Study Type – Diagnostic (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Pelvic floor muscle training (PFMT) and transvaginal electrical stimulation (TES) are two commonly used forms of conservative treatment for stress urinary incontinence (SUI). PFMT may build up the structural support of the pelvis, but many SUI patients are unable to perform PFMT effectively and its primary disadvantage is lack of long‐term patient compliance. TES is a passive treatment that produces PFM contraction and patient compliance with it is good; however, its effect is not as good as that of PFMT when performed correctly. Electrical pudendal nerve stimulation (EPNS) combines the advantages of PFMT and TES and incorporates the technique of deep insertion of long needles. In this study, simultaneous perineal ultrasound and vaginal pressure measurement prove that EPNS can contract the PFM and simulate PFMT. It is shown that EPNS is an alternative therapy for female SUI patients who fail PFMT and TES and the therapy can also be used for severe SUI. OBJECTIVES To prove that electrical pudendal nerve stimulation (EPNS) can contract the pelvic floor muscles (PFM) and simulate pelvic floor muscle training (PFMT). To show that EPNS is an alternative therapy for female stress urinary incontinence (SUI) that does not respond effectively to PFMT and transvaginal electrical stimulation (TES). PATIENTS AND METHODS Thirty‐five female patients with SUI who did not respond effectively to PFMT and TES (group I) were enrolled and 60 other female patients with SUI were allocated to group II (30 patients) and group III (30 patients). Long needles were deeply inserted into four sacral points and electrified to stimulate the pudendal nerves. Group I and group II were treated by a doctor skilled in performing EPNS and group III, by a doctor unskilled in performing EPNS. When EPNS was performed in group I, perineal ultrasonographic PFM movements, vaginal pressure (VP) and PFM electromyography were recorded simultaneously. The therapeutic effects were evaluated according to objective and subjective criteria RESULTS When EPNS was performed correctly, the patient felt strong PFM contractions. Simultaneous recordings in group I showed: B‐mode cranio‐caudal PFM movements; M‐mode PFM movement curves (amplitude: about 1 mm, n= 31); a sawtooth curve of VP changes (2.61 ± 1.29 cmH2O, n= 34); and PFM myoelectric waves (amplitude: 23.9 ± 25.3 µV). If during the EPNS process the electric current was stopped or its intensity was reduced to about 7–12 mA or the two lower needles were drawn back, then the above ultrasonographic PFM movements and VP changes disappeared. In group I, the incontinence severity and quality of life score was 16.5 ± 4.0 before treatment and decreased to 4.2 ± 4.0 after 27.5 ± 11.9 sessions of treatment (P < 0.01). At the end of treatment, 100% improvement occurred in 16 cases (45.7%). A 2‐year follow‐up showed that 100% improvement occurred in 14 of cases (40.0%). In group II, the incontinence sever...

Electrical pudendal nerve stimulation is more effective than transvaginal electrical stimulation in treating drug refractory, female idiopathic urgency urinary incontinence.

Background and Aims Sam50, a key component of the sorting and assembly machinery (SAM) complex, is also involved in bridging mitochondrial outer‐membrane and inner‐membrane contacts. However, the physiological and pathological functions of Sam50 remain largely unknown. Approach and Results Here we show that Sam50 interacts with MICOS (mitochondrial contact site and cristae organizing system) and ATAD3 (ATPase family AAA domain‐containing protein 3) to form the Sam50‐MICOS‐ATAD3‐mtDNA axis, which maintains mtDNA stability. Loss of Sam50 causes mitochondrial DNA (mtDNA) aggregation. Furthermore, Sam50 cooperates with Mic60 to bind to cardiolipin, maintaining the integrity of mitochondrial membranes. Sam50 depletion leads to cardiolipin externalization, which causes mitochondrial outer‐membrane and inner‐membrane (including crista membrane) remodeling, triggering Bax mitochondrial recruitment, mtDNA aggregation, and release. Physiologically, acetaminophen (an effective antipyretic and analgesic)–caused Sam50 reduction or Sam50 liver‐specific knockout induces mtDNA release, leading to activation of the cGAS‐STING pathway and liver inflammation in mice. Moreover, exogenous expression of Sam50 remarkably attenuates APAP‐induced liver hepatoxicity. Conclusions Our findings uncover the critical role of Sam50 in maintaining mitochondrial membrane integrity and mtDNA stability in hepatocytes and reveal that Sam50 depletion–induced cardiolipin externalization is a signal of mtDNA release and controls mtDNA‐dependent innate immunity.

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