Clathrin-mediated trafficking of phospholipid flippases is required for local plasma membrane/cell wall damage repair in budding yeast.

Plasma membrane damage and repair frequently happen in cells. A critical process underlying plasma membrane repair is to redirect repair factors, such as protein kinase C and the exocyst complex, from the polarized site to the damage site. However, the mechanism underlying the repair factor delivery to the damage site remains unknown. Here, we demonstrate that clathrin-mediated trafficking of repair factors is involved in plasma membrane/cell wall repair in budding yeast. Using laser-induced plasma membrane/cell wall damage assay, we identified phospholipid flippases, Lem3-Dnf1/Dnf2 and Cdc50-Drs2, as essential clathrin cargos for plasma membrane/cell wall repair. We found that flippase impairment significantly compromised the recruitment of exocyst Exo70 to the damage site. In contrast, the recruitment of protein kinase C (Pkc1) was only mildly compromised. Taken together, clathrin-mediated trafficking of the phospholipid flippases is critical for the recruitment of exocyst to the damage site. Mechanisms to redirect exocyst via the clathrin and flippase-mediated pathways may be a general feature of effective plasma membrane repair in polarized cells.

Comparison of laparoscopic gastrectomy with 3-D/HD and 2-D/4 K camera system for gastric cancer: a prospective randomized control study.

PURPOSE: We conducted a prospective clinical control study to identify the best imaging technology among three-dimensional (3-D) high-definition (HD) stereovision and two-dimensional (2-D) ultra-high-resolution (4 K) technology and confirm their effects on surgical outcomes of laparoscopic gastrectomy for gastric cancer. METHODS: From April 2018 to August 2019, 50 patients were randomly classified into two groups based on the imaging technology (3-D/HD group = 25, 2-D/4 K = 25). After excluding eight patients based on laparoscopic findings, 42 patients were analyzed (3-D/HD group = 21, 2-D/4 K = 21). The primary endpoint was the operative time; the secondary endpoints were blood loss, postoperative infectious complications, and postoperative hospital stay. RESULTS: The patients' backgrounds were similar (sex, age, body mass index [BMI], stage, procedure, and extent of lymph node dissection). There were no significant differences in operative time (252 vs. 238 min, P = 0.70), total blood loss, postoperative infectious complications, and postoperative hospital stay between the two groups. However, video analysis of surgeries revealed a significantly shortened median operative time (18 vs. 25 min, P = 0.04) in the suturing step with 3-D/HD; the median number of camera cleaning procedures during suprapancreatic lymph node dissection was significantly lower with 2-D/4 K than with 3-D/HD (n = 4.4 vs. 2.8, P = 0.02). CONCLUSION: 3-D/HD and 2-D/4 K laparoscopic radical gastrectomies provide similar surgical outcomes. However, the 3-D monitor reduces suturing time during reconstruction, while the 4 K monitor reduces the number of camera cleaning procedures during lymphadenectomy. TRIAL REGISTRATION: Registered in the University Hospital Medical Information Network Clinical Trials Registry (identification number 000029227).

Taking antithrombic therapy during emergency laparoscopic cholecystectomy for acute cholecystitis does not affect the postoperative outcomes: a propensity score matched study.

BACKGROUND: Continuing antithrombic therapy (ATT) during surgery increases the risk of bleeding. However, it is difficult to discontinue the ATT in emergency surgery. Therefore, safety of emergency laparoscopic cholecystectomy (LC) for acute cholecystitis (AC) is still unclear. We aimed to clarify the affect of ATT during emergency LC for AC. METHODS: Patients with AC were classified into ATT group (n = 30) and non-ATT group (n = 120). Postoperative outcomes were compared after propensity score matching (n = 22). RESULTS: Higher level of c-reactive protein level and shorter activated partial thromboplastin time (APTT) was observed in ATT group than in non-ATT group after matching. No significant difference was found between other patient characteristics and perioperative results. Blood loss over 100 mL was observed in 8 patients. Multivariate analyze showed that APTT was an independent risk factor for bleeding over 100 mL (P = 0.039), while ACT and APT was not. CONCLUSIONS: Taking ATT does not affect the blood loss or complications during emergency LC for AC. Controlling intraoperative bleeding is essential for a safe postoperative outcome.

