Painful losses

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134073/1/jhm2610-sup-0001-suppinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134073/2/jhm2610.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134073/3/jhm2610-sup-0002-suppinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134073/4/jhm2610-sup-0005-suppinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134073/5/jhm2610-sup-0003-suppinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134073/6/jhm2610-sup-0004-suppinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134073/7/jhm2610_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134073/8/jhm2610-sup-0007-suppinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134073/9/jhm2610-sup-0006-suppinfo.pd

Features of successful academic hospitalist programs: Insights from the SCHOLAR (SuCcessful HOspitaLists in academics and research) project

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/1/jhm2603.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/2/jhm2603-sup-0004-suppinfo4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/3/jhm2603-sup-0001-suppinfo1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/4/jhm2603-sup-0010-suppinfo10.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/5/jhm2603-sup-0006-suppinfo6.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/6/jhm2603-sup-0005-suppinfo5.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/7/jhm2603-sup-0009-suppinfo9.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/8/jhm2603-sup-0012-suppinfo12.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/9/jhm2603-sup-0003-suppinfo3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/10/jhm2603-sup-0002-suppinfo2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/11/jhm2603_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/12/jhm2603-sup-0008-suppinfo8.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/13/jhm2603-sup-0011-suppinfo11.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134172/14/jhm2603-sup-0007-suppinfo7.pd

Role of metabolically active hormones in the insulin resistance associated with short-term glucocorticoid treatment

BACKGROUND: The mechanisms by which glucocorticoid therapy promotes obesity and insulin resistance are incompletely characterized. Modulations of the metabolically active hormones, tumour necrosis factor alpha (TNF alpha), ghrelin, leptin and adiponectin are all implicated in the development of these cardiovascular risk factors. Little is known about the effects of short-term glucocorticoid treatment on levels of these hormones. RESEARCH METHODS AND PROCEDURES: Using a blinded, placebo-controlled approach, we randomised 25 healthy men (mean (SD) age: 24.2 (5.4) years) to 5 days of treatment with either placebo or oral dexamethasone 3 mg twice daily. Fasting plasma TNFα, ghrelin, leptin and adiponectin were measured before and after treatment. RESULTS: Mean changes in all hormones were no different between treatment arms, despite dexamethasone-related increases in body weight, blood pressure, HDL cholesterol and insulin. Changes in calculated indices of insulin sensitivity (HOMA-S, insulin sensitivity index) were strongly related to dexamethasone treatment (p < 0.001). DISCUSSION: Our data do not support a role for TNF alpha, ghrelin, leptin or adiponectin in the insulin resistance associated with short-term glucocorticoid treatment

Fibronectin Matrix Assembly Suppresses Dispersal of Glioblastoma Cells

Glioblastoma (GBM), the most aggressive and most common form of primary brain tumor, has a median survival of 12–15 months. Surgical excision, radiation and chemotherapy are rarely curative since tumor cells broadly disperse within the brain. Preventing dispersal could be of therapeutic benefit. Previous studies have reported that increased cell-cell cohesion can markedly reduce invasion by discouraging cell detachment from the tumor mass. We have previously reported that α5β1 integrin-fibronectin interaction is a powerful mediator of indirect cell-cell cohesion and that the process of fibronectin matrix assembly (FNMA) is crucial to establishing strong bonds between cells in 3D tumor-like spheroids. Here, we explore a potential role for FNMA in preventing dispersal of GBM cells from a tumor-like mass. Using a series of GBM-derived cell lines we developed an in vitro assay to measure the dispersal velocity of aggregates on a solid substrate. Despite their similar pathologic grade, aggregates from these lines spread at markedly different rates. Spreading velocity is inversely proportional to capacity for FNMA and restoring FNMA in GBM cells markedly reduces spreading velocity by keeping cells more connected. Blocking FNMA using the 70 KDa fibronectin fragment in FNMA-restored cells rescues spreading velocity, establishing a functional role for FNMA in mediating dispersal. Collectively, the data support a functional causation between restoration of FNMA and decreased dispersal velocity. This is a first demonstration that FNMA can play a suppressive role in GBM dispersal

Dimensions and Latent Classes of Episodic Mania-Like Symptoms in Youth: An Empirical Enquiry

The dramatic increase in diagnostic rates of bipolar disorder in children and adolescents in the USA has led to an intense interest in the phenomenology of the disorder. Here we present data from a newly-developed instrument to assess episodic mania-like symptoms in youth in a large population-based sample (N = 5326) using parent- and self-report. We found that a substantial proportion of children screened positive for having episodes of “going high” and were at an increased risk for morbidity and impairment. Using factor analysis, we identified that episodic mania-like symptoms comprised two dimensions: An under-controlled dimension that was associated with significant impairment, and a low-risk exuberant dimension. Using latent class analysis, we identified a small group of children scoring high on a range of manic symptoms and suffering from severe psychosocial impairment and morbidity. Our results carry implications for the nosology and psychosocial impairment associated with episodic mood changes in young people

Behavioral and Autonomic Responses to Acute Restraint Stress Are Segregated within the Lateral Septal Area of Rats

