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Genetic approach using rat congenic lines between SHRSP/Izm and WKY/Izm identified stromal interaction molecule 1 (Stim1), an essential component of store-operated Ca2+ entry (SOCE), as a promising candidate gene responsible for the exaggerated sympathetic response to stress in SHRSP. Since SHRSP has a nonsense mutation in Stim1 resulting in the expression of a truncated form of STIM1 that caused reduction of SOCE activity in primary cultured cerebral astrocytes, we created SHRSP/Izm knocked-in with the wild-type Stim1 (KI SHRSP) by the CRISPR/Cas9 method to investigate whether the functional recovery of STIM1 would mitigate sympatho-excitation to stress in vivo in SHRSP. No potential off-target nucleotide substitutions/deletions/insertions were found in KI SHRSP. Western blotting and fluorescent Ca2+ imaging of astrocytes confirmed wild-type STIM1 expression and restored SOCE activity in astrocytes from KI SHRSP, respectively. Blood pressure (BP) measured by the tail-cuff method at 12, 16, and 20 weeks of age did not significantly differ between SHRSP and KI SHRSP, while the heart rate of KI SHRSP at 16 and 20 weeks of age was significantly lower than that of age-matched SHRSP. Unexpectedly, the sympathetic response to stress (evaluated with urinary excretion of norepinephrine under cold stress and BP elevation under cold/restraint stress) did not significantly differ between SHRSP and KI SHRSP. The present results indicated that the functional deficit of STIM1 was not a genetic determinant of the exaggerated sympathetic response to stress in SHRSP and that it would be necessary to explore other candidates within the congenic fragment on chromosome 1.

Nutrition and feeding interventions are important for children’s growth and development. Holt International’s Child Nutrition Program (CNP) is a child nutrition and feeding intervention. This study aims to describe and explore the implementation of CNP in Mongolia and the Philippines using mixed methods including qualitative and quantitative data analysis. The analysis framework was guided by the WHO’s Monitoring the Building Blocks of Health Systems. Key informant interviews (KIIs) were conducted, transcribed, translated and coded. Knowledge, Attitude and Practice Surveys (KAPS) and pre-/post-tests from routine program audit data were analyzed. Analysis of nutrition (Mongolia: 95% CI: 7.5-16.6 (p = < 0.0001), Philippines: 95% CI: 7.6-15.7 (p= < 0.0001)) and feeding (Mongolia: 95% CI: 11.7-23.9 (p = < 0.0001), Philippines: 95% CI: 6.6-16.9 (p = < 0.0001)) tests indicate improvement post-training in both countries. KAPS indicate changes in desired practices from pre-training to post-training. Thematic analysis of KIIs highlight essential components for program implementation and effectiveness, including strong leadership, buy-in, secure funding, reliable supply chains, training and adequate staffing. This evaluation of program implementation highlights successful strategies and challenges in implementing CNP to improve the health of children in Mongolia and the Philippines. Lessons learned from the implementation of CNP can inform growth of the program, scaling strategies and provide insights for similar interventions.

Abstract Background There is controversy regarding the relative influence of ‘exogenous’ versus ‘endogenous’ factors on the risk of progression from latent tuberculosis infection to active tuberculosis (TB) disease in children. Methods We conducted a cross-sectional analysis to identify risk factors for active tuberculosis in QuantiFERON®-TB Gold (QFT-G)-positive children aged 6–13 years attending 18 schools in Ulaanbaatar, Mongolia. Children underwent clinical and radiological screening for active tuberculosis, and data relating to potential risk factors for disease progression were collected by questionnaire and determination of serum 25-hydroxyvitamin D (25[OH]D) concentrations. Risk ratios were calculated using generalized estimating equations with adjustment for potential confounders. Results 129/938 (13.8%) QFT-positive children were diagnosed with active tuberculosis. Risk of active tuberculosis was independently associated with household exposure to pulmonary TB (adjusted risk ratio [aRR] 2.40, 95% CI 1.74 to 3.30, P

Background: Vitamin D metabolites support innate immune responses to Mycobacterium tuberculosis. Data from phase 3, randomized, controlled trials of vitamin D supplementation to prevent tuberculosis infection are lacking.Methods: We randomly assigned children who had negative results for M. tuberculosis infection according to the QuantiFERON-TB Gold In-Tube assay (QFT) to receive a weekly oral dose of either 14,000 IU of vitamin D3 or placebo for 3 years. The primary outcome was a positive QFT result at the 3-year follow-up, expressed as a proportion of children. Secondary outcomes included the serum 25-hydroxyvitamin D (25[OH]D) level at the end of the trial and the incidence of tuberculosis disease, acute respiratory infection, and adverse events.Results: A total of 8851 children underwent randomization: 4418 were assigned to the vitamin D group, and 4433 to the placebo group; 95.6% of children had a baseline serum 25(OH)D level of less than 20 ng per milliliter. Among children with a valid QFT result at the end of the trial, the percentage with a positive result was 3.6% (147 of 4074 children) in the vitamin D group and 3.3% (134 of 4043) in the placebo group (adjusted risk ratio, 1.10; 95% confidence interval [CI], 0.87 to 1.38; P = 0.42). The mean 25(OH)D level at the end of the trial was 31.0 ng per milliliter in the vitamin D group and 10.7 ng per milliliter in the placebo group (mean between-group difference, 20.3 ng per milliliter; 95% CI, 19.9 to 20.6). Tuberculosis disease was diagnosed in 21 children in the vitamin D group and in 25 children in the placebo group (adjusted risk ratio, 0.87; 95% CI, 0.49 to 1.55). A total of 29 children in the vitamin D group and 34 in the placebo group were hospitalized for treatment of acute respiratory infection (adjusted risk ratio, 0.86; 95% CI, 0.52 to 1.40). The incidence of adverse events did not differ significantly between the two groups.Conclusions: Vitamin D supplementation did not result in a lower risk of tuberculosis infection, tuberculosis disease, or acute respiratory infection than placebo among vitamin D-deficient schoolchildren in Mongolia. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT02276755.). [ABSTRACT FROM AUTHOR]

In Ulaanbaatar, Mongolia, multidrug-resistant tuberculosis (MDR TB) was diagnosed for more than a third of new sputum smear-positive tuberculosis patients for whom treatment had failed. This finding suggests a significant risk for community-acquired MDR TB and a need to make rapid molecular drug susceptibility testing available to more people.

Background and Objectives: Latino-white disparities in age at autism spectrum disorder (ASD) diagnosis may be modified by primary care pediatrician (PCP) practices and beliefs. The objectives of this study were to assess ASD and developmental screening practices, attitudes toward ASD identification in Latino children, and barriers to ASD identification for Latino children, in a sample of 267 California PCPs., Methods: In mail-based PCP survey, we assessed rates of bilingual general developmental and ASD screening, perceptions of parent ASD knowledge in Latino and white families, reports of difficulty assessing for ASDs in Latino and white children, and perceptions of barriers to early ASD identification for Latinos., Results: Although 81% of PCPs offered some form of developmental screening, 29% of PCPs offered Spanish ASD screening per American Academy of Pediatrics guidelines, and only 10% offered both Spanish general developmental and Spanish ASD screening per American Academy of Pediatrics guidelines. Most PCPs thought that Latino (English and Spanish primary family language) parents were less knowledgeable about ASDs than white parents. PCPs had more difficulty assessing ASD risk for Latino children with Spanish primary family language than for white children, even when the PCP conducted recommended ASD screening or had >25% Latino patients. The most frequent barrier to ASD identification in Latinos was access to developmental specialists., Conclusions: Multiple factors in the primary care setting may contribute to delayed ASD identification for Latinos. Promoting language-appropriate screening, disseminating culturally appropriate ASD materials to Latino families, improving the specialist workforce, and providing PCP support in screening and referral of Latino children may be important ways to reduce racial and ethnic differences in care.