Higher HIV-1 evolutionary rate is associated with cytotoxic T lymphocyte escape mutations in infants.

Escape from cytotoxic T lymphocyte (CTL) responses toward HIV-1 Gag and Nef has been associated with reduced control of HIV-1 replication in adults. However, less is known about CTL-driven immune selection in infants as longitudinal studies of infants are limited. Here, 1,210 gag and 1,264 nef sequences longitudinally collected within 15 months after birth from 14 HIV-1 perinatally infected infants and their mothers were analyzed. The number of transmitted founder (T/F) viruses and associations between virus evolution, selection, CTL escape, and disease progression were determined. The analyses indicated that a paraphyletic-monophyletic relationship between the mother-infant sequences was common (80%), and that the HIV-1 infection was established by a single T/F virus in 10 of the 12 analyzed infants (83%). Furthermore, most HIV-1 CTL escape mutations among infants were transmitted from the mothers and did not revert during the first year of infection. Still, immune-driven selection was observed at approximately 3 months after HIV-1 infection in infants. Moreover, virus populations with CTL escape mutations in gag evolved faster than those without, independently of disease progression rate. These findings expand the current knowledge of HIV-1 transmission, evolution, and CTL escape in infant HIV-1 infection and are relevant for the development of immune-directed interventions in infants.IMPORTANCEDespite increased coverage in antiretroviral therapy for the prevention of perinatal transmission, paediatric HIV-1 infection remains a significant public health concern, especially in areas of high HIV-1 prevalence. Understanding HIV-1 transmission and the subsequent virus adaptation from the mother to the infant's host environment, as well as the viral factors that affect disease outcome, is important for the development of early immune-directed interventions for infants. This study advances our understanding of vertical HIV-1 transmission, and how infant immune selection pressure is shaping the intra-host evolutionary dynamics of HIV-1.

A Scoping Survey to Inform Design of Digital Dementia Risk Reduction Interventions for Adults Concerned about their Cognitive Health.

Background: Digital dementia risk reduction interventions are cost-effective and scalable. However, it is unknown how they are perceived by people already experiencing cognitive concerns or decline. Objective: To understand the current use, interest, and preferences for online learning courses and interest in learning about factors influencing brain health and dementia risk among adults ≥45. To explore potential differences between individuals experiencing cognitive concerns and those without. Methods: Adults aged 45 and older completed a survey on technology use and healthy ageing (n = 249, Mean age = 65.6, 76.3% female). The Memory Assessment Clinic-Questionnaire was used to assess subjective memory decline, and 153 participants met the study criteria for cognitive concerns (≥25). Results: Almost all participants (98.4%) reported using two or more digital devices, and 51.8% reported increasing device usage following COVID-19. Most (92.1%) were interested in learning about healthy living and memory within an online course, and over 80% indicated a high interest in learning about dementia risk factors. People with cognitive concerns were more likely to report using a 'routine or system' to aid memory than people without (82.4% versus 62.9%, p = 0.001). However, no significant difference was found in technology use, course preferences, or interest in learning about different risk factors. Conclusions: We conclude that adults 45 years and over are interested in online methods for learning about brain health and offer unique insights into adapting dementia prevention programs for cognitive concerns.

How Perceptions of Aging Influence Physical Activity and Exercise in Older Age: Exploring the Behavior of People Aged 70+ Years Engaged in Fall Prevention Activities.

For older people, physical inactivity increases fall risk as well as other preventable health conditions. Despite the well-documented benefits of physical activity, uptake and adherence continue to challenge efforts aimed at increasing physical activity and reducing falls. Nested within a randomized controlled trial, this study reports on the factors influencing the physical activity behavior of people, aged between 70 and 90 years, engaged in StandingTall, a home-based balance exercise program proven to reduce falls in the community. The perception of aging, physical activity in older age, and the delivery of exercise were identified as major themes, with the perception of aging an overarching theme influencing both preferences for physical activity in older age and exercise delivery. Findings demonstrate the importance of considering the role of aging, the influence aging has on physical activity and exercise behavior, and how aging influences the delivery and design of exercise programs including falls prevention activities for older people.

The effect of Huntington's disease on cognitive and physical motivation.

Apathy is one of the most common neuropsychiatric features of Huntington's disease. A hallmark of apathy is diminished goal-directed behaviour, which is characterized by a lower motivation to engage in cognitively or physically effortful actions. However, it remains unclear whether this reduction in goal-directed behaviour is driven primarily by a motivational deficit and/or is secondary to the progressive cognitive and physical deficits that accompany more advanced disease. We addressed this question by testing 17 individuals with manifest Huntington's disease and 22 age-matched controls on an effort-based decision-making paradigm. Participants were first trained on separate cognitively and physically effortful tasks and provided explicit feedback about their performance. Next, they chose on separate trials how much effort they were willing to exert in each domain in return for varying reward. At the conclusion of the experiment, participants were asked to rate their subjective perception of task load. In the cognitive task, the Huntington's disease group were more averse to cognitive effort than controls. Although the Huntington's disease group were more impaired than controls on the task itself, their greater aversion to cognitive effort persisted even after controlling for task performance. This suggests that the lower levels of cognitive motivation in the Huntington's disease group relative to controls was most likely driven by a primary motivational deficit. In contrast, both groups expressed a similar preference for physical effort. Importantly, the similar levels of physical motivation across both groups occurred even though participants with Huntington's disease performed objectively worse than controls on the physical effort task, and were aware of their performance through explicit feedback on each trial. This indicates that the seemingly preserved level of physical motivation in Huntington's disease was driven by a willingness to engage in physically effortful actions despite a reduced capacity to do so. Finally, the Huntington's disease group provided higher ratings of subjective task demand than controls for the cognitive (but not physical) effort task and when assessing the mental (but not the physical) load of each task. Together, these results revealed a dissociation in cognitive and physical motivation deficits between Huntington's disease and controls, which were accompanied by differences in how effort was subjectively perceived by the two groups. This highlights that motivation is the final manifestation of a complex set of mechanisms involved in effort processing, which are separable across different domains of behaviour. These findings have important clinical implications for the day-to-day management of apathy in Huntington's disease.

Ageing attenuates exercise-enhanced motor cortical plasticity.

Cardiorespiratory exercise is known to modulate motor cortical plasticity in young adults, but the influence of ageing on this relationship is unknown. Here, we compared the effects of a single session of cardiorespiratory exercise on motor cortical plasticity in young and older adults. We acquired measures of cortical excitatory and inhibitory activity of the primary motor cortex using transcranial magnetic stimulation (TMS) from 20 young (mean ± SD = 25.30 ± 4.00 years, 14 females) and 20 older (mean ± SD = 64.10 ± 6.50 years, 11 females) healthy adults. Single- and paired-pulse TMS measurements were collected before and after a 20 min bout of high-intensity interval cycling exercise or an equivalent period of rest, and again after intermittent theta burst stimulation (iTBS). In both young (P = 0.027, Cohen's d = 0.87) and older adults (P = 0.006, Cohen's d = 0.85), there was an increase in glutamatergic excitation and a reduction in GABAergic inhibition from pre- to postexercise. However, in contrast to younger adults, older adults showed an attenuated plasticity response to iTBS following exercise (P = 0.011, Cohen's d = 0.85). These results demonstrate an age-dependent decline in cortical plasticity and indicate that a preceding bout of high-intensity interval exercise might be less effective for enhancing primary motor cortex plasticity in older adults. Our findings align with the hypothesis that the capacity for cortical plasticity is altered in older age. KEY POINTS: Exercise enhances motor cortical plasticity in young adults, but how ageing influences this effect is unknown. Here, we compared primary motor cortical plasticity responses in young and older adults before and after a bout of high-intensity interval exercise and again after a plasticity-inducing protocol, intermittent theta burst stimulation. In both young and older adults, exercise led to an increase in glutamatergic excitation and a reduction in GABAergic inhibition. Our key result was that older adults showed an attenuated plasticity response to theta burst stimulation following exercise, relative to younger adults. Our findings demonstrate an age-dependent decline in exercise-enhanced cortical plasticity and indicate that a preceding bout of high-intensity interval exercise might be less effective for enhancing primary motor cortex plasticity in older adults.

