Estimated daily intake and cumulative risk assessment of organophosphate esters and associations with DNA damage among e-waste workers in Hong Kong.

Organophosphate esters (OPEs) are extensively used as additives in various products, including electronic equipment, which becomes e-waste when obsolete. Nevertheless, no study has evaluated OPEs exposure levels and the related health risks among e-waste workers in Hong Kong. Therefore, 201 first-spot morning urine samples were collected from 101 e-waste workers and 100 office workers to compare eight urinary OPE metabolites (mOPEs) levels in these groups. The concentrations of six mOPEs were similar in e-waste workers and office workers, except for significantly higher levels of diphenyl phosphate (DPHP) in e-waste workers and bis(1-chloro-2propyl) phosphate (BCIPP) in office workers. Spearman correlation analysis showed that most non-chlorinated mOPEs were correlated with each other in e-waste workers (i.e., nine out of ten pairs, including di-p-cresyl phosphate (DpCP) and di-o-cresyl phosphate (DoCP), DpCP and bis(2-butoxyethyl) phosphate (BBOEP), DpCP and DPHP, DpCP and dibutyl phosphate (DBP), DoCP and BBOEP, DoCP and DPHP, DoCP and DBP, BBOEP and DPHP, DPHP and DBP), indicating that handling e-waste could be the exposure source of specific OPEs. The median values of estimated daily intake (EDI) and hazard quotient (HQ) suggested that the health risks from OPEs exposures were under the recommended thresholds. However, linear regression models, Quantile g-computation, and Bayesian kernel machine regression found that urinary mOPEs elevated 8-hydroxy-2-deoxyguanosine (8-OhdG) levels individually or as a mixture, in which DPHP contributed prominently. In conclusion, although e-waste might not elevate the internal OPEs levels among the participating Hong Kong e-waste workers, attention should be paid to the potential DNA damage stimulated by OPEs under the currently recommended thresholds.

Assessing Neurobehavioral Alterations Among E-waste Recycling Workers in Hong Kong.

Background: E-waste workers in Hong Kong are handling an unprecedented amount of e-waste, which contains various neurotoxic chemicals. However, no study has been conducted to evaluate the neurological health status of e-waste workers in Hong Kong. This study aimed to evaluate the prevalence of neurobehavioral alterations and to identify the vulnerable groups among Hong Kong e-waste workers. Methods: We recruited 109 Hong Kong e-waste workers from June 2021 to September 2022. Participants completed standard questionnaires and wore a GENEActiv accelerometer for seven days. Pittsburgh Sleep Quality Index and Questionnaire 16/18 (Q16/18) were used to assess subjective neurobehavioral alterations. The GENEActiv data generated objective sleep and circadian rhythm variables. Workers were grouped based on job designation and entity type according to the presumed hazardous level. Unconditional logistic regression models measured the associations of occupational characteristics with neurobehavioral alterations after adjusting for confounders. Results: While dismantlers/repairers and the workers in entities not funded by the government were more likely to suffer from neurotoxic symptoms in Q18 (adjusted odds ratio: 3.18 [1.18-9.39] and 2.77 [1.10-7.46], respectively), the workers from self-sustained recycling facilities also have poor performances in circadian rhythm. Results also showed that the dismantlers/repairers working in entities not funded by the government had the highest risk of neurotoxic symptoms compared to the lowest-risk group (i.e., workers in government-funded companies with other job designations). Conclusion: This timely and valuable study emphasizes the importance of improving the working conditions for high-risk e-waste workers, especially the dismantlers or repairers working in facilities not funded by the government.

Systems Analysis of Immune Changes after B-cell Depletion in Autoimmune Multiple Sclerosis.

