A polymorphism in the human serotonin 5-HT2A receptor gene may protect against systemic sclerosis by reducing platelet aggregation

Introduction: Platelet aggregation may contribute to the pathogenesis of systemic sclerosis: following activation, platelets release significant amounts of serotonin - which promotes vasoconstriction and fibrosis, and further enhances aggregation. The C+1354T polymorphism in the exonic region of the serotonin 2A receptor gene determining the His452Tyr substitution was associated with blunted intracellular responses after serotonin stimulation, and may have a role in susceptibility to scleroderma. Methods: One hundred and fifteen consecutive systemic sclerosis patients and 140 well-matched healthy control individuals were genotyped by sequence-specific primer-PCR for the His452Tyr substitution of the serotonin 2A receptor gene, and associations were sought with scleroderma and its main clinical features. The functional relevance of the His452Tyr substitution was also assessed by evaluating the aggregation of platelet-rich plasma from His452/ His452 and His452/Tyr452 healthy individuals after stimulation with adenosine diphosphate ± serotonin. Results: The T allele of the C+1354T polymorphism was underrepresented in scleroderma patients compared with control individuals (5.2% versus 12.4%, P < 0.001, chi-square test and 1,000-fold permutation test) and its carriage reduced the risk for systemic sclerosis (odds ratio = 0.39, 95% confidence interval = 0.19 to 0.85, P < 0.01). Platelets from His452/Tyr452 healthy subjects more weakly responded to serotonin stimulation compared with platelets from His452/His452 individuals (3.2 ± 2.6-fold versus 9.6 ± 8.6-fold increase in aggregation, P = 0.017 by Kolmogorov-Smirnov test and P = 0.003 after correction for baseline adenosine diphosphate-induced aggregation values). Conclusion: The His452Tyr substitution may influence susceptibility to systemic sclerosis by altering platelet aggregation in response to serotonin

Temperature and masting control Norway spruce growth, but with high individual tree variability

Tree growth and reproduction are subject to trade-offs in resource allocation. At the same time, they are both influenced by climate. In this study, we combined long records of reproductive effort at the individual- (29 years), population- (41 years) and regional (up to 53 years) scale, and tree ring chronologies, to investigate the effects of climate and reproductive allocation on radial growth in an Alpine Norway spruce forest. Seed and cone production was highly variable between years (mean individual CV = 1.39, population CV = 1.19), but showed high reproductive synchrony between individuals (mean inter-tree correlation = 0.72). No long-term trend in reproductive effort was detected over four decades of observations. At the stand scale, cone production was dominated by a small number of individuals (\u201csuper-producers\u201d), who remained dominant over three decades. Individual tree growth responded positively to summer temperature, but the response to cone production varied between individual trees. Consequently, we found some evidence that mast years were associated with a divergence in growth between high and low cone producing individuals, and a decline in within-population growth synchrony. At the population level we found limited evidence of a relationship between growth and reproduction. Radial growth was lower than average in some mast years, but not in others. This was partly explained by summer temperature during the year of growth, with growth reductions restricted to mast years that coincided with colder than average summers. Regional mast records and tree ring chronologies provided some support to indicate that our results were consistent in other spruce stands, although the effect of mast years on growth appeared to vary between sites. Tree ring variation at the individual and population level, and between-tree growth synchrony are influenced by masting, and consequently dendrochronologists should consider both the occurrence of masting and the individual differences in reproductive effort when interpreting tree ring datasets. Our results also indicate that tree ring chronologies contain information to facilitate reconstruction of mast events, which will help address outstanding questions regarding the future response of masting to climate change

Observing the products of stellar evolution in the old open cluster M67 with APOGEE

© 2016 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society Recent works have shown how the [C/N] ratio in stars after the first dredge-up (FDU) can be used as an age estimator in virtue of its dependence on stellar mass. For this purpose, precise predictions of the surface chemical composition before and after the mixing takes place in the convective envelope of subgiant stars are necessary. Stellar evolution models can provide us with such predictions, although a comparison with objects of known age is needed for calibration. Open clusters are excellent test cases, as they represent a single stellar population for which the age can be derived through, e.g. isochrone fitting. In this study, we present a detailed analysis of stars belonging to the well-known open cluster M67 observed by the Apache Point Observatory Galactic Evolution Experiment (APOGEE) survey in the twelfth data release of the Sloan Digital Sky Survey and whose chemical properties were derived with the APOGEE Stellar Parameters and Chemical Abundances Pipeline. We find that the [C/N] abundance of subgiant branch stars is overestimated by ∼0.2 dex due to an offset in the determination of the [N/Fe] abundance. Stars on the red giant branch and red clump are shown not to be affected by this offset. We derive [C/N]FDU = −0.46 ± 0.03 dex, which poses a strong constraint on calibrations of [C/N]FDU as age indicator. We also do not find any clear signature of additional chemical mixing processes that set in after the red giant branch bump. The results obtained for M67 indicate the importance of conducting high-resolution spectroscopic studies of open clusters of different ages in order to establish an accurate age-dating method for field stars

