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The Polish Society of Colposcopy and Cervical Pathophysiology and the Polish Society of Gynecologists and Obstetricians provide comprehensive guidelines for colposcopy practice in secondary cervical cancer prevention in Poland. This part of the guidelines, developed by the clinical experts of the Working Group No. 1 (WG1), concerns the colposcopy protocols with the main aim of algorithmizing the procedure, together with all procedure-related processes. The detailed analysis of strong scientific evidence and an extensive literature review of current international colposcopic recommendations were carried out, with also a broad investigation of recently ongoing dynamic changes in national health systems. The attention to colposcopic limitations also occurring in Polish conditions was kept. The overriding goal was the recommended obligatory minimal colposcopy approach introduction. To enhance the standard of colposcopy, adjustment of a precolposcopic assessment, a performance technique, types of used biopsies, as well as the procedure documentation was made. Elements of the risk-based stratification for the increased risk of developing cervical cancer was also included if it was applicable for that part of the guidelines. Comprehensive colposcopy guidelines are a step towards the ongoing era of a precision medicine in cervical cancer prevention in Poland.

Aims/hypothesis Angiopoietin-like 4 (ANGPTL4) is an important regulator of triacylglycerol metabolism, carrying out this role by inhibiting the enzymes lipoprotein lipase and pancreatic lipase. ANGPTL4 is a potential target for ameliorating cardiometabolic diseases. Although ANGPTL4 has been implicated in obesity, the study of the direct role of ANGPTL4 in diet-induced obesity and related metabolic dysfunction is hampered by the massive acute-phase response and development of lethal chylous ascites and peritonitis in Angptl4−/− mice fed a standard high-fat diet. The aim of this study was to better characterise the role of ANGPTL4 in glucose homeostasis and metabolic dysfunction during obesity. Methods We chronically fed wild-type (WT) and Angptl4−/− mice a diet rich in unsaturated fatty acids and cholesterol, combined with fructose in drinking water, and studied metabolic function. The role of the gut microbiota was investigated by orally administering a mixture of antibiotics (ampicillin, neomycin, metronidazole). Glucose homeostasis was assessed via i.p. glucose and insulin tolerance tests. Results Mice lacking ANGPTL4 displayed an increase in body weight gain, visceral adipose tissue mass, visceral adipose tissue lipoprotein lipase activity and visceral adipose tissue inflammation compared with WT mice. However, they also unexpectedly had markedly improved glucose tolerance, which was accompanied by elevated insulin levels. Loss of ANGPTL4 did not affect glucose-stimulated insulin secretion in isolated pancreatic islets. Since the gut microbiota have been suggested to influence insulin secretion, and because ANGPTL4 has been proposed to link the gut microbiota to host metabolism, we hypothesised a potential role of the gut microbiota. Gut microbiota composition was significantly different between Angptl4−/− mice and WT mice. Interestingly, suppression of the gut microbiota using antibiotics largely abolished the differences in glucose tolerance and insulin levels between WT and Angptl4−/− mice. Conclusions/interpretation Despite increasing visceral fat mass, inactivation of ANGPTL4 improves glucose tolerance, at least partly via a gut microbiota-dependent mechanism. Electronic supplementary material The online version of this article (10.1007/s00125-018-4583-5) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

The Polish Society of Colposcopy and Cervical Pathophysiology and the Polish Society of Gynecologists and Obstetricians provide comprehensive guidelines for colposcopy practice in secondary cervical cancer prevention in Poland. This part of the guidelines, developed by the clinical experts of the Working Group No. 1 (WG1), concerns the colposcopy protocols with the main aim of algorithmizing the procedure, together with all procedure-related processes. The detailed analysis of strong scientific evidence and an extensive literature review of current international colposcopic recommendations were carried out, with also a broad investigation of recently ongoing dynamic changes in national health systems. The attention to colposcopic limitations also occurring in Polish conditions was kept. The overriding goal was the recommended obligatory minimal colposcopy approach introduction. To enhance the standard of colposcopy, adjustment of a precolposcopic assessment, a performance technique, types of used biopsies, as well as the procedure documentation was made. Elements of the risk-based stratification for the increased risk of developing cervical cancer was also included if it was applicable for that part of the guidelines. Comprehensive colposcopy guidelines are a step towards the ongoing era of a precision medicine in cervical cancer prevention in Poland.

Type 2 diabetes is characterised by impaired glucose-stimulated insulin secretion (GSIS) from pancreatic islets. Since erythropoietin-producing hepatoma (Eph)-ephrin bidirectional signalling fine-tunes GSIS from pancreatic beta cells, we investigated Eph receptor tyrosine kinases (RTK) as potential drug targets for selectively increasing GSIS.Insulin secretion assays were carried out using mouse and human pancreatic islets as well as mouse insulinoma (MIN6) cells in the presence or absence of two Eph RTK inhibitors. Furthermore, the most potent inhibitor was injected into mice to evaluate its effects on glucose tolerance and plasma insulin levels.We showed that the Eph RTK inhibitors selectively increased GSIS from MIN6 cells as well as mouse and human islets. Our results also showed that the insulin secretory effects of these compounds required Eph-ephrin signalling. Finally, pharmacological inhibition of Eph receptor signalling improved glucose tolerance in mice.We showed for the first time that Eph RTKs represent targets for small molecules to selectively increase GSIS and improve glucose tolerance.

