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Styrene-maleic acid copolymers allow for solubilization and reconstitution of membrane proteins into nanodiscs. These polymer-encased nanodiscs are promising platforms for studies of membrane proteins in a near-physiologic environment without the use of detergents. However, current styrene-maleic acid copolymers display severe limitations in terms of buffer compatibility and ensued flexibility for various applications. Here, we present a new family of styrene-maleic acid copolymers that do not aggregate at low pH or in the presence of polyvalent cations, and can be used to solubilize membrane proteins and produce nanodiscs of controlled sizes.

Purpose While SARS-CoV-2 infection appears not to be clinically evident in the testes, indirect inflammatory effects and fever may impair testicular function. To date, few long-term data of semen parameters impairment after recovery and comprehensive andrological evaluation of recovered patients has been published. The purpose of this study was to investigate whether SARS-CoV-2 infection affect male reproductive health. Methods Eighty patients were recruited three months after COVID-19 recovery. They performed physical examination, testicular ultrasound, semen analysis, sperm DNA integrity evaluation (TUNEL), anti-sperm antibodies (ASA) testing, sex hormone profile evaluation (Total testosterone, LH, FSH). In addition, all patients were administered International Index of Erectile Function questionnaire (IIEF-15). Sperm parameters were compared with two age-matched healthy pre-COVID-19 control groups of normozoospermic (CTR1) and primary infertile (CTR2) subjects. Results Median values of semen parameters from recovered SARS-CoV-2 subjects were within WHO 2010 fifth percentile. Mean percentage of sperm DNA fragmentation (%SDF) was 14.1 ± 7.0%. Gelatin Agglutination Test ( GAT ) was positive in 3.9% of blood serum samples, but no positive semen plasma sample was found. Only five subjects (6.2%) had total testosterone levels below the laboratory reference range. Mean bilateral testicular volume was 31.5 ± 9.6 ml. Erectile dysfunction was detected in 30% of subjects. Conclusion Our data remark that COVID-19 does not seem to cause direct damage to the testicular function, while indirect damage appears to be transient. It is possible to counsel infertile couples to postpone the research of parenthood or ART procedures around three months after recovery from the infection.

PurposeAquablation of the prostate using the AquaBeam™ system promises equivalent functional outcomes, reduced learning curve, and improved sexual function compared to transurethral prostate resection as shown in prospective randomized trials. This prospective cohort study aims to evaluate if published results can be transferred into the clinical routine in a non-selected patient collective.MethodsThis study includes all patients treated between September 2017 and June 2018 with Aquablation of the prostate. Patients have been evaluated prospectively for the perioperative course and early follow-up. Besides voiding parameter and symptom score, TRUS-volume change, ejaculatory function, and adverse events have been recorded.Results118 consecutive patients have been treated in the given time. Aquablation could be carried out successfully in all patients. IPSS, QoL, Qmax, and PVR improved significantly after the procedure and continued to improve during 3-month follow-up. Mean OR time was 20 min, TRUS volume decreased by 65%, and 73% of the patients retained antegrade ejaculation. Thirteen adverse events (> Clavien-Dindo I) occurred in 10 patients.ConclusionThe surgical ablation of the prostate using Aquablation achieved significant and immediate improvement of functional voiding parameters Qmax and PVR as well as symptomatic improvement of IPSS and QoL. Aquablation seems to be safe and effective with a low perioperative complication profile even in a non-selected group of patients.

The proton-coupled folate transporter (PCFT) provides an essential uptake route for the vitamin folic acid (B9) in mammals. In addition, it is currently of high interest for targeting chemotherapeutic agents to tumors due to the increased folic acid requirement of rapidly dividing tumor cells as well as the upregulated PCFT expression in several tumors. To understand its function, determination of its atomic structure and molecular mechanism of transport are essential goals that require large amounts of functional PCFT. Here, we present a high-level heterologous expression system for human PCFT using a recombinant baculovirus and Spodoptera frugiperda (Sf9) insect cells. We demonstrate folate transport functionality along the PCFT expression, isolation, and purification process. Importantly, purified PCFT transports folic acid after reconstitution. We thus succeeded in overcoming heterologous expression as a major bottleneck of PCFT research. The availability of an overexpression system for human PCFT provides the basis for future biochemical, biophysical and structural studies.

Human cytomegalovirus (HCMV) is a high-risk pathogen in immunocompromised individuals, especially in transplant recipients. HCMV viremia must be monitored, and frequently, patients are treated with antiviral agents. HCMV has a variety of strategies to modulate host antiviral responses, and one important player is a viral homolog of the cellular interleukin-10 (cIL-10). The viral UL111A gene produces several HCMV IL-10 transcripts and protein isoforms through alternative splicing. The cmvIL-10 (isoform A) has similar properties to cIL-10, while LAcmvIL-10 (isoform B) has more restricted biological properties. Other isoforms are produced (C to H) but have unknown functions. Here, we investigated the expression of the most abundant transcripts, cmvIL-10 and LAcmvIL-10, in productively and latently infected cells and in peripheral blood mononuclear cells from renal transplant recipients up to 60 days post-transplantation. This study investigated HCMV cmvIL-10 and LAcmvIL-10 transcription profiles in vitro, in productive and latent infection, and in vivo, in peripheral blood mononuclear cells (PBMCs) of renal transplant patients. In vitro, both cmvIL-10 and LAcmvIL-10 transcripts were detected in both types at high levels and low levels in MRC-5 and latent infected (CD14+). When PBMCs from transplant patients were analyzed, LAcmvIL-10 was detected mostly sporadically and in only a few patients, while cmvIL-10 was found in all patients at all time points. Furthermore, it was observed in PBMCs that expression of cmvIL-10 was positively associated with an increase in viral DNA detection in the subsequently collected sample, indicating that expression of cmvIL-10 might precede viral DNA replication. These results contribute to the understanding of HCMV biology in different phases of infection. In addition, our initial analysis suggests that monitoring cmvIL-10, along with viral DNA, could improve early detection of HCMV reactivation in transplant recipients.

Retrograde Intra-Renal Surgery (RIRS) plays a primary role in renal stone treatment context. Energy, frequency and width of laser impulse can be modulated by surgeons to achieve better outcomes. In our study, patients with single renal stone sized 10–20 mm were retrospectively divided into two groups. Patients of Group 1 underwent RIRS with Low-Energy (LE) High-Frequency (HF) settings using Lumenis® 120-W high-power Ho:YAG laser. Patients of Group 2 (control) underwent RIRS using “standard” settings by means of Sphinx® Jr 30 W Ho:YAG system. Follow-up was conducted with a CT scan at 3 months after RIRS in both groups. Procedure success was defined as stone-free or presence of ≤ 4 mm fragments (Clinical Insignificant Residual Fragments—CIRF). A total number of 199 patients were included: 86 LE/HF RIRS (Group 1) vs 113 “conventional” RIRS (Group 2). Mean operative time was 56.6 (± 19.4) min in Group 1 vs 65.2 (± 25.2) min in Group 2 (p = 0.01). Mean hospitalization time was 2.5 ± 1.7 days for Group 1 vs 2.9 ± 3.2 days for Group 2 (p = 0.2). Peri-operative complications were counted: eight in Group 1 and 11 in Group 2 (p > 0.05). At 3-month control, stone-free rate was 69% (59/86 patients) in Group 1 vs 65% (73/113 patients) in Group 2 (p = 0.6). Success rate was 93% (80/86) in Group 1 in comparison to 82% (93/113) in Group 2 (p = 0.03). In conclusion, LE/HF RIRS seems to be a feasible and effective technique with a reduction of operative time and optimal results in terms of “stone-free” and “success” rates. Further studies are needed to ensure the validity of our results and to give evidence-based statements.

