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Lilla A Brody,1,2 Lily Kamalyan,2,3 Kayle Karcher,2 Lesley A Guarena,2 Alexis A Bender,4 Benjamin S McKenna,2 Anya Umlauf,2 Donald Franklin,2 Maria J Marquine,5 Robert K Heaton2 1Division of Geriatrics and Palliative Medicine, Weill Cornell Medicine, New York, NY, USA; 2Department of Psychiatry, HIV Neurobehavioral Research Program, San Diego, CA, USA; 3Joint Doctoral Program in Clinical Psychology, San Diego State University/University of California, San Diego, CA, USA; 4Division of Geriatrics & Gerontology, Department of Medicine, Emory University, Atlanta, GA, USA; 5Division of Geriatrics, Department of Medicine, Duke University School of Medicine, Durham, NC, USACorrespondence: Robert K Heaton, Department of Psychiatry, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, San Diego, CA, 92093-0603, USA, Tel +1 619 497-6659, Fax +1 619 260-8437, Email rheaton@health.ucsd.eduPurpose: Depression and other aspects of emotional health in people with HIV (PWH) can affect functional independence, disease progression, and overall life quality. This study used the NIH Toolbox Emotion Battery (NIHTB-EB), which assesses many features of emotional health, to more comprehensively investigate differences among adults living with and without HIV, and to identify factors associated with emotional health for PWH.Patients and Methods: Participants (n=1451; age: M=50.19, SD=16.84; 47.90% women) included 433 PWH living in southern California seen from 2003 to 2021 (64.72% AIDS, 92.25% on antiretroviral therapy) and 1018 healthy participants from NIHTB-EB national normative cohort. Participants completed the NIHTB-EB and PWH underwent comprehensive HIV disease and psychiatric evaluations. We investigated differences in emotional health by HIV status via independent samples t-tests (continuous scores) and Chi2 tests (“problematic” emotional health scores). Multivariable linear regression models examined correlates of emotional health among PWH.Results: PWH had significantly worse emotional health than people without HIV across Social Satisfaction (Cohen’s d=0.71, p< 0.001), Psychological Well-Being (Cohen’s d=0.49, p< 0.001) and Negative Affect (Cohen’s d=0.19, p< 0.01) summary T-scores, and most component scales. PWH also had higher rates of “problematic” emotional health, particularly in Social Satisfaction (45% vs 17%, p< 0.0001). Poor emotional health among PWH was associated with lifetime Major Depressive and Substance Use Disorders, relationship status (lost relationship versus in relationship), unemployment, and cognitive difficulties and loss of functional independence.Conclusion: The NIHTB-EB identified that difficulties with multiple aspects of emotional health are common among PWH, and appear to be relatively independent of cognitive impairment as well as HIV disease and treatment history, but are strongly associated with everyday functioning. Given the cross-sectional nature of this study, longitudinal studies should be employed to evaluate causality pertaining to predictors of emotional health in PWH. These findings may inform interventions to promote emotional wellbeing in PWH.Keywords: social relationships, depression, emotional health, positive factors, HIV infection

OBJECTIVES: People with HIV (PWH) have high rates of depression and neurocognitive impairment (NCI) despite viral suppression on antiretroviral therapy (ART). Mounting evidence suggests that immunometabolic disruptions may contribute to these conditions in some PWH. We hypothesized that metabolic dysfunction in astrocytes is associated with depressive symptoms and cognitive function in PWH. METHODS: Human astrocytes were exposed to sera from PWH (n=40) with varying degrees of depressive symptomatology and cognitive function. MitoTrackerTM Deep Red FM (MT) was used to visualize mitochondrial activity and glial fibrillary acidic protein (GFAP) as an indicator of astrocyte reactivity using the high-throughput fluorescent microscopy and image analyses platform, CellInsight CX5 (CX5). The Seahorse platform was used to assess glycolytic and mitochondrial metabolism. RESULTS: More severe depression, as indexed by higher Becks Depression Inventory (BDI-II) scores, was associated with lower MT signal measures. Better cognitive function, as assessed by neuropsychiatric testing t-scores, was associated with increased MT signal measures. GFAP intensity negatively correlated with several cognitive t-scores. Age positively correlated with (higher) MT signal measures and GFAP intensity. Worse depressive symptoms (higher BDI-II scores) were associated with decreased oxygen consumption rate and spare respiratory capacity, concomitant with increased extracellular acidification rate in astrocytes. CONCLUSIONS: These findings show that factors in the sera of PWH alter mitochondrial activity in cultured human astrocytes, suggesting that mechanisms that alter mitochondrial and astrocyte homeostasis can be detected peripherally. Thus, in vitro cultures may provide a model to identify neuropathogenic mechanisms of depression or neurocognitive impairment in PWH and test personalized therapeutics for neurologic and psychiatric disorders.

11th Warnemunde Turbulence Days on Linking Ocean Mixing and Circulation at Various Scales What: Forty-five participants from 10 countries met to discuss contemporary issues of marine turbulence with a focus on the linkage between mixing and overturning circulation on all scales (https://www.io-warnemuende.de/wtd-2023.html). When: 17-20 September 2023 Where: Rostock, Germany KEYWORDS: Eddies; Inertia-gravity waves; Meridional overturning circulation; Mixing; Ocean circulation; Turbulence, 1. Introduction Walter Munk, in his famous abyssal recipes, showed more than half a century ago that the strength of the global overturning circulation is closely linked to diapycnal mixing. [...]

