Roles of Semaphorins in Neurodegenerative Diseases

Semaphorins are secreted and transmembrane proteins that bind plexin/neuropilin or integrin receptors, providing paracrine axonal guidance signals and ultimately leading to a functional and developed neuronal network. Following semaphorin’s initial discovery, their relevance in the central nervous system (CNS) soon intrigued researchers about the possible links between semaphorins, their receptors and signaling mechanisms and different neurodegenerative diseases. Here, we explore the current knowledge of semaphorin’s function and signaling in Alzheimer’s disease (AD), Parkinson’s disease (PD), Charcot-Marie-Tooth disease (CMT), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We focus on the effects of the most known semaphorin subclasses 3A and 4D, yet extending our discussion to other semaphorins that have been found involved in specific neuropathologies and the potential effect of semaphorins modulating the immune system in disorders with inflammatory components. Molecular, cellular, and genetic evidences are reviewed, highlighting the relevance of semaphorins on each disease etiology, pathophysiology, and progression. The newly discovered semaphorin functions in neurological disorders even suggest alternative therapies that may be highly valuable in diseases that have no current cure

Nanostructured Ti thin films by magnetron sputtering at oblique angles

The growth of Ti thin films by the magnetron sputtering technique at oblique angles and at room temperature is analysed from both experimental and theoretical points of view. Unlike other materials deposited in similar conditions, the nanostructure development of the Ti layers exhibits an anomalous behaviour when varying both the angle of incidence of the deposition flux and the deposition pressure. At low pressures, a sharp transition from compact to isolated, vertically aligned, nanocolumns is obtained when the angle of incidence surpasses a critical threshold. Remarkably, this transition also occurs when solely increasing the deposition pressure under certain conditions. By the characterization of the Ti layers, the realization of fundamental experiments and the use of a simple growth model, we demonstrate that surface mobilization processes associated to a highly directed momentum distribution and the relatively high kinetic energy of sputtered atoms are responsible for this behaviourJunta de Andalucía P12-FQM- 2265Ministerio de Ciencia e Innovación CSD2008- 00023, MAT2013-42900-P, MAT2013-40852-R, MAT2014-59772-C2-1, MAT2011- 2908

SIRT3-mediated inhibition of FOS through histone H3 deacetylation prevents cardiac fibrosis and inflammation.

Sirtuin 3 (SIRT3) is a deacetylase that modulates proteins that control metabolism and protects against oxidative stress. Modulation of SIRT3 activity has been proposed as a promising therapeutic target for ameliorating metabolic diseases and associated cardiac disturbances. In this study, we investigated the role of SIRT3 in inflammation and fibrosis in the heart using male mice with constitutive and systemic deletion of SIRT3 and human cardiac AC16 cells. SIRT3 knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of AP-1. Consistent with this, SIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-alpha. Notably, these effects were associated with a decrease in the mRNA and protein levels of FOS and the DNA-binding activity of AP-1. Finally, we demonstrated that SIRT3 inhibits FOS transcription through specific histone H3 lysine K27 deacetylation at its promoter. These findings highlight an important function of SIRT3 in mediating the often intricate profibrotic and proinflammatory responses of cardiac cells through the modulation of the FOS/AP-1 pathway. Since fibrosis and inflammation are crucial in the progression of cardiac hypertrophy, heart failure, and diabetic cardiomyopathy, our results point to SIRT3 as a potential target for treating these diseases

Impact of Biological Agents on Postsurgical Complications in Inflammatory Bowel Disease : A Multicentre Study of Geteccu

Background: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. Aims: To evaluate the impact of biologics on the risk of PC. Methods: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered "exposed". The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. Results: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2-2.0), urgent surgery (OR: 1.6; 95% CI: 1.2-2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1-1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3-2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97-1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03-2.27). Conclusions: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Impact of Biological Agents on Postsurgical Complications in Inflammatory Bowel Disease: A Multicentre Study of Geteccu

Background: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. Aims: To evaluate the impact of biologics on the risk of PC. Methods: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered “exposed”. The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. Results: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2–2.0), urgent surgery (OR: 1.6; 95% CI: 1.2–2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1–1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3–2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97–1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03–2.27). Conclusions: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections

Caffeine Supplementation Improves Anaerobic Performance and Neuromuscular Efficiency and Fatigue in Olympic-Level Boxers

Background: this study examined the effects of caffeine supplementation on anaerobic performance, neuromuscular efficiency and upper and lower extremities fatigue in Olympic-level boxers. Methods: Eight male athletes, members of the Spanish National Olympic Team, were enrolled in the study. In a randomized double-blind, placebo-controlled, counterbalanced, crossover design, the athletes completed 2 test sessions after the intake of caffeine (6 mg kg) or placebo. Sessions involved initial measures of lactate, handgrip and countermovement jump (CMJ) performance, followed by a 30-seconds Wingate test, and then final measures of the previous variables. During the sessions, electromiography (EMG) data were recorded on the gluteus maximus, biceps femoris, vastus lateralis, gastrocnemius lateral head and tibialis anterior. Results: caffeine enhanced peak power (6.27%, p < 0.01; E ect Size (ES) = 1.26), mean power (5.21%; p < 0.01; ES = 1.29) and reduced the time needed to reach peak power (9.91%, p < 0.01; ES = 0.58) in theWingate test, improved jump height in the CMJ (+2.4 cm, p < 0.01), and improved neuromuscular e ciency at peak power in the vastus lateralis (ES = 1.01) and gluteus maximus (ES = 0.89), and mean power in the vastus lateralis (ES = 0.95) and tibialis anterior (ES = 0.83). Conclusions: in these Olympic-level boxers, caffeine supplementation improved anaerobic performance without a ecting EMG activity and fatigue levels in the lower limbs. Further benefits observed were enhanced neuromuscular e ciency in some muscles and improved reaction speed

The help4mood wearable sensor network for inconspicuous activity measurement

The Help4Mood EU FP7 project (H4M) [1] proposes to significantly advance the state-ofthe-art in computerized support for people with Major Depression by monitoring mood, physical activity and voice characteristics while promoting activities in reaction to examined inputs. Employing actigraphy can provide supplementary data about patients with depression. Nonetheless, its use is not standardized and there is a lack of public analyses about treated patients with depression using this technique, which is the objective of the project. The purpose of the Personal Monitoring System (PMS) used in H4M is to compile objective data about the changes and trends of activity patterns during long periods of time. This would comprise daily activity, rest time and, if possible, sleep quality. The PMS uses inconspicuous methods but keeping the cost associated with sensor installation at the patient¿s home to a minimum. This work focuses on the Wireless Sensor Network (WSN) enhancements introduced after real testbeds and considering User Quality of Experience (QoE), mainly oriented to reduce energy consumption and required data transmission and consequently improving the autonomy and range of the sensors.Peer Reviewe

The help4mood wearable sensor network for inconspicuous activity measurement

The Help4Mood EU FP7 project (H4M) [1] proposes to significantly advance the state-ofthe-art in computerized support for people with Major Depression by monitoring mood, physical activity and voice characteristics while promoting activities in reaction to examined inputs. Employing actigraphy can provide supplementary data about patients with depression. Nonetheless, its use is not standardized and there is a lack of public analyses about treated patients with depression using this technique, which is the objective of the project. The purpose of the Personal Monitoring System (PMS) used in H4M is to compile objective data about the changes and trends of activity patterns during long periods of time. This would comprise daily activity, rest time and, if possible, sleep quality. The PMS uses inconspicuous methods but keeping the cost associated with sensor installation at the patient¿s home to a minimum. This work focuses on the Wireless Sensor Network (WSN) enhancements introduced after real testbeds and considering User Quality of Experience (QoE), mainly oriented to reduce energy consumption and required data transmission and consequently improving the autonomy and range of the sensors.Peer Reviewe