149 research outputs found

    Cortical fosGFP expression reveals broad receptive field excitatory neurons targeted by POm

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    Neighboring cortical excitatory neurons show considerable heterogeneity in their responses to sensory stimulation. We hypothesized that a subset of layer 2 excitatory neurons in the juvenile (P18 to 27) mouse whisker somatosensory cortex, distinguished by expression of the activity-dependent fosGFP reporter gene, would be preferentially activated by whisker stimulation. In fact, two-photon targeted, dual whole-cell recordings showed that principal whisker stimulation elicits similar amplitude synaptic responses in fosGFP-expressing and fosGFP(-) neurons. FosGFP(+) neurons instead displayed shorter latency and larger amplitude subthreshold responses to surround whisker stimulation. Using optogenetic stimulation, we determined that these neurons are targeted by axons from the posteromedial nucleus (POm), a paralemniscal thalamic nucleus associated with broad receptive fields and widespread cortical projections. We conclude that fosGFP expression discriminates between single- and multi-whisker receptive field layer 2 pyramidal neurons

    Unravelling the genetic causes of mosaic islet morphology in congenital hyperinsulinism

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    Congenital hyperinsulinism (CHI) causes dysregulated insulin secretion which can lead to life-threatening hypoglycaemia if not effectively managed. CHI can be sub-classified into three distinct groups: diffuse, focal and mosaic pancreatic disease. Whilst the underlying causes of diffuse and focal disease have been widely characterised, the genetic basis of mosaic pancreatic disease is not known. To gain new insights into the underlying disease processes of mosaic-CHI we studied the islet tissue histopathology derived from limited surgical resection from the tail of the pancreas in a patient with CHI. The underlying genetic aetiology was investigated using a combination of high depth next-generation sequencing, microsatellite analysis and p57kip2 immunostaining. Histopathology of the pancreatic tissue confirmed the presence of a defined area associated with marked islet hypertrophy and a cytoarchitecture distinct from focal CHI but compatible with mosaic CHI localised to a discrete region within the pancreas. Analysis of DNA extracted from the lesion identified a de novo mosaic ABCC8 mutation and mosaic paternal uniparental disomy which were not present in leukocyte DNA or the surrounding unaffected pancreatic tissue. This study provides the first description of two independent disease-causing somatic genetic events occurring within the pancreas of an individual with localised mosaic CHI. Our findings increase knowledge of the genetic causes of islet disease and provide further insights into the underlying developmental changes associated with ÎČ-cell expansion in CHI.This article is freely available via Open Access. Click on the Publisher URL to read the full-text

    Effect of dielectric constant on estimation of properties of ionic liquids: an analysis of 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide

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    A series of different cationic structures based on 1-alkyl-3-methylimidazolium were combined with a single anion, bis(trifluoromethylsulfonyl)imide (CnmimNTf2, n = 1 to 12) for analyzing the quality of COSMO-RS based estimations. For this purpose, we have studied the structure as well as the estimations of several properties of one ionic liquid (IL). These estimations are obtained from polarization charge distribution in which the IL is embedded. Special attention has been paid to the effect of the dielectric constant value in the predictions. For this purpose, polarization charge density has been modeled using several values of dielectric constant, and properties have been estimated in each case. Thus, σ-profiles and, σ-potentials have been computed and used with COSMO-RS for estimating vapor pressure, as a function of temperature, as well as theoretical values of vaporization enthalpy, density, and viscosity at 298.15 K. The influence of the length of the alkyl chain of ionic liquid in the estimation of these properties has also been tested. Finally, the results have been compared with experimental dataThe authors thank the “Ministerio de Ciencia e InnovaciĂłn” (Project: CTQ2010-19232) and “Comunidad de Madrid” (Project: LIQUORGAS-S2013/MAE-2800) financial suppor

    A Multicenter Experience with Long-Acting Somatostatin Analogues in Patients with Congenital Hyperinsulinism

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    Background/Aims: Congenital hyperinsulinism (CHI) is a rare disease characterized by recurrent severe hypoglycemia. In the diffuse form of CHI, pharmacotherapy is the preferred choice of treatment. Long-acting somatostatin analogues have been used in children as off-label medication. However, the efficacy, outcomes, and adverse effect profiles of long-acting somatostatin analogues have not been described in multicentered studies. The aim of this retrospective study is to summarize the experience with long-acting somatostatin analogues in a large group of children with CHI. Methods: Data were obtained retrospectively from 27 patients with CHI who received long-acting somatostatin analogues in 6 different centers in Europe. These included information on glycemic stability, auxology, and adverse effect profile in clinical follow-up assessments. Results: Blood glucose control improved in most patients (89%). No life-threatening side effects occurred. Thirteen patients (48%) experienced side effects; in 3 patients (11%), the side effects were the main reason for discontinuation of the treatment. The most frequent side effect was elevated liver enzymes (n = 10, 37%). Conclusion: Long-acting somatostatin analogues are effective in glycemic control of patients with CHI. However, in 37% of all patients increased liver enzymes were observed. It is important to monitor liver function in all patients receiving long-acting somatostatin analogue therapy. (C) 2017 S. Karger AG, Base

    Small-molecule inhibition of STOML3 oligomerization reverses pathological mechanical hypersensitivity

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    The skin is equipped with specialized mechanoreceptors that allow the perception of the slightest brush. Indeed, some mechanoreceptors can detect even nanometer-scale movements. Movement is transformed into electrical signals via the gating of mechanically activated ion channels at sensory endings in the skin. The sensitivity of Piezo mechanically gated ion channels is controlled by stomatin-like protein-3 (STOML3), which is required for normal mechanoreceptor function. Here we identify small-molecule inhibitors of STOML3 oligomerization that reversibly reduce the sensitivity of mechanically gated currents in sensory neurons and silence mechanoreceptors in vivo\textit{in vivo}. STOML3 inhibitors in the skin also reversibly attenuate fine touch perception in normal mice. Under pathophysiological conditions following nerve injury or diabetic neuropathy, the slightest touch can produce pain, and here STOML3 inhibitors can reverse mechanical hypersensitivity. Thus, small molecules applied locally to the skin can be used to modulate touch and may represent peripherally available drugs to treat tactile-driven pain following neuropathy.This study was funded by DFG collaborative research grant SFB958 (projects A09 to K.P. and G.R.L., A01 to V.H. and Z02 to J.S.). Additional support was provided by a senior ERC grant (grant number 294678 to G.R.L.) and by the NeuroCure Cluster of Excellence (to V.H., G.R.L. and J.F.A.P.). K.P. was supported by a Cecile-Vogt Fellowship (MDC). S.P. was supported by a Marie Curie Fellowship from the European Union (grant number 253663 Touch in situ). C.P. received a Ph.D. fellowship from the University of Cagliari. J.F.A.P. was funded by a European Research Council (ERC) starting grant (ERC-2010-StG-260590), the DFG (FOR 1341, FOR 2143), the Berlin Institute of Health (BIH) and the European Union (FP7, 3x3Dimaging 323945). R.K. was supported by an ERC Advanced Investigator grant (294293-PAIN PLASTICITY). D.H. was funded by the Berlin Institute of Health (BIH). E.St.J.S., L.E. and M.M. were supported by an Alexander von Humboldt Fellowship

    Infection status and risk factors of HIV, HBV, HCV, and syphilis among drug users in Guangdong, China - a cross-sectional study

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    <p>Abstract</p> <p>Background</p> <p>China has witnessed a remarkable increase in sexually transmitted infections (STIs) and HIV. The study is to assess the prevalence of HIV, HBV, HCV and syphilis and related risk factors among drug users in mandatory detoxification center Qingyuan, Guangdong, China.</p> <p>Method</p> <p>A cross-sectional study on drug use behaviors, sex behaviors, and presence of antibodies to HIV, HCV, Treponema pallidum, and surface antigen of HBV (HBsAg) was conducted among drug users recruited from 3 detoxification centers in Qingyuan, Guangdong, China. Risk factors for each of four infections were analyzed with logistic regression model.</p> <p>Results</p> <p>A total of 740 subjects were recruited, the median age was 31 years old (range 24-38). The seroprevalence rates of HIV, HBsAg, HCV and syphilis were 4.6%, 19.3%, 71.6% and 12.6%, respectively. Risk factors for HIV were intravenous drug use and co-infection with syphilis. Having a regular sexual partner who was a drug user was considered to be a risk factor for HBV. Intravenous drug use was a risk factor for HCV. However, the consistent use of condoms with commercial sex partners was protective for HCV infection. Compared to drug users living in urban area, those living in rural areas were more likely to be infected with syphilis, and there was an association between commercial sex and syphilis.</p> <p>Conclusion</p> <p>The prevalence of HIV, HBV, HCV and syphilis were high among drug users in detoxification centers in Qingyuan, thus, risk reduction programs for the drug user population is urgently required.</p

    Emergency and perioperative management of adrenal insufficiency in children and young people: British Society for Paediatric Endocrinology and Diabetes consensus guidance

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    Adrenal insufficiency (AI) is characterised by lack of cortisol production from the adrenal glands. This can be a primary adrenal disorder or secondary to adrenocorticotropic hormone deficiency or suppression from exogenous glucocorticoids. Symptoms of AI in children may initially be non-specific and include growth faltering, lethargy, poor feeding, weight loss, abdominal pain, vomiting and lingering illnesses. AI is treated with replacement doses of hydrocortisone. At times of physiological stress such as illness, trauma or surgery, there is an increased requirement for exogenous glucocorticoids, which if untreated can lead to an adrenal crisis and death. There are no unified guidelines for those <18 years old in the UK, leading to substantial variation in the management of AI. This paper sets out guidance for intercurrent illness, medical, dental and surgical procedures to allow timely and appropriate recognition and treatment of AI and adrenal crisis for children and young people

    Fatores de risco cardiovascular em pessoas semabrigo e na população geral da cidade do Porto, Portugal

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    We described the distribution of risk factors for cardiovascular disease among homeless people living in the city of Porto, Portugal. Comparisons were made between subsamples of homeless people recruited in different settings and between the overall homeless sample group and a sample of the general population. All "houseless" individuals attending one of two homeless hostels or two institutions providing meal programs on specific days were invited to participate and were matched with subjects from the general population. We estimated sex, age and education-adjusted prevalence ratios or mean differences. The prevalence of previous illicit drug consumption and imprisonment was almost twice as high among the homeless from institutions providing meal programs. This group also showed lower mean systolic and diastolic blood pressure. Prevalence of smoking was almost 50% higher in the overall homeless group. Mean body mass index and waist circumference were also lower in the homeless group and its members were almost five times less likely to report dyslipidemia. Our findings contribute to defining priorities for interventions directed at this segment of society and to reducing inequalities in this extremely underprivileged populatio
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