COVID-19 related deaths in an urban academic medical center in Brooklyn - a descriptive case series.

BACKGROUND: Available studies are lacking in analysis of baseline demographics and hospital presentation of patients at risk of expiring due to coronavirus disease 2019 (COVID-19), particularly Black American patients. We conducted a retrospective chart review to determine similarities in demographics and hospital presentation among patients who expired due to COVID-19 at an academic medical center in Brooklyn, New York. STUDY DESIGN AND METHODS: This is a retrospective observational study of 200 patients who expired due to complications of COVID-19. Patients were included in this study if they had laboratory-confirmed SARS-CoV-2 infection and expired during their admission. Data were collected on patients who expired between March 17 and April 16, 2020. RESULTS: A vast majority of patients were Black Americans (89%) with no history of international travel who had more than one comorbidity (81%), with the most common comorbidities being hypertension (84·5%), diabetes mellitus (57·5%), and obesity (41·5%). Fifty-five percent of our patient population had three or more comorbidities. Among patients with available data, C-reactive protein, lactate dehydrogenase, and ferritin values were elevated above normal limits at admission. Dyspnea was the most common presenting symptom (92·5%). Most (90·5%) presented within the first week of symptoms, with a median time of symptoms prior to expiration being 8·42 days (IQR 5·57-12·72). INTERPRETATION: Socioeconomic status and healthcare inequalities have greatly affected the Black population of Brooklyn, New York, and these disparities become even more apparent in COVID-19 infection. Patients presenting with numerous comorbidities and elevated inflammatory markers represent a population at high risk of in-hospital mortality.

Hippocampal mossy cell involvement in behavioral and neurogenic responses to chronic antidepressant treatment.

Most antidepressants, including selective serotonin reuptake inhibitors (SSRIs), initiate their drug actions by rapid elevation of serotonin, but they take several weeks to achieve therapeutic onset. This therapeutic delay suggests slow adaptive changes in multiple neuronal subtypes and their neural circuits over prolonged periods of drug treatment. Mossy cells are excitatory neurons in the dentate hilus that regulate dentate gyrus activity and function. Here we show that neuronal activity of hippocampal mossy cells is enhanced by chronic, but not acute, SSRI administration. Behavioral and neurogenic effects of chronic treatment with the SSRI, fluoxetine, are abolished by mossy cell-specific knockout of p11 or Smarca3 or by an inhibition of the p11/AnxA2/SMARCA3 heterohexamer, an SSRI-inducible protein complex. Furthermore, simple chemogenetic activation of mossy cells using Gq-DREADD is sufficient to elevate the proliferation and survival of the neural stem cells. Conversely, acute chemogenetic inhibition of mossy cells using Gi-DREADD impairs behavioral and neurogenic responses to chronic administration of SSRI. The present data establish that mossy cells play a crucial role in mediating the effects of chronic antidepressant medication. Our results indicate that compounds that target mossy cell activity would be attractive candidates for the development of new antidepressant medications.

Rates of clinically significant prostate cancer in African Americans increased significantly following the 2012 US Preventative Services Task Force recommendation against prostate specific antigen screening: A Single Institution Retrospective Study.

PURPOSE: We determined the impact of the 2012 US Preventative Services Task Force recommendation against prostate specific antigen screening on detection rates and biopsy patterns in African American and Caucasian patients. MATERIALS AND METHODS: Demographics, PSA, transrectal ultrasonography volume and pathologic data were collected on patients who underwent their first ultrasound-guided prostate biopsy between January 2007 and June 2018 at a New York City Veteran Affairs Hospital. RESULTS: 609 biopsies were analysed preguideline (113 per year), and 487 were analysed postguideline (81 per year). There was no significant difference in the detection rates of low, intermediate or high grade PCa in Caucasians. In contrast, African Americans were significantly more likely to be diagnosed with PCa in the postguideline group (56% pre vs 66% post, P = .016), and significantly more likely to be diagnosed with intermediate-high grade PCa (38% pre vs 47% post, P = .038). Before the 2012 USPSTF recommendation, African American and Caucasian patients undergoing their first biopsy were equally likely to be diagnosed with high-grade PCa (11% AA vs 11% CA). After the 2012 decision, we found that African Americans were 50% more likely than Caucasians to be diagnosed with high-grade PCa on first biopsy (10% AA vs 15% CA, P = .008). CONCLUSIONS: In the 6 years following the 2012 USPSTF recommendation, detection rates of intermediate-high risk disease remained unchanged for Caucasian patients but have increased significantly for African Americans. The results of our study strongly support the role of routine PSA screening, particularly in higher risk patients such as African Americans.

