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Abstract The relationship between amyloidosis and vasculature in cognitive impairment and Alzheimer’s disease (AD) pathogenesis is increasingly acknowledged. We conducted a quantitative and topographic assessment of retinal perivascular amyloid plaque (AP) distribution in individuals with both normal and impaired cognition. Using a retrospective dataset of scanning laser ophthalmoscopy fluorescence images from twenty-eight subjects with varying cognitive states, we developed a novel image processing method to examine retinal peri-arteriolar and peri-venular curcumin-positive AP burden. We further correlated retinal perivascular amyloidosis with neuroimaging measures and neurocognitive scores. Our study unveiled that peri-arteriolar AP counts surpassed peri-venular counts throughout the entire cohort (P

Introduction: Economic disparities in tobacco use and dependence are well-documented among adults but not adolescents. This study aims to examine economic disparities in patterns of tobacco use among a nationally representative sample of high school students in Spring 2021. Methods: We analyzed data from n = 6750 US high school student via the 2021 Adolescent Behaviors and Experiences Survey (ABES). We estimated the association between experiencing homelessness and food insecurity (analyzed independently) and current (past 30-day) and daily (all 30 days) use of four tobacco products (e-cigarettes; cigarettes; cigars; smokeless). Models controlled for sex, race/ethnicity, age, and sexual identity. Results: Overall, ∼1.8 % experienced homelessness and 23.7 % experienced food insecurity. Experiencing homeless was significantly associated with greater odds of current use for e-cigarette (aOR: 3.43), cigarettes (aOR: 5.58), cigars (aOR: 10.47), and smokeless tobacco (aOR: 4.41) as well as greater risk for daily use of e-cigarettes (aOR: 2.66), cigarettes (aOR: 10.94), and cigars (aOR: 5.23) but not smokeless tobacco (aOR: 2.48; 95 %CI: 0.51–12.16). Food insecurity was significantly associated with greater odds of current use of e-cigarettes (aOR: 2.00), cigarettes (aOR: 2.15), and cigars (aOR: 2.44) but not smokeless (aOR: 1.04; 95 % CI: 0.56–1.93). No association was observed between food insecurity and daily tobacco use. Conclusion: Substantial economic disparities in tobacco use were observed in a nationally representative sample of high school students. Interventions should consider prioritizing economic determinants of health during adolescence, including a focus on preventing youth tobacco use as well as addressing upstream determinants of homelessness and food insecurity.

Background: E-cigarette use remains high among adolescents, underscoring the need to identify targetable risk factors for intervention. This study examines associations between two social norms constructs (prevalence misperceptions and social acceptability) and at-risk status for e-cigarette use among Texas early adolescents. Methods: We conducted a cross-sectional analysis of baseline data from the CATCH My Breath study, which included n=1032 Texas sixth graders. Students who had ever used or were susceptible to using e-cigarettes were categorized as at-risk for long-term use. Susceptibility was measured using a 3-item index assessing curiosity, intentions, and receptivity to using e-cigarettes. Multi-level logistic regressions assessed associations between social norm constructs and at-risk status for the full and sex-stratified samples. Covariates were race, ethnicity, academics, household/peer tobacco use. Results: Overall, 36 % of 6th grade students were at-risk for e-cigarette use. Approximately 49 % of students overestimated peer e-cigarette use (“prevalence misperceptions”), and 43 % believed adolescent e-cigarette use is highly acceptable (“social acceptability”). Controlling for covariates, students with medium (aOR=1.89; 95 %CI=1.35–2.65) and high (aOR=1.98; 95 %CI=1.41–2.78) prevalence misperceptions had greater odds of being at-risk for e-cigarette use than those with low misperceptions. Students reporting medium (aOR=2.50; 95 %CI=1.66–3.76) and high (aOR=4.70; 95 %CI=3.21–6.90) social acceptability had greater odds of being at-risk for e-cigarette use than those reporting low acceptability. This association was stronger for females, relative to males. Conclusions: Greater prevalence misperceptions and social acceptability were associated with being at-risk for e-cigarette use among this sample of Texas early adolescents. Interventions should consider incorporating these social norms into intervention content.

Objectives To describe the prevalence of school-based tobacco prevention programme exposure among adolescents in low-income and middle-income countries (LMICs) and its association with psychosocial predictors of smoking.Design Analysis of pooled cross-sectional data.Setting Global Youth Tobacco Survey (GYTS), conducted in 38 LMICs.Participants This was a pooled analysis of data involving a total of 132 755 adolescent respondents to GYTS in 38 LMICs across Africa, Europe and Central/South America between 2014 and 2017.Exposure and outcome measures The primary independent variable for this study was self-reported exposure to school-based tobacco prevention programmes in the past year. Five psychosocial determinants of smoking were explored as outcomes: perceived addictiveness of nicotine, perceived harm of secondhand smoke exposure, support for restricting cigarette smoking at public indoor locations, support for restricting cigarette smoking at public outdoor areas and self-reported prediction of enjoying cigarette smoking. Multivariable logistic regression models were used to examine the relationship between exposure to school-based tobacco prevention programmes and study outcomes, controlling for sociodemographic and smoking-related characteristics of respondents.Results Overall, 59.1% of adolescents in LMICs self-reported exposure to school-based tobacco prevention programmes. The country-specific prevalence of adolescent exposure to school-based tobacco interventions ranged from 24.9% in the Comoros to 99.3% in Turkmenistan. Exposure to school-based tobacco interventions was significantly associated with greater secondhand smoke harm perceptions (adjusted OR (AOR): 1.69; 95% CI: 1.69 to 1.70), perceptions of addictiveness (AOR: 1.37; 95% CI: 1.36 to 1.37) and supporting tobacco use restrictions indoors (AOR: 1.70; 95% CI: 1.69 to 1.70) and outdoors (AOR: 1.59; 95% CI: 1.59 to 1.60). Exposure to school-based tobacco interventions was associated with lower odds of anticipating enjoying cigarette smoking (AOR: 0.76; 95% CI: 0.76 to 0.76).Conclusion Exposure to tobacco prevention programmes in schools is suboptimal in LMICs. Given the protective associations described in this study from school-based tobacco prevention programme exposure, it is imperative that national governments implement school-based programmes into ongoing tobacco control measures.

Abstract Objective Greater perceived social support (PSS) is associated with more favorable changes in weight loss, activity behaviors, and eating regulation after metabolic and bariatric surgery (MBS). However, studies have relied on generic, retrospective PSS measures, and stability of PSS levels and relations with weight loss and weight‐related behaviors over time is unknown. Using smartphone‐based Ecological Momentary Assessment, this study evaluated pre‐to 1‐year post‐MBS changes in daily weight management‐focused PSS and associations with weight loss, device‐measured activity behaviors, and eating regulation before and during the initial year after MBS. Method Adult MBS patients (n = 71) received (1) an accelerometer to measure daily moderate‐to‐vigorous intensity physical activity (MVPA) and sedentary time (ST) minutes/day, and (2) a smartphone to complete morning weight‐focused PSS ratings and eating regulation (dietary restraint/disinhibition) ratings at four semi‐random times daily for 10 days at pre‐ and 3, 6, and 12‐month postoperative. Generalized linear mixed models analyzed the associations of PSS with total weight loss (%TWL) and activity/eating outcomes. Results Participants on average reported relatively stable moderate‐to‐high PSS (3.98 on one to five scale) across assessments. Perceived social support was not related to %TWL, MVPA, or ST. Participants with higher PSS reported lower disinhibition and higher restraint than those with lower PSS (ps

Individual-based models (IBMs) are increasingly used in marine conservation research, making this is an ideal time to assess IBM use in marine policy. IBMs can contribute important information to marine management and policy questions, as they offer complex methods of understanding ecosystems and animal behaviour, by allowing for heterogeneity in both individuals and environments. A review of 108 international peer-review publications utilizing marine IBMs was conducted using Web of Science (WoS). It was determined that 55% of the WoS articles claimed that the IBMs were relevant or important to marine conservation policy or management. A relevant English-language policy document was located for 83% of the IBMs, but only 32% were cited, while 85% of the same policy documents cited a different, non-IBM, modelling method. A separate survey of 175 policy documents from the Government of Canada was conducted. Of the 60 that contained citations, zero documents cited an IBM, while 75% cited a different modelling method. Of 407 webpages reviewed from the National Oceanic and Atmospheric Administration, the New Zealand Department of Conservation, and the UK Government website, only 4% referenced IBMs. This research demonstrates that, despite claims of usefulness by researchers, IBMs are not used to inform policy, while other model methods are commonly cited. Modellers should not assume that their model will inherently be useful for policy and should instead ensure that they are: 1) addressing a policy need; and 2) making the information accessible to policymakers by crafting a communication plan and/or joining a relevant boundary organization.

