Innovative treatments for spinal muscular atrophy (SMA) yield the utmost advantages only within the presymptomatic phase, underlining the significance of newborn screening (NBS). We aimed to establish statewide NBS for SMA in Serbia. Our stepwise implementation process involved technical validation of a screening assay, collaboration with patient organizations and medical professionals, a feasibility study, and negotiation with public health representatives. Over 12,000 newborns were tested during the 17-month feasibility study, revealing two unrelated SMA infants and one older sibling. All three children received therapeutic interventions during the presymptomatic phase and have shown no signs of SMA. No false-negative results were found among the negative test results. As frontrunners in this field in Serbia, we established screening and diagnostic algorithms and follow-up protocols and raised awareness among stakeholders about the importance of early disease detection, leading to the incorporation of NBS for SMA into the national program on 15 September 2023. Since then, 54,393 newborns have been tested, identifying six SMA cases and enabling timely treatment. Our study demonstrates that effective collaborations between academia, non-profit organizations, and industry are crucial in bringing innovative healthcare initiatives to fruition, and highlights the potential of NBS to revolutionize healthcare outcomes for presymptomatic SMA infants and their families.

Completed suicide accounts for over 700,000 deaths worldwide annually, while attempted suicide is 20 times more frequent. Genetic background is an important factor contributing to suicidal behavior, including candidate genes in glutamate, γ-aminobutyric acid (GABA), and polyamine systems. Our aim was to differentiate genetic predispositions underlying different types of suicidal behavior, attempted and completed suicide, in two Balkan populations. Analysis of variants in the genes GRIN2B (rs2268115 and rs220557), GABRG2 (rs424740), and ODC1 (rs1049500 and rs2302614) was performed on a study sample including 173 suicide attempters with comorbid psychiatric disorders, 216 non-suicidal psychiatric patients and 172 healthy controls from Serbia, and 333 suicide completers and 356 non-suicidal autopsy controls from Slovenia. CA genotype of rs220557 in GRIN2B gene increased the risk for completed suicide (P = 0.021), and violent suicide (P = 0.037), compared to controls. In ODC1 gene, CA genotype of rs2302614 decreased the risk for completed suicide compared to suicide attempt (P = 0.012). Marginally, AC haplotype for variants rs1049500-rs2302614 in ODC1 gene decreased the risk for completed suicide compared to suicide attempt (P = 0.052). Specific genetic variants of glutamate and polyamine systems are differently distributed among diverse suicidal phenotypes, providing further information on the implication of these systems in suicidality.

Insufficient effectiveness and adverse effects of immunosuppressive therapy, seen in around 20% of acetylcholine receptor (AChR) positive myasthenia gravis (MG) patients, highlight the need for new biomarkers. MicroRNAs (miRNAs), small regulatory non-coding RNAs with tissue-specific expression, have emerged as potential biomarkers due to their abundance and accessibility in body fluids. Several miRNAs involved in immune system and drug metabolism have been associated with improvement of neuromuscular status or response to immunosuppressive therapy in AChR-positive MG patients in cross-sectional studies. Here, we explored miRNAs as plasma biomarkers for immunosuppressive therapy response in a prospective longitudinal study of newly diagnosed, drug-naïve patients. Clinical examination and plasma sampling were performed at three time points: baseline (pre-treatment), 6-month, and 12-month follow-ups. miRNA levels were quantified by qPCR. Three out of eight analyzed miRNAs (miR-150-5p, miR-27a-3p, and miR-21-5p) showed treatment-related changes. Among them, miR-150-5p level was negatively correlated with patient functionality (MG Activities of Daily Living score - MG-ADL; p=0.007, ρ_s=-0.433), muscle strength and weakness (Quantitative MG score - QMG; p=0.002, ρ_s=-0.355) and overall symptoms (MG Composite score - MGC; p= 7.814e-5, ρ_s=-0.457). Pre-treatment miR-150-5p levels showed excellent prognostic ability to discriminate responders from non-responders based on achieved minimal clinical expression (AUC=0.85, p=0.0076) and MG-ADL (AUC=0.86, p=0.016) at 12-month follow-up. Predictive performance was also acceptable based on QMG and MGC (AUC=0.74, p=0.001 and AUC=0.73, p=0.0002, respectively). Our findings imply plasma miR-150-5p as a potential biomarker for predicting immunosuppressive therapy response in AChR-positive MG, suggesting its further investigation for disease monitoring and a personalized medicine approach.

Myocardial infarction (MI) is a serious cardiovascular disease and the primary cause of mortality, with a complex etiopathology. Identifying the genetic basis of myocardial infarction (MI) is essential for developing personalized medical treatments. This study examined the possible association between polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and MI. In the study, 120 patients with MI and 120 age-and-sex-matched controls were genotyped for C677T and A1298C MTHFR polymorphisms by the allele-specific or amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). In the case of the C677T polymorphism, the T/T and C/T genotypes were associated with a significantly increased risk of MI under the dominant genetic model (odds ratio (OR)=2.060; P=0.006). Although there was no significant association between the A1298C variant and MI, this polymorphism was linked to a higher level of creatinine in MI patients (P<0.002). A similar association was observed for the C677T polymorphism (P=0.003). An A-T haplotype represented an increased risk for MI (OR=1.630; P=0.014), whereas the A-C haplotype had a protective role (R=0.517; P=0.002). These findings indicate that C677T MTHFR polymorphism is strongly associated with and increased risk of MI, making it a potential genetic risk factor and a possible predictor of MI.