Anion Pathways in the NarK Nitrate/Nitrite Exchanger.

NarK nitrate/nitrite antiporter imports nitrate (a mineral form of the essential element nitrogen) into the cell and exports nitrite (a metabolite that can be toxic in high concentrations) out of the cell. However, many details about its operational mechanism remain poorly understood. In this work, we performed steered molecular dynamics simulations of anion translocations and quantum-chemistry model calculations of the binding sites to study the wild-type NarK protein and its R89K mutant. Our results shed light on the importance of the two strictly conserved binding-site arginine residues (R89 and R305) and two glycine-rich signature motifs (G164-M176 and G408-F419) in anion movement through the pore. We also observe conformational changes of the protein during anion migration. For the R89K mutant, our quantum calculations reveal a competition for a proton between the anion (especially nitrite) and lysine, which can potentially slow down or even trap the anion in the pore. Our findings provide a possible explanation for the striking experimental finding that the arginine-to-lysine mutation, despite preserving the charge, impedes or abolishes anion transport in such mutants of NarK and other similar nitrate/nitrite exchangers.

Recurrence, Reoperation, Pregnancy Rates, and Risk Factors for Recurrence after Ovarian Endometrioma Surgery: Long-Term Follow-Up of 756 Women

Purpose@#The aims of this study were to evaluate the cumulative recurrence, reoperation, and pregnancy rates after ovarian endometrioma surgery at a single institution for more than a 5-year follow-up period. @*Materials and Methods@#This study was conducted as a retrospective chart review of patients with ovarian endometrioma who underwent surgery between January 2008 and March 2016. Study subjects included premenopausal women with at least 5 years of follow-up. Exclusion criteria were patients with stage I or II ovarian endometrioma, those who underwent hysterectomy or bilateral oophorectomy, and presence of residual ovarian lesions on the first postoperative ultrasonography at 3–6 months. Recurrence was defined as a cystic mass by ultrasonography. @*Results@#A total of 756 patients were recruited. The median follow-up duration was 85.5 months (interquartile range, 71–107 months). Recurrent endometrioma was detected in 27.9% patients, and reoperation was performed in 8.3% patients. Cumulative rates at 24, 36, 60, and 120 months were 5.8%, 8.7%, 15.5% and 37.6%, respectively, for recurrence and 0.1%, 0.5%, 2.9%, and 15.1%, respectively, for reoperation. After multivariable analysis, age ≤31 years [hazard ratio (HR)=2.108; 95% confidence interval (CI)=1.522–2.921; p<0.001], no subsequent pregnancy (HR=1.851; 95% CI=1.309–2.617; p<0.001), and postoperative hormonal treatment ≤15 months (HR=2.869; 95% CI=2.088–3.941; p<0.001) were significant risk factors for recurrent endometrioma. Among 315 patients who desired pregnancy, 54.0% were able to have a successful pregnancy and delivery. @*Conclusion@#Considering that longer postoperative hormonal treatment is the sole modifiable factor for recurrent endometrioma, we recommend long-term hormonal treatment until subsequent pregnancy, especially in younger women.

Complications Including Capsular Contracture in Direct-to-Implant Breast Reconstruction With Textured Anatomical Versus Smooth Round Implants: A Single Center Retrospective Analysis / 한국유방암학회지

