Репозиторий Университета

© 2019 John Wiley  &  Sons Australia, Ltd. AIM: The aim of this research was to evaluate the possibility of identifying the sex of 1 subject through visual assessment of a frontal photograph of dentition, and to investigate if some morphological characteristics are related to sex determination. METHODS: 5 expert dentists, 5 non-expert dentists and 5 laypeople were made to watch 100 intraoral photographs for 5 seconds each and to establish their sex. The responses of the participants and the baseline characteristics of photographed dentitions were analyzed. RESULTS: The proportion of right answers was 56.0% ± 8.2% in the group of expert dentists, 65.0% ± 6.0% in the group of non-expert dentists and 58.6% ± 4.5% in the group of non-expert people. The round shape of maxillary central incisors was related to the female gender (P = .006). The male condition was correlated with poor oral hygiene for 4 observers. Female sex perception was correlated with round morphology of upper central incisors for 3 observers. CONCLUSION: No difference in the ability to determine the sex was registered among groups, suggesting that sex perception is not strongly influenced by the characteristics of dentition.

© 2019 by the authors. Controlled fabrication of 45 nm width nanowire using simulated emission depletion (STED) direct laser writing with a rod-shape effective focus spot is presented. In conventional STED direct laser writing, normally a donut-shaped depletion focus is used, and the minimum linewidth is restricted to 55 nm. In this work, we push this limit to sub-50 nm dimension with a rod-shape effective focus spot, which is the combination of a Gaussian excitation focus and twin-oval depletion focus. Effects of photoinitiator type, excitation laser power, and depletion laser power on the width of the nanowire are explored, respectively. Single nanowire with 45 nm width is obtained, which is λ/18 of excitation wavelength and the minimum linewidth in pentaerythritol triacrylate (PETA) photoresist. Our result accelerates the progress of achievable linewidth reduction in STED direct laser writing.

The arterial pulse wave (PW) is a rich source of information on cardiovascular (CV) health. It is widely measured by both consumer and clinical devices. However, the physical determinants of the PW are not yet fully understood, and the development of PW analysis algorithms is limited by a lack of PW data sets containing reference CV measurements. Our aim was to create a database of PWs simulated by a computer to span a range of CV conditions, representative of a sample of healthy adults. The typical CV properties of 25-75 yr olds were identified through a literature review. These were used as inputs to a computational model to simulate PWs for subjects of each age decade. Pressure, flow velocity, luminal area, and photoplethysmographic PWs were simulated at common measurement sites, and PW indexes were extracted. The database, containing PWs from 4,374 virtual subjects, was verified by comparing the simulated PWs and derived indexes with corresponding in vivo data. Good agreement was observed, with well-reproduced age-related changes in hemodynamic parameters and PW morphology. The utility of the database was demonstrated through case studies providing novel hemodynamic insights, in silico assessment of PW algorithms, and pilot data to inform the design of clinical PW algorithm assessments. In conclusion, the publicly available PW database is a valuable resource for understanding CV determinants of PWs and for the development and preclinical assessment of PW analysis algorithms. It is particularly useful because the exact CV properties that generated each PW are known.NEW & NOTEWORTHY First, a comprehensive literature review of changes in cardiovascular properties with age was performed. Second, an approach for simulating pulse waves (PWs) at different ages was designed and verified against in vivo data. Third, a PW database was created, and its utility was illustrated through three case studies investigating the determinants of PW indexes. Fourth, the database and tools for creating the database, analyzing PWs, and replicating the case studies are freely available.

