Playing with opening and closing of heterocycles: using the cusmano-ruccia reaction to develop a novel class of oxadiazolothiazinones, active as calcium channel modulators and P-glycoprotein inhibitors.

As a result of the ring-into-ring conversion of nitrosoimidazole derivatives, we obtained a molecular scaffold that, when properly decorated, is able to decrease inotropy by blocking L-type calcium channels. Previously, we used this scaffold to develop a quantitative structure-activity relationship (QSAR) model, and we used the most potent oxadiazolothiazinone as a template for ligand-based virtual screening. Here, we enlarge the diversity of chemical decorations, present the synthesis and in vitro data for 11 new derivatives, and develop a new 3D-QSAR model with recent in silico techniques.

The interleukin (IL)-31/IL-31R axis contributes to tumor growth in human follicular lymphoma.

Interleukin (IL)-31A binds to an heterodimer composed of IL-31 receptor A (IL-31RA) and Oncostatin M Receptor (OSMR). The IL-31/IL-31R complex is involved in the pathogenesis of various skin diseases, including cutaneous T-cell lymphoma. No information is available on the relations between the IL-31/IL-31R complex and B-cell lymphoma.

Implementation strategies of Systems Medicine in clinical research and home care for cardiovascular disease patients.

Insights from the "-omics" science have recently emphasized the need to implement an overall strategy in medical research. Here, the development of Systems Medicine has been indicated as a potential tool for clinical translation of basic research discoveries. Systems Medicine also gives the opportunity of improving different steps in medical practice, from diagnosis to healthcare management, including clinical research.

Risk of neuroblastoma, maternal characteristics and perinatal exposures: the SETIL study.

Purpose: Neuroblastoma (NB) is the most common extra-cranial paediatric solid tumour. Incidence peaks in infancy, suggesting a role of in-utero and neonatal exposures but its aetiology is largely unknown. The aim of the present study is to evaluate the association between maternal characteristics and perinatal factors with the risk of NB, using data from the SETIL database.

Prognosis of untreated hepatocellular carcinoma.

Unlabelled: The prognosis of untreated patients with hepatocellular carcinoma (HCC) is heterogeneous, and survival data were mainly obtained from control arms of randomized studies. Clinical practice data on this topic are urgently needed, so as to help plan studies and counsel patients. We assessed the prognosis of 600 untreated patients with HCC managed by the Italian Liver Cancer Group.

Carotid atherosclerotic plaque stenosis: the stabilizing role of statins.

Background: Both pathophysiology and treatments of carotid atherosclerotic plaque stenosis represent two interesting fields of strong scientific investigation. Among different drugs, safety and efficacy of statin treatment have been widely investigated and proved.

Materials And Methods: This narrative review is based on the material searched for and obtained via MEDLINE and PubMed up to March 2014.

Extreme lateral approach to the spine in degenerative and post traumatic lumbar diseases: selection process, results and complications.

Purpose Of The Study: The aim of this study is to describe clinical and radiological outcomes as well as accompanying complications in a series of consecutive lateral transpsoas approaches (XLIF).

Materials And Methods: A retrospective study of 39 patients treated for degenerative and post-traumatic lumbar diseases was carried out. Functional status, leg and back pain and radiological outcomes were evaluated pre and post-operatively using the Oswestry disability index score (ODI) visual analog scales (VAS) and X-ray studies.

Genetic predisposition to pancreatic cancer.

Pancreatic adenocarcinoma (PC) is the most deadly of the common cancers. Owing to its rapid progression and almost certain fatal outcome, identifying individuals at risk and detecting early lesions are crucial to improve outcome. Genetic risk factors are believed to play a major role.

Liver enzyme elevation during darunavir-based antiretroviral treatment in HIV-1-infected patients with or without hepatitis C coinfection: data from the ICONA foundation cohort.

Objectives: To investigate differences in liver enzyme elevation (LEE) between HIV-infected patients with and without HCV coinfection who start a darunavir/ritonavir-containing regimen.

Methods: HIV-infected patients enrolled in the Italian Cohort of Naïve to Antiretrovirals (ICONA) Foundation Study were included if they started darunavir/ritonavir for the first time. Patients were classified as not HCV coinfected, HCV active coinfected (HCV RNA positive), and HCV nonactive coinfected (HCV-Ab positive/HCV RNA negative).

Treatment with Evasin-3 abrogates neutrophil-mediated inflammation in mouse acute pancreatitis.

Background: Acute pancreatitis is characterized by inflammatory processes affecting not only the pancreas, but also the lung. Here, we investigated timing of leucocyte infiltration and chemokine expression within lung and pancreas during pancreatitis and whether treatments selectively inhibiting chemokines (using Evasins) could improve organ injury.

Material And Methods: C57Bl/6 mice were submitted in vivo to 10-h intraperitoneal injections of cerulein and followed for up to 168 h.

Impact of propofol anaesthesia on cytokine expression profiles in the developing rat brain: a randomised placebo-controlled experimental in-vivo study.

Background: Recent experimental data indicate that volatile anaesthetics can induce a neuroinflammatory response in the central nervous system. The questions of to what extent this occurs in the developing brain and whether nonvolatile anaesthetics are also involved remain unanswered.

Objectives: The objective of this study is to investigate the impact of propofol anaesthesia on cytokine mRNA expression profiles in the neonatal brain at defined stages of the brain growth spurt.

Pyogenic liver abscess caused by Gemella morbillorum.

Even though Gemella morbillorum infection (GMI) is rare in humans, it may nevertheless, cause endocarditis, meningitis, brain abscess, pleural empyema, nephritis, mediastinitis, and--occasionally--liver abscess. We are describing the case of a 64-years-old Caucasian male admitted with fever and abdominal pain. Laboratory parameters revealed inflammation signs, and instrumental examinations showed the presence of diverticula in the ascending colon.

sTRAIL coupled to liposomes improves its pharmacokinetic profile and overcomes neuroblastoma tumour resistance in combination with Bortezomib.

Neuroblastoma (NB), the most common and deadly extracranial solid tumour of childhood, represents a challenging in paediatric oncology. Soluble tumour necrosis factor (TNF)-related apoptosis-inducing ligand (sTRAIL) is a cancer cell-specific molecule exerting remarkable anti-tumour activities against paediatric malignancies both in vitro and in preclinical settings. However, due to its too fast elimination and to the undesired related side effects, the improvement of sTRAIL in vivo bioavailability and the specific delivery to the tumour is mandatory for increasing its therapeutic efficacy.

Utility of a Liquid Formulation of Levo-thyroxine in Differentiated Thyroid Cancer Patients.

The goal of levo-thyroxine (L-T4) administration in differentiated thyroid cancer (DTC) is to suppress thyroid stimulating hormone (TSH) levels. The tolerability and efficacy of a new formulation of liquid L-T4 vs. the previous tablet formulation was evaluated in a cohort of 59 patients with cured DTC.

Emerging roles of heterogeneous nuclear ribonucleoprotein K (hnRNP K) in cancer progression.

The heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a nucleic acid-binding protein that serves as a docking platform integrating transduction pathways to nucleic acid -directed processes. Recently, this protein has emerged as an important player in carcinogenesis process. HnRNP K is overexpressed in several human cancers and its aberrant cytoplasmic localization has been associated with a worse prognosis for patients, suggesting that it has a role in cancer progression.

Progestogen-only contraceptive pill compared with combined oral contraceptive in the treatment of pain symptoms caused by endometriosis in patients with migraine without aura.

Objective: Evaluate patient satisfaction at 6-month treatment in women with symptomatic rectovaginal endometriosis and migraine without aura with (progestogen-only contraceptive pill, POP versus sequential combined oral contraceptives, COC) STUDY DESIGN: A patient preference trial including 144 women (82 in the group COC and 62 in the group POP). Main outcome measure was the degree of patient satisfaction by using a Likert scale. Secondary objectives were to evaluate differences in endometriosis-related pain and changes in migraine features during the treatment.

Potential pathophysiological role for the vitamin D deficiency in essential hypertension.

Vitamin D deficiency has been indicated as a pandemic emerging public health problem. In addition to the well-known role on calcium-phosphorus homeostasis in the bone, vitamin D-mediated processes have been recently investigated on other diseases, such as infections, cancer and cardiovascular diseases. Recently, both the discovery of paracrine actions of vitamin D (recognized as "local vitamin D system") and the link of vitamin D with renin-angiotensin-aldosterone system and the fibroblast growth factor 23/klotho pathways highlighted its active cardiovascular activity.

Effectiveness of complex interventions focused on quality-of-life assessment to improve palliative care patients' outcomes: a systematic review.

Background: One of the most crucial palliative care challenges is in determining how patient' needs are defined and assessed. Assessing quality of life has been defined as a priority in palliative care, and it has become a central concept in palliative care practice.

Aim: To determine to what extent interventions focused on measuring quality of life in palliative care practice are effective in improving outcomes in palliative care patients.

KSRP controls pleiotropic cellular functions.

The single-strand-RNA binding protein KSRP is able to negatively regulate gene expression operating with at least two distinct and integrated postranscriptional mechanisms: (i) by promoting decay of unstable mRNAs and (ii) by favoring maturation from precursors of select microRNAs (miRNAs) including the prototypical tumor suppressor let-7. Studies performed in primary and cultured cells as well as in mice proved that the ability of KSRP to integrate different levels of gene expression is required for proper immune response, lipid metabolism, cell-fate decisions, tissue regeneration, and DNA damage response.

Effect of tumor cells and tumor microenvironment on NK-cell function.

The ability of tumors to manage an immune-mediated attack has been recently included in the "next generation" of cancer hallmarks. In solid tumors, the microenvironment that is generated during the first steps of tumor development has a pivotal role in immune regulation. An intricate net of cross-interactions occurring between tumor components, stromal cells, and resident or recruited immune cells skews the possible acute inflammatory response toward an aberrant ineffective chronic inflammatory status that favors the evasion from the host's defenses.

Advanced glycation end products play adverse proinflammatory activities in osteoporosis.

Osteoporosis is a major public health burden that is expected to further increase as the global population ages. In the last twenty years, advanced glycation end products (AGEs) have been shown to be critical mediators both in the pathogenesis and development of osteoporosis and other chronic degenerative diseases related to aging. The accumulation of AGEs within the bone induces the formation of covalent cross-links with collagen and other bone proteins which affects the mechanical properties of tissue and disturbs bone remodelling and deterioration, underlying osteoporosis.