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Surface curvature both emerges from, and influences the behavior of, living objects at length scales ranging from cell membranes to single cells to tissues and organs. The relevance of surface curvature in biology has been supported by numerous recent experimental and theoretical investigations in recent years. In this review, we first give a brief introduction to the key ideas of surface curvature in the context of biological systems and discuss the challenges that arise when measuring surface curvature. Giving an overview of the emergence of curvature in biological systems, its significance at different length scales becomes apparent. On the other hand, summarizing current findings also shows that both single cells and entire cell sheets, tissues or organisms respond to curvature by modulating their shape and their migration behavior. Finally, we address the interplay between the distribution of morphogens or micro-organisms and the emergence of curvature across length scales with examples demonstrating these key mechanistic principles of morphogenesis. Overall, this review highlights that curved interfaces are not merely a passive by-product of the chemical, biological and mechanical processes but that curvature acts also as a signal that co-determines these processes. This article is protected by copyright. All rights reserved.

Background Although evidence suggests frequent gastrointestinal (GI) involvement during coronavirus disease 2019 (COVID-19), endoscopic findings are scarcely reported. Aims We aimed at registering endoscopic abnormalities and potentially associated risk factors among patients with COVID-19. Methods All consecutive patients with COVID-19 undergoing endoscopy in 16 institutions from high-prevalence regions were enrolled. Mann-Whitney U, χ 2 or Fisher's exact test were used to compare patients with major abnormalities to those with negative procedures, and multivariate logistic regression to identify independent predictors. Results Between February and May 2020, during the first pandemic outbreak with severely restricted endoscopy activity, 114 endoscopies on 106 patients with COVID-19 were performed in 16 institutions (men=70.8%, median age=68 (58-74); 33% admitted in intensive care unit; 44.4% reporting GI symptoms). 66.7% endoscopies were urgent, mainly for overt GI bleeding. 52 (45.6%) patients had major abnormalities, whereas 13 bled from previous conditions. The most prevalent upper GI abnormalities were ulcers (25.3%), erosive/ulcerative gastro-duodenopathy (16.1%) and petechial/haemorrhagic gastropathy (9.2%). Among lower GI endoscopies, 33.3% showed an ischaemic-like colitis. Receiver operating curve analysis identified D-dimers >1850 ng/mL as predicting major abnormalities. Only D-dimers >1850 ng/mL (OR=12.12 (1.69-86.87)) and presence of GI symptoms (OR=6.17 (1.13-33.67)) were independently associated with major abnormalities at multivariate analysis. Conclusion In this highly selected cohort of hospitalised patients with COVID-19 requiring endoscopy, almost half showed acute mucosal injuries and more than one-third of lower GI endoscopies had features of ischaemic colitis. Among the hospitalisation-related and patient-related variables evaluated in this study, D-dimers above 1850 ng/mL was the most useful at predicting major mucosal abnormalities at endoscopy. Trial registration number ClinicalTrial.gov (ID: NCT04318366). ©

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Purpose:The beam monitors for CNAO (Centro Nazionale di Adroterapia Oncologica), developed and built in collaboration between INFN, Torino University and CNAO foundation, are ready to be installed on the CNAO nozzle. A basic debug of the detectors with X-rays was done and a more precise characterization[for full text, please go to the a.m. URL], PTCOG 48; Meeting of the Particle Therapy Co-Operative Group

Background “Gluten-related disorders” is a term that encompasses different diseases induced by the ingestion of gluten-containing food. Because of their incidence the scientific community has been intensively studying them. Aim To support gastroenterologists with a correct nomenclature and diagnostic approach to gluten-related disorders in adulthood. Methods The Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO) commissioned a panel of experts to prepare a position statement clarifying the nomenclature and diagnosis of gluten-related disorders, focusing on those of gastroenterological interest. Each member was assigned a task and levels of evidence/recommendation have been proposed. Results The panel identified celiac disease, wheat allergy and non-celiac gluten sensitivity as the gluten-related disorders of gastroenterological interest. Celiac disease has an autoimmune nature, wheat allergy is IgE-mediated while the pathogenesis of non-celiac gluten sensitivity is still unknown as is the case of non-IgE mediated allergy. Diagnosis should start with the serological screening for celiac disease and wheat allergy. In case of normal values, the response to a gluten-free diet should be evaluated and a confirmatory blind food challenge carried out. Conclusions Gluten-related disorders are clinically heterogeneous. Patients should be carefully managed and specific protocols applied for a correct differential diagnosis in gastroenterological setting.

BackgroundAlthough evidence suggests frequent gastrointestinal (GI) involvement during coronavirus disease 2019 (COVID-19), endoscopic findings are scarcely reported.AimsWe aimed at registering endoscopic abnormalities and potentially associated risk factors among patients with COVID-19.MethodsAll consecutive patients with COVID-19 undergoing endoscopy in 16 institutions from high-prevalence regions were enrolled. Mann-Whitney U, χ2 or Fisher’s exact test were used to compare patients with major abnormalities to those with negative procedures, and multivariate logistic regression to identify independent predictors.ResultsBetween February and May 2020, during the first pandemic outbreak with severely restricted endoscopy activity, 114 endoscopies on 106 patients with COVID-19 were performed in 16 institutions (men=70.8%, median age=68 (58–74); 33% admitted in intensive care unit; 44.4% reporting GI symptoms). 66.7% endoscopies were urgent, mainly for overt GI bleeding. 52 (45.6%) patients had major abnormalities, whereas 13 bled from previous conditions. The most prevalent upper GI abnormalities were ulcers (25.3%), erosive/ulcerative gastro-duodenopathy (16.1%) and petechial/haemorrhagic gastropathy (9.2%). Among lower GI endoscopies, 33.3% showed an ischaemic-like colitis.Receiver operating curve analysis identified D-dimers >1850 ng/mL as predicting major abnormalities. Only D-dimers >1850 ng/mL (OR=12.12 (1.69–86.87)) and presence of GI symptoms (OR=6.17 (1.13–33.67)) were independently associated with major abnormalities at multivariate analysis.ConclusionIn this highly selected cohort of hospitalised patients with COVID-19 requiring endoscopy, almost half showed acute mucosal injuries and more than one-third of lower GI endoscopies had features of ischaemic colitis. Among the hospitalisation-related and patient-related variables evaluated in this study, D-dimers above 1850 ng/mL was the most useful at predicting major mucosal abnormalities at endoscopy.Trial registration numberClinicalTrial.gov (ID: NCT04318366).

Background: the lack of standardized pathways for patients with gastrointestinal bleeding may have led to differences in their management and inequity to medical care access. The "Hub & Spoke" model was adopted to fill this gap in many disciplines, but, to our knowledge, no data exist on its efficacy on mortality in GI bleeding. We aimed to evaluate if the "Hub & Spoke" organizational model has an impact on mortality risk from UGIB. Methods: from January 2014 to December 2015, 3324 consecutive patients admitted for UGIB in 50 Italian hospitals were enrolled (1977 patients in hospitals within the "Hub & Spoke" network for digestive hemorrhagic emergency and 1347 in hospitals outside the "Hub & Spoke" network). Clinical, endoscopic and organizational data were recorded. Results: we observed no differences in mortality between patients admitted to hospitals included or not included in the "Hub & Spoke" network (5.2% vs 6.1%, p = 0.3). On multivariate analysis, admission in gastroenterology wards (OR 0.61, p = 0.001) or an academic hospital (OR 0.65, p < 0.056) were independent protective factors while being in "Hub & Spoke" organization system did not affect mortality (OR 1.09, p = 0.57). Conclusion: the "Hub & Spoke" model per sé does not impact on mortality while being treated in academic hospital or gastroenterology wards improved survival.

Anaemia is a common pathologic condition, present in almost 5% of the adult population. Iron deficiency is the most common cause; other mechanisms can be involved, making anaemia a multi-factorial disorder in most cases. Anaemia being a frequent manifestation in the diseases of the gastrointestinal tract, patients are often referred to gastroenterologists. Furthermore, upper and lower endoscopy and enteroscopy are pivotal to the diagnostic roadmap of anaemia. In spite of its relevance in the daily clinical practice, there is a limited number of gastroenterological guidelines dedicated to the diagnosis of anaemia. For this reason, the Italian Association of Hospital Gastroenterologists and Endoscopists and the Italian Society of Paediatric Gastroenterology, Hepatology and Nutrition commissioned a panel of experts to prepare a specific guideline on anaemia and its diagnostic roadmap in the gastroenterological scenario. The panel also discussed about the potential involvement of gastroenterologists and endoscopists in the management of patients with anaemia, with particular attention to the correct use of investigations. The panel paid particular attention to practical issues with the aim to support gastroenterologists in their clinical practice when dealing with patients with anaemia.

Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS.

CD (coeliac disease) is a frequent autoimmune disorder of the small bowel, which is characterized by an immunological reaction against gluten and transglutaminase in genetically predisposed subjects. However, the molecular determinants underpinning CD pathogenesis are yet to be fully elucidated and little data are available about the involvement of miRNAs (microRNAs) in CD. In the present study, the duodenal mucosa miRNA expression was profiled in adult untreated CD presenting with a classic phenotype or iron-deficiency anaemia, treated patients with or without duodenal normalization, and non-CD subjects as controls. Deregulation of seven miRNAs (miR-31-5p, miR-192-3p, miR-194-5p, miR-551a, miR-551b-5p, miR-638 and miR-1290) was determined in a larger series of CD patients with different clinical phenotypes compared with non-CD subjects. These seven microRNAs were then analysed in duodenal fibroblasts obtained from CD patients and incubated with gliadin peptides (13- and 33-mer). The miRNA cluster miR-192/194, involved in matrix remodelling, was deregulated in CD according to the different clinical presentations, and miR-192-3p levels were modulated by gliadin peptides in vitro. In conclusion, the analysis of miRNAs deserves further consideration for its potential use in the treatment and management of CD. © 2014 Biochemical Society.