© 2019 He et al. Current understanding of flagellum/cilium length regulation focuses on a few model organisms with flagella of uniform length. Leptomonas pyrrhocoris is a monoxenous trypanosomatid parasite of firebugs. When cultivated in vitro, L. pyrrhocoris duplicates every 4.2 ± 0.2 h, representing the shortest doubling time reported for trypanosomatids so far. Each L. pyrrhocoris cell starts its cell cycle with a single flagellum. A new flagellum is assembled de novo, while the old flagellum persists throughout the cell cycle. The flagella in an asynchronous L. pyrrhocoris population exhibited a vast length variation of ∼3 to 24 μm, casting doubt on the presence of a length regulation mechanism based on a single balance point between the assembly and disassembly rate in these cells. Through imaging of live L. pyrrhocoris cells, a rapid, partial disassembly of the existing, old flagellum is observed upon, if not prior to, the initial assembly of a new flagellum. Mathematical modeling demonstrated an inverse correlation between the flagellar growth rate and flagellar length and inferred the presence of distinct, cell cycle-dependent disassembly mechanisms with different rates. On the basis of these observations, we proposed a min-max model that could account for the vast flagellar length range observed for asynchronous L. pyrrhocoris. This model may also apply to other flagellated organisms with flagellar length variation. IMPORTANCE Current understanding of flagellum biogenesis during the cell cycle in trypanosomatids is limited to a few pathogenic species, including Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. The most notable characteristics of trypanosomatid flagella studied so far are the extreme stability and lack of ciliary disassembly/absorption during the cell cycle. This is different from cilia in Chlamydomonas and mammalian cells, which undergo complete absorption prior to cell cycle initiation. In this study, we examined flagellum duplication during the cell cycle of Leptomonas pyrrhocoris. With the shortest duplication time documented for all Trypanosomatidae and its amenability to culture on agarose gel with limited mobility, we were able to image these cells through the cell cycle. Rapid, cell cycle-specific flagellum disassembly different from turnover was observed for the first time in trypanosomatids. Given the observed length-dependent growth rate and the presence of different disassembly mechanisms, we proposed a min-max model that can account for the flagellar length variation observed in L. pyrrhocoris.

© 2019 Elsevier Inc. Background: Low anterior resections are increasingly performed laparoscopically for rectal cancer. Recently, natural orifice specimen extraction surgery (NOSES) has been reported as an alternative approach without additional incisions or extensions. In this study, we aimed to evaluate the safety and feasibility of NOSES by comparing the short-term outcomes with those of conventional laparoscopic resection (CLR) in a multicenter retrospective study from China and Russia. Methods: The retrospective multicenter study was conducted at three centers between January 2015 and December 2017. Relevant collected data included patient demographics, operative parameters, and postoperative complications. All procedures were performed using either a NOSES or a CLR approach. Results: The data of a total of 768 consecutive patients with rectal cancer were retrospectively analyzed, including 412 CLR and 356 NOSES cases. The two groups were comparable for all demographics and characteristics except for the median tumor size (P = 0.038). No difference was found in the operative time and number of retrieved lymph nodes. Intraoperative complications and positive resection margins were nil in both groups. No difference was found in the time to first flatus (P = 0.150), time to first defecation (P = 0.084), length of postoperative hospital stay (P = 0.152), anastomotic leakage (P = 0.377), and intra-abdominal abscess (P = NA). The CLR group but not the NOSES group had incisional hernia or wound infection events, although the difference between groups was not significant (P = 0.253). Conclusions: The NOSES procedure is a well-established strategy and may be considered as an alternative procedure to CLR for rectal cancer. However, the long-term benefits of this approach require further evaluation.

© 2018 Ehlers-Danlos syndrome (EDS) is a heritable connective tissue disorder characterized by skin hyperextensibility, abnormal wound healing, and joint hypermobility with prevalence 1:20 000. Its incidence is probably underestimated due to unknown number of subjects having mild symptoms who may have never been diagnosed through entire life time. Classical EDS is characterized by pathogenic variants of genes encoding type V collagen. The biological effects and health risks of patients with EDS exposure to low doses of ionizing radiation is poorly understood. The aim of this study was to investigate biological effect of low doses of ionizing radiation in children with EDS. Background values of chromosome aberrations in children suffering from classical EDS were determined and compared with control subjects. The in vitro experiment was performed by γ-irradiation of blood lymphocytes from EDS patients and healthy subjects at low doses (0.1, 0.2 and 0.3 Gy). Results show a significant increase level of spontaneous and radiation-induced chromosomal aberrations in children suffering from EDS in comparison with the control subjects (p < 0.05). In conclusion, children with EDS express higher background chromosome aberration frequency and increased radiosensitivity. These findings suggest specific susceptibility of EDS patients and importance of future investigation on risks of diagnostics and therapy which include radiation and genotoxic agents.

