Maternal insulin-like growth factors and insulin-like growth factor-binding proteins for macrosomia prediction in diabetic and nondiabetic pregnancy: A prospective study.

OBJECTIVE: Attributable to the insulin-like growth factor (IGF) axis involvement in fetal growth regulation, possible contribution of the maternal IGF axis to antenatal fetal macrosomia diagnosis is a subject of particular interest in diabetic pregnancy. METHODS: A total of 130 women were prospectively enrolled in a longitudinal single-center cohort study. The four study groups were: type 1 diabetes (n = 40), type 2 diabetes (n = 35), gestational diabetes (n = 40), and control (n = 15). IGF-1 and IGF-2 and insulin-like growth factor-binding protein (IGFBP) 1, 3, 6, and 7 serum levels were analyzed in 11- to 14-week and 30- to 34-week samples with a specific immunoassay. RESULTS: In mothers of large-for-gestational-age neonates (90th percentile), higher (median test) first-trimester IGF-1 (P = 0.007) and lower IGFBP-1 (P = 0.035) were observed. The IGF-1/IGFBP-1 ratio was positively associated with neonatal weight (r = 0.434, P < 0.001). Receiver operating characteristic analysis revealed an association between large for gestational age and the first-trimester IGF-1 (area under the curve [AUC] = 0.747, P < 0.001), IGFBP-1 (AUC = 0.334, P = 0.011), and IGF-1/IGFBP-1 ratio (AUC = 0.750, P < 0.001). IGF-1/IGFBP-1 ratio had better performance for prediction of birth weight over 4000 g (AUC = 0.822, P < 0.001). CONCLUSION: The authors detected different first-trimester IGF-1 and IGF-1/IGFBP-1 thresholds applicable for either supposition or rejection of macrosomia diagnosis. Further investigation is needed to determine how the maternal IGF axis can contribute to fetal macrosomia prediction.

IVF protocol efficacy in women with expected suboptimal response depending on ovary stimulation mode.

INVESTIGATION OBJECTIVE: IVF protocol efficacy estimation in women with expected suboptimal response depending on ovary stimulation mode. MATERIALS AND TECHNIQUE: A randomized controlled study embracing results of 51 IVF cycle in women with ovary suboptimal response. The suboptimal response prognostic analysis was performed basing on ≤9 oocyte cumulus complexes obtained in previous IVF programs, the presence of no less than 5-9 antral follicles in both oocytes and amount of anti-Mullerian Hormone ≥0,8 ng/mL. In Group I (n = 25), the stimulation was performed by recombinant corifollitropin alfa combined with highly purified urinary gonadotropin, while in Group II (n = 26) it was made by means of recombinant follitropin/lutropin alfa within the protocol of applying gonadotropin-releasing hormone antagonists. RESULTS: The total gonadotropin dose in Group II patients was authentically lower compared to Group I (p˂,01). No statistical difference between the two studied groups was detected concerning the number of obtained oocytes, 2pn zygote, good-quality transferred embryos and clinical pregnancy rate (p>.05). Embryo cryopreservation was performed only for group-II patients. CONCLUSION: Corifollitropin alfa administration combined with highly purified menotropin in IVF cycles for suboptimal responders is quite effective, however, this strategy has no preference over other stimulation modes. The strategy of using recombinant follitropin/lutropin alfa can be promotive to IVF outcomes for suboptimal responders by means of embryo banking. ClinicalTrials.gov Identifier: NCT03177538.

Violent Behavior During Psychiatric Inpatient Treatment in a German Prison Hospital.

Violent behavior in correctional facilities is common and differs substantially in type, target, implication, and trigger. Research on frequency and characteristics of violent behavior in correctional facilities and psychiatric hospitals is limited. Results from recent research suggest that comorbidity of severe mental disorder, personality disorder, and diagnosis of substance abuse is related to a higher risk of violent behavior. In the Berlin prison hospital, a database was created to collect data from all violent incidences (n=210) between 1997 and 2006 and between 2010 and 2016. In a retrospective, case-control study, we analyzed specific socioeconomic data and psychiatric diagnosis and compared the group of prisoners with violent behavior with randomly selected prisoners of the same department without violent behavior (n = 210). Diagnosis of schizophrenia, non-German nationality, no use of an interpreter, no children, and no previous sentence remained significantly associated with the dependent variable violent behavior. There were no significant differences regarding age and legal statuses. Practical implications for clinical work are discussed.

Corrigendum: Violent Behavior During Psychiatric Inpatient Treatment in a German Prison Hospital.

[This corrects the article DOI: 10.3389/fpsyt.2019.00762.].

Interactions of NK Cells and Trophoblast Cells. Methodological Aspects.

