A 2-Year, Randomized, Clinical Trial Examining the Effects of Speed of Processing Cognitive Training on Quality-of-Life Indicators in Adults With HIV-Associated Neurocognitive Disorder in Birmingham, Alabama: Results of the Think Fast Study.

ABSTRACT: Speed of processing (SOP) cognitive training may improve indicators of the quality of life (QoL) in people living with HIV. In this 2-year, longitudinal, randomized, controlled trial, 216 participants ages 40 years and older with HIV-associated neurocognitive disorder or borderline HIV-associated neurocognitive disorder were assigned to one of three groups: (a) 10 hr of SOP training (n = 70); (b) 20 hr of SOP training (n = 73), or (c) 10 hr of internet navigation control training (a contact control group; n = 73). Participants completed several QoL measures at baseline, posttest, and Year 1 and Year 2 follow-ups. Using linear mixed-effect models, no strong pattern of training effects across QoL outcomes was apparent, with small-magnitude, nonsignificant, between-group differences in depression, locus of control, and Medical Outcomes Study-HIV scales. In conclusion, despite prior work showing some transfer of SOP cognitive training improving QoL, that was not observed. Implications for research and practice are posited.

A 2-Year Longitudinal Randomized Control Trial of Speed of Processing Cognitive Training in Aging Adults with HIV-Associated Neurocognitive Disorder: Results of the Think Fast Study.

Nearly 40% of people with HIV (PWH) experience HIV-associated Neurocognitive Disorder (HAND). In this 3-group efficacy study, 216 PWH 40 + years with HAND or borderline HAND were randomized to either: (1) 10 h of SOP training (n = 70); (2) 20 h of SOP training (n = 73), or (3) 10 h of Internet navigation training (n = 73; contact control group). Participants were administered a measure of SOP [i.e., the Useful Field of View Test (UFOV®)] at baseline, at posttest immediately after training, and at year 1 and year 2 follow up. Intent-to-treat linear mixed-effect models with subject-specific intercept and slope were fitted to estimate between-group mean differences at the follow-up time-points. At the post-intervention time-point, small beneficial SOP training effects were observed for the 10-h group in UFOV® total (d = 0.28, p = 0.002). Effects were of larger magnitude for the 20-h group in these same outcomes [UFOV® total (d = 0.43, p < 0.001)]. These results indicated better benefit with more training. No intervention effect was observed at year 1. At year 2, beneficial effects of small magnitude were observed again in the 10-h group [UFOV® total (d = 0.22, p = 0.253)] with larger small-to-moderate magnitude in the 20-h group [UFOV® total (d = 0.32, p = 0.104)]. This study suggests that SOP training can improve a key indicator of this cognitive performance and that treatment gains are small-to-moderate over a two-year period. Prior literature suggests slower SOP is predictive of impairment in everyday functioning in older PWH; such an approach could potentially improve everyday functioning in PWH.

Cerca del 40% de las personas viviendo con VIH (PVV) experimentan Trastorno Neurocognitivo Asociado al VIH (HAND, por sus siglas en inglés). En este estudio de eficacia de 3 grupos, se aleatorizó a 216 PVV mayores de 40 años de edad con HAND o HAND límite a: (1) 10 horas de entrenamiento en velocidad de procesamiento (SOP, por sus siglas en inglés) (n = 70); (2) 20 horas de entrenamiento SOP (n = 73), o (3) 10 horas de entrenamiento en navegación por Internet (n = 73; grupo control de contacto). Se administró una medida de SOP a los participantes [la Prueba de Campo de Visión Útil (UFOV®)] al inicio, inmediatamente después del entrenamiento, y en el seguimiento de año 1 y año 2. Los datos se analizaron bajo el principio de intención de tratar, utilizando modelos lineales de efectos mixtos para estimar las diferencias promedio entre grupos en los puntos de seguimiento. En el punto de tiempo de post- entrenamiento, se observaron pequeños efectos beneficiosos del entrenamiento SOP para el grupo de 10 horas en el puntaje total de UFOV® (d = 0.28, p = 0.002). Para esta misma medida, los efectos fueron de mayor magnitud en el grupo de 20 horas [UFOV® total (d = 0.43, p < 0.001)]. Estos resultados indicaron un mayor beneficio con más entrenamiento. No se observó ningún efecto de intervención en el año 1. En el año 2, se observaron efectos beneficiosos de pequeña magnitud nuevamente en el grupo de 10 horas [UFOV® total (d = 0.22, p = 0.253)] y en el grupo de 20 horas [UFOV® total (d = 0.32, p = 0.104)] con una magnitud pequeña a moderada). Este estudio confirma que el entrenamiento SOP puede mejorar un indicador clave de este rendimiento cognitivo y que las ganancias del tratamiento son pequeñas a moderadas durante un período de dos años. La literatura previa sugiere que una SOP más lenta es predictiva de deterioro en el funcionamiento diario en PVV mayores; tal enfoque podría mejorar potencialmente el funcionamiento diario en PVV.

HIV PrEP Coverage Among Black Adults: A Concept Analysis of the Inequities, Disparities, and Implications.

Background: Significant racial disparities exist in HIV pre-exposure prophylaxis (PrEP) coverage in the United States (U.S), with Black individuals experiencing seven times higher new HIV infection rates compared to their White counterparts. Despite being the highest priority population at risk for HIV, Black adults have the lowest PrEP coverage, impacting the overall progress toward meeting the ending the HIV epidemic (EHE) goals in the U.S. Methods: Utilizing the Walker and Avant method, this concept analysis examined existing literature and U.S. Centers for Disease Control and Prevention resources to explore HIV PrEP coverage. Results: Findings highlighted a lack of clarity in the concept, resulting in four operational definitions. To address this ambiguity, a conceptual definition of HIV PrEP coverage was proposed, focusing on equitable access to PrEP medication among sexually active individuals aged 18-64 years, particularly those traditionally underserved and would benefit from PrEP. This inclusive definition aims to align with the dynamics of sexual behavior in racial minority groups. Key attributes of this conceptual definition include estimates of PrEP use, access, need, cost, side effects, frequency of HIV testing, and self-efficacy. Antecedents entail HIV status, testing behaviors, transmission risks, and communication with health care providers. Consequences involve perceptions of risk, screening routines, provider biases, stigma, and potential HIV transmission reduction. Conclusion: Analyzing HIV PrEP coverage offers useful insights into social and structural factors exacerbating health inequities in the field of HIV prevention and control. This concept analysis underscores the importance of unified sexual health communication, diverse approaches to PrEP access for racial minorities, and improved sexual health policies for Black adults. Moreover, understanding and advocating for equity in HIV PrEP coverage is crucial for addressing the existing racial disparities and achieving the EHE objectives in the U.S.

Self-Esteem Among U.S. African American and Latinx Adolescents With Depressive Symptoms and Overweight and/or Obesity.

PURPOSE: To examine the concept of self-esteem among African American and Latinx adolescents with overweight and/or obesity and depressive symptoms in the United States. METHOD: Using key terms in CINAHL, PubMed, and PsycINFO databases, an initial search yielded 371 articles; after examining title, abstract, and full text, 33 articles remained. The concept of adolescent self-esteem was analyzed using Rodger's evolutionary method. RESULTS: Several antecedents of self-esteem in this context were identified, including bullying, negative portrayal in the media, stressors and hassles, low socioeconomic status, dieting, and family dietary influences. Attributes identified were body image and misperception, body image dissatisfaction, diminished social status, and isolation. Consequences included stigma, somatic complaints, decreased earnings over a lifetime, decreased quality of life, lower educational attainment over a lifetime, and increased substance use. Increased self-esteem, increased number of friends, and in-depth friendships were associated with a lower risk of being overweight or obese. CONCLUSION: Adolescent self-esteem varied based on gender, racial and ethnic group, and changed over time in the African American population but remained static in the Latinx population. [Journal of Psychosocial Nursing and Mental Health Services, xx(xx), xx-xx.].

A Biparatopic Intrabody Renders Vero Cells Impervious to Ricin Intoxication.

Expression of camelid-derived, single-domain antibodies (VHHs) within the cytoplasm of mammalian cells as "intrabodies" has opened-up novel avenues for medical countermeasures against fast-acting biothreat agents. In this report, we describe a heterodimeric intrabody that renders Vero cells virtually impervious to ricin toxin (RT), a potent Category B ribosome-inactivating protein (RIP). The intrabody consists of two structurally defined VHHs that target distinct epitopes on RT's enzymatic subunit (RTA): V9E1 targets RTA's P-stalk recruitment site, and V2A11 targets RTA's active site. Resistance to RT conferred by the biparatopic VHH construct far exceeded that of either of the VHHs alone and effectively inhibited all measurable RT-induced cytotoxicty in vitro. We propose that targeted delivery of bispecific intrabodies to lung tissues may represent a novel means to shield the airways from the effects of inhalational RT exposure.

Chronic Pain Resilience Across Clinical Populations: A Concept Analysis.

BACKGROUND: Chronic pain resilience is a concept that is frequently used in research but lacks theoretical clarity. Understanding chronic pain resilience is germane to developing interventions to improve it and the overall quality of life among individuals with chronic pain. AIMS: To uncover and clarify the unique characteristics of the concept of chronic pain resilience. DESIGN: A concept analysis using Rodgers' evolutionary method. METHODS: Full-text articles published after 2000 in English were used to inform the concept analysis. Scopus, PubMed, PsychINFO, Embase, and CINAHL Plus with Full Text were utilized for literature searches. Rodgers' evolutionary approach was used to clarify the attributes, antecedents, and consequences. RESULTS: The search yielded 31 articles that were used in the analysis. The key attributes of chronic pain resilience included engagement in meaningful activities despite pain, maintaining positive psychological homeostasis, buffering against negative mental outcomes, seeking support, and self-empowerment. After considering surrogate terms, antecedents, attributes, and consequences, chronic pain resilience may be defined as the development of the capacity to successfully adapt to chronic pain. This adaptation results in a move toward optimal social, physical, mental, and behavioral functioning by balancing negative and positive psychosocial factors, despite the additional challenges brought about by living with chronic pain.

A Systematic Review and Meta-Analysis of Social Cognition Among People Living with HIV: Implications for Non-Social Cognition and Social Everyday Functioning.

Social cognition-the complex mental ability to perceive social stimuli and negotiate the social environment-has emerged as an important cognitive ability needed for social functioning, everyday functioning, and quality of life. Deficits in social cognition have been well documented in those with severe mental illness including schizophrenia and depression, those along the autism spectrum, and those with other brain disorders where such deficits profoundly impact everyday life. Moreover, subtle deficits in social cognition have been observed in other clinical populations, especially those that may have compromised non-social cognition (i.e., fluid intelligence such as memory). Among people living with HIV (PLHIV), 44% experience cognitive impairment; likewise, social cognitive deficits in theory of mind, prosody, empathy, and emotional face recognition/perception are gradually being recognized. This systematic review and meta-analysis aim to summarize the current knowledge of social cognitive ability among PLHIV, identified by 14 studies focused on social cognition among PLHIV, and provides an objective consensus of the findings. In general, the literature suggests that PLHIV may be at-risk of developing subtle social cognitive deficits that may impact their everyday social functioning and quality of life. The causes of such social cognitive deficits remain unclear, but perhaps develop due to (1) HIV-related sequelae that are damaging the same neurological systems in which social cognition and non-social cognition are processed; (2) stress related to coping with HIV disease itself that overwhelms one's social cognitive resources; or (3) may have been present pre-morbidly, possibly contributing to an HIV infection. From this, a theoretical framework is proposed highlighting the relationships between social cognition, non-social cognition, and social everyday functioning.

Structure of a human monoclonal antibody in complex with Outer surface protein C (OspC) of the Lyme disease spirochete, Borreliella burgdorferi.

Lyme disease is a tick-borne, multisystem infection caused by the spirochete, Borreliella burgdorferi . Although antibodies have been implicated in the resolution of Lyme disease, the specific B cell epitopes targeted during human infections remain largely unknown. In this study, we characterized and defined the structural epitope of a patient-derived bactericidal monoclonal IgG ("B11") against Outer surface protein C (OspC), a homodimeric lipoprotein necessary for B. burgdorferi tick-mediated transmission and early-stage colonization of vertebrate hosts. High-resolution epitope mapping was accomplished through hydrogen deuterium exchange-mass spectrometry (HDX-MS) and X-ray crystallography. Structural analysis of B11 Fab-OspC A complexes revealed the B11 Fabs associated in a 1:1 stoichiometry with the lateral faces of OspC A homodimers such that the antibodies are essentially positioned perpendicular to the spirochete's outer surface. B11's primary contacts reside within the membrane proximal regions of α-helices 1 and 6 and adjacent loops 5 and 6 in one OspC A monomer. In addition, B11 spans the OspC A dimer interface, engaging opposing α-helix 1', α-helix 2', and loop 2-3' in the second OspC A monomer. The B11-OspC A structure is reminiscent of the recently solved mouse transmission blocking monoclonal IgG B5 in complex with OspC A , indicating a mode of engagement with OspC that is conserved across species. In conclusion, we provide the first detailed insight into the interaction between a functional human antibody and an immunodominant Lyme disease antigen long considered an important vaccine target.

Diesel Engine Exhaust Exposure in Relation to Lung Cancer in Long-Haul Truck Drivers: An Eight-Step Concept Analysis.

BACKGROUND: Long-haul truck drivers (LHTDs) face a number of occupational hazards. One such hazard is exposure to diesel engine exhaust (DEE). However, this concept has yet to be analyzed. To address this gap, a concept analysis was conducted to explore the effects of DEE in relation to lung cancer. METHODS: Walker and Avant's eight-step concept analysis method was utilized: concept selection, analysis purpose, concept uses, defining attributes, model case, borderline case, antecedents and consequences, and empirical referents. PubMed, Scopus, and CINAHL databases were searched for relevant literature. FINDINGS: Diesel engine exhaust was identified as a mixture of gases and particulates that are considered carcinogenic. Defining attributes of DEE for truckers include respiratory effects such as decreased peak flow and increased airway resistance leading to symptoms such as a phlegm-producing cough, eye and throat irritation, exacerbation of asthma symptoms, and allergic responses. The identified level of DEE exposure associated with these attributes is 75 µg EC/m3 for 1 to 2 hours daily or a long-term exposure of 10 µg EC/m3. The conceptual definition of DEE in truckers was illustrated by the attributes, antecedents, consequences, model case, and empirical referents. CONCLUSION: Lung cancer was identified as a significant consequence of occupational DEE exposure for LHTDs. This analysis highlights the need for future research to develop interventions that will safeguard truckers from the adverse health effects of DEE exposure.

Single-domain antibodies reveal unique borrelicidal epitopes on the Lyme disease vaccine antigen, outer surface protein A (OspA).

Camelid-derived, single-domain antibodies (VHHs) have proven to be extremely powerful tools in defining the antigenic landscape of immunologically heterogeneous surface proteins. In this report, we generated a phage-displayed VHH library directed against the candidate Lyme disease vaccine antigen, outer surface protein A (OspA). Two alpacas were immunized with recombinant OspA serotype 1 from Borrelia burgdorferi sensu stricto strain B31, in combination with the canine vaccine RECOMBITEK Lyme containing lipidated OspA. The phage library was subjected to two rounds of affinity enrichment ("panning") against recombinant OspA, yielding 21 unique VHHs within two epitope bins, as determined through competition enzyme linked immunosorbent assays (ELISAs) with a panel of OspA-specific human monoclonal antibodies. Epitope refinement was conducted by hydrogen exchange-mass spectrometry. Six of the monovalent VHHs were expressed as human IgG1-Fc fusion proteins and shown to have functional properties associated with protective human monoclonal antibodies, including B. burgdorferi agglutination, outer membrane damage, and complement-dependent borreliacidal activity. The VHHs displayed unique reactivity profiles with the seven OspA serotypes associated with B. burgdorferi genospecies in the United States and Europe consistent with there being unique epitopes across OspA serotypes that should be considered when designing and evaluating multivalent Lyme disease vaccines.

Project EPIC (Empowering People to Independence in COPD): Study protocol for a hybrid effectiveness-implementation pilot randomized controlled trial of telephonic, geriatrics-palliative care nurse-coaching in older adults with COPD and their family caregivers.

BACKGROUND: EPIC (Empowering People to Independence in COPD) is a geriatric-palliative care telephonic, nurse coach intervention informed by Baltes' Theory of Successful Aging and adapted from the ENABLE (Educate, Nurture, Advise, Before Life Ends) intervention. EPIC, focused on improving independence, mobility, well-being, and COPD symptoms, has undergone formative and summative evaluation for adults with COPD. METHODS: The primary study aim is to assess the refined EPIC intervention's feasibility and acceptability via a pilot hybrid effectiveness-implementation randomized control trial in community-dwelling older adults with moderate to severe COPD and their family caregivers. The secondary aim is to explore the impact of EPIC on patient and caregiver outcomes. Older adults with COPD and their family caregivers (target N = 60 dyads) will be randomized to EPIC (intervention) or usual COPD care (control). EPIC includes six patient and four family caregiver weekly, telephone-based nurse coach sessions using a manualized curriculum (Charting Your Course), plus three monthly follow-up calls. Feasibility will be measured as completion of EPIC intervention and trial components (e.g., recruitment, retention, data collection). Acceptability will be evaluated using satisfaction surveys and post-study feedback interviews. A blinded data collector will assess exploratory outcomes (e.g., Life-Space mobility, quality of life, caregiver burden, emotional symptoms, loneliness, cognitive impairment, functional status, healthcare utilization) at baseline, 12, and 24 weeks. DISCUSSION: This intervention fills a gap in addressing the geriatrics and palliative care needs and equity for adults with COPD and their family caregivers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05040386.

Symptomatology and Quality of Life of Older People With HIV and Comorbid Chronic Obstructive Pulmonary Diseases From an HIV Clinic in Birmingham, Alabama.

ABSTRACT: Psychological symptomatology and quality of life (QoL) have been studied in older people with HIV (PWH) and those with chronic obstructive pulmonary disease (COPD), respectively, but there is a dearth of studies in older PWH with COPD. Our study compared depressive symptoms, anxiety, and QoL between older PWH with and without COPD using data from an HIV clinic in Birmingham, Alabama, from January 2018 to February 2020. Data on depressive symptoms (Patient Health Questionnaire-9), anxiety (Patient Health Questionnaire-5 Anxiety), and QoL (EuroQoL-5 Dimension) were analyzed. Among 690 PWH aged 50 years or older, 102 individuals (14.8%) had COPD. Significant differences were found between the two groups in depressive symptoms and components of QoL (e.g., mobility, self-care, usual activities, and pain/discomfort), but not in anxiety and general health. Experiencing COPD may worsen depressive symptomatology and QoL in older PWH, highlighting the need for tailored health care and research for this population.

"As I Grew Older, My Life Got Better": Conceptions of Successful Aging among Older Women Living with or at Risk of HIV.

Successful aging (SA) is an important target for HIV care. However, we have insufficient understanding of how older women living with HIV (OWLH) in the US define SA. We explored conceptions of SA by OWLH and older women at risk of HIV and examined whether SA conceptions differed by (1) HIV serostatus, and (2) participation in the Women's Interagency HIV Study (WIHS). These analyses were part of a larger mixed-methods study with a sequential design. Participants were recruited at two clinical WIHS sites. We enrolled both WIHS participants and non-WIHS clinic patients. Our sample was 84% Black and included 29 OWLH and 15 older women at risk of HIV. We conducted 21 semi-structured interviews and four focus groups. The dataset was analyzed using descriptive, comparative, and relational analysis. We found four interlinked themes: life course perspective, accepting and celebrating aging, taking care of yourself, and looking good. The life course perspective was a core theme: participants assessed their aging in comparison to their earlier life hardships. These themes were similarly present among OWLH and older women at risk of HIV, although OWLH emphasized taking care of HIV. SA conceptualizations by OWLH did not differ whether or not they participated in the WIHS. Women living with or at risk of HIV may experience severe hardships throughout their lives. Overcoming these hardships may be linked to SA. Assessing the needs and connecting women to resources and programs are critical for SA promotion.

Does Olfactory Training Improve Brain Function and Cognition? A Systematic Review.