Neuropsychiatric complications such as neurocognitive impairment and depression are common in people with HIV despite viral suppression on antiretroviral therapy, but these conditions are heterogeneous in their clinical presentations and associated disability. Identifying novel biopsychosocial phenotypes that account for neurocognitive performance and depressive and functional symptoms will better reflect the complexities encountered in clinical practice and may have pathological and therapeutic implications. We classified 1580 people with HIV based on 17 features, including 7 cognitive domains, 4 subscales of the Beck depression inventory-II, 5 components of the patients assessment of own functioning inventory, and dependence in instrumental and basic activities of daily living. A two-stage clustering procedure consisting of dimension reduction with self-organizing maps and Mahalanobis distance-based k-means clustering algorithms was applied to cross-sectional data. Baseline demographic and clinical characteristics were compared between the phenotypes, and their prediction on the biopsychosocial phenotypes was evaluated using multinomial logistic regression. Four distinct phenotypes were identified. Participants in Phenotype 1 overall did well in all domains. Phenotype 2 had mild-to-moderate depressive symptoms and the most substance use disorders. Phenotype 3 had mild-to-moderate cognitive impairment, moderate depressive symptoms, and the worst daily functioning; they also had the highest proportion of females and non-HIV conditions that could affect cognition. Phenotype 4 had mild-to-moderate cognitive impairment but with relatively good mood, and daily functioning. Multivariable analysis showed that demographic characteristics, medical conditions, lifetime cocaine use disorder, triglycerides, and non-antiretroviral therapy medications were important variables associated with biopsychosocial phenotype. We found complex, multidimensional biopsychosocial profiles in people with HIV that were associated with different risk patterns. Future longitudinal work should determine the stability of these phenotypes, assess factors that influence transitions from one phenotype to another, and characterize their biological associations.

ObjectiveMany persons with opioid use disorders (OUDs) have HIV disease and experience clinically significant stress after they enroll in abstinence-based treatment and undergo medically assisted withdrawal. We examined whether opioid withdrawal affects virologic control, inflammatory markers, cognition, and mood in persons with an OUD and HIV, and explored whether measures of withdrawal stress, such as activation of the HPA axis, contribute to alterations in immune function, cognition, and mood.Method and participantsStudy participants were 53 persons with HIV who were admitted for OUD treatment at the City Addiction Hospital in Saint Petersburg, Russian Federation. Participants were examined at admission, at the anticipated peak of withdrawal 3 to 7 days after the last day of a clonidine-based withdrawal process lasting 7 to 14 days, and 3 to 4 weeks after completing withdrawal. At these times, participants received medical exams and were evaluated for symptoms of withdrawal, as well as cognition and mood. Viral load, plasma cortisol, DHEA sulfate ester (DHEA-S), interleukin-6 (IL-6), and soluble CD14 (sCD14) were determined. Multivariable models examined the relationships between markers of HPA activation and the other parameters over time.ResultsHPA activation as indexed by cortisol/DHEA-S ratio increased during withdrawal, as did markers of immune activation, IL-6 and sCD14. There were no significant associations between viral load and indicators of HPA activation. In longitudinal analyses, higher cortisol/DHEA sulfate was related to worse cognition overall, and more mood disturbance. Increase in IL-6 was associated with worse cognitive performance on a learning task. There were no significant associations with sCD14.ConclusionsWorsening of cognition and measures of mood disturbance during withdrawal were associated with activation of the HPA axis and some measures of inflammation. Whether repeated episodes of opioid withdrawal have a cumulative impact on long-term HIV outcomes and neurocognition is a topic for further investigation.

BackgroundHIV-associated neurocognitive disorders (HANDs) remain prevalent despite antiretroviral therapy, particularly among older people with HIV (PWH). However, the diagnosis of HAND is labor intensive and requires expertise to administer neuropsychological tests. Our prior pilot work established the feasibility and accuracy of a computerized self-administered virtual reality program (DETECT; Display Enhanced Testing for Cognitive Impairment and Traumatic Brain Injury) to measure cognition in younger PWH. The present study expands this to a larger sample of older PWH.MethodsWe enrolled PWH who were ≥60 years old, were undergoing antiretroviral therapy, had undetectable plasma viral loads, and were without significant neuropsychological confounds. HAND status was determined via Frascati criteria. Regression models that controlled for demographic differences (age, sex, education, race/ethnicity) examined the association between DETECT's cognition module and both HAND status and Global Deficit Score (GDS) derived via traditional neuropsychological tests.ResultsSeventy-nine PWH (mean age, 66 years; 28% women) completed a comprehensive neuropsychological battery and DETECT's cognition module. Twenty-five (32%) had HAND based on the comprehensive battery. A significant correlation was found between the DETECT cognition module and the neuropsychological battery (r = 0.45, P < .001). Furthermore, in two separate regression models, HAND status (b = -0.79, P < .001) and GDS impairment status (b = -0.83, P < .001) significantly predicted DETECT performance. Areas under the curve for DETECT were 0.78 for differentiating participants by HAND status (HAND vs no HAND) and 0.85 for detecting GDS impairment.ConclusionsThe DETECT cognition module provides a novel means to identify cognitive impairment in older PWH. As DETECT is fully immersive and self-administered, this virtual reality tool holds promise as a scalable cognitive screening battery.

Deficits in social cognition are seen in both people living with HIV (PWH) and people with a history of methamphetamine (METH) dependence. Dually affected individuals may experience additive negative effects on social cognition due to these conditions. We evaluated social cognition in 4 diagnostic groups (HIV-/METH-, HIV-/METH+, HIV+/METH-, HIV+/METH+). First, we used traditional social-emotional functioning assessments, the Difficulties in Emotion Regulation Scale and the Faux Pas Task, to determine any significant effects of METH dependence and HIV on social cognition. Next, we quantified social cognition using the Human Behavioral Pattern Monitor by evaluating social behavior represented by interaction with novel objects. METH dependence significantly affected social-emotional functions and HIV significantly affected on object interactions, however no significant additive effects were observed using these methods. The nuanced relationship between HIV and METH dependence suggests that other factors (i.e., adaptive life skills) likely mediate social cognition-related behaviors.

BackgroundCannabis is increasingly used both medically and recreationally. With widespread use, there is growing concern about how to identify cannabis-impaired drivers.MethodsA placebo-controlled randomized double-blinded protocol was conducted to study the effects of cannabis on driving performance. One hundred ninety-one participants were randomized to smoke ad libitum a cannabis cigarette containing placebo or delta-9-tetrahydrocannabinol (THC) (5.9% or 13.4%). Blood, oral fluid (OF), and breath samples were collected along with longitudinal driving performance on a simulator (standard deviation of lateral position [SDLP] and car following [coherence]) over a 5-hour period. Law enforcement officers performed field sobriety tests (FSTs) to determine if participants were impaired.ResultsThere was no relationship between THC concentrations measured in blood, OF, or breath and SDLP or coherence at any of the timepoints studied (P > 0.05). FSTs were significant (P < 0.05) for classifying participants into the THC group vs the placebo group up to 188 minutes after smoking. Seventy-one minutes after smoking, FSTs classified 81% of the participants who received active drug as being impaired. However, 49% of participants who smoked placebo (controls) were also deemed impaired at this same timepoint. Combining a 2 ng/mL THC cutoff in OF with positive findings on FSTs reduced the number of controls classified as impaired to zero, 86 minutes after smoking the placebo.ConclusionsRequiring a positive toxicology result in addition to the FST observations substantially improved the classification accuracy regarding possible driving under the influence of THC by decreasing the percentage of controls classified as impaired.

The aim of the study was to evaluate the incidence of brain opportunistic pathologies and survival in patients living with HIV from a Romanian tertiary center. A 15-year prospective observational study of brain opportunistic infections diagnosed in HIV-infected patients was performed at Victor Babes Hospital, Bucharest, between January 2006 and December 2021. Characteristics and survival were compared related to modes of HIV acquisition and type of opportunistic infection. A total of 320 patients were diagnosed with 342 brain opportunistic infections (incidence 9.79 per 1000 person-years), 60.2% males with median age at diagnosis of 31 years (IQR 25, 40). Median CD4 cell count and VL were 36/μL (IQR 14, 96) and 5.1 log10 copies/mL (IQR 4, 5.7) respectively. The routes of HIV acquisition were heterosexual (52.6%), parenteral route in early childhood (31.6%), injecting drug use (12.9%), men having sex with men (1.8%), and vertical (1.2%). The most common brain infections were progressive multifocal leukoencephalopathy (31.3%), cerebral toxoplasmosis (26.9%), tuberculous meningitis (19.3%), and cryptococcal meningitis (16.7%). Patients infected by parenteral mode in early childhood were younger at diagnosis of both opportunistic infection and HIV (p  30 years (p = 0.001), injecting drug use (p = 0.003), CD4 +   5 log10 copies/mL at diagnosis (p

BackgroundAnemia is linked to neurocognitive impairment (NCI) in people with HIV (PWH), but its impact within specific ability domains, and in diverse populations with HIV, is uncertain.MethodsParticipants included 1339 PWH enrolled in observational HIV cohort studies with a mean of 3 comprehensive neurocognitive assessments over 30 months. Global and domain-specific neurocognitive function were assessed by the global deficit score and domain deficit score (GDS and DDS, respectively) or as GDS-defined or DDS-defined NCI (GDS ≥ 0.5, DDS > 0.5). Time-dependent associations of anemia or red-cell indices with neurocognitive function were evaluated by multivariable regression.ResultsThe mean age at entry was 43.6 years (85% male, 23.9% Hispanic, 16.7% African ancestry by self-report, and 69.8% virally suppressed). Anemia occurred at entry in 297 (22.2%) and developed subsequently in another 129 (9.6%). Anemia (present in 26.8% of cognitively impaired PWH at entry) and lower hemoglobin were associated with higher (worse) GDS values; the association for anemia persisted after multivariable adjustment and in virally suppressed persons ( P < 0.0001). Anemia was also associated with reduced processing speed, motor function, learning, delayed recall, working memory (all P < 0.01), executive function ( P = 0.021), and verbal fluency ( P = 0.035), and these findings persisted in longitudinal analyses (adjusted P < 0.01 for all domains, except verbal fluency). Higher mean corpuscular volume and mean corpuscular hemoglobin were associated with less impairment in learning and recall (all P < 0.05).ConclusionsAnemia in diverse and virally suppressed PWH associates with reduced neurocognitive performance in multiple domains, cross-sectionally and over time. The impact of identifying and treating anemia to prevent or slow neurocognitive decline in PWH should be prospectively evaluated.

BACKGROUND: Timely, accurate adherence data may support oral pre-exposure prophylaxis (PrEP) success and inform prophylaxis choice. We evaluated a Food and Drug Administration (FDA)-approved digital health feedback system (DHFS) with ingestible-sensor-enabled (IS) tenofovir-disoproxil-fumarate plus emtricitabine (Truvada®) in persons starting oral PrEP. METHODS: Human immunodeficiency virus (HIV)-negative adults were prescribed IS-Truvada® with DHFS for 12 weeks to observe medication taking behavior. Baseline demographics, urine toxicology, and self-report questionnaires were obtained. Positive detection accuracy and adverse events were computed as percentages, with Kaplan Meier Estimate for persistence-of-use. In participants persisting ≥28 days, adherence patterns (taking and timing) were analyzed, and mixed-effects logistic regression modeled characteristics associated with treatment adherence. RESULTS: Seventy-one participants were enrolled, mean age 37.6 years (range 18-69), 90.1% male, 77.5% White, 33.8% Hispanic, 95.8% housed, and 74.6% employed. Sixty-three participants (88.7%) persisted ≥28 days, generating 4987 observation days, average 79.2 (29-105). Total confirmed doses were 86.2% (95% confidence interval [CI] 82.5, 89.4), decreasing over time, odds ratio (OR) 0.899 (95% CI .876, .923) per week, P < .001; 79.4% (95% CI 66.7%, 87.3%) of participants had ≥80% adherence. Pattern analysis showed days without confirmed doses clustered (P = .003); regular dose timing was higher among participants with ≥80% confirmed doses (0.828, 95% CI .796 to .859) than among those with

