Surgical Outcomes and Predictive Factors in Patients With Detrusor Underactivity Undergoing Bladder Outlet Obstruction Surgery.

PURPOSE: This study was conducted to evaluate the efficacy of bladder outlet surgery in patients with detrusor underactivity (DU) and to identify factors associated with successful outcomes. METHODS: We conducted a retrospective review of men diagnosed with DU in urodynamic studies who underwent bladder outlet surgery for lower urinary tract symptoms between May 2018 and April 2023. The International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry (UFM), and multichannel urodynamic studies were administered. Successful treatment outcomes were defined as either an IPSS improvement of at least 50% or the regaining of spontaneous voiding in patients urethral catheterization prior to surgery. RESULTS: The study included 93 male patients. Men diagnosed with significant or equivocal bladder outlet obstruction (BOO) experienced significant postoperative improvements in IPSS (from 20.6 to 6.0 and from 17.4 to 6.5, respectively), maximum urine flow rate (from 5.0 mL/sec to 14.4 mL/sec and from 8.8 mL/sec to 12.2 mL/sec, respectively) and voiding efficiency (from 48.8% to 86.0% and from 61.2% to 85.1%, respectively). However, in the group without obstruction, the improvements in IPSS and UFM results were not significant. The presence of detrusor overactivity (odds ratio [OR], 3.152; P=0.025) and preoperative urinary catheterization (OR, 2.756; P=0.040) were associated with favorable treatment outcomes. Conversely, an unobstructed bladder outlet was identified as a negative prognostic factor. CONCLUSION: In men with DU accompanied by equivocal or significant BOO, surgical intervention to alleviate the obstruction may enhance the IPSS, quality of life, and UFM results. However, those with DU and an unobstructed bladder outlet face a comparatively high risk of treatment failure. Preoperative detrusor overactivity and urinary catheterization are associated with more favorable surgical outcomes. Consequently, active deobstructive surgery should be considered for patients with DU who are experiencing urinary retention.

Association between chronic prostatitis and the subsequent benign prostatic hyperplasia: a population-based national cohort study.

PURPOSE: To explore the association between chronic prostatitis (CP) and the subsequent development of benign prostatic hyperplasia (BPH). METHODS: Data analyzed were medical claims of Taiwan's National Health Insurance program. From 2010 to 2017, 3571 patients ≧20 years with CP diagnosed by certified urologists were enrolled. Patients with past BPH diagnosis and diagnosis of prostate cancer, inguinal hernia, interstitial cystitis, and urethritis in the past and within one year after the first CP diagnosis were excluded. Age-matched controls were randomly selected from all non-CP individuals of the same exclusion criteria in the study period with a CP/non-CP ratio of 1:4. The follow-up was made from the first CP diagnosis to death or the end of 2018. The endpoint was the newly diagnosed BPH. Cox proportional hazard regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of BPH in association with CP. RESULTS: Over a maximum of 8 years of follow-up, 287 (8.03%) and 258 (0.43%) BPH events were noted for the CP and non-CP group, respectively, representing a covariate adjusted HR (aHR) of 4.30 (95% CI, 3.61-5.13). Younger patients tended to suffer from higher aHRs, especially those aged 20-39 years (aHR: 11.45, 95% CI, 5.12-25.64). CONCLUSION: The Taiwan national health database indicated that CP patients had a significantly higher risk of developing BPH later than non-CP patients. Interestingly, the younger the CP is diagnosed (under 40), the greater the risk.

Therapeutic efficacy of 180-W GreenLight laser photoselective vaporization of the prostate for storage symptoms concomitant with benign prostatic obstruction and a search for outcome predictors.