Multiple sclerosis (MS) is a complex genetically mediated autoimmune disease of the central nervous system where anti-CD20-mediated B cell depletion is remarkably effective in the treatment of early disease. While previous studies investigated the effect of B cell depletion on select immune cell subsets using flow cytometry-based methods, the therapeutic impact on patient immune landscape is unknown. In this study, we explored how a therapy-driven " in vivo perturbation " modulates the diverse immune landscape by measuring transcriptomic granularity with single-cell RNA sequencing (scRNAseq). We demonstrate that B cell depletion leads to cell type-specific changes in the abundance and function of CSF macrophages and peripheral blood monocytes. Specifically, a CSF-specific macrophage population with an anti-inflammatory transcriptomic signature and peripheral CD16 + monocytes increased in frequency post-B cell depletion. In addition, we observed increases in TNFα messenger RNA and protein in monocytes post-B cell depletion, consistent with the finding that anti-TNFα treatment exacerbates autoimmune activity in MS. In parallel, B cell depletion also induced changes in peripheral CD4 + T cell populations, including increases in the frequency of TIGIT + regulatory T cells and marked decreases in the frequency of myelin peptide loaded-tetramer binding CD4 + T cells. Collectively, this study provides an exhaustive transcriptomic map of immunological changes, revealing different mechanisms of action contributing to the high efficacy in B cell depletion treatment of MS.

Human Soluble TRAIL Secreted by Modified Lactococcus lactis Bacteria Promotes Tumor Growth in the Orthotopic Mouse Model of Colorectal Cancer.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis of sensitive cancer cells, including colorectal cancer (CRC). Due to its short biological half-life after intravenous administration and related clinical ineffectiveness, novel formulations of TRAIL need to be developed. Here we propose Lactococcus lactis bacteria as a vehicle for local delivery of human soluble TRAIL (hsTRAIL) in CRC. The use of common probiotics targeting guts as carriers for TRAIL could ensure its sustained release at the tumor site and extend the duration of its activity. We have already engineered hsTRAIL-secreting L.lactis bacteria and showed their effectiveness in elimination of human CRC cells in vitro and in vivo in a mouse subcutaneous model. Here, L.lactis(hsTRAIL+) were administered by gastric gavage to SCID mice with orthotopically developed HCT116 tumor in cecum, in monotherapy or in combination with metformin (MetF), already shown to enhance the hsTRAIL anti-tumor activity in subcutaneous CRC model. Oral administration of L.lactis(hsTRAIL+) resulted in significant progression of HCT116 tumors and shortening of the colon crypts. Secretion of hsTRAIL in the colon was accompanied by infiltration of the primary tumor with M2-macrophages, while MetF promoted transient colonization of the gut by L.lactis. Our study indicates that L.lactis bacteria after oral administration enable delivery of biologically active hsTRAIL to colon, however its potential therapeutic effect in CRC treatment is abolished by its pro-tumorigenic signalling, leading to the recruitment of M2-macrophages and tumor growth promotion.

A science mapping-based review of work-related musculoskeletal disorders among construction workers.

INTRODUCTION: Work-related musculoskeletal disorders (WMSDs) are recognized as a leading cause of nonfatal injuries in construction, but no review of existing studies has systematically analyzed and visualized the trends of WMSDs among construction workers. The current science mapping-based review summarized research published between 2000 and 2021 related to WMSDs among construction workers through co-word, co-author, and citation analysis. METHOD: A total of 63 bibliographic records retrieved from the Scopus database were analyzed. RESULTS: The results identified influential authors with high impacts in this research domain. Moreover, the results indicated that MSDs, ergonomics, and construction not only had the highest occurrence of been studied, but also the highest impact in terms of total link strength. In addition, the most significant contributions to research relating to WMSDs among construction workers have originated primarily from the United States, Hong Kong, and Canada. Furthermore, a follow-up in-depth qualitative discussion was conducted to focus on summarizing mainstream research topics, identifying existing research gaps, and proposing directions for future studies. CONCLUSIONS: This review provides an in-depth understanding of related research on WMSDs among construction workers and proposes the emerging trends in this research field.

Simultaneous quantitation of urine aldosterone and tetrahydroaldosterone in healthy Chinese subjects using a validated LC-MS/MS method.

Aldosterone (ALD) is excreted in urine mainly as glucuronide conjugates of ALD and tetrahydroaldosterone. Measuring these urinary metabolites might be an alternative screening test to plasma ALD for primary aldosteronism. We report a validated LC-MS/MS method to measure both analytes simultaneously. Urine samples underwent enzymatic hydrolysis to release the analytes from their glucuronide conjugates followed by organic solvent extraction and LC-MS/MS. The analytical performance of this method was evaluated. The within-batch and between-batch coefficients of variation for urine ALD and urine THA were all ≤5.2 and ≤3.7%. The lower limit of quantification was 0.5 nmol/L, and the linearity was up to at least 2770 nmol/L for both analytes. No significant matrix interference and carryover were observed. Both analytes in urine were stable for at least 48 h at 10°C and at least 18 months at -80°C. Local reference intervals were established from 126 healthy normotensive Chinese subjects (53% women, age: 20-65 years). Reference intervals for urine ALD and tetrahydroaldosterone were 2-38 and 9-139 nmol/day, respectively. This validated method can be applied to screening and diagnosing primary aldosteronism.

Current Practice, Barriers to, and Facilitators of Exercise Testing and Training by Physiotherapists in Cystic Fibrosis Specialized Centres in Canada.

Purpose: This study surveyed physiotherapists working at Canadian cystic fibrosis (CF) specialized centres to investigate the current practice, barriers to, and facilitators of exercise testing and training. Method: Physiotherapists were recruited from 42 Canadian CF centres. They responded to an e-questionnaire regarding their practice. The data were analyzed using descriptive statistics. Results: Eighteen physiotherapists responded (estimated response rate of 23%); median years of clinical experience was 15 (range, min-max, 3-30) years. Aerobic testing was administered by 44% of respondents, strength testing by 39%, aerobic training by 78%, and strength training by 67%. The most frequently reported barriers across all four types of exercise testing and training were insufficient funding (reported by 56%-67% of respondents), time (50%-61%) and staff availability (56%). More late career than early career physiotherapists reported utilizing aerobic testing (50% vs. 33% of respondents), strength testing (75% vs. 33%), aerobic training (100% vs. 67%), and strength training (100% vs. 33%). Conclusions: Exercise testing and training is underutilized in Canadian CF centres. Experienced physiotherapists reported utilizing exercise testing and training more than less-experienced physiotherapists. Post-graduate education and mentorship, especially for less-experienced clinicians, are recommended to emphasize the importance of exercise testing and training. Barriers of funding, time, and staff availability should be addressed to further improve quality of care.

Objectif :sondage auprès de physiothérapeutes qui travaillent dans des centres canadiens spécialisés en fibrose kystique (FK) pour examiner les pratiques, les obstacles et les incitations actuels liés aux épreuves et aux entraînements à l'exercice. Méthodologie: les physiothérapeutes ont été recrutés dans 42 centres canadiens spécialisés en FK. Ils ont répondu à un questionnaire en ligne au sujet de leur pratique. Les données ont été analysées au moyen de statistiques descriptives. Résultats: les 18 physiothérapeutes qui ont répondu (taux de réponse estimatif de 23 %) avaient une médiane de 15 années d'expérience clinique (plage minimale-maximale de trois à 30 ans). Ainsi, 44 % des répondants effectuaient des épreuves d'endurance aérobique, 39 %, des épreuves en résistance, 78 %, un entraînement aérobique et 67 %, un entraînement en résistance. Les obstacles les plus signalés dans les quatre types d'épreuves et d'entraînement à l'exercice étaient un financement insuffisant (par 56 % à 67 % des répondants), le manque de temps (50 % à 61 %) et le peu de disponibilité du personnel (56 %). Plus de physiothérapeutes en fin de carrière qu'en début de carrière ont déclaré utiliser les épreuves d'endurance aérobique (50 % par rapport à 33 % des répondants), les épreuves de résistance (75 % par rapport à 33 %), l'entraînement aérobique (100 % par rapport à 67 %) et l'entraînement en résistance (100 % par rapport à 33 %). Conclusions:  l'épreuve et l'entraînement à l'exercice sont sous-utilisés dans les centres canadiens spécialisés en FK. Les physiothérapeutes d'expérience étaient plus nombreux à avoir déclaré utiliser l'épreuve et l'entraînement à l'exercice que les physiothérapeutes moins expérimentés. Les études supérieures et le mentorat, particulièrement chez les cliniciens moins expérimentés, sont recommandés pour insister sur l'importance de l'épreuve et de l'entraînement à l'exercice. Il faut corriger les obstacles au financement, au temps et à la disponibilité du personnel pour améliorer encore davantage la qualité des soins.