Olfactory training (OT), or smell training,consists of repeated exposure to odorants over time with the intended neuroplastic effect of improving or remediating olfactory functioning. Declines in olfaction parallel declines in cognition in various pathological conditions and aging. Research suggests a dynamic neural connection exists between olfaction and cognition. Thus, if OT can improve olfaction, could OT also improve cognition and support brain function? To answer this question, we conducted a systematic review of the literature to determine whether there is evidence that OT translates to improved cognition or altered brain morphology and connectivity that supports cognition. Across three databases (MEDLINE, Scopus, & Embase), 18 articles were identified in this systematic review. Overall, the reviewed studies provided emerging evidence that OT is associated with improved global cognition, and in particular, verbal fluency and verbal learning/memory. OT is also associated with increases in the volume/size of olfactory-related brain regions, including the olfactory bulb and hippocampus, and altered functional connectivity. Interestingly, these positive effects were not limited to patients with smell loss (i.e., hyposmia & anosmia) but normosmic (i.e., normal ability to smell) participants benefitted as well. Implications for practice and research are provided.

Cognitive prescriptions for reducing dementia risk factors among Black/African Americans: feasibility, acceptability, and preliminary efficacy.

OBJECTIVES: Black/African Americans (B/AAs) have double the risk of Alzheimer's disease and related dementia than Whites, which is largely driven by health behaviors. This study examined the feasibility, acceptability, and preliminary efficacy of a pilot randomized clinical trial of an individualized multidomain health behavior intervention among middle-aged and older B/AAs (dubbed Cognitive Prescriptions [CogRx]). DESIGN: Thirty-nine community-dwelling B/AA participants aged 45-65 without significant cognitive impairment were randomized to one of three groups: CogRx, Psychoeducation, or no-contact control. The Psychoeducation and CogRx groups received material on dementia prevalence, prognosis, and risk factors, while the CogRx group additionally received information on their risk factor profile across the five CogRx domains (physical, cognitive, and social activity, diet, sleep). This information was used for developing tailored 3-month goals in their suboptimal areas. RESULTS: The CogRx program had high retention (all 13 CogRx participants completed the 3-month program and 97% of the full sample completed at least 1 follow-up) and was well-received as exhibited by qualitative and quantitative feedback. Themes identified in the positive feedback provided by participants on the program included: increased knowledge, goal-setting, personalization, and motivation. The COVID-19 pandemic was a consistent theme that emerged regarding barriers of adherence to the program. All three groups improved on dementia knowledge, with the largest effects observed in CogRx and Psychoeducation groups. Increases in cognitive, physical, and overall leisure activities favored the CogRx group, whereas improvements in sleep outcomes favored Psychoeducation and CogRx groups as compared to the control group. CONCLUSION: The CogRx program demonstrated feasibility, acceptability, and preliminary efficacy in increasing dementia knowledge and targeted health behaviors. Further refinement and testing of the implementation and effectiveness of similar person-centered dementia prevention approaches are needed on a larger scale in diverse populations. Such findings may have implications for clinical and public health recommendations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03864536.

A 2-year longitudinal randomized controlled trial examining the transfer of speed of processing training to secondary cognitive domains in middle-aged and older adults with HIV-associated neurocognitive disorder: Results of the think fast study.

OBJECTIVE: As people with HIV (PWH) age, they are at-risk of developing cognitive impairments compared to their seronegative counterparts. Although speed of processing (SOP) training may help improve this cognitive ability, less work has examined transfer to other cognitive domains. This study examined the effect of SOP training has on secondary cognitive domains in PWH aged 40+ years. METHOD: In this 3-group 2-year longitudinal study, 216 PWH with HIV-associated neurocognitive disorder (HAND) or borderline HAND were randomized to either: (1) 10 h of SOP training (n = 70); (2) 20 h of SOP training (n = 73); or (3) 10 h of an active control training (n = 73). Participants completed a comprehensive cognitive battery at baseline, immediately after training, and at 1 and 2 years. This battery yielded global and domain specific T-scores as well as a cognitive impairment variable. Generalized linear mixed-effect models were fitted to estimate between-group mean differences at the follow-up time-points adjusted for baseline. RESULTS: No clinically or statistically significant improvements in any of the cognitive outcomes were observed. A sensitivity analysis was conducted; conclusions replicated those of the main analysis, with two exceptions: Global Function T and Psychomotor Speed T showed relevant training improvements among the intervention groups over the control group at the immediate post time point. CONCLUSIONS: Although SOP training has been shown to improve cognitive abilities that correspond to driving and mobility, such training has limited therapeutic utility in improving cognition in other domains in PWH with HAND.