The LEISURE Study: A Longitudinal Randomized Controlled Trial Protocol for a Multi-Modal Lifestyle Intervention Study to Reduce Dementia Risk in Healthy Older Adults.

Dementia is understood to arise from a mixed etiology, enveloping chronic inflammatory and vascular impacts on the brain, driven by a constellation of modifiable risk factors which are largely mediated by lifestyle-related behaviors. These risk factors manifest over a prolonged preclinical period and account for up to 40% of the population attributable risk for dementia, representing viable targets for early interventions aimed at abating disease onset and progression. Here we outline the protocol for a 12-week randomized control trial (RCT) of a multimodal Lifestyle Intervention Study for Dementia Risk Reduction (LEISURE), with longitudinal follow-up at 6-months and 24-months post-intervention. This trial integrates exercise, diet, sleep, and mindfulness to simultaneously target multiple different etiopathogenetic mechanisms and their interplay in a healthy older adult population (aged 50-85 years), and assesses dementia risk reduction as the primary endpoint. The LEISURE study is located in the Sunshine Coast region of Australia, which has one of the nation's highest proportions of adults aged over 50 years (36.4%), and corresponding dementia prevalence. This trial is novel in its inclusion of mindfulness and sleep as multidomain lifestyle targets, and in its comprehensive suite of secondary outcomes (based on psychological, physical health, sleep activity, and cognitive data) as well as exploratory neuroimaging (magnetic resonance imaging and electroencephalography) and molecular biology measures. These measures will provide greater insights into the brain-behavioral underpinnings of dementia prevention, as well as the predictors and impacts of the proposed lifestyle intervention. The LEISURE study was prospectively registered (ACTRN12620000054910) on 19 January 2020.

A single bout of moderate-intensity aerobic exercise improves motor learning in premanifest and early Huntington's disease.

Introduction: Cardiorespiratory exercise has emerged as a promising candidate to modify disease progression in Huntington's disease (HD). In animal models, exercise has been found to alter biomarkers of neuroplasticity and delay evidence of disease, and some interventions-including exercise-have shown benefits in human HD patients. In healthy human populations, increasing evidence suggests that even a single bout of exercise can improve motor learning. In this pilot study, we investigated the effect of a single bout of moderate intensity aerobic exercise on motor skill learning in presymptomatic and early manifest HD patients. Methods: Participants were allocated to either an exercise (n = 10) or control (n = 10) group. They performed either 20 min of moderate intensity cycling or rest before practicing a novel motor task, the sequential visual isometric pinch force task (SVIPT). After 1 week, the retention of the SVIPT was measured in both groups. Results: We found that the exercise group performed significantly better during initial task acquisition. There were no significant differences in offline memory consolidation between groups, but total skill gain across both acquisition and retention sessions was greater in the group who exercised. The better performance of the exercise group was driven by improvements in accuracy, rather than speed. Discussion: We have shown that a single bout of moderate intensity aerobic exercise can facilitate motor skill learning in people with HD gene-expansion. More research is needed to investigate the underlying neural mechanisms and to further explore the potential for neurocognitive and functional benefits of exercise for people with HD.

The World Health Organization COVID-19 surveillance database.

In January 2020, SARS-CoV-2 virus was identified as a cause of an outbreak in China. The disease quickly spread worldwide, and the World Health Organization (WHO) declared the pandemic in March 2020.From the first notifications of spread of the disease, the WHO's Emergency Programme implemented a global COVID-19 surveillance system in coordination with all WHO regional offices. The system aimed to monitor the spread of the epidemic over countries and across population groups, severity of the disease and risk factors, and the impact of control measures. COVID-19 surveillance data reported to WHO is a combination of case-based data and weekly aggregated data, focusing on a minimum global dataset for cases and deaths including disaggregation by age, sex, occupation as a Health Care Worker, as well as number of cases tested, and number of cases newly admitted for hospitalization. These disaggregations aim to monitor inequities in COVID-19 distribution and risk factors among population groups.SARS-CoV-2 epidemic waves continue to sweep the world; as of March 2022, over 445 million cases and 6 million deaths have been reported worldwide. Of these, over 327 million cases (74%) have been reported in the WHO surveillance database, of which 255 million cases (57%) are disaggregated by age and sex. A public dashboard has been made available to visualize trends, age distributions, sex ratios, along with testing and hospitalization rates. It includes a feature to download the underlying dataset.This paper will describe the data flows, database, and frontend public dashboard, as well as the challenges experienced in data acquisition, curation and compilation and the lessons learnt in overcoming these. Two years after the pandemic was declared, COVID-19 continues to spread and is still considered a Public Health Emergency of International Concern (PHEIC). While WHO regional and country offices have demonstrated tremendous adaptability and commitment to process COVID-19 surveillance data, lessons learnt from this major event will serve to enhance capacity and preparedness at every level, as well as institutional empowerment that may lead to greater sharing of public health evidence during a PHEIC, with a focus on equity.

A qualitative examination of apathy and physical activity in Huntington's and Parkinson's disease.

Aim: In Huntington's disease (HD) and Parkinson's disease (PD), apathy is a frequently cited barrier to participation in physical activity. Current diagnostic criteria emphasize dissociable variants of apathy that differentially affect goal-directed behavior. How these dimensions present and affect physical activity in HD and PD is unknown. Methods: Using a qualitative approach, we examined the experience of apathy and its impact on physical activity in 20 people with early-manifest HD or idiopathic PD. Results: Two major themes emerged: the multidimensionality of apathy, including initiation or goal-identification difficulties, and the interplay of apathy and fatigue; and facilitators of physical activity, including routines, safe environments and education. Conclusion: Physical activity interventions tailored to apathy phenotypes may maximize participant engagement.

Motor cortex plasticity response to acute cardiorespiratory exercise and intermittent theta-burst stimulation is attenuated in premanifest and early Huntington's disease.

Huntington's disease (HD) mouse models suggest that cardiovascular exercise may enhance neuroplasticity and delay disease signs, however, the effects of exercise on neuroplasticity in people with HD are unknown. Using a repeated-measures experimental design, we compared the effects of a single bout of high-intensity exercise, moderate-intensity exercise, or rest, on motor cortex synaptic plasticity in 14 HD CAG-expanded participants (9 premanifest and 5 early manifest) and 20 CAG-healthy control participants, using transcranial magnetic stimulation. Measures of cortico-motor excitability, short-interval intracortical inhibition and intracortical facilitation were obtained before and after a 20-min bout of either high-intensity interval exercise, moderate-intensity continuous exercise, or rest, and again after intermittent theta burst stimulation (iTBS). HD participants showed less inhibition at baseline compared to controls. Whereas the control group showed increased excitability and facilitation following high-intensity exercise and iTBS, the HD group showed no differences in neuroplasticity responses following either exercise intensity or rest, with follow-up Bayesian analyses providing consistent evidence that these effects were absent in the HD group. These findings indicate that exercise-induced synaptic plasticity mechanisms in response to acute exercise may be attenuated in HD, and demonstrate the need for future research to further investigate exercise and plasticity mechanisms in people with HD.

Associations Between Planned Exercise, Walking, Incidental Physical Activity, and Habit Strength in Older People: A Cross-Sectional Study.

Habits play an important role in physical activity (PA) engagement; however, these associations in older people are not well understood. The present study aimed to investigate the relationship between engagement in types of PA and their automaticity in older people, using an observational, cross-sectional design. Current hours engaged in planned exercise (excluding walking), planned walking, and incidental activities and the automaticity of those PA behaviors were measured in 127 community-dwelling Australians aged 65 years and older via an online questionnaire. After controlling for demographic and health factors (age, gender, education level, body mass index, history of falls, and anxiety and depression symptoms), higher automaticity scores were associated with more hours undertaking planned walking and incidental activity but not planned exercise. Although preliminary, these findings indicate that the role of habit in maintaining PA in older people may, therefore, differ depending on the type of activity.

A Short-Term Intervention of High-Intensity Exercise and Anodal-tDCS on Motor Learning in Middle-Aged Adults: An RCT.

High-intensity exercise has enhanced motor learning in healthy young adults. Anodal-transcranial direct current stimulation (a-tDCS) may optimize these effects. This study aimed to determine the effects of a short-term high-intensity interval exercise intervention either with or without a-tDCS on the learning and retention of a novel motor task in middle-aged adults. Forty-two healthy middle-aged adults (age = 44.6 ± 6.3, female = 76%) were randomized into three groups: exercise and active a-tDCS, exercise and sham a-tDCS, and a non-exercise and sham a-tDCS control. Participants completed a baseline testing session, followed by three intervention sessions 48-h apart. The exercise groups completed 20-min of high-intensity exercise followed by a novel sequential visual isometric pinch task (SVIPT) while receiving 20-min of 1.5 mA a-tDCS, or sham tDCS. The control group completed 20-min of reading before receiving sham a-tDCS during the SVIPT. Learning was assessed by skill change within and between intervention sessions. Participants returned 5-7 days after the final intervention session and performed the SVIPT task to assess retention. All three groups showed evidence of learning on the SVIPT task. Neither group displayed enhanced overall learning or retention when compared to the control group. High-intensity exercise with or without a-tDCS did not improve learning or retention of a novel motor task in middle-aged adults. The methodological framework provides direction for future research to investigate the potential of differing exercise intensity effects on learning and retention.

Greater time in bed and less physical activity associate with poorer cognitive functioning performance in Huntington's disease.

Objective: This study aimed to investigate how sleep and physical activity habits related to cognitive functioning, in naturalistic settings, in early Huntington's disease (HD). Method: Forty-two participants with the expanded HD repeat (20 manifest, 22 premanifest) and 29 healthy controls wore Fitbit One sleep and activity monitors for 7 days and 7 nights. They used a smartphone application to complete daily sleep and activity diaries, sleep and mood inventories, and a brief battery of cognitive tests, which were completed on Day 8 of the study. All data were collected in naturalistic home and community settings. Results: Amongst participants with the expanded HD repeat, greater time spent in bed, measured by Fitbit, was associated with poorer accuracy and response speed on a test of visual memory, whereas lower levels of physical activity, measured by Fitbit, were associated with poorer accuracy on a test involving a working memory component. Neither time in bed nor physical activity is associated with a test of psychomotor speed. Groups were mostly similar across a range of Fitbit and self-report measures of sleep and physical activity, although the Manifest-HD group spent more time in bed than the Premanifest-HD and Healthy Control groups and had better self-reported sleep quality and more self-reported time spent sitting than the Healthy Control group and the Premanifest-HD group, respectively. Conclusions: Sleep timing and physical activity relate to cognitive functioning in HD and may be important targets for management in behavioral intervention studies aimed at improving cognition in HD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Multidimensional Apathy: The Utility of the Dimensional Apathy Scale in Huntington's Disease.

