HIV-1-infected T cell clones are shared across cerebrospinal fluid and blood during ART.

The central nervous system HIV reservoir is incompletely understood and is a major barrier to HIV cure. We profiled people with HIV (PWH) and uninfected controls through single-cell transcriptomic and T cell receptor (TCR) sequencing to understand the dynamics of HIV persistence in the CNS. In PWH on ART, we found that most participants had single cells containing HIV-1 RNA, which was found predominantly in CD4 central memory T cells, in both cerebrospinal fluid (CSF) and blood. HIV-1 RNA-containing cells were found more frequently in CSF than blood, indicating a higher burden of reservoir cells in the CNS than blood for some PWH. Most CD4 T cell clones containing infected cells were compartment specific, while some (22%) - including rare clones with members of the clone containing detectable HIV RNA in both blood and CSF - were found in both CSF and blood. These results suggest that infected T cells trafficked between tissue compartments and that maintenance and expansion of infected T cell clones contributed to the CNS reservoir in PWH on ART.

Neurosyphilis is characterized by a compartmentalized and robust neuroimmune response but not by neuronal injury.

BACKGROUND: Neurosyphilis is increasing in prevalence but its pathophysiology remains incompletely understood. This study assessed for CNS-specific immune responses during neurosyphilis compared to syphilis without neurosyphilis and compared these immune profiles to those observed in other neuroinflammatory diseases. METHODS: Participants with syphilis were categorized as having neurosyphilis if their cerebrospinal fluid (CSF)-venereal disease research laboratory (VDRL) test was reactive and as having syphilis without neurosyphilis if they had a non-reactive CSF-VDRL test and a white blood cell count <5/µL. Neurosyphilis and syphilis without neurosyphilis participants were matched by rapid plasma reagin titer and HIV status. CSF and plasma were assayed for markers of neuronal injury and glial and immune cell activation. Bulk RNA sequencing was performed on CSF cells, with results stratified by the presence of neurological symptoms. FINDINGS: CSF neopterin and five CSF chemokines had levels significantly higher in individuals with neurosyphilis compared to those with syphilis without neurosyphilis, but no markers of neuronal injury or astrocyte activation were significantly elevated. The CSF transcriptome in neurosyphilis was characterized by genes involved in microglial activation and lipid metabolism and did not differ in asymptomatic versus symptomatic neurosyphilis cases. CONCLUSIONS: The CNS immune response observed in neurosyphilis was comparable to other neuroinflammatory diseases and was present in individuals with neurosyphilis regardless of neurological symptoms, yet there was minimal evidence for neuronal or astrocyte injury. These findings support the need for larger studies of the CSF inflammatory response in asymptomatic neurosyphilis. FUNDING: This work was funded by the National Institutes of Health, grants K23MH118999 (S.F.F.) and R01NS082120 (C.M.M.).

Sleep deficiency among people living with human immunodeficiency virus: A growing challenge.

PURPOSE OF REVIEW: The purpose of this narrative review is to consolidate and summarize the existing literature on sleep deficiency among people living with human immunodeficiency virus (HIV; PLWH), to discuss the potential impact of antiretroviral therapy on sleep deficiency and to identify priorities for future research in this area. RECENT FINDINGS: Three important domains of sleep deficiency include alterations in sleep quality (including sleep disorders), duration and timing. The existing HIV and sleep deficiency literature, which is robust for sleep quality but sparser for sleep duration or sleep timing, has identified epidemiological correlates and outcomes associated with sleep deficiency including sociodemographic factors, HIV-specific factors, aspects of physical and mental health and cognition. SUMMARY: Sleep deficiency is a common problem among PLWH and is likely underdiagnosed, although more high-quality research is needed in this area. Sleep quality has received the most attention in the literature via methodologies that assess subjective/self-reported sleep quality, objective sleep quality or both. There is significantly less research on sleep duration and minimal research on sleep timing. Use of certain antiretroviral therapy drugs may be associated with sleep deficiency for some individuals. Future research should utilize larger, longitudinal studies with consistent, comprehensive and validated methods to assess both subjective and objective measures of sleep deficiency to better understand the prevalence, correlates and clinical implications of sleep deficiency in PLWH.

Self-Reported Neuropsychiatric Post-COVID-19 Condition and CSF Markers of Neuroinflammation.

This case-control study assesses cerebrospinal fluid markers of neuroinflammation and blood-brain barrier disruption in individuals with post­COVID-19 condition who reported neuropsychiatric symptoms.

Associations Between Bullying and Condition Severity Among Youth With Chronic Health Conditions.

