The global spread of SARS-CoV-2/COVID-19 is devastating health systems and economies worldwide. Recombinant or vaccine-induced neutralizing antibodies are used to combat the COVID-19 pandemic. ...However, the recently emerged SARS-CoV-2 variants B.1.1.7 (UK), B.1.351 (South Africa), and P.1 (Brazil) harbor mutations in the viral spike (S) protein that may alter virus-host cell interactions and confer resistance to inhibitors and antibodies. Here, using pseudoparticles, we show that entry of all variants into human cells is susceptible to blockade by the entry inhibitors soluble ACE2, Camostat, EK-1, and EK-1-C4. In contrast, entry of the B.1.351 and P.1 variant was partially (Casirivimab) or fully (Bamlanivimab) resistant to antibodies used for COVID-19 treatment. Moreover, entry of these variants was less efficiently inhibited by plasma from convalescent COVID-19 patients and sera from BNT162b2-vaccinated individuals. These results suggest that SARS-CoV-2 may escape neutralizing antibody responses, which has important implications for efforts to contain the pandemic.
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•B.1.1.7, B.1.351, and P.1 do not show augmented host cell entry•Entry inhibitors under clinical evaluation block all variants•B.1.351 and P.1 can escape from therapeutic antibodies•B.1.351 and P.1 evade antibodies induced by infection and vaccination
Comparison of the SARS-CoV-2 variants B.1.1.7, B.1.351, and P.1 shows that inhibitors under clinical evaluation are still effective in blocking entry, though the B.1.351 and P.1 variants evade antibody responses induced upon infection as well as vaccination and evade certain therapeutic antibodies.
Celebrating 50 years of penile implants Wilson, Steven K; Gross, Martin S
International journal of impotence research,
11/2023, Letnik:
35, Številka:
7
Journal Article
Aromatase activity has commonly been associated with male infertility characterized by testicular dysfunction with low serum testosterone and/or testosterone to estradiol ratio. In this subset of ...patients, and particularly in those with hypogonadism, elevated levels of circulating estradiol may establish a negative feedback on the hypothalamic-pituitary-testicular axis by suppressing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) production and impaired spermatogenesis. Hormonal manipulation via different agents such as selective estrogen modulators or aromatase inhibitors to increase endogenous testosterone production and improve spermatogenesis in the setting of infertility is an off-label option for treatment. We carried out a systematic review and meta-analysis of the literature of the past 30 years in order to evaluate the benefits of the use of aromatase inhibitors in the medical management of infertile/hypoandrogenic males. Overall, eight original articles were included and critically evaluated. Either steroidal (Testolactone) or nonsteroidal (Anastrozole and Letrozole) aromatase inhibitors were found to statistically improve all the evaluated hormonal and seminal outcomes with a safe tolerability profile. While the evidence is promising, future prospective randomized placebo-controlled multicenter trials are necessary to better define the efficacy of these medications.
A scannable laser beam is used to generate local thermal gradients in metallic (Co2FeAl) or insulating (Y3Fe5O12) ferromagnetic thin films. We study the resulting local charge and spin currents that ...arise due to the anomalous Nernst effect (ANE) and the spin Seebeck effect (SSE), respectively. In the local ANE experiments, we detect the voltage in the Co2FeAl thin film plane as a function of the laser-spot position and external magnetic field magnitude and orientation. The local SSE effect is detected in a similar fashion by exploiting the inverse spin Hall effect in a Pt layer deposited on top of the Y3Fe5O12. Our findings establish local thermal spin and charge current generation as well as spin caloritronic domain imaging.
To evaluate the variability in the criteria of erectile dysfunction (ED) regenerative therapy trials registered on ClinicalTrials.gov.
Interventional trials on ClinicalTrials.gov with the keywords ...“erectile dysfunction” and variations of “shockwave,” “platelet rich plasma,” “stem cell,” “regenerative,” and “restorative” were examined. Inclusion/exclusion criteria and primary/secondary outcomes were compared between extracorporeal shockwave therapy (ESWT), platelet rich plasma and stem cell injections (PRP/SC), and other regenerative therapies (ORT) groups.
Of the 92 trials analyzed, International Index of Erectile Function (IIEF) score was the most common primary outcome (72%), with a higher prevalence in ESWT trials than PRP/SC or ORT trials (89% vs 44% and 58%, P <.001). Safety/tolerability was a primary outcome for 44% of PRP/SC trials and 25% of ORT trials but no ESWT trials (P <.001). ESWT trials more frequently had sexual/romantic relationship-based inclusion criteria and cancer treatment-related exclusion criteria than PRP/SC and ORT trials.
There is substantial variability in the inclusion/exclusion criteria and outcome measures among ED regenerative therapy trials. ESWT trials most frequently utilized IIEF and had the strictest inclusion/exclusion criteria, suggesting more rigorous and functional outcome-based studies. Conversely, PRP/SC and ORT trials, but not ESWT trials, had safety/tolerability as a primary outcome, likely due to the experimental nature of these therapies. The variability in inclusion/exclusion criteria and outcome measures limits comparison of the various ED regenerative therapies.
Priapism is an adverse drug reaction (ADR) associated with phosphodiesterase type 5 inhibitors (PDE5is) in the treatment of erectile dysfunction.
The purpose of this study was to identify the true ...data about PDE5i-associated priapism to properly counsel patients.
We queried the U.S. Food and Drug Administration (FDA) Adverse Reporting System Public Dashboard to identify cases of drug-induced priapism among medications commonly associated with priapism. Next, a systematic review and analysis of publications describing cases of drug-induced priapism were carried out.
The main outome of this study is incidence of PDE5i-induced priapism.
We found 411 cases of drug-induced priapism secondary to Viagra, Cialis, or Levitra reported to the Food and Drug Administration since 1998. Compared with PDE5is, drug-induced priapism was 2.6 (n = 1,065) and 2.0 times (n = 817) more commonly reported for second-generation antipsychotics and the antidepressant/sleep aid trazodone, respectively. A total of 240 manuscripts describing cases of drug-induced priapism in patients with non-sickle cell disease were identified. PDE5i-induced priapism accounted for only 2.9% (n = 7) of drug-induced priapism cases. Second-generation antipsychotics (33.8%), a group of "other" medications (11.3%), and alpha-adrenergic antagonists (8.8%) accounted for the greatest percentage of published drug-induced priapism cases.
Extensive counseling about priapism as an ADR for PDE5i for the routine treatment of erectile dysfunction is likely unnecessary.
The study used national-level data to identify drug-induced priapism cases. Reported and published cases of drug-induced priapism may reflect more severe and atypical cases of this ADR, which may have underestimated our results.
PDE5i-induced priapism is a rare event. Drug-induced priapism should be attributed to a wider spectrum of medications that can cause this condition. Rezaee ME, Gross MS. Are We Overstating the Risk of Priapism With Oral Phosphodiesterase Type 5 Inhibitors? J Sex Med 2020;17:1579-1582.
To determine whether preoperative partner involvement at clinic appointments is associated with deviation from a standardized postoperative care pathway for patients undergoing an inflatable penile ...prosthesis placement.
This is a retrospective study of 170 patients undergoing primary inflatable penile prosthesis placement performed by a single surgeon between 2017 and 2020. A standardized postoperative clinical pathway was used, including planned follow-up visits at 2 weeks (for wound check and device deflation) and 6 weeks (for device teaching). Patient characteristics, including demographics, partner involvement, and the number of follow-up visits were obtained from the medical record. Logistic regression modeling was performed to determine whether partner involvement was associated with unanticipated follow-up visits.
Partners were involved in preoperative visits for 92 patients (54%). Additional unplanned follow-up visits were observed for 58 patients (34%) between 0 and 6 weeks and for 28 patients (16%) after 6 weeks from surgery. Partner involvement was associated with reduced odds of unanticipated follow-up visits, both between 0 and 6 weeks (odds ratios 0.37, 95% CI 0.18-0.75) and after 6 weeks (odds ratios 0.33, 95% CI 0.13-0.81) in adjusted models.
Having a patient’s partner involved during the preoperative period is associated with a significant reduction in unanticipated follow-up. We would recommend that urologists routinely encourage patients considering the insertion of a penile prosthesis to involve their partners in perioperative visits. Further research needed is needed to determine how to best support patients during surgical decision-making and through the postoperative period.
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