Dissecting the cis and trans elements that regulate adjacent-gene coregulation in Saccharomyces cerevisiae.

The relative positions that genes occupy on their respective chromosomes can play a critical role in determining how they are regulated at the transcriptional level. For example, a significant fraction of the genes from a variety of coregulated gene sets, including the ribosomal protein (RP) and the rRNA and ribosome biogenesis (RRB) regulons, exist as immediate, adjacent gene pairs. These gene pairs occur in all possible divergent, tandem, and convergent orientations. Adjacent-gene pairing in these regulons is associated with a tighter transcriptional coregulation than is observed for nonpaired genes of the same regulons. In order to define the cis and trans factors that regulate adjacent-gene coregulation (AGC), we conducted a mutational analysis of the convergently oriented RRB gene pair MPP10-YJR003C. We observed that coupled corepression of the gene pair under heat shock was abrogated when the two genes were separated by an actively expressed RNA polymerase (Pol) II transcription unit (the LEU2 gene) but not when the inserted LEU2 gene was repressed. In contrast, the insertion of an RNA Pol III-transcribed tRNA (Thr) gene did not disrupt the coregulated repression of MPP10 and YJR003C. A targeted screen of mutants defective in regulating chromosome architecture revealed that the Spt20, Snf2, and Chd1 proteins were required for coupling the repression of YJR003C to that of MPP10. Nucleosome occupancy assays performed across the MPP10 and YJR003C promoter regions revealed that the mechanism of corepression of the gene pair was not related to the repositioning of nucleosomes across the respective gene promoters.

The adjacent positioning of co-regulated gene pairs is widely conserved across eukaryotes.

BACKGROUND: Coordinated cell growth and development requires that cells regulate the expression of large sets of genes in an appropriate manner, and one of the most complex and metabolically demanding pathways that cells must manage is that of ribosome biogenesis. Ribosome biosynthesis depends upon the activity of hundreds of gene products, and it is subject to extensive regulation in response to changing cellular conditions. We previously described an unusual property of the genes that are involved in ribosome biogenesis in yeast; a significant fraction of the genes exist on the chromosomes as immediately adjacent gene pairs. The incidence of gene pairing can be as high as 24% in some species, and the gene pairs are found in all of the possible tandem, divergent, and convergent orientations. RESULTS: We investigated co-regulated gene sets in S. cerevisiae beyond those related to ribosome biogenesis, and found that a number of these regulons, including those involved in DNA metabolism, heat shock, and the response to cellular stressors were also significantly enriched for adjacent gene pairs. We found that as a whole, adjacent gene pairs were more tightly co-regulated than unpaired genes, and that the specific gene pairing relationships that were most widely conserved across divergent fungal lineages were correlated with those genes that exhibited the highest levels of transcription. Finally, we investigated the gene positions of ribosome related genes across a widely divergent set of eukaryotes, and found a significant level of adjacent gene pairing well beyond yeast species. CONCLUSION: While it has long been understood that there are connections between genomic organization and transcriptional regulation, this study reveals that the strategy of organizing genes from related, co-regulated pathways into pairs of immediately adjacent genes is widespread, evolutionarily conserved, and functionally significant.