PURPOSE: Benign prostatic obstruction (BPO) is the most common cause of lower urinary tract symptoms among men. GreenLight photoselective vaporization of the prostate (GL-PVP) using a 180-W Xcelerated performance system (XPS) laser is a well-established method for treating BPO-induced voiding symptoms. However, its therapeutic effects on storage symptoms remain unclear. This study aimed to analyze the storage outcomes in patients who underwent 180-W XPS GL-PVP for BPO and to identify outcome predictors. MATERIALS AND METHODS: Patients who underwent 180-W XPS GL-PVP for BPO between May 2018 and May 2021 were retrospectively reviewed. Data on clinical characteristics, prostate volume, preoperative and postoperative International Prostate Symptom Scores (IPSS), and preoperative urodynamic parameters were collected. A favorable storage outcome was defined as ≥50% reduction in the IPSS storage subscore. RESULTS: Ninety-nine male patients were included, with a mean age of 69.4 ± 9.6 years and a baseline prostatic volume of 75.9 ± 33.1 mL. The IPSS total, storage, and voiding subscores significantly decreased after GL-PVP (all p < 0.001). Seventy-two patients achieved favorable storage outcome at 6 months. Multivariate analysis revealed that detrusor underactivity was predictive of unfavorable storage outcomes (p = 0.022), while IPSS voiding-to-storage subscore ratio >1.25 and the presence of detrusor overactivity were predictive of favorable storage outcomes (p = 0.008 and 0.033, respectively). CONCLUSION: 180-W XPS GL-PVP provided excellent outcomes in both voiding and storage lower urinary tract symptoms concomitant with BPO. Preoperative IPSS and multichannel urodynamic parameters including detrusor overactivity and underactivity are valuable predictors of postoperative storage outcomes.

MicroRNA-320a enhances LRWD1 expression through the AGO2/FXR1-dependent pathway to affect cell behaviors and the oxidative stress response in human testicular embryonic carcinoma cells.

BACKGROUND: Testicular cancer is fairly rare but can affect fertility in adult males. Leucine-rich repeats- and WD repeat domain-containing protein 1 (LRWD1) is a sperm-specific marker that mainly affects sperm motility in reproduction. Our previous study demonstrated the impact of LRWD1 on testicular cancer development; however, the underlying mechanisms remain unclear. METHODS: In this study, various plasmids associated with LRWD1 and miR-320a manipulation were used to explore the roles and regulatory effects of these molecules in NT2D1 cellular processes. A Dual-Glo luciferin-luciferase system was used to investigate LRWD1 transcriptional activity, and qRT-PCR and western blotting were used to determine gene and protein expression. RESULTS: The results suggested that miR-320a positively regulated LRWD1 and positively correlated with NT2D1 cell proliferation but negatively correlated with cell migration and invasion ability. In addition, the miRNA-ribonucleoprotein complex AGO2/FXR1 was shown to be essential in the mechanism by which miR-320a regulates LRWD1 mRNA expression. As miR-320a was required to regulate LRWD1 expression through the AGO2 and FXR1 complex, eEF2 and eLF4E were also found to be involved in miR-320a increasing LRWD1 expression. Furthermore, miR-320a and LRWD1 were responsive to oxidative stress, and NRF2 was affected by the presence of miR-320a in response to ROS stimulation. CONCLUSIONS: This is the first study showing the role of miR-320a in upregulating the testicular cancer-specific regulator LRWD1 and the importance of the AGO2/FXR1 complex in miR-320a-mediated upregulation of LRWD1 during testicular cancer progression.

Male infertility.

Clinical infertility is the inability of a couple to conceive after 12 months of trying. Male factors are estimated to contribute to 30-50% of cases of infertility. Infertility or reduced fertility can result from testicular dysfunction, endocrinopathies, lifestyle factors (such as tobacco and obesity), congenital anatomical factors, gonadotoxic exposures and ageing, among others. The evaluation of male infertility includes detailed history taking, focused physical examination and selective laboratory testing, including semen analysis. Treatments include lifestyle optimization, empirical or targeted medical therapy as well as surgical therapies that lead to measurable improvement in fertility. Although male infertility is recognized as a disease with effects on quality of life for both members of the infertile couple, fewer data exist on specific quantification and impact compared with other health-related conditions.

Arteriovenous malformation Map2k1 mutation affects vasculogenesis.

Somatic activating MAP2K1 mutations in endothelial cells (ECs) cause extracranial arteriovenous malformation (AVM). We previously reported the generation of a mouse line allowing inducible expression of constitutively active MAP2K1 (p.K57N) from the Rosa locus (R26GT-Map2k1-GFP/+) and showed, using Tg-Cdh5CreER, that EC expression of mutant MAP2K1 is sufficient for the development of vascular malformations in the brain, ear, and intestines. To gain further insight into the mechanism by which mutant MAP2K1 drives AVM development, we induced MAP2K1 (p.K57N) expression in ECs of postnatal-day-1 pups (P1) and investigated the changes in gene expression in P9 brain ECs by RNA-seq. We found that over-expression of MAP2K1 altered the transcript abundance of > 1600 genes. Several genes had > 20-fold changes between MAP2K1 expressing and wild-type ECs; the highest were Col15a1 (39-fold) and Itgb3 (24-fold). Increased expression of COL15A1 in R26GT-Map2k1-GFP/+; Tg-Cdh5CreER+/- brain ECs was validated by immunostaining. Ontology showed that differentially expressed genes were involved in processes important for vasculogenesis (e.g., cell migration, adhesion, extracellular matrix organization, tube formation, angiogenesis). Understanding how these genes and pathways contribute to AVM formation will help identify targets for therapeutic intervention.

