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Purpose of Review: This review presents a summary of the literature on de-escalation and discontinuation of disease-modifying therapies (DMTs) in multiple sclerosis (MS), especially as it relates to the aging patient. Recent Findings: Currently available DMTs may have less benefit in people with MS who are older, stable and have received years of treatment. Observational studies and interventional trials in people with MS who de-escalate or discontinue their DMTs have demonstrated varied outcomes over the short- to medium-term. Certain factors such as a person's age, type of DMT, length of treatment, and recent presence of disease activity influence the likelihood of MS activity following discontinuation or de-escalation. Summary: Much work remains to be able to accurately predict when it is safe and appropriate for an individual with MS to discontinue or de-escalate from DMTs, though current research has narrowed down the window at which providers should begin to consider these issues. [ABSTRACT FROM AUTHOR]

Purpose of Review: Long-term use of multiple sclerosis (MS) disease-modifying therapies (DMTs) is standard practice to prevent accumulation of disability. Immunosenescence and other age-related changes lead to an altered risk–benefit ratio for older patients on DMTs. This article reviews recent research on the topic of de-escalation and discontinuation of MS DMTs. Recent Findings: Observational and interventional studies have shed light on what happens to patients who de-escalate or discontinue DMTs and the factors, such as age, treatment type, and presence of recent disease activity, that influence outcomes. Summary: Though many questions remain, recent findings have been valuable for the development of an evidence-based approach to making de-escalation and discontinuation decisions in MS. [ABSTRACT FROM AUTHOR]

Epilepsy affects 1% of the general population and 30% of patients are resistant to antiepileptic drugs. Although optogenetics is an efficient antiepileptic strategy, the difficulty of illuminating deep brain areas poses translational challenges. Thus, the search of alternative light sources is strongly needed. Here, we develop pH-sensitive inhibitory luminopsin (pHIL), a closed-loop chemo-optogenetic nanomachine composed of a luciferase-based light generator, a fluorescent sensor of intracellular pH (E2GFP), and an optogenetic actuator (halorhodopsin) for silencing neuronal activity. Stimulated by coelenterazine, pHIL experiences bioluminescence resonance energy transfer between luciferase and E2GFP which, under conditions of acidic pH, activates halorhodopsin. In primary neurons, pHIL senses the intracellular pH drop associated with hyperactivity and optogenetically aborts paroxysmal activity elicited by the administration of convulsants. The expression of pHIL in hippocampal pyramidal neurons is effective in decreasing duration and increasing latency of pilocarpine-induced tonic-clonic seizures upon in vivo coelenterazine administration, without affecting higher brain functions. The same treatment is effective in markedly decreasing seizure manifestations in a murine model of genetic epilepsy. The results indicate that pHIL represents a potentially promising closed-loop chemo-optogenetic strategy to treat drug-refractory epilepsy. Optogenetics is a powerful antiepileptic strategy in cases of drug resistance but light delivery to deep brain structure is hard to achieve. Here, authors develop a closed-loop chemo-optogenetic tool made of a luciferase, a sensor of intracellular pH, and an optogenetic actuator for silencing neuronal hyperactivity. [ABSTRACT FROM AUTHOR]

Chronic HIV disease is associated with a fivefold increase in albuminuria outside of sub-Saharan Africa. However, very little is known about albuminuria risk among people living with HIV (PLWH) in sub-Saharan Africa. Therefore, we conducted a cross-sectional observational HIV clinic-based study of albuminuria among 1533 adults aged 21 years or older between January 2020 and January 2021 in Gaborone, Botswana. Clinical albuminuria was defined using a sex-based albumin‒creatinine ratio (ACR) of 25–355 mg/g for females and 17–250 mg/g for males. The study population mean age was 48.5 (SD 10.3) years, and 764/1533 (49.7%) were female. The overall prevalence of albuminuria was 20.7% (95% CI 18.7%, 22.8%). A higher proportion of males were more likely to be categorized as having albuminuria than females, 25% (95% CI 22.0, 28.2) versus 16.4% (95% CI 13.8,19.2), P value < 0.001. In the final multivariate models, predictors of albuminuria differed by sex group. Larger longitudinal studies are required to evaluate the impact of albuminuria among PLWH with particular emphasis on the effect of sex on the risk of albuminuria. [ABSTRACT FROM AUTHOR]

Modulating brain oscillations has strong therapeutic potential. Interventions that both non-invasively modulate deep brain structures and are practical for chronic daily home use are desirable for a variety of therapeutic applications. Repetitive audio-visual stimulation, or sensory flicker, is an accessible approach that modulates hippocampus in mice, but its effects in humans are poorly defined. We therefore quantified the neurophysiological effects of flicker with high spatiotemporal resolution in patients with focal epilepsy who underwent intracranial seizure monitoring. In this interventional trial (NCT04188834) with a cross-over design, subjects underwent different frequencies of flicker stimulation in the same recording session with the effect of sensory flicker exposure on local field potential (LFP) power and interictal epileptiform discharges (IEDs) as primary and secondary outcomes, respectively. Flicker focally modulated local field potentials in expected canonical sensory cortices but also in the medial temporal lobe and prefrontal cortex, likely via resonance of stimulated long-range circuits. Moreover, flicker decreased interictal epileptiform discharges, a pathological biomarker of epilepsy and degenerative diseases, most strongly in regions where potentials were flicker-modulated, especially the visual cortex and medial temporal lobe. This trial met the scientific goal and is now closed. Our findings reveal how multi-sensory stimulation may modulate cortical structures to mitigate pathological activity in humans. [ABSTRACT FROM AUTHOR]

Approximately one-quarter of people with HIV (PWH) in the U.S. receive coverage through the Medicare program; however, no prior real-world study has examined antiretroviral therapy (ART) gaps and adherence and associated factors in this population. This retrospective cohort analysis used 2013–2018 national Medicare fee-for-service claims data to identify all PWH initiated on a new ART regimen including protease inhibitors [PI], non-nucleoside reverse transcriptase inhibitors [NNRTIs], or integrase strand transfer inhibitors [INSTIs] between 1/1/2014 and 12/31/2017. Study outcomes included ART adherence (based on proportion of days covered [PDC]), continuous treatment gaps ranging from 1 to 6 days to ≥ 180 days, and discontinuation (continuous gap ≥ 90 days) in the 12-month follow-up period. Multivariable regressions were used to assess factors associated with ART adherence and discontinuation. The final sample included 48,627 PWH (mean age: 54.5 years, 74.4% male, 47.5% White, 89.8% disabled). Approximately 53.0% of PWH had a PDC ≥ 0.95, 30.2% had a PDC between 0.70 and < 0.95, and 16.8% had PDC < 0.70. Treatment gaps of at least ≥ 7-days (55.2%) and ≥ 30-days (26.2%) were common and 10.1% PWH discontinued treatment. Younger age, female sex, Black race, higher comorbidity score, mental health conditions, and substance use disorder were associated with higher odds of lower adherence and discontinuation (all p-values < 0.05). In conclusion, suboptimal adherence and treatment gaps in ART use were commonly observed among PWH in Medicare. Interventions and policies to mitigate barriers to adherence are urgently needed in this population to both improve their survival and increase the potential for ending the HIV epidemic in the US. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension is the leading cause of heart disease in the world, and discontinuation or nonadherence of antihypertensive medication constitutes a significant global health concern. Patients with hypertension have high rates of medication nonadherence. Studies of reasons for nonadherence using traditional surveys are limited, can be expensive, and suffer from response, white-coat, and recall biases. Mining relevant posts by patients on social media is inexpensive and less impacted by the pressures and biases of formal surveys, which may provide direct insights into factors that lead to non-compliance with antihypertensive medication. Methods: This study examined medication ratings posted to WebMD, an online health forum that allows patients to post medication reviews. We used a previously developed natural language processing classifier to extract indications and reasons for changes in angiotensin receptor II blocker (ARB) and angiotensin-converting enzyme inhibitor (ACEI) treatments. After extraction, ratings were manually annotated and compared with data from the US Food and Drug administration (FDA) Adverse Events Reporting System (FAERS) public database. Results: From a collection of 343,459 WebMD reviews, we automatically extracted 1867 posts mentioning changes in ACEIs or ARBs, and manually reviewed the 300 most recent posts regarding ACEI treatments and the 300 most recent posts regarding ARB treatments. After excluding posts that only mentioned a dose change or were a false-positive mention, 142 posts in the ARBs dataset and 187 posts in the ACEIs dataset remained. The majority of posts (97% ARBs, 91% ACEIs) indicated experiencing an adverse event as the reason for medication change. The most common adverse events reported mapped to the Medical Dictionary for Regulatory Activities were "musculoskeletal and connective tissue disorders" like muscle and joint pain for ARBs, and "respiratory, thoracic, and mediastinal disorders" like cough and shortness of breath for ACEIs. These categories also had the largest differences in percentage points, appearing more frequently on WebMD data than FDA data (p < 0.001). Conclusion: Musculoskeletal and respiratory symptoms were the most commonly reported adverse effects in social media postings associated with drug discontinuation. Managing such symptoms is a potential target of interventions seeking to improve medication persistence. [ABSTRACT FROM AUTHOR]

The establishment of the Leveraging a Climate-neutral Society–strategic Research Network (LCS–RNet) (then named the International Research Network for Low Carbon Societies) was proposed at the Group of Eight (G8) Environment Ministers' Meeting in 2008. Its 12th annual meeting in December 2021 focused on the discussion on how to transition into a just and sustainable society and how to reduce the risks associated with the transition. This requires comprehensive studies including on the concept of transition, pathways to net-zero societies and how to realise the pathways by collaborating with various stakeholders. This Special Feature provides new insights into sustainability science by linking the scientific knowledge with practical science for the transition through the exploration of studies presented at the annual meeting. Following the opening paper, "A challenge for sustainability science: can we halt climate change?", a wide range of topics were discussed, including practices for sustainable transformation in the Erasmus University, practices in industry, energy transition and international cooperation. [ABSTRACT FROM AUTHOR]

In this paper, we present findings from a systematic review on job creation, quality, and skills, focusing on decarbonisation in the energy sector. We compare a range of gross job employment factors which indicate that overall, investment in renewable energy and energy efficiency can deliver more jobs than gas or coal power generation. In addition, we review a subset of recent studies which estimate the net employment effects of decarbonisation in the energy sector at a national scale, across various international contexts. These national studies largely agree that the most likely outcome over the next few decades is a modest net positive creation of jobs and moderate economic growth. In certain regions within these countries, jobs in fossil fuel industries may be lost faster than the pace at which low carbon energy sectors can offer new employment. There may be mismatches between regions where displaced workers live and where new opportunities become available, which may be a barrier to accepting alternative employment even if former workers have the requisite skills. In these cases national government transition plans are recommended, coordinated with local governments, to manage the impacts of displacement from carbon-intensive sectors and respond to the need to build a new low carbon workforce including through skills development and training. We highlight a lack of metrics and data in the literature on job quality, skills, and the geographic distribution of employment impacts in decarbonising energy systems, and these should be priority areas for further research. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD)1. However, achieving stable recovery is unpredictable2, typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting3. We currently lack objective brain-based biomarkers to guide clinical decisions by distinguishing natural transient mood fluctuations from situations requiring intervention. To address this gap, we used a new device enabling electrophysiology recording to deliver SCC DBS to ten TRD participants (ClinicalTrials.gov identifier NCT01984710). At the study endpoint of 24 weeks, 90% of participants demonstrated robust clinical response, and 70% achieved remission. Using SCC local field potentials available from six participants, we deployed an explainable artificial intelligence approach to identify SCC local field potential changes indicating the patient’s current clinical state. This biomarker is distinct from transient stimulation effects, sensitive to therapeutic adjustments and accurate at capturing individual recovery states. Variable recovery trajectories are predicted by the degree of preoperative damage to the structural integrity and functional connectivity within the targeted white matter treatment network, and are matched by objective facial expression changes detected using data-driven video analysis. Our results demonstrate the utility of objective biomarkers in the management of personalized SCC DBS and provide new insight into the relationship between multifaceted (functional, anatomical and behavioural) features of TRD pathology, motivating further research into causes of variability in depression treatment.This study demonstrates how activity in the cingulate cortex tracks depression recovery, providing symptom relief using deep brain stimulation. [ABSTRACT FROM AUTHOR]

People with HIV (PWH) smoke at higher rates compared with the general population and have lower cessation rates. The primary aim of this study was to examine the impact of the COVID-19 pandemic on smoking in PWH. A survey was administered to participants in two smoking cessation trials in the United States. Mean cigarettes per day was 13.9 (SD 8.6), and participants reported they had smoked on average for 30.93 years (SD 10.4). More than half (55.7%) of participants (N = 140) reported not changing their smoking during the pandemic, while 15% reported decreasing, and 25% reported increasing their smoking. In bivariate analyses, worrying about food due to lack of money (χ2 = 9.13, df 2, p = 0.01) and greater Covid-related worry (rs = 0.19, p = 0.02) were significantly associated with increased smoking. Qualitative research may be needed to more clearly elucidate factors related to smoking behaviors among PWH. [ABSTRACT FROM AUTHOR]

Introduction: Statin discontinuation can have major negative health consequences. Studying the reasons for discontinuation can be challenging as traditional data collection methods have limitations. We propose an alternative approach using social media. Methods: We used natural language processing and machine learning to extract mentions of discontinuation of statin therapy from an online health forum, WebMD (http://www.webmd.com). We then extracted data according to themes and identified key attributes of the people posting for themselves. Results: We identified 2121 statin reviews that contained information on discontinuing at least one named statin. Sixty percent of people posting declared themselves as female and the most common age category was 55–64 years. Over half the people taking statins did so for < 6 months. By far the most common reason given (90%) was patient experience of adverse events, the most common of which were musculoskeletal and connective tissue disorders. The rank order of adverse events reported in WebMD was largely consistent with those reported to regulatory agencies in the US and UK. Data were available on age, sex, duration of statin use, and, in some instances, adverse event resolution and rechallenge. In some instances, details were presented on resolution of the adverse event and rechallenge. Conclusion: Social media may provide data on the reasons for switching or discontinuation of a medication, as well as unique patient perspectives that may influence continuation of a medication. This information source may provide unique data for novel interventions to reduce medication discontinuation. [ABSTRACT FROM AUTHOR]

Purpose of Review: To summarize current evidence and recent developments in the surgical treatment of drug-resistant generalized epilepsy. Recent Findings: Current surgical treatments of drug-resistant generalized epilepsy include vagus nerve stimulation (VNS), deep brain stimulation (DBS) and corpus callosotomy (CC). Neurostimulation with VNS and/or DBS has been shown to be effective in reducing seizure frequency in patients with generalized epilepsy. DBS for generalized epilepsy is primarily consisted of open-loop stimulation directed at the centromedian (CM) nucleus in the thalamus, though closed-loop stimulation and additional targets are being explored. CC can be effective in treating some seizure types and can be performed using traditional surgical techniques or with the less invasive methods of laser ablation and radiosurgery. Summary: This current literature supports the use of VNS, DBS and CC, alone or in combination, as palliative treatments of drug-resistant generalized epilepsy. [ABSTRACT FROM AUTHOR]

Energy, food, or mobility can be conceptualized as provisioning systems which are decisive to sustainability transformations in how they shape resource use and because of emissions resulting from them. To curb environmental pressures and improve societal well-being, fundamental changes to existing provisioning systems are necessary. In this article, we propose that provisioning systems be conceptualized as featuring integrated socio-metabolic and political-economic dimensions. In socio-metabolic terms, material stocks—buildings, infrastructures, and machines, for example—are key components of provisioning systems and transform flows of energy and materials into goods and services. In political-economic terms, provisioning systems are formed by actors, institutions, and capital. We loosely identify and closely analyze, from socio-metabolic and political-economic perspectives, five phases along which provisioning systems are shaped and in which specific opportunities for interventions exist. Relying mainly on examples from the fossil-fueled electricity system, we argue that an integrated conceptualization of provisioning systems can advance understanding of these systems in two essential ways: by (1) facilitating a more encompassing perspective on current forms of provisioning as relying on capitalist regulation and on material stocks and flows and by (2) embedding provisioning systems within their historical context, making it possible to conceive of more sustainable and just forms of provisioning under (radically) altered conditions. [ABSTRACT FROM AUTHOR]

Episodic recall depends upon the reinstatement of cortical activity present during the formation of a memory. Evidence from functional neuroimaging and invasive recordings in humans suggest that reinstatement organizes our memories by time or content, yet the neural systems involved in reinstating these unique types of information remain unclear. Here, combining computational modeling and intracranial recordings from 69 epilepsy patients, we show that two cortical systems uniquely reinstate the semantic content and temporal context of previously studied items during free recall. Examining either the posterior medial or anterior temporal networks, we find that forward encoding models trained on the brain's response to the temporal and semantic attributes of items can predict the serial position and semantic category of unseen items. During memory recall, these models uniquely link reinstatement of temporal context and semantic content to these posterior and anterior networks, respectively. These findings demonstrate how specialized cortical systems enable the human brain to target specific memories. People can search for memories based on their content or context, defined as when and where they were formed. Here, the authors use direct brain recordings to provide evidence in line with the idea that separable neural systems retrieve these two types of information and predict whether recall is organized by time or content. [ABSTRACT FROM AUTHOR]

Psychological reactance is an aversive response to perceived threats against personal agency. For adolescents receiving HIV treatment in Botswana, we utilized a two-question, medication-specific reactance tool to assess whether: (1) verbal reminders to take medicines made adolescents want to avoid taking them, and, (2) whether adolescents felt anger when reminded to take medicines. Reactant adolescents had 2.05-fold (95% CI 1.23, 3.41) greater odds of treatment failure than non-reactant adolescents (p = 0.03). Adjusted risk of treatment failure was 14% (95% CI 3%, 28%) greater for each point elevation in reactance score (p = 0.016). Autonomy over medication-taking did not modify the association between reactance and treatment failure. Psychological reactance may be a useful interventional target for improving adolescent adherence. [ABSTRACT FROM AUTHOR]

The effects of mental health comorbidities and social support on the HIV pre-exposure prophylaxis (PrEP) care continuum are unknown. We conducted a cross-sectional study of men and transgender individuals, ≥ 18 years-old, with ≥ 2 male or transgender partners, or recent condomless anal intercourse. Surveys assessed demographics, mental health treatment, depressive symptomatology, social support, and PrEP-related social contacts. Logistic regression assessed associations between these factors and PrEP uptake and persistence. Participants (n = 247) were 89% cis-male and 46% African-American. Median age was 27 (IQR:23–33). Thirty-seven percent had ever used PrEP, of whom 18% discontinued use. High depressive symptomology was identified in 11% and 9% were receiving mental health treatment. There were no significant associations between depressive symptoms or mental health treatment on the odds of PrEP uptake or discontinuation. Each additional PrEP contact conferred a greater odds of uptake (aOR:1.24, 95% CI: 1.09–1.42). Network-level targets may produce fruitful interventions to increase PrEP uptake. [ABSTRACT FROM AUTHOR]

Rationale: People with HIV (PWH) smoke cigarettes at much higher rates than the general population and evidence-based cessation methods are less effective, putting PWH at greater risk for negative health outcomes. It is critical to identify the factors that underlie this health disparity. Delay discounting—the decline in the value of a reward when it is delayed—may explain this disparity. Objectives: This study aimed to (1) compare delay discounting between adult smokers with HIV and without HIV and (2) evaluate whether acute smoking abstinence disproportionately increases delay discounting among smokers with HIV. Methods: This sub-study was part of a larger study (NCT03169101) examining predictors of smoking cessation outcomes among smokers with HIV (n = 34) and smokers without HIV (n = 46) at two counterbalanced laboratory sessions (once smoking-as-usual and once following 24-h biochemically confirmed abstinence) then again, after 8 weeks of smoking cessation treatment. Results: There were no significant differences in delay discounting rates between HIV status groups (p = 0.49) or within-subject abstinence effects (p = 0.70). However, smokers without HIV exhibited a significant increase in delay discounting following smoking cessation treatment compared to baseline (p = 0.02), whereas the change among smokers with HIV did not reach statistical significance (p = 0.09). Conclusions: These findings do not support differences in delay discounting as a reason for the lower success rates of HIV+ smokers at quitting. Although delay discounting may not explain the disparity in smoking rates between people with and without HIV, future work should focus on additional correlates of higher smoking rates and lower quit rates among people with HIV. [ABSTRACT FROM AUTHOR]