Purpose@#Implant-based breast reconstruction is the most common reconstruction method used after mastectomy in breast cancer patients. Many studies have compared the smooth round implants and textured anatomical implants. This study aimed to compare the complications, including capsular contracture, between these two implants used in direct-toimplant (DTI) breast reconstruction. @*Methods@#This retrospective chart review was performed using a prospectively maintained database from a single center. We identified patients who underwent mastectomy with DTI single-stage breast reconstruction at our hospital between August 2011 and June 2021. The overall complications, including capsular contracture, postoperative infection, seroma, hematoma, implant rupture, implant exposure, rippling, implant malposition, and nipple necrosis, were analyzed. @*Results@#In total, 340 breasts of 323 patients were reconstructed by the DTI approach using either textured anatomical (n = 203) or smooth round (n = 137) implants. The incidence of overall complications and capsular contracture was significantly lower with smooth round implants than with textured anatomical implants. Multivariate analysis showed that smooth round implants were associated with a reduced risk of overall complications (odds ratio [OR], 0.465; 95% confidence interval [CI], 0.265–0.813) and capsular contracture (OR, 0.475; 95% CI, 0.235–0.962). Particularly, smooth round implants were associated with a decreased risk of overall complications in patients not receiving adjuvant chemotherapy and a decreased risk of capsular contracture in patients with body mass index < 25 kg/m2 and in those not receiving adjuvant radiotherapy. @*Conclusion@#Smooth round implants demonstrated a decreased risk of overall complications and capsular contracture when compared with textured anatomical implants. These results may be utilized in counseling patients regarding the advantages and disadvantages of smooth round implants in DTI breast reconstruction.

Dual cortical tunneling method for endoscopic forehead lift

Background@#Endoscopic forehead lift with cortical tunneling is an effective option for rejuvenation of the upper third of the face. Although it has been considered safe and reliable, with relatively consistent long-term results, relapse and weakening of adhesion have been common problems. @*Methods@#We suggest the dual-tunneling method for overcoming these limitations. A total of 100 patients aged 17 to 65 years underwent forehead lifting with cortical tunneling by the senior author from August 2016 to December 2017. The single-tunnel method was applied in one half of the patients and the dual-tunnel method in the other half. Bilateral brow positions were measured immediately following surgery and 6 months later. @*Results@#For all cases, cortical tunneling was done at the central incision and both paramedian incisions; therefore, three tunnels were used in the control group and six tunnels in the experimental group. In the single-tunnel group, relapse distances were 2.39±0.83 mm for the medial brow and 3.26±0.91 mm for the lateral brow (6 months postoperatively; n=100). The dual-tunnel group showed significantly smaller (P<0.001) relapse distances, with values of 1.69±0.46 mm and 2.17±0.59 mm for the medial and lateral brow, respectively (6 months postoperatively; n=100). The experimental group did not show an increase in complications. @*Conclusions@#The dual-tunneling method, designed to minimize the cheese-wiring effect, uses a triangular plane to avoid a focal fixation. The fixation also includes the periosteum to hold the forehead tissue in place, inducing stronger adhesion.

Cumulative Recurrence Rate and Risk Factors for Recurrent Abdominal Wall Endometriosis after Surgical Treatment in a Single Institution

Purpose@#This study aimed to evaluate the cumulative recurrence rate and risk factors for recurrent abdominal wall endometriosis (AWE) after surgical treatment. @*Materials and Methods@#A retrospective cohort study was conducted at a single gynecological surgery center between January 2004 and December 2020. Patients who were surgically treated and followed up for at least 6 months after surgery were selected. @*Results@#Eighteen patients with pathologically diagnosed AWE were included in this study. The median follow-up duration was 22.5 months (range, 6–106). The median age was 37 years (range, 22–48), and 33.3% of the patients were nulliparous. Among the patients included in our study, 55.6% complained of a mass with cyclic pain, and 27.8% had a palpable mass. In addition, 22.2% of patients experienced recurrence with 17.5±9.7 months of mean time to recurrence. The cumulative recurrence rates at 24 and 60 months after surgical treatment of AWE were 23.8% and 39.1%, respectively. There were no statistically significant risk factors for the recurrence of AWE, including postoperative medical treatment. @*Conclusion@#The recurrence rate of AWE appears to be correlated with the follow-up duration. There was no statistically significant risk factor for the recurrence of AWE. Unlike ovarian endometriosis, postoperative hormonal treatment does not seem to lower the recurrence of AWE. The findings of the current study may help healthcare providers in counselling and managing patients with AWE.

