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Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.

Noninvasive ventilation (NIV) is an increasingly used method of respiratory support. The use of NIV is expanding over the time and if properly applied, it can save patients' lives and improve long-term prognosis. However, both knowledge and skills of its proper use as life support are paramount. This systematic review aimed to assess the importance of NIV education and training. Literature search was conducted (MEDLINE: 1990 to June, 2018) to identify randomized controlled studies and systematic reviews with the results analyzed by a team of experts across the world through e-mail based communications. Clinical trials examining the impact of education and training in NIV as the primary objective was not found. A few studies with indirect evidence, a simulation-based training study, and narrative reviews were identified. Currently organized training in NIV is implemented only in a few developed countries. Due to a lack of high-grade experimental evidence, an international consensus on NIV education and training based on opinions from 64 experts across the twenty-one different countries of the world was formulated. Education and training have the potential to increase knowledge and skills of the clinical staff who deliver medical care using NIV. There is a genuine need to develop structured, organized NIV education and training programs, especially for the developing countries. info:eu-repo/semantics/publishedVersion

To celebrate the 20th anniversary of Molecular Medicine, this special issue showcases the fields of science influenced by the most cited scientific contributions to the journal over the past two decades. The authors of these reviews are leaders in the fields of immunology, cancer, atherosclerosis, Alzheimer’s disease and diabetes. We asked them to provide updates that highlight the progress made in the selected fields of research to which their highly cited Molecular Medicine publication contributed. Two reviews discuss key elements in the immune response to tissue injury: one focuses on the fibrocyte, which acts during the earliest phase of the innate immune response, and the other focuses on HMGB1, which acts as a later mediator of inflammation. Richard Bucala reports on the advances made on the “fibrocyte,” the unique collagen-producing leukocyte that he discovered in the 1990s and its role beyond the original context of wound repair. The contribution of this cell type to the pathogenesis of different fibrosing disorders has led to fibrocyte-directed therapies that are currently being tested in the clinic. Huan Yang and colleagues provide an overview of HMGB1, a later mediator of infection and tissue injury. The authors review its multiple functions and complex regulation. They conclude with a discussion on the first two HMGB1-specific antagonists that are paving the way toward future therapeutic applications. A third review by Antonino Nicoletti and colleagues looks at the adaptive immune response in the context of atherosclerosis. The authors discuss the roles that proatherogenic and athero-protective T and B cells play in this disease. They also highlight the different strategies used in preclinical studies with an outlook to clinical applications. Jason A Chesney and Robert A Mitchell follow the saga of macrophage migration inhibitory factor (MIF) from its discovery through the many studies that implicate this cytokine in several aspects of cancer biology. They focus in particular on the role of MIF in tumor neovascularization, which likely participates in primary and metastatic disease progression. The advances made in this field are underscored by the first clinical trial that has been initiated to test anti-MIF therapies. Jennifer Hardingham and colleagues cover the circulating tumor cells (CTCs), another interesting aspect of cancer biology with great implications for clinical applications. Their discussion of various technical efforts that have been made to capture these cells from the patients’ blood, the advances made and the challenges that still remain offer a clear picture of the state of the art of this new approach. These advances will certainly augment the battery of cancer diagnostic tools in the clinic in the not too distant future. Sho-ichi Yamagishi and colleagues tackle the role of advanced glycation end products (AGEs) in diabetes. They describe how the products of reactions occurring between sugars and proteins, lipids and nucleic acids lead to altered function and metabolism of these macromolecules with severe consequences in diabetes and aging-associated disorders. The authors also discuss the potential value of measuring serum levels of AGEs to evaluate organ damage in diabetes. Finally, Jochen Walter summarizes the incredible progress made over the past two decades in understanding the role of presenilins in the onset of Alzheimer’s disease. From the discovery of the gene mutations in inherited familial forms of early onset of Alzheimer’s disease, Walter follows the path of discoveries that leads to the identification of their functions as components of a protease complex responsible for the cleavage of the amyloid precursor protein, an important determinant of the pathophysiology of the disease. He also discusses the hopes associated with the development of several inhibitors of presenilins and the disappointing results of their use in the clinic. Dr. Walter concludes with a positive outlook on development of more selective inhibitors of presenilins that could provide future therapies for Alzheimer’s disease. We are pleased to offer these engaging and interesting historical perspectives of fields that were introduced to the scientific public in our journal and hope that our readers will enjoy them, too.

Si è delineato in questo contributo il quadro offerto dalle recenti ricerche nella necropoli protostorica di Comino presso Guardiagrele. La necropoli venne utilizzata per buona parte del primo millennio a. C. tra il X secolo a. C. e il III secolo a. C. mostrando dunque un impianto a lunga continuità di vita. La fase più interessante che mostra elementi di assoluta novità nel quadro regionale è la fase più antica, compresa nel momento iniziale della prima età del ferro. Appare caratterizzata da sepolture sotto tumulo con importanti corredi già strutturati negli indicatori di sesso e status. Nelle tombe maschili si cominciano a deporre oltre ai rasoi anche le armi (spade e punte di lancia). Nelle tombe femminili compaiono corredi con parures di grandi fibule in bronzo, quasi certamente legate a un uso cerimoniale. Altro elemento di assoluta novità è la ricerca di visibilità esterna delle sepolture : oltre alla presenza del tumulo, sono presenti degli elementi litici, sicuramente lavorati, collocati all’esterno dei tumuli, i cui confronti più significativi sono i semata sepolcrali dalla necropoli di Monte Saraceno sul Gargano. Questi elementi sembrano anticipare i legami con l’area pugliese che verranno poi esplicitati più compiutamente nella stele di Guardiagrele. Per altri reperti sembra di intravedere una circolazione più allargata o «periadriatica » , con particolare riferimento per le fibule a quattro spirali o le spade di tipo Terni. Nel contesto dei siti gravitanti nel comprensorio della Maiella orientale, Comino mostra una ricchezza e una diversità di componenti che arricchisce e integra il quadro più ampio riferito all’Abruzzo meridionale., Ruggieri Maria. La necropoli di Comino a Guardiagrele. In: Mélanges de l'École française de Rome. Antiquité, tome 115, n°1. 2003. Antiquité. pp. 109-127.