NK cells present in different organs differ by their functional characteristics, in particular, proliferative activity. For studying tissue-resident NK cells, tissue-specific microenvironment should be reproduced. In case of decidual NK cells, this microenvironment is created by trophoblast cells. We developed a method for evaluation of proliferative activity of peripheral blood NK cells in the presence of trophoblast cells. Proliferative activity of peripheral blood NK cells was evaluated by the expression of protein Ki-67 after culturing with JEG-3 trophoblast cells. This method allows evaluating the functional state of NK cells in microenvironment specific for the decidua.

Involvement of the heparanase procoagulant domain in bleeding and wound healing.

Essentials Heparanase forms a complex with tissue factor and enhances the generation of factor Xa. The present study was aimed to identify the procoagulant domain of heparanase. Procoagulant peptides significantly shortened bleeding time and enhanced wound healing. Tissue factor pathway inhibitor (TFPI)-2 derived peptides inhibited the procoagulant peptides. SUMMARY: Background Heparanase, which is known to be involved in angiogenesis and metastasis, was shown to form a complex with tissue factor (TF) and to enhance the generation of activated factor X (FXa). Our study demonstrated that peptides derived from TF pathway inhibitor (TFPI)-2 impeded the procoagulant effect of heparanase, and attenuated inflammation, tumor growth, and vascularization. Aims To identify the procoagulant domain in the heparanase molecule, and to evaluate its effects in a model of wound healing that involves inflammation and angiogenesis. Methods Twenty-four potential peptides derived from heparanase were generated, and their effect was studied in an assay of FXa generation. Peptides 14 and 16, which showed the best procoagulant effect, were studied in a bleeding mouse model and in a wound-healing mouse model. Results Peptides 14 and 16 increased FXa levels by two-fold to three-fold, and, at high levels, caused consumption coagulopathy. The TFPI-2-derived peptides explored in our previous study were found to inhibit the procoagulant effect induced by peptides 14 and 16. In the bleeding model, time to clot formation was shortened by 50% when peptide 14 or peptide 16 was topically applied or injected subcutaneously. In the wound-healing model, the wound became more vascular, and its size was reduced to one-fifth as compared with controls, upon 1 week of exposure to peptide 14 or peptide 16 applied topically or injected subcutaneously. Conclusions The putative heparanase procoagulant domain was identified. Peptides derived from this domain significantly shortened bleeding time and enhanced wound healing.

Ectopic pregnancy following in vitro fertilization: meta-analysis and single-center experience during 6 years.

BACKGROUND: Ectopic pregnancy (EP) has been reported to occur in 1.4-5.4% of all clinical pregnancies resulting from in vitro fertilization (IVF) and embryo transfer (ET). Data on factors associated with abnormal embryo implantation following assisted conception are limited. MATERIALS AND METHODS: A systematic review and meta-analysis was performed to determine whether there is an association between the day (cleavage-stage, D3, versus blastocyst, D5) or the type (fresh versus frozen/thawed) of ET and EP rate. Risk factors for EP were evaluated in a retrospective study of 1194 women, who achieved pregnancy at our IVF unit between 2010 and 2016. RESULTS: Sixteen papers were considered for the meta-analysis. EP rate did not differ between D3 and D5 fresh ET groups (RR = 0.99, 95%CI: 0.76-1.30) and was higher after fresh versus frozen ET (RR = 1.56, 95%CI: 1.25-1.95). At our clinic, 21 (1.76%) pregnancies were documented as ectopic. The risk of EP was associated with tubal pathology (OR = 3.37, 95%CI: 1.39-8.2), previous appendectomy and past chlamydial infection. CONCLUSIONS: Present meta-analysis suggests that EP rate is similar following fresh blastocyst and cleavage ETs, but is significantly reduced after frozen compared with fresh ET. Our own findings demonstrate that tubal pathology has the major impact on EP occurrence following assisted conception.

Immunohistochemical criteria for endometrial receptivity in I/II stage endometriosis IVF-treated patients.

Abstracts Background: Implantation failure of in vitro fertilization (IVF) cycles is recognized as one of key problems in contemporary reproductive medicine. Implantation itself is a multifactorial process and one can hardly expect to find a single criterion for the endometrium receptivity. Endometrium biopsy still remains the most applicable technique to diagnose abnormalities causing decrease or complete loss of endometrial receptivity. MATERIALS AND METHODS: We have studied 95 endometrial biopsy samples from 45 patient with I/II stage endometriosis and 40 controls from October 2014 to December 2015. Immunohistochemical analysis of key biological molecules participating in implant window formation (LIF, ER, PR, integrin, TGF-ß1 and VEGF) was done to assess their predicting value for endometrial receptivity troubles. RESULTS: The discriminant analysis demonstrated that highest information capacity was characteristic for LIF expression percent area, integrin αVß3 both percent area and optic density in endometrial stroma and glands and finally TGFß1 and VEGF-А percent area expression in endometrial stroma. The model test done on a checking group showed 89.1% correct discrimination. Cross-checking in a teaching group showed a bit lower but still high correct answer percentage (88.8%). A decision-making classification tree was worked out. CONCLUSION: The produced model is sufficient for predicting IVF treatment failure and allows producing reasonable treatment tactics as well as encourages IVF treatment effectiveness improvement in patients with endometriosis.

