Prevalence of detectable HIV-DNA and -RNA in cerebrospinal fluid of youth with perinatal HIV and impaired cognition on antiretroviral therapy.

OBJECTIVE: Central nervous system (CNS) HIV infection can impact cognition and may be an obstacle to cure in adolescents and young adults with perinatal HIV (AYAPHIV). IMPAACT2015 enrolled AYAPHIV on suppressive antiretroviral therapy (ART) with cognitive impairment to detect and quantify HIV in blood and cerebrospinal fluid (CSF). DESIGN: IMPAACT2015 was a U.S.-based multi-site, exploratory, observational study. METHODS: Cognitive impairment was defined as NIH Toolbox Fluid Cognition Composite score (FCCS) > 1 standard deviation below age-adjusted normative group mean. Cell-free HIV-RNA and cell-associated HIV pol/gag -DNA and 10 biomarkers of inflammation/neuronal injury were measured in paired CSF and blood. ART exposure concentrations were quantified in hair. RESULTS: Among 24 participants, 20 had successful CSF collection and 18 also met viral suppression criteria. 9/18 (50%) were female sex-at-birth, 14/18 (78%) were Black. Median (range) age was 20 years (13-27), time on ART 18.3 years (8.0-25.5), and FCCS 68 (53-80). HIV-DNA was detected in PBMCs from all participants. In CSF, 2/18 (11%, 95% CI: 1.4-34.7%) participants had detectable cell-free HIV-RNA, while HIV gag or pol -DNA was detectable in 13/18 (72%, 95% CI: 47-90%). Detectable HIV-DNA in CSF was associated with male sex-at-birth (p = 0.051), lower CD4 count at enrollment (p = 0.016), and higher PBMC HIV pol -DNA copies (p = 0.058). Hair antiretroviral concentrations and biomarkers were not associated with CSF HIV-DNA detection. CONCLUSIONS: We found a high proportion of AYAPHIV with neurocognitive impairment had CSF cells harboring HIV-DNA during long-term virologic suppression. This evidence of persistent HIV-DNA in CSF suggests that the CNS should be considered in treatment and cure studies.

Psychosocial and palliative care in African national cancer control plans: A qualitative study.

OBJECTIVE: Low and middle income countries of Africa account for a disproportionate amount of the global health burden of cancer. Providing patients access to psychosocial oncology and palliative care through policy structures such as the National Cancer Control Plans (NCCP) is essential to improving the care provided to patients and their families. The first phase of this study sought to determine the extent to which palliative care and psychosocial oncology were integrated in NCCPs in African countries. METHODS: A qualitative thematic analysis of the plans was used using Nvivo, with two-raters coding and continuous team discussions. Data were organized into an infographic map showing the coverage of themes across African countries. RESULTS: Fifty-eight NCCPs and NCD plans were analyzed in the 54 countries in Africa. The findings illustrate a lack of standardization across countries' NCCPs in addressing psychosocial oncology and palliative care themes. Certain areas presented good coverage across several plans, such as barriers to access, education, awareness, and health behaviors, coordination of care, families, caregivers and community involvement, and palliative care. Other themes presented low coverage, such as doctor-patient communication, mental health, bereavement, psychosocial care, survivorship care, and traditional medicine. CONCLUSIONS: One may consider further developing NCCP areas as they pertain to psychosocial oncology and palliative care to ensure their proper place on the policy agenda for a healthier Africa.

EMG-projected MEG High-Resolution Source Imaging of Human Motor Execution: Brain-Muscle Coupling above Movement Frequencies.

Magnetoencephalography (MEG) is a non-invasive functional imaging technique for pre-surgical mapping. However, movement-related MEG functional mapping of primary motor cortex (M1) has been challenging in presurgical patients with brain lesions and sensorimotor dysfunction due to the large numbers of trails needed to obtain adequate signal to noise. Moreover, it is not fully understood how effective the brain communication is with the muscles at frequencies above the movement frequency and its harmonics. We developed a novel Electromyography (EMG)-projected MEG source imaging technique for localizing M1 during ~1 minute recordings of left and right self-paced finger movements (~1 Hz). High-resolution MEG source images were obtained by projecting M1 activity towards the skin EMG signal without trial averaging. We studied delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), and gamma (30-90 Hz) bands in 13 healthy participants (26 datasets) and two presurgical patients with sensorimotor dysfunction. In healthy participants, EMG-projected MEG accurately localized M1 with high accuracy in delta (100.0%), theta (100.0%), and beta (76.9%) bands, but not alpha (34.6%) and gamma (0.0%) bands. Except for delta, all other frequency bands were above the movement frequency and its harmonics. In both presurgical patients, M1 activity in the affected hemisphere was also accurately localized, despite highly irregular EMG movement patterns in one patient. Altogether, our EMG-projected MEG imaging approach is highly accurate and feasible for M1 mapping in presurgical patients. The results also provide insight into movement related brain-muscle coupling above the movement frequency and its harmonics.

Neuropsychological Correlates of Adherence in Youth with Behaviorally Acquired HIV.

Youth living with behaviorally acquired HIV (YLWH) are at-risk for both neuropsychological disorders and antiretroviral therapy (ART) non-adherence; little is known about their interrelationship over time in YLWH. Neuropsychological and psychiatric functioning, substance use, and self-report of 7-day/week and weekend ART adherence were assessed at baseline and Weeks 24, 48, 96 and 144 of a longitudinal study evaluating the impact of early (CD4>350) versus standard of care (CD4≤350) treatment initiation on neuropsychological functioning in 111 treatment-naïve YLWH age 18-24 years at entry. Bayesian multi-level models for adherence (≥ 90% vs. <90%) were fit using random intercepts for repeated measures. Adjusted odds ratios (OR [95% credible interval]) for higher versus lower baseline Motor function for visit adherence were 0.58 (0.25, 1.16), 0.5 (0.15, 1.38), 0.52 (0.16, 1.52), and 0.94 (0.3, 2.8) at Weeks 24, 48, 96, and 144, respectively. Week 24 adherence was associated with higher adjusted odds of Motor function at Week 48 (week: 0.27, -0.05-0.59; weekend: 0.28, -0.07-0.62). Week 96 Complex Executive functioning was associated with higher adjusted odds of adherence at Week 144, OR = 4.26 (1.50, 14.33). Higher Motor functioning emerged most consistently associated with lower odds of adherence in YLWH. Complex Executive functioning was associated with adherence only at end of study, suggesting potential contribution in adherence over the long-term.

Magnetoencephalogram-based brain-computer interface for hand-gesture decoding using deep learning.

Advancements in deep learning algorithms over the past decade have led to extensive developments in brain-computer interfaces (BCI). A promising imaging modality for BCI is magnetoencephalography (MEG), which is a non-invasive functional imaging technique. The present study developed a MEG sensor-based BCI neural network to decode Rock-Paper-scissors gestures (MEG-RPSnet). Unique preprocessing pipelines in tandem with convolutional neural network deep-learning models accurately classified gestures. On a single-trial basis, we found an average of 85.56% classification accuracy in 12 subjects. Our MEG-RPSnet model outperformed two state-of-the-art neural network architectures for electroencephalogram-based BCI as well as a traditional machine learning method, and demonstrated equivalent and/or better performance than machine learning methods that have employed invasive, electrocorticography-based BCI using the same task. In addition, MEG-RPSnet classification performance using an intra-subject approach outperformed a model that used a cross-subject approach. Remarkably, we also found that when using only central-parietal-occipital regional sensors or occipitotemporal regional sensors, the deep learning model achieved classification performances that were similar to the whole-brain sensor model. The MEG-RSPnet model also distinguished neuronal features of individual hand gestures with very good accuracy. Altogether, these results show that noninvasive MEG-based BCI applications hold promise for future BCI developments in hand-gesture decoding.

Association of Perceived Social Support with Viral Suppression Among Young Adults with Perinatally-Acquired HIV in the US-based Pediatric HIV/AIDS Cohort Study (PHACS).

