We have read with great interest the two editorials by Burdorf et al: "The COVID-19 pandemic: one year later - an occupational perspective" (1) and "The COVID-19 (Coronavirus) pandemic: consequences ...for occupational health" (2). The authors highlight the importance of the societal consequences of the outbreak and changes in the world of work to manage occupational health. The key points identified - such as individual socio-economic factors, psychological effects and occupations with highest risk of contamination - modify return-to-work approaches. It is estimated that around 800 million people of working age worldwide were living with disabilities before the SARS-CoV-2 pandemic. In early January 2021, the cumulative COVID-19 hospitalisation rate reached 207.4/100 000 (18-49-year-olds) and 505.7/100 000 (50-64-year-olds), respectively, in the United States (3). In France, the hospitalisation rate was 411.5/100 000 across all ages (4). A recent cohort study of working-age men who were hospitalised for COVID-19 highlighted the long-term health consequences of such a disease (5). The SARS-CoV-2 pandemic creates new challenges for occupational health, shifting attention away from return-to-work after health problems to resuming work during an outbreak, dealing with lockdown, and taking special account of workers with vulnerabilities (6, 7). We recommend considering three different aspects of occupational medicine during a pandemic. Firstly, for most workers at high-risk of severe COVID-19, the issues of work disability and resuming work had never occurred before the epidemic. Recommendations such as physical and social distancing and wearing a facemask are highly advisable to protect against infection but may not be enough to enable some individuals to resume work. Therefore, decision-making requires individual comprehensive assessments of the underlying medical condition, the SARS-CoV-2 contamination risk associated with either regular work or teleworking, and vaccination opportunities. The second situation concerns workers who have suffered from COVID-19. Preliminary studies suggest that long recovery duration is related to high severity (7), but this is still a matter of debate for patients suffering from "long COVID-19" (5, 8, 9), a condition for which the long-term effects remain unknown. Any long-running recovery must be considered to be a potential sign of long COVID-19. These long-lasting syndromes occur among patients with severe symptoms but have also been reported independently of acute phase severity, hospitalisation and receiving medical oxygen (8, 9). Researchers worldwide are currently investigating such syndromes. Strategies promoting return to work for these workers will need to be implemented and could be similar to programmes developed for other chronic conditions. Moreover, numerous more serious sequelae following critical illness suggest the need for enhanced support by rehabilitation and occupational health specialists. Finally, the consequences of the epidemic must be evaluated over time for people who suffered from functional limitations before COVID-19 as their physical and mental condition may be modified by the epidemic and, specifically, the consequences of lockdown (10). In all of these situations, medical, social, financial and working contexts are key elements. In addition to a medical assessment, the use of scales such as the Work Ability Index (WAI) (11) or the Work Productivity and Activity Impairment (WPAI) (12) can help perform long-term follow-up and provide information about work capacity and workload. It also gives a "back to basics" perspective, urging politicians to move towards a `decent-work-for-all` policy, as advocated by the United Nation`s Sustainable Development Goal (SDG) 8, which the WHO has endorsed (13). References 1. Burdorf A, Porru F, Rugulies R. The COVID-19 pandemic: one year later - an occupational perspective. Scand J Work Environ Health - online first. https://doi.org/10.5271/sjweh.3956 2. Burdorf A, Porru F, Rugulies R. The COVID-19 (Coronavirus) pandemic: consequences for occupational health. Scand J Work Environ Health. 2020;46(3):229-230. https://doi:org/10.5271/sjweh.3893. 3. COVID-19 Hospitalizations Internet. Available from: https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html 4. COVID-19 in France, vaccine and allergy management in occupational setting. Descatha A et al. Arch Mal Prof Environ 2021. Accepted for publication. 5. Huang C, Huang L, Wang Y, Li X, Ren L, Gu X, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet 2021;397(10270):220-32 https://doi.org/10.1016/S0140-6736(20)32656-8 6. Shaw WS, Main CJ, Findley PA, Collie A, Kristman VL, Gross DP. Opening the Workplace After COVID-19: What Lessons Can be Learned from Return-to-Work Research? J Occup Rehabil. 2020;30(3):299-302. https://doi.org/10.1007/s10926-020-09908-9 7. Taylor T, Das R, Mueller K, Pransky G, Christian J, Orford R, et al. Safely Returning America to Work: Part I: General Guidance for Employers. J Occup Environ Med. 2020;62(9):771-9. https://doi.org/10.1097/JOM.0000000000001984 8. Carfì A, Bernabei R, Landi F, Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020;324(6):603-5. https://doi.org/10.1001/jama.2020.12603 9. Tenforde MW, Kim SS, Lindsell CJ, Billig Rose E, Shapiro NI, Files DC, et al. Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network - United States, March-June 2020. MMWR Morb Mortal Wkly. 2020;69(30):993-8. https://doi.org/10.15585/mmwr.mm6930e1 10. Chudasama YV, Gillies CL, Zaccardi F, Coles B, Davies MJ, Seidu S, et al. Impact of COVID-19 on routine care for chronic diseases: A global survey of views from healthcare professionals. Diabetes Metab Syndr. 2020;14(5):965-7. https://doi.org/10.1016/j.dsx.2020.06.042 11. Tuomi K. Eleven-year follow-up of aging workers. Scand J Work Environ Health. 1997;23(1):1-71. 12. Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. PharmacoEconomics. 1993;4(5):353-65. https://doi.org/10.2165/00019053-199304050-00006 13. Organization WH. Health in the 2030 agenda for sustainable development. Sixty-Ninth World Health Assembly. Document A. 2016, p69.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, UL, UM, UPUK
•Preparation of stable and robust electrospun chitosan mats.•Covalent immobilization of glucose oxidase on the chitosan membranes.•H2O2 impedes bacterial growth of gram-negative and gram-positive ...representatives.•Biocompatibility proven on mice fibroblasts.
This work presents electrospun chitosan mats, functionalized with glucose oxidase (GOX) to implement an in-situ hydrogen peroxide (H2O2) generation system. The as spun CTS-PEO mats exhibited a smooth and homogenous morphology in combination with a high specific surface area (5.4m2/g) providing an excellent basis for further functionalization and subsequent glutaraldehyde crosslinking provided them with superior mechanical stability in aqueous environments. GOX was covalently immobilized, as proven by XPS, and resulted in activity recoveries between 20 and 40%. The functional mats generated a steady state concentration of ∼60μM H2O2 per cm2 which resulted in growth inhibition of E. coli and of S. aureus already after two hours of incubation. Additional cytotoxicity tests of the modified mats against mouse fibroblasts did not show an influence on the viability of the cells which proved it a functional biomaterial of great potential for biomedical applications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Service learning is a pedagogical approach, in which the format of the course contributes as much to the training of students as the content itself. There has been a substantial increase in interest ...in service learning in various fields, including for medical students and public health courses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Duchenne muscular dystrophy (DMD) is a yet incurable rare genetic disease that affects the skeletal and cardiac muscles, leading to progressive muscle wasting and premature death. DMD is caused by ...the lack of dystrophin, a muscle protein essential for the biochemical support and integrity of muscle fibers. Gene replacement strategies for Duchenne muscular dystrophy (DMD) employing the adeno-associated virus (AAV) face the challenge imposed by the limited packaging capacity of AAV, only allowing the accommodation of a short version of dystrophin (µDys) that is still far removed from correcting human disease. The need to develop strategies leading to the expression of a best performing dystrophin variant led to only few studies reporting on the use of dual vectors, but none reported on a method to assess in vivo transgene reconstitution efficiency, the degree of which directly affects the use of safe AAV dosing. We report here on the generation of a dual AAV vector approach for the expression of a larger dystrophin version (quasidystrophin) based on homologous recombination, and the development of a methodology employing a strategic droplet digital PCR design, to determine the recombination efficiency as well as the occurrence of unwanted concatemerization events or aberrant expression from the single vectors. We demonstrated that, upon systemic delivery in the dystrophic D2.B10-Dmd
/J (DBA2mdx) mice, our dual AAV approach led to high transgene reconstitution efficiency and negligible Inverted Terminal Repeats (ITR)-dependent concatemerization, with consequent remarkable protein restoration in muscles and improvement of muscle pathology. This evidence supports the suitability of our system for gene therapy application and the potential of this methodology to assess and improve the feasibility for therapeutic translation of multiple vector approaches.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•Development of electrospun chitosan/PEO blend fibers with tailored surface properties.•Designing of a response surface model (RSM) exhibiting excellent prediction accuracy.•Chitosan fibers ...exhibiting tailored nitrogen atomic surface content of up to 6.4%.•Nitrogen surface content is significantly determined by chitosan Mw and polymers mixing ratio.•Nitrogen surface content strongly influences the membranes zeta potential.
Chitosan is a promising biocompatible polymer for regenerative engineering applications, but its processing remains challenging due to limited solubility and rigid crystalline structure. This work represents the development of electrospun chitosan/poly(ethylene oxide) blend nanofibrous membranes by means of a numerical analysis in order to identify and tailor the main influencing parameters with respect to accessible surface nitrogen functionalities which are of importance for the biological activity as well as for further functionalization. Depending on the solution composition, both gradient fibers and homogenous blended fiber structures could be obtained with surface nitrogen concentrations varying between 0 and 6.4%. Response surface methodology (RSM) revealed chitosan/poly(ethylene oxide) ratio and chitosan molecular weight as the main influencing factors with respect to accessible nitrogen surface atoms and respective concentrations. The model showed good adequacy hence providing a tool to tailor the surface properties of chitosan/poly(ethylene oxide) blends by addressing the amount of accessible chitosan.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
While the mammalian macrophage phenotypes have been intensively studied in vitro, the dynamic of their phenotypic polarization has never been investigated in live vertebrates. We used the zebrafish ...as a live model to identify and trail macrophage subtypes. We generated a transgenic line whose macrophages expressing tumour necrosis factor alpha (tnfa), a key feature of classically activated (M1) macrophages, express fluorescent proteins Tg(mpeg1:mCherryF/tnfa:eGFP-F). Using 4D-confocal microscopy, we showed that both aseptic wounding and Escherichia coli inoculation triggered macrophage recruitment, some of which started to express tnfa. RT-qPCR on Fluorescence Activated Cell Sorting (FACS)-sorted tnfa(+) and tnfa(-) macrophages showed that they, respectively, expressed M1 and alternatively activated (M2) mammalian markers. Fate tracing of tnfa(+) macrophages during the time-course of inflammation demonstrated that pro-inflammatory macrophages converted into M2-like phenotype during the resolution step. Our results reveal the diversity and plasticity of zebrafish macrophage subsets and underline the similarities with mammalian macrophages proposing a new system to study macrophage functional dynamic.
Biomarkers are critically important for disease diagnosis and monitoring. In particular, close monitoring of disease evolution is eminently required for the evaluation of therapeutic treatments. ...Classical monitoring methods in muscular dystrophies are largely based on histological and molecular analyses of muscle biopsies. Such biopsies are invasive and therefore difficult to obtain. The serum protein creatine kinase is a useful biomarker, which is however not specific for a given pathology and correlates poorly with the severity or course of the muscular pathology. The aim of the present study was the systematic evaluation of serum microRNAs (miRNAs) as biomarkers in striated muscle pathologies. Mouse models for five striated muscle pathologies were investigated: Duchenne muscular dystrophy (DMD), limb-girdle muscular dystrophy type 2D (LGMD2D), limb-girdle muscular dystrophy type 2C (LGMD2C), Emery-Dreifuss muscular dystrophy (EDMD) and hypertrophic cardiomyopathy (HCM). Two-step RT-qPCR methodology was elaborated, using two different RT-qPCR miRNA quantification technologies. We identified miRNA modulation in the serum of all the five mouse models. The most highly dysregulated serum miRNAs were found to be commonly upregulated in DMD, LGMD2D and LGMD2C mouse models, which all exhibit massive destruction of striated muscle tissues. Some of these miRNAs were down rather than upregulated in the EDMD mice, a model without massive myofiber destruction. The dysregulated miRNAs identified in the HCM model were different, with the exception of one dysregulated miRNA common to all pathologies. Importantly, a specific and distinctive circulating miRNA profile was identified for each studied pathological mouse model. The differential expression of a few dysregulated miRNAs in the DMD mice was further evaluated in DMD patients, providing new candidates of circulating miRNA biomarkers for DMD.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Genetic variants in Fukutin‐related protein (FKRP), an essential enzyme of the glycosylation pathway of α‐dystroglycan, can lead to pathologies with different severities affecting the eye, brain, and ...muscle tissues. Here, we generate an in vitro cellular system to characterize the cellular localization as well as the functional potential of the most common FKRP patient missense mutations. We observe a differential retention in the endoplasmic reticulum (ER), the indication of misfolded proteins. We find data supporting that mutant protein able to overcome this ER‐retention through overexpression present functional levels comparable to the wild‐type. We also identify a specific region in FKRP protein localized between residues 300 and 321 in which genetic variants found in patients lead to correctly localized proteins but which are nevertheless functionally impaired or catalytically dead in our model, indicating that this particular region might be important for the enzymatic activity of FKRP within the Golgi. Our system thus allows the functional testing of patient‐specific mutant proteins and the identification of candidate mutants to be further explored with the aim of finding pharmacological treatments targeting the protein quality control system.
Graphical model illustrating the proposed fate of normal and abnormal FKRP proteins.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
It is common knowledge that specialised languages use some aspects of “languages” to express the communicative objectives of specialised communities. Compiling and analysing specialised corpora is ...one way of identifying recurrent features that tend to shed light on these special uses. As a result, it is possible to draw a list of the linguistic characteristics specific to a given specialised language, such as the use of a special lexicon or special lexico-grammatical features. Some of these features are so specific compared to other varieties of languages, whether specialised or not, that they will naturally be identified as typical of, say, legal English, economic English and so on. Therefore, lexis – and, to some extent, grammar – appears to be distinct from one specialised language to another, or from non-specialised languages to specialised languages, which would tend to show that specialised lexicons, together with some grammatical features, are a defining feature of specialised languages. Yet, as we will show, much of legal lexis is shared by other types of language, in particular everyday, non-specialised language, which implies that legal lexis is necessarily polysemous. Therefore the question is: how legal/specialised is legal lexis? Or, put differently: what makes legal lexis legal? Can legal lexis be considered as a characteristic of legal language? This article will first focus on some of the borrowings that characterise legal lexis in English and then look at some of the interpretation difficulties posed by a number of lexical units that do not stand out as being “legal” but yet consistently appear in legal messages and feature, for some of them, in legal dictionaries.
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