a mixed-method approach

Background Sedentary behaviours (SB) can be characterized by low energy expenditure in a reclining position (e.g., sitting) often associated with work and transport. Prolonged SB is associated with increased risk for chronic conditions, and due to technological advances, the working population is in office settings with high occupational exposure to SB. This study aims to assess SB among office workers, as well as barriers and strategies towards reducing SB in the work setting. Methods Using a mixed-methods approach guided by the socio-ecological framework, non-academic office workers from a professional school in a large public university were recruited. Of 180 eligible office workers, 40 enrolled and completed all assessments. Self- reported and objectively measured SB and activity levels were captured. Focus group discussion (FGD) were conducted to further understand perceptions, barriers, and strategies to reducing workplace SB. Environmental factors were systematically evaluated by trained research staff using an adapted version of the Checklist for Health Promotion Environments at Worksites (CHEW). Thematic analysis of FGD was conducted and descriptive analysis of quantitative data was performed. Results The sample was mostly Chinese (n = 33, 80 %) with a total of 24 (60 %) female participants. Most participants worked five days a week for about 9.5(0.5) hrs/day. Accelerometer data show that participants spend the majority of their days in sedentary activities both on workdays (76.9 %) and non-workdays (69.5 %). Self-report data confirm these findings with median sitting time of 420(180) minutes at work. From qualitative analyses, major barriers to reducing SB emerged, including the following themes: workplace social and cultural norms, personal factors, job scope, and physical building/office infrastructure. CHEW results confirm a lack of support from the physical infrastructure and information environment to reducing SB. Conclusions There is high SB among office workers in this sample. We identified multiple levels of influence for prolonged occupational SB, with a particular emphasis on workplace norms and infrastructure as important barriers to reducing SB and increasing PA. A larger, representative sample of the Singaporean population is needed to confirm our findings but it seems that any intervention aimed at reducing SB in the workplace should target individual, environmental, and organizational levels

Assessing and understanding sedentary behaviour in office-based working adults: a mixed-method approach

Abstract Background Sedentary behaviours (SB) can be characterized by low energy expenditure in a reclining position (e.g., sitting) often associated with work and transport. Prolonged SB is associated with increased risk for chronic conditions, and due to technological advances, the working population is in office settings with high occupational exposure to SB. This study aims to assess SB among office workers, as well as barriers and strategies towards reducing SB in the work setting. Methods Using a mixed-methods approach guided by the socio-ecological framework, non-academic office workers from a professional school in a large public university were recruited. Of 180 eligible office workers, 40 enrolled and completed all assessments. Self-reported and objectively measured SB and activity levels were captured. Focus group discussion (FGD) were conducted to further understand perceptions, barriers, and strategies to reducing workplace SB. Environmental factors were systematically evaluated by trained research staff using an adapted version of the Checklist for Health Promotion Environments at Worksites (CHEW). Thematic analysis of FGD was conducted and descriptive analysis of quantitative data was performed. Results The sample was mostly Chinese (n = 33, 80 %) with a total of 24 (60 %) female participants. Most participants worked five days a week for about 9.5(0.5) hrs/day. Accelerometer data show that participants spend the majority of their days in sedentary activities both on workdays (76.9 %) and non-workdays (69.5 %). Self-report data confirm these findings with median sitting time of 420(180) minutes at work. From qualitative analyses, major barriers to reducing SB emerged, including the following themes: workplace social and cultural norms, personal factors, job scope, and physical building/office infrastructure. CHEW results confirm a lack of support from the physical infrastructure and information environment to reducing SB. Conclusions There is high SB among office workers in this sample. We identified multiple levels of influence for prolonged occupational SB, with a particular emphasis on workplace norms and infrastructure as important barriers to reducing SB and increasing PA. A larger, representative sample of the Singaporean population is needed to confirm our findings but it seems that any intervention aimed at reducing SB in the workplace should target individual, environmental, and organizational levels

The Management of Ocular Surface Squamous Neoplasia (OSSN)

The rise of primary topical monotherapy with chemotherapeutic drugs and immunomodulatory agents represents an increasing recognition of the medical management of ocular surface squamous neoplasia (OSSN), which may replace surgery as the standard of care in the future. Currently, there is no consensus regarding the best way to manage OSSN with no existing guidelines to date. This paper seeks to evaluate evidence surrounding available treatment modalities and proposes an approach to management. The approach will guide ophthalmologists in selecting the most appropriate treatment regime based on patient and disease factors to minimize treatment related morbidity and improve OSSN control. Further work can be done to validate this algorithm and to develop formal guidelines to direct the management of OSSN

Calcineurin/NFAT signalling inhibits myeloid haematopoiesis

Nuclear factor of activated T cells (NFAT) comprises a family of transcription factors that regulate T cell development, activation and differentiation. NFAT signalling can also mediate granulocyte and dendritic cell (DC) activation, but it is unknown whether NFAT influences their development from progenitors. Here, we report a novel role for calcineurin/NFAT signalling as a negative regulator of myeloid haematopoiesis. Reconstituting lethally irradiated mice with haematopoietic stem cells expressing an NFAT-inhibitory peptide resulted in enhanced development of the myeloid compartment. Culturing bone marrow cells in media supplemented with Flt3-L in the presence of the calcineurin/NFAT inhibitor Cyclosporin A increased numbers of differentiated DC. Global gene expression analysis of untreated DC and NFAT-inhibited DC revealed differential expression of transcripts that regulate cell cycle and apoptosis. In conclusion, these results provide evidence that calcineurin/NFAT signalling negatively regulates myeloid lineage development. The finding that inhibition of NFAT enhances myeloid development provides a novel insight into understanding how the treatment with drugs targeting calcineurin/NFAT signalling influence the homeostasis of the innate immune system

miR-181a Modulation of ERK-MAPK Signaling Sustains DC-SIGN Expression and Limits Activation of Monocyte-Derived Dendritic Cells.

DC-SIGN+ monocyte-derived dendritic cells (mo-DCs) play important roles in bacterial infections and inflammatory diseases, but the factors regulating their differentiation and proinflammatory status remain poorly defined. Here, we identify a microRNA, miR-181a, and a molecular mechanism that simultaneously regulate the acquisition of DC-SIGN expression and the activation state of DC-SIGN+mo-DCs. Specifically, we show that miR-181a promotes DC-SIGN expression during terminal mo-DC differentiation and limits its sensitivity and responsiveness to TLR triggering and CD40 ligation. Mechanistically, miR-181a sustains ERK-MAPK signaling in mo-DCs, thereby enabling the maintenance of high levels of DC-SIGN and a high activation threshold. Low miR-181a levels during mo-DC differentiation, induced by inflammatory signals, do not support the high phospho-ERK signal transduction required for DC-SIGNhi mo-DCs and lead to development of proinflammatory DC-SIGNlo/-mo-DCs. Collectively, our study demonstrates that high DC-SIGN expression levels and a high activation threshold in mo-DCs are linked and simultaneously maintained by miR-181a

ERS international Congress 2023: highlights from the Basic and Translational Sciences Assembly

In this article, early career members of the Assembly 3: Basic and Translational Sciences of the European Respiratory Society summarise the key messages discussed during six selected sessions that took place at the ERS congress 2023 in Milan, Italy. Aligned with the theme of the congress, the first topic covered is “micro- and macro-environments and respiratory health”, followed by a summary of the “Scientific year in review” session. Next, recent advances in experimental methodologies and new technologies were highlighted within the “tissue modelling and remodelling” session, as well as summary of the translational science session, “what did you always want to know about omics analyses for clinical practice?”, organised as part of the ERS Translational Science Working group's aims. Details on how the next-generation sequencing can be integrated with laboratory methods were provided in the “lost in translation: new insights into cell-to-cell crosstalk in lung disease” session and a final summary of studies presented in the “from the transcriptome landscape to innovative preclinical models in lung diseases” session linking the transcriptome landscape with innovative preclinical models was included in this review. The wide range of topics covered in the selected sessions and the high quality of the research discussed highlight the strength of the basic and translational science being presented at the international respiratory conference organised by the ERS

Whole exome sequencing in three families segregating a pediatric case of sarcoidosis

International audienceAbstractBackgroundSarcoidosis (OMIM 181000) is a multi-systemic granulomatous disorder of unknown origin. Despite multiple genome-wide association (GWAS) studies, no major pathogenic pathways have been identified to date. To find out relevant sarcoidosis predisposing genes, we searched for de novo and recessive mutations in 3 young probands with sarcoidosis and their healthy parents using a whole-exome sequencing (WES) methodology.MethodsFrom the SARCFAM project based on a national network collecting familial cases of sarcoidosis, we selected three families (trios) in which a child, despite healthy parents, develop the disease before age 15 yr. Each trio was genotyped by WES (Illumina HiSEQ 2500) and we selected the gene variants segregating as 1) new mutations only occurring in affected children and 2) as recessive traits transmitted from each parents. The identified coding variants were compared between the three families. Allelic frequencies and in silico functional results were analyzed using ExAC, SIFT and Polyphenv2 databases. The clinical and genetic studies were registered by the ClinicalTrials.gov - Protocol Registration and Results System (PRS) (https://clinicaltrials.gov) receipt under the reference NCT02829853 and has been approved by the ethical committee (CPP LYON SUD EST – 2 – REF IRB 00009118 – September 21, 2016).ResultsWe identified 37 genes sharing coding variants occurring either as recessive mutations in at least 2 trios or de novo mutations in one of the three affected children. The genes were classified according to their potential roles in immunity related pathways: 9 to autophagy and intracellular trafficking, 6 to G-proteins regulation, 4 to T-cell activation, 4 to cell cycle and immune synapse, 2 to innate immunity. Ten of the 37 genes were studied in a bibliographic way to evaluate the functional link with sarcoidosis.ConclusionsWhole exome analysis of case-parent trios is useful for the identification of genes predisposing to complex genetic diseases as sarcoidosis. Our data identified 37 genes that could be putatively linked to a pediatric form of sarcoidosis in three trios. Our in-depth focus on 10 of these 37 genes may suggest that the formation of the characteristic lesion in sarcoidosis, granuloma, results from combined deficits in autophagy and intracellular trafficking (ex: Sec16A, AP5B1 and RREB1), G-proteins regulation (ex: OBSCN, CTTND2 and DNAH11), T-cell activation (ex: IDO2, IGSF3), mitosis and/or immune synapse (ex: SPICE1 and KNL1). The significance of these findings needs to be confirmed by functional tests on selected gene variants