Prediction of incident type 2 diabetes mellitus based on a twenty-year follow-up of the Ventimiglia heart study

A novel algorithm to predict incident type 2 diabetes mellitus (iT2DM) is presented considering data from a 20-year prospective study in a Southern Italy population. Eight hundred and fifty-eight out of 1,351 subjects (24?C85?years range of age) were selected. Incident type 2 diabetes was diagnosed in 103 patients in a 20-year follow-up. The Finnish Diabetes Risk Score (FINDRISC) and the Framingham Offspring Study simple clinical model (FOS) have been used as reference algorithms. Two custom algorithms have been created using Cox parametric hazard models followed by PROBIT analyses: the first one (VHSRISK) includes all the study subjects and the second one (VHS95RISK) evaluates separately subjects with baseline fasting blood glucose (FBG) above/below 5.2?mmol/L (95?mg/dL). The 44 iT2DM cases below 5.2?mmol/L of baseline FBG were predicted by high LDL cholesterol, metabolic syndrome (ATPIII criteria), BMI?>?30?kg/m², and high factor VII activity. The 59 cases above the FBG threshold were predicted by FBG classes, hypertension, and age. ROC areas for iT2DM prediction were: FINDRISC?=?0.759, FOS?=?0.762, VHSRISK?=?0.789, and VHS95RISK?=?0.803. In a Mediterranean population, the use of a custom generated algorithm evaluating separately low/high FBG subjects improves the prediction of iT2DM in subjects classified at lower risk by common estimation algorithms.     

Current Concept in the Pathophysiology of Hepatitis Delta Infection

Hepatitis delta virus (HDV) is a unique human virus, showing similarities with plant viroids. Although impressive knowledge on virus structure and replication has been achieved, several questions like HBV/HDV interaction and post translational modifications of HD antigens remain to be answered. Potential targets for therapeutic strategies are now emerging. To date, eight major genotypes of the HDV have been identified. The HDV-1 is the prevailing genotype in Europe, but migration phenomena may change this profile. Immune response is likely to play an important role in the pathogenesis of HDV-induced liver disease; few data are available on T cells response either during infection and therapy. HDV usually suppresses HBV replication; recent studies show as viral dominances may change over time. Delta infection leads to severe liver disease, with different patterns of progression to liver fibrosis and decompensation. Beside the association between HDV/HBV and HCC is demonstrated a risk specifically related to HDV remains controversial.     

Efficacy and safety of prostate vaporesection using a 120-W 2-μm continuous-wave Tm:YAG laser (RevoLix 2) in patients on continuous oral anticoagulant or antiplatelet therapy

The aim of our current study was to demonstrate the efficacy and safety of vaporesection using a 120-W Tm:YAG laser (Revolix Duo) in patients with BPH receiving systemic anticoagulation or antiplatelet therapy. Between April 2010 and November 2011, a total of 76 patients using oral antiplatelet or anticoagulant (OA) agents affected by LUTS for BPH were underwent thulium vaporesection of the prostate (ThuVARP) using a 120-W 2-μm CW Tm:YAG laser and evaluated at 3- and 6-month follow-up. Of these, in 41 patients (group A) was performed vaporesection while receiving OA therapy. In 35 patients (group B), OA agents were discontinued 10 days before surgery. There were no significant differences in average vaporesection times, catheterization time, or hospital stay. There was no significant change in serum sodium level before and immediately after vaporesection in either group. Significant improvements compared to baseline were observed at each postoperative assessment in both groups for Qmax, PVR, IPSS, and QoL. More specifically, the IPSS score improved from 21.7 at baseline to 5.2 at 6 months in group A and from 20.7 to 4.5 in group B. At 6 months, Qmax increased 226 and 190 % for the 2 groups, respectively. The PVR decreased from 119 at baseline to 11 mL at 6 months in group A and from 125 to 11 mL in group B. ThuVARP is a safe and efficient procedure for patients with BPH, refractory to pharmacotherapy, who require active antiplatelet or anticoagulant therapy.     

Case-control association study of 36 single-nucleotide polymorphisms within 10 candidate genes for major depression and bipolar disorder

In this study we investigated 36 single nucleotide polymorphisms within 10 genes previously associated with major depression and bipolar disorder, as well as with the response to their treatment (ABCB1, ABCB4, TAP2, CLOCK, CPLX1, CPLX2, SYN2, NRG1, 5HTR1A and GPRIN2). No association with mood disorders and clinical outcomes was observed.     

Comment to the article titled: “Autonomic nervous system function in women with anorexia nervosa” by Jenkins and coll

Clinical Autonomic Research -     

Laser-driven structural transformations in dextran-graft-PNIPAM copolymer/Au nanoparticles hybrid nanosystem: the role of plasmon heating and attractive optical forces

Laser induced structural transformations in a dextran grafted-poly(N-isopropylacrylamide) copolymer/Au nanoparticles (D-g-PNIPAM/AuNPs) hybrid nanosystem in water have been observed. The laser induced local plasmonic heating of Au NPs leads to Lower Critical Solution Temperature (LCST) phase transition in D-g-PNIPAM/AuNPs macromolecules accompanied by their shrinking and aggregation. The hysteresis non-reversible character of the structural transformation in D-g-PNIPAM/AuNPs system has been observed at the decrease of laser intensity, i.e. the aggregates remains in solution after the turn-off the laser illumination. This is an essential difference comparing to the case of usual heating–cooling cycles when there is no formation of aggregates and structural transformations are reversible. Such a fundamental difference has been rationalized as the result of action of attractive optical forces arising due to the excitation of surface plasmons in Au NPs. The attractive plasmonic forces facilitate the formation of the aggregates and counteract their destruction. The laser induced structural transformations have been found to be very sensitive to matching conditions of the resonance of the laser light with surface plasmon resonance proving the plasmonic nature of observed phenomena.

Structural transformations in D-g-PNIPAM/AuNPs hybrid nanosystem arise from the synergetic action of plasmonic heating and attractive optical plasmonic forces.     

Cas9-expressing chickens and pigs as resources for genome editing in livestock

Genetically modified animals continue to provide important insights into the molecular basis of health and disease. Research has focused mostly on genetically modified mice, although other species like pigs resemble the human physiology more closely. In addition, cross-species comparisons with phylogenetically distant species such as chickens provide powerful insights into fundamental biological and biomedical processes. One of the most versatile genetic methods applicable across species is CRISPR-Cas9. Here, we report the generation of transgenic chickens and pigs that constitutively express Cas9 in all organs. These animals are healthy and fertile. Functionality of Cas9 was confirmed in both species for a number of different target genes, for a variety of cell types and in vivo by targeted gene disruption in lymphocytes and the developing brain, and by precise excision of a 12.7-kb DNA fragment in the heart. The Cas9 transgenic animals will provide a powerful resource for in vivo genome editing for both agricultural and translational biomedical research, and will facilitate reverse genetics as well as cross-species comparisons.

Chickens and pigs are the most important livestock species worldwide. They are not only important sources of food, but also valuable models for evolutionary biology and biomedical science. Pigs share a high anatomical and physiological similarity with humans and are an important species for translational biomedical research, for example, in the areas of cancer, diabetes, neurodegenerative, and cardiovascular diseases (1–3). They also resemble the human pathophenotype more closely than rodents. For example, pig models for familial adenomatous polyposis (FAP) develop polyps in the large intestine as observed in human patients (4), whereas mouse FAP models develop them in the small intestine (5). In contrast to mammals, chickens are phylogenetically distant vertebrates from humans, but they were instrumental in the field of developmental biology due to the easy access to the embryonated egg. They are used for studying neurological and cardiovascular functions (6–8) and provided key findings in B cell development and graft versus host responses (9–11). Genetically modified livestock species also hold great promise for agriculture by offering new approaches for disease control, such as genome-edited pigs resistant to Porcine Reproductive and Respiratory Syndrome or Avian Leucosis Virus (ALV)-resistant chickens (12–15).Due to the lack of fully functional embryonic stem cells, genetic engineering in pigs and chickens has been a laborious, inefficient, and time-consuming procedure (16). The generation of pigs with precise germline modifications required gene targeting in somatic cells followed by somatic cell nuclear transfer. This also is not practical in chickens, where precise alteration of the genome only became possible with recent improvements in the cultivation and manipulation of germline-competent primordial germ cells (PGCs) (17–19). These modified PGCs can be injected into the blood vessel system of stage 13 to 15 (Hamburger−Hamilton [HH]) embryos to produce germline chimeras and, by further breeding, genetically modified chickens.With the advent of synthetic endonucleases such as CRISPR-Cas9 efficiency of targeted germline modification has improved in both species (20–23). It still requires the generation and breeding of new founder lines, which is time consuming in large animals. To circumvent the need for generating germline-modified animals, attempts have been made to carry out genome editing directly in specific organs or tissues (24–27). But this has been hampered by the need to deliver both Cas9 and the required guide RNA (gRNA) and by the limited cargo capacity of viral vectors. To bypass this drawback, Cas9 transgenic mice have been generated, requiring delivery of only the respective gRNAs (28).Here, we describe the generation of both Cas9 transgenic pigs and chickens that ubiquitously express Cas9 endonuclease and provide proof of its function in vitro and in vivo. These animals provide an innovative and efficient model for in vivo genome editing to assess gene function in health and disease.