Modification of the Diabetes Prevention Program Lifestyle Intervention in Persons with Spinal Cord Injury: Efficacy for Reducing Major Cardiometabolic Risks, Increased Fitness, and Improved Health-Related Quality of Life.

Individuals with chronic spinal cord injury (SCI) face elevated risks of cardiometabolic diseases, including cardiovascular disease and type 2 diabetes, due to factors like physical inactivity, neurogenic obesity, and disrupted glucose and insulin regulation. We conducted a prospective intervention cohort study involving 20 individuals with SCI (aged 28-60) with neurologic injuries at levels C4-T10 and ASIA scale grades A-D, lasting over a year. Our study assessed the impact of a therapeutic lifestyle intervention (TLI) based on the Diabetes Prevention Program (DPP) and its maintenance phase. The TLI comprised circuit resistance training, a Mediterranean-style calorie-restricted diet, and tailored behavioral support. Key outcomes measured included cardiometabolic risks (plasma analytes and disease biomarkers), anthropometrics (body mass, BMI, tissue composition), global metabolism, fitness (aerobic capacity, peak strength), and health-related quality of life (SF36). Results demonstrated a significant reduction in body mass and BMI by 7.5%, a 7% decrease in total fat mass, and substantial improvements in glucose regulation and insulin sensitivity. Lipid profiles improved, with reduced total cholesterol, triglycerides, and LDL-C, and increased HDL-C. Resting energy expenditure and fat oxidation increased by 27.4% and 58.5%, respectively. Aerobic capacity and dynamic strength also improved significantly. The Physical and Mental Composite Scores of the SF36 improved by 22.8% and 30.5%, respectively. Following the maintenance phase, several positive outcomes persisted, indicating a reduction in risk for cardiovascular disease and comorbid disorders. Our findings support the effectiveness of TLI in reducing cardiometabolic risks, enhancing fitness, and improving health-related quality of life in individuals with chronic SCI. Trial Registration: ClinicalTrials.gov, ID: NCT02853149 Registered August 2, 2016.

The associations of spirituality and Hispanic ethnicity with neuroendocrine biomarkers among patients with colorectal cancer.

OBJECTIVE: Dealing with cancer evokes not only physical and emotional distress, but may also promote resilience through spirituality. Patients with cancer are vulnerable to neuroendocrine dysregulation. This longitudinal observational study examined the degree to which spirituality was associated with neuroendocrine biomarkers and the moderating role of Hispanic ethnicity. METHODS: Participants were adults who were recently diagnosed with colorectal cancer (n = 81, 55 years old, 66% male, 63% Hispanic, 72% advanced cancer, 7 months post-diagnosis). The domains of spirituality (faith, meaning, and peace) and ethnicity (Hispanic vs. non-Hispanic) were self-reported. Cortisol and alpha amylase (sAA) were assayed from saliva samples collected at waking and bedtime on seven consecutive days. Mean levels at waking and bedtime, and diurnal slopes over seven days were calculated. Age and cancer stage were covariates. RESULTS: Overall, patients reported moderate to high levels of spirituality. General linear modeling revealed that greater faith was associated with higher levels of sAA at waking and bedtime as well as more blunted diurnal pattern of sAA only among Hispanic patients (p ≤ .045). Greater peace was associated with steeper diurnal pattern of sAA, regardless of ethnicity (B = 0.021, p = .005). Meaning and cortisol were not significantly associated with study variables. CONCLUSIONS: Findings indicate that presence of peace facing a cancer diagnosis associated with neuroendocrine regulation, whereas drawing on one's faith, particularly among Hispanic patients, associated with neuroendocrine dysregulation during the first months after the diagnosis. Further investigations of psychobiobehavioral moderators and mediators for healthy neuroendocrine functioning among patients with cancer are warranted.

Sleep Composition of Patients With Colorectal Cancer and Their Sleep-Partner Caregivers: Physical Health Correlates of Sleep Diary and Actigraphy Measurements.

