Diagnostic performance of the ABC score in the PROPPR trial.

INTRODUCTION: The Assessment of Blood Consumption (ABC) score is used to predict massive transfusions (MT). However, its diagnostic performance has not been widely examined, especially when used as an objective tool to enroll patients in multi-center clinical trials. The purpose of this study was to evaluate the performance of the ABC score in enrolling patients in the Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial. We hypothesized the ABC score would have a similar diagnostic performance to predict the need for massive transfusion as previous studies. METHODS: This is a retrospective analysis of the PROPPR trial. Patients were enrolled either on the basis of an ABC score ≥2, or by Physician Gestalt, when the ABC score was <2. We calculated the sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and likelihood ratios of the ABC score (≥2) for predicting MT (>10 units of red blood cells/24 h or transfusion of >3 units of red blood cells within the first hour). RESULTS: Of the 680 patients, 438 patients (64 %) had an ABC score of ≥2 and 242 (36 %) had an ABC score of <2. An ABC score of ≥2 had 66.8 % sensitivity and 37.0 % specificity for predicting the need for MT, with a PPV of 88.2 % and NPV of 13.1 %. Similarly, an ABC≥2 had 65.6 % sensitivity and 44.6 % specificity for predicting the need for >3 units RBCs in 1 hour, with a PPV of 89.5 % and NPV of 15.3 %. CONCLUSION: The ABC score had lower performance than previously reported for predicting MT, when applied to PROPPR trial patients. The performance for predicting the need for a 3-unit red blood cell transfusion (or more) in the first hour was slightly higher. LEVEL OF EVIDENCE: Level III, Prognostic.

Feasibility of using an automated call service to collect quality of life and functional outcome data in trauma patients.

Objectives: Following up trauma patients after discharge, to evaluate their subsequent quality of life and functional outcomes, is notoriously difficult, time consuming, and expensive. Automated systems are a conceptually attractive solution. We prospectively assessed the feasibility of using a series of automated phone calls administered by Emmi Patient Engagement to survey trauma patients after discharge. Methods: Recruitment into the study was incorporated into the patient discharge process by nursing staff. For this pilot, we included trauma patients discharging home and who were able to answer phone calls. A script was created to evaluate the Extended Glasgow Outcome Scale and the EuroQol EQ-5D to assess functional status and quality of life, respectively. Call attempts were made at 6 weeks, 3 months, 6 months, and 1 year after discharge. Results: A total of 110 patients initially agreed to participate. 368 attempted patient encounters (calls or attempted calls) took place, with 104 (28.3%) patients answering a least one question in the study. 21 unique patients (19.1% of those enrolled) completed 27 surveys. Conclusions: Automated, scripted phone calls to survey patients after discharge are not a feasible way of collecting functional and quality of life data. Level of evidence: Level II/prospective.

Green Oxidation of Aromatic Hydrazide Derivatives Using an Oxoammonium Salt.

Aromatic diazenes are often prepared by oxidation of the corresponding hydrazides using stoichiometric quantities of nonrecyclable oxidants. We developed a convenient alternative protocol for the oxidation of aromatic hydrazides using Bobbitt's salt (1), a metal-free, recyclable, and commercially available oxoammonium reagent. A variety of aryl hydrazides were oxidized within 75 min at room temperature using the developed protocol. Computational insight suggests that this oxidation occurs by a polar hydride transfer mechanism.

Outcomes of patients enrolled in a prospective and randomized trial on basis of gestalt assessment or ABC score.

