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In this article we seek to examine what we might learn about the therapist/psychoanalyst's function as selfobject by examining the relationship between the "vocal persona" and the "instrumental persona" in the art song. The comparison was born out of our own life partnership as a therapist, currently studying in a psychoanalytic-Buddhist training program that stresses the presence of the therapist/psychoanalyst as selfobject; and a collaborative pianist who instructs and performs with singers onstage. The concept of selfobject has offered a compelling and fruitful analogy. We explain and demonstrate this analogy using the terms selfobject and instrumental persona, which have in common the willingness to suspend selfhood in order to stand by another- a patient or a vocal persona- so that the latter might take root and flourish.

Metronomic chemotherapy (MET) has been developed to address the shortcomings of maximum-tolerated chemotherapy (MTD) in regard to toxicity and development of resistance mechanisms in the tumor. In colorectal cancer (CRC), MET is a promising novel strategy to treat locally advanced malignancies when used as neoadjuvant chemotherapy (NAC). However, so far there are no preclinical studies to assess the impact of MET NAC in CRC to assess the benefits and challenges of this approach. Here, we used a primary model of CRC (via azoxymethane) to analyze longitudinal changes in angiogenesis in primary tumors under MET and MTD NAC using a combination of diffuse reflectance spectroscopy and mRNA expression (via qPCR). Our results show that MET and MTD NAC lead to increased mean tissue oxygen saturation (8% and 5%, respectively) and oxyhemoglobin (15% and 10%) between weeks 2 and 5 of NAC, and that such increases are caused by distinct molecular signatures in the angiogenic program. Specifically, we find that in the MET group there is a sustained increase in Hif-1a, Aldoa, and Pgk1 expression, suggesting upregulated glycolysis, whereas MTD NAC causes a significant reduction in the expression of the aforementioned genes and of Vegf, leading to vascular remodeling in MTD-treated tumors. Taken together, this study demonstrates the ability of combined optical and molecular methodologies to provide a holistic picture of tumor response to therapy in CRC in a minimally invasive manner., (Copyright © 2022. Published by Elsevier Inc.)

In biomedical research, the outcome of longitudinal studies has been traditionally analyzed using the repeated measures analysis of variance (rm-ANOVA) or more recently, linear mixed models (LMEMs). Although LMEMs are less restrictive than rm-ANOVA as they can work with unbalanced data and non-constant correlation between observations, both methodologies assume a linear trend in the measured response. It is common in biomedical research that the true trend response is nonlinear and in these cases the linearity assumption of rm-ANOVA and LMEMs can lead to biased estimates and unreliable inference. In contrast, GAMs relax the linearity assumption of rm-ANOVA and LMEMs and allow the data to determine the fit of the model while also permitting incomplete observations and different correlation structures. Therefore, GAMs present an excellent choice to analyze longitudinal data with non-linear trends in the context of biomedical research. This paper summarizes the limitations of rm-ANOVA and LMEMs and uses simulated data to visually show how both methods produce biased estimates when used on data with non-linear trends. We present the basic theory of GAMs and using reported trends of oxygen saturation in tumors, we simulate example longitudinal data (2 treatment groups, 10 subjects per group, 5 repeated measures for each group) to demonstrate their implementation in R. We also show that GAMs are able to produce estimates with non-linear trends even when incomplete observations exist (with 40% of the simulated observations missing). To make this work reproducible, the code and data used in this paper are available at: https://github.com/aimundo/GAMs-biomedical-research., (© 2022 John Wiley & Sons Ltd.)

Ulcerative colitis (UC) is a gastrointestinal, autoimmune disease that causes ulceration and inflammation of the colon with an incidence of 10 out of every 100,000 people in North America and Western Europe. Though the specific cause is unknown, several studies have demonstrated that inflammatory cells as well as environmental variables, genetics, and lifestyle behaviors can play a role in the long-term inflammatory response. Researchers have commonly used immunohistochemistry, western blotting and gene sequencing to establish the cellular processes behind UC relapse and remission. However, because these destructive methods necessitate the removal of a sample, they can only be used on non-living tissues. The use of minimally invasive approaches to evaluate the in vivo , longitudinal effects of UC on the mucosa in the colon is gaining popularity among clinicians and researchers. We have created a dextran sulfate sodium-induced model of UC in C57 mice based on the work of Wirtz et al., and a minimally invasive imaging modality to explore the changes in mucosal tissue during "active" and "in remission" UC. Briefly, C57 mice were given dextran sulfate sodium (DSS) dissolved in water in 5-day cycles with a remission/recovery period of 10 days. After 7 days post-DSS treatment and 7 days post-recovery, mice were anesthetized and exploratory endoscopies were performed to assess the mucosal changes that occur during the "active" and "remission" periods of UC. Value of protocol:•Minimally invasive induction of ulcerative colitis in a murine mouse model.•Minimally invasive longitudinal monitoring of "active" and "in remission" ulcerative colitis.•Our endoscopic based imaging modality can be used to validate the induction of ulcerative colitis and the potential treatment response for pre-clinical trials., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Introduction: Brief hypercapnic challenge causes acute placental hypoperfusion with fetal brain sparing on BOLD-MRI. We hypothesize that this non-invasive imaging strategy can distinguish between normal pregnancy and chronic placental hypoperfusion (using the maternal hypoxia model)., Methods: Eighteen pregnant female ICR mice were randomized to three groups: normoxia, late-onset hypoxia (12%O 2 ;E13.5-17.5) and early-onset hypoxia (12%O 2 ;E10.5-17.5). On E17.5, animals were imaged in a 4.7-T Bruker-Biospec MRI scanner. Fast coronal True-FISP was performed to identify organs of interest (placenta and fetal heart, liver and brain). BOLD-MRI was performed at baseline and during a 4-min hypercapnic challenge (5%CO 2 ). %-change in placental and fetal signal was analyzed from T2*-weighted gradient echo MR images. Following MRI, fetuses and placentas were harvested, weighed and immuno-stained., Results: In normoxic mice, hypercapnia caused reduction in BOLD-MRI signal in placenta (-44% ± 7%; p < 0.0001), fetal liver (-32% ± 7%; p < 0.0001) and fetal heart (-54% ± 12%; p < 0.002), with relative fetal brain sparing (-12% ± 5%; p < 0.0001). These changes were markedly attenuated in both hypoxia groups. Baseline fetal brain/placenta SI ratio was highest in normoxic mice (1.14 ± 0.017) and reduced with increasing duration of hypoxia (late-onset hypoxia: 1.00 ± 0.026; early-onset hypoxia: 0.91 ± 0.016; p = 0.02). Both hypoxic groups exhibited fetal growth restriction with prominent placental glycogen-containing cells, particularly in early-onset hypoxia. There was increased fetal neuro- and intestinal-apoptosis in early-onset hypoxia only., Conclusions: BOLD-MRI with brief hypercapnic challenge distinguished between normoxia and both hypoxia groups, while fetal neuroapoptosis was only observed after early-onset hypoxia. This suggests that BOLD-MRI with hypercapnic challenge can identify chronic fetal asphyxia before the onset of irreversible brain injury., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Diverse populations worldwide are differentially affected by coronavirus disease 2019 (COVID-19). While socioeconomic background has been studied extensively, little is known about the genetic variation underlying this phenomenon. This study is aimed at examining the genetic basis behind the great discrepancies among diverse ethnic groups in terms of COVID-19 susceptibility for viral infection, disease prognosis, and mortality. To this end, in silico analysis of single-nucleotide polymorphisms (SNPs) within regulatory sequences of the human angiotensin-converting enzyme 2 ( ACE2 ) and transmembrane protease serine 2 ( TMPRSS2 )-the virus's gateway to host cells-and their plausible implications on expression levels was conducted. We provide indication that the variation in the human ACE2 and TMPRSS2 regulatory sequences is likely to be involved in and contribute to this phenomenon. SNPs that are abundant in the more susceptible populations introduce binding sites (BSs) for transcription factors or they may invalidate BSs for transcription repressor-both may enhance target gene ( ACE2 or TMPRSS2 ) expression in the relevant target tissues. SNPs that are abundant in the more resistant populations may invalidate BSs for a transcriptional repressor or they may introduce BSs for a transcriptional repressor or initiator of mRNA degradation, which may reduce target gene expression levels. This aspect, when added to the socioeconomic factors, can be a cause for the divergent prevalence of the disease and the different mortality rates within diverse populations. This demonstration may call for a shift in the paradigm of searching for COVID-19 biomarkers, such that SNPs within regulatory sequences should be of high importance., (Copyright © 2020 Barash, Machluf, Ariel and Dekel.)

