The Human Microbiome and Recurrent Abdominal Pain in Children

This project explores the nature of the human intestinal microbiome in healthy children and children with recurrent abdominal pain. The overall goal is to obtain a robust knowledge base of the intestinal microbiome in children without evidence of pain or gastrointestinal disease and in those with recurrent abdominal pain (functional abdominal pain (FAP) and FAP associated with changes in bowel habits, i.e., irritable bowel syndrome or IBS). Specific aims include: 1. Characterize the composition of the gut microbiome in healthy children by DNA sequencing. 2. Determine the presence of disease-specific organism signatures of variable gut microbiomes in children with recurrent abdominal pain. 3. Perform functional gut metagenomics by evaluation of whole community gene expression profiles and discovery of disease-specific pathway signatures. Multiple strategies have been deployed to navigate and understand the nature of the intestinal microbiome in childhood. These strategies included 454 pyrosequencing-based strategies to sequence 16S rRNA genes and understand the detailed composition of microbes in healthy and disease groups. Microarray-based hybridization with the PhyloChip and quantitative real-time PCR (qPCR) probes were applied as complementary strategies to gain an understanding of the intestinal microbiome from various perspectives. Data collected and analyzed during the HMP UH2 Demo project, from a set of healthy and IBS children (7-12 yo) may enable the identification of core microbiomes in children, in addition to variable components that may distinguish healthy from diseased pediatric states. Twenty-two children with IBS and twenty-two healthy children were enrolled and analyzed in the UH2 phase of this study. The planned enrollment targets for the UH2/3 phases include 50 healthy children, 50 children with FAP and 50 children with IBS (minimum of 3 time points per child). We are currently analyzing the dataset for the presence of disease-specific signatures in the human microbiome, and correlating these microbial signatures with pediatric health or IBS disease status in addition to IBS subtype (e.g., diarrhea-vs constipation-predominant). In the next phase, whole genome shotgun sequencing and metatranscriptomics will be performed with a subset of children in each group. This study explores the nature of core and variable human microbiome in pre-adolescent healthy children and children with IBS. 
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A closer look at opioid-induced adrenal insufficiency. A narrative review

Among several opioid-associated endocrinopathies, opioid-associated adrenal insufficiency (OIAI) is both common and not well understood by most clinicians, particularly those outside of endocrine specialization. OIAI is secondary to long-term opioid use and differs from primary adrenal insufficiency. Beyond chronic opioid use, risk factors for OIAI are not well known. OIAI can be diagnosed by a variety of tests, such as the morning cortisol test, but cutoff values are not well established and it is estimated that only about 10% of patients with OIAI will ever be properly diagnosed. This may be dangerous, as OIAI can lead to a potentially life-threatening adrenal crisis. OIAI can be treated and for patients who must continue opioid therapy, it can be clinically managed. OIAI resolves with opioid cessation. Better guidance for diagnosis and treatment is urgently needed, particularly in light of the fact that 5% of the United States population has a prescription for chronic opioid therapy

Survival rights for children : what are the national and global barriers?

Most children die in low and middle-income countries as a result of structural injustice, and while it may not be possible to prove causality between economic policies and breaches of rights, it is possible to audit policy and practices through the lens of human rights. Child health advocates need to highlight the fact that technical interventions, in the absence of action on structural injustice, cannot address the fundamental causes of poor health. It could even be said that we collude in the fallacy that injustices can be solved with technical solutions. The determinants of health, water, food, shelter, primary education and health care are minimum core human rights, are the rights required for survival and today should be available to every child (and their families) in all countries. However, there are national and global limitations on the ability of countries to determine policy and generate the revenue required for core human rights. The authors conducted a review of the literature on the main leakages from government revenues in low and middle-income countries to identify obstacles to children enjoying their right to survival. Based on the review the authors suggest a framework for an upstream audit that can be carried out, country by country, to identify barriers in terms of policies and the generation, allocation and utilisation of revenues. This audit involves systematically screening the policies and practices of the main actors: national governments, high-income country partners, multinational enterprises, and international organisations, for possible influence on the realisation of human rights. Human rights advocates and child health associations could lead or commission an upstream audit on behalf of children in their countries in order to identify the fundamental causes and real remedies.Publisher PDFPeer reviewe

The positive mental health instrument: development and validation of a culturally relevant scale in a multi-ethnic asian population

