👤 Christina Damgaard Buch

Opioid use is disproportionately high among People with HIV (PWH). Although combined anti-retroviral therapy (ART) can dampen HIV-associated dementia, a large fraction of PWH continue to experience neurocognitive deficits which are further exacerbated by opioid use. In the present study, we performed single cell transcriptomic profiling of cerebrospinal fluid (CSF) immune cells to explore their functional characteristics in opioid mediated neurological disorders among PWH using the SIV/rhesus macque model. In this study, we utilized CSF cells from morphine- and saline-administered, SIV-infected, ART-treated rhesus macaques (RMs). The CSF scRNA-Seq was performed longitudinally at baseline, post ramp-up with morphine (pre-infection), during acute infection, and after suppression of viremia to profile cell-specific transcriptomic signatures that mirror the CNS pathogenesis observed in opioid-dependent PWH. We observed the presence of all major immune cells in CSF, including CD4 + T Chronic opioid exposure reprograms CSF monocytes toward a DAM state that persists despite ART-mediated viral suppression, driving maladaptive immune-glial crosstalk and progressive neurocognitive dysfunction in morphine-dependent macaques with possible implications for neuroinflammation and neurodegenerative disorders that are observed in PWH. Show less

Hereditary multiple osteochondromas (HMO) is a genetic skeletal disorder caused by defects in exostosin glycosyltransferase 1 (EXT1) or 2 (EXT2) genes. It develops mainly in the growth period and causes multiple osteochondromas (OC) in the physis of the long bones, leading to discomfort and deformities. This study aimed to investigate the anatomical distribution of OC, the frequency of deformities of the lower limbs, scoliosis and surgeries performed in a cohort of patients with HMO at the time of their enrolment in a regional surveillance programme. The study population included HMO patients from the Centre of Heritable and Complex Diseases (CAKS) in the Region of Southern Denmark. Information on surgical procedures and age at the time of diagnosis was obtained from medical records, while deformities were evaluated on early-onset scoliosis (EOS) scans from time of enrolment in the CAKS. A total of 54 patients were included and 44 patients (82%) had an EOS scan. All except one (98%) HMO patient had OC in the knees at the time of their EOS scan. A total of 12 patients (27%) had leg length discrepancy, 30 (68%) had genu varum or valgum and 13 (30%) had scoliosis. The HMO patients had undergone a median of 2.0 (0-14) surgeries, where a median of four (1-23) OC were removed, mostly in the lower limb (68%). The majority of HMO patients in this cohort suffered from major anatomical burdens, leading to multiple surgeries and deformities. We suggest that a programme, such as the CAKS surveillance programme, may be beneficial to screening and follow-up of OC and deformities in patients with HMO. None. Not relevant. Show less

As per the National Survey on Drug Use and Health, 10.5% of Americans aged 12 years and older are suffering from alcohol use disorder, with a wide range of neurological disorders. Alcohol-mediated neurological disorders can be linked to Alzheimer's-like pathology, which has not been well studied. We hypothesize that alcohol exposure can induce astrocytic amyloidosis, which can be corroborated by the neurological disorders observed in alcohol use disorder. In this study, we demonstrated that the exposure of astrocytes to ethanol resulted in an increase in Alzheimer's disease markers-the amyloid precursor protein, Aβ1-42, and the β-site-cleaving enzyme; an oxidative stress marker-4HNE; proinflammatory cytokines-TNF-α, IL1β, and IL6; lncRNA BACE1-AS; and alcohol-metabolizing enzymes-alcohol dehydrogenase, aldehyde dehydrogenase-2, and cytochrome P450 2E1. A gene-silencing approach confirmed the regulatory role of lncRNA BACE1-AS in amyloid generation, alcohol metabolism, and neuroinflammation. This report is the first to suggest the involvement of lncRNA BACE1-AS in alcohol-induced astrocytic amyloid generation and alcohol metabolism. These findings will aid in developing therapies targeting astrocyte-mediated neurological disorders and cognitive deficits in alcohol users. Show less