Introduction: RBFOX2, an RNA-binding protein, controls tissue-specific alternative splicing of exons in diverse processes of development. The progenitor cytotrophoblast of the human placenta differentiates into either the syncytiotrophoblast, formed via cell fusion, or the invasive extravillous trophoblast lineage. The placenta affords a singular system where a role for RBFOX2 in both cell invasion and cell fusion may be studied. We investigated a role for RBFOX2 in trophoblast cell differentiation, as a foundation for investigations of RBFOX2 in embryo implantation and placental development., Methods: Immunohistochemistry of RBFOX2 was performed on placental tissue sections from three trimesters of pregnancy and from pathological pregnancies. Primary trophoblast cell culture and immunofluorescence were employed to determine RBFOX2 expression upon cell fusion. Knockdown of RBFOX2 expression was performed with βhCG and syncytin-1 as molecular indicators of fusion., Results: In both normal and pathological placentas, RBFOX2 expression was confined to the cytotrophoblast and the extravillous trophoblast, but absent from the syncytiotrophoblast. Additionally, we showed that primary trophoblasts that spontaneously fused in cell culture downregulated RBFOX2 expression. In functional experiments, knockdown expression of RBFOX2 significantly upregulated βhCG, while the upregulation of syncytin-1 did not reach statistical significance., Discussion: RBFOX2, by conferring mRNA diversity, may act as a regulator switch in trophoblast differentiation to either the fusion or invasive pathways. By studying alternative splicing we further our understanding of placental development, yielding possible insights into preeclampsia, where expression of antiangiogenic isoforms produced through alternative splicing play a critical role in disease development and severity., (Copyright © 2020. Published by Elsevier Ltd.)

Objectives: Corin is a protease that converts pro-atrial natriuretic peptide (pro-ANP) to ANP. While the involvement of ANP in the cardiovascular regulation is well established, there is increasing evidence that the pregnant uterus produces ANP, which promotes spiral artery remodeling. The present study examines the alterations in corin and PCSK6, a key enzyme in the conversion of pro-corin to corin, in the placenta of hyperinsulinemic dams (HD) featuring pregnancy-induced hypertension (PIH)., Materials and Methods: The study was conducted on female Wistar rats. Rats were rendered hyperinsulinemic by subcutaneous insulin pellet, mated and followed to the twenty-first day of pregnancy. Normal pregnant dams (NPD) served as controls. Both groups were sacrificed on day 21 of gestation and their placentas were dissected along with the mesometrial triangle (MT). The tissue was then sectioned from the maternal surface to the base of the MT, and processed for histological and molecular biology analysis of Corin, PCSK6 and ANP expression/immunoreactivity., Results: Hyperinsulinemic dams developed PIH, along lower placental and fetal weights. Corin expression and immunoreactivity were significantly decreased in the placenta by ~40-50%, but not in the MT. Similarly, placental but not MT PCSK6 immunoreactivity was lower in HD. Concomitantly with the downregulation of corin/PCSK6, proANP levels increased in the placenta of HD., Conclusions: Corin and PCSK6 are expressed in the placenta and MT. The decline in these two enzymes in the placenta of HD suggests a role of corin/PCSK6 machinery in the development of PIH and intrauterine growth restriction characterizing hyperinsulinemia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

The erratum notes a correction to Fig. 5 for the published article.

Significance: Many studies in colorectal cancer (CRC) use murine ectopic tumor models to determine response to treatment. However, these models do not replicate the tumor microenvironment of CRC. Physiological information of treatment response derived via diffuse reflectance spectroscopy (DRS) from murine primary CRC tumors provide a better understanding for the development of new drugs and dosing strategies in CRC., Aim: Tumor response to chemotherapy in a primary CRC model was quantified via DRS to extract total hemoglobin content (tHb), oxygen saturation (StO2), oxyhemoglobin, and deoxyhemoglobin in tissue., Approach: A multimodal DRS and imaging probe (0.78 mm outside diameter) was designed and validated to acquire diffuse spectra longitudinally-via endoscopic guidance-in developing colon tumors under 5-fluoruracil (5-FU) maximum-tolerated (MTD) and metronomic regimens. A filtering algorithm was developed to compensate for positional uncertainty in DRS measurements Results: A maximum increase in StO2 was observed in both MTD and metronomic chemotherapy-treated murine primary CRC tumors at week 4 of neoadjuvant chemotherapy, with 21  ±  6  %   and 17  ±  6  %   fold changes, respectively. No significant changes were observed in tHb., Conclusion: Our study demonstrates the feasibility of DRS to quantify response to treatment in primary CRC models.

Background: Medical management of retained placenta could be a safe alternative to manual removal., Objective: To evaluate the efficacy of prostaglandin analogues for retained placenta., Search Strategy: MEDLINE, EMBASE, CENTRAL, ICTRP, LILACS, and OpenSIGLE were searched without language restrictions from inception to January 31, 2017, by combining terms for retained placenta and prostaglandin analogues., Selection Criteria: Randomized controlled trials comparing prostaglandin analogues with any other intervention., Data Collection and Analysis: Trials were independently assessed for inclusion, data extraction, and risk of bias. Data were extracted for meta-analyses. GRADE was used to evaluate the quality of data., Main Results: Seven randomized controlled trials (851 patients) were included. Prostaglandins did not increase the placenta expulsion rate (relative risk [RR] 1.40, 95% confidence interval [CI] 0.83-2.36) or decrease maternal transfusion (RR 0.72, 95% CI 0.43-1.22). In comparison with oxytocin, prostaglandins did not modify the expulsion rate (RR 1.26, 95% CI 0.90-1.78), maternal transfusion (RR 1.05, 95% CI 0.27-4.09), or time for delivery of placenta (mean difference -1.56 minutes, 95% CI, -9.25-6.13). Three trials comparing prostaglandins with oxytocin agonists, ergometrine, and manual removal reported similar results., Conclusions: Prostaglandin analogues do not offer an effective alternative for management of retained placenta., (© 2018 International Federation of Gynecology and Obstetrics.)

A case report of a domesticated ferret ( Mustela furo) envenomated by a presumptive rattlesnake ( Crotalus sp.) treated successfully and safely with the novel Fab (2') North American Snake Antivenom (Veteria Labs). The ferret presented with clinical signs of depressed mentation and facial edema following a rattlesnake ( Crotalus sp.) bite. It developed hypotension, thrombocytopenia, and ecchymosis following the envenomation. It was treated with Fab (2') antivenom and given supportive care including crystalloid fluids and analgesia to resolution of clinical signs. This is the first documented case of rattlesnake envenomation in this species. This case supports the efficacy and short-term safety of this Fab (2') antivenom in this species without the use of antihistamines or glucocorticoids. This report also addresses the current standards of care with thorough review of the literature involving rattlesnake envenomation in zoological species.

Prior limited research indicates that children with pulmonary hypertension (PH) have higher rates of adverse perioperative outcomes when undergoing non-cardiac procedures and cardiac catheterizations. We examined a single-center retrospective cohort of children with active or pharmacologically controlled PH who underwent cardiac catheterization or non-cardiac surgery during 2006-2014. Preoperative characteristics and perioperative courses were examined to determine relationships between the severity or etiology of PH, type of procedure, and occurrence of major and minor events. We identified 77 patients who underwent 148 procedures at a median age of six months. The most common PH etiologies were bronchopulmonary dysplasia (46.7%), congenital heart disease (29.9%), and congenital diaphragmatic hernia (14.3%). Cardiac catheterizations (39.2%), and abdominal (29.1%) and central venous access (8.9%) were the most common procedures. Major events included failed planned extubation (5.6%), postoperative cardiac arrest (4.7%), induction or intraoperative cardiac arrest (2%), and postoperative death (1.4%). Major events were more frequent in patients with severe baseline PH ( P = 0.006) and the incidence was associated with procedure type ( P = 0.05). Preoperative inhaled nitric oxide and prostacyclin analog therapies were associated with decreased incidence of minor events (odds ratio [OR] = 0.32, P = 0.046 and OR = 0.24, P = 0.008, respectively), but no change in the incidence of major events. PH etiology was not associated with events ( P = 0.24). Children with PH have increased risk of perioperative complications; cardiac arrest and death occur more frequently in patients with severe PH and those undergoing thoracic procedures. Risk may be modified by using preoperative pulmonary vasodilator therapy and lends itself to further prospective studies.

