Cystic fibrosis (CF) is primarily recognized for its severe systemic effects, especially in the lungs, pancreas and digestive tract. Thus, the effect of CF transmembrane conductance regulator (CFTR) dysfunction on male f...Cystic fibrosis (CF) is primarily recognized for its severe systemic effects, especially in the lungs, pancreas and digestive tract. Thus, the effect of CF transmembrane conductance regulator (CFTR) dysfunction on male fertility has been relatively overlooked despite its important roles in spermatogenesis orchestration and spermatozoa function. CFTR has physiological functions as a chloride and bicarbonate channel and a role in regulating water movement. CFTR participates in spermatogenesis, and evidence suggests its involvement in seminiferous intratubular fluid control, maintenance of the blood-testis barrier, and improvement in follicle-stimulating hormone signalling, among other functions. Emerging evidence also suggests that CFTR variant carriers, typically considered to be healthy, have reduced sperm quality. Diminished CFTR expression has been observed in spermatozoa from men with various sperm quality abnormalities (teratozoospermia, asthenozoospermia and oligozoospermia), and correlates positively with sperm motility and morphology. CFTR is thought to be involved in sperm capacitation and osmoregulation via interactions with ion and water channels. Advances in CF therapy, such as CFTR modulators, gene therapy and liposome-mediated CFTR delivery, might affect CFTR's role in sperm function and could potentially be applied to improve the fertility of individuals with CFTR dysfunction.
Urolithiasis is increasingly common, with rising rates driven by obesity, diabetes and metabolic syndrome. Patients with cancer have additional, unique risks of stone formation owing to effects on fluid and electrolyte b...Urolithiasis is increasingly common, with rising rates driven by obesity, diabetes and metabolic syndrome. Patients with cancer have additional, unique risks of stone formation owing to effects on fluid and electrolyte balance, systemic cancer therapies, tumour lysis syndrome and anatomical alterations after urinary diversion or nephrectomy. Moreover, urolithiasis itself has been linked to increased rates of renal cell carcinoma, urothelial carcinoma and bladder cancer, potentially mediated by chronic inflammation, recurrent infections and shared metabolic or environmental factors. Management in this setting is complex and must be individualized. Percutaneous nephrolithotomy achieves the highest stone-free rates in patients with altered urinary tract anatomy, whereas retrograde intrarenal surgery and shock wave lithotripsy have more selective roles. Preventive strategies focus on thorough metabolic evaluation, hydration optimization and addressing cancer-specific risk factors such as hypercalcaemia, acidosis and chronic urinary stasis. Despite these insights, data on the epidemiology, mechanistic underpinnings and optimal management of urolithiasis in patients with cancer remain limited. Prospective studies are needed to clarify causal relationships, refine preventive strategies and develop evidence-based treatment algorithms for this growing and complex population.
Spinal cord injury (SCI) is a life-changing and costly condition. SCI causes major disturbances in sensory, motor and autonomic function, resulting in permanent loss of function and strongly affecting the physical, psych...Spinal cord injury (SCI) is a life-changing and costly condition. SCI causes major disturbances in sensory, motor and autonomic function, resulting in permanent loss of function and strongly affecting the physical, psychological and social well-being of patients and caregivers. A particularly debilitating consequence of SCI is loss of voluntary control over bladder function, which substantially affects patients' dignity, health and quality of life. Current understanding of the complex pathophysiological mechanisms of SCI and associated comorbidities has heavily relied on the use of animal models, which have also been crucial in devising new therapeutic approaches and fine-tuning existent ones. However, a debate about the persistent challenges in translating preclinical data into treatment is ongoing. Technological advances are generating innovative modelling approaches with the support of regulatory bodies, aiming to reduce or eventually substitute animal use. In this Review, we address the current use of animal SCI models in neuro-urological research and debate whether we will still be using these models by 2035.
Prostate cancer disproportionately affects men of African ancestry, yet the molecular mechanisms underlying these disparities remain poorly defined. Genomic studies have begun to reveal ancestry-linked risk alleles and s...Prostate cancer disproportionately affects men of African ancestry, yet the molecular mechanisms underlying these disparities remain poorly defined. Genomic studies have begun to reveal ancestry-linked risk alleles and somatic alterations, but the role of epigenetic dysregulation is only emerging. Drawing on multi-ancestral comparative analyses, with emphasis on cohorts from sub-Saharan Africa, we speculate that germline and somatic variation converge in epigenetic machinery genes to drive tumour evolution. African tumours harbour a heightened burden and diversity of both inherited and acquired variants, supporting a model of 'oncogenic cooperation' whereby germline diversity interacts with somatic mutations to broaden the range of pathogenic interactions. Limited yet complementary methylation analyses reveal tumour-specific and ancestry-specific reprogramming of promoters, enhancers and heterochromatin, suggesting that African tumours might be epigenetically primed for aggressive phenotypes. Chromatin remodelling defects emerge as potentially under-recognized disparity drivers, promoting genomic instability, altered gene regulation and therapeutic resistance. Collectively, these findings support a genome-epigenome-environment model in which inherited susceptibility, somatic variation and environmentally reinforced epigenetic reprogramming converge to shape aggressive African-associated prostate cancer. However, current insights are limited by European-centred baselines, under-representation of African cohorts and platform mismatches. Reducing prostate cancer health disparities requires equitable prostate cancer genomics and epigenomic research efforts that embrace the rich African ancestral population identifier.
Approximately 1 in 8 men are diagnosed with prostate cancer during their lifetime. However, long-term data have shown that as many as half of diagnosed prostate cancers have low lethal potential. Early detection of prost...Approximately 1 in 8 men are diagnosed with prostate cancer during their lifetime. However, long-term data have shown that as many as half of diagnosed prostate cancers have low lethal potential. Early detection of prostate cancer relying on PSA alone is associated with potential harm to patients owing to false-positive results, prostate biopsy-related complications and over-detection and over-treatment of low-risk cancers. Multiparametric MRI offers an adjunctive strategy for improving the diagnostic yield of prostate biopsy and also for potentially reducing the need for biopsy in selected patients. Prostate MRI can increase the detection of clinically significant prostate cancer through targeted biopsy, especially in patients with a previous negative biopsy who did not undergo initial imaging. Prostate MRI improves clinically significant cancer detection, potentially reducing biopsy burden in patients on active surveillance.
Single-cell RNA sequencing (scRNA-seq) has become an indispensable tool in prostate biology research, considerably advancing our understanding from organ development to disease initiation and progression. This technology...Single-cell RNA sequencing (scRNA-seq) has become an indispensable tool in prostate biology research, considerably advancing our understanding from organ development to disease initiation and progression. This technology has provided profound insights into prostate disease, from benign prostatic hyperplasia to metastatic prostate cancer, particularly with respect to the tumour microenvironment, cellular lineage plasticity and resistance to androgen receptor-dependent therapies. scRNA-seq has revealed complex and potentially targetable interactions between epithelial, stromal and immune subtypes driving disease heterogeneity. As a complementary technology, spatial transcriptomics enables the characterization of tumour architecture using spatial resolution at the single-cell or multi-cell level. Importantly, these approaches also permit bioinformatic inference of large-scale copy number variants, enabling integrated genomic-transcriptomic analysis of clonal evolution and therapy resistance. Understanding the biological consequences of this heterogeneity could support patient sub-stratification, biomarker development and therapeutic strategies targeting genomic instability or tumour microenvironment interactions.
Lower urinary tract dysfunction presents with a wide range of bothersome urinary symptoms, which are common in both men and women, with incidence and prevalence increasing with age. Individuals with lower urinary tract s...Lower urinary tract dysfunction presents with a wide range of bothersome urinary symptoms, which are common in both men and women, with incidence and prevalence increasing with age. Individuals with lower urinary tract symptoms (LUTS) suffer from the chronicity of their symptoms, have a reduced quality of life, and experience high morbidity with associated medical conditions. Various treatment options exist, but many patients do not find satisfactory or lasting relief. The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) was formed in 2012 with the goals of improving methods for assessing patient-reported experiences with LUTS; identifying and describing patient subtypes; and generating data, research tools and biological samples for future studies. LURN developed three self-report instruments for measuring LUTS. More than 1,000 men and women with LUTS seeking treatment were enrolled, and completed a baseline and interval assessments throughout a 12-month observational period. Findings from LURN studies showed that various biological, non-urological, psychosocial and behavioural factors contribute to the development and persistence of LUTS. Additionally, patients seeking care for LUTS often present with a wider variety of urological symptoms than previously thought. Diagnoses for these patients do not reliably fit into traditional categories such as overactive bladder or BPH. LURN has addressed its objectives by creating new, top-tier assessment tools; conducting studies to gather clinically relevant data to identify potential new and accurate patient subtypes; and collecting a wealth of data and biological samples for future research to continue subtype refinement.