Thermo-hygro-chemo-mechanical model of concrete at early ages and its extension to tumor growth numerical analysis.

The aim of the PhD thesis is the development of two multiphase models from a common theoretical basis, applied to two very different research fields: i) the study of the behavior of concrete at early ages, essentially for the prevention of cracking and related issues; ii) the analysis of the physical, chemical and biological processes that govern the growth of cancer. The modeling of concrete at early ages is very important and useful for the design of durable and sustainable structures. The model developed during the PhD thesis has been implemented on the finite element code Cast3M and then validated via the simulation of experimental cases. Nowadays this model allows for several applications: study of stresses and cracking in young concrete, analysis of thermal and hygral gradients, predictions of autogenous and drying shrinkage, creep strain, stress redistribution, study of the inhibition of hydration caused by drying, study of repairs, etc.. In the fight against cancer, the advance of medical strategies based on numerical analysis has a crucial scientific interest and can have a great social impact. The equations which govern the thermo-hygro-chemo-mechanical behavior of concrete at early ages have many formal analogies with those typically used to model tumor growth. Hence, these equations have been readapted and a novel mathematical model for tumor growth has been developed. This model has been implemented in Cast3M and the first numerical results are encouraging since qualitatively close to the experimental data present in the scientific bibliography

How mucosal epithelia deal with stress: Role of NKG2D/NKG2D ligands during inflammation

Mucosal epithelia encounter both physicochemical and biological stress during their life and have evolved several mechanisms to deal with them, including regulation of immune cell functions. Stressed and damaged cells need to be cleared to control local inflammation and trigger tissue healing. Engagement of the activating NKG2D receptor is one of the most direct mechanisms involved in the recognition of stressed cells by the immune system. Indeed, injured cells promptly express NKG2D ligands that in turn mediate the activation of lymphocytes of both innate and adaptive arms of the immune system. This review focuses on different conditions that are able to modulate NKG2D ligand expression on the epithelia. Special attention is given to the mechanisms of immunosurveillance mediated by natural killer cells, which are finely tuned by NKG2D. Different types of stress, including viral and bacterial infections, chronic inflammation, and cigarette smoke exposure, are discussed as paradigmatic conditions for NKG2D ligand modulation, and the implications for tissue homeostasis are discussed

Multi-dimensional gene regulation in innate and adaptive lymphocytes: a view from regulomes

The precise control of cytokine production by innate lymphoid cells (ILCs) and their T cell adaptive system counterparts is critical to mounting a proper host defense immune response without inducing collateral damage and autoimmunity. Unlike T cells that differentiate into functionally divergent subsets upon antigen recognition, ILCs are developmentally programmed to rapidly respond to environmental signals in a polarized manner, without the need of T cell receptor (TCR) signaling. The specification of cytokine production relies on dynamic regulation of cis-regulatory elements that involve multi-dimensional epigenetic mechanisms, including DNA methylation, transcription factor binding, histone modification and DNA-DNA interactions that form chromatin loops. How these different layers of gene regulation coordinate with each other to fine tune cytokine production, and whether ILCs and their T cell analogs utilize the same regulatory strategy, remain largely unknown. Herein, we review the molecular mechanisms that underlie cell identity and functionality of helper T cells and ILCs, focusing on networks of transcription factors and cis-regulatory elements. We discuss how higher-order chromatin architecture orchestrates these components to construct lineage- and state-specific regulomes that support ordered immunoregulation

NCR+ ILC3 maintain larger STAT4 reservoir via T-BET to regulate type 1 features upon IL-23 stimulation in mice

Innate lymphoid cells (ILCs) producing IL-22 and/or IL-17, designated as ILC3, comprise a heterogeneous subset of cells involved in regulation of gut barrier homeostasis and inflammation. Exogenous environmental cues in conjunction with regulated expression of endogenous factors are key determinants of plasticity of ILC3 towards the type 1 fate. Herein, by using mouse models and transcriptomic approaches, we defined at the molecular level, initial events driving ILC3 expressing natural cytotoxicity receptors (NCR+ ILC3) to acquire type 1 features. We observed that NCR+ ILC3 exhibited high basal expression of the signal-dependent transcription factor STAT4 due to T-BET, leading to predisposed potential for the type 1 response. We found that the prototypical inducer of type 3 response, IL-23, played a predominant role over IL-12 by accessing STAT4 and preferentially inducing its phosphorylation in ILC3 expressing T-BET. The early effector program driven by IL-23 was characterized by the expression of IL-22, followed by a production of IFN-γ, which relies on STAT4, T-BET and required chromatin remodeling of the Ifng locus. Altogether, our findings shed light on a feed-forward mechanism involving STAT4 and T-BET that modulates the outcome of IL-23 signaling in ILC3. This article is protected by copyright. All rights reserved

Endoscopic Resection of a Large Colonic Lipoma: Case Report and Review of Literature

Colonic lipomas are uncommon, benign, submucosal adipose tumors that are usually asymptomatic. Large lipomas can cause symptoms such as constipation, abdominal pain, rectal bleeding and intussusception. We report the case of a 60-year-old man with a history of lower abdominal pain and pseudoobstructive symptoms. Colonoscopy revealed a large polypoid sessile lesion in the sigma. We used a standardized technique of polypectomy, preceded by submucosal injection of dilute 5 ml polygelin with epinephrine 1:10,000 solution, to fully resect large colonic lipomas. The lipoma size was 3.5 cm. No bleeding or perforation developed. Histology showed the polyp to be a submucosul lipoma. On follow-up, there was no residual lesion. Colonic lipomas larger than 2 cm can be safely and efficaciously removed using electrosurgical snare polypectomy technique. The technique of submucosal injection before resection and using an electrocautery snare appears to be safe and reduces the risk of perforation reported in the literature

Postoperative laryngeal symptoms in a general surgery setting. Clinical study.

