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.

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.

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.

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.

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.