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Quantification and comparison of senescence metrics aided RIL selection, facilitating exome-capture enabled bulk segregant analysis (BSA). Using BSA we mapped our two staygreen traits to two independent, dominant, loci of 4.8 and 16.7 Mb in size encompassing 56 and 142 genes. Combining association analysis with variant effect prediction, we identified SNPs encoding self-validating mutations located in NAM-1 homoeologues, which we propose as gene candidates.

The role of cardiopulmonary exercise testing (CPET) in predicting major adverse cardiovascular events (MACE) in people with congenital heart disease (ConHD) is unknown. A systematic review with meta-analysis was conducted to report the associations between CPET parameters and MACE in people with ConHD.

Electronic databases were systematically searched on 30 April 2020 for eligible publications. Two authors independently screened publications for inclusion, extracted study data, and performed risk of bias assessment. Primary meta-analysis pooled univariate hazard ratios across studies. A total of 34 studies (18 335 participants; 26.2 ± 10.1 years; 54% ± 16% male) were pooled into a meta-analysis. More than 20 different CPET prognostic factors were reported across 6 ConHD types. Of the 34 studies included in the meta-analysis, 10 (29%), 23 (68%), and 1 (3%) were judged as a low, medium, and high risk of bias, respectively. Primary univariate meta-analysis showed consistent evidence that improved peak and submaximal CPET measures are associated with a reduce risk of MACE. This association was supported by a secondary meta-analysis of multivariate estimates and individual studies that could not be numerically pooled.

Various maximal and submaximal CPET measures are prognostic of MACE across a variety of ConHD diagnoses. Further well-conducted prospective multicentre cohort studies are needed to confirm these findings.

Various maximal and submaximal CPET measures are prognostic of MACE across a variety of ConHD diagnoses. Further well-conducted prospective multicentre cohort studies are needed to confirm these findings.Mediastinal schwannoma arising from brachial plexus are rare, but their surgical treatment could be challenging with a minimally invasive approach, given their position. Furthermore, their proximity to brachial plexus nerve fibres raises the risk for postoperative upper limb deficits. A 72-year-old man presented mediastinal schwannoma arising from the T1 nerve root. Complete surgical excision was achieved via video-assisted thoracic surgery with the aid of intraoperative neuromonitoring, and no postoperative neurological deficit developed after the intervention. Using intraoperative neuromonitoring, radical minimally invasive surgical treatment can be safely achieved for mediastinal schwannoma arising from brachial plexus.

In 2012, the central government of Spain enacted Royal Decree-Law (RDL) 16/2012 and Royal Decree (RD) 1192/2012, which abolished universal healthcare coverage, thus limiting access to care for undocumented immigrants. Free health care was also no longer granted to anyone who has never been employed. In this context, this study investigated the prevalence of late HIV diagnoses (LHDs) among immigrants living in Spain vs. native-born Spaniards.

Data (n = 5943) from the 2010 to 2015 Cohort of the Spanish AIDs Research Network were used, including HIV-positive and antiretroviral therapy (ART)-naïve patients throughout Spain. Multivariate logistic models were fitted to compare the prevalence of LHD among the groups, adjusting for covariates.

The prevalence of LHD in the total sample was 39.5%. Compared with native-born Spaniards (n = 4445), immigrants (n = 1488) were more likely to have LHD (37.4% vs. 45.7%, respectively; P < 0.001). Multivariate analysis showed that the prevalence ratio of LHD among immiges of the disparity and potential social and policy interventions to reduce the prevalence of LHD among immigrants.

Financial stressors such as wealth loss, indebtedness, and bankruptcy have gained the attention of public health scholars since the Great Recession. In this study, we extend this area of research by comparing the mental and physical impact of multiple financial stressors during midlife, a pivotal period in the life course for wealth accumulation and disease onset.

With data from the National Longitudinal Survey of Youth 1979 (www.nlsinfo.org), an ongoing survey of adult men and women in the United States, we used logistic regression to estimate the associations between financial stressors and the risk of a psychiatric disorder or high blood pressure diagnosis from ages 31-39 in 1996 to ages 50-59 in 2016 (N = 7,143). Financial stressors include multiple types of wealth loss, debt, and bankruptcy.

Even after adjusting for a comprehensive set of confounders, many of the financial stressors we considered had similar positive associations with the risk of a psychiatric disorder, whereas only debt and bankruptcy were associated with the risk of high blood pressure. The best-fitting models for both health outcomes included a simple indicator of indebtedness. Stock losses were not significantly associated with either health outcome.

Given the recent volatility in the U.S. economy, our results highlight the potential loss of health that may occur if nothing is done to prevent economically vulnerable populations from sliding into financial crisis. Our results also emphasize the need for additional research to develop individual-level interventions to improve health among those already experiencing financial difficulties.