PurposeDepression and other aspects of emotional health in people with HIV (PWH) can affect functional independence, disease progression, and overall life quality. This study used the NIH Toolbox Emotion Battery (NIHTB-EB), which assesses many features of emotional health, to more comprehensively investigate differences among adults living with and without HIV, and to identify factors associated with emotional health for PWH.Patients and methodsParticipants (n=1451; age: M=50.19, SD=16.84; 47.90% women) included 433 PWH living in southern California seen from 2003 to 2021 (64.72% AIDS, 92.25% on antiretroviral therapy) and 1018 healthy participants from NIHTB-EB national normative cohort. Participants completed the NIHTB-EB and PWH underwent comprehensive HIV disease and psychiatric evaluations. We investigated differences in emotional health by HIV status via independent samples t-tests (continuous scores) and Chi2 tests ("problematic" emotional health scores). Multivariable linear regression models examined correlates of emotional health among PWH.ResultsPWH had significantly worse emotional health than people without HIV across Social Satisfaction (Cohen's d=0.71, p

Background: HIV is a chronic illness that impacts the lives of more than 1 million people in the United States. As persons living with HIV (PWH) are living longer, it is important to understand the influence that religiosity/spirituality has among middle-aged and older PWH.Objective: Compare the degree of religiosity/spirituality among middle-aged and older PWH and HIV-negative individuals, and to identify demographic, clinical, and psychosocial factors associated with religiosity/spirituality among PWH.Method: Baseline data on 122 PWH and 92 HIV-negative individuals (ages 36-65 years; 61.1% Non-Hispanic White) from a longitudinal study were analyzed for the current study. Recruitment occurred through HIV treatment clinics and community organizations in San Diego. Participants completed questionnaires on religiosity, spirituality, and psychosocial functioning. Independent samples t-tests, Pearson correlations, and multiple linear regression analyses were conducted to test the study objective.Results: No significant differences in religiosity/spirituality were found between PWH and HIV-negative individuals. Demographic and psychosocial variables were unrelated to religiously/spirituality among HIV-negative individuals. Among PWH, multiple linear regression models indicated higher daily spirituality was significantly associated with racial/ethnic minority membership (Hispanic/Latino, African American/Black, or Other), fewer years of estimated duration of HIV, greater social support, and higher grit. Greater engagement in private religious practices was significantly associated with racial/ethnic minority membership and higher social support.Conclusions: For PWH, being a racial/ethnic minority and having higher social support was associated with greater engagement in religious/spiritual practices. Future longitudinal studies should examine whether religion/spirituality impacts well-being across the lifespan among racial/ethnic minority groups of PWH.

The article discusses the requirements for the staff of a public library formed by the Internet, management reform, emergence of knowledge society and budget crisis since the ninth decade. The main focus is on the requirements for work in a networked environment: new management, professional development, social and public performance, professional methodical competence and skills. The article is concluded by the discussion how these changes influence the training and continuing education of library staff. The conclusion is made that the staff of a public library is partly competent to perform job in the networked environment, finds many possibilities to acquire necessary competence and has developed self-consciousness and understanding of the adoption of new requirements. However, the professional development system is inadequate and continuing education mainly relies on the personai initiative and activity of a librarian.

# Background Lateral ankle sprain (LAS) is a common injury with incidence rates reported at 7.2 per 1000 person-years. Physical examination strategies provide limited information to guide rehabilitation that can maximize clinical outcomes. Early and accurate diagnostic information using ultrasound imaging enables individualized care and the ability to monitor healing along with its response to activity and rehabilitation. # Purpose The purpose of this study was to describe and observe the outcomes associated with Point of Care Ultrasound (POCUS) guided early management of acute and sub-acute lateral ankle sprains. # Study Design Case series # Methods Individuals with a LAS within the prior 28 days underwent a clinical evaluation to include a POCUS exam to assess ligamentous integrity. Objective and POCUS findings were integrated to classify each LAS into one of four categories. Each grade of ankle sprain corresponded to levels of bracing for the protection of injured structures with each patient receiving physical therapy care based on rehabilitation guidelines. Participants completed the Foot and Ankle Ability Measure (FAAM) activities of daily living and Sports subscale, the Foot and Ankle Outcome Score (FAOS), Patient Reported Outcomes Measurement Information Systems Global Health, Tampa Scale of Kinesiophobia (TSK-11), Cumberland Ankle Instability Tool (CAIT), and the Numeric Pain Rating Scale as well as the Ankle Lunge Test and Figure 8 measurements at baseline, 4 weeks, 8 weeks and 12 weeks post enrollment. The FAAM Sport subscale, all FAOS subscales, and the TSK-11 were also collected at 24 weeks while the CAIT was collected at baseline and 24 weeks. # Results Fourteen participants were enrolled with 11 participants completing all data collection. FAAM Sport scores significantly improved at 4, 8, 12 and 24 weeks. All components of the FAOS significantly increased except for Sport scores at four weeks and Quality of Life scores at four and eight weeks. # Conclusion POCUS guided early management and ligamentous protection of LASs resulted in significant short and long-term improvement in function and return to sporting activity. This case series highlights the feasibility of using ultrasound imaging to assess the severity of ligamentous injury and align bracing strategies for ligamentous protection. The observations from this case series suggest that functional bracing strategies focused on ligamentous protection to promote healing and reduce re-injury rates does not delay improvement in functional outcomes. # Level of Evidence Level IV, Case Series

