COVID-19 mortality among Massachusetts workers and the association with telework ability, 2020.

BACKGROUND: Working outside the home put some workers at risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure and might partly explain elevated coronavirus disease 2019 (COVID-19) mortality rates in the first months of the pandemic in certain groups of Massachusetts workers. To further investigate this premise, we examined COVID-19 mortality among Massachusetts workers, with a specific focus on telework ability based on occupation. METHODS: COVID-19-associated deaths between January 1 and December 31, 2020 among Massachusetts residents aged 18-64 years were analyzed. Deaths were categorized into occupation-based quadrants (Q) of telework ability. Age-adjusted rates were calculated by key demographics, industry, occupation, and telework quadrant using American Community Survey workforce estimates as denominators. Rate ratios (RRs) and 95% confidence intervals comparing rates for quadrants with workers unlikely able to telework (Q2, Q3, Q4) to that among those likely able to telework (Q1) were calculated. RESULTS: The overall age-adjusted COVID-19-associated mortality rate was 26.4 deaths per 100,000 workers. Workers who were male, Black non-Hispanic, Hispanic, born outside the US, and with lower than a high school education level experienced the highest rates among their respective demographic groups. The rate varied by industry, occupation and telework quadrant. RRs comparing Q2, Q3, and Q4 to Q1 were 0.99 (95% confidence interval [CI]: 0.8-1.2), 3.2 (95% CI: 2.6-3.8) and 2.5 (95% CI: 2.0-3.0), respectively. CONCLUSION: Findings suggest a positive association between working on-site and COVID-19-associated mortality. Work-related factors likely contributed to COVID-19 among Massachusetts workers and should be considered in future studies of COVID-19 and similar diseases.

Fatal Occupational Asthma in Cannabis Production - Massachusetts, 2022.

Multiple respiratory hazards have been identified in the cannabis cultivation and production industry, in which occupational asthma and work-related exacerbation of preexisting asthma have been reported. An employee working in a Massachusetts cannabis cultivation and processing facility experienced progressively worsening work-associated respiratory symptoms, which culminated in a fatal asthma attack in January 2022. This report represents findings of an Occupational Safety and Health Administration inspection, which included a worksite exposure assessment, coworker and next-of-kin interviews, medical record reviews, and collaboration with the Massachusetts Department of Public Health. Respiratory tract or skin symptoms were reported by four of 10 coworkers with similar job duties. Prevention is best achieved through a multifaceted approach, including controlling asthmagen exposures, such as cannabis dust, providing worker training, and conducting medical monitoring for occupational allergy. Evaluation of workers with new-onset or worsening asthma is essential, along with prompt diagnosis and medical management, which might include cessation of work and workers' compensation when relation to work exposures is identified. It is important to recognize that work in cannabis production is potentially causative.

Opioid-related overdose deaths by industry and occupation-Massachusetts, 2011-2015.

BACKGROUND: Thousands of people in the United States continue to die from opioid overdoses every year. Work-related injuries and other factors associated with work may increase exposure to opioids and, subsequently, opioid-related overdose deaths (OROD). This study sought to determine whether OROD rates differed by industry and occupation and explored work-related factors that might contribute to these differences. METHODS: We coded industry and occupation information on death certificates for all OROD among Massachusetts residents from 2011 to 2015. We estimated rates of OROD by industry and occupation using Massachusetts employment data. National survey data were used to explore whether work-related factors known to vary by occupation (occupational injury and illness, job insecurity, and paid sick leave) correlate to observed differences in OROD. RESULTS: Several industries and occupation groups had rates of OROD that were significantly higher than the rates for other workers. Construction workers and fishing workers stood out for having OROD rates many times higher than the average for all workers. Occupation groups with high rates of occupational injuries and illnesses, high job insecurity, and low availability of paid sick leave had higher rates of OROD. CONCLUSIONS: These findings underscore the need for policy and educational interventions to reduce OROD tailored to the needs of high rate worker populations. Interventions should address workplace hazards that cause injuries for which opioids are prescribed, as well as best practices in medical management and return to work following injury, safer prescribing, enhanced access to treatment for opioid use disorders, and overdose prevention education.

Application of topical negative pressure (vacuum-assisted closure) to split-thickness skin grafts: a structured evidence-based review.

INTRODUCTION: Significant controversy surrounds the effectiveness of negative pressure wound therapy although it has been in use for decades. Although many clinicians favor this modality in relation to its practicality, ease of use especially in complex wounds, it has faced the same challenges as other dressings in relation to evidence base of efficacy in relation to a number of outcome measures. In view of the current financial pressures on health care systems worldwide, this structured review systematically challenges the evidence for perioperative application of topical negative pressure (TNP) to split-thickness skin grafts (STSGs) through evidence-based critical appraisal, and extrapolate the mechanisms of action on the mechanisms through which TNP may aid wound healing. Weighted evidence-based recommendations regarding the impact of TNP on split skin graft quality and quantity of take as outcomes. METHODS: Phase 1: Structured literature search. Phase 2: Retrieved articles were critically appraised for rigor and methodological validity by 3 independent authors, then stratified according to a validated "levels of evidence" framework. Graded "current best evidence" recommendations could therefore be proposed. RESULTS: Of the 220 studies retrieved in the initial search, 38 studies satisfied our quality of evidence criteria. Current best evidence supports 2 complementary trends explaining the mechanisms whereby STSG benefits from TNP. Active stimulation of epithelial mitosis: TNP creates mechanical stretch which stimulates multiple signaling pathways up-regulating growth- and mitosis-associated epithelial transcription factors. Topical negative pressure also promotes microcirculatory flow (graft and wound edge), stimulates angiogenesis and basement membrane integrity (grade C). Prevention of complications: significant reduction of graft lift-off by edema, exudates, subgraft hematoma, and reduction of shear when compared to traditional dressings (grade B). Topical negative pressure promotes significant qualitative improvement in the final STSG result studies (level 1B). The role of TNP in prevention of infection is, however, equivocal and further research is required. No evidence of harm from TNP application was reported. CONCLUSIONS: Topical negative pressure increases quantity and quality of split skin graft take compared to traditional bolster dressings. The advantages are increased in irregularly contoured, technically difficult wounds and suboptimal recipient wound beds where it seems to be the best modality currently available. Large-scale randomized clinical controlled trials remain scanty in all areas of wound dressing research including negative pressure therapy.

Suicides in Massachusetts by Industry and Occupation, 2016-2019.

OBJECTIVE: To examine suicide deaths among working-age residents in Massachusetts and to determine industries and occupations with high numbers and rates of suicides. METHODS: The Massachusetts Violent Death Reporting System and Massachusetts death certificates were used to analyze suicide deaths from 2016 to 2019. Counts and rates were generated by demographics and industry and occupation groupings. RESULTS: There were 2199 working-age Massachusetts residents who died by suicide. Higher suicide rates were associated with being male, 65 years or older, White, and non-Hispanic or having military background. Suicide rates were higher among the construction industry sector and the construction and extraction occupational group compared with the average rate for all Massachusetts workers. CONCLUSIONS: Suicide rates differed between industries and occupations, suggesting that work-related factors may play a role and should be considered when planning outreach initiatives and interventions.

Identification of CaMKII phosphorylation sites in Connexin43 by high-resolution mass spectrometry.

Connexin43 (Cx43) is a major cardiac gap junction channel protein required for normal electrical and contractile activity. Gap junction channel assembly, function, and turnover are regulated by phosphorylation under both normal and disease conditions. The carboxyl terminus (CT) of Cx43 contains numerous amino acid residues that are phosphorylated by protein kinases. However, our knowledge of the specific residues and kinases involved is incomplete. The objective of this study was to identify amino acid residues in the Cx43-CT that are targets of the multifunctional protein kinase, Ca(2+)/calmodulin protein kinase II (CaMKII), an enzyme known to play critical roles in Ca(2+) homeostasis, transcription, apoptosis, and ischemic heart disease. We subjected fusion protein containing the Cx43-CT to phosphorylation by CaMKII in vitro, digestion with Lys-C and trypsin followed by enrichment for phosphorylated peptides using TiO(2), and analysis in an LTQ XL Orbitrap with collision-induced dissociation and electron transfer dissociation. We deduced the sites of modification by interpreting tandem spectra from these "orthogonal" methods of gas phase peptide fragmentation. We have identified 15 serine residues, including one novel site, in the Cx43-CT that are phosphorylated by CaMKII, the activity of which may be important in regulating Cx43 in normal and diseased hearts.

Media Reports as a Tool for Timely Monitoring of COVID-19-Related Deaths Among First Responders-United States, April 2020.

We aimed to describe coronavirus disease 2019 (COVID-19) deaths among first responders early in the COVID-19 pandemic. We used media reports to gather timely information about COVID-19-related deaths among first responders during March 30-April 30, 2020, and evaluated the sensitivity of media scanning compared with traditional surveillance. We abstracted information about demographic characteristics, occupation, underlying conditions, and exposure source. Twelve of 19 US public health jurisdictions with data on reported deaths provided verification, and 7 jurisdictions reported whether additional deaths had occurred; we calculated the sensitivity of media scanning among these 7 jurisdictions. We identified 97 COVID-19-related first-responder deaths during the study period through media and jurisdiction reports. Participating jurisdictions reported 5 deaths not reported by the media. Sixty-six decedents worked in law enforcement, and 31 decedents worked in fire/emergency medical services. Media reports rarely noted underlying conditions. The media scan sensitivity was 88% (95% CI, 73%-96%) in the subset of 7 jurisdictions. Media reports demonstrated high sensitivity in documenting COVID-19-related deaths among first responders; however, information on risk factors was scarce. Routine collection of data on industry and occupation could improve understanding of COVID-19 morbidity and mortality among all workers.

Diminished zonula occludens-1 expression in the failing human heart.

BACKGROUND: Reduced expression of the major gap junction protein connexin 43 (Cx43) in the failing human heart may lead to arrhythmias and sudden cardiac death. Cx43 interacts with the actin binding protein, zonula occludens-1 (ZO-1), and it has recently been demonstrated that ZO-1 regulates the formation and function of Cx43 gap junctions. We hypothesize that normal expression of ZO-1 and its interaction with Cx43 are required for appropriate assembly and function of Cx43 gap junctions in the heart. Here, we determined whether expression of ZO-1 is altered in patients with heart failure. METHODS: We examined ventricular myocardium from hearts of patients in end-stage heart failure, obtained at transplant, for ZO-1 expression by immunohistochemistry. We also subjected lysates made from this tissue to immunoblotting to determine the level of ZO-1 expression. RESULTS AND CONCLUSIONS: ZO-1 was found at 96% of the intercalated discs in nonfailing control human hearts, where it colocalized with Cx43. In contrast, there was ZO-1 immunostaining at 5% of intercalated discs in failing hearts, coincident with a reduction in Cx43 staining in intercalated discs. Immunoblotting analysis showed that there was a 95% reduction in ZO-1 expression in human heart failure. Loss of ZO-1 at intercalated discs in heart failure may play a critical role in remodeling of Cx43 gap junctions, which may contribute to abnormal impulse propagation and arrhythmogenesis, thereby predisposing patients in heart failure to sudden cardiac death.

Evaluation of a faecal calprotectin care pathway for use in primary care.

BACKGROUND: National Institute for Health and Care Excellence have recommended faecal calprotectin (FC) testing as an option in adults with lower gastrointestinal symptoms for whom specialist investigations are being considered, if cancer is not suspected and it is used to support a diagnosis of inflammatory bowel disease (IBD) or irritable bowel syndrome. York Hospital and Vale of York Clinical Commissioning Group have developed an evidence-based care pathway to support this recommendation for use in primary care. It incorporates a higher FC cut-off value, a 'traffic light' system for risk and a clinical management pathway. OBJECTIVES: To evaluate this care pathway. METHODS: The care pathway was introduced into five primary care practices for a period of six months and the clinical outcomes of patients were evaluated. Negative and positive predictive values (NPV and PPV) were calculated. GP feedback of the care pathway was obtained by means of a web-based survey. Comparator gastroenterology activity in a neighbouring trust was obtained. RESULTS: The care pathway for FC in primary care had a 97% NPV and a 40% PPV. This was better than GP clinical judgement alone and doubled the PPV compared with the standard FC cut-off (250 mcg/g and were diagnosed by 'straight to test' colonoscopy within three weeks. The care pathway was considered helpful by GPs and delivered a higher diagnostic yield after secondary care referral (21%) than the conventional comparator pathway (5%). CONCLUSIONS: A care pathway for the use of FC that incorporates a higher cut-off value, a 'traffic light' system for risk and supports clinical decision making can be achieved safely and effectively. It maintains the balance between a high NPV and an acceptable PPV. A modified care pathway for the use of FC in primary care is proposed.

Pathways for degradation of connexins and gap junctions.

Gap junctional proteins, connexins, and gap junctional plaques are short-lived. Three pathways for their degradation have been proposed: (1) misfolded/abnormally oligomerized connexins are retrogradely translocated and degraded by the proteasome through endoplasmic reticulum-associated degradation; (2) connexins (as monomers or oligomers) may traffic directly from an early secretory compartment to the lysosome for degradation without reaching the plasma membrane; (3) connexins within gap junction plaques are degraded by the lysosome after endocytotic internalization. Degradation of gap junction plaques is proteasome-dependent in some cell types. Degradation may be regulated by ubiquitinylation, phosphorylation, or polypeptide domains that act as sorting signals.

Redistribution of connexin45 in gap junctions of connexin43-deficient hearts.

OBJECTIVE: Adult ventricular myocytes express two gap junction channel proteins: connexin43 (Cx43) and connexin45 (Cx45). Cx43-deficient mice exhibit slow ventricular epicardial conduction, suggesting that Cx43 plays an important role in intercellular coupling in the ventricle. Cx45 is much less abundant than Cx43 in working ventricular myocytes. Its role in ventricular conduction has not been defined, nor is it known whether expression or distribution of Cx45 is altered in Cx43-deficient mice. The present study was undertaken to determine (1) whether expression of Cx45 is upregulated and (2) whether gap junction structure and distribution are altered in Cx43-deficient mice. METHODS: Ventricular tissue from neonatal Cx43(+/+), Cx43(+/-) and Cx43(-/-) and adult Cx43(+/+) and Cx43(+/-) mice was analyzed by immunoblotting and confocal immunofluorescence microscopy. RESULTS: Total Cx45 protein abundance measured by immunoblotting was not different in Cx43-deficient or null hearts compared to wild-type control hearts. However, the amount and distribution of Cx45 immunoreactive signal measured by quantitative confocal analysis were markedly reduced in both Cx43(+/-) and Cx43(-/-) hearts. CONCLUSION: Although the total content of Cx45 is not upregulated in Cx43-deficient hearts, the localization of Cx45 to cardiac gap junctions depends on the expression level of Cx43 and is dramatically altered in mice that express no Cx43.

Barriers to use of workers' compensation for patient care at Massachusetts community health centers.

OBJECTIVES: To examine barriers community health centers (CHCs) face in using workers' compensation insurance (WC). DATA SOURCES/STUDY SETTING: Leadership of CHCs in Massachusetts. STUDY DESIGN: We used purposeful snowball sampling of CHC leaders for in-depth exploration of reimbursement policies and practices, experiences with WC, and decisions about using WC. We quantified the prevalence of perceived barriers to using WC through a mail survey of all CHCs in Massachusetts. DATA COLLECTION/EXTRACTION METHODS: Emergent coding was used to elaborate themes and processes related to use of WC. Numbers and percentages of survey responses were calculated. PRINCIPAL FINDINGS: Few CHCs formally discourage use of WC, but underutilization emerged as a major issue: "We see an awful lot of work-related injury, and I would say that most of it doesn't go through workers' comp." Barriers include lack of familiarity with WC, uncertainty about work-relatedness, and reliance on patients to identify work-relatedness of their conditions. Reimbursement delays and denials lead patients and CHCs to absorb costs of services. CONCLUSION: Follow-up studies should fully characterize barriers to CHC use of WC and experiences in other states to guide system changes in CHCs and WC agencies. Education should target CHC staff and workers about WC.

Mercury (Hg) emissions from domestic biomass combustion for space heating.

Three mercury (Hg) species (gaseous elemental mercury (GEM), gaseous oxidized mercury (GOM), and fine particulate-bound mercury (PBM(2.5))) were measured in the stack of a small scale wood combustion chamber at 400°C, in the stack of an advanced wood boiler, and in two areas influenced by wood combustion. The low temperature process (lab-scale) emitted mostly GEM (∼99% when burning wood pellets and ∼95% when burning unprocessed wood). The high temperature wood boiler emitted a greater proportion of oxidized Hg (approximately 65%) than the low temperature system. In field measurements, mean PBM(2.5) concentrations at the rural and urban sites in winter were statistically significantly higher than in warmer seasons and were well correlated with Delta-C concentrations, a wood combustion indictor measured by an aethalometer (UV-absorbable carbon minus black carbon). Overall the results suggest that wood combustion may be an important source of oxidized mercury (mostly in the particulate phase) in northern climates in winter.

Residual Cx45 and its relationship to Cx43 in murine ventricular myocardium.

Gap junction channels in ventricular myocardium are required for electrical and metabolic coupling between cardiac myocytes and for normal cardiac pump function. Although much is known about expression patterns and remodeling of cardiac connexin(Cx)43, little is known about the less abundant Cx45, which is required for embryonic development and viability, is downregulated in adult hearts, and is pathophysiologically upregulated in human end-stage heart failure. We applied quantitative immunoblotting and immunoprecipitation to native myocardial extracts, immunogold electron microscopy to cardiac tissue and membrane sections, electrophysiological recordings to whole hearts, and high-resolution tandem mass spectrometry to Cx45 fusion protein, and developed two new tools, anti-Cx45 antisera and Cre(+);Cx45 floxed mice, to facilitate characterization of Cx45 in adult mammalian hearts. We found that Cx45 represents 0.3% of total Cx protein (predominantly 200 fmol Cx43 protein/µg ventricular protein) and colocalizes with Cx43 in native ventricular gap junctions, particularly in the apex and septum. Cre(+);Cx45 floxed mice express 85% less Cx45, but do not exhibit overt electrophysiologic abnormalities. Although the basal phosphorylation status of native Cx45 remains unknown, CaMKII phosphorylates 8 Ser/Thr residues in Cx45 in vitro. Thus, although downregulation of Cx45 does not produce notable deficits in electrical conduction in adult, disease-free hearts, Cx45 is a target of the multifunctional kinase CaMKII, and the phosphorylation status of Cx45 and the role of Cx43/Cx45 heteromeric gap junction channels in both normal and diseased hearts merits further investigation.

Connexin43 expression levels influence intercellular coupling and cell proliferation of native murine cardiac fibroblasts.

Little is known about connexin expression and function in murine cardiac fibroblasts. The authors isolated native ventricular fibroblasts from adult mice and determined that although they expressed both connexin43 (Cx43) and connexin45 (Cx45), the relative abundance of Cx45 was greater than that of Cx43 in fibroblasts compared to myocytes, and the electrophoretic mobility of both Cx43 and Cx45 differed in fibroblasts and in myocytes. Increasing Cx43 expression by adenoviral infection increased intercellular coupling, whereas decreasing Cx43 expression by genetic ablation decreased coupling. Interestingly, increasing Cx43 expression reduced fibroblast proliferation, whereas decreasing Cx43 expression increased proliferation. These data demonstrate that native fibroblasts isolated from the mouse heart exhibit intercellular coupling via gap junctions containing both Cx43 and Cx45. Fibroblast proliferation is inversely related to the expression level of Cx43. Thus, connexin expression and remodeling is likely to alter fibroblast function, maintenance of the extracellular matrix, and ventricular remodeling in both normal and diseased hearts.

ZO-1 alters the plasma membrane localization and function of Cx43 in osteoblastic cells.

ZO-1 is the major connexin-interacting protein in ROS 17/2.8 (ROS) osteoblastic cells. We examined the role of ZO-1 in Cx43-mediated gap junction formation and function in ROS cells that expressed the connexin-interacting fragment of ZO-1 (ROS/ZO-1dn) cells. Expression of this ZO-1(7-444) fusion protein in ROS cells disrupted the Cx43/ZO-1 interaction and decreased dye transfer by 85%, although Cx43 was retained on the plasma membrane as assessed by surface biotinylation. Fractionation of lysates derived from ROS/ZO-1dn cells on a 5-30% sucrose flotation gradient showed that 40% of the Cx43 floated into these sucrose gradients, whereas none of the Cx43 in ROS cell lysates entered the gradients, suggesting that more Cx43 is associated with lipid rafts in the transfected ROS cells than in lysates derived from untransfected ROS cells. In contrast to the ROS/ZO-1dn cells, ROS cells that over-expressed ZO-1 protein (ROS/ZO-1myc cells) exhibited increased gap junctional permeability and appositional membrane staining for Cx43. These data demonstrate that ZO-1 regulates Cx43-mediated gap junctional communication in osteoblastic cells and alters the membrane localization of Cx43. They suggest that ZO-1-mediated delivery of Cx43 from a lipid raft domain to gap junctional plaques may be an important regulatory step in gap junction formation.