Effects of Neonatal Hypoxic-Ischemic Injury on Brain Sterol Synthesis and Metabolism.

BACKGROUND: Neonatal hypoxic-ischemic brain injury (HIBI) results from disruptions to blood supply and oxygen in the perinatal brain. The goal of this study was to measure brain sterol metabolites and plasma oxysterols after injury in a neonatal HIBI mouse model to assess for potential therapeutic targets in the brain biochemistry as well as potential circulating diagnostic biomarkers. METHODS: Postnatal day 9 CD1-IGS mouse pups were randomized to HIBI induced by carotid artery ligation followed by 30 minutes at 8% oxygen or to sham surgery and normoxia. Brain tissue was collected for sterol analysis by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Plasma was collected for oxysterol analysis by LC-MS/MS. RESULTS: There were minimal changes in brain sterol concentrations in the first 72 hours after HIBI. In severely injured brains, there was a significant increase in desmosterol, 7-DHC, 8-DHC, and cholesterol 24 hours after injury in the ipsilateral tissue. Lanosterol, 24-dehydrolathosterol, and 14-dehydrozymostenol decreased in plasma 24 hours after injury. Severe neonatal HIBI was associated with increased cholesterol and sterol precursors in the cortex at 24 hours after injury. CONCLUSIONS: Differences in plasma oxysterols were seen at 24 hours but were not present at 30 minutes after injury, suggesting that these sterol intermediates would be of little value as early diagnostic biomarkers.

Community Exercise Program Participation and Mental Well-Being in the U.S. Texas-Mexico Border Region.

Hispanics are disproportionately affected by low rates of physical activity and high rates of chronic diseases. Hispanics generally and Mexican Americans specifically are underrepresented in research on physical activity and its impact on mental well-being. Some community-based interventions have been effective in increasing physical activity among Hispanics. This study examined data from a sample of low-income Hispanic participants in free community exercise classes to characterize the association between self-reported frequency of exercise class attendance, intensity of physical activity, and participant well-being. As part of two cross-sectional samples recruited from a stratified random sample of community exercise classes, 302 participants completed a questionnaire consisting of a modified version of the Godin-Shephard Leisure-Time Exercise Questionnaire (LTEQ) and the Mental Health Continuum Short Form (MHC-SF). Adjusted logistic regression analyses indicated that those who achieve mild, moderate, and strenuous self-reported physical activity have 130% higher odds (p = 0.0422) of positive mental well-being after adjustment for age, frequency of attendance, and self-reported health. This study provides evidence that the intensity of physical activity is associated with flourishing mental well-being among Hispanic adults. The association between physical activity and mental well-being is more pronounced when considering participants engaged in mild levels of physical activity. The study further provides insight into the planning and development of community-based physical activity programming tailored to low-income populations.

The Impact of Prematurity at Birth on Short-Term Postoperative Outcomes Following Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.

Prematurity is associated with surgical complications. This study sought to determine the risk of prematurity on 30-day complications, reoperations, and readmissions following ≥7-level PSF for AIS which has not been established. Utilizing the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP)-Pediatric dataset, all AIS patients undergoing ≥7-level PSF from 2012-2016 were identified. Cases were 1:1 propensity score-matched to controls by age, sex, and number of spinal levels fused. Prematurity sub-classifications were also evaluated: extremely (<28 weeks), very (28-31 weeks), and moderate-to-late (32-36 weeks) premature. Univariate analysis with post hoc Bonferroni compared demographics, hospital parameters, and 30-day outcomes. Multivariate logistic regression identified independent predictors of adverse 30-day outcomes. 5531 patients (term = 5099; moderate-to-late premature = 250; very premature = 101; extremely premature = 81) were included. Premature patients had higher baseline rates of multiple individual comorbidities, longer mean length of stay, and higher 30-day readmissions and infections than the term cohort. Thirty-day readmissions increased with increasing prematurity. Very premature birth predicted UTIs, superficial SSI/wound dehiscence, and any infection, and moderate-to-late premature birth predicted renal insufficiency, deep space infections, and any infection. Prematurity of AIS patients differentially impacted rates of 30-day adverse outcomes following ≥7-level PSF. These results can guide preoperative optimization and postoperative expectations.

Neonatal Hypoxic-Ischemic Brain Injury Alters Brain Acylcarnitine Levels in a Mouse Model.

