The Effect of Movement Rate and Complexity on Functional Magnetic Resonance Signal Change During Pedaling

We used functional magnetic resonance imaging (fMRI) to record human brain activity during slow (30 RPM), fast (60 RPM), passive (30 RPM), and variable rate pedaling. Ten healthy adults participated. After identifying regions of interest, the intensity and volume of brain activation in each region was calculated and compared across conditions (p \u3c .05). Results showed that the primary sensory and motor cortices (S1, M1), supplementary motor area (SMA), and cerebellum (Cb) were active during pedaling. The intensity of activity in these areas increased with increasing pedaling rate and complexity. The Cb was the only brain region that showed significantly lower activity during passive as compared with active pedaling. We conclude that M1, S1, SMA, and Cb have a role in modifying continuous, bilateral, multijoint lower extremity movements. Much of this brain activity may be driven by sensory signals from the moving limbs

Aspergillus fumigatus preexposure worsens pathology and improves control of Mycobacterium abscessus pulmonary infection in mice

ABSTRACT Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Mutations in this chloride channel lead to mucus accumulation, subsequent recurrent pulmonary infections, and inflammation, which, in turn, cause chronic lung disease and respiratory failure. Recently, rates of nontuberculous mycobacterial (NTM) infections in CF patients have been increasing. Of particular relevance is infection with Mycobacterium abscessus , which causes a serious, life-threatening disease and constitutes one of the most antibiotic-resistant NTM species. Interestingly, an increased prevalence of NTM infections is associated with worsening lung function in CF patients who are also coinfected with Aspergillus fumigatus . We established a new mouse model to investigate the relationship between A. fumigatus and M. abscessus pulmonary infections. In this model, animals exposed to A. fumigatus and coinfected with M. abscessus exhibited increased lung inflammation and decreased mycobacterial burden compared with those of mice infected with M. abscessus alone. This increased control of M. abscessus infection in coinfected mice was mucus independent but dependent on both transcription factors T-box 21 (Tbx21) and retinoic acid receptor (RAR)-related orphan receptor gamma t (RORγ-t), master regulators of type 1 and type 17 immune responses, respectively. These results implicate a role for both type 1 and type 17 responses in M. abscessus control in A. fumigatus -coinfected lungs. Our results demonstrate that A. fumigatus , an organism found commonly in CF patients with NTM infection, can worsen pulmonary inflammation and impact M. abscessus control in a mouse model. </jats:p

Pregnancy outcome in patients with fibroid: a retrospective study

Background: Fibroids are benign smooth muscle cell tumour of the uterus. In some patients of pregnancy associated with fibroid, it does not affect the outcome of pregnancy. On the other hand, various complications have been reported. The aim of our study was to evaluate the outcome in antenatal women with fibroids.Methods: This retrospective study was conducted at tertiary care center, obstetrics & gynecology department over a period of eighteen months between June 2018 to November 2019. Total 26 pregnant patients with >3 cm fibroid was included in the study. They were followed during antenatal period. Maternal age, parity, size of fibroid, complications during pregnancy, labour, and delivery, mode of delivery and indications of cesarean section were noted.Results: Out of 26 patients, 15 (57.6%) were between 26-30 years of age group and 16 (61.53%) were multigravidas. Normal vaginal delivery occurred in 8 (33.33%), while 16 (66.66%) delivered by caesarean section. There were 9 (34.61%) patients who had no complication whereas 17 (65.38%) had some complication. Pain was present in 8 (30.76%). PROM and preterm labour were present in 3 (18.75%) and 5 (19.23%) respectively. PPH was present in 2 (7.69%).Conclusions: Pregnant patients who have fibroids are to be carefully screened in the antenatal period, so as to have a regular follow up. The widespread use of ultrasonography has facilitated diagnosis and management of fibroids in pregnancy. The site and size of fibroid is very important to predict its effect on pregnancy

New tools and methods for direct programmatic access to the dbSNP relational database

Genome-wide association studies often incorporate information from public biological databases in order to provide a biological reference for interpreting the results. The dbSNP database is an extensive source of information on single nucleotide polymorphisms (SNPs) for many different organisms, including humans. We have developed free software that will download and install a local MySQL implementation of the dbSNP relational database for a specified organism. We have also designed a system for classifying dbSNP tables in terms of common tasks we wish to accomplish using the database. For each task we have designed a small set of custom tables that facilitate task-related queries and provide entity-relationship diagrams for each task composed from the relevant dbSNP tables. In order to expose these concepts and methods to a wider audience we have developed web tools for querying the database and browsing documentation on the tables and columns to clarify the relevant relational structure. All web tools and software are freely available to the public at http://cgsmd.isi.edu/dbsnpq. Resources such as these for programmatically querying biological databases are essential for viably integrating biological information into genetic association experiments on a genome-wide scale

Practice Readiness? Trends in Chief Resident Year Training Experience Across 13 Residency Programs

IntroductionUrology residency prepares trainees for independent practice. The optimal operative chief resident year experience to prepare for practice is undefined. We analyzed the temporal arc of cases residents complete during their residency compared to their chief year in a multi-institutional cohort.MethodsAccreditation Council for Graduate Medical Education case logs of graduating residents from 2010 to 2022 from participating urology residency programs were aggregated. Resident data for 5 categorized index procedures were recorded: (1) general urology, (2) endourology, (3) reconstructive urology, (4) urologic oncology, and (5) pediatric urology. Interactions were tested between the trends for total case exposure in residency training relative to the chief resident year.ResultsFrom a sample of 479 resident graduates, a total of 1,287,433 total cases were logged, including 375,703 during the chief year (29%). Urologic oncology cases had the highest median percentage completed during chief year (56%) followed by reconstructive urology (27%), general urology (24%), endourology (17%), and pediatric urology (2%). Across the study period, all categories of cases had a downward trend in median percentage completed during chief year except for urologic oncology. However, only trends in general urology (slope of -0.68, P = .013) and endourology (slope of -1.71, P ≤ .001) were significant.ConclusionsOver 50% of cases completed by chief residents are urologic oncology procedures. Current declining trends indicate that residents are being exposed to proportionally fewer general urology and endourology cases during their chief year prior to entering independent practice

Acute kidney disease and renal recovery : consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of > 90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD

The Immune Landscape of Undifferentiated Pleomorphic Sarcoma

INTRODUCTION: Undifferentiated pleomorphic sarcoma (UPS) can be associated with a relatively dense immune infiltration. Immune checkpoint inhibitors (anti-PD1, anti-PDL1, and anti-CTLA4) are effective in 20% of UPS patients. We characterize the immune microenvironment of UPS and its association with oncologic outcomes. MATERIAL AND METHODS: Surgically resected UPS samples were stained by immunohistochemistry (IHC) for the following: tumor-associated immune cells (CD3, CD8, CD163, CD20), immune checkpoints (stimulatory: OX40, ICOS; inhibitory: PD-L1, LAG3, IDO1, PD1), and the adenosine pathway (CD73, CD39). Sections were reviewed for the presence of lymphoid aggregates (LA). Clinical data were retrospectively obtained for all samples. The Wilcoxon rank-sum and Kruskal-Wallis tests were used to compare distributions. Correlations between biomarkers were measured by Spearman correlation. Univariate and multivariate Cox models were used to identify biomarkers associated with overall survival (OS) and disease-free survival (DFS). Unsupervised clustering was performed, and Kaplan-Meier curves and log-rank tests used for comparison of OS and DFS between immune clusters. RESULTS: Samples analyzed (n=105) included 46 primary tumors, 34 local recurrences, and 25 metastases. LA were found in 23% (n=10/43), 17% (n=4/24), and 30% (n=7/23) of primary, recurrent, and metastatic samples, respectively. In primary UPS, CD73 expression was significantly higher after preoperative radiation therapy (p=0.009). CD39 expression was significantly correlated with PD1 expression (primary: p=0.002, recurrent: p=0.004, metastatic: p=0.001), PD-L1 expression (primary: p=0.009), and CD3+ cell densities (primary: p=0.016, recurrent: p=0.043, metastatic: p=0.028). In recurrent tumors, there was a strong correlation between CD39 and CD73 (p=0.015), and both were also correlated with CD163+ cell densities (CD39 p=0.013; CD73 p\u3c0.001). In multivariate analyses, higher densities of CD3+ and CD8+ cells (Cox Hazard Ratio [HR]=0.33; p=0.010) were independently associated with OS (CD3+, HR=0.19, p\u3c0.001; CD8+, HR= 0.33, p=0.010) and DFS (CD3+, HR=0.34, p=0.018; CD8+, HR=0.34, p= 0.014). Unsupervised clustering of IHC values revealed three immunologically distinct clusters: immune high, intermediate, and low. In primary tumors, these clusters were significantly associated with OS (log-rank p\u3c0.0001) and DFS (p\u3c0.001). CONCLUSION: We identified three immunologically distinct clusters of UPS Associated with OS and DFS. Our data support further investigations of combination anti-PD-1/PD-L1 and adenosine pathway inhibitors in UPS