STRATIGRAPHIC AND PALEOGEOGRAPHIC EVOLUTION OF A CARBONATE PLATFORM IN AN EXTENSIONAL TECTONIC REGIME: THE EXAMPLE OF THE DOLOMIA PRINCIPALE IN LOMBARDY (ITALY)

Stratigraphic and sedimentologic studies of the norian succession outcropping in rhe Lombardy Basin allowed the reconstruction of the paleogeographic and strucural evolution oi this area, 1) restricted lagoon and tidal flat are the most common deposits ar the Carnian-Norian boundary (Lower Member of the Dolomia Principale); 2) these are overlain by a thick inner platform succession organized in shallowing upwards cycles (lower Dolomia Principale), with the exception of Idro Lake area where intraplatform basin already generated; 3) the overlying middle-upper Dolomia Principale is dissected by synsedimentary faults with subsequent widespread development of intraplatform basin, margin, and slope facies with marked asymmetric distribution; the inner platform was locally emerged; 4) in the uppermost Dolomia Principale buildup margins become more abundant and the platform partially prograded on the basins; 5) at last the platform drowns and terrigenous sedimentation becomes prevalent (Riva di Solto Shales). The drowning of the platform is favoured by the lack of carbonate production, due to clay pollution and climatic changes in an area with high subsidence rates. The observed asymmetric distribution of buildup margins and fault-scarp related breccias, which outcrop on the western side of the basins west of Iseo Lake and bounding the eastern side of the basins east of Iseo Lake, allows us to propose a model of norian ensialic asymmetric rifting for the Lombardy Basin. This asymmetric rifting could be explained by interpreting the Lombardy Basin as a pull-apart basin, linked to transtension with E-W trending faults

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Acquired Complement Regulatory Gene Mutations and Hematopoietic Stem Cell Transplant–Related Thrombotic Microangiopathy

Abstract Hematopoietic stem cell transplant–related thrombotic microangiopathy (HSCT-TMA) is a severe complication whose pathophysiology is unknown. We describe 6 patients in which the disease was associated with complement regulatory gene abnormalities received from their respective donors. It is suggested that mutated and transplanted monocyte-derived cells are responsible for production of abnormal proteins, complement dysregulation, and, ultimately, for the disease. This observation might have important drawbacks as far as HSCT-TMA pathophysiology and treatment are concerned

In-silico modelling of the mitogen-activated protein kinase (MAPK) pathway in colorectal cancer: mutations and targeted therapy

Introduction: Chemical reaction networks (CRNs) are powerful tools for describing the complex nature of cancer’s onset, progression, and therapy. The main reason for their effectiveness is in the fact that these networks can be rather naturally encoded as a dynamical system whose asymptotic solution mimics the proteins' concentration profile at equilibrium.Methods and Results: This paper relies on a complex CRN previously designed for modeling colorectal cells in their G1-S transition phase and presents a mathematical method to investigate global and local effects triggered on the network by partial and complete mutations occurring mainly in its mitogen-activated protein kinase (MAPK) pathway. Further, this same approach allowed the in-silico modeling and dosage of a multi-target therapeutic intervention that utilizes MAPK as its molecular target.Discussion: Overall the results shown in this paper demonstrate how the proposed approach can be exploited as a tool for the in-silico comparison and evaluation of different targeted therapies. Future effort will be devoted to refine the model so to incorporate more biologically sound partial mutations and drug combinations

Psychological aspects in the management of patients with essential hypertension

The hypertensive patient is the most stable phenotype in psychosomatic medicine. Hypertensive patients represent a vulnerable population that deserves special attention from health care providers and systems, and psychosomatic medicine may be an important tool in the management of high blood pressure. Depression, anxiety disorders and personality features are often associated with elevated blood pressure (BP) and they may have a role in the development of mild high-renin essential hypertension. Besides, "white coat" hypertension and "masked" hypertension demonstrate how clinic blood pressure could be strongly related to trait anxiety. Hypertension is largely asymptomatic, and patients often have little understanding of the importance of achieving BP control. Medication adverse effects may become an important factor in poor adherence to the treatment and the antidepressant use increases the risk of hypertension. So, the challenge in the management of hypertensive patients is the adherence to non-pharmacological and behavioural treatments for hypertension

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape

A yeast two-hybrid system reconstituting substrate recognition of the von Hippel-Lindau tumor suppressor protein

The von Hippel-Lindau tumor suppressor protein (pVHL) is inactivated in the hereditary cancer syndrome von Hippel-Lindau disease and in the majority of sporadic renal carcinomas. pVHL is the substrate-binding subunit of the CBCVHL ubiquitin ligase complex that negatively regulates cell growth by promoting the degradation of hypoxia-inducible transcription factor subunits (HIF1/2α). Proteomics-based identification of novel pVHL substrates is hampered by their short half-life and low abundancy in mammalian cells. The usefulness of yeast two-hybrid (Y2H) approaches, on the other hand, has been limited by the failure of pVHL to adopt its native structure and by the absence of prolylhydroxylase activity critical for pVHL substrate recognition. Therefore, we modified the Y2H system to faithfully reconstitute the physical interaction between pVHL and its substrates. Our approach relies on the coexpression of pVHL with the cofactors Elongin B and Elongin C and with HIF1/2α prolylhydroxylases. In a proof-of-principle Y2H screen, we identified the known substrates HIF1/2α and new candidate substrates including diacylglycerol kinase iota, demonstrating that our strategy allows detection of stable interactions between pVHL and otherwise elusive cellular targets. Additional future applications may include structure/function analyses of pVHL-HIF1/2α binding and screens for therapeutically relevant compounds that either stabilize or disrupt this interaction

What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian consensus conference on pain in neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

Epistolari dal Due al Seicento. Modelli, questioni ecdotiche, edizioni, cantieri aperti (Gargnano del Garda, 29 settembre - 1° ottobre 2014)

Nei secoli passati, la lettera era l'unico mezzo di comunicazione: familiare, amichevole, d'ufficio o di servizio, ma anche strumento di dibattito politico e culturale. Lo studio degli epistolari dei singoli ma anche delle reti di comunicazione e di scambio è uno dei grandi temi della ricerca europea contemporanea. Vi si inserisce questo secondo volume dei "Quaderni di Gargnano", che - volgendosi sia alla produzione latina sia a quella volgare dal Due al Seicento - si sofferma su problemi metodologici e casi significativi, con impostazioni e tagli diversi: dall'ecdotica alla filologia, dall'archivistica, alla storia, alla storia delle discipline

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations