469 research outputs found

    Somatosensory inputs modify auditory spike timing in dorsal cochlear nucleus principal cells

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    In addition to auditory inputs, dorsal cochlear nucleus (DCN) pyramidal cells in the guinea pig receive and respond to somatosensory inputs and perform multisensory integration. DCN pyramidal cells respond to sounds with characteristic spike-timing patterns that are partially controlled by rapidly inactivating potassium conductances. Deactivating these conductances can modify both spike rate and spike timing of responses to sound. Somatosensory pathways are known to modify response rates to subsequent acoustic stimuli, but their effect on spike timing is unknown. Here, we demonstrate that preceding tonal stimulation with spinal trigeminal nucleus (Sp5) stimulation significantly alters the first spike latency, the first interspike interval, and the average discharge regularity of firing evoked by the tone. These effects occur whether the neuron is excited or inhibited by Sp5 stimulation alone. Our results demonstrate that multisensory integration in DCN alters spike-timing representations of acoustic stimuli in pyramidal cells. These changes likely occur through synaptic modulation of intrinsic excitability or synaptic inhibition

    137,138,139^{137,138,139}La(nn, γ\gamma) cross sections constrained with statistical decay properties of 138,139,140^{138,139,140}La nuclei

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    The nuclear level densities and γ\gamma-ray strength functions of 138,139,140^{138,139,140}La were measured using the 139^{139}La(3^{3}He, α\alpha), 139^{139}La(3^{3}He, 3^{3}He^\prime) and 139^{139}La(d, p) reactions. The particle-γ\gamma coincidences were recorded with the silicon particle telescope (SiRi) and NaI(Tl) (CACTUS) arrays. In the context of these experimental results, the low-energy enhancement in the A\sim140 region is discussed. The 137,138,139^{137,138,139}La(n,γ)n, \gamma) cross sections were calculated at ss- and pp-process temperatures using the experimentally measured nuclear level densities and γ\gamma-ray strength functions. Good agreement is found between 139^{139}La(n,γ)n, \gamma) calculated cross sections and previous measurements

    Recent Progress and Recommendations on Celiac Disease From the Working Group on Prolamin Analysis and Toxicity

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    Celiac disease (CD) affects a growing number of individuals worldwide. To elucidate the causes for this increase, future multidisciplinary collaboration is key to understanding the interactions between immunoreactive components in gluten-containing cereals and the human gastrointestinal tract and immune system and to devise strategies for CD prevention and treatment beyond the gluten-free diet. During the last meetings, the Working Group on Prolamin Analysis and Toxicity (Prolamin Working Group, PWG) discussed recent progress in the field together with key stakeholders from celiac disease societies, academia, industry and regulatory bodies. Based on the current state of knowledge, this perspective from the PWG members provides recommendations regarding clinical, analytical and legal aspects of CD. The selected key topics that require future multidisciplinary collaborative efforts in the clinical field are to collect robust data on the increasing prevalence of CD, to evaluate what is special about gluten-specific T cells, to study their kinetics and transcriptomics and to put some attention to the identification of the environmental agents that facilitate the breaking of tolerance to gluten. In the field of gluten analysis, the key topics are the precise assessment of gluten immunoreactive components in wheat, rye and barley to understand how these are affected by genetic and environmental factors, the comparison of different methods for compliance monitoring of gluten-free products and the development of improved reference materials for gluten analysis

    Statement of the Prolamin Working Group on the Determination of Gluten in Fermented Foods Containing Partially Hydrolyzed Gluten

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    On August 12, 2020, the U.S. Food and Drug Administration (FDA) has finalized a rule related to gluten-free labeling for foods containing fermented, hydrolyzed ingredients. The FDA believes that there is no scientifically valid analytical method e ective for determining gluten in fermented or hydrolyzed foods. In the absence of an analytical method, the FDA has decided to evaluate gluten-free claims on these foods based only on evidence that the food or ingredient used is gluten-free before fermentation or hydrolysis. For example, barley-based beers from which gluten is removed during brewing using special filtration, adsorption and/or enzymatic treatment are therefore excluded from bearing a gluten-free label. The Prolamin Working Group (PWG) acknowledges that the FDA rule is a regulatory act and might have to take into consideration several aspects other than scientific evidence, including risk assessment. Nevertheless, the PWG thinks that science has to be the most important driver for regulatory acts in risk management.Fil: Scherf, Katharina Anne. Karlsruher Institut Für Technologie; AlemaniaFil: Catassi, Carlo. Università Politecnica Delle Marche; ItaliaFil: Chirdo, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Ciclitira, Paul J.. University of East Anglia; Reino UnidoFil: Feighery, Conleth Francis. Universidad de Dublin; IrlandaFil: Gianfrani, Carmen. Institute of Biochemistry and Cell Biology; ItaliaFil: Koning, Frits. Leiden University; Países BajosFil: Lundin, Knut E. A.. University of Oslo; NoruegaFil: Masci, Stefania. No especifíca;Fil: Schuppan, Detlef. No especifíca;Fil: Smulders, Marinus J. M.. Wageningen University and Research; Países BajosFil: Tranquet, Olivier. No especifíca;Fil: Troncone, Riccardo. University Federico II; ItaliaFil: Koehler, Peter. No especifíca

    Statement of the Prolamin Working Group on the Determination of Gluten in Fermented Foods Containing Partially Hydrolyzed Gluten

    Get PDF
    On August 12, 2020, the U.S. Food and Drug Administration (FDA) has finalized a rule related to gluten-free labeling for foods containing fermented, hydrolyzed ingredients. The FDA believes that there is no scientifically valid analytical method effective for determining gluten in fermented or hydrolyzed foods. In the absence of an analytical method, the FDA has decided to evaluate gluten-free claims on these foods based only on evidence that the food or ingredient used is gluten-free before fermentation or hydrolysis. For example, barley-based beers from which gluten is removed during brewing using special filtration, adsorption and/or enzymatic treatment are therefore excluded from bearing a gluten-free label

    Transcriptional Profiling of Bacillus anthracis Sterne (34F2) during Iron Starvation

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    Lack of available iron is one of many environmental challenges that a bacterium encounters during infection and adaptation to iron starvation is important for the pathogen to efficiently replicate within the host. Here we define the transcriptional response of B. anthracis Sterne (34F2) to iron depleted conditions. Genome-wide transcript analysis showed that B. anthracis undergoes considerable changes in gene expression during growth in iron-depleted media, including the regulation of known and candidate virulence factors. Two genes encoding putative internalin proteins were chosen for further study. Deletion of either gene (GBAA0552 or GBAA1340) resulted in attenuation in a murine model of infection. This attenuation was amplified in a double mutant strain. These data define the transcriptional changes induced during growth in low iron conditions and illustrate the potential of this dataset in the identification of putative virulence determinants for future study

    Anthroponotic transmission of Cryptosporidium parvum predominates in countries with poorer sanitation - a systematic review and meta-analysis

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    Background: Globally cryptosporidiosis is one of the commonest causes of mortality in children under 24 months old and may be associated with important longterm health effects. Whilst most strains of Cryptosporidium parvum are zoonotic, C. parvum IIc is almost certainly anthroponotic. The global distribution of this potentially important emerging infection is not clear. Methods: We conducted a systematic review of papers identifying the subtype distribution of C. parvum infections globally. We searched PubMed and Scopus using the following key terms Cryptospor* AND parvum AND (genotyp* OR subtyp* OR gp60). Studies were eligible for inclusion if they had found C. parvum within their human study population and had subtyped some or all of these samples using standard gp60 subtyping. Pooled analyses of the proportion of strains being of the IIc subtype were determined using StatsDirect. Meta-regression analyses were run to determine any association between the relative prevalence of IIc and Gross Domestic Product, proportion of the population with access to improved drinking water and improved sanitation. Results: From an initial 843 studies, 85 were included in further analysis. Cryptosporidium parvum IIc was found in 43 of these 85 studies. Across all studies the pooled estimate of relative prevalence of IIc was 19.0% (95% CI: 12.9–25.9%), but there was substantial heterogeneity. In a meta-regression analysis, the relative proportion of all C. parvum infections being IIc decreased as the percentage of the population with access to improved sanitation increased and was some 3.4 times higher in those studies focussing on HIV-positive indivduals. Conclusions: The anthroponotic C. parvum IIc predominates primarily in lower-income countries with poor sanitation and in HIV-positive individuals. Given the apparent enhanced post-infectious virulence of the other main anthroponotic species of Cryptosporidium (C. hominis), it is important to learn about the impact of this subtype on human health

    Anthroponotic transmission of Cryptosporidium parvum predominates in countries with poorer sanitation - a systematic review and meta-analysis

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    Background: Globally cryptosporidiosis is one of the commonest causes of mortality in children under 24 months old and may be associated with important longterm health effects. Whilst most strains of Cryptosporidium parvum are zoonotic, C. parvum IIc is almost certainly anthroponotic. The global distribution of this potentially important emerging infection is not clear. Methods: We conducted a systematic review of papers identifying the subtype distribution of C. parvum infections globally. We searched PubMed and Scopus using the following key terms Cryptospor* AND parvum AND (genotyp* OR subtyp* OR gp60). Studies were eligible for inclusion if they had found C. parvum within their human study population and had subtyped some or all of these samples using standard gp60 subtyping. Pooled analyses of the proportion of strains being of the IIc subtype were determined using StatsDirect. Meta-regression analyses were run to determine any association between the relative prevalence of IIc and Gross Domestic Product, proportion of the population with access to improved drinking water and improved sanitation. Results: From an initial 843 studies, 85 were included in further analysis. Cryptosporidium parvum IIc was found in 43 of these 85 studies. Across all studies the pooled estimate of relative prevalence of IIc was 19.0% (95% CI: 12.9–25.9%), but there was substantial heterogeneity. In a meta-regression analysis, the relative proportion of all C. parvum infections being IIc decreased as the percentage of the population with access to improved sanitation increased and was some 3.4 times higher in those studies focussing on HIV-positive indivduals. Conclusions: The anthroponotic C. parvum IIc predominates primarily in lower-income countries with poor sanitation and in HIV-positive individuals. Given the apparent enhanced post-infectious virulence of the other main anthroponotic species of Cryptosporidium (C. hominis), it is important to learn about the impact of this subtype on human health

    Clinical decision making in the recognition of dying: a qualitative interview study

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    BACKGROUND: Recognising dying is an essential clinical skill for general and palliative care professionals alike. Despite the high importance, both identification and good clinical care of the dying patient remains extremely difficult and often controversial in clinical practice. This study aimed to answer the question: "What factors influence medical and nursing staff when recognising dying in end-stage cancer and heart failure patients?" METHODS: This study used a descriptive approach to decision-making theory. Participants were purposively sampled for profession (doctor or nurse), specialty (cardiology or oncology) and grade (senior vs junior). Recruitment continued until data saturation was reached. Semi-structured interviews were conducted with NHS medical and nursing staff in an NHS Trust which contained cancer and cardiology tertiary referral centres. An interview schedule was designed, based on decision-making literature. Interviews were audio-recorded and transcribed and analysed using thematic framework. Data were managed with Atlas.ti. RESULTS: Saturation was achieved with 19 participants (7 seniors; 8 intermediate level staff; 4 juniors). There were 11 oncologists (6 doctors, 5 nurses) and 8 cardiologists (3 doctors, 5 nurses). Six themes were generated: information used; decision processes; modifying factors; implementation; reflecting on decisions and related decisions. The decision process described was time-dependent, ongoing and iterative, and relies heavily on intuition. CONCLUSIONS: This study supports the need to recognise the strengths and weaknesses of expertise and intuition as part of the decision process, and of placing the recognition of dying in a time-dependent context. Clinicians should also be prepared to accept and convey the uncertainty surrounding these decisions, both in practice and in communication with patients and carers
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