Hormonal and related biological changes associated with giving birth may initiate or precipitate a change in self-esteem. Alternatively, or additionally, the change in lifestyle associated with caring for a young infant, for example changes in normal daily activities, lack of sleep caring for the infant, change in financial security, change in the relationship with her partner, may constitute a set of stresses that have mental health consequences for the mother. Since primigravida women have no previous personal experience with childbirth they might have less of a coping strategy to deal with their emotional changes during childbirth.

Approximately 25% of patients with locoregional esophageal adenocarcinoma (EC) are resistant (marked by minimal tumor regression; TRG 3) to preoperative chemoradiation, including 5FU‐based and CROSS regimens. Previously, an immunohistochemistry (IHC) test that accurately identifies patients as responders (TRG 0‐2) or non‐responders (TRG 3) to neoadjuvant CTRT was developed and validated. The current study was designed to identify gene expression profile (GEP) signatures able to predict response to preoperative treatment. Methods: Formalin‐fixed, paraffin‐embedded (FFPE) tumor tissue from 24 diagnostic biopsies (14 responders, 10 non‐responders) was collected. RNA was isolated, and RT‐PCR performed to assess the expression of 96 candidate genes chosen from in silicoanalysis. Genetic signatures incorporating genes with significant expression differences in pathologically determined responders versus non‐responders were identified, and linear and non‐linear predictive modeling methods were used to assess the accuracy of the signatures for predicting treatment response. Cross validation was performed to attain corrected accuracy values. Ten‐, 18‐, and 24‐gene signatures were identified with significantly different gene expression levels in responders compared to non‐responders (p < 0.05). Functional groups represented by the signatures included DNA damage repair, extracellular matrix remodeling, and 5FU metabolism. Partial Least Squares (PLS) prediction of treatment response was compared to pathologic TRG determined by blinded pathologic reading, and resulted in an area under the curve (AUC) of 0.99 and overall accuracy of 100% for the 24‐gene signature. Corrected AUC of 0.99 and accuracy of 95% resulted from five‐fold cross validation with 20 iterations. Heatmap analysis of the 24‐gene signature separated the EC cases into two distinct clusters, the first with 93% responders and the second with 90% non‐responders. The current study identifies novel gene signatures able to accurately predict EC patient response to preoperative treatment. The GEP may allow non‐responders to avoid unnecessary toxicities associated with chemoradiation therapy.

It is estimated over 20 million people aged 20‐74 have gallbladder disease, with biliary colic being a common and painful symptom in these patients. Likely due to the relatively recent approval of intravenous ibuprofen use for fever and pain in adults, no assessment of its analgesic efficacy for biliary colic currently exists in the literature. In this double‐blind, randomized, controlled trial we aim to assess the analgesic efficacy of intravenous (IV) ibuprofen given in the emergency department (ED) for the treatment of biliary colic. Analgesic efficacy was evaluated using a visual analog scale (VAS) to assess for a decrease in pain scores. A VAS score decrease of 33% in relation to the VAS taken at the time of therapy drug administration was considered a minimum clinically important difference (MCID) in patient‐perceived pain. A VAS was administered in triage upon enrollment, at the time of therapy administration, at 15‐minute intervals during the first hour post‐administration, and 30‐minute intervals in the second hour. As the standard of care for suspected biliary colic at the study institution is administration of a one‐time dose of IV morphine, patients were not denied initial morphine analgesia and were permitted to receive “rescue” morphine analgesia at any point during their ED course. A total of 22 patients completed the study. 9 were randomized to the IV ibuprofen arm, 9 to placebo, and 4 were excluded for a diagnosis other than biliary colic. Mean VAS values at time 0 to time 120 decreased from 5.78 to 2.31 in the ibuprofen group, and from 5.89 to 2.67 in the control group. There was no statistically significant difference in treatment status of ibuprofen vs. placebo (p‐value (p.) 0.93), though there was a significant decrease in the measured VAS scores over time (0 minutes to 120 minutes, p.0.031) in both ibuprofen and placebo groups. A statistically significant and clinically important decrease in average VAS scores were seen in both placebo and ibuprofen groups (55% and 60%, respectively). There was no difference in time needed to achieve a clinically significant reduction in pain between groups. The sample size of this study may be inadequate to fully assess the analgesic efficacy of IV ibuprofen for biliary colic. In the analysis group (n=18) no significant difference in treatment status of ibuprofen vs. placebo was seen, however there was a statistically and clinically significant decrease in pain in both groups. Two potential confounding factors may have affected the trial’s results: administration of standard‐of‐care IV morphine following initial triage assessment, and the inherent episodic and self‐limited nature of biliary colic.

Adolescent Idiopathic Scoliosis (AIS) is typically treated surgically by Posterior Spinal Fusion (PSF) surgery. Intravenous analgesics and oral opioids are commonly used for pain management. Several adjunct therapies are used in addition to the standard treatments. One of these therapies is the use of dexmedetomidine (dex). Though dex has been found to be an effective sedative for post‐operative patients, there are also several adverse effects that are associated with its use. The purpose of this study was to investigate the effectiveness and overall benefit of using dex for pain control for patients undergoing PSF for AIS. IRB approval was obtained. A group of 43 patients with AIS undergoing PSF and using Dex for adjunctive pain control were matched with 43 patients who did not use Dex. The groups were matched based on gender, age, height, weight, and level of spinal fusion. During the patients’ post‐operative hospital stay, the total opioid use and clinical pain scores were compared between the two groups using t‐tests, with significance set at p<0.05. Total opiate use was 239.6 morphine equivalent doses in the non‐Dex (control) group and 246.2 in the group that received Dex (p=0.72). The average pain score in the control group was 2.3, and the group that received Dex was 2.6 (p =0.43). There were no differences in the complication rate between the two groups, specifically the oversedation rates and pulmonary complications. Lastly, the average length of stay for the control group was 4.8 days compared to the dex group, which was 5.0 days (p=0.35). Although adjunctive pain modalities may be very useful in the treatment of postoperative pain after PSF in patients with AIS, the use of Dex in this cohort did not improve pain scores, lower opioid use, or lower the LOS. Based on these results, we do not recommend the routine use of dexmedetomidine as an adjunctive pain control modality. Adjunctive modalities are important in pain control in patients with AIS undergoing PSF, but the use of dexmedotomidine was not effective in improving pain control.

Background: Dengue fever is the most common mosquito borne viral disease in the world. Its symptoms can be fairly nonspecific and most commonly include fever, rash, headache, and eye pain. Passive surveillance is currently the most prevalent method used to detect dengue cases in the United States. Identification of positive cases can be limited by the public’s awareness of the disease’s symptoms, barriers to healthcare seeking behavior, and by physician approval of laboratory testing. Objective: This study sought to evaluate barriers to dengue reporting, as well as the patient‐ level factors that may limit the efficacy of passive surveillance of dengue in Key West, Florida. Methods: Cross‐sectional surveys were administered across Key West, FL. Subjects were asked if they had a recent fever, additional dengue symptoms, and whether they sought medical care for these symptoms. Also the hypothetical question was posed: would you seek medical care for a fever greater than 102 F? Responses were stratified according to patient characteristics and demographics. Results: In Key West, patient‐level factors that influenced the decision to seek medical care for a high fever were: having a specific doctor call when sick (p<0.006), health insurance status (p<0.037), and ethnicity (p<0.005). Additionally, barriers to dengue reporting were identified. The most impactful were the decision to seek medical care for symptoms consistent with dengue fever, and the doctor’s decision to administer confirmatory dengue laboratory tests. Only one person with a recent fever plus one additional classic dengue symptom received laboratory testing, and this was done outside of the United States. There were four individuals who met the current WHO clinical case definition for dengue, yet none were offered laboratory testing or were diagnosed with the disease. Conclusion: This study shows that both patients and doctors in Key West, Florida underestimate the potential for dengue when there are symptoms consistent with the disease. As such, it is certainly possible that there have been unreported cases in the country.

An increasing body of evidence suggests that androgens may exert beneficial effects against the development and progression of vascular inflammation during pathological conditions. Our previous data have shown that the potent androgen receptor (AR) agonist, dihydrotestosterone (DHT), attenuates inflammation-induced vascular cell adhesion molecule-1 (VCAM-1) and cyclooxygenase-2 (COX-2) in human primary vascular smooth muscle (VSM) cells. Although this response was not blocked by the AR antagonist bicalutamide, it is not known if AR expression is altered during an inflammatory insult in VSM. The goal of this study was to investigate the effects of a variety of inflammatory stimuli: Angiotensin II (more recently recognized as a mediator of inflammation in the blood vessel wall (Ruiz-Ortega, et al. 2000) (Alvarez, et al. 2004)), hypoxia, and interleukin-1 beta (IL-1β; cytokine) on AR expression in human VSM cells. Since DHT’s effect in the presence of an inflammatory stimulus is AR independent, we hypothesized levels of AR are decreased favoring less of an androgenic contribution during pro-inflammatory conditions. We initially confirmed that human VSM expresses AR and levels of the receptor are increased following androgen treatment in the absence of an 5 inflammatory stimulus. We further demonstrated that in addition to the full-length AR 110 kDa band detected via anti-AR-N20, we also detected a band migrating near 45 kDa in human VSM that is not present in rat testis lysate. Recent studies describe a variant form of the AR called AR45 expressed in human heart but not in rat (Ahrens-Fath, et al. 2005) (Weiss, Faus and Haendler 2007). Although we did not determine whether the bands migrating near 45 kDa were AR45 or possibly an endogenous break down product of the full-length AR (110 kDa) we did however observe expression of the lower migrating band during conditions of inflammation that may be cardioprotective. In the presence of an inflammatory stimulus we demonstrated that there was a consistent trend for IL-1β and angiotensin II (ang II) to decrease AR expression in human coronary artery VSM. Using an in vivo global ischemic model of inflammation, AR was robustly decreased following a 20- and 30-minute occlusion and 21 hr reperfusion in rat pial arteries. However, unlike ang II, cytokine, or ischemia, in vitro hypoxic exposure in human VSM cells increased the lower migrating band density (45 kDa) and had no effect on band density at 110 kDa. In summary, our results confirm that levels of the classic AR (and possibly the novel AR45 variant form) are present in human VSM. 6 Additionally levels of AR may be altered under conditions of inflammation in human VSM cells and following ischemia/reperfusion in rodent cerebral arteries. We conclude that the AR independent attenuation of COX-2 and VCAM-1 by DHT following an inflammatory insult may be due in part to a decrease of AR levels in the blood vessel wall.