To increase colonoscopy competence in ambiguous situations (e.g. the existence of flat polyps), an explicit in situ (at real time) diagnosis at the molecular level is required. We have previously shown that the affinity of fluorescent cationic polyacrylamide (Flu-CPAA) to malignant regions in the colon mucosa can be improved by conjugating the recognition peptide EPPT1 to the polymer backbone (to form Flu-CPAA-Pep). Using another recognition peptide, namely VRPMPLQ, we elucidated in the present study the effect of linker type and conjugating methods on Flu-CPAA-VRPMPLQ cytotoxicity and on its affinity to cell lines as well as human colorectal cancer (CRC) biopsies. In order to derive the relationship between the response variable and the experimental factors in a minimal set of experiments, a computerized statistical design of experiment (DoE) strategy was implemented. Data were collected in a six-factor factorial design to study the effect of experimental factors (independent variables) on the ability of the Flu-CPAA polymers to bind specifically to the colon cancer cell lines or the human biopsies (the response). It was found that the presence of VRPMPLQ on the Flu-CPAA improved the polymer's affinity to the human CRC biopsies and to the colon cancer cell lines representing stage B in the Duke severity staging system. The cytotoxicity of Flu-CPAA with high charge density was reduced after conjugated with VRPMPLQ. The replacement of Ahx linker by PEG linker of similar length did not affect the affinity to the human biopsies, nor did it affect cytotoxicity. However, elongating the PEG linker reduced the in vitro affinity to the colon cancer cell lines and to human CRC biopsies. Changing the conjugation method from condensation (amide bond formation) to the click conjugation method did not affect the affinity properties of the polymers. It did reduce, however, the polymer cytotoxicity. We suggest that Flu-CPAA-Pep, with the VRPMPLQ peptide as a recognition moiety, could serve for early diagnosis and screening of CRC patients during endoscopic procedures., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A comprehensive study of unusual cases of placental pathology may provide insight into mechanisms of normal human fertilization and early embryonic development by examining the exception to the rule. A gravida three para two 39-year-old woman was monitored by ultrasound from 16 weeks of gestation for cystic placenta. A female newborn was born at 36 weeks gestation. Pathologic examination of the partially cystic placenta revealed a singleton placenta comprised of 2/3 normal placenta and 1/3 complete hydatidiform mole, largely degenerated. Immunostaining for p57 was negative in stromal cells of the molar villi. Chromogenic in-situ hybridization revealed diploidy in both normal and molar parts. A total of 16 microsatellites were studied by short tandem repeat analysis, 11 of which were informative. The analysis revealed bipaternal molar tissue of dispermic origin. The paternal monospermic contribution to the normal part was different from that in the molar part, thus resulting in tripaternal contribution to the conceptus. A chimera is a single organism composed of two or more different populations of genetically distinct cells that originated from different zygotes (tetragametic) whereas mosaic is a mixture of two cell lines in one organism originating from one zygote. The possible mechanisms leading to the formation of chimeric/mosaic placenta in our case (one of the components being complete hydatidiform mole), including twinning, fusion at an early embryonic stage and diploidization of triploids, are discussed., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The emergence of electronic nicotine delivery systems (ENDS, or "e-cigarettes") has resulted in nicotine and tobacco scientists committing increased resources to studying these products. Despite this surge of research on various topics related to e-cigarettes, it is important to characterize the evolving e-cigarette research landscape as a way to identify important future research directions. The purpose of this review was to broadly categorize published scholarly work on e-cigarettes using a structured, multi-level coding scheme., Methods: A systematic literature search was conducted to collect articles on e-cigarettes that were published in peer-reviewed journals from 2006 through 2014. Studies were classified through 3 coding waves. Articles were first divided into research reports, literature reviews and opinions/editorials. Research reports were further categorized to determine the proportion of these studies using human participants. Finally, human studies were classified based on their methodologies: descriptive, predictive, explanatory, and intervention., Results: Research reports (n=224) and opinions/editorials (n=248) were published at similar rates during this time period. All types of articles showed exponential rates of increase in more recent years. 76.4% of human research studies were descriptive in nature, with very little research employing experimental (6.8%) or intervention-based methodologies (5.4%)., Conclusions: This review reinforces the idea that e-cigarettes are a disruptive technology exerting substantial influence on nicotine and tobacco science. This review also suggests that opinions on e-cigarettes may be outpacing our scientific understanding of these devices. Our findings highlight the need for more e-cigarette research involving experimental, intervention, and longitudinal designs., Competing Interests: Author THB receives research support from Pfizer, Inc. All other authors declare no conflicts of interest., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Integration of human papillomavirus (HPV) DNA into human cells accompanied by the disruption of the viral genome has been described as a prerequisite for cancer development. This study aimed to investigate E2 gene integrity of HPV16 and HPV58 viruses isolated from infected women with cervical lesions. Forty-two HPV16- and 31 HPV58-positive samples were analysed. E2 integrity was assumed when all fragments covering the E2 gene were amplified with specific polymerase chain reaction primers. Overall, in 59% of the samples, at least one fragment was not amplified in HPV16- (57%) and HPV58-positive samples (61%). Samples from high-grade squamous intraepithelial lesions had the highest frequency of E2 gene disruptions (73%), followed by samples from low-grade squamous intraepithelial lesions (63%) and, finally, samples from invasive cervical cancer (35%). Association between the integrity status of the E2 gene, and lesion grade was assessed by the chi-squared test applied to the combined set of viruses (p = 0.6555) or to populations of the same virus type (HPV58, p = 0.3101; HPV16, p = 0.3024). In conclusion, in this study, no association was found between the presence of E2 gene disruptions and the grade of cervical lesions caused by HPV16 and HPV58.

Introduction: Rat endovascular trophoblasts (EVasT) express smooth muscle (SM) proteins and contract ex vivo upon exposure to endothelin-1 (ET1) via receptors A and B (ETA, ETB). Presently, we investigated the EVasT response to NOS inhibition (N-Nitro-l-arginine methyl ester hydrochloride, l-NAME), and potentiation by NO donor [S-Nitroso-N-Acetyl-D,l-Penicillamine (SNAP)] following KCl precontraction. M&M: Luminal surface area (LSA) of remodeled spiral artery rings (SAR) devoid of SM was measured ex vivo upon exposure to l-NAME alone; l-NAME and ET1 representing the combined contractile effect of both ET1 receptors; l-NAME with ET1 and ETA antagonist, representing the isolated contractile effect via ETB. In another experiment we administered SNAP to KCl precontracted SAR. Statistical analysis was performed using 2-way mixed ANOVA and repeated measures., Results: l-NAME reduced LSA by 2.22%, 95% CI [0.83%, 3.60%] compared with control. ET1 and l-NAME reduced LSA immediately, compared with a plateau at 60min by ET1 alone. The isolated ET1 constrictive effect via ETB, reduced LSA by 5.94%; 95% CI [3.47%, 8.41%], significantly more than that obtained via ETA following 36 min of the experiment by 0.88%; 95%CI [0.09%, 1.67%]. Addition of KCl reduced LSA by 11.9%, 95% CI [9.6%, 14.1%]. Addition of SNAP increased LSA by 3.0%, 95% CI [1.7%, 4.3%]., Conclusions: EVasT of the rat remodeled spiral artery react to ET1 and KCl similar to vascular SM: contract via both ET1 receptors and KCl and relax by ET1 via ET B and by SNAP. This phenomenon may play a role in rat models of gestational vasoactive systems dysregulation., (Copyright © 2016. Published by Elsevier Ltd.)

Context: -The value of placental examination in investigations of adverse pregnancy outcomes may be compromised by sampling and definition differences between laboratories., Objective: -To establish an agreed-upon protocol for sampling the placenta, and for diagnostic criteria for placental lesions. Recommendations would cover reporting placentas in tertiary centers as well as in community hospitals and district general hospitals, and are also relevant to the scientific research community., Data Sources: -Areas of controversy or uncertainty were explored prior to a 1-day meeting where placental and perinatal pathologists, and maternal-fetal medicine specialists discussed available evidence and subsequently reached consensus where possible., Conclusions: -The group agreed on sets of uniform sampling criteria, placental gross descriptors, pathologic terminologies, and diagnostic criteria. The terminology and microscopic descriptions for maternal vascular malperfusion, fetal vascular malperfusion, delayed villous maturation, patterns of ascending intrauterine infection, and villitis of unknown etiology were agreed upon. Topics requiring further discussion were highlighted. Ongoing developments in our understanding of the pathology of the placenta, scientific bases of the maternofetoplacental triad, and evolution of the clinical significance of defined lesions may necessitate further refinements of these consensus guidelines. The proposed structure will assist in international comparability of clinicopathologic and scientific studies and assist in refining the significance of lesions associated with adverse pregnancy and later health outcomes.

Adipsin is a protease produced at high levels by adipose tissue. It is involved in complement activation and metabolic control. The objective of this study was to determine the changes in adipsin levels during different stages of normal pregnancy, and its association with obstetric outcomes, such as preeclampsia. This nested case-control study in a longitudinal cohort included normal pregnant (n = 54) and preeclamptic (n = 18) women, both followed throughout pregnancy. Additionally, some of the normal pregnant women were followed up three months postpartum (n = 18). Healthy non-pregnant women were also studied during their menstrual cycle (n = 20). The results of this study show that in healthy non-pregnant women, adipsin levels did not change significantly during the menstrual cycle. In normal pregnant women, adipsin levels were lower (p < 0.01) when compared with non-pregnant healthy women, but these serum levels increased again during postpartum (p < 0.001). Adipsin levels were significantly elevated in preeclamptic women in late pregnancy (P < 0.01). A significant correlation was not found between leptin and adipsin during the three periods of gestation studied in healthy pregnant and preeclamptic women. Our results suggest that adipsin may be involved in pregnancy-associated metabolic changes. Moreover, the increase of adipsin levels towards late gestation in preeclamptic women could be related to the pathophysiology of this disease.

Anaerobiospirillum thomasii has been reported as a causative agent of diarrhea in humans; however no bacteremia associated with this pathogen has been described so far. We present here the first case of fatal A. thomasii bacteremia in an alcoholic patient., (Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Meteorin (METRN) is a recently described neutrophic factor with angiogenic properties. This is a nested case-control study in a longitudinal cohort study that describes the serum profile of METRN during different periods of gestation in healthy and preeclamptic pregnant women. Moreover, we explore the possible application of METRN as a biomarker., Methods and Findings: Serum METRN was measured by ELISA in a longitudinal prospective cohort study in 37 healthy pregnant women, 16 mild preeclamptic women, and 20 healthy non-pregnant women during the menstrual cycle with the aim of assessing serum METRN levels and its correlations with other metabolic parameters. Immunostaining for METRN protein was performed in placenta. A multivariate logistic regression model was proposed and a classifier model was formulated for predicting preeclampsia in early and middle pregnancy. The performance in classification was evaluated using measures such as sensitivity, specificity, and the receiver operating characteristic (ROC) curve. In healthy pregnant women, serum METRN levels were significantly elevated in early pregnancy compared to middle and late pregnancy. METRN levels are significantly lower only in early pregnancy in preeclamptic women when compared to healthy pregnant women. Decision trees that did not include METRN levels in the first trimester had a reduced sensitivity of 56% in the detection of preeclamptic women, compared to a sensitivity of 69% when METRN was included., Conclusions: The joint measurements of circulating METRN levels in the first trimester and systolic blood pressure and weight in the second trimester significantly increase the probabilities of predicting preeclampsia.

A simple titration technique utilizing pyridine as a FTIR spectroscopy probe is demonstrated to successfully predict relative Brønsted acid-limited reaction rates in different ionic liquid (IL) environments. Relative acidity is shown to vary across three aprotic ILs in a manner that is specific to the particular acid-IL pairing.

In our previous study we proposed the use of chemical penetration enhancers for noninvasive detection of fetus abnormalities that can also be utilized for direct fetal drug delivery. In an attempt to further increase the mass transport rate across the amniotic membrane, thus shortening the procedure and improving the applicability of the proposed procedure, the effect and mechanism of combining ultrasound exposure with chemical penetration enhancers' application were assessed. The combined effect was evaluated in vitro on post-delivery human amniotic membrane and ex vivo on rat's whole amniotic sac. Ultrasound effect has been assessed by dye experiments using a customized image analysis program. Additional insights of ultrasound effect's mechanism on biological membranes are presented. Previously we have determined that chemical penetration enhancers affect the fetal membranes via two mechanisms termed as 'extractors' and 'fluidizers'. In this study, we found that combining ultrasound with a 'fluidizer' CPE (e.g. bupivacaine) results in a synergistic enhancement (90-fold) of fetal membrane's mass transport, while combining ultrasound with 'extractors' (e.g. ethanol and NMP) results in an antagonistic effect. The combined procedure is faster and gain greater accuracy than the applications of sole chemical penetration enhancers., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: 30% of people with anogenital warts (AGW) have spontaneous regression of lesions but there is no way to determine whether a specific lesion will remain. There are a wide range of options available for treating people with AGW and selection is based on clinician's experience, patient preferences and adverse effects. The imiquimod could offer the advantages of patient-applied therapies without incurring the limitations of provider-administered treatments., Objectives: To assess the effectiveness and safety of imiquimod for the treatment of AGW in non-immunocompromised adults., Search Methods: We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (15 April 2014), CENTRAL (1991 to 15 April 2014), MEDLINE (1946 to 15 April 2014), EMBASE (1947 to 15 April 2014), LILACS (1982 to 15 April 2014), World Health Organization International Clinical Trials Registry (ICTRP) (15 April 2014), ClinicalTrials.gov (15 April 2014), Web of Science (2001 to 15 April 2014) and OpenGrey (15 April 2014). We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies., Selection Criteria: Randomized controlled trials (RCTs) comparing the use of imiquimod with placebo, any other patient-applied or any other provider-administered treatment (excluding interferon and 5-fluorouracil which are assessed in other Cochrane Reviews) for the treatment of AGW in non-immunocompromised adults., Data Collection and Analysis: Three review authors independently assessed trials for inclusion, extracted data and assessed risk of bias. We resolved any disagreements through consensus. The quality of the evidence was assessed using the GRADE approach., Main Results: Ten RCTs (1734 participants) met our inclusion criteria of which six were funded by industry. We judged the risk of bias of the included trials as high. Six trials (1294 participants) compared the use of imiquimod versus placebo. There was very low quality evidence that imiquimod was superior to placebo in achieving complete and partial regression (RR 4.03, 95% CI 2.03 to 7.99; RR 2.56, 95% CI 2.05 to 3.20, respectively). When compared with placebo, the effects of imiquimod on recurrence (RR 2.76, 95% CI 0.70 to 10.91), appearance of new warts (RR 0.76, 95% CI 0.58 to 1.00) and frequency of systemic adverse reactions (RR 0.91, 95% CI 0.63 to 1.32) were imprecise. We downgraded the quality of evidence to low or very low. There was low quality evidence that imiquimod led to more local adverse reactions (RR 1.73, 95% CI 1.18 to 2.53) and pain (RR 11.84, 95% CI 3.36 to 41.63).Two trials (105 participants) compared the use of imiquimod versus any other patient-applied treatment (podophyllotoxin and podophyllin). The estimated effects of imiquimod on complete regression (RR 1.09, 95% CI 0.80 to 1.48), partial regression (RR 0.77, 95% CI 0.40 to 1.47), recurrence (RR 0.49, 95% CI 0.21 to 1.11) or the presence of local adverse reactions (RR 1.24, 95% CI 1.00 to 1.54) were imprecise (very low quality evidence). There was low quality evidence that systemic adverse reactions were less frequent with imiquimod (RR 0.30, 95% CI 0.09 to 0.98).Finally, two trials (335 participants) compared imiquimod with any other provider-administered treatment (ablative methods and cryotherapy). There was very low quality of evidence that imiquimod did not have a lower frequency of complete regression (RR 0.84, 95% CI 0.56 to 1.28). There was very low quality evidence that imiquimod led to a lower rate of recurrence during six-month follow-up (RR 0.24, 95% CI 0.10 to 0.56) but this did not translate in to a lower recurrence from six to 12 months (RR 0.71, 95% CI 0.40 to 1.25; very low quality evidence). There was very low quality evidence that imiquimod was associated with less pain (RR 0.30, 95% CI 0.17 to 0.54) and fewer local reactions (RR 0.55, 95% CI 0.40 to 0.74)., Authors' Conclusions: The benefits and harms of imiquimod compared with placebo should be regarded with caution due to the risk of bias, imprecision and inconsistency for many of the outcomes we assessed in this Cochrane Review. The evidence for many of the outcomes that show imiquimod and patient-applied treatment (podophyllotoxin or podophyllin) confer similar benefits but fewer systematic reactions with the Imiquimod, is of low or very low quality. The quality of evidence for the outcomes assessing imiquimod and other provider-administered treatment were of very low quality.