Introduction: There are few studies assessing how data on adverse drug events from consumers on social media compare with other sources. Aim: The aim of this study was to assess the consistency of adverse event data of statin medications from social media as compared with other sources. Methods: We collected data on the adverse events of statins from Twitter, the US FDA Adverse Event Reporting System (FAERS), the UK Medicines and Healthcare products Regulatory Agency (MHRA), drug information databases (DIDs) and systematic reviews. We manually annotated 12,649 tweets collected between June 2013 and August 2018. We collected 45,447 reports from FAERS, 10,415 from MHRA, identified 17 systematic reviews with relevant data and extracted data from Facts and Comparisons® and Clinical Pharmacology®. We compared the proportion, relative frequencies and rank of each category of adverse event from each source using MedDRA® primary System Organ Class codes. Results: Compared with other sources, patients on social media are proportionally far more likely to complain about musculoskeletal symptoms than other adverse events. Most adverse events showed a high level of agreement between Twitter and regulatory data. DIDs tend to demonstrate similar patterns but not as strongly. Systematic reviews tend to examine pre-specified adverse events or those reported by trial investigators. Conclusions: Combining the data from multiple sources, albeit challenging, may provide a broader safety profile of any medication. Systematically collected social media reports may be able to contribute information on the most pertinent adverse effects to patients. [ABSTRACT FROM AUTHOR]

Despite reductions in smoking rates in the general population, little is known about recent smoking trends among people living with HIV (PLWH). We compared the risk for smoking and temporal trends in smoking among PLWH and the general population in the Philadelphia metropolitan area between 2009 and 2014. We used weighted logistic regression to assess the relation between HIV and smoking, and examined temporal smoking trends. The adjusted odds ratio (OR) for smoking comparing PLWH to the general population was 1.80 (95% CI 1.55–2.09) after adjusting for socio-economic, demographic, and mental health diagnosis variables. Smoking prevalence decreased in both the PLWH and general populations during the study period, and we did not observe a significant difference in rates of decline between groups (P = 0.54). Despite overall progress in smoking cessation, a disparity persisted in smoking rates between PLWH and the general population, with and without adjustment for socio-economic, demographic, and mental health variables. Further research is needed to understand the mechanisms linking HIV and tobacco use in order to inform public health efforts to reduce smoking among PLWH. [ABSTRACT FROM AUTHOR]

People living with HIV (PLWH) in the antiretroviral therapy (ART) era may lose more life-years to tobacco use than to HIV. Yet, smoking rates are more than twice as high among PLWH than the general population, contributing not just to mortality but to other adverse health outcomes, including neurocognitive deficits (neuroHIV). There is growing evidence that synergy with chronic inflammation and immune dysregulation that persists despite ART may be one mechanism by which tobacco smoking contributes to neuroHIV. This review will summarize the differential effects of nicotine vs tobacco smoking on inflammation in addition to the effects of tobacco smoke components on HIV disease progression. We will also discuss biomarkers of inflammation via neuroimaging as well as biomarkers of nicotine dependence (e.g., nicotine metabolite ratio). Tobacco smoking and nicotine may impact ART drug metabolism and conversely, certain ARTs may impact nicotine metabolism. Thus, we will review these bidirectional relationships and how they may contribute to neuroHIV and other adverse outcomes. We will also discuss the effects of tobacco use on the interaction between peripheral organs (lungs, heart, kidney) and subsequent CNS function in the context of HIV. Lastly, given the dramatic rise in the use of electronic nicotine delivery systems, we will discuss the implications of vaping on these processes. Despite the growing recognition of the importance of addressing tobacco use among PLWH, more research is necessary at both the preclinical and clinical level to disentangle the potentially synergistic effects of tobacco use, nicotine, HIV, cognition and immune dysregulation, as well as identify optimal approaches to reduce tobacco use. [ABSTRACT FROM AUTHOR]

Based on rodent models, researchers have theorized that the hippocampus supports episodic memory and navigation via the theta oscillation, a ~4–10 Hz rhythm that coordinates brainwide neural activity. However, recordings from humans have indicated that hippocampal theta oscillations are lower in frequency and less prevalent than in rodents, suggesting interspecies differences in theta’s function. To characterize human hippocampal theta, we examine the properties of theta oscillations throughout the anterior–posterior length of the hippocampus as neurosurgical subjects performed a virtual spatial navigation task. During virtual movement, we observe hippocampal oscillations at multiple frequencies from 2 to 14 Hz. The posterior hippocampus prominently displays oscillations at ~8-Hz and the precise frequency of these oscillations correlates with the speed of movement, implicating these signals in spatial navigation. We also observe slower ~3 Hz oscillations, but these signals are more prevalent in the anterior hippocampus and their frequency does not vary with movement speed. Our results converge with recent findings to suggest an updated view of human hippocampal electrophysiology. Rather than one hippocampal theta oscillation with a single general role, high- and low-frequency theta oscillations, respectively, may reflect spatial and non-spatial cognitive processes. [ABSTRACT FROM AUTHOR]

