Moderate-to-severe cognitive impairment is associated with both recent and chronic alcohol misuse in people with HIV: The New Orleans alcohol use in HIV (NOAH) study.

BACKGROUND: Human immunodeficiency virus (HIV) profoundly impacts the nervous system, leading to neurological deficits including HIV-associated neurocognitive disorder (HAND). HAND represents the most common neurological comorbidity among people with HIV (PWH), and alcohol use may exacerbate cognitive deficits, especially in vulnerable populations. This study investigated relationships between alcohol use and cognition in an underserved cohort of PWH, on the hypothesis that alcohol misuse exacerbates cognitive deficits. METHODS: Data collected from participants (n = 259; 66.7% male; mean age 52 ± 10 years) enrolled in the New Orleans Alcohol Use in HIV (NOAH) study were utilized for cross-sectional analysis. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), and alcohol use was comprehensively measured using four metrics: the Alcohol Use Disorders Identification Test (AUDIT), 30-day timeline follow back (TLFB), lifetime drinking history, and phosphatidylethanol (PEth) levels. RESULTS: The average MoCA score among participants was 20.7 ± 4.5, with 86.5% demonstrating cognitive impairment (MoCA < 26). Individuals with MoCA scores below 18 (moderately or severely cognitively impaired) had a higher frequency of recent severe alcohol misuse and greater lifetime alcohol consumption. Participants at increased risk for AUD (AUDIT ≥ 16) also had worse global cognition and memory task performance than those with lower AUDIT scores; this was particularly true among those aged 50 and older. Analysis of the MoCA sub-score data indicated that participants with increased AUD risk had impairments in the cognitive domains of language and memory. CONCLUSIONS: Our findings demonstrate a high prevalence of cognitive impairment in the NOAH cohort and suggest that alcohol misuse contributes to global cognitive deficits in PWH, especially among individuals aged 50 and older. Further exploration of the impact of alcohol use on specific cognitive domains, including memory and language, should incorporate additional cognitive tasks. These findings highlight the importance of considering alcohol use and AUD risk as significant factors that may exacerbate cognitive deficits in vulnerable populations, including older PWH.

The COVID-19 pandemic and its impacts on mass shootings in six major US cities.

BACKGROUND: The COVID-19 pandemic has significant impacts on the US socioeconomic structure. Gun violence is a major public health issue and the effects on this area have not been well-elucidated. The objective of this study was to determine the impacts of the pandemic on mass shootings in six major United States cities with historically high rates of gun violence. METHODS: Mass shooting data were extracted from an open-source database, Gun Violence Archive. Mass shooting was defined as four or more people shot at a single event. Data from six cities with the highest incidence of mass shootings were analyzed in 2019 versus 2020 (Baltimore, Chicago, Detroit, New Orleans, Philadelphia, and St. Louis). Geographic data were examined to assess changes in each city's mass shooting geographic distribution over time. Quantitative changes were assessed using the Area Deprivation Index (ADI), and qualitative data were assessed using ArcGIS. RESULTS: In 2020, the overall percentage of mass shootings increased by 46.7% though there was no change in the distribution of these events when assessed quantitatively (no change in average ADI) nor qualitatively (using ArcGIS). In the six cities analyzed, the total proportion of mass shooting events was unchanged during the pandemic (21.8% vs 20.6%, p = 0.64). Chicago, the US city with the highest incidence of mass shootings, did not experience a significant change in 2020 (n = 34/91, 37.3% vs. n = 53/126, 42.1%, p = 0.57). Baltimore had a significant decrease in mass shooting events (n = 18/91, 19.8% vs. 10/126, 7.9%, p = 0.01). The other four cities had no significant change in the number of mass shootings (p>0.05). CONCLUSION: This study is the first to use ArcGIS technology to describe the patterns of mass shooting in six major US cities during the COVID-19 pandemic. The number of mass shootings in six US cities remained largely unchanged which suggests that changes in mass shootings is likely occurring in smaller cities. Future studies should focus on the changing patterns of homicides in at-risk communities and other possible social influences.

Immunomodulatory potential of in vivo natural killer T (NKT) activation by NKTT320 in Mauritian-origin cynomolgus macaques.

Invariant natural killer T-lymphocytes (iNKT) are unique immunomodulatory innate T cells with an invariant TCRα recognizing glycolipids presented on MHC class-I-like CD1d molecules. Activated iNKT rapidly secrete pro-and anti-inflammatory cytokines, potentiate immunity, and modulate inflammation. Here, we report the effects of in vivo iNKT activation in Mauritian-origin cynomolgus macaques by a humanized monoclonal antibody, NKTT320, that binds to the invariant region of the iNKT TCR. NKTT320 led to rapid iNKT activation, increased polyfunctionality, and elevation of multiple plasma analytes within 24 hours. Flow cytometry and RNA-Seq confirmed downstream activation of multiple immune subsets, enrichment of JAK/STAT and PI3K/AKT pathway genes, and upregulation of inflammation-modulating genes. NKTT320 also increased iNKT frequency in adipose tissue and did not cause iNKT anergy. Our data indicate that NKTT320 has a sustained effect on in vivo iNKT activation, potentiation of innate and adaptive immunity, and resolution of inflammation, which supports its future use as an immunotherapeutic.

Expanding the clinical and metabolic phenotype of DPM2 deficient congenital disorders of glycosylation.

Pathogenic alterations in the DPM2 gene have been previously described in patients with hypotonia, progressive muscle weakness, absent psychomotor development, intractable seizures, and early death. We identified biallelic DPM2 variants in a 23-year-old male with truncal hypotonia, hypertonicity, congenital heart defects, intellectual disability, and generalized muscle wasting. His clinical presentation was much less severe than that of the three previously described patients. This is the second report on this ultra-rare disorder. Here we review the characteristics of previously reported individuals with a defect in the DPM complex while expanding the clinical phenotype of DPM2-Congenital Disorders of Glycosylation. In addition, we offer further insights into the pathomechanism of DPM2-CDG disorder by introducing glycomics and lipidomics analysis.