BACKGROUND: Disturbed sleep is frequently identified in adult patients with cancer and their caregivers, with detrimental impact on physical health. Less known is the extent to which self-reported and actigraph-measured sleep patterns are similar between patients and their sleep-partner caregivers, and how these different modes of sleep measurements are related to physical health. METHODS: Patients diagnosed with colorectal cancer and their sleep-partner caregivers (81 dyads) completed a questionnaire for physical functioning and collected saliva samples for seven consecutive days, from which cortisol slope was quantified. Additionally, participants completed a daily sleep diary and wore actigraph for 14 consecutive days, from which sleep duration, sleep onset latency (SOL), and duration of wake after sleep onset (WASO) were calculated. RESULTS: Participants reported sleep patterns that fell within or close to the optimal range, which were similar between patients and their caregivers. Self-reported and actigraph-measured sleep duration had moderate levels of agreement (ICC = 0.604), whereas SOL and WASO had poor agreement (ICC = 0.269). Among patients, longer self-reported WASO was associated with poorer physical health and flatter cortisol slope (p ≤ 0.013). Among caregivers, longer self-reported SOL was associated with poorer physical functioning, actigraph-measured WASO was associated with steeper cortisol slope, and longer self-reported sleep markers studied than actigraph-measured were associated with poorer physical functioning (p ≤ 0.042). CONCLUSION: Findings suggest that employing multiple assessment modes for sleep and physical health is vital for comprehensive understanding of sleep health. Furthermore, when addressing patients' sleep health, it may be beneficial to include their sleep-partner caregivers who may experience similar disturbed sleep.

Loneliness, Methamphetamine Use, and Cardiovascular Risk Factors Among Sexual Minority Men in the COVID-19 Era.

BACKGROUND: Important gaps exist in our understanding of loneliness and biobehavioral outcomes among sexual minority men (SMM), such as faster HIV disease progression. At the same time, SMM who use methamphetamine are approximately one-third more likely than non-users to develop cardiovascular disease. This study examined associations of loneliness, stimulant use, and cardiovascular risk in SMM with and without HIV. METHOD: Participants were enrolled from August 2020 to February 2022 in a 6-month prospective cohort study. The study leveraged self-report baseline data from 103 SMM, with a subset of 56 SMM that provided a blood sample to measure markers of cardiovascular risk. RESULTS: Loneliness showed negative bivariate associations with total cholesterol and LDL cholesterol in the cardiometabolic subsample (n = 56). SMM with methamphetamine use (t(101) = 2.03, p < .05; d = .42) and those that screened positive for a stimulant use disorder (t(101) = 2.07, p < .05; d = .46) had significantly higher mean loneliness scores. In linear regression analyses, negative associations of loneliness with LDL and total cholesterol were observed only among SMM who used methamphetamine. CONCLUSION: We observed lower cholesterol in SMM reporting loneliness and methamphetamine use. Thus, in addition to the observed associations of loneliness with cholesterol, there are important medical consequences of methamphetamine use including cardiovascular risk, higher HIV acquisition risk and progression, as well as stimulant overdose death. This cross-sectional study underscores the need for clinical research to develop and test interventions targeting loneliness among SMM with stimulant use disorders.

Salsalate Improves Postprandial Glycemic and Some Lipid Responses in Persons With Tetraplegia: A Randomized Clinical Pilot Trial With Crossover Design.

Objectives: To investigate the effects of salsalate on fasting and postprandial (PP) glycemic, lipidemic, and inflammatory responses in persons with tetraplegia. Methods: This study was a randomized, double-blind, cross-over design. It was conducted at a university laboratory. Ten males aged 25 to 50 years with SCI at C5-8 levels for ≥1 year underwent 1 month of placebo and salsalate (4 g/day) treatment. Blood samples were drawn before and 4 hours after breakfast and lunch fast-food meal consumption. Results: Descriptive statistics indicate that fasting and PP glucose values were reduced with salsalate (pre-post mean difference, 4 ± 5 mg/dL and 8 ± 8 mg/dL, respectively) but largely unchanged with placebo (0 ± 6 mg/dL and -0 ± 7 mg/dL, respectively). Insulin responses were generally reciprocal to glucose, however less pronounced. Fasting free fatty acids were significantly reduced with salsalate (191 ± 216 mg/dL, p = .021) but not placebo (-46 ± 116 mg/dL, p = .878). Results for triglycerides were similar (25 ± 34 mg/dL, p =.045, and 7 ± 29 mg/dL, p = .464). Fasting low-density lipoprotein (LDL) levels were higher after salsalate (-10 ± 12 mg/dL, p = .025) but not placebo (2 ± 9 mg/dL, p = .403) treatment. Inflammatory markers were largely unchanged. Conclusion: In this pilot trial, descriptive values indicate that salsalate decreased fasting and PP glucose response to fast-food meal challenge at regular intervals in persons with tetraplegia. Positive effects were also seen for some lipid but not for inflammatory response markers. Given the relatively "healthy" metabolic profiles of the participants, it is possible that salsalate's effects may be greater and more consistent in people with less favorable metabolic milieus.

