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Summary: Nutraceutical approaches to promote adipose tissue thermogenesis may help to prevent obesity onset. Creatine is a critical regulator of adipose metabolic function and low-dose lithium supplementation has been shown to promote adipose thermogenesis. In the present study, we sought to directly compare the two supplements for their effects on adipose metabolism and thermogenesis. We show that both supplements increase daily energy expenditure (EE) and reduce body mass in male Sprague-Dawley rats. Lithium increased brown adipose tissue (BAT) mitochondrial and lipolytic proteins that are associated with thermogenesis, while creatine increased BAT UCP1 and mitochondrial respiration. The BAT thermogenic findings were not observed in females. White adipose tissue and skeletal muscle markers of thermogenesis were unaltered with the supplements. Together, the data show that low-dose lithium and creatine have diverging effects on markers of BAT thermogenesis and that each increase daily EE and lower body mass in a sex-dependent manner.

Objective: This study evaluated the concordance between clinical evaluation and diagnosis by a physician associate/assistant (PA) and the preoperative and intraoperative evaluations by a pediatric urologic surgeon., Methods: A retrospective chart review was performed for patients independently evaluated and scheduled for surgery by a single PA between 2017 and 2020. Concordance was measured by comparing the PA's office note with the surgeon's preoperative note and operative report., Results: Of the 242 patients scheduled for surgery, 11 underwent an operative report procedure change and 11 others underwent a preoperative note procedure change. Concordance increased from 89.09% in 2017 to 92.31% in 2020; this was not statistically significant ( P = .230). Urologic conditions evaluated demonstrated an increase in the variety and complexity of conditions., Conclusions: A supervisory/collaborative model involving a well-trained PA yields excellent outcomes in terms of concordance with surgical scheduling and procedure performed., (Copyright © 2024 American Academy of Physician Associates.)

Strategies that introduce students to unconscious bias and social determinants of health (SDOH) are critical to develop them as effective health care providers. We developed a semester-long activity that utilizes disease-relevant scientific literature to implement cultural humility training in a second-year rheumatology pharmacy course. Students were first re-introduced to implicit bias and then completed an anonymous survey at the beginning and conclusion of the course using a 5-point Likert scale to assess their perceptions of the role of biases and SDOH in patient care. Throughout the semester, five journal articles were assigned that relate to course material and focus on one characteristic (e.g., gout—gender). Students’ evolved perceptions of SDOH were compared to baseline data and characteristics of assigned articles indicate an improved understanding of SDOH including race/ethnicity (3.0 to 4.4, p < 0.0001); gender (2.8 to 4.0, p < 0.0001); and religion (2.3 to 2.9, p < 0.01). Among characteristics that were not directly discussed in the assignments, only education showed a significant increase (3.0 to 3.6, p < 0.01). Scientific articles that focus on health inequities relevant to course-specific diseases provide a strategy to integrate discussions that help students evaluate their biases and SDOH with the goal of improving patient care.

The fragmented and inefficient healthcare system in the United States leads to many preventable deaths and unnecessary costs every year. During a pandemic, the lives saved and economic benefits of a single-payer universal healthcare system relative to the status quo would be even greater. For Americans who are uninsured and underinsured, financial barriers to COVID-19 care delayed diagnosis and exacerbated transmission. Concurrently, deaths beyond COVID-19 accrued from the background rate of uninsurance. Universal healthcare would alleviate the mortality caused by the confluence of these factors. To evaluate the repercussions of incomplete insurance coverage in 2020, we calculated the elevated mortality attributable to the loss of employer-sponsored insurance and to background rates of uninsurance, summing with the increased COVID-19 mortality due to low insurance coverage. Incorporating the demography of the uninsured with age-specific COVID-19 and nonpandemic mortality, we estimated that a single-payer universal healthcare system would have saved about 212,000 lives in 2020 alone. We also calculated that US$105.6 billion of medical expenses associated with COVID-19 hospitalization could have been averted by a single-payer universal healthcare system over the course of the pandemic. These economic benefits are in addition to US$438 billion expected to be saved by single-payer universal healthcare during a nonpandemic year.

Aims: Self-management for people with epilepsy and a history of negative health events (SMART) is a behavioral intervention that has been demonstrated to reduce epilepsy-related complications and improve physical and mental health functioning among people with epilepsy (PWE) [1]. The Community-SMART (C-SMART) initiative was a 4-month prospective implementation of feasibility and pre/post outcomes of SMART in a community setting and in collaboration with key epilepsy service stakeholders., Methods: Self-management for people with epilepsy and a history of negative health events is a group-format, entirely virtual intervention delivered in eight 60-90 sessions over the course of 8-10 weeks. The C-SMART initiative used research staff to guide intervention performance evaluation and staff of a regional epilepsy advocacy agency to assist with community engagement. Process evaluations included outreach and engagement efforts needed to reach PWE, the barriers and facilitators to roll-out, and participant retention and satisfaction. Outcomes included depressive symptoms and epilepsy self-management competency., Results: Thirty individuals were enrolled in 3 "cohorts" of approximately 10 PWE per cohort. Mean age of participants was 48.50 (standard deviation 16.15) years, 60% were female and 53.3% were African-American. Individuals had epilepsy, on average, for over 2 decades, were on approximately 2 prescribed antiepileptic drugs (AEDs) and had an average of just over 6 seizures in the last 30 days. Over 63% had a comorbid mental health condition. There were 23 individuals (76.7%) who were retained at the 4-month follow-up. Baseline to 4-month outcomes for depression and epilepsy self-management were significantly improved. Most (90%) of participants reported high levels of satisfaction with the program., Conclusions: The SMART epilepsy self-management program can be successfully implemented in partnership with epilepsy-focused community partners, is acceptable to participants and associated with improved outcomes. Future work might consider how to make virtual epilepsy self-management available to the full spectrum of PWE., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To evaluate the outcomes of neonatal circumcision performed by a PA in pediatric urology., Methods: A retrospective review was performed of infants evaluated for neonatal circumcision by a single PA in pediatric urology over 30 months. Technique, age and weight at circumcision, presence or absence of genital anomalies, and complications were gathered., Results: Of the 371 male infants evaluated for neonatal circumcision, 276 underwent the procedure. Complications included retained Plastibell (2.1%), penile adhesions (1.1%), swelling (1.8%), and cosmetic concerns (0.73%). Eighteen unanticipated postprocedure visits occurred-four in the ED and 14 in the outpatient clinic. No acute procedural complications occurred. One patient (0.3%) underwent lysis of penile adhesions at age 19 months., Conclusion: Neonatal circumcisions are commonly performed by nonsurgeons with variable formal circumcision training. These data support that well-trained PAs can perform neonatal circumcisions with low complication rates.

A week-long, city-wide science festival called Everything is Science ( EiS ) was developed to educate the community in an informal manner. The festival serves as a platform for presenters from diverse professions to give engaging talks (without PowerPoint slides) to the public, free of charge, in restaurants and bars around town. Over 350 people attended the events over 5 days with 33 presenters. Surveys completed by attendees and session coordinators indicate strong support for this festival. Altogether, the EiS festival serves as a no-cost method to engage with the community and improve science literacy with potential for adoption in other cities., Competing Interests: Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: People with epilepsy frequently experience negative health events (NHEs), such as emergency room visits or hospitalizations for epilepsy-related complications despite significant advances in care. We developed a novel remotely delivered group-format epilepsy self-management program ("Self-management for people with epilepsy and a history of negative health events"; SMART). In a 6-month randomized controlled trial (RCT), SMART participants had significant decreases in NHEs, as well changes in attitudes and behaviors compared to a wait-list (Sajatovic et al., 2018). This secondary analysis from the RCT characterizes the indirect causal effects of SMART on NHE improvements that may be mediated by specific improvements in self-management, self-efficacy, social support, quality of life, and depression symptom severity., Methods: Participants were adults with epilepsy and a NHE in the prior 6 months. There were 60 participants in each RCT arm (SMART versus wait-list) and assessments were conducted at baseline, 10 weeks and 24 weeks. The outcome was a binary variable measuring NHE improvement at week 24. A counterfactual-based mediation framework was used to determine whether improvements or changes in attitudes and behaviors at specific time points or across the study period, mediated the impact of SMART on NHE improvements., Results: At week 24, SMART contributed to significant improvements in NHEs compared to those in wait-list (odds ratio = 3.2, p = 0.015). SMART was significantly associated with improvements and changes in aspects of self-management, self-efficacy, quality of life, and depression symptom severity at week 10, and significant improvements between baseline and week 24 in overall self-management and quality of life. Mediation analyses demonstrated that a portion of the effect (∼20-30 %; p < 0.05) of SMART on NHE improvement was also indirectly mediated by early improvements in depression symptom severity and quality of life., Conclusions: This mediation analysis of the SMART intervention demonstrates that in addition to its direct effect on improving NHEs in people with epilepsy, early improvements in depression symptom severity and quality of life indirectly mediated ∼20-30 % of the intervention's effect. These results demonstrate the promise of self-management approaches as a key component of an optimal healthcare model for people with epilepsy, particularly those with a recent history of NHEs., Competing Interests: Declaration of Competing Interest Dr. Sajatovic has research grants from Otsuka, Alkermes, Merck, Janssen, Reuter Foundation, Woodruff Foundation, Reinberger Foundation, National Institute of Health (NIH), and the Centers for Disease Control and Prevention (CDC). Dr. Sajatovic is a consultant to Bracket, Otsuka, Supernus, Neurocrine, Health Analytics and Sunovion and has received royalties from Springer Press, Johns Hopkins University Press, Oxford Press, and UpToDate., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A series of strained Ru(II) complexes were studied for potential anticancer activity in hypoxic tissues. The complexes were constructed with methylated ligands that were photolabile and an imidizo[4,5-f][1,10]phenanthroline ligand that contained an appended aromatic group to potentially allow for contributions of ligand-centered excited states. A systematic variation of the size and energy of the aromatic group was performed using systems containing 1-4 fused rings, and the photochemical and photobiological behaviors of all complexes were assessed. The structure and nature of the aromatic group had a subtle impact on photochemistry, altering environmental sensitivity, and had a significant impact on cellular cytotoxicity and photobiology. Up to 5-fold differences in cytotoxicity were observed in the absence of light activation; this rose to 50-fold differences upon exposure to 453 nm light. Most significantly, one complex retained activity under conditions with 1% O 2 , which is used to induce hypoxic changes. This system exhibited a photocytotoxicity index (PI) of 15, which is in marked contrast to most other Ru(II) complexes, including those designed for O 2 -independent mechanisms of action., (© 2019 American Society for Photobiology.)

Six homo- or heteroleptic tricationic Ir(R 1 -tpy)(R 2 -tpy) 3+ complexes ( Ir1 - Ir6 , R 1 /R 2 = Ph, 4'-N(CH 3 ) 2 Ph, pyren-1-yl, or 4'-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}Ph, tpy = 2,2';6',2"-terpyridine) were synthesized and tested for photodynamic therapy (PDT) effects. The ground- and excited-state characteristics of these complexes were studied systematically via spectroscopic methods and quantum chemistry calculations. All complexes possessed intraligand charge transfer ( 1 ILCT) / metal-to-ligand charge transfer ( 1 MLCT) dominated transition(s) in their low-energy absorption bands, which red-shifted with the increased electron-releasing strength of the R 1 /R 2 substituent. Five of the complexes exhibited ligand-centered 3 π,π */ 3 ILCT/ 3 MLCT emission. With a stronger electron-releasing R 1 /R 2 substituent, the degree of charge transfer contribution increased, leading to a decrease of the emission quantum yield. When the 4'-N(CH 3 ) 2 Ph substituent was introduced on both tpy ligands, the emission of Ir3 was completely quenched. Our study on the transient absorption of these complexes demonstrated that they all possessed broadband triplet excited-state absorption in the 400-800 nm region. Pyrenyl substitution of one or more tpy ligands, as in Ir4 and Ir5 , increased the lifetimes of the lowest triplet excited state and the singlet oxygen ( 1 O 2 ) production efficiencies. Ir1 - Ir5 were nontoxic toward SK-MEL-28 cells, with photocytotoxicities that varied from 0.18 to 153 µ M. Among them, Ir4 had the highest 1 O 2 quantum yield (0.81) in cell-free conditions, showing the largest photocytotoxicity against SK-MEL-28 cells for Ir(III) PSs to date, and was the most efficient generator of reactive oxygen species (ROS) in vitro . Ir4 possessed a very large phototherapeutic index (PI = dark EC 50 / light EC 50 ) of >1657, the largest reported for an Ir(III) complex photosensitizer upon broadband visible light (400-700 nm) activation. Ir4 also exhibited a very strong PDT effect toward MCF-7 breast cancer cells and its xenograft tumor model. Upon 450-nm light activation, Ir4 dramatically inhibited the xenograft tumor growth and exhibited negligible side effects upon PDT treatment., Competing Interests: Notes The authors declare no competing financial interest.

