E-MuSER (Enhanced Multiple Sclerosis Expected Rate): a technical improvement

Multiple sclerosis (MS) is an idiopathic chronic inflammatory disease that strikes the Central Nervous System (CNS). Moreover, it is the most diffused disabling neurologic disease, in fact about 12 * 103 new diagnoses/year arise in the United States alone. It is clear that the development of a MS predictive system is necessary, in order to have a reliable biostatistics tool to forecast the incidence value with a significant degree of accuracy in both time and space. Since the reached prevision time was equal to 1 year (namely 2019), the model was ameliorated by unpacking the considered and refined time period. The theoretical MS incidence for 2023 in Italy was calculated to be 12.17% (\ub1 2.04), with a theoretical accuracy of 99.35% (\ub1 1.02). It can be stated E-MuSER (Enhanced Multiple Sclerosis Expected Rate) could reach a higher dependability degree, as well as theoretical accuracy, with the respect to the previous model. Its efficiency will be assessed at the end of year 2023

Microbiota and HCV Infection Interplay

Hepatitis C virus (HCV) is held responsible for about 17.5% of acute hepatitis cases and after acute infection, roughly 65% of patients develops a chronic infection. Intestinal microbiota\u2019s relevance in the pathogenesis of HCV-induced chronic liver diseases is a promising topic within scientific community. Anyway, its role in chronic HCV infection is still not completely unraveled and it needs more detailed investigations. Although results on relationships standing between human microbiota and HCV infections are lacking, the few published articles are highly inspirational for both further studies and theoretical researches, giving a starting substrate to hypothesize the mechanisms underlying the relationships between microbiota and HCV in the context of gut-liver axis. The aim of this short review is to summarize the state of the art of microbiota/HCV interactions and possibily give a novel point of view based on the articles\u2019 conclusions, using an eagle-eye perspective that will allow to open a door to new research studies concerning HCV infection

Prosthetic Joint Infections and Prevention

Prosthetic joint implantation became a broadly diffused surgery routine due to its life quality enhancement potential, but it carries the intrinsic risk of infection that all surgeries have. Currently, millions of devices are being successfully implanted every year worldwide. Although surgical techniques have been optimized and prostheses are safe and built with germ free materials, prosthetic joint infections are a sanitary burden that often leads the patient to death or serious complications. With this in mind, it is clear that new ideas are needed in order to limit this phenomenon and give to this surgical area a life-saving plan. This opinion paper aim is in fact to elaborate a fresh preventive perspective to reduce as much as possible the prosthetic joint infections incidence

Gut Microbiota Role in Liver Regeneration: Evidences and Novel Insights

Human pathophysiological status highly depends on microbiota activity; its presence is in fact necessary to a healthy development, as well as for backing up immune system in the defense from pathogens. Gut microbiota also acts as a metabolic player that takes part in host metabolism by partially regulating bile acids (BAs) metabolism, as well as farnesoid X receptor (FXR) signalling. In fact, if microbiota functions are totally or even partially impaired, its role in supporting both BAs and FXR pathways will be undermined too, resulting in a diminished liver regeneration function. Hepatic pathologies have been associated to impaired gut microbial diversity, that can trigger a positive feedback cycle that worsen liver injury and obstruct liver regeneration process. Alcoholic liver disease subjects were typically infected by Bacteroides species and expanded Proteobacteria ones. Thus, it can be inferred that an intimate relationship between microbiota, hepatic metabolism and injury as well as regeneration is standing. Within this complex scenario, it is not surprising that the gut-liver axis could be also part of the regenerative mechanisms that, under certain circumstances, occur within the hepatic environment. This opinion paper aims to put together some of the evidences related to this thesis in order to consolidate it and give new insights about i

Heart rate detection by Fitbit ChargeHR™: A validation study versus portable polysomnography

Consumer "Smartbands" can collect physiological parameters, such as heart rate (HR), continuously across the sleep-wake cycle. Nevertheless, the quality of HR data detected by such devices and their place in the research and clinical field is debatable, as they are rarely rigorously validated. The objective of the present study was to investigate the reliability of pulse photoplethysmographic detection by the Fitbit ChargeHR (FBCHR, Fitbit Inc.) in a natural setting of continuous recording across vigilance states. To fulfil this aim, concurrent portable polysomnographic (pPSG) and the Fitbit's photoplethysmographic data were collected from a group of 25 healthy young adults, for ≥12hr. The pPSG-derived HR was automatically computed and visually verified for each 1-min epoch, while the FBCHR HR measurements were downloaded from the application programming interface provided by the manufacturer. The FBCHR was generally accurate in estimating the HR, with a mean (SD) difference of -0.66(0.04)beats/min (bpm) versus the pPSG-derived HR reference, and an overall Pearson's correlation coefficient (r) of 0.93 (average per participant r=0.85±0.11), regardless of vigilance state. The correlation coefficients were larger during all sleep phases (rapid eye movement, r=0.9662; N1, r=0.9918; N2, r=0.9793; N3, r=0.9849) than in wakefulness (r=0.8432). Moreover, the correlation coefficient was lower for HRs of >100bpm (r=0.374) than for HRs of <100bpm (r=0.84). Consistently, Bland-Altman analysis supports the overall higher accuracy in the detection of HR during sleep. The relatively high accuracy of FBCHR pulse rate detection during sleep makes this device suitable for sleep-related research applications in healthy participants, under free-living conditions

Integrated analysis of the prostate cancer small-nucleolar transcriptome reveals <i>SNORA55</i> as a driver of prostate cancer progression

Metastasis is the primary cause of death in prostate cancer (PCa) patients. Small nucleolar RNAs (snoRNAs) have long been considered "housekeeping" genes with no relevance for cancer biology. Emerging evidence has challenged this assumption, suggesting that snoRNA expression is frequently modulated during cancer progression. Despite this, no study has systematically addressed the prognostic and functional significance of snoRNAs in PCa. We performed RNA Sequencing on paired metastatic/non-metastatic PCa xenografts derived from clinical specimens. The clinical significance of differentially expressed snoRNAs was further investigated in two independent primary PCa cohorts (131 and 43 patients, respectively). The snoRNA demonstrating the strongest association with clinical outcome was quantified in PCa patient-derived serum samples and its functional relevance was investigated in PCa cells via gene expression profiling, pathway analysis and gene silencing. Our comparison revealed 21 differentially expressed snoRNAs in the metastatic vs. non-metastatic xenografts. Of those, 12 were represented in clinical databases and were further analyzed. SNORA55 emerged as a predictor of shorter relapse-free survival (results confirmed in two independent databases). SNORA55 was reproducibly detectable in serum samples from PCa patients. SNORA55 silencing in PCa cell lines significantly inhibited cell proliferation and migration. Pathway analysis revealed that SNORA55 expression is significantly associated with growth factor signaling and pro-inflammatory cytokine expression in PCa. Our results demonstrate that SNORA55 up-regulation predicts PCa progression and that silencing this non-coding gene affects PCa cell proliferation and metastatic potential, thus positioning it as both a novel biomarker and therapeutic target

D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.2018-05-0

Mutational analysis of Polycomb genes in solid tumours identifies <i>PHC3</i> amplification as a possible cancer-driving genetic alteration.

Background: Polycomb group genes (PcGs) are epigenetic effectors implicated in most cancer hallmarks. The mutational status of all PcGs has never been systematically assessed in solid tumours. Methods: We conducted a multi-step analysis on publically available databases and patient samples to identify somatic aberrations of PcGs. Results: Data from more than 1000 cancer patients show for the first time that the PcG member PHC3 is amplified in three epithelial neoplasms (rate: 8–35%). This aberration predicts poorer prognosis in lung and uterine carcinomas (Po0.01). Gene amplification correlates with mRNA overexpression (Po0.01), suggesting a functional role of this aberration. Conclusion: PHC3 amplification may emerge as a biomarker and potential therapeutic target in a relevant fraction of epithelial tumours

Single cell analysis of kynurenine and System L amino acid transport in T cells

Acknowledgements We thank Cantrell group members for their critical discussion of the data, the Biological Resources unit, Sarah Thomson (for rLM work) and the Flow Cytometry facility (A. Whigham and R. Clarke) at the University of Dundee. This work was supported by the Wellcome Trust (Principal Research Fellowship to D.A.C. 097418/Z/11/Z and 205023/Z/16/Z, and Wellcome Trust Equipment Award 202950/Z/16/Z).Peer reviewedPublisher PD

Right Heart Pulmonary Circulation Unit Response to Exercise in Patients with Controlled Systemic Arterial Hypertension: Insights from the RIGHT Heart International NETwork (RIGHT-NET)

Background. Systemic arterial hypertension (HTN) is the main risk factor for the development of heart failure with preserved ejection fraction (HFpEF). The aim of the study was was to assess the trends in PASP, E/E’ and TAPSE during exercise Doppler echocardiography (EDE) in hypertensive (HTN) patients vs. healthy subjects stratified by age. Methods. EDE was performed in 155 hypertensive patients and in 145 healthy subjects (mean age 62 ± 12.0 vs. 54 ± 14.9 years respectively, p &lt; 0.0001). EDE was undertaken on a semi-recumbent cycle ergometer with load increasing by 25 watts every 2 min. Left ventricular (LV) and right ventricular (RV) dimensions, function and hemodynamics were evaluated. Results. Echo-Doppler parameters of LV and RV function were lower, both at rest and at peak exercise in hypertensives, while pulmonary hemodynamics were higher as compared to healthy subjects. The entire cohort was then divided into tertiles of age: at rest, no significant differences were recorded for each age group between hypertensives and normotensives except for E/E’ that was higher in hypertensives. At peak exercise, hypertensives had higher pulmonary artery systolic pressure (PASP) and E/E’ but lower tricuspid annular plane systolic excursion (TAPSE) as age increased, compared to normotensives. Differences in E/E’ and TAPSE between the 2 groups at peak exercise were explained by the interaction between HTN and age even after adjustment for baseline values (p &lt; 0.001 for E/E’, p = 0.011 for TAPSE). At peak exercise, the oldest group of hypertensive patients had a mean E/E’ of 13.0, suggesting a significant increase in LV diastolic pressure combined with increased PASP. Conclusion. Age and HTN have a synergic negative effect on E/E’ and TAPSE at peak exercise in hypertensive subjects