Italy recorded its first case of confirmed acute respiratory case due to Coronavirus on February 18, 2020, soon after the initial reports in China. Since that time, Italy and nations throughout the world have adopted very stringent and severe measures to protect populations from spread of infection.Despite these measures, the number of infected people is growing exponentially with a significant number of patients developing acute respiratory insufficiency. Endoscopy departments face significant risk for diffusion of respiratory diseases that can be spread via an airborne route, including aspiration of oral and fecal material via endoscopes. The purpose of this article is to discuss the measures, with specific focus on personal protection equipment and dressing code modalities, which have been implemented in our hospital to prevent further dissemination of COVID-19 infection.

IMPORTANCE Coronavirus disease 2019 (COVID-19) is a global pandemic and can involve the gastrointestinal (GI) tract, including symptoms like diarrhea and shedding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in feces. OBJECTIVE To provide a pooled estimate of GI symptoms, liver enzyme levels outside reference ranges, and fecal tests positive for SARS-CoV-2 among patients with COVID-19. DATA SOURCES An electronic literature search was performed for published (using MEDLINE/ PubMed and Embase) and preprint (using bioRxiv and medRxiv) studies of interest conducted from November 1, 2019, to March 30, 2020. Search terms included "COVID-19," "SARS-Cov-2," and/or "novel coronavirus." STUDY SELECTION Eligible studies were those including patients with SARS-CoV-2 infection who reported GI symptoms. DATA EXTRACTION AND SYNTHESIS Data on patients with GI symptoms (ie, diarrhea, nausea, or vomiting), liver enzyme level changes, and fecal shedding of virus were extracted. Quality of studies was examined using methodological index for nonrandomized studies. Pooled estimates (%) were reported with 95% CIs with level of heterogeneity (I 2). MAIN OUTCOMES AND MEASURES Study and patient characteristics with pooled detection rates for diarrhea, nausea or vomiting, liver enzyme levels outside reference ranges, and SARS-CoV-2 positivity in feces tests were analyzed. RESULTS Of 1484 records reviewed, 23 published and 6 preprint studies were included in the analysis, with a total of 4805 patients (mean [SD] age, 52.2 [14.8] years; 1598 [33.2%] women) with COVID-19. The pooled rates were 7.4% (95% CI, 4.3%-12.2%) of patients reporting diarrhea and 4.6% (95% CI, 2.6%-8.0%) of patients reporting nausea or vomiting. The pooled rate for aspartate aminotransferase levels outside reference ranges was 20% (95% CI, 15.3%-25.6%) of patients, and the pooled rate for alanine aminotransferase levels outside reference ranges was 14.6% (95% CI, 12.8%-16.6%) of patients. Fecal tests that were positive for SARS-CoV-2 were reported in 8 studies, and viral RNA shedding was detected in feces in 40.5% (95% CI, 27.4%-55.1%) of patients. There was high level of heterogeneity (I 2 = 94%), but no statistically significant publication bias noted. CONCLUSIONS AND RELEVANCE These findings suggest that that 12% of patients with COVID-19 will manifest GI symptoms; however, SAR-CoV-2 shedding was observed in 40.5% of patients with (continued) Key Points Question What are the incidence rates of gastrointestinal symptoms among patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection? Findings This systematic review and meta-analysis of 23 published and 6 preprint studies found that approximately 12% of patients with SARS-CoV-2 infection reported gastrointestinal symptoms, including diarrhea, nausea, and vomiting. Liver enzyme levels outside reference ranges were observed in 15% to 20% of patients, and SARS-CoV-2 RNA shedding in stool was detected in up to 41% of patients. Meaning These findings suggest that patients w...

U p to 20% of health care personnel (HCP) were found to be infected with coronavirus disease (COVID-19) 1 in the outbreak in northern Italy. 2 Recommendations on patient and HCP protection have been made, such as postponing procedures, triage, use of personal protective equipment (PPE), and creation of differentiated in-hospital pathways. 3,4 However, several barriers against the adoption of these strategies exist, including cultural factors and shortages of medical resources; therefore, there are few reports of real-world experiences and outcomes with their adoption. 5 The aim of this survey was to investigate the burden of COVID-19 on endoscopic activity in a high-risk area of COVID-19 outbreak, approaches to evaluating patients, adoption and compliance of HCP with protective measures, and initial possible viral transmission outcomes from endoscopy units within a large, community-based setting (both between patients and HCP and between HCP). MethodsThe study was conducted as a survey between March 16 and March 21, 2020. Directors of emergency departments in highrisk areas of northern Italy (Supplementary Figure 1) were invited by e-mail to complete a questionnaire (Figure 1 and Supplementary Table 1). Participation was voluntary. Additional methodology is provided in the Supplementary Material. Results Characteristics of the Endoscopy UnitsA total of 42 endoscopy units were invited, of which 41 participated (97.6%). Most respondents (n ¼ 37, 90.2%) were from high-volume endoscopy units, for a total of 968 endoscopy personnel, including 323 endoscopists, 496 nurses, and 149 health care assistants. Changes in Endoscopy Activity Related to Coronavirus Disease 2019All endoscopy units had patients diagnosed with COVID-19 in their hospital. All but 1 center (40/41, 97.6%) reduced Infection Prevention and Control Measures for Coronavirus Disease 2019Regarding the preventive measures taken after the first Italian case (February 18, 2020), 5 (12.2%) endoscopy units did not take any measures, 29 (70.7%) endoscopy units adopted a triage for risk stratification of COVID-19 infection, 7 (17.1%) endoscopy units decreased endoscopic See editorial on page 36.

