NOD2 gene mutations in ulcerative colitis: useless or misunderstood?

PURPOSE: NOD2 mutations have been linked to an increased risk of Crohn's disease and to some of its phenotypes. The association between NOD2 mutations and susceptibility to ulcerative colitis (UC) remains somewhat controversial and potential correlations between these mutations and UC phenotype have not been studied. AIM: To assess whether NOD2 mutations are a risk factor for UC in Portugal and if there are any genotype-phenotype correlations in these patients. METHODS: The three main NOD2 mutations were searched in 200 patients with UC and in 202 healthy controls. RESULTS: NOD2 mutations were present in 28 patients with UC (14.0 %) and in 27 controls (13.4 %) (p = 0.853). Mutation carriers were more likely to receive steroids during the first year of disease than non-carriers (54.2 % vs. 29.6 %, p = 0.018) and among these patients the need for intravenous administration was more frequent in those with the R702W polymorphism (90.0 % vs. 45.5 %, p = 0.014). In patients with severe colitis admitted for intravenous steroids, a greater proportion of mutation carriers was considered intravenous-steroid refractory and required salvage therapy (90.0 % vs. 38.1 %, p = 0.004). Patients with NOD2 mutation were submitted to colectomy more frequently than non-carriers (17.9 % vs. 4.1 %. p = 0.015). No correlation with the need for immunosuppressants/immunomodulators was found. CONCLUSIONS: In the Portuguese population, NOD2 mutations do not increase the risk of UC but are associated with a more aggressive course including greater need of steroids in the first year, increased incidence of intravenous-steroid refractoriness and a higher colectomy rate

A 16-nm SoC for Noise-Robust Speech and NLP Edge AI Inference With Bayesian Sound Source Separation and Attention-Based DNNs

The proliferation of personal artificial intelligence (AI) -assistant technologies with speech-based conversational AI interfaces is driving the exponential growth in the consumer Internet of Things (IoT) market. As these technologies are being applied to keyword spotting (KWS), automatic speech recognition (ASR), natural language processing (NLP), and text-to-speech (TTS) applications, it is of paramount importance that they provide uncompromising performance for context learning in long sequences, which is a key benefit of the attention mechanism, and that they work seamlessly in polyphonic environments. In this work, we present a 25-mm $^2$ system-on-chip (SoC) in 16-nm FinFET technology, codenamed SM6, which executes end-to-end speech-enhancing attention-based ASR and NLP workloads. The SoC includes: 1) FlexASR, a highly reconfigurable NLP inference processor optimized for whole-model acceleration of bidirectional attention-based sequence-to-sequence (seq2seq) deep neural networks (DNNs); 2) a Markov random field source separation engine (MSSE), a probabilistic graphical model accelerator for unsupervised inference via Gibbs sampling, used for sound source separation; 3) a dual-core Arm Cortex A53 CPU cluster, which provides on-demand single Instruction/multiple data (SIMD) fast fourier transform (FFT) processing and performs various application logic (e.g., expectation–maximization (EM) algorithm and 8-bit floating-point (FP8) quantization); and 4) an always-on M0 subsystem for audio detection and power management. Measurement results demonstrate the efficiency ranges of 2.6–7.8 TFLOPs/W and 4.33–17.6 Gsamples/s/W for FlexASR and MSSE, respectively; MSSE denoising performance allowing 6 $\times$ smaller ASR model to be stored on-chip with negligible accuracy loss; and 2.24-mJ energy consumption while achieving real-time throughput, end-to-end, and per-frame ASR latencies of 18 ms

An integrated strategy for the prevention of SARS-CoV-2 infection in healthcare workers: a prospective observational study

