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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Some studies have shown that in patients with upper tract urothelial carcinoma (UTUC) who have undergone hand-assisted laparoscopic nephroureterectomy (HALNU), the narrow working space and inevitable manipulation that occurs during the retroperitoneal approach (RP-HALNU) enhances tumor cell seeding in the bladder mucosa. This study was an attempt to investigate the differences in intravesical recurrence between transperitoneal HALNU (TP-HALNU) and RP-HALNU. Patients and Methods: From 1999 to 2011, a total of 197 patients with UTUC were enrolled. After excluding those with a previous history of bladder cancer, 170 patients were analyzed. Sixty-five of these underwent RP-HALNU, and 105 of these underwent TP-HALNU. The median follow-up periods were 39.2 and 46.2 months. Tumor location was divided into three groups: In the renal pelvis, in the ureter, and in both the renal pelvis and ureter. Results: There was no significant difference in the intravesical recurrence rate in relation to the different surgical approaches (P = 0.10), but tumor location in both the renal pelvis and ureter significantly increased the risk (hazard ratio [HR] = 3.11, P = 0.01). In addition, advanced T stage (HR = 9.63, P < 0.01) was the only significant risk factor related to death. Conclusions: In patients with UTUC, tumor location in both the renal pelvis and ureter determined higher susceptibility to intravesical recurrence. However, different surgical approaches to HALNU were not a significant risk factor for intravesical recurrence. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The association of posterior fossa malformation, facial cavernous hemangioma, arterial anomalies, coarctation of the aorta/cardiac defects and eye abnormalities (PHACE syndrome) represents a rare congenital anomaly with a broad spectrum of clinical manifestations and female predominance. We herein report on a girl who manifested the typical clinical features of PHACE syndrome, unusually associated with severe ipsilateral cerebral atrophy and hemiplegia. She received surgical aortoplasty, local steroid injection and laser therapy for the hemangioma, and intense physical therapy soon after diagnosis. The etiology of PHACE syndrome remains unclear, and its clinical spectrum is broad. The current case suggests that the spectrum of PHACE syndrome should be further expanded to include other forms of cerebral disorder. [Copyright &y& Elsevier]

Aim: To study the effect and mechanism of gonadotrophin-releasing hormone (GnRH) on murine Leydig cell steroidogenesis. Methods: Purified murine Leydig cells were treated with GnRH-I and-II agonists, and testosterone production and steroidogenic enzyme expressions were determined. Results: GnRH-I and-II agonists significantly stimulated murine Leydig cell steroidogenesis 60%–80% in a dose-and time-dependent manner ( P < 0.05). The mRNA expressions of steroidogenic acute regulatory (StAR) protein, P450scc, 3β-hydroxysteroid dehydrogenase (HSD), but not 17α-hydroxylase or 17β-HSD, were significantly stimulated by both GnRH agonists with a 1.5-to 3-fold increase ( P < 0.05). However, only 3β-HSD protein expression was induced by both GnRH agonists, with a 1.6-to 2-fold increase ( P < 0.05). Conclusion: GnRH directly stimulated murine Leydig cell steroidogenesis by activating 3β-HSD enzyme expression. [ABSTRACT FROM AUTHOR]