Asymptomatic bacteriospermia and infertility-what is the connection?

OBJECTIVE: To determine the impact of asymptomatic bacteriospermia on semen quality in subfertile men. METHODS: We conducted a retrospective, single-centre cohort study in 1300 subfertile men. In those diagnosed with asymptomatic bacteriospermia we performed univariate and multivariate logistic regression models to evaluate the strain-specific association with semen parameters. RESULTS: Asymptomatic bacteriospermia was diagnosed in 3.2% of patients. The microbiological semen analysis revealed a poly-microbial result in 60%. The most common bacterial species were coagulase-negative Staphylococci species (71.4%), Streptococcus viridans (50.0%) and Enterococcus faecalis (26.2%). Sexually transmitted pathogens were identified in 11.9% of semen samples. The detection of Streptococcus viridians or Haemophilus parainfluenzae correlated with impaired sperm morphology (p < 0.05). The presence of coagulase-negative Staphylococci species or Enterococcus faecalis was associated with pathological low counts of live spermatozoa (p < 0.05). In multivariate analysis only Enterococcus faecalis showed a significant impact on sperm concentration (OR 4.48; 95% CI 1.06-22.10; p = 0.041). CONCLUSIONS: Asymptomatic bacteriospermia has always been a subject of great controversy. There is still an ongoing debate whether to treat or not to treat. Here, we demonstrate that asymptomatic bacteriospermia is clearly associated with impaired semen quality. Our findings speak in favour of strain-specific interactions with semen parameters. Especially Enterococcus faecalis seriously affects sperm concentration.

Testicular adenosine acts as a pro-inflammatory molecule: role of testicular peritubular cells.

Extracellular ATP has been described to be involved in inflammatory cytokine production by human testicular peritubular cells (HTPCs). The ectonucleotidases ENTPD1 and NT5E degrade ATP and have been reported in rodent testicular peritubular cells. We hypothesized that if a similar situation exists in human testis, ATP metabolites may contribute to cytokine production. Indeed, ENTPD1 and NT5E were found in situ and in vitro in HTPCs. Malachite green assays confirmed enzyme activities in HTPCs. Pharmacological inhibition of ENTPD1 (by POM-1) significantly reduced pro-inflammatory cytokines evoked by ATP treatment, suggesting that metabolites of ATP, including adenosine, are likely involved. We focused on adenosine and detected three of the four known adenosine receptors in HTPCs. One, A2B, was also found in situ in peritubular cells of human testicular sections. The A2B agonist BAY60-6583 significantly elevated levels of IL6 and CXCL8, a result also obtained with adenosine and its analogue NECA. Results of siRNA-mediated A2B down-regulation support a role of this receptor. In mouse peritubular cells, in contrast to HTPCs, all four of the known adenosine receptors were detected; when challenged with adenosine, cytokine expression levels significantly increased. Organotypic short-term testis cultures yielded comparable results and indicate an overall pro-inflammatory action of adenosine in the mouse testis. If transferable to the in vivo situation, our results may implicate that interference with the generation of ATP metabolites or interference with adenosine receptors could reduce inflammatory events in the testis. These novel insights may provide new avenues for treatment of sterile inflammation in male subfertility and infertility.

Impact of antiangiogenic treatment on the erectile function in patients with advanced renal cell carcinoma.

We longitudinally assessed erectile function as well as the willingness to use pro-erectile treatment in a cohort on AAT for advanced RCC. Thirty-seven patients with advanced RCC completed the five-item version of the International Index of Erectile Function (IIEF-5) and other interview items before (T0) and 12 weeks into therapy (T12) with AAT. Patients were further asked if they were willing to use and pay out-of-pocket for on-demand treatment with phosphodiesterase-5-inhibitors (PDE-5i). Statistical analysis was performed using nonparametric hypothesis testing. The IIEF-5 score at T12 was significantly decreased compared with T0 (p < .001). Subjective patient satisfaction regarding their sexual lives was associated with higher IIEF-5 scores at both time points (p = .006 and p = .03, respectively). At T12, subjective sexual contentment showed a nonsignificant trend towards decline (p = .074). Patients who opted for medical treatment of ED showed significantly better IIEF-5 scores at both time points compared with the rest of the cohort (p < .001 and p = .005, respectively). In summary, AAT seems to have a negative effect on erectile function in RCC patients, however, the role of psychosocial issues warrants further elucidation. Affected patients may benefit from a proactive approach promoting medical treatment of erectile dysfunction during AAT.

How do elevated levels of testosterone affect the function of the human fallopian tube and fertility?-New insights.

Excess testosterone levels affect up to 20% of the female population worldwide and are a key component in the pathogenesis of polycystic ovary syndrome. However, little is known about how excess testosterone affects the function of the human fallopian tube-the site of gamete transport, fertilization, and early embryogenesis. Therefore, this study aimed to characterize alterations caused by long-term exposure to male testosterone levels. For this purpose, the Fallopian tubes of nine female-to-male transsexuals, who had been undergoing testosterone treatment for 1-3 years, were compared with the tubes of 19 cycling patients. In the ampulla, testosterone treatment resulted in extensive luminal accumulations of secretions and cell debris which caused ciliary clumping and luminal blockage. Additionally, the percentage of ciliated cells in the ampulla was significantly increased. Transsexual patients, who had had sexual intercourse before surgery, showed spermatozoa trapped in mucus. Finally, in the isthmus complete luminal collapse occurred. Our results imply that fertility in women with elevated levels of testosterone is altered by tubal luminal obstruction resulting in impaired gamete transport and survival.

Hydrogen in methanol catalysts by neutron imaging.

Although of pivotal importance in heterogeneous hydrogenation reactions, the amount of hydrogen on catalysts during reactions is seldom known. We demonstrate the use of neutron imaging to follow and quantify hydrogen containing species in Cu/ZnO catalysts operando during methanol synthesis. The steady-state measurements reveal that the amount of hydrogen containing intermediates is related to the reaction yields of CO and methanol, as expected from simple considerations of the likely reaction mechanism. The time-resolved measurements indicate that these intermediates, despite indispensable within the course of the reaction, slow down the overall reaction steps. Hydrogen-deuterium exchange experiments indicate that hydrogen reduction of Cu/ZnO nano-composites modifies the catalyst in such a way that at operating temperatures, hydrogen is dynamically absorbed in the ZnO-nanoparticles. This explains the extraordinary good catalysis of copper if supported on ZnO by its ability to act as a hydrogen reservoir supplying hydrogen to the surface covered by CO2, intermediates, and products during catalysis.

Should We Use Contrast-Enhanced Ultrasound (CEUS) for the Characterization of Nonpalpable Testicular Lesions? An Analysis from a Cost-Effectiveness Perspective.

PURPOSE: Accurate characterization of testicular lesions is crucial to allow for correct treatment of malignant tumors and to avoid unnecessary procedures in benign ones. In recent years, contrast-enhanced ultrasound (CEUS) proved to be superior in specifying the dignity of small, nonpalpable testicular lesions (< 1.5 cm) compared to native B-mode and color Doppler ultrasound which were previously regarded as the primary imaging method. However, the cost-effectiveness of CEUS has not been evaluated yet. The aim of this study was to analyze the cost-effectiveness of CEUS as compared to unenhanced ultrasound for the characterization of nonpalpable testicular lesions. METHODS: A decision model based on Markov simulations estimated lifetime costs and quality-adjusted life years (QALYs) associated with unenhanced ultrasound and CEUS. Model input parameters were obtained from recent literature. Deterministic sensitivity analysis of diagnostic parameters and costs was performed. Also, probabilistic sensitivity analysis using Monte-Carlo Modelling was applied. The willingness-to-pay (WTP) was set to $100 000/QALY. RESULTS: In the base-case scenario, unenhanced ultrasound resulted in total costs of $5113.14 and an expected effectiveness of 8.29 QALYs, whereas CEUS resulted in total costs of $4397.77 with 8.35 QALYs. Therefore, the unenhanced ultrasound strategy was dominated by CEUS in the base-case scenario. Sensitivity analysis showed CEUS to be the cost-effective alternative along a broad range of costs. CONCLUSION: Contrast-enhanced ultrasound is a cost-effective imaging method for the characterization of nonpalpable testicular lesions.

Depth-Profiling Microanalysis of CoNCN Water-Oxidation Catalyst Using a λ = 46.9 nm Plasma Laser for Nano-Ionization Mass Spectrometry.

Nanoscale depth profiling analysis of a CoNCN-coated electrode for water oxidation catalysis was carried out using table-top extreme ultraviolet (XUV) laser ablation time-of-flight mass spectrometry. The self-developed laser operates at λ = 46.9 nm and represents factor of 4 reduction in wavelength with respect to the 193 nm excimer laser. The reduction of the wavelength is an alternative approach to the reduction of the pulse duration, to enhance the ablation characteristics and obtain smaller quasi-nondestructive ablation pits. Such a XUV-laser ablation method allowed distinguishing different composite components of the catalyst-Nafion blend, used to modify a screen-printed carbon electrode surface. Chemical information was extracted by fragment assignment and relative amplitude analysis of the mass spectrometry peaks. Pure Nafion and the exposed carbon substrate were compared as references. Material specific fragments were clearly identified by the detected nonoverlapping mass-to-charge peaks of Nafion and CoNCN. Three dimensional mapping of relevant mass peak amplitudes was used to determine the lateral distribution and to generate depth profiles from consecutive laser pulses. Evaluating the profiles of pristine electrodes gave insight into fragmentation behavior of the catalyst in a functional ionomer matrix and comparison of post-catalytic electrodes revealed spots of thin localized Co residues.

Long-term kinetics of Zika virus RNA and antibodies in body fluids of a vasectomized traveller returning from Martinique: a case report.

BACKGROUND: The magnitude of the current Zika virus (ZIKV) epidemic has led to a declaration of a Public Health Emergency of International Concern by the WHO. Findings of viable viral particles in semen for several weeks are corroborating reports of sexual transmission of ZIKV. Serious consequences of a positive diagnostic result particularly in the pregnant patient are calling for precise diagnostic tools also at later time points after infection. Currently, recommendations suggest a diagnostic period of direct viral detection of 5 to 7 days after onset of symptoms in serum or plasma, and up to 3 weeks in urine samples. CASE PRESENTATION: A vasectomized 41-year-old German returning from Martinique presented at the outpatient clinic of the Department for Infectious Diseases and Tropical Medicine, Munich, with subfebrile temperature, rash, malaise, severe retro-orbital pain and occipital lymphadenopathy. The main complaints resolved after ten days without specific treatment. We are reporting on clinical course and results of direct and indirect detection methods of ZIKV in different sample types including whole blood, ejaculate, urine, serum, plasma and saliva samples up to 119 days post symptom onset. Ejaculate samples remained PCR positive for ZIKV until day 77, whole blood samples until day 101. CONCLUSIONS: The case presentation adds to the still limited knowledge of kinetics of detection of ZIKV by direct as well as indirect methods. Here, a complete data set including results from PCR, serology and cell culture is provided allowing an improved evaluation of optimum diagnostic periods for testing a variety of sample types. Moreover, a high viral load of ZIKV RNA was detected in ejaculate of the vasectomized patient. This finding sheds new light on the possible localizations of ZIKV replication in the human male reproductive tract.

A nonsense mutation in TMEM95 encoding a nondescript transmembrane protein causes idiopathic male subfertility in cattle.

Genetic variants underlying reduced male reproductive performance have been identified in humans and model organisms, most of them compromising semen quality. Occasionally, male fertility is severely compromised although semen analysis remains without any apparent pathological findings (i.e., idiopathic subfertility). Artificial insemination (AI) in most cattle populations requires close examination of all ejaculates before insemination. Although anomalous ejaculates are rejected, insemination success varies considerably among AI bulls. In an attempt to identify genetic causes of such variation, we undertook a genome-wide association study (GWAS). Imputed genotypes of 652,856 SNPs were available for 7962 AI bulls of the Fleckvieh (FV) population. Male reproductive ability (MRA) was assessed based on 15.3 million artificial inseminations. The GWAS uncovered a strong association signal on bovine chromosome 19 (P = 4.08 × 10(-59)). Subsequent autozygosity mapping revealed a common 1386 kb segment of extended homozygosity in 40 bulls with exceptionally poor reproductive performance. Only 1.7% of 35,671 inseminations with semen samples of those bulls were successful. None of the bulls with normal reproductive performance was homozygous, indicating recessive inheritance. Exploiting whole-genome re-sequencing data of 43 animals revealed a candidate causal nonsense mutation (rs378652941, c.483C>A, p.Cys161X) in the transmembrane protein 95 encoding gene TMEM95 which was subsequently validated in 1990 AI bulls. Immunohistochemical investigations evidenced that TMEM95 is located at the surface of spermatozoa of fertile animals whereas it is absent in spermatozoa of subfertile animals. These findings imply that integrity of TMEM95 is required for an undisturbed fertilisation. Our results demonstrate that deficiency of TMEM95 severely compromises male reproductive performance in cattle and reveal for the first time a phenotypic effect associated with genomic variation in TMEM95.

Drug use among men with unfulfilled wish to father children: a retrospective analysis and discussion of specific drug classes.

PURPOSE: Male infertility is a multifactorial state. Among other risk factors, drugs can adversely affect male fertility and male sexual function. In a retrospective study we aimed to analyse how many involuntarily childless men seeking fertility evaluation consume drugs, which drugs and if these are potentially affecting male reproductive function. METHODS: We retrospectively identified involuntarily childless men presenting for fertility evaluation at an andrologic outpatient department from 2011 to 2014. Medical records were searched for current drug use, age, diseases affecting male fertility, and number and kind of drugs. Drugs were classified according to their Anatomical Therapeutic Chemical code. Adverse drug reactions on male sexual function and fertility were searched in two independent literature sources. RESULTS: Drug use was documented for 244 of 522 patients (46.7%). The patients' mean age was 37.7 ± 8.7; the total number of drug intakes was 554 (mean 2.3 ± 1.9), corresponding to 201 different drugs. The most often involved Anatomical Therapeutic Chemical groups were nervous system (N), alimentary tract/metabolism (A), cardiovascular (C), and respiratory system (R) (n = 277; 50.0%). Fertility impairment was reported for 15.9%, and adverse drug reactions on male sexual function were found for 51.2% of all identified drugs. Underreporting of consumed drugs was likely, especially for non-prescription drugs. CONCLUSIONS: A high percentage of involuntarily childless men is taking drugs that can potentially influence male reproductive function. As drug intake represents a modifiable risk factor, fertility evaluation requires a comprehensive medication review including prescription and non-prescription drugs. Copyright © 2016 John Wiley & Sons, Ltd.

Probe-based confocal laser endomicroscopy (pCLE): a preclinical investigation of the male genital tract.

The aim of this study was to assess the potential of probe-based confocal laser endomicroscopy (pCLE) as a new diagnostic imaging technique for the male genital tract. For this purpose, testes, epididymides, and vasa deferentia were obtained during transsexual surgery of healthy patients (n = 10, 26-52 years). Prior to this, testes of rats (n = 10, Sprague-Dawley) and mice (n = 8, wild-type) were examined. Ex vivo tissues were investigated by pCLE after topical fluorescence staining. Images and pCLE real-time video sequences were compared to images acquired by confocal laser scanning microscopy (CLSM); this allowed the identifying of corresponding microstructures. Interestingly, the seminiferous tubules of transsexual humans contained mainly spermatogonia due to long-term estrogen treatment, whereas the seminiferous tubules of the murine and rat spermatogenesis-related cell types were differentiated. Mosaicking improved the inspection potential by wide-angle views. Similarly, the microarchitecture of the epididymis and the vas deferens was successfully visualized in situ and on a cellular level by pCLE. In summary, pCLE allows for real-time identification of relevant microstructures responsible for spermatogenesis under ex vivo conditions. Additionally, pCLE enabled to localize vital spermatozoa in the testis thus opening up new ways to improve sperm retrieval rates during assisted reproduction. Both clinically relevant experiences hold promise to introduce this diagnostic method into a clinical study, and to investigate its potential as a clinical diagnostic procedure to expedite and improve the medical situation.

