Direct analysis of thymic function in children with Down's syndrome

BACKGROUND: Down's syndrome (DS) is characterized by several immunological defects, especially regarding T cell compartment. DS is considered the best example of accelerated ageing in humans. Direct observations of the thymus have shown that in DS this organ undergoes severe histological and morphological changes. However, no data on its capacity to generate T cells are present in the literature. Here, using a new technology based upon real time PCR, we have investigated the capacity of the thymus to produce and release newly generated T lymphocytes (the so called "recent thymic emigrants", RTE) in children with DS. METHODS: We studied 8 children affected by DS, aged 2–7 years, compared with 8 age- and sex-matched healthy controls. Flow cytometry was used to determine different lymphocytes subsets. Real time PCR with the Taqman system was used to quantify the amount of RTE, i.e. peripheral blood lymphocytes that express the T cell receptor rearrangement excision circles (TREC). RESULTS: In comparison with control children, those with DS had a significant lower number of TREC+ peripheral blood cells. Moreover, in DS children but not in controls, a strong negative correlation between age and the levels of TREC+ cells was found. CONCLUSIONS: The direct measure of thymic output indicates that the impairment of the organ results in a reduced production of newly generated T cells. This observation could suggest that cytokines able to modulate thymic function, such as interleukins, could be useful to improve the functionality of the organ and to treat the immunodeficiency present in DS subjects

REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validate guidelines on the perioperative care of patients with borderline resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC).SUMMARY BACKGROUND DATA: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking.METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to non-surgical guidelines.RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive mean to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ).CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR- and LA-PDAC, and serve as the basis of a new international registry for this patient population.</p

REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validate guidelines on the perioperative care of patients with borderline resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC).SUMMARY BACKGROUND DATA: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking.METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to non-surgical guidelines.RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive mean to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ).CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR- and LA-PDAC, and serve as the basis of a new international registry for this patient population.</p

Nutrition and Inflammation in Older Individuals: Focus on Vitamin D, n-3 Polyunsaturated Fatty Acids and Whey Proteins

Chronic activation of the inflammatory response, defined as inflammaging, is the key physio-pathological substrate for anabolic resistance, sarcopenia and frailty in older individuals. Nutrients can theoretically modulate this phenomenon. The underlying molecular mechanisms reducing the synthesis of pro-inflammatory mediators have been elucidated, particularly for vitamin D, n-3 polyunsaturated fatty acids (PUFA) and whey proteins. In this paper, we review the current evidence emerging from observational and intervention studies, performed in older individuals, either community-dwelling or hospitalized with acute disease, and evaluating the effects of intake of vitamin D, n-3 PUFA and whey proteins on inflammatory markers, such as C-Reactive Protein (CRP), interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor \u3b1 (TNF-\u3b1). After the analysis, we conclude that there is sufficient evidence for an anti-inflammatory effect in aging only for n-3 PUFA intake, while the few existing intervention studies do not support a similar activity for vitamin D and whey supplements. There is need in the future of large, high-quality studies testing the effects of combined dietary interventions including the above mentioned nutrients on inflammation and health-related outcomes

Heremitical places of a modern Arcadia: Ignazio Stern in the Oratory of Saint Onuphrius the Anchorite in Lugo di Romagna

The Oratory of Saint Onuphrius, presently the venue of municipally promoted festivals and art exhibitions, had once a liturgical function related to the charitable activity of the annexed hospital, where needy people of the town could be offered some relief. Despite the present employment, however, the state of preservation and integrity of the Oratory's decorations do allow one's imagination to see such past activity, and so gather a deeper insight as to the choices of the patrons, in relation to their own requirements and to the complex's purpose. In particular, the cycle of paintings dedicated to the stories of the anchorite saint, made between 1716 and 1719 by the Bavarian painter Ignazio Stern, is the expression of a culture that was influenced by Arcadian literature, and that saw the assertion of values based on the Gospel in the voluntary dismissal of the material comforts provided by the civilisation of progress

Valorizzazione e salvaguardiadei prodotti tradizionali: caratteristiche fisiche, chimiche e aromatiche del salame S. Angelo IGP per la caratterizzazione e certificazione di prodotto

The Salami S. Angelo is the oldest Italian pork sausage. Recently this product has obtained by the European Union (G.U.C.E. 2007/C 289/17) the IGP certification mark. In order to characterize this Sicilian product, a study was carried out on 17 "S. Angelo IGP" salami called "sottocularino", of 515g of weight after 55 days (±7) of seasoning, and prepared according to the disciplinary of production of the "Consorzio di tutela del salami S. Angelo". The salami were sampled from the 5 of 7 food industries belonging to the "Consorzio di Tutela del Salame S. Angelo". The physical, chemical and sensorial characteristics of this product were studied. The central part of each salami was sliced, and, on each slice, the colour, the tenderness and the elasticity were determined. Moreover, on each sample homogenized, the pH, the chemical composition and the sensorial characteristics were analysed. The colour of the muscular part showed a red index (a*) of 20,16±2,04, whereas, the yellow index (b*) of the fat was 15,78±1,67. The tenderness was 0,405±0,06 N/mm2 and the elasticity index was 0,09±0,006mm. The mean value of the pH was 5,99±0,15. The chemical composition, expressed in g per 100g of edible part, showed good values of humidity (35,97±2,56g), high values of crude protein (32,02±1,75g), low values of fat (23,03±2,36g) as weel as of NaCl (3,91±0,44g). Fortyfive volatile compound were identified and quantified; the number of identified compound for each class and the incidence of the classes on the aromatic composition were: n.21 terpenes (52,11%), n.5 ketones (24,42%), n.8 alcohols (13,68%), n.4 acids (2,19%), n.2 aldehydes (0,16%) e n.5 miscellaneous (7,44%)

Die Bedeutung der Scherspannungssteigerung für die experimentelle Arteriogenese und die Expression von Cofilin 1 und 2 nach Akutligatur der Arteria femoralis und Anlage einer arterio-venösen Fistel in einem Tiermodell

In dieser Studie wurde ein Tiermodell mit chronischer erhöhter Scherspannung verwendet. Es wurde eine arteriovenöse Seit-zu-Seit-Anastomose zwischen der Arteria und Vena femoralis angelegt, eine Woche nachdem die Arteria femoralis proximal beidseits ligiert wurde. Auf diesem Weg entleerte sich ein großer Teil des Kollateralblutflußes in das venöse Niederdrucksystem, was zu einem erhöhten Fluß führte. Nach einer weiteren Woche wurde das Experiment nach Durchführung einer digitalen Subtraktionsangiographie beendet. Im Anschluß erfolgte die Präparation von Kollateralarterien, Muskel und Kontrollarterien von beiden Seiten. Mit den Gewebeproben wurden 2-dimensionale Polyacrylamid-Gelelektrophoresen, Western und Northern Blots durchgeführt. Im Vergleich zur nur ligierten Seite fand sich auf der Fistelseite eine signifikant erhöhte Zahl an angiographisch sichtbaren Kollateralgefäßen. Die 2- dimensionale Polyacrylamid-Gelelektrophorese zeigte etwa 1000 Spots, von denen fast 50 in ihrer Expression verändert waren; darunter war das auf die Aktindynamik und damit Zellbewegung einwirkende Cofilin, das starke Expressionsunterschiede zwischen Ligatur- und Fistelseite aufwies. Diese Ergebnisse wurden mittels den Blotverfahren bestätigt und die unterschiedliche Ausprägung der Isoformen Cofilin 1 und 2 ausgewertet. Dabei entspricht das erstere dem undifferenzierten Status und das zweite dem differenzierten Status der glatten Muskelzellen. Dieses Tiermodell demonstriert, daß anhaltende Scherkrafterhöhung einen anhaltenden arteriogenetischen Prozeß unterhält und daß Zellmigration eine wichtige Rolle in diesem spielt, was durch die Veränderungen in der Cofilinexpression während der Kollateralentwicklung deutlich wird.In this study we used an animal model with chronically increased shear stress. We constructed a side-to-side arterio-venous fistula between the femoral artery and vein, one week after we have ligated the proximal femoral artery on both sides. On this path a large part of the collateral bloodow was drained in the venous system with a small resistance which increase the ow and shear stress. After one more week we carried out digital subtraction angiography and the animals were euthanised. The dissection of collateral arteries, muscle and contol arteries from both sides follwed and 2-dimensional polyacrylamide gelelectrophoresis, western and northern blot analysis were performed. In comparison to the only ligated side the number of angiographically visible collaterals of the hindlimb with the fistula significantly increased. The 2-D-gel electrophoresis of collateral proteins showed about 1000 spots, of which almost 50 were differentially regulated, containing actin- and thereby cellmotilitymodulating cofilin, which showed high degree of differential expression. These results were confirmed and subdivided into both isoforms cofilin 1 and 2 by the blot analyses; the isoform cofilin 1 comply to the undifferentated state and cofilin 2 to the differantated state of smooth muscle cells. This animal model demonstrates that durable arised levels of shear stress cause an ongoing strong arteriogenic response and that cellmigration plays an important role in the arteriogenic process, demostrated via the changes in cofilin expression during collateral development

Hot Topics in Pneumologia Interventistica – Volume 2

The Master in Interventional Pulmonology aims at training a versatile pulmonologist, with professional skills in diagnostic and operative bronchoscopy, thoracoscopy and artificial respiratory tracts management with the synergistic contribution of university and hospital teachers. Every year, several specialists from all over the national territory take part to the Master. This work is a collection of all the dissertations presented by the attendants of the seventh edition of the Master in Interventional Pulmonology of the academic year 2015/2016, and acts as evidence and worthy conclusion for a demanding but fruitful year of study and practical activities aimed at certifying professional competence, which can be useful and expendable in the curriculum of a pulmonologist

Biochemical Biomarkers and Neurodegenerative Diseases

In this book, we collected scientific articles, including reviews and research articles, showcasing the lastest literature on the importance of biochemical biomarkers in the management of neurodegenerative diseases, from screening to diagnosis, prognosis, and treatment