Hypoxic-ischemic brain injury (HIBI) leads to depletion of ATP, mitochondrial dysfunction, and enhanced oxidant formation. Measurement of acylcarnitines may provide insight into mitochondrial dysfunction. Plasma acylcarnitine levels are altered in neonates after an HIBI, but individual acylcarnitine levels in the brain have not been evaluated. Additionally, it is unknown if plasma acylcarnitines reflect brain acylcarnitine changes. In this study, postnatal day 9 CD1 mouse pups were randomized to HIBI induced by carotid artery ligation, followed by 30 min at 8% oxygen, or to sham surgery and normoxia, with subgroups for tissue collection at 30 min, 24 h, or 72 h after injury (12 animals/group). Plasma, liver, muscle, and brain (dissected into the cortex, cerebellum, and striatum/thalamus) tissues were collected for acylcarnitine analysis by LC-MS. At 30 min after HIBI, acylcarnitine levels were significantly increased, but the differences resolved by 24 h. Palmitoylcarnitine was increased in the cortex, muscle, and plasma, and stearoylcarnitine in the cortex, striatum/thalamus, and cerebellum. Other acylcarnitines were elevated only in the muscle and plasma. In conclusion, although plasma acylcarnitine results in this study mimic those seen previously in humans, our data suggest that the plasma acylcarnitine profile was more reflective of muscle changes than brain changes. Acylcarnitine metabolism may be a target for therapeutic intervention after neonatal HIBI, though the lack of change after 30 min suggests a limited therapeutic window.

Evaluating the Dissemination and Implementation of a Community Health Worker-Based Community Wide Campaign to Improve Fruit and Vegetable Intake and Physical Activity among Latinos along the U.S.-Mexico Border.

This study evaluated the dissemination and implementation of a culturally tailored community-wide campaign (CWC), Tu Salud ¡Si Cuenta! (TSSC), to augment fruit and vegetable (FV) consumption and physical activity (PA) engagement among low-income Latinos of Mexican descent living along the U.S.-Mexico Border in Texas. TSSC used longitudinal community health worker (CHW) home visits as a core vehicle to enact positive change across all socioecological levels to induce behavioral change. TSSC's reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) was examined. A dietary questionnaire and the Godin-Shepherd Exercise Questionnaire measured program effectiveness on mean daily FV consumption and weekly PA engagement, respectively. Participants were classified based on CHW home visits into "low exposure" (2-3 visits) and "high exposure" (4-5 visits) groups. The TSSC program reached low-income Latinos (n = 5686) across twelve locations. TSSC demonstrated effectiveness as, compared to the low exposure group, the high exposure group had a greater FV intake (mean difference = +0.65 FV servings daily, 95% CI: 0.53-0.77) and an increased PA (mean difference = +185.6 MET-minutes weekly, 95% CI: 105.9-265.4) from baseline to the last follow-up on a multivariable linear regression analysis. Multivariable logistic regression revealed that the high exposure group had higher odds of meeting both FV guidelines (adjusted odds ratio (AOR) = 2.03, 95% CI: 1.65-2.47) and PA guidelines (AOR = 1.36, 95% CI: 1.10-1.68) at the last follow-up. The program had a 92.3% adoption rate, with 58.3% of adopting communities meeting implementation fidelity, and 91.7% of communities maintaining TSSC. TSSC improved FV consumption and PA engagement behaviors among low-income Latinos region wide. CHW delivery and implementation funding positively influenced reach, effectiveness, adoption, and maintenance, while lack of qualified CHWs negatively impacted fidelity.

Scaling a Community-Wide Campaign Intervention to Manage Hypertension and Weight Loss.

Public health impacts can be achieved when evidence-based interventions are implemented to those most in need. Too often implementation never or slowly occurs. The community-wide campaign intervention Tu Salud ¡Si Cuenta! has evidence of improving health outcomes related to chronic disease among low-income, Latinos. Using the RE-AIM Framework, this study examined if the scaled-up version of the intervention is associated with improvements in hypertension and obesity in 12 locations. Each element of the RE-AIM framework was examined. For "Effectiveness," we examined outcomes overall and by implementing location. We used linear and logistic regression to assess if exposure in the intervention was associated with improvement in hypertension and weight loss. Participants were stratified into "low exposure" (2-3 outreach visits) vs. "high exposure" (4-5 outreach visits). Based on the RE-AIM Framework, the intervention "reached" its intended population of low-income Latinos, demonstrated "effectiveness" in improving hypertension and obesity, was "adopted" at a high level in all but one site, was "implemented" with fidelity to the intervention model with moderate success across locations, and showed high "maintenance" over time. For effectiveness specifically, we found that out of 5,019 participants, 2,508 (50%) had a baseline hypertensive blood pressure (BP) reading. Of the 2,508, 1,245 (49.9%) recovered to normal blood pressure or pre-hypertension stage by last follow-up. After adjusting for baseline BP and potential confounders in multivariable linear regression models, the high exposure group had significantly more reduction in systolic BP (adjusted mean difference in % change = -0.96; p = 0.002) and diastolic BP (adjusted mean difference in % change = -1.61; p < 0.0001) compared to the low exposure group. After controlling for baseline weight and other confounders, the high exposure group had significantly greater decrease in weight compared to the low exposure group (adjusted mean difference in % change = -1.28; p < 0.0001). Results from the multivariable logistic regression models indicated that compared to the low exposure group the high exposure group was more likely to achieve a clinically significant minimum 5% weight loss [adjusted odds ratio (OR) = 2.97; p < 0.0001). This study contributes evidence that a Community-Wide Campaign model holds promise for addressing hypertension and obesity among low-income Latinos.

