Workplace stressors and their association with hair cortisol concentrations among ready-made garment workers in Bangladesh: A cross-sectional study.

OBJECTIVES: Psychosocial working conditions of ready-made garment (RMG) workers have been associated with poorer self-reported health outcomes. However, no such research has been done with respect to physiological markers that are considered to reflect stress. We consequently aimed to investigate associations of psychosocial working conditions with such a marker, that is, hair cortisol, among RMG workers in Bangladesh. METHODS: We conducted semi-structured face-to-face interviews in labor colonies in the Mirpur area, Dhaka, Bangladesh, in February and March 2021 with individuals identifying as garment workers. The interview inquired after various workplace stressors and resources (i.e., workplace support, workplace bullying, vertical trust, beneficial leadership, work-family conflict, and financial issues including savings, debts, financial obligations, and financial support). In addition, hair samples of 2 cm length were collected from participants. Hair cortisol concentrations (HCC) were determined based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Linear regression models were run to detect possible associations of workplace stressors and resources with HCC. RESULTS: In total, data of 576 participants were included in the analysis (71.9% female, mean age = 25.9 years). Mean HCC was 4.4 pg/mg (standard deviation = 2.1 pg/mg). The sole variable significantly associated with increased HCC was "having to keep your job to support your children or spouse financially" (ß = 0.28 [95% confidence interval 0.02-0.55]). CONCLUSIONS: The sole workplace stressor significantly associated with increased HCC was the necessity to keep one's job to support children or spouse financially. This observation can, however, barely be disentangled from the fact that one has children/a spouse.

Work-family conflict, financial issues and their association with self-reported health complaints among ready-made garment workers in Bangladesh: a cross-sectional study.

OBJECTIVES: This study aims to quantify the degree of work-family conflict (WFC) and financial issues among ready-made garment (RMG) workers in Bangladesh and to investigate their potential associations with self-reported health outcomes. METHODS: We conducted a cross-sectional survey among 1118 RMG workers in labor colonies in Dhaka, Bangladesh, in February and March 2021. Descriptive analyses were performed to characterize WFC (i.e., family life disturbing the job or facing problems in family due to the job) and financial issues (i.e., savings, debt, financial obligations, financial support). We ran multivariable Poisson regression models to examine possible associations between WFC and financial issues and workers' health (self-reported general health and 10 specific health complaints). RESULTS: We found low levels of WFC, low levels of savings, moderate levels of debt, and high levels of financial obligations: virtually all workers agreed they had to keep their job to financially support their spouse, children or other relatives. Only about a third of workers expected they would be able to receive financial support in case of a job loss. Work-family conflict was positively associated with poor health but not consistently with specific symptoms. Financial support was negatively associated, whereas being indebted was weakly positively associated with poor health. CONCLUSIONS: Our findings suggest low levels of WFC among RMG workers but high levels of financial obligations. Work-family conflict was positively associated with poor health, but not consistently with specific symptoms. Being indebted was weakly positively associated with poor health. Future prospective studies are needed to confirm these findings.

Social stressors and social resources at work and their association with self-reported health complaints among ready-made garment workers in Bangladesh: a cross-sectional study.

BACKGROUND: Bangladesh is one of the world's largest garment exporters. Physical working conditions of garment workers are precarious and known to largely affect their health. Research on garment workers' psychosocial working conditions, however, is scarce. We aimed to quantify psychosocial working conditions of garment workers and possible associations with workers' health. METHODS: We conducted a cross-sectional survey among 1,118 ready-made garment (RMG) workers in labor colonies in Dhaka, Bangladesh, in February 2021. Descriptive analyses were performed to characterize social stressors (e.g., being bullied at work, poor leadership) and social resources at work (e.g., receiving support at work, vertical trust between management and employees, beneficial leadership) and workers' health (self-reported overall health and 10 specific health complaints). To examine links of social stressors and social resources with self-reported health outcomes we ran multivariable Poisson regression models yielding prevalence ratios (PR) and 95% confidence intervals (CI). RESULTS: We found low to moderate levels of workplace bullying and high levels of poor leadership (i.e., supervisors not caring about workers' problems). We also found high levels of social support, vertical trust and beneficial leadership (i.e., supervisors taking decisions free of bias). Garment workers frequently suffered from health complaints, first and foremost headache (68.3%), cold (55.3%), and back pain (50.7%). Health outcomes were poorer among workers who reported to be bullied at work versus not bullied (e.g., PR 1.55 [95% CI 1.32-1.92] for poor self-reported health when bullied by colleagues) and health was better among those reporting to feel supported versus unsupported (e.g., PR 0.61 [0.52-0.71] for poor self-reported health when supported by supervisor). Perceived vertical trust between workers and management was weakly associated with better health. Leadership behavior did not display a consistent pattern. CONCLUSIONS: Our findings suggest that working conditions of RMG workers are rather good (e.g., characterized by low levels of bullying and high levels of support, vertical trust and beneficial leadership). The majority of workers reported good or very good health, although health complaints were frequently mentioned, first and foremost headache, cold, and back pain. Associations between psychosocial working conditions and health indicate worse working conditions being associated with poorer health.