Integrated Robot Motion and Process control for manufacturing reshaping

The future of metal manufacturing processes like laser cutting, welding, and additive manufacturing shall rely on intelligent systems spearheaded by Industry 4.0. Such a digital innovation is indeed driving machinery builders to a profound transformation. From custom machines designed and optimized for a specific process, the ambition is to exploit the openness and the large availability of industrial robots to increase flexibility and reconfigurability of multi processes implementations. The challenge is that machinery builders transform themselves into high-knowledge specialized process-driven robot integrators, able to optimize the robot motion with the process controller leveraging on intelligent sensing and cognition. The work describes the multi-annual collaboration of the BLM group and Politecnico di Milano, with the support of CNR, focused on the deployment of a complete working robotic workstation characterized by the full integration of the robot control and motion planning with manufacturing processes

Skull Base Fungal Osteomyelitis: A Case Report and Review of the Literature

Skull base osteomyelitis (SBO) is an invasive infection refractory to therapy, closely linked with malignant otitis externa (MOE). It is characterized by a mild clinical presentation that can delay cross-sectional imaging considered as the key to revealing it. Skull base osteomyelitis typically affects elderly diabetics and immunocompromised patients (>70 years). It most commonly has an otogenic origin due to an extension of MOE. The prognosis can be very poor without the administration of adequate and timely therapy at an early disease stage. Nowadays, Pseudomonas aeruginosa remains the most common pathogen associated with SBO. Fungi are a rare cause of MOE. This report documents a rare case of otogenic SBO caused by Candida parapsilosis in a diabetic patient, with persistent otologic symptoms as clinical onset and resistance to medical treatment. Fungal MOE has more subtle symptoms and is more aggressive than its bacterial counterpart. When MOE is resistant to antibacterial drugs, this should raise the suspicion of a fungal etiology of MOE. The current guidelines do not exhaustively describe the diagnosis, antifungal drugs of choice, and optimum duration of treatment. The description of these rare clinical cases should help with the multidisciplinary management of this disease in order to optimize the diagnosis and therapeutic protocol

Synthesis, biological evaluation and docking analysis of a new series of methylsulfonyl and sulfamoyl acetamides and ethyl acetates as potent COX-2 inhibitors

We report herein the synthesis, biological evaluation and docking analysis of a new series of methylsulfonyl, sulfamoyl acetamides and ethyl acetates that selectively inhibit cyclooxygenase-2 (COX-2) isoform. Among the newly synthesized compounds, some of them were endowed with a good activity against COX-2 and a good selectivity COX-2/COX-1 in vitro as well as a desirable analgesic activity in vivo, proving that replacement of the ester moiety with an amide group gave access to more stable derivatives, characterized by a good COX-inhibition

Anti-inflammatory and immunosuppressive drugs and reproduction

Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given

Ultrastructural evaluation of human metaphase II oocytes after vitrification: closed versus open devices

Objective: To compare the ultrastructural appearance of oocytes after vitrification and warming with two different devices. Design: Oocytes were examined by ultrastructural analysis after vitrification and warming with use of closed (CryoTip; Irvine Scientific, Santa Ana, CA) or open (Cryotop; Kitazato BioPharma Co., Ltd., Shizuoka, Japan) devices. Setting: Pordenone Hospital IVF Unit and Medical Morphological Research Department, University of Udine. Patient(s): Surplus oocytes from 10 patients (aged 31-39 years) undergoing assisted reproductive technologies at the Pathophysiology Unit of Human Reproduction and Sperm Bank between 2006 and 2008. Intervention(s): Oocytes with normal invertoscopic appearance underwent vitrification and warming with closed (CryoTip) or open (Cryotop) devices and were processed for transmission electron microscopy. Main Outcome Measure(s): Cryodamage extent and cell alterations in oocytes after open or closed vitrification and warming procedures and their rehydration rate. Result(s): A higher rate of complete oocyte rehydration and less-severe ultrastructural alterations were observed after vitrification and warming with the open Cryotop device. Conclusion(s): These preliminary data suggest that oocyte ultrastructure is better preserved with an open rather than closed vitrification and warming protocol

Validation of the Italian version of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire

Objectives The primary objective of this study was the translation and validation of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire into Italian, denoted as AAV-PRO_ita. The secondary objective was to evaluate the impact of ANCA-associated vasculitis (AAV) on quality of life (QoL) and work impairment in a large cohort of Italian patients. Methods The study design took a prospective cohort study approach. First, the AAV-PRO was translated into Italian following the step guidelines for translations. The new AAV-PRO_ita questionnaire covered three disease domains: organ-specific and systemic symptoms and signs; physical function; and social and emotional impact. Second, Italian-speaking AAV patients were recruited from 17 Italian centres belonging to the Italian Vasculitis Study Group. Participants completed the AAV-PRO_ita questionnaire at three time points. Participants were also requested to complete the work productivity and activity impairment: general health questionnaire. Results A total of 276 AAV patients (56.5% women) completed the questionnaires. The AAV-PRO_ita questionnaire demonstrated a good internal consistency and test-retest reliability. Female AAV patients scored higher (i.e. worse) in all thee domains, especially in the social and emotional impact domain (P &lt; 0.001). Patients on glucocorticoid therapy (n = 199) had higher scores in all domains, especially in the physical function domain (P &lt; 0.001), compared with patients not on glucocorticoid therapy (n = 77). Furthermore, patients who had at least one relapse of disease (n = 114) had higher scores compared with those who had never had one (n = 161) in any domain (P &lt; 0.05). Finally, nearly 30% of the patients reported work impairment. Conclusion The AAV-PRO_ita questionnaire is a new 29-item, disease-specific patient-reported outcome measuring tool that can be used in AAV research in the Italian language. Sex, glucocorticoids and relapsing disease showed the greatest impact on QoL