Possible monitoring of mesophotic scleractinian corals using an underwater mini-ROV to sample coral eDNA.

Mesophotic coral ecosystems (MCEs) are light-dependent tropical or subtropical communities occurring at depths of 30-150 m. Broader surveys of MCEs are needed to better understand stony corals, the keystone species of coral-reef ecosystems. While MCEs have been studied by professional SCUBA divers and with deep-sea robots, comprehensive surveys of MCEs are required. An eDNA metabarcoding method has recently been used to survey scleractinian corals in shallow reefs. We tested whether MCEs might be more comprehensively surveyed by collecting seawater samples using an underwater mini-remote operated vehicle (mini-ROV). Seawater was collected 1-2 m above reef tops at depths of 20-80 m at 24 sites in six locations around the Zamami Islands (Okinawa, Japan). Water samples were then subjected to coral-specific eDNA amplification. Metabarcoding analyses of amplicons showed that except for one site, coral-specific eDNA from approximately 0.5 l seawater samples was sufficient to identify genera. The proportion of Acropora eDNA was higher at shallow reefs and upper ridges of slopes, while the proportion of Porites increased at mesophotic sites. Although further technical improvements are required, this study suggests that it may be possible to monitor mesophotic corals to the generic level using eDNA collected using mini-ROVs.

Role of PPARα in inflammatory response of C2C12 myotubes.

Recent studies have shown a role of inflammation in muscle atrophy and sarcopenia. However, no anti-inflammatory pharmacotherapy has been established for the treatment of sarcopenia. Here, we investigate the potential role of PPARα and its ligands on inflammatory response and PGC-1α gene expression in LPS-treated C2C12 myotubes. Knockdown of PPARα, whose expression was upregulated upon differentiation, augmented IL-6 or TNFα gene expression. Conversely, PPARα overexpression or its activation by ligands suppressed 2-h LPS-induced cytokine expression, with pemafibrate attenuating NF-κB or STAT3 phosphorylation. Of note, reduction of PGC-1α gene expression by LPS treatment for 24 hours was partially reversed by fenofibrate. Our data demonstrate a critical inhibitory role of PPARα in inflammatory response of C2C12 myotubes and suggest a future possibility of PPARα ligands as a candidate for anti-inflammatory therapy against sarcopenia.

Demonstration of a non-orthogonal Lloyd's mirror interferometer with a spatial light modulator for arbitrary two-dimensional pattern fabrication.

A new, to the best of our knowledge, method of generating interference patterns based on a non-orthogonal Lloyd's mirror interferometer with a spatial phase modulation is proposed. In the proposed method, a spatial light modulator (SLM) is introduced to a conventional non-orthogonal Lloyd's mirror interferometer so that arbitrary interference patterns, such as line interference patterns with varied line-spacing or two-dimensional patterns, can be generated by controlling the wavefronts of the laser beams at each position on the substrate. In this paper, as the first step of the research, the feasibility of the proposed method is theoretically confirmed by calculating interference patterns to be obtained when a spatial modulation of the phase delay is applied to the laser beams. A prototype of a non-orthogonal one-axis Lloyd's mirror interferometer with an SLM in its optical path is also designed and constructed. Some basic experiments are carried out to demonstrate the feasibility of the generation of interference patterns having varied line-spacing and two-dimensional patterns by the proposed method.

MIG6 loss confers resistance to ALK/ROS1 inhibitors in NSCLC through EGFR activation by low-dose EGF.

Although tyrosine kinase inhibitor (TKI) therapy shows marked clinical efficacy in patients with anaplastic lymphoma kinase-positive (ALK+) and ROS proto-oncogene 1-positive (ROS1+) non-small cell lung cancer (NSCLC), most of these patients eventually relapse with acquired resistance. Therefore, genome-wide CRISPR/Cas9 knockout screening was performed using an ALK+ NSCLC cell line established from pleural effusion without ALK-TKI treatment. After 9 days of ALK-TKI therapy, sequencing analysis was performed, which identified several tumor suppressor genes, such as NF2 or MED12, and multiple candidate genes. Among them, this study focused on ERRFI1, which is known as MIG6 and negatively regulates EGFR signaling. Interestingly, MIG6 loss induced resistance to ALK-TKIs by treatment with quite a low dose of EGF, which is equivalent to plasma concentration, through the upregulation of MAPK and PI3K/AKT/mTOR pathways. Combination therapy with ALK-TKIs and anti-EGFR antibodies could overcome the acquired resistance in both in vivo and in vitro models. In addition, this verified that MIG6 loss induces resistance to ROS1-TKIs in ROS1+ cell lines. This study found a potentially novel factor that plays a role in ALK and ROS1-TKI resistance by activating the EGFR pathway with low-dose ligands.

Zinc Administration Favorably Affects Prophylactic Therapy-refractory Migraine Attacks: A Case Series.

Notably, certain nutrients are effective in preventing migraine. Nonetheless, zinc replacement therapy for migraine treatment has yet to be explored. We herein report four patients with migraine who were refractory to prophylactic therapy and whose headache frequency and severity improved with zinc supplementation. Zinc administration may be an option for treating patients with prophylaxis-refractory migraine. Further investigation is required to determine the efficacy of zinc replacement therapy as a treatment option for migraine.

Magnetic resonance imaging findings of the primitive neuroectodermal tumour in lumbosacral spinal cord in a cat.

A 5-year-old, castrated, male domestic short-haired cat presented with neurological deficits in the pelvic limbs, back pain and dysuria. Magnetic resonance imaging showed a mass lesion caudal to the L4 vertebrae. In addition, suspected haemorrhage was observed at the cranial aspect of the mass. There was no evidence to support the presence of extravertebral intrusion or vertebral body, osteolysis. Dorsal laminectomy and durotomy were performed to debulk the intraspinal mass. Histopathological and immunohistochemical assessment revealed a primitive neuroectodermal tumour (PNET). To our knowledge, this is the first report to describe the clinical and pathological features and imaging diagnosis of intraspinal PNET without extraspinal invasion in a cat.

Laparoscopic observations of adhesions between peritoneal dialysis catheters and intraperitoneal organs: A retrospective, observational study.

Laparoscopy provides extensive data for the decannulation of a peritoneal dialysis catheter and is being increasingly used to diagnose encapsulating peritoneal sclerosis. However, there are few reports on the methods of decannulation of peritoneal dialysis catheters. In this study, we examined the laparoscopic findings and postoperative complications of patients undergoing peritoneal dialysis catheter removal. A total of 119 laparoscopic decannulations of peritoneal dialysis catheters were performed between 2003 and 2018 at the Juntendo University Hospital and Juntendo University Nerima Hospital. Laparoscopy was performed during peritoneal dialysis catheter removal by a gastrointestinal surgeon. Patient characteristics such as age, sex, duration of peritoneal dialysis, history of peritonitis and age at the time of peritoneal dialysis termination were assessed. Of these 119 cases, 19 (16.0%) showed adhesion between the peritoneal dialysis catheter and intraperitoneal organs. There were 13 (10.9%) cases involving a tangled omentum, 4 (3.4%) cases involving the small intestine and 2 (1.7%) cases of adhesions extending from the bowels to the abdominal wall. No postoperative complications were associated with the laparoscopic surgery. In these cases, blind decannulation of the peritoneal dialysis catheter may result in injury to the gastrointestinal tract in patients with adhesions. Therefore, we need to pay attention to adhesions between peritoneal dialysis catheters and intraperitoneal organs, and laparoscopy could be a valuable tool in detecting such adhesions and ensuring patient safety.

Water-Content-Dependent Switching of the Bending Behavior of Photoresponsive Hydrogels Composed of Hydrophilic Acrylamide-Based Main Chains and Hydrophobic Azobenzene.

Photoresponsiveness is a promising characteristic of stimulus-responsive materials. Photoresponsiveness can be achieved by incorporating photoresponsive molecules into polymeric materials. In addition, multiple-stimuli-responsive materials have attracted scientists' interest. Among the numerous multiple-stimuli-responsive materials, moisture- and photoresponsive materials are the focus of this report. These stimuli-responsive materials responded to the stimuli synergistically or orthogonally. Unlike most stimulus-responsive materials utilizing moisture and light as stimuli, the materials studied herein switch their photoresponsiveness in the presence of moisture. Appropriate copolymers consisting of hydrophilic acrylamide-based monomers for the main chain and hydrophobic azobenzene moieties switched their bending behaviors at 6-9 wt% water contents. At water contents lower than 6 wt%, the polymeric materials bent away from the light source, while they bent toward the light source at water contents higher than 10 wt%. At a low water content, the bending behaviors can be described on the molecular scale. At a high water content, the bending behavior requires consideration of the phase scale, not only the molecular scale. By controlling the balance between hydrophilicity and hydrophobicity, the switching behavior was achieved. This switching behavior may inspire additional strategies for the application of polymeric material as actuators.

Risk Factors for Elevated D-Dimer Levels in Patients with Gastrointestinal Tumors Treated with Endoscopic Submucosal Dissection.

Endoscopic submucosal dissection (ESD) is almost always performed with a sedative because of the longer procedure times involved. The risk of post-ESD deep vein thrombosis (DVT) has been reported as relatively high, and D-dimer levels are sometimes elevated after ESD. This retrospective study evaluated factors affecting changes in D-dimer levels from before to after ESD to identify causes of elevated D-dimer levels after ESD. This retrospective analysis included 117 patients with gastrointestinal tumors resected using ESD. After excluding eight patients with pre-ESD levels of D-dimer >1.5 µg/mL, factors correlating with changes in D-dimer from before to after ESD were analyzed using logistic regression analysis in 109 patients. Sedation was accomplished primarily using midazolam, but, because the sedative effect of midazolam shows marked inter-individual variability, a "corrected midazolam dose" was determined by dividing the total midazolam dose by the initial dose to correct for inter-individual differences in the sedative effect of midazolam. This value was used as one potential explanatory variable in the subgroup analysis of the 103 patients who received midazolam. In the subgroup analysis using the corrected midazolam dose as an explanatory variable, only the corrected midazolam dose correlated with a change in D-dimer ≥1.0 µg/mL in multivariate analysis (odds ratio (OR) = 1.5, 95% confidence interval (CI) 0.43-0.95; p = 0.030). The corrected midazolam dose correlated with increases in post-ESD D-dimer levels. This potential relationship indicates that patients undergoing ESD and requiring extended sedation may be at increased risk of DVT.

Effect of supplementation with Saccharomyces boulardii CNCM I-1079 on vaccine response to an inactivated bacterial vaccine in young Japanese Black calves: A field trial.

Saccharomyces boulardii group (SB group) calves were fed 2.0 × 1010 CFU/day of S. boulardii in milk replacer after 2 wk of age. All calves received inactivated vaccine for Histophilus somni, Pasteurella multocida, and Mannheimia haemolytica at 3 wk of age and 3 wk later. After vaccination, the SB group calves showed significantly higher (mean difference: 1.56-fold) antibody titer against H. somni than the control group. The number of calves with the antibody titer above the cut-off value for M. haemolytica of the SB group was significantly higher than that of the control, and the percentage was twice as high. In addition, the mRNA transcription of IL4 and IL10 in peripheral blood mononuclear cells at the booster of the SB group was significantly higher than those of the control. In conclusion, S. boulardii may have positively affected immune responses to the inactivated multi-bacterial vaccine in young calves in the field.

Les veaux du groupe Saccharomyces boulardii (groupe SB) ont reçu 2,0 × 1010 UFC/jour de S. boulardii dans du lait de remplacement après l'âge de 2 semaines. Tous les veaux ont reçu un vaccin inactivé contre Histophilus somni, Pasteurella multocida et Mannheimia haemolytica à l'âge de 3 semaines et 3 semaines plus tard. Après vaccination, les veaux du groupe SB ont montré un titre d'anticorps contre H. somni significativement plus élevé (différence moyenne : 1,56 fois) que le groupe témoin. Le nombre de veaux avec un titre d'anticorps supérieur à la valeur seuil pour M. haemolytica du groupe SB était significativement plus élevé que celui du groupe témoin, et le pourcentage était deux fois plus élevé. De plus, la transcription de l'ARNm de l'IL4 et de l'IL10 dans les cellules mononucléaires du sang périphérique lors du rappel du groupe SB était significativement plus élevée que celles du groupe témoin. En conclusion, S. boulardii peut avoir affecté positivement les réponses immunitaires au vaccin multibactérien inactivé chez les jeunes veaux au champ.(Traduit par Docteur Serge Messier).

Ensemble-Learning and Feature Selection Techniques for Enhanced Antisense Oligonucleotide Efficacy Prediction in Exon Skipping.

Antisense oligonucleotide (ASO)-mediated exon skipping has become a valuable tool for investigating gene function and developing gene therapy. Machine-learning-based computational methods, such as eSkip-Finder, have been developed to predict the efficacy of ASOs via exon skipping. However, these methods are computationally demanding, and the accuracy of predictions remains suboptimal. In this study, we propose a new approach to reduce the computational burden and improve the prediction performance by using feature selection within machine-learning algorithms and ensemble-learning techniques. We evaluated our approach using a dataset of experimentally validated exon-skipping events, dividing it into training and testing sets. Our results demonstrate that using a three-way-voting approach with random forest, gradient boosting, and XGBoost can significantly reduce the computation time to under ten seconds while improving prediction performance, as measured by R2 for both 2'-O-methyl nucleotides (2OMe) and phosphorodiamidate morpholino oligomers (PMOs). Additionally, the feature importance ranking derived from our approach is in good agreement with previously published results. Our findings suggest that our approach has the potential to enhance the accuracy and efficiency of predicting ASO efficacy via exon skipping. It could also facilitate the development of novel therapeutic strategies. This study could contribute to the ongoing efforts to improve ASO design and optimize gene therapy approaches.

Preclinical Characterization of the Tau PET Tracer [18F]SNFT-1: Comparison of Tau PET Tracers.

Tau PET tracers are expected to be sufficiently sensitive to track the progression of age-related tau pathology in the medial temporal cortex. The tau PET tracer N-(4-[18F]fluoro-5-methylpyridin-2-yl)-7-aminoimidazo[1,2-a]pyridine ([18F]SNFT-1) has been successfully developed by optimizing imidazo[1,2-a]pyridine derivatives. We characterized the binding properties of [18F]SNFT-1 using a head-to-head comparison with other reported 18F-labeled tau tracers. Methods: The binding affinity of SNFT-1 to tau, amyloid, and monoamine oxidase A and B was compared with that of the second-generation tau tracers MK-6240, PM-PBB3, PI-2620, RO6958948, JNJ-64326067, and flortaucipir. In vitro binding properties of 18F-labeled tau tracers were evaluated through the autoradiography of frozen human brain tissues from patients with diverse neurodegenerative disease spectra. Pharmacokinetics, metabolism, and radiation dosimetry were assessed in normal mice after intravenous administration of [18F]SNFT-1. Results: In vitro binding assays demonstrated that [18F]SNFT-1 possesses high selectivity and high affinity for tau aggregates in Alzheimer disease (AD) brains. Autoradiographic analysis of tau deposits in medial temporal brain sections from patients with AD showed a higher signal-to-background ratio for [18F]SNFT-1 than for the other tau PET tracers and no significant binding with non-AD tau, α-synuclein, transactiviation response DNA-binding protein-43, and transmembrane protein 106B aggregates in human brain sections. Furthermore, [18F]SNFT-1 did not bind significantly to various receptors, ion channels, or transporters. [18F]SNFT-1 showed a high initial brain uptake and rapid washout from the brains of normal mice without radiolabeled metabolites. Conclusion: These preclinical data suggest that [18F]SNFT-1 is a promising and selective tau radiotracer candidate that allows the quantitative monitoring of age-related accumulation of tau aggregates in the human brain.

