We have validated the association of two genes on chromosome 20q13.31-33 with tuberculosis susceptibility. A previous genomewide linkage study performed by Cooke et al identified the genes melanocortin-3-receptor (MC3R) and cathepsin Z (CTSZ) as possible candidates in tuberculosis susceptibility. MC3R has been implicated in obesity studies and is known to play a role in many biological systems including the regulation of energy homeostasis and fat metabolism. CTSZ has been detected in immune cells, such as macrophages and monocytes, and it is hypothesized that the protein may play a role in the immune response. In our South African population a case-control study confirmed the previously reported association with a single-nucleotide polymorphism (SNP) in CTSZ and found an association in MC3R with a SNP not previously implicated in tuberculosis susceptibility. Six SNPs in MC3R and eight in CTSZ were genotyped and haplotypes were inferred. SNP rs6127698 in the promoter region of MC3R (cases¼498; controls¼506) and rs34069356 in the 3¢UTR of CTSZ (cases¼396; controls¼298) both showed significant association with tuberculosis susceptibility (P¼0.0004 and o0.0001, respectively), indicating that pathways involving these proteins, not previously researched in this disease, could yield novel therapies for tuberculosis.

Studies in humans have suggested the possible involvement of melanocortin-3-receptor (MC3R) and other components of the central melanocortin system in host defense against mycobacteria. We report a genomic DNA nucleotide sequence highly homologous to human MC3R in several bovids and non-bovid African wildlife species. Nucleotide sequence analysis indicates that the orthologous genes of cattle and buffalo are highly homologous (89.4 and 90%, respectively) to the human MC3R gene. Sequence results also identified a typical non-functional, duplicated pseudogene, MC3RP, in 7 species from the family Bovidae. No pseudogene was found in animals outside Bovidae. The presence of the pseudogene in tuberculosis-susceptible species could have possible immunomodulatory effects on susceptibility to bovine tuberculosis infection, as well as a considerable influence on energy metabolism and food conversion efficiency.

BackgroundHIV persistence during antiretroviral therapy (ART) is the principal obstacle to cure. Lymphoid tissue is a compartment for HIV, but mechanisms of persistence during ART and viral rebound when ART is interrupted are inadequately understood. Metabolic activity in lymphoid tissue of patients on long-term ART is relatively low, and increases when ART is stopped. Increases in metabolic activity can be detected by 18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and may represent sites of HIV replication or immune activation in response to HIV replication.MethodsFDG-PET imaging will be used to identify areas of high and low metabolic uptake in lymphoid tissue of individuals undergoing long-term ART. Baseline tissue samples will be collected. Participants will then be randomized 1:1 to continue or interrupt ART via analytic treatment interruption (ATI). Image-guided biopsy will be repeated 10 days after ATI initiation. After ART restart criteria are met, image-guided biopsy will be repeated once viral suppression is re-achieved. Participants who continued ART will have a second FDG-PET and biopsies 12–16 weeks after the first. Genetic characteristics of HIV populations in areas of high and low FDG uptake will be assesed. Optional assessments of non-lymphoid anatomic compartments may be performed to evaluate HIV populations in distinct anatomic compartments.Anticipated resultsWe anticipate that PET standardized uptake values (SUV) will correlate with HIV viral RNA in biopsies of those regions and that lymph nodes with high SUV will have more viral RNA than those with low SUV within a patient. Individuals who undergo ATI are expected to have diverse viral populations upon viral rebound in lymphoid tissue. HIV populations in tissues may initially be phylogenetically diverse after ATI, with emergence of dominant viral species (clone) over time in plasma. Dominant viral species may represent the same HIV population seen before ATI.DiscussionThis study will allow us to explore utility of PET for identification of HIV infected cells and determine whether high FDG uptake respresents areas of HIV replication, immune activation or both. We will also characterize HIV infected cell populations in different anatomic locations. The protocol will represent a platform to investigate persistence and agents that may target HIV populations.Study protocol registrationIdentifier: NCT05419024.

Fall prevention strategies are a consistent topic of discussion for healthcare regarding patient safety, as patient falls are costly to the patient and the organization. This project uses the CDC Framework for Program Evaluation to assess the fall prevention policy of a local hospital system, with particular emphasis on the fall risk assessment tool, Hester Davis. This project also explores the risks and benefits of adopting an alternative fall risk assessment tool, predictive analytics. Predictive analytics uses electronic health record (EHR) data analysis to provide a highly individualized patient fall risk score based on a large variety of patient and environmental factors. Comparative analysis of the two tools was performed in 104 chart reviews, which provided evidence for the use of predictive analytics. Recommendations are provided for a development of a new fall prevention policy that includes predictive analytics as the primary fall risk assessment tool. Based on these recommendations, this project also includes a competency-based orientation toolkit, which can be put into place should the organization choose to transition the policy to utilize predictive analytics as the primary fall risk assessment.