Introduction Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been proposed as an effective non-invasive treatment option for erectile dysfunction (ED). Aim To use systematic review and meta-analysis to assess the efficacy of Li-ESWT by comparing change in erectile function as assessed by the erectile function domain of the International Index of Erectile Function (IIEF-EF) in men undergoing Li-ESWT vs sham therapy for the treatment of ED. Methods Systematic search was conducted of MEDLINE, EMBASE, and ClinicalTrials.gov for randomized controlled trials that were published in peer-reviewed journals or presented in abstract form of Li-ESWT used for the treatment of ED from January 2010 through March 2016. Randomized controlled trials were eligible for inclusion if they were published in the peer-reviewed literature and assessed erectile function outcomes using the IIEF-EF score. Estimates were pooled using random-effects meta-analysis. Main Outcome Measures Change in IIEF-EF score after treatment with Li-ESWT in patients treated with active treatment vs sham Li-ESWT probes. Results Data were extracted from seven trials involving 602 participants. The average age was 60.7 years and the average follow-up was 19.8 weeks. There was a statistically significant improvement in pooled change in IIEF-EF score from baseline to follow-up in men undergoing Li-ESWT vs those undergoing sham therapy (6.40 points; 95% CI = 1.78–11.02; I2 = 98.7%; P < .0001 vs 1.65 points; 95% CI = 0.92–2.39; I2 = 64.6%; P < .0001; between-group difference, P = .047). Significant between-group differences were found for total treatment shocks received by patients (P < .0001). Conclusion In this meta-analysis of seven randomized controlled trials, treatment of ED with Li-ESWT resulted in a significant increase in IIEF-EF scores.

Following from our previous Letter on this topic, this Article reports a detailed study of time-of-flight-secondary ion mass spectrometry (TOF-SIMS) positive ion spectra generated from a set of model biocompounds (arginine, trehalose, DPPC, and angiotensin II) by water cluster primary ion beams in comparison to argon cluster beams over a range of cluster sizes and energies. Sputter yield studies using argon and water beams on arginine and Irganox 1010 have confirmed that the sputter yields using water cluster beams lie on the same universal sputtering curve derived by Seah for argon cluster beams. Thus, increased ion yield using water cluster beams must arise from increased ionization. The spectra and positive ion signals observed using cluster beams in the size range from 1,000 to 10,000 and the energy range 5-20 keV are reported. It is confirmed that water cluster beams enhance proton related ionization over against argon beams to a significant degree such that enhanced detection sensitivities from 1 μm(2) in the region of 100 to 1,000 times relative to static SIMS analysis with Ar2000 cluster beams appear to be accessible. These new studies show that there is an unexpected complexity in the ionization enhancement phenomenon. Whereas optimum ion yields under argon cluster bombardment occur in the region of E/n ≥ 10 eV (where E is the beam energy and n the number of argon atoms in the cluster) and fall rapidly when E/n < 10 eV; for water cluster beams, ion yields increase significantly in this E/n regime (where n is the number of water molecules in the cluster) and peak for 20 keV beams at a cluster size of 7,000 or E/n ∼3 eV. This important result is explored further using D2O cluster beams that confirm that in this low E/n regime protonation does originate to a large extent from the water molecules. The results, encouraging in themselves, suggest that for both argon and water cluster beams, higher energy beams, e.g., 40 and 80 keV, would enable larger cluster sizes to be exploited with significant benefit for ion yield and hence analytical capability.

Introduction: Selective androgen receptor modulators (SARMs) differentially bind to androgen receptors depending on each SARM’s chemical structure. As a result, SARMs result in anabolic cellular activity while avoiding many of the side effects of currently available anabolic steroids. SARMs have been studied in the treatment of breast cancer and cachexia and have also been used as performance enhancing agents. Here, we evaluate and summarize the current literature on SARMs. Aims: To present the background, mechanisms, current and potential clinical applications, as well as risks and benefits of SARMs. Methods: A literature review was performed in MEDLINE using the terms selective androgen receptor modulator, hypogonadism, cachexia, breast cancer, benign prostatic hyperplasia, libido and lean muscle mass. Both basic research and clinical studies were included. Results: While there are currently no FDA-approved indications for SARMs, investigators are exploring the potential uses for these compounds. Basic research has focused on the pharmacokinetics and pharmacodynamics of these agents, demonstrating good availability with a paucity of drug interactions. Early clinical studies have demonstrated potential uses for SARMs in the treatment of cancer-related cachexia, benign prostatic hyperplasia, hypogonadism, and breast cancer, with positive results. Conclusion: SARMs have numerous possible clinical applications, with promise for the safe use in the treatment of cachexia, BPH, hypogonadism, breast cancer, and prostate cancer.

The reactivity of asparagine residues in Cu, Zn superoxide dismutase (SOD1) to deamidate to aspartate remains uncharacterized; its occurrence in SOD1 has not been investigated, and the biophysical effects of deamidation on SOD1 are unknown. Deamidation is, nonetheless, chemically equivalent to Asn-to-Asp missense mutations in SOD1 that cause amyotrophic lateral sclerosis (ALS). This study utilized computational methods to identify three asparagine residues in wild-type (WT) SOD1 (i.e., N26, N131, and N139) that are predicted to undergo significant deamidation (i.e., to >20%) on time scales comparable to the long lifetime (>1 year) of SOD1 in large motor neurons. Site-directed mutagenesis was used to successively substitute these asparagines with aspartate (to mimic deamidation) according to their predicted deamidation rate, yielding: N26D, N26D/N131D, and N26D/N131D/N139D SOD1. Differential scanning calorimetry demonstrated that the thermostability of N26D/N131D/N139D SOD1 is lower than WT SOD1 by ~2-8 °C (depending upon the state of metalation) and <3 °C lower than the ALS mutant N139D SOD1. The triply deamidated analog also aggregated into amyloid fibrils faster than WT SOD1 by ~2-fold (p < 0.008**) and at a rate identical to ALS mutant N139D SOD1 (p > 0.2). A total of 534 separate amyloid assays were performed to generate statistically significant comparisons of aggregation rates among WT and N/D SOD1 proteins. Capillary electrophoresis and mass spectrometry demonstrated that ~23% of N26 is deamidated to aspartate (iso-aspartate was undetectable) in a preparation of WT human SOD1 (isolated from erythrocytes) that has been used for decades by researchers as an analytical standard. The deamidation of asparagine--an analytically elusive, sub-Dalton modification--represents a plausible and overlooked mechanism by which WT SOD1 is converted to a neurotoxic isoform that has a similar structure, instability, and aggregation propensity as ALS mutant N139D SOD1.

The COVID-19 pandemic has brought unique challenges to the delivery of undergraduate medical education, particularly for current third-year medical students who are preparing to apply to residency. In mid-March, medical schools suspended all clinical rotations for the remainder of the 2019–2020 academic year. As such, third-year medical students may not be able to complete sufficient clinical experiences to make important career choices before they have to submit their residency applications. While the decision to suspend clinical rotations was necessary to protect students, specialty organizations and residency programs must mitigate the deficits in students’ clinical education caused by the COVID-19 pandemic. In this Perspective, the authors identify potential challenges for third-year medical students and advocate for solutions to improve the residency application process for students and programs. First, they propose delaying the date that programs can access applicant data through the Electronic Residency Application Service, thereby affording students more time to complete clinical experiences, solidify their specialty decision, and strengthen their residency application. Second, the authors recommend a restriction on the number of visiting rotations that students are expected to complete to allow for a more equitable distribution of these important experiences. Third, they suggest that program directors from each specialty agree on a maximum number of applications per applicant (based on historical data) to curb an upsurge in applications that may stem from the unique circumstances created by COVID-19 without causing applicants undue stress. Lastly, the authors advocate that residency programs develop infrastructure to conduct video-based interviews and engage students through virtual networking events. Amidst the unique environment created by COVID-19, the authors urge governing bodies, specialty organizations, and residency programs to consider these recommendations to improve the efficiency and reduce the stress surrounding the 2021 Match.

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IMPORTANCE The opportunity to discuss fertility preservation is essential for patients of reproductive age with newly diagnosed cancer before the initiation of treatment. OBJECTIVE To identify factors associated with fertility preservation counseling among patients of reproductive age before initiating chemotherapy. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study used data obtained from the American Society of Clinical Oncology (ASCO) Quality Oncology Practice Initiative, an oncologist-led quality assessment program that surveys approximately 400 oncology practices biannually, from January, 2015, to June, 2019. MAIN OUTCOMES AND MEASURES The primary outcome was whether reproductive risks were discussed before initiation of chemotherapy. Multivariate logistic regression was performed to identify factors associated with fertility preservation counseling, controlling for age, sex, race/ ethnicity, cancer type, year of study, region, clinic type (academic vs private), annual clinic volume, and rates of insurance coverage. RESULTS Among the 6976 patients of reproductive age (3571 men [51%]; mean (SD) age, 42.5 [7.1] years), with reproductive age ranging from 18 to 40 years for 3405 women and from 18 to 50 years for 3571 men, clinics reported that 3036 of 6976 patients (44%) received counseling regarding the risk of infertility associated with chemotherapy. Women were more likely to be informed (1912 of 3405 [56%]) compared with men (1126 of 3571 [32%]) (P < .001). Factors associated with reduced likelihood of fertility risk discussion included male sex (odds ratio [OR], 0.73; 95% CI, 0.60-0.90), increasing age (OR, 0.93; 95% CI, 0.92-0.94), private practice setting (OR, 0.70; 95% CI, 0.53-0.93), and lack of multidisciplinary team planning (OR, 0.54; 95% CI, 0.41-0.70). Factors associated with increased likelihood of fertility risk discussion included having breast cancer (OR, 1.39; 95% CI,

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