<p>Abstract</p> <p>Background</p> <p>Instruments to measure mental health and well-being are largely developed and often used within Western populations and this compromises their validity in other cultures. A previous qualitative study in Singapore demonstrated the relevance of spiritual and religious practices to mental health, a dimension currently not included in exiting multi-dimensional measures. The objective of this study was to develop a self-administered measure that covers all key and culturally appropriate domains of mental health, which can be applied to compare levels of mental health across different age, gender and ethnic groups. We present the item reduction and validation of the Positive Mental Health (PMH) instrument in a community-based adult sample in Singapore.</p> <p>Methods</p> <p>Surveys were conducted among adult (21-65 years) residents belonging to Chinese, Malay and Indian ethnicities. Exploratory and confirmatory factor analysis (EFA, CFA) were conducted and items were reduced using item response theory tests (IRT). The final version of the PMH instrument was tested for internal consistency and criterion validity. Items were tested for differential item functioning (DIF) to check if items functioned in the same way across all subgroups. <b>Results: </b>EFA and CFA identified six first-order factor structure (General coping, Personal growth and autonomy, Spirituality, Interpersonal skills, Emotional support, and Global affect) under one higher-order dimension of Positive Mental Health (RMSEA = 0.05, CFI = 0.96, TLI = 0.96). A 47-item self-administered multi-dimensional instrument with a six-point Likert response scale was constructed. The slope estimates and strength of the relation to the theta for all items in each six PMH subscales were high (range:1.39 to 5.69), suggesting good discrimination properties. The threshold estimates for the instrument ranged from -3.45 to 1.61 indicating that the instrument covers entire spectrums for the six dimensions. The instrument demonstrated high internal consistency and had significant and expected correlations with other well-being measures. Results confirmed absence of DIF.</p> <p>Conclusions</p> <p>The PMH instrument is a reliable and valid instrument that can be used to measure and compare level of mental health across different age, gender and ethnic groups in Singapore.</p

Reference to the index of papers of Robert Mather (1782-1855) and the Mather Family

Robert Mather (1782-1855) settled in V.D.L. in 1822 with his family. He had married in 1811 Ann Benson (1786-1831), daughter of Rev. Joseph Benson, and their children were: Sarah Benson, who married George Washington Walker in 1840, Joseph Benson, Robert Andrew, John, Samuel. See also M.l0 and R.7 for other papers of the Mather family. Papers include letters of various Mather family members to other family members and friends; marriage and birth certificates and obituaries; notes on the history of Quakers; other miscellaneous Quaker correspondence; Andrew Mather Drapery business and the Friends School

Experience of an NIHR Clinical Lectureship (medical/dental) and the determining factors for a clinical academic career post lectureship:a mixed-method evaluation

Objectives: The objective of this study is to investigate early-to-late postdoctoral clinical academic progression and the experiences of NIHR Clinical Lectureship (CL) fellows, considering enablers and barriers to success, and identifying the factors associated with immediate progression to a clinical academic role following completion of the award. Setting: Datasets of CL awardees across the UK. Participants: For semistructured interviews, n=40 CL awardees that had finished their award within the previous 5 years. For quantitative analysis, n=1226 completed or currently active CL awardees. Outcome measures: The responses from the semistructured interviews to the defined questions on experiences during the award, postaward progression, and enablers and barriers to academic progression. Other primary outcome measures were quantitative data on first destinations postaward, demographic data, and whether an awardee had previously held an NIHR Academic Clinical Fellowship (ACF) or was a recipient of the Academy of Medical Sciences (AMS) Starter Grant. Results: CL awardees identified numerous benefits to the award, with the majority achieving their aims. Most awardees progressed to a clinical academic role; however, some returned to a clinical only position, citing concerns around the time pressure associated with balancing clinical and academic responsibilities, and the competition to attain further postdoctoral awards. The region of the award partnership, year of award end and success in applying for an AMS Starter Grant were associated with progression to a clinical academic role. Gender, holding an ACF and having a craft or non-craft specialty had no independent statistical association with clinical academic progression. Conclusions: The CL is a valued element of the Integrated Academic Pathway. By addressing issues around later postdoctoral progression opportunities, responding to challenges experienced by CLs, and by understanding the factors identified in this study associated with clinical academic progression, it should be possible to increase the proportion of CLs that become fully independent clinical academic research leaders. Participants: 1226 NIHR CLs active or completed on the award between 2006 and 2020

Cytokinin induces genome-wide binding of the type-B response regulator ARR10 to regulate growth and development in Arabidopsis

Cytokinins, like other plant hormones, affect a diverse array of plant growth and development processes and responses to the environment. How a signaling molecule mediates such a diverse array of outputs and how these response pathways are integrated with other inputs remain fundamental questions in plant biology. An integrated set of approaches was used to define the targets of the type-B response regulators, a key set of transcription factors that control cytokinin-dependent gene expression. Results shed light on the physiological role of the type-B ARRs in regulating the cytokinin response, mechanism of type-B ARR activation, and basis by which cytokinin regulates diverse aspects of growth and development as well as responses to biotic and abiotic factors

Social Network–Based Recruitment Successfully Reveals HIV-1 Transmission Networks Among High-Risk Individuals in El Salvador

HIV in Central America is concentrated among certain groups such as men who have sex with men (MSM) and female sex workers (FSW). We compared social recruitment chains and HIV transmission clusters from 699 MSM and 757 FSW to better understand factors contributing to ongoing HIV transmission in El Salvador