BACKGROUND: Apathy is a disorder of motivation common to Huntington's disease (HD). Recent conceptual frameworks suggest that apathy is not unitary but consists of discrete subtypes ("dimensions"). Which of the proposed dimensions are preferentially affected in HD, and how these dimensions evolve with disease progression is unknown. OBJECTIVES: The Dimensional Apathy Scale (DAS) separates apathy into Executive, Initiation and Emotional subscales. Using the DAS, we aimed to: 1) Determine the apathy subtypes prevalent in HD; 2) Compare the DAS against a unitary measure of apathy (Apathy Evaluation Scale, AES); 3) Assess the reliability of self- and observer-ratings; and 4) Determine the relationship between the DAS, and disease burden, total functional capacity (TFC) and the AES. METHOD: Fifty pre-manifest, 51 manifest-HD, 87 controls, and 50 HD-observers completed the DAS, AES, and TFC. RESULTS: Manifest-HD participants had the highest levels of apathy across all dimensions (30.4% on Executive subscale, 34.8% on Initiation subscale, and 15.2% on Emotional subscale), relative to pre-manifest and control participants. Self- and observer-ratings on the DAS did not differ. Hierarchical regressions across the entire gene-expanded sample showed that scores on the Initiation subscale correlated with AES scores; higher Executive subscale scores were related to higher disease burden; and Emotional subscale scores with lower total functional capacity. CONCLUSIONS: In this first study of the DAS in HD, manifest-HD participants were more apathetic than pre-manifest and control participants across all apathy subtypes. The DAS may be a useful tool for measuring different aspects of apathy in people with HD.

Feasibility and initial validation of 'HD-Mobile', a smartphone application for remote self-administration of performance-based cognitive measures in Huntington's disease.

OBJECTIVE: Smartphone-based cognitive assessment measures allow efficient, rapid, and convenient collection of cognitive datasets. Establishment of feasibility and validity is essential for the widespread use of this approach. We describe a novel smartphone application (HD-Mobile) that includes three performance-based cognitive tasks with four key outcome measures, for use with Huntington's disease (HD) samples. We describe known groups and concurrent validity, test-retest reliability, sensitivity, and feasibility properties of the tasks. METHODS: Forty-two HD CAG-expanded participants (20 manifest, 22 premanifest) and 28 healthy controls completed HD-Mobile cognitive tasks three times across an 8-day period, on days 1, 4, and 8. A subsample of participants had pen-and-paper cognitive task data available from their most recent assessment from their participation in a separate observational longitudinal study, Enroll-HD. RESULTS: Manifest-HD participants performed worse than healthy controls for three of four HD-Mobile cognitive measures, and worse than premanifest-HD participants for two of four measures. We found robust test-retest reliability for manifest-HD participants (ICC = 0.71-0.96) and with some exceptions, in premanifest-HD (ICC = 0.52-0.96) and healthy controls (0.54-0.96). Correlations between HD-Mobile and selected Enroll-HD cognitive tasks were mostly medium to strong (r = 0.36-0.68) as were correlations between HD-Mobile cognitive tasks and measures of expected disease progression and motor symptoms for the HD CAG-expanded participants (r = - 0.34 to - 0.54). CONCLUSIONS: Results indicated robust known-groups, test-retest, concurrent validity, and sensitivity of HD-Mobile cognitive tasks. The study demonstrates the feasibility and utility of HD-Mobile for conducting convenient, frequent, and potentially ongoing assessment of HD samples without the need for in-person assessment.

Dissociable Motivational Deficits in Pre-manifest Huntington's Disease.

Motivation is characterized by a willingness to overcome both cognitive and physical effort costs. Impairments in motivation are common in striatal disorders, such as Huntington's disease (HD), but whether these impairments are isolated to particular domains of behavior is controversial. We ask whether HD differentially affects the willingness of individuals to overcome cognitive versus physical effort. We tested 20 individuals with pre-manifest HD and compared their behavior to 20 controls. Across separate trials, participants made choices about how much cognitive or physical effort they were willing to invest for reward. Our key results were that individuals with pre-manifest HD were less willing than controls to invest cognitive effort but were no different in their overall preference for physical effort. These results cannot be explained by group differences in neuropsychological or psychiatric profiles. This dissociation of cognitive- and physical-effort-based decisions provides important evidence for separable, domain-specific mechanisms of motivation.

Investigating the psychological mechanisms underlying the relationship between nightmares, suicide and self-harm.

Evidence suggests that nightmares increase the risk of suicide and self-harm, independently of insomnia, PTSD, anxiety and depression. A better understanding of this relationship is vital for the development of effective suicide and self-harm interventions. A systematic review of the research investigating the mechanisms underlying the nightmare and suicide/self-harm relationship was therefore conducted. Findings from twelve studies were critically appraised and synthesised under the headings of affect/emotion regulation, cognitive appraisals, psychosocial factors, acquired capability and depression. Despite clear variability in the methodology employed by the studies, the initial evidence suggests cognitive appraisals and affect/emotion regulation play a key role in the nightmare and suicide/self-harm relationship. Consideration is given for the first time to the differences in the mechanisms underlying the relationship between nightmares and suicide. In order to further elucidate and support these findings however, future research utilising longitudinal designs, objective measures of sleep disturbance and investigating the emotional content of nightmares is vital. There is also a call for studies investigating the impact of nightmare interventions on subsequent suicidal thoughts and behaviours, and self-harm. This is especially so given that individuals might find it easier to seek help for nightmares than for suicidality or self-harm.

Structure of HIV-2 Nef Reveals Features Distinct from HIV-1 Involved in Immune Regulation.

The human immunodeficiency virus (HIV) accessory protein Nef plays a major role in establishing and maintaining infection, particularly through immune evasion. Many HIV-2-infected people experience long-term viral control and survival, resembling HIV-1 elite control. HIV-2 Nef has overlapping but also distinct functions from HIV-1 Nef. Here we report the crystal structure of HIV-2 Nef core. The di-leucine sorting motif forms a helix bound to neighboring molecules, and moreover, isothermal titration calorimetry demonstrated that the CD3 endocytosis motif can directly bind to HIV-2 Nef, ensuring AP-2-mediated endocytosis for CD3. The highly conserved C-terminal region forms a α-helix, absent from HIV-1. We further determined the structure of simian immunodeficiency virus (SIV) Nef harboring this region, demonstrating similar C-terminal α-helix, which may contribute to AP-1 binding for MHC-I downregulation. These results provide insights into the distinct pathogenesis of HIV-2 infection.

Intensity Matters: High-intensity Interval Exercise Enhances Motor Cortex Plasticity More Than Moderate Exercise.

A single bout of cardiovascular exercise can enhance plasticity in human cortex; however, the intensity required for optimal enhancement is debated. We investigated the effect of exercise intensity on motor cortex synaptic plasticity, using transcranial magnetic stimulation. Twenty healthy adults (Mage = 35.10 ± 13.25 years) completed three sessions. Measures of cortico-motor excitability (CME) and inhibition were obtained before and after a 20-min bout of either high-intensity interval exercise, moderate-intensity continuous exercise, or rest, and again after intermittent theta burst stimulation (iTBS). Results showed that high-intensity interval exercise enhanced iTBS plasticity more than rest, evidenced by increased CME and intracortical facilitation, and reduced intracortical inhibition. In comparison, the effect of moderate-intensity exercise was intermediate between high-intensity exercise and rest. Importantly, analysis of each participant's plasticity response profile indicated that high-intensity exercise increased the likelihood of a facilitatory response to iTBS. We also established that the brain-derived neurotrophic factor Val66Met polymorphism attenuated plasticity responses following high-intensity exercise. These findings suggest that high-intensity interval exercise should be considered not only when planning exercise interventions designed to enhance neuroplasticity, but also to maximize the therapeutic potential of non-invasive brain stimulation. Additionally, genetic profiling may enhance efficacy of exercise interventions for brain health.