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Objective: To characterize the relationship between maternal obesity, fetal abdominal size, and neonatal morbidity in pregnancies complicated by fetal growth restriction (FGR). Study design: Pregnancies complicated by FGR which resulted in delivery of a live, singleton, non-anomalous infant at a single center between 2002 and 2013 were identified in a large, NIH-funded database of detailed pregnancy and delivery information extracted by trained research nurses. Pregnancies complicated by diabetes were excluded. Fetal biometry measurements from 3rd trimester ultrasounds performed at the same institution were extracted from another institutional database. Pregnancies were divided into cohorts based on fetal abdominal circumference (AC) gestational age percentile (30 kg/m2. The primary outcome was a composite of neonatal morbidity (CM) including 5-minute Apgar 50th or 30-49th ‘centile, those these differences did not reach statistical significance (Table 2). Conclusion: Our study identified no significant difference in risk of CM among growth-restricted infants of obese vs. non-obese mothers, including among infants with very small AC. More research is needed to further examine the potential relationships postulated here.

Objective This study aimed to the assess risk of respiratory morbidity in neonates born to women with gestational diabetes mellitus (GDM) delivered after labor compared with those delivered without exposure to labor. Study Design This is a secondary analysis of a prospective single-center cohort study of singleton pregnancies complicated by GDM. Neonates who were liveborn and delivered at ≥34 weeks' gestation were included. The primary outcome was respiratory morbidity defined as respiratory distress syndrome (RDS) or transient tachypnea of the newborn (TTN) resulting in neonatal intensive care unit (NICU) admission. Neonates born after labor (either spontaneous or induced) were compared with those delivered by cesarean delivery without labor. Associations between labor and neonatal morbidities were estimated using logistic regression. Covariates were adjusted for if they differed significantly between neonates exposed to and not exposed to labor (p Results Of the 581 neonates meeting study inclusion criteria, 23.2% delivered without exposure to labor. Those who did and did not experience labor delivered at similar gestational ages (38.6 vs. 38.4 weeks). Thirty-six neonates (6.2%) developed RDS or TTN and were admitted to the NICU. Exposure to labor was associated with a lower frequency of respiratory morbidity requiring admission to NICU, 4.9% (22/446) versus 10.4% (14/135) (p = 0.04). After adjusting for parity, body mass index, birth weight, gestational weight gain more than Institute of Medicine guidelines, race, and exposure to labor were associated with an adjusted odds ratio of 0.41 (95% confidence interval: 0.18–0.89). Conclusion Exposure to labor was associated with decreased odds of respiratory morbidity in neonates born to mothers with GDM. Limiting elective cesarean in this population can reduce health care costs and optimize neonatal health. Key Points

Although circular RNAs (circRNAs) are enriched in the brain, their relevance for brain function and psychiatric disorders is poorly understood. Here, we show that circHomer1 is inversely associated with relative HOMER1B mRNA isoform levels in both the orbitofrontal cortex (OFC) and stem-cell-derived neuronal cultures of subjects with psychiatric disorders. We further demonstrate that in vivo circHomer1 knockdown (KD) within the OFC can inhibit the synaptic expression of Homer1b mRNA. Furthermore, we show that circHomer1 directly binds to Homer1b mRNA and that Homer1b-specific KD increases synaptic circHomer1 levels and improves OFC-mediated behavioral flexibility. Importantly, double circHomer1 and Homer1b in vivo co-KD results in a complete rescue in circHomer1-associated alterations in both chance reversal learning and synaptic gene expression. Lastly, we uncover an RNA-binding protein that can directly bind to circHomer1 and promote its biogenesis. Taken together, our data provide mechanistic insights into the importance of circRNAs in brain function and disease.

Although circular RNAs (circRNAs) are abundantly expressed in the mammalian brain and preferentially-derived from synaptic genes, their relevance for brain function and psychiatric disorders and their interactions with neuronal protein-coding gene expression still remain poorly understood. Here we show that alterations in the levels of circHomer1, a neuronal-enriched circRNA altered in psychiatric disease that has been shown to influence OFC-mediated cognitive flexibility, are inversely associated with the relative expression of the long linear HOMER1B mRNA isoform in both the orbitofrontal cortex (OFC) and stem cell-derived neuronal cultures of subjects with psychiatric disorders. Using in vivo mature circHomer1-specific knockdown (KD) in adult mouse OFC, we further demonstrate that downregulation of circHomer1 results in increased synaptic expression of Homer1b mRNA. Furthermore, we utilize circRNA antisense purification to show that circHomer1 directly binds to Homer1b mRNA. We then demonstrate that in vivo Homer1b-specific KD increases synaptic circHomer1 levels within the OFC and improves OFC-mediated behavioral flexibility. Importantly, we show that double circHomer1 and Homer1b in vivo co-KD results in a complete rescue in circHomer1-associated alterations in both chance reversal learning and synaptic gene expression. Lastly, we demonstrate that circHomer1 is an experience-dependent circRNA that is significantly altered during chance reversal learning and that variability in its baseline expression within the OFC is significantly inversely correlated to behavioral performance during chance reversal learning. Taken together our data provide novel mechanistic insights into the importance of circRNAs in brain function and disease.

Background Pressure cookers are common kitchen appliances with a good safety record and only rare associated explosions. Case Report Here we present a case of unintentional pressure cooker explosion leading to polytrauma with injuries including pneumothorax, intracranial hemorrhage, open skull fracture, and multiple facial fractures. Why Should an Emergency Physician Be Aware of This? Extreme forces and temperatures are involved in pressure cooking. Given the infrequent but real risk of mechanical failure and the increasing use of such devices to create intentional explosions, emergency physicians should be aware of the potentially significant blast injuries that can be associated with them.

Fetal tachycardia is a rare complication during pregnancy. After exclusion of maternal and fetal conditions that can result in a secondary fetal tachycardia, supraventricular tachycardia is the most common cause of a primary sustained fetal tachyarrhythmia. In cases of sustained fetal supraventricular tachycardia, maternal administration of digoxin, flecainide, sotalol, and more rarely amiodarone, is considered. As these medications have the potential to cause significant adverse effects, we sought to examine maternal safety during transplacental treatment of fetal supraventricular tachycardia. In this narrative review we summarize the literature addressing pharmacologic properties, monitoring, and adverse reactions associated with medications most commonly prescribed for transplacental therapy of fetal supraventricular tachycardia. We also describe maternal monitoring practices and adverse events currently reported in the literature. In light of our findings, we provide clinicians with a suggested maternal monitoring protocol aimed at optimizing safety.

Highlights • Femoral herniation of transplanted ureter is a rare occurrence and has not been documented in the literature to date. • Such patients may present with transplant kidney failure due to obstructive uropathy. • Diagnosis includes physical exam, transplant kidney ultrasound or CT of abdomen and pelvis. • Treatment should include urgent repair of hernia to salvage the transplant ureter and kidney., Introduction Herniation of the ureter after kidney transplant is a rare and under documented event. Many of these herniations are due to abdominal wall defects or ureteral redundancy. After an extensive review of available literature, there has not been a reported case of a femoral herniation of ureter after kidney transplant. We report a case of late allograft renal transplant failure due to ureteral obstruction secondary to femoral herniation of the ureter. Case presentation We report a case of 64 year old male with a history of kidney transplant, who was found to have an inguinal bulge. He was diagnosed with a femoral hernia containing transplant ureter using transplant kidney ultrasound and CT of the abdomen and pelvis. Subsequently he developed transplant kidney failure due to obstructive uropathy from the femoral hernia. The patient underwent a femoral hernia repair with biologic mesh. Compromised ureter was excised and a neoureterocystostomy was created. Post operatively his creatinine returned to baseline. Discussion In our literature search there are two types of inguinal ureteral hernias described. Paraperitoneal, which makes up the majority of the cases, and extraperitoneal. There are no classifications for ureteral femoral hernias. We may extract these definitions to femoral hernias, as evidenced by our case where we encountered a paraperitoneal femoral hernia containing transplant kidney ureter. Conclusion To the best of our knowledge this is the first reported case of a femoral ureter hernia. Due to its rarity in the literature, an understanding of management is critical to patient outcome.

Ghrelin receptors are expressed by key components of the arousal system. Exogenous ghrelin induces behavioral activation, promotes wakefulness and stimulates eating. We hypothesized that ghrelin-sensitive mechanisms play a role in the arousal system. To test this, we investigated the responsiveness of ghrelin receptor knockout (KO) mice to two natural wake-promoting stimuli. Additionally, we assessed the integrity of their homeostatic sleep-promoting system using sleep deprivation. There was no significant difference in the spontaneous sleep-wake activity between ghrelin receptor KO and wild-type (WT) mice. WT mice mounted robust arousal responses to a novel environment and food deprivation. Wakefulness increased for 6 h after cage change accompanied by increases in body temperature and locomotor activity. Ghrelin receptor KO mice completely lacked the wake and body temperature responses to new environment. When subjected to 48 h food deprivation, WT mice showed marked increases in their waking time during the dark periods of both days. Ghrelin receptor KO mice failed to mount an arousal response on the first night and wake increases were attenuated on the second day. The responsiveness to sleep deprivation did not differ between the two genotypes. These results indicate that the ghrelin-receptive mechanisms play an essential role in the function of the arousal system but not in homeostatic sleep-promoting mechanisms.

Background In pharmacologic management of fetal supraventricular tachycardia (SVT), antiarrhythmic agents are administered to the pregnant patient serving as a vehicle of transplacental delivery to the fetus. Given that antiarrhythmic therapy can have profound maternal adverse effects, administration of initial loading and dose adjustments should involve deliberate attention to pharmacologic principles with close maternal monitoring for adverse effects. We reviewed current monitoring practices and maternal complications of transplacental antiarrhythmic therapy for fetal SVT. Methods A query of the Embase database for search terms ”Fetal” or ”Foetal” and ”Supraventricular Tachycardia” or ”SVT” yielded 93 titles, of which 19 articles detailing the modalities of therapy for Fetal SVT were reviewed. Results The 19 articles represented 565 cases of fetal SVT, 111 of which had developed hydrops fetalis. Of these cases, 184 received a course of digoxin alone and 33, 56, and 5 cases received a combination therapy of digoxin with flecainide, sotalol, or amiodarone. Flecainide, Sotalol, and amiodarone were given as monotherapy in 89, 77, and 6 cases, respectively. Maternal monitoring information was available in 15 studies. Investigators performed electrocardiograms (EKGs) at baseline and during follow-up in 12 studies, and monitored electrolytes in five. Two studies reported a mandatory cardiologist consultation for all mothers and two studies considered performing echocardiography in select mothers. Digoxin and flecainide levels were measured in eight and four studies, respectively. Toxicity was reported in 5 patients: two on digoxin monotherapy, two on flecainide monotherapy, and one on combination of digoxin and flecainide. Conclusion Pharmacologic management of fetal SVT is generally safe for mothers with normal baseline cardiac assessments and close monitoring of symptoms, EKG, electrolytes, and/or drug levels. Future prospective studies on the treatment of fetal SVT should also include a systematic monitoring strategy for mothers, with consistent reporting of adverse reactions.

Purpose: Although the genetic alterations in glioblastoma have been well characterized, reports regarding their prognostic effects have been inconsistent. Experimental Design: In this series of 140 consecutive cases of glioblastoma treated at a single center, we analyzed the frequency, age dependency and prognostic effects of TP53 mutation, CDKN2A/p16 deletion, EGFR amplification, as well as loss of chromosome 1p, chromosome 10q, and chromosome 19q. The complete set of genetic alterations was available on 60 of 140 patients. Results: In this cohort of glioblastoma cases, TP53 mutation was significantly associated with patient age. The prognostic effects of TP53 mutation, EGFR amplification, CDKN2A/p16 alterations, and loss of chromosome 1p were dependent on the age of the patient. Conclusions: This is the first observation that the prognostic effects of TP53, 1p, and CDKN2A/p16 alterations are dependent on patient age. These observations concerning the interactions of age and genetic changes in glioblastoma suggest that tumorigenic pathways to glioblastoma vary with the age of the patient and that future molecular marker studies should carefully evaluate the potential age-dependent prognostic effects of these biological variables. The inconsistent or negative prognostic effects of molecular markers reported in prior studies of glioblastoma may be because different effects at different ages may have resulted in a cancellation of an overall effect in the entire cohort.

