An international prospective general population-based study of respiratory work disability

Background: Previous cross-sectional studies have shown that job change due to breathing problems at the workplace (respiratory work disability) is common among adults of working age. That research indicated that occupational exposure to gases, dust and fumes was associated with job change due to breathing problems, although causal inferences have been tempered by the cross-sectional nature of previously available data. There is a need for general population-based prospective studies to assess the incidence of respiratory work disability and to delineate better the roles of potential predictors of respiratory work disability.Methods: A prospective general population cohort study was performed in 25 centres in 11 European countries and one centre in the USA. A longitudinal analysis was undertaken of the European Community Respiratory Health Survey including all participants employed at any point since the baseline survey, 6659 subjects randomly sampled and 779 subjects comprising all subjects reporting physician-diagnosed asthma. The main outcome measure was new-onset respiratory work disability, defined as a reported job change during follow-up attributed to breathing problems. Exposure to dusts (biological or mineral), gases or fumes during follow-up was recorded using a job-exposure matrix. Cox proportional hazard regression modelling was used to analyse such exposure as a predictor of time until job change due to breathing problems.Results: The incidence rate of respiratory work disability was 1.2/1000 person-years of observation in the random sample (95% CI 1.0 to 1.5) and 5.7/1000 person-years in the asthma cohort (95% CI 4.1 to 7.8). In the random population sample, as well as in the asthma cohort, high occupational exposure to biological dust, mineral dust or gases or fumes predicted increased risk of respiratory work disability. In the random sample, sex was not associated with increased risk of work disability while, in the asthma cohort, female sex was associated with an increased disability risk (hazard ratio 2.8, 95% CI 1.3 to 5.9).Conclusions: Respiratory work disability is common overall. It is associated with workplace exposures that could be controlled through preventive measures

General and oral aspects in Apert syndrome: report of a case

Background: The present paper describes the general and oral manifestations in a 32-year-old man previously diagnosed with Apert syndrome. Clinical examination revealed features of acrocephalosyndactyly. The patient was found to have a flattened occiput with frontal prominence, abnormal contour of head (brachycephaly), shallow and downward slanting orbits with bilateral proptosis, hypertelorism, retruded midface, and prognathic mandible.Dental anormalies were present in a patient. Intraoral evaluation revealed normal mouth opening with anterior severe skeletal open bite and Byzantine-arch palate, maxillary alveolar ridges with crowding of maxillary and mandibular teeth, poor hygiene with heavy dental calculus and periodontal pseudopocket, dental caries, severe anterior open bite and crossbite, macroglosia and smooth tongue. The high prevalence of dental anomalies and ectopic eruption may suggest a possible etiologic relationship with the Apert syndrome. Keywords Acrocephalosyndactylia, Craniosynostosis, Tooth abnormalities, Mouth abnormalities, Apert Syndrom

Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft-versus-host disease control

Producción CientíficaThe mechanistic target of rapamycin (mTOR) pathway is crucial for the activation and function of T cells, which play an essential role in the development of graft-versus-host disease (GvHD). Despite its partial ability to block mTOR pathway, the mTORC1 inhibitor rapamycin has shown encouraging results in the control of GvHD. Therefore, we considered that simultaneous targeting of both mTORC1 and mTORC2 complexes could exert a more potent inhibition of T cell activation and, thus, could have utility in GvHD control. To assess this assumption, we have used the dual mTORC1/mTORC2 inhibitors CC214-1 and CC214-2. In vitro studies confirmed the superior ability of CC214-1 versus rapamycin to block mTORC1 and mTORC2 activity and to reduce T cell proliferation. Both drugs induced a similar decrease in Th1/Th2 cytokine secretion, but CC214-1 was more efficient in inhibiting na€ıve T cell activation and the expression of Tcell activation markers. In addition, CC214-1 induced specific tolerance against alloantigens, while preserving anti-cytomegalovirus response. Finally, in a mouse model of GvHD, the administration of CC214-2 significantly improved mice survival and decreased GvHD-induced damages. In conclusion, the current study shows, for the first time, the immunosuppressive ability of CC214-1 on T lymphocytes and illustrates the role of CC214-2 in the allogeneic transplantation setting as a possible GvHD prophylaxis agent.Gerencia Regional de Salud de Castilla y León (Proyecto GRS 726/A13

The Slab Puzzle of the Alpine‐Mediterranean Region: Insights from a new, High‐Resolution, Shear‐Wave Velocity Model of the Upper Mantle

Mediterranean tectonics since the Lower Cretaceous has been characterized by a multi‐phase subduction and collision history with temporally and spatially‐variable, small‐scale plate configurations. A new shear‐wave velocity model of the Mediterranean upper mantle (MeRE2020), constrained by a very large set of over 200,000 broadband (8‐350 s), inter‐station, Rayleigh‐wave, phase‐velocity curves, illuminates the complex structure and fragmentation of the subducting slabs. Phase‐velocity maps computed using these measurements were inverted for depth‐dependent, shear‐wave velocities using a stochastic particle‐swarm‐optimization algorithm (PSO). The resulting three‐dimensional (3‐D) model makes possible an inventory of slab segments across the Mediterranean. Fourteen slab segments of 200‐800 km length along‐strike are identified. We distinguish three categories of subducted slabs: attached slabs reaching down to the bottom of the model; shallow slabs of shorter length in down‐dip direction, terminating shallower than 300 km depth; and detached slab segments. The location of slab segments are consistent with and validated by the intermediate‐depth seismicity, where it is present. The new high‐resolution tomography demonstrates the intricate relationships between slab fragmentation and the evolution of the relatively small and highly curved subduction zones and collisional orogens characteristic of the Mediterranean realm

Socio-oceanography: an opportunity to integrate marine social and natural sciences

Marine natural sciences have been instrumental in helping society understand how ocean systems operate and the threats they face. However, there is a growing realisation that the societal challenges related to the marine environment can only be addressed through more effective integration with all aspects of social sciences. Nevertheless, to date, social sciences remain insufficiently integrated into marine research. Recognising historical weaknesses and drawing on the authors’ own experience of interdisciplinary research, albeit writing primarily from a natural marine science perspective, we propose a series of steps to promote integrated marine research inclusive of strong social science. We suggest that changing the perspectives and attitudes of natural scientists is key. The inherent interconnectivity between the ocean and society ensures that nearly everything we do in the marine natural sciences has the potential to influence and, perhaps address, ongoing and future societal challenges. Consequently, a key challenge for natural scientists is to recognise and communicate this in an accessible manner outside their own disciplines. To attempt to address these issues, we introduce the concept of “Socio-oceanography” which we define as an area of research that takes a “whole system” approach to the marine environment. It focuses on the challenges which require advancement of both natural and social science components, especially on those where the feedbacks between social and natural components are beginning to emerge. Here, we discuss its scope, challenges to its effective application and key steps to catalyse interdisciplinary approaches using this concept

Sex and gender differences in acute stroke care: metrics, access to treatment and outcome. A territorial analysis of the Stroke Code System of Catalonia

Introduction: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia. Patients and methods: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy. Results: A total of 23,371 stroke code activations were registered (54% men, 46% women). No differences in prehospital time metrics were observed. Women more frequently had a final diagnosis of stroke mimic, were older and had a previous worse functional situation. Among ischemic stroke patients, women had higher stroke severity and more frequently presented proximal large vessel occlusion. Women received more frequently reperfusion therapy (48.2% vs 43.1%, p < 0.001). Women tended to present a worse outcome at 90 days, especially for the group receiving only IVT (good outcome 56.7% vs 63.8%; p < 0.001), but not for the group of patients treated with IVT + MT or MT alone, although sex was not independently associated with clinical outcome in logistic regression analysis (OR 1.07; 95% CI, 0.94–1.23; p = 0.27) nor in the analysis after matching using the propensity score (OR 1.09; 95% CI, 0.97–1.22). Discussion and conclusion: We found some differences by sex in that acute stroke was more frequent in older women and the stroke severity was higher. We found no differences in medical assistance times, access to reperfusion treatment and early complications. Worse clinical outcome at 90 days in women was conditioned by stroke severity and older age, but not by sex itself

Comparison of oxidative properties, light absorbance, total and elemental mass concentration of ambient PM2.5 collected at 20 European sites.

OBJECTIVE: It has been proposed that the redox activity of particles may represent a major determinant of their toxicity. We measured the in vitro ability of ambient fine particles [particulate matter with aerodynamic diameters<or=2.5 microm (PM2.5)] to form hydroxyl radicals (.OH) in an oxidant environment, as well as to deplete physiologic antioxidants (ascorbic acid, glutathione) in the naturally reducing environment of the respiratory tract lining fluid (RTLF). The objective was to examine how these toxicologically relevant measures were related to other PM characteristics, such as total and elemental mass concentration and light absorbance. DESIGN: Gravimetric PM2.5 samples (n=716) collected over 1 year from 20 centers participating in the European Community Respiratory Health Survey were available. Light absorbance of these filters was measured with reflectometry. PM suspensions were recovered from filters by vortexing and sonication before dilution to a standard concentration. The oxidative activity of these particle suspensions was then assessed by measuring their ability to generate .OH in the presence of hydrogen peroxide, using electron spin resonance and 5,5-dimethyl-1-pyrroline-N-oxide as spin trap, or by establishing their capacity to deplete antioxidants from a synthetic model of the RTLF. RESULTS AND CONCLUSION: PM oxidative activity varied significantly among European sampling sites. Correlations between oxidative activity and all other characteristics of PM were low, both within centers (temporal correlation) and across communities (annual mean). Thus, no single surrogate measure of PM redox activity could be identified. Because these novel measures are suggested to reflect crucial biologic mechanisms of PM, their use may be pertinent in epidemiologic studies. Therefore, it is important to define the appropriate methods to determine oxidative activity of PM