Environmental Heat Exposure and Heat-Related Symptoms in United States Coast Guard Deepwater Horizon Disaster Responders.

OBJECTIVES: The response to the 2010 Deepwater Horizon oil spill was impacted by heat. We evaluated the association between environmental heat exposure and self-reported heat-related symptoms in US Coast Guard Deepwater Horizon disaster responders. METHODS: Utilizing climate data and postdeployment survey responses from 3648 responders, we assigned heat exposure categories based on both wet bulb globe temperature (WBGT) and heat index (HI) measurements (median, mean, maximum). We calculated prevalence ratios (PRs) and 95% confidence intervals (CIs) via adjusted Poisson regression models with robust error variance to estimate associations with reported heat-related symptoms. We also evaluated the association between use of personal protective equipment (PPE) and heat-related symptoms. RESULTS: Those in the highest WBGT median-based heat exposure category had increased prevalence of heat-related symptoms compared to those in the lowest category (PR=2.22 [95% CI: 1.61, 3.06]), and there was a significant exposure-response trend (P<.001). Results were similar for exposure categories based on WBGT and HI metrics. Analyses stratified by use of PPE found significantly stronger associations between environmental heat exposure and heat-related symptoms in those who did not use PPE (PR=2.23 [95% CI: 1.10, 4.51]) than in those who did (PR=1.64 [95% CI: 1.14, 2.36]). CONCLUSIONS: US Coast Guard Deepwater Horizon disaster responders who experienced higher levels of environmental heat had higher prevalences of heat-related symptoms. These symptoms may impact health, safety, and mission effectiveness. As global climate change increases the frequency of disasters and weather extremes, actions must be taken to prevent heat-related health impacts among disaster responders. (Disaster Med Public Health Preparedness. 2019;13:561-569).

Mitogen-activated protein kinases as therapeutic targets in osteoarthritis.

PURPOSE OF REVIEW: The mitogen-activated protein (MAP) kinases are intracellular signaling proteins which play a central role in controlling the activity of pathways that regulate production and activity of multiple mediators of joint tissue destruction. The therapeutic potential of MAP kinase inhibition in osteoarthritis was reviewed. RECENT FINDINGS: Results from basic research studies support the role of MAP kinases as central mediators that regulate expression of proinflammatory cytokines and metalloproteinases but also as potential pain mediators as well. Cell culture and animal model studies suggest that inhibition of MAP kinases might slow progression of osteoarthritis but trials of MAP kinase inhibitors in humans with osteoarthritis have not yet been reported. Safety concerns of the currently available inhibitors have limited their initial use to trials in conditions considered more severe than osteoarthritis. SUMMARY: MAP kinase inhibition has the potential to slow disease progression in osteoarthritis and also might reduce pain; however, safety concerns have limited the use of general MAP kinase inhibitors in humans. Further understanding of the function of specific isoforms of the MAP kinases as well as upstream and downstream effectors may lead to the development of more specific inhibitors with less toxicity that could eventually be used as structure-modifying drugs for osteoarthritis.

Endogenous production of reactive oxygen species is required for stimulation of human articular chondrocyte matrix metalloproteinase production by fibronectin fragments.

The objective of the present study was to determine if reactive oxygen species (ROS) are required as secondary messengers for fibronectin fragment-stimulated matrix metalloproteinase (MMP) production in human articular chondrocytes. Cultured cells were stimulated with 25 microg/ml of the alpha5beta1 integrin-binding 110-kDa fibronectin fragment (FN-f) in the presence and absence of various antioxidants including Mn(III) tetrakis(4-benzoic acid)porphyrin (MnTBAP). FN-f stimulation significantly increased intracellular levels of ROS in articular chondrocytes. Pretreatment of cells with 250 microM MnTBAP or 40 mM N-acetyl-L-cysteine, but not inhibitors of nitric oxide synthase, completely prevented FN-f-stimulated MMP-3, -10, and -13 production. MnTBAP also blocked FN-f-induced phosphorylation of the MAP kinases and NF-kappaB-associated proteins and blocked activation of an NF-kappaB promoter-reporter construct. Overexpression of catalase, superoxide dismutase, or glutathione peroxidase also inhibited FN-f-stimulated MMP-13 production. Preincubation of chondrocytes with rotenone, an inhibitor of the mitochondrial electron transport chain, or nordihydroguaiaretic acid (NDGA), a selective 5-lipoxygenase inhibitor, partially prevented FN-f-stimulated MMP-13 production and decreased MAP kinase and NF-kappaB phosphorylation. These results show that increased production of ROS but not nitric oxide as obligatory secondary messengers in the chondrocyte FN-f signaling pathway leads to the increased production of MMPs, including MMP-13.

Insomnia and motor vehicle accident-related injuries, active component, U.S. Armed Forces, 2007-2016.

Insomnia is the most common sleep disorder in adults, and its incidence is increasing in the U.S. Armed Forces. A potential consequence of insomnia (including medications used to treat it) is increased risk of motor vehicle accidents (MVAs), which cause significant morbidity and mortality in service members. To examine the relationship between insomnia and MVA-related injuries in the U.S. Armed Forces, this retrospective cohort study compared incidence rates of MVA-related injuries from 2007 through 2016 between service members with diagnosed insomnia and an unexposed cohort. After adjustment for multiple covariates, service members with insomnia had more than double the rate of MVA-related injuries, compared to service members without insomnia (adjusted incidence rate ratio: 2.08; 95% CI: 1.95-2.22). A subanalysis of service members with insomnia during 2014-2016 found no difference in risk of MVA-related injury based on days' supply of sleep aid medications prescribed in 365 days following insomnia diagnosis. Insomnia is an important potential risk factor for MVAs in the military. Sleep health should be a component of MVA prevention efforts.

Awake High-Flow Extracranial to Intracranial Bypass for Complex Cerebral Aneurysms: Institutional Clinical Trial Results.

OBJECTIVE: Assess the potential added benefit to patient outcomes of "awake" neurological testing when compared with standard neurophysiologic testing performed under general endotracheal anesthesia. METHODS: Prospective study of 30 consecutive adult patients who underwent awake high flow extracranial to intracranial (HFEC-IC) bypass. Clinical neurological and neurophysiologic findings were recorded. Primary outcome measures were the incidence of stroke/cerebrovascular accident (CVA), length of stay, discharge to rehabilitation, 30-day modified Rankin scale score, and death. An analysis was also performed of a retrospective control cohort (n = 110 patients who underwent HFEC-IC for internal carotid artery (ICA) aneurysms under standard general endotracheal anesthesia). RESULTS: Five patients (16.6%) developed clinical awake neurological changes (4, contralateral hemiparesis; 1, ipsilateral visual changes) during the 10-minute ICA occlusion test. These patients had 2 kinks in the graft, 1 vasospasm, 1 requiring reconstruction of the distal anastomosis, and 1 developed blurring of vision that reversed after the removal of the distal permanent clip on the ICA. Three of these 5 patients had asynchronous clinical "awake" neurological and neurophysiologic changes. Two patients (7%) developed CVA. Median length of stay was 4 days. Twenty-eight of 30 patients were discharged to home. Median modified Rankin scale score was 1. There were no deaths in this series. Absolute risk reduction in the awake craniotomy group (n = 30) relative to control retrospective group (n = 110) was 7% for CVA, 9% for discharge to rehabilitation, and 10% for graft patency. CONCLUSIONS: Temporary ICA occlusion during HFEC-IC bypass for ICA aneurysms in conjunction with awake intraoperative clinical testing was effective in detecting a subset of patients (n = 3, 10%) in whom neurological deficit was not detected by neurophysiologic monitoring alone.

The social consequences of expressive suppression.

At times, people keep their emotions from showing during social interactions. The authors' analysis suggests that such expressive suppression should disrupt communication and increase stress levels. To test this hypothesis, the authors conducted 2 studies in which unacquainted pairs of women discussed an upsetting topic. In Study 1, one member of each pair was randomly assigned to (a) suppress her emotional behavior, (b) respond naturally, or (c) cognitively reappraise in a way that reduced emotional responding. Suppression alone disrupted communication and magnified blood pressure responses in the suppressors' partners. In Study 2, suppression had a negative impact on the regulators' emotional experience and increased blood pressure in both regulators and their partners. Suppression also reduced rapport and inhibited relationship formation.

Role of heparan sulfate in interactions of Listeria monocytogenes with enterocytes.

Heparan sulfate is known to participate in binding a wide variety of microbes to mammalian cells, but few studies have focused on the enterocyte. Normal human colonic and small intestinal enterocytes, and cultured HT-29 (but not Caco-2) enterocytes, reacted prominently with antibodies specific for heparan sulfate and for the core protein of syndecan-1 (a heparan sulfate proteoglycan). The heparan sulfate analog, heparin, inhibited interactions of Listeria monocytogenes (adherence and internalization) with HT-29, but not Caco-2, enterocytes. Internalization of L. monocytogenes by HT-29 enterocytes was inhibited by heparan sulfate and to a lesser extent by chondroitin sulfate, but not by the non-sulfated glycosaminoglycan hyaluronic acid. Compared to plasmid control ARH-77 cells, adherence of L. monocytogenes, was increased using ARH-77 cells transfected with syndecan-1 cDNA. Heparin binding protein(s) on L. monocytogenes were confirmed using biotinylated heparin. To determine if these in vitro observations might have in vivo relevance, L. monocytogenes was preincubated with heparin and then orally inoculated into mice. Compared to L. monocytogenes not pretreated with heparin, L. monocytogenes pretreated with heparin was associated with decreased extraintestinal dissemination to the mesenteric lymph nodes and liver of orally inoculated mice. Thus, heparan sulfate (possibly as the heparan sulfate proteoglycan syndecan-1) appears to participate in interactions of L. monocytogenes with enterocytes.

Effect of lipopolysaccharide on virulence of intestinal candida albicans.

BACKGROUND: Candida albicans is a polymorphic fungus that frequently causes systemic infection in postsurgical and trauma patients. Others have reported that Escherichia coli lipopolysaccharide (LPS) acts as a copathogen to enhance the virulence of parenteral C. albicans. Experiments were designed to clarify the effect of parenteral LPS on systemic candidiasis initiated via the oral route. MATERIALS AND METHODS: Antibiotic-treated mice were orally inoculated with C. albicans CAF2 (wild-type) or mutant HLC54 (defective in filament formation), and were given 100 microg parenteral LPS 16 h before sacrifice. Separate groups of mice were additionally exposed to intermittent hypoxia prior to LPS. At sacrifice, cecal flora and microbial translocation to the mesenteric lymph nodes were quantified. C. albicans adherence to cultured HT-29 and Caco-2 enterocytes (pretreated with LPS, or calcium-free medium to expose the enterocyte lateral surface, or both) was quantified by enzyme-linked immunoabsorbent assay. RESULTS: All mice had high numbers of cecal C. albicans, and LPS was associated with an additional increase in cecal concentrations of HLC54 but not CAF2. Translocation of HLC54, but not CAF2, appeared facilitated by hypoxia, but LPS did not facilitate translocation in any treatment group. Exposure of the lateral surface of cultured enterocytes had no effect on C. albicans adherence, although LPS consistently decreased adherence of both C. albicans strains. CONCLUSIONS: In contrast to experiments where systemic candidiasis was initiated by the parenteral route, parenteral LPS did not act as a copathogen in mice with systemic candidiasis initiated by the oral route, and these results might be related to LPS-induced alterations in C. albicans adherence to host enterocytes.