Abdominal/pelvic pain is one of the most common reasons that patients present to hospital emergency departments (ED). With 129.8 million emergency department visits per year nationally, efficient triage and admission of these patients from the ED is essential. At the New York Methodist Hospital (NYMH) ED, patients presenting with abdominal/pelvic pain are evaluated based on a series of factors such as pain scores, past medical history, physical exam, and laboratory tests. Depending on these factors, clinicians observe, evaluate, and treat their patients requiring varying lengths of stay in the emergency department before either being discharged or admitted to the hospital. Physicians must weigh the benefits and risks of each evaluation they perform knowing that their resources may be needed more urgently by other patients. Determine the quantitative factors correlated with an increased length of stay for adults presenting to the emergency department with abdominal or pelvic pain. Increases in factors such as age, pain, BMI, and vital signs will correlate with an increased length of stay in the emergency department as well as an increased rate of admission to the hospital. Data regarding the above factors were abstracted from a sample of adult patients (n=347) presenting to the New York Methodist hospital emergency department from June 1st, 2013 to May 31st, 2014. The review of patients presenting to the emergency department with abdominal/pelvic pain demonstrated that patients with lengths of stay greater than four hours had a significantly higher value for age, weight, BMI, and blood pressure compared to those with lengths of stay less than four hours. Additionally, patients that were admitted to the hospital had a statistically significantly higher value for age, pain scores, systolic blood pressure, and heart rate. The identification of factors associated with longer lengths of stay provides the first step in identifying how to improve patients’ access to care in a more time efficient manner. Understanding what factors account for delays in care and discharge will allow for more efficient allocation of time and resources to the patients that need it most.

Background: Recent studies in noise-induced and idiopathic sensorineural hearing loss have suggested that magnesium supplementation may lessen both hearing loss and the severity of tinnitus in patients. Further epidemiological evidence indicates that all age groups of Americans fall short of the recommended daily allowance for magnesium by 100 mg daily. Purpose: The purpose of this study was to examine any potential benefit in lessening the severity of tinnitus in patients taking supplemental magnesium. Research Design: The study was a single-arm, open-label, before-and-after study of oral magnesium (532 mg per day) in 26 patients for 3 months. Tinnitus severity was evaluated and recorded daily by the patient using the Tinnitus Distress Rating (TDR) scale of 0 (no tinnitus) to 10 (worst possible tinnitus). The Tinnitus Handicap Inventory (THI) was administered before and at the end of the study, and scores were converted to the grades of the 5-item Tinnitus Severity Scale (TSS).As a phase 2 study, the current design could not distinguish the effect of treatment from a placebo effect or regression to the mean. All data were collected at Mayo Clinic in Scottsdale, Arizona. 3 Study Sample: Patients with moderate to very severe tinnitus (TDR score of 3 through 8). Intervention: Daily magnesium supplementation, 532 mg; patient completion of the THI; and daily self-report of TDR. Data Collection and Analysis: The main outcome measures were mean TDR scale scores and THI scores as converted to TSS grades. The primary analysis was done on the basis of intention to treat. Results: Twenty-six patients were enrolled; 19 completed the study. The extent of handicap, as measured by THI/TSS, for subjects with slight or greater impairment was significantly decreased (P=.03). Patients who ranked slight or greater on the THI/TSS before intervention showed a significant decrease in the severity of their tinnitus at post-testing (P=.008). Conclusion: The results suggest that magnesium may have a beneficial effect on perception of tinnitus-related handicap when scored with the THI. Keywords: Magnesium; Tinnitus; Tinnitus Distress Rating; Tinnitus Handicap Inventory; Tinnitus Severity Scale

Introduction: Myocardial protection strategies are a central component of neonatal arterial switch operations. Traditionally antegrade cardioplegia through the aortic root has been the method of delivery, but use of retrograde cardioplegia via the coronary sinus has become the standard of practice by many in the field. Methods: After obtaining IRB approval and informed consent, a retrospective chart review was done to assess outcomes between 48 patients receiving antegrade (n= 5) and retrograde (n= 43) cardioplegia during neonatal switch operations. Preoperative demographics and postoperative outcomes were compared between the two groups. Results: Patients from the retrograde cardioplegia group demonstrated a trend towards shorter postoperative ventilation days (6.67 +/- 8.57 vs. 10.2 +/- 10.1) and hospital length of stay (18.3 +/- 15.3 vs. 24.8 +/- 11.8) which were not statistically significant. Patients receiving retrograde cardioplegia demonstrated a trend towards an increased incidence of postoperative arrhythmias which was not statistically significant. The retrograde group also demonstrated an increased cardiopulmonary bypass (CPB) time (95.6 +/- 36.59 vs. 146.74 +/- 44.26) and a trend towards an increased aortic cross clamp (ACC) time (74.4 +/- 24.42 vs. 101.30 +/- 29.56) which was not statistically significant. All patients survived to discharge in both groups. With results trending towards shorter hospital length of stays, postoperative ventilation days and zero mortality in patients receiving retrograde cardioplegia, it can be utilized as a safe and efficacious strategy for myocardial protection during neonatal switch operations.

Vitamin D and resveratrol have been widely researched in recent years, especially their apparent abilities to impact a host of physiological processes. Resveratrol, a phytoalexin found in various berries, peanuts, and other vegetables, is purported to possess anti-aging, anti-inflammatory, antioxidant, anticancer, neuroprotective, and antiarthritic properties, while the classical endocrine functions of vitamin D are the control of calcium and phosphate homeostasis. The biologically active metabolite of vitamin D, 1,25-dihydroxyvitamin D (1,25D), is typically synthesized in the kidney, bound to vitamin D binding protein, and shuttled to cellular target sites. Mounting data on the effect of locally synthesized 1,25D in immune, epithelial, neural, and other tissues have led to an increased awareness of the myriad functions of vitamin D, including detoxification, cellular aging and its modulation, immune regulation, neurotransmitter activity, and metabolic control. Both endocrine and intracrine actions of vitamin D are mediated by the vitamin D receptor (VDR), a nuclear receptor that controls vitamin D-directed transcription of target genes. Importantly, the VDR has numerous polymorphisms, one of which results in two phenotypically distinct isoforms, designated M1 and M4. VDR M4 is postulated to be more active than M1 in vitamin D-dependent transactivation. Variable binding affinities between the two isoforms and VDR interacting proteins such as TFIIB and RXR have also been observed. Another protein known to interact with VDR is β-catenin, the mediator of the Wnt/β-catenin signaling pathway that can drive colorectal carcinogenesis. The goal of this study was to investigate the ability of vitamin D and resveratrol to regulate the Wnt/β-catenin system via stimulation of β-catenin-VDR (both M1 and M4) interaction and subsequent inhibition of β-catenin-mediated transcription. The current data reported herein support and extend previous work by demonstrating that VDR binds directly to β-catenin and that both vitamin D and resveratrol appear to enhance this interaction. We also present data that 1,25D-stimulated VDR is capable of inhibiting β-catenin transcriptional activity. Significantly, we have shown that the two common VDR polymorphisms M1 and M4, are functionally variable, both in their induction of vitamin D-dependent genes and in their inhibition of β-catenin-mediated transcription. VDR M4 exhibits both elevated transactivation and amplified capacity for β-catenin suppression compared to M1, and studies employing site-directed mutagenesis of VDR implicate the glutamic acid at position 2 as being responsible for the reduced activity of the M1 variant. Both polymorphic VDR variants display 1,25D-mediated enhancement of -catenin association, with the M1 SNP possessing a lower basal (-1,25D) binding to this protein partner but a higher fold stimulation in -catenin interaction in the presence of 1,25D. Taken together, these data support the notions that VDR influences pathways important for colorectal carcinoma (CRC) development, and that supplementation with vitamin D and resveratrol may reduce colon cancer risk in the general population, especially in individuals with the less active M1 VDR polymorphism. A comprehensive understanding of 1,25D and resveratrol action in VDR signaling may allow for a more personalized approach toward treating vitamin D–related disorders and evaluating risk for carcinogenesis.