Background: HIV-exposed seronegative people who inject drugs (HESN-PWID) have been shown to have increased natural killer (NK) cell and myeloid activation when compared with control donors., Methods: We investigated potential mechanisms maintaining NK activation by conducting quantitative proteome comparisons of NK cells from HESN-PWID subjects and control donors. Proteins upregulated in NK cells were measured in the plasma of HESN-PWID subjects by ELISA and further investigated for their ability to induce innate immune activation in vitro., Results: The NK cell proteome comparison showed markedly higher levels of interferon-stimulated proteins and S100 proteins, including S100A14. Consistent with these results, we observed significantly higher levels of S100A14 in the plasma of HESN-PWID subjects compared with controls (P = 0.033, n = 25). In vitro, the addition of recombinant S100A14 protein significantly activated NK cells in a peripheral blood mononuclear cell mixture (P = 0.011, n = 9), but not purified NK cells alone. Treatment of purified monocytes with recombinant S100A14 protein induced secretion of TNF-alpha and led to significantly higher NK CD69 activation (P = 0.0156, n = 7) in a co-culture through a TLR4-dependent interaction., Conclusions: Our study identified S100A14 as a novel protein increased within NK cells and plasma of HESN-PWID subjects with the capacity to sustain NK activation through TLR4-dependent activation of myeloid cells.

Aims: Comorbid mental health conditions (MHCs) such as depression and anxiety are common in people with epilepsy. Targeted Self-Management for Epilepsy and Mental Illness (TIME) is a behavioral program that targets mood symptoms in adults with epilepsy and comorbid MHCs. Building upon positive findings of a randomized controlled study to establish the efficacy of TIME, the Community-TIME (C-TIME) initiative assessed the implementation feasibility and pre-/post-outcomes of this new evidence-based epilepsy self-management intervention in a community setting and in collaboration with key stakeholders., Methods: The C-TIME program is a group-format curriculum-based intervention delivered in ten 60-90 sessions over the course of 12 weeks. The C-TIME initiative used research staff to guide intervention performance evaluation, staff of a regional epilepsy advocacy agency to assist with community engagement and a county mental health services agency to support the transition from science to service. Process evaluations included outreach and engagement efforts needed to reach people with epilepsy and MHCs, the barriers and facilitators to roll out, and the participants' retention and satisfaction. The primary intervention participant outcome was depressive symptom severity at 4-month follow-up., Results: Referrals came from a variety of sources and approximately 1 in 3 referrals resulted in an enrollment. Thirty individuals were enrolled in 3 "cohorts" of 10. The most common reason for not being enrolled postscreening was that individuals did not show up for the baseline evaluation. Mean age of participants was 49.1 (12.8) years, 50% (N = 15) female, 55.2% (N = 16) white, 34.5% (N = 10) African-American. With respect to participation, 2/3 of the enrolled sample attended at least 7 out of the maximum 10 C-TIME sessions. Mean number of C-TIME sessions attended was 6.9 (4.1). Five participants (17%) had family members attend the C-TIME sessions, although family members were encouraged to play a supportive rather than primary role. Four-month follow-up outcome evaluation was available for 66% of the enrolled group. There was a significant reduction in depression severity, and patient satisfaction was over 90%., Conclusions: The C-TIME program can be successfully implemented in the community and is associated with improved outcomes in adults with epilepsy and comorbid MHCs. Continued and broader scale-up of C-TIME and similar approaches could reach larger groups of adults with epilepsy and improve the health of our communities., (Copyright © 2018 Elsevier Inc. All rights reserved.)

HIV-associated neurocognitive disorders (HAND) are prevalent despite combined antiretroviral therapy, affecting nearly half of HIV-infected patients worldwide. During HIV infection of macrophages secretion of the lysosomal protein, cathepsin B, is increased. Secreted cathepsin B has been shown to induce neurotoxicity. Oxidative stress is increased in HIV-infected patients, while antioxidants are decreased in monocytes from patients with HIV-associated dementia (HAD). Dimethyl fumarate (DMF), an antioxidant, has been reported to decrease HIV replication and neurotoxicity mediated by HIV-infected macrophages. Thus, we hypothesized that DMF will decrease cathepsin B release from HIV-infected macrophages by preventing oxidative stress and enhancing lysosomal function. Monocyte-derived macrophages (MDM) were isolated from healthy donors, inoculated with HIV-1 ADA, and treated with DMF following virus removal. After 12 days post-infection, HIV-1 p24 and total cathepsin B levels were measured from HIV-infected MDM supernatants using ELISA; intracellular reactive oxygen and nitrogen species (ROS/RNS) were measured from MDM lysates, and functional lysosomes were assessed using a pH-dependent lysosomal dye. Neurons were incubated with serum-free conditioned media from DMF-treated MDM and neurotoxicity was determined using TUNEL assay. Results indicate that DMF reduced HIV-1 replication and cathepsin B secretion from HIV-infected macrophages in a dose-dependent manner. Also, DMF decreased intracellular ROS/RNS levels, and prevented HIV-induced lysosomal dysfunction and neuronal apoptosis. In conclusion, the improvement in lysosomal function with DMF treatment may represent the possible mechanism to reduce HIV-1 replication and cathepsin B secretion. DMF represents a potential therapeutic strategy against HAND.

A series of cationic dinuclear iridium(III) complexes (Ir1-Ir5) bearing terpyridine-capped fluorenyl bridging ligands and different polypyridyl or cyclometalating terminal tridentate ligands were synthesized, characterized, and evaluated for their photophysical and photobiological activities. The influence of the bridging and terminal ligands on the photophysical properties of the complexes was investigated by UV-vis absorption, emission, and transient absorption spectroscopy and simulated by TDDFT calculations. All of the complexes displayed strong bridging-ligand localized visible 1 π,π* absorption and red- or near-infrared phosphorescence as well as broad triplet excited-state absorption across both visible and NIR wavelengths. These triplet states were assigned as predominantly 3 π,π* for Ir1 (τ = 3.1 μs) and Ir4 (τ = 48 μs) and 3 CT (charge transfer) for Ir2, Ir3, and Ir5 (τ = 1.7-2.7 μs). Complexes Ir1-Ir5 acted as in vitro photodynamic therapy (PDT) agents toward human SK-MEL-28 melanoma cells when activated with visible light, with submicromolar photocytotoxicity and phototherapeutic indices ranging from 20 to almost 300. The in vitro PDT effects with visible light did not correlate with singlet oxygen ( 1 O 2 ) quantum yields or DNA photocleaving capacity probed under cell-free conditions. All of the Ir(III) complexes phosphoresced brightly when associated with compromised cells (with or without light treatment) and exhibited photoactivated cellular uptake, highlighting the theranostic potential of this new class of Ir(III) complex photosensitizers.

Objectives This exploratory study identifies barriers and facilitators to self-management to inform future epilepsy self-management interventions for persons who have epilepsy complicated by co-morbid mental health conditions and serious medical events. Methods Focus group methods were used in a series of community advisory board meetings. Analysis was conducted using a thematic, constant comparative approach aiming to describe the range of barriers and facilitators salient to participants. There were a total of 22 participants, including 8 health professionals, 9 patients with epilepsy, and 5 care partners. Mean age was 49.1 (SD = 11.0, range 32-69), 11 (50%) were female, and 11 (50%) were male. For those with epilepsy, mean years having epilepsy was 24.7 (SD = 19.9, range 1-58 years). Results Individual psychological barriers (mental illness, fatigue, and psychological distress) prominently interfered with health behaviors. Community and family barriers included stigma, lack of epilepsy knowledge, and poor social support. Facilitators included planning for seizures, learning about medications, stress management, socializing with others, and talking with other epilepsy patients. Discussion Qualitative evidence in this study suggests a linkage between social integration and positive health behaviors. Future efforts to embed patients with epilepsy and their caregivers into clinical care processes could offset barriers and enhance facilitators.

Background: Depression is common in people with Parkinson's disease (PD), and exercise is known to improve depression and PD. However, lack of motivation and low self-efficacy can make exercise difficult for people with PD and comorbid depression (PD-Dep). A combined group exercise and chronic disease self-management (CDSM) program may improve the likeli-hood that individuals will engage in exercise and will show a reduction in depression symptoms. The purpose of this study was to compare changes in depression in PD-Dep between individual versus group exercise plus CDSM and to examine participant adherence and perception of the interventions., Methods: Participants (N=30) were randomized to either Enhanced EXerCisE thErapy for PD (EXCEED; group CDSM and exercise) or self-guided CDSM plus exercise. Outcomes were change in depression assessed with the Montgomery-Asberg Depression Rating Scale (MADRS), cognition, apathy, anxiety, sleep, quality of life, motor function, self-efficacy, and patient satisfaction., Results: Both groups showed significant improvement in MADRS ( P <0.001) with no significant group difference. Individuals in EXCEED group enjoyed the group dynamics but noted difficulty with the fixed-time sessions., Conclusion: Both group CDSM plus exercise and self-guided CDSM plus exercise can improve depression in PD-Dep. These findings suggest that development of a remotely delivered group-based CDSM format plus manualized exercise program could be useful for this population., Competing Interests: Disclosure MS has research grants from Pfizer, Merck, Alkermes, Janssen, Reuter Foundation, Woodruff Foundation, Reinberger Foundation, National Institute of Health (NIH), and Centers for Disease Control (CDC). She is a consultant to Bracket, Otsuka, Pfizer, Neurocrine, and Supernus, and has received royalties from Springer Press, Johns Hopkins University Press, Oxford Press, UpToDate, and Lexicomp. EM Walter is a consultant to US WorldMeds and Teva. BLW has research grants from NIH/NINDS, Teva Pharmaceuticals, UCB, Inc., Medtronic, and US WorldMeds. He is a consultant to Teva and Medtronic and is on the speaker’s bureau for Teva, Medtronic, US WorldMeds, and UCB, Inc. The other authors report no conflicts of interest in this work.

Background: The burden of stroke is severe among African-Americans. Despite overall declines in the rate of stroke since 2000, outcomes are largely unimproved or have worsened for African-American men. Adverse psychosocial challenges may hinder adherence to a regimen of risk factor reduction., Methods and Results: Focus group analysis was combined with a review of current published guidelines and epidemiologic evidence on risk factors to better understand stroke health disparities and potential policy solutions. Transcripts from three focus groups with ten African-American male stroke survivors under age 65 and their care partners (N = 7) were analyzed and compared with existing published data on (a) the burden of stroke (b) trends in clinical risk factors, and (c) trends in behavioral risk factors. Participants described myriad psychosocial barriers that impede reduction of risk indicators, including low trust in providers, poor social support, access difficulties, depression, and distress., Conclusions: In order to be effective, policies and programs must target mechanisms consistent with the challenges faced by African-American men. Infrastructure is needed to better identify and share practices effective for improving cardiovascular outcomes within specific racial and ethnic groups.

