Music from noise-canceling headphones is beneficial against anxiety in male bladder cancer patients undergoing follow-up cystoscopy: A prospective randomized trial.

INTRODUCTION: Bladder cancer, with a greater incidence in males than in females, requires frequent cystoscopies. We aim to evaluate the effect of music played through noise-canceling headphones on male bladder cancer patients during follow-up cystoscopy. METHODS: A total of 160 male bladder cancer patients undergoing follow-up flexible cystoscopy were randomly divided into the noise-canceling headphones without music group and the noise-canceling headphones with music group (groups 1 and 2, respectively; n = 80 per group). The patients' clinical characteristics were examined and objective and subjective measurements were compared before and after cystoscopy. The primary outcomes that were evaluated included the visual analog scale (VAS, 0-10) and the state-trait anxiety inventory (STAI, 20-80). Other outcomes, including vital signs and scores for assessing satisfaction and the willingness to repeat the procedure, were also examined. RESULTS: The characteristics of the patients in groups 1 and 2, and their pre-cystoscopy status, did not differ significantly. Although post-cystoscopy vital signs for the objective parameters and VAS pain scores were similar between the groups, subjective parameters were not. When compared with group 1, post-cystoscopy STAI-state scores were significantly lower in group 2, whereas patients' satisfaction scores and the willingness to repeat the procedure were significantly higher in group 2 (p = 0.002, 0.001, and 0.001, respectively). Additionally, in group 2, STAI-state scores changed significantly after the procedure when compared with before the procedure (p = 0.002). CONCLUSION: In male bladder cancer patients, music from noise-canceling headphones might have reduced anxiety and improved satisfaction and the willingness to repeat cystoscopy.

Stripping versus ligation of vas deferens in microscopic denervation of spermatic cord in men with chronic orchialgia: A multicenter study.

BACKGROUND: Microdenervation of the spermatic cord (MSCD) is an effective treatment modality for men with intractable scrotal content pain. For patients not interested in preserving fertility, some centers advocate ligation of the vas during denervation, while others prefer stripping of the vas deferens to preserve the vasal artery, hence preserving vasculature to the testis and possibly decreasing post-operative congestion pain. OBJECTIVE: To compare outcomes of patients with chronic orchialgia, who underwent MSCD by either stripping or ligating the vas deferens. MATERIALS AND METHODS: A retrospective chart review of 85 patients who underwent MSCD from 2017-2023 was performed. Patients' demographics including history of prior surgical procedures were recorded. Response to surgery was evaluated as either complete resolution of pain, partial resolution of pain, or no improvement in pain. RESULTS: Eighty-five patients underwent MSCD with a median (interquartile range, IQR) age of 36 (25.5-46.5) years and median duration of pain of 16 (6-31) months. Thirty-seven patients underwent stripping of vas, while 48 underwent ligation of vas during MSCD. Median follow up was 12 months. Twenty-one (43.5%) patients had prior inguinal scrotal surgery in the ligation group compared to 5 (13.5%) in the stripping group, p = 0.003. The etiology of pain was similar between the groups. The response to MSCD between the two groups was similar, 67.6% of patients who underwent stripping had complete resolution of pain versus 66.7% of those who had ligation (p = 0.968), with similar rates of post-operative complications (p-value = 0.132). CONCLUSIONS: In men with intractable chronic scrotal content pain with no interest in preserving fertility, ligation, or stripping of the vas deferens yields similar outcomes with regard to pain resolution. Both techniques are safe with no reports of any testicular atrophy.

Evaluation of the efficiency of thermostable L-asparaginase from B. licheniformis UDS-5 for acrylamide mitigation during preparation of French fries.

A thermostable L-asparaginase was produced from Bacillus licheniformis UDS-5 (GenBank accession number, OP117154). The production conditions were optimized by the Plackett Burman method, followed by the Box Behnken method, where the enzyme production was enhanced up to fourfold. It secreted L-asparaginase optimally in the medium, pH 7, containing 0.5% (w/v) peptone, 1% (w/v) sodium chloride, 0.15% (w/v) beef extract, 0.15% (w/v) yeast extract, 3% (w/v) L-asparagine at 50 °C for 96 h. The enzyme, with a molecular weight of 85 kDa, was purified by ion exchange chromatography and size exclusion chromatography with better purification fold and percent yield. It displayed optimal catalysis at 70 °C in 20 mM Tris-Cl buffer, pH 8. The purified enzyme also exhibited significant salt tolerance too, making it a suitable candidate for the food application. The L-asparaginase was employed at different doses to evaluate its ability to mitigate acrylamide, while preparing French fries without any prior treatment. The salient attributes of B. licheniformis UDS-5 L-asparaginase, such as greater thermal stability, salt stability and acrylamide reduction in starchy foods, highlights its possible application in the food industry.

Cost and utilization analysis of concurrent versus staged testicular prosthesis implantation for radical orchiectomy.

PURPOSE: American Urological Association guidelines recommend testicular prosthesis discussion prior to orchiectomy. Utilization may be low. We compared outcomes and care utilization between concurrent implant (CI) and staged implant (SI) insertion after radical orchiectomy. MATERIALS & METHODS: The MarketScan Commercial claims database (2008-2017) was queried for men ages >18 years who underwent radical orchiectomy for testicular mass, stratified as orchiectomy with no implant, CI, or SI. 90-day outcomes included rate of reoperation, readmission, emergency department (ED) presentation, and outpatient visits. Regression models provided rate ratio comparison. RESULTS: 8803 patients (8564 no implant, 190 CI, 49 SI; 2.7% implant rate) were identified with no difference in age, Charlson Comorbidity Index, insurance plan, additional cancer treatment, or metastasis. Median perioperative cost at orchiectomy (+/- implant) for no implant, CI, and SI were $5682 (3648-8554), $7823 (5403-10973), and $5380 (4130-10521), respectively (p<0.001). Median perioperative cost for SI at implantation was $8180 (4920-14591) for a total cost (orchiectomy + implant) of $13650 (5380 + 8180). CI patients were more likely to have follow-up (p = 0.006) with more visits (p = 0.030) compared to the SI group post-implantation but had similar follow-up (p = 0.065) and less visits (p = 0.025) compared to the SI patients' post-orchiectomy period. Overall explant rates were 4.7% for CI and 14.3% for SI (p = 0.04) with a median time to explant of 166 (IQR: 135-210) and 40 days (IQR: 9.5-141.5; p = 0.06). Median cost of removal was $2060 (IQR: 967-2880). CONCLUSIONS: CI placement has less total perioperative cost, lower explant rate, and similar postoperative utilization to SI.

The impact of obesity and metabolic health on male fertility: a systematic review.

The impact of paternal obesity and metabolic disease on semen quality and fertility outcomes is not fully appreciated. With increasing obesity rates, researchers have studied the intricate relationship between paternal body mass index, metabolic health, and male fertility. This systematic review identified 112 articles in the MEDLINE database between 2013 and 2023 that investigated the effects of body mass index, diabetes, metabolic syndrome, exercise, weight loss medication, or bariatric surgery on semen parameters, sperm quality, or fertility outcomes. This review suggests that obesity, diabetes, and metabolic syndrome have a negative impact on various parameters of male fertility, from semen quality to sperm deoxyribonucleic acid integrity. There is also mounting evidence that male obesity is correlated negatively with live births via both natural conception and assisted reproductive technologies. Lifestyle interventions, such as physical exercise, generally appear to improve male fertility markers; however, the type and intensity of exercise may play a crucial role. Pharmacologic treatments for weight loss, such as metformin and glucagon-like peptide 1 agonists, present a more complex picture, with studies suggesting both beneficial and detrimental effects on male reproductive health. Similarly, surgical interventions, such as gastric bypass surgery, show promise in improving hormonal imbalances but have mixed effects on semen parameters. Future research is needed to clarify these associations and inform clinical guidelines. In the interim, health practitioners should incorporate these insights into clinical practices, encouraging proactive lifestyle changes and providing targeted treatments to improve male reproductive health.

Comparative yield of molecular diagnostic algorithms for autism spectrum disorder diagnosis in India: evidence supporting whole exome sequencing as first tier test.

