Notes

Connection of Reduce Socioeconomic Position as well as SARS-CoV-2 Positivity within Los Angeles, California.
The percentage of admissions captured in both data sources improved over time. Cancer characteristics (site, stage and grade) had little effect on how AMI was captured.

MINAP and HES define different populations of patients with AMI. However, cancer characteristics do not substantially impact on case-ascertainment. These findings support a strategy of using multiple linked data sources for observational cardio-oncological research into AMI.
MINAP and HES define different populations of patients with AMI. However, cancer characteristics do not substantially impact on case-ascertainment. These findings support a strategy of using multiple linked data sources for observational cardio-oncological research into AMI.
Brain white matter (WM) microstructural changes evaluated by diffusion MRI were well documented in patients with systemic lupus erythematosus (SLE). Yet, conventional diffusion tensor imaging technique fails to differentiate WM changes that originate from tissue alterations from those due to increased extracellular free water (FW) related to neuroinflammation, microvascular disruption, atrophy, or other extracellular processes. Veliparib Here, we sought to delineate changes in WM tissue microstructure and extracellular FW volume and examine their relationships with neurocognitive function in SLE patients.

Twenty SLE patients (16 females, aged 36.0±10.6) without clinically-overt neuropsychiatric manifestation and 61 healthy controls (HC) (29 females, aged 29.2±9.4) underwent diffusion MRI and computerized neuropsychological assessments cross-sectionally. The FW imaging method was applied to compare microstructural tissue changes and extracellular FW volume of the brain WM between SLE patients and HC. Association betoinflammation in SLE patients with clinically-inactive disease. The mechanistic impact of cumulative glucocorticoids on WM FW deserves further evaluation.Sleeping for a short period (i.e., napping) may help mitigate impairments in cognitive processing caused by sleep deprivation, but there is limited research on effects of brief naps in particular. Here, we tested the effect of a brief nap opportunity (30- or 60-min) during a period of sleep deprivation on two cognitive processes with broad scope, placekeeping and vigilant attention. In the evening, participants (N = 280) completed a placekeeping task (UNRAVEL) and a vigilant attention task (Psychomotor Vigilance Task [PVT]) and were randomly assigned to either stay awake overnight or sleep at home. Sleep-deprived participants were randomly assigned to receive either no nap opportunity, a 30-min opportunity, or a 60-min opportunity. Participants who napped were set up with polysomnography. The next morning, sleep participants returned, and all participants completed UNRAVEL and the PVT. Sleep deprivation impaired performance on both tasks, but nap opportunity did not reduce the impairment, suggesting that naps longer than those tested may be necessary to cause group differences. However, in participants who napped, more time spent in slow-wave sleep (SWS) was associated with reduced performance deficits on both tasks, effects we interpret in terms of the role of SWS in alleviating sleep pressure and facilitating memory consolidation.
Due to the significant mortality and morbidity consequences of the coronavirus 2019 (COVID-19) pandemic among older adults, these individuals were urged to avoid going out in public and socializing with others, among other major disruptions to daily life. While these significant and often unavoidable disruptions have been shown to bear consequences for mental health, less attention has been devoted to behavioral changes, such as changes to sleeping or eating due to the COVID-19 pandemic, and their implications for emotional well-being.

We utilized data from a nationally representative survey of Medicare beneficiaries (aged ≥65 years), which was administered between June and October 2020 (n=3,122). We examine the relationship between self-reported changes to daily behaviors (e.g., sleep, drinking alcohol, and exercise) and emotional impacts of COVID-19 (i.e., feelings of depression and anxiety about the COVID-19 pandemic) using stepwise hierarchical multivariable Poisson regression.

We found that worse sially modifiable behaviors, such as sleep and exercise. Our findings highlight the behavioral changes associated with adverse emotional impacts among older adults during the COVID-19 pandemic. Future research may evaluate whether behavioral interventions may aim to attenuate the impact of pandemics on daily, modifiable behaviors to buffer against adverse emotional impacts.Store-operated Ca2+ entry is a central component of intracellular Ca2+ signaling pathways. The Ca2+ release-activated channel (CRAC) mediates store-operated Ca2+ entry in many different cell types. The CRAC channel is composed of the plasma membrane (PM)-localized Orai1 channel and endoplasmic reticulum (ER)-localized STIM1 Ca2+ sensor. Upon ER Ca2+ store depletion, Orai1 and STIM1 form complexes at ER-PM junctions, leading to the formation of activated CRAC channels. Although the importance of CRAC channels is well described, the underlying mechanisms that regulate the recruitment of Orai1 to ER-PM junctions are not fully understood. Here, we describe the rapid and transient S-acylation of Orai1. Using biochemical approaches, we show that Orai1 is rapidly S-acylated at cysteine 143 upon ER Ca2+ store depletion. Importantly, S-acylation of cysteine 143 is required for Orai1-mediated Ca2+ entry and recruitment to STIM1 puncta. We conclude that store depletion-induced S-acylation of Orai1 is necessary for recruitment to ER-PM junctions, subsequent binding to STIM1 and channel activation.
To investigate the utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in assessing disease activity in Takayasu arteritis (TA).

Ninety-one patients with TA, were recruited from a Chinese cohort. Clinical data, acute-phase reactants (APRs), and 18F-FDG-PET/CT findings were simultaneously recorded. The value of using 18F-FDG-PET/CT to identify active disease was evaluated, using erythrocyte sedimentation rate (ESR) as a reference. Disease activity assessment models were constructed and concordance index (C-index), net reclassification index (NRI), and integrated discrimination index (IDI) were evaluated to compare the benefits of the new modes with ESR and Kerr score.

In total, 64 (70.3%) cases showed active disease. Higher levels of ESR and CRP, and lower interleukin (IL)-2R levels, were observed in active cases. 18F-FDG-PET/CT parameters, including SUVmean, SUVratio1, SUVratio2, sum of SUVmean, and sum of SUVmax, were significantly higher in active disease groups. The C index threshold of ESR to indicate active disease was 0.78 (95% CI 0.69-0.88). The new activity assessment model combining ESR, sum of SUVmean, and IL-2R showed significant improvement in C index over the ESR method (0.96 vs 0.78, p < 0.01; NRI 1.63, p < 0.01; and IDI 0.48, p < 0.01). The new model also demonstrated modest superiority to Kerr score assessment (0.96 vs 0.87, p = 0.03; NRI 1.19, p < 0.01; and IDI 0.33 p < 0.01).

A novel 18F-FDG-PET/CT-based method that involves combining the sum of SUVmean with ESR score and IL-2R levels demonstrated superiority in identifying active TA compared with conventional methods.
A novel 18F-FDG-PET/CT-based method that involves combining the sum of SUVmean with ESR score and IL-2R levels demonstrated superiority in identifying active TA compared with conventional methods.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing eosinophil-rich vasculitis. Specific cardiomyopathy (CM) was described in old studies as the most important predictor of mortality. We aimed to revisit EGPA-related CM and its outcome in recent decades.

We reviewed all EGPA patients managed from 2000 to 2019 in our vasculitis clinic. Baseline characteristics and outcomes were analyzed. EGPA-related CM was defined as clinical or extra-clinical manifestations of patent myocardial involvement, after exclusion of other causes.

We included 176 patients. Median age was 47 years (IQR 36-58 years). Specific CM was observed in 70 patients (40%). Cardiac symptoms were observed in 81% of CM+ patients, including mainly typical or atypical chest pain and peripheral edema. Abnormal EKG, TTE and cardiac magnetic resonance imaging (CMRI) were found in 72%, 72% and 99% in CM+ patients, respectively, contrasting with abnormalities in 32%, 38% and 60% in CM-negative patients. Late gadolinium enhancement (LGE) was the most frequent abnormality on CMRI (70%). CM+ patients were less frequently ANCA-positive, had less frequent peripheral neuropathy and had higher eosinophil count. Major adverse cardiovascular events (MACE) occurred in 13%, both in CM+ and CM- patients. Abnormal EKG and LGE on CMRI were associated with the occurrence of MACE. Four patients died, but none from cardiac causes.

Specific cardiomyopathy is frequent in EGPA, especially in ANCA-negative patients with high eosinophil counts. Long-term outcome was better than previously reported. Abnormal EKG and LGE on CMRI were associated with the occurrence of MACE.
Specific cardiomyopathy is frequent in EGPA, especially in ANCA-negative patients with high eosinophil counts. Long-term outcome was better than previously reported. Abnormal EKG and LGE on CMRI were associated with the occurrence of MACE.
The prevalence of Gestational Diabetes Mellitus (GDM) is increasing, and intrauterine hyperglycemia is suspected to affect offspring cognitive function.

We assessed academic performance by grade point average (GPA) in children aged 15-16 years at compulsory school graduation, comparing offspring exposed to GDM (O-GDM) with offspring from the background population (O-BP).

Cohort study.

Register-based.

All singletons born in Denmark between 1994 and 2001 (O-GDM n=4,286; O-BP n=501,045). Standardized and internationally comparable GPAs were compared in univariate- and multivariate linear models.

Adjusted mean difference in GPA. We additionally analyzed the probability of having a high GPA, a GPA below passing, and no GPA registered.

O-GDM had a GPA of 6.29 (SD 2.52), while O-BP had a GPA of 6.78 (SD 2.50). The adjusted mean difference was -0.36 [95% confidence interval (CI) -0.44; -0.29], corresponding to a Cohens D of 0.14. O-GDM had a lower probability of obtaining a high GPA (adjusted odds ratio (aOR) 0.68 [95 CI 0.59; 0.79]), while their risk of obtaining a GPA below passing was similar to O-BP (aOR 1.20 [95 CI 0.96; 1.50]). O-GDM had a higher risk of not having a GPA registered (aOR of 1.38 [95% CI 1.24; 1.53]).

Academic performance in O-GDM was marginally lower than in O-BP. However, this difference is unlikely to be of clinical importance.
Academic performance in O-GDM was marginally lower than in O-BP. However, this difference is unlikely to be of clinical importance.Molecular chaperones are essential components of the protein quality control system and maintenance of homeostasis. Heat Shock Protein 70 (HSP70), a highly evolutionarily conserved family of chaperones is a key regulator of protein folding, oligomerisation and prevents the aggregation of misfolded proteins. HSP70 chaperone function depends on the so-called 'HSP70-cycle', where HSP70 interacts with and is released from substrates via ATP hydrolysis and the assistance of HSP70 co-factors/co-chaperones, which also provide substrate specificity. The identification of regulatory modules for HSP70 allows the elucidation of HSP70 specificity and target selectivity. Here, we discuss how the HSP70 cycle is functionally linked with the cycle of the Ubiquitin-like molecule NEDD8. Using as an example the DNA damage response, we present a model where HSP70 acts as a sensor of the NEDD8 cycle. The NEDD8 cycle acts as a regulatory module of HSP70 activity, where conversion of poly-NEDD8 chains into mono-NEDD8 upon DNA damage activates HSP70, facilitating the formation of the apoptosome and apoptosis execution.
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