Pseudomonas aeruginosa PA80 is a cystic fibrosis isolate deficient in RhlRI quorum sensing.

Pseudomonas aeruginosa uses quorum sensing (QS) to modulate the expression of several virulence factors that enable it to establish severe infections. The QS system in P. aeruginosa is complex, intricate and is dominated by two main N-acyl-homoserine lactone circuits, LasRI and RhlRI. These two QS systems work in a hierarchical fashion with LasRI at the top, directly regulating RhlRI. Together these QS circuits regulate several virulence associated genes, metabolites, and enzymes in P. aeruginosa. Paradoxically, LasR mutants are frequently isolated from chronic P. aeruginosa infections, typically among cystic fibrosis (CF) patients. This suggests P. aeruginosa can undergo significant evolutionary pathoadaptation to persist in long term chronic infections. In contrast, mutations in the RhlRI system are less common. Here, we have isolated a clinical strain of P. aeruginosa from a CF patient that has deleted the transcriptional regulator RhlR entirely. Whole genome sequencing shows the rhlR locus is deleted in PA80 alongside a few non-synonymous mutations in virulence factors including protease lasA and rhamnolipid rhlA, rhlB, rhlC. Importantly we did not observe any mutations in the LasRI QS system. PA80 does not appear to have an accumulation of mutations typically associated with several hallmark pathoadaptive genes (i.e., mexT, mucA, algR, rpoN, exsS, ampR). Whole genome comparisons show that P. aeruginosa strain PA80 is closely related to the hypervirulent Liverpool epidemic strain (LES) LESB58. PA80 also contains several genomic islands (GI's) encoding virulence and/or resistance determinants homologous to LESB58. To further understand the effect of these mutations in PA80 QS regulatory and virulence associated genes, we compared transcriptional expression of genes and phenotypic effects with isogenic mutants in the genetic reference strain PAO1. In PAO1, we show that deletion of rhlR has a much more significant impact on the expression of a wide range of virulence associated factors rather than deletion of lasR. In PA80, no QS regulatory genes were expressed, which we attribute to the inactivation of the RhlRI QS system by deletion of rhlR and mutation of rhlI. This study demonstrates that inactivation of the LasRI system does not impact RhlRI regulated virulence factors. PA80 has bypassed the common pathoadaptive mutations observed in LasR by targeting the RhlRI system. This suggests that RhlRI is a significant target for the long-term persistence of P. aeruginosa in chronic CF patients. This raises important questions in targeting QS systems for therapeutic interventions.

Impact of the societal response to COVID-19 on access to healthcare for non-COVID-19 health issues in slum communities of Bangladesh, Kenya, Nigeria and Pakistan: results of pre-COVID and COVID-19 lockdown stakeholder engagements.

INTRODUCTION: With COVID-19, there is urgency for policymakers to understand and respond to the health needs of slum communities. Lockdowns for pandemic control have health, social and economic consequences. We consider access to healthcare before and during COVID-19 with those working and living in slum communities. METHODS: In seven slums in Bangladesh, Kenya, Nigeria and Pakistan, we explored stakeholder perspectives and experiences of healthcare access for non-COVID-19 conditions in two periods: pre-COVID-19 and during COVID-19 lockdowns. RESULTS: Between March 2018 and May 2020, we engaged with 860 community leaders, residents, health workers and local authority representatives. Perceived common illnesses in all sites included respiratory, gastric, waterborne and mosquitoborne illnesses and hypertension. Pre-COVID, stakeholders described various preventive, diagnostic and treatment services, including well-used antenatal and immunisation programmes and some screening for hypertension, tuberculosis, HIV and vectorborne disease. In all sites, pharmacists and patent medicine vendors were key providers of treatment and advice for minor illnesses. Mental health services and those addressing gender-based violence were perceived to be limited or unavailable. With COVID-19, a reduction in access to healthcare services was reported in all sites, including preventive services. Cost of healthcare increased while household income reduced. Residents had difficulty reaching healthcare facilities. Fear of being diagnosed with COVID-19 discouraged healthcare seeking. Alleviators included provision of healthcare by phone, pharmacists/drug vendors extending credit and residents receiving philanthropic or government support; these were inconsistent and inadequate. CONCLUSION: Slum residents' ability to seek healthcare for non-COVID-19 conditions has been reduced during lockdowns. To encourage healthcare seeking, clear communication is needed about what is available and whether infection control is in place. Policymakers need to ensure that costs do not escalate and unfairly disadvantage slum communities. Remote consulting to reduce face-to-face contact and provision of mental health and gender-based violence services should be considered.

Natural quorum sensing inhibitors effectively downregulate gene expression of Pseudomonas aeruginosa virulence factors.

At present, anti-virulence drugs are being considered as potential therapeutic alternatives and/or adjuvants to currently failing antibiotics. These drugs do not kill bacteria but inhibit virulence factors essential for establishing infection and pathogenesis through targeting non-essential metabolic pathways reducing the selective pressure to develop resistance. We investigated the effect of naturally isolated plant compounds on the repression of the quorum sensing (QS) system which is linked to virulence/pathogenicity in Pseudomonas aeruginosa. Our results show that trans-cinnamaldehyde (CA) and salicylic acid (SA) significantly inhibit expression of QS regulatory and virulence genes in P. aeruginosa PAO1 at sub-inhibitory levels without any bactericidal effect. CA effectively downregulated both the las and rhl QS systems with lasI and lasR levels inhibited by 13- and 7-fold respectively compared to 3- and 2-fold reductions with SA treatment, during the stationary growth phase. The QS inhibitors (QSI) also reduced the production of extracellular virulence factors with CA reducing protease, elastase and pyocyanin by 65%, 22% and 32%, respectively. The QSIs significantly reduced biofilm formation and concomitantly with repressed rhamnolipid gene expression, only trace amount of extracellular rhamnolipids were detected. The QSIs did not completely inhibit virulence factor expression and production but their administration significantly lowered the virulence phenotypes at both the transcriptional and extracellular levels. This study shows the significant inhibitory effect of natural plant-derived compounds on the repression of QS systems in P. aeruginosa.

A discontinuous autoinhibitory module masks the A1 domain of von Willebrand factor.

Essentials The mechanism for the auto-inhibition of von Willebrand factor (VWF) remains unclear. Hydrogen exchange of two VWF A1 fragments with disparate activities was measured and compared. Discontinuous residues flanking A1 form a structural module that blocks A1 binding to the platelet. Our results suggest a potentially unified model of VWF activation. Click to hear an ISTH Academy presentation on the domain architecture of VWF and activation by elongational flow by Dr Springer SUMMARY: Background How von Willebrand factor (VWF) senses and responds to shear flow remains unclear. In the absence of shear flow, VWF or its fragments can be induced to bind spontaneously to platelet GPIbα. Objectives To elucidate the auto-inhibition mechanism of VWF. Methods Hydrogen-deuterium exchange (HDX) of two recombinant VWF fragments expressed from baby hamster kidney cells were measured and compared. Results The shortA1 protein contains VWF residues 1261-1472 and binds GPIbα with a significantly higher affinity than the longA1 protein that contains VWF residues 1238-1472. Both proteins contain the VWF A1 domain (residues 1272-1458). Many residues in longA1, particularly those in the N- and C-terminal sequences flanking the A1 domain, and in helix α1, loops α1ß2 and ß3α2, demonstrated markedly reduced HDX compared with their counterparts in shortA1. The HDX-protected region in longA1 overlaps with the GPIbα-binding interface and is clustered with type 2B von Willebrand disease (VWD) mutations. Additional comparison with the HDX of denatured longA1 and ristocetin-bound longA1 indicates the N- and C-terminal sequences flanking the A1 domain form cooperatively an integrated autoinhibitory module (AIM) that interacts with the HDX-protected region. Binding of ristocetin to the C-terminal part of the AIM desorbs the AIM from A1 and enables longA1 binding to GPIbα. Conclusion The discontinuous AIM binds the A1 domain and prevents it from binding to GPIbα, which has significant implications for the pathogenesis of type 2B VWD and the shear-induced activation of VWF activity.