Background Thermogenic supplements are often consumed by individuals seeking to improve energy levels and reduce body fat. These supplements are sold in powdered or ready-to-drink (RTD) forms and consist of a blend of ingredients such as caffeine, green tea extract, and other botanical compounds. While there is evidence that thermogenic supplements can positively affect resting energy expenditure (REE), the effect varies based on the combination of active ingredients. Additionally, there is some concern that thermogenic supplements may cause unwanted side effects on hemodynamic variables, like heart rate (HR) and blood pressure (BP). Therefore, further investigation into the efficacy and safety of commercially available products is warranted. Methods Twenty-eight individuals (14 F, 14 M; age: 23.3 ± 3.9 yrs; height: 169.4 ± 8.6 cm; body mass: 73.3 ± 13.1 kg) completed two visits in a randomized, double-blind, crossover fashion. Each visit began with baseline REE, HR, and BP assessments, which were followed by ingestion of an active RTD thermogenic beverage (RTD; OxyShred Ultra Energy) or placebo (PL). Assessments were repeated at the intervals of 35–50- and 85–100-minutes post-ingestion. In addition, subjective outcomes of energy, focus, concentration, alertness, and mood were collected five times throughout each visit. Repeated-measures analysis of variance was performed with condition and time specified as within-subjects factors and sex and resistance training (RT) status as between-subjects factors. Statistical significance was accepted at p

Despite clear evidence of the public health benefits of the human papillomavirus (HPV) vaccine in preventing HPV-related cancers and genital warts, underutilization of HPV vaccination in the United States persists. Interventions targeting multi-level determinants of vaccination behavior are crucial for improving HPV vaccination rates. The study’s purpose was to implement and evaluate the adapted Adolescent Vaccination Program (AVP), a clinic-based, multi-level, multi-component intervention aimed at increasing HPV vaccine initiation and completion rates in a five-clinic pediatric network in Bexar County, Texas. The adaptation process was guided by established frameworks and involved formative work with clinic stakeholders. The study utilized a quasi-experimental single group pre- and post- study design, with an external comparison data using the National Immunization Survey-Teen (NIS-Teen) datasets for the same time period to examine the AVP’s effect on HPV vaccination initiation and completion. A series of interrupted time series analyses (ITSA) compared the clinic system patient outcomes (HPV vaccination initiation and completion rates) in the post-intervention to the general adolescent population (NIS-Teen). Of the 6438 patients (11–17 years) with clinic visits during the 3-year study period, HPV vaccination initiation rates increased from 64.7% to 80.2% (p < 0.05) and completion rates increased from 43.2% to 60.2% (p < 0.05). The AVP was effective across various demographic and economic subgroups, demonstrating its generalizability. ITSA findings indicated the AVP improved HPV vaccination initiation and completion rates in clinic settings and that AVP strategies facilitated resilience during the pandemic. The minimal adaptation required for implementation in a new clinic system underscores its feasibility and potential for widespread adoption.

BackgroundMetabolic and bariatric surgery (MBS) is the most effective and durable obesity treatment. However, there is heterogeneity in weight outcomes, which is partially attributed to variability in appetite and eating regulation. Patients with a strong desire to eat in response to the reward of palatable foods are more likely to overeat and experience suboptimal outcomes. This subgroup, classified as at risk, may benefit from repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation technique that shows promise for reducing cravings and consumption of addictive drugs and food; no study has evaluated how rTMS affects the reinforcing value of food and brain reward processing in the context of MBS. ObjectiveThe goal of the Transcranial Magnetic Stimulation to Reduce the Relative Reinforcing Value of Food (RESTRAIN) study is to perform an initial rTMS test on the relative reinforcing value (RRV) of food (the reinforcing value of palatable food compared with money) among adult patients who are pursuing MBS and report high food reinforcement. Using a within-participants sham-controlled crossover design, we will compare the active and sham rTMS conditions on pre- to posttest changes in the RRV of food (primary objective) and the neural modulation of reward, measured via electroencephalography (EEG; secondary objective). We hypothesize that participants will show larger decreases in food reinforcement and increases in brain reward processing after active versus sham rTMS. MethodsParticipants (n=10) will attend 2 study sessions separated by a washout period. They will be randomized to active rTMS on 1 day and sham rTMS on the other day using a counterbalanced schedule. For both sessions, participants will arrive fasted in the morning and consume a standardized breakfast before being assessed on the RRV of food and reward tasks via EEG before and after rTMS of the left dorsolateral prefrontal cortex. ResultsRecruitment and data collection began in December 2022. As of October 2023, overall, 52 patients have been screened; 36 (69%) screened eligible, and 17 (47%) were enrolled. Of these 17 patients, 3 (18%) were excluded before rTMS, 5 (29%) withdrew, 4 (24%) are in the process of completing the protocol, and 5 (29%) completed the protocol. ConclusionsThe RESTRAIN study is the first to test whether rTMS can target neural reward circuits to reduce behavioral (RRV) and neural (EEG) measures of food reward in patients who are pursuing MBS. If successful, the results would provide a rationale for a fully powered trial to examine whether rTMS-related changes in food reinforcement translate into healthier eating patterns and improved MBS outcomes. If the results do not support our hypotheses, we will continue this line of research to evaluate whether additional rTMS sessions and pulses as well as different stimulation locations produce clinically meaningful changes in food reinforcement. Trial RegistrationClinicalTrials.gov NCT05522803; https://clinicaltrials.gov/study/NCT05522803 International Registered Report Identifier (IRRID)DERR1-10.2196/50714

Background There is substantial consumer and practitioner interest in an emerging supplement class known as multi-ingredient pre-workout supplements (MIPS), largely due to their prevalence in resistance training communities as well as research findings demonstrating the ergogenic impact of caffeine on muscular performance. However, limited research has examined the potential efficacy of non-caffeinated MIPS, despite their growing popularity among those who are caffeine-sensitive or who train later in the day. Methods Twenty-four resistance-trained college-aged males (n = 12) and females (n = 12) completed three visits in which they ingested either a caffeinated MIPS (C), an otherwise identical non-caffeinated MIPS (NC), or placebo in a double-blind, counterbalanced, crossover fashion. Squat isometric peak force (PFiso), rate of force development (RFD), and isokinetic performance were assessed. Upper and lower body maximal muscular strength and endurance were evaluated using the bench press and leg press, respectively. Visual analog scales for energy, focus, and fatigue were completed five times throughout the testing protocol. The effects of supplementation and biological sex on all variables were examined using linear mixed effects models. Results Significantly greater PFiso was observed in both C (b: 0.36 transformed units [0.09, 0.62]) and NC (b: 0.32 transformed units [95% CI: 0.05, 0.58]) conditions, relative to placebo. Early RFD (RFD50) may have been higher with supplementation, particularly in females, with no effects for late RFD (RFD200) or peak RFD. In addition, increases in subjective energy after supplement ingestion were noted for C, but not NC. No effects of supplementation on traditional resistance exercise performance or isokinetic squat performance were observed, other than a lower leg press one-repetition maximum for males in the NC condition. Conclusions These data indicate that acute ingestion of either a caffeinated or non-caffeinated pre-workout formulation improved maximal force production during an isometric squat test but did not provide additional benefit to leg press, bench press, or isokinetic squat performance over placebo, within the context of a laboratory environment. The consumption of a caffeinated, but not non-caffeinated, MIPS increased subjective ratings of energy over placebo when assessed as part of a testing battery.