Retinoic acid-loaded PLGA nanocarriers targeting cell cholesterol potentialize the antitumour effect of PD-L1 antibody by preventing epithelial-mesenchymal transition mediated by M2-TAM in colorectal cancer.

Tumour-associated macrophages (TAMs) often promote cancer progression through immunosuppression in the tumour microenvironment (TME). However, the signalling pathways crosstalk responsible for this mechanism remain unclear. The aim of our study was to investigate whether the interaction between TAMs and colorectal cancer cells could be down-regulated by nanoparticles (NPs) loaded with retinoic acid (RA) and coated with cholesterol (CHO), in combination with an anti-PD-L1 immune checkpoint inhibitor. Tumours were evaluated by qRT-PCR and immunohistochemistry from allographic tumour growth model. In addition, human tumours were evaluated by Tissue Microarray (TMA) and immunohistochemistry. Complementary analysis of epithelial-mesenchymal transition, cell migration, and macrophage polarisation were evaluated in vitro. We showed that the IL-10R/IL-10 axis is involved in overstimulation of the STAT3 pathway as well as downregulation of the NF-κB signalling pathway, which supports a loop of immunosuppressive cytokines that induces the M2-TAM phenotype. Furthermore, our combined findings suggest that the upregulation of STAT3/NF-κB pathways crosstalk mediated by immunosuppressive cytokines, such as IL-10/PD-L1/TGF-ß, via M2-TAMs in the TME, leads to immunosuppression and epithelial-mesenchymal-transition of the colorectal cancer for stimulating Vimentin, CXCL12 and CD163 in the primary tumours. Importantly, NPs holding RA and coated with CHO in combination with anti-PD-L1 were more efficient in blocking this signalling pathway. These results contribute to our understanding of the immunological mechanisms, especially the re-educating of TAMs, and provide a novel management strategy for aggressive colorectal cancers using anti-PD-L1-conjugated nanocarriers.

Motivation to interaction media: The impact of automation trust and self-determination theory on intention to use the new interaction technology in autonomous vehicles.

Introduction: This research investigated the effects of three psychological needs (competence, autonomy, and relatedness) of self-determination theory (SDT) and automation trust on the intention of users to employ new interaction technology brought by autonomous vehicles (AVs), especially interaction mode and virtual image. Method: This study focuses on the discussion from the perspective of psychological motivation theory applied to AV interaction technology. With the use of a structured questionnaire, participants completed self-report measures related to these two interaction technologies; a total of 155 drivers' responses were analyzed. Result: The results indicated that users' intentions were directly predicted by their perceived competence, autonomy, and relatedness of SDT and automation trust, which jointly explained at least 66% of the variance in behavioral intention. In addition to these results, the contribution of predictive components to behavioral intention is influenced by the type of interaction technology. Relatedness and competence significantly impacted the behavioral intention to use the interaction mode but not the virtual image. Discussion: These findings are essential in that they support the necessity of distinguishing between types of AV interaction technology when predicting users' intentions to use.

Investigation on the effects of presentation modality for spatial signals on human performance using a dual task paradigm.

A dual task was designed to involve a tracking mission with various tracking speeds and a spatial compatibility task with various signal-key mappings and presentation modalities. This dual task was used to investigate the effects of workload and resource competition in distinct parts of the dual-task process. The results demonstrated that increasing the tracking speed adversely affected the tracking performance but led to positive arousal to the secondary discrete response task. Visual spatial signals gave the shortest reaction time due to the optimal time-sharing of the visual resources in the focal and ambient channels. Compared with visual spatial signals, spatial signals of auditory and tactile modalities did not lead to an improved performance because of their cross-modality nature. These findings provided practical design guidelines for dual tasks in which the operators need to complete a continuous monitoring task visually and elicit timely and accurate responses to spatial information.