The MAEL expression in mitochondria of human spermatozoa and the association with asthenozoospermia.

PURPOSE: The maelstrom spermatogenic transposon silencer (MAEL) function in postmeiotic germ cells remains unclear, and its protein localization in human testis and spermatozoa awaits determination. This study aims to clarify the MAEL expression in human spermatogenesis and to explore its role in sperm function. MATERIALS AND METHODS: Twenty-seven asthenozoospermic men, 40 normozoospermic controls, and three obstructive azoospermic men were enrolled. The transcripts of MAEL in the seminiferous epithelium and MAEL downstream targets were identified by bioinformatics analysis. MAEL protein expression in human testis and ejaculated sperms were examined by immunohistochemical and immunogold staining, respectively. The roles of MAEL in mitochondria function were investigated by siRNA knockdown in human H358 cells. The association between MAEL protein levels and clinical sperm features was evaluated. RESULTS: Abundant MAEL was expressed in spermatid and spermatozoa of the human testis. Remarkably, MAEL was located in the mitochondria of ejaculated sperm, and bioinformatics analysis identified GPX4 and UBL4B as MAEL's downstream targets. Knockdown of MAEL sabotaged mitochondria function and reduced adenosine triphosphate (ATP) production in H358 cells. MAEL, GPX4, and UBL4B expression levels were significantly decreased in asthenozoospermic sperms than in controls. The MAEL protein levels were positively correlated with GPX4 and UBL4B in human sperm. Total motile sperm count (TMSC) was positively correlated with protein levels of MAEL, GPX4, and UBL4B in ejaculated sperms. CONCLUSIONS: We highlight prominent MAEL expression in the intratesticular spermatid and the mitochondria of ejaculated spermatozoa. MAEL directly binds to GPX4 and UBL4B, and loss of MAEL induces mitochondrial dysfunction. MAEL-mitochondrial function-motility relationship might advance our understanding of the causes of asthenozoospermia.

The sufficient multidisciplinary specialists under a government-led health care system associated with the downward mortality trend of Fournier's gangrene in Taiwan.

OBJECTIVES: To explore the trends in Fournier's gangrene (FG) incidence and mortality rate in Taiwan and to investigate the contributing factors to such changes. METHODS: Between 2002 and 2016, hospitalized FG patients who underwent subsequent surgical intervention were included in this retrospective study. Incidence, outcomes, age-adjusted Charlson Comorbidity Index (ACCI), hospitalization cost, surgical timing, and the number of multidisciplinary specialists involved in the first-line management of FG in each year were collected. Simple linear regression and Pearson correlation coefficient (r) were used for the subsequent analysis. RESULTS: The national cohort enrolled 2183 FG patients from 2002 to 2016 in Taiwan. The age-standardized incidence rate of FG was between 0.4 and 0.8 per 100 000 population, and overall mortality was 7.8% in these 15 years. We illustrated the downward trendline of FG mortality with a 0.62 coefficient of determination. The mortality of FG patients who underwent surgery within 24 h and after 24 h were found to be 8.3 ± 3.9% and 14.6 ± 25.2%, respectively (p = 0.02). The numbers of urologists, anesthesiologists, emergency doctors, and physicians per 100 000 population had a strong negative linear correlation with FG mortality (r = 0.8, p < 0.001). ACCI score had a moderate linear relationship with FG mortality (r = 0.57, p = 0.027). The hospitalization cost showed a weak linear correlation with FG mortality (r = -0.03, p = 0.92). CONCLUSIONS: We demonstrated the downward trend of the FG mortality rate in Taiwan from 2002 to 2016. Besides underlying comorbidities and surgical timing, sufficient multidisciplinary specialists are essential for the survival benefit of FG patients in Taiwan experience.

Endothelial cell expression of mutant Map2k1 causes vascular malformations in mice.

