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Three different, multifunctional acrylic monomers were photopolymerized in a matrix of poly(lactic acid), PLA, using 2-hydroxy-2-methyl-1-phenyl-propan-1-one as a photoinitiator. The kinetics of the photopolymerization of monomers in PLA, studied with Fourier Transform Infrared Spectroscopy, has been compared to analogous processes of pure monomers under the same conditions (room temperature, air atmosphere). Additionally, poly(ethylene glycol) was added to acrylate/PLA blends as plasticizer.The highly crosslinked networks obtained were characterized by FTIR and optical microscopy. The amount of insoluble gel has been estimated gravimetrically. It was found that the studied systems are characterized by very high polymerization rate, moreover, efficient grafting of polyacrylates on PLA takes place. The observed morphology indicates the heterogeneity of formed networks. The glass transition temperature of PLA in studied blends has been determined by differential scanning calorimetry.

ABSTRACT Introduction To assess predictive value of new tumor markers, precursor of prostate specific antigen (p2PSA) and its derivates-%p2PSA and prostate health index (PHI) in detection of patients with indolent and aggressive prostate cancer (PC) in a subcohort of man whose total PSA ranged from 2 to 10ng/mL. Materials and Methods This cross-sectional study included 129 consecutive male patients aged over 50 years, with no previous history of PC and with normal digital rectal examination findings, but with serum PSA in interval between 2 and 10ng/mL. All patients underwent standard transrectal ultrasonography guided prostate biopsy for the first time. For all patients, serum PSA, free PSA (fPSA) and p2PSA were measured and PHI and %p2PSA were calculated. Results PHI and %p2PSA levels were significanlty higher in patients with PC compared to those without this malignancy. The same findings have been observed in group of patients with Gleason score ≥7 compared to those with Gleason score

Abstract We analyze a novel approach to gauging rigid higher derivative (higher spin) symmetries of free relativistic actions defined on flat spacetime, building on the formalism originally developed by Bonora et al. and Bekaert et al. in their studies of linear coupling of matter fields to an infinite tower of higher spin fields. The off-shell definition is based on fields defined on a 2d-dimensional master space equipped with a symplectic structure, where the infinite dimensional Lie algebra of gauge transformations is given by the Moyal commutator. Using this algebra we construct well-defined weakly non-local actions, both in the gauge and the matter sector, by mimicking the Yang-Mills procedure. The theory allows for a description in terms of an infinite tower of higher spin spacetime fields only on-shell. Interestingly, Euclidean theory allows for such a description also off-shell. Owing to its formal similarity to non-commutative field theories, the formalism allows for the introduction of a covariant potential which plays the role of the generalised vielbein. This covariant formulation uncovers the existence of other phases and shows that the theory can be written in a matrix model form. The symmetries of the theory are analyzed and conserved currents are explicitly constructed. By studying the spin-2 sector we show that the emergent geometry is closely related to teleparallel geometry, in the sense that the induced linear connection is opposite to Weitzenböck’s.

Background/Objectives: Hepatocyte growth factor (HGF) is a protective factor against acute renal injury and chronic renal fibrosis. A positive correlation between HGF and blood pressure (BP) has been established. This study aimed to determine the association between serum HGF concentration and albuminuria in subjects with optimal blood pressure (OBP) and untreated arterial hypertension (UAH), as well as its association with BP levels, serum glucose levels, and inflammatory markers. Methods: Data from 563 subjects were analyzed. Albuminuria was normalized to urine creatinine and expressed as the albumin/creatinine ratio (ACR). HGF, serum glucose, C-reactive protein, and blood leucocyte counts were measured. BP was measured and subjects were divided into optimal blood pressure (BP < 120/80 mmHg, N = 295) and untreated arterial hypertension (BP > 140/90 mmHg, N = 268) groups. Results: The subjects with UAH were significantly older and had higher values of body mass index, waist circumference, serum total and LDL cholesterol levels, triglyceride levels, fasting glucose levels, and ACR (all p < 0.001). A significant positive correlation was found between serum HGF concentration and ACR in both groups. There was no difference or correlation between HGF and BP or inflammatory markers in either group. The multivariate regression analysis identified serum HGF concentration as a strong predictor of ACR increase (Beta = 0.376, p < 0.001). Conclusion: This study found that serum HGF concentration is associated with albuminuria not only in individuals with untreated arterial hypertension, but also in those with optimal blood pressure. The results suggest that serum HGF is an independent predictor of ACR increase in both groups.

ANCA-associated vasculitides (AAVs) are rare diseases with a prevalence of less than 200 cases per million persons and an incidence of less than 25 cases per million person-years. Their presenting features can vary from prodromal and nonspecific symptoms to dramatic organ-specific symptoms such as respiratory failure due to diffuse alveolar hemorrhage (DAH) and acute kidney injury (AKI). The latter two are hallmark features of pulmonary-renal syndrome, a potentially fatal condition that necessitates early recognition and treatment in intensive care units (ICUs) and rapid induction of immunosuppressive therapy. Background and case summaries : We described three patients with newly diagnosed AAV during the treatment of critical illness. All patients had DAH and two had AKI. The initial disease severity was extremely high in patients with myeloperoxidase (MPO)-AAV, reaching Sequential Organ Failure Assessment (SOFA) scores of 15 and 14 with predicted mortality ≥ 95.2%. Both patients needed mechanical ventilation, one additional venovenous extracorporeal membrane oxygenation (VV-ECMO), and renal replacement therapy. The patient with proteinase 3 (PR3)-AAV had a less severe disease, SOFA 3, requiring only modest oxygen supplementation and exhibiting only hematuria with normal renal function parameters. Immunosuppressive therapy was initiated during the ICU stay. The patient with the most severe clinical presentation died during the ICU stay because of sepsis, and the other two patients were discharged home. Conclusions : Patients with AAV presenting with pulmonary-renal syndrome necessitate various degrees of organ support. Nevertheless, these patients can be successfully treated in the early, critical stages of the disease and achieve remission.