BACKGROUND: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial rapidly enrolled patients based on an Assessment of Blood Consumption (ABC) ≥ 2 score, or physician gestalt (PG) when ABC score was <2. The objective of this study was to describe what patients were enrolled by the two methods and whether patient outcomes differed based on these enrollments. We hypothesized that there would be no differences in outcomes based on whether patients were enrolled via ABC score or PG. METHODS: Patients were enrolled with an ABC ≥ 2 or by PG when ABC was <2 by the attending trauma surgeon. We compared 1-hour, 3-hour, 6-hour, 12-hour, 18-hour, and 24-hour mortality, 30-day mortality, time to hemostasis, emergent surgical or interventional radiology procedure and the proportion of patients who required either >10 units of blood in 24 hours or >3 units in 1 hour. RESULTS: Of 680 patients, 438 (64%) were enrolled on the basis of an ABC score ≥2 and 242 (36% by PG when the ABC score was <2). Patients enrolled by PG were older (median, 44; interquartile range [IQR], 28-59; p < 0.001), more likely to be White (70.3% vs. 60.3%, p = 0.014), and more likely to have been injured by blunt mechanisms (77.3% vs. 37.2%, p < 0.001). They were also less hypotensive and less tachycardic than patients enrolled by ABC score (both p < 0.001). The groups had similar Injury Severity Scores in the ABC ≥ 2 and PG groups (26 and 27, respectively) and were equally represented (49.1% and 50.8%, respectively) in the 1:1:1 treatment arm. There were no significant differences between the ABC score and PG groups for mortality at any point. Time to hemostasis (108 for patients enrolled on basis of Gestalt, vs. 100 minutes for patients enrolled on basis of ABC score), and the proportion of patients requiring a massive transfusion (>10 units/24 hours) (44.2% vs. 47.3%), or meeting the critical administration threshold (>3 unit/1 hour) (84.7% vs. 89.5%) were similar ( p = 0.071). CONCLUSION: Early identification of trauma patients likely to require a massive transfusion is important for clinical care, resource use, and selection of patients for clinical trials. Patients enrolled in the PROPPR trial based on PG when the ABC score was <2 represented 36% of the patients and had identical outcomes to those enrolled on the basis of an ABC score of ≥2. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Recent advancements in the use of Bobbitt's salt and 4-acetamidoTEMPO.

Recent advances in synthetic methodologies for selective, oxidative transformations using Bobbitt's salt (4-acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium tetrafluoroborate, 1) and its stable organic nitroxide counterpart ACT (4-acetamidoTEMPO, 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxyl, 2) have led to increased applications across a broad array of disciplines. Current applications and mechanistic understanding of these metal-free, environmentally benign, and easily accessible organic oxidants now span well-beyond the seminal use of 1 and 2 in selective alcohol oxidations. New synthetic methodologies for the oxidation of alcohols, ethers, amines, thiols, C-H bonds and other functional groups with 1 and 2 along with the field's current mechanistic understandings of these processes are presented alongside our contributions in this area. Exciting new areas harnessing the unique properties of these oxidants include: applications to drug discovery and natural product total synthesis, the development of new electrocatalytic methods for depolymerization of lignin and modification of other biopolymers, in vitro and in vivo nucleoside modifications, applications in supramolecular catalysis, the synthesis of new polymers and materials, enhancements in the design of organic redox flow batteries, uses in organic fuel cells, applications and advancements in energy storage, the development of electrochemical sensors, and the production of renewable fuels.

Brain Specific Estrogen Ameliorates Cognitive Effects of Surgical Menopause in Mice.

Menopause is a major endocrinological shift that leads to an increased vulnerability to the risk factors for cognitive impairment and dementia. This is thought to be due to the loss of circulating estrogens, which exert many potent neuroprotective effects in the brain. Systemic replacement of estrogen post-menopause has many limitations, including increased risk for estrogen-sensitive cancers. A more promising therapeutic approach therefore might be to deliver estrogen only to the brain thus limiting adverse peripheral side effects. We examined whether we could enhance cognitive performance by delivering estrogen exclusively to the brain in post-menopausal mice. We modeled surgical menopause via bilateral ovariectomy (OVX). We treated mice with the pro-drug 10ß,17ß-dihydroxyestra-1,4-dien-3-one (DHED), which can be administered systemically but is converted to 17ß-estradiol only in the brain. Young (2.5-month) and middle-aged (11-month-old) female C57BL/6J mice received ovariectomy and a subcutaneous implant containing vehicle (cholesterol) or DHED. At 3.5 months old (young group) and 14.5 months old (middle-aged group), mice underwent behavior testing to assess memory. DHED did not significantly alter metabolic status in middle-aged, post-menopausal mice. In both young and middle-aged mice, the brain-specific estrogen DHED improved spatial memory. Additional testing in middle-aged mice also showed that DHED improved working and recognition memory. These promising results lay the foundation for future studies aimed at determining if this intervention is as efficacious in models of dementia that have comorbid risk factors.

The molecular phenotype of kisspeptin neurons in the medial amygdala of female mice.

Reproduction is regulated through the hypothalamic-pituitary-gonadal (HPG) axis, largely via the action of kisspeptin neurons in the hypothalamus. Importantly, Kiss1 neurons have been identified in other brain regions, including the medial amygdala (MeA). Though the MeA is implicated in regulating aspects of both reproductive physiology and behavior, as well as non-reproductive processes, the functional roles of MeA Kiss1 neurons are largely unknown. Additionally, besides their stimulation by estrogen, little is known about how MeA Kiss1 neurons are regulated. Using a RiboTag mouse model in conjunction with RNA-seq, we examined the molecular profile of MeA Kiss1 neurons to identify transcripts that are co-expressed in MeA Kiss1 neurons of female mice and whether these transcripts are modulated by estradiol (E2) treatment. RNA-seq identified >13,800 gene transcripts co-expressed in female MeA Kiss1 neurons, including genes for neuropeptides and receptors implicated in reproduction, metabolism, and other neuroendocrine functions. Of the >13,800 genes co-expressed in MeA Kiss1 neurons, only 45 genes demonstrated significantly different expression levels due to E2 treatment. Gene transcripts such as Kiss1, Gal, and Oxtr increased in response to E2 treatment, while fewer transcripts, such as Esr1 and Cyp26b1, were downregulated by E2. Dual RNAscope and immunohistochemistry was performed to validate co-expression of MeA Kiss1 with Cck and Cartpt. These results are the first to establish a profile of genes actively expressed by MeA Kiss1 neurons, including a subset of genes regulated by E2, which provides a useful foundation for future investigations into the regulation and function of MeA Kiss1 neurons.

The females have spoken: A patient-centered national survey on the administration of emergent transfusions with the potential for future fetal harm.

BACKGROUND: Traumatic hemorrhage is the leading cause of preventable death. Early in the resuscitation, only RhD-positive red blood cells are likely to be available, which poses a small risk of causing harm to a future fetus if transfused to an RhD-negative females of childbearing age (CBA), that is, 15 to 49 years old. We sought to characterize how the population, in particular females of CBA, felt about emergency blood administration vis-a-vis potential future fetal harm. METHODS: A national survey was performed using Facebook advertisements in three waves from January 2021 to January 2022. The advertisements directed users to the survey site with seven demographic questions and four questions on accepting transfusion with differing probabilities for future fetal harm (none/any/1:100/1:10,000). Acceptance of transfusion questions were scored on 3-point Likert scale (likely/neutral/unlikely). Only completed responses by females were analyzed. RESULTS: Advertisements were viewed 16,600,430 times by 2,169,805 people with 15,396 advertisement clicks and 2,873 surveys initiated. Most (2,256 of 2,873 [79%]) were fully completed. Majority (2,049 of 2,256 [90%]) of respondents were female. Eighty percent of females (1,645 of 2,049) were of CBA. Most females responded "likely" or "neutral" when asked whether they would accept a lifesaving transfusion if the following risk of fetal harm were present: no risk (99%), any risk (83%), 1:100 risk (85%), and 1:10,000 risk (92%). There were no differences between females of CBA versus non-CBA with respect to the likelihood of accepting lifesaving transfusion with any potential for future fetal harm ( p = 0.24). CONCLUSION: This national survey suggests that most females would accept lifesaving transfusion even with the potential low risk of future fetal harm. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Chemoselective Oxidation of Thiols with Oxoammonium Cations.

The oxidation of various aryl and aliphatic thiols with the commercially available and environmentally benign reagent Bobbitt's salt (1) has been investigated. The reaction affords the corresponding disulfide products in good to excellent yields (71-99%) and can be accomplished in water, methanol, or acetonitrile solvent. Moreover, the process is highly chemoselective, tolerating traditionally oxidation-labile groups such as free amines and alcohols. Combined experimental and computational studies reveal that the oxidation takes place via a polar two-electron process with concomitant and unexpected deoxygenation of the oxoammonium cation through homolysis of the weak N-O bond, differing from prototypical radical-based thiol couplings. This unusual consumption of the oxidant has significant implications for the development of new nitroxide-based radical traps for probing S-centered radicals, the advancement of new electrochemical or catalytic processes involving nitroxide/oxoammonium salt redox couples, and applications to biological systems.

Immune signaling in sex-specific neural and behavioral development: Adolescent opportunity.

Sex differences in neural and behavioral development are integral to understanding neurodevelopmental, mental health, and neurodegenerative disorders. Much of the literature has focused on late prenatal and early postnatal life as a critical juncture for establishing sex-specific developmental trajectories, and data are now clear that immune signaling plays a central role in establishing sex differences early in life. Adolescence is another developmental period during which sex differences arise. However, we know far less about how immune signaling plays a role in establishing sex differences during adolescence. Herein, we review well-defined examples of sex differences during adolescence and then survey the literature to speculate how immune signaling might be playing a role in defining sex-specific adolescent outcomes. We discuss open questions in the literature and propose experimental design tenets that may assist in better understanding adolescent neurodevelopment.

Airway strategy and ventilation rates in the pragmatic airway resuscitation trial.

BACKGROUND: We sought to describe ventilation rates during out-of-hospital cardiac arrest (OHCA) resuscitation and their associations with airway management strategy and outcomes. METHODS: We analyzed continuous end-tidal carbon dioxide capnography data from adult OHCA enrolled in the Pragmatic Airway Resuscitation Trial (PART). Using automated signal processing techniques, we determined continuous ventilation rates for consecutive 10-second epochs after airway insertion. We defined hypoventilation as a ventilation rate < 6 breaths/min. We defined hyperventilation as a ventilation rate > 12 breaths/min. We compared differences in total and percentage post-airway hyper- and hypoventilation between airway interventions (laryngeal tube (LT) vs. endotracheal intubation (ETI)). We also determined associations between hypo-/hyperventilation and OHCA outcomes (ROSC, 72-hour survival, hospital survival, hospital survival with favorable neurologic status). RESULTS: Adequate post-airway capnography were available for 1,010 (LT n = 714, ETI n = 296) of 3,004 patients. Median ventilation rates were: LT 8.0 (IQR 6.5-9.6) breaths/min, ETI 7.9 (6.5-9.7) breaths/min. Total duration and percentage of post-airway time with hypoventilation were similar between LT and ETI: median 1.8 vs. 1.7 minutes, p = 0.94; median 10.5% vs. 11.5%, p = 0.60. Total duration and percentage of post-airway time with hyperventilation were similar between LT and ETI: median 0.4 vs. 0.4 minutes, p = 0.91; median 2.1% vs. 1.9%, p = 0.99. Hypo- and hyperventilation exhibited limited associations with OHCA outcomes. CONCLUSION: In the PART Trial, EMS personnel delivered post-airway ventilations at rates satisfying international guidelines, with only limited hypo- or hyperventilation. Hypo- and hyperventilation durations did not differ between airway management strategy and exhibited uncertain associations with OCHA outcomes.

Multicenter social media community consultation for an exception from informed consent trial of the XStat device (PhoXStat trial).