Rationale: Barriers to smoking cessation, including negative affect and cognitive dysfunction, may contribute to high smoking rates among people living with HIV/AIDS (PLWH). Varenicline may help PLWH quit smoking by improving mood and cognition, yet this has not been explored. Objectives: The goal of this study was to evaluate the effect of varenicline on mood and cognition among PLWH enrolled in a smoking cessation clinical trial. Methods: In this secondary analysis of a varenicline trial (NCT01710137), we assessed mood (depression, anxiety) and cognition (attention, working memory) at weeks 0 (baseline), 1, 3, and 12 (end-of-treatment, EOT). Primary outcomes were changes in mood and cognition from baseline to EOT. Secondarily, mood and cognition were evaluated as predictors of biochemically confirmed 7-day point-prevalence abstinence at EOT. Results: Overall, 173 subjects (87 varenicline, 86 placebo) were included. At EOT, varenicline reduced anxiety (P < 0.001), vs. placebo (P = 0.31; interaction P = 0.05). Across both treatment arms, reductions in anxiety from baseline to EOT were associated with a higher likelihood of abstinence (OR = 1.3, 95% CI 1.1 to 1.6, P = 0.01). There were no significant treatment by time interactions for cognition or depression. Conclusions: These data suggest that varenicline operates, at least in part, by reducing anxiety. Anxiety should be an intervention target for smokers with HIV interested in quitting. [ABSTRACT FROM AUTHOR]

The original article can be found online at https://doi.org/10.1007/s40264-023-01366-5.Correction to: Drug Safetyhttps://doi.org/10.1007/s40264-023-01366-5In the 'Funding' section of this article the grant number relating to National Institutes of Health (NIH) National Library of Medicine was incorrectly given as NIH NLM 1R01 when it should have been R01LM011176.The original article has been corrected.By Cristina Micale; Su Golder; Karen O'Connor; Davy Weissenbacher; Robert Gross; Sean Hennessy and Graciela Gonzalez-HernandezReported by Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

Copyright of AIDS & Behavior is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of AIDS & Behavior is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of AIDS & Behavior is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Objective: Efavirenz is commonly used in Africa and is frequently associated with neurocognitive toxicity, which may compromise clinical outcomes. Older individuals are at increased risk for drug toxicity and clinical outcomes may be worse in older age, particularly among those individuals with cytochrome P450 (CYP) 2B6 polymorphisms associated with slower efavirenz metabolism. The aim of this study was to determine if the CYP2B6 polymorphisms differentially impacts loss to care in older people.Methods: We conducted a prospective cohort study of 914 treatment-naïve HIV+ adults initiating efavirenz-based antiretroviral treatment at public HIV clinics in Gaborone, Botswana between 2009 and 2013. Older age, defined as age ≥ 50 years, was the primary exposure and loss to care at 6 months was the primary outcome. Interaction between age and CYP2B6 516G>T and 983T>C polymorphisms, defined as extensive, intermediate, and slow metabolism, was assessed. Neurocognitive toxicity was measured using a symptom questionnaire. Age-stratified logistic regression was performed to identify factors associated with loss to care.Results: Older age was associated with loss to care (OR 1.95, 95% CI 1.30-2.92). Age modified the effect of CYP2B6 genotype on loss to care with older, slow metabolizers at over four-fold higher risk when compared to older, intermediate metabolizers (OR 4.06 95% CI 1.38-11.89); neurocognitive toxicity did not mediate this risk. CYP2B6 metabolism genotype did not increase risk of loss to care in younger participants.Conclusion: Older age was associated with loss to care, especially among those with slow efavirenz metabolism. Understanding the relationship between older age and CYP2B6 genotype will be important to improving outcomes in an aging population initiating efavirenz-based ART in similar settings. [ABSTRACT FROM AUTHOR]

Memory failures are frustrating and often the result of ineffective encoding. One approach to improving memory outcomes is through direct modulation of brain activity with electrical stimulation. Previous efforts, however, have reported inconsistent effects when using open-loop stimulation and often target the hippocampus and medial temporal lobes. Here we use a closed-loop system to monitor and decode neural activity from direct brain recordings in humans. We apply targeted stimulation to lateral temporal cortex and report that this stimulation rescues periods of poor memory encoding. This system also improves later recall, revealing that the lateral temporal cortex is a reliable target for memory enhancement. Taken together, our results suggest that such systems may provide a therapeutic approach for treating memory dysfunction. [ABSTRACT FROM AUTHOR]

HIV-infected smokers lose more years of life to tobacco-related disease than HIV. Since neurocognitive deficits are common among those with HIV and are associated with smoking persistence, these deficits may be a unique barrier to smoking cessation among HIV-infected smokers. Documenting unique differences in and correlates of cognition among HIV-infected smokers is a critical step towards developing a population-specific tobacco cessation treatment. We compared neurocognitive function between HIV-infected ( n = 103) and HIV-uninfected smokers ( n = 70), accounting for demographic and smoking-related variables. We also evaluated whether HIV-related health outcomes (e.g., CD4 count, viral load, depression ratings, quality of life [QoL]) and HAART adherence were associated with cognition. Participants completed neurocognitive tasks (N-back and Continuous Performance Task [CPT]) measuring working memory, attention, and processing speed, and intra-individual variability. Stepwise regression models were conducted and validated with resampling techniques. HIV-infected smokers performed worse than HIV-uninfected smokers on working memory, processing speed, and intra-individual variability (all p < 0.01). ROC analysis for the model including cognitive measures demonstrated 85% area under the curve, which indicates 'good prediction' for distinguishing between HIV-infected and HIV-uninfected smokers. This was a significant improvement over the model including demographic and smoking-related variables only ( p = 0.0003). Among HIV-infected smokers, neurocognitive performance was negatively associated with QoL and depression ratings. Smoking cessation interventions for HIV-infected smokers should consider cognitive neurorehabilitation as a potential strategy to decrease the likelihood of nicotine relapse and decrease tobacco-related morbidity in this population. [ABSTRACT FROM AUTHOR]

Copyright of AIDS & Behavior is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of AIDS & Behavior is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of AIDS & Behavior is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Recent studies have shown that fibroblast transplantation can modify the activity of basal ganglia networks in models of Parkinson's disease. To determine its effects on parkinsonian motor symptoms, we performed autologous dermal fibroblast transplantation into the internal pallidum (GPi) in two parkinsonian rhesus monkeys with stable levodopa-induced dyskinesias (LIDs). Levodopa responses were assessed every week after transplantation for three months. A reduction of between 58% and 64% in total LIDs on the contralateral side was observed in both animals. No clear LID changes were observed on the ipsilateral side. These effects lasted the entire 3-month period in one monkey, but declined after 6-8 weeks in the other. The antiparkinsonian effects of levodopa did not diminish. The results of this pilot study indicate that fibroblast transplantation into the GPi may have beneficial effects on LIDs and warrant further investigation for potential therapeutic use. [ABSTRACT FROM AUTHOR]

White belts of snow clad mountains all over the world each winter. Even if there is no snow, the tourism industry is able to produce the white finery at the push of the button, thereby consuming large amounts of water. Studying Damüls, a well-known ski resort in Austria's westernmost province Vorarlberg, we can show that the development of a service sector within agro-pastoral landscapes was connected with novel water uses and massive interventions into Alpine landscapes. Human niche construction theory offers a unique avenue for studying the development of Alpine communities, but also highlights side effects accompanying the change from agrarian to tourism livelihoods. One aim of this paper is to broaden the scope of human niche construction theory. Inceptive, counteractive and relocational niche construction activities were coupled to the differentiation of actor groups. To incorporate social dynamics, indispensable for studies in environmental history, we propose the concept of socio-ecological niche construction. The paper investigates how villagers balanced resource limitations typical for an agrarian society with the differentiation of sub-niches, mediating selective forces on the population. When the valleys were industrialized, Damüls was almost given up as a permanent settlement. Then, tourists entered the stage, by and by turning the wheel of local development into a different direction. A tourism niche based on natural snow evolved from the 1930s onwards. While the socio-ecological niches of agriculture and tourism coexisted in the interwar years, this changed when ski lifts were built, embedded into a debt-based economy that made the tourism niche vulnerable to snow availability. Snow-dependency became a powerful selective force. It was mediated by the ski lift companies through a range of niche construction activities that turned water into an important resource of snowmaking systems. [ABSTRACT FROM AUTHOR]

Copyright of AIDS & Behavior is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Improving outcomes for people with HIV and mental illness will be critical to meeting the goals of the US National HIV/AIDS Strategy. In a retrospective analysis of the 2008-2010 cycles of the locally representative Philadelphia Medical Monitoring Project, we compared the proportions of HIV-infected adults with and without mental illness: (1) retained in care (≥2 primary HIV visits separated by ≥90 days in a 12-month period); (2) prescribed antiretroviral therapy (ART) at any point in a 12-month period; and (3) virally suppressed (HIV-1 RNA ≤200 copies/mL at the last measure in the 12-month period). Multivariable regression assessed associations between mental illness and the outcomes, adjusting for age, gender, race/ethnicity, insurance, alcohol abuse, injection drug use, CD4 count, and calendar year. Of 730 HIV-infected persons, representative of 9409 persons in care for HIV in Philadelphia, 49.0 % had mental illness. In adjusted analyses, there were no significant differences in retention (91.3 vs. 90.3 %; AOR 1.30, 95 % CI 0.63-2.56) and prescription of ART (83.2 vs. 88.7 %; AOR 0.79, 95 % CI 0.49-1.25) between those with and without mental illness. However, mentally ill patients were less likely to achieve viral suppression than those without mental illness (65.9 vs. 74.4 %; AOR 0.64, 95 % CI 0.46-0.90). These findings argue for the need to optimize ART adherence in this population. [ABSTRACT FROM AUTHOR]

Real-time amplification and quantification of specific nucleic acid sequences plays a major role in medical and biotechnological applications. In the case of infectious diseases, such as HIV, quantification of the pathogen-load in patient specimens is critical to assess disease progression and effectiveness of drug therapy.Typically, nucleic acid quantification requires expensive instruments, such as real-time PCR machines, which are not appropriate for on-site use and for low-resource settings. This paper describes a simple,low-cost, reaction-diffusion based method for end-point quantification of target nucleic acids undergoing enzymatic amplification. The number of target molecules is inferred from the position of the reaction-diffusion front, analogous to reading temperature in a mercury thermometer. The method was tested for HIV viral load monitoring and performed on par with conventional benchtop methods. The proposed method is suitable for nucleic acid quantification at point of care, compatible with multiplexing and high-throughput processing, and can function instrument-free. [ABSTRACT FROM AUTHOR]

