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Introduction Type 2 diabetes mellitus (T2DM) is a powerful risk factor for cardiovascular disease (CVD), conferring a greater relative risk in women than men. We sought to examine sex differences in cardiometabolic risk factors and management in the contemporary cohort represented by the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).Research design and methods GRADE enrolled 5047 participants (1837 women, 3210 men) with T2DM on metformin monotherapy at baseline. The current report is a cross-sectional analysis of baseline data collected July 2013 to August 2017.Results Compared with men, women had a higher mean body mass index (BMI), greater prevalence of severe obesity (BMI≥40 kg/m2), higher mean LDL cholesterol, greater prevalence of low HDL cholesterol, and were less likely to receive statin treatment and achieve target LDL, with a generally greater prevalence of these risk factors in younger women. Women with hypertension were equally likely to achieve blood pressure targets as men; however, women were less likely to receive ACE inhibitors or angiotensin receptor blockers. Women were more likely to be divorced, separated or widowed, and had fewer years of education and lower incomes.Conclusions This contemporary cohort demonstrates that women with T2DM continue to have a greater burden of cardiometabolic and socioeconomic risk factors than men, particularly younger women. Attention to these persisting disparities is needed to reduce the burden of CVD in women.Trial registration number ClinicalTrials.gov (NCT01794143)

Introduction The shape of the glucose curve during an oral glucose tolerance test (OGTT) reflects β-cell function in populations without diabetes but has not been as well studied in those with diabetes. A monophasic shape has been associated with higher risk of diabetes, while a biphasic pattern has been associated with lower risk. We sought to determine if phenotypic or metabolic characteristics were associated with glucose response curve shape in adults with type 2 diabetes treated with metformin alone.Research design and methods This is a cross-sectional analysis of 3108 metformin-treated adults with type 2 diabetes diagnosed

Aging dogs serve as a valuable preclinical model for Alzheimer's disease (AD) due to their natural age-related development of β-amyloid (Aβ) plaques, human-like metabolism, and large brains that are ideal for studying structural brain aging trajectories from serial neuroimaging. Here we examined the effects of chronic treatment with the calcineurin inhibitor (CNI) tacrolimus or the nuclear factor of activated T cells (NFAT)-inhibiting compound Q134R on age-related canine brain atrophy from a longitudinal study in middle-aged beagles (36 females, 7 males) undergoing behavioral enrichment. Annual MRI was analyzed using modern, automated techniques for region-of-interest-based and voxel-based volumetric assessments. We found that the frontal lobe showed accelerated atrophy with age, while the caudate nucleus remained relatively stable. Remarkably, the hippocampus increased in volume in all dogs. None of these changes were influenced by tacrolimus or Q134R treatment. Our results suggest that behavioral enrichment can prevent atrophy and increase the volume of the hippocampus but does not prevent aging-associated prefrontal cortex atrophy.

The direction of individual B8 solar neutrinos has been reconstructed using the SNO+ liquid scintillator detector. Prompt, directional Cherenkov light was separated from the slower, isotropic scintillation light using time information, and a maximum likelihood method was used to reconstruct the direction of individual scattered electrons. A clear directional signal was observed, correlated with the solar angle. The observation was aided by a period of low primary fluor concentration that resulted in a slower scintillator decay time. This is the first time that event-by-event direction reconstruction in high light-yield liquid scintillator has been demonstrated in a large-scale detector.

Relational savoring (RS) is a brief, strengths-based approach to heightening attentional focus to moments of positive connectedness within relationships. RS can be administered preventatively or within an intervention context when a therapist aspires to foster more optimal relational functioning. Typically administered within a one-on-one therapy setting, RS has demonstrated efficacy in enhancing intra- and interpersonal outcomes. To increase access to mental health services, the developers of RS are committed to engaging in an iterative approach of enhancing the cultural congruence and accessibility of this intervention within various cultural contexts, beginning with Latine groups in Southern California. In this article, we describe relational savoring and its theoretical and empirical support, including the process of culturally adapting the intervention within the context of three major studies, each with a distinct focus on Latine groups, a community that is underserved in mental health care settings. We then provide a vision for future research to improve upon the intervention's compatibility for Latine families and other populations.

The US National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institute of Health (NIH), convened a virtual workshop on August 8-9th, 2023 to explore potential synergies between HIV vaccine approaches that are designed to induce cellular or humoral immune responses. The goal of this workshop was to review data on leading vaccine candidates and to discuss the best strategies for combining these approaches to optimize immunity against HIV. Here, we summarize the findings reviewed at the workshop and discuss the knowledge gaps and priorities for future studies that will help accelerate the development of a preventive HIV vaccine.