© 2019 International Union of Crystallography. This study of 3-(5-phenyl-1,3,4-oxadiazol-2-yl)-2H-chromen-2-one, C17H10N2O3, 1, and 3-[5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl]-2H-chromen-2-one, C16H9ON3O3, 2, was performed on the assumption of the potential anticancer activity of the compounds. Three polymorphic structures for 1 and two polymorphic structures for 2 have been studied thoroughly. The strongest intermolecular interaction is stacking of the 'head-to-head' type in all the studied crystals. The polymorphic structures of 1 differ with respect to the intermolecular interactions between stacked columns. Two of the polymorphs have a columnar or double columnar type of crystal organization, while the third polymorphic structure can be classified as columnar-layered. The difference between the two structures of 2 is less pronounced. Both crystals can be considered as having very similar arrangements of neighbouring columns. The formation of polymorphic modifications is caused by a subtle balance of very weak intermolecular interactions and packing differences can be identified only using an analysis based on a study of the pairwise interaction energies.

© 2019 Elsevier Ltd Four inhibitors of human carbonic anhydrase II (hCA II) were designed based on the previously reported subnanomolar 1,3-oxazole-based sulfonamide inhibitors of the enzyme to incorporate primary and secondary amine functionality in the carboxamide side chain. The new hydrophilic compounds were found to inhibit the target isoform in sub-nanomolar to low nanomolar range with a good degree of selectivity to several other hCA isoforms. The hydrophilic character of these compounds is advantageous for intraocular residence time but not for corneal permeability which generally requires that a drug be sufficiently lipophilic. Two of the four compounds investigated, however, were found to exert comparable efficacy as 1% eye drops in PBS to that of the clinically used 2% dorzolamide (Trusopt®) eye drops. This indicated that the absorption of the compounds may occur via alternative route across conjunctiva and sclera.

© 2019, The Author(s). Objectives: This study was aimed to assess hemostatic disturbances in female patients with established rheumatoid arthritis (RA) in relation to menopausal status and disease activity. Method: Ninety women were included in the study, 42 patients and 48 age-matched healthy controls. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. Two global hemostatic assays were employed, namely endogenous thrombin potential (ETP) and overall hemostasis potential (OHP). The parameters of the ETP assay (ETP, C-max, t-lag, t-max) and OHP assay (overall coagulation potential (OCP) and overall fibrinolytic potential (OFP)) were assessed. Moreover, the parameters of the fibrin clot (lag time, Max Abs, and slope) were measured by clot turbidity and scanning electron microscopy (SEM). Both patients and controls were divided into four subgroups according to menopause status. Results: The premenopausal controls differed significantly from all other subgroups in terms of diminished levels of ETP (p = 0.02), C-max (p = 0.01), OCP (p = 0.02), OHP (p = 0.001), and Max Abs (p = 0.008), while OFP (p = 0.0001) was increased. This tendency was not seen in the premenopausal RA patients compared with the postmenopausal RA patients. SEM images showed denser clots composed of thinner fibers in samples from RA patients. The disease activity measured by DAS28 correlated with OCP and OHP (r = 0.54; p = 0.001 and r = 0.44; p = 0.003, respectively) indicating persistent hypercoagulable condition in the whole group of RA patients. Conclusions: Our results point towards coagulation activation in premenopausal women with established RA. The patients were well characterized, which enabled assessment in a real-life setting.Key Points• Extensive assessment points towards persistent coagulation activation in premenopausal women with established rheumatoid arthritis.• Impaired thrombin generation and fibrin formation are associated with menopause in healthy women, while rheumatoid arthritis closes the gap within patients regarding menopause.• Fibrin morphology is unfavorably altered and fibrinolysis is decreased in patients with established rheumatoid arthritis.• Increased activity of thrombin activatable fibrinolysis inhibitor (TAFI) may contribute to impaired fibrinolysis in patients with rheumatoid arthritis.

