Transcranial direct current stimulation improves the QT variability index and autonomic cardiac control in healthy subjects older than 60 years

Background: Noninvasive brain stimulation technique is an interesting tool to investigate the causal relation between cortical functioning and autonomic nervous system (ANS) responses. Objective: The objective of this report is to evaluate whether anodal transcranial direct current stimulation (tDCS) over the temporal cortex influences short-period temporal ventricular repolarization dispersion and cardiovascular ANS control in elderly subjects. Subjects and methods: In 50 healthy subjects (29 subjects younger than 60 years and 21 subjects older than 60 years) matched for gender, short-period RR and systolic blood pressure spectral variability, QT variability index (QTVI), and noninvasive hemodynamic data were obtained during anodal tDCS or sham stimulation. Results: In the older group, the QTVI, low-frequency (LF) power expressed in normalized units, the ratio between LF and high-frequency (HF) power, and systemic peripheral resistances decreased, whereas HF power expressed in normalized units and α HF power increased during the active compared to the sham condition (P,0.05). Conclusion: In healthy subjects older than 60 years, tDCS elicits cardiovascular and autonomic changes. Particularly, it improves temporal ventricular repolarization dispersion, reduces sinus sympathetic activity and systemic peripheral resistance, and increases vagal sinus activity and baroreflex sensitivity

Pruritus in chronic plaque psoriasis: a questionnaire-based study on 230 Italian patients

In the past, several textbooks defined psoriasis as a non-pruritic dermatosis, but the most recent data in the literature emphasizes the high frequency of pruritus in psoriasis and its impact on the quality of life of patients with psoriasis.Aim of this study was to explore the sensory and affective dimensions of pruritus as well as to assess the impact of itch on quality of life and to evaluate the influence of lifestyles, habits, and various anti-pruritic therapies on pruritus in a large group of psoriatic subjects. The structured Yosipovitch itch questionnaire was given to 240 psoriatic patients. 230 patients returned a complete and detailed questionnaire. Pruritus was referred to by 80% of the patients. Psoriasis area and severity index (PASI) was significantly higher in itching-patients (P=0.04). In half of the patients, itching appeared daily, particularly in the evening. Significant aggravating factors of pruritus were stress, skin dryness, hot water, sweating, elevated ambient temperature, exercise, abundant meals, bad moods, lying position, and contact with clothes. Cold water is the only factor that showed to significantly relieve the pruritus. Anti-pruritic therapies had limited effect.Pruritus is a common, bothersome, and poorly responsive symptom in patients with psoriasis.</p

Hepatitis C Virus (HCV) genotypes distribution among hepatocellular carcinoma patients in Southern Italy: a three year retrospective study

Abstract Background Hepatocellular carcinoma (HCC) is one of the major cause for cancer in the world. Aim of this case-control study was to investigate the distribution pattern of HCV genotypes among HCC patients and suggest whether infection with specific subtypes may be associated with an increased risk of progression to cancer. Methods 152 HCC anti-HCV positive patients, fulfilling the criteria from the Barcelona 2000 EASL conference, and 568 patients HCV chronically infected but without HCC as control group were included in the study. Serum of each patient was evaluated for viral load estimation and genotyping. Results Males with HCC significantly showed to have quite 2 times higher risk of exposure to HCV infection (OR = 1.72; 95% CI = 1.15–2.58). Moreover, HCC was significantly associated with older age. In fact, > 50 years older patients showed to have a higher risk of developing HCC (OR = 17.4; 95% CI = 4.24 to 71.36) compared to younger patients. HCV RNA rate was significantly higher (83.7%) among HCC patients than in the control group (61.4%, p < 0.001) and the most prevalent genotype was 1b (68.0% in HCC vs 54.4% in the control group, p < 0.005). HCC patients significantly have a risk of exposure to HCV 1b infection almost 2 times greater than the control group (OR = 1.8; 95% CI = 1.11–2.82). The multivariate-adjusted OR (95% CI) of developing HCC for HCV 1b comparing to non-1b was 1.65 (1.16–2.33). Conclusions Our study detected a significantly higher rate of HCV RNA positivity and a higher rate of HCV 1b infection in HCC patients, suggesting the strict association between subtype 1b infection and HCC. A prospective study with larger number of samples would be needed to confirm our results

Peripheral Blood Hemopoietic Stem Cell Mobilization Regimens in POEMS Syndrome: A Retrospective Study at 2 Hematologic Italian Centers.

ABSTRACT Autologous peripheral blood stem cell transplantation should be considered first-line therapy in young patients with POEMS. The best protocol to collect peripheral blood stem cells remains to be defined, because of the disease rarity and the heterogeneity of published case series. We collected clinical and laboratory data from 25 patients undergoing mobilization, of whom 11 were mobilized using cyclophosphamide (CY) followed by granulocyte colony-stimulating factor (G-CSF) and 14 patients using G-CSF. The incidence of poor mobilization was low and not statistically different between the 2 groups. Both schemes (CY plus G-CSF versus G-CSF alone) were able to harvest a sufficient CD34+ cell dose

Gefitinib in Non Small Cell Lung Cancer

Gefitinib is an oral, reversible, tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) that plays a key role in the biology of non small cell lung cancer (NSCLC). Phase I studies indicated that the recommended dose of gefitinib was 250 mg/day. Rash, diarrhea, and nausea were the most common adverse events. The positive results obtained in early phase 2 clinical trials with gefitinib were not confirmed in large phase 3 trials in unselected patients with advanced NSCLC. The subsequent discovery that the presence of somatic mutations in the kinase domain of EGFR strongly correlates with increased responsiveness to EGFR tyrosine kinase inhibitors prompted phase 2 and 3 trials with gefitinib in the first line-treatment of EGFR-mutated NSCLC. The results of these trials have demonstrated the efficacy of gefitinib that can be now considered as the standard first-line treatment of patients with advanced NSCLC harbouring activating EGFR mutations

Clinical features and lifestyle of patients with amyotrophic lateral sclerosis in Campania: brief overview of an Italian database

Background. Physical activity and occupational exposures appeared to play a relevant role in pathogenesis of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease of unknown origin. Materials and methods. We aimed to make an overview of the clinical characteristics and life - style (occupation and sport) of a population of 395 patients with ALS from campania, in southern Italy. Results. ALS onset resulted anticipated of about 11 years in industry workers, whilst the more frequent site of onset among farmers was upper limbs. compared to non-athletes, athletes, particu- larly soccer players, showed a 7 years anticipation of ALS onset, with higher mortality after 5 years. Discussion and conclusions. We suggest that subjects genetically prone to abnormal response to hy - poxia during strenuous physical activity or exposed to neurotoxic agents, such as athletes, farmers or industry workers, might present increased risk to develop ALS. Future case-control and follow-up studies on our population should be implemented to deepen the present results. Riassunto (Caratteristiche cliniche e stile di vita di pazienti con sclerosi laterale amiotrofica in Campania: breve panoramica di un database italiano). Introduzione. Attivita fisica ed esposizione professionale a sostanze tossiche sembrano svolgere un ruolo rilevante nella patogenesi della sclerosi laterale amiotrofica (SLA), una malattia neurodegenerativa di origine sconosciuta. Materiali e metodi. ci siamo proposti di effettuare una panoramica delle caratteristiche cliniche e dello stile di vita (attivita lavorativa e sport) di una popolazione di 395 pazienti affetti da SLA provenienti dalla regione campania, in Italia meridionale. Risultati. L'insorgenza della SLA e risultata anticipata di circa 11 anni nei lavoratori dell'industria, mentre il sito piu frequente di insorgenza tra i contadini era caratterizzato dagli arti superiori. Rispetto ai non- sportivi, gli sportivi, soprattutto i calciatori, hanno mostrato un'anticipazione di 7 anni nell'insorgenza della SLA, con maggiore mortalita a 5 anni. Discussione e conclusioni. Abbiamo ipotizzato che i soggetti geneticamente predisposti a risposte anomale all'ipossia durante l'attivita fisica intensa o esposti ad agenti neurotossici, come gli sportivi, gli agricoltori o i lavoratori dell'industria, possano presentare un aumen - tato rischio di sviluppare la SLA. Futuri studi caso-controllo e di follow-up sulla nostra popolazione dovrebbero essere effettuati per approfondire i risultati attuali