Background: The purpose was to assess in Italy the clinical features at diagnosis of inflammatory bowel disease (IBD) in children. Methods: In 1996 an IBD register of disease onset was established on a national scale. Results: Up to the end of 2003, 1576 cases of pediatric IBD were recorded: 810 (52%) ulcerative colitis (UC), 635 (40%) Crohn's disease (CD), and 131 (8%) indeterminate colitis (IC). In the period 1996–2003 an increase of IBD incidence from 0.89 to 1.39/105 inhabitants aged <18 years was observed. IBD was more frequent among children aged between 6 and 12 years (57%) but 20% of patients had onset of the disease under 6 years of age; 28 patients were <1 year of age. Overall, 11% had 1 or more family members with IBD. The mean interval between onset of symptoms and diagnosis was higher in CD (10.1 months) and IC (9 months) versus UC (5.8 months). Extended colitis was the most frequent form in UC and ileocolic involvement the most frequent in CD. Upper intestinal tract involvement was present in 11% of CD patients. IC locations were similar to those of UC. Bloody diarrhea and abdominal pain were the most frequent symptoms in UC and IC, and abdominal pain and diarrhea in CD. Extraintestinal symptoms were more frequent in CD than in UC. Conclusions The IBD incidence in children and adolescents in Italy shows an increasing trend for all 3 pathologies. UC diagnoses exceeded CD. (Inflamm Bowel Dis 2008)

SummarySynthesis and scission of phosphodiester bonds in DNA and RNA regulate vital processes within the cell. Enzymes that catalyze these reactions operate mostly via the recognized two-metal-ion mechanism. Our analysis reveals that basic amino acids and monovalent cations occupy structurally conserved positions nearby the active site of many two-metal-ion enzymes for which high-resolution (<3 Å) structures are known, including DNA and RNA polymerases, nucleases such as Cas9, and splicing ribozymes. Integrating multiple-sequence and structural alignments with molecular dynamics simulations, electrostatic potential maps, and mutational data, we found that these elements always interact with the substrates, suggesting that they may play an active role for catalysis, in addition to their electrostatic contribution. We discuss possible mechanistic implications of this expanded two-metal-ion architecture, including inferences on medium-resolution cryoelectron microscopy structures. Ultimately, our analysis may inspire future experiments and strategies for enzyme engineering or drug design to modulate nucleic acid processing.

b2 microglobulin (b2m) is the light chain of class-I major histocompatibility complex (MHC-I). Its accumulation in the blood of patients affected by kidney failure leads to amyloid deposition around skeletal joints and bones, a severe condition known as Dialysis Related Amyloidosis (DRA). In an effort to dissect the structural determinants of b2m aggregation, several b2m mutants have been previously studied. Among these, three single-residue mutations in the loop connecting strands D and E (W60G, W60V, D59P) have been shown to affect b2m amyloidogenic properties, and are here considered. To investigate the biochemical and biophysical properties of wild-type (w.t.) b2m and the three mutants, we explored thermal unfolding by Trp fluorescence and circular dichroism (CD). The W60G mutant reveals a pronounced increase in conformational stability. Protein oligomerization and reduction kinetics were investigated by electrospray-ionization mass spectrometry (ESI-MS). All the mutations analyzed here reduce the protein propensity to form soluble oligomers, suggesting a role for the DE-loop in intermolecular interactions. A partially folded intermediate, which may be involved in protein aggregation induced by acids, accumulates for all the tested proteins at pH 2.5 under oxidizing conditions. Moreover, the kinetics of disulfide reduction reveals specific differences among the tested mutants. Thus, b2m DE-loop mutations display long-range effects, affecting stability and structural properties of the native protein and its low-pH intermediate. The evidence presented here hints to a crucial role played by the DE-loop in determining the overall properties of native and partially folded b2m.

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High-throughput screening highlighted 9-oxo-9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile (1) as an active inhibitor of ubiquitin-specific proteases (USPs), a family of hydrolytic enzymes involved in the removal of ubiquitin from protein substrates. The chemical behavior of compound 1 was examined. Moreover, the synthesis and in vitro evaluation of new compounds, analogues of 1, led to the identification of potent and selective inhibitors of the deubiquitinating enzyme USP8.