Parental influences on tobacco use and likelihood of future use among sexual minority young adult men and women in the United States.

BACKGROUND AND OBJECTIVES: Limited research has examined mechanisms, including parenting behaviors, contributing to tobacco use disparities among sexual minority young adults (SMYAs). METHODS: Participants were 644 young adult (ages 18-29; 36.5% racial/ethnic minority) women (N = 416; 44.7% bisexual, 7.2% lesbian, 48.1% heterosexual) and men (N = 288; 11.0% bisexual, 13.2% gay, 75.9% heterosexual). Bivariate analyses examined differences among sex-by-sexual identity subgroups in perceived parenting (psychological control, behavioral control, knowledge, autonomy support, warmth, communication), past 30-day cigarette, e-cigarette, and cigar use, and likelihood of future use. Multivariable regression examined associations of sexual identity subgroup and parenting behaviors to tobacco use outcomes among women and men. RESULTS: Bisexual (vs. heterosexual) women reported greater parental psychological control and less autonomy support, warmth, and communication. Bisexual (vs. heterosexual) women had greater odds of past 30-day cigarette and cigar use and greater likelihood of future cigarette and e-cigarette use, and parenting behaviors were associated with past 30-day cigarette (knowledge, warmth), e-cigarette (psychological control, autonomy support, warmth), and cigar use (behavioral control, warmth) and likelihood of future cigarette (psychological control, warmth) and e-cigarette use (autonomy support, communication). Gay (vs. heterosexual) men reported greater parental behavioral control, less knowledge, autonomy support, warmth, and communication. Sexual identity and parenting behaviors were largely not associated with tobacco use among men. DISCUSSION AND CONCLUSIONS: Findings highlight the role of parenting behaviors as potential mechanisms contributing to tobacco use disparities among SMYA women. SCIENTIFIC SIGNIFICANCE: Tobacco prevention/cessation programs should be tailored toward specific SMYA subgroups, combinations of parenting behaviors, and patterns of tobacco use.

Improving African American women's engagement in clinical research: A systematic review of barriers to participation in clinical trials.

BACKGROUND: Despite multiple efforts, African American women continue to be inadequately represented in clinical research while being overrepresented in disease, producing research results with limited generalizability to this specific population. Our understanding of the barriers to participation in clinical trials among racial/ethnic minority patients in general has evolved, but few studies have examined the reasoning behind African American women's decision to not participate in clinical trials. OBJECTIVE: The primary aim was to conduct a systematic review to identify the barriers reported by African American women regarding participation in clinical research to help explain the low levels of enrollment. We also suggest strategies that can be implemented by the research community to lessen the effect of those barriers. METHODS: Searches were conducted through MEDLINE, SCOPUS, Web of Science, and Google Scholar. Following a set of eligibility criteria, a total of 18 peer-reviewed journal articles were selected and analyzed to render categories and themes. RESULTS: Across studies aimed at examining their unique perspective, the reasons mentioned by African American women for not participating in clinical research were grouped in three broad categories: 1) weak relationship with the medical and research community, 2) high cost to participation, and 3) personal and "out-of-reach" circumstances. Reasons pertaining to participants' relationship with physicians/researchers were most salient. DISCUSSION: A targeted and comprehensive understanding of the barriers impacting African American women's decision to participate in clinical research informs population-specific recruitment and research strategies for future studies. Additional studies assessing barriers to clinical trial research participation that intentionally report on disaggregated data by not only race/ethnicity but also sex are essential to improving the risk/benefit profile for a wide range of prevention and treatment efforts. This improved understanding of the differences between subgroups within minority populations has implications for bolstering culturally sensitive messages to enhance the engagement of minority communities in clinical trial research.

Cross-Sectional Retrospective Assessments versus Longitudinal Prospective Assessments of Substance Use Change among Young Adults during COVID-19: Magnitude and Correlates of Discordant Findings.

Significance: Findings regarding changes in substance use since COVID-19 have been mixed, potentially due to differences in methods used to assess change. Thus, we compared changes in substance use per retrospective self-report at one time-point (March-May 2020) versus prospective, longitudinal self-report across 2 time-points (Sept-Dec 2019; March-May 2020), and identified predictors of discordance. Methods: We analyzed data from a longitudinal study of 1,082 young adults from 6 metropolitan areas. Across cigarettes, e-cigarettes, marijuana, and alcohol, participants were categorized as Increasers (increased based on both methods), Decreasers/Stable (decreased/same per both methods), Over-reporters (decreased/same per longitudinal data/increased via retrospective report), or Under-reporters (increased per longitudinal data/decreased/same via retrospective report). We identified predictors (e.g., sociodemographics, pre-pandemic substance use levels) of Under-reporting. Results: In this sample (Mage=24.77; 45.7% male, 32.1% sexual minority, 4.0% Black, 12.4% Asian, 12.6% Hispanic), longitudinal data indicated that the proportions of cigarette, e-cigarette, marijuana, and alcohol users who increased their use were 43.3%, 41.7%, 52.6%, and 55.6%, respectively. Examining concordance/discordance groups, Under-reporters accounted for between 17.7% (alcohol) and 26.8% (e-cigarette) of users; over-reporters comprised among the smallest proportions of each group (17.4% for alcohol to 22.2% for marijuana). Multivariable regression indicated that predictors of Under-reporting were less pre-pandemic use across substances; being older for e-cigarettes; and being older, male, and Asian for alcohol. Conclusions: Findings highlight methodological variability as a potential reason for mixed findings regarding pandemic-related substance use change and underscore the need for rigorously designed research to accurately assess the population impact of COVID-19 and other historical events.

Effectiveness and Cost-Benefit of an Elementary School-Based Telehealth Program.

Utilization of telehealth in school-based health centers (SBHCs) is increasing rapidly during the COVID-19 pandemic. This study used a quasi-experimental design to evaluate the effect on school absences and cost-benefit of telehealth-exclusive SBHCs at 6 elementary schools from 2015-2017. The effect of telehealth on absences was estimated compared to students without telehealth using negative binomial regression controlling for absences and health suite visits in 2014 and sociodemographic characteristics. The sample included 7,164 observations from 4,203 students. Telehealth was associated with a 7.7% (p = 0.025; 95% CI: 1.0%, 14%) reduction in absences (0.60 days/year). The program cost $189,000/yr and an estimated total benefit of $384,995 (95% CI: $60,416; $687,479) and an annual net benefit of $195,873 (95% CI: -$128,706; $498,357). While this cost-benefit analysis is limited by a lack of data on total healthcare utilization, the use of telehealth-exclusive SBHCs can improve student health and attendance while delivering cost savings to society.

Identifying Essential Components of School-Linked Mental Health Services for Refugee and Immigrant Children: A Comparative Case Study.

BACKGROUND: Foreign-born children rarely use traditional school mental health services. Comprehensive programs that combine mental health services with academic, economic, and socioemotional supports reach more foreign-born children and improve wellbeing. However, little practical guidance exists regarding how to best combine these diverse services. METHODS: To identify essential service components and their organization, we interviewed 92 parents, school staff, mental health providers, and community agency staff from 5 school-linked mental health programs designed specifically to serve immigrant and refugee youth. RESULTS: Foreign-born parents did not distinguish between academic, behavioral, and emotional help for their children; these western categorizations of functioning were not meaningful to them. Consequently, programs needed to combine 4 components, organized in a pyramid: family engagement, assistance with basic needs, assistance with adaptation to a new culture, and emotional and behavioral supports. Family engagement was the foundation upon which all other services depended. Assistance with economic and cultural stressors directly promoted emotional wellbeing and helped parents trust clinical mental health interventions. CONCLUSIONS: Specific strategies to implement the 4 essential components include home visits by program staff, a one-stop parent center located in the school to help with basic needs, working with cultural brokers, and informed consent procedures that clearly explain recommended care without requiring immigrant and refugee parents to internalize western conceptualizations of psychopathology. Future evaluations should assess the cost and effectiveness of these strategies. These data are essential to advocate payment for these nonclinical services by traditional funding mechanisms.

Systematic Review of School Telehealth Evaluations.

School telehealth is an alternative delivery model to increase student health-care access with minimal evaluation to aid decision makers in the adoption or expansion of programs. This systematic review assesses school-based telehealth programs using a dissemination and implementation (D&I) framework to inform practitioners and decision makers of the value of school telehealth. We assessed findings from 20 studies on telehealth published between January 2006 and June 2018 and summarized program evaluation on a range of D&I constructs. The sample population included children in school- or center-based early childhood education under age 22 and included parents, providers, and school personnel across urban and suburban locations. There is some evidence that school telehealth can reduce emergency department visits and improve health status for children with chronic and acute illnesses. Future research should report on barriers and facilitators of implementation of programs, including costs related to application of telehealth services and utilization rates.

Integration of Unaccompanied Migrant Youth in the United States: A Call for Research.

Between October 2013 and July 2016, over 156,000 children traveling without their guardians were apprehended at the US-Mexico border and transferred to the care of the Office of Refugee Resettlement (ORR). During that same period, ORR placed over 123,000 unaccompanied migrant youth-predominantly from Central America-with a parent or other adult sponsor residing in the US. Following placement, local communities are tasked with integrating migrant youth, many of whom experience pre- and in-transit migration traumas, family separation, limited/interrupted schooling, and unauthorised legal status, placing them at heightened risk for psychological distress, academic disengagement, maltreatment, and human trafficking. Nonetheless, fewer than 10% of young people receive formal post-release services. This paper addresses the paucity of research on the experiences of the 90% of children and youth without access to post-release services. To bridge this gap, this article: (a) describes the post-release experiences of unaccompanied youth, focusing on legal, family, health, and educational contexts; (b) identifies methodological and ethical challenges and solutions in conducting research with this population of young people and their families; and (c) proposes research to identify structural challenges to the provision of services and to inform best practices in support of unaccompanied youth.

Enhancing Educator Engagement in School Mental Health Care Through Digital Simulation Professional Development.

BACKGROUND: Despite the critical role of educators as gatekeepers for school mental health services, they receive limited training to support student mental health. We report findings from a trial of an online mental health role-play simulation for elementary school teachers on changes in attitudes and self-reported helping behaviors for students experiencing psychological distress. METHODS: We randomly assigned 18,896 elementary school teachers to wait-list control or intervention conditions in which they received the 45- to 90-minute online role-play simulation. We administered a version of the validated Gatekeeper Behavior Scale at baseline and postintervention, which measures attitudinal dimensions shown to predict teacher helping behavior change. Self-reported helping behaviors were collected at baseline and 3-month follow-up. Outcomes were compared between the intervention follow-up and control group baseline measures. RESULTS: The intervention group posttraining scores were significantly higher (p < .001) than the control group for all the preparedness, likelihood, and self-efficacy Gatekeeper Behavior subscales. All 5 helping behaviors were significantly higher among the intervention group at follow-up compared to the control group at baseline. CONCLUSIONS: We found that a brief online role-play simulation was an effective strategy for improving teacher attitudes and behaviors needed to perform a positive mental health gatekeeper role in schools.

An integrin antagonist (MK-0429) decreases proteinuria and renal fibrosis in the ZSF1 rat diabetic nephropathy model.

Multiple integrins have been implicated in modulating renal function. Modulation of integrin function can lead to pathophysiological processes associated with diabetic nephropathy such as alterations in the glomerular filtration barrier and kidney fibrosis. The complexity of these pathophysiological changes implies that multiple integrin subtypes might need to be targeted to ameliorate the progression of renal disease. To address this hypothesis, we investigated the effects of MK-0429, a compound that was originally developed as an αvß3 inhibitor for the treatment of osteoporosis, on renal function and fibrosis. We demonstrated that MK-0429 is an equipotent pan-inhibitor of multiple av integrins. MK-0429 dose-dependently inhibited podocyte motility and also suppressed TGF-ß-induced fibrosis marker gene expression in kidney fibroblasts. Moreover, in the obese ZSF1 rat model of diabetic nephropathy, chronic treatment with MK-0429 resulted in significant reduction in proteinuria, kidney fibrosis, and collagen accumulation. In summary, our results suggest that inhibition of multiple integrin subtypes might lead to meaningful impact on proteinuria and renal fibrosis in diabetic nephropathy.

Chronic Inhibition of Renal Outer Medullary Potassium Channel Not Only Prevented but Also Reversed Development of Hypertension and End-Organ Damage in Dahl Salt-Sensitive Rats.

The renal outer medullary potassium (ROMK) channel mediates potassium recycling and facilitates sodium reabsorption through the Na+/K+/2Cl- cotransporter in the loop of Henle and potassium secretion at the cortical collecting duct. Evidence from the phenotype of humans and rodents with functional ROMK deficiency supports the contention that selective ROMK inhibitors (ROMKi) will represent a novel diuretic with potential of therapeutic benefit for hypertension. ROMKi have recently been synthesized by Merck & Co, Inc. The present studies were designed to examine the effects of ROMKi B on systemic hemodynamics, renal function and structure, and vascular function in Dahl salt-sensitive rats. Four experimental groups-control, high-salt diet alone; ROMKi B 3 mg·kg-1·d-1; ROMKi B 10 mg·kg-1·d-1; and hydrochlorothiazide 25 mg·kg-1·d-1-were included in prophylactic (from week 1 to week 9 on high-salt diet) and therapeutic studies (from week 5 to week 9 on high-salt diet), respectively. ROMKi B produced sustained blood pressure reduction and improved renal and vascular function and histological alterations induced by a high-salt diet. ROMKi B was superior to hydrochlorothiazide at reducing blood pressure. Furthermore, ROMKi B provided beneficial effects on both the plasma lipid profile and bone mineral density. Chronic ROMK inhibition not only prevented but also reversed the development of hypertension and end-organ damage in Dahl salt-sensitive rats. Our findings suggest a potential utility of ROMKi B as a novel antihypertensive agent, particularly for the treatment of the salt-sensitive hypertension patient population.

The Renal Outer Medullary Potassium Channel Inhibitor, MK-7145, Lowers Blood Pressure, and Manifests Features of Bartter's Syndrome Type II Phenotype.

The renal outer medullary potassium (ROMK) channel, located at the apical surface of epithelial cells in the thick ascending loop of Henle and cortical collecting duct, contributes to salt reabsorption and potassium secretion, and represents a target for the development of new mechanism of action diuretics. This idea is supported by the phenotype of antenatal Bartter's syndrome type II associated with loss-of-function mutations in the human ROMK channel, as well as, by cardiovascular studies of heterozygous carriers of channel mutations associated with type II Bartter's syndrome. Although the pharmacology of ROMK channels is still being developed, channel inhibitors have been identified and shown to cause natriuresis and diuresis, in the absence of any significant kaliuresis, on acute oral dosing to rats or dogs. Improvements in potency and selectivity have led to the discovery of MK-7145 [5,5'-((1R,1'R)-piperazine-1,4-diylbis(1-hydroxyethane-2,1-diyl))bis(4-methylisobenzofuran-1(3H)-one)], a potential clinical development candidate. In spontaneously hypertensive rats, oral dosing of MK-7145 causes dose-dependent lowering of blood pressure that is maintained during the entire treatment period, and that displays additive/synergistic effects when administered in combination with hydrochlorothiazide or candesartan, respectively. Acute or chronic oral administration of MK-7145 to normotensive dogs led to dose-dependent diuresis and natriuresis, without any significant urinary potassium losses or changes in plasma electrolyte levels. Elevations in bicarbonate and aldosterone were found after 6 days of dosing. These data indicate that pharmacological inhibition of ROMK has potential as a new mechanism for the treatment of hypertension and/or congestive heart failure. In addition, Bartter's syndrome type II features are manifested on exposure to ROMK inhibitors.

Acute hemodynamic and renal effects of glucagon-like peptide 1 analog and dipeptidyl peptidase-4 inhibitor in rats.

BACKGROUND: Glucagon-like peptide 1 (GLP-1) analogs and dipeptidyl peptidase-4 (DPP4) inhibitors are a newer class of antidiabetics named as incretin-based therapy. In addition to the homeostatic control of glucose, the incretin-based therapy has shown beneficial effects on the cardiovascular system in preclinical and clinical studies. However, there is limited information on their renal effects. To this end, we assessed the acute hemodynamic and renal effects of a GLP-1 analog, Liraglutide, and a DPP4 inhibitor, MK-0626. METHODS: Experiments were performed in anesthetized male Sprague-Dawley rats. Three ascending doses of Liraglutide (3, 9, and 27 nmol/kg/h) or MK-0626 (1 mg/kg) with or without GLP-1 peptide (2.4, 4.8, or 9.6 pmol/kg/min) were administered. Blood pressure (BP) and heart rate (HR) were recorded from an indwelling catheter. Glomerular filtration rate (GFR) and renal blood flow (RBF) were assessed by inulin and para-aminohippurate clearance, respectively. Renal excretory function was assessed in metabolic studies. RESULTS: Both Liraglutide and MK-0626 plus GLP-1 evoked significant diuretic and natriuretic responses and increased GFR. MK-0626 alone increased RBF. Liraglutide at 27 nmol//kg/h and MK-0626 plus GLP-1 at 9.6 pmol/kg/min also increased HR, whereas BP was not affected. CONCLUSION: The results of the present study demonstrated that a GLP-1 analog and a DPP4 inhibitor may have beneficial effects on renal sodium and water handling. Additionally, the DPP4 inhibitor, MK-0626, favorably affects renal hemodynamics by increasing RBF. However, exceedingly high levels of GLP-1 receptor agonists may adversely affect the cardiovascular system in acute setting, as demonstrated by an acute increase in HR.

Static and turnover kinetic measurement of protein biomarkers involved in triglyceride metabolism including apoB48 and apoA5 by LC/MS/MS.

LC/MS quantification of multiple plasma proteins that differ by several orders of magnitude in concentration from a single sample is challenging. We present a strategy that allows the simultaneous determination of the concentration and turnover kinetics of higher and lower abundant proteins from a single digestion mixture. Our attention was directed at a cluster of proteins that interact to affect the absorption and interorgan lipid trafficking. We demonstrate that apos involved in TG metabolism such as apoC2, C3, E, and A4 (micromolar concentration), and apoB48 and apoA5 (single-digit nanomolar concentration) can be quantified from a single digestion mixture. A high degree of correlation between LC/MS and immunobased measurements for apoC2, C3, E, and B48 was observed. Moreover, apoA5 fractional synthesis rate was measured in humans for the first time. Finally, the method can be directly applied to studies involving nonhuman primates because peptide sequences used in the method are conserved between humans and nonhuman primates.

Genetic deletion and pharmacological inhibition of phosphodiesterase 10A protects mice from diet-induced obesity and insulin resistance.

Phosphodiesterase 10A (PDE10A) is a novel therapeutic target for the treatment of schizophrenia. Here we report a novel role of PDE10A in the regulation of caloric intake and energy homeostasis. PDE10A-deficient mice are resistant to diet-induced obesity (DIO) and associated metabolic disturbances. Inhibition of weight gain is due to hypophagia after mice are fed a highly palatable diet rich in fats and sugar but not a standard diet. PDE10A deficiency produces a decrease in caloric intake without affecting meal frequency, daytime versus nighttime feeding behavior, or locomotor activity. We tested THPP-6, a small molecule PDE10A inhibitor, in DIO mice. THPP-6 treatment resulted in decreased food intake, body weight loss, and reduced adiposity at doses that produced antipsychotic efficacy in behavioral models. We show that PDE10A inhibition increased whole-body energy expenditure in DIO mice fed a Western-style diet, achieving weight loss and reducing adiposity beyond the extent seen with food restriction alone. Therefore, chronic THPP-6 treatment conferred improved insulin sensitivity and reversed hyperinsulinemia. These data demonstrate that PDE10A inhibition represents a novel antipsychotic target that may have additional metabolic benefits over current medications for schizophrenia by suppressing food intake, alleviating weight gain, and reducing the risk for the development of diabetes.