[Methodological approaches to quantitative immunohistochemical evaluation of expression of breast apoptosis and proliferation markers].

Apoptosis and proliferative markers were studied in fibroadenoma and fibrocystic breast lesions. A quantitative immunohistochemical test for these factors using computer system of microscopic images is presented. It provides the advantages for interpretation of immunohistochemical reactions by design of expression standards for different pathologies in the breast.

Risk factors associated with candidaemia in the neonatal intensive care unit: a case-control study.

The incidence of candidaemia is steadily increasing in neonatal intensive care units (NICUs). Several neonatal risk factors for candidaemia have been identified, however, the number of cases in controlled studies is small and knowledge concerning maternal and perinatal risk factors is limited. The present study attempted to identify modifiable, independent maternal, perinatal and neonatal risk factors for candidaemia using a retrospective case-control study in the NICU of a tertiary-care paediatric medical centre. The study group consisted of 56 neonates admitted to the NICU between 1996 and 2000 who acquired candidaemia. The control group comprised the first infant admitted immediately after each study infant matched for gestational age (+/-10 days) and birthweight (+/-200 g). Potential maternal, perinatal and neonatal risk factors were compared between the groups using statistical methods and analysed by univariate and multivariate stepwise logistic regression models. The independent risk factors found to be significantly associated with increased risk of candidaemia were duration of ventilation and presence of bacteraemia before candidaemia. Maternal steroids had a significant protective effect. The positive predictive value using these three parameters was 78.38%. Maximizing in-utero steroid treatment in high-risk pregnancies, minimizing the days of mechanical ventilation and investment of efforts in prevention of bacteraemia may help to reduce the incidence of candidaemia in the NICU.

A monomer is the minimum functional unit required for channel and ATPase activity of the cystic fibrosis transmembrane conductance regulator.

The cystic fibrosis transmembrane conductance regulator (CFTR) normally functions as a phosphorylation-regulated chloride channel on the apical surface of epithelial cells, and lack of this function is the primary cause for the fatal disease cystic fibrosis (CF). Previous studies showed that purified, reconstituted CFTR can function as a chloride channel and, further, that its intrinsic ATPase activity is required to regulate opening and closing of the channel gate. However, these previous studies did not identify the quaternary structure required to mediate conduction and catalysis. Our present studies show that CFTR molecules may self-associate in CHO and Sf9 membranes, as complexes close to the predicted size of CFTR dimers can be captured by chemical cross-linking reagents and detected using nondissociative PAGE. However, CFTR function does not require a multimeric complex for function as we determined that purified, reconstituted CFTR monomers are sufficient to mediate regulated chloride conduction and ATPase activity.

Perturbation of the pore of the cystic fibrosis transmembrane conductance regulator (CFTR) inhibits its atpase activity.

Mutations in the cystic fibrosis gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) lead to altered chloride (Cl(-)) flux in affected epithelial tissues. CFTR is a Cl(-) channel that is regulated by phosphorylation, nucleotide binding, and hydrolysis. However, the molecular basis for the functional regulation of wild type and mutant CFTR remains poorly understood. CFTR possesses two nucleotide binding domains, a phosphorylation-dependent regulatory domain, and two transmembrane domains that comprise the pore through which Cl(-) permeates. Mutations of residues lining the channel pore (e.g. R347D) are typically thought to cause disease by altering the interaction of Cl(-) with the pore. However, in the present study we show that the R347D mutation and diphenylamine-2-carboxylate (an open pore inhibitor) also inhibit CFTR ATPase activity, revealing a novel mechanism for cross-talk from the pore to the catalytic domains. In both cases, the reduction in ATPase correlates with a decrease in nucleotide turnover rather than affinity. Finally, we demonstrate that glutathione (GSH) inhibits CFTR ATPase and that this inhibition is altered in the CFTR-R347D variant. These findings suggest that cross-talk between the pore and nucleotide binding domains of CFTR may be important in the in vivo regulation of CFTR in health and disease.

Variation in the branching of the axillary artery. A description of a rare case.