A framework of transient hypercapnia to achieve an increased cerebral blood flow induced by nasal breathing during aerobic exercise.

During exercise, cerebral blood flow (CBF) is expected to only increase to a maximal volume up to a moderate intensity aerobic effort, suggesting that CBF is expected to decline past 70 % of a maximal aerobic effort. Increasing CBF during exercise permits an increased cerebral metabolic activity that stimulates neuroplasticity and other key processes of cerebral adaptations that ultimately improve cognitive health. Recent work has focused on utilizing gas-induced exposure to intermittent hypoxia during aerobic exercise to maximize the improvements in cognitive function compared to those seen under normoxic conditions. However, it is postulated that exercising by isolating breathing only to the nasal route may provide a similar effect by stimulating a transient hypercapnic condition that is non-gas dependent. Because nasal breathing prevents hyperventilation during exercise, it promotes an increase in the partial arterial pressure of CO2. The rise in systemic CO2 stimulates hypercapnia and permits the upregulation of hypoxia-related genes. In addition, the rise in systemic CO2 stimulates cerebral vasodilation, promoting a greater increase in CBF than seen during normoxic conditions. While more research is warranted, nasal breathing might also promote benefits related to improved sleep, greater immunity, and body fat loss. Altogether, this narrative review presents a theoretical framework by which exercise-induced hypercapnia by utilizing nasal breathing during moderate-intensity aerobic exercise may promote greater health adaptations and cognitive improvements than utilizing oronasal breathing.

Low-Dose Chidamide Treatment Displays Sex-Specific Differences in the 3xTg-AD Mouse.

Epigenetic compounds have become attractive small molecules for targeting the multifaceted aspects of Alzheimer's disease (AD). Although AD disproportionately affects women, most of the current literature investigating epigenetic compounds for the treatment of AD do not report sex-specific results. This is remarkable because there is rising evidence that epigenetic compounds intrinsically affect males and females differently. This manuscript explores the sexual dimorphism observed after chronic, low-dose administration of a clinically relevant histone deacetylase inhibitor, chidamide (Tucidinostat), in the 3xTg-AD mouse model. We found that chidamide treatment significantly improves glucose tolerance and increases expression of glucose transporters in the brain of males. We also report a decrease in total tau in chidamide-treated mice. Differentially expressed genes in chidamide-treated mice were much greater in males than females. Genes involved in the neuroinflammatory pathway and amyloid processing pathway were mostly upregulated in chidamide-treated males while downregulated in chidamide-treated females. This work highlights the need for drug discovery projects to consider sex as a biological variable to facilitate translation.

Reversal of Experimental Autoimmune Diabetes With an sCD39/Anti-CD3 Treatment.

Extracellular (e)ATP, a potent proinflammatory molecule, is released by dying/damaged cells at the site of inflammation and is degraded by the membrane ectonucleotidases CD39 and CD73. In this study, we sought to unveil the role of eATP degradation in autoimmune diabetes. We then assessed the effect of soluble CD39 (sCD39) administration in prevention and reversal studies in NOD mice as well as in mechanistic studies. Our data showed that eATP levels were increased in hyperglycemic NOD mice compared with prediabetic NOD mice. CD39 and CD73 were found expressed by both α- and ß-cells and by different subsets of T cells. Importantly, prediabetic NOD mice displayed increased frequencies of CD3+CD73+CD39+ cells within their pancreata, pancreatic lymph nodes, and spleens. The administration of sCD39 into prediabetic NOD mice reduced their eATP levels, abrogated the proliferation of CD4+- and CD8+-autoreactive T cells, and increased the frequency of regulatory T cells, while delaying the onset of T1D. Notably, concomitant administration of sCD39 and anti-CD3 showed a strong synergism in restoring normoglycemia in newly hyperglycemic NOD mice compared with monotherapy with anti-CD3 or with sCD39. The eATP/CD39 pathway plays an important role in the onset of T1D, and its targeting might represent a potential therapeutic strategy in T1D.

Estrogen-Based Gender-Affirming Hormone Therapy and Subclinical Cardiovascular Disease in Transgender Women with HIV.

Purpose: Transgender women (TW) are disproportionately affected by HIV infection and cardiovascular disease (CVD). This study evaluated whether estrogen-based gender-affirming hormone therapy (GAHT) in TW with HIV (TWH-GAHT) is associated with indices of subclinical CVD. Methods: Of the 40 HIV-seropositive persons enrolled, 20-60 years of age, on antiretroviral treatment with undetectable viral load, assessments were performed on 15 TWH; of these persons, 11 were GAHT treated. These TWH-GAHT were matched with HIV+ cisgender men and women based on age, ethnicity/race, body mass index, and antihypertensive medication use. Sex hormones, and cardiometabolic (waist circumference, blood pressure, insulin resistance, lipid profile, and C-reactive protein), vascular (flow-mediated dilation [FMD] and arterial stiffness), and proinflammatory measures were obtained. Results: TWH-GAHT displayed elevated estradiol and suppressed testosterone levels relative to normative ranges. Analyses indicated the TWH-GAHT displayed lower low-density lipoprotein compared with cisgender groups (p < 0.05). Although no difference was seen on FMD, the central augmentation index of aortic stiffness was higher in cisgender HIV+ women than cisgender HIV+ men (p < 0.05). No other group difference on subclinical CVD markers was observed. For TWH, partial correlations indicated associations of certain sex hormones with selected cardiometabolic outcomes and the inflammatory cytokine, interleukin-8. Conclusion: When well matched to HIV+ cisgender men and women, subclinical CVD pathophysiology did not appear elevated in TWH-GAHT, although tendencies emerged suggesting that some subclinical CVD indices may be higher, but others lower than cisgender groups. Longitudinal studies of TWH are needed to more precisely evaluate the moderating effect of GAHT on cardiometabolic pathophysiology.

Roles of benefit finding in psychological and inflammatory adjustments in persons with colorectal cancer: a prospective analysis on the multidimensionality of benefit finding.

OBJECTIVE: This study examined the unique associations of different dimensions of the resilience factor, benefit finding, on concurrent and prospective psychological and biological adjustment outcomes over the first year after a colorectal cancer diagnosis. METHODS AND MEASURES: Individuals newly diagnosed with colorectal cancer (n = 133, mean age = 56 years old, 59% female, 46% Hispanic) completed questionnaires assessing the multidimensional aspects of benefit finding around 4 months post-diagnosis (T1). Psychological (depressive symptoms and life satisfaction) and biological [C-reactive protein (CRP) and interleukin-10 (IL-10)] adjustments were assessed at T1 and one-year post-diagnosis (T2). RESULTS: Structural equation modeling revealed that at T1, greater reprioritization was concurrently related to higher depressive symptoms (p=.020). Lower acceptance, lower empathy, and greater positive self-view predicted higher life satisfaction at T2 (ps<.010). Additionally, lower empathy and greater family valuation predicted higher CRP at T2 (ps<.004), whereas greater positive self-view predicted higher IL-10 at T2 (p=.039). Greater overall benefit finding was associated with lower IL-10 at T1 (p=.013). CONCLUSION: Various aspects of benefit finding differentially relate to psychological and inflammatory markers during the first year after diagnosis in persons with colorectal cancer. Interventions designed to specifically enhance positive self-view may promote both the psychological and biological health of individuals with cancer.

Health Care Provider Discussions Regarding HIV/Sexually Transmitted Infection Risk Factors and Associations with HIV/Sexually Transmitted Infection Screening Among Men.

Little is known regarding the specific discussions health care providers (HCP) have with their patients and how these discussions may increase rates of HIV/STI screening. The main objective of this study was to examine the content of HCP-patient discussions and associations with HIV/STI screening while adjusting for patient characteristics. Using the 2017-2019 National Survey of Family Growth data, seven survey-weighted multivariable multinomial/binary logistic regression models were analyzed in men ages 15-49 years old (N = 4260). Patients had significantly higher odds of a lifetime HIV test when their HCP asked about number of sexual partners (adjusted odds ratio [aOR] = 2.325; 95% CI 1.379-3.919) and discussed HIV/AIDS (aOR = 4.149; 95% CI 2.877-5.983). Odds of a recent STI screening were higher among patients with HCP that asked about: sexual orientation (aOR = 1.534; 95% CI 1.027-2.291), number of sexual partners (aOR = 2.123; 95% CI 1.314-3.430), use of condoms (aOR = 2.295 95% CI 1.484-3.548), type of sexual intercourse (aOR = 1.900; 95% CI 1.234-2.925), and discussed HIV/AIDS (aOR = 1.549; 95% CI 1.167-2.056). Results may provide insight on how HCPs may potentially promote HIV/AIDS and STI screening among men and which patient groups are more likely to receive a discussion of risks factors from their HCPs.