Impact of the 'repositioning test' on postoperative outcome of retroluminar transobturator male sling implantation.

OBJECTIVE: To evaluate prospectively the value of the 'repositioning test' (RT) in preoperative patient selection for the efficacy of male stress urinary incontinence (SUI) treatment using a retroluminar transobturator male sling (AdVance sling). PATIENTS AND METHODS: 65 consecutive patients with SUI after radical prostatectomy were included in this single-center prospective study. Preoperatively, patients were classified into those with 'positive' and 'negative' RT. Postoperative results were analyzed and the association between the result of the RT and postoperative outcome was evaluated. RESULTS: 53 patients (81.5%) showed preoperatively a positive RT and 12 patients (18.5%) a negative RT. After a follow-up of 12 months, patients with positive RT showed a cure rate (0 pads/day) of 83% and patients with a negative RT showed only a cure rate of 25%. A positive RT significantly correlated with cure in outcome (p < 0.001). CONCLUSIONS: Patients with positive RT have a significantly better chance for successful AdVance sling implantation. The RT is minimally invasive, easy to learn and easy to perform. Therefore, the RT is a very useful tool for preoperative patient selection.

Profound Effects of Dexamethasone on the Immunological State, Synthesis and Secretion Capacity of Human Testicular Peritubular Cells.

The functions of human testicular peritubular cells (HTPCs), forming a small compartment located between the seminiferous epithelium and the interstitial areas of the testis, are not fully known but go beyond intratesticular sperm transport and include immunological roles. The expression of the glucocorticoid receptor (GR) indicates that they may be regulated by glucocorticoids (GCs). Herein, we studied the consequences of the GC dexamethasone (Dex) in cultured HTPCs, which serves as a unique window into the human testis. We examined changes in cytokines, mainly by qPCR and ELISA. A holistic mass-spectrometry-based proteome analysis of cellular and secreted proteins was also performed. Dex, used in a therapeutic concentration, decreased the transcript level of proinflammatory cytokines, e.g., IL6, IL8 and MCP1. An siRNA-mediated knockdown of GR reduced the actions on IL6. Changes in IL6 were confirmed by ELISA measurements. Of note, Dex also lowered GR levels. The proteomic results revealed strong responses after 24 h (31 significantly altered cellular proteins) and more pronounced ones after 72 h of Dex exposure (30 less abundant and 42 more abundant cellular proteins). Dex also altered the composition of the secretome (33 proteins decreased, 13 increased) after 72 h. Among the regulated proteins were extracellular matrix (ECM) and basement membrane components (e.g., FBLN2, COL1A2 and COL3A1), as well as PTX3 and StAR. These results pinpoint novel, profound effects of Dex in HTPCs. If transferrable to the human testis, changes specifically in ECM and the immunological state of the testis may occur in men upon treatment with Dex for medical reasons.

Validation of a CE-IVD, urine exosomal RNA expression assay for risk assessment of prostate cancer prior to biopsy.

Improved risk stratification of patients suspected of prostate cancer prior to biopsy continues to be an unmet clinical need. ExoDx Prostate (IntelliScore) "EPI" is a non-invasive urine test utilizing RNA from exosomes to provide a risk score that correlates with the likelihood of finding high grade prostate cancer at biopsy. Here, we present the results from a prospective clinical validation study of EPI-CE, a CE-marked in-vitro diagnostic (IVD) assay, specifically developed for use in European clinical laboratories. The study (NCT04720599) enrolled patients with ≥ 50 years, PSA 2-10 ng/mL, prior to MRI, who were scheduled for initial biopsy. First catch urine samples were collected from participants without prior digital rectal examination or prostate massage. Exosomal RNA was isolated and expression levels of three biomarkers ERG, PCA3 and SPDEF were analyzed according to the EPI-CE Instructions For Use. In the study cohort of N = 109 patients, EPI-CE was validated to have a Negative Predictive Value of 89%, a Sensitivity of 92% and a superior performance to two commonly used multiparametric risk calculators (PCPT and ERSPC) in both Receiver Operating Characteristics with a higher Area Under the Curve for EPI-CE 0.67 (95% CI 0.56-0.77) versus PCPT 0.59 (95% CI 0.47-0.71) and ERSPC 0.60 (95% CI 0.49-0.72) and higher Net Benefits analysis across a wide range of risk acceptance levels. This is the first clinical study reporting on the performance of EPI-CE. We demonstrate that EPI-CE provides information beyond standard clinical parameters and provides a better risk assessment prior to MRI, of patients suspected of prostate cancer, than the commonly used multiparametric risk calculators.

Risk factors for pelvic lymphoceles post-radical prostatectomy.

BACKGROUND: Lymphoceles (LC) represent a well-described rare complication post-radical prostatectomy (RP). Our aim was to determine risk factors and to develop possible prevention strategies for LC in a community-based study. METHODS: Data from 1163 RP-patients from 67 clinics between January 2002 and December 2004 were retrospectively evaluated. Patients underwent pelvic imaging procedures/LC-management during 3 weeks of rehabilitation post-RP. RESULTS: LC were identified in 304 patients (26%). Lymphadenectomy was carried out in 92% of patients (1001/1086 patients), from which 28% had LC (n = 277) versus 14% without lymphadenectomy (12/85, P = 0.007). Complications (lower limb edema, pain, thrombosis, infection and bladder compression) were observed in 9% of patients (28/304; 2.4% of total patients); necessitating therapy. LC therapy was carried out in 59 patients (5.9%) with pelvic lymph node dissection (PLND) and in no patients (0%) without PLND (P = 0.021). Risk factors included were patients' age, body mass index, prostate volume, TNM-classification, number of removed lymph nodes, previous surgery/therapy, heparin prophylaxis, surgical instruments and pelvic lymphadenectomy. Univariate analysis showed lymphadenectomy as the only significant risk factor for the development of LC post-RP (P = 0.007). When applying multivariate analyses using stepwise logistic regression, only lymphadenectomy was associated with a significant risk for lymphoceles (odds ratio = 2.6, 95% CI = 1.3-4.9, P = 0.004). Adjusting for other factors, no other factor came close to being significant (P < 0.05). All symptomatic LC were successfully treated without further sequelae. CONCLUSIONS: Subclinical LC post-RP are more common than thought, and rarely necessitate intervention. Pelvic lymphadenectomy represents the only significant factor contributing to LC-development. Because of this, prevention remains difficult.

Single-Incision Laparoscopic Surgery (SILS) in Reconstructive Urological Cases.

Single-incision laparoscopic surgery (SILS) is a recent development in minimally invasive surgery. This is an initial SILS experience in reconstructive urology to prove feasibility and provide a comparison with conventional laparoscopy during perioperative and convalescent periods. A single surgeon performed two complex SILS operations (psoas bladder hitch with Boari flap for high ureteric stricture [SILS-PB] and nephropexy for severe nephroptosis [SILS-Np]). A group of 6 patients with previous experience with conventional laparoscopy by the same surgeon with the same operation complexity was selected for retrospective comparison. SILS was performed through multichannel port (intraumbilical or retroperitoneal). There was no conversion to laparoscopy. Operative time (Or-t) was 365 and 185 minutes for SILS-PB and SILS-Np, respectively. Blood loss was 100 ml for SILS-PB without any intraoperative complications. Baseline demographics, Or-t, blood loss, and hospital stay were comparable to the laparoscopic group. Except for prolonged Or-t, patients undergoing SILS had similar surgical outcomes and comparable convalescent periods. Follow-up was uneventful for both groups. Patients' global satisfaction and willingness to recommend their procedure to others were favorable and equivalent between groups. Thus, SILS-reconstructive operations for high ureteric strictures and severe nephroptosis are feasible. It seems equally as efficacious as conventional laparoscopy maintaining surgical standards without differences in perioperative outcomes and convalescence.