Cholesterol metabolism and brain injury in neonatal encephalopathy.

Neonatal encephalopathy (NE) results from impaired cerebral blood flow and oxygen delivery to the brain. The pathophysiology of NE is complex and our understanding of its underlying pathways continues to evolve. There is considerable evidence that cholesterol dysregulation is involved in several adult diseases, including traumatic brain injury, stroke, Huntington's disease, and Parkinson's disease. Although the research is less robust in pediatrics, there is emerging evidence that aberrations in cholesterol metabolism may also be involved in the pathophysiology of neonatal NE. This narrative review provides an overview of cholesterol metabolism in the brain along with several examples from the adult literature where pathologic alterations in cholesterol metabolism have been associated with inflammatory and ischemic brain injury. Using those data as a background, the review then discusses the current preclinical data supporting the involvement of cholesterol in the pathogenesis of NE as well as how brain-specific cholesterol metabolites may serve as serum biomarkers for brain injury. Lastly, we review the potential for using the cholesterol metabolic pathways as therapeutic targets. Further investigation of the shifts in cholesterol synthesis and metabolism after hypoxia-ischemia may prove vital in understanding NE pathophysiology as well as providing opportunities for rapid diagnosis and therapeutic interventions. IMPACT: This review summarizes emerging evidence that aberrations in cholesterol metabolism may be involved in the pathophysiology of NE. Using data from NE as well as analogous adult disease states, this article reviews the potential for using cholesterol pathways as targets for developing novel therapeutic interventions and using cholesterol metabolites as biomarkers for injury. When possible, gaps in the current literature were identified to aid in the development of future studies to further investigate the interactions between cholesterol pathways and NE.

A Tale of Two Brothers: Familial Voltage-Gated Potassium Channel Autoimmune Encephalitis.

This is the first reported case of familial voltage-gated potassium channel (VGKC) autoimmune encephalitis. The symptoms of autoimmune encephalitis can mimic infectious encephalitis with headache, fatigue, and neuropsychiatric symptoms. Autoimmunity is emerging as a distinct cause of encephalitis in the children. Prompt recognition, diagnosis, and treatment are important to prevent brain damage. Two brothers presented two years apart with different symptoms. The explanation for their distinct symptoms lies in the multifactorial development of autoimmunity. The presentation of autoimmune encephalitis can depend on the offending antibodies. The most common are antibodies against the N-methyl-D-aspartic acid (NMDA) receptor and the VGKC complex. Antibodies to the VGKC complex are divided into three different groups depending on their antigenic target: leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-like 2 (CASPR2), or neither. Anti-VGKC antibodies in children are associated with neuroinflammation and encephalitis. Autoimmunity to LGI1 and CASPR2 antigens is associated with distinct human leukocyte antigen (HLA) alleles. Different HLA isotypes are involved in antigen processing and presentation and can lead to a genetic predisposition to autoimmunity. VGKC autoimmune encephalitis can present with memory changes, psychiatric symptoms, and motor abnormalities. Both brothers presented with these symptoms in their own unique way. Efficient diagnosis and immunosuppression helped improve their outcomes.

Trends and Variation in Care and Outcomes for Children Hospitalized With Acute Gastroenteritis.