INTRODUCTION: Community consultation (CC) is a key step for exception from informed consent research. Using social media to conduct CC is becoming more widely accepted but has largely been conducted by single sites. We describe our experience of a social media-based CC for a multicenter clinical trial, coordinated by the lead clinical site. METHODS: Multicenter CC was administered by the lead site and conducted in preparation for a three-site prehospital randomized clinical trial. We used Facebook and Instagram advertisements targeted to the population of interest. When "clicked," the advertisements directed individuals to study-specific websites, providing additional information and the opportunity to opt out. The lead institution and one other hospital relied on a single website, whereas the third center set up their own website. Site views were evaluated using Google analytics. RESULTS: The CC took 8 weeks to complete for each site. The advertisements were displayed 9.8 million times, reaching 332,081 individuals, of whom 1,576 viewed one of the study-specific websites. There were no requests to opt out. The total cost was $3,000. The costs per person reached were $1.88, $2.00, and $1.85 for each of the three sites. A number of site-specific issues (multiple languages, hosting of study-specific websites) were easily resolved. CONCLUSION: This study suggests that it is possible for one institution to conduct multiple, simultaneous, social media-based CC campaigns, on behalf of participating trial sites. Our results suggest that this social media CC model reaches many more potential subjects and is economical and more efficient than traditional methods. LEVEL OF EVIDENCE: Epidemiological, level IV.

Understanding the geography of trauma: Combining spatial analysis and funnel plots to create comprehensive spatial injury profiles.

BACKGROUND: Understanding geographic patterns of injury is essential to operating an effective trauma system and targeting injury prevention. Choropleth maps are helpful in showing spatial relationships but are unable to provide estimates of spread or degrees of confidence. Funnel plots overcome this issue and are a recommended graphical aid for comparisons that allow quantification of precision. The purpose of this project was to demonstrate the complementary roles of choropleth maps and funnel plots in providing a thorough representation of geographic trauma data. METHODS: This is a retrospective analysis of emergency medical service transport data of adult patients in Alabama from July 2015 to June 2020. Choropleth maps of case volume and observed-to-expected ratios of incidence were created using US Census Bureau data. Funnel plots were created to relate incidence rate to county population. Subgroup analyses included patients with critical physiology, penetrating, blunt, and burn injuries. RESULTS: We identified 65,247 trauma incidents during the study period. The overall statewide incidence rate was 133 per 10,000 persons. The highest number of incidents occurred in the most populous counties (Jefferson, 10,768; Mobile, 5,642). Choropleth maps for overall incidence and subgroups highlighted that spatial distribution of overall case volume and observed-to-expected ratios are not always congruent. Funnel plots identified possible and probable outliers, and revealed skewed or otherwise unique patterns among injury subgroups. CONCLUSION: This study demonstrates the complementarity of choropleth maps and funnel plots in describing trauma patterns. Comprehensive geospatial analyses may help guide a data-driven approach to trauma system optimization and injury prevention. Combining maps of case counts, incidence, and funnel plots helps to not only identify geographic trends in data but also quantify outliers and display how far results fall outside the expected range. The combination of these tools provides a more comprehensive geospatial analysis than either tool could provide on its own. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level IV.

Exception from informed consent trials: social-media-based community consultation campaigns are representative of target communities.

BACKGROUND: 'Community consultation' (CC) is a key step when conducting Exception From Informed Consent research. Social-media-based CC has been shown to reach more people than traditional methods, but it is unclear whether those reached are representative of the community as a whole. METHODS: This is a retrospective analysis of the CC performed in preparation for the PHOXSTAT trial. Social media advertisement campaigns were conducted in the catchment areas of the three participating trauma centers and evaluated by examining Facebook user statistics. We compared these data to georeferenced population data obtained from the U.S. Census Bureau. We examined variations in the proportion of each age group reached, by gender. RESULTS: Our social media advertisements reached a total of 332 081 individuals in Los Angeles, Birmingham, and Nashville. Although there were differences in the proportion of individuals reached within each age group and gender groups, compared with the population in each area, these were small (within 5%). In Birmingham, participants 55 to 64 years old, 25 to 34 years old, and females 18 to 24 years old were slightly over-represented (a larger proportion of individuals in this age group were reached by the social media campaign, compared with the population resident in this area). In contrast, in Nashville, female participants 45 to 64 years old, and males 25 to 64 years old were over-represented. In Los Angeles, females 45 to 64 years old, and males 25 to 64 years and over were over-represented. DISCUSSION: In conclusion, this study demonstrates that social media CC campaigns can be used to reach a sample of the community broadly representative of the population as a whole, in terms of age and gender. This finding is helpful to IRBs and investigators, as it lends further support to the use of social media to conduct CC. Further work is needed to analyze how representative community samples are in terms of other characteristics, such as race, ethnicity, and socioeconomic status. LEVEL III EVIDENCE: Economic & Value-based Evaluations.

Perception of risk in massive transfusion as it relates to fetal outcomes: A survey of surgeons and nurses at one American trauma center.

BACKGROUND: The use of blood products early in the resuscitation of bleeding trauma patients is widely accepted, but made difficult by limited supplies of D- red blood cell (RBC)-containing products. Use of D+ RBC-containing products would alleviate this issue, but could lead to alloimmunization. Risk associated with transfusing D+ RBC in emergency bleeding situations is being reconsidered. The level of concern surrounding emergency transfusion as it relates to future fetal harm was surveyed among surgeons and nurses. METHODS: Faculty and staff in the Departments of Surgery and Nursing were surveyed on the risks of receiving an emergency RBC transfusion and the subsequent potential for fetal harm. Answers were grouped as likely to accept (likely/very likely) or refuse transfusion (unlikely/very unlikely). Participants were compared by sex, and women by child-bearing age, ([15-50 years] vs. [>50 years]). RESULTS: Ninety surveys were initiated with 76 fully completed. Male (n = 39) and female (n = 37) respondents were comparable. Most female respondents (30/37, 81%) were of childbearing age. Overall, both males (38/39, 95%) and females (33/37, 89%; p = .19) were likely to accept a transfusion in an emergency. There was no difference in transfusion acceptance if the risk of fetal harm was presented as 1% (p = .73) or 0.1% (p = .51). Most females (34/37, 92%) were not opposed to transfusion even if there was an unspecified risk of future fetal harm. CONCLUSION: Most of the surgeons and nurses who responded would accept a transfusion in an emergency situation even if it might lead to harming a future fetus.

Advanced prehospital resuscitative care: Can we identify trauma patients who might benefit?

BACKGROUND: Uncontrolled truncal hemorrhage remains the most common cause of potentially preventable death after injury. The notion of earlier hemorrhage control and blood product resuscitation is therefore attractive. Some systems have successfully implemented prehospital advanced resuscitative care (ARC) teams. Early identification of patients is key and is reliant on rapid decision making and communication. The purpose of this simulation study was to explore the feasibility of early identification of patients who might benefit from ARC in a typical US setting. METHODS: We conducted a prospective observational/simulation study at a level I trauma center and two associated emergency medical service (EMS) agencies over a 9-month period. The participating EMS agencies were asked to identify actual patients who might benefit from the activation of a hypothetical trauma center-based ARC team. This decision was then communicated in real time to the study team. RESULTS: Sixty-three patients were determined to require activation. The number of activations per month ranged from 2 to 15. The highest incidence of calls occurred between 4 pm to midnight. Of the 63 patients, 33 were transported to the trauma center. The most common presentation was with penetrating trauma. The median age was 27 years (interquartile range, 24-45 years), 75% were male, and the median Injury Severity Score was 11 (interquartile range, 7-20). Based on injury patterns, treatment received, and outcomes, it was determined that 6 (18%) of 33 patients might have benefited from ARC. Three of the patients died en-route to or soon after arrival at the trauma center. CONCLUSION: The prehospital identification of patients who might benefit from ARC is possible but faces challenges. Identifying strategies to adapt existing processes may allow better utilization of the existing infrastructure and should be a focus of future efforts. LEVEL OF EVIDENCE: Prognostic/Epidemiologic, level III.

Estrogen Regulation of the Molecular Phenotype and Active Translatome of AVPV Kisspeptin Neurons.