Abstract Background Characterizing immune cells and conditions that govern their recruitment and function in autoimmune diseases of the nervous system or in neurodegenerative processes is an area of active investigation. We sought to analyze the origin of antigen presenting cells associated with the induction of retinal autoimmunity using a system that relies on spontaneous autoimmunity, thus avoiding uncertainties associated with immunization with adjuvants at remotes sites or adoptive transfer of in vitro activated T cells. Methods R161H mice (B10.RIII background), which spontaneously and rapidly develop severe spontaneous autoimmune uveoretinitis (SAU), were crossed to CD11cDTR/GFP mice (B6/J) allowing us to track the recruitment to and/or expansion within the retina of activated, antigen presenting cells (GFPhi cells) in R161H+/− × CD11cDTR/GFP F1 mice relative to the course of SAU. Parabiosis between R161H+/− × CD11cDTR/GFP F1 mice and B10.RIII × B6/J F1 (wild-type recipient) mice was done to explore the origin and phenotype of antigen presenting cells crucial for the induction of autoimmunity. Analysis was done by retinal imaging, flow cytometry, and histology. Results Onset of SAU in R161H+/− × CD11cDTR/GFP F1 mice was delayed relative to B10.RIII-R161H+/− mice revealing a disease prophase prior to frank autoimmunity that was characterized by expansion of GFPhi cells within the retina prior to any clinical or histological evidence of autoimmunity. Parabiosis between mice carrying the R161H and CD11cDTR/GFP transgenes and transgene negative recipients showed that recruitment of circulating GFPhi cells into retinas was highly correlative with the occurrence of SAU. Conclusions Our results here contrast with our previous findings showing that retinal antigen presenting cells expanding in response to either sterile mechanical injury or neurodegeneration were derived from myeloid cells within the retina or optic nerve, thus highlighting a unique facet of retinal autoimmunity.

The extracellular matrix (ECM) is a dynamic structure of molecules that can be divided into six different categories and are collectively called the matrisome. The ECM plays pivotal roles in physiological processes in many tissues, including the nervous system. Intriguingly, alterations in ECM molecules/pathways are associated with painful human conditions and murine pain models. Nevertheless, mechanistic insight into the interplay of normal or defective ECM and pain is largely lacking. The goal of this study was to integrate bulk, single-cell, and spatial RNA sequencing (RNAseq) datasets to investigate the expression and cellular origin of matrisome genes in male and female murine and human dorsal root ganglia (DRG). Bulk RNAseq showed that about 65% of all matrisome genes were expressed in both murine and human DRG, with proportionally more core matrisome genes (glycoproteins, collagens, and proteoglycans) expressed compared to matrisome-associated genes (ECM-affiliated genes, ECM regulators, and secreted factors). Single cell RNAseq on male murine DRG revealed the cellular origin of matrisome expression. Core matrisome genes, especially collagens, were expressed by fibroblasts whereas matrisome-associated genes were primarily expressed by neurons. Cell–cell communication network analysis with CellChat software predicted an important role for collagen signaling pathways in connecting vascular cell types and nociceptors in murine tissue, which we confirmed by analysis of spatial transcriptomic data from human DRG. RNAscope in situ hybridization and immunohistochemistry demonstrated expression of collagens in fibroblasts surrounding nociceptors in male and female human DRG. Finally, comparing human neuropathic pain samples with non-pain samples also showed differential expression of matrisome genes produced by both fibroblasts and by nociceptors. This study supports the idea that the DRG matrisome may contribute to neuronal signaling in both mouse and human, and that dysregulation of matrisome genes is associated with neuropathic pain.

Purpose . Identifying factors that influence moderate-to-vigorous intensity physical activity (MVPA) and sedentary time in metabolic and bariatric surgery (MBS) patients is necessary to inform the development of interventions. Weather/environmental factors may be especially important considering rapid climate change and the vulnerability of people with obesity to heat and pollution. Our study aimed to examine the associations of weather (maximal, average and Wet Bulb Globe Temperatures), and air pollution indices (air quality index [AQI]) with daily physical activity (PA) of both light (LPA) and MVPA and sedentary time before and after MBS. Materials and methods . Participants (n = 77) wore an accelerometer at pre- and 3, 6, and 12-months post-MBS to assess LPA/MVPA/ sedentary time (min/d). These data were combined with participants’ local (Boston, MA or Providence, RI, USA) daily weather and AQI data (extracted from federal weather and environmental websites). Results . Multilevel generalized additive models showed inverted U-shaped associations between weather indices and MVPA, with a marked reduction in MVPA for daily maximal temperatures ≥20 °C. Sensitivity analysis showed a less marked decrease of MVPA (min/d) during higher temperatures after versus before MBS. Both MVPA before and after MBS and sedentary time before MBS were negatively impacted by higher AQI levels. Conclusion . This study is the first to show that weather and air pollution indices, even in locations with good AQI and moderate temperatures, are related to variability in activity behaviors, particularly MVPA, during pre- and post-MBS. Weather/environmental conditions should be considered in MVPA prescription/strategies for adults who have undergone MBS.

Summary: Appropriate cytoskeletal organization is essential for vascular smooth muscle cell (VSMC) conditions such as hypertension. This study identifies FXR1 as a key protein linking cytoskeletal dynamics with mRNA stability. RNA immunoprecipitation sequencing (RIP-seq) in human VSMCs identifies that FXR1 binds to mRNA associated with cytoskeletal dynamics, and FXR1 depletion decreases their mRNA stability. FXR1 binds and regulates actin polymerization. Mass spectrometry identifies that FXR1 interacts with cytoskeletal proteins, particularly Arp2, a protein crucial for VSMC contraction, and CYFIP1, a WASP family verprolin-homologous protein (WAVE) regulatory complex (WRC) protein that links mRNA processing with actin polymerization. Depletion of FXR1 decreases the cytoskeletal processes of adhesion, migration, contraction, and GTPase activation. Using telemetry, conditional FXR1SMC/SMC mice have decreased blood pressure and an abundance of cytoskeletal-associated transcripts. This indicates that FXR1 is a muscle-enhanced WRC modulatory protein that regulates VSMC cytoskeletal dynamics by regulation of cytoskeletal mRNA stability and actin polymerization and cytoskeletal protein-protein interactions, which can regulate blood pressure.

