Age, Gender, and Liver Enzyme Impact Hospital Stay in COVID-19 Minority Patient with Cancer in the USA: Does Race Matters in the Pandemic?

Patients with cancer are known to have a poor prognosis when infected with SARS-CoV-2 infection. We aimed in this study to assess health outcomes in COVID-19 patients with different cancers in comparison to non-cancer COVID-19 patients from different centers in the United States (US). We evaluated medical records of 1,943 COVID-19 Cancer patients from 3 hospitals admitted between December 2019 to October 2021 and compared them with non-cancer COVID-19 patients. Among 1,943 hospitalized COVID-19 patients, 18.7% (n=364) have an active or previous history of cancer. Among these 364 cancer patients, 222 were African Americans (61.7%) and 121 were Caucasians (33.2%). Cancer patients had significantly longer hospitalization compared to controls (8.24 vs 6.7 days). Overall, Lung cancer is associated with high mortality. Patients with a previous history of cancer were more prone to death (p=0.04) than active cancer patients. In univariate and multivariate analyses, predictors of death among cancer patients were male sex, older age, presence of dyspnea, elevated troponin, elevated AST (0.001) and ALT (0.05), low albumin (p=0.04) and mechanical ventilation (p=0.001). Patients with a previous history of cancer were more prone to death when compared to active cancer COVID-19 patients. Early recognition of cancer COVID-19 patients' death-associated risk factors can help determine appropriate treatment and management plans for better prognosis and outcome.

Treatment of enterocutaneous fistula: a systematic review and meta-analysis.

BACKGROUND: Enterocutaneous fistula (ECF) is an abnormal communication between the gastrointestinal tract and skin, with a myriad of etiologies and therapeutic options. Management is influenced by etiology and specifics of the ECF, and patient-related factors. The aim of this study was to assess overall success, recurrence, and mortality rates of treatment for ECF. MATERIALS: A systematic search of PubMed and Google Scholar was performed through October 2021 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Case reports, reviews, animal studies, studies not reporting outcomes, had no available English text, included patients < 16 years old or those assessing other abdominocutaneous/internal fistulas were excluded. RESULTS: Fifty-three studies, between 1975 and 2020, incorporating 3078 patients were included. Patient age ranged between 16 and 87 years with a male:female ratio of 1.14:1. ECF developed postoperatively in 89.4%. Other common etiologies were inflammatory bowel disease, trauma, malignancy, and radiation. At least 28% of patients had complex fistulae (reported in 18 studies). Most common fistula site was small bowel. In 34 publications, 62.4% (n = 1371) patients received parenteral nutrition. In 45 publications, 72.5% underwent surgery to treat the fistula. Meta-analysis revealed an 89% healing rate; recurrence rate after initial successful treatment was 11.1%, and mortality rate was 8.5%. In a subgroup of patients who underwent combined ECF takedown and abdominal wall reconstructions (n = 315), 78% achieved fascial closure, mesh was used in 72%, hernia, and fistula recurrence rates were 19.7% and 7.6%, respectively. CONCLUSIONS: Treatment of ECF must be individualized according to specific etiology and location of the fistula and the patient's associated conditions.

Environmentally associated chromosomal structural variation influences fine-scale population structure of Atlantic Salmon (Salmo salar).

Chromosomal rearrangements (e.g., inversions, fusions, and translocations) have long been associated with environmental variation in wild populations. New genomic tools provide the opportunity to examine the role of these structural variants in shaping adaptive differences within and among wild populations of non-model organisms. In Atlantic Salmon (Salmo salar), variations in chromosomal rearrangements exist across the species natural range, yet the role and importance of these structural variants in maintaining adaptive differences among wild populations remains poorly understood. We genotyped Atlantic Salmon (n = 1429) from 26 populations within a highly genetically structured region of southern Newfoundland, Canada with a 220K SNP array. Multivariate analysis, across two independent years, consistently identified variation in a structural variant (translocation between chromosomes Ssa01 and Ssa23), previously associated with evidence of trans-Atlantic secondary contact, as the dominant factor influencing population structure in the region. Redundancy analysis suggested that variation in the Ssa01/Ssa23 chromosomal translocation is strongly correlated with temperature. Our analyses suggest environmentally mediated selection acting on standing genetic variation in genomic architecture introduced through secondary contact may underpin fine-scale local adaptation in Placentia Bay, Newfoundland, Canada, a large and deep embayment, highlighting the importance of chromosomal structural variation as a driver of contemporary adaptive divergence.

Synthesis of Functional Building Blocks for Type III-B Rotaxane Dendrimer.

Second-generation type III-B rotaxane dendrons, equipped with succinimide and acetylene functional groups, were synthesized successfully and characterized by NMR spectroscopy and mass spectrometry. A cell viability study of a dendron with a normal cell line of L929 fibroblast cells revealed no obvious cytotoxicity at a range of 5 to 100 µM. The nontoxic properties of the sophisticated rotaxane dendron building blocks provided a choice of bio-compatible macromolecular machines that could be potentially developed into polymeric materials.

The role of propeptide-mediated autoinhibition and intermolecular chaperone in the maturation of cognate catalytic domain in leucine aminopeptidase.

Leucyl aminopeptidase A from Aspergillus oryzae RIB40 (AO-LapA) is an exo-acting peptidase, widely utilised in food debittering applications. AO-LapA is secreted as a zymogen by the host and requires enzymatic cleavage of the autoinhibitory propeptide to reveal its full activity. Scarcity of structural data of zymogen aminopeptidases hampers a better understanding of the details of their molecular action of autoinhibition and how this might be utilised to improve the properties of such enzymes by recombinant methods for more effective bioprocessing. To address this gap in the literature, herein we report high-resolution crystal structures of recombinantly expressed AO-LapA precursor (AO-proLapA), mature LapA (AO-mLapA) and AO-mLapA complexed with reaction product l-leucine (AO-mLapA-Leu), all purified from Pichia pastoris culture supernatant. Our structures reveal a plausible molecular mechanism of LapA catalytic domain autoinhibition by propeptide and highlights the role of intramolecular chaperone (IMC). Our data suggest an absolute requirement for IMC in the maturation of cognate catalytic domain of AO-LapA. This observation is reinforced by our expression and refolding data of catalytic domain only (AO-refLapA) from Escherichia coli inclusion bodies, revealing a limited active conformation. Our work supports the notion that known synthetic aminopeptidase inhibitors and substrates mimic key polar contacts between propeptide and corresponding catalytic domain, demonstrated in our AO-proLapA zymogen crystal structure. Furthermore, understanding the atomic details of the autoinhibitory mechanism of cognate catalytic domains by native propeptides has wider reaching implications toward synthetic production of more effective inhibitors of bimetallic aminopeptidases and other dizinc enzymes that share an analogous reaction mechanism.

Re-expression of miR-200s in claudin-low mammary tumor cells alters cell shape and reduces proliferation and invasion potentially through modulating other miRNAs and SUZ12 regulated genes.

BACKGROUND: MicroRNAs are a class of non-coding RNAs that regulate gene expression through binding to mRNAs and preventing their translation. One family of microRNAs known as the miR-200 family is an important regulator of epithelial identity. The miR-200 family consists of five members expressed in two distinct clusters; the miR-200c/141 cluster and the miR-200b/200a/429 cluster. We have found that murine and human mammary tumor cells with claudin-low characteristics are associated with very low levels of all five miR-200s. METHODS: To determine the impact of miR-200s on claudin-low mammary tumor cells, the miR-200c/141 cluster and the miR-200b/200a/429 cluster were stably re-expressed in murine (RJ423) and human (MDA-MB-231) claudin-low mammary tumor cells. Cell proliferation and migration were assessed using BrdU incorporation and transwell migration across Matrigel coated inserts, respectively. miRNA sequencing and RNA sequencing were performed to explore miRNAs and mRNAs regulated by miR-200 re-expression while Enrichr-based pathway analysis was utilized to identify cellular functions modified by miR-200s. RESULTS: Re-expression of the miR-200s in murine and human claudin-low mammary tumor cells partially restored an epithelial cell morphology and significantly inhibited proliferation and cell invasion in vitro. miRNA sequencing and mRNA sequencing revealed that re-expression of miR-200s altered the expression of other microRNAs and genes regulated by SUZ12 providing insight into the complexity of miR-200 function. SUZ12 is a member of the polycomb repressor complex 2 that suppresses gene expression through methylating histone H3 at lysine 27. Flow cytometry confirmed that re-expression of miR-200s increased histone H3 methylation at lysine 27. CONCLUSIONS: Re-expression of miR-200s in claudin-low mammary tumor cells alters cell morphology and reduces proliferation and invasion, an effect potentially mediated by SUZ12-regulated genes and other microRNAs.

Young African American women's participation in an m-Health study in cardiovascular risk reduction: Feasibility, benefits, and barriers.