In females, ovarian estradiol (E2) exerts both negative and positive feedback regulation on the neural circuits governing reproductive hormone secretion, but the cellular and molecular mechanisms underlying this remain poorly understood. In rodents, estrogen receptor α-expressing kisspeptin neurons in the hypothalamic anteroventral periventricular region (AVPV) are prime candidates to mediate E2 positive feedback induction of preovulatory gonadotropin-releasing hormone and luteinizing hormone (LH) surges. E2 stimulates AVPV Kiss1 expression, but the full extent of estrogen effects in these neurons is unknown; whether E2 stimulates or inhibits other genes in AVPV Kiss1 cells has not been determined. Indeed, understanding of the function(s) of AVPV kisspeptin cells is limited, in part, by minimal knowledge of their overall molecular phenotype, as only a few genes are currently known to be co-expressed in AVPV Kiss1 cells. To provide a more detailed profiling of co-expressed genes in AVPV Kiss1 cells, including receptors and other signaling factors, and test how these genes respond to E2, we selectively isolated actively translated mRNAs from AVPV Kiss1 cells of female mice and performed RNA sequencing (RNA-seq). This identified >13 000 mRNAs co-expressed in AVPV Kiss1 cells, including multiple receptor and ligand transcripts positively or negatively regulated by E2. We also performed RNAscope to validate co-expression of several transcripts identified by RNA-seq, including Pdyn (prodynorphin), Penk (proenkephalin), Vgf (VGF), and Cartpt (CART), in female AVPV Kiss1 cells. Given the important role of AVPV kisspeptin cells in positive feedback, E2 effects on identified genes may relate to the LH surge mechanism and/or other physiological processes involving these cells.

Highs, Lows, and Health Hazards of Herbology: A Review of Herbal Medications with Psychotropic Effects.

Mental health disorders, including depression, anxiety, and insomnia, are leading causes of hospitalization and disability for young and middle-aged adults. Approximately one-half of Americans will be diagnosed with a mental illness during their lifetime. Plants and roots have been used as medicinal agents since the beginning of recorded time. Complementary and alternative medicine or complementary integrative medicine use has been increasing throughout most socioeconomic classes, cultures, and age categories. This article reviews herbal and alternative therapies used to treat anxiety, depression, and insomnia. Indications for use, patient education, and possible interactions with conventional prescribed psychotropic medications are analyzed.

A pilot randomized controlled trial of endovascular coils and vascular plugs for proximal splenic artery embolization in high-grade splenic trauma.

PURPOSE: To evaluate the feasibility of enrolling patients in a randomized controlled trial (RCT) comparing endovascular coils (EC) and vascular plugs (VP) for proximal splenic artery embolization (pSAE) in high-grade splenic trauma, and to collect data to inform the design of a larger clinical effectiveness trial. METHODS: Single-center, prospective, RCT of patients with Grade III-V splenic injuries selected for nonoperative management. Patients were randomized to pSAE with EC or VP. The main outcome was feasibility. We also evaluated technical success, time to stasis, complications, mortality, and splenectomy rates, by estimating rates and 95% confidence intervals. RESULTS: 46 of 50 eligible patients were enrolled (92%, 95% CI 90-100%). Overall, splenic salvage was 98% (45/46; 95% CI 94-100%). Primary technical success was observed in 22 EC patients (96%; 95% CI 87-100%) and 20 VP patients (87%; 95% CI 73-100%). Bayesian analysis suggests a > 80% probability that primary technical success is higher for EC. Two complications (one major and one minor) occurred in the EC group (9%; CI 0-20%) and one major complication occurred in the VP group (4%; CI 0-13%). CONCLUSIONS: Randomized comparisons of endovascular devices used for pSAE after trauma are feasible. pSAE using either EC or VP results in excellent rates of splenic salvage in trauma patients with high-grade splenic injuries. These high rates of splenic salvage and low rates of complications make their use as a primary outcome in a future trial problematic. Consideration should be given to technical parameters as a primary outcome for future trials.