Background: The Lateral Septal Area (LSA) is involved with autonomic and behavior responses associated to stress. In rats, acute restraint (RS) is an unavoidable stress situation that causes autonomic (body temperature, mean arterial pressure (MAP) and heart rate (HR) increases) and behavioral (increased anxiety-like behavior) changes in rats. The LSA is one of several brain regions that have been involved in stress responses. The aim of the present study was to investigate if the neurotransmission blockade in the LSA would interfere in the autonomic and behavioral changes induced by RS. Methodology/Principal Findings: Male Wistar rats with bilateral cannulae aimed at the LSA, an intra-abdominal datalogger (for recording internal body temperature), and an implanted catheter into the femoral artery (for recording and cardiovascular parameters) were used. They received bilateral microinjections of the non-selective synapse blocker cobalt chloride (CoCl2, 1 mM / 100 nL) or vehicle 10 min before RS session. The tail temperature was measured by an infrared thermal imager during the session. Twenty-four h after the RS session the rats were tested in the elevated plus maze (EPM). Conclusions/Significance: Inhibition of LSA neurotransmission reduced the MAP and HR increases observed during RS. However, no changes were observed in the decrease in skin temperature and increase in internal body temperature observed during this period. Also, LSA inhibition did not change the anxiogenic effect induced by RS observed 24 h later in the EPM. The present results suggest that LSA neurotransmission is involved in the cardiovascular but not the temperatur

Biology and biotechnology of Trichoderma

Fungi of the genus Trichoderma are soilborne, green-spored ascomycetes that can be found all over the world. They have been studied with respect to various characteristics and applications and are known as successful colonizers of their habitats, efficiently fighting their competitors. Once established, they launch their potent degradative machinery for decomposition of the often heterogeneous substrate at hand. Therefore, distribution and phylogeny, defense mechanisms, beneficial as well as deleterious interaction with hosts, enzyme production and secretion, sexual development, and response to environmental conditions such as nutrients and light have been studied in great detail with many species of this genus, thus rendering Trichoderma one of the best studied fungi with the genome of three species currently available. Efficient biocontrol strains of the genus are being developed as promising biological fungicides, and their weaponry for this function also includes secondary metabolites with potential applications as novel antibiotics. The cellulases produced by Trichoderma reesei, the biotechnological workhorse of the genus, are important industrial products, especially with respect to production of second generation biofuels from cellulosic waste. Genetic engineering not only led to significant improvements in industrial processes but also to intriguing insights into the biology of these fungi and is now complemented by the availability of a sexual cycle in T. reesei/Hypocrea jecorina, which significantly facilitates both industrial and basic research. This review aims to give a broad overview on the qualities and versatility of the best studied Trichoderma species and to highlight intriguing findings as well as promising applications

Shared and Disorder-Specific Event-Related Brain Oscillatory Markers of Attentional Dysfunction in ADHD and Bipolar Disorder.

Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) often present with overlapping symptoms and cognitive impairments, such as increased fluctuations in attentional performance measured by increased reaction-time variability (RTV). We previously provided initial evidence of shared and distinct event-related potential (ERP) impairments in ADHD and BD in a direct electrophysiological comparison, but no study to date has compared neural mechanisms underlying attentional impairments with finer-grained brain oscillatory markers. Here, we aimed to compare the neural underpinnings of impaired attentional processes in ADHD and BD, by examining event-related brain oscillations during a reaction-time task under slow-unrewarded baseline and fast-incentive conditions. We measured cognitive performance, ERPs and brain-oscillatory modulations of power and phase variability in 20 women with ADHD, 20 women with BD (currently euthymic) and 20 control women. Compared to controls, both ADHD and BD groups showed increased RTV in the baseline condition and increased RTV, theta phase variability and lower contingent negative variation in the fast-incentive condition. Unlike controls, neither clinical group showed an improvement from the slow-unrewarded baseline to the fast-incentive condition in attentional P3 amplitude or alpha power suppression. Most impairments did not differ between the disorders, as only an adjustment in beta suppression between conditions (lower in the ADHD group) distinguished between the clinical groups. These findings suggest shared impairments in women with ADHD and BD in cognitive and neural variability, preparatory activity and inability to adjust attention allocation and activation. These overlapping impairments may represent shared neurobiological mechanisms of attentional dysfunction in ADHD and BD, and potentially underlie common symptoms in both disorders.We thank all who made this research possible: The National Adult ADHD Clinic at the South London and Maudsley Hospital, Dr Helen Costello, Prof Sophia Frangou, Prof Anne Farmer, Jessica Deadman, Hannah Collyer, Sarah-Jane Gregori, and all participants who contributed their time to the study. Dr Giorgia Michelini was supported by a 1+3 PhD studentship awarded by the MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London (G9817803). This project was supported by an Economic and Social Research Council studentship to Dr Viryanaga Kitsune (ES/100971X/1). Dr Giorgia Michelini and Prof Philip Asherson are supported by generous grants from the National Institute for Health Research Biomedical Research Centre for Mental Health at King’s College London, Institute of Psychiatry, Psychology and Neuroscience and South London and Maudsley National Health Service (NHS) Foundation Trust. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication