Association of NEF2L2 Rs35652124 Polymorphism with Nrf2 Induction and Genotoxic Stress Biomarkers in Autism.

Increased oxidative/genotoxic stress is known to impact the pathophysiology of ASD (autism spectrum disorder). Clinical studies, however, reported limited, heterogeneous but promising responses to treatment with antioxidant remedies. We determined whether the functional polymorphism of the Nrf2 gene, master regulator of anti-oxidant adaptive reactions to genotoxic stress, links to the genotoxic stress responses and to an in vitro effect of a NRF2 inductor in ASD children. Oxidative stress biomarkers, adaptive responses to genotoxic/oxidative stress, levels of master antioxidant regulator Nrf2 and its active form pNrf2 before and after inducing by dimethyl fumarate (DMF), and promotor rs35652124 polymorphism of NFE2L2 gene encoding Nrf2 were studied in children with ASD (n = 179). Controls included healthy adults (n = 101). Adaptive responses to genotoxicity as indicated by H2AX and cytoprotection by NRF2 contents positively correlated in ASD children with a Spearman coefficient of R = 0.479 in T+, but not CC genotypes. ASD children with NRF2 rs35652124 CC genotype demonstrated significantly higher H2AX content (0.652 vs. 0.499 in T+) and pNrf2 induction by DMF, lowered 8-oxo-dG concentration in plasma and higher cfDNA/plasma nuclease activity ratio. Our pilot findings suggest that in ASD children the NEF2L2 rs35652124 polymorphism impacts adaptive responses that may potentially link to ASD severity. Our data warrant further studies to reveal the potential for NEF2L2 genotype-specific and age-dependent repurposing of DMF and/or other NRF2-inducing drugs.

Non-suicidal self-injuries and suicide risk in adolescent girls with eating disorders: associations with weight control, body mass index, and interpersonal sensitivity.

BACKGROUND: Eating disorders (EDs) are associated with a risk of premature death, as well as suicidal and self-injurious behavior. A low or high body mass index (BMI) and weight control behavior can also have an impact on self-injurious and suicidal behavior. While some studies show that interpersonal sensitivity is a risk factor for EDs, affective disorders, and self-injurious behavior, in-depth studies of these issues have not been done. AIM: The present study investigates how self-injurious and suicidal behavior relate to weight control behavior, BMI, and interpersonal sensitivity in adolescent girls from a clinical population with diagnosed EDs compared with adolescent girls from the general population. METHODS: The main group was comprised of 31 girls with a diagnosis of ED (as the main diagnosis or co-occurring with affective disorders, M=151.13 years), being treated in in the Eating Disorder Clinic of the Scientific and Practical Center for Mental Health of Children and Adolescents named after G.E. Sukhareva. The comparison group consisted of 27 adolescent girls recruited from Proton Educational Center (M=15.511.09 years). The measures included a qualitative survey that yielded data on weight control behavior, and self-injurious behavior, a Blitz questionnaire probing the suicide risk (used only in the main group), and the Interpersonal Sensitivity Measure. Height and weight data were also recorded for BMI calculation. RESULTS: The qualitative analysis of weight control behavior yielded the following results: purging behavior, restrictive behavior, and corrective behavior. Participants in the main group used purging and restrictive behavior more often, whereas participants in the comparison group used strategies associated with a healthy lifestyle. The main group and participants who practiced purging and restrictive weight control in the overall sample had the smallest BMI. Self-injurious behavior was approximately evenly distributed both amongst the main and comparison groups. Self-cutting was the most prevalent type of self-injury. In the main group, self-injury was associated with a smaller BMI, while in the comparison group it was associated with an increase in the fear of rejection and overall interpersonal sensitivity. Based on the assessment of the suicide risk, six participants in the main group were deemed high-risk; they also displayed increased fear of rejection, dependence on the assessments of others, and overall interpersonal sensitivity. All girls in the suicide risk subgroup had non-suicidal self-injuries. CONCLUSION: The results of our study broaden our understanding of the risk factors of suicidal and self-injurious behavior in adolescent girls with EDs and reveal the characteristics of the type of weight control behavior used by this group in comparison with adolescent girls in the general population. Girls with EDs who were considered at the risk of committing suicide demonstrated high interpersonal sensitivity, which provides a rationale for further studying the general interpersonal mechanisms that underlie the pathogenesis of EDs, as well as that of self-injurious and suicidal behavior.

Treatment challenges and health conditions among people living with HIV with or without substance use disorder in the Russian Federation.

We quantified treatment challenges faced by people living with HIV (PLHIV) in Russia. Cross-sectional data of 150 PLHIV in Russia were from the 2019 Positive Perspectives Survey. Mean age was 38.3 y. Two-thirds (68.0%[102/150]) had ever disguised their HIV pills, and 43.3%[65/150] said they would be stressed if someone saw their HIV pills. Overall, 14.7%[22/150] reported being ever diagnosed with substance use disorder (SUD). Self-rated optimal health was significantly lower among those with vs without a report of SUD on multiple health domains: sexual (40.9%[9/22] vs. 70.3%[90/128], p = 0.007), physical (22.7%[5/22] vs. 68.0%[87/128], p < 0.001), and overall health (27.3%[6/22] vs. 68.8%[88/128], p < 0.001). Those reporting SUD were more likely to miss HIV medication ≥ 1 time in the past month because they used recreational drugs (age and gender-adjusted prevalence ratio [APR] = 8.23, 95%CI = 6.99-9.68), could not afford their medication (APR = 3.28, 95%CI = 2.90-3.72), had to work (APR = 3.27, 95%CI = 2.97-3.60), or to avoid side effects (APR = 2.62, 95%CI = 2.37-2.89). Furthermore, self-reported SUD was strongly associated with numerous poor health conditions, including self-reported diagnosis of cancer (APR = 6.67, 95%CI = 5.24-8.48), mental illness (APR = 5.01, 95%CI = 4.53-5.55), and liver disease (APR = 4.29, 95%CI = 3.98-4.61). The distinct patterns of poorer health-related outcomes among PLHIV with SUD underscore the need to address behavioral and psychosocial challenges as part of holistic HIV care.

Oxidized cell-free DNA as a stress-signaling factor activating the chronic inflammatory process in patients with autism spectrum disorders.

BACKGROUND: Autism spectrum disorders (ASD) are known to be associated with an inflammatory process related to immune system dysfunction. This study's aim was to investigate the role of cell-free DNA in chronic inflammatory process in ASD patients. METHODS: The study included 133 ASD patients and 27 healthy controls. Sixty-two ASD patients were demonstrated to have mild-to-moderate disease severity (group I) and 71 individuals to have severe ASD (group II). Plasma cell-free (cf) DNA characteristics, plasma cytokine concentrations, expression of the genes for NFкB1 transcription factor and pro-inflammatory cytokines TNFα, IL-1ß and IL-8 in peripheral blood lymphocytes (PBL) of ASD patients, and unaffected controls were investigated. Additionally, in vitro experiments with oxidized DNA supplementation to PBL cultures derived from ASD patients and healthy controls were performed. RESULTS: The data indicates that ASD patients have demonstrated increased cfDNA concentration in their circulation. cfDNA of patients with severe ASD has been characterized by a high abundance of oxidative modification. Furthermore, ASD patients of both groups have shown elevated plasma cytokine (IL-1ß, IL-8, IL-17A) levels and heightened expression of genes for NFкB1 nuclear factor and pro-inflammatory cytokines TNFα, IL-1ß, and IL-8 in PBL. In vitro experiments have shown that NF-κB/cytokine mRNA expression profiles of ASD patient PBL treated with oxidized DNA fragments were significantly different from those of healthy controls. CONCLUSIONS: It may be proposed that oxidized cfDNA plays a role of stress-signaling factor activating the chronic inflammatory process in patients with ASD.