Purpose: To determine the relationship between perceived social support and viral suppression among young adults with perinatally-acquired HIV (YAPHIV). Participants and Methods: We included YAPHIV ≥18 years enrolled in AMP Up, a study of PHACS (Pediatric HIV/AIDS Cohort Study), with social support evaluations and ≥1 HIV viral load (VL) measured over the next year. We evaluated emotional, instrumental, and friendship social support via the NIH Toolbox. We defined social support, measured at study entry and year 3 (if available), as low (T-score ≤40), average (41-59) or high (≥60). We defined viral suppression as all VL <50 copies/mL over the one year after social support measures. We fit multivariable Poisson regression models using generalized estimating equations, and evaluated transition from pediatric to adult care as an effect modifier. Results: Among 444 YAPHIV, low emotional and instrumental support and friendship at entry were reported by 37%, 32% and 36%. Over the next year, 44% were virally suppressed. Of 136 with year 3 data, 45% were suppressed. Average or high levels of all three social support measures were associated with higher likelihood of viral suppression. Instrumental support was associated with viral suppression among those in pediatric (adjusted proportion suppressed among those with average/high vs low support=51.2% vs 28.9%; risk ratio (RR)=1.77, 95% confidence interval (CI)=1.37, 2.29), but not adult care (40.0% vs 40.8%; RR=0.98, 95% CI=0.67, 1.44). Conclusion: Sufficient social support increases likelihood of viral suppression among YAPHIV. Strategies to enhance social support may promote viral suppression as YAPHIV prepare for adult clinical care transition.

Adolescents Living With or at Risk for HIV: A Pooled Descriptive Analysis of Studies From the Adolescent Medicine Trials Network for HIV/AIDS Interventions.

PURPOSE: This study aims to describe the cohort of Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) research program participants and evaluate whether the ATN's recently completed 5-year cycle recruited study participants who parallel the populations most impacted by HIV in the United States. METHODS: Harmonized measures across ATN studies collected at baseline were aggregated for participants aged 13-24 years. Pooled means and proportions stratified by HIV status (at risk for or living with HIV) were calculated using unweighted averages of study-specific aggregate data. Medians were estimated using a weighted median of medians method. Public use 2019 Centers for Disease Control and Prevention surveillance data for state-level new HIV diagnoses and HIV prevalence among US youth aged 13-24 years were obtained for use as reference populations for ATN at-risk youth and youth living with HIV (YLWH), respectively. RESULTS: Data from 3,185 youth at-risk for HIV and 542 YLWH were pooled from 21 ATN study phases conducted across the United States. Among ATN studies tailored to at-risk youth, a higher proportion of participants were White and a lower proportion were Black/African American and Hispanic/Latinx compared to youth newly diagnosed with HIV in the United States in 2019. Participants in ATN studies tailored to YLWH were demographically similar to YLWH in the United States. DISCUSSION: The development of data harmonization guidelines for ATN research activities facilitated this cross-network pooled analysis. These findings suggest the ATN's YLWH are representative, but that future studies of at-risk youth should prioritize recruitment strategies to enroll more participants from African American and Hispanic/Latinx populations.

Executive functions mediate the association between alcohol use and declarative memory symptoms in daily life.

Alcohol use is associated with memory problems in young adults with HIV, but the cognitive mechanisms of that association are not known. Sixty adults (aged 19-24 years) living with HIV were administered the Alcohol, Smoking, and Substance Involvement Screening Test to assess alcohol use, Behavior Rating Inventory of Executive Function for self-reported executive functions, and the Prospective and Retrospective Memory Questionnaire (PRMQ) for dailiy memory functioning. Controlling for mood, self-reported executive functions fully mediated the relationship between alcohol use and memory (indirect effect b=.568, 95%CI [.209,.888]). Findings suggest that self-reported executive dysregulation of memory processes (e.g., Strategic encoding and retrieval) may drive the effects of alcohol use on daily memory symptoms.

Communicating bad news to patients and families in African oncology settings.

AIMS: To assess clinicians' self-reported knowledge of current policies in African oncology settings, of their personal communication practices around sharing bad news with patients, and to identify barriers to the sharing of serious news in these settings. METHODS: A cross-sectional study of cancer care providers in African oncology settings (N = 125) was conducted. Factor analysis was used to assess cross-cultural adaptation and uptake of an evidence-based protocol for disclosing bad news to patients with cancer and of providers' perceived barriers to disclosing bad news to patients with cancer. Analysis of Various (ANOVA) was used to assess strength of association with each dimension of these two measurement models by various categorical variables. RESULTS: Providers from Nigeria, Kenya, Ghana, and Rwanda represented 85% of survey respondents. Two independent, psychometrically reliable, multi-dimensional measurement models were derived to assess providers' personal communication practices and providers' perceived barriers to disclosing a cancer diagnosis. Forty percent (40%) of respondent nurses but only 20% of respondent physicians had had formal communications skills training. Approximately 20%-25% of respondent physicians and nurses reported having a consistent plan or strategy for communicating bad news to their cancer patients. CONCLUSIONS: Results show that effective communication about cancer diagnosis and prognosis requires an appreciation and clinical skill set that blends an understanding of cancer-related internalized stigmas harbored by patient and family, dilemmas posed by treatment affordability, and the need to navigate family wishes about cancer-related diagnoses in the context of African oncology settings. Findings underscore the need for culturally grounded communications research and program design.

Health Insurance Coverage, Clinical Outcomes, and Health-Related Quality of Life Among Youth Born to Women Living With HIV.

BACKGROUND: Although sustained access to health care is essential, little is known about the relationship between insurance coverage and health among people born to women living with HIV (WLHIV). SETTING: Prospective cohort studies of youth and young adults born to WLHIV from 2007 to 2019. METHODS: We used adjusted generalized estimating equation models to estimate mean differences in, and relative risks (RRs) of, health-related quality of life (HR-QoL) and HIV disease measures over time by insurance status. HR-QoL scales with limited variability were dichotomized. Modified Poisson models were used to estimate RRs. RESULTS: Six hundred sixty-nine Adolescent Master Protocol (AMP) youth [66% living with perinatally-acquired HIV (PHIV), 72% Black] and 939 AMP Up/AMP Up Lite young adults (89% PHIV, 68% Black) reported insurance. Most were publicly insured (87% youth, 67% young adults). Privately insured young adults living with PHIV had lower risk of antiretroviral therapy nonadherence [adjusted RR (aRR): 0.82, 95% CI: 0.70 to 0.97] than those with public insurance. There was a lower risk of suboptimal role functioning for young adults with private insurance (aRR: 0.58, 95% CI: 0.35 to 0.97) and those unaware of their coverage (aRR: 0.41, 95% CI: 0.21 to 0.78). Young adults with private insurance had higher health perception scores than those with public insurance (adjusted mean difference: 3.87, 95% CI: 0.37 to 7.38). For youth, we observed no differences in HR-QOL and HIV disease measures by insurance. CONCLUSION: These findings suggest meaningful differences in antiretroviral therapy adherence and some HR-QoL outcomes by health insurance coverage among young adults born to WLHIV.

Ageing with HIV: a longitudinal study of markers of resilience in young adults with perinatal exposure to HIV, with or without perinatally acquired HIV.

INTRODUCTION: Medical challenges, including perinatally acquired HIV (PHIV), can be considered adversity with the potential to compromise individuals' ability to meet societal expectations across the lifespan. Studies suggest that resilience, defined as positive adaptation in the context of adversity, helps individuals overcome challenges and improve their quality of life. Few longitudinal studies have examined resilience in young adults with perinatally acquired HIV (YAPHIV) or perinatal HIV exposure, uninfected (YAPHEU). We examined three young adult milestones, which can affect the life-long quality of life, as markers of resilience: high school graduation, postsecondary education and current employment. METHODS: Analyses included YAPHIV and YAPHEU, ages 19-27 years, followed in longitudinal cohort studies: Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol (AMP) (7-17 years) and AMP Up (≥18 years). Factors known to influence the attainment of milestones (outcomes) were examined: executive function, cognitive efficiency (working memory and processing speed), behavioural/social-emotional functioning, parent/caregiver mental/physical health and cumulative risk. HIV disease markers for YAPHIV were examined. The most recent AMP assessment was used for each factor; outcomes were measured at AMP Up 1-year follow-up. Separate robust Poisson regression models were used to assess associations of each factor with each outcome; PHIV status was explored as an effect modifier of each association. RESULTS: Participants (N = 315; YAPHIV = 228): 58% female, 67% Black and 27% Hispanic. Compared to YAPHEU, YAPHIV were older and from families with higher median income and fewer symptoms of parent/caregiver mental health/substance use disorders. Proportions of YAPHIV and YAPHEU, respectively, who achieved each milestone were comparable: 82% versus 78% for high school graduation (p = 0.49), 45% versus 51% for postsecondary education (p = 0.35) and 48% versus 54% for current employment (p = 0.32). Higher cognitive efficiency was positively associated with postsecondary education and current employment. Higher executive function, age-appropriate behavioural/social-emotional functioning and lower cumulative risk were associated with academic milestones. Among YAPHIV, positive associations were: higher current CD4 with postsecondary education and lower nadir CD4 with current employment. PHIV status did not modify any association. CONCLUSIONS: YAPHIV and YAPHEU demonstrated resilience, attaining at least one young adult milestone. Cognitive, behavioural and social resources to support resilience in childhood and adolescence may provide the foundation for continued achievement throughout adulthood.

Detection of Chronic Blast-Related Mild Traumatic Brain Injury with Diffusion Tensor Imaging and Support Vector Machines.

Blast-related mild traumatic brain injury (bmTBI) often leads to long-term sequalae, but diagnostic approaches are lacking due to insufficient knowledge about the predominant pathophysiology. This study aimed to build a diagnostic model for future verification by applying machine-learning based support vector machine (SVM) modeling to diffusion tensor imaging (DTI) datasets to elucidate white-matter features that distinguish bmTBI from healthy controls (HC). Twenty subacute/chronic bmTBI and 19 HC combat-deployed personnel underwent DTI. Clinically relevant features for modeling were selected using tract-based analyses that identified group differences throughout white-matter tracts in five DTI metrics to elucidate the pathogenesis of injury. These features were then analyzed using SVM modeling with cross validation. Tract-based analyses revealed abnormally decreased radial diffusivity (RD), increased fractional anisotropy (FA) and axial/radial diffusivity ratio (AD/RD) in the bmTBI group, mostly in anterior tracts (29 features). SVM models showed that FA of the anterior/superior corona radiata and AD/RD of the corpus callosum and anterior limbs of the internal capsule (5 features) best distinguished bmTBI from HCs with 89% accuracy. This is the first application of SVM to identify prominent features of bmTBI solely based on DTI metrics in well-defined tracts, which if successfully validated could promote targeted treatment interventions.

Central Nervous System Impact of Perinatally Acquired HIV in Adolescents and Adults: an Update.

PURPOSE OF REVIEW: Perinatally acquired HIV infection (PHIV) can confer neurodevelopmental risk. As children with PHIV increasingly survive through adolescence and into adulthood, understanding its long-term central nervous system (CNS) impacts is critical for maximizing adult outcomes and quality of life. RECENT FINDINGS: Recently published neurocognitive and neuroimaging findings show impacts on the CNS associated with early HIV disease progression that endure into adolescence and young adulthood. Although developmental trajectories in adolescence largely appear stable, further research on maturational processes is indicated. Although early antiretroviral therapy in infancy appears to be protective, it is not universally available and current youth largely developed without its benefit. The neurocognitive effects of HIV and the multiple other risks to neurodevelopment experienced by youth with PHIV call for further longitudinal research and a multifaceted approach to prevention and intervention.

Components of metabolic syndrome associated with lower neurocognitive performance in youth with perinatally acquired HIV and youth who are HIV-exposed uninfected.