Given the recent volatility in the U.S. economy, our results highlight the potential loss of health that may occur if nothing is done to prevent economically vulnerable populations from sliding into financial crisis. Our results also emphasize the need for additional research to develop individual-level interventions to improve health among those already experiencing financial difficulties.Autophagy receptor p62/SQSTM1 signals a complex network that links autophagy-lysosomal system to proteasome. Phosphorylation of p62 on Serine 349 (P-Ser349 p62) is involved in a cell protective, antioxidant pathway. We have shown previously that P-Ser349 p62 occurs and is rapidly degraded during human synovial fibroblasts autophagy. In this work we observed that fingolimod (FTY720), used as a medication for multiple sclerosis, induced coordinated expression of p62, P-Ser349 p62 and inhibitory TFEB form, phosphorylated on Serine 211 (P-Ser211 TFEB), in human synovial fibroblasts. These effects were mimicked and potentiated by proteasome inhibitor MG132. In addition, FTY720 induced autophagic flux, LC3B-II up-regulation, Akt phosphorylation inhibition on Serine 473 but down-regulated TFEB, suggesting stalled autophagy. FTY720 decreased cytoplasmic fraction contained TFEB but induced TFEB in nuclear fraction. FTY720-induced P-Ser211 TFEB was mainly found in membrane fraction. Autophagy and VPS34 kinase inhibitor, autophinib, further increased FTY720-induced P-Ser349 p62 but inhibited concomitant expression of P-Ser211 TFEB. These results suggested that P-Ser211 TFEB expression depends on autophagy. Overexpression of GFP tagged TFEB in HEK293 cells showed concomitant expression of its phosphorylated form on Serine 211, that was down-regulated by autophinib. These results suggested that autophagy might be autoregulated through P-Ser211 TFEB as a negative feedback loop. Of interest, overexpression of p62, p62 phosphorylation mimetic (S349E) mutant and phosphorylation deficient mutant (S349A) in HEK293 cells markedly induced P-Ser211 TFEB. These results showed that p62 is involved in regulation of TFEB phosphorylation on Serine 211 but that this involvement does not depend on p62 phosphorylation on Serine 349.

Greater trochanter pain syndrome (GTPS) is characterized by a persistent and debilitating pain around the greater trochanter. GTPS can be caused by a combination of gluteus medius or minimus tendinopathy, snapping hip or trochanteric bursitis.

Recent published literatures identified from PubMed, EMBASE, Google Scholar, Scopus.

Platelet rich plasma (PRP) and corticosteroids (CCS) injections are useful options to manage symptoms of GTPS.

Whether PRP leads to superior outcomes compared to CCS injections is unclear.

A systematic review and meta-analysis comparing PRP versus CCS in the management of GTPS was conducted.

PRP injections are more effective than CCS at approximately 2 years follow-up.

PRP injections are more effective than CCS at approximately 2 years follow-up.

To identify differences related to sex and define autism spectrum disorder (ASD) comorbidities female-enriched through a comprehensive multi-PheWAS intersection approach on big, real-world data. Although sex difference is a consistent and recognized feature of ASD, additional clinical correlates could help to identify potential disease subgroups, based on sex and age.

We performed a systematic comorbidity analysis on 1860 groups of comorbidities exploring all spectrum of known disease, in 59 140 individuals (11 440 females) with ASD from 4 age groups. We explored ASD sex differences in 2 independent real-world datasets, across all potential comorbidities by comparing (1) females with ASD vs males with ASD and (2) females with ASD vs females without ASD.

We identified 27 different comorbidities that appeared significantly more frequently in females with ASD. The comorbidities were mostly neurological (eg, epilepsy, odds ratio [OR] > 1.8, 3-18 years of age), congenital (eg, chromosomal anomalies, OR &gs, as well as the identification of distinct comorbidity patterns influencing anticipatory treatment or referrals. The code is publicly available (https//github.com/hms-dbmi/sexDifferenceInASD).The lysosomal degradation of heparan sulfate is mediated by the concerted action of nine different enzymes. Within this degradation pathway, Arylsulfatase G (ARSG) is critical for removing 3-O-sulfate from glucosamine, and mutations in ARSG are causative for Usher syndrome type IV. We developed a specific ARSG enzyme assay using sulfated monosaccharide substrates, which reflect derivatives of its natural substrates. These sulfated compounds were incubated with ARSG, and resulting products were analyzed by reversed-phase HPLC after chemical addition of the fluorescent dyes 2-aminoacridone or 2-aminobenzoic acid, respectively. Ertugliflozin chemical structure We applied the assay to further characterize ARSG regarding its hydrolytic specificity against 3-O-sulfated monosaccharides containing additional sulfate-groups and N-acetylation. The application of recombinant ARSG and cells overexpressing ARSG as well as isolated lysosomes from wild-type and Arsg knockout mice validated the utility of our assay. We further exploited the assay to determine the sequential action of the different sulfatases involved in the lysosomal catabolism of 3-O-sulfated glucosamine residues of heparan sulfate. Our results confirm and extend the characterization of the substrate specificity of ARSG and help to determine the sequential order of the lysosomal catabolic breakdown of (3-O-)sulfated heparan sulfate.

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