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ObjectivePeople commonly cope with chronic low back pain (cLBP) by ignoring and distraction. Can mindful interoceptive exposure to the pain sensation itself and its phenomenological components be an alternative approach?MethodsSingle-arm feasibility study in patients with cLBP using a 2-minute attention exercise guided by a smartphone app several times per day over 8 weeks. We assessed feasibility, pre/post pain, function, and psychological parameters using mixed methods: standard questionnaires, ecological momentary assessment, and exit interviews that included micro-phenomenology technique and subsequent reflexive thematic qualitative analysis.ResultsWe enrolled 31 participants, mostly female, mean age 48, the majority had pain for >5 years; 29 completed. Mean pain intensity [0-10] improved from 4.8 ±1.7 to 3.1 ±1.9 (p < .0001); mean PEG scores (intensity and interference with daily life; range 0-30) improved from 13.7 ±6.2 to 8.4 ±6.6 (p < .0001); pain impact (9 items incl physical function) 22.3 ±8.7 to 19.7 ±8.1 (p = .0010). Twenty-one of 29 improved PEG score ≥30%. There were significant improvements in PCS Rumination and MAIA Not-Worrying. Participants became aware of their usual habit of avoidance and the challenge of and resistance to focusing on pain. They were surprised how pain sensations varied over time, and that pain intensity and the threat value of pain could diminish by focusing on it. They described a variety of 3D pain shapes (e.g., football, pool ball, rod, nail, brick, stars) with a range of colors, transparency, temperature, and density that for some changed with mindful attention. Most struggled to find appropriate words for sensory awareness and attention regulation and found that the threat value of their pain diminished.ConclusionsMindful interoceptive exposure to the sensations of their cLBP using a 2-minute attention exercise with a phone app-rather than ignoring and distracting from it-may be a beneficial intervention for cLBP.Trial registrationClinicalTrials.gov #NCT06186193.

BackgroundA very low-carbohydrate (VLC) nutritional strategy may improve glycemic control and weight loss in adults with type 2 diabetes (T2D). However, the supplementary behavioral strategies that might be able to improve outcomes using this nutritional strategy are uncertain.ObjectiveThis study aims to compare the impact of adding 3 different supplementary behavioral strategies to a web-based VLC diet intervention. To our knowledge, this is the first trial to randomize participants to different frequencies of dietary self-monitoring.MethodsThe study included 112 overweight adults with T2D (hemoglobin A1c ≥6.5%) taking no antiglycemic medications or only metformin. They received a remotely delivered 12-month VLC diet intervention. Participants were randomly assigned through a full factorial 2×2×2 design to supplementary strategies: either daily or monthly dietary self-monitoring, either mindful eating training or not, and either positive affect skills training or not. Our research goal was to determine whether 3 different supplemental strategies had at least a medium effect size (Cohen d=0.5).ResultsOverall, the VLC intervention led to statistically significant improvements in glycemic control (-0.70%, 95% CI -1.04% to -0.35%; P

BackgroundOptimal carbohydrate intake is an important and controversial area in the nutritional management of type 2 diabetes. Some evidence indicates that reducing overall carbohydrate intake with a low- or very low-carbohydrate eating plan can improve glycemic control compared to following eating plans that involve greater carbohydrate intake. However, critical knowledge gaps currently prevent clear recommendations about carbohydrate intake levels.MethodsThe LEGEND (Lifestyle Education about Nutrition for Diabetes) Trial aims to compare a very low-carbohydrate diet to a moderate-carbohydrate plate-method diet for glycemic control in adults with type 2 diabetes. This two-site trial plans to recruit 180 adults with type 2 diabetes. We will randomize participants to either a 20-session group-based diet and lifestyle intervention that teaches either a very low-carbohydrate diet or a moderate-carbohydrate plate-method diet. We will assess participants at study entry and 4 and 12 months later. The primary outcome is HbA1c, and secondary outcomes include inflammation (high sensitivity C-reactive protein), body weight, changes in diabetes medications, lipids (small particle LDL, HDL, triglycerides), skeletal metabolism (bone mineral density from dual-energy x-ray absorptiometry and bone turnover markers serum procollagen type I N propeptide and serum C-terminal telopeptide of type I collagen), and body composition (percent body fat, percent lean body mass).DiscussionThe LEGEND trial is a randomized controlled trial to assess optimal carbohydrate intake in type 2 diabetes by evaluating the effects of a very low-carbohydrate diet vs. a moderate-carbohydrate plate-method diet over a year-long period. The research addresses important gaps in the evidence base for the nutritional management of type 2 diabetes by providing data on potential benefits and adverse effects of different levels of carbohydrate intake.Trial registrationClinicalTrials.gov NCT05237128. Registered on February 11, 2022.

As concerns related to the COVID-19 pandemic continue, it is critical to understand the impact of vaccination type on neutralizing antibody response durability as well as to identify individual difference factors related to decline in neutralization. This was a head-to-head comparison study following 498 healthy, community volunteers who received the BNT162b2 (n = 287), mRNA-1273 (n = 149), and Ad26.COV2.S (n = 62). Participants completed questionnaires and underwent blood draws prior to vaccination, 1 month, and 6 months after the vaccination series, and neutralizing antibody (nAB) titers at 1- and 6-months post vaccination were quantified using a high-throughput pseudovirus assay. Over 6 months of follow-up, nABs declined in recipients of BNT162b2 and mRNA-1273, while nABs in recipients of Ad26.COV2.S showed a significant increase. At the 6-month time point, nABs to Ad26.COV2.S were significantly higher than nABs to BNT162b2 and equivalent to mRNA-1273. Irrespective of follow-up timing, being older was associated with lower nAB for participants who received BNT162b2 and Ad26.COV2.S but not for those who received mRNA-1273. A higher baseline BMI was associated with a lower nAB for Ad26.COV2.S recipients but not for recipients of other vaccines. Women and non-smokers showed higher nAB compared to men and current smokers, respectively. The durability of neutralizing antibody responses differed by vaccine type and several sociodemographic factors that predicted response. These findings may inform booster recommendations in the future.

BackgroundThe Mindfulness-Based Interventions: Teaching Assessment Criteria (MBI:TAC) is an important tool for assessing teacher skill and aspects of the fidelity of mindfulness-based interventions, but prior research on and implementation of the MBI:TAC has used video recordings, which can be difficult to obtain, share for assessments, and which increase privacy concerns for participants. Audio-only recordings might be a useful alternative, but their reliability is unknown.ObjectiveTo assess evaluator perception of the rating process and inter-rater reliability of MBI:TAC ratings using audio-only recordings.MethodsWe prepared audio-only files from video recordings of 21 previously rated Mindfulness-Based Stress Reduction teachers. Each audio recording was rated by 3 trained MBI:TAC assessors drawn from a pool of 12 who had previously participated in rating the video recordings. Teachers were rated by evaluators who had not viewed the video recording and did not know the teacher. We then conducted semi-structured interviews with evaluators.ResultsOn the 6 MBI:TAC domains, the intraclass correlation coefficients (ICCs) for audio recordings ranged from .53 to .69 using an average across 3 evaluators. Using a single rating resulted in lower ICCs (.27-.38). Bland-Altman plots showed audio ratings had little consistent bias compared to video recordings and agreed more closely for teachers with higher ratings. Qualitative analysis identified 3 themes: video recordings were particularly helpful when rating less skillful teachers, video recordings tended to provide a more complete picture for rating, and audio rating had some positive features.ConclusionsInter-rater reliability of the MBI:TAC using audio-only recordings was adequate for many research and clinical purposes, and reliability is improved when using an average across several evaluators. Ratings using audio-only recordings may be more challenging when rating less experienced teachers.

BackgroundMindfulness-based cognitive therapy (MBCT) is an effective group intervention for reducing rates of depression relapse. However, about one-third of graduates experience relapse within 1 year of completing the course.ObjectiveThe current study aimed to explore the need and strategies for additional support following the MBCT course.MethodsWe conducted 4 focus groups via videoconferencing, two with MBCT graduates (n = 9 in each group) and two with MBCT teachers (n = 9; n = 7). We explored participants' perceived need for and interest in MBCT programming beyond the core program and ways to optimize the long-term benefits of MBCT. We conducted thematic content analysis to identify patterns in transcribed focus group sessions. Through an iterative process, multiple researchers developed a codebook, independently coded the transcripts, and derived themes.ResultsParticipants said the MBCT course is highly valued and was, for some, "life changing." Participants also described challenges with maintaining MBCT practices and sustaining benefits after the course despite using a range of approaches (ie, community and alumni-based meditation groups, mobile applications, taking the MBCT course a second time) to maintain mindfulness and meditative practice. One participant described finishing the MBCT course as feeling like "falling off a cliff." Both MBCT graduates and teachers were enthusiastic about the prospect of additional support following MBCT in the form of a maintenance program.ConclusionSome MBCT graduates experienced difficulty maintaining practice of the skills they learned in the course. This is not surprising given that maintained behavior change is challenging and difficulty sustaining mindfulness practice after a mindfulness-based intervention is not specific to MBCT. Participants shared that additional support following the MBCT program is desired. Therefore, creating an MBCT maintenance program may help MBCT graduates maintain practice and sustain benefits longer-term, thereby decreasing risk for depression relapse.

ObjectiveThis study tested whether a mindfulness-based intervention for obesity that included components aimed at emotion regulation and mindful eating improved psychological outcomes including stress, anxiety, positive emotion, and depression, during the intervention period and at longer-term follow-up.MethodsAdults with obesity (N=194) were randomized to a 5.5-month diet-exercise weight loss intervention with or without mindfulness training focused on emotion regulation and mindful eating. Participants completed self-report measures of mindfulness and psychological well-being, which were planned secondary outcomes, at baseline, mid-intervention (3 months), and at 6-, 12-, and 18-months post-baseline (maintenance period). Mixed effects models and linear regression were used to test between- and within-group changes in psychological well-being. Finally, this study explored whether changes in mindfulness (from baseline to each 6- and 18-months post-baseline) mediated the effects of intervention arm on changes in psychological outcomes during those respective time periods. This study explored whether changes in mindfulness from baseline to 6 months mediated the effects of intervention arm on changes in psychological outcomes from baseline to 18 months.ResultsParticipants randomized to the mindfulness arm had significant increases in positive emotions at all follow-up times compared to controls. There were statistically significant increases in mindfulness, psychological flexibility, and reflection, as well as decreases in anxiety and depressive symptoms at 12 months compared to control participants. These changes remained significant for psychological flexibility and reflection at 18 months. There were no significant differences in perceived stress. Among mindfulness participants, greater increases in mindfulness from 6-18 months was associated with greater positive emotions and psychological flexibility as well as lower perceived stress, anxiety, depressive symptoms, and rumination at 18 months, adjusting for 6-month values. Mediation analyses indicated that randomization to the mindfulness intervention arm was associated with 6-month increases in mindfulness, and these increases were in turn associated with improved psychological outcomes at 6 months and 18 months. Changes from baseline to 18 months did not mediate 18-month changes in psychological outcomes.ConclusionsMindfulness training in emotion regulation and mindful eating may provide greater longer-term psychological well-being benefits in non-clinical populations with obesity compared to conventional diet-exercise interventions.

There is significant variability in neutralizing antibody responses (which correlate with immune protection) after COVID-19 vaccination, but only limited information is available about predictors of these responses. We investigated whether device-generated summaries of physiological metrics collected by a wearable device correlated with post-vaccination levels of antibodies to the SARS-CoV-2 receptor-binding domain (RBD), the target of neutralizing antibodies generated by existing COVID-19 vaccines. One thousand, one hundred and seventy-nine participants wore an off-the-shelf wearable device (Oura Ring), reported dates of COVID-19 vaccinations, and completed testing for antibodies to the SARS-CoV-2 RBD during the U.S. COVID-19 vaccination rollout. We found that on the night immediately following the second mRNA injection (Moderna-NIAID and Pfizer-BioNTech) increases in dermal temperature deviation and resting heart rate, and decreases in heart rate variability (a measure of sympathetic nervous system activation) and deep sleep were each statistically significantly correlated with greater RBD antibody responses. These associations were stronger in models using metrics adjusted for the pre-vaccination baseline period. Greater temperature deviation emerged as the strongest independent predictor of greater RBD antibody responses in multivariable models. In contrast to data on certain other vaccines, we did not find clear associations between increased sleep surrounding vaccination and antibody responses.

BackgroundDaily symptom reporting collected via web-based symptom survey tools holds the potential to improve disease monitoring. Such screening tools might be able to not only discriminate between states of acute illness and non-illness, but also make use of additional demographic information so as to identify how illnesses may differ across groups, such as biological sex. These capabilities may play an important role in the context of future disease outbreaks.ObjectiveUse data collected via a daily web-based symptom survey tool to develop a Bayesian model that could differentiate between COVID-19 and other illnesses and refine this model to identify illness profiles that differ by biological sex.MethodsWe used daily symptom profiles to plot symptom progressions for COVID-19, influenza (flu), and the common cold. We then built a Bayesian network to discriminate between these three illnesses based on daily symptom reports. We further separated out the COVID-19 cohort into self-reported female and male subgroups to observe any differences in symptoms relating to sex. We identified key symptoms that contributed to a COVID-19 prediction in both males and females using a logistic regression model.ResultsAlthough the Bayesian model performed only moderately well in identifying a COVID-19 diagnosis (71.6% true positive rate), the model showed promise in being able to differentiate between COVID-19, flu, and the common cold, as well as periods of acute illness vs. non-illness. Additionally, COVID-19 symptoms differed between the biological sexes; specifically, fever was a more important symptom in identifying subsequent COVID-19 infection among males than among females.ConclusionWeb-based symptom survey tools hold promise as tools to identify illness and may help with coordinated disease outbreak responses. Incorporating demographic factors such as biological sex into predictive models may elucidate important differences in symptom profiles that hold implications for disease detection.

Early detection of diseases such as COVID-19 could be a critical tool in reducing disease transmission by helping individuals recognize when they should self-isolate, seek testing, and obtain early medical intervention. Consumer wearable devices that continuously measure physiological metrics hold promise as tools for early illness detection. We gathered daily questionnaire data and physiological data using a consumer wearable (Oura Ring) from 63,153 participants, of whom 704 self-reported possible COVID-19 disease. We selected 73 of these 704 participants with reliable confirmation of COVID-19 by PCR testing and high-quality physiological data for algorithm training to identify onset of COVID-19 using machine learning classification. The algorithm identified COVID-19 an average of 2.75 days before participants sought diagnostic testing with a sensitivity of 82% and specificity of 63%. The receiving operating characteristic (ROC) area under the curve (AUC) was 0.819 (95% CI [0.809, 0.830]). Including continuous temperature yielded an AUC 4.9% higher than without this feature. For further validation, we obtained SARS CoV-2 antibody in a subset of participants and identified 10 additional participants who self-reported COVID-19 disease with antibody confirmation. The algorithm had an overall ROC AUC of 0.819 (95% CI [0.809, 0.830]), with a sensitivity of 90% and specificity of 80% in these additional participants. Finally, we observed substantial variation in accuracy based on age and biological sex. Findings highlight the importance of including temperature assessment, using continuous physiological features for alignment, and including diverse populations in algorithm development to optimize accuracy in COVID-19 detection from wearables.