© 2019 American Academy of Allergy, Asthma  &  Immunology Background: Mepolizumab is an anti–IL-5 antibody approved for the treatment of severe eosinophilic asthma. However, the prevalence of patients with severe asthma eligible for mepolizumab remains unknown, especially among children. Objective: To determine, in a population of patients with severe asthma from a tertiary referral center, the proportion of patients with an eosinophilic phenotype who would be eligible for mepolizumab, when stratified for the age of onset of asthma, and the prevalence of phenotypic features that favor mepolizumab therapy. Methods: An extensive database of 245 adults and children referred for severe asthma was used. The prevalence of severe asthma was estimated by using the European Respiratory Society/American Thoracic Society criteria. Patients with an eosinophilic uncontrolled phenotype qualified for mepolizumab. Results: In our cohort, 216 (88%) had severe asthma. Based on blood eosinophils of either greater than or equal to 150 cells/μL or greater than or equal to 300 cells/μL, 61%/41% had an eosinophilic phenotype, while 49%/34% were eligible for mepolizumab therapy. A greater percentage of adults (60%/47% of adults with asthma onset in adulthood [AoA] and 48%/26% adults with childhood-onset asthma [<18 years, CoA]) were eligible compared with children (33%/24%), for eosinophil counts of ≥150 and ≥300 cells/μL, respectively; P < .05. Compared with adults, children had a similar number of exacerbations while having better lung function (P < .05). Among adults, those with AoA were older, were more likely to have nasal polyps (28% vs 5%; P < .05), and had higher blood eosinophil counts (272 vs 150 cells/μL; P < .05) compared with those with CoA, with no difference in lung function noted between the 2 groups. Subjects showing greater than or equal to 500 eosinophils/μL, a strong indicator for mepolizumab therapy, had more nasal polyps, higher inhaled steroid dose, lower lung function, and AoA predominance than did those with less than 500 eosinophils/μL (P < .05). Conclusions: A smaller percentage of children with severe asthma were eligible for mepolizumab compared with their adult peers. Severe AoA has distinct phenotypic features that favor treatment with mepolizumab, including greater eosinophilia and nasal polyposis, in contrast to CoA, which appears to have fewer features of type 2 mucosal inflammation.

