Knowledge about various contraceptive methods in young women with and without eating disorders.

OBJECTIVE: To determine if young women with eating disorders (EDs) have altered views about the risks/benefits of different forms of birth control than the general population. METHOD: Data was collected using a cross-sectional, survey-based study of postmenarchal women aged 13-25 years with a diagnosed ED (n = 50) or no history of disordered eating patterns (n =57). RESULTS: Despite having a higher level of education (p = 0.04) and no differences in sexual history (p = 0.16), ED patients were less knowledgeable than controls about the health risks and benefits, effectiveness in preventing HIV, and effectiveness in preventing pregnancy of various methods of birth control (p≤ 0.05). DISCUSSION: ED patients may be incorrectly presumed to be asexual while working on recovery; physicians may need to take extra time to educate ED patients about their personal risks of unintended pregnancy, sexually transmitted infections, and the benefits that different methods of contraception can provide.

Corrigendum: An Immunomodulatory Transcriptional Signature Associated With Persistent Listeria Infection in Hepatocytes.

[This corrects the article DOI: 10.3389/fcimb.2021.761945.].

Hemorrhagic Resuscitation Guided by Viscoelastography in Far-Forward Combat and Austere Civilian Environments: Goal-Directed Whole-Blood and Blood-Component Therapy Far from the Trauma Center.

Modern approaches to resuscitation seek to bring patient interventions as close as possible to the initial trauma. In recent decades, fresh or cold-stored whole blood has gained widespread support in multiple settings as the best first agent in resuscitation after massive blood loss. However, whole blood is not a panacea, and while current guidelines promote continued resuscitation with fixed ratios of blood products, the debate about the optimal resuscitation strategy-especially in austere or challenging environments-is by no means settled. In this narrative review, we give a brief history of military resuscitation and how whole blood became the mainstay of initial resuscitation. We then outline the principles of viscoelastic hemostatic assays as well as their adoption for providing goal-directed blood-component therapy in trauma centers. After summarizing the nascent research on the strengths and limitations of viscoelastic platforms in challenging environmental conditions, we conclude with our vision of how these platforms can be deployed in far-forward combat and austere civilian environments to maximize survival.

Viscoelastic Hemostatic Assays: A Primer on Legacy and New Generation Devices.

Viscoelastic hemostatic assay (VHAs) are whole blood point-of-care tests that have become an essential method for assaying hemostatic competence in liver transplantation, cardiac surgery, and most recently, trauma surgery involving hemorrhagic shock. It has taken more than three-quarters of a century of research and clinical application for this technology to become mainstream in these three clinical areas. Within the last decade, the cup and pin legacy devices, such as thromboelastography (TEG® 5000) and rotational thromboelastometry (ROTEM® delta), have been supplanted not only by cartridge systems (TEG® 6S and ROTEM® sigma), but also by more portable point-of-care bedside testing iterations of these legacy devices (e.g., Sonoclot®, Quantra®, and ClotPro®). Here, the legacy and new generation VHAs are compared on the basis of their unique hemostatic parameters that define contributions of coagulation factors, fibrinogen/fibrin, platelets, and clot lysis as related to the lifespan of a clot. In conclusion, we offer a brief discussion on the meteoric adoption of VHAs across the medical and surgical specialties to address COVID-19-associated coagulopathy.

Immuno-Thrombotic Complications of COVID-19: Implications for Timing of Surgery and Anticoagulation.

Early in the coronavirus disease 2019 (COVID-19) pandemic, global governing bodies prioritized transmissibility-based precautions and hospital capacity as the foundation for delay of elective procedures. As elective surgical volumes increased, convalescent COVID-19 patients faced increased postoperative morbidity and mortality and clinicians had limited evidence for stratifying individual risk in this population. Clear evidence now demonstrates that those recovering from COVID-19 have increased postoperative morbidity and mortality. These data-in conjunction with the recent American Society of Anesthesiologists guidelines-offer the evidence necessary to expand the early pandemic guidelines and guide the surgeon's preoperative risk assessment. Here, we argue elective surgeries should still be delayed on a personalized basis to maximize postoperative outcomes. We outline a framework for stratifying the individual COVID-19 patient's fitness for surgery based on the symptoms and severity of acute or convalescent COVID-19 illness, coagulopathy assessment, and acuity of the surgical procedure. Although the most common manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is COVID-19 pneumonitis, every system in the body is potentially afflicted by an endotheliitis. This endothelial derangement most often manifests as a hypercoagulable state on admission with associated occult and symptomatic venous and arterial thromboembolisms. The delicate balance between hyper and hypocoagulable states is defined by the local immune-thrombotic crosstalk that results commonly in a hemostatic derangement known as fibrinolytic shutdown. In tandem, the hemostatic derangements that occur during acute COVID-19 infection affect not only the timing of surgical procedures, but also the incidence of postoperative hemostatic complications related to COVID-19-associated coagulopathy (CAC). Traditional methods of thromboprophylaxis and treatment of thromboses after surgery require a tailored approach guided by an understanding of the pathophysiologic underpinnings of the COVID-19 patient. Likewise, a prolonged period of risk for developing hemostatic complications following hospitalization due to COVID-19 has resulted in guidelines from differing societies that recommend varying periods of delay following SARS-CoV-2 infection. In conclusion, we propose the perioperative, personalized assessment of COVID-19 patients' CAC using viscoelastic hemostatic assays and fluorescent microclot analysis.

An Immunomodulatory Transcriptional Signature Associated With Persistent Listeria Infection in Hepatocytes.

Listeria monocytogenes causes severe foodborne illness in pregnant women and immunocompromised individuals. After the intestinal phase of infection, the liver plays a central role in the clearance of this pathogen through its important functions in immunity. However, recent evidence suggests that during long-term infection of hepatocytes, a subpopulation of Listeria may escape eradication by entering a persistence phase in intracellular vacuoles. Here, we examine whether this long-term infection alters hepatocyte defense pathways, which may be instrumental for bacterial persistence. We first optimized cell models of persistent infection in human hepatocyte cell lines HepG2 and Huh7 and primary mouse hepatocytes (PMH). In these cells, Listeria efficiently entered the persistence phase after three days of infection, while inducing a potent interferon response, of type I in PMH and type III in HepG2, while Huh7 remained unresponsive. RNA-sequencing analysis identified a common signature of long-term Listeria infection characterized by the overexpression of a set of genes involved in antiviral immunity and the under-expression of many acute phase protein (APP) genes, particularly involved in the complement and coagulation systems. Infection also altered the expression of cholesterol metabolism-associated genes in HepG2 and Huh7 cells. The decrease in APP transcripts was correlated with lower protein abundance in the secretome of infected cells, as shown by proteomics, and also occurred in the presence of APP inducers (IL-6 or IL-1ß). Collectively, these results reveal that long-term infection with Listeria profoundly deregulates the innate immune functions of hepatocytes, which could generate an environment favorable to the establishment of persistent infection.

Thromboelastography-Guided Anticoagulant Therapy for the Double Hazard of Thrombohemorrhagic Events in COVID-19: A Report of 3 Cases.

BACKGROUND The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), often manifests a coagulopathy in severely ill patients, which may cause hemorrhage and/or thrombosis of varying severity. This report comprises the cases of 3 patients with COVID-19-associated coagulopathy who were evaluated with thromboelastography (TEG) and activated partial thromboplastin time (aPTT) to enable personalized anticoagulant therapy. CASE REPORT Three patients presented with COVID-19 pneumonia, confirmed by reverse transcription-polymerase chain reaction, who developed thrombohemorrhagic coagulopathy.Case 1: A 72-year-old woman on long-term warfarin therapy for a history of venous thromboembolism developed a right upper lobe pulmonary embolus, despite an international normalized ratio of 6.4 and aPTT of 120.7 s. TEG enabled successful anticoagulation with heparin, and her pulmonary infarct was no longer present 2 weeks later.Case 2: A 55-year-old woman developed a rectus sheath hematoma while on heparin, and TEG demonstrated increased fibrinolysis despite COVID-19 patients more commonly undergoing fibrinolytic shutdown.Case 3: A 43-year-old woman had significant thrombus burden while severely hypocoagulable according to laboratory testing. As the venous thrombi enlarged in a disseminated intravascular coagulopathic-like state, the heparin dose was escalated to achieve a target aPTT of 70 to 80 s, resulting in a flat line TEG tracing. CONCLUSIONS These 3 cases of COVID-19 pneumonia with complex and varied clinical histories demonstrated the clinical value of TEG combined with the measurement of aPTT to facilitate personalized anticoagulation, resulting in good clinical outcomes.

