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Median bowel function score was significantly lower in HSCR patients than in controls, 14 versus 19 (

 < 0.001). Twenty-one of the HSCR patients reported impaired bowel function compared with two of the controls (

 < 0.001). The overall prevalence of LUTS was 11 (38%) in the HSCR patients compared with seven (23%) in the controls (

 = 0.751). HSCR patients reported a slightly lower QoL in the KIDSCREEN domain "financial resources" compared with controls (

 = 0.008).

 According to Clavien-Dindo, short-term postoperative complications occurred in 20% of the patients. Impaired bowel function persists throughout childhood for most HSCR patients. The prevalence of LUTS and QoL is not affected in HSCR patients compared with controls.

 According to Clavien-Dindo, short-term postoperative complications occurred in 20% of the patients. Impaired bowel function persists throughout childhood for most HSCR patients. The prevalence of LUTS and QoL is not affected in HSCR patients compared with controls.

The prevention of dementia, especially the cardiovascular prevention of cognitive disorders, is increasingly coming into the focus of health services research. The aim of this study is to determine the possible target population for dementia prevention approaches as well as frequency of health examinations (HE) in individual general practitioner offices (GP).

987 GP practices, which are covered by the nationwide IMS Disease Analyzer database (IQVIA) have been investigated for the prevalence of the following diagnoses, which are considered risk factors for the development of dementia Hypertension, obesity, hearing loss in each age group 45-65 and diabetes and depression in the age group 65 and older. In addition, it was recorded how many of these patients received a HE).

In a sample of 2,398,405 patients receiving primary care, the target population relevant for dementia prevention measures in 2018 consisted of 191,883 patients with hypertension, 23,308 with obesity, 5,059 with hearing loss, 120,200 witht diagnoses obesity and hearing loss than for the much more frequent treatment diagnoses hypertension, diabetes and depression.Developing methods to study tissue mechanics and myofibroblast activation may lead to new targets for therapeutic treatments that are urgently needed for fibrotic disease. Microtissue arrays are a promising approach to conduct relatively high-throughput research into fibrosis as they recapitulate key biomechanical aspects of the disease through a relevant 3D extracellular environment. In early work, our group developed a device called the MVAS-force to stretch microtissues while enabling simultaneous assessment of their dynamic mechanical behavior. Here, we investigated TGF-β1-induced fibroblast to myofibroblast differentiation in microtissue cultures using our MVAS-force device through assessing α-SMA expression, contractility and stiffness. In doing so, we linked cell-level phenotypic changes to functional changes that characterize the clinical manifestation of fibrotic disease. As expected, TGF-β1 treatment promoted a myofibroblastic phenotype and microtissues became stiffer and possessed increased contractility. These changes were partially reversible upon TGF-β1 withdrawal under a static condition, while, in contrast, long-term cyclic stretching maintained myofibroblast activation. This pro-fibrotic effect of mechanical stretching was absent when TGF-β1 receptors were inhibited. Furthermore, stretching promoted myofibroblast differentiation when microtissues were given latent TGF-β1. Altogether, these results suggest that external mechanical stretch may activate latent TGF-β1 and, accordingly, might be a powerful stimulus for continued myofibroblast activation to progress fibrosis. Further exploration of this pathway with our approach may yield new insights into myofibroblast activation and more effective therapeutic treatments for fibrosis.

The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) are scoring systems to predict metastatic potential in pheochromocytomas (PCC) and paragangliomas (PGLs). The goal of this study is to assess PASS and GAPP as metastatic predictors and to correlate with survival outcomes.

The cohort included PCC/PGL with ≥5 years of follow-up or known metastases. Surgical pathology slides were rereviewed. PASS and GAPP scores were assigned. Univariable and multivariable logistic regression, Kaplan-Meier survival analysis, and Cox proportional hazards were performed to assess recurrence-free survival (RFS) and disease-specific survival (DSS).

