Репозиторий Университета

© 2021, The Author(s). Background: The synaptic vesicle glycoprotein 2 (SV2) family is essential to the synaptic machinery involved in neurotransmission and vesicle recycling. The isoforms SV2A, SV2B and SV2C are implicated in neurological diseases such as epilepsy, Alzheimer’s and Parkinson’s disease. Suitable cell systems for studying regulation of these proteins are essential. Here we present gene expression data of SV2A, SV2B and SV2C in two human neuroblastoma cell lines after differentiation. Methods: Human neuroblastoma cell lines SiMa and IMR-32 were treated for seven days with growth supplements (B-27 and N-2), all-trans-retinoic acid (ATRA) or vasoactive intestinal peptide (VIP) and gene expression levels of SV2 and neuronal targets were analyzed. Results: The two cell lines reacted differently to the treatments, and only one of the three SV2 isoforms was affected at a time. SV2B and choline O-acetyltransferase (CHAT) expression was changed in concert after growth supplement treatment, decreasing in SiMa cells while increasing in IMR-32. ATRA treatment resulted in no detected changes in SV2 expression in either cell line while VIP increased both SV2C and dopamine transporter (DAT) in IMR-32 cells. Conclusion: The synergistic expression patterns between SV2B and CHAT as well as between SV2C and DAT mirror the connectivity between these targets found in disease models and knock-out animals, although here no genetic alteration was made. These cell lines and differentiation treatments could possibly be used to study SV2 regulation and function.

© 2021, The Author(s). Background: The synaptic vesicle glycoprotein 2 (SV2) family is essential to the synaptic machinery involved in neurotransmission and vesicle recycling. The isoforms SV2A, SV2B and SV2C are implicated in neurological diseases such as epilepsy, Alzheimer’s and Parkinson’s disease. Suitable cell systems for studying regulation of these proteins are essential. Here we present gene expression data of SV2A, SV2B and SV2C in two human neuroblastoma cell lines after differentiation. Methods: Human neuroblastoma cell lines SiMa and IMR-32 were treated for seven days with growth supplements (B-27 and N-2), all-trans-retinoic acid (ATRA) or vasoactive intestinal peptide (VIP) and gene expression levels of SV2 and neuronal targets were analyzed. Results: The two cell lines reacted differently to the treatments, and only one of the three SV2 isoforms was affected at a time. SV2B and choline O-acetyltransferase (CHAT) expression was changed in concert after growth supplement treatment, decreasing in SiMa cells while increasing in IMR-32. ATRA treatment resulted in no detected changes in SV2 expression in either cell line while VIP increased both SV2C and dopamine transporter (DAT) in IMR-32 cells. Conclusion: The synergistic expression patterns between SV2B and CHAT as well as between SV2C and DAT mirror the connectivity between these targets found in disease models and knock-out animals, although here no genetic alteration was made. These cell lines and differentiation treatments could possibly be used to study SV2 regulation and function.

The family of Tribbles proteins play many critical nonenzymatic roles and regulate a wide range of key signaling pathways. Tribbles homolog 2 (Trib2) is a pseudo serine/threonine kinase that functions as a scaffold or adaptor in various physiological and pathological processes. Trib2 can interact with E3 ubiquitin ligases and control protein stability of downstream effectors. This protein is induced by mitogens and enhances the propagation of several cancer cells, including myeloid leukemia, liver, lung, skin, bone, brain, and pancreatic. Thus, Trib2 can be a predictive and valuable biomarker for the diagnosis and treatment of cancer. Recent studies have illustrated that Trib2 plays a major role in cell fate determination of stem cells. Stem cells have the capacity to self-renew and differentiate into specific cell types. Stem cells are important sources for cell-based regenerative medicine and drug screening. Trib2 has been found to increase the self-renewal ability of embryonic stem cells, the reprogramming efficiency of somatic cells, and chondrogenesis. In this review, we will focus on the recent advances of Trib2 function in tumorigenesis and stem cell fate decisions. [MediaObject not available: see fulltext.]

Background: Migraine and depression are highly prevalent and partly overlapping disorders that cause strong limitations in daily life. Patients tend to respond poorly to the therapies available for these diseases. OnabotulinumtoxinA has been proven to be an effective treatment for both migraine and depression. While many studies have addressed the effect of onabotulinumtoxinA in migraine or depression separately, a growing body of evidence suggests beneficial effects also for patients comorbid with migraine and depression. The current meta-analysis systematically investigates to what extent onabotulinumtoxinA is efficient in migraineurs with depression. Methods: A systematic literature search was performed based on PubMed, Scopus and Web of Science from the earliest date till October 30 th, 2020. Mean, standard deviation (SD) and sample size have been used to evaluate improvement in depressive symptoms and migraine using random-effects empirical Bayes model. Results: Our search retrieved 259 studies, eight of which met the inclusion criteria. OnabotulinumtoxinA injections administered to patients with both chronic migraine and major depressive disorder led to mean reduction of -8.94 points (CI [-10.04,-7.84], p < 0.01) in the BDI scale, of -5.90 points (CI [-9.92,-1.88], p < 0.01) in the BDI-II scale and of -6.19 points (CI [-9.52,-2.86], p < 0.01) in the PHQ-9 scale, when evaluating depressive symptoms. In the case of the migraine-related symptoms, we found mean reductions of -4.10 (CI [-7.31,-0.89], p = 0.01) points in the HIT6 scale, -32.05 (CI [-55.96,-8.14], p = 0.01) in the MIDAS scale, -1.7 (CI [-3.27,-0.13], p = 0.03) points in the VAS scale and of -6.27 (CI [-8.48,-4.07], p < 0.01) migraine episodes per month. Comorbid patients showed slightly better improvements in BDI, HIT6 scores and migraine frequency compared to monomorbid patients. The latter group manifested better results in MIDAS and VAS scores. Conclusion: Treatment with onabotulinumtoxinA leads to a significant reduction of disease severity of both chronic migraine and major depressive disorder in patients comorbid with both diseases. Comparative analyses suggest an equivalent strong effect in monomorbid and comorbid patients, with beneficial effects specifically seen for certain migraine features.

Background: Low endometrial receptivity is one of the major factors affecting successful implantation in assisted reproductive technologies (ART). Infertile patients with thin endometrium have a significantly lower cumulative clinical pregnancy rate than patients with normal endometrium. Molecular pathophysiology of low receptivity of thin endometrium remains understudied. We have investigated composition of glycocalyx of the apical surface of luminal and glandular epithelial cells in thin endometrium of infertile women. Methods: Thirty-two patients with tubal-peritoneal infertility undergoing in vitro fertilization (IVF) were included in the study. Endometrial samples were obtained in a natural menstrual cycle. Patients were divided into two groups: patients with normal endometrium (≥8 mm) and with thin endometrium (< 8 mm). Histochemical and immunohistochemical analysis of paraffin-embedded endometrial samples was performed using six biotinylated lectins (UEA-I, MAL-II, SNA, VVL, ECL, Con A) and anti-Le  and MECA-79 monoclonal antibodies (MAbs). Results: Complex glycans analysis taking into account the adjusted specificity of glycan-binding MAbs revealed 1.3 times less expression of MECA-79 glycans on the apical surface of the luminal epithelial cells of thin endometrium compared to normal endometrium; this deficiency may adversely affect implantation, since MECA-79 glycans are a ligand of L-selectin and mediate intercellular interactions. The glycans containing a type-2 unit Galβ1-4GlcNAcβ (LacNAc) but lacking sulfo-residues at 6-OH of GlcNAcβ, and binding to MECA-79 MAbs were found; they can be considered as potential markers of endometrium receptivity. Expression of the lectins-stained glycans on the apical surfaces of the luminal and glandular epithelial cells did not differ significantly. Correlation between the expression of difucosylated oligosaccharide Le  on the apical surfaces of the luminal and glandular epithelial cells was found in patients with thin endometrium and recurrent implantation failure. A similar relationship was shown for mannose-rich glycans. Conclusions: Specific features of key glycans expression in epithelial compartments of thin endometrium may be essential for morphogenesis of the endometrial functional layer and explain its low receptivity. Y Y

Background: Low endometrial receptivity is one of the major factors affecting successful implantation in assisted reproductive technologies (ART). Infertile patients with thin endometrium have a significantly lower cumulative clinical pregnancy rate than patients with normal endometrium. Molecular pathophysiology of low receptivity of thin endometrium remains understudied. We have investigated composition of glycocalyx of the apical surface of luminal and glandular epithelial cells in thin endometrium of infertile women. Methods: Thirty-two patients with tubal-peritoneal infertility undergoing in vitro fertilization (IVF) were included in the study. Endometrial samples were obtained in a natural menstrual cycle. Patients were divided into two groups: patients with normal endometrium (≥8 mm) and with thin endometrium (< 8 mm). Histochemical and immunohistochemical analysis of paraffin-embedded endometrial samples was performed using six biotinylated lectins (UEA-I, MAL-II, SNA, VVL, ECL, Con A) and anti-Le  and MECA-79 monoclonal antibodies (MAbs). Results: Complex glycans analysis taking into account the adjusted specificity of glycan-binding MAbs revealed 1.3 times less expression of MECA-79 glycans on the apical surface of the luminal epithelial cells of thin endometrium compared to normal endometrium; this deficiency may adversely affect implantation, since MECA-79 glycans are a ligand of L-selectin and mediate intercellular interactions. The glycans containing a type-2 unit Galβ1-4GlcNAcβ (LacNAc) but lacking sulfo-residues at 6-OH of GlcNAcβ, and binding to MECA-79 MAbs were found; they can be considered as potential markers of endometrium receptivity. Expression of the lectins-stained glycans on the apical surfaces of the luminal and glandular epithelial cells did not differ significantly. Correlation between the expression of difucosylated oligosaccharide Le  on the apical surfaces of the luminal and glandular epithelial cells was found in patients with thin endometrium and recurrent implantation failure. A similar relationship was shown for mannose-rich glycans. Conclusions: Specific features of key glycans expression in epithelial compartments of thin endometrium may be essential for morphogenesis of the endometrial functional layer and explain its low receptivity. Y Y

Background: There is currently a wide therapeutic arsenal for migraine patients, without a single first-line preventive drug and we choose the different available alternatives taking into account comorbidities, national guidelines, previous treatments and personal experiences. Our objective was to evaluate the differences in the use of migraine treatments between neurologists from different countries. Methods: This is a multi-centre observational study carried out by neurologists from specialized headache units in seven countries, retrospective with consecutive inclusion of all patients presenting with a migraine diagnosis, over a period of three months. Results: A total of 734 patients were recruited but only 600 were considered in the analysis in order to homogenize the patient cohorts from countries: 200 Spain (ES), 100 Italy (IT), 85 Russia (RUS), 80 Germany (DE), 60 Portugal (PT), 45 Poland (PL) and 30 Australia (AU). 85.4 % of patients were women with a mean age of 42.6 ± 11.8 years. Considering previous and current preventive treatment, the order of use was: antidepressants (69.3 %), antiepileptic drugs (54.7 %), beta-blockers and antihypertensive drugs (49.7 %), OnabotulinumtoxinA (44.0 %) and others (36.2 %). Statistically significant differences were found between all pharmacological classes: antidepressants were commonly used in all countries, with the exception of Poland (AU: 76.7 %, IT: 71.0 %, DE: 60.0 %, PL: 31.1 %, PT: 71.7 %, RUS: 70.6 %, ES: 78.5 %; p < 0.0001); antiepileptic drugs were more frequently prescribed in Portugal, Australia and Spain (AU: 73.3 %, IT: 40.0 %, DE: 37.5 %, PL: 48.9 %, PT: 85.0 %, RUS: 29.4 % and ES: 69.0 %; p < 0.0001); beta-blockers and antihypertensive drugs were frequently used in all countries except Italy (AU: 60.0 %, IT: 14.0 %, DE: 53.8 %, PL: 48.9 %, PT: 68.3 %, RUS: 49.4 % and ES: 59.0 %; p < 0.0001); BTX-A were predominately used in Spain, Italy and Australia (AU:56.7 %, IT:58.0 %, DE:20.0 %, PL: 42.2 %, PT: 26.7 %, RUS: 24.7 % and ES: 58.5 %; p < 0.0001) and others were most frequently used in Poland (AU: 0.0 %, IT: 19.0 %, DE: 42.5 %, PL: 95.6 %, PT: 31.7 %, RUS: 3.5 % and ES: 49.5 %; p < 0.0001). If only patients without comorbidities are considered (200/600), statistically differences between countries persist in all preventive treatments. Conclusions: There is heterogeneity in the choice of preventive treatment between different countries. Prospective comparative studies of the different oral and subcutaneous alternatives would help to create a global therapeutic algorithm that would guarantee the best option for our patients.

© 2020 Elsevier Inc. Despite high prevalence, medical impact and societal burden, anxiety, depression and other affective disorders remain poorly understood and treated. Clinical complexity and polygenic nature complicate their analyses, often revealing genetic overlap and cross-disorder heritability. However, the interplay or overlaps between disordered phenotypes can also be based on shared molecular pathways and ‘crosstalk’ mechanisms, which themselves may be genetically determined. We have earlier predicted (Kalueff et al., 2014) a new class of ‘interlinking’ brain genes that do not affect the disordered phenotypes per se, but can instead specifically determine their interrelatedness. To test this hypothesis experimentally, here we applied a well-established rodent chronic social defeat stress model, known to progress in C57BL/6J mice from the Anxiety-like stage on Day 10 to Depression-like stage on Day 20. The present study analyzed mouse whole-genome expression in the prefrontal cortex and hippocampus during the Day 10, the Transitional (Day 15) and Day 20 stages in this model. Our main question here was whether a putative the Transitional stage (Day 15) would reveal distinct characteristic genomic responses from Days 10 and 20 of the model, thus reflecting unique molecular events underlining the transformation or switch from anxiety to depression pathogenesis. Overall, while in the Day 10 (Anxiety) group both brain regions showed major genomic alterations in various neurotransmitter signaling pathways, the Day 15 (Transitional) group revealed uniquely downregulated astrocyte-related genes, and the Day 20 (Depression) group demonstrated multiple downregulated genes of cell adhesion, inflammation and ion transport pathways. Together, these results reveal a complex temporal dynamics of mouse affective phenotypes as they develop. Our genomic profiling findings provide first experimental support to the idea that novel brain genes (activated here only during the Transitional stage) may uniquely integrate anxiety and depression pathogenesis and, hence, determine the progression from one pathological state to another. This concept can potentially be extended to other brain conditions as well. This preclinical study also further implicates cilial and astrocytal mechanisms in the pathogenesis of affective disorders.

© 2020 The Authors The assessment of behavioral outcomes is a central component of neuroscientific research, which has required continuous technological innovations to produce more detailed and reliable findings. In this article, we provide an in-depth review on the progress and future implications for three model organisms (mouse, rat, and Drosophila) essential to our current understanding of behavior. By compiling a comprehensive catalog of popular assays, we are able to compare the diversity of tasks and usage of these animal models in behavioral research. This compilation also allows for the evaluation of existing state-of-the-art methods and experimental applications, including optogenetics, machine learning, and high-throughput behavioral assays. We go on to discuss novel apparatuses and inter-species analyses for centrophobism, feeding behavior, aggression and mating paradigms, with the goal of providing a unique view on comparative behavioral research. The challenges and recent advances are evaluated in terms of their translational value, ethical procedures, and trustworthiness for behavioral research.

© 2020 The Authors The assessment of behavioral outcomes is a central component of neuroscientific research, which has required continuous technological innovations to produce more detailed and reliable findings. In this article, we provide an in-depth review on the progress and future implications for three model organisms (mouse, rat, and Drosophila) essential to our current understanding of behavior. By compiling a comprehensive catalog of popular assays, we are able to compare the diversity of tasks and usage of these animal models in behavioral research. This compilation also allows for the evaluation of existing state-of-the-art methods and experimental applications, including optogenetics, machine learning, and high-throughput behavioral assays. We go on to discuss novel apparatuses and inter-species analyses for centrophobism, feeding behavior, aggression and mating paradigms, with the goal of providing a unique view on comparative behavioral research. The challenges and recent advances are evaluated in terms of their translational value, ethical procedures, and trustworthiness for behavioral research.

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Web-surveys are one of the most popular forms of primary data collection used for various researches. However, mass surveys involve some challenges. It is required to consider different platforms and browsers, as well as different data transfer rates using connections in different regions of the country. Ensuring guaranteed data delivery in these conditions should determine the right choice of technologies for implementing web-surveys. The paper describes the solution to transfer a questionnaire to the client side in the form of an archive. This technological solution ensures independence from the data transfer rate and the stability of the communication connection with significant survey filling time. The conducted survey benefited the service of education psychologists under the federal Ministry of Education. School psychologists consciously took part in the survey, realizing the importance of their opinion for organizing and improving their professional activities. The desire to answer open-ended questions in detail created a part of the answers in the dataset, where there were several sentences about different aspects of professional activity. An important challenge of the problem is the Russian language, for which there are not as many tools as for the languages more widespread in the world. The survey involved 20,443 school psychologists from all regions of the Russian Federation, both from urban and rural areas. The answers did not contain spam, runaround answers, and so on as evidenced by the average response time. For the surveys, an authoring development tool DigitalPsyTools.ru was used. Dataset: http://dx.doi.org/10.17632/m32kz6jjcx.1 Dataset License: CC-BY-4.0.

© 2018, © 2018 Informa UK Limited, trading as Taylor  &  Francis Group. Background: Antiphospholipid antibodies (aPL) have a multifaceted effect on the hemostatic system, damaging all its protective links. Aim: To study the effect of APA on outcomes of assisted reproductive technologies (ART). Study design: We examined 267 women with infertility, who planned pregnancy using ART. They included 178 women with IVF failure (I group) and 89 women with pregnancy after the IVF program (II group). The comparison group consisted of 80 pregnant women after IVF (male factor); a control group included 80 pregnant women with physiological pregnancy. Results of study demonstrated a high frequency of aPL circulation in a group of women with IVF failures. Overall, the proportion of aPL among all 267 women who planned pregnancy with ART was 32.6%. Elevated levels of aPL in the structure of causes of IVF failures (group I) were observed in 42.1% of them. Among women whose pregnancy occurred with ART (II group) the rate of APA was 19.1%. In the comparison group, in 6.3% of cases, aPL circulation was observed. In the control group, the rate was 3.4%. Conclusion: Considering the high percentage of aPL circulation in the case of IVF failures, authors think that high titers of aPL are a temporary contraindication for IVF. Patients with a history of aPL circulation are required to receive anticoagulant therapy from the first days of the hormonal protocol. The drug of choice is a group of low molecular weight heparins (LMWH). An individual approach is extremely important with the possible identification of causes of IVF failures and selective therapy, which leads to a significant improvement in the outcomes of the IVF program.

© 2018, © 2018 Informa UK Limited, trading as Taylor  &  Francis Group. Background: Antiphospholipid antibodies (aPL) have a multifaceted effect on the hemostatic system, damaging all its protective links. Aim: To study the effect of APA on outcomes of assisted reproductive technologies (ART). Study design: We examined 267 women with infertility, who planned pregnancy using ART. They included 178 women with IVF failure (I group) and 89 women with pregnancy after the IVF program (II group). The comparison group consisted of 80 pregnant women after IVF (male factor); a control group included 80 pregnant women with physiological pregnancy. Results of study demonstrated a high frequency of aPL circulation in a group of women with IVF failures. Overall, the proportion of aPL among all 267 women who planned pregnancy with ART was 32.6%. Elevated levels of aPL in the structure of causes of IVF failures (group I) were observed in 42.1% of them. Among women whose pregnancy occurred with ART (II group) the rate of APA was 19.1%. In the comparison group, in 6.3% of cases, aPL circulation was observed. In the control group, the rate was 3.4%. Conclusion: Considering the high percentage of aPL circulation in the case of IVF failures, authors think that high titers of aPL are a temporary contraindication for IVF. Patients with a history of aPL circulation are required to receive anticoagulant therapy from the first days of the hormonal protocol. The drug of choice is a group of low molecular weight heparins (LMWH). An individual approach is extremely important with the possible identification of causes of IVF failures and selective therapy, which leads to a significant improvement in the outcomes of the IVF program.

© 2020 Global-Science Press In this paper we introduce a new mathematical model for the active contraction of cardiac muscle, featuring different thermo-electric and nonlinear conductivity properties. The passive hyperelastic response of the tissue is described by an orthotropic exponential model, whereas the ionic activity dictates active contraction incorporated through the concept of orthotropic active strain. We use a fully incompressible formulation, and the generated strain modifies directly the conductivity mechanisms in the medium through the pull-back transformation. We also investigate the influence of thermo-electric effects in the onset of multiphysics emergent spatiotemporal dynamics, using nonlinear diffusion. It turns out that these ingredients have a key role in reproducing pathological chaotic dynamics such as ventricular fibrillation during inflammatory events, for instance. The specific structure of the governing equations suggests to cast the problem in mixed-primal form and we write it in terms of Kirchhoff stress, displacements, solid pressure, dimensionless electric potential, activation generation, and ionic variables. We also advance a new mixed-primal finite element method for its numerical approximation, and we use it to explore the properties of the model and to assess the importance of coupling terms, by means of a few computational experiments in 3D.

© 2019 Background: Iron (Fe), copper (Cu), and manganese (Mn) play a significant role in female reproduction and fetal development. At the same time, high levels of metals may exert toxic effects. Correspondingly, both excess and deficiency of essential trace elements were shown to be associated with female infertility and adverse pregnancy outcome, although the existing data are rather contradictory. Therefore, the objective of the present study was to reveal the potential role of altered iron, copper, and manganese status in female reproductive health problems through assessment of serum metal levels in healthy non-pregnant and pregnant women, as well as patients with miscarriage and primary infertility. Methods: A total of 150 healthy controls, 169 pregnant women (II trimester of pregnancy), 75 women with miscarriage, and 91 patients with primary infertility were enrolled. Serum metal levels were assessed using ICP-MS. Results: Pregnant women are characterized by a significant increase in serum Cu an Mn levels by 40% (p < 0.001) and 16% (p = 0.043) as compared to the controls, respectively. Serum Cu levels in women with miscarriage and infertility were 30% and 35% lower than those in pregnant women (p < 0.001). No significant difference in serum iron levels were observed between the control and pregnant women. Women who had miscarriage were characterized by 13% (p = 0.042) higher serum Fe levels as compared to the pregnant ones. Multiple regression analysis demonstrated that serum copper levels was significantly associated both with pregnancy (β = 0.436; p < 0.001) and reproductive health problems in women (β = −0.272; p < 0.001). The latter was improved significant after adjustment for serum Fe and Mn levels, age, and BMI (β = −0.431; p < 0.001). The model incorporating serum Cu, Fe, Mn, and anthropometric parameters accounted for 23% of variability in reproductive status (p < 0.001). Conclusions: It is proposed that the lack of pregnancy-associated increase in metal levels in miscarriage and infertility may be indicative of at least partial role of metal insufficiency in impaired pregnancy and reproductive function in general. However, detailed clinical studies as well as experimental investigations are required for assessment of the potential causes and mechanisms of the observed associations.

© 2019 The purpose of this study was to assess the prognostic value of lactate dehydrogenase (LDH) in patients with metastatic prostate cancer (PC). A systematic review and meta-analysis was performed in March 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared patients with PC with high versus low LDH to determine the predictive value of LDH for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). We performed a formal meta-analysis for both OS and PFS. A total of 59 articles with 14,851 patients were included in the systematic review and 45 studies with 12,224 patients for the qualitative assessment. High LDH was associated with both worse OS (pooled hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.75-2.44) and PFS (pooled HR, 1.08; 95% CI, 1.01-1.16). In subgroup analyses of both patients with castration-resistant prostate cancer (CRPC) and those with hormone-sensitive prostate cancer (HSPC), LDH was associated with OS (pooled HR, 2.02; 95% CI, 1.69-2.42 and pooled HR, 2.25; 95% CI, 1.78-2.84, respectively). In patients with CRPC, LDH was associated with OS in those treated with docetaxel systemic chemotherapy and androgen receptor–axis-targeting agents (pooled HR, 2.03; 95% CI, 1.37-3.00 and pooled HR, 1.79; 95% CI, 1.25-2.57, respectively). Elevated serum levels of LDH were associated with an increased risk of mortality and progression in patients with metastatic PC. LDH was independently associated with OS in both patients with CRPC and HSPC. LDH could be integrated into prognostic tools that help guide treatment strategy, thereby facilitating the shared decision-making process.

© 2019, Springer Nature B.V. Objectives: Various techniques can be used for endoscopic enucleation of the prostate (EEP): removal of all nodes as a single unit (en bloc) or a step-by-step removal of adenomatous nodes (two- and three-lobe techniques). The objective of this study was to perform a comparative analysis of en bloc and two-lobe techniques for holmium laser enucleation of the prostate (HoLEP) and thulium fiber laser enucleation of the prostate (ThuFLEP). Methods: Retrospective assessment included patients with bladder outlet obstruction (IPSS > 20, Qmax < 10) secondary to BPH treated from January 2013 to December 2018. All the patients were assessed prior to surgery, as well as at 1, 3 and 6 months after surgery. Results: The data of 1115 patients who underwent HoLEP or ThuFLEP were analyzed. Two techniques were used: en bloc (406 patients) and two-lobe (709 patients). Mean prostate volumes were comparable between groups. Mean surgery times (68.8 ± 30.6 min vs 67.4 ± 30.1 min; p = 0.604) and enucleation rates (1.9 ± 0.74 g/min vs 1.9 ± 0.69 g/min; p = 0.217) were also comparable. Morcellation rate was lower in en bloc patients with prostate > 150 cc (2.8 ± 1.1 g/min vs 3.7 ± 2.3 g/min; p < 0.001). At 6 months, no differences in functional outcomes (IPSS, PVR, Qmax and QoL) were found. Conclusions: Outcomes and complication rates of en bloc and two-lobe EEP techniques were comparable. En bloc technique was found to have less favorable outcomes in morcellation rate for prostates > 150 cc. The choice of the technique should depend on surgeon’s preferences.

© 2019 Elsevier B.V. S-Methyl methanethiosulfonate (MMTS) is used in experimental biochemistry for alkylating thiol groups of protein cysteines. Its applications include mainly trapping of natural thiol-disulfide states of redox-sensitive proteins and proteins which have undergone S-nitrosylation. The reagent can also be employed as an inhibitor of enzymatic activity, since nucleophilic cysteine thiolates are commonly present at active sites of various enzymes. The advantage of using MMTS for this purpose is the reversibility of the formation of methylthio mixed disulfides, compared to irreversible alkylation using conventional agents. Additional benefits include good accessibility of MMTS to buried protein cysteines due to its small size and the simplicity of the protection and deprotection procedures. In this study we report examples of MMTS application in experiments involving oxidoreductase (glyceraldehyde-3-phosphate dehydrogenase, GAPDH), redox-regulated protein (recoverin) and cysteine protease (triticain-α). We demonstrate that on the one hand MMTS can modify functional cysteines in the thiol enzyme GAPDH, thereby preventing thiol oxidation and reversibly inhibiting the enzyme, while on the other hand it can protect the redox-sensitive thiol group of recoverin from oxidation and such modification produces no impact on the activity of the protein. Furthermore, using the example of the papain-like enzyme triticain-α, we report a novel application of MMTS as a protector of the primary structure of active cysteine protease during long-term purification and refolding procedures. Based on the data, we propose new lines of MMTS employment in research, pharmaceuticals and biotechnology for reversible switching off of undesirable activity and antioxidant protection of proteins with functional thiol groups.

© Mattioli 1885. Background and aim: The studies of Nobel laureate Robert Geoffrey Edwards led to the first in vitro fertilization and embryo transfer in 1978. Since then, reproductive medicine has made huge advances. Methods available to sterile couples now include: purchasing oocytes and sperm, uterus surrogacy, pre-implantation or pre-natal diagnosis, embryo/fetal selection. Here we highlight the fact that combinations of existing technologies could threaten the non-marketability of human life. Methods: We searched PubMed and websites to find articles regarding assisted reproduction techniques. Results: These methods, taken separately, provide support for natural fertilization, but when used together, they may lead to genuine “baby factories”. In poor countries, such “factories” exist and often act illegally. Conclusions: We highlight the need for deeper bioethical studies and better legislation regarding the combined use of medically-assisted reproductive techniques.

Heart failure is a complex syndrome whose phenotypic presentation and disease progression depends on a complex network of adaptive and maladaptive responses. One of these responses is the endothelial release of NRG (neuregulin)-1-a paracrine growth factor activating ErbB2 (erythroblastic leukemia viral oncogene homolog B2), ErbB3, and ErbB4 receptor tyrosine kinases on various targets cells. NRG-1 features a multitasking profile tuning regenerative, inflammatory, fibrotic, and metabolic processes. Here, we review the activities of NRG-1 on different cell types and organs and their implication for heart failure progression and its comorbidities. Although, in general, effects of NRG-1 in heart failure are compensatory and beneficial, translation into therapies remains unaccomplished both because of the complexity of the underlying pathways and because of the challenges in the development of therapeutics (proteins, peptides, small molecules, and RNA-based therapies) for tyrosine kinase receptors. Here, we give an overview of the complexity to be faced and how it may be tackled.