Clinical trials including an analytical treatment interruption (ATI) are vital for evaluating the efficacy of novel strategies for HIV remissions. We briefly describe an interactive tool for predicting viral rebound timing in ATI trials and the impact of posttreatment controller (PTC) definitions on PTC frequency estimates. A 4-week viral load threshold of 1000 cps/ml provides both high specificity and sensitivity for PTC detection. PTC frequency varies greatly based on the definition of a PTC.

Future HIV-1 curative therapies require a thorough understanding of the distribution of genetically-intact HIV-1 within T-cell subsets during antiretroviral therapy (ART) and the cellular mechanisms that maintain this reservoir. Therefore, we sequenced near-full-length HIV-1 genomes and identified genetically-intact and genetically-defective genomes from resting naive, stem-cell memory, central memory, transitional memory, effector memory, and terminally-differentiated CD4+ T-cells with known cellular half-lives from 11 participants on ART. We find that a higher infection frequency with any HIV-1 genome was significantly associated with a shorter cellular half-life, such as transitional and effector memory cells. A similar enrichment of genetically-intact provirus was observed in these cells with relatively shorter half-lives. We found that effector memory and terminally-differentiated cells also had significantly higher levels of expansions of genetically-identical sequences, while only transitional and effector memory cells contained genetically-intact proviruses that were part of a cluster of identical sequences. Expansions of identical sequences were used to infer cellular proliferation from clonal expansion. Altogether, this indicates that specific cellular mechanisms such as short half-life and proliferative potential contribute to the persistence of genetically-intact HIV-1. IMPORTANCE The design of future HIV-1 curative therapies requires a more thorough understanding of the distribution of genetically-intact HIV-1 within T-cell subsets as well as the cellular mechanisms that maintain this reservoir. These genetically-intact and presumably replication-competent proviruses make up the latent HIV-1 reservoir. Our investigations into the possible cellular mechanisms maintaining the HIV-1 reservoir in different T-cell subsets have revealed a link between the half-lives of T-cells and the level of proviruses they contain. Taken together, we believe our study shows that more differentiated and proliferative cells, such as transitional and effector memory T-cells, contain the highest levels of genetically-intact proviruses, and the rapid turnover rate of these cells contributes to the expansion of genetically-intact proviruses within them. Therefore, our study delivers an in-depth assessment of the cellular mechanisms, such as cellular proliferation and half-life, that contribute to and maintain the latent HIV-1 reservoir.

IntroductionSuboptimal and differential participant engagement in randomized trials-including retention at primary outcome assessments and attendance at intervention sessions-undermines rigor, internal validity, and trial conclusions.MethodsFirst, this study describes Methods-Motivational Interviewing approach and strategies for implementation. This approach engages potential participants before randomization through interactive, prerequisite orientation sessions that illustrate the scientific rationale behind trial methods in accessible language and use motivational interviewing to diffuse ambivalence about participation. Then, this study examines the potential improvements in retention (proportion of participants assessed at follow-up visits) and attendance (e.g., mean percentage of intervention sessions attended, percentage of participants who attended 0 sessions) in 3 randomized weight-management trials that quickly added prerequisite orientations to their protocols following early signs of suboptimal or differential participant engagement (Supporting Health by Integrating Nutrition and Exercise [2009-2013, n=194]; Get Social [2016-2020, n=217]; GestationaL Weight Gain and Optimal Wellness [2014-2018, n=389]). Using a pre-post analytical design, adjusted estimates from regression models controlling for condition and assessment timepoint (analyses from 2020) are reported.ResultsAfter adding prerequisite orientations, all 3 trials attained higher participant engagement. Retention at assessments was 11.4% and 17.3% higher (Get Social and Supporting Health by Integrating Nutrition and Exercise, respectively). Mean percentage of attendance at intervention sessions was 8.8% higher (GestationaL Weight Gain and Optimal Wellness), and 10.1% fewer participants attended 0 intervention sessions (Get Social). Descriptively, all the remaining retention and attendance outcomes were consistently higher but were nonsignificant. Across the trials, adding prerequisite orientations did not impact the proportion of eligible participants enrolled or the baseline demographics.ConclusionsThe Methods-Motivational Interviewing approach shows promise for increasing the rigor of randomized trials and is readily adaptable to in-person, webinar, and conference call formats.Trial registrationAll 3 trials are registered at www.clinicaltrials.gov (Supporting Health by Integrating Nutrition and Exercise: NCT00960414; Get Social: NCT02646618; and GestationaL Weight Gain and Optimal Wellness: NCT02130232).

The decades-long dietary experiment embodied in the Dietary Guidelines for Americans (DGA) focused on limiting fat, especially saturated fat, and higher carbohydrate intake has coincided with rapidly escalating epidemics of obesity and type 2 diabetes (T2D) that are contributing to the progression of cardiovascular disease (CVD) and other diet-related chronic diseases. Moreover, the lack of flexibility in the DGA as it pertains to low carbohydrate approaches does not align with the contemporary trend toward precision nutrition. We argue that personalizing the level of dietary carbohydrate should be a high priority based on evidence that Americans have a wide spectrum of metabolic variability in their tolerance to high carbohydrate loads. Obesity, metabolic syndrome, and T2D are conditions strongly associated with insulin resistance, a condition exacerbated by increased dietary carbohydrate and improved by restricting carbohydrate. Low-carbohydrate diets are grounded across the time-span of human evolution, have well-established biochemical principles, and are now supported by multiple clinical trials in humans that demonstrate consistent improvements in multiple established risk factors associated with insulin resistance and cardiovascular disease. The American Diabetes Association (ADA) recently recognized a low carbohydrate eating pattern as an effective approach for patients with diabetes. Despite this evidence base, low-carbohydrate diets are not reflected in the DGA. As the DGA Dietary Patterns have not been demonstrated to be universally effective in addressing the needs of many Americans and recognizing the lack of widely available treatments for obesity, metabolic syndrome, and T2D that are safe, effective, and sustainable, the argument for an alternative, low-carbohydrate Dietary Pattern is all the more compelling.

BackgroundDespite early antiretroviral therapy (ART), ART-suppressed people with human immunodeficiency virus (HIV) (PWH) remain at higher risk for infections and infection-related cancers than the general population. The immunologic pathways that remain abnormal in this setting, potentially contributing to these complications, are unclear.MethodsART-suppressed PWH and HIV-negative controls, all cytomegalovirus seropositive and enriched for HIV risk factors, were sampled from an influenza vaccine responsiveness study. PWH were stratified by timing of ART initiation (within 6 months of infection [early ART] vs later) and nadir CD4+ T-cell count among later initiators. Between-group differences in kynurenine-tryptophan (KT) ratio, interferon-inducible protein 10, soluble CD14 and CD163, soluble tumor necrosis factor receptor 2, interleukin 6, and soluble urokinase plasminogen activator receptor were assessed after confounder adjustment.ResultsMost participants (92%) were male, reflecting the demographics of early-ART initiators in San Francisco. Most biomarkers were higher among later-ART initiators. Participants in the early-ART group achieved near-normal soluble tumor necrosis factor receptor 2, interleukin 6, and soluble urokinase plasminogen activator receptor levels, but substantially higher KT ratio than those without HIV after confounder adjustment (P = .008). Soluble CD14, soluble CD163, and interferon-inducible protein 10 trended similarly.ConclusionsWhile early-ART initiators restore near-normal levels of many inflammatory markers, the kynurenine pathway of tryptophan catabolism remains abnormally high. Because this pathway confers adaptive immune defects and predicts tuberculosis and cancer progression, this it may contribute to persistent risks of these complications in this setting.

ObjectiveTo determine the effects of ESRT (an iteratively adapted and tailored MBI) on perceived stress, executive cognitive function, psychosocial well-being (ie, burnout, mindfulness), and pro-inflammatory gene expression in surgical (ESRT-1) and mixed specialty (ESRT-2) PGY-1 volunteers.Summary of background and dataTailored MBIs have proven beneficial in multiple high-stress and high-performance populations. In surgeons, tailored MBIs have been shown to be feasible and potentially beneficial, but whether mindfulness-based cognitive training can improve perceived stress, executive function, well-being or physiological distress in surgical and nonsurgical trainees is unknown.MethodsIn 2 small single-institution randomized clinical trials, ESRT, a tailored mindfulness-based cognitive training program, was administered and iteratively adapted for first-year surgical (ESRT-1, 8 weekly, 2-hour classes, n = 44) and mixed specialty (ESRT-2, 6 weekly, 90-minute classes, n = 45) resident trainees. Primary and secondary outcomes were, respectively, perceived stress and executive function. Other prespecified outcomes were burnout (assessed via Maslach Burnout Inventory), mindfulness (assessed via Cognitive Affective Mindfulness Scale - Revised), and pro-inflammatory gene expression (assessed through the leukocyte transcriptome profile "conserved transcriptional response to adversity").ResultsNeither version of ESRT appeared to affect perceived stress. Higher executive function and mindfulness scores were seen in ESRT-1, and lower emotional exhaustion and depersonalization scores in ESRT-2, at pre-/postintervention and/or 50-week follow-up (ESRT-1) or at 32-week follow-up (ESRT-2), compared to controls. Pooled analysis of both trials found ESRT-treated participants had reduced pro-inflammatory RNA expression compared to controls.ConclusionsThis pilot work suggests ESRT can variably benefit executive function, burnout, and physiologic distress in PGY-1 trainees, with potential for tailoring to optimize effects.

Although many HIV cure strategies seek to expand HIV-specific CD8+ T cells to control the virus, all are likely to fail if cellular exhaustion is not prevented. A loss in stem-like memory properties (i.e., the ability to proliferate and generate secondary effector cells) is a key feature of exhaustion; little is known, however, about how these properties are regulated in human virus-specific CD8+ T cells. We found that virus-specific CD8+ T cells from humans and nonhuman primates naturally controlling HIV/SIV infection express more of the transcription factor TCF-1 than noncontrollers. HIV-specific CD8+ T cell TCF-1 expression correlated with memory marker expression and expansion capacity and declined with antigenic stimulation. CRISPR-Cas9 editing of TCF-1 in human primary T cells demonstrated a direct role in regulating expansion capacity. Collectively, these data suggest that TCF-1 contributes to the regulation of the stem-like memory property of secondary expansion capacity of HIV-specific CD8+ T cells, and they provide a rationale for exploring the enhancement of this pathway in T cell-based therapeutic strategies for HIV.

The precise role of CD4 T cell turnover in maintaining HIV persistence during antiretroviral therapy (ART) has not yet been well characterized. In resting CD4 T cell subpopulations from 24 HIV-infected ART-suppressed and 6 HIV-uninfected individuals, we directly measured cellular turnover by heavy water labeling, HIV reservoir size by integrated HIV-DNA (intDNA) and cell-associated HIV-RNA (caRNA), and HIV reservoir clonality by proviral integration site sequencing. Compared to HIV-negatives, ART-suppressed individuals had similar fractional replacement rates in all subpopulations, but lower absolute proliferation rates of all subpopulations other than effector memory (TEM) cells, and lower plasma IL-7 levels (p = 0.0004). Median CD4 T cell half-lives decreased with cell differentiation from naïve to TEM cells (3 years to 3 months, p

PurposeA metastatic cancer diagnosis is associated with high levels of distress in patients and caregivers, which may be alleviated by mindfulness interventions. Research on scalable, tailored, online mindfulness training programs is needed. We sought to test the feasibility and acceptability of a remotely delivered 8-week mindfulness-based intervention, Being Present 2.0 (BP2.0).MethodsWe performed a single-arm feasibility study of BP2.0 among patients with any metastatic gastrointestinal cancer receiving chemotherapy, with or without an informal caregiver. Participants were instructed to practice mindfulness using pre-recorded guided meditations 5 times per week using a study-specific website and to attend a weekly live, interactive virtual meeting facilitated by a trained instructor. The web-based platform enabled direct measurement of adherence.ResultsThe study enrolled 46 of 74 (62%) patients contacted, together with 23 caregivers (69 participants total), from May to October 2018. Median patient age was 52 (range 20-70 years), 39% were male, 67% non-Hispanic white, 65% had colorectal cancer, and 78% lived outside of San Francisco. The top reasons cited for participation were to reduce stress/anxiety and learn how to meditate. Mean baseline National Comprehensive Cancer Network Distress Thermometer (NCCN DT) scores were 4.7 (patients) and 5.8 (caregivers). The study discontinuation rate was 20% (eight patients and six caregivers). Among the remaining 55 participants, 43 (78%) listened to at least one audio recording and/or attended at least one virtual meeting, although adherence data was incomplete. The retention rate was 71%, with 39 participants completing at least one follow-up assessment. In post-intervention qualitative interviews, 88% of respondents reported a positive experience. Compared to baseline, participants reported significantly reduced post-intervention NCCN DT scores (mean 3.1; P = .012).ConclusionThe BP2.0 online mindfulness-based program is feasible and acceptable for patients with metastatic gastrointestinal cancer and caregivers. These results will guide plans for a follow-up efficacy study. ClinicalTrials.gov Identifier: NCT03528863.

Elevated core temperature constitutes an important biomarker for COVID-19 infection; however, no standards currently exist to monitor fever using wearable peripheral temperature sensors. Evidence that sensors could be used to develop fever monitoring capabilities would enable large-scale health-monitoring research and provide high-temporal resolution data on fever responses across heterogeneous populations. We launched the TemPredict study in March of 2020 to capture continuous physiological data, including peripheral temperature, from a commercially available wearable device during the novel coronavirus pandemic. We coupled these data with symptom reports and COVID-19 diagnosis data. Here we report findings from the first 50 subjects who reported COVID-19 infections. These cases provide the first evidence that illness-associated elevations in peripheral temperature are observable using wearable devices and correlate with self-reported fever. Our analyses support the hypothesis that wearable sensors can detect illnesses in the absence of symptom recognition. Finally, these data support the hypothesis that prediction of illness onset is possible using continuously generated physiological data collected by wearable sensors. Our findings should encourage further research into the role of wearable sensors in public health efforts aimed at illness detection, and underscore the importance of integrating temperature sensors into commercially available wearables.

BackgroundAdults with type 2 diabetes may experience health benefits, including glycemic control and weight loss, from following a very low-carbohydrate, ketogenic (VLC) diet. However, it is unclear which ancillary strategies may enhance these effects.ObjectiveThis pilot study aims to estimate the effect sizes of 3 intervention enhancement strategies (text messages, gifts, and breath vs urine ketone self-monitoring) that may improve outcomes of a 12-month web-based ad libitum VLC diet and lifestyle intervention for adults with type 2 diabetes. The primary intervention also included other components to improve adherence and well-being, including positive affect and mindfulness as well as coaching.MethodsOverweight or obese adults (n=44; BMI 25-45 kg/m2) with type 2 diabetes (glycated hemoglobin [HbA1c] ≥6.5%), who had been prescribed either no glucose-lowering medications or metformin alone, participated in a 12-month web-based intervention. Using a 2×2×2 randomized factorial design, we compared 3 enhancement strategies: (1) near-daily text messages about the intervention's recommended behaviors (texts n=22 vs no texts n=22), (2) mailed gifts of diet-relevant foods and cookbooks (6 rounds of mailed gifts n=21 vs no gifts n=23), and (3) urine- or breath-based ketone self-monitoring (urine n=21 vs breath n=23). We assessed HbA1c and weight at baseline and at 4, 8, and 12 months. We evaluated whether each strategy exerted a differential impact on HbA1c and weight at 12 months against an a priori threshold of Cohen d of 0.5 or greater.ResultsWe retained 73% (32/44) of the participants at 12 months. The intervention, across all conditions, led to improvements in glucose control and reductions in body weight at the 12-month follow-up. In intent-to-treat (ITT) analyses, the mean HbA1c reduction was 1.0% (SD 1.6) and the mean weight reduction was 5.3% (SD 6.0), whereas among study completers, these reductions were 1.2% (SD 1.7) and 6.3% (SD 6.4), respectively, all with a P value of less than .001. In ITT analyses, no enhancement strategy met the effect size threshold. Considering only study completers, 2 strategies showed a differential effect size of at least a d value of 0.5 or greater.ConclusionsText messages, gifts of food and cookbooks, and urine-based ketone self-monitoring may potentially enhance the glycemic or weight loss benefits of a web-based VLC diet and lifestyle intervention for individuals with type 2 diabetes. Future research could investigate other enhancement strategies to help create even more effective solutions for the treatment of type 2 diabetes.Trial registrationClinicalTrials.gov NCT02676648; http://clinicaltrials.gov/ct2/show/NCT02676648.

Purpose: Chinese Americans (CAs) with diabetes and limited English proficiency often struggle to adhere to standard diabetes diets focused on food measurement/restriction. Chinese medicine principles commonly inform food choices among CAs but are rarely acknowledged in nutritional interventions. We developed and tested feasibility of a theoretically informed integrative nutritional counseling (INC) program that combines Chinese medicine principles with biomedical nutrition standards. Methods: We randomized diabetes self-management education (DSME) classes to include either: (1) usual nutrition curriculum based on American Diabetes Association (ADA) recommendations delivered by a diabetes educator (control) or (2) INC curriculum based on a combination of ADA recommendations and Chinese medicine principles delivered by a diabetes educator and a licensed acupuncturist (intervention). All DSME enrollees were invited to participate in research entailing data collection at three time points: baseline, after the DSME nutrition class, and at 6-month follow-up. Using validated measures, we collected dietary self-efficacy, diabetes distress, diet satisfaction, and dietary adherence. We also measured weight and glycemic control. Results: Study participants were 18 Cantonese-speaking patients with diabetes who were predominantly female and older, with low levels of income and acculturation. Intervention and control groups were similar at baseline. INC performed similarly to usual DSME with 100% of participants reporting the INC booklet helped their learning. Dietary adherence significantly improved in participants who received the INC curriculum. Conclusion: INC is feasible to implement as part of DSME classes and shows promise as a complementary culturally sensitive addition to usual diabetes nutrition education for CA patients.

Proliferation of CD4+ T cells harboring HIV-1 proviruses is a major contributor to viral persistence in people on antiretroviral therapy (ART). To determine whether differential rates of clonal proliferation or HIV-1-specific cytotoxic T lymphocyte (CTL) pressure shape the provirus landscape, we performed an intact proviral DNA assay (IPDA) and obtained 661 near-full-length provirus sequences from 8 individuals with suppressed viral loads on ART at time points 7 years apart. We observed slow decay of intact proviruses but no changes in the proportions of various types of defective proviruses. The proportion of intact proviruses in expanded clones was similar to that of defective proviruses in clones. Intact proviruses observed in clones did not have more escaped CTL epitopes than intact proviruses observed as singlets. Concordantly, total proviruses at later time points or observed in clones were not enriched in escaped or unrecognized epitopes. Three individuals with natural control of HIV-1 infection (controllers) on ART, included because controllers have strong HIV-1-specific CTL responses, had a smaller proportion of intact proviruses but a distribution of defective provirus types and escaped or unrecognized epitopes similar to that of the other individuals. This work suggests that CTL selection does not significantly check clonal proliferation of infected cells or greatly alter the provirus landscape in people on ART.

While the relationship of protective human leukocyte antigen (HLA) class I alleles and HIV progression is well defined, the interaction of HLA-mediated protection and CD8 T-cell exhaustion is less well characterized. To gain insight into the influence of HLA-B*57:01 on the deterioration of CD8 T-cell responses during HIV infection in the absence of antiretroviral treatment, we compared HLA-B*57:01-restricted HIV-specific CD8 T-cell responses to responses restricted by other HLA class I alleles longitudinally after control of peak viremia. Detailed characterization of polyfunctionality, differentiation phenotypes, transcription factor, and inhibitory receptor expression revealed progression of CD8 T-cell exhaustion over the course of the infection in both patient groups. However, early effects on the phenotype of the total CD8 T-cell population were apparent only in HLA-B*57-negative patients. The HLA-B*57:01-restricted, HIV epitope-specific CD8 T-cell responses showed beneficial functional patterns and significantly lower frequencies of inhibitory receptor expression, i.e., PD-1 and coexpression of PD-1 and TIGIT, within the first year of infection. Coexpression of PD-1 and TIGIT was correlated with clinical markers of disease progression and declining percentages of the T-bethi Eomesdim CD8 T-cell population. In accordance with clinical and immunological deterioration in the HLA-B*57:01 group, the difference in PD-1 and TIGIT receptor expression did not persist to later stages of the disease.IMPORTANCE Given the synergistic nature of TIGIT and PD-1, the coexpression of those inhibitory receptors should be considered when evaluating T-cell pathogenesis, developing immunomodulatory therapies or vaccines for HIV, and when using immunotherapy or vaccination for other causes in HIV-infected patients. HIV-mediated T-cell exhaustion influences the patient´s disease progression, immune system and subsequently non-AIDS complications, and efficacy of vaccinations against other pathogens. Consequently, the possibilities of interfering with exhaustion are numerous. Expanding the use of immunomodulatory therapies to include HIV treatment depends on information about possible targets and their role in the deterioration of the immune system. Furthermore, the rise of immunotherapies against cancer and elevated cancer incidence in HIV-infected patients together increase the need for detailed knowledge of T-cell exhaustion and possible interactions. A broader approach to counteract immune exhaustion to alleviate complications and improve efficacy of other vaccines also promises to increase patients' health and quality of life.

ObjectiveThe contribution of HLA-DR+ memory CD4 T cells to the HIV reservoir during prolonged antiretroviral therapy is unclear as these cells are commonly excluded when assessing for replication-competent HIV. To address this issue, we examined the distribution of genetically intact HIV DNA within HLA-DR- and HLA-DR+ memory CD4 T cells and the RNA transcriptional profile of these cells during antiretroviral therapy.Design/methodsFull-length DNA sequencing was used to examine the HIV DNA landscape within HLA-DR+ and HLA-DR- memory CD4 T cells. RNA quantification and sequencing was used to interrogate the relationship between HLA-DR status and HIV RNA transcription.ResultsHLA-DR+ CD4 T cells contained a high frequency of genetically intact HIV genomes, contributing over half of the genetically intact viral sequences to the reservoir. Expansions of genetically identical sequences were identified in all T-cell subsets, indicating that cellular proliferation maintains genetically intact and defective viral DNA during therapy. Intracellular HIV RNA levels in HLA-DR+ and HLA-DR- T cells were not statistically different by either long terminal repeat quantitative PCR quantification or single-genome RNA sequencing of the p6-RT region.ConclusionThe high proportion of intact viral DNA sequences in the proliferative HLA-DR+ subset suggests they are critical in maintaining HIV infection during effective therapy. As such, these cells should be included in any immune intervention targeting HIV during effective therapy.

BackgroundIdentifying where human immunodeficiency virus (HIV) persists in people living with HIV and receiving antiretroviral therapy is critical to develop cure strategies. We assessed the relationship of HIV persistence to expression of chemokine receptors and their chemokines in blood (n = 48) and in rectal (n = 20) and lymph node (LN; n = 8) tissue collected from people living with HIV who were receiving suppressive antiretroviral therapy.MethodsCell-associated integrated HIV DNA, unspliced HIV RNA, and chemokine messenger RNA were quantified by quantitative polymerase chain reaction. Chemokine receptor expression on CD4+ T cells was determined using flow cytometry.ResultsIntegrated HIV DNA levels in CD4+ T cells, CCR6+CXCR3+ memory CD4+ T-cell frequency, and CCL20 expression (ligand for CCR6) were highest in rectal tissue, where HIV-infected CCR6+ T cells accounted for nearly all infected cells (median, 89.7%). Conversely in LN tissue, CCR6+ T cells were infrequent, and there was a statistically significant association of cell-associated HIV DNA and RNA with CCL19, CCL21, and CXCL13 chemokines.ConclusionsHIV-infected CCR6+ CD4+ T cells accounted for the majority of infected cells in rectal tissue. The different relationships between HIV persistence and T-cell subsets and chemokines in rectal and LN tissue suggest that different tissue-specific strategies may be required to eliminate HIV persistence and that assessment of biomarkers for HIV persistence may not be generalizable between blood and other tissues.

ObjectiveWe aimed to understand the associations of compulsive eating (CE) and stress eating (SE) with metabolic health among adults with obesity and whether mindfulness-based weight loss training may buffer these associations.MethodWe used data from a trial in which we randomized 194 participants with obesity to a diet-exercise weight loss intervention with either mindful eating training plus mindfulness-based eating awareness and stress management training (n = 100) or active control components (n = 94). We measured CE, SE, weight, and fasting blood glucose (FBG) at baseline, and 6, 12 months, and 18 months. We tested CE and SE as both moderators and mediators of intervention effects on changes in metabolic health.ResultsParticipants higher (+ 1 SD) in CE at baseline randomized to the mindfulness (vs. control) intervention had greater improvements in FBG at 18 months (p = .05). Twelve-month reductions in CE mediated the effect of the intervention on changes in FBG and weight at 12 and 18 months postbaseline (p ≤ .05). Furthermore, those higher (+ 1 SD) in SE at baseline were nearly 2 BMI points higher than those lower (-1 SD) in SE (p < .01). Decreases in SE (B = 3.42; p < .001; 95% CI [2.55, 4.30]) and CE (B = 0.45; p < .001; 95% CI [0.36, 0.54]) in all participants at 6 months were associated with greater weight loss at 18 months.ConclusionsThose with greater compulsive eating may reduce risk for metabolic decline by participating in a mindfulness-based weight loss program. Future obesity interventions should consider tailoring treatment toward trait-level characteristics, such as compulsive eating. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Understanding the impact of antiretroviral therapy (ART) duration on HIV-infected cells is critical for developing successful curative strategies. To address this issue, we conducted a cross-sectional/inter-participant genetic characterization of HIV-1 RNA from pre- and on-therapy plasmas and HIV-1 DNA from CD4+ T cell subsets derived from peripheral blood (PB), lymph node (LN), and gut tissues of 26 participants after 3 to 17.8 years of ART. Our studies revealed in four acute/early participants who had paired PB and LN samples a substantial reduction in the proportion of HIV-infected cells per year on therapy within the LN. Extrapolation to all 12 acute/early participants estimated a much smaller reduction in the proportion of HIV-1-infected cells within LNs per year on therapy that was similar to that in the participants treated during chronic infection. LN-derived effector memory T (TEM) cells contained HIV-1 DNA that was genetically identical to viral sequences derived from pre- and on-therapy plasma samples. The proportion of identical HIV-1 DNA sequences increased within PB-derived TEM cells. However, the infection frequency of TEM cells in PB was stable, indicating that cellular proliferation that compensates for T cell loss over time contributes to HIV-1 persistence. This study suggests that ART reduces HIV-infected T cells and that clonal expansion of HIV-infected cells maintains viral persistence. Importantly, LN-derived TEM cells are a probable source of HIV-1 genomes capable of producing infectious HIV-1 and should be targeted by future curative strategies.IMPORTANCE HIV-1 persists as an integrated genome in CD4+ memory T cells during effective therapy, and cessation of current treatments results in resumption of viral replication. To date, the impact of antiretroviral therapy duration on HIV-infected CD4+ T cells and the mechanisms of viral persistence in different anatomic sites is not clearly elucidated. In the current study, we found that treatment duration was associated with a reduction in HIV-infected T cells. Our genetic analyses revealed that CD4+ effector memory T (TEM) cells derived from the lymph node appeared to contain provirus that was genetically identical to plasma-derived virions. Moreover, we found that cellular proliferation counterbalanced the decay of HIV-infected cells throughout therapy. The contribution of cellular proliferation to viral persistence is particularly significant in TEM cells. Our study emphasizes the importance of HIV-1 intervention and provides new insights into the location of memory T cells infected with HIV-1 DNA, which is capable of contributing to viremia.

BackgroundThe Mindfulness-Based Interventions: Teaching Assessment Criteria (MBI:TAC) is a widely used tool for assessing fidelity in mindfulness-based program (MBP) research and training. It also supports MBP teacher reflective and skill development. MBI:TAC assessors review MBP teaching and rate the teaching on 6 domains. The MBI:TAC yields individual domain and overall scores, using 6 levels of competence. Although the MBI:TAC is widely used in MBP research and training, research is at an early stage.ObjectiveWe developed and tested a method of training MBI:TAC assessors to use the tool reliably and examined interrater reliability of the tool.MethodsA total of 31 international senior MBP teachers were recruited to join an online training to build their skills in using the MBI:TAC. The training systematically and iteratively built familiarity and skills in assessing the 6 MBI:TAC domains. Qualitative and quantitative data on trainee's experience of the training were gathered. Interrater reliability in using the tool was tested each week of the training. At the end of the training, interrater reliability was tested by asking trainees to individually assess videos that they had not previously seen. Their ratings were compared to benchmark assessments, which had been established via consensus agreement between 4 expert users of the MBI:TAC.ResultsThe training was well received and appreciated, with some challenges experienced in applying the assessment methodology. Participants' ratings became progressively more in line with one another and the benchmark ratings during the training. At the end, interrater reliability was high (ranging from 0.67 to 1.0).ConclusionIt is possible for senior MBP trainers, coming from different regions in the world, to align toward common understandings of the elements of MBP teaching competence and program integrity. An assessor training methodology was tested, and the learning from this project has led to refinements for future delivery.

Meditation practices are often used to cultivate interoception or internally-oriented attention to bodily sensations, which may improve health via cognitive and emotional regulation of bodily signals. However, it remains unclear how meditation impacts internal attention (IA) states due to lack of measurement tools that can objectively assess mental states during meditation practice itself, and produce time estimates of internal focus at individual or group levels. To address these measurement gaps, we tested the feasibility of applying multi-voxel pattern analysis (MVPA) to single-subject fMRI data to: (1) learn and recognize internal attentional states relevant for meditation during a directed IA task; and (2) decode or estimate the presence of those IA states during an independent meditation session. Within a mixed sample of experienced meditators and novice controls (N = 16), we first used MVPA to develop single-subject brain classifiers for five modes of attention during an IA task in which subjects were specifically instructed to engage in one of five states [i.e., meditation-related states: breath attention, mind wandering (MW), and self-referential processing, and control states: attention to feet and sounds]. Using standard cross-validation procedures, MVPA classifiers were trained in five of six IA blocks for each subject, and predictive accuracy was tested on the independent sixth block (iterated until all volumes were tested, N = 2,160). Across participants, all five IA states were significantly recognized well above chance (>41% vs. 20% chance). At the individual level, IA states were recognized in most participants (87.5%), suggesting that recognition of IA neural patterns may be generalizable for most participants, particularly experienced meditators. Next, for those who showed accurate IA neural patterns, the originally trained classifiers were applied to a separate meditation run (10-min) to make an inference about the percentage time engaged in each IA state (breath attention, MW, or self-referential processing). Preliminary group-level analyses demonstrated that during meditation practice, participants spent more time attending to breath compared to MW or self-referential processing. This paradigm established the feasibility of using MVPA classifiers to objectively assess mental states during meditation at the participant level, which holds promise for improved measurement of internal attention states cultivated by meditation.

Mindfulness and compassion meditation are thought to cultivate prosocial behavior. However, the lack of diverse representation within both scientific and participant populations in contemplative neuroscience may limit generalizability and translation of prior findings. To address these issues, we propose a research framework called Intersectional Neuroscience which adapts research procedures to be more inclusive of under-represented groups. Intersectional Neuroscience builds inclusive processes into research design using two main approaches: 1) community engagement with diverse participants, and 2) individualized multivariate neuroscience methods to accommodate neural diversity. We tested the feasibility of this framework in partnership with a diverse U.S. meditation center (East Bay Meditation Center, Oakland, CA). Using focus group and community feedback, we adapted functional magnetic resonance imaging (fMRI) screening and recruitment procedures to be inclusive of participants from various under-represented groups, including racial and ethnic minorities, gender and sexual minorities, people with disabilities, neuropsychiatric disorders, and/or lower income. Using person-centered screening and study materials, we recruited and scanned 15 diverse meditators (80% racial/ethnic minorities, 53% gender and sexual minorities). The participants completed the EMBODY task - which applies individualized machine learning algorithms to fMRI data - to identify mental states during breath-focused meditation, a basic skill that stabilizes attention to support interoception and compassion. All 15 meditators' unique brain patterns were recognized by machine learning algorithms significantly above chance levels. These individualized brain patterns were used to decode the internal focus of attention throughout a 10-min breath-focused meditation period, specific to each meditator. These data were used to compile individual-level attention profiles during meditation, such as the percentage time attending to the breath, mind wandering, or engaging in self-referential processing. This study provides feasibility of employing an intersectional neuroscience approach to include diverse participants and develop individualized neural metrics of meditation practice. Through inclusion of more under-represented groups while developing reciprocal partnerships, intersectional neuroscience turns the research process into an embodied form of social action.

[This corrects the article DOI: 10.3389/fpsyg.2020.573134.].

PurposeOngoing symptoms and impairments in quality of life (QOL) among breast cancer survivors remain a significant problem. We tested the feasibility and acceptability of a manualized Ayurvedic nutrition and lifestyle intervention for breast cancer survivors.MethodsEligible participants had Stage I-III breast cancer, underwent treatment within the past year that included chemotherapy, and were without active disease. The 4-month individualized Ayurvedic intervention included counseling on nutrition, lifestyle, yoga, and marma (like acupressure) during 8 one-on-one visits with an Ayurvedic practitioner. Feasibility and acceptability were the primary outcomes. QOL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ C30]) and symptoms-sleep disturbance (General Sleep Disturbance Scale [GSDS]), fatigue (Lee Fatigue Scale [LFS]), depressive symptoms (Center for Epidemiological Studies-Depression Scale [CES-D]), anxiety (Spielberger State-Trait Anxiety Inventory [STAI-S, STAI-T]), and stress (Perceived Stress Scale [PSS])-were measured prior to, at midpoint, and at the end of the 4-month intervention. Effect sizes (Cohen's d) were calculated along with paired t tests comparing baseline to end of month 4 time points. Mixed effects models were used for repeated measures analyses.ResultsParticipants (n = 32) had a mean age of 48 years (SD = 10). Retention at the end of the intervention was 84%. Among those who completed the intervention (n = 27), adherence was high (99.5% of visits with practitioners attended). Large improvements were seen in QLQ-C30 emotional functioning (d = 0.84, P

ObjectiveMindfulness-based interventions have been found to reduce psychological and physiological stress reactivity. In obesity, however, stress reactivity is complex, with studies showing both exaggerated and blunted physiological responses to stressors. A nuanced view of stress reactivity is the "challenge and threat" framework, which defines adaptive and maladaptive patterns of psychophysiological stress reactivity. We hypothesized that mindfulness training would facilitate increased challenge-related appraisals, emotions, and cardiovascular reactivity, including sympathetic nervous system activation paired with increased cardiac output (CO) and reduced total peripheral resistance (TPR) compared to a control group, which would exhibit an increased threat pattern of psychophysiological reactivity to repeated stressors.MethodsAdults (N=194) with obesity were randomized to a 5.5-month mindfulness-based weight loss intervention or an active control condition with identical diet-exercise guidelines. Participants were assessed at baseline and 4.5 months later using the Trier Social Stress Task. Electrocardiogram, impedance cardiography, and blood pressure were acquired at rest and during the speech and verbal arithmetic tasks to assess pre-ejection period (PEP), CO, and TPR reactivity.ResultsMindfulness participants showed significantly greater maintenance of challenge-related emotions and cardiovascular reactivity patterns (higher CO and lower TPR) from pre to post-intervention compared to control participants, but groups did not differ in PEP. Findings were independent of changes in body mass index.ConclusionsMindfulness training may increase the ability to maintain a positive outlook and mount adaptive cardiovascular responses to repeated stressors among persons with obesity though findings need to be replicated in other populations and using other forms of mindfulness interventions.

BackgroundA carbohydrate-restricted (CR) diet can improve glycemic control in people with type 2 diabetes mellitus (T2DM). There are concerns, however, that the high dietary fat content of CR diets can increase low-density lipoprotein cholesterol (LDL-C), thus increasing cardiovascular disease (CVD) risk. Quantifying CVD risk associated with changes in LDL-C in the context of CR diets is complicated by the fact that LDL-C reflects heterogeneous lipids. For example, small LDL particle number (sLDL-P) is more closely associated with CVD risk than is total LDL-C, and CR diets tend to decrease the proportion of sLDL-C in LDL-C, which standard lipid measures do not indicate. Advanced lipoprotein assays, such as nuclear magnetic resonance (NMR) testing, can subfractionate lipoproteins by size and density and may better depict the effects of CR diets on CVD risk.MethodsAdults (N = 58) with T2DM (n = 37 women; baseline HbA1c ≥ 6.5%) completed a 6-month group-based CR diet intervention. We obtained a standard lipid panel, advanced lipoprotein assays (NMR testing), and two 24-h diet recalls at baseline and post-intervention (6 months). Participants also completed home-based blood ketone testing (a biological index of dietary adherence) during the final five weeks of the intervention.ResultsFrom baseline to post-intervention, participants had increased mean HDL-C, decreased triglycerides and triglyceride/HDL ratio, decreased mean sLDL-P, and increased LDL size, which reflect reductions in CVD risk (ps

ObjectiveExisting pharmacologic approaches for painful diabetic neuropathy (PDN) are limited in efficacy and have side effects. We examined the feasibility, acceptability, and effects of group acupuncture for PDN.Design and settingWe randomized patients with PDN from a public safety net hospital to 1) usual care, 2) usual care plus 12 weeks of group acupuncture once weekly, or 3) usual care plus 12 weeks of group acupuncture twice weekly.MethodsThe primary outcome was change in weekly pain intensity (daily 0-10 numerical rating scale [NRS] averaged over seven days) from baseline to week 12. We also assessed health-related quality of life and related symptoms at baseline and weeks 6, 12, and 18.ResultsWe enrolled 40 patients with PDN (baseline pain = 5.3). Among participants randomized to acupuncture, 92% attended at least one treatment (mean treatments = 10.1). We observed no significant differences between once- vs twice-weekly acupuncture and combined those groups for the main analyses. Compared with usual care, participants randomized to acupuncture experienced greater decreases in pain during the 12-week intervention period (between-group differences from baseline = -2.06, 95% confidence interval [CI] = -3.01 to -1.10), but benefits were not maintained after acupuncture ended (baseline to week 18 = -0.61, 95% CI = -1.46 to 0.24). Quality of life improved for acupuncture participants (baseline to week 12 difference = 11.79, 95% CI = 1.92 to 21.66), but group differences were not significant compared with usual care (25.58, 95% CI = -3.90 to 55.06).ConclusionsGroup acupuncture is feasible and acceptable among linguistically and racially diverse safety net patients. Findings suggest clinically relevant reduction in pain from PDN and quality of life improvements associated with acupuncture, with no differences based on frequency.

Background A key research priority for developing a human immunodeficiency virus (HIV) cure strategy is to define the viral dynamics and biomarkers associated with sustained posttreatment control. The ability to predict the likelihood of sustained posttreatment control or noncontrol could minimize the time off antiretroviral therapy (ART) for those destined to be controllers and anticipate longer periods off ART for those destined to be controllers. Methods Mathematical modeling and machine learning were used to characterize virologic predictors of long-term virologic control, using viral kinetics data from several studies in which participants interrupted ART. Predictors of post-ART outcomes were characterized using data accumulated from the time of treatment interruption, replicating real-time data collection in a clinical study, and classifying outcomes as either posttreatment control (plasma viremia, ≤400 copies/mL at 2 of 3 time points for ≥24 weeks) or noncontrol. Results Potential predictors of virologic control were the time to rebound, the rate of initial rebound, and the peak plasma viremia. We found that people destined to be noncontrollers could be identified within 3 weeks of rebound (prediction scores: accuracy, 80%; sensitivity, 82%; specificity, 71%). Conclusions Given the widespread use of analytic treatment interruption in cure-related trials, these predictors may be useful to increase the safety of analytic treatment interruption through early identification of people who are unlikely to become posttreatment controllers. [ABSTRACT FROM AUTHOR]

HIV persists in latently infected CD4+ T cells during antiretroviral therapy (ART). Immune checkpoint molecules, including PD-1, are preferentially expressed at the surface of persistently infected cells. However, whether PD-1 plays a functional role in HIV latency and reservoir persistence remains unknown. Using CD4+ T cells from HIV-infected individuals, we show that the engagement of PD-1 inhibits viral production at the transcriptional level and abrogates T-cell receptor (TCR)-induced HIV reactivation in latently infected cells. Conversely, PD-1 blockade with the monoclonal antibody pembrolizumab enhances HIV production in combination with the latency reversing agent bryostatin without increasing T cell activation. Our results suggest that the administration of immune checkpoint blockers to HIV-infected individuals on ART may facilitate latency disruption.

PurposeAcupressure and therapeutic touch may be beneficial for symptom management and increasing general well-being for children undergoing cancer treatment. Acupressure has the benefit of stimulating targeted acupuncture points while providing therapeutic touch. We sought to explore the relationship between acupressure and the experience of well-being among children being treated for cancer who received acupressure.MethodsIn the Acupressure for Children in Treatment for a Childhood Cancer trial, hospitalized children received acupressure using specified acupressure points for symptom control as well as points for general well-being. Acupressure was delivered by professionals and by caregivers, following training by the professional. Qualitative data were collected through semistructured interviews with a purposive sample of professional acupressure providers (n = 3) and primary caregivers (n = 13), combined with participant observation during the acupressure intervention. Data were analyzed using grounded theory methods.ResultsAnalysis of provider interview, caregiver interview, and participation observation yielded 3 prominent themes: (1) well-being elicited by acupressure, (2) well-being elicited by touch, and (3) well-being experienced as relational and intersubjective. These themes, taken together, illustrate the intricate ways in which an intervention like acupressure can help alleviate the difficulties of a childhood cancer illness experience by promoting well-being in the child as well as the caregiver. Acupressure brought symptom relief, physical relaxation, and comforting touch to the child, allowing the caregiver to also feel relief and relaxation as caregiver-child experience of well-being are closely intertwined.ConclusionsData from the 3 sources provided distinct and overlapping insights suggesting the versatile benefits of acupressure in promoting well-being during childhood cancer treatment. Professional acupressure combined with training of caregivers for childhood cancer may be a relational intervention that facilitates the experience of well-being for both the caregiver and the child.

[This corrects the article DOI: 10.1186/s12986-019-0383-2.].

BackgroundWe describe the study design and protocol of a pragmatic randomized controlled trial (RCT) Acupressure for Children in Treatment for a Childhood Cancer (ACT-CC).ObjectiveTo describe the feasibility and effectiveness of an acupressure intervention to decrease treatment-related symptoms in children in treatment for cancer or recipients of a chemotherapy-based hematopoietic stem cell transplant (HSCT).DesignTwo-armed RCTs with enrollment of 5 to 30 study days.SettingTwo pediatric teaching hospitals.PatientsEighty-five children receiving cancer treatment or a chemotherapy-based HSCT each with 1 parent or caregiver.InterventionPatients are randomized 1:1 to receive either usual care plus daily professional acupressure and caregiver delivered acupressure versus usual care alone for symptom management. Participants receive up to 20 professional treatments.Main outcomeA composite nausea/vomiting measure for the child.Secondary outcomesChild's nausea, vomiting, pain, fatigue, depression, anxiety, and positive affect.Parent outcomesDepression, anxiety, posttraumatic stress symptoms, caregiver self-efficacy, and positive affect. Feasibility of delivering the semistandardized intervention will be described. Linear mixed models will be used to compare outcomes between arms in children and parents, allowing for variability in diagnosis, treatment, and age.DiscussionTrial results could help childhood cancer and HSCT treatment centers decide about the regular inclusion of trained acupressure providers to support symptom management.