Effects of hypobaric hypoxia during a simulated ultra-long-haul flight on inflammation and regeneration after muscle trauma and muscle trauma-hemorrhagic shock.

INTRODUCTION/AIMS: Because wounded warfighters or trauma victims may receive en route care to the closest medical facility via airplane transport, we investigated the effects of extended mild hypobaric hypoxia (HB), the environmental milieu of most airplanes, on inflammation and regeneration after muscle trauma or monotrauma (MT) and muscle trauma-hemorrhagic shock or polytrauma (PT). METHODS: Male C57BL/6N mice were assigned to one of six groups pertaining to injury (control/uninjured, MT, and PT) and atmospheric pressure exposure (HB and normobaric normoxia, NB). Body mass, blood and muscle leukocyte number by flow cytometry, immunohistochemistry, or both, and the muscle relative mRNA level of selected genes involved in inflammation and muscle regeneration were examined at ~1.7, 4, 8, and 14 days post trauma (dpt). At 14 dpt, the proportion of smaller- and larger-sized myofibers at the regenerating site of MT mice was determined. RESULTS: Greater body mass loss, an increased number of blood and muscle leukocytes, and differential muscle relative mRNA levels were observed in MT and PT groups compared to controls. The MT+HB or PT+HB mice demonstrated more body mass loss and altered relative mRNA level than the corresponding NB mice. Additionally, a subgroup of MT+HB mice demonstrated a greater proportion of smaller myofibers (250 to 500 µm2 ) than MT+NB mice at 14 dpt. DISCUSSION: HB exposure after muscle trauma alone may prolong regeneration. Following HB exposure, therapies that promote oxygenation may be needed during this muscle recovery.

SARS-CoV-2 surveillance with environmental surface sampling in public areas.

Contaminated surfaces are one of the ways that coronavirus disease 2019 (COVID-19) may be transmitted. SARS-CoV-2 can be detected on environmental surfaces; however, few environmental sampling studies have been conducted in nonclinical settings. The objective of this study was to detect SARS-CoV-2 RNA on environmental surfaces in public areas in Las Vegas, Nevada. In total, 300 surface samples were collected from high-touch surfaces from high-congregate public locations and from a public health facility (PHF) that was visited by COVID-19 patients. Environmental samples were analyzed with quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) using SARS-CoV-2 specific primers and probes for three target genes. Results showed that 31 out of 300 (10.3%) surface samples tested positive for SARS-CoV-2, 24 at the PHF and 7 in high-congregate public locations. Concentrations ranged from 102 to 106 viral particles per 3 ml sample on a wide variety of materials. The data also showed that the N gene assay had greater sensitivity compared to the S and ORF gene assays. Besides frequently touched surfaces, SARS-CoV-2 was detected in restrooms, on floors and surfaces in contact with floors, as well as in a mop water sample. The results of this study describe the extent and distribution of environmental SARS-CoV-2 contamination in public areas in Las Vegas, Nevada. A method using the N gene PCR assay was developed for SARS-CoV-2 environmental monitoring in public areas. Environmental monitoring with this method can determine the specific sites of surface contamination in the community and may be beneficial for prevention of COVID-19 indirect transmission, and evaluation and improvement of infection control practices in public areas, public health facilities, universities, and businesses.

Mild hypobaric hypoxia influences splenic proliferation during the later phase of stress erythropoiesis.

Tissue trauma and hemorrhagic shock are common battlefield injuries that can induce hypoxia, inflammation, and/or anemia. Inflammation and hypoxia can initiate adaptive mechanisms, such as stress erythropoiesis in the spleen, to produce red blood cells and restore the oxygen supply. In a military context, mild hypobaric hypoxia-part of the environmental milieu during aeromedical evacuation or en route care-may influence adaptive mechanisms, such as stress erythropoiesis, and host defense. In the present study, healthy (control), muscle trauma, and polytrauma (muscle trauma and hemorrhagic shock) mice were exposed to normobaric normoxia or hypobaric hypoxia for ∼17.5 h to test the hypothesis that hypobaric hypoxia exposure influences splenic erythropoiesis and splenic inflammation after polytrauma. This hypothesis was partially supported. The polytrauma + hypobaric hypoxia group exhibited more splenic neutrophils, fewer total spleen cells, and fewer splenic proliferating cells than the polytrauma+normobaric normoxia group; however, no splenic erythroid cell differences were detected between the two polytrauma groups. We also compared splenic erythropoiesis and myeloid cell numbers among control, muscle trauma, and polytrauma groups. More reticulocytes at 1.7 days (40 h) post-trauma (dpt) and neutrophils at 4 dpt were produced in the muscle trauma mice than corresponding control mice. In contrast to muscle trauma, polytrauma led to a reduced red blood cell count and elevated serum erythropoietin levels at 1.7 dpt. There were more erythroid subsets and apoptotic reticulocytes in the polytrauma mice than muscle trauma mice at 4 and 8 dpt. At 14 dpt, the red blood cell count of the polytrauma + normobaric normoxia mice was 12% lower than that of the control + normobaric normoxia mice; however, no difference was observed between polytrauma + hypobaric hypoxia and control + hypobaric hypoxia mice. Our findings suggest muscle trauma alone induces stress erythropoiesis; in a polytrauma model, hypobaric hypoxia exposure may result in the dysregulation of splenic cells, requiring a treatment plan to ensure adequate immune functioning.

Circadian Rhythms in Sudden Cardiac Arrest: A Review.

BACKGROUND: Sudden cardiac arrest (SCA) is a serious public health issue caused by the cessation of cardiac electrical and mechanical activity. Despite advances in pedestrian lifesaving technologies like defibrillators, the SCA mortality rate remains high, and survivors are at risk of suffering ischemic injury to various organs. Understanding the contributing factors for SCA is essential for improving morbidity and mortality. One factor capable of influencing SCA incidence and survival is the time of day at which SCA occurs. OBJECTIVES: This review focused on the effect of time of day on SCA incidence, survival rate, and survival to discharge over the past 30 years and the role of age, sex, and SCA location in modulating the timing of SCA. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews criteria guided this review. Four databases (PubMed, Cochrane Libraries, Scopus, and Cumulative Index to Nursing and Allied Health Literature) were queried for research reports or articles addressing time of day and cardiac arrest, which were subsequently screened by the authors for inclusion in this analysis. RESULTS: A total of 48 articles were included in the final analysis. This analysis showed a bimodal SCA distribution with a primary peak in the morning and a secondary peak in the afternoon; these peaks were dependent on age (older persons), sex (more frequent in males), and the location of occurrence (out-of-hospital cardiac arrest vs. in-hospital cardiac rest). Survival following SCA was lowest between midnight and 06:00 a.m. DISCUSSION: The circadian rhythm likely plays an important role in the time-of-day-dependent pattern that is evident in both the incidence of and survival following SCA. There is a renewed call for nursing research to examine or address circadian rhythm as an element in studies involving older adults and activities affecting cardiovascular or respiratory parameters.

Scald Injury-Induced T Cell Dysfunction Can Be Mitigated by Gr1+ Cell Depletion and Blockage of CD47/CD172a Signaling.

Infection is a common and severe complication of burn injury: Sepsis accounts for 47% of postburn mortality. Burn-induced T cell suppression likely contributes to the increased infection susceptibility in burn patients. However, little is known about the kinetics of T cell dysfunction after burn and its underlying mechanisms. In this study, we show in a murine scald injury model that T cell activation of both CD4+ and CD8+ T cells as well as T cell cytokine production is suppressed acutely and persistently for at least 11 days after burn injury. Purified T cells from scald-injured mice exhibit normal T cell functions, indicating an extrinsically mediated defect. We further show that T cell dysfunction after burn appears to be cell-to-cell contact dependent and can be ameliorated by depletion of myeloid-derived suppressor cells. These cells expand after burn injury, particularly a subset expressing the checkpoint inhibitor CD172a, and infiltrate germinal centers. Expression of CD172a appears to be driven by ingestion of immature reticulocytes. Immature reticulocytes are drastically increased in the spleen of scald mice and may contribute to immunosuppression through more direct mechanisms as well. Overall, our study newly identifies two cell populations, myeloid-derived suppressor cells and immature reticulocytes, as well as the CD47/CD172a-signaling pathways as mediators of T cell suppressors after burn and thus opens up new research opportunities in the search for new therapies to combat increased infection susceptibility and the associated morbidity and mortality in burn victims.

Mild Hypobaric Hypoxia Effects on Murine Skeletal Muscle Morphology and Macrophages and Well-Being.

BACKGROUND: In the last 10 yr, the number of ultra-haul flights-defined as flights greater than 12 h of flying time-has increased. While the medical complications of these flights are well-known, the underlying cellular effects are less clear. The primary objective of this study was to test the effects of extended mild hypobaric hypoxia on overall well-being and skeletal muscle morphology and macrophage populations.METHODS: A total of 22 male C57BL/6 mice were assigned to a normobaric (NB) or hypobaric (HB) chamber for 14-17 h. Overall mouse well-being and the general morphology and resident macrophage number in hindlimb muscles were compared between the two pressure conditions.RESULTS: During mild hypobaric hypoxia, the mice behaved normally and no changes were observed in general muscle morphology. Regarding resident macrophages, the mean antigen area of CD206 in the hindlimb muscles, lateral gastrocnemius (LG, 33.8 ± 2.0 vs. 35.3 ± 1.6), medial gastrocnemius (MG, 32.4 ± 1.6 vs. 32.6 ± 1.5), and quadriceps femoris (QF, 36.3 ± 1.2 vs. 34.3 ± 1.1) were similar between NB and HB conditions, and the number of CD68-positive cells in the LG and QF were similar between the two conditions. Significantly fewer CD206-positive cells were counted in the LG muscle under the HB condition.CONCLUSION: Our findings indicate that extended exposure to mild hypobaric hypoxia, similar to that of an ultra-long-haul flight, does not adversely affect healthy skeletal muscle.Zhang L, Soulakova J, St. Pierre Schneider B. Mild hypobaric hypoxia effects on murine skeletal muscle morphology and macrophages and well-being. Aerosp Med Hum Perform. 2019; 90(12):1050-1054.

Time Course of Inflammatory Gene Expression Following Crush Injury in Murine Skeletal Muscle.

BACKGROUND: Early inflammation and secretion of proinflammatory cytokines such as IL-1ß, IL-6, and TNF-α act as the key drivers to regulate inflammation after muscle injury. However, the effects of these key proinflammatory drivers in a noninvasive crush injury model are not well known. Understanding these effects is important for treating crush injuries that occur during natural disasters and military conflicts. PURPOSE: We studied the timed mRNA expression of IL-1ß, IL-6, and TNF-α in a noninvasive murine crush injury model to further understand their impact on proinflammatory cytokine pathways that are activated within the first 48 hours after a crush muscle injury. METHODS: A total of 25 mice were anesthetized and placed on a crush injury apparatus platform with the apparatus piston situated in direct contact with intact skin overlying the right gastrocnemius muscle. Pressure at 45 psi was applied to the piston for 30 seconds for two applications. The mice recovered for either 4, 8, 24, or 48 hours postinjury, after which we harvested the gastrocnemius muscle of both legs. Microarray, confirmatory real-time polymerase chain reaction, and immunolabeling experiments were followed by a microarray time-course analysis. RESULTS: Muscle IL-1ß mRNA rose 270-fold within 4 hours and declined rapidly at 8 hours to 196-fold, 24 hours to 96-fold, and 48 hours to 10-fold. Muscle IL-6 followed the same pattern, with a 34-fold increase at 4 hours, 29-fold increase at 8 hours, 10-fold increase at 24 hours, and 5-fold increase at 48 hours. Ingenuity Pathway Analysis of IL-6 identified activation of two major downstream signaling pathways (IL-6/Stat3 and IL-1ß/Egr1) as key activators of inflammation, regeneration, and fibrosis. DISCUSSION: Closed crush muscle injury produced robust muscle cytokine expression levels, and the microarray findings allowed us to generate our most novel hypothesis: that high expression of IL-1ß, IL-6, and TNF-α may be related to the downregulation of mitochondrial genes early after injury and triggers activation of genes in the repair and fibrosis machinery. The significance of these findings and the identified expression pathways of IL1-ß, IL-6, and TNF-α and their downstream targets in skeletal muscle will allow us to further investigate targets for improved muscle recovery and limb-saving interventions.

Effectiveness of a reference accuracy strategy for peer-reviewed journal articles.

Dissemination of information through peer-reviewed journal articles is an important requirement of success in academia. Despite the importance of publishing articles, about 25% to 45% of articles published in nursing journals have at least 1 reference error in the reference list. The authors discuss the implementation and outcomes of an internal copyeditor strategy aimed at reducing reference inaccuracy in faculty-authored journal articles.

Simulated flight, muscle genetics, and inflammatory indicators in mice.

INTRODUCTION: Skeletal muscle discomfort commonly occurs during long-distance air travel. Although the effects of high altitude on muscle have been well-studied, the effects of short-term exposure to the altitude at which aircraft cabins are pressurized, 2438 m, have not. The primary aim of this study was to examine global gene expression in the gastrocnemius muscle after simulated flight. Inflammatory indicators were also assessed in the muscle. METHODS: Thirty-five mice were evenly exposed to normobaria or hypobaria (2438 m) for -8-9 h. Microarray and ribonucleic acid (RNA) analyses were performed. Additionally, macrophage and neutrophil presence was examined. RESULTS: Fourteen genes were downregulated in females after hypobaria. These genes included those related to epithelial homeostasis, such as the keratins, and genes activated by cellular insult. In contrast, four noncoding, regulatory RNAs were upregulated in males. No difference in proinflammatory cytokine gene and messenger RNA (mRNA) expression was detected between normobaria and hypobaria. The mean number of CD68-positive leukocytes per mm2 and mean area percentage of the CD68 antigen in muscle of normobaric (NB) and hypobaric (HB) mice were 53-54 and -0.2%, respectively. DISCUSSION: Simulated flight does not activate a proinflammatory response in healthy muscle. However, epithelial and cellular defense genes may be downregulated in females, whereas regulatory RNAs may be upregulated in males.

Nursing's leadership in positioning human health at the core of urban sustainability.

The United Nations predicts that by 2050 nearly three fourths of the world's population will live in urban areas, including cities. People are attracted to cities because these urban areas offer diverse opportunities, including the availability of goods and services and a higher quality of life. Cities, however, may not be sustainable with this population boom. To address sustainability, urban developers and engineers are building green structures, and businesses are creating products that are safe for the environment. Additionally, efforts are needed to place human health at the core of urban sustainability. Without human health, cities will not survive for future generations. Nursing is the discipline that can place human health in this position. Nursing's initiatives throughout history are efforts of sustainability-improving human health within the physical, economic, and social environments. Therefore, nursing must take a leadership role to ensure that human health is at the core of urban sustainability.

CD11b+ neutrophils predominate over RAM11+ macrophages in stretch-injured muscle.

The purpose of this study was to determine whether both neutrophils and macrophages infiltrate the hematoma site of stretch-injured rabbit tibialis anterior muscle. The Mab.198 antibody was used to detect CD11b(+) neutrophils or macrophages. Neutrophils were identified specifically by using the RPN3/57 antibody. The RAM11 antibody was used to detect macrophages. The histological characteristics of the hematoma site, torn fibers or inflammatory cells, were present primarily at 4 and 24 h, but not at 48 and 72 h after injury. A difference in the Mab.198(+) cellular concentration was detected over time between uninjured and injured muscles (P = 0.03). The injured-uninjured difference in the RPN3/57(+) or RAM11(+) cellular concentrations approached significance (P = 0.07) or else was deemed insignificant (P = 0.13), respectively. Therefore, neutrophils may predominate over RAM11(+) macrophages in stretch-injured muscle. These findings may influence the antiinflammatory strategies used to treat stretch injuries.

Preformed anti-human leukocyte antigen antibodies jeopardize cardiac transplantation in patients with a left ventricular assist device.

In 1997, 15% of patients who received a cardiac transplant in the United States needed a mechanical circulatory support device before transplantation. One device that patients received was the left ventricular assist device (LVAD). During the LVAD support period, approximately 30% to 80% of LVAD recipients have positive test results for panel reactive antibodies (PRAs). Many of these antibodies form against human leukocyte antigens (HLA). These antigens are present on most cells and stimulate antibody production when a person receives unrelated donor cells. Several pre-LVAD and post-LVAD factors contribute to anti-HLA antibody formation. These antibody levels must be lowered before transplantation because the presence of anti-HLA antibodies makes it more difficult to find a suitable donor and increases the risk of rejection. The objectives of this article are to describe anti-HLA antibody formation in LVAD recipients, review its major consequences and treatments, and discuss nursing actions associated with anti-HLA antibody formation.