OBJECTIVES: Assess trends in inpatient acute gastroenteritis (AGE) management across children's hospitals and identify elements of AGE management associated with resource use. METHODS: We examined inpatient stays for children 6 months to 18 years hospitalized with AGE from 2009 to 2018 using the Pediatric Health Information System database. We characterized demographics, hospital-level resource use (ie, medications, laboratories, and imaging), and outcomes (ie, cost per case, 14-day revisit rates, and length of stay [LOS]). We compared demographic characteristics and resource use between 2009 to 2013 and 2014 to 2018 using χ2 and Wilcoxon rank-sum tests. We grouped hospitals on the basis of 2009 use of each resource and trended use over time using logistic regression. Annual change in mean cost and LOS were estimated by using models of log-transformed data. RESULTS: Across 32 354 hospitalizations at 38 hospitals, there was a high use of electrolyte testing (85.4%) and intravenous fluids (84.1%) without substantial changes over time. There were significant reductions in the majority of laboratory, medication, and imaging resources across hospitals over the study period. The most notable reductions were for rotavirus and stool testing. Many hospitals saw a decrease in LOS, with only 3 noting an increased revisit rate. Reductions in cost per case over time were most associated with decreases in imaging, laboratory testing, and LOS. CONCLUSIONS: Significant variation in resource use for children hospitalized with AGE coupled with high use of resources discouraged in AGE guidelines highlights potential opportunities to improve resource use that may be addressed in future AGE guidelines and quality improvement initiatives.

Make Your Move Experience: A Worksite Wellness Pilot in South Texas.

PURPOSE: To describe the implementation of Make Your Move Experience (MYME) between 2015 and 2017. DESIGN: Cross-sectional. SETTING: Make Your Move Experience is a culturally sensitive worksite wellness program in South Texas designed to encourage sedentary workers to engage in physical activity. PARTICIPANTS: In total, 681 individuals from 19 different organizations. INTERVENTION: UTHealth School of Public Health in Brownsville staff recruited individuals within local organizations to join MYME. At the end of the 3 months, organizations in which employees met MYME goals earned an incentive-bike rack or hydration station-selected to be permanent features of the local environment and facilitate physical activity. MEASURES: Participant self-reported gender, physical activity level prior to joining MYME (beginner or experienced), and weekly miles of biking, walking, or running completed. ANALYSIS: Mean number of miles biked, walked, and ran each month were compared between (1) beginners and experienced, (2) men and women, and (3) in fall 2016 and spring 2017 using t tests. RESULTS: Beginners initiated physical activity by walking. Men biked more miles than women did (P < .05 all 3 years). Bike riders cycled fewer miles (20.2 miles vs 44.9 miles; P = .03) and walkers covered fewer miles (195.4 miles vs 266.7 miles; P = .04) in fall 2016 compared to spring 2017. CONCLUSIONS: Participation in MYME, a culturally appropriate intervention delivered at the worksite, facilitated an increase in physical activity levels among sedentary individuals.

The Need for Cultural Competency and Healthcare Literacy with Refugees.

In order to best provide appropriate healthcare to individuals of a variety of ethnic and socio-economic backgrounds, a healthcare provider should be aware of the variables that affect not only an individual's access to healthcare, but variables that may hinder the patient from navigating the healthcare system effectively. Refugees faces diverse and extensive challenges as they adjust to living in the United States. Collaboration and communication; as well as frequent reassessment of that communication is essential to culturally appropriate care.

Verification of Diagnosis in Tuberculosis: A Case Report and Discussion.

Tuberculosis (TB), caused by strains of Mycobacterium tuberculosis complex (M. tuberculosis), is a pulmonary infection that is spread by airborne droplet transmission. The development and spread of drug-resistant strains of M. tuberculosisgreatly jeopardize TB control efforts. We report the case of a previously healthy 43-year-old male, visiting from China, who presented to the emergency department complaining of hemoptysis of 10 days' duration. Cultures were positive for acid fast bacteria and negative for fungi. M. tuberculosis infection was confirmed by a deoxyribonucleic acid (DNA) probe. The patient was initially started on first-line therapy of isoniazid, rifampin, pyrazinamide, and ethambutol, with pyridoxine. His country of origin, China, increased suspicion for drug-resistant tuberculosis. Two weeks later, susceptibility testing of the M. tuberculosis isolate showed resistance to isoniazid, pyrazinamide, and ethambutol. Therapy was subsequently changed to amikacin, linezolid, moxifloxacin, and rifampin. The isolate was subsequently sent to the Center for Disease Control (CDC) for evaluation. Repeat testing showed that the isolate was susceptible to rifampin, pyrazinamide, and ethambutol. The patient was then restarted on his initial anti-TB regimen and was able to return to China. The main goals for the treatment of TB are to treat the individual patient and to minimize transmission. Clues that point to the possibility of multiple drug resistant tuberculosis (MDR-TB) include contact with a patient with MDR-TB, origin from an endemic region, or failure of therapy with documented supervision. Collaboration with experts was imperative in ensuring appropriate patient care.

