Notes

Stomach emptying time of a pair of various degrees of apparent liquids in youngsters: Any double-blinded randomized governed research.
Strong evidence supports a role for protein degradation in fear memory formation. However, these data have been largely done in only male animals. Here, we found that following contextual fear conditioning, females, but not males, had increased levels of proteasome activity and K48 polyubiquitin protein targeting in the dorsal hippocampus, the latter of which occurred at chaperones or RNA processing proteins. In vivo CRISPR-dCas9-mediated repression of protein degradation in the dorsal hippocampus impaired contextual fear memory in females, but not males. These results suggest a sex-specific role for protein degradation in the hippocampus during the consolidation of a contextual fear memory.
To examine the association between psoriatic arthritis (PsA) and all-cause mortality from a large population-based database.

Patients with PsA from the Clalit Health Services database were identified between 2003-2018 and matched to 4 controls by age, sex, ethnicity, and index date. Patient demographics, comorbidities, and treatments were extracted. Mortality data were obtained from the Israeli Notification of Death certificate. The proportionate mortality rate (PMR) of the leading causes of death was calculated and compared to that of the general population. Cox proportional hazard regression models were used to estimate the crude and the multivariate adjusted HR for the association between PsA and all-cause mortality and for factors associated with mortality within the PsA group.

There were 5275 patients with PsA and 21,011 controls included and followed for 7.2 ± 4.4 years. The mean age was 51.7 ± 15.4 years, and 53% were females. Among patients with PsA, 38.2% were on biologics. Four hundred seventy-one (8.9%) patients died in the PsA group compared to 1668 (7.9%) in the control group. The crude HR for the association of PsA and all-cause mortality was 1.16 (95% CI 1.04-1.29) and 1.02 (95% CI 0.90-1.15) on multivariate analysis. Malignancy was the leading cause of death (26%), followed by ischemic heart disease (15.8%); this is in keeping with the leading causes of death in the general population. Older age, male sex, lower socioeconomic status, increased BMI, increased Charlson comorbidity index scores, and history of psoriasis or hospitalization in 1 year prior to entry were positive predictors for mortality.

No clinically relevant increase in mortality rate was observed in patients with PsA, and specific PMRs were similar to those of the general population.
No clinically relevant increase in mortality rate was observed in patients with PsA, and specific PMRs were similar to those of the general population.
Although there are different tools to evaluate axial spondyloarthritis (axSpA), they are hardly used in clinical routine due to time constraints. The Routine Assessment of Patient Index Data 3 (RAPID3) is a composite measure feasible to be used as a sole metric in busy clinics. We aimed to test its measurement properties in patients with axial SpA in a real clinical setting.

Cross-sectional study that included 131 consecutive patients with axial SpA. The convergent (Spearman's rho) and discriminant (ROC curve analysis) validity of RAPID3 were tested against several axSpA-specific measures (BASDAI, ASDAS, BASFI, mSASSS). A multivariate model was built to detect disease factors associated with RAPID3 remission (values ≤3).

The study included 82 men and 49 women, median age of 55 years (IQR 46-61), and median disease duration of 11 years (IQR 6-24). Mean RAPID3 was 9.45 ± 6.7. The BASDAI showed moderate correlation with ASDAS (rho 0.66, p < 0.0001), but higher with BASFI (rho 0.78, p < 0.0001) and RAbe useful for a more comprehensive assessment of axSpA in busy clinical settings.
To investigate the association between Raynaud phenomenon (RP) and coronary microvascular dysfunction, we measured myocardial flow reserve (MFR) using positron emission tomography/computed tomography (PET/CT) in patients with primary and secondary RP and controls.

Patients with RP, patient controls, and healthy participants who underwent dynamic rest-stress 82-rubidium PET/CT were studied. Differences in heart rate-blood pressure product-corrected MFR and clinical predictors of reduced MFR (< 2.0) were determined.

Forty-nine patients with RP (80% female; aged 65 ± 11 yrs; 11 with primary RP, 18 with systemic sclerosis [SSc], and 20 with other autoimmune rheumatic diseases [AIRDs] including 6 with systemic lupus erythematosus, 6 with rheumatoid arthritis, 4 with overlap syndrome, 2 with Sjögren syndrome, and 2 with inflammatory arthritis), 49 matched patients without RP or AIRD (78% female; 64 ± 13 yrs), and 14 healthy participants (50% female; 35 ± 5 yrs) were studied. Patients with primary RP, matchy elucidate the prognostic value of MFR in patients with secondary RP.
To identify clinical factors, including esophageal dilation on chest high-resolution computed tomography (HRCT), that are associated with pulmonary function decline in patients with systemic sclerosis (SSc).

Patients fulfilled 2013 SSc criteria and had ≥1 HRCT and ≥2 pulmonary function tests (PFTs). According to published methods, widest esophageal diameter (WED) and radiographic interstitial lung disease (ILD) were assessed, and WED was dichotomized as dilated (≥19mm) vs. not dilated (<19mm). Clinically meaningful PFT decline was defined as %-predicted change in forced vital capacity (FVC) ≥5 and/or diffusion capacity for carbon monoxide (DLCO) ≥15. Linear mixed effect models were used to model PFT change over time.

138 SSc patients met study criteria 100 (72%) had radiographic ILD; 49 (35%) demonstrated FVC decline (median follow-up 2.9y). Patients with Scl-70 autoantibodies had 5- year %-predicted FVC decline (-6.3; 95% CI -9.9, -2.8), while patients without Scl-70 autoantibodies demonstrated 5-yeSSc-ILD patients with esophageal dilation.Malignant pleural diseases, comprising metastatic lung and breast cancers and malignant pleural mesothelioma (MPM), are aggressive solid tumors with poor therapeutic response. We developed and conducted a first-in-human, phase I study of regionally delivered, autologous, mesothelin-targeted chimeric antigen receptor (CAR) T-cell therapy. Intrapleural administration of 0.3M-60M CAR T cells/kg in 27 patients (25 with MPM) was safe and well tolerated. CAR T-cells were detected in peripheral blood for >100 days in 39% of patients. Following our demonstration that PD-1 blockade enhances CAR T-cell function in mice, 18 patients with MPM also received pembrolizumab safely. Among those patients, median overall survival from CAR T-cell infusion was 23.9 months (1-year overall survival, 83%). Stable disease was sustained for greater than or equal to6 months in 8 patients; 2 exhibited complete metabolic response on PET scan. Combination immunotherapy with CAR T cells and PD-1 blockade agents should be further evaluated in patients with solid tumors.
Obesity has rapidly become a major problem for children that has adverse effects on respiratory health. We sought to assess the impact of obesity on health-related quality of life (HRQOL) and hospital outcomes for children hospitalized with asthma or pneumonia.

In this multicenter prospective cohort study, we evaluated children (aged 2-16 years) hospitalized with an acute asthma exacerbation or pneumonia between July 1, 2014, and June 30, 2016. Subjects or their family completed surveys for child HRQOL (PedsQL Physical Functioning and Psychosocial Functioning Scales, with scores ranging from 0 to 100) on hospital presentation and 2-6 weeks after discharge. BMI categories were defined as normal weight, overweight, and obesity on the basis of BMI percentiles for age and sex per national guidelines. Multivariable regression models were used to examine associations between BMI category and HRQOL, length of stay, and 30-day reuse.

Among 716 children, 82 (11.4%) were classified as having overweight and 138 (19.3%) as having obesity. For children hospitalized with asthma or pneumonia, obesity was not associated with worse HRQOL at presentation or 2-6 weeks after discharge, hospital length of stay, or 30-day reuse.

Nearly 1 in 3 children seen in the hospital for an acute asthma exacerbation or pneumonia had overweight or obesity; however, among the population of children in our study, obesity alone does not appear to be associated with worse HRQOL or hospital outcomes.
Nearly 1 in 3 children seen in the hospital for an acute asthma exacerbation or pneumonia had overweight or obesity; however, among the population of children in our study, obesity alone does not appear to be associated with worse HRQOL or hospital outcomes.
Although patients with kidney disease may be particularly susceptible to the adverse health effects associated with lead exposure, whether levels of lead found commonly in drinking water are associated with adverse outcomes in patients with ESKD is not known.

To investigate associations of lead in community water systems with hemoglobin concentrations and erythropoietin stimulating agent (ESA) use among incident patients with ESKD, we merged data from the Environmental Protection Agency (EPA) Safe Drinking Water Information System (documenting average 90
percentile lead concentrations in community water systems during 5 years before dialysis initiation, according to city of residence) with patient-level data from the United States Renal Data System.

Among 597,968 patients initiating dialysis in the United States in 2005 through 2017, those in cities with detectable lead levels in community water had significantly lower pre-ESKD hemoglobin concentrations and more ESA use per 0.01 mg/L increase in 90
vels and higher ESA use among patients with advanced kidney disease.Ongoing SARS-CoV-2 vaccine development is focused on identifying stable, cost-effective, and accessible candidates for global use, specifically in low and middle-income countries. Here, we report the efficacy of a rapidly scalable, novel yeast expressed SARS-CoV-2 specific receptor-binding domain (RBD) based vaccine in rhesus macaques. We formulated the RBD immunogen in alum, a licensed and an emerging alum adsorbed TLR-7/8 targeted, 3M-052-alum adjuvants. The RBD+3M-052-alum adjuvanted vaccine promoted better RBD binding and effector antibodies, higher CoV-2 neutralizing antibodies, improved Th1 biased CD4+T cell reactions, and increased CD8+ T cell responses when compared to the alum-alone adjuvanted vaccine. Hedgehog antagonist RBD+3M-052-alum induced a significant reduction of SARS-CoV-2 virus in respiratory tract upon challenge, accompanied by reduced lung inflammation when compared with unvaccinated controls. Anti-RBD antibody responses in vaccinated animals inversely correlated with viral load in nasal secretions and BAL. RBD+3M-052-alum blocked a post SARS-CoV-2 challenge increase in CD14+CD16++ intermediate blood monocytes, and Fractalkine, MCP-1, and TRAIL in the plasma. Decreased plasma analytes and intermediate monocyte frequencies correlated with reduced nasal and BAL viral loads. Lastly, RBD-specific plasma cells accumulated in the draining lymph nodes and not in the bone marrow, contrary to previous findings. Together, these data show that a yeast expressed, RBD-based vaccine+3M-052-alum provides robust immune responses and protection against SARS-CoV-2, making it a strong and scalable vaccine candidate.
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