BACKGROUND: Autism spectrum disorder (ASD) affects 1 in 100 children globally with a rapidly increasing prevalence. To the best of our knowledge, no data exists on the genetic architecture of ASD in India. This study aimed to identify the genetic architecture of ASD in India and to assess the use of whole exome sequencing (WES) as a first-tier test instead of chromosomal microarray (CMA) for genetic diagnosis. METHODS: Between 2020 and 2022, 101 patient-parent trios of Indian origin diagnosed with ASD according to the Diagnostic and Statistical Manual, 5th edition, were recruited. All probands underwent a sequential genetic testing pathway consisting of karyotyping, Fragile-X testing (in male probands only), CMA and WES. Candidate variant validation and parental segregation analysis was performed using orthogonal methods. RESULTS: Of 101 trios, no probands were identified with a gross chromosomal anomaly or Fragile-X. Three (2.9%) and 30 (29.7%) trios received a confirmed genetic diagnosis from CMA and WES, respectively. Amongst diagnosis from WES, SNVs were detected in 27 cases (90%) and CNVs in 3 cases (10%), including the 3 CNVs detected from CMA. Segregation analysis showed 66.6% (n = 3 for CNVs and n = 17 for SNVs) and 16.6% (n = 5) of the cases had de novo and recessive variants respectively, which is in concordance with the distribution of variant types and mode of inheritance observed in ASD patients of non-Hispanic white/ European ethnicity. MECP2 gene was the most recurrently mutated gene (n = 6; 20%) in the present cohort. Majority of the affected genes identified in the study cohort are involved in synaptic formation, transcription and its regulation, ubiquitination and chromatin remodeling. CONCLUSIONS: Our study suggests de novo variants as a major cause of ASD in the Indian population, with Rett syndrome as the most commonly detected disorder. Furthermore, we provide evidence of a significant difference in the diagnostic yield between CMA (3%) and WES (30%) which supports the implementation of WES as a first-tier test for genetic diagnosis of ASD in India.

Integrated Urology and Primary Care Model Improves Outcomes for Men With Testosterone Deficiency.

INTRODUCTION: Many men presenting with testosterone deficiency do not have access to a primary care provider. We sought to integrate primary care into initial urological evaluation to better identify and manage undertreated comorbidities. METHODS: New patients presenting with testosterone deficiency were offered primary care provider evaluation within a men's health center between October 2019 and 2022. Data collected from the electronic health record included age, race, BMI, access to prior primary care provider, new diagnoses, prescriptions, and referrals. RESULTS: Eighty-one men were evaluated over the 3-year study period. Thirty-three men (41%) did not have a preexisting primary care provider. Older men were significantly more likely to have a preexisting primary care provider (OR 1.06 [95% CI: 1.02-1.10], P < .001). Hispanic men were significantly less likely to have an existing primary care provider (OR 0.16 [95% CI: 0.03-0.84], P = .01). Forty-eight men (59%) established continuity of care. Newly diagnosed comorbidities included hypertension (41%), obesity (37%), hyperlipidemia (27%), obstructive sleep apnea (25%), depression (23%), and diabetes (14%). Forty-one patients (51%) were prescribed a new medication. Twenty-one patients (26%) were referred to nutrition, with mean BMI decrease of 1.75 kg/m2. Twenty-six patients (32%) underwent sleep medicine evaluation for obstructive sleep apnea. Twenty-seven (33%) and 37 patients (46%) received a flu vaccination and immunization updates. Eleven patients (14%) were referred for screening colonoscopy. CONCLUSIONS: This is the first report of integrated primary care and urology evaluation for testosterone deficiency. This comprehensive model results in improved outcomes including increased access to subspecialty referrals, objective weight loss, treatment of new diagnoses, updated immunizations, and cancer screening.

A case of unprovoked segmental proximal partial thrombosis of the corpus cavernosum.