Eukaryotic gene expression is regulated at the transcriptional and post-transcriptional levels, with disruption of regulation contributing significantly to human diseases. The 5' m7G mRNA cap is a central node in post-transcriptional regulation, participating in both mRNA stabilization and translation efficiency. In mammals, DCP1a and DCP1b are paralogous cofactor proteins of the mRNA cap hydrolase DCP2. As lower eukaryotes have a single DCP1 cofactor, the functional advantages gained by this evolutionary divergence remain unclear. We report the first functional dissection of DCP1a and DCP1b, demonstrating that they are non-redundant cofactors of DCP2 with unique roles in decapping complex integrity and specificity. DCP1a is essential for decapping complex assembly and interactions between the decapping complex and mRNA cap-binding proteins. DCP1b is essential for decapping complex interactions with protein degradation and translational machinery. DCP1a and DCP1b impact the turnover of distinct mRNAs. The observation that different ontological groups of mRNA molecules are regulated by DCP1a and DCP1b, along with their non-redundant roles in decapping complex integrity, provides the first evidence that these paralogs have qualitatively distinct functions., (© 2024 Vukovic et al.)

Considering the divergent biological behaviors of certain histological subtypes of urothelial carcinoma, it would be of great importance to examine the impact of variant histology and to predict its presence in patients with bladder cancer. A single-center cohort study included 459 patients who underwent radical cystectomy for urothelial carcinoma between 2017 and 2021. Patients were followed up with until July 2022. We compared clinical, laboratory, and histopathologic characteristics and the overall survival between patients with pure urothelial carcinoma and variant histologies. Our results showed that the patients with variant histology were older and preoperatively more frequently had hydronephrosis and higher values of leukocytes and neutrophils. Also, we found a significant association between variant histology and an advanced stage of tumor disease, the presence of lymphovascular invasion, positive surgical margins, and metastases in surgically resected lymph nodes. The number of neutrophils was identified as an independent preoperative predictor of the presence of variant histology after a radical cystectomy. The overall survival of the patients with variant histology was significantly lower compared to the patients with pure urothelial carcinoma. According to our results, the presence of variant histology represents a more aggressive form of the disease. Preoperative neutrophil counts may indicate the presence of variant histology of urothelial carcinoma in patients with bladder cancer.

Innate and adaptive immune responses exert their role in CIDP pathogenesis through cytokine production. Single-nucleotide polymorphisms (SNPs) may alter cytokine gene expression, with a potential influence on the pathogenesis of autoimmune diseases. However, cytokine gene SNPs have not been assessed in CIDP patients yet. We assessed functional SNPs in the genes encoding IL-10 (rs1800896, rs1800871, rs1800872 and rs3024505), IL-6 (rs1800795), TNF (rs1800629 and rs361525), IL-12B (rs3212227), IFN-γ (rs2430561), GM-CSF (rs25882) and IL-17F (rs11465553) in a cohort of 88 CIDP patients and 486 healthy controls (HCs) via qPCR. We found an association of SNP in the IL10 promotor and CIDP occurrence. Major homozygotes (AA) were more frequent in the HCs compared to CIDP patients ( p = 0.049), but the GA genotype prevailed among the patients ( p = 0.032). A lower frequency of the C allele was observed for rs1800871 and rs1800872 in CIDP patients compared to the HCs ( p = 0.048). A higher proportion of A carriers at position -1082 (rs1800896) (presumed to be a low IL-10 producer) was noted in patients with milder disability (low INCAT). All mild-INCAT patients were C carriers for rs1800871 and rs1800872 in IL10 ( p = 0.038). Furthermore, the IL6 rs1800795 GG genotype was more frequent in patients ( p = 0.049) and the CG heterozygote in the HCs ( p = 0.013). Among the CIDP patients, being a G carrier for this SNP was associated with a higher frequency of type 2 diabetes (T2D) compared to being a non-carrier ( p = 0.032). Our data indicate a possible association of the IL10 and IL6 SNPs with CIDP, but also with disease severity and T2D occurrence. Given the paucity of CIDP patients, multicentric studies are necessary to draw definite conclusions on these associations.

At the time when mass COVID-19 vaccination began, providing appropriate vaccination advice to uro-oncology patients became a challenge. This was a single-center cross-sectional observational study aimed to investigate the rate of COVID-19 vaccination among uro-oncology patients receiving systemic therapy for metastatic renal cell carcinoma and metastatic castration-resistant prostate cancer. Furthermore, we aimed to assess patients' attitudes and identify factors influencing their decision to vaccinate against COVID-19. Data on patients' sociodemographic characteristics, vaccination status, and awareness and attitudes about COVID-19 vaccination were collected from questionnaires completed by the patients. A total of 173 patients were enrolled in this study, and 124 (71.7%) of them completed the COVID-19 vaccination. Significantly higher vaccination rates were found in male patients, and also in older patients, highly educated patients, and those who lived with one household member. Furthermore, we found significantly higher vaccination rates in patients who had consulted with doctors involved in their treatment, particularly with urologists. A significant association was observed between COVID-19 vaccination and doctor's advice, family member influence, and personal beliefs toward the vaccination. Our study showed multiple associations of patients' sociodemographic characteristics with vaccination rates. Furthermore, consultation with doctors who are particularly involved in oncology treatment and advice received from them were associated with significantly higher vaccination rates among uro-oncology patients.

Cervical cancer is one of the leading causes of cancer-related death in women of reproductive age. The established fertility-sparing approaches for the management of early-stage cervical cancer for women who plan pregnancy are associated with a decline in fecundity and an increased risk of pregnancy complications. This article aims to offer an overview of fertility-sparing approaches and the management of potential subfertility and pregnancy complications after these treatments. An extensive search for the available data about infertility and cervical cancer, fertility-sparing techniques in patients with cervical cancer, fertility treatment, obstetrical complications, and pregnancy outcomes in cervical cancer patients was completed. Fertility-preserving procedures such as loop electrosurgical excision procedure (LEEP), cold-knife conization, and trachelectomy in women diagnosed with cervical cancer can be considered as safe and effective treatments that preserve reproductive potential. Current fertility-preserving procedures, based on the balance of the oncological characteristics of patients as well as their desire for reproduction, allow one to obtain acceptable reproductive and obstetric outcomes in women treated for cervical cancer. Nevertheless, careful monitoring of pregnancies obtained after fertility-preserving procedures is recommended, since this cohort of patients should be considered at higher risk compared with a healthy population.

