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Background: Preeclampsia is a pregnancy-related hypertensive disease. Aberrant hormone levels have been implicated in blood pressure disorders. This study investigated the association of postpartum maternal serum hormone levels of estradiol, progesterone, prolactin, and ß-HCG with poorer PE-related complications including arterial hypertension. Methods: Thirty patient women with preeclampsia, and twenty women with uncomplicated pregnancy were included in this study. Serum levels of estradiol, progesterone, prolactin, and ß-HCG were determined immediately after delivery, and on the first and third postpartum days by means of ECLIA. Results: Compared with normal pregnancy cases, preeclampsia cases had higher serum levels of ß-HCG levels on Day-0 (319%), of progesterone on Day-0 (207%) and Day-1 (178%), and of estradiol on Day-1 (187%) and Day-3 (185%). Increased prolactin levels were positively associated with disease severity and estradiol and progesterone levels were decreased in poorer preeclampsia features including disease onset and IUGR diagnosis. No significant correlation between different hormone levels and blood pressure measurements was reported. Conclusions: This study is the first that detected postpartum maternal serum hormone levels and their correlation with blood pressure measurements in preeclampsia. We believe that the persistent arterial hypertension in the puerperium in preeclampsia as well as poorer disease specifications are most likely not of hormonal origin. Larger, well-defined prospective studies are recommended. [ABSTRACT FROM AUTHOR]

Cryptophane-D is composed of two nonequivalent cyclotribenzylenecaps bound together by three OCH2CH2O bridgesin a syn arrangement. Host–guest complexes with chloroformand dichloromethane were investigated in solution by NMR spectroscopy.Variable temperature NMR 1H and 13C spectrashowed effects of chemical exchange between the free and bound guestand of conformational exchange for the host, strongly and specificallyaffected by guest binding. We found in particular that the carbon-13chemical shifts for the linkers connecting the two cyclotribenzyleneunits are very informative. The NMR results were supported by DFTcalculations. The guest exchange was also studied quantitatively,either by EXSY measurements (for chloroform as guest) or by line-shapeanalysis (for dichloromethane as guest). In the case of chloroformguest, we also investigated cross-relaxation between the guest andhost protons, as well as carbon-13 longitudinal relaxation and heteronuclearNOE at three different fields. The results were interpreted in termsof orientation and dynamics of the guest inside the host cavity. Puttingtogether various types of evidence resulted in remarkably detailedinsight into the process of molecular recognition of the two guestsby cryptophane-D host. [ABSTRACT FROM AUTHOR]

Venomous animals immobilize prey using protein toxins that act on ion channels and other targets of biological importance. Broad use of toxins for biomedical research, diagnosis, and therapy has been limited by inadequate target discrimination, for example, among ion channel subtypes. Here, a synthetic toxin is produced by a new strategy to be specific for human Kv1.3 channels, critical regulators of immune T cells. A phage display library of 11,200 de novo proteins is designed using the α-KTx scaffold of 31 scorpion toxin sequences known or predicted to bind to potassium channels. Mokatoxin-1(moka1) is isolated by affinity selection on purified target. Mokal blocks Kv1.3 at nanomolar levels that do not inhibit Kvl.1, Kv1.2, or KCa1.1. As a result, mokal suppresses CD3/28-induced cytokine secretion by T cells without cross-reactive gastrointestinal hyperactivity. The 3D structure of mokal rationalizes its specificity and validates the engineering approach, revealing a unique interaction surface supported on an α-KTx scaffold. This scaffold-based/target-biased strategy overcomes many obstacles to production of selective toxins. [ABSTRACT FROM AUTHOR]

Abstract: The Hylobatidae (gibbons) are among the most endangered primates and their evolutionary history and systematics remain largely unresolved. We have investigated the species-level phylogenetic relationships among hylobatids using 1257 bases representing all species and an expanded data set of up to 2243 bases for select species from the mitochondrial ND3–ND4 region. Sequences were obtained from 34 individuals originating from all 12 recognized extant gibbon species. These data strongly support each of the four previously recognized clades or genera of gibbons, Nomascus, Bunopithecus, Symphalangus, and Hylobates, as monophyletic groups. Among these clades, there is some support for either Bunopithecus or Nomascus as the most basal, while in all analyses Hylobates appears to be the most recently derived. Within Nomascus, Nomascus sp. cf. nasutus is the most basal, followed by N. concolor, and then a clade of N. leucogenys and N. gabriellae. Within Hylobates, H. pileatus is the most basal, while H. moloch and H. klossii clearly, and H. agilis and H. muelleri likely form two more derived monophyletic clades. The segregation of H. klossii from other Hylobates species is not supported by this study. The present data are (1) consistent with the division of Hylobatidae into four distinct clades, (2) provide the first genetic evidence for all the species relationships within Nomascus, and (3) call for a revision of the current relationships among the species within Hylobates. We propose a phylogenetic tree as a working hypothesis against which intergeneric and interspecific relationships can be tested with additional genetic, morphological, and behavioral data. [Copyright &y& Elsevier]

Snake α-neutotoxins of Elapidae venoms are grouped into two structural classes, short-chain and long-chain α-neutotoxins. While these two classes share many chemical and biological characteristics, there are also distinct dissimilarities between them, including their binding site on the nicotinic acetylcholine receptor (nAChR), specificity among species of Chordata, and the associated pharmacological effects. In the present study we test the hypothesis that structural motifs that evolved to confer natural resistance against conspecific long-chain α-neurotoxins in Elapidae snakes also interfere with the biological action of short-chain α-neurotoxins. We expressed functional nAChRs that contains segments or single residues of the Elapidae nAChR ligand binding domain and tested the effect of short-chain α-neurotoxin erabutoxin-a (ETX-a) from the Erabu sea snake Laticauda semifasciata on the acetylcholine-induced currents as measured by two-microelectrode voltage clamp. Our results show that the Elapidae nAChR α subunit segment T154–L208 ligand binding domain has an inhibitory effect on the pharmacological action of ETX-a. This effect is primarily attributed to the presence of glycosylation at position N189. If the glycosylation is removed from the T154–L208 segment, the nAChR will be inhibited, however, to a lesser extent than seen in the mouse. This effect correlates with the variations in α-neurotoxin sensitivity of different species and, importantly, reflects the evolutionary conservation of the binding site on the nAChR polypeptide backbone per se. Phylogenetic analysis of α-neurotoxin resistance suggests that α-neurotoxin-resistant nAChR evolved first, which permitted the evolution of snake venom α-neurotoxins. A model describing α-neurotoxin resistance in Elapidae snakes is presented. [ABSTRACT FROM AUTHOR]

Introduction: fetal rhabdomyoma is the most common fetal cardiac tumor and is often associated with tuberous sclerosis. Usually the tumors are relatively small and show no mediastinal shift. Fetal hydrops and pericardial effusion are rarely seen. Case: in this case report we present the neonatal clinical course of a case of prenatal diagnosis of giant cardiac rhabdomyomas. Conclusion: an early prenatal diagnosis may help for an adequate planning of perinatal monitoring and treatment with involvement of a multidisciplinary team. [ABSTRACT FROM AUTHOR]

In the absence of targeted treatment options, neoadjuvant chemotherapy (NACT) is applied widely for triple-negative breast cancer (TNBC). Response to NACT is an important parameter predictive of oncological outcomes (progression-free and overall survival). An approach to the evaluation of predictive markers enabling therapy individualization is the identification of tumor driver genetic mutations. This study was conducted to investigate the role of SEC62, harbored at 3q26 and identified as a driver of breast cancer pathogenesis, in TNBC. We analyzed SEC62 expression in The Cancer Genome Atlas database, and immunohistologically investigated SEC62 expression in pre- and post-NACT tissue samples from 64 patients with TNBC treated at the Department of Gynecology and Obstetrics/Saarland University Hospital/Homburg between January 2010 and December 2018 and compared the effect of SEC62 on tumor cell migration and proliferation in functional assays. SEC62 expression dynamics correlated positively with the response to NACT (p ≤ 0.01) and oncological outcomes (p ≤ 0.01). SEC62 expression stimulated tumor cell migration (p ≤ 0.01). The study findings indicate that SEC62 is overexpressed in TNBC and serves as a predictive marker for the response to NACT, a prognostic marker for oncological outcomes, and a migration-stimulating oncogene in TNBC. [ABSTRACT FROM AUTHOR]

