Functional Impact Score of Mitochondrial Variants and Its Relationship With Functional Connectivity of the Brain: Potential Origins of Premature Aging in Young Adulthood

22 Jan

GLP-1 Receptor Agonists for Secondary Prevention After Myocardial Infarction and Stroke in Type 2 Diabetes: Nationwide Real-World Evidence

Aims: Glucagon-like peptide-1 receptor agonists (GLP-1RA) reduce cardiovascular risk in patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease and are recommended in guidelines. We evaluated the real-world effectiveness of GLP-1RA therapy on cardiovascular outcomes in patients with T2D after myocardial infarction (MI) or ischemic stroke and examined trends and disparities.

Methods: Using nationwide Czech registry data (2015-2024), we identified patients with incident nonfatal MI or ischemic stroke and confirmed T2D. GLP-1RA users-initiating therapy within 12 months post-event-were propensity score-matched to non-users. The primary outcome was major adverse cardiovascular events (MACE: nonfatal MI, nonfatal stroke, cardiovascular death); secondary outcomes included individual components and all-cause mortality.

Results: GLP-1RA therapy was initiated in only ∼2% of MI and stroke survivors with T2D. Among 126,845 MI survivors, 28,206 had T2D; the matched cohort comprised 2,271 patients (401 GLP-1RA; median follow-up 35 months). GLP-1RA use was associated with lower risk of MACE (HR:0.7; 95%CI:0.52-0.93), all-cause (HR:0.61;95%CI:0.47-0.80) and cardiovascular death (HR:0.54, 95%CI:0.36-0.80). Among 177,115 stroke survivors, 73,750 had T2D; the matched cohort comprised 2,235 patients (385 GLP-1RA; median follow-up 27 months). 

22 Jan

The Assessment of RAB32 p.Ser71Arg Variant Prevalence in Parkinson's Disease Across Selected African, European, and South American Cohorts

Monogenic forms of Parkinson's disease (PD) have demonstrated a heterogeneous disorder involving multiple biological pathways.¹ Familial forms of PD have been linked to variants in LRRK2, SNCA, VPS35, PARKIN, and PINK1.¹ Heterozygous GBA mutation carriers are associated with higher disease risk, earlier onset, and accelerated clinical progression.¹

Recently, RAB32 has emerged as a nominated PD gene. It encodes a Rab GTPase involved in mitochondrial and vesicular trafficking pathways. A rare substitution, p.Ser71Arg (rs200251693), has been proposed as a potential susceptibility factor.^2, 3 Reported carriers exhibit late-onset, levodopa-responsive parkinsonism with familial clustering; the only available autopsy case lacked Lewy bodies.^1-3 Across published studies, RAB32 c.213C>G was detected in 0.22% to 2.3% of patients, primarily within Mediterranean and North American cohorts, and was absent in large East Asian datasets. This pattern suggests regional specificity and a possible shared Mediterranean haplotype.^2-6 Limited data exist from several regions, including Eastern Europe, Ireland, sub-Saharan Africa, and South America.