© 2019, International League of Associations for Rheumatology (ILAR). Background: Patients with rheumatoid arthritis (RA) are at a high risk for life-threatening conditions requiring admission to the intensive care unit (ICU), but the data regarding the outcomes of these patients is limited. The present study investigated the clinical characteristics and outcomes of RA patients admitted to an ICU. Methods: This retrospective cohort study included RA patients admitted to the general ICU of the Sheba Medical Center during 2002–2018. The main outcome was 30-day mortality. Using Student’s t test, χ2, and multivariable analyses, we compared the demographic, clinical, and laboratory parameters of the survivors and the non-survivors. Figures with p value < 0.05 were considered statistically significant. Results: Forty-three RA patients were admitted to the ICU during the study period (mean age, 64.0 ± 13.1 years; 74.4% female). The leading causes of ICU admission were infection (72.1%), respiratory failure (72.1%), renal failure (60.5%), and septic shock (55.8%). The 30-day mortality rate was 34.9%, with infection (9/15, 60%) as the most frequent cause. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were 19.7 ± 12.5 and 7.0 ± 4.5, respectively. Multivariable analysis showed that heart failure (p = 0.023), liver failure (p = 0.012), SOFA score (p = 0.007), and vasopressor treatment in ICU (p = 0.039) were significantly associated with overall mortality. SOFA score was linked with overall mortality (area under the curve (AUC) = 0.781 ± 0.085, p = 0.003) and mortality from respiratory failure (AUC = 0.861 ± 0.075, p = 0.002), while APACHE II score was only correlated with mortality from infection (AUC = 0.735 ± 0.082, p = 0.032). Conclusions: Our study demonstrated a relatively high mortality rate among RA patients who were admitted to the general ICU. RA patients with risk factors such as heart failure, liver failure, elevated SOFA score, and vasopressor treatment in ICU should be promptly identified and treated accordingly.Key Points• The 30-day mortality rate of patients with RA that were admitted to the general ICU of a tertiary hospital was 34.9%.• The most common causes of ICU admission among patients with RA were infections and respiratory failure. Infections were the most common cause of death among these patients.• Patients with RA that present to the ICU with heart failure, liver failure, elevated SOFA score, and/or require vasopressor treatment in ICU should be promptly identified and treated accordingly.

© 2019 The Authors Background: The aim was to estimate the prevalence of harmful alcohol use in relation to socio-demographic characteristics among acutely ill medical patients, and examine identification measures of alcohol use, including the alcohol biomarker phosphatidylethanol 16:0/18:1 (PEth). Methods: A cross-sectional study, lasting one year at one hospital in Oslo, Norway and one in Moscow, Russia recruiting acute medically ill patients (≥ 18 years), able to give informed consent. Self-reported data on socio-demographics, mental distress (Symptom Check List-5), alcohol use (Alcohol Use Disorder Identification Test-4 (AUDIT-4) and alcohol consumption past 24 h were collected. PEth and alcohol concentration were measured in whole blood. Results: Of 5883 participating patients, 19.2% in Moscow and 21.1% in Oslo were harmful alcohol users, measured by AUDIT-4, while the prevalence of PEth-positive patients was lower: 11.4% in Oslo, 14.3% in Moscow. Men in Moscow were more likely to be harmful users by AUDIT-4 and PEth compared to men in Oslo, except of those being ≥ 71 years. Women in Oslo were more likely to be harmful users compared to those in Moscow by AUDIT-4, but not by PEth for those aged < 61 years. Conclusions: The prevalence of harmful alcohol use was high at both study sites. The prevalence of harmful alcohol use was lower when assessed by PEth compared to AUDIT-4. Thus, self-reporting was the most sensitive measure in revealing harmful alcohol use among all groups except for women in Moscow. Hence, screening and identification with objective biomarkers and self-reporting might be a method for early intervention.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. The objective of the present study was to assess the levels of Se, as well as other essential and toxic trace elements in wheat grains and traditional Roti-bread from whole-grain flour in a seleniferous area of Punjab (India) using inductively-coupled plasma mass-spectrometry. Wheat grain and bread selenium levels originating from seleniferous areas exceeded the control values by a factor of more than 488 and 179, respectively. Se-rich wheat was also characterized by significantly increased Cu and Mn levels. Se-rich bread also contained significantly higher levels of Cr, Cu, I, Mn, and V. The level of Li and Sr was reduced in both Se-enriched wheat and bread samples. Roti bread from Se-enriched wheat was also characterized by elevated Al, Cd, and Ni, as well as reduced As and Hg content as compared to the respective control values. Se intake with Se-rich bread was estimated as more than 13,600% of RDA. Daily intake of Mn with both Se-unfortified and Se-fortified bread was 133% and 190% of RDA. Therefore, Se-rich bread from wheat cultivated on a seleniferous area of Punjab (India) may be considered as a potent source of selenium, although Se status should be monitored throughout dietary intervention.