Purpose: Liquid-based cytology (LBC) is routinely used in gynecology but is rarely applied in head and neck oncology though many suspicious lesions are easily accessible. While several studies have evaluated the potential use of LBC for early detection and molecular characterization of head and neck squamous cell carcinomas (HNSCCs), no study investigated its potential role in surgical management and therapy planning so far. Methods: Twenty-five patients with cT1-2 squamous cell carcinomas of the oral cavity and oropharynx were prospectively enrolled in this study and were randomized to two treatment arms: in the control arm, a diagnostic panendoscopy with incisional biopsy was followed by a second operation with transoral tumor resection ± neck dissection and tracheostomy. In the intervention arm, patients underwent LBC diagnostics and in case of a positive result received one single operation with panendoscopy and incisional biopsy for confirmation of LBC result by rapid section histology followed by transoral tumor resection ± neck dissection and tracheostomy in the same session. Results: Time between clinical diagnosis and definitive surgical treatment was significantly shorter in the intervention group compared with the control group (p < 0.0001). Additionally, time of hospitalization (p < 0.0001) and cumulative operation time (p = 0.062) were shorter in the intervention group. No significant differences in overall, progression-free, and disease-specific survival were observed. Conclusion: Cytology-based cancer surgery is a promising therapeutic strategy that can potentially be considered for a well-defined group of early-stage HNSCC patients and help to avoid repetitive general anesthesia, shorten the diagnosis-to-treatment interval and spare operation as well as hospitalization time. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The aim of this study was to evaluate whether abdominal myomectomy could be a choice for patients with symptomatic fibroids above the age of 48 years, who wish to get hormonal replacement therapy and desire to retain their uterus. Methods: We performed 504 abdominal myomectomies between 1990 and 2004. The mean age was 33±4.09 years, 9 (1.8%; 9/504) patients were above 48 years and 6 (1.19%; 6/504) of them requested hormonal replacement therapy (HRT) after the enucleation of fibroids. Data of these nine cases were compared to a matched control group of patients who had hysterectomy in the same year in 3 months to those who underwent abdominal myomectomy with same indications for surgery, same location, size and number of fibroids. The main aim of our study was to compare perioperative morbidity, duration of hospital stay between myomectomy and hysterectomy groups and determine the recurrence of fibroids and/or symptoms in 1 year with HRT in the myomectomy group. Results: The perioperative morbidity did not differ between the compared groups. In the myomectomy group with 1-year HRT we did not observe the recurrence of fibroids and symptoms. Conclusion: Our data suggest that abdominal myomectomy may be a satisfactory option for perimenopausal women with symptomatic fibroids who wish to retain their uterus and get HRT. [Copyright &y& Elsevier]

Objective: To examine whether the timing of pronuclear breakdown can be a predictor of embryo quality and viability. Design: Retrospective comparison of the development and quality of early and late developing zygotes. Setting: Infertility and endocrinology unit in a university hospital. Patient(s): One thousand seven hundred eighty-two zygotes obtained in 383 consecutive IVF cycles. Intervention(s): Culture of all fertilized embryos. Main Outcome Measure(s): Number of fertilized zygotes showing early pronuclear breakdown at 22–25 hours postinsemination, embryo quality, pregnancy rates (PR), implantation rates. Result(s): Early pronuclear breakdown embryos had a significantly higher cell number (4.4 ± 1.2) compared with the late pronuclear breakdown embryos (3.6 ± 1.4). When comparing the frequency of the early pronuclear breakdown embryos according to the method of fertilization, we failed to find any significant difference between the IVF (37.1%) and the intracytoplasmic sperm injection (ICSI) (41.1%) groups. The transfer of early pronuclear breakdown embryos resulted in a significantly higher clinical pregnancy rate than those with late pronuclear breakdown (48.3% vs. 27.3%). The implantation rate was higher in the early pronuclear breakdown group than in the late pronuclear breakdown group (26.5% vs. 15.1%). Conclusion(s): Early pronuclear breakdown is a strong indicator of embryo viability, and may be used as an additional criterion in the selection of embryos for transfer. [Copyright &y& Elsevier]

Lignocellulosic biomass, especially lignin and extractives, has the potential to substitute fossil precursors in the chemical industry. The conversion of lignin has been intensively researched, but challenges remain as high temperatures and increased pressure are commonly used, which is not energy efficient. Lignin and wood extractives bear chromophoric groups that can absorb light in the ultraviolet (UV) region, which enables photochemical reactions. Ultraviolet light emitting diodes (UV-LEDs) are an emerging technology; they are cheap, versatile, and energy-efficient compared to existing mercury lamps. UV-LEDs were used in this study as a proof of concept for the valorisation of a lignocellulosic residual stream from the pulp and paper industry, sawdust. In a process at ambient temperature and pressure and without the use of a catalyst, we have shown that lignin and extractives can be valorised using light from UV-LEDs. Simplified lignin model compounds were used to pinpoint chemical reactions during irradiation, and to ease the analysis of the sawdust samples. The rate of conversion upon irradiation of the model compounds was found to be 0.7–2.3 g L−1 h−1, depending on the concentration of the starting compounds. [ABSTRACT FROM AUTHOR]

Hemizygous cryptic deletions of the q11 band of human chromosome 22 have been associated with a number of psychiatric and behavioural phenotypes, including schizophrenia. Here we report the isolation and characterization of PRODH, a human homologue of Drosophila melanogaster sluggish-A (slgA), which encodes proline dehydrogenase responsible for the behavioural phenotype of the slgA mutant. PRODH is localized at chromosome 22q11 in a region deleted in some psychiatric patients. We also isolated the mouse homologue of slgA (Prodh), identified a mutation in this gene in the Pro/Re hyperprolinaemic mouse strain and found that these mice have a deficit in sensorimotor gating accompanied by regional neurochemical alterations in the brain. Sensorimotor gating is a neural filtering process that allows attention to be focused on a given stimulus, and is affected in patients with neuropsychiatric disorders. Furthermore, several lines of evidence suggest that proline may serve as a modulator of synaptic transmission in the mammalian brain. Our observations, in conjunction with the chromosomal location of PRODH, suggest a potential involvement of this gene in the 22q11-associated psychiatric and behavioural phenotypes. [ABSTRACT FROM AUTHOR]

Purpose: To assess changes in the pelvic floor anatomy that cause pelvic floor disorders (PFDs) in primigravidae during and after pregnancy and to evaluate their impact on women's quality of life (QoL). Methods: POP-Q and translabial ultrasound examination was performed in the third trimester and 3 months after delivery in a cohort of primigravidae with singleton pregnancy delivering in a tertiary center. Results were analyzed regarding mode of delivery and other pre- and peripartal factors. Two individualized detailed questionnaires were distributed at 3 months and at 12 months after childbirth to determinate QoL. Results: We recruited 45 women, of whom 17 delivered vaginally (VD), 11 received a vacuum extraction delivery (VE) and 17 a Cesarean section in labor (CS). When comparing third-trimester sonography to 3 months after delivery, bladder neck mobility increased significantly in each delivery group and hiatal area increased significantly in the VD group. A LAM avulsion was found in two women after VE. Connective tissue weakness (p = 0.0483) and fetal weight at birth (p = 0.0384) were identified as significant risk factors for the occurrence of PFDs in a multivariant regression analysis. Urinary incontinence was most common with 15% and 11% of cases at 3, respectively, 12 months after delivery. 42% of women reported discomfort during sexual intercourse, 3 months after delivery and 24% 12 months postpartum. Although 93% of women engage a midwife after delivery, only 56% participated in pelvic floor muscle training. Conclusion: Connective tissue weakness and high fetal weight at birth are important risk factors for the occurrence of PFDs. Nevertheless, more parturients should participate in postpartal care services to prevent future PFDs. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the interaction between Wnt/β-catenin and estrogen signaling pathways in endometrial cancer (EC). Methods: 119 women were involved in this study, including 65 women with histologically confirmed EC and 54 healthy women as a control group. Serum protein levels of Dkk1 were measured using ELISA. Protein expression levels of Dkk1, β-catenin, ER-β isoforms (β1, β2, β5), and ER-α were tested in paraffin-embedded tissues using IHC. Gene expression levels of Dkk1, CTNNB, ESR1, and ESR2 were tested in fresh tumorous and normal endometrium tissues using RT-PCR. Results: EC patients had significantly higher serum levels of Dkk1 protein compared with healthy women. Dkk1 and β-catenin showed different expression pattern in tumor cells compared to it in normal cells at the protein level but not at the gene level. Protein expression levels of ERβ2 and ERα were significantly lower in tumor cells compared with tumor-adjacent normal cells. Increased protein expression levels of ERα were associated with favorable clinicopathological features and better overall survival rate (OS). Protein expression levels of ERα were correlated with protein expression levels of Dkk1 and cytoplasmic β-catenin. The association between ERα expression levels and OS was no more significant when tested in regard to Dkk1- and cytoplasmic β-catenin expression levels. Conclusions: Our data demonstrated that Wnt/β-catenin and estrogen signaling systems are dysregulated in EC showing; for the first time, a potential crosstalk between certain components of these two pathways, which in turn has affected the specificity of these molecules in disease characteristics. Understanding the signaling networks in EC is crucial in designing clinical trials to evaluate the efficacy of molecular-targeted agents and providing more successful therapies in the future. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects of two different intraoperative CO2 pressures (8 and 15 mmHg) during laparoscopic hysterectomy for benign uterine pathologies in terms of postoperative abdominal and shoulder pain, laparoscopy-mediated vegetative alterations, pain medication requirement, arterial CO2 pressure (pCO2 ), surgical parameters, and safety.Design: Prospective randomised controlled study.Setting: German university hospital.Population: Female patients undergoing laparoscopic hysterectomy for benign uterine pathologies.Methods: Patients were randomised to a standard pressure (SP; 15 mmHg, control) or low-pressure (LP; 8 mmHg, experimental) group.Main Outcome Measures: Primary outcomes were postoperative abdominal and shoulder pain intensities, measured via numeric rating scale (NRS) and vegetative parameters (fatigue, nausea, vomiting, bloating) at 3, 24, and 48 hours postoperatively. Secondary outcomes were pain medication requirement (mg) and arterial pCO2 (mmHg). Surgical parameters and intra- and postoperative complications were also recorded.Results: In total, 178 patients were included. Patients in the LP group (n = 91) showed significantly lower postoperative abdominal and shoulder pain scores, fewer vegetative alterations, lower pain medication requirements, a shorter postoperative hospitalization, and lower intra- and postoperative arterial pCO2 values compared with the SP group (n = 87; P ≤ 0.01). No differences in intra- and postoperative complications were observed between groups.Conclusions: Low-pressure laparoscopy seems to be an effective and safe technique for the reduction of postoperative pain and laparoscopy-induced metabolic and vegetative alterations following laparoscopic hysterectomy for benign indications.Tweetable Abstract: Low-pressure laparoscopy seems to be an effective and safe technique for reduction of pain following laparoscopic hysterectomy. [ABSTRACT FROM AUTHOR]

The accuracy and practicality of measuring heteronuclear scalar coupling constants, nJCH, from modern NMR experimental methods is examined, based on F1 or F2 evolution of nJCH in HSQMBC (including EXSIDE) and HMBC experiments. The results from these methods are compared to both robust experimental data (derived from coupled 13C spectra), computed (Density Functional Theory) and literature values where available. We report on the accuracy, ease of use and time efficiency of these multi-dimensional methods and highlight their extent and limitations. [ABSTRACT FROM AUTHOR]