Efficacy and safety of intravenous administration of high-dose selenium for preventing chemotherapy-induced peripheral neuropathy in platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer: study protocol for a phase III, double-blind, randomized study / 부인종양

The second-line chemotherapy using paclitaxel, carboplatin, and bevacizumab for treating platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer frequently cause chemotherapy-induced peripheral neuropathy (CIPN), which is significantly associated with deterioration of quality of life. Despite the potential of some agents to prevent and treat CIPN, and there is still a lack of evidence of the effect. Although selenium has been suggested as an antioxidant candidate to prevent CIPN, there are insufficient data regarding its effect due to its low dose by oral administration. Thus, we hypothesized intravenous administration of high-dose selenium (2,000 µg/day) at each cycle of the second-line chemotherapy would prevent and reduce CIPN in patients with platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer.MethodThis trial is an investigator-initiated, phase III, double-blinded, randomized controlled trial to evaluate the efficacy and safety of intravenous administration of high-dose selenium (2,000 µg/day) for preventing CIPN in patients with platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer who receive paclitaxel, carboplatin, and bevacizumab. A total of 68 patients will be randomly assigned to the experimental and control groups at a 1:1 ratio. As the primary endpoint, the incidence rate of CIPN three months after six cycles of chemotherapy will be compared between the two groups according to the combined criteria of neuropathy using the World Health Organization-CIPN criteria and Common Terminology Criteria for Adverse Events version 5.0. As secondary endpoints, we will compare adverse events, patient-reported quality of life, and requirement of concomitant drugs for reducing CIPN between the two groups.

Vaginal delivery after robot-assisted uterine artery-preserving radical trachelectomy for early-stage cervical cancer

Radical trachelectomy is conducted in women with early stage cervical cancer who strongly desire fertility preservation. To improve fertility outcomes, the preservation of the uterine artery has been suggested, which can be feasible by minimally invasive surgery using laparoscopy or robots. Although cesarean delivery is required for maternal and fetal health, vaginal delivery is a concern due to the fast delivery process of risk of preterm labor. We report a case of a 32-year-old nulliparous woman with stage IB1 cervical cancer who underwent robot-assisted uterine artery-preserving radical trachelectomy for improving fertility. This case is meaningful because she delivered by vaginal delivery after incision of the fibrotic ring at the level of uterovaginal anastomosis because delivery proceeded too quickly prior to the preparation of the cesarean delivery.

Clinical features that affect the number of pelvic lymph nodes harvested in patients with cervical cancer stage IB1 to IIA2

Objective@#To investigate clinical features that affect the number of pelvic lymph nodes (PLNs) harvested and prognostic significance of the number of PLNs removed in patients with stage IB1 to IIA2 cervical cancer. @*Methods@#Data from patients with cervical cancer whom underwent hysterectomy with PLN dissection between June 2004 and July 2015 were reviewed retrospectively. Data on clinicopathologic factors including age, height, and weight were collected. Data on the presence of PLN metastasis on imaging studies prior to surgery, number of PLNs harvested, and presence of metastasis in the harvested PLNs were retrieved from medical records. Clinical features associated with the number of PLNs harvested were analyzed. Disease-free survival (DFS) and overall survival (OS) according to the number of PLNs harvested were analyzed. @*Results@#During the study period, 210 patients were included. The height and weight of patients and preoperative positive positron emission tomography findings were significantly associated with a higher number of PLNs harvested. As a pathologic factor, larger tumor size was associated with a higher number of PLNs harvested. Furthermore, a higher number of PLNs harvested was associated with a higher number of metastatic PLNs and patients undergoing postoperative concurrent chemoradiation therapy. Patient height and tumor size were independent factors affecting the number of PLNs harvested in multivariate analysis. However, the number of PLNs harvested was not associated with DFS or OS. @*Conclusion@#The number of PLNs harvested during surgery was associated with patient height; however, this was not related to the prognosis of the disease.

