Creation of the Person-Centered Wellness Home in Older Adults

Background and Objectives: Extending the Patient-Centered Medical Home (PCMH) model into the community may address the poor linkage between medical clinics and underserved communities. Our first of three objectives was to determine if peer leaders and wellness coaches can be the relationship center of wellness care. We evaluated the Self-management Resource Center Small Group Programs (SMRCSGP), plus wellness coaching, as a booster intervention in older adults with chronic diseases. Second, we evaluated the role of personal health records (PHR) prototype as the linkage between the clinic and community. Using input from these two objectives, we lay the groundwork for the Person-centered Wellness Home (PCWH). Research Design and Methods: Participants enrolled from five South Bronx New York City Housing Authority communities. We conducted a pragmatic, randomized controlled trial using two arms (n = 121): (1) SMRCSGP and (2) SMRCSGP plus wellness coaching initiated as a booster after SMRCSGP completion. Adjusted individual growth models compared the slope differences for outcomes. We conducted a social networking analysis on the ties between wellness coaches and participants. PCMH-certified physicians completed in-depth interviews on the PHR prototype. An adaptation from the consensus-workshop model summarized the priority PCWH items. Results: There was an improvement in self-reported physical functioning (2.0 T-score units higher, p = .03) by the wellness coaching group, but the groups did not differ on physical activity. From the social networking analysis, connections were stable over time with wellness-coaches and participants. The Consensus Conference identified eight major components of the PCWH. Discussion and Implications: Wellness coaching post-SMRCSGP was a booster to physical function, an upstream outcome for physical activity. During the Consensus-Conference, community-based prevention marketing and personal navigators for connecting to a PCMH emerged as novel components. This supports future work in training community health workers as peer leaders to provide evidence-based programs and other PCWH components

Social support and older adult falls

Background Social support has been shown to be associated with various positive health outcomes among older adults but has not been previously examined in relation to falls, which are a serious health concern among older adults. Findings This study (n = 1000) uses multivariable logistic regression to evaluate the relationship between social contact and perceived availability of social support and falls among older adults. When adjusting for demographic and other covariates neither relationship was significant. Conclusions This study does not find evidence to suggest that social support could be a prevention measure for falls. Future research on this topic should focus on careful definition and precise measurement of the social support construct

Altered emotional interference processing in the amygdala and insula in women with Post-Traumatic Stress Disorder

AbstractBackgroundPost-Traumatic Stress Disorder (PTSD) is characterized by distinct behavioral and physiological changes. Given the significant impairments related to PTSD, examination of the biological underpinnings is crucial to the development of theoretical models and improved treatments of PTSD.MethodsWe used an attentional interference task using emotional distracters to test for top-down versus bottom-up dysfunction in the interaction of cognitive-control circuitry and emotion-processing circuitry. A total of 32 women with PTSD (based on an interpersonal trauma) and 21 matched controls were tested. Event-related functional magnetic resonance imaging was carried out as participants directly attended to, or attempted to ignore, fear-related stimuli.ResultsCompared to controls, patients with PTSD showed hyperactivity in several brain regions, including the amygdala, insula, as well as dorsal lateral and ventral PFC regions.ConclusionsThese results are consistent with previous studies that have higher amygdala and insular activation in PTSD subjects. However, inhibition of suppression of PFC regions is inconsistent with the fear circuitry model hypothesized by prior research. We suggest that the specific emotional conflict task used appears to target implicit or automatic emotional regulation instead of explicit or effortful emotional regulation. This is particularly relevant as it posited that emotional regulatory difficulties in anxiety disorders such as PTSD appear to occur in implicit forms of emotion regulation

Non-perturbative dynamics of hot non-Abelian gauge fields: beyond leading log approximation

Many aspects of high-temperature gauge theories, such as the electroweak baryon number violation rate, color conductivity, and the hard gluon damping rate, have previously been understood only at leading logarithmic order (that is, neglecting effects suppressed only by an inverse logarithm of the gauge coupling). We discuss how to systematically go beyond leading logarithmic order in the analysis of physical quantities. Specifically, we extend to next-to-leading-log order (NLLO) the simple leading-log effective theory due to Bodeker that describes non-perturbative color physics in hot non-Abelian plasmas. A suitable scaling analysis is used to show that no new operators enter the effective theory at next-to-leading-log order. However, a NLLO calculation of the color conductivity is required, and we report the resulting value. Our NLLO result for the color conductivity can be trivially combined with previous numerical work by G. Moore to yield a NLLO result for the hot electroweak baryon number violation rate.Comment: 20 pages, 1 figur

Phase 1 Trial of the Plasmodium falciparum Blood Stage Vaccine MSP142-C1/Alhydrogel with and without CPG 7909 in Malaria Naïve Adults

-C1 was formulated with Alhydrogel plus the novel adjuvant CPG 7909.-C1/Alhydrogel +/− CPG 7909. Sixty volunteers were enrolled in dose escalating cohorts and randomized to receive three vaccinations of either 40 or 160 µg protein adsorbed to Alhydrogel +/− 560 µg CPG 7909 at 0, 1 and 2 months.-C1/Alhydrogel alone (p<0.0001). After the third immunization, functionality of the antibody was tested by an in vitro growth inhibition assay. Inhibition was a function of antibody titer, with an average of 3% (range −2 to 10%) in the non CPG groups versus 14% (3 to 32%) in the CPG groups.-C1/Alhydrogel is being combined with other blood stage antigens and will be taken forward in a formulation adjuvanted with CPG 7909

Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3.

Epitranscriptome modifications are required for structure and function of RNA and defects in these pathways have been associated with human disease. Here we identify the RNA target for the previously uncharacterized 5-methylcytosine (m(5)C) methyltransferase NSun3 and link m(5)C RNA modifications with energy metabolism. Using whole-exome sequencing, we identified loss-of-function mutations in NSUN3 in a patient presenting with combined mitochondrial respiratory chain complex deficiency. Patient-derived fibroblasts exhibit severe defects in mitochondrial translation that can be rescued by exogenous expression of NSun3. We show that NSun3 is required for deposition of m(5)C at the anticodon loop in the mitochondrially encoded transfer RNA methionine (mt-tRNA(Met)). Further, we demonstrate that m(5)C deficiency in mt-tRNA(Met) results in the lack of 5-formylcytosine (f(5)C) at the same tRNA position. Our findings demonstrate that NSUN3 is necessary for efficient mitochondrial translation and reveal that f(5)C in human mitochondrial RNA is generated by oxidative processing of m(5)C.This work was funded by the Medical Research Council (MRC; as part of the core funding for the Mitochondrial Biology Unit MC_U105697135 and by the G0801904 grant), the European Research Council (ERC; 310360), Cancer Research UK (CR-UK; C10701/ A15181), European Commission (FP7/2007-2013, under grant agreement number no.262055 (ESGI), as a Transnational Access project of the European Sequencing and Genotyping Infrastructure), core support grant from the Wellcome Trust and MRC to the Wellcome Trust-MRC Cambridge Stem Cell Institute, the European Commission (Horizon2020, under grant agreement number 633974), the Bundesministerium fur Bildung und Forschung (BMBF) (through the German Network for mitochondrial disorders (mitoNET, 01GM1113C) and through the European network for mitochondrial disorders (E-Rare project GENOMIT, 01GM1207)) and by EMBO (ALFT 701-2013).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1203

Health and population effects of rare gene knockouts in adult humans with related parents.

Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British adults of Pakistani heritage with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of function (knockouts) in 781 genes. We observed 13.7% fewer homozygous knockout genotypes than we expected, implying an average load of 1.6 recessive-lethal-equivalent loss-of-function (LOF) variants per adult. When genetic data were linked to the individuals' lifelong health records, we observed no significant relationship between gene knockouts and clinical consultation or prescription rate. In this data set, we identified a healthy PRDM9-knockout mother and performed phased genome sequencing on her, her child, and control individuals. Our results show that meiotic recombination sites are localized away from PRDM9-dependent hotspots. Thus, natural LOF variants inform on essential genetic loci and demonstrate PRDM9 redundancy in humans.The study was funded by the Wellcome Trust (WT102627 and WT098051), Barts Charity (845/1796), Medical Research Council (MR/M009017/1). This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Collaboration for Applied Health Research and Care (CLAHRC) for Yorkshire and Humber. Core support for Born in Bradford is also provided by the Wellcome Trust (WT101597). V.N. was supported by the Wellcome Trust PhD Studentship (WT099769). D.G.M. and K.K. were supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R01GM104371. E.R.M. is funded by NIHR Cambridge Biomedical Research Centre. H.H. is supported by awards to establish the Farr Institute of Health Informatics Research, London, from the Medical Research Council, Arthritis Research UK, British Heart Foundation, Cancer Research UK, Chief Scientist Office, Economic and Social Research Council, Engineering and Physical Sciences Research Council, NIHR, National Institute for Social Care and Health Research, and Wellcome Trust.This is the author accepted manuscript. The final version is available from the American Association for the Advancement of Science via https://doi.org/10.1126/science.aac862

