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Background Metabolic syndrome is characterized by insulin resistance, which impairs intracellular signaling pathways and endothelial NO bioactivity, leading to cardiovascular complications. Extracellular signal-regulated kinase (ERK) is a major component of insulin signaling cascades that can be activated by many vasoactive peptides, hormones, and cytokines that are elevated in metabolic syndrome. The aim of this study was to clarify the role of endothelial ERK2 in vivo on NO bioactivity and insulin resistance in a mouse model of metabolic syndrome. Methods and Results Control and endothelial-specific ERK2 knockout mice were fed a high-fat/high-sucrose diet (HFHSD) for 24 weeks. Systolic blood pressure, endothelial function, and glucose metabolism were investigated. Systolic blood pressure was lowered with increased NO products and decreased thromboxane A2/prostanoid (TP) products in HFHSD-fed ERK2 knockout mice, and Nω-nitro-l-arginine methyl ester (L-NAME) increased it to the levels observed in HFHSD-fed controls. Acetylcholine-induced relaxation of aortic rings was increased, and aortic superoxide level was lowered in HFHSD-fed ERK2 knockout mice. S18886, an antagonist of the TP receptor, improved endothelial function and decreased superoxide level only in the rings from HFHSD-fed controls. Glucose intolerance and the impaired insulin sensitivity were blunted in HFHSD-fed ERK2 knockout mice without changes in body weight. In vivo, S18886 improved endothelial dysfunction, systolic blood pressure, fasting serum glucose and insulin levels, and suppressed nonalcoholic fatty liver disease scores only in HFHSD-fed controls. Conclusions Endothelial ERK2 increased superoxide level and decreased NO bioactivity, resulting in the deterioration of endothelial function, insulin resistance, and steatohepatitis, which were improved by a TP receptor antagonist, in a mouse model of metabolic syndrome.

The molecular basis of the D variant phenotype in the Chinese differs greatly from that of the Caucasian. Adapting a specific D typing strategy to the spectrum of prevalent RHD variant alleles is necessary.

Blood samples with ambiguous D phenotypes were collected in the Southern Chinese population. A special three-step typing strategy was applied. First, the common DVI type 3 was identified from epitope profiles of D antigen. Then, another common weak D type 15 (RHD*845A) was identified by epitope profiles of D antigen and Sanger sequencing of RHD exon 6. Finally, the remaining D variants were genotyped mainly by Sanger sequencing. For the novel RHD alleles in the coding region and exon-intron junction, in vitro transfection and minigene splicing assays were performed, respectively. The anti-D investigation was performed.

DVI type 3 (65/253, 25.7%) and weak D type 15 (62/253, 24.5%) were common Chinese D variants, and RHD*960A, DFR, RHD*weak D type 25, 72, and 136 were frequent variant RHD alleles. Besides, twenty-two sporadic and seven novel RHD alleles (RHD*188A; RHD*688C; RHD*782 T; RHD*1181C; RHD*165 T, 993A; RHD*148 + 3G > T and RHD*1227 + 5G > C) were identified. The deleterious effect of the novel RHD alleles on D antigen or mRNA expression was confirmed. Anti-D was detected in two DVI type 3 pregnant women.

The three-step typing strategy provides an effective approach for Chinese D variant typing. It can be anticipated that commercially available RHD genotyping kits have limitations for testing Chinese D variants, as some of the frequent variants are not interrogated.

The three-step typing strategy provides an effective approach for Chinese D variant typing. It can be anticipated that commercially available RHD genotyping kits have limitations for testing Chinese D variants, as some of the frequent variants are not interrogated.The nervous system is composed of a variety of neurons and glial cells with different morphology and functions. In the mammalian peripheral nervous system (PNS) or the lower vertebrate central nervous system (CNS), most neurons can regenerate extensively after axotomy, while the neurons in the mammalian CNS possess only limited regenerative ability. This heterogeneity is common within and across species. The studies about the transcriptomes after nerve injury in different animal models have revealed a series of molecular and cellular events that occurred in neurons after axotomy. However, responses of various types of neurons located in different positions of individuals were different remarkably. Thus, researchers aim to find the key factors that are conducive to regeneration, so as to provide the molecular basis for solving the regeneration difficulties after CNS injury. Here we review the heterogeneity of axonal regeneration among different cell subtypes in different animal models or the same organ, emphasizing the importance of comparative studies within and across species.Background Descriptions of do not attempt resuscitation (DNAR) orders in heart failure (HF) are limited. We describe use of DNAR orders in HF hospitalizations relative to other common conditions, focusing on race. Methods and Results This was a retrospective study of all adult hospitalizations for HF, acute myocardial infarction (AMI), chronic obstructive pulmonary disease (COPD), and pneumonia from 2010 to 2016 using the California State Inpatient Dataset. Using a hierarchical multivariable logistic regression model with random effects for the hospital, we identified factors associated with DNAR orders for each condition. For racial variation, hospitals were divided into quintiles based on proportion of Black patients cared for. Our cohort comprised 399 816 HF, 190 802 AMI, 192 640 COPD, and 269 262 pneumonia hospitalizations. DNAR orders were most prevalent in HF (11.9%), followed by pneumonia (11.1%), COPD (7.9%), and AMI (7.1%). Prevalence of DNAR orders did not change from 2010 to 2016 for each condition. For all conditions, DNAR orders were more common in elderly people, women, and White people with significant site-level variation across 472 hospitals. For HF and COPD, hospitalizations at sites that cared for a higher proportion of Black patients were less likely associated with DNAR orders. For AMI and pneumonia, conditions such as dementia and malignancy were strongly associated with DNAR orders. Conclusions DNAR orders were present in 12% of HF hospitalizations, similar to pneumonia but higher than AMI and COPD. For HF, we noted significant variability across sites when stratified by proportion of Black patients cared for, suggesting geographic and racial differences in end-of-life care.