ObjectivesWe investigated the impact of culturally relevant social, educational, and language factors on cognitive test performance among Spanish speakers living near the US-Mexico border.MethodsParticipants included 254 healthy native Spanish speakers from the Neuropsychological Norms for the US-Mexico Border Region in Spanish (NP-NUMBRS) project (Age: M = 37.3, SD = 10.4; Education: M = 10.7, SD = 4.3; 59% Female). A comprehensive neuropsychological battery was administered in Spanish. Individual test scaled scores and T-scores (based on region-specific norms adjusted for age, education, and sex) were averaged to create Global Mean Scaled and T-scores. Measures of culturally relevant factors included a self-reported indicator of educational quality/access (proportion of education in Spanish-speaking country, quality of school/classroom setting, stopped attending school to work), childhood socioeconomic environment (parental education, proportion of time living in Spanish-speaking country, childhood socioeconomic and health status, access to basic resources, work as a child), and Spanish/English language use and fluency.ResultsSeveral culturally relevant variables were significantly associated with unadjusted Global Scaled Scores in univariable analyses. When using demographically adjusted T-scores, fewer culturally relevant characteristics were significant. In multivariable analyses, being bilingual (p = .04) and working as a child for one's own benefit compared to not working as a child (p = .006) were significantly associated with higher Global Mean T-score, accounting for 9% of variance.ConclusionsDemographically adjusted normative data provide a useful tool for the identification of brain dysfunction, as these account for much of the variance of sociocultural factors on cognitive test performance. Yet, certain culturally relevant variables still contributed to cognitive test performance above and beyond basic demographics, warranting further investigation.

Abstract Brain atrophy associated with valproate therapy is known from single case reports and is frequently accompanied by cognitive deterioration. We present a case series of incidental findings of brain volume loss in children treated with valproate and employed automatic brain volumetry to assess the effect size of volume loss. 3D T1w datasets were automatically segmented into white matter, gray matter, and cerebrospinal fluid using the SPM‐12 algorithm. Respective volumes of cerebrum and cerebellum were read out and normalized to the total intracranial volume. We identified six patients (median age 148.5 [85–178] months) who had received valproate for a median time of 5 (2–23) months prior to MRI in which a loss of brain volume was noted. None had reported the occurrence of new clinical symptoms. Volumetry showed a volume loss of up to 28% for cerebral GM, 25% for cerebellar GM, 10% for cerebral WM, and 20% for cerebellar WM. A volume loss of >5% in at least one of the subvolumes was found in all patients, with the more prominent volume loss in the cerebrum and in gray matter. In one patient, post‐valproate MRI was available and showed normalization of brain volume. Our case series indicates that valproate therapy might be associated with an asymptomatic volume loss of brain parenchyma in children with epilepsy and that this volume loss is assessable with automatic volumetry.

Turbulent diapycnal mixing is important for the estuarine circulation between basins of the Baltic Sea as well as for its local ecosystems, in particular with regard to eutrophication and anoxic conditions. While the interior of the basins is overall relatively calm, stratified flow over steep bathymetric features is known as a source of strong turbulent mixing. Yet, current in situ observations often cannot capture the spatio-temporal development of dynamic and intermittent turbulent mixing related to overflows over rough bathymetry. We present observational oceanographic data together with openly accessible high-resolution bathymetry from a prototypical sill and an adjacent deep channel in the sparsely sampled Southern Quark located in the Åland Sea, connecting the northern Baltic Proper with the Bothnian Sea. Our data were acquired during two 1-week cruises on R/V Electra in February–March 2019 and 2020. We collected high-resolution broadband acoustic observations of turbulent mixing together with in situ microstructure profiler measurements, and current velocities from acoustic Doppler current profilers. We found that a temporally reversing non-tidal stratified flow over the steep bathymetric sill created a dynamic and extremely energetic environment. The observed flow reversed during both cruises on timescales of a few days. Saltier, warmer, and less oxygenated deep water south of the sill was partly blocked, the reversing flow was at times hydraulically controlled with hydraulic jumps occurring on both sides of the sill, and high spatial variability occurred in the surface layer on small scales. Dissipation rates of turbulent kinetic energy, vertical turbulent diffusivities, and vertical salt flux rates were increased by 3–4 orders of magnitude in the entire water column in the vicinity of the sill compared to reference stations not directly influenced by the overflow with average dissipation rates near the sill between 10−7 and 10−6 W kg−1, average vertical diffusivities of 0.001 m2 s−1 in the halocline and up to 0.1 m2 s−1 below the halocline, and average vertical salt flux rates around 0.01 g m−2 s−1 in the halocline and between 0.1 and 1 g m−2 s−1 below the halocline. We suggest, based on acoustic observations and in situ measurements, that the underlying mechanism for the highly increased mixing across the halocline is a combination of shear and topographic lee waves breaking at the halocline interface. We anticipate that the resulting deep- and surface-water modification in the Southern Quark directly impacts exchange processes between the Bothnian Sea and the northern Baltic Proper and that the observed mixing is likely important for oxygen and nutrient conditions in the Bothnian Sea.

Abstract BackgroundA digital health technology’s success or failure depends on how it is received by users. ObjectivesWe conducted a user experience (UX) evaluation among persons who used the Food and Drug Administration–approved Digital Health Feedback System incorporating ingestible sensors (ISs) to capture medication adherence, after they were prescribed oral pre-exposure prophylaxis (PrEP) to prevent HIV infection. We performed an association analysis with baseline participant characteristics, to see if “personas” associated with positive or negative UX emerged. MethodsUX data were collected upon exit from a prospective intervention study of adults who were HIV negative, prescribed oral PrEP, and used the Digital Health Feedback System with IS-enabled tenofovir disoproxil fumarate plus emtricitabine (IS-Truvada). Baseline demographics; urine toxicology; and self-report questionnaires evaluating sleep (Pittsburgh Sleep Quality Index), self-efficacy, habitual self-control, HIV risk perception (Perceived Risk of HIV Scale 8-item), and depressive symptoms (Patient Health Questionnaire–8) were collected. Participants with ≥28 days in the study completed a Likert-scale UX questionnaire of 27 questions grouped into 4 domain categories: overall experience, ease of use, intention of future use, and perceived utility. Means and IQRs were computed for participant total and domain subscores, and linear regressions modeled baseline participant characteristics associated with UX responses. Demographic characteristics of responders versus nonresponders were compared using the Fisher exact and Wilcoxon rank-sum tests. ResultsOverall, 71 participants were enrolled (age: mean 37.6, range 18-69 years; n=64, 90% male; n=55, 77% White; n=24, 34% Hispanic; n=68, 96% housed; and n=53, 75% employed). No demographic differences were observed in the 63 participants who used the intervention for ≥28 days. Participants who completed the questionnaire were more likely to be housed (52/53, 98% vs 8/10, 80%; PPPPPPP ConclusionsThe UX among persons using IS-enabled PrEP (IS-Truvada) to prevent HIV infection was positive. Association analysis of baseline participant characteristics linked higher self-efficacy with positive UX, more depressive symptoms with higher perceived utility, and poor sleep with negative UX.