Extracranial arteriovenous malformation (AVM) is a congenital vascular anomaly causing disfigurement, bleeding, ulceration, and pain. Most lesions are associated with somatic MAP2K1 activating mutations in endothelial cells (ECs). The purpose of this study was to determine if EC expression of mutant activated MAP2K1 is sufficient to produce vascular malformations in mice. We generated mice with a ROSA26 allele containing a lox-stop-lox gene trap (GT), Map2k1 cDNA with an activating p.K57N missense mutation, an internal ribosomal entry site, and green fluorescent protein cDNA (R26GT-Map2k1-GFP). We expressed mutant MAP2K1 and GFP in ECs of fetal and newborn mice using Tg-Cdh5Cre or Tg-Cdh5CreER alleles. Tg-Cdh5Cre+/-;R26GT-Map2k1-GFP/+ animals that express mutant MAP2K1 in ECs in utero developed diffuse vascular abnormalities and died by embryonic (E) day 16.5. Tg-Cdh5CreER+/-;R26GT-Map2k1-GFP/+ animals in which mutant MAP2K1 expression was induced in ECs by tamoxifen at postnatal (P) day 1 developed vascular malformations in the brain, ear, and intestines by P23. The lesions consisted of abnormal networks of blood vessels containing recombined and non-recombined ECs. In conclusion, expression of MAP2K1 p.K57N is sufficient to cause vascular malformations in mice. This model can be used to study the malformation process and for pre-clinical pharmacologic studies.

The Association between Monthly, Yearly, and Lifetime Cannabis Use, and Semen Parameters in Asian-American Men.

PURPOSE: Medicinal and recreational cannabis use has grown exponentially, however, its effect on testicular function and spermatogenesis remains uncertain. The aim of this study was to evaluate the association between cannabis use and semen parameters in a cohort of Asian-American men with unknown fertility. MATERIALS AND METHODS: Asian men were recruited to complete an online survey and submit a semen sample. Semen analysis, demographic data, lifestyle factors, and cannabis use habits were collected. Linear and logistic regression analyses were used to determine. RESULTS: Among the 112 men included in this study, 51 used cannabis at least once in their lifetime, 30 men used cannabis at least once in the last 12 months, and 26 men used cannabis at least once in the last 30 days. Adjusted linear regression analyses identified an association between cannabis use in the previous 30 days and worse sperm morphology (ß: -0.45, p=0.025) and sperm motility (ß: -1.64, p=0.016). However, when stratifying by subfertile semen quality (i.e., WHO criteria), no association was identified between semen quality and cannabis use. Lower sperm morphology and motility are partially associated with recent cannabis use, while all other semen parameters are not. CONCLUSIONS: We did not observe any consistent associations between cannabis use on any semen parameters in Asian-American men. Further studies within the field are needed to explore racial and ethnic differences in semen quality and lifestyle factors.

Site specific NMR characterization of abeta-40 oligomers cross seeded by abeta-42 oligomers.

Extracellular accumulation of ß amyloid peptides of 40 (Aß40) and 42 residues (Aß42) has been considered as one of the hallmarks in the pathology of Alzheimer's disease. In this work, we are able to prepare oligomeric aggregates of Aß with uniform size and monomorphic structure. Our experimental design is to incubate Aß peptides in reverse micelles (RMs) so that the peptides could aggregate only through a single nucleation process and the size of the oligomers is confined by the physical dimension of the reverse micelles. The hence obtained Aß oligomers (AßOs) are 23 nm in diameter and they belong to the category of high molecular-weight (MW) oligomers. The solid-state NMR data revealed that Aß40Os adopt the structural motif of ß-loop-ß but the chemical shifts manifested that they may be structurally different from low-MW AßOs and mature fibrils. From the thioflavin-T results, we found that high-MW Aß42Os can accelerate the fibrillization of Aß40 monomers. Our protocol allows performing cross-seeding experiments among oligomeric species. By comparing the chemical shifts of Aß40Os cross seeded by Aß42Os and those of Aß40Os prepared in the absence of Aß42Os, we observed that the chemical states of E11, K16, and E22 were altered, whereas the backbone conformation of the ß-sheet region near the C-terminus was structurally invariant. The use of reverse micelles allows hitherto the most detailed characterization of the structural variability of Aß40Os.

Incorporating sperm DNA fragmentation index with computer-assisted semen morphokinematic parameters as a better window to male fertility.