INTRODUCTION: Vocal cord injuries (VI), postoperative hoarseness (PH), dysphonia (DN), dysphagia (DG) and sore throat (ST) are common complications after general anesthesia; there is actually a lack of consensus to support the proper timing for post-operative laryngoscopy that is reliable to support the diagnosis of laryngeal or vocal fold lesions after surgery and there are no valid studies about the entity of laryngeal trauma in oro-tracheal intubation. Aim of our study is to evaluate the statistical relation between anatomic, anesthesiological and surgical variables in the case of PH, DG or impaired voice register. MATERIALS AND METHODS: 50 patients (30 thyroidectomies, 8 videolaparoscopic cholecistectomies, 2 right emicolectomies, 2 left emicolectomies, 1 gastrectomy, 1 hemorrhoidectomy, 1 nefrectomy, 1 diagnostic videothoracoscopy, 1 superior right lung lobectomy, 1 appendicectomy, 1 incisional hernia repair, 1 low anterior rectal resection, 1 radical hysterectomy) underwent clinical evaluation and direct laryngoscopy before surgery, within 6 hours, after 72 hours and after 30 days, to evaluate motility and breathing space, phonatory motility, true and false vocal folds and arytenoids oedema. We evaluated also mean age (56.6 ± 3.6 years), male:female ratio (1:1.5), cigarette smoke (20%), atopic comorbidity (17/50 = 34%), Mallampati class (32% 1, 38% 2, 26% 3, 2% 4), mean duration of intubation (159 minutes, range 50 - 405 minutes), Cormack-Lehane score (34% 1, 22% 2, 22% 3, 2% 4), difficult intubation in 9 cases (18%). No complication during the laryngoscopy were registered. We investigated the statistic relationship between pre and intraoperative variables and laryngeal symptoms and lesions. RESULTS: In our experience, statistically significant relations were found in prevalence of vocal folds oedema in smokers (p < 0.005), self limiting DG and DN in younger patients (p < 0.005) and in thyroidectomy (p < 0.01), DG after thyroidectomy (p < 0.01). The short preoperative use of steroids and antihistaminic to prevent allergic reactions appears not related to reduction or prevention of DN, DG, PH and ST. No statistical relation in incidence of postoperative complications was found for the prolonged intubation, gastro-esophageal reflux, BURP manoeuvre (backward upward right sided pressure) and Mallampati and Cormack-Lehane class more than 2, maintenance with sevoflurane 2% and use of stilet. CONCLUSIONS: Direct laryngoscopy is essential for the detection of arytenoid lesions after orotracheal intubation for general anesthesia. In our opinion, a part of temporary post-operative DN or PH is due to monolateral or bilateral arytenoids oedema, secondary to prolonged or difficult orotracheal intubation, valuable with laryngoscopy 72 hours after surgery. Is necessary to adjunct these complications in the surgical informed consensus scheme

A Strange Case of Left Bowel Ischemia after Right Hernioplasty

We report the first observed case of a young man who suffered of large and unsuspected left bowel ischemia following an elective right open hernioplasty. A 54-year-old man had a 2-year history of right inguinal reducible mass and was admitted to hospital for an elective day case open inguinal hernioplasty for a direct right inguinal hernia. Apart from mild hypertension controlled with ACE inhibitor, he was medically fit and well. The patient was submitted to open tension-free mesh repair with polypropylene preshaped mesh with local infiltration anesthesia and additive sedation with midazolam. The local anesthesia and surgery were uneventful and he was discharged home on the same day as per day case protocol. He was readmitted about 12 h after discharge with a history of central and left lower abdominal pain with palpable mass, and distension and fever (38°C). After imaging and laboratory studies the patient was submitted to explorative surgery with the suspicion of left colonic ischemia. After intraoperative confirmation we performed standard left hemicolectomy. The postoperative course was uneventful; the patient was discharged in good general condition on the 7th postoperative day. Actually, the patient is in follow-up, with normal coagulation and hemochromocytometric pattern, asymptomatic for hypercholesterolemia and atrial flutter/fibrillation. Complications relating to bowel during open techniques of hernia repair are limited to two situations: the freeing of an incarcerated or strangulated segment of bowel and inadvertent laceration of large bowel in the presence of a sliding hernia. Following this strange case of colonic ischemia, a boolean Medline search (terms: hernia, complication, repair, groin, herniorrhaphy, hernioplasty, all major MESH subjects without language restriction) revealed no previous similar cases reported. However, to our knowledge, there is another trouble hypothesis: not causality but casualty. In conclusion, to our knowledge this is the first reported case of large left bowel ischemia following right open hernioplasty. We can conclude that the presence of a dolichocolon is an added risk factor for this rare and uneventful complication, but further investigations and case reports are necessary to estabilish the real causality