Partial thrombosis of the corpus cavernosum is an extremely rare and likely underdiagnosed urologic condition. We discuss a case of a 25-year-old male who presented with severe perineal pain and was diagnosed with idiopathic proximal partial thrombosis of the corpus cavernosum via ultrasound and MRI. The patient experienced symptom resolution with evidence of disease regression on follow up MRI after treatment with direct oral anticoagulation. Further studies are needed to fully delineate the pathophysiology of this condition to facilitate development of standardized diagnostic and treatment algorithms.

Male delayed orgasm and anorgasmia: a practical guide for sexual medicine providers.

Delayed orgasm (DO) is defined as increased latency of orgasm despite adequate sexual stimulation and desire. Anorgasmia (AO) is characterized as the absence of orgasm. Etiologies of DO/AO include medication-induced, psychogenic, endocrine, and genitopelvic dysesthesia. Given the multifactorial complex nature of this disorder, a thorough history and physical examination represent the most critical components of patient evaluation in the clinical setting. Treating DO/AO can be challenging due to the lack of standardized FDA-approved pharmacotherapies. There is no standardized treatment plan for DO/AO, though common treatments plans are often multidisciplinary and may include adjustment of offending medications and sex therapy. In this review, we summarize the etiology, diagnosis, and treatment of DO/AO.

Emerging concepts in male contraception: a narrative review of novel, hormonal and non-hormonal options.

Access to reliable contraception is a pillar of modern society. The burden of unintended pregnancy has fallen disproportionately on the mother throughout human history; however, recent legal developments surrounding abortion have sparked a renewed interest in male factor contraceptives beyond surgical sterilization and condoms. Modern efforts to develop reversible male birth control date back nearly a century and initially focused on altering the hypothalamic-pituitary-testes axis. These hormonal contraceptives faced multiple barriers, including systemic side effects, challenging dosing regimens, unfavorable routes of delivery, and the public stigma surrounding steroid use. Novel hormonal agents are seeking to overcome these barriers by limiting the side effects and simplifying use. Non-hormonal contraceptives are agents that target various stages of spermatogenesis; such as inhibitors of retinoic acid, Sertoli cell-germ cell interactions, sperm ion channels, and other small molecular targets. The identification of reproductive tract-specific genes associated with male infertility has led to more targeted drug development, made possible by advances in CRISPR and proteolysis targeting chimeras (PROTACs). Despite multiple human trials, no male birth control agents have garnered regulatory approval in the United States or abroad. This narrative review examines current and emerging male contraceptives, including hormonal and non-hormonal agents.

Predicting Delayed Shock in Multisystem Inflammatory Disease in Children: A Multicenter Analysis From the New York City Tri-State Region.

OBJECTIVES: Patients with multisystem inflammatory disease in children (MIS-C) are at risk of developing shock. Our objectives were to determine independent predictors associated with development of delayed shock (≥3 hours from emergency department [ED] arrival) in patients with MIS-C and to derive a model predicting those at low risk for delayed shock. METHODS: We conducted a retrospective cross-sectional study of 22 pediatric EDs in the New York City tri-state area. We included patients meeting World Health Organization criteria for MIS-C and presented April 1 to June 30, 2020. Our main outcomes were to determine the association between clinical and laboratory factors to the development of delayed shock and to derive a laboratory-based prediction model based on identified independent predictors. RESULTS: Of 248 children with MIS-C, 87 (35%) had shock and 58 (66%) had delayed shock. A C-reactive protein (CRP) level greater than 20 mg/dL (adjusted odds ratio [aOR], 5.3; 95% confidence interval [CI], 2.4-12.1), lymphocyte percent less than 11% (aOR, 3.8; 95% CI, 1.7-8.6), and platelet count less than 220,000/uL (aOR, 4.2; 95% CI, 1.8-9.8) were independently associated with delayed shock. A prediction model including a CRP level less than 6 mg/dL, lymphocyte percent more than 20%, and platelet count more than 260,000/uL, categorized patients with MIS-C at low risk of developing delayed shock (sensitivity 93% [95% CI, 66-100], specificity 38% [95% CI, 22-55]). CONCLUSIONS: Serum CRP, lymphocyte percent, and platelet count differentiated children at higher and lower risk for developing delayed shock. Use of these data can stratify the risk of progression to shock in patients with MIS-C, providing situational awareness and helping guide their level of care.