Abstract Background Bariatric surgery produces weight loss in part by impacting appetite and eating behavior. Research suggests physical activity (PA) assists with regulation of appetite and eating during non‐surgical weight loss, although whether PA carries similar benefits in the context of bariatric surgery is unknown. Objective Evaluate associations of moderate‐to‐vigorous intensity PA (MVPA) and sedentary time (ST) with appetite sensations (hunger [homeostatic/hedonic], satiety) and eating regulation behaviors (restraint, disinhibition) before and during the initial year following bariatric surgery. Method Adult bariatric patients received an accelerometer to measure MVPA/ST and a smartphone to complete appetite/eating ratings at four semi‐random times daily for 10 days at pre‐ and 3‐, 6‐, and 12‐months post‐surgery. Data were analyzed using generalized linear mixed models. Results Higher MVPA levels related to more satiety across time (p = 0.045) and more restraint at 3‐months post‐surgery (p

This study examined the impact of a hypercaloric high-fat high-fructose diet (HFFD) in dogs as a potential model for human impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). The HFFD not only led to weight gain but also triggered metabolic alterations akin to the precursors of human T2DM, notably insulin resistance and β-cell dysfunction. Following the HFFD intervention, the dogs exhibited a 50% decrease in insulin sensitivity within the first four weeks, paralleling observations in the progression from normal to IGT in humans. Calculations of the insulinogenic index using both insulin and C-peptide measurements during oral glucose tolerance tests revealed a significant and sustained decrease in early-phase insulin release, with partial compensation in the later phase, predominantly stemming from reduced hepatic insulin clearance. In addition, the Disposition Index, representing the β-cell's capacity to compensate for diminished insulin sensitivity, fell dramatically. These results confirm that a HFFD can instigate metabolic changes in dogs akin to the early stages of progression to T2DM in humans. The study underscores the potential of using dogs subjected to a HFFD as a model organism for studying human IGT and T2DM.

BackgroundCarbohydrate and protein dietary proportions have been debated as to whether higher or lower levels are optimal for diabetes metabolic control.ObjectiveThe objective of this study was to investigate the associations, interactions, and mediational relationships between a polygenic risk score (PRS), carbohydrate and protein intake, and physical activity level on type 2 diabetes (T2DM) by genetic ancestry, in European Americans and African Americans. A secondary objective examined the biological pathways associated with the PRS-linked genes and their relationships to dietary intake.MethodsWe performed a cross-sectional study in 9,393 participants: 83.3% European Americans and 16.7% African Americans from 7-NHLBI Care studies obtained from the database of Genotypes and Phenotypes. The main outcome was T2DM. Carbohydrate and protein intake derived from food frequency questionnaires were calculated as percent calories. Data were analyzed using multivariable generalized estimation equation models to derive odds ratios (OR) and 95% confidence intervals (CI). Ancestry-specific PRSs were constructed using joint-effects Summary Best Linear Unbiased Estimation in the train dataset and replicated in the test dataset. Mediation analysis was performed using VanderWeele's method.ResultsThe PRS in the highest tertile was associated with higher risk of T2DM in European Americans (OR = 1.25;CI = 1.03-1.51) and African Americans (OR = 1.54;1.14-2.09). High carbohydrate and low protein intake had lower risks of T2DM when combined with the PRS after adjusting for covariates. In African Americans, high physical activity combined with the high PRS and high protein diet was associated with a 28% lower incidence of T2DM when compared to low physical activity. In mediational models in African Americans, the PRS-T2DM association was mediated by protein intake in the highest tertile by 55%. The top PRS tertile had the highest magnitude of risks with metabolic factors that were significantly associated with T2DM, especially in European Americans. We found metabolic pathways associated with the PRS-linked genes that were related to insulin/IGF and ketogenesis/ketolysis that can be activated by moderate physical activity and intermittent fasting for better T2DM control.ConclusionsClinicians may want to consider diets with a higher portion of carbohydrates than protein, especially when the burden of high-risk alleles is great in patients with T2DM. In addition, clinicians and other medical professionals may want to emphasize the addition of physical activity as part of treatment regimen especially for African Americans. Given the metabolic pathways we identified, moderate physical activity and intermittent fasting should be explored. Researchers may want to consider longitudinal or randomized clinical trials to determine the predictive ability of different dietary patterns to inhibit T2DM in the presence of obesity and an elevated PRS.

The testing of engineered enzymes represents a bottleneck. Here the authors report a screening method combining microfluidics and mass spectrometry, to map the catalysis of a mutated enzyme, characterise the range of products generated and recover the sequences of variants with desired activities.

Abstract Background Associations have been observed among genetic variants, dietary patterns, and metabolic syndrome (MetS). A gap in knowledge is whether a genetic risk score (GRS) and dietary patterns interact to increase MetS risk among African Americans. We investigated whether MetS risk was influenced by interaction between a GRS and dietary patterns among Whites and African Americans. A secondary aim examined if molecular genetic clusterings differed by racial ancestry. Methods We used longitudinal data over 4-visits (1987–1998) that included 10,681 participants aged 45–64y at baseline from the Atherosclerosis Risk in Communities study (8451 Whites and 2230 African Americans). We constructed a simple-count GRS as the linear weighted sum of high-risk alleles (0, 1, 2) from cardiovascular disease polymorphisms from the genome-wide association studies catalog associated with MetS risk. Three dietary patterns were determined by factor analysis of food frequency questionnaire data: Western, healthy, and high-fat dairy. MetS was defined according to the 2016 National Cholesterol Education Program Adult Treatment Panel III criteria but used 2017 American Heart Association/American College of Cardiology criteria for elevated blood pressure. Analyses included generalized linear model risk ratios (RR), 95% confidence intervals (CI), and Bonferroni correction for multiple testing. Results The Western dietary pattern was associated with higher risk for MetS across increasing GRS tertiles among Whites (p

Abstract Membrane lipids serve as substrates for the generation of numerous signaling lipids when plants are exposed to environmental stresses, and jasmonic acid, an oxidized product of 18‐carbon unsaturated fatty acids (e.g., linolenic acid), has been recognized as the essential signal in wound‐induced gene expression. Yet, the contribution of individual membrane lipids in linolenic acid generation is ill‐defined. In this work, we performed spatial lipidomic experiments to track lipid changes that occur locally at the sight of leaf injury to better understand the potential origin of linolenic and linoleic acids from individual membrane lipids. The central veins of tomato leaflets were crushed using surgical forceps, leaves were cryosectioned and analyzed by two orthogonal matrix‐assisted laser desorption/ionization mass spectrometry imaging platforms for insight into lipid spatial distribution. Significant changes in lipid composition are only observed 30 min after wounding, while after 60 min lipidome homeostasis has been re‐established. Phosphatidylcholines exhibit a variable pattern of spatial behavior in individual plants. Among lysolipids, lysophosphatidylcholines strongly co‐localize with the injured zone of wounded leaflets, while, for example, lysophosphatidylglycerol (LPG) (16:1) accumulated preferentially toward the apex in the injured zone of wounded leaflets. In contrast, two other LPGs (LPG [18:3] and LPG [18:2]) are depleted in the injured zone. Our high‐resolution co‐localization imaging analyses suggest that linolenic acids are predominantly released from PCs with 16_18 fatty acid composition along the entire leaf, while it seems that in the apex zone PG (16:1_18:3) significantly contributes to the linolenic acid pool. These results also indicate distinct localization and/or substrate preferences of phospholipase isoforms in leaf tissue.

