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Objective: Polybrominated diphenyl ethers (PBDEs) enhance basal and bacteria-stimulated production of proinflammatory cytokines by the placenta and may also increase the risk of preterm birth and neurodevelopmental disorders. Whether or not other brominated flame retardants such as Tetrabromobisphenol A (TBBPA) have similar properties is unclear. Therefore, we evaluated the effects of TBBPA on the production of steroids, as well as biomarkers for inflammation, oxidative stress, and neurodevelopment by the placenta., Methods: Placental explant cultures were established from women undergoing elective Cesarean sections at term and treated with 5-50,000 nM TBBPA in the presence and absence of 10 7  CFU/ml heat-killed E. coli. Concentrations of P 4 , E 2 , testosterone (T), IL-1β, TNF-α, IL-10, HO-1, IL-6, 8-IsoP and BDNF were quantified in the conditioned medium., Results: In the absence of bacteria, TBBPA tended to increase P 4 and T as well as IL-6 and 8-IsoP. For bacteria-treated cultures, TBBPA generally inhibited P 4 , IL-1β, and HO-1 production but enhanced TNF-α and IL-6 production., Conclusions: TBBPA alters placental steroidogenesis to favor T production and increases oxidative stress and placental inflammation as suggested by its promotion of 8-IsoP and IL-6 production. TBBPA may also function as a risk modifier where it enhances bacteria-stimulated production TNF-α and IL-6 but reduces HO-1 production, however, this was balanced by reductions in IL-1β. Further studies are warranted to determine if TBBPA increases the risk of adverse pregnancy outcomes such as preterm birth, pPROM and neurodevelopmental disorders such as autism that have been associated with increased production of proinflammatory cytokines, oxidative stress and/or T., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Even when diagnosed prior to metastasis, pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with almost 90% lethality, emphasizing the need for new therapies optimally targeting the tumors of individual patients., Experimental Design: We first developed a panel of new physiologic models for study of PDAC, expanding surgical PDAC tumor samples in culture using short-term culture and conditional reprogramming with the Rho kinase inhibitor Y-27632, and creating matched patient-derived xenografts (PDX). These were evaluated for sensitivity to a large panel of clinical agents, and promising leads further evaluated mechanistically., Results: Only a small minority of tested agents was cytotoxic in minimally passaged PDAC cultures in vitro Drugs interfering with protein turnover and transcription were among most cytotoxic. Among transcriptional repressors, triptolide, a covalent inhibitor of ERCC3, was most consistently effective in vitro and in vivo causing prolonged complete regression in multiple PDX models resistant to standard PDAC therapies. Importantly, triptolide showed superior activity in MYC-amplified PDX models and elicited rapid and profound depletion of the oncoprotein MYC, a transcriptional regulator. Expression of ERCC3 and MYC was interdependent in PDACs, and acquired resistance to triptolide depended on elevated ERCC3 and MYC expression. The Cancer Genome Atlas analysis indicates ERCC3 expression predicts poor prognosis, particularly in CDKN2A-null, highly proliferative tumors., Conclusions: This provides initial preclinical evidence for an essential role of MYC-ERCC3 interactions in PDAC, and suggests a new mechanistic approach for disruption of critical survival signaling in MYC-dependent cancers. Clin Cancer Res; 22(24); 6153-63. ©2016 AACR., Competing Interests: The authors disclose no potential conflicts of interest., (©2016 American Association for Cancer Research.)

Background: Computed tomography (CT) has been validated to identify and classify placental abruption following blunt trauma. The purpose of this study was to demonstrate improvement in fetal survival when delivery occurs by protocol at the first sign of class III fetal heart rate tracing in pregnant trauma patients with a viable fetus on arrival and CT evidence of placental perfusion 50% or less secondary to placental abruption., Methods: This is a retrospective review of pregnant trauma patients at 26 weeks' gestation or greater who underwent abdominopelvic CT as part of their initial evaluation. Charts were reviewed for CT interpretation of placental pathology with classification of placental abruption based upon enhancement (Grade 1, >50% perfusion; Grade 2, 25%-50% perfusion; Grade 3, <25% perfusion), as well as need for delivery and fetal outcomes., Results: Forty-one patients met inclusion criteria. Computed tomography revealed evidence of placental abruption in six patients (15%): Grade 1, one patient, Grade 2, one patient, and Grade 3, four patients. Gestational ages ranged from 26 to 39 weeks. All patients with placental abruption of Grade 2 or greater developed concerning fetal heart tracings and underwent delivery emergently at first sign. Abruption was confirmed intraoperatively in all cases. Each birth was viable, and Apgar scores at 10 minutes were greater than 7 in 80% of infants, all of whom were ultimately discharged home. The remaining infant was transferred to an outside facility., Conclusions: Delivery at first sign of nonreassuring fetal heart rate tracings in pregnant trauma patients (third trimester) with placental abruption of Grade 2 or greater can lead to improved fetal outcome., Level of Evidence: Therapeutic/care management study, level III.

Study Objective: In 2006, the Institute of Medicine emphasized substantial potential to expand organ donation opportunities through uncontrolled donation after circulatory determination of death (uDCDD). We pilot an out-of-hospital uDCDD kidney program for New York City in partnership with communities that it was intended to benefit. We evaluate protocol process and outcomes while identifying barriers to success and means for improvement., Methods: We conducted a prospective, participatory action research study in Manhattan from December 2010 to May 2011. Daily from 4 to 12 pm, our organ preservation unit monitored emergency medical services (EMS) frequencies for cardiac arrests occurring in private locations. After EMS providers independently ordered termination of resuscitation, organ preservation unit staff determined clinical eligibility and donor status. Authorized parties, persons authorized to make organ donation decisions, were approached about in vivo preservation. The study population included organ preservation unit staff, authorized parties, passersby, and other New York City agency personnel. Organ preservation unit staff independently documented shift activities with daily operations notes and teleconference summaries that we analyzed with mixed qualitative and quantitative methods., Results: The organ preservation unit entered 9 private locations; all the deceased lacked previous registration, although 4 met clinical screening eligibility. No kidneys were recovered. We collected 837 notes from 35 organ preservation unit staff. Despite frequently recounting protocol breaches, most responses from passersby including New York City agencies were favorable. No authorized parties were offended by preservation requests, yielding a Bayesian posterior median 98% (95% credible interval 76% to 100%)., Conclusion: In summary, the New York City out-of-hospital uDCDD program was not feasible. There were frequent protocol breaches and confusion in determining clinical eligibility. In the small sample of authorized persons we encountered during the immediate grieving period, negative reactions were infrequent., (Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

The Sleep and Pain Diathesis (SAPD) Model predicts that sleep quality is related to Fibromylagia (FM) outcomes such as disability and depression and that these relationships are mediated by both pain and impaired emotional dysregulation. The purpose of this paper is to provide a preliminary test of this model using cross-sectional data. 35 adult women, who had been living with FM for an average of 13 years, completed a battery of questionnaires that included reports of pain, sleep, affect, and disability. Consistent with this model, FM patients who reported more disrupted sleep also reported higher levels of psychological disability (i.e., BDI depression symptoms) and physical disability. Moreover, the trajectory of the relationship between sleep and pain appears to be mediated by cognitive processes such as increased pain helplessness and, thus, the relationship between sleep and disability appears to be mediated via pain. These data are consistent with the SAPD model, and lend support for the need to include sleep related factors as a critical contributor to our understanding of FM.

Excessively hot tap water results in an estimated 1500 hospital admissions and up to 50 deaths in the United States every year. This study reviewed the current state of tap water temperature regulation in the United States, including the model plumbing code standards on which state legislation in this area is based; assessed the level of public awareness regarding the risk, prevalence, and severity of such injuries; and identified specific prevention measures. Relevant information was obtained from state legislative codes, model code development organizations, the US Consumer Product Safety Commission, and a survey of knowledge, attitudes, and behaviors related to tap water temperature safety. Model building and plumbing codes related to tap water temperature regulation and their subsequent adoption by state legislatures vary widely across the United States. The states also vary with respect to the authority provided to lower levels of government (counties or municipalities) to modify and enforce code provisions. Public awareness of hot tap water hazards and implementation of preventive measures are limited. A broader and more uniform application of codes for regulating tap water temperature in both institutional and residential settings can be achieved through input from affected users, government agencies, legislators, advocacy organizations, and the general public. Safer hot water temperatures and a reduction in scald injuries can be achieved through regulating hot water temperature level at the thermostat, installing temperature-regulating valves at the tap, and raising public awareness of hot tap water hazards.

The group psychotherapy of adolescents comorbid for psychiatric and substance abuse problems is fraught with inconsistent attendance, frequent verbal and physical disruptions by the adolescents, and intense countertransference toward patients and their parents on the part of treating staff. A relational constructionist approach assists staff and patients in overcoming these obstacles and in focusing on the adolescents' search for personal meaning. Multiple group psychotherapy conducted in a combined day treatment and high school program is described and illustrated by case examples during the course of a year of treatment. These examples illustrate the importance of a relational non-hierarchical approach to adolescent patients by treating staff.

Patients with end-stage renal disease (ESRD) have an annual mortality rate exceeding 20%, although some survive many years. The ESRD population has a high incidence of sleep disorders, including sleep apnea and periodic limb movements in sleep (PLMS). Sleep disorders result in sleep deprivation, which can negatively affect immune function and cardiovascular-related outcomes, common causes of death in patients with ESRD. This study examined predictors of mortality in patients with ESRD with sleep problems. Twenty-nine consecutive patients with ESRD reporting disrupted sleep or daytime sleepiness were studied by all-night polysomnography. All patients were followed up until death, transplantation, or study termination. Among the variables studied, including such previously reported predictors as serum albumin level, urea reduction ratio, and hematocrit, only the PLMS index (PLMSI), arousing PLMSI (APLMSI), and total number of arousals per hour of sleep significantly predicted mortality. The 20-month survival rate with a PLMSI less than 20 was greater than 90% versus 50% for a PLMSI of 20 or greater (exact log-rank, P = 0.007). For the deceased versus survivor groups, mean PLMSI was 119.1 versus 19.8 (P = 0.01) and APLMSI was 48.1 versus 7.8 (P = 0.00006), with a mean survival of 10.3 versus greater than 25.5 months, respectively (P = 0.001). Median survival of patients with a PLMSI greater than 80 was only 6 months. PLMSI, APLMSI, and total arousals per hour of sleep were strongly associated with mortality in patients with ESRD with sleep disorders independent of other factors and may be novel predictors of near-term mortality.

End-stage renal disease (ESRD) is commonly associated with complaints of disturbed sleep and sleep disorders, frequently related to periodic limb movements in sleep (PLMS) or sleep apnea that may result in daytime sleepiness and other sequelae. Improvements in quality of life, including subjective sleep quality, have been reported in ESRD patients treated with recombinant human erythropoietin (rHuEPO). We investigated the objective effects of normalizing hematocrit on sleep disorders, sleep patterns, and daytime ability to remain awake in ESRD patients. Ten hemodialysis patients with sleep complaints while on rHuEPO therapy were studied by polysomnography while moderately anemic (mean hematocrit, 32.3%) and again when hematocrit was normalized (mean hematocrit, 42.3%) by increased rHuEPO dosing. Sleep patterns and associated parameters were monitored. Delivered dialysis dose and iron storage factors were monitored. Maintenance of Wakefulness Testing (MWT) was performed to assess daytime alertness/sleepiness. All 10 subjects experienced highly statistically significant reductions in the total number of arousing PLMS (P = 0.002). Nine of 10 subjects showed reductions in both the Arousing PLMS Index (P < 0.01) and the PLMS Index (P = 0.03) when hematocrit was normalized. Measures of sleep quality showed trends to improved quality of sleep. MWT demonstrated significant improvement in the length of time patients were able to remain awake (9.7 versus 17.1 minutes; P = 0.04). RHuEPO therapy with full correction of anemia reduces PLMS, arousals from sleep, and sleep fragmentation while allowing for more restorative sleep and improved daytime alertness. These findings may explain one mechanism for the improved quality-of-life parameters reported in ESRD patients treated with rHuEPO.

Multiple group psychotherapy was employed as the primary treatment modality in a day-treatment program as an innovative multifaceted approach to treating adolescents comorbid for psychiatric and substance abuse diagnoses. The concurrent educational program included a high school on site. The groups included Substance Abuse Group, which promoted the 12-step model; Health Group; Psychotherapy Group; Leisure Time Group; Self-Awareness Group; and Multiple Family Group. The effect of the multiple groups was to provide a variety of experiences focusing on varied aspects of normal and dysfunctional adolescent development. Together the combination of groups served to strengthen the participants' cohesiveness, communicating skills, and hopefulness.