The Genome Sequence of Caenorhabditis briggsae: A Platform for Comparative Genomics

The soil nematodes Caenorhabditis briggsae and Caenorhabditis elegans diverged from a common ancestor roughly 100 million years ago and yet are almost indistinguishable by eye. They have the same chromosome number and genome sizes, and they occupy the same ecological niche. To explore the basis for this striking conservation of structure and function, we have sequenced the C. briggsae genome to a high-quality draft stage and compared it to the finished C. elegans sequence. We predict approximately 19,500 protein-coding genes in the C. briggsae genome, roughly the same as in C. elegans. Of these, 12,200 have clear C. elegans orthologs, a further 6,500 have one or more clearly detectable C. elegans homologs, and approximately 800 C. briggsae genes have no detectable matches in C. elegans. Almost all of the noncoding RNAs (ncRNAs) known are shared between the two species. The two genomes exhibit extensive colinearity, and the rate of divergence appears to be higher in the chromosomal arms than in the centers. Operons, a distinctive feature of C. elegans, are highly conserved in C. briggsae, with the arrangement of genes being preserved in 96% of cases. The difference in size between the C. briggsae (estimated at approximately 104 Mbp) and C. elegans (100.3 Mbp) genomes is almost entirely due to repetitive sequence, which accounts for 22.4% of the C. briggsae genome in contrast to 16.5% of the C. elegans genome. Few, if any, repeat families are shared, suggesting that most were acquired after the two species diverged or are undergoing rapid evolution. Coclustering the C. elegans and C. briggsae proteins reveals 2,169 protein families of two or more members. Most of these are shared between the two species, but some appear to be expanding or contracting, and there seem to be as many as several hundred novel C. briggsae gene families. The C. briggsae draft sequence will greatly improve the annotation of the C. elegans genome. Based on similarity to C. briggsae, we found strong evidence for 1,300 new C. elegans genes. In addition, comparisons of the two genomes will help to understand the evolutionary forces that mold nematode genomes

Common genetic variation drives molecular heterogeneity in human iPSCs.

Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells

A Complex Cell Division Machinery Was Present in the Last Common Ancestor of Eukaryotes

Background: The midbody is a transient complex structure containing proteins involved in cytokinesis. Up to now, it has been described only in Metazoa. Other eukaryotes present a variety of structures implied in the last steps of cell division, such as the septum in fungi or the phragmoplast in plants. However, it is unclear whether these structures are homologous (derive from a common ancestral structure) or analogous (have distinct evolutionary origins). Recently, the proteome of the hamster midbody has been characterized and 160 proteins identified. Methodology/Principal Findings: Using phylogenomic approaches, we show here that nearly all of these 160 proteins (95%) are conserved across metazoan lineages. More surprisingly, we show that a large part of the mammalian midbody components (91 proteins) were already present in the last common ancestor of all eukaryotes (LECA) and were most likely involved in the construction of a complex multi-protein assemblage acting in cell division. Conclusions/Significance: Our results indicate that the midbodies of non-mammalian metazoa are likely very similar to the mammalian one and that the ancestor of Metazoa possessed a nearly modern midbody. Moreover, our analyses support the hypothesis that the midbody and the structures involved in cytokinesis in other eukaryotes derive from a large and complex structure present in LECA, likely involved in cytokinesis. This is an additional argument in favour of the idea of a comple