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Background: Diabetic peripheral neuropathy (DPN) is a chronic microvascular complication in diabetic mellitus patients due to chronic hyperglycemia, resulting in platelet hyperactivity and dyslipidemia. Alpha-lipoic acid (ALA) is a potent antioxidant which has antiplatelet activity and lipid-modulating characteristics and plays a major role in the prevention of disease progression. Aim: To evaluate the effect of ALA on inhibition of platelet aggregation and lipid profile. Settings and Design: This was a prospective, randomized, double-blind, placebo-controlled study conducted at the Department of Clinical Pharmacology and Therapeutics at a tertiary care hospital. Materials and Methods: We recorded efficacy parameters including changes in inhibition of platelet aggregation, lipid profile, blood sugars, and glycated hemoglobin over 12 weeks of ALA (600 mg once daily orally) supplementation in DPN patients on gabapentin (300 mg twice daily [BD]) or pregabalin (75 mg BD) compared to placebo. We used Student's t-test paired and unpaired for within-group and between-group comparisons, respectively. Results: A total of 52 study participants (males = 22, females = 30) with a mean age 55.63 ± 7.5 years were randomized to receive either ALA or placebo. Between-group analysis at 12 weeks showed that ALA significantly inhibited both collagen-induced platelet aggregation (from 32.61 ± 8.00 to 24.88 ± 5.30; P < 0.001) and adenosine diphosphate-induced platelet aggregation (from 34.00 ± 6.97 to 25.96 ± 6.45; P < 0.001) compared to placebo. Significant reduction in total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglycerides was found in the ALA group at 12 weeks compared to baseline. No serious adverse events were reported. Conclusion: ALA, an antioxidant, demonstrated a protective effect against DPN by the virtue of its inhibitory effect on platelet aggregation and lipid-modulating effects and was found to have good safety. [ABSTRACT FROM AUTHOR]

We present a genotypic analysis of 108 DMD/BMD patients from India (64), South Africa (41) and Brazil (3), recruited through the International Centre for Genomic Medicine in Neuromuscular Diseases. 106/108 (98%) attained a genetic diagnosis (81 DMD, 23 BMD, 2 symptomatic females), through multiplex ligation probe amplification (91) or whole exome sequencing (WES) (15). 85 (80%) had deletions (del), 12 (11%) nonsense variants (NV), 7 (7%) duplications (dup), and 2 (2%) splice variants (SV). All BMD patients had in frame del/dup. The prevalence of different types of DMD variants varied significantly between India and South Africa (p=<0.001), with a higher prevalence of del in India (94% vs 60%). Two solved Brazilian patients had both a del and a NV. Exons 45-50 and 10-20 were del/dup hotspots, as a result of the recurrent intronic del/dup breakpoints 45 (29/92), 46 (10/92) and 48 (15/92). Cumulatively, introns 45-48 were breakpoints in 59% of 54 cases of del/dup. 74% of these were from India vs 24% from South Africa. We found a higher proportion of del/dup with 5' breakpoints (before exon 10) in the South African cohort (9/31), vs the Indian one (3/60). WES identified two novel pathogenic DMD variants (1 SV, 1 del). 52% of patients with del (33 Indian and 11 South African) are amenable to antisense oligonucleotide mediated exon skipping therapies (ASO), 29 amenable to licenced ASO targeting exons 45 (9 pts), 51 (14 pts) and 53 (5 pts); One patient had an exon 52 del amenable to exon 51 or 53 skipping. Of the remaining 15 patients, 40% would be amenable to skipping of exon 44, an ASO currently in clinical trials. Our data highlights potential genotypic differences between South African and Indian DMD/BMD cohorts and a notable lack of dup and lower proportion of 5' region del/dup in the Indian cohort. These findings may have implications for clinical trial and therapeutic eligibility. [ABSTRACT FROM AUTHOR]

Background: Neuromyelitis optica (NMO) is an autoimmune demyelinating disorder, mainly characterized by severe optic neuritis, transverse myelitis and the high levels of antibodies against NMO-immunoglobulin G (IgG) or aquaporin-4 (AQP4). HLA-DR and HLA-DQ alleles within the HLA class II region on chromosome 6p21 are known to play a significant role in several autoimmune diseases including NMO. The rationale of the current case-control study is to explore the association of HLA-DRB1 and HLA-DQB1 alleles with the risk of NMO and its association with the clinical and serological markers., Methods: A total of 158 samples (38 NMO cases and 120-age and ethnicity matched controls) were genotyped for the HLA-DRB1 and HLA-DQB1 alleles by using PCR-SSP method., Results: Our analysis showed significant association of HLA-DRB1*10 allele (OR 2.63, 95% CI: 1.18-5.83, p=0.02) with NMO whereas DRB1*14 showed protective role against NMO (OR 0.33: 95% CI: 0.11-0.94, p=0.043). HLA-DRB1*10 allele also showed significant association in patients with NMO-IgG positive antibody (OR 3.28: 95% CI: 1.42-7.5, p=0.006). There was no association of HLA DQB1 alleles with NMO and also with NMO-IgG antibody. Among the haplotypes groups, HLA-DRB1*10-DQB1*05 (OR 2.61, 95% CI: 1.11-6.1, p=0.03), HLA-DRB1*15-DQB1*03 (OR 4.5, 95% CI: 1.81-11.5, p=0.001) were strongly associated with the risk of NMO, whereas DRB1*14-DQB1*05 (OR 0.20, 95% CI: 0.060-0.721, p=0.008) showed negative association with NMO., Conclusion: From this study, it is concluded that the HLA-DRB1*10 and DRB1*10-DQB1*05 and HLA-DRB1*15-DQB1*03 haplotypes may influence the susceptibility to NMO among the South Indians. Additionally we found DRB1*14 allele and DRB1*14-DQB1*05 haplotype showed protective role for NMO., Competing Interests: None