We investigated the association of metabolic syndrome (MetS) and its components [abdominal obesity, elevated triglycerides (TG), low HDL cholesterol, elevated blood pressure (BP), and impaired fasting glycemia (IFG)] with neurocognitive impairment in youth with perinatally acquired HIV (YPHIV) or who are perinatally HIV-exposed uninfected (YPHEU). This was an observational study with a comparison group of 350 YPHIV and 68 YPHEU ages 10-19 years. Youth with MetS components measured between 1 year before and 3 months after a baseline neurocognitive assessment (Wechsler Intelligence Scale) were selected from the Pediatric HIV/AIDS Cohort Study (PHACS). A sub-group completed another assessment 3 years later. We assessed the association of each baseline MetS component with five standardized neurocognitive indices at baseline and changes in indices over time. At baseline, 15% of YPHIV and 18% of YPHEU met criteria for ≥ 2 MetS components. Among YPHIV, there was no association between MetS components and neurocognitive indices at baseline; however, over time, elevated baseline BP was associated with a greater decrease in mean Perceptual Reasoning scores (-4.3;95%CI: -8.8,0.3) and ≥ 2 MetS components with a greater decrease in mean Processing Speed scores (-5.1;95%CI: -9.4, -0.8). Among YPHEU, elevated TG was associated with lower mean Verbal Comprehension, Perceptual Reasoning, and Full-scale IQ scores at baseline, and IFG with lower mean Verbal Comprehension scores. Components of MetS in YPHIV (elevated BP) and YPHEU (elevated TG and IFG) were associated with lower neurocognitive performance index scores. Studies to elucidate how modifying metabolic risk factors early in life may improve neurocognitive outcomes in this population are warranted.

The Role of Behavioral and Neurocognitive Functioning in Substance Use Among Youth with Perinatally Acquired HIV Infection and Perinatal HIV Exposure Without Infection.

This study examined associations of self-regulatory behavior and cognitive functioning with substance use (SU) to inform interventions for youth with perinatal HIV infection (YPHIV) or exposure but uninfected (YPHEU). Youth aged 7-15 years (YPHIV, n = 390; YPHEU, n = 211) were followed longitudinally with cognitive testing and behavioral questionnaires including self-report of alcohol, marijuana, tobacco, and other SU. Cox proportional hazards analyses were used to examine correlates of initiating each substance for those without prior use at baseline and generalized estimating equation analyses were used to address associations of cognitive/behavioral measurements with SU prevalence for the entire sample. Lower self-reported self-regulation skills, but higher cognitive functioning abilities, were associated with initiation and prevalent use of alcohol and marijuana regardless of HIV status. Our findings suggest SU screening tools and self-regulation interventions developed for general adolescent populations should be implemented for those with PHIV, who may be at heightened risk for SU-related health consequences.

RESUMEN: En este estudio se examina el vínculo del comportamiento autorregulado y la función cognoscitiva con el consumo de sustancias para argumentar intervenciones para los jóvenes con infección perinatal por el VIH (JIPVIH) y los jóvenes con exposición perinatal sin infección por el VIH (JEPSIVIH). Se hizo un seguimiento longitudinal de jóvenes de 7 a 15 años de edad (JIPVIH, n = 390; JEPSIVIH, n = 211) por medio de pruebas cognoscitivas y cuestionarios sobre el comportamiento, incluyendo el autoinforme de consumo de alcohol, marihuana, tabaco y otras sustancias. Se usaron los análisis Cox de riesgos proporcionales para examinar factores correlacionados con el inicio del consumo de cada sustancia por personas no consumidoras en el punto de referencia inicial. Asimismo, se usaron análisis de ecuaciones de estimación generalizadas para examinar la asociación entre la prevalencia del consumo de sustancias y las medidas cognoscitivas y las medidas conductuales para toda la muestra. Habilidades de autorregulación disminuidas, según autoinforme, pero capacidades superiores de función cognoscitiva, fueron vinculadas con el inicio y consumo frecuente de alcohol y marihuana, independientemente de la condición de VIH. Nuestros hallazgos sugieren que herramientas para detectar el consumo de sustancias e intervenciones de autorregulación creadas para la población general de adolescentes se deberían implementar para los JIPVIH que podrían correr mayores riesgos de sufrir consecuencias en la salud relacionadas con el consumo de sustancias.

Trajectories of Depressive Symptoms, Neurocognitive Function, and Viral Suppression With Antiretroviral Therapy Among Youth With HIV Over 36 months.