A hallmark feature of type 1 and type 2 diabetes mellitus is the progressive dysfunction and loss of insulin-producing pancreatic beta cells, and inflammatory cytokines are known to trigger beta cell death. Here we asked whether the anti-oxidant protein DJ-1 encoded by the Parkinson's disease gene PARK7 protects islet cells from cytokine- and streptozotocin-mediated cell death. Wild type and DJ-1 knockout mice (KO) were treated with multiple low doses of streptozotocin (MLDS) to induce inflammatory beta cell stress and cell death. Subsequently, glucose tolerance tests were performed, and plasma insulin as well as fasting and random blood glucose concentrations were monitored. Mitochondrial morphology and number of insulin granules were quantified in beta cells. Moreover, islet cell damage was determined in vitro after streptozotocin and cytokine treatment of isolated wild type and DJ-1 KO islets using calcein AM/ethidium homodimer-1 staining and TUNEL staining. Compared to wild type mice, DJ-1 KO mice became diabetic following MLDS treatment. Insulin concentrations were substantially reduced, and fasting blood glucose concentrations were significantly higher in MLDS-treated DJ-1 KO mice compared to equally treated wild type mice. Rates of beta cell apoptosis upon MLDS treatment were twofold higher in DJ-1 KO mice compared to wild type mice, and in vitro inflammatory cytokines led to twice as much beta cell death in pancreatic islets from DJ-1 KO mice versus those of wild type mice. In conclusion, this study identified the anti-oxidant protein DJ-1 as being capable of protecting pancreatic islet cells from cell death induced by an inflammatory and cytotoxic setting.

Autoimmune disturbances and metabolic abnormalities observed in vitiligo, a disease of still unclear etiology, may provide evidence on the systemic nature of the disease. The aim of the study was to assess functional and morphological parameters of the liver and spleen, as well as the lipid profile in vitiligo-affected children, in order to ascertain whether any metabolic abnormalities or structural changes in these organs accompanied the course of vitiligo. The study included 34 patients with vitiligo hospitalized at the Department of Dermatology at the Medical University of Lublin and a control group of 35 healthy individuals, aged 7-15 years. Children with the active phase of vitiligo and at least 6 month history of vitiligo lesions were studied. Ultrasound examination of the liver and spleen enabled assessment of the size and parenchyma of the organs. Liver and spleen functions were assessed by means of the following additional examinations: blood test, transaminases, protein electrophoresis, lipid profile, autoantibodies, and HCV antibodies. The size of the liver was not significantly different in the vitiligo and control groups. The ultrasonographic pictures of the spleen revealed no abnormalities in organ size and structure. The concentration of HDL-cholesterol was significantly lower, whereas the concentration of LDL-cholesterol was significantly higher in patients with vitiligo than in healthy controls. The value of the LDL/HDL ratio was significantly higher in vitiligo patients. The results of our study indicate lipid disturbances in vitiligo-affected children. Since no structural and functional abnormalities in the liver and spleen were found, it seems likely that lipid disturbances in vitiligo may result from disturbed metabolic processes in the adipose tissue as well as from oxidative stress.

Background: Given the important role of ERCC4 gene in multiple DNA repair systems, we hypothesized that genetic variations within this gene may be a cervical squamous cell carcinoma (CSCC) risk and disease modulatory factor.Methods: In population-based, case-control association study including 143 CSCC patients and 207 healthy women, two ERCC4tagSNPs were studied.Results: A significant protective effect against CSCC was observed assuming a dominant model in case of ERCC4rs3136176 ([AA]+[AT]vs.[TT]: p=0.04,OR=0.43), and genotype [AA] strongly protects against poorly (G3) differentiated CSCC (pcorreced=0.008,OR=0.15) and significantly increased the disease remission rate (p=0.05,OR=0.48).A statistically significant increase frequency of ERCC4rs1799798 [A] allele was seen in patients with well differentiated (G1) CSCC (p=0.02, OR=2.40). Contrary, an opposite trend was observed when G1 was compared with G2 (moderately differentiated) CSCC (p=0.06). Furthermore, ERCC4rs1799798 [A] allele tended to be increased in patients with carcinoma planoepitheliale keratodes (Cpk) (p=0.07).Haplotype ERCC4rs3136176[A]/ERCC4rs1799798[G] significantly decreased risk of G1 as well as G3 CSCC (p=0.02,OR=0.50, and p=0.017,OR=0.42, respectively) and only tended to decrease risk of CSCC (p=0.07,OR=0.758) as well as carcinoma planoepitheliale akeratodes (Cpa) (p=0.059,OR=0.71).In contrast haplotype AA significantly increased risk of G1 CSCC and risk of Cpk (p=0.01, OR=2.51, and p=0.049, OR=1.96, respectively), whereas haplotype TG increased risk of G3 CSCC (p=0.037, OR=2.17).The overall survival rates showed similar mean survival rates according to patients' genotypes at both studied SNPs.Conclusion: The above findings consistently suggested that genetic variants in ERCC4 gene may play significant role in CSCC pathophysiology.

Purpose The purpose of this study was assessment of nailfold capillary changes and their possible relation to polymorphism of a gene encoding endothelial nitric oxide synthase (eNOS) in normal tension glaucoma (NTG) patients Methods The study included 35 normal-tension glaucoma (NTG) patients (23 female and 12 male). Capillaroscopic examination of the nailfold capillaries of II to V fingers of both hands was performed (before and after the cold provocation test) by means of a videocapillaroscope. T786C eNOS gene polymorphism was determined by RT- PCR methods. Results 31 (88.6%) patients suffered from cold extremities. In 24 (68.5%) patients nailfold capillaroscopy was within normal limits, in 11 (31.5%) patients the results were abnormal, 4 (11.4%) of them mimicked changes observed in sclerodermia. The cold provocation test was positive in 43.5% of NTG patients. The patients with NTG presented the following nailfold capillaries: megacapilaries or dilatated capillaries (44.4%), ramified/bushy (18.9%), coiled (17.1%). Assessing the T786C polymorphism of eNOS gene in NTG patients, TT genotype was present in 36% patients, TC in 52.6% and CC in 11.3%. There were no correlation between SNP variants and capillaroscopy results nor cold provocation test ( p=0.9 and 0.5, respectively). Conclusion The T786C polymorphism of eNOS gene does not influence the capillaroscopy results. The high incidence of sclerodermia - like changes in capillaroscopy in NTG needs further studies.

An important question is how growing tissues establish a blood vessel network. Here we study vascular network formation in pancreatic islets, endocrine tissues derived from pancreatic epithelium. We find that depletion of integrin-linked kinase (ILK) in the pancreatic epithelial cells of mice results in glucose intolerance due to a loss of the intra-islet vasculature. In turn, blood vessels accumulate at the islet periphery. Neither alterations in endothelial cell proliferation, apoptosis, morphology, Vegfa expression and VEGF-A secretion nor ‘empty sleeves’ of vascular basement membrane are found. Instead, biophysical experiments reveal that the biomechanical properties of pancreatic islet cells, such as their actomyosin-mediated cortex tension and adhesive forces to endothelial cells, are significantly changed. These results suggest that a sorting event is driving the segregation of endothelial and epithelial cells and indicate that the epithelial biomechanical properties determine whether the blood vasculature invades or envelops a growing epithelial tissue., Nature Communications, 7, ISSN:2041-1723

In this study the activity of neutrophils, measured using the chemiluminescence tests, was estimated in 91 children with food allergy. It was shown that the average chemiluminescence values without as well as after stimulation by FMLP, PMA and NZ were considerably higher in children with allergy in comparison to children from the control group.

In this study, the activity of neutrophils measured using the chemiluminescence test was estimated in 49 children with food allergy. It was shown that average chemiluminescence values without, as well as after, stimulation by formyl-methionyl-leucine phenylalanine and phorbol myristate acetate were considerably higher in children with allergy in comparison to those in the control group. The correlation between the production of reactive oxygen intermediates and interleukin (IL)-4, IL-5 and IL-10 concentration suggests that an autocrine regulatory mechanism may play a role in allergy in children.

Introduction A review of published studies shows that depressive disorders are correlated with specific defense patterns which may underlie particular personality trials. High comorbidity among depressive and personality conditions is a consistent but not well-understood finding. Objectives We assessed the relations between defense mechanisms and MMPI-2 profiles used by depressive patients. Aims The aim of the present study was to investigate how depressive disorders are related to the use of specific defenses and how it is corelated with particular MMPI-2 scales. Methods Authors examinated a sample of 50 adult outpatients aged 21 to 55 diagnosed with depressive disorders according to DSM-IV. The Bond Defense Style Questionnaire (DSQ) was used to assess defense styles. Patients were also examined with MMPI-2. Results Depressive disorder patients scored higher for the immature defense styles. Increased scores in psychopatological scales in MMPI-2 were positively related to the immature, neurotic and particular narcistic, and negatively to the mature defense mechanisms. Conclusions These findings suggest that interpretation of defense styles and particular MMPI-2 scales is useful for the psychological and personological diagnosis to direct psychological assistance. These findings could lead to the development of specific psychotherapeutic interventions.

NMDA receptor dependent anti-diabetic effects Jan Marquard, Silke Otter, Alena Welters, Diran Herebian, Fatih Demir, Annett Schroeter, Olaf Kletke, Martin Kragl, Daniel Eberhard, Barbara Bartosinska, Masa Skelin Klemen, Andraz Stozer, Martin Kohler, Alin Stirban, Freimut Schliess, Tim Heise, Stephan Wnendt, Marjan Slak Rupnik, Per-Olof Berggren, Nikolaj Klocker, Thomas Meissner, Ertan Mayatepek, Eckhard Lammert