Robot assisted exploration of the Alcock canal: a novel surgical technique.

OBJECTIVE: To demonstrate a safe and reproducible surgical approach to the Alcock canal with a full decompression of the pudendal nerve. SETTING: Pudendal neuralgia, a condition causing debilitating pelvic pain, is traditionally managed through a trans-gluteal incision.1-2 This surgical approach offers limited visualization and ability for nerve decompression.3 With the current technique, a full exposure and decompression of the pudendal nerve was achieved. PARTICIPANTS: A 44-year-old para 2 with symptoms of left pudendal neuralgia. INTERVENTIONS: A 44-year-old para 2 presented with burning vaginal pain radiating to the left groin that was aggravated with sitting. She underwent a robotic-assisted left sacrospinous ligament transection and fasciotomy of the obturator internus muscle for suspected pudendal neuralgia. The surgery was performed with three robotic ports using the daVinci® Xi robotic system. CONCLUSION: With the enhanced access to the pudendal nerve provided by the novel surgical technique demonstrated in this study, a more comprehensive nerve decompression can be performed. This technique was successfully applied to a patient with pudendal neuralgia. There were no immediate intra-operative or post-operative complications. In short-term follow-up, the patient had significant relief of preoperative symptoms. While all surgical procedures for pudendal neuralgia have a risk of pudendal nerve and vessel injury,4 the presented technique has the potential to limit these risks by providing an enhanced view of the relevant anatomy. Future adaptation and refinement of this technique may contribute to the advancement of the surgical management of pudendal neuralgia.

"I just need to be with my family": resettlement experiences of asylum seeker and refugee survivors of torture.

A global migration of individuals fleeing persecution, violence and armed conflict reached almost 60 million world-wide in 2015. This world-wide crisis of displacement reflects people seeking safety across borders and oceans; dangerous journeys that compound the trauma endured by these women, men and children. Refugees/asylum seekers face barriers upon entry to the U.S. The Western New York Center for Survivors (WNYCST) provides care coordination/trauma-informed care to mitigate these challenges. The objective of this study was to explore the resettlement experiences of survivors of torture living in Western New York, who had received services from the WNYCST; identifying challenges, unmet needs, and services that were helpful. Secondarily, we describe the experiences of asylum seekers and legally resettled refugees, who due to their differing legal status, might be expected to have different experiences. Data were collected using semi-structured qualitative interviews. RESULTS: Three themes emerged: mental health challenges, relating to their experiences in their home country and their separation from family; unmet needs, including lack of a sense of purpose and meaning, difficulty navigating services, and missing connections to community; and coping strategies, including WNYCST assistance with connecting with sources of social support in their new community. WNYCST services were helpful, particularly the assistance and connection with care coordinators and local support groups. This care and outreach helped to mitigate feelings of separation and apartness from their home countries and families. CONCLUSIONS: Some refugees/asylum seekers continue to struggle with unmet needs, issues of loss and isolation. If care providers recognize signs of stress early, appropriate interventions can be implemented. Care connections and trauma informed treatment with an emphasis on recreating ties with communities, may be one important factor in ensuring successful integration.

FOXQ1 controls the induced differentiation of melanocytic cells.

Oncogenic transcription factor FOXQ1 has been implicated in promotion of multiple transformed phenotypes in carcinoma cells. Recently, we have characterized FOXQ1 as a melanoma tumor suppressor that acts via repression of N-cadherin gene, and invasion and metastasis. Here we report that FOXQ1 induces differentiation in normal and transformed melanocytic cells at least partially via direct transcriptional activation of MITF gene, melanocytic lineage-specific regulator of differentiation. Importantly, we demonstrate that pigmentation induced in cultured melanocytic cells and in mice by activation of cAMP/CREB1 pathway depends in large part on FOXQ1. Moreover, our data reveal that FOXQ1 acts as a critical mediator of BRAFV600E-dependent regulation of MITF levels, thus providing a novel link between two major signal transduction pathways controlling MITF and differentiation in melanocytic cells.

Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1.

Lineage-specific regulation of tumor progression by the same transcription factor is understudied. We find that levels of the FOXQ1 transcription factor, an oncogene in carcinomas, are decreased during melanoma progression. Moreover, in contrast to carcinomas, FOXQ1 suppresses epithelial-to-mesenchymal transition, invasion, and metastasis in melanoma cells. We find that these lineage-specific functions of FOXQ1 largely depend on its ability to activate (in carcinomas) or repress (in melanoma) transcription of the N-cadherin gene (CDH2). We demonstrate that FOXQ1 interacts with nuclear ß-catenin and TLE proteins, and the ß-catenin/TLE ratio, which is higher in carcinoma than melanoma cells, determines the effect of FOXQ1 on CDH2 transcription. Accordingly, other FOXQ1-dependent phenotypes can be manipulated by altering nuclear ß-catenin or TLE proteins levels. Our data identify FOXQ1 as a melanoma suppressor and establish a mechanism underlying its inverse lineage-specific transcriptional regulation of transformed phenotypes.

Complex mutual regulation of facilitates chromatin transcription (FACT) subunits on both mRNA and protein levels in human cells.

Facilitates chromatin transcription (FACT) is a chromatin remodeling complex with two subunits: SSRP1 and SPT16. Mechanisms controlling FACT levels are of interest, since the complex is not expressed in most differentiated cells, but is frequently upregulated in cancer, particularly in poorly differentiated, aggressive tumors. Moreover, inhibition of FACT expression or function in tumor cells interferes with their survival. Here we demonstrate that SSRP1 and SPT16 protein levels decline upon induction of cellular differentiation or senescence in vitro and that similar declines in protein levels for both SSRP1 and SPT16 occur upon RNAi-mediated knockdown of either SSRP1 or SPT16. The interdependence of SSRP1 and SPT16 protein levels was found to be due to their association with SSRP1 and SPT16 mRNAs, which stabilizes the proteins. In particular, presence of SSRP1 mRNA is critical for SPT16 protein stability. In addition, binding of SSRP1 and SPT16 mRNAs to the FACT complex increases the stability and efficiency of translation of the mRNAs. These data support a model in which the FACT complex is stable when SSRP1 mRNA is present, but quickly degrades when SSRP1 mRNA levels drop. In the absence of FACT complex, SSRP1 and SPT16 mRNAs are unstable and inefficiently translated, making reactivation of FACT function unlikely in normal cells. Thus, we have described a complex and unusual mode of regulation controlling cellular FACT levels that results in amplified and stringent control of FACT activity. The FACT dependence of tumor cells suggests that mechanisms controlling FACT levels could be targeted for anticancer therapy.