Most U.S. Servicemembers (SMs) get less than the recommended amount of sleep per night, which has been shown to be directly influenced by local leadership. Previous research demonstrated that a brief sleep leadership training (SLT) protocol resulted in improved knowledge and attitudes regarding sleep among U.S. Army leaders, and improvements in the sleep health of their SMs. Human Performance Teams (HPT) offer one solution to propel the cultural change related to sleep, however, little is known about HPT members' own sleep related knowledge, practices, attitudes, and beliefs. This mixed-methods study determined the effect of (SLT) on the sleep-related knowledge, practices, attitudes, beliefs, and perceived competency of HPT members, explored their experiences addressing SM sleep, and gauged their perceived value in receiving the training. Thirty-one individuals received 2 days of SLT. Baseline and 6-week post training follow-up measures were collected, and participants were invited to participate in semi-structured interviews to explore their unique experiences addressing sleep, as well as their perceived value in receiving SLT. Training had no significant effects on HPT members' sleep practices or sleep beliefs, some significant effects on their attitudes and knowledge about sleep, and significant effects on their perceived competence to address sleep in their units. Results suggest that HPT members benefited from the training through enhancement of their competence to address sleep with leadership. However, they struggle to obtain sufficient sleep themselves. More research is needed to identify methods of overcoming specific barriers to sleep imposed on SMs.

Summary: Spatial genome organization within the nucleus influences major biological processes and is impacted by the configuration of linear chromosomes. Here, we applied 3D spatial statistics and modeling on high-resolution telomere and centromere 3D-structured illumination microscopy images in cancer cells. We found a multi-scale organization of telomeres that dynamically evolved from a mixed clustered-and-regular distribution in early G1 to a purely regular distribution as cells progressed through the cell cycle. In parallel, our analysis revealed two pools of peripheral and internal telomeres, the proportions of which were inverted during the cell cycle. We then conducted a targeted screen using MadID to identify the molecular pathways driving or maintaining telomere anchoring to the nuclear envelope observed in early G1. Lamina-associated polypeptide (LAP) proteins were found transiently localized to telomeres in anaphase, a stage where LAP2α initiates the reformation of the nuclear envelope, and impacted telomere redistribution in the next interphase together with their partner barrier-to-autointegration factor (BAF).

BackgroundWe hypothesized that the induction of monocyte activation biomarkers, especially soluble urokinase-type plasminogen activator receptor (suPAR) and interferon γ-inducible protein 10 (IP-10), is lower in HIV-1C than HIV-1B, owing to a defective Tat cysteine dimotif (C30S).MethodsA total of 68 paired cerebrospinal fluid (CSF) and blood samples from people with HIV (PWH), free of CNS opportunistic infections, from a Southern Brazil outpatient HIV clinic were evaluated such as HIV-1B subtype (n = 27), HIV-1C (n = 26), other (n = 15), and 19 HIV-negative controls. The levels of suPAR, IP-10, neopterin, and β2 microglobulin (β2m) in the CSF and serum were quantified using different immunoassays.ResultsOverall, in PWH, increases in CSF suPAR, CSF/serum suPAR, and CSF/serum β2m correlated with worse working memory deficits (r = 0.303, 0.353, and 0.289, respectively, all P < 0.05). The medians of IP-10, suPAR, neopterin, and β2m in CSF and serum and the CSF/serum ratio and suPAR index were comparable between the HIV-1B and HIV-1C subtypes. CSF IP-10 and neopterin and serum IP-10 and suPAR levels were higher in PWH than the HIV-negative controls (P = 0.015, P = 0.001, P < 0.0001, and P < 0.001, respectively). The serum β2m level was higher in HIV-associated dementia than neuropsychologically normal or asymptomatic (P = 0.024).DiscussionWe observed that higher levels of CSF suPAR and the suPAR quotient correlated with worse working memory deficit. Elevated levels of monocyte activation were similar in both HIV-1 B and C subtypes, providing no evidence of reduced neuropathogenicity of HIV-1 subtype C Tat compared with subtype B.

ImportanceExpanding cannabis medicalization and legalization increases the urgency to understand the factors associated with acute driving impairment.ObjectiveTo determine, in a large sample of regular cannabis users, the magnitude and time course of driving impairment produced by smoked cannabis of different Δ9-tetrahydrocannabinol (THC) content, the effects of use history, and concordance between perceived impairment and observed performance.Design, setting, and participantsThis double-blind, placebo-controlled parallel randomized clinical trial took place from February 2017 to June 2019 at the Center for Medicinal Cannabis Research, University of California San Diego. Cannabis users were recruited for this study, and analysis took place between April 2020 and September 2021.InterventionsPlacebo or 5.9% or 13.4% THC cannabis smoked ad libitum.Main outcomes and measuresThe primary end point was the Composite Drive Score (CDS), which comprised key driving simulator variables, assessed prior to smoking and at multiple time points postsmoking. Additional measures included self-perceptions of driving impairment and cannabis use history.ResultsOf 191 cannabis users, 118 (61.8%) were male, the mean (SD) age was 29.9 (8.3) years, and the mean (SD) days of use in the past month was 16.7 (9.8). Participants were randomized to the placebo group (63 [33.0%]), 5.9% THC (66 [34.6%]), and 13.4% THC (62 [32.5%]). Compared with placebo, the THC group significantly declined on the Composite Drive Score at 30 minutes (Cohen d = 0.59 [95% CI, 0.28-0.90]; P

