Limited evidence for genetic differentiation or adaptation in two amphibian species across replicated rural-urban gradients.

Urbanization leads to complex environmental changes and poses multiple challenges to organisms. Amphibians are highly susceptible to the effects of urbanization, with land use conversion, habitat destruction, and degradation ranked as the most significant threats. Consequently, amphibians are declining in urban areas, in both population numbers and abundance, however, the effect of urbanization on population genetic parameters remains unclear. Here, we studied the genomic response to urbanization in two widespread European species, the common toad Bufo bufo (26 localities, 480 individuals), and the smooth newt Lissotriton vulgaris (30 localities, 516 individuals) in three geographic regions: southern and northern Poland and southern Norway. We assessed genome-wide SNP variation using RADseq (ca. 42 and 552 thousand SNPs in toads and newts, respectively) and adaptively relevant major histocompatibility complex (MHC) class I and II genes. The results linked most of the genetic differentiation in both marker types to regional (latitudinal) effects, which also correspond to historical biogeography. Further, we did not find any association between genetic differentiation and level of urbanization at local scales for either species. However, urban smooth newts, but not toads, have lower levels of within-population genome-wide diversity, suggesting higher susceptibility to the negative effects of urbanization. A decreasing level of genetic diversity linked to increasing urbanization was also found for MHC II in smooth newts, while the relationship between MHC class I diversity and urbanization differed between geographic regions. We did not find any effects of urbanization on MHC diversity in the toad populations. Although two genetic environment association analyses of genome-wide data, LFMM and BayPass, revealed numerous (219 in B. bufo and 7040 in L. vulgaris) SNPs statistically associated with urbanization, we found a marked lack of repeatability between geographic regions, suggesting a complex and multifaceted response to natural selection elicited by life in the city.

The genomic response to urbanization in the damselfly Ischnura elegans.

The complex and rapid environmental changes brought about by urbanization pose significant challenges to organisms. The multifaceted effects of urbanization often make it difficult to define and pinpoint the very nature of adaptive urban phenotypes. In such situations, scanning genomes for regions differentiated between urban and non-urban populations may be an attractive approach. Here, we investigated the genomic signatures of adaptation to urbanization in the damselfly Ischnura elegans sampled from 31 rural and urban localities in three geographic regions: southern and northern Poland, and southern Sweden. Genome-wide variation was assessed using more than 370,000 single nucleotide polymorphisms (SNPs) genotyped by ddRADseq. Associations between SNPs and the level of urbanization were tested using two genetic environment association methods: Latent Factors Mixed Models and BayPass. While we found numerous candidate SNPs and a highly significant overlap between candidates identified by the two methods within the geographic regions, there was a distinctive lack of repeatability between the geographic regions both at the level of individual SNPs and of genomic regions. However, we found "synapse organization" at the top of the functional categories enriched among the genes located in the proximity of the candidate urbanization SNPs. Interestingly, the overall significance of "synapse organization" was built up by the accretion of different genes associated with candidate SNPs in different geographic regions. This finding is consistent with the highly polygenic nature of adaptation, where the response may be achieved through a subtle adjustment of allele frequencies in different genes that contribute to adaptive phenotypes. Taken together, our results point to a polygenic adaptive response in the nervous system, specifically implicating genes involved in synapse organization, which mirrors the findings from several genomic and behavioral studies of adaptation to urbanization in other taxa.

Magnetic anisotropy in the exchange-biased laser-patterned thin Co/CoO films.

Materials exhibiting an exchange bias effect are a class of magnetic systems that have a wide range of possible technological applications e.g. in sensors, read heads, and spintronic devices. In this study, we demonstrate the effect of laser interference patterning on the magnetic properties of Pd/CoO/Co/Pd multilayers. Laser patterning creates arrays of well-ordered stripes, rectangles, and squares on the substrate surface. We found that the laser treatment caused magnetic softening of the structure edges while the centers of the objects remained unchanged and exhibited the exchange bias effect. In this study we focused on the shape and configurational magnetic anisotropies induced by patterning and showed that the magnetic properties varied depending on the angle at which the external magnetic field was applied with respect to the pattern geometry.

Immunohistochemical study on the development of cholinergic and nitrergic nerve structures in the bovine esophageal groove.

The proper functioning of the perinatal sucking reflex in calves is essential for the prevention of milk leakage into the rumen. The complex process behind its regulation is mediated at the gut level via multiple excitatory and inhibitory neurotransmitters, of which acetylcholine and nitric oxide are of fundamental importance. The aim of our study was to depict age-related alterations in the cholinergic and nitrergic innervation of the esophageal groove (EG) using immunohistochemistry and Real-Time PCR methods. We found out that the highest number of cholinergic nerve cells was present in the second trimester fetuses. From this developmental stage onward, their amount was gradually decreasing and reached the lowest value in 4-year-old cows. The same developmental pattern was observed for nitrergic nerve structures with the highest percentage of nitrergic neurons in the third trimester fetuses. Our observations prove that both neuronal populations are crucial for a proper closure of EG in calves. Therefore, their contribution to a general neuronal activity in the ENS diminishes with age as the high motility of a gastric groove is not necessarily required in older cattle.

Rezum water vapor therapy in multimorbid patients with urinary retention and catheter dependency.

BACKGROUND: Water vapor thermal therapy (Rezum) is a minimally invasive treatment for benign prostatic enlargement (BPE). We report on safety and efficacy of this method for treatment of recurrent urinary retention and relief of catheter dependency owing to BPE in multimorbid patients, considered unfit for surgery. METHODS: We retrospectively evaluated 136 patients with recurrent urinary retention who underwent water vapor therapy in an ambulatory setting with periprostatic block and optional sedation between 11/2017 and 02/2021 in three urological departments. The objective was successful catheter withdrawal and continuing catheter independency after 3- and 12-months following treatment. RESULTS: Mean patient age was 80.3 years (±7.8), mean prostate volume 54 ml (±27.3), and mean catheter dependency before treatment was 4.8 months (±6.0). ASA classification was a followed: II: 10%, III: 71%, and IV: 19%. All procedures were performed successfully in an ambulatory setting. Perioperative complications were infrequent and minor (Clavien-Dindo Grade 1-2) and included haematuria in 4.4% and urinary tract infection in 3.9% of all cases. A total of 103 patients (78.6%) were able to void spontaneously after a median of 31 days. No significant differences in age, prostate volume, duration of catheter dependency, vapor injections, and ASA score were found between patients with successful or unsuccessful outcome. The mean follow-up period was 6.1 months (±5.9, range 1-22 months). A 3-month follow-up was available for 77 patients (75%) and 34 patients (33%) were followed for 12 months. After 3 and 12 months, 93.5 and 91% of patients remained catheter independent. Fifteen patients (11%) died during follow-up, with a mean overall survival of 7.7 months (±4.7). CONCLUSIONS: Water vapor therapy may prove to be a useful, minimally invasive treatment in a multimorbid population with catheter dependency after urinary retention, secondary to BPE, considered at highest risk or unfit for surgery. Future studies are warranted.

Bistability of magnetic states in Fe-Pd nanocap arrays.

Magnetic bistability between vortex and single domain states in nanostructures are of great interest from both fundamental and technological perspectives. In soft magnetic nanostructures, the transition from a uniform collinear magnetic state to a vortex state (or vice versa) induced by a magnetic field involves an energy barrier. If the thermal energy is large enough for overcoming this energy barrier, magnetic bistability with a hysteresis-free switching occurs between the two magnetic states. In this work, we tune this energy barrier by tailoring the composition of FePd alloys, which were deposited onto self-assembled particle arrays forming magnetic vortex structures on top of the particles. The bifurcation temperature, where a hysteresis-free transition occurs, was extracted from the temperature dependence of the annihilation and nucleation field which increases almost linearly with Fe content of the magnetic alloy. This study provides insights into the magnetization reversal process associated with magnetic bistability, which allows adjusting the bifurcation temperature range by the material properties of the nanosystem.

Apparent diffusion coefficient values obtained by unenhanced MRI predicts disease-specific survival in bladder cancer.

AIM: To assess the ability of apparent diffusion coefficient (ADC) measurements obtained by MRI to predict disease-specific survival (DSS) in patients with bladder cancer and compare it with established clinico-pathological prognostic factors. MATERIAL AND METHODS: The ethical review board approved this cross-sectional study. Patients with suspected bladder cancer receiving diagnostic 3 T diffusion-weighted imaging (DWI) of the bladder before transurethral resection of the bladder (TUR-B) or radical cystectomy were evaluated prospectively. Two independent radiologists measured ADC values in bladder cancer lesions in regions of interest. Associations between ADC values and pathological features with DSS were tested statistically. A combined model was established using artificial neuronal network (ANN) methodology. RESULTS: A total of 51 patients (median age 69 years, range 41-89 years) were included. Three patients were lost to follow-up, leaving 48 patients for survival analysis. Seven patients died during the 795 months studied. ADC showed significant potential to predict DSS (p<0.05). Except for grading, all pathological features as assessed by TUR-B could predict DSS (p<0.05, respectively). The combined ANN classifier showed the highest accuracy to predict DSS (0.889, 95% confidence interval: 0.732-1, p=0.001) compared to all single parameters. ADC was the second important predictor of the ANN. CONCLUSIONS: ADC measurements obtained by unenhanced MRI predicts DSS in bladder cancer patients. A combined classifier including ADC and clinico-pathological information showed high accuracy to identify patients at high risk for disease-related death.

Immunohistochemical characterization of the jugular (superior vagal) ganglion in the pig.

The study was carried out on three 4-month old female pigs. All the animals were deeply anesthetized and transcardially perfused with 4% buffered paraformaldehyde (pH 7.4). Left and right superior vagal ganglia (SVG) were collected and processed for immunofluorescence labeling method. The preparations were examined under a Zeiss LSM 710 confocal microscope equipped with adequate filter block. Neurons forming SVG were round or oval in shape with a round nucleus in the center. The majority of them (52%) were medium (M) (31-50 µm in diameter) while 7% and 41% were small (S) (up to 30µm in diameter) or large (L) (above 50 µm in diameter) in size, respectively. Double-labeling immunofluorescence revealed that SVG neurons stained for CGRP (approx. 57%; among them 37%, 9% and 54% were M, S and L in size, respectively), SP (14.5%; 72.4% M, 3.4% S, 24.2% L), VACHT (26%; 63% M, 24% S and 13% L), GAL (14%; 57% M, 29% S, 14% L), NPY (12%; 53% M, 12% S, 35% L), Met-Enk (5%; 40% M, 6% S and 54% L), PACAP (15%; 52% M, 24% S and 24% L), VIP (6.3%; 67% M, 8% S and 25% L), and NOS-positive (6%; 31% M and 69% L). The most abundant populations of intraganglionic nerve fibers were those which stained for CGRP or GAL, whereas only single SP-, PACAP- or Met-ENK-positive nerve terminals were observed.

European temporal trends in the use of lymph node dissection in patients with renal cancer.