© 2019 Nordic Federation of Societies of Obstetrics and Gynecology Introduction: The aim of this systematic review was to explore the outcome of fetuses with a prenatal diagnosis of isolated talipes. Material and methods: Medline, Embase, Cinahl, and Clinicaltrials.gov databases were searched. The outcomes explored were: associated anomalies detected at follow-up ultrasound examination; fetal magnetic resonance imaging (MRI) and birth; chromosomal abnormalities detected with standard and chromosomal microarray analysis, intrauterine, neonatal, and perinatal death, and termination of pregnancy; rate of surgical and nonsurgical treatment; neurodevelopmental outcome; and false-positive rate of prenatal diagnosis. Meta-analyses of proportions were used to combine data. Results: Twenty-five studies (1567 fetuses) were included. Associated anomalies were detected in 7.8% (95% CI 0.1%-29.3%) of cases at follow-up ultrasound, and in 4.0% (95% CI 0.1%-13.2%) of cases, fetal MRI identified anomalies not detected at ultrasound assessment. Similarly, 7.0% (95% CI 3.4%-11.7%) of cases labeled as isolated talipes on prenatal imaging were found to have associated anomalies at birth. Abnormal karyotype was present in 3.6% (95% CI 1.7%-6.2%) of fetuses, whereas no anomaly was found at chromosomal microarray analysis, although this outcome was reported by only 1 study. Intrauterine death occurred in 0.99% (95% CI 0.4%-1.9%) of fetuses, whereas the corresponding figures for neonatal death and termination of pregnancy were 1.5% (95% CI 0.6%-2.6%) and 2.2% (95% CI 1.2%-3.4%), respectively. Surgical management of anomalies after birth was found in 41.7% (95% CI 27.0%-57.2%) of fetuses with isolated talipes, and 54.8% (95% CI 31.5%-77.0%) had nonsurgical management of the anomalies after birth. Abnormal neurodevelopmental outcome was reported in 7.6% (95% CI 1.0%-19.4%) of children, although this analysis was affected by the small number of included cases and short time of follow up. Conclusions: Isolated talipes detected on prenatal ultrasound carries a generally good prognosis. The incidence of additional abnormalities detected on fetal MRI, aneuploidy, or neurodevelopmental disability is relatively low. However, longitudinal ultrasound assessment during pregnancy and a thorough postnatal evaluation are recommended to rule out associated anomalies that may significantly impact short- and long-term prognosis.

© 2019 John Wiley  &  Sons Ltd Background: Understanding consumer perceptions is crucial if effective food safety policy and risk communication are to be developed and implemented. We sought to understand how those living with food allergy assess risk with precautionary allergen labelling (PAL) and their preference in how risks are communicated within a quantitative risk assessment (QRA) framework. Methods: The Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM) labelling online survey was developed for adults and parents of children with food allergy and distributed across Germany, Ireland, Netherlands, Spain and UK via patient support groups. Results: There were 1560 complete responses. ‘This product is not suitable for’ was selected as first choice for PAL by 46% overall and ‘May contain’ was selected as the first choice by 44%. Seventy-three percent reported that it would improve their trust in a product if a QRA process had been used to make a decision about whether to include ‘may contain’. Overall, 66% reported that a ‘statement + symbol’ on the label indicating a QRA, would help them to understand the risk assessment process that had been used by the food manufacturer. Conclusions: Consumers want to know what process has actually taken place for the placing of a PAL and/or risk assessment statement on a particular food product. Our findings provide a basis for the development of more informative communication around food allergen risk and safety and support evidence-based policy-making in the context of the legislative requirements of the European Union's Food Information for Consumers Regulation.