Abstract: Neurocognitive impairment is prevalent among persons with HIV (PWH), particularly among Hispanics/Latinos/as/x (henceforth Hispanics). We examined disparities in HIV-associated neurocognitive function between older Hispanic and non-Hispanic White PWH, and the potential role of metabolic syndrome (MetS) in explaining these disparities. Participants included 116 community-dwelling PWH ages 50-75, who were enrolled in a cohort study in southern California (58 Hispanic [53% Spanish-speaking] and 58 age-comparable non-Hispanic White; Overall group: Age: M=57.9, SD=5.7; Education: M=13, SD=3.4; 83% male, 58% AIDS, 94% on antiretroviral therapy [ART], 4% detectable plasma RNA). A global neurocognition score was derived from T-Scores on a comprehensive neurocognitive battery, with separate demographic adjustments for English and Spanish-speakers. MetS was ascertained via standard criteria that considered central obesity, elevated triglycerides, low high-density lipoprotein cholesterol, and elevated fasting glucose, as well as current medical treatment for these conditions. Covariates examined included sociodemographic, psychiatric, substance use and HIV-disease characteristics. Hispanics had higher rates of MetS (56%) than non-Hispanic Whites (37%; p

PurposeColorectal cancer (CRC) is a leading cause of international morbidity and is the second highest cause of cancer-related mortality in the world. The purpose of this study was to investigate the relationship between international health care spending on CRC mortality over time.MethodsThis is a retrospective study using a publicly available data from the WHO Global Health Observatory database. General estimating equations were used to analyze the relationship between total health care expenditure per capita (THEpc) and CRC mortality at the country level. The primary predictors of interest were quartiles of THEpc. Other exposure variables included gross domestic product per capita (GDPpc), smoking (% of adult population smoking), physician density (per 10,000), and time.ResultsMortality decreased significantly from 2000 to 2016 (coefficient [95% CI], -2.2 [-3.3 to -1.1]; P < .001). THEpc, GDPpc, time, and percentage of adult population smoking were significant predictors of CRC mortality. Patients in the top two quartiles of THEpc had 3% higher rates of CRC mortality compared with countries in Q1 THEpc (Q3: 3.4 [1.9-4.8], P < .001; Q4: 3.2 [1.4-5.0], P = .001). Similar trends were seen in GDPpc (Q4: 3.2 [1.4-5.0], P = .001; Q3: 3.4 [1.9-4.8], P < .001; Q2: 1.7 [0.7-2.6], P < .001; Q1: reference).ConclusionOverall, mortality decreased significantly over the study period. Countries with higher health expenditures and higher gross domestic products experienced higher rates of CRC mortality. Further research will be necessary to determine the cause for this, but we postulate that it may be a result of more robust diagnostic and follow-up methods in countries with more resources.

For people living with HIV (PLWH) and sexual minorities (SM), the intersection of identities can compound experiences like stigma and discrimination resulting in poor emotional health. We investigated the separate and interactive associations of HIV serostatus and sexual identity with emotional health. Our dataset included 371 participants. Emotional health was assessed by the NIH Toolbox emotion battery which yields negative affect, social satisfaction, and psychological well-being. Regressions were conducted for each composite, with HIV serostatus, sexual identity, and their interaction as independent variables along with covariates. The HIV serostatus x SM identity interaction was statistically significant in the regression of Negative Affect (p = .01): heterosexuals living with HIV had worse Negative Affect compared to heterosexual HIV-persons (p = .01). The interaction terms were for social satisfaction and psychological well-being were not significant. However, among PLWH, sexual minorities reported better Social Satisfaction (p = .03) and marginally better psychological well-being (p = .07) compared to heterosexuals.

ObjectiveRecent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis's anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH.Methods263 individuals were categorized into four groups: HIV- non-cannabis users (n = 65), HIV+ non-cannabis users (n = 105), HIV+ moderate cannabis users (n = 62), and HIV+ daily cannabis users (n = 31). Differences in pro-inflammatory biomarkers (IL-6, MCP-1/CCL2, IP-10/CXCL10, sCD14, sTNFR-II, TNF-α) by study group were determined by Kruskal-Wallis tests. Multivariable linear regressions examined relationships between biomarkers and seven cognitive domains, adjusting for age, sex/gender, race, education, and current CD4 count.ResultsHIV+ daily cannabis users showed lower MCP-1 and IP-10 levels in CSF compared to HIV+ non-cannabis users (p = .015; p = .039) and were similar to HIV- non-cannabis users. Plasma biomarkers showed no differences by cannabis use. Among PWH, lower CSF MCP-1 and lower CSF IP-10 were associated with better learning performance (all ps < .05).ConclusionsCurrent daily cannabis use was associated with lower levels of pro-inflammatory chemokines implicated in HIV pathogenesis and these chemokines were linked to the cognitive domain of learning which is commonly impaired in PWH. Cannabinoid-related reductions of MCP-1 and IP-10, if confirmed, suggest a role for medicinal cannabis in the mitigation of persistent inflammation and cognitive impacts of HIV.