A novel case of two siblings harbouring homozygous variant in the NEUROG1 gene with autism as an additional phenotype: a case report.

INTRODUCTION: NEUROG1 gene is yet to be associated with a set of human phenotypes in the OMIM database. Three cases have previously been diagnosed with cranial dysinnervation due to biallelic variants in the NEUROG1 gene. This is the fourth and a novel report of a sibling pair harboring a homozygous variant in the NEUROG1 gene with autism as an additional phenotype. A brief review of the literature in conjunction with a genotype-phenotype correlation has been described. A potential hypothesis for the presence of the autistic phenotype in the present case has also been elucidated. CASE PRESENTATION: A female aged 6 years and 9 months born to endogamous and phenotypically healthy parents was diagnosed with global developmental delay, autism spectrum disorder, hearing loss, corneal opacity and no eye blinking. Her MRI of the brain revealed mild peritrigonal white matter hyperintensity, and MRI and CT scan of the temporal bones showed abnormal cranial nerves. The proband's younger sister, aged 4-years, was similarly affected. Whole exome sequencing was performed in the proband, which revealed a novel homozygous, likely pathogenic, truncating frameshift variant, c.228_231dup (p.Thr78ProfsTer122) in exon 1 of the NEUROG1 gene (ENST00000314744.4). Segregation analysis by Sanger sequencing showed the proband and her younger sister to be homozygotes and their parents to be heterozygous carriers. CONCLUSION: This is the fourth report across the globe with a variant identified in the NEUROG1 gene to be associated with cranial dysinnervation phenotype. An additional phenotype of autism in two female siblings was a novel observation. We provide a hypothetical framework which could explain the pleiotropic effect of a dysfunctional NEUROG1 protein leading to autism and posit it as a candidate for diagnosis of autism spectrum disorder with congenital cranial dysinnervation disorder.

Outcomes of Daptomycin Plus Ceftaroline Versus Alternative Therapy for Persistent Methicillin-resistant Staphylococcus aureus (MRSA) Bacteraemia.

OBJECTIVES: This study aimed to evaluate both efficacy and safety of combination therapy with daptomycin plus ceftaroline (DAP/CPT) versus alternative therapy in the treatment of persistent methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB). METHODS: This retrospective, single-centre study investigated adult patients who underwent a change in antibiotic therapy for persistent MRSAB. Daptomycin plus ceftaroline was compared with alternative therapy after initial treatment with vancomycin or DAP monotherapy was modified. The primary outcome was in-hospital mortality, and several secondary efficacy and safety outcomes were evaluated. RESULTS: A total of 68 patients with persistent MRSAB had initial therapy switched to DAP/CPT (n = 43) or alternative therapy (n = 25). In-hospital mortality was similar with DAP/CPT versus alternative therapy (16.3% vs. 16%; P = 1.0). On average, the total duration of bacteraemia was numerically 1 day less in patients switched to DAP/CPT (11.4 days vs. 12.5 days; P = 0.5). Daptomycin plus ceftaroline was de-escalated in 81% of patients after receiving combination therapy for an average of 12.5 days. Secondary outcomes, including rates of adverse events and emergence of antimicrobial resistance, were similar between the two groups. CONCLUSIONS: Switching to DAP/CPT after approximately 1 week of persistent MRSA bacteraemia may result in similar clinical outcomes when compared with alternative therapy. Rates of adverse events and emergence of antimicrobial resistance were low without a statistically significant difference observed between DAP/CPT and alternative therapy. These findings, as well as the impact of earlier switch or prolonged treatment with the combination, require further investigation.

Organophosphate pesticides an emerging environmental contaminant: Pollution, toxicity, bioremediation progress, and remaining challenges.