Heterozygous disruption of renal outer medullary potassium channel in rats is associated with reduced blood pressure.

The renal outer medullary potassium channel (ROMK, KCNJ1) mediates potassium recycling and facilitates sodium reabsorption through the Na(+)/K(+)/2Cl(-) cotransporter in the loop of Henle and potassium secretion at the cortical collecting duct. Human genetic studies indicate that ROMK homozygous loss-of-function mutations cause type II Bartter syndrome, featuring polyuria, renal salt wasting, and hypotension; humans heterozygous for ROMK mutations identified in the Framingham Heart Study have reduced blood pressure. ROMK null mice recapitulate many of the features of type II Bartter syndrome. We have generated an ROMK knockout rat model in Dahl salt-sensitive background by using zinc finger nuclease technology and investigated the effects of knocking out ROMK on systemic and renal hemodynamics and kidney histology in the Dahl salt-sensitive rats. The ROMK(-/-) pups recapitulated features identified in the ROMK null mice. The ROMK(+/-) rats, when challenged with a 4% salt diet, exhibited a reduced blood pressure compared with their ROMK(+/+) littermates. More importantly, when challenged with an 8% salt diet, the Dahl salt-sensitive rats with 50% less ROMK expression showed increased protection from salt-induced blood pressure elevation and signs of protection from renal injury. Our findings in ROMK knockout Dahl salt-sensitive rats, together with the previous reports in humans and mice, underscore a critical role of ROMK in blood pressure regulation.

Nicotinic acid and DP1 blockade: studies in mouse models of atherosclerosis.

The use of nicotinic acid to treat dyslipidemia is limited by induction of a "flushing" response, mediated in part by the interaction of prostaglandin D(2) (PGD(2)) with its G-protein coupled receptor, DP1 (Ptgdr). The impact of DP1 blockade (genetic or pharmacologic) was assessed in experimental murine models of atherosclerosis. In Ptgdr(-/-)ApoE(-/-) mice versus ApoE(-/-) mice, both fed a high-fat diet, aortic cholesterol content was modestly higher (1.3- to 1.5-fold, P < 0.05) in Ptgdr(-/-)ApoE(-/-) mice at 16 and 24 weeks of age, but not at 32 weeks. In multiple ApoE(-/-) mouse studies, a DP1-specific antagonist, L-655, generally had a neutral to beneficial effect on aortic lipids in the presence or absence of nicotinic acid treatment. In a separate study, a modest increase in some atherosclerotic measures was observed with L-655 treatment in Ldlr(-/-) mice fed a high-fat diet for 8 weeks; however, this effect was not sustained for 16 or 24 weeks. In the same study, treatment with nicotinic acid alone generally decreased plasma and/or aortic lipids, and addition of L-655 did not negate those beneficial effects. These studies demonstrate that inhibition of DP1, with or without nicotinic acid treatment, does not lead to consistent or sustained effects on plaque burden in mouse atherosclerotic models.

Chronic antagonism of the mineralocorticoid receptor ameliorates hypertension and end organ damage in a rodent model of salt-sensitive hypertension.

We investigated the effects of chronic mineralocorticoid receptor blockade with eplerenone on the development and progression of hypertension and end organ damage in Dahl salt-sensitive rats. Eplerenone significantly attenuated the progressive rise in systolic blood pressure (SBP) (204 ± 3 vs. 179±3 mmHg, p < 0.05), reduced proteinuria (605.5 ± 29.6 vs. 479.7 ± 26.1 mg/24h, p < 0.05), improved injury scores of glomeruli, tubules, renal interstitium, and vasculature in Dahl salt-sensitive rats fed a high-salt diet. These results demonstrate that mineralocorticoid receptor antagonism provides target organ protection and attenuates the development of elevated blood pressure (BP) in a model of salt-sensitive hypertension.