On the Conformation of the COOH-terminal Domain of the Large Mechanosensitive Channel MscL

COOH-terminal (S3) domains are conserved within the MscL family of bacterial mechanosensitive channels, but their function remains unclear. The X-ray structure of MscL from Mycobacterium tuberculosis (TbMscL) revealed cytoplasmic domains forming a pentameric bundle (Chang, G., R.H. Spencer, A.T. Lee, M.T. Barclay, and D.C. Rees. 1998. Science. 282:2220–2226). The helices, however, have an unusual orientation in which hydrophobic sidechains face outside while charged residues face inside, possibly due to specific crystallization conditions. Based on the structure of pentameric cartilage protein , we modeled the COOH-terminal region of E. coli MscL to better satisfy the hydrophobicity criteria, with sidechains of conserved aliphatic residues all inside the bundle. Molecular dynamic simulations predicted higher stability for this conformation compared with one modeled after the crystal structure of TbMscL, and suggested distances for disulfide trapping experiments. The single cysteine mutants L121C and I125C formed dimers under ambient conditions and more so in the presence of an oxidant. The double-cysteine mutants, L121C/L122C and L128C/L129C, often cross-link into tetrameric and pentameric structures, consistent with the new model. Patch-clamp examination of these double mutants under moderately oxidizing or reducing conditions indicated that the bundle cross-linking neither prevents the channel from opening nor changes thermodynamic parameters of gating. Destabilization of the bundle by replacing conservative leucines with small polar residues, or complete removal of COOH-terminal domain (Δ110–136 mutation), increased the occupancy of subconducting states but did not change gating parameters substantially. The Δ110–136 truncation mutant was functional in in vivo osmotic shock assays; however, the amount of ATP released into the shock medium was considerably larger than in controls. The data strongly suggest that in contrast to previous gating models (Sukharev, S., M. Betanzos, C.S. Chiang, and H.R. Guy. 2001a. Nature. 409:720–724.), S3 domains are stably associated in both closed and open conformations. The bundle-like assembly of cytoplasmic helices provides stability to the open conformation, and may function as a size-exclusion filter at the cytoplasmic entrance to the MscL pore, preventing loss of essential metabolites

Antegrade pampiniform plexus venography in recurrent varicocele: Case report and anatomy review

Varicoceles are often treated with percutaneous embolization, using fibered coils and sclerosing agents, with the latter targeted at occlusion of pre-existing collateral veins. While various methods of surgical and embolization treatment are available, varicoceles may still recur from venous collateralization. We present a case, where following demonstration of complete occlusion of the right and left gonadal veins, direct puncture of the pampiniform venous plexus under ultrasound guidance revealed recurrent varicoceles supplied by anastomoses from the ipsilateral saphenous and femoral veins to the pampiniform plexus. In doing so, we describe a technique of percutaneous pampiniform venography in a case where the pertinent anatomy was not easily demonstrated by other methods

Repair of a Post-Hepatectomy Posterior Sectoral Duct Injury Secondary to Anomalous Bile Duct Anatomy Using a Novel Combined Surgical-Interventional Radiologic Approach

A 64-year-old woman with a completely transected posterior sectoral duct following extended hepatectomy underwent a combined operative procedure with interventional radiology and surgery to restore biliary-enteric drainage. The anterior and posterior sectoral ducts were identified, and catheters were inserted into both systems. The posterior sectoral catheter was placed intraoperatively through a preoperatively placed sheath, and a new tunnel was created through the regenerated liver surface. Biliary-enteric anastomoses were created over the stents

Sequential Interventional Management of Osseous Neoplasms via Embolization, Cryoablation, and Osteoplasty

© 2019 Sri Hari Sundararajan et al. The purpose of this study is to determine if sequential interventional therapy can become a mainstay option in providing palliation from fastidious osseous neoplasms in patients with pain refractory to oral analgesia and radiotherapy. This retrospective monocentric study was approved by our institutional review board. Between July 2012 and August 2014, we reviewed 15 patients (6 women, 9 men; age range of 36-81 years) who underwent embolization followed by cryoablation, with or without osteoplasty. Patient demographics and tumor characteristics, including primary histology and the location of metastasis, were included in our review. Pain intensity at baseline, after radiotherapy, and after sequential interventional therapy was reviewed using the hospital electronic medical record. The use of oral analgesia and procedural complications was also noted. Data was then assessed for normality and a two-tailed Student\u27s t-test was performed on mean pain scores for difference phases of treatment. While radiotherapy offers pain relief with a mean pain score of 7.25 ±1.5 (p =\u3c.0001), sequential interventional therapy results in better comfort as demonstrated by a mean pain score of 3.9 ± 2.6 (p=.0015). Moreover, all patients who reported oral analgesic use at presentation reported a decrease in their requirement after sequential interventional therapy. Embolization and cryoablation were performed in all patients, while osteoplasty was indicated in 6 cases. There was no difference in postprocedural pain intensity between patients who required osteoplasty and patients who did not (p = 0.7514). There were no complications observed during treatment. This retrospective study shows that sequential intervention with transarterial embolization, cryoablation, and osteoplasty is both safe and efficacious for bone pain refractory to the current standard of care. We demonstrated that this combination therapy has the potential to become an effective mainstay treatment paradigm in the palliative care of osseous neoplasm to improve quality of life

Sequential Interventional Management of Osseous Neoplasms via Embolization, Cryoablation, and Osteoplasty

The purpose of this study is to determine if sequential interventional therapy can become a mainstay option in providing palliation from fastidious osseous neoplasms in patients with pain refractory to oral analgesia and radiotherapy. This retrospective monocentric study was approved by our institutional review board. Between July 2012 and August 2014, we reviewed 15 patients (6 women, 9 men; age range of 36-81 years) who underwent embolization followed by cryoablation, with or without osteoplasty. Patient demographics and tumor characteristics, including primary histology and the location of metastasis, were included in our review. Pain intensity at baseline, after radiotherapy, and after sequential interventional therapy was reviewed using the hospital electronic medical record. The use of oral analgesia and procedural complications was also noted. Data was then assessed for normality and a two-tailed Student’s t-test was performed on mean pain scores for difference phases of treatment. While radiotherapy offers pain relief with a mean pain score of 7.25 ±1.5 (p =<.0001), sequential interventional therapy results in better comfort as demonstrated by a mean pain score of 3.9 ± 2.6 (p=.0015). Moreover, all patients who reported oral analgesic use at presentation reported a decrease in their requirement after sequential interventional therapy. Embolization and cryoablation were performed in all patients, while osteoplasty was indicated in 6 cases. There was no difference in postprocedural pain intensity between patients who required osteoplasty and patients who did not (p = 0.7514). There were no complications observed during treatment. This retrospective study shows that sequential intervention with transarterial embolization, cryoablation, and osteoplasty is both safe and efficacious for bone pain refractory to the current standard of care. We demonstrated that this combination therapy has the potential to become an effective mainstay treatment paradigm in the palliative care of osseous neoplasm to improve quality of life