Anterior and posterior thalamic volumes differentially correlate with memory, attention, and motor processes in HIV infection and alcohol use disorder comorbidity.

The thalamus, with its reciprocal connections to and from cortical, subcortical, and cerebellar regions, is a central active participant in multiple functional brain networks. Structural MRI studies measuring the entire thalamus without respect to its regional or nuclear divisions report volume shrinkage in diseases including HIV infection, alcohol use disorder (AUD), and their comorbidity (HIV+AUD). Here, we examined relations between thalamic subregions (anterior, ventral, medial, and posterior) and neuropsychological functions (attention/working memory, executive functioning, episodic memory, and motor skills).

Immune tolerance promotion by LSEC-specific lentiviral vector-mediated expression of the transgene regulated by the stabilin-2 promoter.

Liver sinusoidal endothelial cells (LSECs) are specialized endocytic cells that clear the body from blood-borne pathogens and waste macromolecules through scavenger receptors (SRs). Among the various SRs expressed by LSECs is stabilin-2 (STAB2), a class H SR that binds to several ligands, among which endogenous coagulation products. Given the well-established tolerogenic function of LSECs, we asked whether the STAB2 promoter (STAB2p) would enable us to achieve LSEC-specific lentiviral vector (LV)-mediated transgene expression, and whether the expression of this transgene would be maintained over the long term due to tolerance induction.

Frontal cortical volume deficits as enduring evidence of childhood abuse in community adults with AUD and HIV infection comorbidity.

Background: Childhood abuse is an underappreciated source of stress, associated with adverse mental and physical health consequences. Childhood abuse has been directly associated with risky behavior thereby increasing the likelihood of alcohol misuse and risk of HIV infection, conditions associated with brain structural and functional deficits. Here, we examined the neural and behavioral correlates of childhood trauma history in alcohol use disorder (AUD), HIV infection (HIV), and their comorbidity (AUD+HIV).

Episodic memory deficit in HIV infection: common phenotype with Parkinson's disease, different neural substrates.

Episodic memory deficits occur in people living with HIV (PLWH) and individuals with Parkinson's disease (PD). Given known effects of HIV and PD on frontolimbic systems, episodic memory deficits are often attributed to executive dysfunction. Although executive dysfunction, evidenced as retrieval deficits, is relevant to mnemonic deficits, learning deficits may also contribute.

A prospective study revealing a compounded burden of COVID-19, sex, and clinical diagnosis of alcohol use disorder and HIV infection on quality of life, anxiety, and alcohol use.

The COVID-19 pandemic led to unprecedented restrictions to mitigate disease spread, leading to consequences affecting mental health. Many studies examining COVID-19 pandemic effects on well-being and mental health initiated inquiry after the pandemic onset, whereas we used self-report questionnaires obtained before the pandemic to re-assess the same functions during the pandemic. Participants were drawn from our ongoing longitudinal studies of people with HIV infection, alcohol use disorder (AUD), HIV + AUD comorbidity, and controls.

The effects of mood and cognition on daily functioning and quality of life in older people living with HIV and people with Parkinson's disease.

Objective: In light of the increased longevity of people living with HIV infection (PLWH) undergoing antiretroviral therapy (ART), the present study aimed to determine the effects of mood disturbances alongside cognitive and motor symptoms on activities of daily living (ADLs) and quality of life (QOL) in older PLWH in comparison to an aging control sample without notable medical history (CTL) and individuals with Parkinson's disease (PD).

Method: Forty-one PLWH, 41 individuals with PD, and 37 CTL, aged 45-79 years, underwent neuropsychological, psychological, and neurological assessment including depressive and anxiety symptoms, physical (ADL-p) and instrumental (ADL-i) daily activities, Unified Parkinson's Disease Rating Scale motor ADLs (ADL-UPDRS-II), QOL, and cognitive and motor functions. Hierarchical regression analyses assessed the relative contribution of predictors including demographics, disease-related factors, comorbid conditions, and mood-related factors for ADL and QOL scales.

Alcohol Use Disorder and Its Comorbidity With HIV Infection Disrupts Anterior Cingulate Cortex Functional Connectivity.

Background: Individuals with alcohol use disorder (AUD) have a heightened risk of contracting HIV infection. The effects of these two diseases and their comorbidity on brain structure have been well described, but their effects on brain function have never been investigated at the scale of whole-brain connectomes.

Methods: In contrast with prior studies that restricted analyses to specific brain networks or examined relatively small groups of participants, our analyses are based on whole-brain functional connectomes of 292 participants.

Alcohol's Unique Effects on Cognition in Women: A 2020 (Re)view to Envision Future Research and Treatment.

Alcohol use and misuse is increasing among women. Although the prevalence of drinking remains higher in men than women, the gender gap is narrowing. This narrative review focuses on the cognitive sequelae of alcohol consumption in women.

Deciphering the Ets-1/2-mediated transcriptional regulation of F8 gene identifies a minimal F8 promoter for hemophilia A gene therapy.