Surgical Treatment Outcomes of Patients with Non-Small Cell Lung Cancer and Lymph Node Metastases.

This study aimed to investigate the appropriate subgroups for surgery and adjuvant chemotherapy in patients with non-small-cell lung cancer (NSCLC) and nodal metastases. We retrospectively reviewed 210 patients with NSCLC and nodal metastases who underwent surgery and examined the risk factors for poor overall survival (OS) and recurrence-free probability (RFP) using multivariate Cox proportional hazards analysis. Pathological N1 and N2 were observed in 114 (52.4%) and 96 (47.6%) patients, respectively. A single positive node was identified in 102 patients (48.6%), and multiple nodes were identified in 108 (51.4%). Multivariate analysis revealed that vital capacity < 80% (hazard ratio [HR]: 2.678, 95% confidence interval [CI]: 1.483-4.837), radiological usual interstitial pneumonia pattern (HR: 2.321, 95% CI: 1.506-3.576), tumor size > 4.0 cm (HR: 1.534, 95% CI: 1.035-2.133), and multiple-node metastases (HR: 2.283, 95% CI: 1.517-3.955) were significant independent risk factors for poor OS. Tumor size > 4.0 cm (HR: 1.780, 95% CI: 1.237-2.562), lymphatic permeation (HR: 1.525, 95% CI: 1.053-2.207), and multiple lymph node metastases (HR: 2.858, 95% CI: 1.933-4.226) were significant independent risk factors for recurrence. In patients with squamous cell carcinoma (n = 93), there were no significant differences in OS or RFP between those who received platinum-based adjuvant chemotherapy (n = 25) and those who did not (n = 68), at p = 0.690 and p = 0.292, respectively. Multiple-node metastases were independent predictors of poor OS and recurrence. Patients with NSCLC and single-node metastases should be considered for surgery despite N2 disease. Additional treatment with platinum-based adjuvant chemotherapy may be expected, especially in patients with squamous cell carcinoma.

Confocal probe based on the second harmonic generation for measurement of linear and angular displacements.

A measurement method based on a confocal probe on the second harmonic generation that can measure linear and angular displacements in the focusing point is proposed. In the proposed method, a pinhole or an optical fiber placed in front of the detector in conventional confocal probes is replaced by a nonlinear optical crystal, which is utilized as a medium generating second harmonic wave whose light intensity changes by the linear and angular displacements of a target under measurement. The feasibility of the proposed method is verified by theoretical calculations and experiments with the newly designed optical setup. Experimental results have demonstrated that the developed confocal probe has a resolution of 20 nm and 5 arc-seconds for measurement of linear and angular displacements, respectively.

Rituximab/bendamustine/cytarabine for transplant-eligible patients with mantle cell lymphoma: A retrospective study.

BACKGROUND: Mantle cell lymphoma is considered an aggressive B-cell lymphoma. The optimal induction regimen remains controversial as no randomized controlled trial has compared the efficacy of different induction therapies. METHOD: Herein, we performed a retrospective analysis of the clinical characteristics of 10 patients who received induction treatment consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, bendamustine, and cytarabine (R-BAC) at Toranomon Hospital between November 2016 and February 2022. RESULT: Although one patient discontinued R-BAC therapy due to a rash, the other nine completed the scheduled chemotherapy. All patients achieved complete response, underwent high-dose chemotherapy and autologous stem cell transplantation, and maintained complete remission with a median follow-up of 15 months. Hematological adverse events (AEs) occurred in all patients; however, none developed documented infection. There were also no fatal non-hematological AEs specific to R-BAC. CONCLUSION: R-CHOP/R-BAC may be a good induction therapy for transplant-eligible patients with mantle cell lymphoma.

Outpatient clinic specific for end-stage renal disease improves patient survival rate after initiating dialysis.

The importance of a shared decision-making (SDM) approach is widely recognized worldwide. In Japan, hospital accreditation involves the promotion of SDM for patients with end-stage renal disease (ESRD) when considering renal replacement therapy (RRT). This study aimed to clarify the effectiveness and long-term medical benefits of SDM in RRT. Patients with ESRD who underwent dialysis therapy were retrospectively divided into those who visited outpatient clinics specific for ESRD (ESRD clinic) supporting RRT selection with an SDM approach (visited group) and those who did not visit the ESRD clinic (non-visited group). Data of 250 patients (129 in the non-visited group and 121 in the visited group) were analyzed. Mortality was significantly higher in the non-visited group than in the visited group. Not seeing an ESRD specialist was associated with emergent initiation of dialysis and subsequent 1 year mortality. The number of patients who chose peritoneal dialysis as a modality of RRT was significantly larger in the visited group. These findings demonstrate the association between the ESRD clinic, 1 year survival in patients with ESRD after initiating dialysis, and the different RRT modalities. This specific approach in the ESRD clinic may improve the management of patients with ESRD.

Rare Case of BCOR::CCNB3 Sarcoma of Bone.

BACKGROUND BCOR: CCNB3 sarcoma is a rare mesenchymal tumor that was formerly included in the undifferentiated/unclassified sarcoma group and was recently reclassified as one of undifferentiated small round cell sarcomas with a genetically distinct subtype in the WHO 2020 classification. Because of its rarity, still not much is known, especially about its clinical features. CASE REPORT A 15-year-old boy presented with almost 1-year intermittent thigh pain. On the first visit, a pathologic fracture of the femur and a big mass expanding through the femoral cortex with lobular shape and homogenous appearance were recognized on radiography and magnetic resonance imaging. Plain radiography, which was taken 6 months before at a local clinic, showed an expansion and thickening of the right proximal femoral shaft. Biopsy specimen of the lesion revealed a proliferation of round to spindle tumor cells with diffuse and strong immunohistochemical nuclear positivity for BCOR and CCNB3. Under the diagnosis of BCOR::CCNB3 sarcoma of the femur, a chemotherapy based on a protocol of Ewing sarcoma, followed by a wide resection and total femoral replacement surgery, were conducted. The effect of chemotherapy was favorable, showing no microscopic residual tumor. Although postoperative chemotherapy was not completed because of a minor infection detected on the surgical site, the patient was doing well, without any recurrence, for 26 months. CONCLUSIONS BCOR: CCNB3 sarcoma of the bone is a quite rare tumor with much lower incidence than Ewing sarcoma. Notable clinical characteristics of the current case were a 1-year-long symptomatic period and homogenous appearance on MRI.

Impact of anemia treatment for left ventricular hypertrophy using long-acting erythropoietin-stimulating agents from the pre-dialysis to maintenance dialysis period in patients with chronic kidney disease, retrospective longitudinal cohort study.

