely associated with both early (HR 1.28 per year decrease in age at PHV, 95% CI 1.21, 1.36) and late (HR 1.13, 95% CI 1.06, 1.19) type 2 diabetes. After adjustment for childhood BMI, the associations between age at PHV and both early (HR 1.24, 95% CI 1.17, 1.31) and late (HR 1.11, 95% CI 1.05, 1.17) type 2 diabetes were similar. Moreover, early age at PHV predicted insulin treatment of type 2 diabetes (OR 1.25 per year decrease in age at PHV, 95% CI 1.17, 1.33). Assuming a higher risk among those with an age at PHV below the median, the population attributable factor indicates that 15% fewer of the diagnosed individuals would have developed type 2 diabetes had they not reached puberty early. CONCLUSIONS/INTERPRETATION These findings indicate that early puberty may be a novel independent risk factor for type 2 diabetes.Hidradenitis suppurativa is a chronic skin disease characterized by inflammation and disfiguring scarring in the intertriginous body areas. Hidradenitis suppurativa is associated with overweight and impaired quality of life. This study sought to describe Body Image Quality of Life (BI-QoL) in patients with hidradenitis suppurativa and to compare it with patients with other skin diseases (controls). A total of 285 participants were recruited, 141 with hidradenitis suppurativa and 144 controls, at the Department of Dermatology at Zealand University Hospital, Denmark (during 2017-18). The Danish "Body Image Quality of Life Inventory" questionnaire measured BI-QoL. Patients with hidradenitis suppurativa had significantly lower mean BI-QoL than controls Hidradenitis suppurativa BI-QoL (standard deviation; SD) -0.87 (0.98) vs. control BI-QoL (SD) 0.01 (1.11), p  less then  0.001. Predictors of negative BI-QoL were hidradenitis suppurativa, increased body mass index, female sex, symptoms of depression, and body mass index moderated by hidradenitis suppurativa. These data suggest that BI-QoL is impaired in patients with hidradenitis suppurativa compared with patients with other skin diseases after adjusting for confounders.BACKGROUND Parechovirus-A3 (PeV-A3) and enteroviruses (EV) are the most common viruses causing sepsis and meningoencephalitis in neonates and young infants. Clinical manifestations of PeV-A3 infection are more severe than those of EV infection, and no pleocytosis with a positive PCR result for PeV-A3 in cerebrospinal fluid (CSF) are characteristic findings. We hypothesized that innate immune responses to PeV-A3 and EV are distinct in serum and CSF. METHODS We evaluated 22 cytokines/chemokines in serum and CSF from PeV-A3- or EV-infected patients younger than 4 months in Niigata, Japan, from 2015 through 2018. Infection was diagnosed with real-time PCR followed by sequencing. Febrile neonates and infants with sepsis-like syndrome who had negative bacterial culture and viral PCR for both PeV-A and EV were also included (non-PeV-A/EV patients). RESULTS Among 192 febrile patients, we evaluated 16 PeV-A3-infected, 15 EV-infected, and 8 non-PeV-A/EV patients. Serum pro-/anti-inflammatory cytokine/chemokine levels were higher in PeV-A3-infected patients than in EV-infected patients (P less then .02). While most cytokine/chemokine were elevated in CSF from EV-infected patients, levels were low or undetectable in PeV-A3-infected and non-PeV-A/EV patients (P less then .001). CONCLUSIONS Distinct cytokine/chemokine patterns in serum and CSF may explain the different clinical manifestations of PeV-A3-infected and EV-infected neonates and young infants. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail [email protected] are a major group of plant-specific metabolites that determine flower and seed coloration. In plant cells, flavonoids are synthesized at the cytosolic surface of the endoplasmic reticulum and are sequestered in the vacuole. It is possible that membrane trafficking, including vesicle trafficking and organelle dynamics, contributes to flavonoid transport and accumulation. However, the underlying mechanism remains to be fully elucidated. Here we show that the Arabidopsis ECHIDNA protein plays a role in flavonoid accumulation in the vacuole and protein trafficking to the vacuole. We found defective pigmentation patterns in echidna seed, possibly caused by reduced levels of proanthocyanidins, which determine seed coloration. The echidna mutant has defects in protein sorting to the protein storage vacuole as well as vacuole morphology. These findings indicate that ECHIDNA is involved in the vacuolar trafficking pathway in addition to the previously described secretory pathway. In addition, we found a genetic interaction between echidna and green fluorescent seed 9 (gfs9), a membrane trafficking factor involved in flavonoid accumulation. Our findings suggest that vacuolar trafficking and/or vacuolar development, both of which are collectively regulated by ECHIDNA and GFS9, are required for flavonoid accumulation, resulting in seed coat pigmentation. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email [email protected] This Phase 1b study evaluated the pharmacokinetics, safety and antiviral effects of the respiratory syncytial virus (RSV)-specific fusion inhibitor JNJ-53718678 (JNJ8678) in hospitalized RSVinfected patients (aged >1-≤24 months). METHODS Patients categorized by age (Cohort 1 ≥6-≤24 months; Cohort 2 ≥3-1- less then 3 months) were randomized to oral JNJ-8678 or placebo once-daily for 7 days. Dose increases followed Data Review Committee recommendations (doses respectively Cohort 1 2/6/8/9 mg/kg; Cohort 2 1.5/4.5/6 mg/kg; Cohort 3 1/3/5 mg/kg). Cohort 1 included a 9 mg/kg dose, as target exposures were not reached at lower doses. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modeling. Safety was assessed by adverse events (AEs), laboratory tests and electrocardiograms. To assess antiviral effects, RSV RNA viral load from nasal swabs was quantified over time using qRT-PCR. RESULTS Patients received JNJ-8678 (n=37) or placebo (n=7). Pharmacokinetic parameters were similar at the highest doses for Cohorts 1-3 (AUC24h at Day 7; 35,840, 34,980 and 39,627 ng.hr/mL, respectively). Two grade 3 AEs were reported (both bronchiolitis; 1 [JNJ-8678], 1 [placebo]); reported as serious AEs; all other AEs were grade 1 or 2. Two additional serious AEs were reported (rhinitis [JNJ-8678], pneumonia [placebo]). No deaths, grade 4 AEs or AEs leading to discontinuation were reported. Median RSV viral load change from baseline in JNJ-8678 vs placebo by Day 3 was 1.98 vs -0.32 log10 copies/mL. CONCLUSION In RSV-infected infants, JNJ-8678 was well tolerated. Target exposures were reached and antiviral activity was observed. © The Author(s) 2020. GSK-3 beta phosphorylation Published by Oxford University Press for the Infectious Diseases Society of America.BACKGROUND This study aims to analyse changes in the prevalence of cervical cancer (CCa) and breast cancer (BCa) screening among women in the Brazilian capitals and Federal District in the last decade (2007-16). METHODS Data from the surveillance system of risk and protective factors for chronic diseases through telephone interviews (n = 267 949) were used. Adequate screening consisted of, at least, one Pap test biannually, for women aged between 25 and 64 years, and mammography exam triennially, for women aged between 50 and 69 years. The prevalence of adequate screening was investigated for each type of cancer isolated and combined (women aged between 50 and 64 years). The prevalence of adequate screening was estimated for the total population and according to socioeconomic variables. Linear regression models were used. RESULTS The prevalence of adequate screening test for CCa remained stable, around 82%, while the screening test for BCa increased from 71 to 78% between 2007 and 2016. Higher increases were observed among women with low schooling and from less developed regions. The percentage of adequate screening (considering both types), for women aged between 25 and 69 years, remained stable, close to 78%. CONCLUSIONS Screening for BCa increased significantly. Smaller coverage rates are verified among women with low schooling and from less developed regions. © The Author(s) 2020. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail [email protected] Few studies have examined the association between mental health and satisfaction with primary care services in community-dwelling older adults. OBJECTIVE To examine the association between mental health in older adults and low satisfaction with primary care services within four dimensions of care. METHODS This secondary data analysis included 1624 older adults participating in the 'Étude sur la Santé des Aînés Services' (ESA-Services study) and recruited in primary care practices between 2011 and 2013 in the province of Quebec. Patient satisfaction and experience with care were assessed during face-to-face interviews with questions adapted from the Primary Care Assessment Survey. Self-reported mental health indicators included depression, anxiety, suicidal ideation, psychological distress and cognition. We conducted four logistic regressions to examine the associations between mental health and low satisfaction in the following dimensions of care continuity of care, provider-patient interactions, adequacy of care and physical environment. RESULTS Nearly half of participants (48.5%) reported low satisfaction in at least one dimension of care examined. High psychological distress was associated with low satisfaction with provider-patient interactions [odds ratio (OR) = 1.02; 95% confidence interval (CI) = 1.00-1.04] and adequacy of care (OR = 1.04; 95% CI = 1.01-1.06). The presence of an anxiety disorder was associated with low satisfaction in adequacy of care (OR = 1.64; 95% CI = 1.00-2.72). Worse cognitive functioning was associated with low satisfaction in continuity of care, provider-patient interaction and adequacy of care. CONCLUSIONS Mental health was consistently associated with low satisfaction within dimensions of care. Results support the need for increased attention when delivering care to older adults with mental health problems. © The Author(s) 2020. Published by Oxford University Press. All rights reserved.For permissions, please e-mail [email protected].
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