A Case Series of Thromboelastography-Guided Anticoagulation in COVID-19 Patients with Inherited and Acquired Hypercoagulable States.

One of the complications of the novel coronavirus disease 2019 (COVID-19) is hypercoagulability. For this reason, patients presenting with COVID-19 are often put on therapeutic or intermediate anticoagulation upon hospitalization. A common issue of this anticoagulation is the progression to hypocoagulability resulting in hemorrhage. Therefore, monitoring the hemostatic integrity of critically ill COVID-19 patients is of utmost importance. In this case series, we present the cases of three coagulopathic COVID-19 patients whose anticoagulation was guided by thromboelastography (TEG). In each case, TEG permitted the clinical team to simultaneously prevent thrombotic and hemorrhagic events, a difficult task for COVID-19 patients admitted to the intensive care unit. The first two cases illustrate the utility of TEG to guide anticoagulant dosing for COVID-19 patients when the activated partial thromboplastin time (aPTT) is inaccurate. The first case was a severely ill COVID-19 patient with end-stage renal disease and a falsely elevated aPTT secondary to hypertriglyceridemia. The second case was a severely ill COVID-19 patient with chronic pulmonary disease who demonstrated a falsely elevated aPTT due to polycythemia and hemoconcentration. In both cases, TEG was sensitive to the hypercoagulability caused by the metabolic derangements which enabled the goal-directed titration of anticoagulants. The last case depicts a severely ill COVID-19 patient with an inherited factor V Leiden mutation who required abnormally high dosing to achieve therapeutic anticoagulation, guided by TEG. Hypercoagulopathic COVID-19 patients are difficult to anticoagulate without development of hypocoagulopathy. Treatment of these patients demands goal-directed therapy by diligent laboratory monitoring. This can be accomplished by the use of TEG coupled with aPTT to guide anticoagulation. This case series illustrates the necessity for active hemostatic monitoring of critically ill COVID-19 patients.

Tension pneumomediastinum and diffuse subcutaneous emphysema with severe acute respiratory syndrome coronavirus 2 infection requiring operative management for impending airway collapse: A case report.

Tension pneumomediastinum is a rare complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that has increased in incidence with the novel coronavirus disease 2019 pandemic. Although traditionally managed with conservative measures, we present the indications and methods for the first operative management of tension pneumomediastinum with concomitant SARS-CoV-2 infection.

Impact of a clinical pharmacist on ultrasound-guided venous thromboembolism screening in hospitalized COVID-19 patients: a pilot prospective study.

BACKGROUND: The recognition, prevention and treatment of venous thromboembolism (VTE) remains a major challenge in the face of the recent COVID-19 pandemic which has been associated with significant cardiovascular, renal, respiratory and hematologic complications related to hypercoagulability. There has been little literature thus far on the utility of screening ultrasound and the role of the clinical pharmacist in treating these patients. METHODS: We present a prospective pilot program of thirty-one consecutive COVID-19 patients who were provided four extremity screening ultrasounds for VTE on admission. This was coordinated by a clinical pharmacist as part of a multidisciplinary approach. Quantitative and qualitative data were recorded with the goal of describing the utility of the clinical pharmacist in ultrasound screening. Data collected include demographics, information on clinical symptoms or signs at presentation, and laboratory and radiologic results during the hospitalization from each individual electronic medical record. RESULTS: Nine of the thirty-one patients presented with VTE. Of the nine patients, there were twenty-two total clotted vessels, all of which were asymptomatic. The clinical pharmacist, as the coordinator for a multidisciplinary COVID-19 associated coagulopathy management team, drafted a screening and treatment protocol for anticoagulation prophylaxis and therapy of VTE after ultrasound findings. CONCLUSION: VTE screening of hospitalized COVID-19 patients reveals a significant number of asymptomatic VTEs and justifies diagnostic, prophylactic, and treatment measures coordinated by a clinical pharmacist.

Preventing Thrombohemorrhagic Complications of Heparinized COVID-19 Patients Using Adjunctive Thromboelastography: A Retrospective Study.

BACKGROUND: The treatment of COVID-19 patients with heparin is not always effective in preventing thrombotic complications, but can also be associated with bleeding complications, suggesting a balanced approach to anticoagulation is needed. A prior pilot study supported that thromboelastography and conventional coagulation tests could predict hemorrhage in COVID-19 in patients treated with unfractionated heparin or enoxaparin, but did not evaluate the risk of thrombosis. METHODS: This single-center, retrospective study included 79 severely ill COVID-19 patients anticoagulated with intermediate or therapeutic dose unfractionated heparin. Two stepwise logistic regression models were performed with bleeding or thrombosis as the dependent variable, and thromboelastography parameters and conventional coagulation tests as the independent variables. RESULTS: Among all 79 patients, 12 (15.2%) had bleeding events, and 20 (25.3%) had thrombosis. Multivariate logistic regression analysis identified a prediction model for bleeding (adjusted R2 = 0.787, p < 0.001) comprised of increased reaction time (p = 0.016), decreased fibrinogen (p = 0.006), decreased D-dimer (p = 0.063), and increased activated partial thromboplastin time (p = 0.084). Multivariate analysis of thrombosis identified a weak prediction model (adjusted R2 = 0.348, p < 0.001) comprised of increased D-dimer (p < 0.001), decreased reaction time (p = 0.002), increased maximum amplitude (p < 0.001), and decreased alpha angle (p = 0.014). Adjunctive thromboelastography decreased the use of packed red cells (p = 0.031) and fresh frozen plasma (p < 0.001). CONCLUSIONS: Significantly, this study demonstrates the need for a precision-based titration strategy of anticoagulation for hospitalized COVID-19 patients. Since severely ill COVID-19 patients may switch between thrombotic or hemorrhagic phenotypes or express both simultaneously, institutions may reduce these complications by developing their own titration strategy using daily conventional coagulation tests with adjunctive thromboelastography.

Partnership for Families Program: philanthropy for in vitro fertilization patients.

OBJECTIVE: To describe our Partnership for Families Program, which was established to provide second in vitro fertilization (IVF) cycles for couples who pay for one IVF cycle, do not get pregnant and cannot afford a second IVF cycle. In addition, this program provides funding for fertility-sparing procedures for financially needy cancer patients. STUDY DESIGN: Retrospective description of the Partnership for Families' first 5 years of operation. RESULTS: In its 5 years of operation, the Partnership for Families Program has provided 137 infertile couples with a second IVF cycle, resulting in 68 ongoing or delivered pregnancies. It has also provided funding for 19 fertility-sparing procedures for cancer patients. CONCLUSION: Because of the high costs of IVF, alternative funding sources, specifically philanthropy, must be explored to provide increased access to IVF. The Partnership for Families Program, started by patients in a single practice, has in 5 years provided over 151 infertile and cancer patients IVF or egg-freezing cycles that they otherwise could not have afforded. This is a program that can be emulated by other fertility centers.

Estimating actual foot size from a static bare foot print in a White British Population.

In forensic intelligence-gathering it would be useful to be able to estimate the size of a perpetrator's foot from a standing bare footprint found at the scene of crime. Currently, the advice is to add a fixed amount to the length of the footprint (typically 1.5 or 2.0 cm), but there is little evidence for this approach. This study used measured footprint and actual foot lengths from 146 participants from the white British student population of a University in the UK. Data were analysed using multiple regression with foot length as the dependent (outcome) variable and footprint length and sex as the independent variable/factor respectively. Sex was not a significant predictor. The regression equation for the best estimate of the foot length is 19.89 + 0.95 × print length ±â€¯8 mm.

Regulation of the response to Nodal-mediated mesoderm induction by Xrel3.