PURPOSE: Children with chronic conditions are at increased risk of bullying involvement. In addition to examining associations between chronic health conditions and both victimization and perpetration, this study investigated whether condition severity is associated with bullying involvement. METHODS: A secondary analysis of the 2018-2019 National Survey of Children's Health was performed. Children ages six-17 (n = 42,716) were classified as perpetrators (if bullied others ≥one-two times/month), victims-only (if victimized ≥one-two times/month and not a perpetrator) or uninvolved in bullying (neither perpetrator nor victim-only). Survey-weighted multinomial logistic regressions were used to investigate associations between bullying involvement and 13 chronic medical and developmental/mental health conditions. For children with conditions associated with being a victim and/or perpetrator, multinomial logistic regressions were used to further investigate associations between condition severity and victimization or perpetration. RESULTS: All 13 conditions were associated with higher odds of victimization. Seven developmental/mental health conditions were associated with higher odds of perpetration. Condition severity was associated with at least one domain of bullying involvement for one chronic medical and six developmental/mental health conditions. Notably, among children with attention-deficit/hyperactivity disorder, learning disability, or anxiety, condition severity was associated with higher odds of being a victim or bully/bully-victim. DISCUSSION: Condition severity may be a risk-factor for bullying involvement for many developmental/mental health conditions. Future condition-specific analyses are needed that directly examine bullying involvement among children with varying severity of individual conditions like attention-deficit/hyperactivity disorder, learning disability, and anxiety, using a clear operational definition for bullying, objective measures of condition severity, and multiple informants of bullying involvement.

Characterization of the tilt (tt) phenotype in Drosophila melanogaster.

In the early 20th century, Calvin Bridges and Thomas Morgan identified a number of spontaneous mutations that displayed visible phenotypes in adult flies and subsequent analysis of these mutations over the past century have provided fundamental insights into subdisciplines of biology such as genetics, developmental, and cell biology. One of the mutations they identified in 1915 was named tilt ( tt ) and was described by Bridges and Morgan as having two visible phenotype characteristics in the wing. The wings were "held out at a wider angle from the body" and had a break in wing vein L3. Subsequent analysis of the tilt phenotype identified another phenotype: the wings were missing a varying number of campaniform sensilla on L3. Though Bridges and Morgan provided an ink drawing of the wing posture phenotype, only the vein and campaniform sensilla loss images have been published. Here we confirm and document the tilt phenotypes that have been previously described. We also show the penetrance of these phenotypes: the vein break and the distinct outward wing posture have decreased since its discovery.

Wandering behavior in children with autism spectrum disorder and other developmental disabilities.

PURPOSE OF REVIEW: Approximately one in four children with autism spectrum disorder (ASD) 'elope' or wander away from supervision each year; however, many caregivers do not receive adequate information on how to address wandering behavior. The purpose of this review is to summarize the available research on elopement frequency, wandering patterns, and interventions to provide pediatricians and other childcare professionals with appropriate strategies to address wandering behavior. RECENT FINDINGS: Despite the high prevalence of wandering by children with ASD or other developmental disabilities, there is relatively limited research in this area. Recent research has identified common patterns and factors associated with risk of elopement and elopement frequency. SUMMARY: Pediatricians should counsel families on the common issues and intervention strategies related to elopement. By increasing awareness of wandering in children with ASD, caregivers can feel better prepared to make informed decisions regarding their child's wellbeing and safety.

Reporting of child maltreatment during the SARS-CoV-2 pandemic in New York City from March to May 2020.

BACKGROUND: School closures and other public health responses have decreased the extent that children interact with mandated reporters and other professionals trained to detect child maltreatment. OBJECTIVE: To assess associations between the pandemic public health response and the number of allegations of child abuse or neglect. METHODS: This study analyzed monthly data from New York City of the number of child maltreatment allegations, stratified by reporter type (e.g., mandated reporter, education personnel, healthcare personnel), as well as the number of Child Protective Services (CPS) investigations warranting child welfare preventative services. SARIMA models were trained using data from January 2015 to February 2020 to predict expected values for March, April, and May 2020. Observed values were compared against predicted values at an alpha of .05. RESULTS: Substantially fewer allegations of child maltreatment were reported than expected in March (-28.8 %, deviation: 1848, 95 % CI: [1272, 2423]), April (-51.5 %, deviation: 2976, 95 % CI: [2382, 3570]), and May 2020 (-46.0 %, deviation: 2959, 95 % CI: [2347, 3571]). Significant decreases in child maltreatment reporting were also noted for all reporter subtypes examined for March, April, and May 2020. Fewer CPS investigations warranted preventative services than expected in March 2020 (-43.5 %, deviation: 303, 95 % CI: [132, 475]). CONCLUSIONS: Precipitous drops in child maltreatment reporting and child welfare interventions coincided with social distancing policies designed to mitigate COVID-19 transmission. In light of these findings, educators and healthcare providers must be especially vigilant when engaging online with children and their families for signs of child abuse and/or neglect.