Membrane proteins (MPs) are essential to many organisms’ major functions. They are notorious for being difficult to isolate and study, and mimicking native conditions for studies in vitro has proved to be a challenge. Lipid nanodiscs are among the most promising platforms for MP reconstitution, but they contain a relatively labile lipid bilayer and their use requires previous protein solubilization in detergent. These limitations have led to the testing of copolymers in new types of nanodisc platforms. Polymer-encased nanodiscs and polymer nanodiscs support functional MPs and address some of the limitations present in other MP reconstitution platforms. In this review, we provide a summary of recent developments in the use of polymers in nanodiscs.

ContextLarge and complex renal stones are usually treated with percutaneous nephrolithotomy (PCNL). One of the crucial steps in this procedure is the access to the collecting system with the percutaneous puncture and this maneuver leads to a risk of vascular and neighboring organs’ injury. In the last years, the application of virtual image-guided surgery has gained wide diffusion even in this specific field.ObjectivesTo provide a short overview of the most recent evidence on current applications of virtual imaging guidance for PCNL.Evidence acquisitionA non-systematic review of the literature was performed. Medline, PubMed, the Cochrane Database and Embase were screened for studies regarding the use virtual imaging guidance for PCNL.Evidence synthesis3D virtual navigation technology for PCNL was first used in urology with the purpose of surgical training and surgical planning; subsequently, the field of surgical navigation with different modalities (from cognitive to augmented reality or mixed reality) had been explored. Finally, anecdotal preliminary experiences explored the potential application of artificial intelligence guidance for percutaneous puncture.ConclusionNowadays, many experiences proved the potential benefit of virtual guidance for surgical simulation and training. Focusing on surgery, this tool revealed to be useful both for surgical planning, allowed to achieve a better surgical performance, and for surgical navigation by using augmented reality and mixed reality systems aimed to assist the surgeon in real time during the intervention.

In addition to gap junctional channels that mediate cell-to-cell communication, connexins form hemichannels that are present at the plasma membrane. Since hemichannels are permeable to small hydrophilic compounds, including metabolites and signaling molecules, their abnormal opening can cause or contribute to cell damage in disorders such as cardiac infarct, stroke, deafness, skin diseases, and cataracts. Therefore, hemichannels are potential pharmacological targets. A few aminoglycosides, well-known broad-spectrum antibiotics, have been shown to inhibit hemichannels. Here, we tested several commercially available aminoglycosides for inhibition of human connexin hemichannels using a cell-based bacterial growth complementation assay that we developed recently. We found that kanamycin A, kanamycin B, geneticin, neomycin, and paromomycin are effective inhibitors of hemichannels formed by connexins 26, 43, and 46 (Cx26, Cx43, and Cx46). Because of the >70 years of clinical experience with aminoglycosides and the fact that several of the aminoglycosides tested here have been used in humans, they are promising starting points for the development of effective connexin hemichannel inhibitors.

Summary The advent of modern treatments together with the improvement of the surgical techniques has significantly increased 5‐year survival rates of young patients with cancer. Although the deleterious effects of chemotherapy and radiation are well documented, controversies exist about the effect of cancer itself on semen parameters before treatment. We collected data on 236 patients representative of different types of cancers reoffered at our institution for sperm cryopreservation with the aim to correlate the pre‐freeze semen parameters with type of cancer, disease stage and with semen quality of 102 fertile and healthy men. The median baseline semen parameters of all our patients with cancer are placed above the 5th percentile of the World Health Organization reference value, but the type of cancer may impact the sperm parameters. In testicular tumours and in Hodgkin lymphoma, we show a semen concentration statistically lower than in the fertile population, while in patients with other cancers, there is no difference with the healthy men. We found no correlation between semen quality and disease stage. Eighty‐six per cent of our patients do not have children at the time of semen cryopreservation, and the only established clinical option for preserving fertility of these men is cryopreservation of spermatozoa.