Difficult Percutaneous Closure of Axillary Access.

This case illustrates step-by-step troubleshooting in difficult axillary access closure. A standard balloon-assisted dry closure technique; escalation of wire support; trial of different closure devices with understanding in their mechanisms of failure; meticulous deployment of closure devices under fluoroscopy; a novel approach in deliverance of Angio-Seal device in a hydrophilic braided sheath all contributed to successful hemostasis.

Improving the Safety Performance of Construction Workers through Individual Perception and Organizational Collectivity: A Contrastive Research between Mainland China and Hong Kong.

Considering the increasing number in construction accidents in Mainland China and Hong Kong, research on improving the safety performance of construction personnel is important, given the essential role it plays in occupational safety development in industries. The present study aimed to assess the improving channels of safety performance through individual perception and organizational collectivity in a quantitative way by integrating safety motivation as the transition role between individual and organizational levels. The questionnaire survey was conducted with 180 participants from Hong Kong and 197 responses from Mainland China. Structural equation modeling was applied to investigate and compare the direct, indirect, and mediating effects among different safety constructs. This study is unique, as it firstly integrates the theories of personal cognition and group interaction together with the mechanism of safety performance development. Such integration can increase the effectiveness of reducing the unsafety of construction workers at both individual and organizational levels, thereby reducing the numbers of construction accidents, and promoting healthy occupational development of the personnel.

Cross-Regional Research in Demographic Impact on Safety Consciousness and Safety Citizenship Behavior of Construction Workers: A Comparative Study between Mainland China and Hong Kong.

The construction industry has rapidly developed with continuous prosperity in Hong Kong and Mainland China, although accidents still occur with unacceptable frequency and severity. For promoting the safety issue of workers in construction industry, safety citizenship behavior (SCB) and safety consciousness (SC) were considered two influential constructs and further studied with integration of sociodemographic theories by scholars. However, no study has compared the SC and SCB of construction workers in terms of the demographic influence between Mainland China and Hong Kong. To fill this research gap, this study investigated the territorial difference between these two regions by conducting a cross-sectional questionnaire survey with recruitment of 253 Mainland construction workers and 256 Hong Kong construction workers. Significant similarities and differences of SC and SCB performance were revealed in terms of the workers with different genders, education levels, weekly working hours, and ages. This study provides insights into the comparison of demographic influence on SC and SCB of construction workers between Hong Kong and Mainland China, which is unique as it can yield useful managerial knowledge relevant to the personal safety of targeted groups of construction workers with particular demographic characteristics in both regions and contribute the implementation of safety interventions in line with the specific distinction in the territorial aspect.

VA-ECMO With Pericardiocentesis and Autologous Blood Transfusion - Stabilisation Strategy in Acute Cardiac Free Wall Rupture.

A 68-year old lady present with left ventricular free wall rupture and cardiac arrest post-myocardial infarction. This article illustrates a strategy combining pericardiocentesis with autologous transfusion together with VA-ECMO as a bridge to definitive surgical repair.

Erratum: Exosomal microRNAs synergistically trigger stromal fibroblasts in breast cancer.

[This corrects the article DOI: 10.1016/j.omtn.2022.02.013.].

Thermosensitive Injectable Hydrogels for Intra-Articular Delivery of Etanercept for the Treatment of Osteoarthritis.