This study aimed to assess (1) the reproducibility of three sperm chromatin dispersion (SCD) assays for sperm DNA fragmentation, i.e., LensHooke R10® (R10), Halosperm G2® (G2), and BASO® (BA); (2) the correlation between computer-assisted semen analyzer (CASA) morphokinematic parameters and sperm DNA fragmentation index (DFI), and (3) the diagnostic value for male reproduction by combining semen morphokinematic parameters and DFI. Total 50 male participants were recruited, and all collected semen samples underwent semen analyses and SCD assays. Intra- and inter-observer variability of DFI data from different SCD measures was tested. In addition, the predictive ability of CASA parameters and DFI (with different cutoffs, i.e., 15% and 20%) for infertility was assessed using receiver operating characteristic curve analysis. We found that the G2 and R10 produced satisfactory variance coefficients (5.53%, 5.67%) compared to BA (14.8%). The DFI data from the R10 had lower intra-observer variability, in terms of higher intra-class coefficient (0.9615), than that of the G2 (0.8847) or BA (0.8824). Inter-observer variability of three SCD kits in scoring the DFI was comparable and satisfactory (concordance correlation coefficients ranging 0.9895-0.9630). The CASA parameters (i.e., total motility [r = -0.57], progression motility [r = -0.55], and rapidly progressive motility [r = -0.55]) were significantly correlated with DFI (P < 0.001). The predictive ability of the 15%-cutoff DFI data was better than that of the 20%-cutoff or continuous DFI data. The model comprising the CASA parameters, 15%-cutoff DFI, and 4%-cutoff normal morphology had the highest area under curve (0.8125) for infertility. For SCD assay, the R10 was the most reliable SCD assay to detect sperm DNA fragmentation. Combining the sperm DFI with CASA parameters might be a better diagnostic tool for male reproduction.

The fertility preservation decision-making and testicular sperm retrieval outcome in older adolescents with nonmosaic Klinefelter syndrome and azoospermia.

BACKGROUND: This study aims to analyze the fertility preservation decision-making and the sperm retrieval rate (SRR) in older adolescents (age 15-19 years) with nonmosaic Klinefelter syndrome (KS) and azoospermia in a male reproductive clinic, and to determine the accumulated SRR in older adolescents by literature review. METHODS: Older adolescents with nonmosaic KS and azoospermia referred for hypogonadism and fertility concerns were enrolled. Reproductive counseling and fertility preservation options were offered to patients/parents. The acceptability and the reasons affecting the reproductive decision-making were analyzed. Patients/parents who agreed on fertility preservation received microdissection testicular sperm extraction (mTESE) and cryopreservation. A comprehensive literature review regarding the SRRs in older adolescents with KS was conducted. RESULTS: A total of eight older adolescents were enrolled. After fertility preservation counseling, three patients/parents (37.5%) agreed to receive mTESE, and spermatozoa were successfully retrieved in two. "Lack of interest" and "inconsistent sperm retrieval result" were the main reasons for refusal. A total of 89 older adolescents from nine articles, and ours were collected for SRR analysis. Most of the reports had a limited number of cases, and none of them described the acceptance rate of sperm retrieval in adolescents. Forty-three out of 89 older adolescents (48.3%) had successful sperm retrieval, and there was no significant difference in the SRR between the mTESE and conventional TESE. CONCLUSION: Successful testicular sperm retrieval in older adolescents with KS is not superior to those reported in adults. Adolescents and their parents should undergo a detailed reproductive consultation process and shared decision-making discussion before considering testicular sperm retrieval.

Risk factors for postoperative urinary retention following elective spine surgery: a meta-analysis.