In recent years, the focus of numerous studies has been the predictive value of inflammatory and nutritional parameters in oncology patients. The aim of our study was to examine the relationship between the inflammatory and nutritional parameters and the histopathological characteristics of patients with bladder cancer. A retrospective study included 491 patients who underwent radical cystectomy for bladder cancer between 2017 and 2021. We calculated the preoperative values of the neutrophil-to-lymphocyte ratio (NLR), the derived neutrophil-to-lymphocyte ratio (dNLR), the systemic immune-inflammation index (SII), the systemic inflammatory response index (SIRI), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), the prognostic nutritional index (PNI), and the geriatric nutritional risk index (GNRI). Statistically significant positive correlations were observed between NLR, dNLR, SII, SIRI, and PLR and the pathological stage of the tumor. We observed statistically significant inverse correlations for LMR, PNI, and GNRI with the tumor stage. SIRI was identified as an independent predictor of the presence of LVI. dNLR was identified as an independent predictor of positive surgical margins. GNRI was identified as an independent predictor of the presence of metastases in the lymph nodes. We noticed the predictive value of SIRI, dNLR, and GNRI in the pathology of bladder cancer patients.

AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolic and immune functions mainly through the inhibition of the mechanistic target of rapamycin (mTOR)-dependent anabolic pathways and the activation of catabolic processes such as autophagy. The AMPK/mTOR signaling pathway and autophagy markers were analyzed by immunoblotting in blood mononuclear cells of 20 healthy control subjects and 23 patients with an acute demyelinating form of Guillain-Barré syndrome (GBS). The activation of the liver kinase B1 (LKB1)/AMPK/Raptor signaling axis was significantly reduced in GBS compared to control subjects. In contrast, the phosphorylated forms of mTOR activator AKT and mTOR substrate 4EBP1, as well as the levels of autophagy markers LC3-II, beclin-1, ATG5, p62/sequestosome 1, and NBR1 were similar between the two groups. The downregulation of LKB1/AMPK signaling, but not the activation status of the AKT/mTOR/4EBP1 pathway or the levels of autophagy markers, correlated with higher clinical activity and worse outcomes of GBS. A retrospective study in a diabetic cohort of GBS patients demonstrated that treatment with AMPK activator metformin was associated with milder GBS compared to insulin/sulphonylurea therapy. In conclusion, the impairment of the LKB1/AMPK pathway might contribute to the development/progression of GBS, thus representing a potential therapeutic target in this immune-mediated peripheral polyneuropathy., Competing Interests: The authors declare no conflict of interest. The sponsors had no role in the design, execution, interpretation, or writing of the study.

Background and Aims: We report the first two cases of familial lecithin:cholesterol acyltransferase (LCAT) deficiency in Croatia with classical clinical and biochemical features., Patients and Methods: A 30-year-old man with nephrotic syndrome, corneal opacities, hepatosplenomegaly, anemia, low high-density lipoprotein (HDL)-cholesterol levels and arterial hypertension (blood pressure >200/100 mmHg) was admitted to our department. At admission, he had an elevated creatinine serum level (233 μmol/L), proteinuria of 12 g in 24-h urine (g/24 h), 3-7 erythrocytes in urine sediment and notable anemia (hemoglobin level 90 g/l). His HDL-cholesterol was significantly low (0.42 mmol/L). Besides chronic kidney disease (CKD), other secondary causes of hypertension were ruled out. The patient was previously diagnosed with membranous nephropathy and treated unsuccessfully with immunosuppressive agents (steroids, cyclosporine, cyclophosphamide). Re-evaluation of histopathological findings of kidney biopsy revealed massive deposition of lipid material in the glomerular basal membrane and in the mesangial region. His 4-year younger brother was also evaluated due to corneal opacities and new-onset arterial hypertension. Nephrotic range proteinuria with preserved global renal function was determined. He also had very low HDL-cholesterol levels., Results: Kidney biopsies from both patients were consistent with LCAT deficiency. The disease was confirmed by measurement of LCAT enzyme activity, plasma cholesterol esterification rate, and genetic testing. Two novel missense variants in the LCAT gene (c.496G > A and c.1138T  >  C) were found., Conclusions: To our knowledge, the presented cases are the first reported cases of genetic LCAT deficiency in Croatia. Given the clinical presentation, the complete lack of LCAT activity and cholesterol esterification rate, diagnosis of familial LCAT deficiency was made., Competing Interests: Margareta Fistrek Prlic – none, Marijana Coric – none, Laura Calabresi – none, Chiara Pavanello – none, Lorena Mosca – none, Ugo Cavallari – none, Ivana Vukovic Brinar – none, Sandra Karanovic – none, Mario Laganovic-none, Bojan Jelakovic-none., (© 2022 The Authors.)

HLA eplet matching is a novel approach to define acceptable HLA mismatches for transplant recipients. We performed an eplet analysis of three different transplant case-series to determine if the available software programs gave accurate results. Eplet analysis was performed for three different transplant case-series typed by NGS for all HLA class I and II loci. The three different HLA datasets were entered into both the HLAMatchmaker program (v2.1) and OLI Fusion MatchMaker (v4.2) software tools. Eplet results which were discordant were cross referenced against eplet registry and published HLA allele sequence data to determine the correct assignments. The comparison reveals that there was poor concordance between the two eplet programs. Analysis of the same donor/recipient pair often gave rise to different total eplet scores, incorrect eplet mismatches and antibody verification status, and both programs have eplets assigned to incorrect HLA alleles. Overall, the OLI Fusion MatchMaker eplet tool gave more accurate and useful eplet results. Eplet matching is still primarily a research tool. Before eplet matching can enter routine clinical practice further work is required to validate the accuracy of available eplet software programs. Incorrect eplet assignment could have serious adverse consequences in the clinical transplant setting., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purposes: The aim of the study was to determine optimal threshold of the Prostate Health Index (Phi) for predicting aggressive prostate cancer (PCa), taking into account misclassification costs, prevalence, and plausible risk factors., Methods: This prospective cohort study analyzed patients undergoing prostate biopsy and Phi testing. The primary endpoint was aggressive PCa, defined as biopsy Gleason score ≥ 7. The data about age, total prostate-specific antigen (PSA), percentage of free PSA (%fPSA), and digital rectal examination (DRE) were extracted from the patient files. We divided the patients to the low- and high-risk group. The clinical usefulness of the Phi was assessed by the decision curve analysis. The predictive performance was assessed using the area under the receiver operating characteristic curve (AUC), per-class metrics, and the potential reduction in unnecessary biopsies. The uncertain interval of Phi values was also determined., Results: There were 200 men included in the study, 35 (17.5%) of them having aggressive PCa. Important predictors of aggressive PCa were %fPSA, DRE, Phi, and belonging to the high-risk group. With optimal threshold of 30.7, about 32% unnecessary biopsies would be avoided. The optimal threshold of Phi was lower in the high-risk group than in the low-risk group. The AUC for detection of aggressive PCa was 0.791. Per-class metrics showed that the Phi has insufficient diagnostic accuracy. The lower and upper limits of the uncertain interval were 41.8 and 51.4, respectively., Conclusion: Different thresholds of the Phi could be optimal, depending on prevalence, patient characteristics, and misclassification costs. Further studies with a larger patient sample are necessary to confirm our conclusions.

2,6-Dichlorohydroquinone 1,2-dioxygenase (PcpA) is a non-heme Fe(II) enzyme that is specific for ortho-dihalohydroquinones. Here we deconvolute the role of halogen polarizability vs. substrate pK a in defining this specificity, and show how substrate binding compares to the structurally homologous catechol extradiol dioxygenases. The substrates 2,6-dichloro- and 2,6-dibromohydroquinone (polarizable halogens, pK a1  = 7.3), 2,6-difluorohydroquinone (nonpolarizable halogens, pK a1  = 7.5), and 2-chloro-6-methylhydroquinone (polarizable halogen, pK a1  = 9.0) were examined through spectrophotometric titrations and steady-state kinetics. The results show that binding of the substrates to the enzyme decreased [Formula: see text] by about 0.5, except for 2,6-difluorohydroquinone, which showed no change. Additionally, the K d values of 2,6-dichloro- and 2,6-dibromohydroquinone are about equal to their respective [Formula: see text]. For comparison, with catechol 2,3-dioxygenase (XylE), the substrates 4-methyl- and 3-bromocatechol are bound to the enzyme exclusively in the monoanion form over a wide pH range, indicating a [Formula: see text] of at least - 2.9 and - 1.2, respectively. The steady-state kinetic studies showed that 2,6-difluorohydroquinone is a poor substrate, with [Formula: see text] approximately 40-fold lower and [Formula: see text] 20-fold higher than 2,6-dichlorohydroquinone, despite its similar pK a1 . Likewise, the pH dependence of [Formula: see text] for 2-chloro-6-methylhydroquinone is nearly identical to that of 2,6-dichlorohydroquinone, despite its very different pK a1 . These results show that (1) it is clearly the halogen polarizability and not the lower substrate pK a that determines the substrate specificity of PcpA, and (2) that PcpA, unlike the catechol extradiol dioxygenases, lacks an active site base that assists with substrate deprotonation, highlighting a key functional difference in what are otherwise similar active sites that defines their different reactivity.

Background: We analysed outcome domains and pain outcome measures in randomized controlled trials of interventions for postoperative pain management in children and adolescents and compared them to the core outcome set recommended by the Pediatric Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (PedIMMPACT)., Methods: Systematic literature search was conducted in MEDLINE, CDSR, DARE, CINAHL and PsycINFO up to 31 January 2017. One author extracted data and second verified the extraction. Outcome domains and pain outcome measures were analysed and compared with the PedIMMPACT core outcome set., Results: We included 337 trials. Median number of reported outcomes was five (range 1-11) for the included trials and two (range 0-6) for PedIMMPACT. The most commonly analysed PedIMMPACT outcome domains were pain intensity (93%) and "symptoms and adverse events" (83%). The remaining four PedIMMPACT outcomes were present in under 30% of included randomized controlled trials. Proportion of PedIMMPACT outcome domains did not change after the PedIMMPACT was published in 2008. Of the 312 trials that reported pain intensity, 303 (97%) also specified pain assessment tools, in which the most common was the visual analogue scale (24%) followed by the Children's Hospital of Eastern Ontario Pain Scale (18%)., Conclusion: Analysed trials about interventions for pediatric postoperative pain insufficiently used the recommended core outcome set for acute pain in children. Relevance of the PedIMMPACT core outcome set, as well as the reasons behind its limited uptake, need to be further evaluated., Significance: Recommended core outcomes have been insufficiently used in randomized controlled trials about postoperative pain in children, which hinders comparability of studies and makes synthesis of evidence difficult., (© 2018 European Pain Federation - EFIC®.)

Background: Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology in which genetic factors contribute to development of disease. Single nucleotide polymorphisms (SNPs) in multidrug resistance 1 (MDR1) gene encoding transporter P-glycoprotein have been associated with IBD, but their role in disease susceptibility remains unclear. Therefore, the aim of this study was to investigate the association of three MDR1 polymorphisms, C1236T (rs1128503), G2677T/A (rs2032582) and C3435T (rs1045642), with Serbian IBD patients., Methods: A total of 206 IBD patients, 107 Crohn's disease (CD) and 99 ulcerative colitis (UC), and 255 healthy controls were included in the study. All subjects were genotyped using TaqMan SNP genotyping assays. Comparisons between the groups were performed using the Pearson Chi-square test. False discovery rate according to Benjamini-Hochberg procedure was applied to adjust for multiple comparisons., Results: Carriers of T allele of all three MDR1 SNPs were more common in UC patients compared to healthy controls, suggesting predisposing role of T allele of these SNPs in UC pathogenesis. Consistently, TT genotype of C1236T and TTT haplotype were also found more frequently in UC patients. On the other hand, C allele and CC genotype of C1236T and C3435T, as well as G allele and GG genotype of G2677T/A were more frequent in healthy subjects, implying protective role of these variants in UC. Likewise, CGC haplotype and CGC/CGC diplotype were more frequent in controls. Contrary to UC, no statistical difference was observed between CD patients and controls in any of the SNPs analyzed., Conclusion: MDR1 gene variants and haplotypes were associated with UC in Serbian IBD patients, further supporting their potential role in susceptibility to UC.

Background and Objectives: To evaluate the results of testis-sparing surgery (TSS) in patients, with small testicular lesions and a normal contralateral testicle., Methods: In all, 28 patients were treated with TSS for small testicular lesions and a normal contralateral testicle. TSS was considered in patients with testicular lesions smaller than 2 cm and no evidence of metastatic disease., Results: The mean age of patients was 35.3 ± 7.3 years, while the mean diameter of the testicular lesions was 11.4 ± 3.7 mm. After pathological examination, 18 patients (64.3%) were diagnosed with stromal tumors and miscellaneous lesions, while 10 (35.7%) had a germ cell tumor. The median follow-up time for the former group was 33 months and no recurrences were observed. In one patient with germ cell tumor, immediate orchiectomy was performed, while the remaining nine were followed-up (median time, 45 months). One patient developed local recurrence after 39 months., Conclusions: Excellent outcomes for benign lesions could be achieved using TSS. TSS could be offered safely in highly selected patients with germ cell tumors, specifically within a clinical trial but there is more data needed regarding the potential risks and benefits. J. Surg. Oncol. 2017;115:287-290. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Introduction: To assess predictive value of new tumor markers, precursor of prostate specific antigen (p2PSA) and its derivates-%p2PSA and prostate health index (PHI) in detection of patients with indolent and aggressive prostate cancer (PC) in a subcohort of man whose total PSA ranged from 2 to 10ng/mL., Materials and Methods: This cross-sectional study included 129 consecutive male patients aged over 50 years, with no previous history of PC and with normal digital rectal examination findings, but with serum PSA in interval between 2 and 10ng/mL. All patients underwent standard transrectal ultrasonography guided prostate biopsy for the first time. For all patients, serum PSA, free PSA (fPSA) and p2PSA were measured and PHI and %p2PSA were calculated., Results: PHI and %p2PSA levels were significanlty higher in patients with PC compared to those without this malignancy. The same findings have been observed in group of patients with Gleason score ≥7 compared to those with Gleason score <7. ROC analysis reveled the highest area under the curve with these two markers. Multivariate logistic regression showed significant improvement in PC detection and its agressive form (assumed as Gleason score ≥7)., Conclusions: New markers, derivates of p2PSA (especially %p2PSA and PHI), represente potentially very important clinical tool for predicting presence of PC, and even more important, to discriminate patients with Gleason score <7 from those with Gleason score ≥7 with total PSA in range from 2 to 10ng/mL., Competing Interests: CONFLICT OF INTEREST None declared., (Copyright® by the International Brazilian Journal of Urology.)

Purpose: Whether cycloplegics affect standard keratorefractometric and tomographic measurements is unknown. The purpose of our study was to compare the effects of cycloplegics (cyclopentolate and atropine) on corneal shape and refractive power of the eye., Methods: This study was performed on 84 eyes of 49 study participants. Patients were randomized into two groups: atropine 1% (32 eyes) and cyclopentolate 1% (52 eyes). Corneal tomography was performed with the Orbscan IIz. To evaluate the corneal shape, simulated keratometry values, anterior and posterior best-fit sphere, white-to-white and tangential and axial corneal power were performed for the anterior and posterior corneal surfaces before and during cycloplegia. Pupil diameter, anterior chamber depth, corneal thickness at the 3, 5 and 7mm optical zones, thinnest area of the cornea and corneal thickness at the visual axis were examined. Data were analyzed using an SPSS statistical package., Results: The anterior and posterior BFS (in the atropine 1% group, anterior BFS was P=0.188; anterior BFS in the cyclopentolate group was P=0.227) and tangential and axial corneal power showed no change during cycloplegia in either group. SimK showed no statistical significance. The ACD was deeper when using atropine than cyclopentolate. Corneal thickness remained unchanged during cycloplegia in both groups. Pupil diameter was larger in light-colored irides in the cyclopentolate group than the atropine group. There was no change in W to W before (P=0.473) and during cycloplegia (P=0.287) in either group., Conclusions: Our results suggest that usage of atropine or cyclopentolate does not alter corneal shape., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Vascular age (VA) represents chronological age (CA) adjusted for individual's atherosclerotic burden. The presence of erectile dysfunction (ED) has been considered as a clinical sentinel of premature atherosclerosis. The objective of this study was to explore the predictive value of ED in assessing the discrepancy between VA and CA. In the period from 1 January 2014 to 1 January 2015, all consecutive men referring to the outpatient departments of the Clinics of Urology and Cardiology in Belgrade (Serbia) were considered for enrolment in this cross-sectional study. General exclusion criteria were: age below 18, heart failure, history of myocardial infarction, impaired renal and liver function, acute infection, history of endocrine disease other than type 2 diabetes, pelvic surgery or trauma, and acute coronary syndrome within the last 6 months. According to the presence of ED, hypertension, type 2 diabetes and history of coronary artery disease participants were assigned into five study groups. Hierarchical multiple regression analysis was conducted to identify the predictive value of ED in detection of advanced VA. The mean age of males enrolled in the study was 52.9 ± 7.7 years. The predominance of VA over CA was statistically significantly higher in the group of participants with coexistence of ED and hypertension compared to the group of patients with ED and type 2 diabetes (p = 0.027) and the group of patients with ED (p = 0.014) and control group (p < 0.01). Regression analysis highlighted that ED represented a highly important marker (p < 0.01) of advanced VA, which independently accounted for 6.1% of the variance in the discrepancy between VA and CA. Our study suggests that assessment of ED could be a part of a more comprehensive prediction of patients' advanced VA. Screening among such a highly selected population may help identify those that would most benefit from drug treatments and life style changes., (© 2015 American Society of Andrology and European Academy of Andrology.)