From 143 subjects, 106 tumors were PCC and 37 were PGL. Metastases developed in 24%. The median PASS score was 6.5 (interquartile range [IQR] 4.0-8.0) and median GAPP score was 3.0 (IQR 2.0-4.0). Interrater reliability was low-moderate for PASS (intraclass correlation coefficient [ICC] 0.6082) aner variability. Scoring systems for predicting metastatic PCC/PGL may be improved by incorporation of histopathology, clinical data, and germline and somatic tumor markers.Diabetes mellitus (DM) is a multisystem disease that affects millions of people worldwide. The vascular and cardiac effects of DM have been well-studied, but little is known about the prevalence of musculoskeletal (MSK) conditions in patients with DM. This review provides an in-depth analysis of a cross-sectional study investigating the presence of several common MSK disorders in patients with DM. This review also analyzes current literature to update health care professionals about the MSK conditions associated with DM.Multi-phenotypic screening of zebrafish larvae, such as monitoring the heart and tail activities, is important in biological assays. Microfluidic devices have been developed for zebrafish phenotypic assays, but simultaneous lateral-dorsal screening of the same larva in a single chip is yet to be achieved. We present a multi-phenotypic microfluidic device for monitoring of tail movement and heart rate (HR) of 5-7-day postfertilization zebrafish larvae. Tail movements were stimulated using electric current and quantified in terms of response duration (RD) and tail beat frequency (TBF). The positioning of a right-angle prism provided a lateral view of the larvae and enabled HR monitoring. Investigations were performed on zebrafish larvae exposed to 3% ethanol, 250 μM 6-hydroxydopamine (6-OHDA) or 1 mM levodopa. Larvae exposed to ethanol showed a significant drop in HR, whereas electric stimulation increased the HR temporarily. Larvae experienced a significant drop in RD, TBF and HR when exposed to 6-OHDA. HR was not affected by levodopa post-treatment, whereas RD and TBF were restored to normal levels. The results showed potential for applications that involve monitoring of cardiac and behavioral parameters in zebrafish larvae. Tests can be done using the same chip, without changing the larvae's orientation. This eliminates undue stress caused by reorientation, which may affect their behavior, and the use of separate devices to obtain dorsal and lateral views. The device can be implemented to improve multi-phenotypic and quantitative screening of zebrafish larvae in response to chemical and physical stimuli in different zebrafish disease models.DNA replication is a fundamental process in all organisms; this event initiates at sites termed origins of replication. The characteristics of eukaryotic replication origins are best understood in Saccharomyces cerevisiae. For this species, origin prediction algorithms or web servers have been developed based on the sequence features of autonomously replicating sequences (ARSs). However, their performances are far from satisfactory. By utilizing the Z-curve methodology, we present a novel pipeline, Ori-Finder 3, for the computational prediction of replication origins in S. cerevisiae at the genome-wide level based solely on DNA sequences. The ARS exhibiting both an AT-rich stretch and ARS consensus sequence element can be predicted at the single-nucleotide level. For the identified ARSs in the S. cerevisiae reference genome, 83 and 60% of the top 100 and top 300 predictions matched the known ARS records, respectively. Based on Ori-Finder 3, we subsequently built a database of the predicted ARSs identified in more than a hundred S. cerevisiae genomes. Consequently, we developed a user-friendly web server including the ARS prediction pipeline and the predicted ARSs database, which can be freely accessed at http//tubic.tju.edu.cn/Ori-Finder3.

SARS-CoV-2 has become a global pandemic. Given the challenges in implementing widespread SARS-CoV-2 testing, there is increasing interest in alternative surveillance strategies.

We tested nasopharyngeal swabs from 1094 decedents in the Wayne County Medical Examiner's office for SARS-CoV-2. All decedents were assessed by a COVID-19 checklist, and decedents flagged by the checklist (298) were preferentially tested. A random sample of decedents not flagged by the checklist were also tested (796). We statistically analyzed the characteristics of decedents (age, sex, race, and manner of death), differentiating between those flagged by the checklist and not and between those SARS-CoV-2 positive and not.

A larger percentage of decedents overall were male (70% vs 48%) and Black (55% vs 36%) compared to the catchment population. Seven-day average percent positivity among flagged decedents closely matched the trajectory of percent positivity in the catchment population, particularly during the peak of the outbreak (March and April). After a lull in May to mid-June, new positive tests in late June coincided with increased case detection in the catchment. We found large racial disparities in test results despite no statistical difference in the racial distribution between those flagged and not, SARS-CoV-2 positive decedents were substantially more likely to be Black (82% vs 51%). SARS-CoV-2 positive decedents were also more likely to be older and to have died of natural causes, including of COVID-19 disease.

Disease surveillance through medical examiners and coroners could supplement other forms of surveillance and may serve as a possible early outbreak warning sign.

Disease surveillance through medical examiners and coroners could supplement other forms of surveillance and may serve as a possible early outbreak warning sign.Neutrophil dysfunction has been described with age, appears exaggerated in infection, with altered phosphoinositol signaling a potential mechanism. Resveratrol However, functional aging is heterogeneous. Frailty is a negative health status and is more common in older adults. We hypothesized that neutrophil migration may be compromised in frailty, associated with the degree of frailty experienced by the older person. We compared measures of frailty, neutrophil function, and systemic inflammation in 40 young and 77 older community-dwelling adults in the United Kingdom. Systemic neutrophils exhibited an age-associated reduction in the accuracy of migration (chemotaxis) which was further blunted with frailty. The degree of migratory inaccuracy correlated with physical (adjusted hand grip strength) and cognitive (Stroop test) markers of frailty. Regression analysis demonstrated that age, Charlson comorbidity index, and frailty index were able to predict neutrophil chemotaxis. Reduced chemotaxis of neutrophils from frail adults could be reversed using selective PI3K inhibitors.

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