Consanguinity and rare mutations outside of MCCC genes underlie nonspecific phenotypes of MCCD

Purpose: 3-Methylcrotonyl-CoA carboxylase deficiency (MCCD) is an autosomal recessive disorder of leucine catabolism that has a highly variable clinical phenotype, ranging from acute metabolic acidosis to nonspecific symptoms such as developmental delay, failure to thrive, hemiparesis, muscular hypotonia, and multiple sclerosis. Implementation of newborn screening for MCCD has resulted in broadening the range of phenotypic expression to include asymptomatic adults. The purpose of this study was to identify factors underlying the varying phenotypes of MCCD. Methods: We performed exome sequencing on DNA from 33 cases and 108 healthy controls. We examined these data for associations between either MCC mutational status, genetic ancestry, or consanguinity and the absence or presence/specificity of clinical symptoms in MCCD cases. Results: We determined that individuals with nonspecific clinical phenotypes are highly inbred compared with cases that are asymptomatic and healthy controls. For 5 of these 10 individuals, we discovered a homozygous damaging mutation in a disease gene that is likely to underlie their nonspecific clinical phenotypes previously attributed to MCCD. Conclusion: Our study shows that nonspecific phenotypes attributed to MCCD are associated with consanguinity and are likely not due to mutations in the MCC enzyme but result from rare homozygous mutations in other disease genes

Active Living for Rural Youth [Policy Brief]

Childhood obesity and inactivity are significant and growing problems in many rural areas where the prevalence of obesity and overweight has been shown to be 25 percent higher than urban rates, even after controlling for income, race, physical activity and other known risk factors. While rural areas are often viewed as an ideal setting for an active childhood, kids face a variety of obstacles to incorporating physical activity in their daily lives. Active living research to date has focused largely on urban and suburban environments. This study investigates the complex web of determinants that support or undermine physical activity in rural youth. We visited three very different small Maine towns (Waldoboro, Dover-Foxcroft and Houlton), where we led youth focus groups and interviewed key informants including rural town planners, school personnel, recreation directors and parents. We also conducted townscape surveys of the physical characteristics of each community. Obesity and inactivity have roots in many aspects of rural life, from the physical environment, to social, policy and programmatic factors

The Role of State Flex Programs in Supporting Quality Improvement in CAHs (Policy Brief #16)

This study examined QI activities supported by the Flex Program in nine states, assessed the role of the State Flex Programs in developing and supporting QI activities, and explored the effect of these initiatives on CAH QI efforts. Key Findings: The Flex Program has been instrumental in funding and providing leadership for the development of CAH quality improvement initiatives. Collaborative shared learning strategies have been central to the success of Flex Program QI programs. Scaling QI program activities to the capacity and resources of CAHs is critical to success. Administrative, clinical, and board leadership and buy-in are also critical to the success of CAH QI initiatives. Despite widespread support for these QI initiatives, there is limited hard evidence on their impact. Overlap between the quality measures in Hospital Compare and those used by state and multi-state QI reporting and benchmarking programs offers the opportunity for developing a common set of “rural relevant” hospital quality measures

Models for Quality Improvement in CAHs: The Role of State Flex Programs (Briefing Paper #25)

A central goal of the Flex Program, as defined in the original and reauthorizing legislation, is to help Critical Access Hospitals (CAHs) develop and sustain effective quality improvement (QI) programs. This study examined the range of multi-CAH QI and performance measurement reporting initiatives supported by the Flex Program in nine states, assessed the role of State Flex Programs in developing and supporting these initiatives, and explored their impact on the QI programs of CAHs. Key Findings: State Flex Program funding was frequently the primary, if not sole, source of funding to support these efforts. Collaboration and shared learning are common Flex Program strategies underlying state QI initiatives. Quality measurement and reporting is a challenge due to a lack of agreement on common measures across state QI and benchmarking systems and a common belief that Hospital Compare measures are not “rurally relevant” (i.e., specific to the needs of CAHs). Administrative, clinical, and board leadership and buy-in were consistently identified as crucial to the success and sustainability of CAH-level QI initiatives. States reported that the scope of their QI has to be scaled to the available resources and capacity of CAHs to avoid QI fatigue among CAH staff. There is limited hard evidence on the impact of the QI initiatives adopted by State Flex Programs; much of the “evidence” supporting these initiatives is anecdotal or based on postconference or webinar evaluations

Two-neutron knockout from neutron-deficient 34^{34}Ar, 30^{30}S, and 26^{26}Si

Two-neutron knockout reactions from nuclei in the proximity of the proton dripline have been studied using intermediate-energy beams of neutron-deficient $^{34}$Ar, $^{30}$S, and $^{26}$Si. The inclusive cross sections, and also the partial cross sections for the population of individual bound final states of the $^{32}$Ar, $^{28}$S and $^{24}$Si knockout residues, have been determined using the combination of particle and $\gamma$-ray spectroscopy. Similar to the two-proton knockout mechanism on the neutron-rich side of the nuclear chart, these two-neutron removal reactions from already neutron-deficient nuclei are also shown to be consistent with a direct reaction mechanism.Comment: Phys. Rev. C, rapid communication, in pres

Telemental Health in Today\u27s Rural Health System

Telemental health has long been promoted in rural areas to address chronic access barriers to mental health care. While support and enthusiasm for telemental health in rural areas remains quite high, we lack a clear picture of the reality of telemental health in rural areas, compared to its promise. This Research & Policy Brief reports on the first part of our study—the online survey of 53 telemental health programs—and describes the organizational setting, services provided, and the staff mix of these programs. We draw from our telephone interviews with 23 of these programs to help describe the organizational context of telemental health programs