Summary Background Despite plausibility of migraine headaches contributing to impaired sexual function among women, data are inconsistent and point to obesity as a potential confounder. Prospective studies that assess the relative importance of migraine improvements and weight loss in relation to sexual function could help elucidate associations among migraine, obesity and female sexual dysfunction (FSD). Objective To evaluate sexual function changes and predictors of improvement after behavioural weight loss (BWL) intervention for migraine or migraine education (ME). Methods Women with migraine and overweight/obesity were randomized to 16 weeks of BWL (n = 54) or ME (n = 56). Participants completed a 4‐week smartphone headache diary and the Female Sexual Function Index (FSFI) at pre‐ and post‐treatment. A validated FSFI total cut‐off score defined FSD. We compared changes in FSFI scores and FSD rates between conditions and evaluated migraine improvements and weight loss as predictors of sexual functioning in the full sample. Results Among treatment completers (n = 85), 56 (65.9%) participants who reported sexual activity at pre‐ and post‐treatment were analysed. Migraine improvements were similar between conditions, whereas BWL had greater weight losses compared with ME. FSD rates did not change overall (48.2% to 44.6%, p = .66) or by condition (BWL: 56.0% to 40.0% vs. ME: 41.9% to 48.4%, p = .17). Similar patterns were observed for changes in FSFI total and subscale scores. Across conditions, larger weight losses predicted greater improvements in FSFI total and arousal subscale scores, whereas larger migraine headache frequency reductions predicted greater improvements in FSFI satisfaction subscale scores. Conclusion Sexual functioning did not improve with either BWL or ME despite migraine headache improvements in both conditions and weight loss after BWL. However, weight loss related to improvements in physiological components of the sexual response (i.e., arousal) and overall sexual functioning, whereas reduced headache frequency related to improved sexual satisfaction. Additional research with larger samples is needed.

Summary Objective Commercial online weight management programmes are popular and easily accessible but often lack training in empirically validated behaviour change strategies and produce suboptimal outcomes. This study evaluated the effects of a Web‐based virtual reality (VR) programme for enhancing behavioural skills training and weight loss when offered as an adjunct to a commercial online weight management programme. Methods N = 146 adults with overweight/obesity (body mass index [BMI] 27‐40 kg/m2) were randomized to 6 months of no‐cost access to the Weight Watchers (WW) online platform alone or enhanced with the Experience Success (WW + ES) programme, consisting of four Web‐based VR sessions for training in behavioural weight‐loss skills related to the home environment, the workplace, physical activity and social situations (i.e., a party at a friend's house). Weight was measured at the research centre at baseline, 3 and 6 months. Results Both groups achieved statistically significant weight loss across the trial, with no difference in mean ± standard error (SE) weight loss between WW and WW + ES at 3 months (2.7 ± 1.1 kg vs. 4.2 ± 1.1 kg, respectively; P = .086) but greater weight loss in WW + ES at 6 months (2.6 ± 1.3 kg vs. 4.9 ± 1.3 kg, respectively; P = .042). Conclusions This study demonstrates the potential of Web‐based VR skills training to enhance outcomes of commercial online weight management programmes that are widely accessible. Compared with traditional didactic methods for online skills training, VR simulation provides opportunities to learn behavioural skills via modelling and experiment with skills in real‐world situations. More research is needed to identify specific behavioural mechanisms by which ES may improve outcomes.

Summary Background Migraine and obesity are comorbid particularly in women of reproductive age. Obesity treatment involves reducing energy intake and improving dietary quality but the effect of these changes on migraine is largely unknown. Objective To determine if adherence to dietary intervention targets (ie, total energy, dietary fat intake, and dietary quality) were associated with improvements in migraine and weight. Methods Eighty‐four women with overweight/obesity and migraine were randomized to and completed either a 16‐week behavioral weight loss (BWL) or a migraine education (ME) intervention. For 28 days at baseline and posttreatment, women recorded monthly migraine days, duration, and maximum pain intensity via smartphone‐based diary. At each assessment, weight was measured and dietary intake (total energy intake, percent (%) energy from fat, and diet quality, as measured by the Healthy Eating Index, 2010 [HEI‐2010]) was assessed using three nonconsecutive 24‐hour diet recalls. Results There were no significant group differences in change mean migraine days per month (BWL: ‐2.6+4.0, ME: ‐4.0+4.4; p = 0.1). Participants in BWL significantly reduced their percent fat intake 3.8% (p = 0.004) and improved total diet quality (HEI‐2010) by 6.7 points (p = 0.003) relative to baseline and those in ME (%fat: +0.3%; p = 0.821; HEI‐2010: +0.7; p = 0.725). After controlling for race/ethnicity and weight change, changes in dietary intake were not related to changes in migraine characteristics or weight loss among BWL participants (p's > 0.05). Conclusions Changes in dietary intake among participants were small and may have been insufficient to improve migraine in women with overweight/obesity and migraine.

Background Studies show smoking and vaping behaviors increase risk of contracting and worse symptoms of COVID-19. This study examines whether past 30-day youth and young adult users of marijuana, e-cigarettes, and cigarettes self-reported changes in their use of these substances due to the COVID-19 pandemic; and cross-sectional associations between perceived stress, nicotine or marijuana dependence, and COVID-19–related changes in use. Methods Participants were 709 past 30-day self-reported substance users from the Texas Adolescent Tobacco and Marketing Surveillance study (TATAMS; mean age = 19; 58% female; 38% Hispanic, 35% white). Multiple logistic regression models assessed cross-sectional associations between perceived stress and dependence and increased, decreased, or sustained past 30-day use of marijuana, e-cigarettes, and cigarettes due to COVID-19 (e.g., “Has your marijuana use changed due to the COVID-19 outbreak?”). Covariates included age, race/ethnicity, socio-economic status (SES), dependence (exposure: stress), and stress (exposure: dependence). Results Most participants reported sustained (41%, 43%, 49%) or increased (37%, 34%, 25%) use of marijuana, e-cigarettes, and cigarettes due to COVID-19, respectively. Participants who reported symptoms of dependence were significantly more likely than their non-dependent peers to report increasing their marijuana (AOR: 1.66; 95% CI: 1.15–2.39) and e-cigarette (AOR: 2.57; 95% CI: 1.38–4.77) use. Those who reported higher perceived stress were significantly more likely to report increasing their marijuana use (AOR: 1.55; 95% CI: 1.01–2.42). Conclusions Most youth and young adults did not decrease their substance use amid a global, respiratory disease pandemic. Health messaging and interventions that address the health effects of smoking and vaping as well as factors like stress and dependence that may be barriers to decreasing use are vital in curbing the COVID-19 pandemic.

Abstract Background Microglia are essential to the development of the CNS and its homeostasis. Our prior findings suggested a niche model to describe the behaviors of retinal microglia. Here, we ask whether new myeloid cells recruited to the retina are constrained to resemble endogenous microglia morphologically and functionally. Methods Use of CD11cDTR/GFP transgenic mouse allowed identification of two niches of retinal microglia distinguished by being GFPlo or GFPhi. We also used transgenic mice in which CX3CR1+ cells expressed YFP and were depletable following tamoxifen-induced expression of diphtheria toxin subunit A. We employed several ablation and injury stimulation protocols to examine the origin and fate of myeloid cells repopulating the retina. Analysis of retinal myeloid cells was done by microscopy, flow cytometry, and qRT-PCR. Results We found that the origin of new GFPhi and GFPlo myeloid cells in the retina of CD11cDTR/GFP mice, whether recruited or local, depended on the ablation and stimulation protocols. Regardless of origin, new GFPlo and GFPhi retinal myeloid cells were CD45medCD11b+Ly6G−Ly6CloIba1+F4/80+, similar to endogenous microglia. Following tamoxifen-induced diphtheria toxin ablation, myeloid cell repopulation differed in the retina compared to the brain and optic nerve. Stimulation of replacement GFPhi cells was substantially attenuated in repopulating retinas after tamoxifen-induced diphtheria toxin ablation compared to control or radiation-ablated mice. In radiation bone marrow chimeric mice, replacement GFPhi myeloid cells from the circulation were slow to repopulate the retina unless stimulated by an optic nerve crush injury. However, once stimulated, recruited GFPhi cells were found to concentrate on injured retinal ganglion cells and were morphologically similar to GFPhi cells in non-ablated control CD11cDTR/GFP mice. Conclusions The results support the idea that GFPhi cells in the CD11cDTR/GFP mouse, whether recruited or from resident microglia, mark a unique niche of activated retinal myeloid cells. We conclude that the retinal environment has a potent influence on the function, morphology, and proliferative capacity of new myeloid cells regardless of their origin, compelling them to be equivalent to the endogenous microglia.

Abstract The objective of this study was to assess the safety of surgical common hepatic artery denervation (CHADN). This procedure has previously been shown to improve glucose tolerance in dogs fed a high‐fat high‐fructose (HFHF) diet. We assessed the hypoglycemic response of dogs by infusing insulin at a constant rate (1.5 mU/kg/min) for 3 h and monitoring glucose and the counterregulatory hormones (glucagon, catecholamine, and cortisol). After an initial hypoglycemic study, the dogs were randomly assigned to a SHAM surgery (n = 4) or hepatic sympathetic denervation (CHADN, n = 5) and three follow‐up studies were performed every month up to 3 months after the surgery. The level of norepinephrine (NE) in the liver and the pancreas was significantly reduced in the CHADN dogs, showing a decrease in sympathetic tone to the splanchnic organs. There was no evidence of any defect of the response to hypoglycemia after the CHADN surgery. Indeed, the extent of hypoglycemia was similar in the SHAM and CHADN groups (~45 mg/dl) for the same amount of circulating insulin (~50 µU/ml) regardless of time or surgery. Moreover the responses of the counterregulatory hormones were similar in extent and pattern during the 3 h of hypoglycemic challenge. Circulating lactate, glycerol, free fatty acids, and beta‐hydroxybutyrate were also unaffected by CHADN during fasting conditions or during the hypoglycemia. There were no other notable surgery‐induced changes over time in nutrients, minerals, and hormones clinically measured in the dogs nor in the blood pressure and heart rate of the animals. The data suggest that the ablation of the sympathetic nerve connected to the splanchnic bed is not required for a normal counterregulatory response to insulin‐induced hypoglycemia and that CHADN could be a safe new therapeutic intervention to improve glycemic control in individuals with metabolic syndrome or type 2 diabetes.

ObjectiveTo examine the relationship between current cigarette smoking patterns and three established risk factors for suicide using nationally representative data of high school students in the United States.MethodsWe analyzed cross-sectional data from the national Youth Risk Behavior Surveillance Survey (YRBSS)-United States, 2017. Multivariable, logistic regressions examined the association between 3 cigarette smoking behaviors [i.e., past 30-day cigarette (n = 13,731), frequent (n = 1,093) and heavy (n = 880) smoking] and 3 risk factors for suicidal outcomes [feeling sad or hopeless, suicidal ideation, suicide plan] assessed over the previous year.ResultsAmong high school cigarette smokers, smoking 11 or more cigarettes per day (i.e., heavy smoking) was associated with 3.43 (95% CI: 1.69, 6.94) greater odds of reporting feeling sad or hopeless, 2.97 (95% CI: 1.60, 5.51) greater odds of reporting suicidal ideations, and 2.11 (95% CI: 1.34, 3.32) greater odds of reporting having ever planned a suicide attempt, controlling for covariates.ConclusionsOur study shows that it is not simply cigarette smoking, but heavy cigarette smoking that is a risk factor for suicidal outcomes among adolescents.Public health implicationsA comprehensive plan is needed to accommodate heavy adolescent smokers who are at increased suicidal risk.

BackgroundAlthough the benefits of physical activity (PA) are well known, physical inactivity is highly prevalent among people with obesity. The objective of this systematic review was to i) appraise knowledge on PA motives, barriers, and preferences in individuals with obesity, and ii) quantify the most frequently reported PA motives, barriers and preferences in this population.MethodsSix databases (Pubmed, CINAHL, Psyarticle, SportDiscus, Web of science and Proquest) were searched by independent reviewers to identify relevant quantitative or qualitative articles reporting PA motives, barriers or preferences in adults with body mass index ≥ 30 kg/m2 (last searched in June 2020). Risk of bias for each study was assessed by two independent reviewers with the Mixed Methods Appraisal Tool (MMAT).ResultsFrom 5,899 papers identified, a total of 27 studies, 14 quantitative, 10 qualitative and 3 mixed studies were included. About 30% of studies have a MMAT score below 50% (k = 8). The three most reported PA motives in people with obesity were weight management, energy/physical fitness, and social support. The three most common PA barriers were lack of self-discipline/motivation, pain or physical discomfort, and lack of time. Based on the only 4 studies available, walking seems to be the preferred mode of PA in people with obesity.ConclusionsWeight management, lack of motivation and pain are key PA motives and barriers in people with obesity, and should be addressed in future interventions to facilitate PA initiation and maintenance. Further research is needed to investigate the PA preferences of people with obesity.

Abstract Introduction Despite advances in imaging retinal amyloidosis, a quantitative and topographical investigation of retinal amyloid beta burden in patients with cognitive decline has never been reported. Methods We used the specific amyloid‐binding fluorophore curcumin and laser ophthalmoscopy to assess retinal amyloid imaging (RAI) in 34 patients with cognitive decline. We automatically quantified retinal amyloid count (RAC) and area in the superotemporal retinal sub‐regions and performed correlation analyses with cognitive and brain volumetric parameters. Results RAC significantly and inversely correlated with hippocampal volume (HV; r = ‐0.39, P = .04). The proximal mid‐periphery (PMP) RAC and RA areas were significantly greater in patients with Montreal Cognitive Assessment (MOCA) score < 26 (P = .01; Cohen d = 0.83 and 0.81, respectively). PMP showed significantly more RAC and area in subjects with amnestic mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared to cognitively normal (P = .04; Cohen d = 0.83). Conclusion Quantitative RAI is a feasible technique and PMP RAC may predict HV. Future larger studies should determine RAI's potential as a biomarker of early AD.

In this study, we report a biohybrid oriented fibrous scaffold based on nanofibers of poly(l-lactic acid) (PLLA)/fibrin produced by electrospinning and subsequent post-treatment. Induced hydrolytic degradation of the fibers in 0.25 M NaOH solution for various time periods followed by the immobilization of fibrin on the hydrolyzed fiber surfaces was shown to significantly affect the mechanical properties, with the tensile strength (40.6 MPa ± 1.3) and strain at failure (38% ± 4.5) attaining a value within the range of human ligaments and ligament-replacement grafts. Unidirectional electrospinning with a mandrel rotational velocity of 26.4 m/s produced highly aligned fibers with an average diameter of 760 ± 96 nm. After a 20-min hydrolysis treatment in NaOH solution, this was further reduced to an average of 457 ± 89 nm, which is within the range of collagen bundles found in ligament tissue. Based on the results presented herein, the authors hypothesize that a combination of fiber orientation/alignment and immobilization of fibrin can result in the mechanical and morphological modification of PLLA tissue scaffolds for ligament-replacement grafts. Further, it was found that treatment with NaOH enhanced the osteogenic differentiation of hMSCs and the additional inclusion of fibrin further enhanced osteogenic differentiation, as demonstrated by decreased proliferative rates and increased ALP activity.

Abstract Using mice expressing green fluorescent protein (GFP) from a transgenic CD11c promoter we found that a controlled optic nerve crush (ONC) injury attracted GFPhi retinal myeloid cells to the dying retinal ganglion cells and their axons. However, the origin of these retinal myeloid cells was uncertain. In this study we use transgenic mice in conjunction with ONC, partial and full optic nerve transection (ONT), and parabiosis to determine the origin of injury induced retinal myeloid cells. Analysis of parabiotic mice and fate mapping showed that responding retinal myeloid cells were not derived from circulating macrophages and that GFPhi myeloid cells could be derived from GFPlo microglia. Comparison of optic nerve to retina following an ONC showed a much greater concentration of GFPhi cells and GFPlo microglia in the optic nerve. Optic nerve injury also induced Ki67+ cells in the optic nerve but not in the retina. Comparison of the retinal myeloid cell response after full versus partial ONT revealed fewer GFPhi cells and GFPlo microglia in the retina following a full ONT despite it being a more severe injury, suggesting that full transection of the optic nerve can block the migration of responding myeloid cells to the retina. Our results suggest that the optic nerve can be a reservoir for activated microglia and other retinal myeloid cells in the retina following optic nerve injury.

The objectives of this study were to implement, test adherence to and examine the preliminary effectiveness of a summertime weight-gain prevention intervention in youth from a low-income, Rhode Island community. In 2016, 51 children, ages 6–12 years, participated in a daily, summertime intervention, which offered a minimum of two hours of physical activity programming and free lunch through the USDA's Summer Food Service Program (SFSP). Thirty children from the same community with similar SFSP access served as a comparison group. Height and weight were measured before and at the end of summer to assess change in body mass index z-score (BMIz). Diet and physical activity were assessed midsummer. Multivariate mixed models were used to test group differences in change in BMIz over the summer and weight-related behaviors midsummer. Repeated measures ANOVA was used to examine the relationships of intervention participation with change in BMIz and weight-related behaviors in intervention participants. On average, intervention participants attended 65.6% of program sessions. They lost 0.04 BMIz units, while those in the comparison group gained 0.03 BMIz units (p = 0.07). Midsummer, intervention participants spent 4.6% less time sedentary on weekdays as compared to comparison participants (p = 0.03). Among intervention participants, attendance was significantly associated with change in BMIz (p = 0.01), spending 41 more minutes in moderate to vigorous physical activity (MVPA) (p = 0.004) and 8.5% less time sedentary (p

Abstract Background Reductions in physical activity (PA) are common throughout young adulthood and low PA is associated with weight gain. The SNAP Trial previously reported that two self-regulation approaches to weight gain prevention reduced weight gain over a 2-year period in 18–35 year olds. Presented here are secondary analyses examining changes in PA and the relationship between PA and weight change over 2 years. Methods 599 young adults (age: 27.4 ± 4.4 yrs.; BMI: 25.4 ± 2.6 kg/m2) were randomly assigned to 1 of 3 treatment arms: Small Changes (reduce calorie intake by 100 kcals/day & add 2000 steps/day), Large Changes (lose 2.3–4.5 kg initially & increase PA to ≥250 min/wk), or Self-guided (control condition). Small and Large Changes received 10, face-to-face group sessions (months 1–4), and two 4-week refresher courses each subsequent year. Body weight and PA were objectively-measured at baseline, 4 months, 1 and 2 years. Daily steps and bout-related moderate-to-vigorous intensity PA (MVPA: ≥3 METs, ≥10-min bouts) was calculated. Results Changes in bout-related MVPA and daily steps did not differ among treatment groups over the 2-year period (p’s > 0.16). Collapsed across groups, participants gaining >1 lb. (n = 187; 39.6%) had smaller changes in bout-related MVPA at 4 months, 1 and 2 years relative to those maintaining or losing weight (≤1 lb. weight gain; n = 282, 60.4%, p’s 1 lb. did not differ on daily steps (p’s > 0.10). Among participants engaging in ≥250 min/wk. of MVPA at 2 years (n = 181), 30% gained >1 lb. from baseline to 2 years, which was not different from those engaging in 150–250 min/wk. (n = 87; 36%; p = 0.40), but this percentage was significantly lower when compared to those engaging in 150 min/week of MVPA is needed for weight gain prevention and that increasing MVPA, rather than steps, should be targeted. Trial registration www.clinicaltrials.gov (NCT01183689). Registered Aug 13, 2010.

Introduction: Retinal imaging is a non-invasive tool to study both retinal vasculature and neurodegeneration. In this exploratory retinal curcumin-fluorescence imaging (RFI) study, we sought to determine whether retinal vascular features combined with retinal amyloid burden correlate with the neurocognitive status. Methods: We used quantitative RFI in a cohort of patients with cognitive impairment to automatically compute retinal amyloid burden. Retinal blood vessels were segmented, and the vessel tortuosity index (VTI), inflection index, and branching angle were quantified. We assessed the correlations between retinal vascular and amyloid parameters, and cognitive domain Z-scores using linear regression models. Results: Thirty-four subjects were enrolled and twenty-nine (55% female, mean age 64 ± 6 years) were included in the combined retinal amyloid and vascular analysis. Eleven subjects had normal cognition and 18 had impaired cognition. Retinal VTI was discriminated among cognitive scores. The combined proximal mid-periphery amyloid count and venous VTI index exhibited significant differences between cognitively impaired and cognitively normal subjects (0.49 ± 1.1 vs. 0.91 ± 1.4, p = 0.006), and correlated with both the Wechsler Memory Scale-IV and SF-36 mental component score Z-scores (p < 0.05). Conclusion: This pilot study showed that retinal venular VTI combined with the proximal mid-periphery amyloid count could predict verbal memory loss. Future research is needed to finesse the clinical application of this retinal imaging-based technology.

Abstract Background Pain catastrophizing (PC) is associated with more severe and disabling migraine attacks. However, factors that moderate this relationship are unknown. Failure of inhibitory control (IC), or the ability to suppress automatic or inappropriate responses, may be one such factor given previous research showing a relationship between higher PC and lower IC in non-migraine samples, and research showing reduced IC in migraine. Therefore, we examined whether lower IC interacts with increased PC to predict greater migraine severity as measured by pain intensity, attack frequency, and duration. Methods Women (n = 105) aged 18–50 years old (M = 38.0 ± 1.2) with overweight/obesity and migraine who were seeking behavioral treatment for weight loss and migraine reduction completed a 28-day smartphone-based headache diary assessing migraine headache severity. Participants then completed a modified computerized Stroop task as a measure of IC and self-report measures of PC (Pain Catastrophizing Scale [PCS]), anxiety, and depression. Linear regression was used to examine independent and joint associations of PC and IC with indices of migraine severity after controlling for age, body mass index (BMI) depression, and anxiety. Results Participants on average had BMI of 35.1 ± 6.5 kg/m2and reported 5.3 ± 2.6 migraine attacks (8.3 ± 4.4 migraine days) over 28 days that produced moderate pain intensity (5.9 ± 1.4 out of 10) with duration of 20.0 ± 14.2 h. After adjusting for covariates, higher PCS total (β = .241, SE = .14, p = .03) and magnification subscale (β = .311, SE = .51, p

A protocol for a prospective single-blind parallel four-arm randomized placebo-controlled trial with repeated measures was designed to test the effects of various acupuncture methods compared with sham. Eighty self-selected participants with myofascial pain in the upper trapezius muscle were randomized into four groups. Group 1 received acupuncture to a myofascial trigger point (MTrP) in the upper trapezius. Group 2 received acupuncture to the MTrP in addition to relevant distal points. Group 3 received acupuncture to the relevant distal points only. Group 4 received a sham treatment to both the MTrP and distal points using a deactivated acupuncture laser device. Treatment was applied four times within 2 weeks with outcomes measured throughout the trial and at 2 weeks and 4 weeks posttreatment. Outcome measurements were a 100-mm visual analog pain scale, SF-36, pressure pain threshold, Neck Disability Index, the Upper Extremity Functional Index, lateral flexion in the neck, McGill Pain Questionnaire, Massachusetts General Hospital Acupuncture Sensation Scale, Working Alliance Inventory (short form), and the Credibility Expectance Questionnaire. Two-way analysis of variance (ANOVA) with repeated measures were used to assess the differences between groups.