Enantioseparation of 3-Hydroxycarboxylic Acids via Diastereomeric Salt Formation by 2-Amino-1,2-diphenylethanol (ADPE) and Cinchonidine.

Enantioseparation of 3-hydroxycarboxylic acids via diastereomeric salt formation was demonstrated using 2-amino-1,2-diphenylethanol (ADPE) and cinchonidine as the resolving agents. Racemic 3-hydroxy-4-phenylbutanoic acid (rac-1), 3-hydroxy-4-(4-chlorophenyl)butanoic acid (rac-2), and 3-hydroxy-5-phenylpentanoic acid (rac-3) were efficiently resolved using these resolving agents. Moreover, the successive crystallization of the less-soluble diastereomeric salt of 1 and cinchonidine using EtOH yielded pure (R)-1 · cinchonidine salt in a high yield. The crystal structures of less-soluble diastereomeric salts were elucidated and it was revealed that hydrogen bonding and CH/π interactions play an important role in reinforcing the structure of the less-soluble diastereomeric salts.

Preoperative endoscopic tattooing using India ink to determine the resection margins during totally laparoscopic distal gastrectomy for gastric cancer.

PURPOSE: This study was conducted to determine whether establishing the proximal resection line using India ink tattooing can ensure safe resection margins during totally laparoscopic distal gastrectomy. METHODS: This retrospective study included 81 patients who underwent totally laparoscopic distal gastrectomy for gastric cancer on the lower two-thirds of the stomach. The proximal resection margins were analyzed with respect to the macroscopic type and clinical T stage, and the intraoperative appearance of the stain on the serosa was classified by reviewing surgical videos. RESULTS: R0 resection was performed in all patients. The rates of the intended margins were 89.2% in patients without a frozen section diagnosis and 84.2% in patients with differentiated type lesions who underwent a frozen section diagnosis; however, most patients with undifferentiated advanced lesions failed to achieve the intended resection margins. Intraoperative appearance revealed that 85.2% of patients had localized type stains, whereas 11.1% had widespread-type stains. CONCLUSIONS: Our procedure to determine the proximal resection line in totally laparoscopic distal gastrectomy is oncologically safe. However, careful observation of the resected specimen and a frozen section analysis should be performed for undifferentiated advanced lesions.

Feasibility of laparoscopic endoscopic cooperative surgery for non-ampullary superficial duodenal neoplasms: Single-arm confirmatory trial.

OBJECTIVE: Laparoscopic endoscopic cooperative surgery for duodenal tumors (D-LECS) has been developed to prevent duodenal leakage by reinforcing the endoscopic submucosal dissection site. However, there has been no prospective trial showing the feasibility of D-LECS. Herein, we conducted a single-arm confirmatory trial to evaluate the safety of D-LECS for non-ampullary superficial duodenal neoplasms. METHODS: This prospective single-center single-arm confirmatory trial analyzed patients with non-ampullary superficial duodenal neoplasms who underwent D-LECS. The primary endpoint was the incidence of any postoperative leakage occurring on the duodenal wall within 1 month postoperatively. The planned sample size was 20 patients, considering a threshold of 28% and one-sided alpha value of 5%. RESULTS: Between January 2015 and September 2018, 20 eligible patients were enrolled. Sixteen tumors were located in the second portion, three in the first portion, and one in the third portion of the duodenal region. The median operative time was 225 (134-361) min and the median blood loss was 0 (0-150) mL. Curative resection (R0) with negative margins was achieved in 19 cases. One case of postoperative leakage and one case of bleeding of grade 2 according to the Clavien-Dindo classification were observed in this series. The median duration of postoperative hospital stay was 9 (5-12) days. No local recurrence was observed in any patient during the median follow-up of 15.0 (12.0-38.0) months. CONCLUSIONS: This trial confirmed the safety and feasibility of D-LECS for non-ampullary superficial duodenal neoplasms with respect to the low incidence of postoperative duodenal leakage.