© 2019 Context: This overview presents the updated European Association of Urology (EAU) guidelines for non–muscle-invasive bladder cancer (NMIBC), TaT1, and carcinoma in situ (CIS). Objective: To provide practical recommendations on the clinical management of NMIBC with a focus on clinical presentation and recommendations. Evidence acquisition: A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines has been performed annually since the last published version in 2017. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned. Evidence synthesis: Tumours staged as Ta, T1, and/or CIS are grouped under the heading of NMIBC. Diagnosis depends on cystoscopy and histological evaluation of the tissue obtained by transurethral resection (TURB) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TURB is essential for the patient's prognosis and correct diagnosis. Where the initial resection is incomplete, where there is no muscle in the specimen, or where a T1 tumour is detected, a second TURB should be performed within 2–6 wk. The risks of both recurrence and progression may be estimated for individual patients using the European Organisation for Research and Treatment of Cancer (EORTC) scoring system. Stratification of patients into low-, intermediate-, and high-risk groups is pivotal to the recommendation of adjuvant treatment. In patients with tumours presumed to be at a low risk and in those presumed to be at an intermediate risk with a low previous recurrence rate and an expected EORTC recurrence score of <5, one immediate chemotherapy instillation is recommended. Patients with intermediate-risk tumours should receive 1 yr of full-dose bacillus Calmette-Guérin (BCG) intravesical immunotherapy or instillations of chemotherapy for a maximum of 1 yr. In patients with high-risk tumours, full-dose intravesical BCG for 1–3 yr is indicated. In patients at the highest risk of tumour progression, immediate radical cystectomy should be considered. Cystectomy is recommended in BCG-unresponsive tumours. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/non-muscle-invasive-bladder-cancer/. Conclusions: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice. Patient summary: The European Association of Urology Non–muscle-invasive Bladder Cancer (NMIBC) Panel has released an updated version of their guidelines, which contains information on classification, risk factors, diagnosis, prognostic factors, and treatment of NMIBC. The recommendations are based on the current literature (until the end of 2018), with emphasis on high-level data from randomised clinical trials and meta-analyses. Stratification of patients into low-, intermediate-, and high-risk groups is essential for deciding appropriate use of adjuvant intravesical chemotherapy or bacillus Calmette-Guérin (BCG) instillations. Surgical removal of the bladder should be considered in case of BCG-unresponsive tumours or in NMIBCs with the highest risk of progression.

© Author(s) (or their employer(s)) 2019. Objectives To investigate the influence of vasodilator drugs on the occurrence of features depending on myocardial ischaemia/fibrosis (ventricular arrhythmias, Q waves, cardiac blocks, pacemaker implantation, left ventricular ejection fraction (LVEF) <55%, and/or congestive heart failure and sudden cardiac death) in systemic sclerosis (SSc). Methods 601 patients with SSc were enrolled from 1 December 2012 to 30 November 2015 and had a second visit 0.5-4 years apart. 153 received no vasodilators; 448 received vasodilator therapy (ie, calcium channel blockers and/or ACE inhibitors or angiotensin II receptor blockers or combinations of them), 89 of them being also treated with either endothelin receptor antagonists or PDE5 inhibitors or prostanoids. Associations between the occurrence of myocardial disease manifestations and any demographic, disease and therapeutic aspect were investigated by Cox regression analysis. A Cox frailty survival model with centre of enrolment as random effect was performed. Results During 914 follow-up patient-years, 12 ventricular arrhythmias, 5 Q waves, 40 cardiac blocks, 6 pacemaker implantations and 19 reduced LVEF and/or congestive heart failure (CHF) occurred. In multivariate Cox regression analysis, vasodilator therapy was associated with a lower incidence of ventricular arrhythmias (p=0.03); low-dose acetylsalicylic acid (ASA) with a lower incidence of cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.02); active disease with a higher incidence of LVEF <55% and/or CHF and cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.05). Conclusions The present study might suggest a preventative effect on the occurrence of distinct myocardial manifestations by vasodilator therapy and low-dose ASA.

