👤 Maryam M Sani

Fentanyl is a potent, fast-acting synthetic opioid that has played a major role in the opioid overdose crisis in the United States for over five decades, with opioid-related deaths increasing sharply in recent years. This study investigates the behavioral, histological, and molecular changes in the hippocampus of rats subjected to sub-acute fentanyl exposure. Two groups of rats were studied: one group received multiple fentanyl injections over approximately one week, while the control group received no fentanyl. A battery of behavioral tests related to memory and depression-including the Y-maze, shuttle box, tail suspension test, elevated plus maze, Barnes maze, Morris water maze, and forced swimming test-was administered. Electrophysiological assessments, including field potential recording and electromyography (EMG), were conducted to evaluate neural activity. Western blot analysis was performed to quantify the expression of brain-derived neurotrophic factor (BDNF) and RE1-silencing transcription factor (REST), while immunohistochemical analyses assessed hippocampal cellular alterations. Results showed that sub-acute fentanyl administration impaired behavioral performance in memory assessment tests (Y maze ( Show less

To quantify international variations in lipid-lowering therapies (LLT) use among patients with coronary heart disease (CHD) and attainment of European guideline-recommended lipid goals. INTERASPIRE is an observational study (2020-23) covering 14 countries from all WHO regions. Patients (18-79 years) hospitalized in the preceding 6-36 months with CHD were invited for standardized interviews and examination, with central laboratory analyses for low-density lipoprotein cholesterol (LDL-C), non-HDL-C, and apolipoprotein B (apoB). Valid lipid data meeting quality control standards were available from 13 countries. Lipid goals followed the 2019 guidelines of the European Atherosclerosis Society and the European Society of Cardiology: LDL-C < 1.4 mmol/L, non-HDL-C < 2.2 mmol/L, and apoB <65 mg/dL.Among 4061 patients (78.8% male, mean age 60.3 years), between index event and interview, 66.3% had no change in treatment intensity. LLT use at interview was largely statin monotherapy: 49.6% high-intensity (inter-country range 5.3%-77.3%) and 24.1% low/moderate-intensity (inter-country range 5.1%-70.1%). Otherwise, 12.2% (inter-country range 0.2%-41.1%) were on combination therapy, and 12.7% on no LLT (inter-country range 3.5%-36.7%). Goal attainment for LDL-C was 17.5%. Corresponding non-HDL-C and apoB goals were achieved by 29.9% and 29.2%, respectively. Higher-income countries (defined by the World Bank's 2024-25 classification of income levels) did better in goal attainment than lower-middle-income countries. In this international study, contemporary lipid goals were not achieved in most CHD patients, with lower-middle-income countries having the worst goal attainment. Contributory factors include absence of any LLT use, low use of combinations and a failure to up-titrate LLT to achieve guideline targets. Show less

Phosphorylation of alpha-synuclein (αsyn) at serine 129 (PS129) marks aggregates in synucleinopathies but also occurs physiologically, potentially signaling protein interactions during neuronal activity. Technical barriers, including postmortem dephosphorylation, have hindered the study of physiological PS129 in the human brain. Using biotinylation by antibody recognition (BAR) on surgically resected temporal lobectomy tissues (without post-mortem interval), we mapped physiological PS129 and total αsyn interactomes. BAR identified 1,095 interactions with 513 αsyn-specific, 524 shared, and 58 PS129-specific, mostly associated with vesicles at presynaptic nerve terminals. PS129-specific interactions were uniquely associated with postsynaptic density proteins SHANK1/3, DLGAP1-4, DLGAP1-3, and DLG2-4, as well as nuclear-associated proteins HUWE1, HNRNPM, RBM14, ITCH, OGT, PHF24, and PPP2R5E. Fluorescent staining confirmed physiological PS129 proximal to dendrites and within the nucleus. Confirmation in healthy cynomolgus macaques (62% αsyn and 41% PS129 overlap) demonstrated that the interactomes were physiological rather than disease- or aggregate-associated. We conclude that physiological PS129 plays a unique and underappreciated role in postsynaptic neurons extending from the postsynaptic active zone to the nucleus. These interactomes benchmark normal αsyn biology, illuminating the transition to synucleinopathy pathology. Disease-associated αsyn phosphorylation (PS129) was recently identified in healthy mammalian brain and may signal αsyn-protein interactions during neuronal activity. Here, we surmounted technical hurdles and characterized αsyn and PS129 interactomes directly in the human brain. Results showed a unique significance for PS129 in post-synaptic active zones and nuclear compartments, which was confirmed in healthy non-human primates. These αsyn interactomes will be a valuable reference for understanding synucleinopathy mechanisms in the context of normal αsyn biology. Show less

Camels are increasingly recognized for their potential to meet future nutritional and medical needs due to their unique qualities. This study aims to advance our understanding of the genetic basis of body size in dromedaries by employing confirmatory factor analysis (CFA) and genome-wide association studies (GWAS). We used phenotypic data from 9 body measurements of 96 Iranian male camels to develop a latent variable model for body size. The CFA model demonstrated excellent fit (CFI = 0.99, TLI = 0.99, RMSEA = 0.05, SRMR = 0.02), confirming that the selected biometric traits effectively capture the body size latent variable. Subsequent GWAS, utilizing 14,522 SNPs, identified 13 significant SNPs associated with body size across several chromosomes. The candidate genes linked to these SNPs, including Show less

Lipoprotein(a) (Lp(a)) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and has been linked to ventricular arrhythmias (VA). Beyond its role in cholesterol metabolism, Lp(a) promotes endothelial dysfunction, thrombogenesis, and inflammation, which may contribute to arrhythmogenesis independent of ASCVD. This study aimed to evaluate the association between Lp(a) levels and the incidence of VA in a large, population-based cohort. Adults aged ≥18 years with available Lp(a) measurements were identified from the TriNetX research network. Patients were stratified into low (≤75 nmol/L) and high Lp(a) groups (>75 nmol/L). The primary outcome was the incidence of VA, defined as ventricular tachycardia, fibrillation, flutter, or cardiac arrest owing to cardiac causes. Propensity score matching was used to adjust for demographics, ASCVD risk factors, and comorbidities. Kaplan-Meier survival analysis and Cox proportional hazards models were performed after matching. Before propensity score matching, 75,655 patients were in the low Lp(a) group and 40,860 in the high Lp(a) group. After matching, each cohort included 39,414 patients. VA occurred in 889 patients in the low and 718 in the high Lp(a) cohort. Mean follow-up was 3.35 years [low Lp(a)] and 1.90 years [high Lp(a)]. The high Lp(a) group had lower VA-free survival (84.30% vs 86.06%, Elevated Lp(a) levels are independently associated with a higher incidence of VA, even after adjusting for ASCVD and its downstream consequences. Future research should explore mechanisms and therapeutic implications. Show less

The coat color of dromedary is usually uniform and varies from black to white, although dark- to light-brown colors are the most common phenotypes. This project was designed to gain knowledge on novel color-related variants using genotyping-by-sequencing (GBS). The association between the SNPs and coat color was tested using MLM (mixed linear models) with kinship matrix. Three GWAS models including white color vs. non-white color, black vs. non-black color, and light-brown vs. dark-brown color were performed. There were no distinct genetic clusters detected based on the color phenotypes. However, admixture occurred among all individuals of the four different coat color groups. We identified nine significant SNPs associated with white color after Bonferroni correction, located close to Show less