Organophosphates (OPs) are an integral part of modern agriculture; however, due to overexploitation, OPs pesticides residues are leaching and accumulating in the soil, and groundwater contaminated terrestrial and aquatic food webs. Acute exposure to OPs could produce toxicity in insects, plants, animals, and humans. OPs are known for covalent inhibition of acetylcholinesterase enzyme in pests and terrestrial/aquatic organisms, leading to nervous, respiratory, reproductive, and hepatic abnormalities. OPs pesticides also disrupt the growth-promoting machinery in plants by inhibiting key enzymes, permeability, and trans-cuticular diffusion, which is crucial for plant growth. Excessive use of OPs, directly/indirectly affecting human/environmental health, raise a thoughtful global concern. Developing a safe, reliable, economical, and eco-friendly methods for removing OPs pesticides from the environment is thus necessary. Bioremediation techniques coupled with microbes or microbial-biocatalysts are emerging as promising antidotes for OPs pesticides. Here, we comprehensively review the current scenario of OPs pollution, their toxicity (at a molecular level), and the recent advancements in biotechnology (modified biocatalytic systems) for detection, decontamination, and bioremediation of OP-pesticides in polluted environments. Furthermore, the review focuses on onsite applications of OPs degrading enzymes (immobilizations/biosensors/others), and it also highlights remaining challenges with future approaches.

Investigating the influence of an effort-reward interaction on cognitive fatigue in individuals with multiple sclerosis.

This study examined whether an alteration in the effort-reward relationship, a theoretical framework based on cognitive neuroscience, could explain cognitive fatigue. Forty persons with MS and 40 healthy age- and education-matched cognitively healthy controls (HC) participated in a computerized switching task with orthogonal high- and low-demand (effort) and reward manipulations. We used the Visual Analog Scale of Fatigue (VAS-F) to assess subjective state fatigue before and after each condition during the task. We used mixed-effects models to estimate the association and interaction between effort and reward and their relationship to subjective fatigue and task performance. We found the high-demand condition was associated with increased VAS-F scores (p < .001), longer response times (RT) (p < .001) and lower accuracy (p < .001). The high-reward condition was associated with faster RT (p = .006) and higher accuracy (p = .03). There was no interaction effect between effort and reward on VAS-F scores or performance. Participants with MS reported higher VAS-F scores (p = .02). Across all conditions, participants with MS were slower (p < .001) and slower as a function of condition demand compared with HC (p < .001). This behavioural study did not find evidence that an effort-reward interaction is associated with cognitive fatigue. However, our findings support the role of effort in subjective cognitive fatigue and both effort and reward on task performance. In future studies, more salient reward manipulations could be necessary to identify effort-reward interactions on subjective cognitive fatigue.

Strategizing Drug Therapies in Pulmonary Hypertension for Improved Outcomes.

Pulmonary hypertension (PH) is characterized by a resting mean pulmonary artery pressure (PAP) of 20 mmHg or more and is a disease of multiple etiologies. Of the various types of PH, pulmonary arterial hypertension (PAH) is characterized by elevated resistance in the pulmonary arterial tree. It is a rare but deadly disease characterized by vascular remodeling of the distal pulmonary arteries. This paper focuses on PAH diagnosis and management including current and future treatment options. Over the last 15 years, our understanding of this progressive disease has expanded from the concept of vasoconstrictive/vasodilatory mismatch in the pulmonary arterioles to now a better appreciation of the role of genetic determinants, numerous cell signaling pathways, cell proliferation and apoptosis, fibrosis, thrombosis, and metabolic abnormalities. While knowledge of its pathophysiology has expanded, the majority of the treatments available today still modulate the same three vasodilatory pathways that have been targeted for over 30 years (endothelin, nitric oxide, and prostacyclin). While modifying these pathways may help improve symptoms and quality of life, none of these directly modify the underlying disease pathogenesis. However, there are now studies ongoing with new drugs that can prevent or reverse these underlying causes of PAH. This review discusses the evidence base for the current treatment algorithms for PAH, as well as discusses novel therapies in development.

Retropharyngeal abscess in the setting of multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a potentially severe inflammatory syndrome following recent infection with SARS-CoV-2 (COVID-19). In this report, we describe a 13-year-old boy with a retropharyngeal abscess unresponsive to initial antibiotic therapy who was found to have findings consistent with MIS-C, which included elevated interleukin-6, ferritin, and troponin levels. The patient had COVID-19 infection due to the Omicron variant.