Is autopsy tissue a valid control for epilepsy surgery tissue in microRNA studies?

MicroRNAs (miRNAs) are differentially expressed in the brain under pathologic conditions and may therefore represent both therapeutic targets and diagnostic or prognostic biomarkers for neurologic diseases, including epilepsy. In fact, miRNA expression profiles have been investigated in the hippocampi of patients with epilepsy in comparison with control, nonepileptic cases. Unfortunately, the interpretation of these data is difficult because surgically resected epileptic tissue is generally compared with control tissue obtained from autopsies. To challenge the validity of this approach, we performed an miRNA microarray on the laser microdissected granule cell layer of the human hippocampus obtained from surgical samples of patients with epilepsy, autoptic nonepileptic controls, and patients with autoptic epilepsy, using the latter as internal control. Unfortunately, it is extremely difficult to collect autopsy material from documented epilepsy individuals who died of non–epilepsy-related causes—we found only two such cases. However, hierarchical clustering of all samples showed that those obtained from autopsies of patients with epilepsy segregated with the other autoptic samples (controls) and not with the bioptic tissues from the surgery patients, suggesting that the origin of the tissue (surgery or autopsy) may be prevalent over the underlying pathology (epilepsy or not epilepsy). Even taking into account the limitations due to the small number of cases, this observation arises concerns on the use of autopsy tissue as control for this kind of studies

The Collaborative for the Research on Black Women and Girls

<p>Seven patients per group. **P<0.01 Mann-Whitney U test. Representative granule cell layer hippocampal sections from patients without granule cell pathology (B) or with type-2 GCP (C) exhibiting DAB-labeled ANTXR1-like immunoreactivity (LI). Omitting the primary antibody to estimate nonspecific signal yielded completely negative labeling (data not shown). Note a widespread increase in ANTXR1-LI in granule cells from patients with type-2 GCP (C).</p

Development of a Training Program for Meta-Analytical Research:A Novel Approach to Minimizing Errors in Medical Systematic Reviews and Meta-Analyses

PURPOSE: The Global Andrology Forum (GAF) has developed an innovative training method to equip novice researchers with the fundamental skills to conduct high-quality systematic reviews and meta-analyses (SRMAs) under the supervision of senior experts. This article aims to describe and evaluate the effectiveness of the GAF training program in enhancing these skills.MATERIALS AND METHODS: A six-module training program was designed to cover the key steps in SRMA studies, enabling GAF members to conduct high-quality SRMAs. Initially launched as a synchronous (remote) training program, it was later transitioned into an asynchronous format and implemented on the Moodle platform. Trainees participating in the synchronous training program were asked to evaluate the course using a specially designed questionnaire. Participants' assessments of the asynchronous course were collected at various stages. Data from both training models were statistically analyzed.RESULTS: Among the trainees who participated in the questionnaire on the original synchronous course (n=101), the majority rated the material and assessments as clear, helpful, and effective in enhancing their knowledge. Additionally, the trainees indicated that the features offered in the training made them feel comfortable and engaged. Of the 29 participants enrolled in the asynchronous program, 22 took part in the assessment. Among them, 12 (54.5%) completed all course requirements, achieving an average score of 83.7%, qualifying them for conducting SRMAs.CONCLUSIONS: The GAF SRMA online training program has proven to be an effective and well-received initiative for equipping researchers with essential skills to conduct high-quality SRMAs. By addressing the diverse needs of trainees through its innovative and flexible design, the program has demonstrated its capacity to enhance knowledge and engagement. The successful implementation of this training program highlights its potential to significantly improve the quality of SRMAs in medical research, thereby contributing to the advancement of evidence-based medical practice on a broader scale.</p

Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations

PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial

Consensus and Diversity in the Management of Varicocele for Male Infertility: Results of a Global Practice Survey and Comparison with Guidelines and Recommendations

PURPOSE: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility. MATERIALS AND METHODS: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field. RESULTS: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available. CONCLUSIONS: This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men

The Global State of Contemporary Andrology Practice:A Comprehensive Analysis of Clinical Practice, Training Pathways, and Emerging Challenges

PURPOSE: This study evaluates the current state of andrology practice worldwide, identifies challenges faced by clinicians, and explores training, certification, and research opportunities. It also seeks to redefine the qualifications necessary to be recognized as an andrologist and to propose areas for standardization and improvement.MATERIALS AND METHODS: A global, cross-sectional survey was conducted using a 48-question online questionnaire designed by international experts. The survey, distributed in English, covered various domains of modern andrology practice. Responses from 405 participants across 59 countries were analyzed using R version 4.1.2, with categorical variables reported as frequencies and percentages.RESULTS: Among respondents, 47.3% held medical doctor (MD) degrees, with urologists (31.1%) and clinical andrologists (25.3%) being the most represented specialties. Formal, board-certified andrological training was reported as available in only 48.1% of countries. While half of the respondents identified as andrologists based on experience, only one-third did so through certification, obtained from diverse, nationally recognized organizations. The primary areas of practice included male infertility (36.7%), male sexual dysfunction (27.2%), and sexually transmitted infections (14.5%). Many participants were actively engaged in assisted reproductive technologies, imaging, and andrological surgical emergencies. Despite strong interest in clinical, basic, and translational research, respondents highlighted significant challenges, including inconsistent training pathways, insufficient certification standards, and the complexity of managing diverse andrological conditions.CONCLUSIONS: Andrology is an evolving multidisciplinary specialty where board-certified urologists, clinical andrologists, and reproductive medicine specialists collaborate to address male reproductive and sexual health challenges. Despite their advanced competencies in medical, surgical, and laboratory interventions, specialists face significant global disparities in training and certification. This survey highlights the urgent need for standardized training, evidence-based guidelines, and unified certification to ensure consistency, enhance patient care, and advance andrology's academic and clinical excellence worldwide.</p

Technical aspects and clinical limitations of sperm DNA fragmentation testing in male infertility: A global survey, current guidelines, and expert recommendations

Purpose Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. Materials and Methods Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. Results The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). Conclusions This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial