Leptin-Mediated Induction of IL-6 Expression in Hofbauer Cells Contributes to Preeclampsia Pathogenesis.

Leptin plays a crucial role in regulating energy homoeostasis, neuroendocrine function, metabolism, and immune and inflammatory responses. The adipose tissue is a main source of leptin, but during pregnancy, leptin is also secreted primarily by the placenta. Circulating leptin levels peak during the second trimester of human pregnancy and fall after labor. Several studies indicated a strong association between elevated placental leptin levels and preeclampsia (PE) pathogenesis and elevated serum interleukin-6 (IL-6) levels in PE patients. Therefore, we hypothesized that a local increase in placental leptin production induces IL-6 production in Hofbauer cells (HBCs) to contribute to PE-associated inflammation. We first investigated HBCs-specific IL-6 and leptin receptor (LEPR) expression and compared their immunoreactivity in PE vs. gestational age-matched control placentas. Subsequently, we examined the in vitro regulation of IL-6 as well as the phosphorylation levels of intracellular signaling proteins STAT3, STAT5, NF-κB, and ERK1/2 by increasing recombinant human leptin concentrations (10 to 1000 ng/mL) in primary cultured HBCs. Lastly, HBC cultures were incubated with leptin ± specific inhibitors of STAT3 or STAT5, or p65 NF-κB or ERK1/2 MAPK signaling cascades to determine relevant cascade(s) involved in leptin-mediated IL-6 regulation. Immunohistochemistry revealed ~three- and ~five-fold increases in IL-6 and LEPR expression, respectively, in HBCs from PE placentas. In vitro analysis indicated that leptin treatment in HBCs stimulate IL-6 in a concentration-dependent manner both at the transcriptional and secretory levels (p < 0.05). Moreover, leptin-treated HBC cultures displayed significantly increased phosphorylation levels of STAT5, p65 NF-κB, and ERK1/2 MAPK and pre-incubation of HBCs with a specific ERK1/2 MAPK inhibitor blocked leptin-induced IL-6 expression. Our in situ results show that HBCs contribute to the pathogenesis of PE by elevating IL-6 expression, and in vitro results indicate that induction of IL-6 expression in HBCs is primarily leptin-mediated. While HBCs display an anti-inflammatory phenotype in normal placentas, elevated levels of leptin may transform HBCs into a pro-inflammatory phenotype by activating ERK1/2 MAPK to augment IL-6 expression.

Spiritual Caregiving and Assessments for America's Religious 'Nones': A Chaplaincy Perspective.

One in four American patients now identify as religiously unaffiliated. This study utilizes thematic analysis to deliver qualitative results from in-depth interviews conducted with five chaplains at a premier cancer research institution in Florida to envision what care for their spiritual dimension should look like in practice. It demonstrates why the chaplains interviewed suggested that spiritual caregiving still contributes to their holistic wellbeing, and it suggests how spiritual care and assessments may be provided to so-called religious 'nones'-or those who identify as spiritual but not religious, not religiously affiliated, secular humanist, atheist, agnostic, and so on. We conclude with a novel spirituality assessment for use while serving this patient population.

Ethanol-regulated genes that contribute to ethanol sensitivity and rapid tolerance in Drosophila.

BACKGROUND: Increased ethanol intake, a major predictor for the development of alcohol use disorders, is facilitated by the development of tolerance to both the aversive and pleasurable effects of the drug. The molecular mechanisms underlying ethanol tolerance development are complex and are not yet well understood. METHODS: To identify genetic mechanisms that contribute to ethanol tolerance, we examined the time course of gene expression changes elicited by a single sedating dose of ethanol in Drosophila, and completed a behavioral survey of strains harboring mutations in ethanol-regulated genes. RESULTS: Enrichment for genes in metabolism, nucleic acid binding, olfaction, regulation of signal transduction, and stress suggests that these biological processes are coordinately affected by ethanol exposure. We also detected a coordinate up-regulation of genes in the Toll and Imd innate immunity signal transduction pathways. A multi-study comparison revealed a small set of genes showing similar regulation, including increased expression of 3 genes for serine biosynthesis. A survey of Drosophila strains harboring mutations in ethanol-regulated genes for ethanol sensitivity and tolerance phenotypes revealed roles for serine biosynthesis, olfaction, transcriptional regulation, immunity, and metabolism. Flies harboring deletions of the genes encoding the olfactory co-receptor Or83b or the sirtuin Sir2 showed marked changes in the development of ethanol tolerance. CONCLUSIONS: Our findings implicate novel roles for these genes in regulating ethanol behavioral responses.

Vasectomy Simulation Curriculum and Trainer with Enhanced Face, Content and Construct Validity.

INTRODUCTION: We assessed the face, content and construct validity of a newly created vasectomy simulation module. METHODS: Pre-simulation and post-simulation surveys quantifying simulation effectiveness, impact on confidence level and critiques of the overall design were obtained in July 2015 to assess face and content validity. Residents were subdivided based on year of residency and construct validity was ascertained via a 20-objective checklist and individual Likert score as graded by a single attending physician in a blinded fashion. RESULTS: Two medical students and 8 residents (2 Pre-Urology, 2 Uro-1, 2 Uro-2 and 2 Uro-3) were included in the analysis. The response rate was 100% (10 of 10) for the simulation exercise and all residents (100%, 8 of 8) were used in the metric data analysis. Simulation increased the confidence to perform a vasectomy independently on average 1.58 points based on pre-simulation and post-simulation questionnaire analysis (95% CI 1.09-2.89, p=0.02). Training year had a significantly positive association (overall p <0.01) with number of objectives completed. CONCLUSIONS: Our enhanced vasectomy simulation module demonstrated excellent face, content and construct validity.

Ethanol sensitivity and tolerance in long-term memory mutants of Drosophila melanogaster.

BACKGROUND: It has become increasingly clear that molecular and neural mechanisms underlying learning and memory and drug addiction are largely shared. To confirm and extend these findings, we analyzed ethanol-responsive behaviors of a collection of Drosophila long-term memory mutants. METHODS: For each mutant, sensitivity to the acute uncoordinating effects of ethanol was quantified using the inebriometer. Additionally, 2 distinct forms of ethanol tolerance were measured: rapid tolerance, which develops in response to a single brief exposure to a high concentration of ethanol vapor; and chronic tolerance, which develops following a sustained low-level exposure. RESULTS: Several mutants were identified with altered sensitivity, rapid or chronic tolerance, while a number of mutants exhibited multiple defects. CONCLUSIONS: The corresponding genes in these mutants represent areas of potential overlap between learning and memory and behavioral responses to alcohol. These genes also define components shared between different ethanol behavioral responses.

Synthesis and Bioconversion of Curcumin Analogs.

Hydrogdnation of curcumin (1), a chemopreventive agent from Turmeric (Curcuma longa L.) yielded three major compounds: 1,7-bis(4-hydroxy-3- methoxyphenyl)heptane-3,5-dione (2), 5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptan-3-one (3), and 1,7-bis(4-hydroxy-3-methoxyphenyl)heptane- 3,5-diol (4). Incubation of compound (2) with Beauveria bassiana ATCC 7159 afforded the hexahydrocurcumin (3) as the sole metabolite while biotransformation.of curcumin (1) with B. bassiana gave metabolites 2-4 along with the curcumin-4'-0-4"'-O-methyl-ß-D-glucopyranoside (5) and octahydrocurcumih-4'-O-4"'-O-methyl--ß-D-glucopyranoside (6). The bioconversion of curcumin (1) with Rhizopus oryzae ATCC 11145 yielded analogs 2-4 while no transformation of curcumin (1) was observed with Aspergillus niger ATCC 16888. The preparation, structural elucidation and biological activities of these metabolites are reported herein.

Evidence-Based Management of Infertility in Women With Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a polygenic disorder with a variable phenotype that commonly affects women of reproductive age. It can significantly affect a woman's ability to conceive and her quality of life. Effective treatment includes a multidisciplinary team approach that addresses the physiological and psychosocial manifestations of the disorder. Nurses have an important role in promoting early detection, education, and identification of services and resources to improve a woman's fertility and lifelong health.

Open Roux-en-Y gastric bypass in 925 patients without mortality.

BACKGROUND: Open Roux-en-Y gastric bypass has become the gold standard for bariatric surgery. Safety has always been a concern with this elective surgery, especially among the general public. With increasing numbers of bariatric surgeries being performed, the public eye is once again focused on safety and outcomes for these patients. METHODS: Nine hundred twenty-five consecutive open Roux-en-Y gastric bypass patients were reviewed. Charts were retrospectively reviewed for early complications, late complications, and resolution of medical comorbidities. RESULTS: There were no deaths in this study group. The average body mass index (BMI) was 51. Eight leaks at the anastomosis occurred with no reoperations. Hypertension resolved in 70% and diabetes mellitus resolved in 58% of patients. CONCLUSIONS: Open Roux-en-Y gastric bypass is a safe operation, even with increasing numbers of surgeries being performed. Major complications are low and improvement of medical comorbidities is significant. A multidisciplinary team approach helps to improve care and clinical outcomes.

Courtship communication and perception.

Although ethologists have detailed courtship rituals for many species, courting behavior of humans has not received extensive study from an ethological standpoint. Yet there are clearly facial expressions and gestures that are commonly labeled "flirting behaviors." These nonverbal signals have been documented recently by several investigators in field studies, but the receptivity of nonverbal courtship signals is still in question. The current research project attempted to assess the perceptual skill of naive male and female observers who were presented videotaped samples of females' nonverbal courtship and rejection behaviors and asked to rate their intensity. The results showed that overall, men rated invitational behaviors more positively than women. In contrast, signals of rejection were seen by men as sending a less potent message than that perceived by women. Evolutionary theory may offer a framework for understanding these results.

An evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol.

Anaplastic lymphoma kinase (Alk) is a gene expressed in the nervous system that encodes a receptor tyrosine kinase commonly known for its oncogenic function in various human cancers. We have determined that Alk is associated with altered behavioral responses to ethanol in the fruit fly Drosophila melanogaster, in mice, and in humans. Mutant flies containing transposon insertions in dAlk demonstrate increased resistance to the sedating effect of ethanol. Database analyses revealed that Alk expression levels in the brains of recombinant inbred mice are negatively correlated with ethanol-induced ataxia and ethanol consumption. We therefore tested Alk gene knockout mice and found that they sedate longer in response to high doses of ethanol and consume more ethanol than wild-type mice. Finally, sequencing of human ALK led to the discovery of four polymorphisms associated with a low level of response to ethanol, an intermediate phenotype that is predictive of future alcohol use disorders (AUDs). These results suggest that Alk plays an evolutionary conserved role in ethanol-related behaviors. Moreover, ALK may be a novel candidate gene conferring risk for AUDs as well as a potential target for pharmacological intervention.

Human nonverbal courtship behavior--a brief historical review.

This article reviews research findings documenting the nature of nonverbal courtship behavior compiled through both observation and self-report methods. I briefly present the major theoretical perspectives guiding research methodologies used in the field and in the laboratory. Studies of verbal courtship, including those conducted via computer, via text messaging, or through personal advertisement, are not included in this review. The article ends by elucidating some key features of human nonverbal courtship behavior that have become apparent after scrutinizing these data.

Rapid and chronic: two distinct forms of ethanol tolerance in Drosophila.

BACKGROUND: Ethanol tolerance, defined as a reduction in the intensity of the effects of ethanol upon continuous or repeated exposure, is a hallmark of alcoholism. Tolerance may develop at the cellular or neural systems levels. The molecular changes underlying ethanol tolerance are not well understood. We therefore explored the utility of Drosophila, with its accessibility to genetic, molecular, and behavioral analyses, as a model organism to study tolerance development in response to different ethanol-exposure regimens. METHODS: We describe a new assay that quantifies recovery from ethanol intoxication in Drosophila. Using this recovery assay, we define ethanol pre-exposure paradigms that lead to the development of tolerance. We also use the inebriometer, an assay that measures the onset of intoxication, to study the effects of pharmacological and genetic manipulations on tolerance development. RESULTS: We show that flies develop different forms of ethanol tolerance: rapid tolerance, induced by a single short exposure to a high concentration of ethanol, and chronic tolerance, elicited by prolonged exposure to a low concentration of the drug. Neither rapid nor chronic tolerance involves changes in ethanol pharmacokinetics, implying that they represent functional rather than dispositional tolerance. Chronic and rapid tolerance can be distinguished mechanistically: chronic tolerance is disrupted by treatment with the protein synthesis inhibitor cycloheximide, whereas rapid tolerance is resistant to this treatment. Furthermore, rapid and chronic tolerance rely on distinct genetic pathways: a mutant defective for octopamine biosynthesis shows reduced rapid tolerance but normal chronic tolerance. CONCLUSIONS: Flies, like mammals, develop tolerance in response to different ethanol-exposure regimens, and this tolerance affects both the onset of and the recovery from acute intoxication. Two forms of tolerance, rapid and chronic, are mechanistically distinct, because they can be dissociated genetically and pharmacologically.