Background: Chromosome 3 amplification affecting the 3q26 region is a common genomic alteration in cervical cancer, typically marking the transition of precancerous intraepithelial lesions to an invasive phenotype. Though potential 3q encoded target genes of this amplification have been identified, a functional correlation of potential oncogenic function is still missing. In this study, we investigated copy number changes and the expression level of SEC62 encoded at 3q26.2 as a new potential 3q oncogene in dysplastic cervical lesions and analyzed its role in cervical cancer cell biology.Methods: Expression levels of Sec62 and vimentin were analyzed in liquid based cytology specimens from 107 women with varying grades of cervical dysplasia ranging from normal cases to cancer by immunofluorescence cytology. Additionally, a subset of 20 representative cases was used for FISH analyses targeting SEC62. To further explore the functional role of Sec62 in cervical cancer, HeLa cells were transfected with a SEC62 plasmid or SEC62 siRNA and analyzed for their proliferation and migration potential using real-time monitoring and trans-well systems as well as changes in the expression of EMT markers.Results: FISH analyses of the swabbed cells showed a rising number of SEC62 gains and amplifications correlating to the grade of dysplasia with the highest incidence in high grade squamous intraepithelial lesions and squamous cell carcinomas. When analyzing the expression level of Sec62 and vimentin, we found a gradually increasing expression level of both proteins according to the severity of the dysplasia. In functional analyses, SEC62 silencing inhibited and SEC62 overexpression stimulated the migration of HeLa cells with only marginal effects on cell proliferation, the expression level of EMT markers and the cytoskeleton structure.Conclusions: Our study suggests SEC62 as a target gene of 3q26 amplification and a stimulator of cellular migration in dysplastic cervical lesions. Hence, SEC62 could serve as a potential marker for 3q amplification, providing useful information about the dignity and biology of dysplastic cervical lesions. [ABSTRACT FROM AUTHOR]

Conservation of sea snakes is virtually nonexistent in Asia, and its role in human-snake interactions in terms of catch, trade, and snakebites as an occupational hazard is mostly unexplored. We collected data on sea snake landings from the Gulf of Thailand, a hotspot for sea snake harvest by squid fishers operating out of the ports of Song Doc and Khanh Hoi, Ca Mau Province, Vietnam. The data were collected during documentation of the steps of the trading process and through interviewers with participants in the trade. Squid vessels return to ports once per lunar synodic cycle and fishers sell snakes to merchants who sort, package, and ship the snakes to various destinations in Vietnam and China for human consumption and as a source of traditional remedies. Annually, 82 t, roughly equal to 225,500 individuals, of live sea snakes are brought to ports. To our knowledge, this rate of harvest constitutes one of the largest venomous snake and marine reptile harvest activities in the world today. Lapemis curtus and Hydrophis cyanocinctus constituted about 85% of the snake biomass, and Acalyptophis peronii, Aipysurus eydouxii, Hydrophis atriceps, H. belcheri, H. lamberti, and H. ornatus made up the remainder. Our results establish a quantitative baseline for characteristics of catch, trade, and uses of sea snakes. Other key observations include the timing of the trade to the lunar cycle, a decline of sea snakes harvested over the study period (approximately 30% decline in mass over 4 years), and the treatment of sea snake bites with rhinoceros horn. Emerging markets in Southeast Asia drive the harvest of venomous sea snakes in the Gulf of Thailand and sea snake bites present a potentially lethal occupational hazard. We call for implementation of monitoring programs to further address the conservation implications of this large-scale marine reptile exploitation. Cosecha de Serpientes Marinas en el Golfo de Tailandia [ABSTRACT FROM AUTHOR]

Purpose Fibroids may cause infertility and recurrent pregnancy loss. Studies have analysed the reproductive results after myomectomy according to the size, location and number of fibroids removed, but data are insufficient about comparison of opening the uterine cavity or not during surgery. Methods Two hundred twenty-nine abdominal myomectomies with the indication of infertility and/or recurrent pregnancy loss were analysed retrospectively. The main purpose was to compare postoperative pregnancy, delivery and miscarriage rates according to either the uterine cavity was opened or not during the surgery. As a secondary outcome postoperative pregnancy rates were assessed by location, size and number of fibroids. Results There was no significant difference in reproductive results according to either the uterine cavity was opened or remained closed. Preoperative location, size and number of fibroids did not influence significantly the postoperative pregnancy rates. Conclusions Opening the uterine cavity does not impair postoperative pregnancy rates. Preoperative location, size and number of fibroids do not influence postoperative reproductive results. [ABSTRACT FROM AUTHOR]