Monitoring of colon activity is currently limited to tethered systems like anorectal manometry. These systems have significant drawbacks, but fundamentally limit the observation time of colon activity, reducing the likelihood of detecting specific clinical events. While significant technological advancement has been directed to mobile sensor capsules, this work describes the development and feasibility of a stationary sensor for describing the coordinated activity between neighboring segments of the colon. Unlike wireless capsules, this device remains in position and measures propagating pressure waves and impedances between colon segments to describe activity and motility. This low-power, flexible, wireless sensor-the colon monitor to capture activity (ColoMOCA) was validated in situ and in vivo over seven days of implantation. The ColoMOCA diameter was similar to common endoscopes to allow for minimally invasive diagnostic placement. The ColoMOCA included two pressure sensors, and three impedance-sensing electrodes arranged to describe the differential pressures and motility between adjacent colon segments. To prevent damage after placement in the colon, the ColoMOCA was fabricated with a flexible polyimide circuit board and a silicone rubber housing. The resulting device was highly flexible and suitable for surgical attachment to the colon wall. In vivo testing performed in eleven animals demonstrated suitability of both short term (less than 3 hours) and 7-day implantations. Data collected wirelessly from animal experiments demonstrated the ColoMOCA described colon activity similarly to wired catheters and allowed untethered, conscious monitoring of organ behavior.

BackgroundMethamphetamine use disorder (MethUD) disproportionately affects men who have sex exclusively with men or with men and women (collectively MSM/W), compared to men who have sex with women (MSW). This study is the first MethUD medication trial to compare treatment effect for these groups, hypothesizing that extended-release injectable naltrexone 380mg every 3 weeks plus oral extended-release bupropion 450mg daily would be less effective for MSM/W than MSW.MethodsData come from men (N = 246) in a multi-site, double-blind, randomized, placebo-controlled trial with sequential parallel comparison design. In Stage 1 (6-weeks), participants were randomized to active treatment or placebo. In Stage 2 (6-weeks), Stage 1 placebo non-responders were rerandomized. Treatment response was ≥3 methamphetamine-negative urine samples, out of four obtained at the end of Stages 1 and 2. Treatment effect was the active-versus-placebo between-group difference in the weighted average Stages 1 and 2 responses.ResultsMSM/W (n = 151) were more likely than MSW (n = 95) to be Hispanic, college-educated, and living with HIV. Adjusting for demographics, among MSM/W, response rates were 13.95 % (active treatment) and 2.78 % (placebo) in Stage 1; 23.26 % (active treatment) and 4.26 % (placebo) in Stage 2. Among MSW, response rates were 7.69 % (active treatment) and 5.80 % (placebo) in Stage 1; 3.57 % (active treatment) and 0 % (placebo) in Stage 2. Treatment effect was significantly larger for MSM/W (h = 0.1479) than MSW (h = 0.0227) (p = 0.04).ConclusionsFindings suggest efficacy of extended-release naltrexone plus bupropion for MSM/W, a population heavily burdened by MethUD. While a secondary outcome, this intriguing finding merits testing in prospective trials.

OBJECTIVE: To explore trends in documented sexual abuse/assault (SA) related episodes in California hospitals and emergency departments (ED), including the impact of a change in health care service reporting codification (from ICD-9-CM to ICD-10-CM) that more clearly defined SA in October 2015. DATA SOURCES: Hospital and ED data were drawn from Californias Office of Statewide Health Planning and Development (OSHPD). STUDY DESIGN: Descriptive and trend analyses of SA-related hospital and ED records (including patients demographic information) were conducted to determine whether changes in ICD codification had an impact on documented SA-related episodes. DATA COLLECTION: All SA-related episodes (ICD-9-CM codes 995.83, 995.53; ICD-10-CM codes T74.21-T74.22, T76.21-T76.22) in California hospitals and EDs for the last decade of available data (2008-2017) were analyzed (n = 20,215). PRINCIPAL FINDINGS: An abrupt increase in documented SA episodes in hospitals and EDs began in October 2015, when specific ICD10 codes for suspected cases of SA were created. Documented SA-related episodes doubled in 1 month (164 vs. 385 episodes in September 2015 and October 2015, respectively). More than half (58.2%) of all SA-related episodes documented in Oct 2015 were coded as suspicious. The number of documented SA-related episodes continued increasing to the end of the time series (December 2017). Overall, the annual number of documented SA-related episodes increased by over 700% in only 4 years (900 vs. 6441 in 2013 and 2017, respectively), suggesting high rates of prior under-reporting and the need to introduce the new codes. African Americans were disproportionally impacted; however, the highest increases in age-adjusted rates between the ICD-9-CM and the ICD-10 codification period were found among the White population (2.46 vs. 16.53 per 100,000 inhabitants). CONCLUSIONS: SA episodes in the clinical population have been underestimated for many decades. Identifying SA victims and measuring SA-related health care utilization is a real challenge that needs further investigation.