Dimerization of glycoprotein Ibα is not sufficient to induce platelet clearance.

UNLABELLED: ESSENTIALS: Many anti-glycoprotein (GP)Ibα antibodies induce platelet clearance in a dimer-dependent manner. Characterization of monoclonal antibodies that bind the mechanosensitive domain (MSD) of GPIbα. An anti-MSD antibody binds two copies of GPIbα in platelets but does not induce platelet clearance. The prevailing clustering model of GPIbα signaling is incorrect or needs revision. BACKGROUND: The mechanism of platelet clearance is not clear. Many antibodies binding the membrane-distal ligand-binding domain of glycoprotein (GP)Ibα induce rapid clearance of platelets and acute thrombocytopenia, which requires the bifurcated antibody structure. It was thought that binding of these antibodies induced lateral dimerization or clustering of GPIbα in the plasma membrane, which leads to downstream signaling and platelet clearance. However, many antibodies targeting GPIbß and GPIX, which are associated with GPIbα in the GPIb-IX complex, do not induce platelet clearance, which is in contradiction to the clustering model. OBJECTIVES: To test whether dimerization or clustering of GPIbα is sufficient to transmit the signal that leads to platelet clearance. METHODS: We have recently raised several mAbs targeting the mechanosensitive domain (MSD) of GPIbα. Binding of these anti-MSD antibodies was characterized with biochemical methods. Their ability to stimulate platelets and induce platelet clearance in mice was assessed. RESULTS AND CONCLUSION: Infusion of anti-MSD antibodies does not cause thrombocytopenia in mice. These antibodies show no detectable effects on platelet activation and aggregation in vitro. Further biochemical investigation showed that the anti-MSD antibody 3D1 binds two copies of GPIbα on the platelet surface. Therefore, lateral dimerization of GPIbα induced by antibody binding is not sufficient to initiate GPIb-IX signaling and induce platelet clearance. Our results suggest that a factor other than or in addition to clustering of GPIbα is required to induce platelet clearance.

Intestinal obstruction by an unusual foreign body.

The case is described of a patient with complete small bowel obstruction 13 days after swallowing a condom containing hashish. Treatment by enzymatic dissolution was obviously impossible. The small bowel was emptied preoperatively by a Dennis long-tube, and the impacted bolus was removed by enterotomy.

The continuity of right and left ventricular myocardial sinusoidal spaces and its relation to right ventricular implants.

Evidence is presented which indicates that blood leaving side branches of an internal mammary artery implanted into the anterior wall of the right ventricle flows from the tunnel in which it lies through myocardial sinusoidal spaces of the anterior right ventricular wall across the midline to fill corresponding spaces in the anterior wall of the left ventricle and thence is carried to the left coronary sinus. The myocardial sinusoidal spaces of right and left ventricles have been well outlined, using injections of polyvinyl acetate and the technique of digestion casts. We have been able to show that there is no barrier between the myocardial sinusoids of the right circulation and those related to the anterior descending branch of the left coronary artery. In structure, these myocardial sinusoidal spaces are quite different from the intramyocardial coronary arteriolar zones which, in 93% of human hearts, are separated from one another without collateral communication.The continuity of the right and left ventricular myocardial sinusoids explains why implantation of a right internal mammary artery into the anterior wall of the right ventricle combined with a corresponding left implant, epicardiectomy and free omental graft, has been so effective in our hands in the treatment of far-advanced human coronary artery insufficiency.