Diarrhea Is a Hallmark of Inflammation in Pediatric COVID-19

: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pathogen with enteric tropism. We compared the clinical, biochemical and radiological features of children hospitalized for acute SARS-CoV-2 infection, classified in two groups based on the presence of diarrhea. Logistic regression analyses were used to investigate the variables associated with diarrhea. Overall, 407 children were included in the study (226 males, 55.5%, mean age 3.9 ± 5.0 years), of whom 77 (18.9%) presented with diarrhea, which was mild in most cases. Diarrhea prevalence was higher during the Alpha (23.6%) and Delta waves (21.9%), and in children aged 5-11 y (23.8%). Other gastrointestinal symptoms were most commonly reported in children with diarrhea (p < 0.05). Children with diarrhea showed an increased systemic inflammatory state (higher C-reactive protein, procalcitonin and ferritin levels, p < 0.005), higher local inflammation as judged by mesenteric fat hyperechogenicity (adjusted Odds Ratio 3.31, 95%CI 1.13-9.70) and a lower chance of previous immunosuppressive state (adjusted Odds Ratio 0.19, 95%CI 0.05-0.70). Diarrhea is a frequent feature of pediatric COVID-19 and is associated with increased systemic inflammation, which is related to the local mesenteric fat inflammatory response, confirming the implication of the gut not only in multisystem inflammatory syndrome but also in the acute phase of the infection

Exon-trapping assay improves clinical interpretation of COL11A1 and COL11A2 intronic variants in stickler syndrome type 2 and otospondylomegaepiphyseal dysplasia

Stickler syndrome (SS) is a hereditary connective tissue disorder affecting bones, eyes, and hearing. Type 2 SS and the SS variant otospondylomegaepiphyseal dysplasia (OSMED) are caused by deleterious variants in COL11A1 and COL11A2, respectively. In both genes, available database information indicates a high rate of potentially deleterious intronic variants, but published evidence of their biological effect is usually insufficient for a definite clinical interpretation. We report our previously unpublished intronic variants in COL11A1 (c.2241 + 5G&gt;T, c.2809 − 2A&gt;G, c.3168 + 5G&gt;C) and COL11A2 (c.4392 + 1G&gt;A) identified in type 2 SS/OSMED individuals. The pathogenic effect of these variants was first predicted in silico and then investigated by an exon-trapping assay. We demonstrated that all variants can induce exon in-frame deletions, which lead to the synthesis of shorter collagen XI α1 or 2 chains. Lacking residues are located in the α-triple helical region, which has a crucial role in regulating collagen fibrillogenesis. In conclusion, this study suggests that these alternative COL11A1 and COL11A2 transcripts might result in aberrant triple helix collagen. Our approach may help to improve the diagnostic molecular pathway of COL11-related disorder

A novel bistable device to study mechanosensitive cell responses to instantaneous stretch

The behavior of cells and tissues in vivo is determined by the integration of multiple biochemical and mechanical signals. Of the mechanical signals, stretch has been studied for decades and shown to contribute to pathophysiological processes. Several different stretch devices have been developed for in vitro investigations of cell stretch. In this work, we describe a new 3D-printed uniaxial stretching device for studying cell response to rapid deformation. The device is a bistable compliant mechanism holding two equilibrium states—an unstretched and stretched configuration—without the need of an external actuator. Furthermore, it allows multiple simultaneous measurements of different levels of stretch on a single substrate and is compatible with standard immunofluorescence imaging of fixed cells as well as live-cell imaging. To demonstrate the effectiveness of the device to stretch cells, a test case using aligned myotubes is presented. Leveraging material area changes associated with deformation of the substrate, changes in nuclei density provided evidence of affine deformation between cells and substrate. Furthermore, intranuclear deformations were also assessed and shown to deform non-affinely. As a proof-of-principle of the use of the device for mechanobiological studies, we uniaxially stretched aligned healthy and dystrophic myotubes that displayed different passive mechanical responses, consistent with previous literature in the field. We also identified a new feature in the mechanoresponse of dystrophic myotubes, which is of potential interest for identifying the diseased cells based on a quick mechanical readout. While some applications of the device for elucidating passive mechanical responses are demonstrated, the simplicity of the device allows it to be potentially used for other modes of deformation with little modifications.ISSN:2772-950

FACING UNTREATED PROSTATE CANCER ON ACTIVE SURVEILLANCE: WHO IS AT RISK FOR INCREASED ANXIETY?

Introduction. “Living with untreated prostate cancer (PCa)” may cause distress in men on Active Surveillance (AS). We aimed to evaluate PCa-related anxiety (anx) over the first 2 years on AS. Patients and Methods. Between 2007-2014, 207 patients (pts) progressively completed the Memorial Anxiety Scale for Prostate Cancer (MAX-PC), a self-report tool providing 4 indexes: PCa anx, PSA anx, fear of recurrence, MAX-PC total score. Assessment was conducted at entrance in AS protocol (T0), 2 months before first re-biopsy from diagnostic one (T1), after re-biopsy (T2) and 1 year after re-biopsy (T3). Cronbach’s α was calculated to estimate internal consistency for each index. Descriptive analyses were performed. Wilcoxon test was used to detect statistically significant changes over time. Results. Mean age of sample at diagnosis was 64 years (SD=7; 42-79 yrs). Figure 1 shows results of descriptive analyses. The majority of pts had low scores in all the subscales and the MAX-PC total index (skewness>0). Cronbach’s α was ≥ 0.70 for all indexes, indicating good internal consistency. Wilcoxon test showed statistically significant reductions in MAX-PC total score (61% of pts, p=0,0006) and PCa anx (58% of pts, p=0,0012) between T1 and T2. Conclusions. This is the first study to report on PCa-related anx over the first 2 years on AS, which emerged as favourably low. Internal consistency analyses showed that MAX-PC is reliable tool to assess anxiety in men on AS despite it was developed for patients undergoing radical prostatectomy. Further research is needed to confirm its validity in the population of AS pts. In particular for “fear of recurrence”, originally designed to measure worry for cancer relapse after radical treatment. Yet, items seem to be properly applicable to fear for disease progression. The concurrence of decrease in anx with the first re-biopsy highlights a potentially reassuring role of the AS monitoring scheme

Electroclinical features of MEF2C haploinsufficiency-related epilepsy: A multicenter European study

Purpose: Epilepsy is a main manifestation in the autosomal dominant mental retardation syndrome caused by heterozygous variants in MEF2C. We aimed to delineate the electro-clinical features and refine the genotype phenotype correlations in patients with MEF2C haploinsufficiency. Methods: We thoroughly investigated 25 patients with genetically confirmed MEF2C-syndrome across 12 different European Genetics and Epilepsy Centers, focusing on the epileptic phenotype. Clinical features (seizure types, onset, evolution, and response to therapy), EEG recordings during waking/sleep, and neuroimaging findings were analyzed. We also performed a detailed literature review using the terms "MEF2C", "seizures", and "epilepsy". Results: Epilepsy was diagnosed in 19 out of 25 (-80%) subjects, with age at onset &lt;30 months. Ten individuals (40%) presented with febrile seizures and myoclonic seizures occurred in-50% of patients. Epileptiform abnormalities were observed in 20/25 patients (80%) and hypoplasia/partial agenesis of the corpus callosum was detected in 12/25 patients (-50%). Nine patients harbored a 5q14.3 deletion encompassing MEF2C and at least one other gene. In 7 out of 10 patients with myoclonic seizures, MIR9-2 and LINC00461 were also deleted, whereas ADGRV1 was involved in 3/4 patients with spasms. Conclusion: The epileptic phenotype of MEF2C-syndrome is variable. Febrile and myoclonic seizures are the most frequent, usually associated with a slowing of the background activity and irregular diffuse discharges of frontally dominant, symmetric or asymmetric, slow theta waves with interposed spike-and-waves complexes. The haploinsufficiency of ADGRV1, MIR9-2, and LINC00461 likely contributes to myoclonic seizures and spasms in patients with MEF2C syndrome

The dual-mirror Small Size Telescope for the Cherenkov Telescope Array

In this paper, the development of the dual mirror Small Size Telescopes (SST) for the Cherenkov Telescope Array (CTA) is reviewed. Up to 70 SST, with a primary mirror diameter of 4 m, will be produced and installed at the CTA southern site. These will allow investigation of the gamma-ray sky at the highest energies accessible to CTA, in the range from about 1 TeV to 300 TeV. The telescope presented in this contribution is characterized by two major innovations: the use of a dual mirror Schwarzschild-Couder configuration and of an innovative camera using as sensors either multi-anode photomultipliers (MAPM) or silicon photomultipliers (SiPM). The reduced plate-scale of the telescope, achieved with the dual-mirror optics, allows the camera to be compact (40 cm in diameter), and low-cost. The camera, which has about 2000 pixels of size 6x6 mm^2, covers a field of view of 10{\deg}. The dual mirror telescopes and their cameras are being developed by three consortia, ASTRI (Astrofisica con Specchi a Tecnologia Replicante Italiana, Italy/INAF), GATE (Gamma-ray Telescope Elements, France/Paris Observ.) and CHEC (Compact High Energy Camera, universities in UK, US and Japan) which are merging their efforts in order to finalize an end-to-end design that will be constructed for CTA. A number of prototype structures and cameras are being developed in order to investigate various alternative designs. In this contribution, these designs are presented, along with the technological solutions under study