A 39-Year-Old Pregnant Woman with Pulmonary Emboli on Long Term Anticoagulation.

We present the case of a 39-year-old pregnant woman with Klippel-Trenaunay syndrome (KTS). We demonstrate the risks of multiple, co-existing pro-thrombotic states (pregnancy, KTS), discuss complications of KTS (deep venous thromboembolisms and pulmonary emboli) and highlight general and disease-specific preventive measures against venous thromboembolic events (VTE). KTS is a rare condition and it's co-existence with pregnancy and VTEs is rarer still.

Improved identification and enrolment into care of HIV-exposed and -infected infants and children following a community health worker intervention in Lilongwe, Malawi.

BACKGROUND: Early identification and entry into care is critical to reducing morbidity and mortality in children with HIV. The objective of this report is to describe the impact of the Tingathe programme, which utilizes community health workers (CHWs) to improve identification and enrolment into care of HIV-exposed and -infected infants and children. METHODS: Three programme phases are described. During the first phase, Mentorship Only (MO) (March 2007-February 2008) on-site clinical mentorship on paediatric HIV care was provided. In the second phase, Tingathe-Basic (March 2008-February 2009), CHWs provided HIV testing and counselling to improve case finding of HIV-exposed and -infected children. In the final phase, Tingathe-PMTCT (prevention of mother-to-child transmission) (March 2009-February 2011), CHWs were also assigned to HIV-positive pregnant women to improve mother-infant retention in care. We reviewed routinely collected programme data from HIV testing registers, patient mastercards and clinic attendance registers from March 2005 to March 2011. RESULTS: During MO, 42 children (38 HIV-infected and 4 HIV-exposed) were active in care. During Tingathe-Basic, 238 HIV-infected children (HIC) were newly enrolled, a six-fold increase in rate of enrolment from 3.2 to 19.8 per month. The number of HIV-exposed infants (HEI) increased from 4 to 118. During Tingathe-PMTCT, 526 HIC were newly enrolled over 24 months, at a rate of 21.9 patients per month. There was also a seven-fold increase in the average number of exposed infants enrolled per month (9.5-70 patients per month), resulting in 1667 enrolled with a younger median age at enrolment (5.2 vs. 2.5 months; p < 0.001). During the Tingathe-Basic and Tingathe-PMTCT periods, CHWs conducted 44,388 rapid HIV tests, 7658 (17.3%) in children aged 18 months to 15 years; 351 (4.6%) tested HIV-positive. Over this time, 1781 HEI were enrolled, with 102 (5.7%) found HIV-infected by positive PCR. Additional HIC entered care through various mechanisms (including positive linkage by CHWs and transfer-ins) such that by February 2011, a total of 866 HIC were receiving care, a 23-fold increase from 2008. CONCLUSIONS: A multipronged approach utilizing CHWs to conduct HIV testing, link HIC into care and provide support to PMTCT mothers can dramatically improve the identification and enrolment into care of HIV-exposed and -infected children.

Outcome of adolescents with eating disorders from an adolescent medicine service at a large children's hospital.

OBJECTIVE: To describe outcomes of adolescents with eating disorders treated by an interdisciplinary adolescent medicine service at a large children's hospital and to identify factors, including hospitalization, associated with outcome. DESIGN: The study design was a retrospective chart review of patients. SETTING: The setting was an inpatient and outpatient adolescent service in a large urban children's hospital. PARTICIPANTS: A total of 218 adolescents diagnosed with anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified participated in the study. INTERVENTION: Interdisciplinary inpatient and outpatient treatment for eating disorders was adopted for intervention. OUTCOME MEASURES: Patient outcomes were categorized as fully recovered, partially recovered/improved, or poorly recovered/exhibiting chronicity. RESULTS: Being admitted to the study hospital once and longer duration of follow-up were associated with full or partial recovery. In contrast, being readmitted to the study hospital and longer duration of illness prior to the initial contact with this service were associated with poor recovery. Premorbid obesity was unrelated to outcome. CONCLUSIONS: Earlier detection and referral of adolescents with eating disorders are needed because a high percentage of patients, especially those with anorexia nervosa, required hospitalization at initial contact. The benefits of inpatient admission may extend beyond medical stabilization of the most medically compromised patients to include improved therapeutic relationship with the treatment team and improved follow-up. Many patients prematurely terminate treatment; factors contributing to premature termination of therapy need further exploration.