Many workers shifted to working from home due to the COVID-19 pandemic. This review aims to investigate if this sudden change caused an increase in TElewoRk-RelAted stress (TERRA) which is defined as physical and mental stress caused by telework.

A systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed of three scientific databases (PubMed, ISI Web of Knowledge, and Scopus), which also included a quality assessment. read more Articles measuring stress, psychological or physical, in remote workers, published from December 2019 through August 2021 were included in the review. Results were extracted by reporting authors, country, study design, type of workers, sample, questionnaires and measurements, and outcomes. Data were synthesized quantitatively for country, type of workers, and outcomes.

Out of the 518 articles found in the three databases, 19 articles were included in the systematic review (10,012 participants overall), and 78.9% of thend technical support to prevent TERRA in remote workers.Background We investigated the longitudinal association of herpes zoster (HZ), commonly known as "shingles," and long-term risk of stroke or coronary heart disease (CHD) among participants in 3 large US cohorts, the NHS (Nurses' Health Study), NHS II (Nurses' Health Study II), and HPFS (Health Professionals Follow-Up Study). Methods and Results Participants were 79 658 women in the NHS (2000-2016), 93 932 women in the NHS II (2001-2017), and 31 440 men in the HPFS (2004-2016), without prior stroke or CHD. Information on HZ, stroke, and CHD was collected on biennial questionnaires and confirmed by medical record review. Cox proportional hazards regression models were used to estimate multivariable-adjusted hazard ratios for stroke and for CHD according to years since HZ compared with never HZ. During >2 million person-years of follow-up, 3603 incident stroke and 8620 incident CHD cases were documented. History of HZ was significantly and independently associated with higher long-term risk of stroke and CHD. In pooled analyses, compared with individuals with no history of HZ, the multivariable-adjusted hazard ratios (95% CIs) for stroke were 1.05 (0.88-1.25) among those with 1 to 4 years since HZ, 1.38 (1.10-1.74) for among those with 5 to 8 years since HZ, 1.28 (1.03-1.59) among those with for 9 to 12 years since HZ, and 1.19 (0.90-1.56) among those with ≥13 years since HZ. For CHD, the corresponding multivariable-adjusted hazard ratios (95% CIs) were 1.13 (1.01-1.27) for 1 to 4 years, 1.16 (1.02-1.32) for 5 to 8 years, 1.25 (1.07-1.46) for 9 to 12 years, and 1.00 (0.83-1.21) for ≥13 years. Conclusions HZ is associated with higher long-term risk of a major cardiovascular event. These findings suggest there are long-term implications of HZ and underscore the importance of prevention.

To compare QuantiFERON-TB Gold-in-Tube (QFT) and tuberculin skin test (TST) in the diagnosis of latent tuberculosis infection (LTBI) among people living with HIV (PLWHIV).

A cross-sectional study was carried out between 2017-2018. Tuberculin skin test and QFT were performed and their concordance was measured. The gold standard for LTBI was defined as positivity to any of the tests. A logistic regression model was carried out to predict the QFT result in patients with a negative TST.

A total of 510 PLWHIV were included, with 409 (80.2%) being male. The mean age of the patients was 41.3 ± 11.8years. The median time since HIV diagnosis was 5years (IQR 2-10), with a median CD4

count of 541 (IQR 340-757) cells/mm

. Overall, 20 patients had an isolated TST+, 22 an isolated QFT+ and 15 had both positive. Concordance between tests showed a kappa coefficient of .37. Overcrowding was the only predictor for a positive QFT after a negative TST (

= .003).

There was fair agreement between tests in PLWHIV. In conditions of limited access to QTF, a TST-based strategy could be considered, with sequential use of QTF in high-risk patients with a negative result, especially those who live in overcrowded conditions.

There was fair agreement between tests in PLWHIV. In conditions of limited access to QTF, a TST-based strategy could be considered, with sequential use of QTF in high-risk patients with a negative result, especially those who live in overcrowded conditions.Background To date, assessment of right ventricular (RV) function in mice has relied extensively on invasive measurements. Echocardiographic advances have allowed adaptation of measures used in humans for serial, noninvasive RV functional assessment in mice. We evaluated the diagnostic performance of tricuspid annular plane systolic excursion (TAPSE), RV peak systolic myocardial velocity (s'), RV myocardial performance index (MPI), and RV fractional area change (FAC) in a mouse model of pulmonary hypertension. Methods and Results Echocardiography was performed on mice at baseline and 3 weeks after induction of pulmonary hypertension using inhaled bleomycin or saline, including adapted measures of TAPSE, s', MPI, and FAC. RV systolic pressure was measured by invasive catheterization, and RV contractility was measured as the peak slope of the RV systolic pressure recording (maximum change pressure/change time). Postmortem morphological assessment of RV hypertrophy was performed. RV systolic pressure was elevated and maximum change pressure/change time was reduced in bleomycin versus control (n=8; P=0.