BACKGROUND: Anemia in patients with chronic kidney disease (p-CKDs) may initiate or exacerbate left ventricular hypertrophy (LVH). This study aimed to determine whether treatment using long-acting erythropoietin-stimulating agents (L-ESAs) is independently associated with LVH during the pre-dialysis to maintenance dialysis period in p-CKDs. METHODS: Physical and laboratory examinations were performed 120 days before initiating dialysis in p-CKDs (baseline). To evaluate the left ventricular mass index (LVMI) after starting dialysis, the mean hemoglobin (Hb) was defined as the average at the start of dialysis and 6 months after starting dialysis. Changes in the LVMI were observed in three groups according to mean Hb levels (Hb < 10.1, 10.1 < Hb < 11.0, and Hb > 11.0 g/dL for Groups 1, 2, and 3, respectively). LVMI was evaluated using echocardiography at the pre-dialysis, initiation, and maintenance dialysis periods. RESULTS: A lower LVMI at dialysis initiation and an improvement in LVMI were detected in the highest tertile group of mean Hb (11.0 g/dl). Consequently, in the high Hb group (Hb level > 11.0 g/dl), LVMI remained low from dialysis initiation until after 6 months.The relationship between Hb and LVMI was not significant; however, a constant correlation with ß ≥ 0.4 in the absolute value was maintained. CONCLUSION: L-ESAs may correlate with Hb and LVMI after administration, independent of the baseline LVMI and Hb values. These findings have therapeutic implications in the treatment strategies for p-CKDs during the pre-dialysis to maintenance dialysis period.

Statins inhibit protein kinase D (PKD) activation in intestinal cells and prevent PKD1-induced growth of murine enteroids.

We examined the impact of statins on protein kinase D (PKD) activation by G protein-coupled receptor (GPCR) agonists. Treatment of intestinal IEC-18 cells with cerivastatin inhibited PKD autophosphorylation at Ser916 induced by angiotensin II (ANG II) or vasopressin in a dose-dependent manner with half-maximal inhibition at 0.2 µM. Cerivastatin treatment inhibited PKD activation stimulated by these agonists for different times (5-60 min) and blunted HDAC5 phosphorylation, a substrate of PKD. Other lipophilic statins, including simvastatin, atorvastatin, and fluvastatin also prevented PKD activation in a dose-dependent manner. Using IEC-18 cell lines expressing PKD1 tagged with EGFP (enhanced green fluorescent protein), cerivastatin or simvastatin blocked GPCR-mediated PKD1-EGFP translocation to the plasma membrane and its subsequent nuclear accumulation. Similar results were obtained in IEC-18 cells expressing PKD3-EGFP. Mechanistically, statins inhibited agonist-dependent PKD activation rather than acting directly on PKD catalytic activity since exposure to cerivastatin or simvastatin did not impair PKD autophosphorylation or PKD1-EGFP membrane translocation in response to phorbol dibutyrate, which bypasses GPCRs and directly stimulates PKC and PKD. Furthermore, cerivastatin did not inhibit recombinant PKD activity determined via an in vitro kinase assay. Using enteroids generated from intestinal crypt-derived epithelial cells from PKD1 transgenic mice as a model of intestinal regeneration, we show that statins oppose PKD1-mediated increase in enteroid area, complexity (number of crypt-like buds), and DNA synthesis. Our results revealed a previously unappreciated inhibitory effect of statins on receptor-mediated PKD activation and in opposing the growth-promoting effects of PKD1 on intestinal epithelial cells.

[Analysis of Surgical Margin Recurrence Following Segmentectomy for Early-stage Non-small Cell Lung Cancer].

BACKGROUND: Surgical margin recurrence following segmentectomy is a critical issue because it may have been avoided by lobectomy. METHODS: Between January 2000 and December 2018, we retrospectively investigated 199 patients who underwent segmentectomy for c-StageⅠ non-small cell lung cancer at our hospital. RESULTS: Recurrence occurred in 20 cases, of which 3 cases had surgical margin recurrence. In our previous study, the recurrence risk factor after segmentectomy was radiologic solid tumor size( cut-off value 1.5 cm). Of the 130 patients in the low-risk group with radiologic solid tumor size of less than 1.5 cm, five had any recurrence, three of which had surgical margin recurrence. In the high-risk group with radiologic solid tumor size of 1.5 cm or more, no surgical margin recurrence was observed. Three cases of surgical margin recurrence were accompanied by lepidic components, and the tumors were difficult to identify intraoperatively and were located close to adjacent areas. CONCLUSION: Surgical margin recurrence may be avoided by carefully considering the segments to be resected and improving the method for identifying the intersegmental plane.