BACKGROUND: Depression and neurocognitive impairment are highly prevalent among persons living with HIV and associated with poorer clinical outcomes; however, longitudinal studies of depression-neurocognition relationships in youth living with HIV (YLWH), and the role of antiretroviral therapy (ART), are lacking. This study tested whether (1) depressive symptomatology, across somatic, cognitive, and affective symptom domains, improved with ART and (2) more severe depressive symptoms at baseline were associated with poorer neurocognitive function and poorer HIV suppression. SETTING: Data were collected from 181 YLWH (18-24 years) who were treatment-naive, a subset of whom (n = 116) initiated ART. METHODS: Participants were categorized into elevated (DS) or nonelevated (non-DS) depressive symptom groups at entry (Beck Depression Inventory-II ≥14) and followed for 36 months. Neurocognition (5-domain battery) and depressive symptoms were repeatedly assessed. Longitudinal models examined depressive symptomatology, neurocognition, and odds of HIV nonsuppression by group. RESULTS: Greater improvements in depressive symptoms were observed in the DS group over 36 months [beta = -0.14, (-0.24 to -0.03)], particularly within cognitive and affective domains. Verbal learning performance increased in the DS group [beta = 0.13, (0.01 to 0.24)], whereas psychomotor function improved somewhat in the non-DS group [beta = -0.10, (-0.22 to 0.00)]. Adjusted for ART adherence, odds of HIV nonsuppression did not significantly differ by group [odds ratio = 0.22, (0.04 to 1.23)]; however, greater somatic symptoms at study entry were associated with an increased risk of nonsuppression over time [odds ratio = 2.33 (1.07 to 5.68)]. CONCLUSION: Depressive symptoms were associated with differential neurocognitive trajectories, and somatic depressive symptoms at baseline may predict poorer subsequent HIV suppression. Identifying and treating depressive symptoms at ART initiation may benefit neurocognitive and clinical outcomes in YLWH.

Resting-state magnetoencephalography source magnitude imaging with deep-learning neural network for classification of symptomatic combat-related mild traumatic brain injury.

Combat-related mild traumatic brain injury (cmTBI) is a leading cause of sustained physical, cognitive, emotional, and behavioral disabilities in Veterans and active-duty military personnel. Accurate diagnosis of cmTBI is challenging since the symptom spectrum is broad and conventional neuroimaging techniques are insensitive to the underlying neuropathology. The present study developed a novel deep-learning neural network method, 3D-MEGNET, and applied it to resting-state magnetoencephalography (rs-MEG) source-magnitude imaging data from 59 symptomatic cmTBI individuals and 42 combat-deployed healthy controls (HCs). Analytic models of individual frequency bands and all bands together were tested. The All-frequency model, which combined delta-theta (1-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), and gamma (30-80 Hz) frequency bands, outperformed models based on individual bands. The optimized 3D-MEGNET method distinguished cmTBI individuals from HCs with excellent sensitivity (99.9 ± 0.38%) and specificity (98.9 ± 1.54%). Receiver-operator-characteristic curve analysis showed that diagnostic accuracy was 0.99. The gamma and delta-theta band models outperformed alpha and beta band models. Among cmTBI individuals, but not controls, hyper delta-theta and gamma-band activity correlated with lower performance on neuropsychological tests, whereas hypo alpha and beta-band activity also correlated with lower neuropsychological test performance. This study provides an integrated framework for condensing large source-imaging variable sets into optimal combinations of regions and frequencies with high diagnostic accuracy and cognitive relevance in cmTBI. The all-frequency model offered more discriminative power than each frequency-band model alone. This approach offers an effective path for optimal characterization of behaviorally relevant neuroimaging features in neurological and psychiatric disorders.

Genomics Links Inflammation With Neurocognitive Impairment in Children Living With Human Immunodeficiency Virus Type-1.

BACKGROUND: We identified host single-nucleotide variants (SNVs) associated with neurocognitive impairment (NCI) in perinatally HIV-infected (PHIV) children. METHODS: Whole-exome sequencing (WES) was performed on 217 PHIV with cognitive score for age (CSA) < 70 and 247 CSA ≥ 70 (discovery cohort [DC]). SNVs identified in DC were evaluated in 2 validation cohorts (VC). Logistic regression was used to estimate adjusted odds ratios (ORs) for NCI. A human microglia NLRP3 inflammasome assay characterized the role of identified genes. RESULTS: Twenty-nine SNVs in 24 genes reaching P ≤ .002 and OR ≥ 1.5 comparing CSA < 70 to CSA ≥ 70 were identified in the DC, of which 3 SNVs were identified in VCs for further study. Combining the 3 cohorts, SNV in CCRL2 (rs3204849) was associated with decreased odds of NCI (P < .0001); RETREG1/FAM134B (rs61733811) and YWHAH (rs73884247) were associated with increased risk of NCI (P < .0001 and P < .001, respectively). Knockdown of CCRL2 led to decreased microglial release of IL-1ß following exposure to ssRNA40 while knockdown of RETREG1 and YWHAH resulted in increased IL-1ß release. CONCLUSIONS: Using WES and 2 VCs, and gene silencing of microglia we identified 3 genetic variants associated with NCI and inflammation in HIV-infected children.

Venous thromboembolism after penetrating femoral and popliteal artery injuries: an opportunity for increased prevention.

BACKGROUND: Trauma patients with penetrating vascular injuries have a higher rate of venous thromboembolism (VTE). The objective of this study was to determine the risk of VTE formation in penetrating femoral and popliteal vascular injuries and the effects of endovascular management of these injuries. METHODS: A retrospective study of Pennsylvania Trauma Outcome Study registry was conducted during a 5-year period (2013-2017). All adult patients with a penetrating mechanism with femoral/popliteal vascular injuries were studied. Primary outcome was incidence of VTE in patients with isolated arterial injuries versus combined arterial/venous injuries. Secondary endpoints were intensive care unit (ICU) length of stay (LOS), hospital LOS and mortality. Statistical comparisons were accomplished using Fisher's exact tests, and parametric two-sample t-tests or non-parametric Wilcoxon rank-sum tests for categorical and continuous variables, respectively. RESULTS: Of the 865 patients with penetrating extremity vascular injuries, 207 had femoral or popliteal artery injuries. Patients with isolated arterial injuries (n=131) had a significantly lower deep venous thrombosis (DVT) rate compared with those with concurrent venous injuries (n=76) (3.1% vs. 13.2%, p=0.008). There were 14 patients in the study who developed DVTs. Among the four patients with isolated femoral or popliteal arterial injuries who had developed DVTs, three had an open repair. Among patients with isolated arterial injuries, those with DVT spend significantly more time on the ventilator (median=2 vs. 0, p=0.0020) compared with patients without DVT. Patients with DVT also had longer stay in the hospital (median=17.5 vs. 8, p=0.0664) and in the ICU (median=3 vs. 1, p=0.0585). CONCLUSIONS: Risk of DVT exists in patients with penetrating isolated femoral and popliteal artery trauma. Open repair was associated with significantly higher DVT rates in isolated arterial injuries. LEVEL OF EVIDENCE: Level IV therapeutic care/management.

Brain morphometric differences in youth with and without perinatally-acquired HIV: A cross-sectional study.

Youth with perinatally-acquired HIV (PHIV) experience specific and global cognitive deficits at increased rates compared to typically-developing HIV-uninfected youth. In youth with PHIV, HIV infects the brain early in development. Neuroimaging studies have demonstrated altered grey matter morphometry in youth with PHIV compared to typically-developing youth. This study examined cortical thickness, surface area, and gyrification of grey matter in youth (age 11-20 years old) with PHIV (n = 40) from the Pediatric HIV/AIDS Cohort Study (PHACS) compared to typically-developing presumed HIV uninfected and unexposed youth (n = 80) from the Pediatric Imaging, Neurocognition and Genetics Study (PING) using structural magnetic resonance imaging. This study also examined the relationship between grey matter morphometry and age. Youth with PHIV had reduced cortical thickness, surface area, and gyrification compared to typically-developing youth. In addition, an inverse relationship between age and grey matter volume was found in typically-developing youth, but was not observed in youth with PHIV. Longitudinal studies are necessary to understand the neurodevelopmental trajectory of youth with PHIV.