The intra-articular administration of drugs has attracted great interest in recent decades for the treatment of osteoarthritis. The use of modified drugs has also attracted interest in recent years because their intra-articular administration has demonstrated encouraging results. The objective of this work was to prepare injectable-thermosensitive hydrogels for the intra-articular administration of Etanercept (ETA), an inhibitor of tumor necrosis factor-α. Hydrogels were prepared from the physical mixture of chitosan and Pluronic F127 with ß-glycerolphosphate (BGP). Adding ß-glycerolphosphate to the system reduced the gelation time and also modified the morphology of the resulting material. In vitro studies were carried out to determine the cytocompatibility of the prepared hydrogels for the human chondrocyte line C28/I2. The in vitro release study showed that the incorporation of BGP into the system markedly modified the release of ETA. In the in vivo studies, it was verified that the hydrogels remained inside the implantation site in the joint until the end of the study. Furthermore, ETA was highly concentrated in the blood of the study mice 48 h after the loaded material was injected. Histological investigation of osteoarthritic knees showed that the material promotes cartilage recovery in osteoarthritic mice. The results demonstrate the potential of ETA-loaded injectable hydrogels for the localized treatment of joints.

Chinese normotensive and essential hypertensive reference intervals for plasma aldosterone and renin activity by liquid chromatography-tandem mass spectrometry.

OBJECTIVES: The renin-angiotensin-aldosterone system (RAAS) regulates blood pressure. Plasma renin activities (PRA) and plasma aldosterone concentrations (PAC) are biomarkers related to RAAS. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based measurements for PRA and PAC have become popular. Method-specific reference intervals (RIs) are required. METHODS: Routine PRA and PAC services in a Hong Kong teaching hospital were based on LC-MS/MS methods. PRA and PAC RIs were developed for normotensive subjects and essential hypertensive (EH) patients. Healthy volunteers were recruited to establish normotensive RIs. PRA and PAC results of hypertensive patients with urine aldosterone tests for primary aldosteronism (PA) screening were retrieved from the laboratory information system. Patients without PA were included. Patients with secondary hypertension and patients on medications affecting the RAAS were excluded. The central 95% RIs were established based on the recommendations of the Clinical and Laboratory Standards Institute guideline C28-A3. RESULTS: PRA and PAC of 170 normotensive volunteers and 362 EH patients were analysed. There was no sex-specific difference in PRA and PAC for normotensive and EH reference subjects. Differences for PRA and PAC were noted between normotensive subjects aged below 45 and their older counterparts. However, such a difference was only identified for PRA but not PAC in EH patients. Age-specific RIs were established accordingly. CONCLUSIONS: This study presented age-specific LC-MS/MS RIs of PRA and PAC for both normotensive and EH populations for local Chinese in Hong Kong.

PLGA Nanoparticles Grafted with Hyaluronic Acid to Improve Site-Specificity and Drug Dose Delivery in Osteoarthritis Nanotherapy.

Nanoparticles (NPs) have a tremendous potential in medicinal applications, and recent studies have pushed the boundaries in nanotherapy, including in osteoarthritis treatments. The aim of this study was to develop new poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) surfaces decorated with hyaluronic acid (HA) to enhance targeted drug specificity to the osteoarthritic knee joint. HA was selected since it binds to specific receptors expressed in many cells, such as the cluster determinant 44 (CD44), a major receptor of chondrocytes, and because of its function in the synovial fluid (SF), such as maintenance of high fluid viscosity. The PLGA polymer was grafted to sodium hyaluronate using dimethoxy-PEG (PLGA-HA) and compared with control PLGA NPs (not grafted). NPs were characterized by 1H-NMR and IR spectroscopy. Then, near-infrared (NIR) dye and gold (20 nm) were encapsulated in the formulated NPs and used to access NPs' performance in in vitro, in vivo, and ex vivo experiments. To test the NPs' CD44 receptor specificity, an antibody assay was performed. All NPs presented a size in the range viable for cell-uptake, no cytotoxicity to chondrocytes was registered. Although all the NPs had a high capacity to be absorbed by the cells, PLGA-HA NPs showed significantly higher affinity towards the chondrocytic C28/I2 cell line. In conclusion, PLGA NPs grafted to sodium hyaluronate showed increased binding to cartilage cells and tissue and enhanced accumulation at the target site. Thus, this study presents a safe drug-delivery system with improved receptor specificity, which may represent an advantageous alternative to current nanotherapies.