Phase 1/2 study of valproic acid and short-course radiotherapy plus capecitabine as preoperative treatment in low-moderate risk rectal cancer-V-shoRT-R3 (Valproic acid--short Radiotherapy--rectum 3rd trial).

BACKGROUND: Locally advanced rectal cancer (LARC) is a heterogeneous group of tumors where a risk-adapted therapeutic strategy is needed. Short-course radiotherapy (SCRT) is a more convenient option for LARC patients than preoperative long-course RT plus capecitabine. Histone-deacetylase inhibitors (HDACi) have shown activity in combination with RT and chemotherapy in the treatment of solid tumors. Valproic acid (VPA) is an anti-epileptic drug with HDACi and anticancer activity. In preclinical studies, our group showed that the addition of HDACi, including VPA, to capecitabine produces synergistic antitumour effects by up-regulating thymidine phosphorylase (TP), the key enzyme converting capecitabine to 5-FU, and by downregulating thymidylate synthase (TS), the 5-FU target. METHODS/DESIGN: Two parallel phase-1 studies will assess the safety of preoperative SCRT (5 fractions each of 5 Gy, on days 1 to 5) combined with (a) capecitabine alone (increasing dose levels: 500-825 mg/m2/bid), on days 1-21, or (b) capecitabine as above plus VPA (oral daily day -14 to 21, with an intra-patient titration for a target serum level of 50-100 microg/ml) followed by surgery 8 weeks after the end of SCRT, in low-moderate risk RC patients. Also, a randomized phase-2 study will be performed to explore whether the addition of VPA and/or capecitabine to preoperative SCRT might increase pathologic complete tumor regression (TRG1) rate. A sample size of 86 patients (21-22/arm) was calculated under the hypothesis that the addition of capecitabine or VPA to SCRT can improve the TRG1 rate from 5% to 20%, with one-sided alpha = 0.10 and 80% power.Several biomarkers will be evaluated comparing normal mucosa with tumor (TP, TS, VEGF, RAD51, XRCC1, Histones/proteins acetylation, HDAC isoforms) and on blood samples (polymorphisms of DPD, TS, XRCC1, GSTP1, RAD51 and XRCC3, circulating endothelial and progenitors cells; PBMCs-Histones/proteins acetylation). Tumor metabolism will be measured by 18FDG-PET at baseline and 15 days after the beginning of SCRT. DISCUSSION: This project aims to improve the efficacy of preoperative treatment of LARC and to decrease the inconvenience and the cost of standard long-course RT. Correlative studies could identify both prognostic and predictive biomarkers and could add new insight in the mechanism of interaction between VPA, capecitabine and RT.EudraCT Number: 2012-002831-28. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01898104

Observing the Evolution of the Universe

How did the universe evolve? The fine angular scale (l>1000) temperature and polarization anisotropies in the CMB are a Rosetta stone for understanding the evolution of the universe. Through detailed measurements one may address everything from the physics of the birth of the universe to the history of star formation and the process by which galaxies formed. One may in addition track the evolution of the dark energy and discover the net neutrino mass. We are at the dawn of a new era in which hundreds of square degrees of sky can be mapped with arcminute resolution and sensitivities measured in microKelvin. Acquiring these data requires the use of special purpose telescopes such as the Atacama Cosmology Telescope (ACT), located in Chile, and the South Pole Telescope (SPT). These new telescopes are outfitted with a new generation of custom mm-wave kilo-pixel arrays. Additional instruments are in the planning stages.Comment: Science White Paper submitted to the US Astro2010 Decadal Survey. Full list of 177 author available at http://cmbpol.uchicago.ed