Maternal BMI as a predictor of methylation of obesity-related genes in saliva samples from preschool-age Hispanic children at-risk for obesity.

BackgroundThe study of epigenetic processes and mechanisms present a dynamic approach to assess complex individual variation in obesity susceptibility. However, few studies have examined epigenetic patterns in preschool-age children at-risk for obesity despite the relevance of this developmental stage to trajectories of weight gain. We hypothesized that salivary DNA methylation patterns of key obesogenic genes in Hispanic children would 1) correlate with maternal BMI and 2) allow for identification of pathways associated with children at-risk for obesity.ResultsGenome-wide DNA methylation was conducted on 92 saliva samples collected from Hispanic preschool children using the Infinium Illumina HumanMethylation 450 K BeadChip (Illumina, San Diego, CA, USA), which interrogates >484,000 CpG sites associated with ~24,000 genes. The analysis was limited to 936 genes that have been associated with obesity in a prior GWAS Study. Child DNA methylation at 17 CpG sites was found to be significantly associated with maternal BMI, with increased methylation at 12 CpG sites and decreased methylation at 5 CpG sites. Pathway analysis revealed methylation at these sites related to homocysteine and methionine degradation as well as cysteine biosynthesis and circadian rhythm. Furthermore, eight of the 17 CpG sites reside in genes (FSTL1, SORCS2, NRF1, DLC1, PPARGC1B, CHN2, NXPH1) that have prior known associations with obesity, diabetes, and the insulin pathway.ConclusionsOur study confirms that saliva is a practical human tissue to obtain in community settings and in pediatric populations. These salivary findings indicate potential epigenetic differences in Hispanic preschool children at risk for pediatric obesity. Identifying early biomarkers and understanding pathways that are epigenetically regulated during this critical stage of child development may present an opportunity for prevention or early intervention for addressing childhood obesity.Trial registrationThe clinical trial protocol is available at ClinicalTrials.gov ( NCT01316653 ). Registered 3 March 2011

Ten-year trends in traumatic brain injury: a retrospective cohort study of California emergency department and hospital revisits and readmissions.

OBJECTIVE:To describe visits and visit rates of adults presenting to emergency departments (EDs) with a diagnosis of traumatic brain injury (TBI). TBI is a major cause of death and disability in the USA; yet, current literature is limited because few studies examine longer-term ED revisits and hospital readmission patterns of TBI patients across a broad spectrum of injury severity, which can help inform potential unmet healthcare needs. DESIGN:We performed a retrospective cohort study. SETTING:We analysed non-public patient-level data from California's Office of Statewide Health Planning and Development for years 2005 to 2014. PARTICIPANTS:We identified 1.2 million adult patients aged ≥18 years presenting to California EDs and hospitals with an index diagnosis of TBI. PRIMARY AND SECONDARY OUTCOME MEASURES:Our main outcomes included revisits, readmissions and mortality over time. We also examined demographics, mechanism and severity of injury and disposition at discharge. RESULTS:We found a 57.7% increase in the number of TBI ED visits, representing a 40.5% increase in TBI visit rates over the 10-year period (346-487 per 100 000 residents). During this time, there was also a 33.8% decrease in the proportion of patients admitted to the hospital. Older, publicly insured and black populations had the highest visit rates, and falls were the most common mechanism of injury (45.5% of visits). Of all patients with an index TBI visit, 40.5% of them had a revisit during the first year, with 46.7% of them seeking care at a different hospital from their initial hospital or ED visit. Additionally, of revisits within the first year, 13.4% of them resulted in hospital readmission. CONCLUSIONS:The large proportion of patients with TBI who are discharged directly from the ED, along with the high rates of revisits and readmissions, suggest a role for an established system for follow-up, treatment and care of TBI

Predictors of Water Quality in Rural Healthcare Facilities in 14 Low- and Middle-Income Countries

Many healthcare facilities (HCFs) in rural areas of low- and middle-income countries (LMICs) lack safe, sufficient water supplies. We sought to understand which factors affect water quality in rural HCF in LMICs. In Ethiopia, Kenya, Rwanda, Uganda, Tanzania, Malawi, Mozambique, Zambia, Zimbabwe, Ghana, Mali, Niger, India, and Honduras, doctors and nurses were interviewed at 2,035 HCFs about their water source, staff training, and management practices. Water samples were also tested for E. coli contamination. We generated descriptive analyses and logistic regressions. Use of an improved water source (OR≈1.4), treatment of water (OR=1.26), management by a person with medical training (OR≈3.7), and presence of a protocol for operations and management (OR=1.29) were associated with safer water. These results suggest that in addition to addressing water source, storage, and treatment, stakeholders can also target organizational factors in order to improve water quality in HCFs.Master of Scienc

Illumination Variation Correction Using Image Synthesis For Unsupervised Domain Adaptive Person Re-Identification

Unsupervised domain adaptive (UDA) person re-identification (re-ID) aims to learn identity information from labeled images in source domains and apply it to unlabeled images in a target domain. One major issue with many unsupervised re-identification methods is that they do not perform well relative to large domain variations such as illumination, viewpoint, and occlusions. In this paper, we propose a Synthesis Model Bank (SMB) to deal with illumination variation in unsupervised person re-ID. The proposed SMB consists of several convolutional neural networks (CNN) for feature extraction and Mahalanobis matrices for distance metrics. They are trained using synthetic data with different illumination conditions such that their synergistic effect makes the SMB robust against illumination variation. To better quantify the illumination intensity and improve the quality of synthetic images, we introduce a new 3D virtual-human dataset for GAN-based image synthesis. From our experiments, the proposed SMB outperforms other synthesis methods on several re-ID benchmarks.Comment: 10 pages, 5 figures, 5 table

Interactions between the NR2B receptor and CaMKII modulate synaptic plasticity and spatial learning.

The NR2B subunit of the NMDA receptor interacts with several prominent proteins in the postsynaptic density, including calcium/calmodulin-dependent protein kinase II (CaMKII). To determine the function of these interactions, we derived transgenic mice expressing a ligand-activated carboxy-terminal NR2B fragment (cNR2B) by fusing this fragment to a tamoxifen (TAM)-dependent mutant of the estrogen receptor ligand-binding domain LBD(G521R). Here, we show that induction by TAM allows the transgenic cNR2B fragment to bind to endogenous CaMKII in neurons. Activation of the LBD(G521R)-cNR2B transgenic protein in mice leads to the disruption of CaMKII/NR2B interactions at synapses. The disruption decreases Thr286 phosphorylation of alphaCaMKII, lowers phosphorylation of a key CaMKII substrate in the postsynaptic membrane (AMPA receptor subunit glutamate receptor 1), and produces deficits in hippocampal long-term potentiation and spatial learning. Together our results demonstrate the importance of interactions between CaMKII and NR2B for CaMKII activity, synaptic plasticity, and learning

No-Regret Learning in Dynamic Competition with Reference Effects Under Logit Demand

This work is dedicated to the algorithm design in a competitive framework, with the primary goal of learning a stable equilibrium. We consider the dynamic price competition between two firms operating within an opaque marketplace, where each firm lacks information about its competitor. The demand follows the multinomial logit (MNL) choice model, which depends on the consumers' observed price and their reference price, and consecutive periods in the repeated games are connected by reference price updates. We use the notion of stationary Nash equilibrium (SNE), defined as the fixed point of the equilibrium pricing policy for the single-period game, to simultaneously capture the long-run market equilibrium and stability. We propose the online projected gradient ascent algorithm (OPGA), where the firms adjust prices using the first-order derivatives of their log-revenues that can be obtained from the market feedback mechanism. Despite the absence of typical properties required for the convergence of online games, such as strong monotonicity and variational stability, we demonstrate that under diminishing step-sizes, the price and reference price paths generated by OPGA converge to the unique SNE, thereby achieving the no-regret learning and a stable market. Moreover, with appropriate step-sizes, we prove that this convergence exhibits a rate of $\mathcal{O}(1/t)$

Electro-Gene Transfer to Skin Using a Noninvasive Multielectrode Array

Because of its large surface area and easy access for both delivery and monitoring, the skin is an attractive target for gene therapy for cutaneous diseases, vaccinations and several metabolic disorders. The critical factors for DNA delivery to the skin by electroporation (EP) are effective expression levels and minimal or no tissue damage. Here, we evaluated the non-invasive multielectrode array (MEA) for gene electrotransfer. For these studies we utilized a guinea pig model, which has been shown to have a similar thickness and structure to human skin. Our results demonstrate significantly increased gene expression 2 to 3 logs above injection of plasmid DNA alone over 15 days. Furthermore, gene expression could be enhanced by increasing the size of the treatment area. Transgene-expressing cells were observed exclusively in the epidermal layer of the skin. In contrast to caliper or plate electrodes, skin EP with the MEA greatly reduced muscle twitching and resulted in minimal and completely recoverable skin damage. These results suggest that EP with MEA can be an efficient and non-invasive skin delivery method with less adverse side effects than other EP delivery systems and promising clinical applications

What are the main symptoms and concerns reported by patients with advanced chronic heart failure?—a secondary analysis of the Palliative care Outcome Scale (POS) and Integrated Palliative care Outcome Scale (IPOS)

© Annals of Palliative Medicine. All rights reserved. There is a lack of valid disease-specific patient-reported outcome measures (PROMs) for detecting symptoms and concerns in patients with advanced chronic heart failure (CHF). The Palliative care Outcome Scale (POS) and Integrated Palliative care Outcome Scale (IPOS) are specifically developed to capture the main symptoms and concerns of people severely affected by advanced disease. The aim of this study was to determine whether POS and IPOS captures the main symptoms and concerns self-reported by patients with advanced CHF. A secondary analysis of existing POS/IPOS data collected in three longitudinal studies was conducted. POS and IPOS start with an open-ended question for patients to report their main problems and concerns, followed by subsequent closed questions on a range of symptoms and other concerns. Descriptive statistics were used to report the results. The 102 participants from the three datasets had median age 81 years (SD ±9.84 years); 62% male; 87% white. A total of 107 concerns were reported in the first, open POS/IPOS question seeking the patient’s main concerns. Of these, 83 (77%) were reflected in the subsequent IPOS/POS closed questions. The high correspondence between the free-text responses and the closed questions indicates that most issues are captured by the POS/IPOS items. In conclusion, the generic versions of POS and IPOS do capture the main problems and concerns of patients with advanced CHF. Minor adaptations and further psychometric validation of POS and IPOS are needed in this population