Muscle function impairment in cancer patients in pre-cachexia stage

Cancer cachexia has been reported to be directly responsible for at least 20% of cancer deaths. Management of muscle wasting in cancer-associated cachexia appears to be of pivotal importance for survival of patients. In this regard, it would be interesting to identify before its patent appearance eventual functional markers of muscle damage, to plan specific exercise protocols to counteract cachexia. The muscle function of 13 oncologic patients and 15 controls was analyzed through: i) analysis of the oxidative metabolism, indirectly evaluated trough dosage of blood lactate levels before and after a submaximal incremental exercise on a treadmill; ii) analysis of strength and, iii) endurance, in both lower and upper limbs muscles, employing an isokinetic dynamometer. Statistical analyses were carried out to compare the muscle activities between groups. Analysis of oxidative metabolism during the incremental exercise on a treadmill showed that patients performed a shorter exercise than controls. Lactate levels were significantly higher in patients both at baseline and after the task. Muscle strength analysis in patients group showed a reduction of Maximum Voluntary Contraction during the isometric contraction and, a tendency to fatigue during endurance task. Data emerging from this study highlight an impairment of muscle oxidative metabolism in subjects affected by a pre-cachexia stage of cancer. A trend of precocious fatigability and an impairment of muscle strength production were also observed. This evidence underlines the relevance of assessing muscle function in order to develop novel rehabilitative approaches able to counteract motor impairment and eventually to prevent cachexia in these patients

Alpha Cluster Structure in16O

The main purpose of the present work is the investigation of the α-cluster phenomenon in 16 O. The 12 C( 6 Li,d) 16 O reaction was measured at a bombarding energy of 25.5 MeV employing the Sao Paulo Pelletron-Enge-Spectrograph facility and the nuclear emulsion detection technique. Resonant states around 4α threshold were measured and an energy resolution of 15 keV allows to define states previously unresolved. The angular distributions of the absolute cross sections were determined in a range of 4-40 degree in the center of mass system. The upper limit for the resonance widths was obtained, indicating that the α cluster structure information in this region should be revised

An inherited duplication at the gene p21 protein-activated Kinase 7 (PAK7) is a risk factor for psychosis

FUNDING Funding for this study was provided by the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z), the Wellcome Trust (072894/Z/03/Z, 090532/Z/09/Z and 075491/Z/04/B), NIMH grants (MH 41953 and MH083094) and Science Foundation Ireland (08/IN.1/B1916). We acknowledge use of the Trinity Biobank sample from the Irish Blood Transfusion Service; the Trinity Centre for High Performance Computing; British 1958 Birth Cohort DNA collection funded by the Medical Research Council (G0000934) and the Wellcome Trust (068545/Z/02) and of the UK National Blood Service controls funded by the Wellcome Trust. Chris Spencer is supported by a Wellcome Trust Career Development Fellowship (097364/Z/11/Z). Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust. ACKNOWLEDGEMENTS The authors sincerely thank all patients who contributed to this study and all staff who facilitated their involvement. We thank W. Bodmer and B. Winney for use of the People of the British Isles DNA collection, which was funded by the Wellcome Trust. We thank Akira Sawa and Koko Ishzuki for advice on the PAK7–DISC1 interaction experiment and Jan Korbel for discussions on mechanism of structural variation.Peer reviewedPublisher PD

