NEW THERAPEUTIC PERSPECTIVES IN IRRITABLE BOWEL SYNDROME: TARGETING LOW-GRADE INFLAMMATION, IMMUNO-NEUROENDOCRINE AXIS, MOTILITY, SDECRETION AND BEYOND

Irritable bowel syndrome (IBS) is a chronic, recurring, and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain, distention, and changes in bowel habits. Although there are several drugs for IBS, effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed. Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism, neurohormonal regulation, immune, dysfunction, the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS. With regards to therapies for restoring intestinal permeability, multiple studies with prebiotics and probiotics are ongoing, even if to date their efficacy has been limited. In parallel, much progress has been made in targeting low-grade inflammation, especially through the introduction of drugs such as mesalazine and rifaximin, even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs. This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS, most recently developed in preclinical as well as Phase 1 and Phase 2 clinical studies

Unobtrusive Storage Maintenance

Storage systems rely on maintenance tasks, such as backup and defragmentation, to provide a multitude of guarantees that range from data availability and security, to good performance. These tasks access large amounts of data and can significantly impact foreground applications. The work presented as part of this thesis outlines the challenges of storage maintenance and provides mechanisms that lower its impact, allowing it to be performed more efficiently. Maintenance operations act as insurance for storage systems. To avoid the prohibitive cost incurred in their absence, storage operators pay the price of performing them periodically. In the case of reliability, for example, we find that the error characteristics of hard disk drives in Google's data centers are diverse across models and operating environments. Due to this unpredictability, the use of periodic maintenance becomes unavoidable. Furthermore, recent research efforts on disaster prediction depend on metrics collected through periodic maintenance operations. Unfortunately, periodic storage maintenance requires data to be accessed multiple times. As a case in point, we find that customers of Symantec and Veritas schedule backups multiple times a week. This often results in excess maintenance work that fails to complete within the scheduled downtime periods. At this point, foreground workload impact becomes unavoidable in order to maintain the same reliability guarantees. To lessen this impact, maintenance I/O can be scheduled only when storage devices are otherwise idle. To achieve this, idleness must be predicted accurately. Fortunately, our extensive study of disk workloads reveals characteristics that allow idleness to be predicted accurately by simple models. Given the number of maintenance tasks available today, idle time can prove insufficient. For such scenarios we present Duet, a framework that provides notifications to tasks about relevant changes in the system cache. Using this mechanism, tasks can reduce their I/O by prioritizing processing of cached data. Data can be cached either due to other maintenance tasks requesting it previously, or due to overlapping foreground I/O activity. In other words, tasks running concurrently can implicitly collaborate, collectively reducing the I/O required for maintenance and, by extension, the idle time needed to execute it.Ph.D

Superior mesenteric artery syndrome: Clinical, endoscopic, and radiological findings

Background. The superior mesenteric artery (SMA) syndrome is a rare entity presenting with upper gastrointestinal tract obstruction and weight loss. Studies to determine the optimal methods of diagnosis and treatment are required. Aims and Methods. This study aims at analyzing the clinical presentation, diagnosis, and management of SMA syndrome. Ten cases of SMA syndrome out of 2074 esophagogastroduodenoscopies were suspected. A contrast-enhanced computed tomography (CECT) scan was performed to confirm the diagnosis. After, a gastroenterologist and a nutritionist personalized the therapy. Furthermore, we compared the demographical, clinical, endoscopic, and radiological parameters of these cases with a control group consisting of 10 cases out of 2380 EGDS of initially suspected (but not radiologically confirmed) SMA over a follow-up 2-year period (2015-2016). Results. The prevalence of SMA syndrome was 0.005%. Median age and body mass index were 23.5 years and 21.5 kg/m2, respectively. Symptoms developed between 6 and 24 months. Median aortomesenteric angle and aorta-SMA distance were 22 and 6 mm, respectively. All patients improved on conservative treatment. In our series, a marked (>5 kg) weight loss (p=0.006) and a long-standing presentation (more than six months in 80% of patients) (p=0.002) are significantly related to a diagnosis of confirmed SMA syndrome at CECT after an endoscopic suspicion. A "resembling postprandial distress syndrome dyspepsia" presentation may be helpful to the endoscopist in suspecting a latent SMA syndrome (p=0.02). The narrowing of both the aortomesenteric angle (p=0.001) and the aortomesenteric distance (p<0.001) was significantly associated with the diagnosis of SMA after an endoscopic suspicion; however, the narrowing of the aortomesenteric distance seemed to be more accurate, rather than the narrowing of the aortomesenteric angle. Conclusion. SMA syndrome represents a diagnostic and therapeutic challenge. Our results show the following findings: the importance of the endoscopic suspicion of SMA syndrome; the preponderance of a long-standing and chronic onset; a female preponderance; the importance of the nutritional counseling for the treatment; no need of surgical intervention; and better diagnostic accuracy of the narrowing of the aorta-SMA distance. Larger prospective studies are needed to clarify the best diagnosis and management of the SMA syndrome

An Unusual Presentation of Zollinger-Ellison Syndrome

Zollinger-Ellison syndrome is an often progressive, persistent and frequently life-threatening disease, described for the first time as characterized by ulceration of the upper jejunum, hypersecretion of gastric acid and non-beta islet cell tumors of the pancreas; this syndrome is due to the hypersecretion of gastrin. We report a case of Zollinger-Ellison syndrome presenting as severe esophagitis evolving in stenosis, which demonstrates how a delayed diagnosis may induce risk of disease spreading. In this setting new diagnostic approaches, such as somatostatin receptor scanning and positron emission tomography with 68 Ga-labeled octreotide, could be particularly useful, as well as further new therapeutic options, such as molecular targeted treatments and peptide receptor radionuclide therapy, though surgery is currently the only form of curative treatment, and the role of the therapeutic options mentioned needs to be clarified by forthcoming studies

Endoscopy units and the COVID-19 Outbreak: A Multi-Center Experience from Italy

experience of endoscopic unit during covid outbrea

COSMOS-Web: An Overview of the JWST Cosmic Origins Survey

We present the survey design, implementation, and outlook for COSMOS-Web, a 255 hour treasury program conducted by the James Webb Space Telescope in its first cycle of observations. COSMOS-Web is a contiguous 0.54 deg$^2$ NIRCam imaging survey in four filters (F115W, F150W, F277W, and F444W) that will reach 5$\sigma$ point source depths ranging $\sim$27.5-28.2 magnitudes. In parallel, we will obtain 0.19 deg$^2$ of MIRI imaging in one filter (F770W). COSMOS-Web will build on the rich heritage of multiwavelength observations and data products available in the COSMOS field. The design of COSMOS-Web is motivated by three primary science goals: (1) to discover thousands of galaxies in the Epoch of Reionization ($64$ and place constraints on the formation of the Universe's most massive galaxies ($M_\star>10^{10}$ M$_\odot$), and (3) directly measure the evolution of the stellar mass to halo mass relation using weak gravitational lensing out to $z\sim2.5$ and measure its variance with galaxies' star formation histories and morphologies. In addition, we anticipate COSMOS-Web's legacy value to reach far beyond these scientific goals, touching many other areas of astrophysics, such as the identification of the first direct collapse black hole candidates, ultracool sub-dwarf stars in the Galactic halo, and possibly the identification of $z>10$ pair-instability supernovae. In this paper we provide an overview of the survey's key measurements, specifications, goals, and prospects for new discovery