Recent studies have shown that Borrelia burgdorferi can form antibiotic-tolerant persisters in the presence of microbiostatic drugs such as doxycycline. Precisely how this occurs is yet unknown. Our goal was to examine gene transcription by B. burgdorferi following doxycycline treatment in an effort to identify both persister-associated genes and possible targets for antimicrobial intervention. To do so, we performed next-generation RNA sequencing on doxycycline-treated spirochetes and treated spirochetes following regrowth, comparing them to untreated B. burgdorferi. A number of genes were perturbed and most of those which were statistically significant were down-regulated in the treated versus the untreated or treated/re-grown. Genes upregulated in the treated B. burgdorferi included a number of Erp genes and rplU, a 50S ribosomal protein. Among those genes associated with post-treatment regrowth were bba74 (Oms28), bba03, several peptide ABC transporters, ospA, ospB, ospC, dbpA and bba62. Studies are underway to determine if these same genes are perturbed in B. burgdorferi treated with doxycycline in a host environment.

Summary Objective The typical Western diet is deficient in omega‐3 and high in omega‐6 fatty acids (FAs). These FAs may play a role in depressive symptoms via inflammatory processes, especially in the context of obesity, a pro‐inflammatory state. This study investigated associations between omega‐3 and omega‐6 FA intake and depressive symptoms in adults seeking behavioural weight loss treatment (BWLT). Methods One hundred eighty‐eight persons with overweight or obesity (83.50% women, 93.10% White, 55.01 ± 10.09 years old, body mass index 36.02 ± 15.79 kg/m) seeking BWLT completed the Block Food Frequency Questionnaire, which provides estimates of dietary FA intake, daily total energy intake (TEI) and macronutrient composition of the diet. Depressive symptoms were measured via the Center for Epidemiological Studies Depression Scale. Correlation and linear regression estimated associations between depressive symptoms and FAs. Results On average, participants reported consuming 1866.2 ± 665.1 kcals/d, with 38% of TEI from fat and an omega‐6:3 ratio of 9.2 (13.9 g omega‐6 to 1.5 g omega‐3). In univariate models, omega‐6 intake was associated with depressive symptoms (r = .182, p = .012); however, this association was no longer statistically significant after controlling for TEI. Omega‐3 intake was not associated with depressive symptoms. Conclusion The expected association between omega‐3 and omega‐6 FAs and depressive symptoms was largely unsupported. A robust association between FA intake and depressive symptoms may have been masked by a high level of chronic inflammation in this sample caused by excess weight and overall poor diet. Additional research is needed to determine whether BWLT improves FA intake, and whether associations between FA intake and depressive symptoms are strengthened after successful weight loss and improved diet.

Given the benefits of habitual physical activity for migraine management and overall health, it is important to understand the reasons for low physical activity levels in those with migraine. Beliefs that physical activity can trigger and/or worsen migraine pain may contribute to low physical activity levels via intentional avoidance of physical activity, particularly of higher intensities. This study evaluated intentional avoidance of physical activity at varying intensity levels and its association with (a) leisure-time physical activity levels, (b) beliefs that physical activity will trigger and/or worsen migraine, and (c) migraine characteristics. Participants were women ( n = 100) who screened positive for migraine on the IDMigraine and completed an online survey on physical activity and migraine. The majority of the sample (78%) reported avoiding physical activity to manage migraine attacks at least once in the past month, and most reported avoidance of both moderate- and vigorous-intensity activity. Among those who reported avoidance, moderate- and vigorous-intensity physical activity was avoided on an average of 4.0 ± 2.0 and 4.1 ± 2.2 days/week, respectively. More frequent avoidance of vigorous-intensity physical activity (but not moderate-intensity) was significantly correlated with lower vigorous-intensity physical activity indicated by fewer days/week ( r = −0.28, p = 0.016) and fewer minutes/day ( r = −0.29, p = 0.011). The frequency of physical activity avoidance was significantly correlated with stronger expected likelihood that physical activity, at both intensity levels, will both trigger ( r = 0.39–0.43, p < 0.01) and worsen ( r = 0.24–0.25, p < 0.05) migraine attacks. Individuals who avoided physical activity reported a significantly higher number of migraine attacks in the past month and were more likely to have chronic migraine, compared to those who did not report avoidance. Intentional avoidance of moderate- and vigorous-intensity physical activity is a common migraine management strategy that is associated with lower levels of vigorous-intensity physical activity, stronger beliefs that physical activity will trigger or worsen migraine, and more frequent migraine attacks. Individuals with migraine who avoid physical activity may benefit from targeted intervention to address beliefs about physical activity and migraine, which has the strong potential to improve both migraine and health outcomes.

Lyme disease (Borrelia burgdorferi infection) is increasingly recognized as a significant source of morbidity worldwide. Here, we show that blood plasmablasts and CD27− memory B cells are elevated in untreated Lyme disease, with higher plasmablast levels associated with more rapid resolution of clinical symptoms. Stronger serum reactivity to surface proteins and peptides from B. burgdorferi was also associated with faster resolution of clinical symptoms. Through molecular identifier-enabled antibody heavy-chain sequencing of bulk B cells and single-cell paired-chain antibody sequencing of blood plasmablasts, we characterized immunoglobulin gene usage patterns specific to B. burgdorferi infection. Recombinantly expressed antibodies from expanded lineages bound B. burgdorferi antigens, confirming that these clones are driven by the infection. Furthermore, recombinant sequence-derived antibodies were functional, inhibiting growth of B. burgdorferi in vitro. Elevations and clonal expansion of blood plasmablasts were associated with rapid return to health, while poor plasmablast responses were associated with a longer duration of symptoms following treatment. Plasmablasts induced by B. burgdorferi infection showed preferential antibody gene segment usage, while bulk sequencing of total B cells revealed convergent CDR3 motifs specific to B. burgdorferi-infected patients. Our results show that robust plasmablast responses encoding Bb-static antibodies are associated with more rapid resolution of Lyme disease, and these antibodies could provide the basis for next-generation therapeutics for Lyme disease.

Bats are highly diverse and ecologically valuable mammals. They serve as host to bacteria, viruses and fungi that are either beneficial or harmful to its colony as well as to other groups of cave organisms. The bacterial diversity of two bat guano samples, C1 and C2, from Cabalyorisa Cave, Mabini, Pangasinan, Philippines were investigated using 16S rRNA gene amplicon sequencing. V3-V4 hypervariable regions were amplified and then sequenced using Illumina MiSeq 250 PE system. Reads were processed using Mothur and QIIME pipelines and assigned 12,345 OTUs for C1 and 5,408 OTUs for C2. The most dominant OTUs in C1 belong to the Proteobacteria (61.7%), Actinobacteria (19.4%), Bacteroidetes (4.2%), Firmicutes (2.7%), Chloroflexi (2.5%), candidate phylum TM7 (2.3%) and Planctomycetes (1.9%) while Proteobacteria (61.7%) and Actinobacteria (34.9%) dominated C2. Large proportion of sequence reads mainly associated with unclassified bacteria indicated possible occurrence of novel bacteria in both samples. XRF spectrophotometric analyses of C1 and C2 guano revealed significant differences in the composition of both major and trace elements. C1 guano recorded high levels of Si, Fe, Mg, Al, Mn, Ti and Cu while C2 samples registered high concentrations of Ca, P, S, Zn and Cr. Community structure of the samples were compared with other published community profiling studies from Finland (SRR868695), Meghalaya, Northeast India (SRR1793374) and Maharashtra State, India (CGS). Core microbiome among samples were determined for comparison. Variations were observed among previously studied guano samples and the Cabalyorisa Cave samples were attributed to either bat sources or age of the guano. This is the first study on bacterial diversity of guano in the Philippines through high-throughput sequencing.

[This corrects the article DOI: 10.1371/journal.pone.0200095.].

[This corrects the article DOI: 10.1371/journal.pone.0187875.].