Cardiovascular disease (CVD) is the leading cause of death worldwide. Despite current lipid-lowering therapies, residual CVD risk in patients maximally treated with lipid-lowering agents remains a significant unmet clinical need. Large-scale genetic studies have identified >300 coronary artery disease (CAD) associated loci, yet the majority of causal genes that drive atherosclerosis remain unknown. Vascular smooth muscle cells (SMC) play an essential role in atherosclerosis, but even less is known about CAD-associated loci that control SMC function and identity during atherosclerosis progression. To identify novel SMC causal CAD genes, we developed a gene discovery pipeline that integrates large-scale human WGS/WES studies, rare variant analysis of human “knockouts” (homozygous for predicted loss-of-function variants pLoFs) from the Pakistani Genomics Resource (PGR), and previous SMC single cell profiling previously published by our lab. Starting at non-lipid CAD loci from a large multi-ethnic meta-analysis (1.1 million participants), we prioritized genes with high expression in SMC scRNA-seq, bulk RNAseq, and eQTL SNP datasets during atherosclerosis. Through gene burden testing of rare pLoFs and damaging variants in the largest CAD WES/WGS meta-analyses, including PGR (114,596 CAD cases and 481,375 controls), we identified multiple SMC causal candidate genes, including HHIPL1 , RAB23 , and SERPINH1 . Initial replication analyses across independent cohorts validated the association between rare HHIPL1 pLoF variants and CAD. Moreover, analysis of FinnGen, a geographically and genetically unique cohort, independently validated the causal association of HHIPL1 pLoFs and CAD, supporting allelic and ancestral generalizability. Phenome-wide association studies (PheWAS) showed a significant association between HHIPL1 and atherosclerosis phenotypes, reinforcing disease specificity. Leveraging high consanguinity in PGR, we identified and recruited multiple families harboring rare HHIPL1 pLoF variants for recall and mechanistic studies. In silico structural modeling of PGR HHIPL1 pLoF protein variants revealed disruption of a highly conserved domain predicted to bind SHH, thus providing insights into the possible mechanism underlying HHIPL1 -CAD function. In conclusion, we have developed a novel discovery pipeline for SMC-specific genes causative for CAD that has identified multiple candidates, including HHIPL1 and RAB23 , both of which modulate vascular SHH signaling.
ObjectiveDiabetes represents a major public health burden in the Middle East and North Africa (MENA) region. However, limited research has explored patients’ lived experiences and perspectives on diabetes management, particularly nutrition, within the Arab region. This study examined factors influencing adherence to dietitian-led counseling among adults with diabetes in the United Arab Emirates (UAE), with a focus on social support, outcome expectations, and patient suggestions to enhance motivation for dietary adherence.MethodsA qualitative study using semi-structured individual interviews was conducted with 44 adults with diabetes attending a diabetes management clinic in the UAE. Audio-recorded interviews were transcribed and analyzed using NVivo-12. Inductive thematic analysis guided by Social Cognitive Theory (SCT) was used to identify key concepts related to outcome expectations and social support. Participants’ suggestions for improving motivation to seek nutrition advice from dietitians were also explored.ResultsFour main themes emerged from the analysis: (1) positive expectations, (2) negative expectations, (3) enablers and motivators, and (4) participant suggestions. Positive outcome expectations, including improved health, better glycemic control, and weight management, motivated adherence to dietary advice. Social support from family members, friends, and healthcare professionals facilitated adherence and attendance at dietitian consultations. In contrast, misinformation, low awareness of the role of dietitians in diabetes management, and skepticism toward nutrition advice acted as barriers. Participants encouraged others with diabetes to consult dietitians and adopt healthier lifestyle behaviors.ConclusionEnhancing culturally appropriate social support and addressing informational barriers may improve dietary adherence, increase engagement in dietitian-led counseling, and improve nutrition-related diabetes outcomes.
The theory is under development. If you have questions, would like to contribute, offer criticism, or point out inaccuracies, please write to Majorz@mail.ru.
BACKGROUND:COVID-19 vaccine booster doses counteract waning immunity and vaccine escape by emerging variants. We evaluated long-term immunogenicity and safety of fractional and standard BNT162b2 vaccine booster doses in Mongolia. METHODS:In this randomised, controlled, non-inferiority trial, adults primed with two doses of ChAdOx1-S, BBIBP-CorV, or Gam-COVID-Vac were randomised (1:1) to receive a 15 μg (fractional dose) or 30 μg (standard dose) BNT162b2 booster. Geometric mean ratios (GMR) of IgG and surrogate virus neutralising test (sVNT) levels (Wuhan-Hu-1 and Omicron BA.1) were compared over 12 months. SARS-CoV-2 infections, and adverse and serious adverse events (SAEs), were documented. CLINICALTRIALS:gov Identifier: NCT05265065. RESULTS:Of 601 participants randomised between May 27th and September 30th, 2022, 2 (0.3 %) were lost to follow-up and 19 (3.2 %) withdrew by 12 months. IgG levels declined from 28 days to six months, stabilising thereafter. At 12 months, IgG levels were lower in the fractional compared with the standard arm for ChAdOx1-S primed participants (GMR 0.78 [95 % CI 0.63-0.96], p = 0.017). At six and 12 months, the median sVNT inhibition percentages were comparable by study arm and priming strata. Documented SARS-CoV-2 infections occurred in 25 participants (fractional dose arm n = 12; standard dose arm n = 13). From 28 days, 228 undocumented infections (≥ 1.2-fold IgG increase) occurred (fractional arm n = 112; standard arm n = 116). SAEs (n = 41) were balanced between arms, with no severe vaccine-related AEs or SAEs reported. CONCLUSIONS:15 μg and 30 μg BNT162b2 boosters demonstrated comparable immunogenicity and favourable safety. 15 μg BNT162b2 booster doses may improve vaccine acceptability due to lower reactogenicity.
This study systematically assessed chemical and physical hazards in 28 educational laboratories at the Qazvin University of Medical Sciences using the assessment and classification of hazards in laboratories (ACHiL) framework. The assessment involved walkthrough inspections, interviews, and checklist-based evaluations aligned with the guidelines of the Occupational Safety and Health Administration (OSHA), Globally Harmonized System (GHS) for Classification and Labeling of Chemicals, and National Fire Protection Association (NFPA). Among the 540 chemicals analyzed, 57% were classified as high risk, including substances such as methanol, phenol, nitric acid, and sulfuric acid. The Toxicology, Environmental Health, and Microbiology laboratories showed the highest concentrations of hazardous chemicals. Physical hazards, including electrical risks, ultraviolet radiation, and hot surfaces, were also identified and classified based on WHO and NFPA protocols. The results underscore the urgent need for enhanced chemical safety training, consistent use of personal protective equipment (PPE), improved ventilation systems, and regular inventory updates. This methodology offers a replicable model for laboratory risk assessment and contributes to the advancement of occupational health and safety in academic environments.