The Xenopus egg has a yolk-laden vegetal hemisphere juxtaposed to a darkly pigmented animal hemisphere. Mesoderm is derived from the marginal zone, located at the interface between the two hemispheres. The vegetal-most cells become endoderm and release TGF-beta-related factors, including the Xenopus Nodal related (Xnr) proteins, which diffuse to induce the marginal zone to form mesoderm. The remaining animal cells become ectoderm, but our understanding of the mechanisms that limit the response to induction is incomplete. In this study, we provide evidence to suggest that Xrel3, a member of the Rel/NF-kappaB family, plays a role in defining the boundary separating induced from uninduced cells by regulating Xnr-responsive gene transcription. Ectopic Xrel3 expressed in prospective mesoderm caused repression of mesoderm-specific genes resulting in loss-of-function phenotypes that were rescued by co-expression of Xnr2. Depletion of Xrel3 from embryos with antisense morpholinos increased Xnr-dependent transcription, broadened expression of the pan-mesoderm marker Xbra and sensitized animal cells to mesoderm induction by Xnr2. We propose that an additional component to the mechanism that differentiates the ectoderm from the mesoderm involves regulation of nodal-dependent gene transcription by Xrel3.

Protein expression of the transcriptional regulator MI-ER1 alpha in adult mouse tissues.

MI-ER1 is a novel transcriptional regulator that plays a critical role in embryonic development and is differentially expressed in breast carcinoma. The MI-ER1 protein sequence is highly conserved among species, with 95% identity between mouse and humans and 72% between Xenopus and mouse. There are two major protein isoforms, MI-ER1alpha and MI-ER1beta, which differ in the sequence of their C-terminus. MI-ER1alpha is of particular interest because it contains a consensus LXXLL nuclear receptor interaction motif and the current study was undertaken to determine the expression pattern of MI-ER1alpha protein in adult mouse tissues. Immunohistochemical analysis of paraffin-embedded tissue using an MI-ER1alpha-specific antibody revealed that the majority of mouse adult tissues examined showed very weak or no immunoreactivity; these included tissues of the lung, liver, intestine, uterus, spleen, lymph node, bladder as well as skeletal muscle. Interestingly, a subset of endocrine tissues displayed intense staining for MI-ER1alpha. Specifically, the islets of Langerhans, the zona glomerulosa and medulla of the adrenal gland, the ovary and the hypothalamus were intensely stained. In addition, both anterior and posterior pituitary showed moderate immunoreactivity, as did the parafollicular cells of the thyroid gland and Leydig cells and spermatids in the testes. Negative endocrine tissues included follicular cells of the thyroid gland and the X zone of the adrenal cortex. A few non-endocrine tissues displayed moderate immunoreactivity; these included all tubules and collecting ducts in the kidney, myocardial and endocardial layers of the heart, the hippocampal formation, pyramidal neurons in the cortex and the ductal epithelium of the mammary gland. In all cases, MI-ER1alpha immunoreactivity was cytoplasmic. This study represents the first immunohistochemical analysis of MI-ER1alpha expression in mammals and our data suggest that this transcriptional regulator plays a role in specific endocrine pathways.

Human MI-ER1 alpha and beta function as transcriptional repressors by recruitment of histone deacetylase 1 to their conserved ELM2 domain.

mi-er1 (previously called er1) was first isolated from Xenopus laevis embryonic cells as a novel fibroblast growth factor-regulated immediate-early gene. Xmi-er1 was shown to encode a nuclear protein with an N-terminal acidic transcription activation domain. The human orthologue of mi-er1 (hmi-er1) displays 91% similarity to the Xenopus sequence at the amino acid level and was shown to be upregulated in breast carcinoma cell lines and tumors. Alternative splicing at the 3' end of hmi-er1 produces two major isoforms, hMI-ER1alpha and hMI-ER1beta, which contain distinct C-terminal domains. In this study, we investigated the role of hMI-ER1alpha and hMI-ER1beta in the regulation of transcription. Using fusion proteins of hMI-ER1alpha or hMI-ER1beta tethered to the GAL4 DNA binding domain, we show that both isoforms, when recruited to the G5tkCAT minimal promoter, function to repress transcription. We demonstrate that this repressor activity is due to interaction and recruitment of a trichostatin A-sensitive histone deacetylase 1 (HDAC1). Furthermore, deletion analysis revealed that recruitment of HDAC1 to hMI-ER1alpha and hMI-ER1beta occurs through their common ELM2 domain. The ELM2 domain was first described in the Caenorhabditis elegans Egl-27 protein and is present in a number of SANT domain-containing transcription factors. This is the first report of a function for the ELM2 domain, highlighting its role in the regulation of transcription.

Differential HDAC1 and 2 Recruitment by Members of the MIER Family.

The mier family consists of three related genes encoding ELM2-SANT containing proteins. MIER1 has been well characterized and is known to function in transcriptional repression through its ability to recruit HDAC1 and 2. Little is known about MIER2 or MIER3 function and no study characterizing these two proteins has been published. In this report, we investigate MIER2 and MIER3 localization and function. Confocal analysis revealed that, while MIER2 and MIER3 are mainly nuclear proteins, a substantial proportion (32%) of MIER2 is localized in the cytoplasm. Co-immunoprecipitation experiments demonstrated that the MIER proteins do not dimerize; that MIER2, but not MIER3, can recruit HDACs; and that recruitment is cell line-dependent. MIER2 was associated with HDAC1 and HDAC2 in HEK293 cells, but only with HDAC1 in MCF7 and HeLa cells. Little or no MIER3 co-immunoprecipitated with either HDAC1 or 2 in any of the three cell lines tested. By contrast, HDAC1 and 2 were readily detected in MIER1α complexes in all three cell lines. Histone deacetylase assays confirmed that MIER2, but not MIER3 complexes, have associated deacetylase activity, leading to the conclusion that MIER3 does not function in HDAC recruitment in these cell lines. In contrast to what has been reported for other ELM2-SANT associated HDACs, addition of D-myo-inositol-1,4,5,6-tetrakisphosphate led to only a small increase in MIER1α associated deacetylase activity and no effect on that associated with MIER2. Deletion analysis revealed that HDAC recruitment occurs through the ELM2 domain. Finally, using site-directed mutagenesis, we show that, like MIER1, 228W in the ELM2 domain is a critical residue for HDAC recruitment by MIER2.

Developmentally regulated cytoplasmic retention of the transcription factor XMI-ER1 requires sequence in the acidic activation domain.

Xmi-er1 is a fibroblast growth factor regulated immediate-early gene that is activated during mesoderm induction in Xenopus embryonic explants. This gene encodes a nuclear protein with potent transcriptional regulator activity and overexpression of XMI-ER1 in Xenopus embryos inhibits mesoderm induction and leads to truncations along the anteroposterior axis. We showed previously that XMI-ER1 is retained in the cytoplasm during cleavage stages and only begins to appear in the nucleus at mid-blastula. Such developmentally regulated nuclear translocation may represent an important mechanism for regulating XMI-ER1 activity in the early embryo. Here, we investigate different mechanisms that might control nuclear translocation of XMI-ER1. Using alpha-amanitin to inhibit transcription, we show that nuclear localization is not dependent on zygotic transcription. Nor is it the result of a developmentally regulated import pathway, as the XMI-ER1 nuclear localization signal (NLS) fused to beta-galactosidase (betagal) was able to direct nuclear translocation prior to mid-blastula. Fusion of an additional, heterologous NLS to the N-terminus of XMI-ER1 was not sufficient to overcome cytoplasmic retention, indicating that retention does not involve NLS masking, but rather binding to a cytoplasmic anchor. The anchoring molecule is not an RNA, as microinjection of RNase A did not affect the timing of nuclear translocation. Western blot analysis using antibodies that recognize phosphorylated residues revealed that, while XMI-ER1 is not itself phosphorylated, it is associated with two differentially phosphorylated proteins, suggesting that the anchoring mechanism may involve interaction with a cytoplasmic protein(s). A series of XMI-ER1 deletion mutants was utilized to map the putative retention domain. Our analysis revealed that amino acids 144-175, containing the fourth acidic stretch of the acidic activation domain, are required for retention. These results suggest that XMI-ER1 is retained in the cytoplasm of the early embryo by interaction of the region containing amino acids 144-175 with a cytoplasmic anchor.