BACKGROUND: Young black women have an increased risk of cardiovascular disease, and thus identifying innovative prevention strategies is essential. A potential preventive strategy is mobile health; however, few studies have tested this strategy in young black women. AIM: The purpose of this study was to assess the feasibility of a mobile health intervention through a digital application to reduce cardiovascular disease risk factors in young black women, and identify benefits and barriers to participation. METHODS: Forty black women aged 25-45 years completed four sessions of cardiovascular disease risk reduction education and a six-month smartphone cardiovascular disease risk reduction monitoring and coaching intervention, targeting heart-healthy behavior modifications. At follow-up, women responded to a semi-qualitative online survey assessing the user-friendliness and perceived helpfulness of the intervention. RESULTS: Of 40 women, 38 completed the follow-up survey. Sixty per cent of participants reported that the applications were easy or very easy to maintain, 90% reported that the application was easy or very easy to use. Over 60% observed that their family's nutrition improved "a lot" or "a medium amount," and many participants noted positive changes in their children's diets. Only 8% of participants cited time or cost required to prepare healthy foods as barriers to implementing dietary changes. CONCLUSIONS: The m-Health intervention was feasible as a means of cardiovascular disease risk reduction for young black women. In addition, we found that targeting women provided indirect benefits for other family members, especially children. Most of the participants did not encounter systemic barriers to participation, suggesting that mobile health interventions can be effective tools to improve health behaviors in vulnerable populations.

Cognitive effects of mifepristone in overweight, euthymic adults with depressive disorders.

BACKGROUND: Previous studies have shown that individuals with mood disorders have a higher prevalence of both hypercortisolemia and insulin resistance. Insulin resistance is posited to contribute to the cognitive deficits observed in individuals who have depression. However, the mechanistic relationship between cortisol and insulin within the central nervous system remains to be further elucidated. This study aimed to evaluate the effects of the antiglucocorticoid agent, mifepristone, on metabolic function and cognitive performance in individuals receiving treatment for depressive disorders who were euthymic at baseline. METHODS: Participants were administered a 600 mg/day dose of mifepristone for 28 days. Oral glucose tolerance tests (OGTTs) and cognitive assessments measuring verbal memory and executive functioning were administered at baseline and after 28 days of treatment. RESULTS: Improvements in attention and verbal learning were associated with reduction of fasting plasma glucose (FPG) in response to mifepristone treatment. LIMITATIONS: Limitations include the open-label design of this study and a small sample size. CONCLUSIONS: The findings from this study suggest that improvement in fasting plasma glucose levels, upon administration of mifepristone, is associated with the improvement in early input of verbal information. Further studies are warranted in order to better evaluate the use of mifepristone or other antiglucocorticoid agents in treatment of mood disorders characterized by metabolic dysfunction.

Diabetes UK evidence-based nutrition guidelines for the prevention and management of diabetes.

A summary of the latest evidence-based nutrition guidelines for the prevention and management of diabetes is presented. These guidelines are based on existing recommendations last published in 2011, and were formulated by an expert panel of specialist dietitians after a literature review of recent evidence. Recommendations have been made in terms of foods rather than nutrients wherever possible. Guidelines for education and care delivery, prevention of Type 2 diabetes, glycaemic control for Type 1 and Type 2 diabetes, cardiovascular disease risk management, management of diabetes-related complications, other considerations including comorbidities, nutrition support, pregnancy and lactation, eating disorders, micronutrients, food supplements, functional foods, commercial diabetic foods and nutritive and non-nutritive sweeteners are included. The sections on pregnancy and prevention of Type 2 diabetes have been enlarged and the weight management section modified to include considerations of remission of Type 2 diabetes. A section evaluating detailed considerations in ethnic minorities has been included as a new topic. The guidelines were graded using adapted 'GRADE' methodology and, where strong evidence was lacking, grading was not allocated. These 2018 guidelines emphasize a flexible, individualized approach to diabetes management and weight loss and highlight the emerging evidence for remission of Type 2 diabetes. The full guideline document is available at www.diabetes.org.uk/nutrition-guidelines.

Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity.

Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells. carCTL receptors associated with the synapse were found to be disrupted and formed a convoluted multifocal pattern of Lck microclusters. Both proximal and distal receptor signaling pathways were induced more rapidly and subsequently decreased more rapidly in carCTL than in tcrCTL. The functional consequence of this rapid signaling in carCTL cells included faster lytic granule recruitment to the immune synapse, correlating with faster detachment of the CTL from the target cell. This study provides a mechanism for how CAR-T cells can debulk large tumor burden quickly and may contribute to further refinement of CAR design for enhancing the quality of signaling and programming of the T cell.

Evaluation of optimal water fluoridation on the incidence and skeletal distribution of naturally arising osteosarcoma in pet dogs.

Experimental toxicological studies in laboratory animals and epidemiological human studies have reported a possible association between water fluoridation and osteosarcoma (OSA). To further explore this possibility, a case-control study of individual dogs evaluated by the UC Davis Veterinary Medical Teaching Hospital was conducted using ecologic data on water fluoridation based on the owner's residence. The case group included 161 dogs with OSA diagnosed between 2008-2012. Two cancer control groups included dogs diagnosed with lymphoma (LSA) or hemangiosarcoma (HSA) during the same period (n = 134 and n = 145, respectively). Dogs with OSA were not significantly more likely to live in an area with optimized fluoride in the water than dogs with LSA or HSA. Additional analyses within OSA patients also revealed no significant differences in age, or skeletal distribution of OSA cases relative to fluoride status. Taken together, these analyses do not support the hypothesis that optimal fluoridation of drinking water contributes to naturally occurring OSA in dogs.

Enrofloxacin enhances the effects of chemotherapy in canine osteosarcoma cells with mutant and wild-type p53.

Adjuvant chemotherapy improves survival time in dogs receiving adequate local control for appendicular osteosarcoma, but most dogs ultimately succumb to metastatic disease. The fluoroquinolone antibiotic enrofloxacin has been shown to inhibit survival and proliferation of canine osteosarcoma cells in vitro. Others have reported that fluoroquinolones may modulate cellular responses to DNA damaging agents and that these effects may be differentially mediated by p53 activity. We therefore determined p53 status and activity in three canine osteosarcoma cell lines and examined the effects of enrofloxacin when used alone or in combination with doxorubicin or carboplatin chemotherapy. Moresco and Abrams canine osteosarcoma cell lines contained mutations in p53, while no mutations were identified in the D17 cells or in a normal canine osteoblast cell line. The addition of enrofloxacin to either doxorubicin or carboplatin resulted in further reductions in osteosarcoma cell viability; this effect was apparent regardless of p53 mutational status or downstream activity.

Use of high-density SNP data to identify patterns of diversity and signatures of selection in broiler chickens.

The development of broiler chickens over the last 70 years has been accompanied by large phenotypic changes, so that the resulting genomic signatures of selection should be detectable by current statistical techniques with sufficiently dense genetic markers. Using two approaches, this study analysed high-density SNP data from a broiler chicken line to detect low-diversity genomic regions characteristic of past selection. Seven regions with zero diversity were identified across the genome. Most of these were very small and did not contain many genes. In addition, fifteen regions were identified with diversity increasing asymptotically from a low level. These regions were larger and thus generally included more genes. Several candidate genes for broiler traits were found within these 'regression regions', including IGF1, GPD2 and MTNR1AI. The results suggest that the identification of zero-diversity regions is too restrictive for characterizing regions under selection, but that regions showing patterns of diversity along the chromosome that are consistent with selective sweeps contain a number of genes that are functional candidates for involvement in broiler development. Many regions identified in this study overlap or are close to regions identified in layer chicken populations, possibly due to their shared precommercialization history or to shared selection pressures between broilers and layers.

Alternative Locales for the Health Promotion of African American Men: A Survey of African American Men in Chicago Barbershops.

African American men (AA) carry unequal burdens of several conditions including cancer, diabetes, hypertension, and HIV. Engagement of diverse populations including AA men in research and health promotion practice is vital to examining the health disparities that continue to plague many racially and ethnically diverse communities. To date, there is little research on best practices that indicate locations, community areas and settings to engage AA men in research and health promotion. Traditionally, the AA church has been a key area to engage AA men and women. However, changing tides in attendance of AA parishioners require additional information to identify areas where AAs, particularly, AA men congregate. The AA barbershop has been identified as a place of social cohesion, cultural immersion and solidarity for AA men but specific sub-populations of AA men may be underrepresented. To further investigate additional locales where AA men congregate, this study engaged AA barbers and clients in several urban community barbershops in Chicago, Illinois. 127 AA men over age 18y/o receiving grooming services in 25 Chicago area barbershops across 14 predominantly AA communities were consented and recruited for a quantitative survey study. The self-administered surveys were completed in ~15 min and $10 compensation was provided to men. Descriptive statistics were reported for demographic variables and for frequency of responses for locations to find AA men of specific age ranges for health promotion and screening activities. Outside of the traditionally used churches or barbershops, the top recommended recruitment sites by age were: 18-29y/o- city park or a recreational center; 30-39y/o- gym, bars or the street; 40-49y/o- various stores, especially home improvement stores, and the mall; and 50y/o+- fast food restaurants in the mornings, such as McDonalds, and individual's homes. The study participants also reported that locations where AA men congregate vary by age. Findings from this study illustrate that AA barbers and barbershops remain a key stakeholder in health promotion among AA men. The findings also demonstrate the need for additional research to examine best practices for identifying locations where diverse groups of AA men that vary by age and sexual orientation may congregate in order to support increased health promotion among AA men.

Past and projected temporal trends in arthroscopic hip surgery in England between 2002 and 2013.

INTRODUCTION: Hip arthroscopy is increasingly adopted for the treatment of intra-articular and extra-articular pathologies. Studies from USA demonstrate a 365% increase in the number of procedures performed between 2004 and 2009 and 250% increase between 2007 and 2011. There is limited evidence of long-term efficacy for this procedure and hip arthroscopy is not universally funded across England. The aim of this study is to describe temporal trends in the adoption of hip arthroscopy in England between 2002 and 2013 and to forecast trends for the next 10 years. METHODS: A search of the Hospital Episodes Database was performed for all codes describing arthroscopic hip procedures with patient age, sex and area of residence. RESULTS: 11 329 hip arthroscopies were performed in National Health Service hospitals in England between 2002 and 2013. The number of hip arthroscopies performed increased by 727% (p<0.0001) during this period and is forecast to increase by 1388% in 2023. Females represent 60% of all patients undergoing hip arthroscopy (p<0.001). Median age category is 40-44 for females and 35-39 for males and average age decreased during the study period (p<0.0001). There is significant regional variation in procedure incidence. In the final year of this study the highest incidence was in the Southwest (8.63/100 000 population) and lowest in East Midlands (1.29/100 000 population). CONCLUSIONS: The increase in number of hip arthroscopies performed in England reflects trends in USA and continued increases are forecast. Evidence from robust clinical trials is required to justify the increasing number of procedures performed and regional variation suggests potential inequality in the provision of this intervention.

UK guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016.

The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the diagnosis and management of the full spectrum of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and SJS-TEN overlap in adults during the acute phase of the disease. The document aims to.

Reducing Staphylococcus aureus bloodstream infections associated with peripheral intravenous cannulae: successful implementation of a care bundle at a large Australian health service.

BACKGROUND: Healthcare-associated Staphylococcus aureus bacteraemia (HA-SAB) results in morbidity, mortality, and increased healthcare costs, and these infections are frequently regarded as preventable. AIM: To implement a multi-modal prevention programme for improved processes regarding peripheral intravenous cannula (PIVC) insertion and maintenance, in order to reduce PIVC-associated HA-SAB events in a large Australian health service. METHODS: Baseline clinical practice was evaluated for a 12-month pre-intervention period. Measures to reduce HA-SAB risk were introduced between January and September 2013: staff education, improved documentation (including phlebitis scoring), and availability of standardized equipment. Post-intervention auditing was performed during the 27 months following intervention. Baseline and post-intervention HA-SAB and PIVC-associated infection rates were compared. Interrupted time-series and Bayesian change-point analyses were applied to determine the impact of interventions and timing of change. FINDINGS: Significantly improved documentation regarding PIVC insertion and management was observed in the post-intervention period, with fewer PIVCs left in situ for ≥4 days (2.6 vs 6.9%, P<0.05). During the baseline period a total of 68 HA-SAB events occurred [1.01/10,000 occupied bed-days (OBDs)] and 24 were PIVC-associated (35% of total, rate 0.39 per 10,000 OBDs). In the post-intervention period, a total of 83 HA-SAB events occurred (0.99 per 10,000 OBDs) and 12 were PIVC-associated (14.4% of total, rate 0.14 per 10,000 OBDs). PIVC-associated SAB rates were 63% lower in the post-intervention period compared to baseline (P=0.018) with a change point observed following full bundle implementation in October 2013. CONCLUSION: A successful multi-modal hospital-wide campaign was introduced to reduce PIVC-associated SAB rates. Evaluation of cost-effectiveness and sustainability is required.