BACKGROUND: The role of lymph node dissection (LND) in renal cell carcinoma (RCC) is still under debate. We aimed to assess the utilization rates of LND over time in Europe. METHODS: A multi-institutional database of 13,581 RCC patients who underwent radical nephrectomy (RN) or nephron sparing surgery (NSS) between 1988 and 2014 was created within an European consortium. We analysed temporal trends in the frequency of LND by using Joinpoint regression. Logistic regression models were used to identify predictors of LND. RESULTS: Overall, 5114 patients (42.7%) underwent LND. Lymph node invasion was recorded in 566 cases (11% of LND patients) which represents 4.7% of the whole study cohort. A gradual decline in the use of LND started in the 1990s. After 2008 LND decreased significantly by 21.5% per year (95%CI -33.3 to -7.5, p < 0.01) until 2011 and stabilized thereafter (Annual Percentage Change 4.9%, 95%CI -3.4 to 13.8, p = 0.2). At multivariable analyses, patient age (OR 0.98, p < 0.0001), type of surgery (RN vs. NSS: OR 5.46, p < 0.0001), surgical approach (open vs. minimally invasive: OR 1.75, p < 0.0001), T stage (T2 vs. T1: OR 1.57; T3-4 vs. T1: OR 1.44, p < 0.0001), clinical tumour size (OR 1.14, p < 0.0001), and year of surgery (OR 0.95, p < 0.0001) were associated with higher probability of LND at nephrectomy. CONCLUSIONS: A trend towards lower LND was observed over time for RCC patients who underwent RN or NSS. LND is more frequently performed in younger patients, locally advanced diseases and in case of open surgery.

The effect of Fe on the structure and electrical conductivity of sodium borosilicate glasses.

We report the synthesis and characterization of iron-bearing sodium borosilicate glasses with an Fe2O3 content lower than 10 mol%. Using Mössbauer spectroscopy we demonstrate that Fe ions most probably have a tetrahedral oxygen environment for an iron oxide content higher than 5 mol%. Additionally, the Mössbauer results along with the X-ray diffraction studies indicate the formation of magnetite nanoclusters. The electrical conductivity of iron-containing sodium borosilicate glasses is studied over a wide temperature range. The impact of iron content on the dielectric permittivity and electrical properties is discussed. Finally, ionic conduction is identified in the high temperature region and its physical origin is explained. A similar activation energy of the dc conductivity and the activation energy of the electrical relaxation suggest that both the relaxation and conduction processes can be ascribed to the same type of entities.

Fabrication of flexible highly ordered porous alumina templates by combined nanosphere lithography and anodization.

In this work, we propose a new method for the large-scale production of flexible, periodic alumina arrays with well-ordered pores. We show the incorporation of pre-patterning based on polystyrene (PS) nanosphere lithography into an aluminium anodization process. We prepared ordered monolayers of PS spheres with average diameters of (510 ± 10) nm and (430 ± 10) nm on a large area (1.5 × 1.5 cm2) of the Si substrate. Next, we deposited a 5 µm aluminium layer on arrays of PS nanospheres using the sputtering technique. After the deposition, we covered the aluminium film with a polymer Scotch adhesive tape, and separated it from the silicon substrate by ultrasonic-assisted lift-off. Finally, we performed the anodization of the aluminium. We compared the pore and cell sizes, and the pore distance for the templates obtained by this technique, with reference to the templates prepared by a two-step anodization process. Using this new approach, we obtained highly ordered hexagonal 2D lattices over a large area of up to 2 cm2 with sparse defects, amounting to not more than four defects per 1000 µm2 on average. Here, we show that the use of indentation techniques is not necessary and can be replaced by a fast, cheap and easy pre-patterning step based on nanosphere lithography.

Magnetic transition from dot to antidot regime in large area Co/Pd nanopatterned arrays with perpendicular magnetization.

We have studied the transition between two different magnetization reversal mechanisms for thin Co/Pd multilayers with perpendicular magnetic anisotropy, appearing in magnetic dot and antidot arrays, which were prepared by nanosphere lithography. Various ordered arrays of nanostuctures, both magnetic dots and antidots, were created by varying size and distance between the nanospheres employing RF-plasma etching. We have shown that the coercivity values reach a maximum for the array of antidots with a separation length close to the domain wall width. In this case, each area between three adjacent holes corresponds to a single domain configuration, which can be switched individually. On the contrary, small hole sizes and large volume of material between them results in domain wall propagation throughout the system accompanied by strong domain wall pinning at the holes. We have also shown the impact of edge effects on the magnetic anisotropy energy.

Ordered FePdCu nanoisland arrays made by templated solid-state dewetting.

Ordered FePdCu nanoisland arrays were formed by annealing at 600 °C, which caused solid state dewetting of [Cu/Fe/Pd] multilayers deposited on self-assembled SiO2 nanospheres with a size of 100 nm. A single FePdCu island was formed on the top of each SiO2 nanosphere. The structure of the obtained system was studied by x-ray diffraction (XRD), while its magnetic properties were studied by SQUID magnetometry. A partially ordered L10 alloy appeared in the annealed films, leading to magnetic hardening of the material. The paper presents the influence of the patterning on the system properties. It is shown that templated dewetting is a method providing nanoislands with well-controlled sizes and positions. The role of copper admixture in controlling the structural and magnetic properties is also discussed.

AMN082, a metabotropic glutamate receptor 7 allosteric agonist, attenuates locomotor sensitization and cross-sensitization induced by cocaine and morphine in mice.

Previous studies have indicated that metabotropic glutamate receptors 7 (mGluR7s) are involved in drug addiction. However, the role of these receptors in drug-induced behavioral sensitization is unknown. The aim of the present study was to determine whether systemic injection of AMN082, a selective mGluR7 allosteric agonist, reduces the cocaine- and morphine-induced hyperactivity and the development and expression of locomotor sensitization, and also affects the reciprocal cross-sensitization to the stimulant effect of cocaine and morphine in mice. AMN082 (1.25-10.0 mg/kg, i.p.) did not have an impact on locomotion of naive mice and did not affect the acute cocaine- or morphine-induced hyperactivity, except the dose of 10 mg/kg that suppressed the locomotor effect of both drugs. Repeated exposure to cocaine or morphine (10 mg/kg, 5× every 3 days) gradually increased locomotion during induction of sensitization and after 4 (cocaine) or 7 day (morphine) withdrawal phase when challenged with cocaine (10 mg/kg, i.p.) or morphine (10 mg/kg, i.p.) on day 17 or 20, respectively. Pretreatment of animals with the lower doses of AMN082 (1.25-5.0 mg/kg, i.p.), 30 min before every cocaine or morphine injection during repeated drug administration or before cocaine or morphine challenge, dose-dependently attenuated the development, as well as the expression of cocaine or morphine locomotor sensitization. AMN082 also inhibited the reciprocal cross-sensitization between these drugs. Prior to administration of MMPIP (10 mg/kg, i.p.), a selective mGluR7 antagonist reversed the inhibitory effect of AMN082 on the development or expression of cocaine or morphine sensitization. These data indicate that AMN082 attenuated the development and expression of cocaine and morphine sensitization, and the reciprocal cross-sensitization via a mechanism that involves mGluR7s. Thus, AMN082 might have therapeutic implications not only in the treatment of cocaine or opioid addiction but also in the treatment of cocaine/opioid polydrug-abusers.

Management of localized and locally advanced renal tumors. A contemporary review of current treatment options.

About 70% of patients with renal cell carcinoma present with localized or locally advanced disease at primary diagnosis. Whereas these patients are potentially curable by surgical treatment alone, a further 20% to 30% of patients are diagnosed with primary metastatic disease. Although over the past years medical treatment for metastatic patients has nearly completely changed from immunotherapy to effective treatment with targeted agents, metastatic disease still represents a disease status which is not curable. Also in patients with metastatic disease, surgical treatment of the primary tumor plays an important role, since local tumor related complications can be avoided or minimized by surgery. Furthermore, also improvement of overall survival has been proven for surgery in metastatic patients when combined with cytokine treatment. Hence, surgical combined with systemic treatment as a multi-modal, adjuvant, and neo-adjuvant treatment is also required in patients with advanced or metastatic disease. A growing number of elderly and comorbid patients are currently diagnosed with small renal masses, which has led to increased attention paid to alternative ablative treatment modalities as well as active surveillance strategies, which are applied in order to avoid unnecessary overtreatment in these patients. Since surgical treatment also might enhance the risk of chronic kidney disease with consecutive cardiac disorders as well as reduced overall survival, ablative techniques and active surveillance are increasingly applied. In this review article we focus on current surgical and none-surgical treatment options for the management of patients with localized, locally advanced, and metastatic renal cell carcinoma.

Grade IV renal trauma in a patient with a solitary kidney.

A 60-year-old woman with a grade IV trauma to a solitary kidney was referred to our hospital. After primary conservative management, a continuous decline of the renal function required surgical exploration with decompression and renal reconstruction on the 4th day after the trauma. Postsurgical anuria prompted insertion of a ureteral stent; thereafter the renal function recovered quickly. A urinoma caused by a urinary fistula emerged 6 months after the trauma and was treated by percutaneous drainage, ureteral stenting, and percutaneous occlusion with fibrin sealant. Twelve months after the trauma, the patient is symptom free with a normal renal function.

Is the metabolic syndrome a risk factor for female sexual dysfunction in sexually active women?

Despite of the high prevalence, pathogenesis of female sexual dysfunction (FSD) is still poorly understood. A consecutive series of sexually active women underwent a health investigation and completed a questionnaire on FSD. Metabolic syndrome (MS) was defined according to the International Diabetes Federation definition. A total of 538 women with a mean age of 44 years (range: 30-69) was analysed. The premenopausal group comprised 329 women (61.2%) with a mean age of 38.5 years; the postmenopausal cohort contained 209 women (38.8%) with a mean age of 52.7 years. In the total cohort (n=538) MS was present in 17.6%, 8.5% in the premenopausal group and 32.6% in the postmenopausal women. In premenopausal women, the MS was an independent risk factor for impaired sexual desire (P=0.03) with an age-adjusted odds ratio of 3.3 (95% confidence interval: 1.5-7.3). In premenopausal female sexual life, the MS represents an independent role via its correlation to impaired desire.

[Benign prostate hyperplasia: success and limitations of pharmacological therapy]. / Benigne Prostatahyperplasie : Erfolge und Grenzen der Pharmakotherapie.

A profound knowledge of pathogenesis and natural history enables a differentiated therapy for elderly men with lower urinary tract symptoms due to benign prostatic hyperplasia (BPH). The role of phytotherapy is still controversially discussed and, therefore, not clearly recommended by any BPH-guideline. alpha(1)-blockers are the therapy of choice for symptomatic patients at a low risk of disease progression (prostate volume <30-40 ml). 5alpha-reductase inhibitors (5ARI) reduce the prostate volume by 20-25% and the risk for acute urinary retention/surgery by more than 50% compared to placebo. Combination therapy (alpha(1)-blocker plus 5ARI) is superior to either monotherapy, though this advantage is only demonstrable after a prolonged treatment period (>12 months).

[Epidemiology of BPH and medication approaches]. / Epidemiologie der BPH und medikamentöse Ansätze.

A more profound knowledge on the pathogenesis, the natural history and the risk of progression enablesa more differentiated therapy of elderly men with lower urinary tract symptoms due to benign prostatic hyperplasia (BPH) and benign prostatic enlargement as compared to 15 years ago. Phytotherapy is currently not recommended by any international BPH-guideline, because the definitive clinical proof for their clinical efficacy has not been made. alpha1-blockers and 5alpha-reductase inhibitors (5ARIs) are established world-wide. Alpha1-blockers are the medical therapy of choice for symptomatic patients with a low risk of clinical progression (e.g. prostate volume < 30-40 ml). Recent long-term data indicate that alpha1-blockers have no effect on the long-term risk of acute urinary retention and the risk of surgery. 5ARIs should be reserved for patients with a higher risk of progression (e.g. prostate volume > 30-40 ml). 5ARIs significantly reduce the risk of acute urinary retention and the need for surgery.