Prevalence of Testing for Human Immunodeficiency Virus, Hepatitis B Virus, and Hepatitis C Virus Among Medicaid Enrollees Treated With Medications for Opioid Use Disorder in 11 States, 2016-2019.

BACKGROUND: Limited information exists about testing for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) among Medicaid enrollees after starting medication for opioid use disorder (MOUD), despite guidelines recommending such testing. Our objectives were to estimate testing prevalence and trends for HIV, HBV, and HCV among Medicaid enrollees initiating MOUD and examine enrollee characteristics associated with testing. METHODS: We conducted a serial cross-sectional study of 505 440 initiations of MOUD from 2016 to 2019 among 361 537 Medicaid enrollees in 11 states. Measures of MOUD initiation; HIV, HBV, and HCV testing; comorbidities; and demographics were based on enrollment and claims data. Each state used Poisson regression to estimate associations between enrollee characteristics and testing prevalence within 90 days of MOUD initiation. We pooled state-level estimates to generate global estimates using random effects meta-analyses. RESULTS: From 2016 to 2019, testing increased from 20% to 25% for HIV, from 22% to 25% for HBV, from 24% to 27% for HCV, and from 15% to 19% for all 3 conditions. Adjusted rates of testing for all 3 conditions were lower among enrollees who were male (vs nonpregnant females), living in a rural area (vs urban area), and initiating methadone or naltrexone (vs buprenorphine). Associations between enrollee characteristics and testing varied across states. CONCLUSIONS: Among Medicaid enrollees in 11 US states who initiated medications for opioid use disorder, testing for human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and all 3 conditions increased between 2016 and 2019 but the majority were not tested.

Advanced imaging use and payment trends in a large pediatric accountable care organization.

BACKGROUND: Pediatric imaging use and payment trends in accountable care organizations (ACOs) are seldom studied but are important for health policy decisions and resource allocation. OBJECTIVE: To evaluate patterns of advanced imaging use and associated payments over a 7-year period at a large ACO in the USA serving a Medicaid population. MATERIALS AND METHODS: We reviewed paid claims data from 2011 through 2017 from an ACO, analyzing the MRI, CT and US use trends and payments from emergency department (ED) and outpatient encounters. We defined "utilization rate" as the number of advanced imaging procedures per 100 enrolled children per calendar year. Average yearly utilization and payments trends were analyzed using Pearson correlation. RESULTS: Across 7 years, 186,552 advanced imaging procedures were performed. The average overall utilization rate was 6.99 (95% confidence interval [CI]: 6.9-7.1). In the ED this was 2.7 (95% CI: 2.6-2.8) and in outpatients 4.3 (95% CI: 4.2-4.3). The overall utilization rate grew by 0.7% yearly (P=0.077), with US growing the most at 4.0% annually (P=0.0005), especially in the ED in the US, where it grew 10.8% annually (P=0.000019). The overall payments were stable from 2011 to 2017, with outpatient MRI seeing the largest payment decrease at 1.8% (P=0.24) and ED US showing the most growth at 3.3% (P=0.00016). Head CT and abdominal US were the two most common procedures. CONCLUSION: Over the study period, advanced imaging utilization at this large pediatric ACO serving the Medicaid population increased, especially with US use in the ED. Overall payments related to advanced imaging remained stable over this period.

Promoting Pediatric Preventive Visits Through Quality Improvement Initiatives in the Primary Care Setting.

OBJECTIVE: To evaluate whether quality improvement (QI) capacity-building in affiliated primary care practices could increase well care visit uptake. STUDY DESIGN: Partners For Kids (PFK) is an accountable care organization caring for pediatric Medicaid beneficiaries in Ohio. PFK QI specialists recruited practices to develop QI projects around increasing well care visit rates (proportion of eligible children with well care visits during calendar year) for children aged 3-6 years and adolescents. The QI specialists supported practice teams in implementing interventions and collecting data through monthly or bimonthly practice visits. RESULTS: Ten practices, serving more than 26 000 children, participated in QI projects for a median of 8.5 months (IQR 5.3-17.6). Well care visit rates in the QI-engaged practices significantly improved from 2016 to 2018 (P < .001 for both age groups). Over time, well care visit rates for 3- to 6-year-old children increased by 11.8% (95% CI 5.4%-18.2%) in QI-engaged practices, compared with 4.1% (95% CI 0.1%-7.4%) in non-engaged practices (P = .233). For adolescents, well care visit rates increased 14.3% (95% CI -2.6% to 31.2%) compared with 5.4% (95% CI 1.8%-9.0%) in QI-engaged vs non-engaged practices over the same period (P = .215). Although not statistically significant, QI-engaged practices had greater magnitudes of rate increases for both age groups. CONCLUSIONS: Through practice facilitation, PFK helped a diverse group of community practices substantially improve preventive visit uptake over time. QI programs in primary care can reach patients early to promote preventive services that potentially avoid costly downstream care.

Providers' Behaviors and Beliefs on Prescribing Antipsychotic Medication to Children: A Qualitative Study.

Fragmentation in behavioral and mental health care to children has resulted in suboptimal care and high rates of psychotropic medication use, especially antipsychotic medications (APM). A qualitative study, based on the Theory of Planned Behavior (TPB), aimed to better understand prescribing practices, barriers to optimal treatment, and potential interventions to safeguard the use of APM for children in Kentucky. The most common barrier to optimal care was access to mental health specialists. Social norms and pressure from families contribute to increased medication use. We identify promising interventions to safeguard the use of APM through the lens of the TPB.

Spatial relationships between lead sources and children's blood lead levels in the urban center of Indianapolis (USA).

Urban children remain disproportionately at risk of having higher blood lead levels than their suburban counterparts. The Westside Cooperative Organization (WESCO), located in Marion County, Indianapolis, Indiana, has a history of children with high blood lead levels as well as high soil lead (Pb) values. This study aims at determining the spatial relationship between soil Pb sources and children's blood lead levels. Soils have been identified as a source of chronic Pb exposure to children, but the spatial scale of the source-recipient relationship is not well characterized. Neighborhood-wide analysis of soil Pb distribution along with a furnace filter technique for sampling interior Pb accumulation for selected homes (n = 7) in the WESCO community was performed. Blood lead levels for children aged 0-5 years during the period 1999-2008 were collected. The study population's mean blood lead levels were higher than national averages across all ages, race, and gender. Non-Hispanic blacks and those individuals in the Wishard advantage program had the highest proportion of elevated blood lead levels. The results show that while there is not a direct relationship between soil Pb and children's blood lead levels at a spatial scale of ~100 m, resuspension of locally sourced soil is occurring based on the interior Pb accumulation. County-wide, the largest predictor of elevated blood lead levels is the location within the urban core. Variation in soil Pb and blood lead levels on the community level is high and not predicted by housing stock age or income. Race is a strong predictor for blood lead levels in the WESCO community.

Impact of robotic surgery on patient flow and resource use intensity in ovarian cancer.

There is an emerging focus on the role of robotic surgery in ovarian cancer. To date, the operational and cost implications of the procedure remain unknown. The objective of the current study was to evaluate the impact of integrating minimally invasive robotic surgery on patient flow, resource utilization, and hospital costs associated with the treatment of ovarian cancer during the in-hospital and post-discharge processes. 261 patients operated for the primary treatment of ovarian cancer between January 2006 and November 2014 at a university-affiliated tertiary hospital were included in this study. Outcomes were compared by surgical approach (robotic vs. open surgery) as well as pre- and post-implementation of the robotics platform for use in ovarian cancer. The in-hospital patient flow and number of emergency room visits within 3 months of surgery were evaluated using multi-state Markov models and generalized linear regression models, respectively. Robotic surgery cases were associated with lower rates of postoperative complications, resulted in a more expedited postoperative patient flow (e.g., shorter time in the recovery room, ICU, and inpatient ward), and were between $10,376 and $7,421 less expensive than the average laparotomy, depending on whether or not depreciation and amortization of the robotic platform were included. After discharge, patients who underwent robotic surgery were less likely to return to the ER (IRR 0.42, p = 0.02, and IRR 0.47, p = 0.055, in the univariate and multivariable models, respectively). With appropriate use of the technology, the addition of robotics to the medical armamentarium for the management of ovarian cancer, when clinically feasible, can bring about operational efficiencies and entails cost savings.

Left behind again: Rural home health services in a Medicaid pediatric accountable care organization.

PURPOSE: To contrast trends in rural and urban pediatric home health care use among Medicaid enrollees. METHODS: Medicaid administrative claims data were used to assess differences in home health care use for child members in a large pediatric accountable care organization (ACO) in Ohio. Descriptive statistics assessed rural and urban differences in health care use over a 10-year period between 2010 and 2019. FINDINGS: Pediatric home health care use increased markedly in the low-income (CFC) and disabled (ABD) Medicaid categories. Over the past 10 years, CFC-enrolled children from urban communities have seen more home health visits, fewer emergency department (ED) visits, and more well child visits compared to rural CFC-enrolled children. Children enrolled due to disabilities in urban communities have also seen more home health visit use but fewer preventive care visits than their rural counterparts. CONCLUSIONS: Within a pediatric ACO, rural home health care use has remained relatively stagnant over a 10-year period, a stark contrast to increases in home health care use among comparable urban populations. There are likely multiple explanations for these differences, including overuse in urban communities, lack of access in rural communities, and changes to home health reimbursement. More can be done to improve rural home health access. Such improvement will likely necessitate large-scale changes to home health care delivery, workforce, and financing. Improvements should be evaluated for return-on-investment not only in terms of direct costs, that is, reduced inpatient or ED costs, but also in terms of patient and family quality-of-life or key indicators of child well-being such as educational attainment.

Syringe services programs in the Bluegrass: Evidence of population health benefits using Kentucky Medicaid data.

PURPOSE: To evaluate whether Kentucky counties that established a new syringe services program realized a significant decline in the incidence rate of a set of infectious disease diagnoses commonly transmitted via injection drug use. METHODS: Longitudinal count models of within-county rates of newly diagnosed infections among populations at risk were estimated using Medicaid claims/encounters data. Generalized estimating equation models were used to report incident rate ratios of 6 diagnoses: (1) HIV; (2) hepatitis C; (3) hepatitis B; (4) osteomyelitis; (5) endocarditis; and (6) skin/soft tissue infection. To investigate whether a delay in effect was present, separate models were fit to estimate the effects of establishing a syringe services program: at its opening date, and again at 1, 3, and 6 months postopening date. FINDINGS: Taken together, the aggregated within-county incidence rate of these 6 diagnoses was significantly lower following the implementation of a syringe services program (P < .05). Our models estimated that counties which opted to open a syringe services program realized an approximate month-over-month decline in new diagnoses of 0.5% among the population at risk. CONCLUSIONS: These results lend further support to previous conclusions made in the public health literature regarding the efficacy of syringe services programs. Specifically, declines in incidence rates were observable beginning at 1 month post syringe services program opening. These results are particularly notable due to the typical setting in which these syringe services programs operated-rural communities of fewer than 40,000 residents.

The role of perceived parent monitoring and support on urban child and adolescent problem behavior.

Parental practices on problem behavior based on gender and age effects with urban youth were studied. Participants were 8-17 years old (N = 3,658; 66% African-American) and logistic regression models were conducted. For pre-teen females, decreased friend monitoring was related to high problem behavior; for teen females, lower maternal support and decreased home monitoring were significant. None of the models were significant for pre-teen males and lack of home monitoring was significant for teen males. Strategies for preventing problem behavior within urban communities will be more effective if they are tailored to gender and developmental factors.

Contribution of Social Determinant of Health Factors to Rural-Urban Preventive Care Differences Among Medicaid Enrollees.

OBJECTIVE: 1) Assess whether rural-urban disparities are present in pediatric preventive health care utilization; and 2) use regression decomposition to measure the contribution of social determinants of health (SDH) to those disparities. METHODS: With an Ohio Medicaid population served by a pediatric Accountable Care Organization, Partners For Kids, between 2017 and 2019, we used regression decomposition (a nonlinear multivariate regression decomposition model) to analyze the contribution of patient, provider, and SDH factors to the rural-urban well-child visit gap among children in Ohio. RESULTS: Among the 453,519 eligible Medicaid enrollees, 61.2% of urban children received a well-child visit. Well-child visit receipt among children from large rural cities/towns and small/isolated towns was 58.2% and 55.5%, respectively. Comparing large rural towns to urban centers, 55.8% of the 3.0 percentage-point difference was explained by patient, provider, and community-level SDH factors. In comparing small/isolated town to urban centers, 89.8% of the 5.7 percentage-point difference was explained by these characteristics. Of provider characteristics, pediatrician providers were associated with increased well visit receipt. Of the SDH factors, unemployment and education contributed the most to the explained difference in large rural towns while unemployment, education, and food deserts contributed significantly to the small/isolated town difference. CONCLUSIONS: The receipt of pediatric preventive care is slightly lower in rural communities. While modest, the largest part of the rural-urban preventive care gap can be explained by differences in provider type, poverty, unemployment, and education levels. More could be done to improve pediatric preventive care in all communities.

Trends in healthcare utilisation for firearm-related injuries among a cohort of publicly insured children in Ohio.

OBJECTIVE: To examine healthcare utilisation for all firearm-related injuries among publicly insured children. METHODS: A retrospective analysis of firearm injury medical claims among paediatric (<21 years) Medicaid beneficiaries in Ohio from 2010 to 2018. Factors associated with unintentional and intentional firearm injury were explored using multivariable logistic regression. Average annual patient healthcare costs were determined in 2019 US$. RESULTS: There were 1061 firearm injury-related claims (853 (80%) unintentional; 154 (15%) intentional; 54 (5%) unknown) occurring in 663 children over 2 736 517 available person-years. From 2010 to 2018, yearly total firearm claims rose from 19.7 to 31.3 per 100 000 persons (p=0.033). Urban children experienced a non-significant increase in firearm claims rate over time (26.1 vs 35.0/100 000; p=0.066) while the claims rate nearly tripled among those in rural areas (8.4 vs 24.0/100 000; p=0.012). Younger age, females and rural residence were associated with reduced odds of injury claims. The average annual costs for emergency department and inpatient visits, respectively, were $260 and $5735. CONCLUSION: Risk and type of firearm injury claims among low-income children in Ohio varies by age, sex and residence. Prevention programmes should be tailored based on these demographics.

Gender differences in the association between perceived discrimination and adolescent smoking.

OBJECTIVES: We examined associations between perceived racial/ethnic discrimination, gender, and cigarette smoking among adolescents. METHODS: We examined data on Black and Latino adolescents aged 12 to 19 years who participated in the Moving to Opportunity study (N = 2561). Perceived discrimination was assessed using survey items asking about unfair treatment because of race/ethnicity in the prior 6 months. We used logistic regression to investigate associations between discrimination and smoking, stratified by gender and controlling for covariates. RESULTS: One fourth of adolescents reported that discrimination had occurred in at least 1 location. Discrimination was associated with increased odds of smoking among boys (odds ratio [OR] = 1.9; 95% confidence interval [CI] = 1.2, 3.0) and decreased odds among girls (OR = 0.6; 95% CI = 0.3, 1.1). Discrimination at school or work contributed to associations for girls (OR = 0.3; 95% CI = 0.1, 0.9), and discrimination at shops (OR = 2.0; 95% CI = 1.1, 3.8) and by police (OR = 2.0; 95% CI = 1.2, 3.4) contributed to associations for boys. CONCLUSIONS: Associations between discrimination and smoking differ by gender. Girls' decreased smoking in higher-discrimination settings may be a result of protective factors associated with where they spend time. Boys' increased smoking in higher-discrimination settings may reflect increased stress from gender-specific targeting by police and businesses.

A Machine Learning Approach to Uncovering Hidden Utilization Patterns of Early Childhood Dental Care Among Medicaid-Insured Children.

Background: Early childhood dental care (ECDC) is a significant public health opportunity since dental caries is largely preventable and a prime target for reducing healthcare expenditures. This study aims to discover underlying patterns in ECDC utilization among Ohio Medicaid-insured children, which have significant implications for public health prevention, innovative service delivery models, and targeted cost-saving interventions. Methods: Using 9 years of longitudinal Medicaid data of 24,223 publicly insured child members of an accountable care organization (ACO), Partners for Kids in Ohio, we applied unsupervised machine learning to cluster patients based on their cumulative dental cost curves in early childhood (24-60 months). Clinical validity, analytical validity, and reproducibility were assessed. Results: The clustering revealed five novel subpopulations: (1) early-onset of decay by age (0.5% of the population, as early as 28 months), (2) middle-onset of decay (3.0%, as early as 35 months), (3) late-onset of decay (5.8%, as early as 44 months), (4) regular preventive care (67.7%), and (5) zero utilization (23.0%). Patients with early-onset of decay incurred the highest dental cost [median annual cost (MAC) = $9,499, InterQuartile Range (IQR): $7,052-$11,216], while patients with regular preventive care incurred the lowest dental cost (MAC = $191, IQR: $99-$336). We also found a plausible correlation of early-onset of decay with complex medical conditions diagnosed at 0-24 months. Almost one-third of patients with early-onset of decay had complex medical conditions diagnosed at 0-24 months. Patients with early-onset of decay also incurred the highest medical cost (MAC = $7,513, IQR: $4,527-$12,546) at 0-24 months. Conclusion: Among Ohio Medicaid-insured children, five subpopulations with distinctive clinical, cost, and utilization patterns were discovered and validated through a data-driven approach. This novel discovery promotes innovative prevention strategies that differentiate Medicaid subpopulations, and allows for the development of cost-effective interventions that target high-risk patients. Furthermore, an integrated medical-dental care delivery model promises to reduce costs further while improving patient outcomes.

Using GPS-enabled cell phones to track the travel patterns of adolescents.

BACKGROUND: Few tools exist to directly measure the microsocial and physical environments of adolescents in circumstances where participatory observation is not practical or ethical. Yet measuring these environments is important as they are significantly associated with adolescent health-risk. For example, health-related behaviors such as cigarette smoking often occur in specific places where smoking may be relatively surreptitious. RESULTS: We assessed the feasibility of using GPS-enabled cell phones to track adolescent travel patterns and gather daily diary data. We enrolled 15 adolescent women from a clinic-based setting and asked them to carry the phones for 1 week. We found that these phones can accurately and reliably track participant locations, as well as record diary information on adolescent behaviors. Participants had variable paths extending beyond their immediate neighborhoods, and denied that GPS-tracking influenced their activity. CONCLUSION: GPS-enabled cell phones offer a feasible and, in many ways, ideal modality of monitoring the location and travel patterns of adolescents. In addition, cell phones allow space- and time-specific interaction, probing, and intervention which significantly extends both research and health promotion beyond a clinical setting. Future studies can employ GPS-enabled cell phones to better understand adolescent environments, how they are associated with health-risk behaviors, and perhaps intervene to change health behavior.

Association Between Residential Greenness and Cardiovascular Disease Risk.

Background Exposure to green vegetation has been linked to positive health, but the pathophysiological processes affected by exposure to vegetation remain unclear. To study the relationship between greenness and cardiovascular disease, we examined the association between residential greenness and biomarkers of cardiovascular injury and disease risk in susceptible individuals. Methods and Results In this cross-sectional study of 408 individuals recruited from a preventive cardiology clinic, we measured biomarkers of cardiovascular injury and risk in participant blood and urine. We estimated greenness from satellite-derived normalized difference vegetation index ( NDVI ) in zones with radii of 250 m and 1 km surrounding the participants' residences. We used generalized estimating equations to examine associations between greenness and cardiovascular disease biomarkers. We adjusted for residential clustering, demographic, clinical, and environmental variables. In fully adjusted models, contemporaneous NDVI within 250 m of participant residence was inversely associated with urinary levels of epinephrine (-6.9%; 95% confidence interval, -11.5, -2.0/0.1 NDVI ) and F2-isoprostane (-9.0%; 95% confidence interval, -15.1, -2.5/0.1 NDVI ). We found stronger associations between NDVI and urinary epinephrine in women, those not on ß-blockers, and those who had not previously experienced a myocardial infarction. Of the 15 subtypes of circulating angiogenic cells examined, 11 were inversely associated (8.0-15.6% decrease/0.1 NDVI ), whereas 2 were positively associated (37.6-45.8% increase/0.1 NDVI ) with contemporaneous NDVI . Conclusions Independent of age, sex, race, smoking status, neighborhood deprivation, statin use, and roadway exposure, residential greenness is associated with lower levels of sympathetic activation, reduced oxidative stress, and higher angiogenic capacity.

Green neighborhoods, food retail and childhood overweight: differences by population density.

PURPOSE: This study examines relationships between overweight in children and two environmentalfactors--amount of vegetation surrounding a child's place of residence and proximity of the child's residence to various types of food retail locations. We hypothesize that living in greener neighborhoods, farther from fast food restaurants, and closer to supermarkets would be associated with lower risk of overweight. DESIGN: Cross-sectional study. SETTING: Network of primary care pediatric clinics in Marion County, Indiana. SUBJECTS: We acquired data for 7334 subjects, ages 3 to 18 years, presenting for routine well-child care. MEASURES: Neighborhood vegetation and proximity to food retail were calculated using geographic information systems for each subject using circular and network buffers. Child weight status was defined using body mass index percentiles. Analysis. We used cumulative logit models to examine associations between an index of overweight, neighborhood vegetation, and food retail environment. RESULTS: After controlling for individual socio-demographics and neighborhood socioeconomic status, measures of vegetation and food retail significantly predicted overweight in children. Increased neighborhood vegetation was associated with decreased risk for overweight, but only for subjects residing in higher population density regions. Increased distance between a subject's residence and the nearest large brand name supermarkets was associated with increased risk of overweight, but only for subjects residing in lower population density regions. CONCLUSIONS: This research suggests that aspects of the built environment are determinants of child weight status, ostensibly by influencing physical activity and dietary behaviors.

Use of unstructured parent narratives to evaluate medical student competencies in communication and professionalism.

OBJECTIVE: Medical education programs across the country are now required to conduct meaningful assessments of trainees' competencies, although uniform standards for conducting these evaluations have yet to be established. In 1999, the Indiana University School of Medicine introduced a comprehensive competency-based undergraduate curriculum. The overall goal of the curriculum is to make medical students' day-to-day experiences of training a source of learning about professionalism, communication, and aspects of medicine beyond factual knowledge. We sought to examine free-text comments by parents of pediatric inpatients as substrate for competency evaluation and feedback for third-year students on their pediatrics rotation. METHODS: The study was conducted from June 2001 to February 2004. Parents of hospitalized children completed a short medical student evaluation form that included 2 questions inviting free-text response. We used narrative analysis, a qualitative research technique, to describe both the content and meaning of the parents' responses. RESULTS: We collected 573 evaluations with narrative comments about 412 students. The most common aspect of medical student performance commented on by parents related to communication (53.8%). The next most common narrative comment was some form of affirmation of the student as a health care professional (26.0%). Other themes included establishing context for the comment, perceptions of the health care system, criticizing medical student performance, perceptions of the role of medical students, physical approach to the patient, expression of humility by the student, holistic approach to the patient, physical appearance of the student, superlative description of student, and advocating for the patient. Multiple themes were identified in 232 narrative comments (40.4%). Examples of each theme are provided. CONCLUSIONS: Family members of pediatric inpatients are a valuable source of information about medical student performance in at least 2 of the Accreditation Council for Graduate Medical Education competency areas (Communication and Professionalism). Themes identified in this study could be used to inform the design of a comprehensive 360-degree student evaluation strategy.

Zinc delays the progression of obesity-related glomerulopathy in mice via down-regulating P38 MAPK-mediated inflammation.

OBJECTIVE: Obesity, particularly child obesity, is one of the most common public health problems in the world and raises the risk of end-stage renal disease. Zinc (Zn) is essential for multiple organs in terms of normal structure and function; however, effects of Zn deficiency or supplementation among young individuals with obesity have not been well studied. METHODS: Weaned mice were fed high-fat diets (HFD) with varied contents of Zn (Zn deficient, adequate, and supplemented) for 3 or 6 months. This study examined associations between renal pathogenesis and dietary Zn levels, specifically assessing inflammatory pathways by utilizing P38 MAPK inhibitor SB203580. RESULTS: HFD feeding induced typical syndromes of obesity-related renal disorders, which worsened by Zn marginal deficiency. The progression of obesity-related renal disorders was delayed by Zn supplementation. HFD induced renal inflammation, reflected by increased P38 MAPK phosphorylation along with increases of inflammatory cytokines MCP-1, IL-1ß, IL-6, and TNF-α. P38 MAPK inhibition prevented renal pathological changes in mice fed with HFD and HFD/Zn deficiency. CONCLUSIONS: P38 MAPK mediated the renal inflammatory responses, which played a central role in the pathogenesis of HFD-induced renal disorders. Zn could delay the progression of obesity-related kidney disease by down-regulating P38 MAPK-mediated inflammation.

Up-regulation of Nrf2 is involved in FGF21-mediated fenofibrate protection against type 1 diabetic nephropathy.

The lipid lowering medication, fenofibrate (FF), is a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, possessing beneficial effects for type 2 diabetic nephropathy (DN). We investigated whether FF can prevent the development of type 1 DN, and the underlying mechanisms. Diabetes was induced by a single intraperitoneal injection of streptozotocin in C57BL/6J mice. Mice were treated with oral gavage of FF at 100mg/kg every other day for 3 and 6 months. Diabetes-induced renal oxidative stress, inflammation, apoptosis, lipid and collagen accumulation, and renal dysfunction were accompanied by significant decrease in PI3K, Akt, and GSK-3ß phosphorylation as well as an increase in the nuclear accumulation of Fyn [a negative regulator of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)]. All these adverse effects were significantly attenuated by FF treatment. FF also significantly increased fibroblast growth factor 21 (FGF21) expression and enhanced Nrf2 function in diabetic and non-diabetic kidneys. Moreover, FF-induced amelioration of diabetic renal damage, including the stimulation of PI3K/Akt/GSK-3ß/Fyn pathway and the enhancement of Nrf2 function were abolished in FGF21-null mice, confirming the critical role of FGF21 in FF-induced renal protection. These results suggest for the first time that FF prevents the development of DN via up-regulating FGF21 and stimulating PI3K/Akt/GSK-3ß/Fyn-mediated activation of the Nrf2 pathway.

Zinc deficiency exacerbates while zinc supplement attenuates cardiac hypertrophy in high-fat diet-induced obese mice through modulating p38 MAPK-dependent signaling.

Childhood obesity often leads to cardiovascular diseases, such as obesity-related cardiac hypertrophy (ORCH), in adulthood, due to chronic cardiac inflammation. Zinc is structurally and functionally essential for many transcription factors; however, its role in ORCH and underlying mechanism(s) remain unclear and were explored here in mice with obesity induced with high-fat diet (HFD). Four week old mice were fed on either HFD (60%kcal fat) or normal diet (ND, 10% kcal fat) for 3 or 6 months, respectively. Either diet contained one of three different zinc quantities: deficiency (ZD, 10mg zinc per 4057kcal), normal (ZN, 30mg zinc per 4057kcal) or supplement (ZS, 90mg zinc per 4057kcal). HFD induced a time-dependent obesity and ORCH, which was accompanied by increased cardiac inflammation and p38 MAPK activation. These effects were worsened by ZD in HFD/ZD mice and attenuated by ZS in HFD/ZS group, respectively. Also, administration of a p38 MAPK specific inhibitor in HFD mice for 3 months did not affect HFD-induced obesity, but completely abolished HFD-induced, and zinc deficiency-worsened, ORCH and cardiac inflammation. In vitro exposure of adult cardiomyocytes to palmitate induced cell hypertrophy accompanied by increased p38 MAPK activation, which was heightened by zinc depletion with its chelator TPEN. Inhibition of p38 MAPK with its specific siRNA also prevented the effects of palmitate on cardiomyocytes. These findings demonstrate that ZS alleviates but ZD heightens cardiac hypertrophy in HFD-induced obese mice through suppressing p38 MAPK-dependent cardiac inflammatory and hypertrophic pathways.