A Delphi Panel Study for Public Education about Vascularized Composite Allograft Donation in the United States.

Introduction: Improving public awareness about the opportunity to become a vascularized composite allograft (VCA) donor is crucial to increasing access to organs. Prior research identified a need for comprehensive and comprehensible public education materials. A 2-round Delphi panel was conducted to garner US expert consensus on the topics and language to include in public education materials via an organ procurement organization-hosted website. Methods: The round 1 survey assessed the importance of educational topics and statements (n = 19) using 5-point Likert scales. The round 2 survey asked experts to rate new and repeated educational topics (n = 27). Open-ended comment boxes elicited experts' feedback and language revisions for educational statements. Responses were analyzed using descriptive statistics and rapid qualitative analysis. Findings: Eighteen experts responded to the round 1 survey and 15 to round 2. After round 2, 20 topics had mean (M) importance greater than neutral (M > 3.00) and were retained in the educational materials. The 5 most important topics by mean Likert ratings were: consent process for donation (M = 4.73), potential recipients (M = 4.73), most common vascularized composite organs transplanted (M = 4.47), purpose (M = 4.47), and definition (M = 4.47). Seven themes emerged from experts' open-ended comments about the importance and language of educational statements. Conclusions: Delphi panel findings identified expert-endorsed topics and educational statements for public education about vascularized composite organ donation via an educational website. Future research should assess the website's impact on public knowledge of VCA donation.

The Relative Burden of Occupational Injuries and Illnesses in Firefighters: An Analysis of Washington Workers' Compensation Claims, 2006-2020.

Firefighters face many hazards on the job and have a high rate of work-related injuries and illnesses (WRII). We analyzed Washington workers' compensation claims from 2006-2020 to characterize WRII in firefighters compared to law enforcement officers and "all other" workers. There were 9187 compensable claims for firefighters, 7801 for law enforcement officers, and 586,939 for "all other" workers. Nearly 40% of claims for firefighters were work-related musculoskeletal disorders (WMSDs). The claim rate per 10,000 full-time equivalent (FTE) firefighters was 716.4, which is significantly higher than that of law enforcement officers (510.0) and "all other" workers (163.2). The rate per 10,000 FTE of WMSD claims was also higher in firefighters (277.0) than in law enforcement officers (76.2) and "all other" workers (57.6). Additional WRII among firefighters commonly included being struck or caught in objects, slipping or tripping, and exposure to caustic or noxious substances; and amongst law enforcement, transportation accidents and violence. Medical costs and time-loss days per claim were lower for firefighters and law enforcement than for "all other" workers. Common tasks associated with WMSDs in firefighters included lifting and transporting patients, using specific tools and equipment, and physical training. WMSDs stand out as an area for prevention and intervention activities.

Hypoxia Promotes Atrial Tachyarrhythmias via Opening of ATP-Sensitive Potassium Channels.

BACKGROUND: Hypoxia-ischemia predisposes to atrial arrhythmia. Atrial ATP-sensitive potassium channel (KATP) modulation during hypoxia has not been explored. We investigated the effects of hypoxia on atrial electrophysiology in mice with global deletion of KATP pore-forming subunits. METHODS: Whole heart KATP RNA expression was probed. Whole-cell KATP current and action potentials were recorded in isolated wild-type (WT), Kir6.1 global knockout (6.1-gKO), and Kir6.2 global knockout (6.2-gKO) murine atrial myocytes. Langendorff-perfused hearts were assessed for atrial effective refractory period (ERP), conduction velocity, wavefront path length (WFPL), and arrhymogenicity under normoxia/hypoxia using a microelectrode array and programmed electrical stimulation. Heart histology was assessed. RESULTS: Expression patterns were essentially identical for all KATP subunit RNA across human heart, whereas in mouse, Kir6.1 and SUR2 (sulphonylurea receptor subunit) were higher in ventricle than atrium, and Kir6.2 and SUR1 were higher in atrium. Compared with WT, 6.2-gKO atrial myocytes had reduced tolbutamide-sensitive current and action potentials were more depolarized with slower upstroke and reduced peak amplitude. Action potential duration was prolonged in 6.1-gKO atrial myocytes, absent of changes in other ion channel gene expression or atrial myocyte hypertrophy. In Langendorff-perfused hearts, baseline atrial ERP was prolonged and conduction velocity reduced in both KATP knockout mice compared with WT, without histological fibrosis. Compared with baseline, hypoxia led to conduction velocity slowing, stable ERP, and WFPL shortening in WT and 6.1-gKO hearts, whereas WFPL was stable in 6.2-gKO hearts due to ERP prolongation with conduction velocity slowing. Tolbutamide reversed hypoxia-induced WFPL shortening in WT and 6.1-gKO hearts through ERP prolongation. Atrial tachyarrhythmias inducible with programmed electrical stimulation during hypoxia in WT and 6.1-gKO mice correlated with WFPL shortening. Spontaneous arrhythmia was not seen. CONCLUSIONS: KATP block/absence leads to cellular and tissue level atrial electrophysiological modification. Kir6.2 global knockout prevents hypoxia-induced atrial WFPL shortening and atrial arrhythmogenicity to programmed electrical stimulation. This mechanism could be explored translationally to treat ischemically driven atrial arrhythmia.

Baseline and Dynamic Changes in Hemoglobin Levels Predict Treatment Response and Prognosis in Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Study.

INTRODUCTION: Clinical markers of response in metastatic renal cell carcinoma (mRCC) are lacking. Low hemoglobin (Hb) is associated with poor outcomes in the IMDC risk score. This study evaluates the role of Hb as a marker of treatment outcomes in mRCC. PATIENTS AND METHODS: This multicenter retrospective study evaluated 276 patients with mRCC treated with frontline immune checkpoint inhibitor (ICI) therapy, ICI and vascular endothelial growth factor (VEGF) inhibitor (VEGFI) combinations (ICI/VEGFI), or VEGFI monotherapy between 2014 and 2021. Hb levels at baseline, week 6 and 12 and at disease progression or death were recorded. Patients were categorized as responders (CR+PR) or nonresponders (SD+PD) using cross-sectional imaging at week 12. The association between baseline and dynamic changes in Hb and oncological outcomes was assessed. RESULTS: Thirty-seven percent, 40% and 22% of patients received ICIs, ICI/VEGFI and VEGFI respectively. In patients receiving ICIs, there was a significant increase in Hb amongst responders from baseline to week 12 (P= .02). Amongst patients receiving ICI/VEGFI, there was an increase in Hb from baseline to week 12 which was greater in responders (P< .001). In patients receiving VEGFI monotherapy, responders had a higher Hb at baseline (P= .01), week 6 (P= .04), and week 12 (P= .003). An increase in Hb was a significant independent predictor of progression-free survival amongst patients receiving ICIs (HR 0.40, 95%CI, 0.19-0.83, P= .009). CONCLUSION: Baseline and dynamic changes in Hb are associated with first-line treatment outcomes in patients with mRCC and represent a pragmatic early serological marker.

Public Perceptions and Information Needs of VCA Transplantation and Donation: A Mixed Methods Study.

Vascularized Composite Allotransplantation (VCA) involves transplantation of multiple tissues from a donor to a recipient (e.g., skin, muscle, bone). Little is known about the US public's perceptions of and attitudes toward VCA organ donation. This multi-site, cross-sectional, mixed methods study involved focus groups and surveys to assess members of the general public's attitudes about VCA, and willingness and barriers to donate VCA organs. Qualitative data were analyzed by thematic analysis; quantitative data were analyzed by descriptive statistics. In focus groups (n = 6, 42 participants), most participants were female (57%) and Black (62%) with mean age of 42.6 years. Three main themes emerged: 1) awareness and perceptions of VCA, 2) purpose of VCA donation, 3) and barriers to VCA donation. Participants had heard little about VCA and sought information about VCA donation. Participants perceived VCA as challenging their concepts of "normality" and voiced concerns that VCA would create "Frankenstein[s]." Barriers to VCA donation included disruptions to end-of-life arrangements and information gaps regarding the donation process. Participants reported moderate to high willingness to donate their hands (69%) and face (50%) Public education efforts should address the specific needs and concerns of the public to facilitate VCA donation and family authorization.

Multispecies Outbreak of Nocardia Infections in Heart Transplant Recipients and Association with Climate Conditions, Australia.

A multispecies outbreak of Nocardia occurred among heart transplant recipients (HTR), but not lung transplant recipients (LTR), in Sydney, New South Wales, Australia, during 2018-2019. We performed a retrospective review of 23 HTR and LTR who had Nocardia spp. infections during June 2015-March 2021, compared risk factors for Nocardia infection, and evaluated climate conditions before, during, and after the period of the 2018-2019 outbreak. Compared with LTR, HTR had a shorter median time from transplant to Nocardia diagnosis, higher prevalence of diabetes, greater use of induction immunosuppression with basiliximab, and increased rates of cellular rejection before Nocardia diagnosis. During the outbreak, Sydney experienced the lowest monthly precipitation and driest surface levels compared with time periods directly before and after the outbreak. Increased immunosuppression of HTR compared with LTR, coupled with extreme weather conditions during 2018-2019, may explain this outbreak of Nocardia infections in HTR.

The job demand-control-support model and work-related musculoskeletal complaints in daytime and nighttime janitors: The mediating effect of burnout.

Janitors' jobs require repetitive work with low control (skill discretion, decision authority) and social support. Previous studies have found this constellation of work conditions leads to high stress levels. This study investigated the relationships among job demand-control-support, burnout, and musculoskeletal symptoms for commercial janitors in Washington State. Structural equation modeling was performed using data from 208 participants with analyses comparing models of daytime and nighttime janitors. Burnout fully mediated the relationship between job demands and musculoskeletal complaints among daytime janitors. Among nighttime janitors, burnout mediated between job demands, job control, and social support, and musculoskeletal complaints. The nighttime janitors' model was more fully supported compared to the daytime model. This study is one of a small number that examine and bring attention to the importance of janitors' burnout. Recommendations to improve the psychosocial work environment toward mitigating burnout and reducing musculoskeletal complaints are provided.

Implementation and modification of an organizational-level intervention: a prospective analysis.

BACKGROUND: Modifications to interventions can jeopardize intervention outcomes. Pre-existing perceived barriers and facilitators to the intervention arising in the implementation preparation phase may help explain why modifications to the intervention may occur during the implementation phase. This two-site comparative case study describes modifications made to a complex organizational-level intervention and examines how known implementation science factors may have enabled such changes to occur. METHODS: Northwestern Medicine'sTM Hispanic Kidney Transplant Program (HKTP) is a culturally competent transplant center-based intervention designed to reduce disparities in living donor kidney transplantation among Hispanics. In-depth qualitative interviews and discussions were longitudinally conducted with transplant stakeholders (i.e., physicians, administrators, clinicians) at two kidney transplant programs with large Hispanic populations during implementation preparation and implementation phases. The Consolidated Framework for Implementation Research (CFIR) guided interview design and qualitative analysis, and Stirman's Framework for Reporting Adaptations and Modifications-Expanded (FRAME) guided modification classification. RESULTS: Across sites, 57 stakeholders participated in an interview, group discussion, and/or learning collaborative discussion. Site-B made more modifications than Site-A (n = 29 versus n = 18). Sites differed in the proportions of delaying/skipping (Site-A 50% versus Site-B 28%) and adding (Site-A 11% versus Site-B 28%) but had comparable substituting (Site-A 17% versus Site-B 17%) and tweaking (Site-A 17% versus Site-B 14%) modification types. Across sites, the transplant team consistently initiated the most modifications (Site-A 66%; Site-B 62%). While individuals initiated slightly more modifications at Site-B (21% versus Site-A 17%), institutions instigated proportionately slightly more modifications at Site-A (17% versus Site-B 10%). CFIR inner setting factors (i.e., structural characteristics, culture, available resources, implementation climate) that prominently emerged during the implementation preparation phase explained similarities and differences in sites' modification numbers, types, and agents in the implementation phase. CONCLUSION: Organizations implementing a culturally competent care intervention made modifications. CFIR inner setting factors emerging in the implementation preparation phase largely explained similarities and differences in study sites' modifications. Identifying factors contributing to modifications may help institutions become better prepared to implement an intervention by addressing known factors in advance, which may foster greater fidelity leading to desired outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03276390 . We registered the study retrospectively on 9-7-17.

Sustainment of a complex culturally competent care intervention for Hispanic living donor kidney transplantation: A longitudinal analysis of adaptations.

Introduction: Sustainment refers to continued intervention delivery over time, while continuing to produce intended outcomes, often with ongoing adaptations, which are purposeful changes to the design or delivery of an intervention to improve its fit or effectiveness. The Hispanic Kidney Transplant Program (HKTP), a complex, culturally competent intervention, was implemented in two transplant programs to reduce disparities in Hispanic/Latinx living donor kidney transplant rates. This study longitudinally examined the influence of adaptations on HKTP sustainment. Methods: Qualitative interviews, learning collaborative calls, and telephone meetings with physicians, administrators, and staff (n = 55) were conducted over three years of implementation to identify HKTP adaptations. The Framework for Reporting Adaptations and Modifications-Expanded was used to classify adaptation types and frequency, which were compared across sites over time. Results: Across sites, more adaptations were made in the first year (n = 47), then fell and plateaued in the two remaining years (n = 35). Adaptations at Site-A were consistent across years (2017: n = 18, 2018: n = 17, 2019: n = 14), while Site-B made considerably fewer adaptations after the first year (2017: n = 29, 2018: n = 18, 2019: n = 21). Both sites proportionally made mostly skipping (32%), adding (20%), tweaking (20%), and substituting (16%) adaptation types. Skipping- and substituting-type adaptations were made due to institutional structural characteristics and lack of available resources, respectively. However, Site-A's greater proportion of skipping-type adaptations was attributed to greater system complexity, and Site-B's greater proportion of adding-type adaptation was attributed to the egalitarian team-based culture. Conclusion: Our findings can help prepare implementers to expect certain context-specific adaptations and preemptively avoid those that hinder sustainment.

Work-related injury burden, workers' compensation claim filing, and barriers: Results from a statewide survey of janitors.

BACKGROUND: Janitors are a low-wage, ethnically and linguistically diverse, hard-to-reach population of workers with a high burden of occupational injury and illness. METHODS: Data from an extensive multimodal (mail, phone, web) survey of janitors in Washington State were analyzed to characterize their working conditions and occupational health experiences. The survey included questions on demographics, work organization and tasks, health and safety topics, and discrimination and harassment. The survey was administered in eight languages. RESULTS: There were 620 complete interviews. The majority completed the survey by mail (62.6%), and in English (85.8%). More than half of responding janitors were female (56.9%), and the mean age was 45 years. Twenty percent reported having a (health-care-provider diagnosed) work-related injury or illness (WRII) in the past twelve months. Women and janitors who were Latino had significantly higher relative risk of WRII. Increased risk was also associated with several work organization factors that may indicate poor working conditions, insufficient sleep, and possible depression. Half of injured janitors did not file workers' compensation (WC) claims. CONCLUSIONS: Janitors reported a high percentage of WRII, which exceeded previously published estimates from Washington State. Women and Latino janitors had significantly increased risk of WRII, and janitors' working conditions may influence the unequal distribution of risk. WRII surveillance via WC or medical care usage in janitors and other low-wage occupations may reflect substantial underreporting. Characterizing the nature of janitors' work experience can help identify avenues for prevention, intervention, and policy changes to protect the health and safety of janitors.

An Investigation into the Influence of Different Types of Nesting Materials upon the Welfare of Captive Chimpanzees (Pan troglodytes).

Ensuring the welfare of captive chimpanzees (Pan troglodytes) is crucial, in part because they can act as a conservation resource in the case of wild populations becoming extinct. One strategy often adopted to ensure animal welfare is environmental enrichment. In this study, we investigated the impact of different nesting materials (leaves and branches, long grass, cotton sheets, and shredded newspaper) upon the welfare of chimpanzees housed at Tacugama Chimpanzee Sanctuary (Sierra Leone). Data was collected on 20 subjects (aged 4 to 15 years) between November 2019 and March 2020. Welfare was based on individuals' relative frequency of affiliative, abnormal and agonistic behaviours, as well as their social and behavioural competence. We found that individuals' welfare was higher when presented with nesting materials (compared to the control and post-treatment conditions), particularly when given shredded newspaper, regardless of whether the material was presented separately or in conjunction with another. In addition, welfare was highest: during the morning (vs evening); in groups of older individuals (vs younger); with females engaging in less agonistic behaviours compared to males; and males displaying relatively higher behavioural competence. Our results support previous research that captive chimpanzees be supplied with destructible nesting materials, and demonstrate that synthetic enrichments can indeed have a more positive impact upon welfare than their natural alternatives.

Implementing culturally competent transplant care and implications for reducing health disparities: A prospective qualitative study.

BACKGROUND: Despite available evidence-based interventions that decrease health disparities, these interventions are often not implemented. Northwestern Medicine's® Hispanic Kidney Transplant Program (HKTP) is a culturally and linguistically competent intervention designed to reduce disparities in living donor kidney transplantation (LDKT) among Hispanics/Latinos. The HKTP was introduced in two transplant programs in 2016 to evaluate its effectiveness. OBJECTIVE: This study assessed barriers and facilitators to HKTP implementation preparation. METHODS: Interviews and group discussions were conducted with transplant stakeholders (ie administrators, nurses, physicians) during implementation preparation. The Consolidated Framework for Implementation Research (CFIR) guided interview design and qualitative analysis. RESULTS: Forty-four stakeholders participated in 24 interviews and/or 27 group discussions. New factors, not found in previous implementation preparation research in health-care settings, emerged as facilitators and barriers to the implementation of culturally competent care. Implementation facilitators included: stakeholders' focus on a moral imperative to implement the HKTP, personal motivations related to their Hispanic heritage, and perceptions of Hispanic patients' transplant education needs. Implementation barriers included: stakeholders' perceptions that Hispanics' health insurance payer mix would negatively impact revenue, a lack of knowledge about LDKT disparities and patient data disaggregated by ethnicity/race, and a perception that the family discussion component was immoral because of the possibility of coercion. DISCUSSION AND CONCLUSIONS: Our study identified novel barriers and facilitators to the implementation preparation of a culturally competent care intervention. Healthcare administrators can facilitate organizations' implementation of culturally competent care interventions by understanding factors challenging care delivery processes and raising clinical team awareness of disparities in LDKT.

Public education materials about Vascular Composite Allotransplantation and donation in the United States: Current scope and limitations.

As the field of Vascular Composite Allotransplantation (VCA) grows, demand for VCA donations will increase. The public should be made aware of this treatment option to support patients' informed decision-making and authorization for deceased donation. We assessed the availability and quality of existing VCA public education materials from organ procurement organizations (OPOs), transplant centers, the Organ Procurement and Transplant Network, Veterans Affairs, and the Department of Defense. A content analysis was performed to identify topics covered and important gaps. In total, 1314 public education materials were analyzed, including OPO Facebook posts (61.6%), OPO Twitter posts (29.9%), websites (6.4%), and written documents (eg, fact sheets, research reports) (2.1%). Upper extremity (34.7%) and face (34.5%) transplants were more commonly covered than reproductive (6.4%) or other VCA types (2.8%). Most materials (76.6%) referenced a specific VCA story. However, few materials described which patient population could benefit from VCA (eg, Veterans, amputees, burn victims, 16.4%), the authorization requirements for VCA donation (6.6%), or the appearance of transplanted VCA organs (1.2%). Current VCA public education materials do not adequately educate the public. More comprehensive education materials are needed to prepare the public to authorize VCA donation, become potential donors, or learn about transplant options.

Endothelial ATP-Sensitive Potassium Channel Protects Against the Development of Hypertension and Atherosclerosis.

In the endothelium, ATP-sensitive potassium (KATP) channels are thought to couple cellular metabolism with membrane excitability, calcium entry, and endothelial mediator release. We hypothesized that endothelial KATP channels have a broad role protecting against high blood pressure and atherosclerosis. Endothelial-specific Kir6.1 KO mice (eKO) and eKO mice on an apolipoprotein E KO background were generated (A-eKO) to investigate the role of KATP channels in the endothelium. Basal blood pressure was not elevated in eKO mice. However, when challenged with a high-salt diet and the eNOS inhibitor L-NAME, eKO mice became more hypertensive than their littermate controls. In aorta, NO release at least partly contributes to the endothelium-dependent vasorelaxation induced by pinacidil. In A-eKO mice atherosclerotic plaque density was significantly greater than in their littermate controls when challenged with a high-fat diet, particularly in the aortic arch region. Levels of endothelial dysfunction markers were higher in eKO compared with WT mice; however, these were not significant for A-eKO mice compared with their littermate controls. Furthermore, decreased vascular reactivity was observed in the mesenteric arteries of A-eKO mice, but not in aorta when on a high-fat diet. Our data support a role for endothelial Kir6.1-containing KATP channels in the endothelial protection against environmental stressors: the maintenance of blood pressure homeostasis in response to high salt and endothelial integrity when challenged with a high-fat diet.

Vascular KATP channels protect from cardiac dysfunction and preserve cardiac metabolism during endotoxemia.

KATP channels in the vasculature composed of Kir6.1 regulate vascular tone and may contribute to the pathogenesis of endotoxemia. We used mice with cell-specific deletion of Kir6.1 in smooth muscle (smKO) and endothelium (eKO) to investigate this question. We found that smKO mice had a significant survival disadvantage compared with their littermate controls when treated with a sub-lethal dose of lipopolysaccharide (LPS). All cohorts of mice became hypotensive following bacterial LPS administration; however, mean arterial pressure in WT mice recovered to normal levels, whereas smKO struggled to overcome LPS-induced hypotension. In vivo and ex vivo investigations revealed pronounced cardiac dysfunction in LPS-treated smKO, but not in eKO mice. Similar results were observed in a cecal slurry injection model. Metabolomic profiling of hearts revealed significantly reduced levels of metabolites involved in redox/energetics, TCA cycle, lipid/fatty acid and amino acid metabolism. Vascular smooth muscle-localised KATP channels have a critical role in the response to systemic infection by normalising cardiac function and haemodynamics through metabolic homeostasis. KEY MESSAGES: • Mice lacking vascular KATP channels are more susceptible to death from infection. • Absence of smooth muscle KATP channels depresses cardiac function during infection. • Cardiac dysfunction is accompanied by profound changes in cellular metabolites. • Findings from this study suggest a protective role for vascular KATP channels in response to systemic infection.

Using Behavioral Risk Factor Surveillance System Data as an Occupational Health Profile: Washington State Janitors, 2011 to 2017.

OBJECTIVE: Janitorial workers have a high burden of occupational injury and illness, but little information exists on their overall health. METHODS: Data from the Washington State Behavioral Risk Factor Surveillance System (BRFSS) were analyzed to characterize the working population of Janitors in Washington State from 2011 to 2017 (n = 490) as compared with all other workers (n = 38,885). RESULTS: Compared with other workers, Janitors were significantly more diverse, had lower socioeconomic status, and reported poorer general health and higher rates of arthritis and depression. Janitors were less likely to have adequate sleep, health insurance, and access to technology. Janitors reported higher rates of smoking and marijuana use. CONCLUSIONS: Multiple risk factors compound the vulnerability of Janitors. BRFSS data can be used to characterize the health of occupational groups. Identifying overall health needs can better inform policy and help formulate strategies to improve workers' health.

A critical role for the ATP-sensitive potassium channel subunit KIR6.1 in the control of cerebral blood flow.

KIR6.1 (KCNJ8) is a subunit of ATP sensitive potassium channel (KATP) that plays an important role in the control of peripheral vascular tone and is highly expressed in brain contractile cells (vascular smooth muscle cells and pericytes). This study determined the effect of global deletion of the KIR6.1 subunit on cerebral blood flow, neurovascular coupling and cerebral oxygenation in mice. In KIR6.1 deficient mice resting cerebral blood flow and brain parenchymal partial pressure of oxygen (PO2) were found to be markedly lower compared to that in their wildtype littermates. However, cortical blood oxygen level dependent responses triggered by visual stimuli were not affected in conditions of KIR6.1 deficiency. These data suggest that KATP channels containing KIR6.1 subunit are critically important for the maintenance of normal cerebral perfusion and parenchymal PO2 but play no significant role in the mechanisms underlying functional changes in brain blood flow.

Occupational Injuries of Aquaculture Workers: Washington State.

OBJECTIVE: To characterize occupational injuries of aquaculture workers in Washington State. METHODS: We reviewed accepted Washington State workers' compensation claims from January 1, 2006 to December 31, 2014. Trends in employment, worker demographics (including age, sex, and body mass index), claim rate, and injury characteristics were summarized for accepted claims in the Washington State risk classes that include aquaculture workers. RESULTS: During the nine-year study period, there were 1,180 accepted claims, 836 (65.1%) were medical-aid only and 344 (26.8%) were compensable. Most commonly reported injury types included being struck by/against an object (n = 420) and work-related musculoskeletal disorders (n = 310). Over the study period, there was no statistically significant change in claim rates in aquaculture (p = 0.77), though they were elevated compared to claim rates for all WA industries combined. A significant upward trend (p = 0.003) in aquaculture employment was observed during our study period. CONCLUSIONS: Given the growth in aquaculture production, and that aquaculture workers in Washington are experiencing higher occupational injury rates compared to other workers in the state, our study suggests that the industry should devote greater attention to prevention of work-related injuries, especially those resulting in being struck by/against objects or work-related musculoskeletal disorders. Enhanced occupational safety and health programs for this industry could help reduce injuries, as well as the cost of workers' compensation claims.

Defective Vagal Innervation in Murine Tbx1 Mutant Hearts.

Haploinsufficiency of the T-box transcription factor TBX1 is responsible for many features of 22q11.2 deletion syndrome. Tbx1 is expressed dynamically in the pharyngeal apparatus during mouse development and Tbx1 homozygous mutants display numerous severe defects including abnormal cranial ganglion formation and neural crest cell defects. These abnormalities prompted us to investigate whether parasympathetic (vagal) innervation of the heart was affected in Tbx1 mutant embryos. In this report, we used an allelic series of Tbx1 mouse mutants, embryo tissue explants and cardiac electrophysiology to characterise, in detail, the function of Tbx1 in vagal innervation of the heart. We found that total nerve branch length was significantly reduced in Tbx1+/- and Tbx1neo2/- mutant hearts expressing 50% and 15% levels of Tbx1. We also found that neural crest cells migrated normally to the heart of Tbx1+/-, but not in Tbx1neo2 mutant embryos. In addition, we showed that cranial ganglia IXth and Xth were fused in Tbx1neo2/- but neuronal differentiation appeared intact. Finally, we used telemetry to monitor heart response to carbachol, a cholinergic receptor agonist, and found that heart rate recovered more quickly in Tbx1+/- animals versus controls. We speculate that this condition of decreased parasympathetic drive could result in a pro-arrhythmic substrate in some 22q11.2DS patients.

ATP-sensitive potassium channels in the sinoatrial node contribute to heart rate control and adaptation to hypoxia.

ATP-sensitive potassium channels (KATP) contribute to membrane currents in many tissues, are responsive to intracellular metabolism, and open as ATP falls and ADP rises. KATP channels are widely distributed in tissues and are prominently expressed in the heart. They have generally been observed in ventricular tissue, but they are also expressed in the atria and conduction tissues. In this study, we focused on the contribution and role of the inwardly rectifying KATP channel subunit, Kir6.1, in the sinoatrial node (SAN). To develop a murine, conduction-specific Kir6.1 KO model, we selectively deleted Kir6.1 in the conduction system in adult mice (cKO). Electrophysiological data in single SAN cells indicated that Kir6.1 underlies a KATP current in a significant proportion of cells and influences early repolarization during pacemaking, resulting in prolonged cycle length. Implanted telemetry probes to measure heart rate and electrocardiographic characteristics revealed that the cKO mice have a slow heart rate, with episodes of sinus arrest in some mice. The PR interval (time between the onset of the P wave to the beginning of QRS complex) was increased, suggesting effects on the atrioventricular node. Ex vivo studies of whole heart or dissected heart regions disclosed impaired adaptive responses of the SAN to hypoxia, and this may have had long-term pathological consequences in the cKO mice. In conclusion, Kir6.1-containing KATP channels in the SAN have a role in excitability, heart rate control, and the electrophysiological adaptation of the SAN to hypoxia.