BACKGROUND: Since the beginning of SARS-CoV-2 outbreak, a large number of infections have been reported among healthcare workers (HCWs). The aim of this study was to investigate the occurrence of SARS-CoV-2 infection among HCWs involved in the first management of infected patients and to describe the measures adopted to prevent the transmission in the hospital. METHODS: This prospective observational study was conducted between February 21 and April 16, 2020, in the Padua University Hospital (north-east Italy). The infection control policy adopted consisted of the following: the creation of the "Advanced Triage" area for the evaluation of SARS-CoV-2 cases, and the implementation of an integrated infection control surveillance system directed to all the healthcare personnel involved in the Advance Triage area. HCWs were regularly tested with nasopharyngeal swabs for SARS-CoV-2; body temperature and suggestive symptoms were evaluated at each duty. Demographic and clinical data of both patients and HCWs were collected and analyzed; HCWs' personal protective equipment (PPE) consumption was also recorded. The efficiency of the control strategy among HCWs was evaluated identifying symptomatic infection (primary endpoint) and asymptomatic infection (secondary endpoint) with confirmed detection of SARS-CoV-2. RESULTS: 7595 patients were evaluated in the Advanced Triage area: 5.2% resulted positive and 72.4% was symptomatic. The HCW team was composed of 60 members. A total of 361 nasopharyngeal swabs were performed on HCWs. All the swabs resulted negative and none of the HCWs reached the primary or the secondary endpoint. CONCLUSIONS: An integrated hospital infection control strategy, consisting of dedicated areas for infected patients, strict measures for PPE use and mass surveillance, is successful to prevent infection among HCWs

Transverse Plane Tendon and Median Nerve Motion in the Carpal Tunnel: Ultrasound Comparison of Carpal Tunnel Syndrome Patients and Healthy Volunteers

The median nerve and flexor tendons are known to translate transversely in the carpal tunnel. The purpose of this study was to investigate these motions in differential finger motion using ultrasound, and to compare them in healthy people and carpal tunnel syndrome patients.Transverse ultrasounds clips were taken during fist, index finger, middle finger and thumb flexion in 29 healthy normal subjects and 29 CTS patients. Displacement in palmar-dorsal and radial-ulnar direction was calculated using Analyze software. Additionally, the distance between the median nerve and the tendons was calculated.We found a changed motion pattern of the median nerve in middle finger, index finger and thumb motion between normal subjects and CTS patients (p<0.05). Also, we found a changed motion direction in CTS patients of the FDS III tendon in fist and middle finger motion, and of the FDS II and flexor pollicis longus tendon in index finger and thumb motion, respectively (p<0.05). The distance between the median nerve and the FDS II or FPL tendon is significantly greater in patients than in healthy volunteers for index finger and thumb motion, respectively (p<0.05).Our results suggest a changed motion pattern of the median nerve and several tendons in carpal tunnel syndrome patients compared to normal subjects. Such motion patterns may be useful in distinguishing affected from unaffected individuals, and in studies of the pathomechanics of carpal tunnel syndrome

Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants.

Dietary intervention with extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG (EHCF+LGG) accelerates tolerance acquisition in infants with cow's milk allergy (CMA). We examined whether this effect is attributable, at least in part, to an influence on the gut microbiota. Fecal samples from healthy controls (n=20) and from CMA infants (n=19) before and after treatment with EHCF with (n=12) and without (n=7) supplementation with LGG were compared by 16S rRNA-based operational taxonomic unit clustering and oligotyping. Differential feature selection and generalized linear model fitting revealed that the CMA infants have a diverse gut microbial community structure dominated by Lachnospiraceae (20.5±9.7%) and Ruminococcaceae (16.2±9.1%). Blautia, Roseburia and Coprococcus were significantly enriched following treatment with EHCF and LGG, but only one genus, Oscillospira, was significantly different between infants that became tolerant and those that remained allergic. However, most tolerant infants showed a significant increase in fecal butyrate levels, and those taxa that were significantly enriched in these samples, Blautia and Roseburia, exhibited specific strain-level demarcations between tolerant and allergic infants. Our data suggest that EHCF+LGG promotes tolerance in infants with CMA, in part, by influencing the strain-level bacterial community structure of the infant gut

GLAST: Understanding the High Energy Gamma-Ray Sky

We discuss the ability of the GLAST Large Area Telescope (LAT) to identify, resolve, and study the high energy gamma-ray sky. Compared to previous instruments the telescope will have greatly improved sensitivity and ability to localize gamma-ray point sources. The ability to resolve the location and identity of EGRET unidentified sources is described. We summarize the current knowledge of the high energy gamma-ray sky and discuss the astrophysics of known and some prospective classes of gamma-ray emitters. In addition, we also describe the potential of GLAST to resolve old puzzles and to discover new classes of sources.Comment: To appear in Cosmic Gamma Ray Sources, Kluwer ASSL Series, Edited by K.S. Cheng and G.E. Romer

Consensus Document on Coding of Cardiac Magnetic Resonance Examinations in Portugal

Um dos obstáculos a uma utilização mais frequente e apropriada da ressonância magnética cardíaca (RMC) em Portugal tem sido a ausência de códigos específicos que descrevam adequadamente os exames tal como são efetuados actualmente. Este documento de consenso fornece recomendações para a atualização e uniformização dos códigos empregues na RMC. São igualmente feitas recomendações quanto às técnicas e códigos a utilizar nas indicações clínicas mais frequentes

Genetically-Determined Hyperfunction of the S100B/RAGE Axis Is a Risk Factor for Aspergillosis in Stem Cell Transplant Recipients

Invasive aspergillosis (IA) is a major threat to the successful outcome of hematopoietic stem cell transplantation (HSCT), although individual risk varies considerably. Recent evidence has established a pivotal role for a danger sensing mechanism implicating the S100B/receptor for advanced glycation end products (RAGE) axis in antifungal immunity. The association of selected genetic variants in the S100B/RAGE axis with susceptibility to IA was investigated in 223 consecutive patients undergoing HSCT. Furthermore, studies addressing the functional consequences of these variants were performed. Susceptibility to IA was significantly associated with two distinct polymorphisms in RAGE (-374T/A) and S100B (+427C/T) genes, the relative contribution of each depended on their presence in both transplantation counterparts [patient SNPRAGE, adjusted hazard ratio (HR), 1.97; P = 0.042 and donor SNPRAGE, HR, 2.03; P = 0.047] or in donors (SNPS100B, HR, 3.15; P = 7.8e-4) only, respectively. Functional assays demonstrated a gain-of-function phenotype of both variants, as shown by the enhanced expression of inflammatory cytokines in RAGE polymorphic cells and increased S100B secretion in vitro and in vivo in the presence of the S100B polymorphism. These findings point to a relevant role of the danger sensing signaling in human antifungal immunity and highlight a possible contribution of a genetically-determined hyperfunction of the S100B/RAGE axis to susceptibility to IA in the HSCT setting

S100A14 Stimulates Cell Proliferation and Induces Cell Apoptosis at Different Concentrations via Receptor for Advanced Glycation End Products (RAGE)

S100A14 is an EF-hand containing calcium-binding protein of the S100 protein family that exerts its biological effects on different types of cells. However, exact extracellular roles of S100A14 have not been clarified yet. Here we investigated the effects of S100A14 on esophageal squamous cell carcinoma (ESCC) cell lines. Results demonstrated that low doses of extracellular S100A14 stimulate cell proliferation and promote survival in KYSE180 cells through activating ERK1/2 MAPK and NF-κB signaling pathways. Immunoprecipitation assay showed that S100A14 binds to receptor for advanced glycation end products (RAGE) in KYSE180 cells. Inhibition of RAGE signaling by different approaches including siRNA for RAGE, overexpression of a dominant-negative RAGE construct or a RAGE antagonist peptide (AmphP) significantly blocked S100A14-induced effects, suggesting that S100A14 acts via RAGE ligation. Furthermore, mutation of the N-EF hand of S100A14 (E39A, E45A) virtually reduced 10 µg/ml S100A14-induced cell proliferation and ERK1/2 activation. However, high dose (80 µg/ml) of S100A14 causes apoptosis via the mitochondrial pathway with activation of caspase-3, caspase-9, and poly(ADP-ribose) polymerase. High dose S100A14 induces cell apoptosis is partially in a RAGE-dependent manner. This is the first study to demonstrate that S100A14 binds to RAGE and stimulates RAGE-dependent signaling cascades, promoting cell proliferation or triggering cell apoptosis at different doses