Chemotactic response and adaptation dynamics in Escherichia coli

Adaptation of the chemotaxis sensory pathway of the bacterium Escherichia coli is integral for detecting chemicals over a wide range of background concentrations, ultimately allowing cells to swim towards sources of attractant and away from repellents. Its biochemical mechanism based on methylation and demethylation of chemoreceptors has long been known. Despite the importance of adaptation for cell memory and behavior, the dynamics of adaptation are difficult to reconcile with current models of precise adaptation. Here, we follow time courses of signaling in response to concentration step changes of attractant using in vivo fluorescence resonance energy transfer measurements. Specifically, we use a condensed representation of adaptation time courses for efficient evaluation of different adaptation models. To quantitatively explain the data, we finally develop a dynamic model for signaling and adaptation based on the attractant flow in the experiment, signaling by cooperative receptor complexes, and multiple layers of feedback regulation for adaptation. We experimentally confirm the predicted effects of changing the enzyme-expression level and bypassing the negative feedback for demethylation. Our data analysis suggests significant imprecision in adaptation for large additions. Furthermore, our model predicts highly regulated, ultrafast adaptation in response to removal of attractant, which may be useful for fast reorientation of the cell and noise reduction in adaptation.Comment: accepted for publication in PLoS Computational Biology; manuscript (19 pages, 5 figures) and supplementary information; added additional clarification on alternative adaptation models in supplementary informatio

Effect of zinc intake on serum/plasma zinc status in infants: A meta-analysis

A systematic review and meta-analysis of available RCTs was conducted to evaluate the effect of zinc (Zn) intake on serum/plasma Zn status in infants. Out of 5500 studies identified through electronic searches and reference lists, 9 RCTs were selected after applying the exclusion/inclusion criteria. The influence of zinc intake on serum/plasma Zn concentration was considered in the overall meta-analysis. Other variables were also taken into account as possible effect modifiers: doses of zinc intake, intervention duration, nutritional status and risk of bias. From each selected study, final measures of serum/plasma Zn were assessed. RESULTS: The pooled β of status was 0.09 (95%CI 0.06 to 0.12). However, a substantial heterogeneity was present in the analyses (I2=95%; p=0.00001). When we performed a meta-regression, the effect of Zn intake on serum/plasma Zn status changed depending on the duration of the intervention, the dose of supplementation and the nutritional situation (p ANCOVA= 0.005; 20 weeks). A positive effect was seen also when doses ranged from 8.1 to 12 mg/day. In all cases, the pooled β showed high evidence of heterogeneity. CONCLUSION: Zinc supplementation increases serum/plasma Zn status in infants, although high evidence of heterogeneity was found. Further standardized research is urgently needed to reach evidence-based conclusions to clarify the role of zinc supplementation upon infant serum/plasma Zn status, particularly in Europe

Effectiveness of a complex, pre-conception intervention to reduce the risk of diabetes by reducing adiposity in young adults in Malaysia:The Jom Mama project - A randomised controlled trial

Background: Pre-conception interventions have the potential to lower non-communicable disease risk in prospective parents and reduce transmission of risk factors such as obesity to the next generation. The Jom Mama project in Malaysia investigated the effectiveness of a combined behaviour change communication and e-health intervention in young married couples prior to first pregnancy. This paper reports the evaluation of the effectiveness of this trial. Methods: Jom Mama was a non-blinded, randomised controlled trial (RCT) conducted in Seremban, Malaysia, over a period of 33 weeks, covering six contact points between trained community health workers and newly married couples before the conception of a first child. Out of 2075 eligible nulliparous women, 549 participated and 305 completed the intervention, with 145 women in the intervention and 160 in the control group. The intervention group received a complex behavioural change intervention, combining behaviour change communication provided by community health promoters and access to a habit formation mobile application, while the control group received the standard care provided by public health clinics in Malaysia. The primary outcome was a change in the woman's waist circumference. Secondary outcomes were anthropometric and metabolic measures, dietary intake (Food Frequency Questionnaire, FFQ), physical activity (International Physical Activity Questionnaire, IPAQ) and mental health (Depression Anxiety Stress Scale, DASS 21). An extensive process evaluation was conducted alongside the trial in order to aid the interpretation of the main findings. Results: There were no significant differences of change in the woman's waist circumference between intervention and control groups at the start and end of the intervention. While the weight, waist circumference and Body Mass Index (BMI) of women in both groups increased, there was a significantly lower increase in the intervention vs the control group over the period of the trial among women who are obese (0.1 kg vs 1.7 kg; P = 0.023, in the intervention and control group respectively). In terms of BMI, the obese intervention subgroup showed a slight reduction (0.01) compared to the obese control subgroup whose BMI increased by 0.7 (P = 0.015). There were no changes in the other secondary outcomes. Conclusions: The Jom Mama pre-conception intervention did not lead to a reduction in waist circumference or significant changes in other secondary outcomes over the eight months prior to conception. However, there was a significantly smaller weight gain in the intervention vs the control group, predominantly in women with pre-existing obesity

PainDroid: An android-based virtual reality application for pain assessment

Earlier studies in the field of pain research suggest that little efficient intervention currently exists in response to the exponential increase in the prevalence of pain. In this paper, we present an Android application (PainDroid) with multimodal functionality that could be enhanced with Virtual Reality (VR) technology, which has been designed for the purpose of improving the assessment of this notoriously difficult medical concern. Pain- Droid has been evaluated for its usability and acceptability with a pilot group of potential users and clinicians, with initial results suggesting that it can be an effective and usable tool for improving the assessment of pain. Participant experiences indicated that the application was easy to use and the potential of the application was similarly appreciated by the clinicians involved in the evaluation. Our findings may be of considerable interest to healthcare providers, policy makers, and other parties that might be actively involved in the area of pain and VR research