© 2019, The Author(s). Abstract: In 2014 the International Endohernia Society (IEHS) published the first international “Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias”. Guidelines reflect the currently best available evidence in diagnostics and therapy and give recommendations to help surgeons to standardize their techniques and to improve their results. However, science is a dynamic field which is continuously developing. Therefore, guidelines require regular updates to keep pace with the evolving literature. Methods: For the development of the original guidelines all relevant literature published up to year 2012 was analyzed using the ranking of the Oxford Centre for Evidence-Based-Medicine. For the present update all of the previous authors were asked to evaluate the literature published during the recent years from 2012 to 2017 and revise their statements and recommendations given in the initial guidelines accordingly. In two Consensus Conferences (October 2017 Beijing, March 2018 Cologne) the updates were presented, discussed, and confirmed. To avoid redundancy, only new statements or recommendations are included in this paper. Therefore, for full understanding both of the guidelines, the original and the current, must be read. In addition, the new developments in repair of abdominal wall hernias like surgical techniques within the abdominal wall, release operations (transversus muscle release, component separation), Botox application, and robot-assisted repair methods were included. Results: Due to an increase of the number of patients and further development of surgical techniques, repair of primary and secondary abdominal wall hernias attracts increasing interests of many surgeons. Whereas up to three decades ago hernia-related publications did not exceed 20 per year, currently this number is about 10-fold higher. Recent years are characterized by the advent of new techniques—minimal invasive techniques using robotics and laparoscopy, totally extraperitoneal repairs, novel myofascial release techniques for optimal closure of large defects, and Botox for relaxing the abdominal wall. Furthermore, a concomitant rectus diastasis was recognized as a significant risk factor for recurrence. Despite still insufficient evidence with respect to these new techniques it seemed to us necessary to include them in the update to stimulate surgeons to do research in these fields. Conclusion: Guidelines are recommendations based on best available evidence intended to help the surgeon to improve the quality of his daily work. However, science is a continuously evolving process, and as such guidelines should be updated about every 3 years. For a comprehensive reference, however, it is suggested to read both the initially guidelines published in 2014 together with the update. Moreover, the presented update includes also techniques which were not known 3 years before.

© 2019 National Academy of Sciences. All rights reserved. Intracortical microstimulation (ICMS) of the primary somatosensory cortex (S1) can produce percepts that mimic somatic sensation and, thus, has potential as an approach to sensorize prosthetic limbs. However, it is not known whether ICMS could recreate active texture exploration—the ability to infer information about object texture by using one’s fingertips to scan a surface. Here, we show that ICMS of S1 can convey information about the spatial frequencies of invisible virtual gratings through a process of active tactile exploration. Two rhesus monkeys scanned pairs of visually identical screen objects with the fingertip of a hand avatar—controlled first via a joystick and later via a brain–machine interface—to find the object with denser virtual gratings. The gratings consisted of evenly spaced ridges that were signaled through individual ICMS pulses generated whenever the avatar’s fingertip crossed a ridge. The monkeys learned to interpret these ICMS patterns, evoked by the interplay of their voluntary movements and the virtual textures of each object, to perform a sensory discrimination task. Discrimination accuracy followed Weber’s law of just-noticeable differences (JND) across a range of grating densities; a finding that matches normal cutaneous sensation. Moreover, 1 monkey developed an active scanning strategy where avatar velocity was integrated with the ICMS pulses to interpret the texture information. We propose that this approach could equip upper-limb neuroprostheses with direct access to texture features acquired during active exploration of natural objects.

Here we report sequence and phylogenetic analysis of two new isolates of Leishmania RNA virus 2 (LRV2) found in Leishmania major isolated from human patients with cutaneous leishmaniasis in south Uzbekistan. These new virus-infected flagellates were isolated in the same region of Uzbekistan and the viral sequences differed by only nineteen SNPs, all except one being silent mutations. Therefore, we concluded that they belong to a single LRV2 species. New viruses are closely related to the LRV2-Lmj-ASKH documented in Turkmenistan in 1995, which is congruent with their shared host (L. major) and common geographical origin.