Although the function and mechanism of action of long non-coding RNAs (lncRNA) is still not completely known, studies have shown their potential role in the control of gene expression and regulation, in cellular proliferation and invasiveness at the transcriptional level via multiple mechanisms. Recently, colon cancer associated transcript 1 (CCAT1) lncRNA was found to be expressed in colorectal cancer (CRC) tumors but not in normal tissue. This study aimed to study the ability of a CCAT1-specific peptide nucleic acid (PNA) based molecular beacons (TO-PNA-MB) to serve as a diagnostic probe for in vitro, ex vivo, and in situ (human colon biopsies) detection of CRC. The data showed enhanced fluorescence upon in vitro hybridization to RNA extracted from CCAT1 expressing cells (HT-29, SW-480) compared to control cells (SK-Mel-2). Uptake of TO-PNA-MBs into cells was achieved by covalently attaching cell penetrating peptides (CPPs) to the TO-PNA-MB probes. In situ hybridization of selected TO-PNA-MB in human CRC specimens was shown to detect CCAT1 expression in all (4/4) subjects with pre-cancerous adenomas, and in all (8/8) patients with invasive adenocarcinoma (penetrating the bowel wall) tumors. The results showed that CCAT1 TO-PNA-MB is a powerful diagnostic tool for the specific identification of CRC, suggesting that with the aid of an appropriate pharmaceutical vehicle, real time in vivo imaging is feasible. TO-PNA-MB may enable identifying occult metastatic disease during surgery, or differentiating in real time in vivo imaging, between benign and malignant lesions., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The immiscibility of poly(dimethylsiloxane) (PDMS) and ionic liquids (ILs) was overcome to create PDMS-supported IL gels (ionogels) with IL loadings of up to 80% by mass through a simple sol-gel reaction at room temperature. By stirring a mixture of a functionalized PDMS oligomer, formic acid, and an IL (or lithium-in-IL solution), a resin was formed that could be cast to create a freestanding, flexible ionogel. PDMS-supported ionogels exhibited favorable ionic conductivity (ca. 3 mS cm(-1)) and excellent mechanical behavior (elastic modulus: ca. 60 kPa; fatigue life: >5000 cycles; mechanically stable at temperatures up to 200 °C). The activation energy of ionic conductivity was shown to be nearly identical for the ionogel and the neat IL, in contrast to ionogel systems wherein the scaffold material is miscible with the IL. This similarity indicates that IL/scaffold chemical interactions are key to the understanding of ionogel electrical performance, especially at elevated temperatures., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Similarities of the rat to the human placenta make rat pregnancy models relevant to the study of human gestational diseases. Understanding of species differences is necessary to extrapolate from animal models to humans. We observed alpha-smooth muscle actin (αSMA) expression in rat endovascular trophoblasts (EVasT) and investigated the spatial and temporal expression of smooth muscle (SM) proteins and their potential function in remodeled spiral artery., Methods: Rat placentas were examined from gestational day 13 to term, and were immunostained for cytokeratin, αSMA, alpha heavy chain of SM myosin, non-muscle myosin, Rho proteins, regulators of SM gene expression, myocardin, an early marker of SM differentiation and endothelin receptors A and B (ETA, ETB). Transmission electron microscopy (TEM) was performed. Modified spiral artery rings were studied ex vivo for endothelin-1- induced contraction., Results: EVasT expressed SM proteins co-localizing with cytokeratin confirming their trophoblastic origin from gestational day 13 to term. Thin fibers, consistent with actin fibers, were observed by TEM, in the cellular localization of αSMA in EVasT. Functional experiments revealed that addition of 10(-7) M endothelin-1 ex vivo reduced vascular lumen area by 11.1% ± 1.8% compared with control. This effect was reduced to only 1.0 ± 1.7% with ETA antagonist, and to 5.4 ± 1.7% contraction by ETB antagonist, p < 0.002, for all., Discussion: The expression of SM proteins in EVasT along with the contractibility of the rat remodeled spiral artery ex vivo, suggest that some vascular tone is potentially maintained by endothelin-1, and may play a role in situations of dysregulation of the vasoactive systems., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: Pregnancy is characterized by several metabolic changes that promote fat gain and later onset of insulin resistance. As Brain-derived neurotrophic factor (BDNF) decreases hyperglycaemia and hyperphagia, we aimed to investigate the potential role of placental and circulating BDNF levels in these pregnancy-related metabolic changes in rats and humans., Design and Methods: We identified the mRNA and protein expression of placental BDNF and its receptor TrkB using real-time PCR, Western blot and immunohistochemical approaches in both rat and humans. Serum BDNF was measured by ELISA. We also did a longitudinal prospective cohort study in 42 pregnant women to assess BDNF levels and correlations with other metabolic parameters., Results: We found that BDNF and TrkB are expressed in both rat and human placenta. In rat, both placental mRNA and serum levels are increased throughout pregnancy, whereas their protein levels are significantly decreased at the end of gestation. Serum BDNF levels in pregnant women are significantly lower in the first trimester when compared to the second and third trimester (P < 0·0148, P < 0·0012, respectively). Serum BDNF levels were negatively correlated with gestational age at birth and fasting glucose levels., Conclusion: Our findings suggest that both BDNF and its receptor TrkB are expressed in rodent and human placenta being regulated during pregnancy. Taken together, these findings support a role of BDNF in the regulation of several metabolic functions during pregnancy., (© 2013 John Wiley & Sons Ltd.)

Context: Irisin is a recently discovered adipomyokine that regulates the differentiation and phenotype of adipose tissue., Objective: In this study, we investigated the levels of irisin over the three trimesters of gestation in healthy and preeclamptic women and during the follicular and luteal phase of the menstrual cycle in a cohort of healthy eumenoherric women., Methods: Serum irisin was measured by an ELISA in a longitudinal prospective cohort study in 40 healthy pregnant women, 10 mild preeclamptic women, and 20 healthy eumenoherric women during the menstrual cycle to assess irisin levels and correlations with other metabolic parameters. We identified the protein expression of fibronectin type III domain-containing protein 5, the irisin precursor, in human placenta using immunohistochemical approaches in humans., Results: Serum irisin levels are higher in the luteal than in the follicular phase in eumenorrheic women. Fibronectin type III domain-containing protein 5, the irisin precursor, is expressed in human placenta, and its serum levels are higher during the entire pregnancy when compared with nonpregnant women. Serum irisin correlates positively with the homeostasis model assessment of estimated insulin resistance in the first trimester of normal pregnancy. Serum irisin levels do not change throughout gestation in preeclamptic women; however, there were lower irisin levels during the third trimester when compared with the normal pregnant group., Conclusion: Our results suggest that irisin may be involved in reproductive function and in the pregnancy-associated metabolic changes, and this condition may be an irisin-resistant state during gestation.

Background: Retained placenta affects 0.5% to 3% of women following delivery and it is a major cause of maternal death due to postpartum haemorrhage. Usually, retained placenta has been managed by manual removal or curettage under anaesthesia, which may be associated with haemorrhage, infection and uterine perforation. Medical management to facilitate the delivery of the retained placenta could be a safe alternative avoiding surgical intervention., Objectives: To assess the effectiveness and safety of prostaglandins for the management of retained placenta., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 December 2013), LILACS (1982 to 1 December 2013), SciELO (1998 to 1 December 2013), Web of Science (2001 to 1 December 2013), openSIGLE (1997 to 1 December 2013), World Health Organization International Clinical Trials Registry Platform (ICTRP) (1 December 2013) and the metaRegister of Controlled Trials (mRCT) (1 December 2013). We also contacted authors of included studies and reviewed the reference lists of retrieved studies., Selection Criteria: Randomised controlled clinical trials comparing the use of prostaglandins (or prostaglandin analogues) with placebo, expectant management, tocolytic drugs, any other prostaglandins or surgical interventions for the management of retained placenta after vaginal delivery of singleton live infants of 20 or more weeks of gestation., Data Collection and Analysis: Two review authors independently assessed trials for inclusion and assessed trial quality. Two review authors independently extracted data. Data were checked for accuracy. Any disagreements were resolved through consensus or consultation with a third review author when required. Authors of the included studies were contacted for additional information., Main Results: We included three trials, involving 244 women. The studies were considered to be at high risk of bias.The prostaglandins used were PG E2 analogue (sulprostone) in 50 participants and PG E1 analogue (misoprostol) in 194 participants at a dose of 250 mcg and 800 mcg respectively. The prostaglandins compared with placebo, were not superior in reducing the rate of manual removal of placenta (average risk ratio (RR) 0.82; 95% confidence interval (CI) 0.54 to 1.27), severe postpartum haemorrhage (RR 0.80; 95% CI 0.55 to 1.15), need for blood transfusion (RR 0.72; 95% CI 0.43 to 1.22), mean blood loss (mean difference (MD) -205.26 mL; 95% CI -536.31 to 125.79, random-effects) and the mean time from injection to placental removal (MD -7.00 minutes; 95% CI -21.20 to 7.20). Side-effects were no different between groups (vomiting, headache, pain and nausea between injection and discharge from the labour ward), with the exception of shivering, which was more frequent in women receiving prostaglandins (RR 10.00; 95% CI 1.40 to 71.49). We did not obtain any data for the primary outcomes of maternal mortality and the need to add another therapeutic uterotonic., Authors' Conclusions: Currently there is limited, very low-quality evidence relating to the effectiveness and the safety using prostaglandins for the management of retained placenta. Use of prostaglandins resulted in less need for manual removal of placenta, severe postpartum haemorrhage and blood transfusion but none of the differences reached statistical significance. Much larger, adequately powered studies are needed to confirm that these clinically important beneficial effects are not just chance findings.Similarly, no differences were detected between prostaglandins and placebo in mean blood loss or the mean time from injection to placental removal (minutes) or side-effects (vomiting, headache, pain and nausea between injection and discharge from the labour ward) except for 'shivering' which was more frequent in women who received prostaglandin. The included studies were of poor quality and there is little confidence in the effect estimates; the true effect is likely to be substantially different. We can not make any recommendations about changes to clinical practice. More high-quality research in this area is needed.

An integrative taxonomic analysis of three newly discovered populations of the gekkonid genus Cyrtodactylus Gray from Merapoh, Pahang; Gunung Stong, Kelantan; and Gunung Tebu, Terengganu indicate they are part of the C. pulchellus complex and each is a new species and thusly named Cyrtodactylus sharkari sp. nov., C. jelawangensis sp. nov., and C. timur sp. nov., respectively. Each species bears a unique suite of morphological and color pattern characters separating them from each other and all other nominal species in the C. pulchellus complex. Their phylogenetic relationships to each other and other species in the C. pulchellus complex were unexpected in that they are not in accordance with the general distribution of the species in this complex, underscoring the intricate historical biogeography of the Thai-Malay Peninsula. These descriptions highlight our current lack of knowledge concerning the herpetological diversity and distribution of species in northeastern Peninsular Malaysia.

A new species of karst-adapted gekkonid lizard of the genus Cnemaspis Strauch is described from Gua Gunting and Gua Goyang in a karst region of Merapoh, Pahang, Peninsular Malaysia whose unique limestone formations are in immediate danger of being quarried. The new species differs from all other species of Cnemaspis based on its unique suite of morphological and color pattern characters. Its discovery underscores the unique biodiversity endemic to karst regions and adds to a growing list of karst-adapted reptiles from Peninsular Malaysia. We posit that new karst-adapted species endemic to limestone forests will continue to be discovered and these regions will harbor a significant percentage of Peninsular Malaysia's biodiversity and thusly should be conserved rather than quarried.

The multinucleate syncytiotrophoblast of the human placenta is formed by fusion of the underlying cytotrophoblast progenitor cells. The large surface area of the syncytiotrophoblast is necessary for transport functions while it also serves as the site of synthesis of hormones and steroids. Studies of syncytiotrophoblast transcription are puzzling, demonstrating that many of the nuclei in the multinucleated syncytium are transcriptionally inactive. To further elucidate RNA activity in the syncytiotrophoblast, we investigated expression of snRNAs involved in RNA splicing. Using RNA in situ hybridization, we observed that snRNAs were markedly reduced in the syncytium throughout the course of pregnancy. Recapitulating these results in primary trophoblasts and in trophoblast cell lines in vitro, we found, using qRT-PCR and RNA in situ hybridization, that snRNA expression is reduced in trophoblasts cultured under fusion conditions. Our finding that snRNA is markedly reduced in the syncytiotrophoblast suggests that the placenta has evolved a balance between the large surface area essential for its transport function and the need to regulate protein production in the multinucleated syncytium.

Background: Unplanned reoperations have been proposed as a quality indicator in surgery but have not been studied extensively, especially concerning risk factors., Methods: This was a prospective cohort study in a third-level general surgery service. Data regarding patients operated on between July 2007 and February 2008 and followed up for 30 postoperative days were collected. Unplanned reoperations were the primary end point. The secondary end points were 30-d mortality and length of stay. A multivariate logistic regression analysis evaluated the hypothesis that patients operated on in emergency conditions had a greater chance of being reoperated on, after adjusting for relevant covariates., Results: There was a 5.9% cumulative incidence of unplanned reoperations. Patients operated on in emergency conditions had a 1.79 crude relative risk (RR) (95% confidence interval [CI], 1.15-2.78) of reoperation. Reoperated patients' RR of mortality was 8.94 (95% CI, 6.11-13.07). The mean postoperative hospital stay was 3d for patients who were not reoperated on and 19d for those who were reoperated on (P=0.00001). The logistic regression model gave a 2.83 odds ratio (95% CI, 1.65-4.87) for reoperation on emergency patients when adjusted for age, gender, body mass index, American Society of Anesthesiology classification, intraoperative inotropic use, and operation complexity., Conclusions: Tertiary general surgery service patients had a significantly increased risk of being reoperated on if the initial surgery was an emergency surgery compared with elective surgery. Unplanned reoperations led to a significantly increased mortality risk and a longer postoperative hospital stay, which could be regarded as warning signs in the care of surgical patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

During gestation there are important changes in maternal metabolism and an increase in insulin resistance, coinciding with an increase in adiposity. Chemerin is an adipocytokine which is expressed and secreted in various tissues, including placenta, and may play an important role in metabolic regulation during pregnancy. The aim of this study was to determine serum levels of chemerin during gestation and compare them to other indicators of insulin resistance. A cross-sectional study was carried out analyzing serum chemerin levels of 20 pregnant women during three gestational periods, early, middle, and late (between the 10th and 14th, the 23rd and 26th, and the 34th and 37th week) and 20 non-pregnant women were used as a control group. An analysis of chemerin levels during the menstrual cycle was performed in an eumenorrheic group (n=16) in the early follicular (cycle day 4±1) and the midluteal phase (cycle day 22±1), demonstrating that serum chemerin levels did not fluctuate significantly. Serum levels of chemerin were significantly elevated during late gestation when compared to early (P<0.001) and middle (P=0.001) gestation and a negative correlation between serum chemerin and adiponectin levels (r=-0.1643) became more significant when the non-pregnant group was included in the calculations (r=-0.2471). There was no significant association of triglycerides, total cholesterol, LDL, HDL, insulin, and HOMA levels with chemerin. Although chemerin rose significantly and is negatively associated with adiponectin levels, it is not correlated with other markers of insulin sensitivity, suggesting that more study is needed to determine whether chemerin is useful in predicting insulin resistance during gestation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

A review of the taxonomic status of the Asian Slug Snake, Asthenodipsas vertebralis (Boulenger, 1900) based on an integrative taxonomic approach using molecular, morphological, color pattern, and ecological data indicate it is composed of three well supported monophyletic lineages: (1) Pulau Tioman and Fraser's Hill, Pahang and Bukit Larut, Perak; Peninsular Malaysia; (2) its sister lineage from Northern Sumatra; and (3) the remaining basal lineage from Peninsular Malaysia. Furthermore, we consider the high sequence divergence (6.3%-10.2%) between these lineages (especially in areas of sympatry) and discrete differences in their morphology, color pattern, and microhabitat preference as evidence they are not conspecific. As such, we resurrect the name A. tropidonotus (Lidth de Jeude, 1923) for the Sumatra populations, restrict the name A. vertebralis to the populations from Pulau Tioman, Genting Highlands, Fraser's Hill, Gunung Benom, and Bukit Larut that contain terrestrial, banded adults; and consider A. lasgalenensis sp. nov. to be restricted to the populations from Fraser's Hill, Cameron Highlands, and Bukit Larut that contain arboreal, unbanded adults.

Real time detection of biomarkers at the mucosal level is imperative for the prevention and efficient treatment of colorectal cancer. Cationized polyacrylamide (CPAA) with increasing charge densities was prepared by radical polymerization of acrylamide and different mol% ratios of N-acryloyl, N'-(tert-butyl-carbonyl) diaminoethane. The NIR fluorophore derivative of IR-783, IR-783-S-Ph-COOH, was attached to the CPAA to give CPAA-783. After selecting the optimal IR-783-S-Ph-COOH ratio that avoids quenching, the preferential binding of the polymer was tested in SW-620, SW-480, HT-29, and LS-174T cancer cells. The optimal polymeric product was tested in situ in gut sac preparations of the dimethylhydrazine induced rat model. To increase the detection capabilities of CPAA-783, the FITC-labeled peptide EPPT1, that targets the cell transmembrane underglycosylated MUC-1 (uMUC-1), was conjugated to the polymer to obtain CPAA-783-EPPT1. The dually labeled modified polymer was tested in HT-29 and LS-174T cells (over expressing uMUC-1), followed by an examination in an orthotopic mouse model. CPAA-783 preferentially bound to the cancer cells, depending on CRC staging. The best binding occurred when the fraction of the cationic monomer was 100 mol%, labeled with 0.75 mol% of IR-783-S-Ph-COOH. An increase in the recognition of the dually labeled polymeric product, CPAA-783-EPPT1, towards HT-29 and LS-174T cells occurred in the lowest EPPT1molar ratio (0.63 mol%) only, probably due to quenching phenomena and steric hindrance. Similar observation was obtained in the orthotopic mice. It is concluded that fluorescently tagged CPAA can be used for the detection of malignant tissues in colorectal cancer after luminal instillation. Dually targeted CPAA with EPPT1is feasible, but requires further optimization., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The configuration and activation of memory networks have been theorized as mechanisms that underlie the often observed link between alcohol expectancies and drinking. A key component of this network is the expectancy "drunk." The memory network configuration of "drunk" was mapped by using cluster analysis of data gathered from the paired-similarities task (PST) and the Alcohol Expectancy Multi-Axial Assessment (AEMAX). A third task, the free associates task (FA), assessed participants' strongest alcohol expectancy associates and was used as a validity check for the cluster analyses. Six hundred forty-seven 18-19-year-olds completed these measures and a measure of alcohol consumption at baseline assessment for a 5-year longitudinal study. For both the PST and AEMAX, "drunk" clustered with mainly negative and sedating effects (e.g., "sick," "dizzy," "sleepy") in lighter drinkers and with more positive and arousing effects (e.g., "happy," "horny," "outgoing") in heavier drinkers, showing that the cognitive organization of expectancies reflected drinker type (and might influence the choice to drink). Consistent with the cluster analyses, in participants who gave "drunk" as an FA response, heavier drinkers rated the word as more positive and arousing than lighter drinkers. Additionally, gender did not account for the observed drinker-type differences. These results support the notion that for some emerging adults, drinking may be linked to what they mean by the word "drunk.", (PsycINFO Database Record (c) 2012 APA, all rights reserved.)

Horse body size varies greatly due to intense selection within each breed. American Miniatures are less than one meter tall at the withers while Shires and Percherons can exceed two meters. The genetic basis for this variation is not known. We hypothesize that the breed population structure of the horse should simplify efforts to identify genes controlling size. In support of this, here we show with genome-wide association scans (GWAS) that genetic variation at just four loci can explain the great majority of horse size variation. Unlike humans, which are naturally reproducing and possess many genetic variants with weak effects on size, we show that horses, like other domestic mammals, carry just a small number of size loci with alleles of large effect. Furthermore, three of our horse size loci contain the LCORL, HMGA2 and ZFAT genes that have previously been found to control human height. The LCORL/NCAPG locus is also implicated in cattle growth and HMGA2 is associated with dog size. Extreme size diversification is a hallmark of domestication. Our results in the horse, complemented by the prior work in cattle and dog, serve to pinpoint those very few genes that have played major roles in the rapid evolution of size during domestication.

Background: Exogenous hyperisulinemia causes pregnancy, induced hypertension and intrauterine growth restriction (IUGR) in pregnant rats. Hyperinsulinemia may increase production of endothelin-1 (ET-1), produced by sequential proteolysis of the big endothelin by the endothelin-converting enzyme (ECE)-1, the expression of which is examined here in the placenta, kidney, heart, and liver., Methods: Rats were rendered hyperinsulinemic by subcutaneous insulin pellet, mated and followed to the twenty-first day of pregnancy. They were then killed, and their fetuses and placentas were examined., Results: Hyperinsulinemic dams (HD) had higher blood pressure (BP) (130 ± 17 mm Hg in HD vs. 115 ± 16 mm Hg in normal pregnant dams (NPD), P < 0.05), lower placenta weight (0.44 ± 0.08 g in HD vs. 0.47 ± 0.08 NPD, P < 0.05) and lower fetus weight: males 4.9 ± 0.4 g in HD vs. 5.5 ± 0.4 g in NPD, P < 0.0001; females 4.7 ± 0.4 g in HD vs. 5.2 ± 0.4 g in NPD (P < 0.0001). ECE-1 expression as determined by western blot was significantly increased in the placenta and its implantation site, i.e., the mesometrial triangle (MT) of HD by 46 and 48%, respectively. In the kidney and heart of HD ECE-1, protein expression was increased by 230 and 220%, respectively, but its level in the liver was similar in both groups. Immunohistochemical staining revealed ECE-1 expression in endothelial cells and trophoblastic cells of the placenta and MT. Endothelin receptor A (ET-A), a mediator of vasoconstriction by ET-1, was also expressed in the endothelium and in trophoblasts of the placenta and MT. The expression of both ECE-1 and ET-A, as measured by automated image analysis, was generally stronger in placentas of HD., Conclusions: ECE-1 and ET-A are expressed in the trophoblastic cells of the placenta and MT. This may affect local endothelin levels, BP and IUGR.

Human cytomegalovirus (HCMV) is the leading cause of congenital infection, associated with severe birth defects and intrauterine growth retardation. The mechanism of HCMV transmission via the maternal-fetal interface is largely unknown, and there are no animal models for HCMV. The initial stages of infection are believed to occur in the maternal decidua. Here we employed a novel decidual organ culture, using both clinically derived and laboratory-derived viral strains, for the ex vivo modeling of HCMV transmission in the maternal-fetal interface. Viral spread in the tissue was demonstrated by the progression of infected-cell foci, with a 1.3- to 2-log increase in HCMV DNA and RNA levels between days 2 and 9 postinfection, the expression of immediate-early and late proteins, the appearance of typical histopathological features of natural infection, and dose-dependent inhibition of infection by ganciclovir and acyclovir. HCMV infected a wide range of cells in the decidua, including invasive cytotrophoblasts, macrophages, and endothelial, decidual, and dendritic cells. Cell-to-cell viral spread was revealed by focal extension of infected-cell clusters, inability to recover infectious extracellular virus, and high relative proportions (88 to 93%) of cell-associated viral DNA. Intriguingly, neutralizing HCMV hyperimmune globulins exhibited inhibitory activity against viral spread in the decidua even when added at 24 h postinfection-providing a mechanistic basis for their clinical use in prenatal prevention. The ex vivo-infected decidual cultures offer unique insight into patterns of viral tropism and spread, defining initial stages of congenital HCMV transmission, and can facilitate evaluation of the effects of new antiviral interventions within the maternal-fetal interface milieu.

Objective: To study the association between placenta accreta (PA) and in vitro fertilisation (IVF) pregnancies., Design: Retrospective chart review., Setting: Tertiary care centre in Jerusalem, Israel., Sample: During January 2004-February 2009, 25,193 deliveries occurred in our hospital, including 752 (3%) deliveries of IVF pregnancies., Methods: Placenta accreta was only diagnosed when there were histological findings from the placenta associated with the suitable clinical course. Demographic, obstetrical and fertility characteristics of these patients were retrieved from hospital files., Main Outcome Measure: Rates of PA in pregnancies achieved with IVF versus rates of PA in spontaneous pregnancies., Results: The rate of PA in the IVF group was 12/752 (16/1000) pregnancies, compared with 30/24,441 (1.2/1000) among spontaneous pregnancies (P < 0.0001; OR 13.2; 95% CI 6.7-25.8). Among the variables examined, parity, rate of caesarean delivery in the index pregnancy, and birthweight differed significantly between IVF and spontaneous pregnancies., Conclusions: The odds of developing PA are significantly higher in IVF pregnancies than in spontaneous pregnancies. These differences may stem from differences in the endometrial environment, or from changes to the endometrium wrought by IVF treatment protocols., (© 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.)

Background: Multifocality is an important factor when recommending surgery for papillary thyroid cancer (PTC). The aim of this study is to assess the incidence and characterize the spread pattern of multifocal PTC (mPTC) in patients undergoing total thyroidectomy., Methods: All thyroidectomies performed between 2003 and 2008 were reviewed identifying 289 patients. Data were obtained for demographics, clinical data, and histopathological findings., Results: Of the patients with papillary carcinoma, mPTC was identified in 150 patients (57%), of which 71% had lesions in the contralateral lobe. There were no significant differences in multifocality rate for gender, pathology type, and all tumor size subgroups including ≤1 cm. Pathology examination of representative sections versus the entire gland examination resulted in a significantly lower incidence of contralateral disease (P = .04)., Conclusions: Multifocal and contralateral lesions are common in PTC and their incidence is not related to tumor size. Pathology entire gland examination is strongly recommended to properly assess the rate of mPTC., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Although thyroid nodules are common and diagnosed in over 5% of the adult population, only 5% harbor malignancy. Patients with clinically suspicious thyroid nodules need to undergo fine-needle aspiration biopsy (FNAB). The main limitation of FNAB remains indeterminate cytopathology. Only 20%-30% of the indeterminate nodules harbor malignancy, and therefore up to 80% of patients undergo unnecessary thyroidectomy. The aim of this study was to identify and validate a panel of microRNAs (miRNAs) that could serve as a platform for an FNAB-based diagnostic for thyroid neoplasms., Methods: The study population included 27 consecutive patients undergoing total thyroidectomy for FNAB-based papillary thyroid cancer (n = 20) and benign disorders (n = 7). Aspiration biopsy was performed from the index lesion and from the opposite lobe normal tissue in all study patients at the time of operation. RNA was extracted from all aspiration biopsy samples. Quantitative polymerase chain reaction on a panel of previously selected miRNAs was performed. Polymerase chain reaction results were compared with final histopathology. miRNA from tumor tissues was amplified using the highest value of each miRNA expression in normal tissue as a threshold for malignancy detection., Results: Diagnostic characteristics were most favorable for mir-221 in differentiating benign from malignant thyroid pathology. mir-221 was overexpressed in 19 patients (p < 0.0001) with a sensitive yield of 95%. Specificity, negative and positive predictive value, and accuracy of the miRNA panel were 100%, 96%, 100%, and 98%, respectively., Conclusions: miRNA quantification for differential diagnosis of thyroid neoplasms within aspiration biopsy samples is feasible and may improve the accuracy of FNAB cytology.

Serum amyloid A (SAA) is an acute phase protein which is expressed primarily in the liver as a part of the systemic response to various injuries and inflammatory stimuli; its expression in ovarian tumors has not been described. Here, we investigated the expression of SAA in human benign and malignant ovarian epithelial tumors. Non-radioactive in situ hybridization applied on ovarian paraffin tissue sections revealed mostly negative SAA mRNA expression in normal surface epithelium. Expression was increased gradually as epithelial cells progressed through benign and borderline adenomas to primary and metastatic adenocarcinomas. Similar expression pattern of the SAA protein was observed by immunohistochemical staining. RT-PCR analysis confirmed the overexpression of the SAA1 and SAA4 genes in ovarian carcinomas compared with normal ovarian tissues. In addition, strong expression of SAA mRNA and protein was found in the ovarian carcinoma cell line OVCAR-3. Finally, patients with ovarian carcinoma had high SAA serum levels, which strongly correlated with high levels of CA-125 and C-reactive protein. Enhanced expression of SAA in ovarian carcinomas may play a role in ovarian tumorigenesis and may have therapeutic application.

Antenatal presentation of carnitine palmitoyltransferase type II deficiency due to mutations in the CPT2 gene has been rarely reported. We report an Ashkenazi Jewish family with 3 terminated pregnancies for multicystic kidneys and/or hydrocephalus. Fetal autopsy after termination of the couple's 4th pregnancy (sib 2) showed renal parenchyma replaced by cysts that appeared to increase in diameter toward the medulla. Fetopsy after termination of the 7th pregnancy (sib 3) revealed micrognathia; hypospadias; cystic renal dysplasia; hepatosteatosis; and lipid accumulation in the renal tubular epithelium, myocardium, and skeletal muscle. Microvascular proliferative changes and focal polymicrogyria were seen in the brain. A beta-oxidative enzyme deficiency was suspected. CPT2 gene analysis showed a homozygous complex haplotype for the F448L mutation associated with a c.del1238&#95;1239AG (p.Q413fs) truncating mutation in exon 4. Carnitine palmitoyltransferase type II deficiency should be included in the differential diagnosis in fetuses of Ashkenazi origin with multicystic kidneys and unusual cerebral findings.

Nitric oxide synthase (NOS) plays an important role in hypertensive disorders of pregnancy. In the context of the known association between hyperinsulinemia and hypertension, we studied the expression of the 3 isoforms of NOS (neuronal-nNOS, inducible-iNOS, and endothelial-eNOS) in the placenta and implantation site of our insulin-induced intrauterine growth restriction (IUGR) rat model in which the normal gestational blood pressure decline is abrogated. The fetuses of hyperinsulinemic dams were significantly smaller than those of normal pregnant dams (male fetal weight=4.8+/-0.5 g vs. 5.4+/-0.4 g, hyperinsulinemic vs. control, respectively; female fetal weight=4.5+/-0.5 g vs. 5.1+/-0.4 g, hyperinsulinemic vs control, respectively, p<0.0001). Their placentas weighed less than those of normal pregnant dams (0.44+/-0.08 g in hyperinsulinemic dams vs. 0.50+/-0.09 g, p<0.0001) and their implantation site, designated the mesometrial triangle, was also smaller. Endovascular trophoblasts were found more often and in greater depth in normal pregnant dams. Possibly as a compensatory mechanism, the endovascular trophoblasts formed cell groups rather than a monolayer and occupied a larger portion of the arterial perimeter in arteries of hyperinsulinemic dams. iNOS expression increased by 80% (p<0.0001) and 180% (p=0.045) in placenta and mesometrial triangle of hyperinsulinemic dams, respectively. The expression of eNOS was reduced by 17% (p=0.048) in the placenta and did not change significantly in the mesometrial triangle (p>0.05). nNOS expression was decreased by 37% (p=0.03) in the placenta and increased by 53% (p=0.035) in the mesometrial triangle of hyperinsulinemic dams. Immunohistochemistry revealed prominent expression of iNOS in the placental junctional zone and in interstitial and endovascular trophoblasts in the mesometrial triangle. Assuming a role in trophoblastic invasion, the increased expression of iNOS in hyperinsulinemic dams explains the "compensatory" pattern of trophoblastic invasion. Expression of eNOS was prominent in endothelial cells and weak in endovascular trophoblasts. In our model of gestational hyperinsulinemia-induced IUGR, we found not only differing expression of the 3 NOS isoforms in the cellular elements of the placenta and mesometrial triangle, but also divergent modes of altered NOS isoform expression. These findings suggest, in accordance with other publications, that each isoform may have a distinct function in the placenta and placental bed. The differing expression of the 3 NOS isoforms in the placenta and in the mesometrial triangle in rat IUGR seems to result from the hyperinsulinemia and the resulting IUGR phenotype.

Objective: To identify how treatment processes are related to functional outcomes for patients seeking treatment for musculoskeletal impairments while controlling for demographic and health characteristics at intake., Design: Prospective, observational cohort study. Treatment processes were not altered. Data were collected continuously from June 2005 to January 2008. Descriptive statistics were applied to compare patient characteristics, interventions, and outcomes between impairment categories. Ordinary least-squares multiple regressions were used to examine associations between patient characteristics at intake, treatment processes, and functional outcomes., Setting: Fifty-four community-based outpatient physical therapy clinics of Maccabi Healthcare Services, a public health plan in Israel., Participants: A consecutive sample of 22,019 adult patients (mean age 51.2 y, standard deviation=15.7, range 18-96, 58% women) seeking treatment due to lumbar spine, knee, cervical spine, or shoulder impairments with functional measurements at intake and discharge., Interventions: Not applicable., Main Outcome Measure: Functional status at discharge., Results: Explanatory power ranged from 30% to 39%. Better outcomes were associated with patient compliance with self-exercise and therapy attendance, application of therapeutic exercise and manual therapy, and completion of 3 or more functional surveys during the episode of care. Worse outcomes were associated with women, electrotherapy for pain management, and therapeutic ultrasound for shoulder impairments. Mixed results were found for group exercise programs., Conclusions: The study of associations between treatment processes, patient characteristics, and outcomes helps to describe practice and can be used to suggest ways to improve outcomes in outpatient physical therapy practice.