BackgroundSarbecoviruses are a subgenus of Coronaviridae that mostly infect bats with known potential to infect humans (SARS-CoV and SARS-CoV-2). Populations in Southeast Asia, where these viruses are most likely to emerge, have been undersurveyed to date.MethodsWe surveyed communities engaged in extractive industries and bat guano harvesting from rural areas in Myanmar. Participants were screened for exposure to sarbecoviruses, and their interactions with wildlife were evaluated to determine the factors associated with exposure to sarbecoviruses.ResultsOf 693 people screened between July 2017 and February 2020, 12.1% were seropositive for sarbecoviruses. Individuals were significantly more likely to have been exposed to sarbecoviruses if their main livelihood involved working in extractive industries (logging, hunting, or harvesting of forest products; odds ratio [OR] = 2.71, P = 0.019) or had been hunting/slaughtering bats (OR = 6.09, P = 0.020). Exposure to a range of bat and pangolin sarbecoviruses was identified.ConclusionExposure to diverse sarbecoviruses among high-risk human communities provides epidemiologic and immunologic evidence that zoonotic spillover is occurring. These findings inform risk mitigation efforts needed to decrease disease transmission at the bat-human interface, as well as future surveillance efforts warranted to monitor isolated populations for viruses with pandemic potential.

The neurosteroid allopregnanolone (ALLO) is under investigation as a treatment for benzodiazepine-refractory status epilepticus (SE). Here, we assess the cardiopulmonary safety of intravenous ALLO by itself and after a clinically recommended dose of midazolam (MDZ) in two healthy adult beagles. Each dog received ALLO (1 mg/kg, IV), and after a washout period of 2 weeks, each dog was dosed with MDZ (0.2 mg/kg, IV) followed 10 minutes later by ALLO. Behavioral state, vital signs, arterial blood gases, blood chemistries, and plasma ALLO concentrations were monitored for up to 6 hours after dosing. The dogs appeared sleepy but were fully responsive after both treatments. No depression of mean arterial pressure or respiratory rate was noted. Blood gas measurements failed to show evidence of drug-induced acute respiratory acidosis. Estimated maximum plasma ALLO concentrations were in the range of 1500 to 3000 ng/ml. The results indicate that intravenous ALLO can be used safely to treat benzodiazepine-refractory SE, even when administered shortly after a benzodiazepine.

The US Food and Drug Administration (FDA) applies the Population Health Standard in tobacco product review processes by weighing anticipated health benefits against risks associated with a given commercial tobacco product at the population level. However, systemic racism (ie, discriminatory policies and practices) contributes to an inequitable distribution of tobacco-related health benefits and risks between white and Black/African Americans at the population level. Therefore, Black-centered, antiracist data standards for tobacco product review processes are needed to achieve racial equity and social justice in US tobacco control policy. Regardless of whether FDA implements such data standards, non-industry tobacco scientists should prioritise producing and disseminating Black-centred data relevant to FDA's regulatory authority. We describe how systemic racism contributes to disparities in tobacco-related outcomes and why these disparities are relevant for population-level risk assessments, then discuss four possible options for Black-centred data standards relevant to tobacco product review processes.

The SNO+ Collaboration reports the first evidence of reactor antineutrinos in a Cherenkov detector. The nearest nuclear reactors are located 240 km away in Ontario, Canada. This analysis uses events with energies lower than in any previous analysis with a large water Cherenkov detector. Two analytical methods are used to distinguish reactor antineutrinos from background events in 190 days of data and yield consistent evidence for antineutrinos with a combined significance of 3.5σ.

