Targeted Electromyographic Biofeedback With Endoanal Electrostimulation for Anal Incontinence.

Purpose. Anal incontinence (AI) is a disabling condition with a variable response to conservative physical therapies. We assess the utility of combining electromyographic biofeedback with endoanal electrostimulation targeted to the weakest areas of the pelvic floor using the MAPLe® probe (Multiple Array Probe Leiden Novuqare). Methods. Patients with AI unresponsive to conservative measures were assessed before and after treatment with anorectal manometry (ARM), electromyography (EMG), Wexner Continence Scoring, Visual Analog Scoring (VAS), FIQL and SF-12 quality of life determination. Results. Of 29 patients in the final analysis, there was an improvement in the mean Wexner continence score from 13.59 to 8.03 and a concomitant improvement in the reported VAS from 3.45 to 6.72. Both Wexner continence and VAS scores were maintained during follow-up. Maximum voluntary manometric contraction significantly improved from 91.76 mmHg to 110.33 mmHg with no changes in resting pressure. The EMG values ​​(µV) that significantly improved included the average and peak resistance, the average general voluntary contraction, and the average and peak voluntary contraction for both the external anal sphincter and the puborectalis. In the FIQL, behavior, depression and shame domains improved after treatment and during follow-up with lifestyle improvements detected at 6 and 12 months. Physical and mental components of the SF-12 improved at 6 and 12 months. Conclusions. Targeted electromyographic biofeedback and endoanal electrostimulation using MAPLe® probe in AI patients sustainably improves objective ARM and EMG parameters along with subjective reporting of continence severity, VAS, and quality of life.

Coordinated and sequential activation of neutral and acidic DNases during interdigital cell death in the embryonic limb.

Interdigital tissue regression during embryonic development is one of the most representative model systems of morphogenetic cell death, but the degenerative cascade accounting for this process awaits clarification. Although the canonical apoptotic caspase pathway appears to be activated in the interdigital mesenchyme committed to die, neither genetic nor chemical blockage of caspases or their downstream effectors, is sufficient to prevent cell death. Hence, alternative and/or complementary dying pathways must also be responsible for this degenerative process. In this work we have chosen to study the endonucleases during the regression of the interdigital tissue of avian embryos to gain insights into the molecular mechanisms accounting for programmed cell death in this system. We show that caspase activated DNase, which is a neutral DNase associated with the caspase apoptotic pathway, appears to be the main endonuclease only at an initial phase of interdigit regression. However at peak stages of the degenerative process, the acidic DNases L-DNase II and lysosomal DNase IIB become predominant in the system and markers for cell autophagy become moderately up-regulated. Consistent with the activation of acidic endonucleases we observed that microenvironmental pH value in the interdigits decreased to levels only appropriate for acidic enzymes. Furthermore, we found that overexpression of lysosomal DNase IIB in embryonic limb mesoderm promoted cell death, which was also accompanied by up-regulation and activation of L-DNase II. Up-regulation of acidic DNases was maintained in interdigits explanted to culture dishes, where the participation of exogenous professional phagocytes of hematopoietic origin is avoided. Finally, and consistent with all our findings, up-regulation of acidic DNases was much reduced in the webbed interdigits of duck embryos, characterized by a rudimentary interdigital degenerative process. We conclude that the regression of the interdigital tissue involves a coordinated and sequential activation of the caspase and lysosomal degenerative molecular cascades.