Experimental study on carbon fragmentation for hadrontherapy

Nowadays, one of the most advanced methods for solid tumors treatment is represented by hadrontherapy, a radiotherapy technique which applies collimated beams of protons or heavier ions for the sterilization of tumor cells. Due to their very favorable profile of the released dose in tissue, the charged hadron beams can be very effective in destroying the tumor and sparing the adjacent healthy tissue in comparison to the standard X-ray based treatments. The most important difference between protons and heavier ions is the increased biological effectiveness of the latter, i.e. a lower physical dose is needed with ions to obtain a given biological effect. For carbon ions, which are considered the optimal choice, the effect of the favourable absorbed dose distribution, which is highly localized, is enhanced by the large relative biological effectiveness (RBE) towards the end of the particle range. Nevertheless, when the carbon beam penetrates matter, the primary ions can be fragmented as a result of the collisions with the tissue atomic nuclei. The collisions along the carbon path lead to the attenuation of the primary beam intensity and the production of secondary fragments. These lighter particles have longer ranges and wider energy distributions with respect to the primary particles and give rise to a characteristic dose tail behind the Bragg peak. As far as the biological effect of ion radiation is dependent on the particle field composition, a detailed knowledge of the fragmentation process is essential in order to guarantee the appropriate treatment accuracy. Currently, the Monte Carlo codes are the most powerful tools able to precisely compute the biological dose to be delivered. However, the accuracy of a Monte Carlo simulation is associated to the reliability of the physical processes implemented in the code which, for a realistic estimation of fragmentation products, have to be validated versus experimental data, which are still a small amount in the literature. As a consequence, the main goal of the present work consist in estimating the double-differential fragmentation cross sections in the energy range of interest for hadrontherapy. After an overview of the historical development of hadrontherapy, the physical and biological rationale of carbon ions application in tumor treatments are dealt with in Chapter 1, focusing particularly on the fragmentation issue. In order to extract fragmentation cross sections in different experimental conditions, two measurements were performed at intermediate energies on both a thin carbon target and different tissue-equivalent targets, and a third one were done in the relativistic energy domain on a thicker carbon target. In Chapter 2 the experimental devices used in order to perform the three experiments have been described. The first two experiments were carried out at the LNS-INFN in Catania with a beam of carbon ions at 62 AMeV. The cross sections angular and energy distributions were obtained for the thin carbon target analysis and also a comparison with those extracted by means of the GEANT4 Monte Carlo code were performed. The results are shown and discussed in Chapter 3 together with those associated to the second experiment, done at the same energy but on thick tissue-equivalent targets. In Chapter 4 the preliminary results of the measurement performed at the GSI laboratory (Darmstadt, Germany) with a 400 AMeV carbon beam and the comparison with those obtained with the FLUKA Monte Carlo code are presented and discussed. In the end, the conclusions of the whole work done are drawn and the future perspectives are outlined

Clinical and genetic Rett syndrome variants are defined by stable electrophysiological profiles

Abstract Background Rett Syndrome (RTT) is a complex neurodevelopmental disorder, frequently associated with epilepsy. Despite increasing recognition of the clinical heterogeneity of RTT and its variants (e.g Classical, Hanefeld and PSV(Preserved Speech Variant)), the link between causative mutations and observed clinical phenotypes remains unclear. Quantitative analysis of electroencephalogram (EEG) recordings may further elucidate important differences between the different clinical and genetic forms of RTT. Methods Using a large cohort (n = 42) of RTT patients, we analysed the electrophysiological profiles of RTT variants (genetic and clinical) in addition to epilepsy status (no epilepsy/treatment-responsive epilepsy/treatment-resistant epilepsy). The distribution of spectral power and inter-electrode coherence measures were derived from continuous resting-state EEG recordings. Results RTT genetic variants (MeCP2/CDLK5) were characterised by significant differences in network architecture on comparing first principal components of inter-electrode coherence across all frequency bands (p < 0.0001). Greater coherence in occipital and temporal pairs were seen in MeCP2 vs CDLK5 variants, the main drivers in between group differences. Similarly, clinical phenotypes (Classical RTT/Hanefeld/PSV) demonstrated significant differences in network architecture (p < 0.0001). Right tempero-parietal connectivity was found to differ between groups (p = 0.04), with greatest coherence in the Classical RTT phenotype. PSV demonstrated a significant difference in left-sided parieto-occipital coherence (p = 0.026). Whilst overall power decreased over time, there were no difference in asymmetry and inter-electrode coherence profiles over time. There was a significant difference in asymmetry in the overall power spectra between epilepsy groups (p = 0.04) in addition to occipital asymmetry across all frequency bands. Significant differences in network architecture were also seen across epilepsy groups (p = 0.044). Conclusions Genetic and clinical variants of RTT are characterised by discrete patterns of inter-electrode coherence and network architecture which remain stable over time. Further, hemispheric distribution of spectral power and measures of network dysfunction are associated with epilepsy status and treatment responsiveness. These findings support the role of discrete EEG profiles as non-invasive biomarkers in RTT and its genetic/clinical variants

The Performance of Serum Antimullerian Hormone and Antral Follicle Count in Predicting the Ovarian Response in Intrauterine Insemination

The Performance of Serum Antimullerian Hormone and Antral Follicle Count in Predicting the Ovarian Response in Intrauterine Inseminatio

Illness Severity, Social and Cognitive Ability, and EEG Analysis of Ten Patients with Rett Syndrome Treated with Mecasermin (Recombinant Human IGF-1)

Rett Syndrome (RTT) is a severe neurodevelopmental disorder characterized by an apparently normal development followed by an arrest and subsequent regression of cognitive and psychomotor abilities. At present, RTT has no definitive cure and the treatment of RTT represents a largely unmet clinical need. Following partial elucidation of the underlying neurobiology of RTT, a new treatment has been proposed, Mecasermin (recombinant human Insulin-Like Growth Factor 1), which, in addition to impressive evidence from preclinical murine models of RTT, has demonstrated safety in human studies of patients with RTT. The present clinical study examines the disease severity as assessed by clinicians (International Scoring System: ISS), social and cognitive ability assessed by two blinded, independent observers (RSS: Rett Severity Score), and changes in brain activity (EEG) parameters of ten patients with classic RTT and ten untreated patients matched for age and clinical severity. Significant improvement in both the ISS (p=0.0106) and RSS (p=0.0274) was found in patients treated with IGF1 in comparison to untreated patients. Analysis of the novel RSS also suggests that patients treated with IGF1 have a greater endurance to social and cognitive testing. The present clinical study adds significant preliminary evidence for the use of IGF-1 in the treatment of RTT and other disorders of the autism spectrum

Anti-Müllerian hormone concentrations and antral follicle counts for the prediction of pregnancy outcomes after intrauterine insemination

Objective To evaluate anti-Müllerian hormone (AMH) concentrations and antral follicle counts (AFCs) in the prediction of pregnancy outcomes after controlled ovarian stimulation among women undergoing intrauterine insemination. Methods A retrospective study included women with unexplained infertility aged 41 years or younger who attended a fertility clinic in Italy between December 2009 and May 2014. Ovarian stimulation was achieved with recombinant follicle-stimulating hormone or highly purified human menopausal gonadotropin. Receiver operating characteristic curves were generated to predict ongoing pregnancy. The primary outcome was the association between AMH/AFC and ongoing pregnancy, and was assessed by logistic regression. Results Overall, 276 women were included, of whom 43 (15.6%) achieved ongoing pregnancy. Multivariate analysis showed that women with a serum day-3 concentration of AMH higher than 2.3 ng/mL were more likely to have ongoing pregnancy than were those with a concentration lower than 2.3 ng/mL (odds ratio 5.84, 95% confidence interval 2.38-14.31; P < 0.001). No associations were recorded for AFCs. Conclusion AMH should be used to predict the pregnancy outcome of intrauterine insemination

Anti-M\ufcllerian hormone concentrations and antral follicle counts for the prediction of pregnancy outcomes after intrauterine insemination

Objective To evaluate anti-M\ufcllerian hormone (AMH) concentrations and antral follicle counts (AFCs) in the prediction of pregnancy outcomes after controlled ovarian stimulation among women undergoing intrauterine insemination. Methods A retrospective study included women with unexplained infertility aged 41 years or younger who attended a fertility clinic in Italy between December 2009 and May 2014. Ovarian stimulation was achieved with recombinant follicle-stimulating hormone or highly purified human menopausal gonadotropin. Receiver operating characteristic curves were generated to predict ongoing pregnancy. The primary outcome was the association between AMH/AFC and ongoing pregnancy, and was assessed by logistic regression. Results Overall, 276 women were included, of whom 43 (15.6%) achieved ongoing pregnancy. Multivariate analysis showed that women with a serum day-3 concentration of AMH higher than 2.3 ng/mL were more likely to have ongoing pregnancy than were those with a concentration lower than 2.3 ng/mL (odds ratio 5.84, 95% confidence interval 2.38-14.31; P < 0.001). No associations were recorded for AFCs. Conclusion AMH should be used to predict the pregnancy outcome of intrauterine insemination