Type III Mixed Cryoglobulinemia and Antiphospholipid Syndrome in a Patient With Partial DiGeorge Syndrome

We studied a 14 year-old boy with partial DiGeorge syndrome (DGS), status post complete repair of Tetralogy of Fallot, who developed antiphospholipid syndrome (APS) and type III mixed cryoglobulinemia. He presented with recurrent fever and dyspnea upon exertion secondary to right pulmonary embolus on chest computed tomography (CT). Coagulation studies revealed homozygous methylene tetrahydrofolate reductase 677TT mutations, elevated cardiolipin IgM antibodies, and elevated β2-glycoprotein I IgM antibodies. Infectious work-up revealed only positive anti-streptolysin O (ASO) and anti-DNAse B titers. Autoimmune studies showed strongly positive anti-platelet IgM, elevated rheumatoid factor (RF), and positive cryocrit. Renal biopsy for evaluation of proteinuria and hematuria showed diffuse proliferative glomerulonephritis (DPGN) with membranoproliferative features consistent with cryoglobulinemia. Immunofixation showed polyclonal bands. Our patient was treated successfully with antibiotics, prednisone, and mycophenolate mofetil (MMF). This is the first report of a patient with partial DGS presenting with APS and type III mixed cryoglobulinemia possibly due to Streptococcal infection

Global State Measures of the Dentate Gyrus Gene Expression System Predict Antidepressant-Sensitive Behaviors

Background Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are the most common form of medication treatment for major depression. However, approximately 50% of depressed patients fail to achieve an effective treatment response. Understanding how gene expression systems respond to treatments may be critical for understanding antidepressant resistance. Methods We take a novel approach to this problem by demonstrating that the gene expression system of the dentate gyrus responds to fluoxetine (FLX), a commonly used antidepressant medication, in a stereotyped-manner involving changes in the expression levels of thousands of genes. The aggregate behavior of this large-scale systemic response was quantified with principal components analysis (PCA) yielding a single quantitative measure of the global gene expression system state. Results Quantitative measures of system state were highly correlated with variability in levels of antidepressant-sensitive behaviors in a mouse model of depression treated with fluoxetine. Analysis of dorsal and ventral dentate samples in the same mice indicated that system state co-varied across these regions despite their reported functional differences. Aggregate measures of gene expression system state were very robust and remained unchanged when different microarray data processing algorithms were used and even when completely different sets of gene expression levels were used for their calculation. Conclusions System state measures provide a robust method to quantify and relate global gene expression system state variability to behavior and treatment. State variability also suggests that the diversity of reported changes in gene expression levels in response to treatments such as fluoxetine may represent different perspectives on unified but noisy global gene expression system state level responses. Studying regulation of gene expression systems at the state level may be useful in guiding new approaches to augmentation of traditional antidepressant treatments

Fibroblast and Lymphoblast Gene Expression Profiles in Schizophrenia: Are Non-Neural Cells Informative?

Lymphoblastoid cell lines (LCLs) and fibroblasts provide conveniently derived non-neuronal samples in which to investigate the aetiology of schizophrenia (SZ) using gene expression profiling. This assumes that heritable mechanisms associated with risk of SZ have systemic effects and result in changes to gene expression in all tissues. The broad aim of this and other similar studies is that comparison of the transcriptomes of non-neuronal tissues from SZ patients and healthy controls may identify gene/pathway dysregulation underpinning the neurobiological defects associated with SZ. Using microarrays consisting of 18,664 probes we compared gene expression profiles of LCLs from SZ cases and healthy controls. To identify robust associations with SZ that were not patient or tissue specific, we also examined fibroblasts from an independent series of SZ cases and controls using the same microarrays. In both tissue types ANOVA analysis returned approximately the number of differentially expressed genes expected by chance. No genes were significantly differentially expressed in either tissue when corrected for multiple testing. Even using relaxed parameters (p≤0.05, without multiple testing correction) there were still no differentially expressed genes that also displayed ≥2-fold change between the groups of SZ cases and controls common to both LCLs and fibroblasts. We conclude that despite encouraging data from previous microarray studies assessing non-neural tissues, the lack of a convergent set of differentially expressed genes associated with SZ using fibroblasts and LCLs indicates the utility of non-neuronal tissues for detection of gene expression differences and/or pathways associated with SZ remains to be demonstrated

Logistic support provided to Australian disaster medical assistance teams: results of a national survey of team members

Background: It is likely that calls for disaster medical assistance teams (DMATs) continue in response to international disasters. As part of a national survey, the present study was designed to evaluate the Australian DMAT experience and the need for logistic support.\ud \ud Methods: Data were collected via an anonymous mailed survey distributed via State and Territory representatives on the Australian Health Protection Committee, who identified team members associated with Australian DMAT deployments from the 2004 Asian Tsunami disaster.\ud \ud Results: The response rate for this survey was 50% (59/118). Most of the personnel had deployed to the South East Asian Tsunami affected areas. The DMAT members had significant clinical and international experience. There was unanimous support for dedicated logistic support with 80% (47/59) strongly agreeing. Only one respondent (2%) disagreed with teams being self sufficient for a minimum of 72 hours. Most felt that transport around the site was not a problem (59%; 35/59), however, 34% (20/59) felt that transport to the site itself was problematic. Only 37% (22/59) felt that pre-deployment information was accurate. Communication with local health providers and other agencies was felt to be adequate by 53% (31/59) and 47% (28/59) respectively, while only 28% (17/59) felt that documentation methods were easy to use and reliable. Less than half (47%; 28/59) felt that equipment could be moved easily between areas by team members and 37% (22/59) that packaging enabled materials to be found easily. The maximum safe container weight was felt to be between 20 and 40 kg by 58% (34/59).\ud \ud Conclusions: This study emphasises the importance of dedicated logistic support for DMAT and the need for teams to be self sufficient for a minimum period of 72 hours. There is a need for accurate pre deployment information to guide resource prioritisation with clearly labelled pre packaging to assist access on site. Container weights should be restricted to between 20 and 40 kg, which would assist transport around the site, while transport to the site was seen as problematic. There was also support for training of all team members in use of basic equipment such as communications equipment, tents and shelters and water purification systems

A Low Dose of Dietary Resveratrol Partially Mimics Caloric Restriction and Retards Aging Parameters in Mice

Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg−1 day−1), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles. We report a striking transcriptional overlap of CR and resveratrol in heart, skeletal muscle and brain. Both dietary interventions inhibit gene expression profiles associated with cardiac and skeletal muscle aging, and prevent age-related cardiac dysfunction. Dietary resveratrol also mimics the effects of CR in insulin mediated glucose uptake in muscle. Gene expression profiling suggests that both CR and resveratrol may retard some aspects of aging through alterations in chromatin structure and transcription. Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics some aspects of CR

UK guideline on transition of adolescent and young persons with chronic digestive diseases from paediatric to adult care

The risks of poor transition include delayed and inappropriate transfer that can result in disengagement with healthcare. Structured transition care can improve control of chronic digestive diseases and long-term health-related outcomes. These are the first nationally developed guidelines on the transition of adolescent and young persons (AYP) with chronic digestive diseases from paediatric to adult care. They were commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology under the auspices of the Adolescent and Young Persons (A&YP) Section. Electronic searches for English-language articles were performed with keywords relating to digestive system diseases and transition to adult care in the Medline (via Ovid), PsycInfo (via Ovid), Web of Science and CINAHL databases for studies published from 1980 to September 2014. The quality of evidence and grading of recommendations was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The limited number of studies in gastroenterology and hepatology required the addition of relevant studies from other chronic diseases to be included. These guidelines deal specifically with the transition of AYP living with a diagnosis of chronic digestive disease and/or liver disease from paediatric to adult healthcare under the following headings; 1. Patient populations involved in AYP transition 2. Risks of failing transition or poor transition 3. Models of AYP transition 4. Patient and carer/parent perspective in AYP transition 5. Surgical perspectiv

Loss of STOP Protein Impairs Peripheral Olfactory Neurogenesis

International audienceIn conclusion, STOP protein seems to be involved in the establishment of synapses in the olfactory glomerulus. Our results indicate that the olfactory system of STOP null mice is a well-suited experimental model (1) for the study of the mechanism of action of STOP protein in synaptic function/plasticity and (2) for pathophysiological studies of the mechanisms of altered neuronal connections in schizophrenia

Laser spectroscopy for breath analysis : towards clinical implementation

Detection and analysis of volatile compounds in exhaled breath represents an attractive tool for monitoring the metabolic status of a patient and disease diagnosis, since it is non-invasive and fast. Numerous studies have already demonstrated the benefit of breath analysis in clinical settings/applications and encouraged multidisciplinary research to reveal new insights regarding the origins, pathways, and pathophysiological roles of breath components. Many breath analysis methods are currently available to help explore these directions, ranging from mass spectrometry to laser-based spectroscopy and sensor arrays. This review presents an update of the current status of optical methods, using near and mid-infrared sources, for clinical breath gas analysis over the last decade and describes recent technological developments and their applications. The review includes: tunable diode laser absorption spectroscopy, cavity ring-down spectroscopy, integrated cavity output spectroscopy, cavity-enhanced absorption spectroscopy, photoacoustic spectroscopy, quartz-enhanced photoacoustic spectroscopy, and optical frequency comb spectroscopy. A SWOT analysis (strengths, weaknesses, opportunities, and threats) is presented that describes the laser-based techniques within the clinical framework of breath research and their appealing features for clinical use.Peer reviewe

Software for the frontiers of quantum chemistry:An overview of developments in the Q-Chem 5 package

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange–correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear–electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an “open teamware” model and an increasingly modular design