Identification of genetic markers associated with hyperketonemia patterns in early lactation Holstein cows.

Ketosis, evidenced by hyperketonemia with elevated blood β-hydroxybutyrate (BHB) levels, is a significant metabolic disorder of dairy cattle, typically diagnosed within the first 6 weeks post-calving when high energy levels are essential to milk production. Our study aimed to identify genetic markers linked to hyperketonemia (HYK) patterns in Holstein cows during early lactation and compare these to HYK-negative cows. We screened 964 cows for HYK using a threshold of BHB ≥1.2 mmol/L during the first 2 weeks postpartum (screening period, SP). Cows that tested negative initially were retested the following week. Cows were deemed HYK-negative (CON group) if BHB levels were below 1.2 mmol/L in both tests, while those with BHB levels exceeding this threshold at any test were treated and classified as HYK-positive (HYK+). Post-treatment, HYK+ cows were monitored for two-week follow-up period (FP) and classified based on their recovery: cured (CUR; consistently low BHB), recurrent (REC; fluctuating BHB levels), severe (SEV; high initial BHB that decreased), or chronic (CHR; persistently high BHB). Using 489 cows that were genotyped, a GWAS was conducted using GCTA software, revealing significant associations of several SNPs across different HYK patterns when compared to the CON group. These SNPs were primarily linked to genes affecting milk traits and were enriched in biological pathways relevant to protein glycosylation, inflammatory response, glucose homeostasis, and fatty acid synthesis. Our findings highlight genomic regions, potential candidate genes, and biological pathways related to ketosis, underscoring potential targets for improving health management in dairy cattle. These insights could lead to better strategies for managing ketosis through genetic selection, ultimately enhancing dairy cattle welfare and productivity. Further research with a larger number of cows is recommended to validate these findings and help confirm the implicated SNPs and genes

HIV-associated morbidity and mortality in a setting of high ART coverage: prospective surveillance results from a district hospital in Botswana

Introduction Antiretroviral therapy (ART) has significantly improved survival in Africa in recent years. In Botswana, where adult HIV prevalence is 21.9%, AIDS‐related mortality is estimated to have declined by 58% between 2005 and 2013 following the initial wide‐spread introduction of ART, and ART coverage has steadily increased reaching 84% in 2016. However, there remains little data about the burden of HIV and its impact on mortality in the hospital setting where most deaths occur. We aimed to describe the burden of HIV and related morbidity and mortality among hospitalized medical patients in a district hospital in southern Botswana in the era of widespread ART coverage. Methods We prospectively reviewed medical admissions to Scottish Livingstone Hospital from December 2015 to November 2017 and recorded HIV status, demographics, clinical characteristics and final diagnoses at discharge, death or transfer. We ascertained outcomes and determined factors associated with mortality. Results were compared with similar surveillance data collected at the same facility in 2011 to 2012. Results A total of 2316 admissions occurred involving 1969 patients; 42.4% were of HIV‐positive patients, 46.9% of HIV‐negative patients and 10.7% of patients with unknown HIV status. Compared to HIV‐negative patients, HIV‐positive patients had younger age (mean 42 vs. 64 years, p < 0.0001) and higher mortality (22.2% vs. 18.0%, p = 0.03). Tuberculosis was the leading diagnosis among mortality cases in both groups but accounted for a higher proportion of deaths among HIV‐positive admissions (44.5%) compared with HIV‐negative admissions (19.4%, p < 0.0001). Compared with similar surveillance in 2011 to 2012, HIV prevalence was lower (42.4% vs. 47.6%, p < 0.01), and among HIV‐positive admissions: ART coverage was higher (72.2% vs. 56.2%, p < 0.0001), viral load suppression was similar (78.6% vs. 80.3%, p = 0.77), CD4 counts were higher (55.0% vs. 44.6% with CD4 ≥200 cells/mm3, p < 0.001), mortality was similar (22.2 vs. 22.7%, p = 0.93), tuberculosis diagnoses increased (27.5% vs. 20.1%, p < 0.01) and tuberculosis‐associated mortality was higher (35.9% vs. 24.7%, p = 0.05). Conclusions Despite high ART‐coverage in Botswana, HIV‐positive patients continue to be disproportionately represented among hospital admissions and deaths. Deaths from tuberculosis may be contributing to lack of reduction in inpatient mortality. Our findings suggest that control of HIV and tuberculosis remain top priorities for reducing inpatient mortality in Botswana

Identification of genetic markers associated with hyperketonemia patterns in early lactation Holstein cows

Additional File 1- Table S1. Descriptive statistics for blood BHB concentration (mmol/L) in Holstein cows were included in an observational study to assess their hyperketonemia patterns in the two weeks postpartum followed by diagnosis and treatment of the condition. Additional File 1- Table S2. Results indicated differences in blood BHB concentration (mmol/L) among HYK patterns in Holstein cows were included in an observational study to assess their hyperketonemia patterns in the two weeks postpartum followed by diagnosis and treatment of the condition. Additional File 2- Spreadsheet S1. List of genes, SNP and their functional consequences associated with HYK identified through cured vs. control (CUR-CON) contrast. Spreadsheet S2. List of genes, SNP and their functional consequences associated with HYK identified through severe vs. control (SEV-CON) contrast. Spreadsheet S3. List of genes, SNP and their functional consequences associated with HYK identified through chronic vs. control (CHR-CON) contrast, Spreadsheet S4. List of genes, SNP and their functional consequences associated with HYK identified through recurrent vs. control (REC-CON) contrast. Additional File 3- Spreadsheet S1. Pathways associated with genes identified to cured vs. control (CUR-CON) contrast, Spreadsheet S2. Pathways associated with genes identified to severe vs. control (SEV-CON) contrast, Spreadsheet S3. Pathways associated with genes identified to chronic vs. control (CHR-CON) contrast, Spreadsheet S4. Pathways associated with genes identified to recurrent vs. control (REC-CON) contrast, Spreadsheet S6. Pathways associated with genes set identified among 4 analyzed contrasts (Cured-CUR, severe-SEV, chronic-CHR and recurrent-RECU compared with control-CON, respectively), Spreadsheet S7. Protein Interaction network associated with genes set identified among 4 analyzed contrasts (Cured-CUR, severe-SEV, chronic-CHR and recurrent-RECU compared with control-CON, respectively). Additional File 4- Spreadsheet S1. Go terms and QTL associated with genes and SNPs related to HYK identified through cured vs. control (CUR-CON) contrast analysis, Spreadsheet S2. Go terms and QTL associated with genes and SNPs related to HYK identified through severe vs. control (SEV-CON) contrast, Spreadsheet S3. Go terms and QTL associated with genes and SNPs related to HYK identified through chronic vs. control (CHR-CON) contrast, Spreadsheet S4. Go terms and QTL associated with genes and SNPs related to HYK were identified through recurrent vs. control (REC-CON) contrast