Skeletal muscle loss after laparoscopic gastrectomy assessed by measuring the total psoas area.

PURPOSE: Skeletal muscle loss after gastrectomy can worsen patients' quality of life and prognosis. Laparoscopic gastrectomy is less invasive than open gastrectomy and has become commonly performed. However, the degree of skeletal muscle loss after laparoscopic procedures remains unclear. We herein report the degree and risk factors of psoas muscle loss after laparoscopic gastrectomy for gastric cancer. METHODS: The total psoas area (TPA) on computed tomography of 50 consecutive patients who underwent laparoscopic total gastrectomy (LTG) and 167 consecutive patients who underwent laparoscopic distal gastrectomy (LDG) for gastric cancer was retrospectively evaluated at one postoperative year. The TPA loss was compared between LDG and LTG and univariate and multivariate analyses were performed to identify the risk factors for TPA loss > 10%. RESULTS: The median TPA decrease rate was 5.9% in the LDG group and 15.6% in the LTG group. LTG and postoperative respiratory complications were independent factors associated with a severe TPA loss of > 10%. In the LTG group, no independent factors were identified in a multivariate analysis. In the LDG group, postoperative complications were identified as an independent risk factor for TPA loss > 10%. CONCLUSIONS: Laparoscopic gastrectomy leads to postoperative TPA loss, especially in patients who underwent LTG and had postoperative respiratory complications. Postoperative complications after LDG were also a risk factor for TPA loss.

Meaning of C-reactive protein around esophagectomy for cStage III esophageal cancer.

PURPOSE: The prognosis of esophageal cancer is dismal, and the 3-year overall survival of cStage III does not reach 50.0%. C-reactive protein (CRP) is a well-known protein that reflects the short- and long-term operative outcomes of esophageal cancer. However, since elevated CRP levels are often observed in cStage III esophageal cancer, whether or not CRP still reflects the prognosis is unclear. METHODS: Eighty-four patients who were diagnosed with cStage III esophageal cancer and underwent R0/1 operation from January 2007 to December 2014 were retrospectively evaluated. RESULTS: The mean age was 66.8 years, and the majority of patients were male. The median preoperative and postoperative CRP levels were 0.15 and 1.47 mg/dl, respectively. A majority of the patients underwent thoracoscopic surgery, and the median blood loss and operation duration were 456 ml and 11.6 h, respectively. Forty-six patients (54.8%) died during the observation period, and the 3-year overall survival was 52.4%. A multivariate analysis showed that the preoperative CRP level, postoperative albumin level, blood loss, and complications were independent prognostic factors. A multiple linear regression analysis showed that an elevated postoperative CRP level was affected by the operation duration and preoperative CRP levels. CONCLUSIONS: These findings suggest that the preoperative CRP level is a prognostic factor for cStage III esophageal cancer and that postoperative elevation in the CRP level is affected by the operation duration.

[A Case of Severe Bradycardia Induced by Combination Chemotherapy with Cisplatin and 5-Fluorouracil].

A 78-year-old man with Stage III esophageal cancer was referred to our hospital. Combination chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5-FU) was initiated. The patient experienced bradycardia episodes after starting the cisplatin infusion on day 1; he was otherwise asymptomatic. Therefore, combination chemotherapy was continued. However, on day 4, his heart rate dropped to 22 beats/min, with no other symptoms; however, treatment was stopped. After treatment was stopped, the patient's heart rate improved gradually and returned to normal in a few days. Combination chemotherapy with CDDP and 5-FU is a useful treatment for esophageal cancer, but it may induce severe bradycardia. Therefore, we must perform infusion therapy with caution.

Evaluation of attenuation correction method for head holder in brain perfusion single-photon emission computed tomography.

Head holder attenuation affects brain perfusion single-photon emission computed tomography (SPECT) image quality. Here, we proposed a head holder-attenuation correction (AC) method using attenuation coefficient maps calculated by Chang's method from CT images. Then, we evaluated the effectiveness of the head holder-AC method by numerical phantom and clinical cerebral perfusion SPECT studies. In the numerical phantom, the posterior counts were 10.7% lower than the anterior counts without head holder-AC method. However, by performing head holder-AC, the posterior count recovered by approximately 6.8%, approaching the true value. In the clinical study, the normalized count ratio was significantly increased by performing the head holder-AC method in the posterior-middle cerebral artery, posterior cerebral artery and cerebellum regions. There were no significant increases in other regions. The head holder-AC method can correct the counts attenuated by the head holder.

Gonial angle and late implant loss: A retrospective clinical study.

PURPOSE: Occlusal overload can cause late implant loss. However, whether the magnitude of the occlusal force is a risk factor for late implant loss remains unclear. Thus, this clinical study aimed to determine the relationship between the gonial angle (GoA), which is associated with the magnitude of occlusal force, and late implant loss. METHODS: All implants with fixed prostheses placed at the Niigata University Hospital between April 2006 and August 2019 were included in this retrospective study. The implants with and without late loss were compared. Relevant variables, including smoking habits, diabetes mellitus status, remaining dentition, implant length and diameter, prosthesis design, retention systems, splinting, and GoA were assessed. Log-rank test and Cox proportional hazards regression analysis were used to estimate the adjusted hazard ratio (aHR) and to calculate the corresponding 95% confidence intervals (CI) for late implant loss. RESULTS: A total of 919 patients (349 men and 570 women) with 2512 implants were included in this study. Cox proportional hazards regression analysis revealed that a 10° decrease in the GoA (aHR, 1.588; 95% CI, 1.115-1.766; P = 0.010), smoking habits (aHR, 3.909; 95% CI, 2.131-7.168; P < 0.001), and male sex (aHR, 2.584; 95% CI, 1.376-4.850; P = 0.003) were significantly associated with late implant loss. CONCLUSIONS: Within the limitations of this retrospective study of 2512 implants, smaller GoA, smoking habits, and male sex were risk factors for late implant loss.

Rare Coexistence of Aldosterone-producing Adrenocortical Adenoma Confirmed by an Immunohistochemical Analysis of Steroidogenic Enzymes with Adrenal Ectopic Thyroid Tissue: A Case Report and Literature Review.

A 56-year-old man presented with a history of hypertension; clinically, the patient had primary aldosteronism (PA) and a 4-cm left adrenal tumor. The left adrenal glands, resected by adrenalectomy, also contained ectopic thyroid tissue (ETT). An immunohistochemical analysis of steroid-converting enzymes revealed an aldosterone-producing adenoma (APA). Among 19 previously reported cases of adrenal ETT, 4 had adrenal hormonal abnormalities, all of which were PA. This is the first case of adrenal ETT coexisting with APA, confirmed by steroid-converting enzyme expression. Further analyses using cumulative case data are required to clarify the correlation between adrenal ETT and APA.

Plasma membrane damage limits replicative lifespan in yeast and induces premature senescence in human fibroblasts.

Plasma membrane damage (PMD) occurs in all cell types due to environmental perturbation and cell-autonomous activities. However, cellular outcomes of PMD remain largely unknown except for recovery or death. In this study, using budding yeast and normal human fibroblasts, we found that cellular senescence-stable cell cycle arrest contributing to organismal aging-is the long-term outcome of PMD. Our genetic screening using budding yeast unexpectedly identified a close genetic association between PMD response and replicative lifespan regulations. Furthermore, PMD limits replicative lifespan in budding yeast; upregulation of membrane repair factors ESCRT-III (SNF7) and AAA-ATPase (VPS4) extends it. In normal human fibroblasts, PMD induces premature senescence via the Ca2+-p53 axis but not the major senescence pathway, DNA damage response pathway. Transient upregulation of ESCRT-III (CHMP4B) suppressed PMD-dependent senescence. Together with mRNA sequencing results, our study highlights an underappreciated but ubiquitous senescent cell subtype: PMD-dependent senescent cells.

Masseter muscle cross-sectional area and late implant failure: A case-control study.

INTRODUCTION: Occlusal overload is considered to be one of the causes of late implant failure. However, it is unclear whether the magnitude of the patient's occlusal force is a risk factor for late implant failure. PURPOSE: This case-control study aimed to clarify the association between the cross-sectional area (CSA) of the masseter muscle and late implant failure. METHODS: This case-control study was limited to implant-supported fixed prostheses. We compared cases with at least one late implant failure (n = 25 patients) to controls (n = 82 patients) without implant failure. Patients were matched by age, sex, year of surgery, jaw and tooth type, and bone graft. Log-rank and Cox proportional hazard regression analyses were used to identify possible risk factors for late implant failure. RESULTS: The incidence of late implant failure was significantly associated with masseter muscle CSA ≥504.5 mm2 (hazard ratio: 4.43; 95% CI: 1.82-10.79; p < 0.01). CONCLUSION: Higher masseter muscle CSA increases the risk of late implant failure.

Factor analysis for construct validity of a trunk impairment scale in Parkinson's disease: a cross-sectional study.

Objectives: To investigate the construct validity of the Trunk Impairment Scale (TIS), which was developed to assess trunk impairment in patients with stroke, in patients with Parkinson's disease (PD). Design: This retrospective, cross-sectional study enrolled consecutive PD inpatients. Correlation analysis was performed to clarify whether the TIS assessment was related to other balance functions, lower extremity muscle strength, or walking ability. Factor analysis was performed to see how the background factors of TIS differ from balance function, lower limb muscle strength, and walking ability. Results: Examining the data of 471 patients with PD, there were relationships between TIS and the Mini-Balance Evaluation Systems Test (r = 0.67), Barthel Index (r = 0.57), general lower limb extension torque (r = 0.51), two-minute walk test (r = 0.54), Hoehn and Yahr stage (r = -0.61), and Movement Disorder Society Unified Parkinson's Disease Rating Scale part III total points (r = -0.59). Factor analysis showed that TIS items were divided into three factors (an abdominal muscles and righting reflex component; a perception and verticality component; and a rotational component), differing from other scales that included clinical assessment items. Conclusion: The TIS can be useful for assessing the underlying trunk impairment as a basis for activities of daily living, gait function, and balance ability in patients with PD.

Distance of Peritoneum to Inferior Mesenteric Artery Predicts the Operation Time During Laparoscopic Colectomy for Sigmoid or Rectosigmoid Colon Cancer.

Background/Aim: Obesity is a major technical limiting factor for laparoscopic surgery because abundant visceral fat is known to extend the operation time. However, special hardware is needed to assess it. We hypothesized that the depth from the peritoneum to the bifurcation of the inferior mesenteric artery (IMA) defined as 'peritoneum to IMA distance (PID)' might be a simple predictive factor for extended operation time during laparoscopic colectomy. Patients and Methods: One hundred twenty-four patients who were diagnosed with sigmoid or rectosigmoid colon cancer and underwent laparoscopic colectomy were included. The patients were divided into two groups based on the operation time (210 min). The vertical distance from the peritoneum to the bifurcation of the inferior mesenteric artery was defined as PID. The factors eliciting an operation time longer than 210 min were investigated. Results: There was significant difference in sex, BMI, cT, cN, and PID between the Early group (<210 min) and Late group (≥210 min). Less blood loss was observed in the Early group than in the Late group. Multivariate analysis showed that PID was the only independent factor that affected operation time (p<0.001). Conclusion: PID predicts the operation time during laparoscopic colectomy for sigmoid or rectosigmoid colon cancer.

Quantitative Comparison of Surgical Device Usage in Laparoscopic Gastrectomy Between Surgeons' Skill Levels: an Automated Analysis Using a Neural Network.

BACKGROUND: Whether surgical device usage in laparoscopic gastrectomy differs with respect to operator's skill levels is unknown. Further, device usage analysis using artificial intelligence has not been reported to date. Herein, we compared the patterns of surgical device usage during laparoscopic gastrectomy for gastric cancer among surgeons at different skill levels. The data of device usage was acquired from laparoscopic video recordings using an automated surgical-instrument detection system. METHODS: In total, 100 video recordings of infrapyloric lymphadenectomy and 33 of D2 suprapancreatic lymphadenectomy during laparoscopic gastrectomy for gastric cancer were analyzed in this retrospective study. The system's accuracy was evaluated by comparing the automatic and the manual usage time. Surgical device usage patterns were compared between qualified and nonqualified surgeons of The Japan Society for Endoscopic Surgery Endoscopic Surgical Skill Qualification System. RESULTS: For every device, the automatic detection time and manual detection time were consistent with each other. In infrapyloric lymphadenectomy, the usage time proportions of dissector forceps and clip applier were higher among nonqualified operators than among qualified operators (dissector, 5.1% vs. 2.3%, P < 0.001; clip applier, 1.6% vs. 1.3%, P < 0.01). In suprapancreatic lymphadenectomy, the usage time proportions of energy devices, clip applier, and grasper forceps were significantly different (energy devices, 59.6% vs. 50.6%, P < 0.001; clip applier, 1.4% vs. 0.9%, P < 0.001; only grasper forceps; 18.3% vs. 27.9%, P = 0.022). CONCLUSIONS: Quantitative analysis of laparoscopic device usage using the automated surgical device detection system showed that the patterns of device usage during laparoscopic gastrectomy differed depending on surgeons' skill levels. These differences could suggest how the qualified and nonqualified surgeons performed the procedures.

Light Scattering and Rheological Studies of 3D/4D Printable Shape Memory Gels Based on Poly (N,N-Dimethylacrylamide-co-Stearyl Acrylate and/or Lauryl Acrylates).

In this work, we present the structural analysis of 3D/4D printable N,N-dimethylacrylamide (DMAAm)-co-stearyl acrylate (SA) and/or lauryl acrylate (LA)-based shape memory gels (SMGs). We characterized these gels by scanning microscopic light scattering technique (SMILS) where a time- and space-averaged correlation function is obtained to overcome the inhomogeneous media. Thus, the characteristic size of the gel internal network (mesh size, ξ) and crosslinking densities are estimated from the Einstein-Stokes formula. The rheological study of the SMGs revealed information about their mechanical strength and transition temperature. From the experimental storage modulus measured by rheological study, crosslinking density and mesh size of the network were also calculated. Both the techniques suggest that SMG with high crystalline content of SA monomer in the gel network contain smaller mesh size (1.13 nm for SMILS and 9.5 nm for rheology study) and high crosslinking density. The comparative study between the light scattering technique and rheological analysis through the quantitative analysis of crosslinking densities will be important to understand the structural properties of the SMGs.

Automated Surgical Instrument Detection from Laparoscopic Gastrectomy Video Images Using an Open Source Convolutional Neural Network Platform.

BACKGROUND: The common use of laparoscopic intervention produces impressive amounts of video data that are difficult to review for surgeons wishing to evaluate and improve their skills. Therefore, a need exists for the development of computer-based analysis of laparoscopic video to accelerate surgical training and assessment. We developed a surgical instrument detection system for video recordings of laparoscopic gastrectomy procedures. This system, the use of which might increase the efficiency of the video reviewing process, is based on the open source neural network platform, YOLOv3. STUDY DESIGN: A total of 10,716 images extracted from 52 laparoscopic gastrectomy videos were included in the training and validation data sets. We performed 200,000 iterations of training. Video recordings of 10 laparoscopic gastrectomies, independent of the training and validation data set, were analyzed by our system, and heat maps visualizing trends of surgical instrument usage were drawn. Three skilled surgeons evaluated whether each heat map represented the features of the corresponding operation. RESULTS: After training, the testing data set precision and sensitivity (recall) was 0.87 and 0.83, respectively. The heat maps perfectly represented the devices used during each operation. Without reviewing the video recordings, the surgeons accurately recognized the type of anastomosis, time taken to initiate duodenal and gastric dissection, and whether any irregular procedure was performed, from the heat maps (correct answer rates ≥ 90%). CONCLUSIONS: A new automated system to detect manipulation of surgical instruments in video recordings of laparoscopic gastrectomies based on the open source neural network platform, YOLOv3, was developed and validated successfully.