Objectives: Exercise can improve motor function in people with Parkinson's disease but depression reduces the motivation to participate in regular exercise. The aim of this study was to develop a novel Enhanced Exercise Therapy program that uses manual-driven guided exercise and peer-facilitated psychoeducation for individuals with Parkinson's disease and depression., Design: 24 week randomized controlled design., Methods: Thirty individuals were randomized to Enhanced Exercise Therapy or self-guided therapy, and evaluated at baseline, 12-weeks and at 24-weeks. Enhanced Exercise Therapy included group exercise and group psychoeducation for 12 weeks. Between 13 and 24 weeks, individuals had access to the fitness facility but group sessions were not held. Self-guided therapy included written guidelines for a self-paced exercise program and psychoeducation. Primary outcome measures included the number of exercise sessions and International Physical Activity Questionnaire score. Secondary measures included resting heart rate, supine blood pressure, estimated VO2max and incidence of orthostatic hypotension., Results: Twenty four individuals completed the study (80% retention) and both groups attended similar number of exercise sessions. There were no significant changes in cardiovascular fitness measures but there was a significant increase in the amount of physical activity in the Enhanced Exercise Therapy group and a decrease in the self-guided therapy group during the post-intervention period., Conclusions: Enhanced Exercise Therapy appears to promote engagement in an exercise program and more physical activity, even after group sessions were concluded in individuals with Parkinson's disease and depression., (Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Objective: HIV-1 variants with different tropisms are associated with various neuropathologies. This study intends to determine if this correlation is determined by unique viral env sequences. We hypothesize that HIV-1 envelope gene sequence changes are associated with cognition status., Methods: Viral RNA was extracted from peripheral blood mononuclear cells (PBMCs) co-cultures derived from HIV-1 infected Hispanic women that had been characterized for HIV associated neurocognitive disorders (HAND)., Results: Analyses of the C2V4 region of HIV gp120 demonstrated that increased sequence diversity correlates with cognition status as sequences derived from subjects with normal cognition exhibited less diversity than sequences derived from subjects with cognitive impairment. In addition, differences in V3 and V4 loop charges were also noted as well as differences in the N-glycosylation of the V4 region., Conclusions: Our data suggest that the genetic signature within the C2V4 region may contribute to the pathogenesis of HAND. HIV env sequence characteristics for the isolates grouped in milder forms of HAND can provide insightful information of prognostic value to assess neurocognitive status in HIV + subjects, particularly during the era of highly prevalent milder forms of HAND.

This article examines the beliefs and experiences of individuals living in underserved ethnically diverse communities in Cleveland, Ohio, regarding the influence of genetic, social, and environmental factors on health and health inequalities. Using a community-engaged methodological approach, 13 focus groups were conducted with African American, Hispanic, and White individuals residing in the Cleveland area to explore attitudes and beliefs about genetics, genetic research, and health disparities and inequalities. Results of this study highlight the range of meanings that individuals attach to genetic variation, genomic research, and gene-environment interactions, and their implications for addressing health inequalities. The majority of participants in all focus groups reported that social and environmental factors were more important than genetics in contributing to health inequalities. Most participants were unfamiliar with genetic research. These data have implications for how genetic information and research might be applied in conjunction with addressing social determinants of health to improve prevention strategies in underserved communities and ultimately reduce health inequalities.

Cystatin B and signal transducer and activator of transcription-1 (STAT-1) phosphorylation have recently been shown to increase human immunodeficiency virus-1 (HIV-1) replication in monocyte-derived macrophages (MDM), but the molecular pathways by which they do are unknown. We hypothesized that cystatin B inhibits the interferon (IFN) response and regulates STAT-1 phosphorylation by interacting with additional proteins. To test if cystatin B inhibits the IFN-β response, we performed luciferase reporter gene assays in Vero cells, which are IFN deficient. Interferon-stimulated response element (ISRE)-driven expression of firefly luciferase was significantly inhibited in Vero cells transfected with a cystatin B expression vector compared to cells transfected with an empty vector. To determine whether cystatin B interacts with other key players regulating STAT-1 phosphorylation and HIV-1 replication, cystatin B was immunoprecipitated from HIV-1-infected MDM. The protein complex was analyzed by liquid chromatography tandem mass spectrometry. Protein interactions with cystatin B were verified by Western blots and immunofluorescence with confocal imaging. Our findings confirmed that cystatin B interacts with pyruvate kinase M2 isoform, a protein previously associated cocaine enhancement of HIV-1 replication, and major vault protein (MVP), an IFN-responsive protein that interferes with JAK/STAT signals. Western blot studies confirmed the interaction with pyruvate kinase M2 isoform and MVP. Immunofluorescence studies of HIV-1-infected MDM showed that upregulated MVP colocalized with STAT-1. To our knowledge, the current study is the first to demonstrate the coexpression of cystatin B, STAT-1, MVP, and pyruvate kinase M2 isoform with HIV-1 replication in MDM and thus suggests novel targets for HIV-1 restriction in macrophages, the principal reservoirs for HIV-1 in the central nervous system.