The nature and characteristics of hypertriglyceridemia in a large cohort with type 2 diabetes.

AIMS: To determine the prevalence of mild, moderate and severe hypertriglyceridemia (HTG) in a large, diverse healthcare system cohort with type 2 diabetes (T2D) and to study associations between triglyceride levels and demographic factors, glycemic control, body weight and to investigate whether triglyceride levels associate with markers of fatty liver and renal disease. METHODS: 19,086 individuals with T2D were studied between 2015 and 2020. We compared groups with normotriglyceridemia (<150 mg/dl [<1.7 mmol/l]), mild (150-199 mg/dl [1.7-2.25 mmol/l]), moderate (200-499 mg/dl [2.26-5.64 mmol/l]) or severe HTG (>499 mg/dl [>5.64 mmol/l]). We also performed univariate and multivariate correlational analyses with triglyceride level as a continuous variable. RESULTS: 39 % had triglyceride levels ≥150 mg/dl (<1.7 mmol/l), 19 % had moderate and 2 % had severe HTG. There was a lower proportion of Blacks in all HTG categories compared to Whites. There was no overall gender difference in prevalence except that severe HTG was more common in men and as HTG severity worsened mean age fell. Triglycerides correlated with HbA1c and associated with BMI, LDL-C, diastolic BP, transaminases and urine albumin/creatinine ratio, independent of HbA1c. CONCLUSION: This study fills gaps in our knowledge of the distribution and clinical associations of HTG in T2D and characterizes the features of the small but important group with severe HTG. We demonstrate the influence of age, sex and race, confirm the moderate effects of glycemic control and obesity on triglyceride level, and provide evidence that triglyceride levels may be a marker for fatty liver and nephropathy independent of glycemic control.

Characterization of Gastrointestinal Hormone Dysfunction and Metabolic Pathophysiology in Experimental Spinal Cord Injury.

Cardiometabolic disease is a leading complication of spinal cord injury (SCI) that contributes to premature all-cause cardiovascular morbidity and early death. Despite widespread reports that cardioendocrine disorders are more prevalent in individuals with SCI than those without disability, a well-defined pathophysiology has not been established. Autonomic dysfunction accompanying disruption of autonomic spinal tracts may contribute to dysregulation of energy metabolism via uncoupling of integrated hunger and satiation signals. In governing human feeding behaviors, these signals are controlled by a network of enteroendocrine cells that line the gastrointestinal (GI) tract. These cells regulate GI peptide release and autonomic systems that maintain direct neuroendocrine communication between the GI tract and appetite circuitry of the hypothalamus and brainstem. Here we investigate gene-expression and physiological changes in GI peptides and hormones, as well as changes in physiological response to feeding, glucose and insulin challenge, and evaluate GI tissue cytoarchitecture after experimental SCI. Adult female mice (C57BL/6) were subjected to a severe SCI (65 kDyne) at T9, and a sham control group received laminectomy only. The SCI results in chronic elevation of fasting plasma glucose levels and an exaggerated glucose response after an oral glucose and insulin tolerance test. Mice with SCI also exhibit significant alteration in gut hormone genes, plasma levels, physiological response to prandial challenge, and cell loss and gross tissue damage in the gut. These findings demonstrate that SCI has widespread effects on the GI system contributing to component cardiometabolic disease risk factors and may inform future therapeutic and rehabilitation strategies in humans.

Advances in human oxytocin measurement: challenges and proposed solutions.

Oxytocin, a neuropeptide known for its role in reproduction and socioemotional processes, may hold promise as a therapeutic agent in treating social impairments in patient populations. However, research has yet to uncover precisely how to manipulate this system for clinical benefit. Moreover, inconsistent use of standardized and validated oxytocin measurement methodologies-including the design and study of hormone secretion and biochemical assays-present unresolved challenges. Human studies measuring peripheral (i.e., in plasma, saliva, or urine) or central (i.e., in cerebrospinal fluid) oxytocin concentrations have involved very diverse methods, including the use of different assay techniques, further compounding this problem. In the present review, we describe the scientific value in measuring human endogenous oxytocin concentrations, common issues in biochemical analysis and study design that researchers face when doing so, and our recommendations for improving studies using valid and reliable methodologies.

Oxytocin reactivity to a lab-based stressor predicts support seeking after stress in daily life: Implications for the Tend-and-Befriend theory.

Social relationships play an important role in mental and physical health, particularly during times of stress. However, little is known about the biological mechanisms underlying the tendency to seek support following stress. The Tend-and-Befriend theory suggests that oxytocin (OT) may enhance the desire for social contact in response to stress. Yet, no studies in humans have provided empirical support for the connection between stress-induced changes in endogenous OT and increased support seeking after stress. In the present study, 94 participants performed a standardized laboratory stressor and then completed two weeks of daily assessments of support seeking after stress. In line with preregistered hypotheses, stress-induced plasma OT reactivity to the laboratory stressor was associated with more frequent support seeking behaviors following stress in daily life (i.e., outside of the laboratory). Additional results suggested that attachment anxiety (but not avoidance) strengthened this association. Our findings implicate the OT system in affiliative behaviors following stress, providing empirical support for the Tend-and-Befriend theory.

Mouse Model of Heart Failure With Preserved Ejection Fraction Driven by Hyperlipidemia and Enhanced Cardiac Low-Density Lipoprotein Receptor Expression.

Background The pathways of diastolic dysfunction and heart failure with preserved ejection fraction driven by lipotoxicity with metabolic syndrome are incompletely understood. Thus, there is an urgent need for animal models that accurately mimic the metabolic and cardiovascular phenotypes of this phenogroup for mechanistic studies. Methods and Results Hyperlipidemia was induced in WT-129 mice by 4 weeks of biweekly poloxamer-407 intraperitoneal injections with or without a single intravenous injection of adeno-associatedvirus 9-cardiac troponin T-low-density lipoprotein receptor (n=31), or single intravenous injection with adeno-associatedvirus 9-cardiac troponin T-low-density lipoprotein receptor alone (n=10). Treatment groups were compared with untreated or placebo controls (n=37). Echocardiography, blood pressure, whole-body plethysmography, ECG telemetry, activity wheel monitoring, and biochemical and histological changes were assessed at 4 to 8 weeks. At 4 weeks, double treatment conferred diastolic dysfunction, preserved ejection fraction, and increased left ventricular wall thickness. Blood pressure and whole-body plethysmography results were normal, but respiration decreased at 8 weeks (P<0.01). ECG and activity wheel monitoring, respectively, indicated heart block and decreased exercise activity (P<0.001). Double treatment promoted elevated myocardial lipids including total cholesterol, fibrosis, increased wet/dry lung (P<0.001) and heart weight/body weight (P<0.05). Xanthelasma, ascites, and cardiac ischemia were evident in double and single (p407) groups. Sudden death occurred between 6 and 12 weeks in double and single (p407) treatment groups. Conclusions We present a novel model of heart failure with preserved ejection fraction driven by dyslipidemia where mice acquire diastolic dysfunction, arrhythmia, cardiac hypertrophy, fibrosis, pulmonary congestion, exercise intolerance, and preserved ejection fraction in the absence of obesity, hypertension, kidney disease, or diabetes. The model can be applied to dissect pathways of metabolic syndrome that drive diastolic dysfunction in this lipotoxicity-mediated heart failure with preserved ejection fraction phenogroup mimic.

Social anxiety is associated with greater peripheral oxytocin reactivity to psychosocial stress.

To date, it has been difficult to establish reliable biomarkers associated with specific forms of psychopathology. Social anxiety, for example, is associated with inconsistent biological responses to psychosocial stress on markers including cortisol and salivary alpha-amylase. Thus, it is critical that studies identify more reliable biomarkers that index patterns associated with social anxiety. Two potential candidates are the neuropeptides oxytocin and vasopressin, which have been implicated in stress responsivity across species. Studies have demonstrated a reliable increase in oxytocin, and a surrogate marker for vasopressin, following engagement in the most widely used lab-based psychosocial stress paradigm: the Trier Social Stress Test (TSST). However, no study has examined whether social anxiety moderates peripheral oxytocin or vasopressin reactivity to psychosocial stress. In 101 young adult participants, dimensionally assessed social anxiety was associated with greater plasma oxytocin, but not vasopressin, reactivity to the TSST. Results were maintained following the inclusion of depression as a covariate. Findings suggest that studying changes in peripheral oxytocin concentrations may be a method of differentiating individuals with higher levels of social anxiety.

Abacavir antiretroviral therapy and indices of subclinical vascular disease in persons with HIV.

OBJECTIVE: Indices of cardiovascular disease (CVD) risk, vascular endothelial dilation, arterial stiffness and endothelial repair were examined in persons with HIV (PWH) on an antiretroviral therapy (ART) that included abacavir (ABC+) in comparison with PWH on ART without abacavir (ABC-), and with HIV seronegative (HIV-) individuals. APPROACH: The 115 participants (63% men), aged 30-50 years, did not have CVD, metabolic, endocrine, or chronic renal conditions. PWH were on stable ART for six-months or more. Vascular assessments included flow-mediated dilation (FMD), aortic, radial and femoral arterial stiffness (cAIx, crPWV, cfPWV), and thigh and calf arterial compliance (Vmax50). Endothelial repair was indexed by endothelial progenitor cell colony forming units (EPC-CFU). Traditional CVD risk measures included blood pressure, central adiposity, lipids, insulin resistance (HOMA-IR), CRP and ASCVD score. Analyses controlled for demographics (age, sex, education), medications (antihypertensive, statin/fibrate, antipsychotic), and substance abuse (ASSIST). RESULTS: No group differences were observed in central adiposity, HOMA-IR, CRP, or ASCVD risk score. However, the ABC- group displayed greater dyslipidemia. The ABC+ group displayed no difference on FMD, cAIx, cfPWV or calf Vmax50 compared with other groups. When CD4 count and viral load were controlled, no additional differences between the ABC+ and ABC- groups emerged. Analyses of crPWV and thigh Vmax50 suggested supported by a trend toward lower EPC-CFU in the HIV+ groups than the HIV- group. CONCLUSIONS: Findings indicate that ABC treatment of 30-50 year-old PWH on stable ART is not likely to contribute in a robust way to higher CVD risk.

Compounds targeting OSBPL7 increase ABCA1-dependent cholesterol efflux preserving kidney function in two models of kidney disease.

Impaired cellular cholesterol efflux is a key factor in the progression of renal, cardiovascular, and autoimmune diseases. Here we describe a class of 5-arylnicotinamide compounds, identified through phenotypic drug discovery, that upregulate ABCA1-dependent cholesterol efflux by targeting Oxysterol Binding Protein Like 7 (OSBPL7). OSBPL7 was identified as the molecular target of these compounds through a chemical biology approach, employing a photoactivatable 5-arylnicotinamide derivative in a cellular cross-linking/immunoprecipitation assay. Further evaluation of two compounds (Cpd A and Cpd G) showed that they induced ABCA1 and cholesterol efflux from podocytes in vitro and normalized proteinuria and prevented renal function decline in mouse models of proteinuric kidney disease: Adriamycin-induced nephropathy and Alport Syndrome. In conclusion, we show that small molecule drugs targeting OSBPL7 reveal an alternative mechanism to upregulate ABCA1, and may represent a promising new therapeutic strategy for the treatment of renal diseases and other disorders of cellular cholesterol homeostasis.

Evaluating and re-evaluating intra- and inter-species social transmission of food preferences in domestic dogs.

Social-transmission of food preference is a robust behavioral phenomenon in rodents and other species, but less work has evaluated this phenomenon in broader taxa and to what degree social-transmission can occur between species. Here we show that over the span of three experiments that consisted of a human-dog, a dog-dog, and a replication study of a dog-dog demonstrator-observer test, we did not observe successful social transmission of food preferences across all three experiments. For our first experiment, we investigated whether pet dogs acquire food preference from their owners using a two-bowl preference test. The results suggested that our dogs did not acquire a preference for the flavor consumed by their owners. This then led us to investigate whether this failure was the result of an inter-species failure, so we replicated the experiment using two familiar dogs as the demonstrator and observer. The results for Experiment Two also suggested that our participant dogs do not acquire food preference from a canine demonstrator. A third experiment attempted a direct replication of the Lupfer-Johnson and Ross (2007) that found dog-dog transmission of food preferences. Our results again indicated that our participant dogs did not acquire food preference from demonstrators. Over the span of three experiments, our results did not show clear canine food preferences for the food consumed by a demonstrator (human or dog).