A case is described in which a rare variation of a branch arising from the axillary artery is defined as a thoracoepigastric artery. This variation was observed in the cadaver of a 72-year-old man. This artery branched from the axillary artery, passing as a common trunk between the roots of the median nerve, and divided into two branches. The lateral one gave rise to muscular branches supplying the shoulder and fasciae, while the medial one descended on the anterior aspect of the axillary fossa, reaching the hypogastric region, and anastomosed with the superficial epigastric artery, which is a branch of the femoral artery. To our best knowledge, no variation similar to this one has been described. We suggest naming this artery the thoracoepigastric artery.

Prostate-specific antigen induction by a steroid hormone in T47D cells growing in SCID mice.

Previous studies revealed that prostate-specific antigen (PSA) is present in > 30% of human breast tumor cytosols. Survival analysis showed that patients with PSA-producing tumors have a reduced risk for relapse, suggesting PSA to be an independent favorable prognostic marker for a large subset of breast cancer patients. The present investigation established an in vivo model for the induction of PSA in human breast cancer tumors growing as xenografts in severe combined immunodeficient (SCID) mice. The human mammary cancer cell-line T47D was grown i.m. in female mice. When the tumor and leg diameter reached 10 mm, the mice were stimulated daily with norgestrel for either 5 or 7 days to produce PSA, and sacrificed on day 8. The prostate cancer cell-line LNCaP was grown in male mice and functioned as a positive control for PSA production. After T47D and LNCaP mice were sacrificed, a highly sensitive immunofluorometric assay was used to analyze the PSA concentration in the tumor, muscle, liver, and kidney cytosols. Norgestrel-stimulated T47D mice showed significantly more PSA in the tumors compared to tumors of the control mice. However, PSA levels in tumors of the stimulated mice were significantly lower than those in the LNCaP xenografts. No PSA levels above background were present in the blood and normal tissue of the norgestrel-stimulated or control T47D xenografts. This mouse model will be a valuable tool for investigating and screening new therapies for a subgroup of breast cancer patients who have significant PSA concentrations in their tumors.

Obstructive sleep apnea and acute myocardial infarction: clinical implications of the association.

It is not known whether patients with acute myocardial infarction (MI) with coexistent obstructive sleep apnea (OSA) have a poor clinical course during the acute phase of MI. Therefore, we investigated the impact of OSA on in-hospital morbidity and mortality during an acute MI. Patients admitted to the intensive cardiac unit (ICU) with acute MI underwent Holter monitoring and night pulse oximetry (SpO2). During the first complete day at the ICU, both recordings (ECG and SpO2) were matched in time to determine association between cardiac arrhythmias and hypoxemia episodes. We identified and compared 55 heavy snorers with daytime sleepiness who showed more than 10 episodes of desaturation per hour on pulse oximetry (OSA group), and 196 nonOSA patients. There was an increase in the incidence of premature ventricular contraction (PVC, p < 0.05) and couplets PVC (p < 0.05) in OSA patients; the proportion of those arrhythmias increased in parallel with desaturation episodes in the OSA group. There were no differences between OSA and nonOSA groups for major MI complications (38.2% vs 34.2%, p > 0.05), ICU/hospital stay (3.6 +/- 1.2 vs 2.7 +/- 0.9 days, p > 0.05), or mortality within 30 days (14.5% vs 12.2%, p > 0.05). In conclusion, despite the greater incidence of some types of cardiac arrhythmias during an acute MI in OSA, these patients have the same clinical course in hospital and mortality rate as nonOSA patients.

[Reparative characteristics of gastric and duodenal mucosa in ulcer]. / Kharakter reparatsii slizistoí obolochki zheludka i dvenadtsatiperstnoí kishki pri iazvennoí bolezni.

Mucosal repair in the stomach and duodenum was assessed clinically and morphologically in various ulcer phases in 475 patients with gastroduodenal ulcer. It was found that poorly scarring ulcers are characterized by severe impairment of regeneration with epithelial proliferation prevailing over its differentiation. Participation of immune system, primarily T-cell component, in regeneration regulation is shown. Helicobacter pylori is not involved in repair. Superoxide dismutase activity in red cells and ulcer edges mucosa is prognostically significant indicating the disease phase, completeness of ulcer process.

[The effect of head-down tilt bed rest on metabolism of erythrocytes and functional state of membranes in females]. / Dinamika sdvigov gematologicheskikh sdvigov u zhenshchin v usloviiakh antiortostaticheskoi gipokinezii.

Metabolism of erythrocytes and the structural/functional state of membranes were studied in females in the 120-day head-down bed rest and the subsequent period of recovery. As was stated, prolonged bed rest and early recovery cause shifts in the metabolic and structural parameters of erythrocytes and ensuing degradation of the functional state of erythrocytes, i.e. changes in deformability and echinocytosis. The system of countermeasures including exercise and a set of alimentary supplements with polysaturated fat acids and antioxidants, proved to moderate the changes although it failed to fully eliminate them.