BACKGROUND: Women are at increased risk for psychosocial stress-related anxiety disorders, yet mechanisms regulating this risk are unknown. Psychosocial stressors activate microglia, and the resulting neuroimmune responses that females exhibit heightened sensitivity to may serve as an etiological factor in their elevated risk. However, studies examining the role of microglia during stress in females are lacking. METHODS: Microglia were manipulated in the stress-sensitive locus coeruleus (LC) of female rats in the context of social stress in two ways. First, intra-LC lipopolysaccharide (LPS; 0 or 3 μg/side, n = 5-6/group), a potent TLR4 agonist and microglial activator, was administered. One hour later, rats were exposed to control or an aggressive social defeat encounter between two males (WS, 15-min). In a separate study, females were treated with intra-LC or intra-central amygdala mannosylated liposomes containing clodronate (m-CLD; 0 or 25 μg/side, n = 13-14/group), a compound toxic to microglia. WS-evoked burying, cardiovascular responses, and sucrose preference were measured. Brain and plasma cytokines were quantified, and cardiovascular telemetry assessed autonomic balance. RESULTS: Intra-LC LPS augmented the WS-induced burying response and increased plasma corticosterone and interleukin-1β (IL-1β). Further, the efficacy and selectivity of microinjected m-CLD was fully characterized. In the context of WS, intra-LC m-CLD attenuated the hypervigilant burying response during WS as well as the accumulation of intra-LC IL-1β. Intra-central amygdala m-CLD had no effect on WS-evoked behavior. CONCLUSIONS: These studies highlight an innovative method for depleting microglia in a brain region specific manner and indicate that microglia in the LC differentially regulate hypervigilant WS-evoked behavioral and autonomic responses.

Parenting young children poses numerous emotion regulation challenges, and prevention programs that promote emotion regulation skills can help with this important task of parenthood. Relational savoring (RS), which entails savoring a positive experience of interpersonal connectedness, is a brief manualized intervention program, 4 weeks in length, grounded in positive psychology and attachment theory. In the current longitudinal, randomized, controlled trial, we examined the impacts of RS compared with an active control (personal savoring [PS], defined as savoring a positive individual experience) in a sample of N = 164 mothers of toddlers (Mage = 20.93 months) on outcomes that were assessed immediately postintervention (positive emotion, closeness to child) and at a 3-month follow-up visit (parenting sensitivity, reflective functioning [RF], savoring uptake, and parenting wellness). Compared with mothers assigned to the PS condition, mothers in the RS condition had greater immediate response to the intervention (greater increases in positive emotions [gratitude, pride], closeness to their child) as well as greater increase in sensitivity to toddlers' cues at the three-month follow-up. Neither RS nor PS increased overall parenting wellness at the three-month follow-up. Latina mothers (but not non-Latina mothers) in the RS condition had higher RF and greater savoring uptake than Latina mothers in the PS condition at follow-up. Findings provide preliminary evidence of the efficacy of RS in modifying therapeutic targets and suggest evidence of the cultural congruence of RS for Latina mothers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Eos is a technology demonstrator, designed to explore the capabilities of hybrid event detection technology, leveraging both Cherenkov and scintillation light simultaneously. With a fiducial mass of four tons, Eos is designed to operate in a high-precision regime, with sufficient size to utilize time-of-flight information for full event reconstruction, flexibility to demonstrate a range of cutting edge technologies, and simplicity of design to facilitate potential future deployment at alternative sites. Results from Eos can inform the design of future neutrino detectors for both fundamental physics and nonproliferation applications. This paper describes the conceptual design and potential applications of the Eos detector.

BackgroundExtremely preterm (EPT) birth has been related to dysregulation of stress responses and behavioral/learning problems at school age. Early adverse experiences can blunt HPA axis reactivity. We hypothesized that an attenuated cortisol awakening response would be associated with developmental and behavioral problems at school age in EPT children.MethodsThis secondary analysis of a sub-cohort of the SUPPORT study included children born between 24 and 27 weeks, evaluated at 6-7 years with a neurodevelopmental battery and cortisol measures. Differences were tested between EPT and a term-born group. Relationships of cortisol awakening response to test scores were analyzed.ResultsCortisol was measured in 110 EPT and 29 term-born 6-7 year olds. Unadjusted WISC-IV and NEPSY-II scores were significantly worse among EPT children only. Conners Parent Rating Scale behavior scores were significantly worse among EPT children. After adjusting for covariates, blunted cortisol awakening responses were found to be associated with poorer scores on memory tests and greater problems with inattention for the EPT group (p