BACKGROUND CONTEXT: Limited studies have investigated risk factors for postoperative urinary retention (POUR) following elective spine surgery. Furthermore, some discrepancies have been found in the results of existing observational studies. PURPOSE: This study aimed to review the available literature on risk factors associated with POUR following elective spine surgery. STUDY DESIGN: A systematic review with meta-analysis was performed. PATIENT SAMPLE: A total of 31,251 patients (POUR=2,858, no POUR=28,393) were included in the meta-analysis. OUTCOME MEASURES: Demographics, type of elective spine surgery, country, definition of POUR, and potential risk factors for POUR were evaluated. METHODS: The Cochrane Library, Embase, and Medline electronic databases were searched to identify relevant studies. Binary outcomes were reported as odds ratio (OR). Weighted mean differences (WMD) or standardized mean differences (SMD), with 95% confidence intervals (CI), were used for meta-analysis of continuous outcomes. RESULTS: Eleven studies (2 prospective and 9 retrospective) were included in the analysis. Patients with POUR were older than those without POUR (WMD, 7.13; 95% CI, 4.50-9.76). Male patients were found to have an increased risk of POUR (OR, 1.31; 95% CI, 1.04-1.64). The following variables were also identified as significant risk factors for POUR: benign prostatic hyperplasia (BPH; OR, 3.79; 95% CI, 1.89-7.62), diabetes mellitus (DM; OR, 1.50; 95% CI, 1.17-1.93), and previous urinary tract infection (UTI; OR, 1.70; 95% CI, 1.28-2.24). Moreover, longer operative time (WMD, 19.88; 95% CI, 5.01-34.75) and increased intraoperative fluid support (SMD, 0.37; 95% CI, 0.23-0.52) were observed in patients with POUR. In contrast, spine surgical procedures involving fewer levels (OR, 0.75; 95% CI, 0.65-0.86), and ambulation on the same day as surgery (OR, 0.65; 95% CI, 0.52-0.81) were associated with a decreased risk of POUR. CONCLUSIONS: Based on our meta-analysis, older age, male gender, BPH, DM, and a history of UTI are risk factors for POUR following elective spine surgery. We also found that longer operative time and increased intravenous fluid support would increase the risk of POUR. Additionally, multi-level spine surgery may have a negative effect on postoperative voiding.

Kidney Stone History and Adverse Outcomes After Percutaneous Coronary Intervention.

OBJECTIVE: To determine whether kidney stone history is associated with adverse outcomes after percutaneous coronary intervention (PCI). Kidney stone formers have an increased risk of developing coronary artery disease; however, whether these patients have worse cardiac outcomes is unknown. MATERIALS AND METHODS: We identified adult patients who underwent first-time PCI in Vanderbilt University Medical Center (VUMC) Synthetic Derivative from 2008 to 2016 (n = 11,289) and in a nationwide database of Taiwan (NHIRD) from 2005 to 2012 (n = 155,762). Odds ratios (ORs) of 30-day in-hospital mortality and hazard ratios (HRs) of 1-year and 3-year adverse outcomes associated with kidney stone history were estimated using a propensity score approach. RESULTS: Overall, 294 and 12,286 stone formers undergoing PCI were identified in the VUMC and NHIRD, respectively. After matching, stone formers at VUMC were at higher risks of 30-day in-hospital mortality (OR 2.79, 95% CI 1.15-6.69) and 1-year (HR 1.59, 95% CI 1.13-2.24) and 3-year (HR 1.36, 95% CI 1.02-1.81) myocardial infarction. In the NHIRD, kidney stone history was associated with 1-year (HR 1.12, 95% CI 1.03-1.21) and 3-year (HR 1.14, 95% CI 1.06-1.22) myocardial infarction. In a sensitivity analysis, stone formers undergoing kidney stone surgery were marginally associated with 30-day in-hospital mortality (OR 1.21, 95% CI 0.99-1.48) and were associated with 3-year myocardial infarction (HR 1.13, 95% CI 1.02-1.25). CONCLUSION: Kidney stone history is associated with poorer cardiac outcomes after PCI. Improving secondary cardiac prevention strategies after PCI may be necessary for patients with a history of kidney stone disease.

Incorporating Simplified Fournier's Gangrene Severity Index with early surgical intervention can maximize survival in high-risk Fournier's gangrene patients.

OBJECTIVES: To determine the optimal surgical timing in high-risk patients with Fournier's gangrene by the Simplified Fournier's Gangrene Severity Index. METHODS: From 1989 to 2018, 118 male patients diagnosed with Fournier's gangrene with complete medical records were retrospectively reviewed. Patients' demographics, laboratory parameters at initial diagnosis, Fournier's Gangrene Severity Index and Simplified Fournier's Gangrene Severity Index, and the time interval from emergency room arrival to surgical intervention were collected. The Fournier's gangrene patients were categorized into low-risk (Simplified Fournier's Gangrene Severity Index ≤2) and high-risk groups (Simplified Fournier's Gangrene Severity Index >2). Differences between the variables within the two groups were analyzed. The optimal surgical timing was analyzed with the receiver operating characteristic curve in high-risk Fournier's gangrene patients. RESULTS: The overall mortality of 118 Fournier's gangrene patients was 14.4%. After risk stratification with the Simplified Fournier's Gangrene Severity Index scoring system, the mortality of low-risk and high-risk Fournier's gangrene patients was 1.3% and 41.0%, respectively. In the high-risk group, the time interval from emergency room arrival to surgical intervention was the only variable with a significant difference between survivors and non-survivors (P = 0.039). The optimal surgical timing was determined at 14.35 h, which allowed the highest sensitivity (0.688) and specificity (0.762) to affect mortality. The mortality was significantly lower in high-risk Fournier's gangrene patients with early surgical intervention compared with late intervention (23.8% vs 68.8%, P = 0.007). CONCLUSIONS: The Simplified Fournier's Gangrene Severity Index is a quick and reliable screening tool for first-line physicians to identify high-risk patients with Fournier's gangrene (Simplified Fournier's Gangrene Severity Index >2) who have poor survival outcomes. We recommended early surgical intervention within 14.35 h to maximize the survival of high-risk Fournier's gangrene patients.