Radical cystectomy in the elderly patient: a contemporary comparison of perioperative complications in a single institution series.

PURPOSE: To report on our recent experience with peri- and postoperative morbidity of radical cystectomy in patients 75 years and older compared to younger patients. PATIENTS AND METHODS: Medical records of 326 consecutive patients undergoing radical cystectomy from May 2004 through April 2008 were reviewed. RESULTS: Eighty-five of 326 patients (26%) were > or =75 years (75-95) old. ASA score was equal 3 or greater in 51% of patients > or =75 years and 32% of patients <75 years. Ileal conduit was performed in 83% of patients > or =75, 16% received an ileal neobladder compared to 46 and 51%, respectively, in patients <75. A total of 33 patients (39%) in the older patient group received blood transfusions intraoperatively compared to 76 patients (32%) in the younger age group. In 6 patients > or =75 years (7.1%) and 17 patients <75 (7.1%) open surgical revision was necessary, perioperative complication rate was 22 and 21%, respectively. The most common complications were wound dehiscence (5.9 vs. 7.5%), infections (4.7 vs. 4.6%), and pulmonary embolism (3.5 vs. 2.1%). Perioperative mortality was 1.2% (1 patient) in the elderly versus 0.4% (1 patient) in the younger age group. CONCLUSION: Our data show that radical cystectomy can be offered to the elderly patient with acceptable morbidity. Because of higher comorbidity rate in the elderly, therapeutic decision for radical cystectomy in elderly patients should be made carefully and individually. Nevertheless our results demonstrate that age itself is not a main criterion which has to be considered strongly in decision making for radical cystectomy.

Palmitic Acid Targets Human Testicular Peritubular Cells and Causes a Pro-Inflammatory Response.

Palmitic acid (PA) is a major fatty acid, derived from diet and endogenous production, which is being linked to inflammation. While such actions of PA at the level of the testis remain difficult to examine, we reasoned that studies in human testicular cells may be instructive. Human testicular peritubular cells (HTPCs) can be isolated from men and cultured. They have contractile properties but also produce Interleukin 6 (IL6), express the inflammasome member NLRP3, and via glia cell line derived neurotrophic factor (GDNF), they contribute to the spermatogonial stem cell niche. We found that PA at 100 µM significantly increased the levels of IL6, while NLRP3 or the related Interleukin 1 beta (IL1beta) were not affected. The contractility marker calponin (CNN1) and the growth factor GDNF were likewise not affected. ELISA studies confirmed the stimulatory PA actions on IL6. Hence, PA derived from diet and/or endogenous sources may be able to foster a pro-inflammatory milieu in the testis. A possible link of these results to diet and high fat intake and obesity is indicated by the about 12-fold elevated testicular levels of IL6 in testes of obese rhesus monkeys (n = 3), fed with a Western Style diet. They had elevated 2-5-fold increased body fat and increased circulating triglyceride levels. Further consequences of PA and obesity for testicular functions remain to be evaluated.

Scaling Up Electrodes for Photoelectrochemical Water Splitting: Fabrication Process and Performance of 40†cm2 LaTiO2 N Photoanodes.

A scalable process for fabrication of particle-based photoanodes is developed. The electrodes are versatilely made of photocatalytically active semiconductor particles, in this case LaTiO2 N, and optionally coated with cocatalysts and protecting components, all immobilized on a conducting substrate. The involved fabrication steps are restricted to scalable processes such as electrophoretic deposition, annealing in air, and dip coating. Special care is taken to ensure efficient charge transport in-between particles and to the substrate by incorporating conducting connectors. By adapting the fabrication steps, the electrode geometrical dimension is increased from the size of a typical lab electrode of 1 to 40 cm2 . The quality of the scale-up process is characterized by comparing the photoanodes in terms of thickness, light-absorption properties, and morphology. For several compositions, the electrochemical performance of both electrode sizes is assessed by measuring the photocurrents and faradaic efficiencies. The comparison revealed a complex upscaling behavior and showed that the photoelectrode size affects performance already on the 0.1 m scale.