ObjectiveThe Paced Auditory Serial Addition Test (PASAT) and Wechsler Adult Intelligence Scale Letter Number Sequencing subtest (LNS) are two commonly used measures of working memory. Demographic variables (age, education, ethnicity, etc.) can impact performance on these measures, underscoring the need for demographically adjusted norms. We aimed to develop normative data for the PASAT and LNS for Spanish-speaking adults living in the U.S.-Mexico border region as part of a larger normative effort.MethodParticipants were native Spanish-speakers from the Neuropsychological Norms for the U.S. Mexico Border Region in Spanish (NP-NUMBRS) project. Two hundred and forty-nine participants completed the PASAT and 202 participants completed LNS. Ages ranged from 19 to 60 and education from 0 to 20 years.ResultsOlder age was associated with lower scores on LNS (p < .01) but not PASAT. Lower education was associated with lower scores on both tests (ps < .001). Women obtained lower raw scores than men on PASAT (ps < .003), and there were no significant main effects of gender on LNS raw scores. Raw-to-scaled score conversions were calculated, and fractional polynomial equations were developed to calculate demographically-adjusted T-scores accounting for age, education, and gender. Published norms for English-speaking non-Hispanic Whites substantially overestimated rates of impairment (defined as T-score < 40) on both the PASAT and LNS.ConclusionsThe use of the population-specific normative data may improve detection of working memory dysfunction in U.S. Spanish-speaking adults and contribute to improved diagnostic accuracy and treatment planning in this population. Whether the norms generalize to U.S. Spanish-speakers from other countries remains to be determined.

ObjectiveVerbal fluency tests are sensitive to various disorders affecting the central nervous system and are commonly included in neuropsychological evaluations. We aimed to develop normative data for two verbal fluency tests in a sample of native Spanish-speakers living in the US-Mexico border region.MethodParticipants included 254 adults from the Neuropsychological Norms for the US-Mexico Border Region in Spanish (NP-NUMBRS) Project (Age: range = 19-60; Education: range = 0-20, 59% female). Participants completed two verbal fluency tests (i.e., letter [PMR] and semantic/category fluency [Animal Naming]) as part of a larger neuropsychological test battery. We examined linear and nonlinear effects of demographic factors (age, education, and gender) on verbal fluency raw scores, and developed T-scores using fractional polynomial equations controlling for demographics. We also calculated the rates of "impairment" (T-scores < 40) that would be obtained by applying the newly developed norms and available norms for non-Hispanic English-speakers on comparable tests.ResultsThere were positive small effects of age and medium effects of education on verbal fluency raw scores. The normalized distribution of T-scores with the new norms showed expected psychometric properties. However, rates of impairment for both letter and semantic fluency were significantly higher when applying non-Hispanic White norms, and significantly lower when applying non-Hispanic Black norms.ConclusionsWe provide norms for Spanish-speakers living along the US-Mexico border region for two verbal fluency tests that are co-normed with a more extensive neuropsychological battery. These regional norms will improve interpretation of verbal fluency test performance in Spanish-speakers living in the US-Mexico borderland.

ObjectiveWe developed demographically-corrected norms for Spanish-speakers from the U.S.-Mexico border regions of California and Arizona on two tests of motor skills - the Grooved Pegboard Test (Pegboard) and Finger Tapping Test (Tapping) - as part of a larger normative effort.MethodParticipants were native Spanish-speakers from the Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) Project (Pegboard: N = 254; Tapping: N = 183; age: 19-60 years; education: 0-20 years; 59% women). We examined the association of demographics (age, education and gender) with raw scores. Raw test scores were then converted to demographically-corrected T-scores via fractional polynomial equations. We also examined rates of impairment (T-score

ObjectiveThe Wisconsin Card Sorting Test (WCST) is among the most commonly used tests of executive functioning. We aimed to generate normative data on the 64-item version of this test (WCST-64) for Spanish-speakers living in the U.S.-Mexico Border region.MethodsParticipants included 189 native Spanish-speakers (Age: 19-60; Education: 0-20; 59.3% female) from the Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) project who completed the WCST-64. Univariable and interactive associations between demographic variables and raw scores were examined via Spearman correlations, Wilcoxon Rank-sum tests and linear regressions. T-scores for various WCST-64 measures (Total Errors, Perseverative Responses, Perseverative Errors, Conceptual Level Responses and Number of Categories) were obtained using fractional polynomial equations with weights for age, education, and gender. Percentile scores were reported for Failures to Maintain Set. Rates of impairment (T-score < 40) were calculated by applying the newly developed norms and published norms for non-Hispanic English-speaking Whites and Blacks.ResultsOlder age was associated with worse performance and education was linked to better performance on most WCST-64 raw scores, with stronger education effects among females than males. The norms developed here resulted in expected rates of impairment (14-16% across measures). Applying published norms for non-Hispanic Blacks resulted in generally comparable impairment rates. In contrast, applying previously published norms for non-Hispanic Whites overestimated impairment (38-52% across measures).ConclusionsThese data will enhance interpretation performance on the WCST-64 for Spanish-speakers living in the U.S.-Mexico Border region. Future work will need to examine the generalizability of these norms to other Hispanic/Latino groups.

ObjectiveThe present study aimed to develop norms applicable to Spanish-speakers living in the United States (U.S.)- Mexico border region for the Halstead Category Test (HCT), a test of executive function.MethodsHealthy native Spanish-speakers (N = 252; Age: range 19-60 years, M = 37.28, SD = 10.24; Education: range 0-20 years; M = 10.65, SD = 4.33; 58.33% women) living in the U.S.-Mexico border region of California and Arizona completed the HCT as part of a comprehensive neuropsychological test battery. The univariable and interactive effects of demographic variables on HCT raw scores were examined. Total scores were normed using fractional polynomial equations, controlling for age, education, and gender. T-scores were also computed for HCT scores of the current Spanish-speaking normative sample using published, demographically-adjusted norms for English-speaking non-Hispanic Whites and Blacks. Impairment rates (T-Scores < 40) were calculated using published and current norms.ResultsAge was significantly associated with increased number of errors, and education and male gender were associated with decreased number of HCT errors (total raw scores). Applying norms developed for English-speaking non-Hispanic Whites and Blacks resulted in overestimation of impairment rates in the current sample (impairment: 48% with White norms and 27% with Black norms). This pattern was evident across levels of education except in participants with 13+ years of education, where rates of impairment using non-Hispanic Black norms were comparable to those based on newly developed norms.ConclusionThe present study presents norms for the HCT in a sample of U.S. Spanish-speakers, providing an important tool for identifying executive dysfunction in this population.