Ghrelin receptors are expressed by key components of the arousal system. Exogenous ghrelin induces behavioral activation, promotes wakefulness and stimulates eating. We hypothesized that ghrelin-sensitive mechanisms play a role in the arousal system. To test this, we investigated the responsiveness of ghrelin receptor knockout (KO) mice to two natural wake-promoting stimuli. Additionally, we assessed the integrity of their homeostatic sleep-promoting system using sleep deprivation. There was no significant difference in the spontaneous sleep-wake activity between ghrelin receptor KO and wild-type (WT) mice. WT mice mounted robust arousal responses to a novel environment and food deprivation. Wakefulness increased for 6 h after cage change accompanied by increases in body temperature and locomotor activity. Ghrelin receptor KO mice completely lacked the wake and body temperature responses to new environment. When subjected to 48 h food deprivation, WT mice showed marked increases in their waking time during the dark periods of both days. Ghrelin receptor KO mice failed to mount an arousal response on the first night and wake increases were attenuated on the second day. The responsiveness to sleep deprivation did not differ between the two genotypes. These results indicate that the ghrelin-receptive mechanisms play an essential role in the function of the arousal system but not in homeostatic sleep-promoting mechanisms.

Objective Although platinum-based chemotherapy is widely used in malignant pleural mesothelioma, its modest therapeutic effect warrants identification of enhancing agents. As with many cancers, the phosphatidylinositol 3-kinase/Akt pathway is often activated in malignant pleural mesothelioma and has been implicated in the tumor's aggressiveness. Sirolimus is a well-established inhibitor of the mammalian target of rapamycin. We sought to determine whether combination treatment with sirolimus and cisplatin would enhance cell death in malignant pleural mesothelioma. Methods Human malignant pleural mesothelioma cell lines were incubated with sirolimus or cisplatin alone or in combination and assayed for cell viability. To characterize phosphorylation status after treatment, Akt and downstream proteins of mammalian target of rapamycin pathway, p70 S6 kinase and 4E-BP1, were analyzed by Western blot. Effect of combination treatment was also analyzed with extreme drug resistance assay in 12 human malignant pleural mesothelioma tumors with varying resistance to cisplatin. Results Individual malignant pleural mesothelioma cell lines exhibited a range of sensitivities to each drug without correlation with subtype. Sirolimus and cisplatin significantly (P = .029) increased cell death versus either drug alone in 4 cell lines. Combined treatment caused dephosphorylation of Akt, 4E-BP1, and p70 S6 kinase. Cell proliferation was significantly decreased in tumors subjected to sirolimus and cisplatin versus cisplatin or sirolimus alone. Conclusions Sirolimus appears to enhance the cytotoxicity of cisplatin in malignant pleural mesothelioma cell lines through the mammalian target of rapamycin pathway. These results provide a basis for the clinical evaluation of combined sirolimus and cisplatin chemotherapy in malignant pleural mesothelioma.

The goal of this study was to provide nationally representative data on characteristics of patients who died after hip and knee arthroplasty and to determine risk factors for such outcome. Using national in-patient data collected between 1990 and 2004, we identified a cumulative in-hospital mortality rate of 0.35% among an estimated 6 901 324 procedures. The strongest independent risk factors for in-hospital mortality were pulmonary embolism and cerebrovascular complications, which increased the odds for a fatal outcome by approximately 40-fold. Preoperative risk factors for in-hospital mortality were revision total hip arthroplasty, advanced age, and the presence of a number of comorbid diseases, predominantly dementia, renal, and cerebrovascular disease. Our results can be used to identify patients at risk for fatal outcome and implement interventions to reduce such risk.