Background and Objective: To assess the oncologic and functional outcomes of testicular sparing surgery (TSS) based on a single institution experience., Methods: Forty-one patients with bilateral and 3 patients with solitary testicle tumors were referred to our institution. The inclusion criteria for TSS were normal serum testosterone levels, and tumor size (<2 cm). Sperm analysis and hormone status evaluation were performed preoperatively and postoperatively. None of the patients underwent local radiation therapy following TSS for reasons of fertility preservation., Results: A total of 26 TSS were performed in 24 patients. The median follow-up period was 51.0 months. Seven patients developed local recurrence, of which 5 had TIN and were subjected to radical orchiectomy, whereas re-do TSS was done in remaining 2 patients. The overall survival of the study group was 100%, and the presence of testicular intraepithelial neoplasia (TIN) was associated with worse recurrence-free survival (P=0.031, log-rank). Testosterone values were normal in all of the patients, while 4 patients achieved conception., Conclusions: TSS is acceptable from an oncological point of view, and it enables continuation of a patient's life without lifelong hormonal substitution. Additionally, local irradiation therapy could be delayed in patients with TIN who wish to father children, but with high local recurrence rate., (© 2014 Wiley Periodicals, Inc.)

Despite scientific advances, diabetic nephropathy remains both a therapeutical challenge, and one of the major diabetic complications. Chemical structure of gangliosides, the most complex of glycosphingolipids, is characterised by one or more sialic acids and carbohydrate groups linked to a ceramide structure. Their potential pathogenetic role in a number of disorders linked to diabetes mellitus has recently been conjectured, due to evidence of their negative modulation of the insulin-mediated signaling and general effects on key cell functions like proliferation, differentiation, apoptosis, cellular signaling and adhesion. Elevated levels of advanced glycation products (AGE) usually found in diabetic conditions seem to be responsible for increased concentration of a-series gangliosides in tissues, most notably GM3. GM3 was shown to compromise the renal pericyte and mesangial cell regeneration via the inactivation of VEGF receptor and the receptor-associated Akt signaling pathway. Likewise, the lipid raft theory opened a new research area for GM3 influence, since in the glycosynapse model glycosphingolipids have a key cell-to-cell communication unit with modulating capabilities on signaling receptors. The goal of this review is to provide insight into currently available theories on proposed mechanisms that mark the GM3 as a pathophysiological mediator in the development of diabetic nephropathy., (© 2015 S. Karger AG, Basel.)

Nanoporous metal foams possess a unique combination of properties - they are catalytically active, thermally and electrically conductive, and furthermore, have high porosity, high surface-to-volume and strength-to-weight ratio. Unfortunately, common approaches for preparation of metallic nanostructures render materials with highly disordered architecture, which might have an adverse effect on their mechanical properties. Block copolymers have the ability to self-assemble into ordered nanostructures and can be applied as templates for the preparation of well-ordered metal nanofoams. Here we describe the application of a block copolymer-based supramolecular complex - polystyrene-block-poly(4-vinylpyridine)(pentadecylphenol) PS-b-P4VP(PDP) - as a precursor for well-ordered nickel nanofoam. The supramolecular complexes exhibit a phase behavior similar to conventional block copolymers and can self-assemble into the bicontinuous gyroid morphology with two PS networks placed in a P4VP(PDP) matrix. PDP can be dissolved in ethanol leading to the formation of a porous structure that can be backfilled with metal. Using electroless plating technique, nickel can be inserted into the template's channels. Finally, the remaining polymer can be removed via pyrolysis from the polymer/inorganic nanohybrid resulting in nanoporous nickel foam with inverse gyroid morphology.

Objective: To evaluate the prognostic factors for survival and disease recurrence in patients treated surgically for upper tract urothelial carcinoma (UTUC), focusing especially on the impact of history of non-muscle-invasive bladder cancer., Patients and Methods: A single-center series of 221 consecutive patients who were treated surgically for UTUC between January 1999 and December 2010 was evaluated. Patients who had a history of bladder tumor at a higher stage than the upper tract disease, preoperative chemotherapy, or previous contralateral UTUC were excluded. None of the patients included in this study had distant metastasis at diagnosis of UTUC. In total, 183 patients (mean age 66 years, range 36-88) were then available for evaluation. Tumor multifocality was defined as the synchronous presence of 2 or more pathologically confirmed tumors in any upper urinary tract location (renal pelvis or ureter). All patients were treated with either open radical nephroureterectomy (RNU) or open conservative surgery. Recurrence-free probabilities and cancer-specific survival were estimated using the Kaplan-Meier method and Cox regression analyses., Results: Fifty-one patients (28%) had previous carcinoma not invading bladder muscle. Previous history of non-muscle-invasive bladder cancer was significantly associated with tumor multifocality (P < 0.001), concomitant bladder cancer (P < 0.001), higher tumor stage (P = 0.020), and lymphovascular invasion (P = 0.026). Using univariate analyses, history of non-muscle-invasive bladder cancer was significantly associated with an increased risk of both any recurrence (HR = 2.17; P = 0.003) and bladder-only recurrence (HR = 3.17; P = 0.001). Previous carcinoma not invading bladder muscle (HR = 2.58; P = 0.042) was an independent predictor of bladder-only recurrence. Overall 5-year disease recurrence-free (any recurrence and bladder-only recurrence) survival rates were 66.7% and 77%, respectively. Previous history of non-muscle-invasive bladder cancer was not associated with cancer-specific survival. Our results are subject to the inherent biases associated with high-volume tertiary care centers., Conclusions: Patients with previous history of non-muscle-invasive bladder cancer had a higher risk of having multifocal and UTUC with higher tumor stages (pT3 or greater). History of bladder tumor was an independent predictor of bladder cancer recurrence but had no effect on non-bladder recurrence, and cancer-specific survival in patients who underwent surgical treatment of UTUC., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The phase behavior of block copolymer based supramolecular complexes polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP) and amphiphilic pentadecylphenol (PDP) molecules resembles the phase behavior of conventional block copolymers. Several PS-b-P4VP(PDP) complexes are found to self-assemble into gyroid nanostructures. Typically, the grains are randomly oriented with a maximal size of several micrometers. Here, the orientation of a gyroid PS-b-P4VP(PDP) complex upon shearing is reported. It is found that the (111) gyroid lattice direction orients parallel to the shear direction after only several seconds of large amplitude oscillatory shearing. Oriented gyroid complexes can be used as templates for the preparation of metal nanofoams with improved ordering with potentially superior properties., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To identify the impact of tumour location on the disease recurrence and survival of patients who were treated surgically for upper urinary tract transitional cell carcinoma (UUT-TCC)., Patients and Methods: A single-centre series of 189 consecutive patients who were treated surgically for UUT-TCC between January 1999 and December 2009 was evaluated. Patients who had previously undergone radical cystectomy, preoperative chemotherapy or contralateral UUT-TCC were excluded. In all, 133 patients were available for evaluation. Tumour location was categorized as renal pelvis or ureter based on the location of the dominant tumour. Recurrence-free probabilities and cancer-specific survival were estimated using the Kaplan-Meier method and Cox regression analyses., Results: The 5-year recurrence-free and cancer-specific survival estimates for the cohort in the present study were 66% and 62%, respectively. The 5-year bladder-only recurrence-free probability was 76%. Using multivariate analysis, only pT classification (hazard ratio, HR, 2.46; P = 0.04) and demographic characteristics (HR, 2.86 for areas of Balkan endemic nephropathy, vs non-Balkan endemic nephropathy areas; 95% confidence interval, 1.37-5.98; P = 0.005) were associated with disease recurrence. Tumour location was not associated with disease recurrence in any of the analyses. There was no difference in cancer-specific survival between renal pelvis and ureteral tumours (P = 0.476). Using multivariate analysis, pT classification (HR, 8.04; P = 0.001) and lymph node status (HR, 4.73; P = 0.01) were the only independent predictors associated with a worse cancer-specific survival., Conclusion: Tumour location is unable to predict outcomes in a single-centre series of consecutive patients who were treated with radical nephroureterectomy for UUT-TCC., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Metal nanofoams with a porosity above 50% v/v have recently attracted great interest in materials science due to their interesting properties. We demonstrate a new straightforward route to prepare such nanofoams using diblock copolymer-based PS-block-P4VP(PDP) supramolecules that self-assemble into a bicontinuous gyroid morphology, consisting of PS network channels in a P4VP(PDP) matrix. After dissolving the PDP, the P4VP collapses onto the PS struts and a free-standing bicontinuous gyroid template of 50-100 μm thickness and interconnected, uniformly sized pores is formed. The hydrophilic P4VP corona facilitates the penetration of water-based plating reagents into the porous template and enables a successful metal deposition. After plating, the polymer is simply degraded by heating, resulting in a well-ordered inverse gyroid nickel foam. Essential to this approach is the removal of only one part of the matrix (i.e., PDP). Therefore, the template accounts for 50% v/v or more. The porosity characteristics (amount, size of pores) can be tuned by selecting the appropriate copolymer and by adjusting the amount of PDP., (© 2011 American Chemical Society)

The self-assembly in diblock copolymer-based supramolecules, obtained by hydrogen bonding short side chains to one of the blocks, as well as in two-length-scale linear terpolymers results in hierarchical structure formation. The orientation of the different domains, e.g. layers in the case of a lamellar-in-lamellar structure, is determined by the molecular architecture, graft-like versus linear, and the relative magnitude of the interactions involved. In both cases parallel and perpendicular arrangements have been observed. The comb-shaped supramolecules approach is ideally suited for the preparation of nanoporous structures. A bicontinuous morphology with the supramolecular comb block forming the channels was finally achieved by extending the original approach to suitable triblock copolymer-based supramolecules.

Supramolecular complexes of a poly(tert-butoxystyrene)-block-polystyrene-block-poly(4-vinylpyridine) triblock copolymers and less than stoichiometric amounts of pentadecylphenol (PDP) are shown to self-assemble into a core-shell gyroid morphology with the core channels formed by the hydrogen-bonded P4VP(PDP)complexes. After structure formation, PDP was removed using a simple washing procedure, resulting in well-ordered nanoporous films that were used as templates for nickel plating., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Specific language impairment (SLI) is usually defined as a developmental language disorder which does not result from a hearing loss, autism, neurological and emotional difficulties, severe social deprivation, low non-verbal abilities. Children affected with SLI typically have difficulties with the acquisition of different aspects of language and by definition, their impairment is specific to language and no other skills are affected. However, there has been a growing body of literature to suggest that children with SLI also have non-linguistic deficits, including impaired motor abilities. The aim of the current study is to investigate language and motor abilities of a group of thirty children with SLI (aged between 4 and 7) in comparison to a group of 30 typically developing children matched for chronological age. The results showed that the group of children with SLI had significantly more difficulties on the language and motor assessments compared to the control group. The SLI group also showed delayed onset in the development of all motor skills under investigation in comparison to the typically developing group. More interestingly, the two groups differed with respect to which language abilities were correlated with motor abilities, however Imitation of Complex Movements was the unique skill which reliably predicted expressive vocabulary in both typically developing children and in children with SLI., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The Republic of Croatia, with a gross domestic product per capita of US$11,554 in 2008, is an economically less-developed Western country. The goal of the present investigation was to prove that a well-organized primary percutaneous coronary intervention network in an economically less-developed country equalizes the prospects of all patients with acute ST-segment elevation myocardial infarction at a level comparable to that of more economically developed countries. We prospectively investigated 1,190 patients with acute ST-segment elevation myocardial infarction treated with primary PCI in 8 centers across Croatia (677 nontransferred and 513 transferred). The postprocedural Thrombolysis In Myocardial Infarction flow, in-hospital mortality, and incidence of major adverse cardiovascular events (ie, mortality, pectoral angina, restenosis, reinfarction, coronary artery bypass graft, and cerebrovascular accident rate) during 6 months of follow-up were compared between the nontransferred and transferred subgroups and in the subgroups of older patients, women, and those with cardiogenic shock. In all investigated patients, the average door-to-balloon time was 108 minutes, and the total ischemic time was 265 minutes. Postprocedural Thrombolysis In Myocardial Infarction 3 flow was established in 87.1% of the patients, and the in-hospital mortality rate was 4.4%. No statistically significant difference was found in the results of treatment between the transferred and nontransferred patients overall or in the subgroups of patients >75 years, women, and those with cardiogenic shock. In conclusion, the Croatian Primary Percutaneous Coronary Intervention Network has ensured treatment results of acute ST-segment elevation myocardial infarction comparable to those of randomized studies and registries of more economically developed countries., (Copyright 2010 Elsevier Inc. All rights reserved.)

Unlabelled: In this study we investigated the recovery patterns of language and cognitive functions in patients with post-traumatic language processing deficits and in patients with aphasia following a stroke. The correlation of specific language functions and cognitive functions was analyzed in the acute phase and 6 months later. Significant recovery of the tested functions was observed in both groups. However, in patients with post-traumatic language processing deficits the degree of recovery of most language functions and some cognitive functions was higher. A significantly greater correlation was revealed within language and cognitive functions, as well as between language functions and other aspects of cognition in patients with post-traumatic language processing deficits than in patients with aphasia following a stroke. Our results show that patients with post-traumatic language processing deficits have a different recovery pattern and a different pattern of correlation between language and cognitive functions compared to patients with aphasia following a stroke., Learning Outcomes: (1) Better understanding of the differences in recovery of language and cognitive functions in patients who have suffered strokes and those who have experienced traumatic brain injury. (2) Better understanding of the relationship between language and cognitive functions in patients with post-traumatic language processing deficits and in patients with aphasia following a stroke. (3) Better understanding of the factors influencing recovery.

Objective: To compare the effects of low-dose transdermal estradiol (E2)/norethisterone acetate (NETA) patches (Estalis 25/125) with low-dose oral E2/NETA (Activelle) on cardiovascular biochemical markers after 12 and 52 weeks of treatment in postmenopausal women with intact uteri., Design: Participants were randomly assigned to receive either transdermal E2/NETA (delivering daily doses of 25 microg E2 and 125 microg NETA, applied every 3-4 d) or oral E2/NETA (1 mg E2 and 0.5 mg NETA, given daily) in this open-label study. The following markers or their stable metabolites in serum or urine were assessed: P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, matrix metalloproteinase-9, homocysteine, cyclic guanosine monophosphate, serotonin, prostacyclin, thromboxane, and urodilatin., Results: Significant decreases were found for P-selectin, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and homocysteine for both hormone therapy (HT) regimens compared with baseline. Matrix metalloproteinase-9 was increased only by oral HT. The urinary concentrations of cyclic guanosine monophosphate, the ratio of prostacyclin to thromboxane metabolite, and the serotonin metabolite were significantly increased for both HT application modes, although the oral treatment showed a significantly greater increase than the transdermal one with respect to baseline. Urodilatin excretion was increased only by the oral regimen., Conclusions: Low-dose transdermal and oral HTs using E2 and NETA elicit favorable effects on cardiovascular biochemical markers. For most markers the magnitude of changes found were similar with respect to baseline; however, in some cases oral HT led to a significantly greater change, whereas in other cases the transdermal formulations seemed to provide greater benefits. Whether these differences may be attributed to the different administration routes or to different pharmacokinetic properties remains an open question. Overall low-dose transdermal HT seems to provoke the same benefit on the cardiovascular system as oral HT, as suggested by the results on vascular markers.

Objectives: To determine the phenotypical state of smooth muscle cells during the pathogenesis of an atherosclerotic lesion, and to determine the morphological state of the endothelium and the origin of foam cells., Methods: Twenty-one samples of atherosclerotically changed right coronary arteries, which were divided into six subgroups based on the stage of atherosclerosis, were analyzed. The tissues were fixed in formalin and embedded in paraffin. Sections of 5 mum thickness were stained immunocytochemically using a labelled streptavidin-biotin/horse radish peroxidase kit (Dako, Denmark) for the identification of vimentin, alpha-smooth muscle actin, myosin heavy chains, desmin, S-100 protein, CD3, CD31, CD34, CD45, CD68 and proliferating cell nuclear antigen protein., Results: The present study showed that there is first functional and then morphological damage of the endothelium in the late stages of atherosclerosis. The preatheroma stage revealed the presence of intimal changes of smooth muscle cells, with expression of vimentin and alpha-smooth muscle actin and a lack of expression of desmin, which led to a switch to a synthetic phenotype. The described changes progressed into the later stages of atherosclerosis. Along with these changes, a large number of foam cells of variant origin were observed; some of the foam cells developed from monocyte-macrophage lineage (CD68-immunoreactive) and others originated from smooth muscle cells (vimentin- and S-100-immunoreactive). The late stages of atherosclerosis development, such as the atheroma stage, include intimal changes with the formation of a lipid core (S-100-immunoreactive cells and cell necrosis), while fibrosis in the lipid core and the accumulation of collagen fibres with extreme hypocellularity are characteristics of the fibroatheroma stage.

The purpose of this study was 1) to answer whether the reduction in spleen size in breath-hold apnea is an active contraction or a passive collapse secondary to reduced splenic arterial blood flow and 2) to monitor the spleen response to repeated breath-hold apneas. Ten trained apnea divers and 10 intact and 7 splenectomized untrained persons repeated five maximal apneas (A1-A5) with face immersion in cold water, with 2 min interposed between successive attempts. Ultrasonic monitoring of the spleen and noninvasive cardiopulmonary measurements were performed before, between apneas, and at times 0, 10, 20, 40, and 60 min after the last apnea. Blood flows in splenic artery and splenic vein were not significantly affected by breath-hold apnea. The duration of apneas peaked after A3 (143, 127, and 74 s in apnea divers, intact, and splenectomized persons, respectively). A rapid decrease in spleen volume ( approximately 20% in both apnea divers and intact persons) was mainly completed throughout the first apnea. The spleen did not recover in size between apneas and only partly recovered 60 min after A5. The well-known physiological responses to apnea diving, i.e., bradycardia and increased blood pressure, were observed in A1 and remained unchanged throughout the following apneas. These results show rapid, probably active contraction of the spleen in response to breath-hold apnea in humans. Rapid spleen contraction and its slow recovery may contribute to prolongation of successive, briefly repeated apnea attempts.