Vaginal delivery after robot-assisted uterine artery-preserving radical trachelectomy for early-stage cervical cancer

Radical trachelectomy is conducted in women with early stage cervical cancer who strongly desire fertility preservation. To improve fertility outcomes, the preservation of the uterine artery has been suggested, which can be feasible by minimally invasive surgery using laparoscopy or robots. Although cesarean delivery is required for maternal and fetal health, vaginal delivery is a concern due to the fast delivery process of risk of preterm labor. We report a case of a 32-year-old nulliparous woman with stage IB1 cervical cancer who underwent robot-assisted uterine artery-preserving radical trachelectomy for improving fertility. This case is meaningful because she delivered by vaginal delivery after incision of the fibrotic ring at the level of uterovaginal anastomosis because delivery proceeded too quickly prior to the preparation of the cesarean delivery.

A new 3, 4-epoxyfurocoumarin from Heracleum moellendorffii Roots

Activity-guided isolation of Heracleum moellendorffii roots led to four coumarin derivatives as acetylcholinesterase inhibitors. The structures of these isolates were characterized by spectroscopic method to be angelicin (1), isobergapten (2), pimpinellin (3), and (3S, 4R)-3, 4-epoxypimpinellin (4). All the isolated compounds 1, 2, 3, and 4 showed moderate inhibition activities against acetylcholinesterase with the IC₅₀ values of 10.2, 18.1, 21.5 and 22.9 µM, respectively. (3S, 4R)-3, 4-Epoxypimpinellin (4) was newly isolated from the plant source.

Upregulation of CD47 in Regulatory T Cells in Atopic Dermatitis

PURPOSE: Regulatory T (Treg) cells are key modulators in the immune system. Recent studies have shown that atopic dermatitis (AD) patients have higher numbers of Treg cells; however, little is known about the specific phenotype and function of Treg cells in AD. MATERIALS AND METHODS: To identify differentially expressed proteins in peripheral induced Treg cells in AD and naturally derived Treg cells in normal controls, CD4?CD25? Treg cells were isolated from thymus tissue of normal mice and the spleens of AD mice. Membrane proteins were extracted, and quantitative proteomics labeling with Tandem Mass Tags (TMT) was performed, followed by one-dimensional liquid chromatography/tandem mass spectrometry analysis. RESULTS: Using TMT labeling, we identified 510 proteins, including 63 membrane proteins and 16 plasma membrane proteins. CD47 was one of the upregulated proteins in Treg cells in AD spleens. Although CD47 was expressed in all CD4? and CD8? T cells, a significantly higher expression of CD47 was observed in the Treg cells of AD mice and AD patients than in those of normal mice and healthy controls. Furthermore, Treg cells from the spleen showed a significantly higher expression of CD47 than those from the thymus. CONCLUSION: We found that CD47 is highly expressed in the Treg cells of AD mice, particularly in the spleen. Based on our results, we propose that CD47(high) Treg cells are likely induced Treg cells and that upregulated CD47 in the Treg cells of AD patients may play a role in the increased population of Treg cells in AD.

Upregulation of CD47 in Regulatory T Cells in Atopic Dermatitis

PURPOSE: Regulatory T (Treg) cells are key modulators in the immune system. Recent studies have shown that atopic dermatitis (AD) patients have higher numbers of Treg cells; however, little is known about the specific phenotype and function of Treg cells in AD. MATERIALS AND METHODS: To identify differentially expressed proteins in peripheral induced Treg cells in AD and naturally derived Treg cells in normal controls, CD4?CD25? Treg cells were isolated from thymus tissue of normal mice and the spleens of AD mice. Membrane proteins were extracted, and quantitative proteomics labeling with Tandem Mass Tags (TMT) was performed, followed by one-dimensional liquid chromatography/tandem mass spectrometry analysis. RESULTS: Using TMT labeling, we identified 510 proteins, including 63 membrane proteins and 16 plasma membrane proteins. CD47 was one of the upregulated proteins in Treg cells in AD spleens. Although CD47 was expressed in all CD4? and CD8? T cells, a significantly higher expression of CD47 was observed in the Treg cells of AD mice and AD patients than in those of normal mice and healthy controls. Furthermore, Treg cells from the spleen showed a significantly higher expression of CD47 than those from the thymus. CONCLUSION: We found that CD47 is highly expressed in the Treg cells of AD mice, particularly in the spleen. Based on our results, we propose that CD47(high) Treg cells are likely induced Treg cells and that upregulated CD47 in the Treg cells of AD patients may play a role in the increased population of Treg cells in AD.

Membrane Docking of the Synaptotagmin 7 C2A Domain: Electron Paramagnetic Resonance Measurements Show Contributions from Two Membrane Binding Loops.

The synaptotagmin (Syt) family of proteins plays an important role in vesicle docking and fusion during Ca(2+)-induced exocytosis in a wide variety of cell types. Its role as a Ca(2+) sensor derives primarily from its two C2 domains, C2A and C2B, which insert into anionic lipid membranes upon binding Ca(2+). Syt isoforms 1 and 7 differ significantly in their Ca(2+) sensitivity; the C2A domain from Syt7 binds Ca(2+) and membranes much more tightly than the C2A domain from Syt1, at least in part because of greater contributions from the hydrophobic effect. While the structure and membrane activity of Syt1 have been extensively studied, the structural origins of differences between Syt1 and Syt7 are unknown. This study used site-directed spin labeling and electron paramagnetic resonance spectroscopy to determine depth parameters for the Syt7 C2A domain, for comparison to analogous previous measurements with the Syt1 C2A domain. In a novel approach, the membrane docking geometry of both Syt1 and Syt7 C2A was modeled by mapping depth parameters onto multiple molecular dynamics-simulated structures of the Ca(2+)-bound protein. The models reveal membrane penetration of Ca(2+) binding loops 1 (CBL1) and 3 (CBL3), and membrane binding is more sensitive to mutations in CBL3. On average, Syt7 C2A inserts more deeply into the membrane than Syt1 C2A, although depths vary among the different structural models. This observation provides a partial structural explanation for the hydrophobically driven membrane docking of Syt7 C2A.

Membrane Docking of the Synaptotagmin 7 C2A Domain: Computation Reveals Interplay between Electrostatic and Hydrophobic Contributions.

The C2A domain of synaptotagmin 7 (Syt7) is a Ca(2+) and membrane binding module that docks and inserts into cellular membranes in response to elevated intracellular Ca(2+) concentrations. Like other C2 domains, Syt7 C2A binds Ca(2+) and membranes primarily through three loop regions; however, it docks at Ca(2+) concentrations much lower than those required for other Syt C2A domains. To probe structural components of its unusually strong membrane docking, we conducted atomistic molecular dynamics simulations of Syt7 C2A under three conditions: in aqueous solution, in the proximity of a lipid bilayer membrane, and embedded in the membrane. The simulations of membrane-free protein indicate that Syt7 C2A likely binds three Ca(2+) ions in aqueous solution, consistent with prior experimental reports. Upon membrane docking, the outermost Ca(2+) ion interacts directly with lipid headgroups, while the other two Ca(2+) ions remain chelated by the protein. The membrane-bound domain was observed to exhibit large-amplitude swinging motions relative to the membrane surface, varying by up to 70° between a more parallel and a more perpendicular orientation, both during and after insertion of the Ca(2+) binding loops into the membrane. The computed orientation of the membrane-bound protein correlates well with experimental electron paramagnetic resonance measurements presented in the preceding paper ( DOI: 10.1021/acs.biochem.5b00421 ). In particular, the strictly conserved residue Phe229 inserted stably ∼4 Å below the average depth of lipid phosphate groups, providing critical hydrophobic interactions anchoring the domain in the membrane. Overall, the position and orientation of Syt7 C2A with respect to the membrane are consistent with experiments.

Eccrine Poroma Clinically Mimicking Ingrowing Toenail Complicated with Granulation Tissue

No abstract available.