Copyright of AIDS & Behavior is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Receiving care at multiple clinics may compromise the therapeutic patient-provider alliance and adversely affect the treatment of people living with HIV. We evaluated 12,759 HIV-infected adults in Philadelphia, PA between 2008 and 2010 to determine the effects of using multiple clinics for primary HIV care. Using generalized estimating equations with logistic regression, we examined the relationship between receiving care at multiple clinics (≥1 visit to two or more clinics during a calendar year) and two outcomes: (1) use of ART and (2) HIV viral load ≤200 copies/mL for patients on ART. Overall, 986 patients (8 %) received care at multiple clinics. The likelihood of attending multiple clinics was greater for younger patients, women, blacks, persons with public insurance, and for individuals in their first year of care. Adjusting for sociodemographic factors, patients receiving care at multiple clinics were less likely to use ART (AOR = 0.62, 95 % CI 0.55-0.71) and achieve HIV viral suppression (AOR = 0.78, 95 % CI 0.66-0.94) than individuals using one clinic. Qualitative data are needed to understand the reasons for visiting multiple clinics. [ABSTRACT FROM AUTHOR]

Non-adherence to safer sex and non-adherence to ART can each have adverse health consequences for HIV-infected individuals and their sex partners, but little is known about the association of these behaviors with each other. This 'dual risk' has potential negative public health consequences since non-adherence can lead to the development of resistant virus that can then be transmitted to sex partners. Among participants in the Multi-site Adherence Collaboration in HIV we examined, at study baseline, the association between the frequency of unprotected sex (assessed by self-report) and ART adherence (assessed by Medication Event Monitoring System, Aardex) among the sexually active participants in the five studies ( N = 459) that collected sexual risk behavior. The bivariate association between sexual risk behaviors and ART adherence was assessed by Pearson correlations; subsequently regression analyses were used to evaluate the role of demographic characteristics, depression and substance use in explaining the 'dual risk' outcome (sexual risk and non-adherence). Among participants who had been sexually active, more unprotected anal/vaginal sex was weakly associated with poorer ART adherence (r = −0.12, p = 0.01 for the overall sample). Further analysis showed this association was driven by the heterosexual men in the sample (r = −0.29, p < 0.001), and was significant only for this group, and not for gay/bisexual men or for women (heterosexual and homosexual). Neither substance use nor depression accounted for the association between sexual risk and ART adherence. HIV-infected heterosexual men who are having difficulty adhering to ART are also more likely to engage in risky sexual behaviors and therefore may benefit from counseling about these risk behaviors. We must identify procedures to screen for these risk behaviors and develop interventions, appropriately tailored to specific populations and identified risk factors, that can be integrated into routine clinical care for people living with HIV. This will become increasingly important in the context of wider access to treatment globally, including new recommendations for ART initiation earlier in a patients' disease course (e.g., 'Test and Treat' paradigms). [ABSTRACT FROM AUTHOR]

Emergency Departments (EDs) provide primary healthcare to many underserved persons without access to preventive healthcare elsewhere. We conducted a cross-sectional study to test the hypothesis that patients are more likely to express a willingness to accept rapid HIV testing in the ED if they lack access to preventive healthcare elsewhere. Medicaid insurance, younger age, lack of a usual place of healthcare, high perceived HIV risk, and actual HIV risk were associated with increased HIV test acceptance. These results support the need for and acceptability of rapid HIV testing in the ED particularly for individuals who may lack access to this preventive healthcare screening elsewhere. [ABSTRACT FROM AUTHOR]

Using biomass to provide energy services is a strategically important option for increasing the global uptake of renewable energy. Yet the practicalities of accelerating deployment are mired in controversy over the potential resource conflicts that might occur, particularly over land, water and biodiversity conservation. This calls into question whether policies to promote bioenergy are justified. Here we examine the assumptions on which global bioenergy resource estimates are predicated. We find that there is a disjunct between the evidence that global bioenergy studies can provide and policymakers' desire for estimates that can straightforwardly guide policy targets. We highlight the need for bottom-up assessments informed by empirical studies, experimentation and cross-disciplinary learning to better inform the policy debate. [ABSTRACT FROM AUTHOR]

Technological innovations have driven the advancement of the surgical treatment of movement disorders, from the invention of the stereotactic frame to the adaptation of deep brain stimulation (DBS). Along these lines, this review will describe recent advances in inserting neuromodulation modalities, including DBS, to the target, and in the delivery of therapy at the target. Recent radiological advances are altering the way that DBS leads are targeted and inserted, by refining the ability to visualize the subcortical targets using high-field strength magnetic resonance imaging and other innovations, such as diffusion tensor imaging, and the development of novel targeting devices enabling purely anatomical implantations without the need for neurophysiological monitoring. New portable computed tomography scanners also are facilitating lead implantation without monitoring, as well as improving radiological verification of DBS lead location. Advances in neurophysiological mapping include efforts to develop automatic target verification algorithms, and probabilistic maps to guide target selection. The delivery of therapy at the target is being improved by the development of the next generation of internal pulse generators (IPGs). These include constant current devices that mitigate the variability introduced by impedance changes of the stimulated tissue and, in the near future, devices that deliver novel stimulation patterns with improved efficiency. Closed-loop adaptive IPGs are being tested, which may tailor stimulation to ongoing changes in the nervous system, reflected in biomarkers continuously recorded by the devices. Finer-grained DBS leads, in conjunction with new IPGs and advanced programming tools, may offer improved outcomes via current steering algorithms. Finally, even thermocoagulation-essentially replaced by DBS-is being advanced by new minimally-invasive approaches that may improve this therapy for selected patients in whom it may be preferred. Functional neurosurgery has a history of being driven by technological innovation, a tradition that continues into its future. [ABSTRACT FROM AUTHOR]