A major challenge in the development of a gene therapy for hemophilia A (HA) is the selection of cell type- or tissue-specific promoters to ensure factor VIII (FVIII) expression without eliciting an immune response. As liver sinusoidal endothelial cells (LSECs) are the major FVIII source, understanding the transcriptional F8 regulation in these cells would help optimize the minimal F8 promoter (pF8) to efficiently drive FVIII expression. In silico analyses predicted several binding sites (BS) for the E26 transformation-specific (Ets) transcription factors Ets-1 and Ets-2 in the pF8.

Identification and functional characterization of a novel splicing variant in the F8 coagulation gene causing severe hemophilia A.

Background: We have identified a synonymous F8 variation in a severe hemophilia A (HA) patient who developed inhibitors following factor VIII (FVIII) prophylaxis. The unreported c.6273 G > A variant targets the consensus splicing site of exon 21.

Cognitive impairment severity in relation to signs of subclinical Wernicke's encephalopathy in HIV and alcoholism comorbidity.

Objectives: The comorbidity of HIV infection and alcoholism (ALC) is prevalent. Wernicke's encephalopathy, a neurological disorder resulting from thiamine depletion, has been generally associated with alcoholism but has also been reported in HIV infection. This study examined whether subclinical Wernicke's encephalopathy signs could contribute to the heterogeneity of cognitive and motor deficits observed in individuals with both disease conditions (HIV+ALC).

Introduction to the special section on alcohol: Review of cognitive, emotional, and neural deficits and recovery with sustained abstinence and treatment.

Objective: Cognitive, behavioral, emotional, and neural dysfunction have been associated with misuse of alcohol for centuries.

Method: Multidisciplinary research efforts have shed much light on the profile of impaired and spared functions associated with excessive heavy drinking, with heterogeneity noted among alcoholic individuals.

Results: Myriad factors may moderate or mediate the untoward effects of misuse of alcohol and an individual's likelihood of initiation and maintenance of abstinence.

FVIII expression by its native promoter sustains long-term correction avoiding immune response in hemophilic mice.

Here we describe a successful gene therapy approach for hemophilia A (HA), using the natural F8 promoter (pF8) to direct gene replacement to factor VIII (FVIII)-secreting cells. The promoter sequence and the regulatory elements involved in the modulation of F8 expression are still poorly characterized and biased by the historical assumption that FVIII expression is mainly in hepatocytes. Bioinformatic analyses have highlighted an underestimated complexity in gene expression at this locus, suggesting an activation of pF8 in more cell types than those previously expected.

Information processing deficit in older adults with HIV infection: A comparison with Parkinson's disease.

Objective: Individuals with HIV treated with antiretroviral therapy can expect to reach average life span, making them susceptible to combined disease and aging effects on cognitive and motor functions. Slowed processing speed in HIV is a concern for cognitive and everyday functioning and is sensitive to declines in aging. We hypothesized that information processing (IP) deficits, over and above that expected with normal aging, would occur in older HIV patients similar to those observed in Parkinson's disease (PD) patients, with both conditions affecting frontostriatal pathways.

Celebrating the 125th anniversary of the American Psychological Association: A quarter century of neuropsychology.

Objective: The American Psychological Association (APA) celebrated its 125th anniversary in 2017. As part of this celebration, the APA journal has published in its November 2017 issue 11 papers describing some of the advances in the field of neuropsychology over the past 25 years.

Method: The papers address three broad topics: assessment and intervention, brain imaging, and theory and methods.

Neurological, nutritional and alcohol consumption factors underlie cognitive and motor deficits in chronic alcoholism.

Variations in pattern and extent of cognitive and motor impairment occur in alcoholism (ALC). Causes of such heterogeneity are elusive and inconsistently accounted for by demographic or alcohol consumption differences. We examined neurological and nutritional factors as possible contributors to heterogeneity in impairment.

Executive Functions, Memory, and Social Cognitive Deficits and Recovery in Chronic Alcoholism: A Critical Review to Inform Future Research.

Alcoholism is a complex and dynamic disease, punctuated by periods of abstinence and relapse, and influenced by a multitude of vulnerability factors. Chronic excessive alcohol consumption is associated with cognitive deficits, ranging from mild to severe, in executive functions, memory, and metacognitive abilities, with associated impairment in emotional processes and social cognition. These deficits can compromise efforts in initiating and sustaining abstinence by hampering efficacy of clinical treatment and can obstruct efforts in enabling good decision making success in interpersonal/social interactions, and awareness of cognitive and behavioral dysfunctions.

Effects of prior testing lasting a full year in NCANDA adolescents: Contributions from age, sex, socioeconomic status, ethnicity, site, family history of alcohol or drug abuse, and baseline performance.

Longitudinal study provides a robust method for tracking developmental trajectories. Yet inherent problems of retesting pose challenges in distinguishing biological developmental change from prior testing experience. We examined factors potentially influencing change scores on 16 neuropsychological test composites over 1year in 568 adolescents in the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) project.

Effects of Childhood Trauma and Alcoholism History on Neuropsychological Performance in Adults with HIV Infection: An Initial Study.

Background: Childhood trauma carries heightened risk for neuropsychological impairment and is a frequent concomitant of HIV infection (H) and alcoholism (Alc). Little is known about compounded effects of childhood trauma and these diseases on cognitive and motor functioning. We queried the relation between childhood trauma history (experiencing at least 1 of 13 specified traumas before age 18) and cognitive and motor performance in HIV infection with and without lifetime alcoholism.