Duodenal Signet Ring Cell Carcinoma in a Celiac Patient

Celiac disease results from damage to the small intestinal mucosa due to an inappropriate immune response to a cereal protein. Long-standing or ‘refractory’ celiac disease is associated with an increased risk of autoimmunity and malignancy. We produced a brief literature review starting from a case of duodenal cancer in a celiac patient. The patient with an history of celiac disease since six months presented with acute manifestation of gastric outlet syndrome. A duodenal stricture was diagnosed at upper gastrointestinal endoscopy and confirmed by abdominal computed tomography. He was successfully treated by segmental duodenal resection. In the resected specimens, the diagnosis was duodenal signet cell adenocarcinoma. 6-month follow-up is uneventful. Primary carcinoma of the duodenum is rare (duodenal adenocarcinoma accounts for less than 0.5% of all gastrointestinal cancers and 30–45% of small intestinal cancers). Some patients with duodenal carcinoma are potentially curable by surgery, but conflicting opinions exist on the factors influencing the survival rate and on surgical treatment as the gold standard. Nevertheless, the goal in surgical treatment is to achieve clear margins. At present, surgical resection (pancreaticoduodenectomy or pancreas-sparing duodenal segmental resection) is the only available option for cure of this disease

Thermodynamically constrained averaging theory for cancer growth modelling

In Systems Biology, network models are often used to describe intracellular mechanisms at the cellular level. The obtained results are difficult to translate into three-dimensional biological systems of higher order. The multiplicity and time dependency of cellular system boundaries, mechanical phenomena and spatial concentration gradients affect the intercellular relations and communication of biochemical networks. These environmental effects can be integrated with our promising cancer modelling environment, that is based on thermodynamically constrained averaging theory (TCAT). Especially, the TCAT parameter viscosity can be used as critical player in tumour evolution. Strong cell-cell contacts and a high degree of differentiation make cancer cells viscous and support compact tumour growth with high tumour cell density and accompanied displacement of the extracellular material. In contrast, dedifferentiation and losing of cell-cell contacts make cancer cells more fluid and lead to an infiltrating tumour growth behaviour without resistance due to the ECM. The fast expanding tumour front of the invasive type consumes oxygen and the limited oxygen availability behind the invasive front results automatically in a much smaller average tumour cell density in the tumour core. The proposed modelling technique is most suitable for tumour growth phenomena in stiff tissues like skin or bone with high content of extracellular matrix

La gastrostomia percutanea endoscopica (PEG) metodo pull: nostra esperienza

Obiettivi: scopo del lavoro è valutare le indicazioni al posizionamento, i risultati e le eventuali complicanze della gastrostomia percutanea endoscopica (PEG), posizionata routinariamente in pazienti disfagici (per patologia neurologica, portatori di neoplasie del distretto cervico-faciale, esofagee o affetti da disturbi psicologici). Tipo di studio: valutazione retrospettiva dei pazienti sottoposti a PEG dal 2003 al 2005. Ambiente: Unità Operativa Semplice di Chirurgia Endoscopica (Responsabile: Prof. C. Sciumè) nell’ambito della Unità Operativa Complessa di Chirurgia Generale ad Indirizzo Toracico (Direttore: Prof. G. Modica) del Policlinico Universitario “Paolo Giaccone” di Palermo. Pazienti e metodi: 50 pazienti (11 donne e 39 uomini) sono stati sottoposti a posizionamento di PEG. Le indicazioni includevano disturbi neurologici di varia natura (82%), neoplasie esofagee inoperabili (6%), neoplasie del cardias inoperabili (4%), esiti di ictus cerebrale (2%), anoressia (2%), ostruzione faringo-esofagea (2%), neoplasia del distretto cervico-faciale (2%). Tutti i pazienti hanno ricevuto antibioticoprofilassi short-term. Risultati: sono state posizionate 51 PEG in 50 pazienti. Non si sono registrate complicanze maggiori; 45 pazienti (90%) sono vivi al follow-up ad 1 anno e non si è registrata mortalità procedura-correlata. La rimozione della PEG è stata eseguita in 2 pazienti (fine dell’utilità terapeutica) e quindi 43 pazienti in atto hanno ancora una PEG in situ. Conclusioni: il posizionamento di PEG in regime ambulatoriale in sedazione conscia è un metodo sicuro ed efficace per la nutrizione enterale, tanto da costituire il gold standard in caso di pazienti disfagici per patologie neurologiche o in previsione di interventi chirurgici demolitivi del distretto cervico-faciale. I pazienti devono essere seguiti e valutati attentamente da una equipe multidisciplinare per identificare candidati idonei. Riteniamo utile il ricorso all’antibioticoprofilassi short-term per la riduzione e la prevenzione delle infezioni della cute attorno alla gastrostomia