The Effect of iCook 4-H, a Childhood Obesity Prevention Program, on Blood Pressure and Quality of Life in Youth and Adults: A Randomized Control Trial

Objective: Obesity increases the risk of developing hypertension and from population-based samples with estimations that of 2-4% of the U.S. pediatric population has hypertension, which may affect quality of life. This study examined the effects of an obesity prevention program on blood pressure and quality of life in youth and adult participants. Methods: A multi-state research team recruited treatment dyads (youth and their adult meal preparer) to participate in a 12-week randomized control trial and follow-up through 24 months. The treatment group received a cooking and physical activity intervention, followed by booster sessions and mailed newsletters over the remaining two-year period. The control group received no intervention. Resting blood pressure and health related quality of life (HRQOL) surveys were administered at 0,4,12 and 24 months. Results: 228 dyads were recruited (n=77 control and n=151 for treatment). Youth and adult systolic blood pressure (SBP) increased over the 24 months (p=0.003 and p=0.03, respectively) with no differences between groups. From baseline to 24 months both control and treatment youths’ physical and psychological HRQOL increased (p=0.01 and p=0.002, respectively). At 0 and 4 months, youth and adult SBP was positively correlated (r=0.24, p=0.003 and r=0.33, p\u3c0.001, respectively). In the treatment group, there was an inverse association between adult SBP and youth psychological HRQOL at 4 months (r=-0.20, p=0.04), and a similar trend in adult SBP and youth physical HRQOL at 4 months in the treatment group (r=-0.19, p=0.05). Conclusion: A youth-adult dyad obesity prevention program consisting of culinary, mealtime and physical activity education, elicited improvements in HRQOL in youth participants

Group-based trajectories of maternal intake of sugar-sweetened beverage and offspring oral health from a prospective birth cohort study

OBJECTIVES: To investigate the trajectory of maternal intake of sugar-sweetened beverages (SSB) during the first five years of their child's life and its effect on the child's dental caries at five years-of-age. METHODS: This is an ongoing prospective population-based birth cohort study in Adelaide, Australia. Mothers completed questionnaires on their SSB intake, socioeconomic factors and health behaviors at the birth of their child and at the ages of one, two and five years. Child dental caries measured as decayed, missing, or filled tooth surfaces was collected by oral examination. Maternal SSB intake was used to estimate the trajectory of SSB intake. The trajectories then became the main exposure of the study. Dental caries at age five years were the primary outcomes. Adjusted mean- and prevalence-ratios were estimated for dental caries, controlling for confounders. RESULTS: 879 children had dental examinations at five years-of-age. Group-based trajectory modeling identified three trajectories of maternal SSB intake: 'Stable low' (40.8%), 'Moderate but increasing' (13.6%), and 'High early' trajectory (45.6%). Multivariable regression analysis found children of mothers in the 'High early' and 'Moderate but increasing' groups to have greater experience of dental caries (MR: 1.37 (95%CI 1.01-1.67), and 1.24 (95%CI 0.96-1.60) than those in the 'Stable low' trajectory, respectively. CONCLUSION: Maternal consumption of SSB during pregnancy and in the early postnatal period influenced their offspring's oral health. It is important to create a low-sugar environment from early childhood. The results suggest that health promotion activities need to be delivered to expecting women or soon after childbirth

Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma

Neuroblastomas are tumors of peripheral sympathetic neurons and are the most common solid tumor in children. To determine the genetic basis for neuroblastoma we performed whole-genome sequencing (6 cases), exome sequencing (16 cases), genome-wide rearrangement analyses (32 cases), and targeted analyses of specific genomic loci (40 cases) using massively parallel sequencing. On average each tumor had 19 somatic alterations in coding genes (range, 3–70). Among genes not previously known to be involved in neuroblastoma, chromosomal deletions and sequence alterations of chromatin remodeling genes, ARID1A and ARID1B, were identified in 8 of 71 tumors (11%) and were associated with early treatment failure and decreased survival. Using tumor-specific structural alterations, we developed an approach to identify rearranged DNA fragments in sera, providing personalized biomarkers for minimal residual disease detection and monitoring. These results highlight dysregulation of chromatin remodeling in pediatric tumorigenesis and provide new approaches for the management of neuroblastoma patients

Meeting Report of the Third Annual Tri-Service Microbiome Consortium Symposium

The Tri-Service Microbiome Consortium (TSMC) was founded to enhance collaboration, coordination, and communication of microbiome research among U.S. Department of Defense (DoD) organizations and to facilitate resource, material and information sharing among consortium members. The 2019 annual symposium was held 22–24 October 2019 at Wright-Patterson Air Force Base in Dayton, OH. Presentations and discussions centered on microbiome-related topics within five broad thematic areas: 1) human microbiomes; 2) transitioning products into Warfighter solutions; 3) environmental microbiomes; 4) engineering microbiomes; and 5) microbiome simulation and characterization. Collectively, the symposium provided an update on the scope of current DoD microbiome research efforts, highlighted innovative research being done in academia and industry that can be leveraged by the DoD, and fostered collaborative opportunities. This report summarizes the presentations and outcomes of the 3rd annual TSMC symposium

Avelumab Alone or in Combination With Chemotherapy Versus Chemotherapy Alone in Platinum-Resistant or Platinum-Refractory Ovarian Cancer (JAVELIN Ovarian 200): An Open-Label, Three-Arm, Randomised, Phase 3 Study

The majority of patients with ovarian cancer will experience relapse and develop platinum-resistant disease after being treated with frontline platinum-based chemotherapy. Treatment options for platinum-resistance or platinum-refractory disease are very limited, usually involving nonplatinum chemotherapy, and they are associated with poor objective response rates and life expectancy

Identification of microbial DNA in human cancer

<p>Abstract</p> <p>Background</p> <p>Microorganisms have been associated with many types of human diseases; however, a significant number of clinically important microbial pathogens remain to be discovered.</p> <p>Methods</p> <p>We have developed a genome-wide approach, called Digital Karyotyping Microbe Identification (DK-MICROBE), to identify genomic DNA of bacteria and viruses in human disease tissues. This method involves the generation of an experimental DNA tag library through Digital Karyotyping (DK) followed by analysis of the tag sequences for the presence of microbial DNA content using a compiled microbial DNA virtual tag library.</p> <p>Results</p> <p>To validate this technology and to identify pathogens that may be associated with human cancer pathogenesis, we used DK-MICROBE to determine the presence of microbial DNA in 58 human tumor samples, including brain, ovarian, and colorectal cancers. We detected DNA from Human herpesvirus 6 (HHV-6) in a DK library of a colorectal cancer liver metastasis and in normal tissue from the same patient.</p> <p>Conclusion</p> <p>DK-MICROBE can identify previously unknown infectious agents in human tumors, and is now available for further applications for the identification of pathogen DNA in human cancer and other diseases.</p

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: diagnostic and mechanistic relevance

Background & Aims: Serum microRNAs (miRNAs) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages.Methods: We profiled 2,083 serum miRNAs in a discovery cohort (183 NAFLD cases representing the complete NAFLD spectrum and 10 population controls). MiRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional NAFLD cases and 15 population controls by quantitative reverse transcriptase-polymerase chain reaction.Results: Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages but miR-193a-5p consistently the showed increased levels in all comparisons. Relative to NAFL/NASH with mild fibrosis (stage 0/1), three miRNAs (miR-193a-5p, miR-378d and miR378d) were increased in cases with NASH and clinically significant fibrosis (stage 2-4), seven (miR193a-5p, miR-378d, miR-378e, miR-320b, c, d & e) increased in cases with NAFLD Activity Score (NAS) 5-8 compared with lower NAS, and three (miR-193a-5p, miR-378d, miR-378e) increased but one (miR-19b-3p) decreased in steatosis, activity, and fibrosis "activity" (SAF-A) score 2-4 compared with lower SAF-A. The significant findings for miR-193a-5p were replicated in the additional NAFLD cohort. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n=80); liver GPX8 levels correlated positively with serum miR-193a-5p. Conclusions: Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD