Environmental Exposures and Risks During Pregnancy.

The Women in Wilderness Medicine Research Committee of the Wilderness Medical Society conducted a narrative review to address considerations for pregnant individuals in wilderness environments. There is limited evidence behind many opinion-based recommendations on the safety of various environmental exposures in pregnancy. The authors reviewed the literature for the best available evidence, including observational studies, case series, limited controlled trials, and extrapolation from physiological data, as well as evaluating expert consensus statements. The benefits of exposure to natural environments include better pregnancy outcomes and improved maternal mental and physical health. Risks are similar to nonpregnant individuals with the added risks associated with maternal-fetal physiology in wilderness environments and difficulties of evacuation. This narrative review discusses pregnancy-specific concerns in extreme environments, including high altitude, hypothermia, hyperthermia, lightning strikes, envenomations, and common outdoor exposures.

First-Trimester Pregnancy: Considerations for Wilderness and Remote Travel.

Women increasingly participate in outdoor activities in wilderness and remote environments. We performed a literature review to address diagnostic and therapeutic considerations during first-trimester pregnancy for remote multiday travel. Pretrip planning for pregnant patients traveling outside access to advanced medical care should include performing a transvaginal ultrasound to confirm pregnancy location and checking D rhesus status. We discuss the risk of potential travel-related infections and recommended vaccinations prior to departure based on destination. Immediate evacuation to definitive medical care is required for patients with a pregnancy of unknown location and vaginal bleeding. We propose algorithms for determining the need for evacuation and present therapeutic options for nausea and vomiting, urinary tract infections, and candidiasis in the field.

Evaluation of Escherichia coli Inactivation at High Altitudes Using Solar Water Disinfection.

INTRODUCTION: Solar disinfection (SODIS) is an effective method for microbiologic inactivation of contaminated water using ultraviolet rays at low elevations. The aim of this study was to determine the effectiveness of SODIS at higher elevations. METHODS: The ability of SODIS to inactivate Escherichia coli bacteria was evaluated at an altitude of ≥1600 m using Nalgene bottles, disposable plastic water bottles, and Ziploc plastic bags. Bacterial viability was determined through measurement of colony forming units (CFUs). Decreases in CFUs were determined at each time point relative to those at the baseline, and a multivariable regression analysis was used to assess significant changes in CFUs. RESULTS: Bacterial CFUs in exposed containers decreased by >5 log after 6 h of exposure to sunlight. In contrast, the CFUs remained nearly unchanged in unexposed containers, showing a mean decrease of 0.3 log. By 2 h, bacterial inactivation at high altitudes was 1.7-fold greater than that at lower altitudes (P<0.05). By 6 h, nearly all bacteria were inactivated at high or low altitudes. At 6 h, no statistical difference was observed in the efficiency of inactivation between elevations. Compared with Nalgene bottles, plastic bottles had a 1.4-fold greater decrease in CFUs (P<0.05). No statistical difference in bacterial inactivation was found between plastic bottles and plastic bags. CONCLUSIONS: At high altitudes, SODIS is an effective method for inactivating E coli. Further research investigating other microorganisms is warranted to determine whether SODIS is suitable for disinfecting contaminated water at high altitudes.

Temporal associations between emergency department and telehealth volumes during the COVID-19 pandemic: A time-series analysis from 2 academic medical centers.

BACKGROUND: The COVID-19 pandemic compelled healthcare systems to rapidly adapt to changing healthcare needs as well as identify ways to reduce COVID transmission. The relationship between pandemic-related trends in emergency department (ED) visits and telehealth urgent care visits have not been studied. METHODS: We performed an interrupted time series analysis to evaluate trends between ED visits and telehealth urgent medical care visits at two urban healthcare system in Colorado. We performed pairwise comparisons between baseline versus each COVID-19 surge and all three surges combined, for both ED and telehealth encounters at each site and used Wilcoxon rank sum test to compare median values. RESULTS: During the study period, 595,350 patient encounters occurred. We saw ED visits decline in correlation with rising telehealth visits during each COVID surge. CONCLUSIONS: During initial COVID surges, ED visits declined while telehealth visits rose in inverse correlation with falling ED visits, suggesting that some patients shifted their preferred location for clinical care. As EDs cope with future staffing during the ongoing COVID pandemic, telehealth represents an opportunity for emergency physicians and a means to align patients desires for virtual care with ED volumes and staffing.

Antibiotic Prescribing Patterns for Sinusitis Within a Direct-to-Consumer Virtual Urgent Care.

Background:Direct-to-consumer virtual visits are increasingly popular across both for-profit and nonprofit healthcare systems.Introduction:Virtual visits offer a convenient affordable way for patients to obtain medical care for simple conditions such as sinusitis and uncomplicated urinary tract infections. However, virtual visits have been associated with increased antibiotic utilization when compared with traditional in-person care.Methods:In this retrospective cohort study, antibiotic utilization for acute sinusitis was compared between patients treated through a direct-to-consumer virtual urgent care versus a matched cohort treated through traditional urgent care.Results:Fifty-seven patients were treated for acute sinusitis within the virtual care cohort, whereas 100 patients were treated in the traditional care arm. Antibiotic utilization for acute sinusitis was lower when care was delivered virtually using live-interactive video (67%) than when using traditional urgent care (92%) (p < 0.001). When care was delivered virtually, age, gender, and care delivery modality (telephone vs. video) were not associated with antibiotic utilization for acute sinusitis.Discussion:Concerns have been raised that care delivered virtually does not meet expected quality standards when compared with traditional care. Antibiotic utilization has been used as an example of this quality gap. In this study, we demonstrate that antibiotic utilization was lower in a virtual care cohort than when care was delivered by emergency medicine physicians based in an academic setting. This suggests that awareness and sensitivity to prescribing guidelines may be more important than care delivery modality as it relates to antibiotic utilization.Conclusions:It is possible to deliver care virtually for acute sinusitis without increasing antibiotic utilization.

Positive Toxoplasma IgG Serology Is Associated with Increased Overall Mortality - A Propensity Score-Matched Analysis.

Toxoplasma gondii is a prevalent parasitic disease with significant morbidity and mortality in immunocompromised populations. We lack long-term outcomes for latent infections. We aimed to elucidate the relationship between latent T. gondii infection and mortality risk. We queried TriNetX, a international multicenter network, to validate mortality risk differences among patients with positive or negative toxoplasma IgG through propensity score matching (PSM). We excluded patients with toxoplasmosis disease by International Classification of Diseases codes or polymerase chain reaction testing. We found 28,138 patients with available toxoplasma IgG serology. Seropositive patients were older and had a male preponderance. More seropositive patients identified as Hispanic, Latino, or Black persons. Patients who were positive for T. gondii IgG serology were slightly more likely to have underlying heart failure, a transplanted organ or tissue, malignant neoplasms of lymphoid or hematopoietic tissues, and diseases of the nervous system than seronegative controls. After PSM of patients with positive (N = 6,475) and negative (N = 6,475) toxoplasma IgG serologies, toxoplasmosis-positive patients were more likely to have long-term drug use but less likely to suffer from behavioral disorders. The overall PSM 1- and 5-year mortality was higher among patients with a positive toxoplasma IgG serology. The risk of schizophrenia was increased at 5 years. We found a prevalence of toxoplasma IgG positivity of 0.03% during the last 3 years. Latent T. gondii associates with a higher overall mortality risk. The study of social determinants of health and follow-up studies are necessary to corroborate the findings and find possible causal mechanisms.

Breast Imaging and Social Media: A Model Specialty for Increasing Interest and Awareness of Radiology in Pre-Medical Students.

OBJECTIVE: To assess how a virtual shadowing (VS) session on breast imaging (BI), shared through social media, can increase interest and awareness of radiology in pre-medical students. METHODS: This study was IRB exempt. A VS slide presentation on BI mentorship, didactic lecture, and deidentified image-rich, case-based learning was created. This session was advertised and presented live through an Instagram page (Pre-Health Virtual Shadowing, @virtualshadowing) geared toward pre-health students. Students were asked to complete a two-question self-assessment using a 5-point Likert scale on which 1 was "least" and 5 was "most." Question 1 read: "Please rate your overall knowledge about radiology and what a radiologist does," and question 2 read: "Please rate your interest in possibly looking into radiology as a potential career." RESULTS: A total of 420 participants logged into the VS session; 82% (345/420) answered the pre-session survey and 48% (202/420) answered the post-session survey. Of post-survey respondents, 84% (170/202) were female and 70% (143/202) were 22 years old or younger. There was a significant difference in mean pre-session survey responses to question 1 when compared to mean post-session survey responses (2.67 vs 3.55, P < 0.001). There was also a significant difference in mean pre-session survey responses to question 2 when compared to mean post-session survey responses (3.16 vs 3.58, P < 0.001). Our VS session remains on YouTube and has 6157 views to date. CONCLUSION: When shared through VS on social media, breast imaging can increase interest and awareness of radiology in pre-medical students.

Prevention of yellow fever in travellers: an update.

For centuries, yellow fever virus infection generated substantial fear among explorers, tourist travellers, workers, military personnel, and others entering areas of transmission. Currently, there is transmission only in some areas of tropical South America and sub-Saharan Africa. When symptomatic, yellow fever infection causes severe liver dysfunction and coagulopathy with elevated mortality rates. Since there is no effective treatment, vaccination against yellow fever, available since 1937, represents an important preventive intervention in endemic areas. Every year, an increasing number of individuals are travelling to yellow fever endemic areas, many of whom have complex medical conditions. Travel health practitioners should do individualised assessments of the risks and benefits of yellow fever vaccination to identify potential contraindications. The most relevant contraindications include a history of thymoma or thymus dysfunction, AIDS, and individuals receiving immunosuppressive drugs including biological therapies or chemotherapy. We briefly review strategies to prevent yellow fever infection in travellers with the use of yellow fever vaccination and the use of personal protection measures to avoid mosquito bites.

Ensuring the Safety of Yellow Fever Vaccination in Travelers-The Experience at a Large U.S. Academic Medical Center in Colorado.

Background: Yellow fever (YF) virus has the potential to cause fatal outcomes among at-risk individuals visiting endemic areas. Vaccinating travelers who are at risk is necessary to prevent virus-related life-threatening complications. We lack data on the clinical features of persons seeking YF vaccination. We aim to describe the characteristics of a cohort of persons receiving the YF vaccine before travel. Methods: A retrospective analysis of 964 travelers receiving the YF vaccine (Stamaril®) from Oct 2016 to Jul 2019 was performed at the University of Colorado Hospital, U.S. Percentages, means, and standard deviations were calculated. A multivariate logistic regression model was built to evaluate the association between receiving YF vaccination less than 10 days before departure and visiting friends and relatives (VFR). Results: The average age of the subjects was 39 ± 18 years with a range of nine months to 83 years. Persons who were 60 years of age and older represented 17%. Women consisted of 52%, and most of the travelers were Caucasians (64%). Travelers reported traveling to Africa (57%) or South America (40%). The primary destinations for travelers overall were Kenya (19%), Uganda (11%), and Tanzania (11%) in Africa; and Peru (14%) and Brazil (13%) in South America. The most common reasons for travel included leisure (44%), VFR (18%), and mission trips (10%). Comorbidities included a history of hematologic disorders (4%), HIV infection (2%), and diabetes mellitus (3%). The average duration between vaccine administration and travel was 43 days. Those VFR were two times more likely to receive the YF vaccination <10 days before departure. Conclusions: Identifying the type of travel, itinerary, and underlying medical conditions allows providers to administer the YF vaccine to travelers safely. There is a need to identify strategies to improve the timing of YF vaccination among VFR travelers.

Protein kinase C alpha-dependent signaling mediates endometrial cancer cell growth and tumorigenesis.

Endometrial cancer is the most common invasive gynecologic malignancy, yet molecular mechanisms and signaling pathways underlying its etiology and pathophysiology remain poorly characterized. We sought to define a functional role for the protein kinase C (PKC) isoform, PKCalpha, in an established cell model of endometrial adenocarcinoma. Ishikawa cells depleted of PKCalpha protein grew slower, formed fewer colonies in anchorage-independent growth assays and exhibited impaired xenograft tumor formation in nude mice. Consistent with impaired growth, PKCalpha knockdown increased levels of the cyclin-dependent kinase (CDK) inhibitors p21(Cip1/WAF1) (p21) and p27(Kip1) (p27). Despite the absence of functional phosphatase and tensin homolog (PTEN) protein in Ishikawa cells, PKCalpha knockdown reduced Akt phosphorylation at serine 473 and concomitantly inhibited phosphorylation of the Akt target, glycogen synthase kinase-3beta (GSK-3beta). PKCalpha knockdown also resulted in decreased basal ERK phosphorylation and attenuated ERK activation following EGF stimulation. p21 and p27 expression was not increased by treatment of Ishikawa cells with ERK and Akt inhibitors, suggesting that PKCalpha regulates CDK expression independently of Akt and ERK. Immunohistochemical analysis of Grade 1 endometrioid adenocarcinoma revealed aberrant PKCalpha expression, with foci of elevated PKCalpha staining, not observed in normal endometrium. These studies demonstrate a critical role for PKCalpha signaling in endometrial tumorigenesis by regulating expression of CDK inhibitors p21 and p27 and activation of Akt and ERK-dependent proliferative pathways. Thus, targeting PKCalpha may provide novel therapeutic options in endometrial tumors.

c-Jun N-terminal kinase regulates apoptosis in endometrial cancer cells.

c-Jun N-terminal kinases (JNKs) are important regulators of cell proliferation and apoptosis that have been implicated in tumorigenesis. We investigated the role of JNKs in apoptotic responses in Ishikawa and HEC-50 cells, models of type I and type II endometrial cancer, respectively. Etoposide treatment or UV irradiation resulted in sustained activation of JNK, correlating with the induction of apoptosis. Inhibition of JNK, or MAP kinase kinase 4 (MKK4), selectively suppressed apoptotic responses in both Ishikawa and HEC-50 cells. Knockdown of protein kinase C delta (PKCdelta) also attenuated apoptosis in endometrial cancer cells and inhibited the sustained, UV-mediated JNK activation in HEC-50, but not Ishikawa cells. Etoposide-induced JNK phosphorylation was unaffected by PKCdelta knockdown, implying that JNK can regulate apoptosis by PKCdelta-dependent and independent pathways, according to stimulus and cell type. Thus, expression and activity of JNK and PKCdelta in endometrial cancer cells modulate apoptosis and sensitivity to chemotherapeutic agents and may function as tumor suppressors in the endometrium.

The Complexity of Diagnosing High-Altitude Pulmonary Edema: A Case Report and Review of the Differential Diagnosis of Greater Than Expected Hypoxemia at Altitude.

High-altitude pulmonary edema (HAPE) is a common presumptive diagnosis for a patient who experiences significant dyspnea and cyanosis at altitude. In this study, we present a case of a 58-year-old woman who was initially diagnosed with HAPE, although further evaluation revealed the presence of two underlying contributors to her significant hypoxemia at altitude. We discuss the medical workup for causes of greater than expected hypoxemia at altitude and the role some relevant medical comorbidities may play.

Science Policy Training for a New Physician Leader: Description and Framework of a Novel Climate and Health Science Policy Fellowship.

The accelerating health impacts of climate change are undermining global health, and the roles of the health sector in addressing the many challenges of climate change are being articulated by governments, multilateral institutions, and professional societies. Given the paucity of physician engagement on this issue to date, there now exists a clear need for health professionals to meet this new challenge with the development and cultivation of new knowledge and skill sets in public health, environmental science, policy, and communication. We describe a novel GME fellowship in climate and health science policy, designed to train a new generation of clinicians to provide the necessary perspective and skills for effective leadership in this field. This fellowship identifies available university resources and leverages external collaborations (government, medical consortiums, affiliate institutions in public health, and environmental science), which we describe as being replicatable to similar training programs of any number of medical specialties and likewise bring meaningful opportunities to their respective training programs and academic departments. The creation of this novel fellowship in climate and health policy provides a roadmap and potential path for similar programs to join us in addressing the defining health issue of this generation and many to follow.

Analysis of protein kinase C delta (PKC delta) expression in endometrial tumors.

Endometrial cancer is the most common gynecologic malignancy in the United States. However, its underlying molecular mechanisms are poorly understood; and few prognostic indicators have been identified. The protein kinase C (PKC) family has been shown to regulate pathways critical to malignant transformation; and in endometrial tumors, changes in PKC expression and activity have been linked to a more aggressive phenotype and poor prognosis. We have recently shown that PKC delta is a critical regulator of apoptosis and cell survival in endometrial cancer cells; however, PKC delta levels in endometrial tumors had not been determined. We used immunohistochemistry to examine PKC delta protein levels in normal endometrium and endometrioid carcinomas of increasing grade. Normal endometrium exhibited abundant nuclear and cytoplasmic staining of PKC delta confined to glandular epithelium. In endometrial tumors, decreased PKC delta expression, both in intensity and fraction of epithelial cells stained, was observed with increasing tumor grade, with PKC delta being preferentially lost from the nucleus. Consistent with these observations, endometrial cancer cell lines derived from poorly differentiated tumors exhibited reduced PKC delta levels relative to well-differentiated lines. Treatment of endometrial cancer cells with etoposide resulted in a translocation of PKC delta from cytoplasm to nucleus concomitant with induction of apoptosis. Decreased PKC delta expression, particularly in the nucleus, may compromise the ability of cells to undergo apoptosis, perhaps conferring resistance to chemotherapy. Our results indicate that loss of PKC delta is an indicator of endometrial malignancy and increasing grade of cancer. Thus, PKC delta may function as a tumor suppressor in endometrial cancer.

Suicide and High Altitude: An Integrative Review.

Reno, Elaine, Talia L. Brown, Marian E. Betz, Michael H. Allen, Lilian Hoffecker, Jeremy Reitinger, Robert Roach, and Benjamin Honigman. Suicide and high altitude: an integrative review. High Alt Med Biol 19:99-108, 2018. INTRODUCTION: Suicide rates are greater at high altitudes, and multiple mechanisms have been suggested for this relationship, including hypoxia, differences in population density, characteristics of suicide victims, and firearms ownership and access. To better understand these potential mechanisms, studies evaluating the associations between high altitude and suicide were examined. METHODS: A literature review of published studies on high altitude and suicide was conducted in Medline, Embase, Web of Science, the Cochrane Database of Systematic Reviews, and the Cochrane CENTRAL database. We extracted and analyzed all studies that met the inclusion criteria, excluding foreign language studies and letters. Most of the measurements and results were synthesized using modified Letts' criteria. RESULTS: Searches using an extensive list of keywords returned 470 articles, but only 6 met the inclusion criteria. The studies' samples ranged in size from 8871 to 596,704, while studies which did not document sample size reported suicide rates. In five of the studies selected, individuals living at high altitudes were at greater risk of suicide. Four studies used aggregated data at a county or state level to analyze variables, such as age, gender, race, socioeconomic factors, and firearms access. All the studies found that high altitude was independently associated with suicide. One study found that many individual characteristics of those who committed suicide were different at high altitudes than low altitude, including a lack of access or barriers to mental healthcare. Depression exacerbated by hypoxia was hypothesized as a possible biologic mechanism in three studies. CONCLUSION: These research studies published since 2009 support an association between high altitude and suicide rates at the state or county level, but do not provide sufficient data to estimate the effect of high altitude on an individuals' suicide risk. Although the impact of hypoxia on mood and depression has been hypothesized to be a contributing cause, many other individual factors likely play more important roles.

History of Migraine Predicts Headache at High Altitude.

Davis, Christopher, Elaine Reno, Edward Maa, and Robert Roach. History of Migraine Predicts Headache at High Altitude. High Alt Med Biol. 17:300-304, 2016.-Objective: To characterize the spectrum of headaches and their association with migraine history within a population of recreational hikers above 4300 m. METHODS: Using a cross-sectional survey design, a convenience sample of 667 hikers participated in a written survey after descent from Mount Gray/Torreys (4349 m). Headaches were characterized as migraine, high altitude headache (HAH), and/or acute mountain sickness (AMS) using International Headache Society Lake Louise AMS scoring criteria. A univariate odds ratio was calculated to determine whether a history of migraine increased the risk of migrainous headache. Multivariate logistic regression was used to assess whether a priori identified risk factors such as age, sex, recent alcohol consumption, home elevation, and self-reported fluid intake and whether summit success increased the risk of any headache at altitude. RESULTS: Sixty percent of hikers were male with an age range of 17-62 years. Eighty percent reached the summit of Mount Grays/Torreys (4349 m). Seventy-nine percent of participants resided in Colorado; the median elevation of residence for subjects was 1697 m (interquartile range 1557-1765 m). HAH occurred in 39% of hikers, while AMS occurred in 26% of hikers. A history of migraine was associated with increased risk of any headache at altitude (OR: 2.49, 95% CI: 1.62-3.65) and was strongly associated with the development of migrainous headache while at altitude (OR: 14.05, 95% CI: 5.49-35.93). CONCLUSIONS: A history of migraine is a risk factor for the development of headache at altitude and is strongly associated with the development of migrainous headache.

Gene expression profiling of multiple leiomyomata uteri and matched normal tissue from a single patient.

OBJECTIVE: To identify differentially expressed genes between fibroid and adjacent normal myometrium in an identical hormonal and genetic background. DESIGN: Array analysis of three leiomyomata and matched adjacent normal myometrium in a single patient. SETTING: University of Colorado Hospital. PATIENT(S): A single female undergoing medically indicated hysterectomy for symptomatic fibroids. INTERVENTIONS(S): mRNA isolation and microarray analysis, reverse-transcriptase polymerase chain reaction, Western blotting, and immunohistochemistry. MAIN OUTCOME MEASURE(S): Changes in mRNA and protein levels in leiomyomata and matched normal myometrium. RESULT(S): Expression of 197 genes was increased and 619 decreased significantly by at least twofold, in leiomyomata relative to normal myometrium. Expression profiles between tumors were similar and normal myometrial samples showed minimal variation. Changes in, and variation of, expression of selected genes were confirmed in additional normal and leiomyoma samples from multiple patients. CONCLUSION(S): Analysis of multiple tumors from a single patient confirmed changes in expression of genes described in previous, apparently disparate, studies, and identified novel targets. Gene expression profiles in leiomyomata are consistent with increased activation of mitogenic pathways and inhibition of apoptosis. Down-regulation of genes implicated in invasion and metastasis, of cancers, was observed in fibroids. This expression pattern may underlie the benign nature of uterine leiomyomata and may aid in the differential diagnosis of leiomyosarcoma.