Preparation of fibril nuclei of beta-amyloid peptides in reverse micelles.

We report the preparation of protofibrils from oligomeric Aß40 aggregates, which have been incubated under spatially constrained conditions. The molecular structure of the resultant protofibrils is highly homogeneous, suggesting that the phenomenon of structural polymorphism commonly observed in Aß40 fibrils may be largely due to multiple nucleation events.

MAEL promoter hypermethylation is associated with de-repression of LINE-1 in human hypospermatogenesis.

STUDY QUESTION: Does the hypermethylation of the maelstrom spermatogenic transposon silencer (MAEL) promoter and subsequent de-repression of transposable elements represent one of the causes of spermatogenic failure in infertile men? SUMMARY ANSWER: Experimental hypermethylation of a specific region (-131 to +177) of the MAEL promoter leads to decreased expression of MAEL with increased expression of the transposable element LINE-1 (L1) and in infertile men methylation of the MAEL promoter is associated with the severity of spermatogenic failure. WHAT IS KNOWN ALREADY: MAEL induces transposon repression in the male germline and is required for mammalian meiotic progression and post-meiotic spermiogenesis. Patients with non-obstructive azoospermia (NOA), defined as no sperm in the ejaculate due to spermatogenic failure, and histopathologically proven hypospermatogenesis (HS) is not uncommon and its etiology is largely unknown. STUDY DESIGN, SIZE, DURATION: Luciferase reporter assay and a targeted DNA methylation model were used to explore the effects of hypermethylation of MAEL promoter on gene expression. Germ cell-enriched testicular cells from infertile patients were used to determine the methylation levels of MAEL and expressions of MAEL and L1. PARTICIPANTS/MATERIALS, SETTING, METHODS: Twenty-six patients with histopathologically proven NOA and HS and 12 patients with obstructive azoospermia and normal spermatogenesis (NS) were enrolled in this study. Demographic and clinical information were obtained. The severity of HS was determined by a spermatogenic scoring system. The methylation levels of 26 CpGs in the MAEL promoter was measured, and quantitative real-time RT-PCR was used to determine the expressional levels of MAEL and L1. MAIN RESULTS AND THE ROLE OF CHANCE: Targeted DNA methylation of MAEL promoter suppressed MAEL expression and de-repressed L1 activity in vitro. Patients with HS had significantly higher mean methylation levels of 26 consecutive CpGs in the MAEL promoter, compared to patients with NS. The MAEL methylation levels were negatively correlated with MAEL transcript levels and higher methylation level of MAEL was associated with severe spermatogenic defect. L1 transcript level was significantly higher in patients with HS. No differences in age, frequency of testicular insults and genetic anomalies was noted between patients with high or low MAEL methylation levels. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Because of the difficulty in the use of human germ cells for study, the in vitro targeted DNA methylation model was performed by using human NCI-H358 cells to explore the effects of MAEL methylation on transposable elements activity. Because the germ cell-enriched testicular cells isolated from a testicular sample were relatively few, the purity of cell populations was not determined. WIDER IMPLICATIONS OF THE FINDINGS: Measurement of the methylation level of MAEL gene may be feasible to predict the severity of spermatogenic failure or the outcome of testicular sperm retrieval. STUDY FUNDING/COMPETING INTERESTS: This work was supported through grants from the Ministry of Science and Technology of Taiwan (100-2314-B-006-017) and National Cheng Kung University Hospital, Tainan, Taiwan (NCKUH 20120266). The authors declare no conflicts of interest.