UNASSIGNED: To describe vaccine and booster uptake by neighborhood-level factors in California.
UNASSIGNED: We examined trends in COVID-19 vaccination up to September 21, 2021, and boosters up to March 29, 2022 using data from the California Department of Public Health. Quasi-Poisson regression was used to model the association between neighborhood-level factors and fully vaccinated and boosted among ZIP codes. Sub-analyses on booster rates were compared among the 10 census regions.
UNASSIGNED: In a minimally adjusted model, a higher proportion of Black residents was associated with lower vaccination (HR = 0.97; 95%CI: 0.96-0.98). However, in a fully adjusted model, proportion of Black, Hispanic/Latinx, and Asian residents were associated with higher vaccination rates (HR = 1.02; 95%CI: 1.01-1.03 for all). The strongest predictor of low vaccine coverage was disability (HR = 0.89; 95%CI: 0.86-0.91). Similar trends persisted for booster doses. Factors associated with booster coverage varied by region.
UNASSIGNED: Examining neighborhood-level factors associated with COVID-19 vaccination and booster rates uncovered significant variation within the large and geographically and demographically diverse state of California. Equity-based approaches to vaccination must ensure a robust consideration of multiple social determinants of health.

The use of computer-aided methods have continued to propel accelerated drug discovery across various disease models, interestingly allowing the specific inhibition of pathogenic targets. Chloride Intracellular Channel Protein 4 (CLIC4) is a novel class of intracellular ion channel highly implicated in tumor and vascular biology. It regulates cell proliferation, apoptosis and angiogenesis; and is involved in multiple pathologic signaling pathways. Absence of specific inhibitors however impedes its advancement to translational research. Here, we integrate structural bioinformatics and experimental research approaches for the discovery and validation of small-molecule inhibitors of CLIC4. High-affinity allosteric binders were identified from a library of 1615 Food and Drug Administration (FDA)-approved drugs via a high-performance computing-powered blind-docking approach, resulting in the selection of amphotericin B and rapamycin. NMR assays confirmed the binding and conformational disruptive effects of both drugs while they also reversed stress-induced membrane translocation of CLIC4 and inhibited endothelial cell migration. Structural and dynamics simulation studies further revealed that the inhibitory mechanisms of these compounds were hinged on the allosteric modulation of the catalytic glutathione (GSH)-like site loop and the extended catalytic β loop which may elicit interference with the catalytic activities of CLIC4. Structure-based insights from this study provide the basis for the selective targeting of CLIC4 to treat the associated pathologies.

Cirrhosis predisposes to abnormalities in energy, hormonal, and immunological homeostasis. Disturbances in these metabolic processes create susceptibility to sarcopenia or pathological muscle wasting. Sarcopenia is prevalent in cirrhosis and its presence portends significant adverse outcomes including the length of hospital stay, infectious complications, and mortality. This highlights the importance of identification of at-risk individuals with early nutritional, therapeutic and physical therapy intervention. This manuscript summarizes literature relevant to sarcopenia in cirrhosis, describes current knowledge, and elucidates possible future directions.

UNASSIGNED: To evaluate the safety of antimotility agents (AAs) in a population of patients with hematologic malignancies and concurrent Clostridioides difficile infection (CDI) and to describe the outcomes of AA use in a hospital setting.
UNASSIGNED: We used the electronic health record to identify patients who were hospitalized in the adult malignant hematology service who had 1 or more toxin-positive C difficile stool assay between April 1, 2012, and September 21, 2017. We reviewed medical charts to obtain information on the use of AAs and any subsequent gastrointestinal complications.
UNASSIGNED: There were 339 patients who were stool toxin positive for CDI during the study period. Of those, 94 patients (27%) were prescribed AAs within 14 days of CDI diagnosis. All patients received CDI antimicrobial therapy within the first 24 hours. There were 2 adverse gastrointestinal events in the group that received AAs and 6 in the group that did not receive AAs. The risk of adverse events did not differ between patients who received AAs and those who did not (adjusted odds ratio, 0.36; 95% CI, 0.06 to 2.10). The mean age of the full cohort was 52.7±15.5 years, and the mean length of stay was 26.7±22.6 days. Early AA use (<48 hours of diagnosis) was not associated with increased adverse effects.
UNASSIGNED: There was no increase in the incidence of gastrointestinal events in the arm that used AAs compared with the control arm. The evidence suggests that for patients with hematologic malignancies and CDI, the addition of AAs to appropriate antimicrobial therapy poses no additional risk.

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Hepatocellular Carcinoma (HCC) continues to present major challenges in management, which is further complicated by the presence of associated chronic liver disease. Key issues in surgical resection of HCC include the site, size, and number of lesions, the severity of the chronic liver disease, and the size of the functional liver remnant. De novo HCC in the absence of chronic liver disease can be treated by major liver resection with little risk of postoperative liver failure. Liver resection can also be used a bridge to liver transplantation as it affords the possibility of determining the pathologic grade of the tumortumor and its invasiveness, and thereby the prognosis. This review summarizes the current treatment approaches to surgical resection for HCC.