Differentiation of Human-induced Pluripotent Stem Cell-derived Dental Stem Cells through Epithelial-Mesenchymal Interaction.

Research on tooth regeneration using human-induced pluripotent stem cells (hiPSCs) is valuable for autologous dental regeneration. Acquiring mesenchymal and epithelial cells as a resource for dental regeneration is necessary because mesenchymal-epithelial interactions play an essential role in dental development. We reported the establishment of hiPSCs-derived dental epithelial-like cell (EPI-iPSCs), but hiPSCs-derived dental mesenchymal stem cells (MSCs) have not yet been reported. This study was conducted to establish hiPSCs-derived MSCs and to differentiate them into dental cells with EPI-iPSCs. Considering that dental MSCs are derived from the neural crest, hiPSCs were induced to differentiate into MSCs through neural crest formation to acquire the properties of dental MSCs. To differentiate hiPSCs into MSCs through neural crest formation, established hiPSCs were cultured and differentiated with PA6 stromal cells and differentiated hiPSCs formed neurospheres on ultralow-attachment plates. Neurospheres were differentiated into MSCs in serum-supplemented medium. Neural crest-mediated MSCs (NC-MSCs) continuously showed typical MSC morphology and expressed MSC markers. After 8 days of odontogenic induction, the expression levels of odontogenic/mineralization-related genes and dentin sialophosphoprotein (DSPP) proteins were increased in the NC-MSCs alone group in the absence of coculturing with dental epithelial cells. The NC-MSCs and EPI-iPSCs coculture groups showed high expression levels of amelogenesis/odontogenic/mineralization-related genes and DSPP proteins. Furthermore, the NC-MSCs and EPI-iPSCs coculture group yielded calcium deposits earlier than the NC-MSCs alone group. These results indicated that established NC-MSCs from hiPSCs have dental differentiation capacity with dental epithelial cells. In addition, it was confirmed that hiPSCs-derived dental stem cells could be a novel cell source for autologous dental regeneration.

The Role of Adipokines in Tumor Progression and Its Association with Obesity.

Obesity is a well-established risk factor for various malignancies and emerging evidence suggests that adipokines play a pivotal role in linking excess adiposity to tumorigenesis. Adipokines are bioactive molecules secreted by adipose tissue and their altered expression in obesity contributes to a pro-inflammatory, pro-angiogenic, and growth-promoting microenvironment conducive to tumorigenesis. Leptin, a key adipokine, activates survival and proliferative signaling pathways whereas adiponectin exhibits tumor-suppressive effects by inducing apoptosis and cell cycle arrest. Visfatin has also been documented to promote tumor growth, angiogenesis, migration, and invasion. Moreover, emerging studies suggest that adipokines, such as resistin, apelin, and chemerin, which are overexpressed in obesity, may also possess oncogenic functions. Despite advancements in our understanding of the roles of individual adipokines in cancer, the intricate interplay and crosstalk between adipokines, tumor cells, and the tumor microenvironment remain complex and multifaceted. This review highlights the evolving knowledge of how adipokines contribute to obesity-related tumorigenesis, shedding light on the potential of targeting adipokine signaling pathways as a novel therapeutic approach for obesity-associated cancers. Further research on the specific mechanisms and interactions between adipokines and tumor cells is crucial for a comprehensive understanding of obesity-associated cancer pathogenesis.

Antarctic Krill Oil from Euphausia superba Ameliorates Carrageenan-Induced Thrombosis in a Mouse Model.

FJH-KO obtained from Antarctic krill, especially Euphausia superba, has been reported to contain high amounts of omega-3 polyunsaturated fatty acids (n-3 PUFA) and to exhibit anticancer and anti-inflammatory properties. However, its antithrombotic effects have not yet been reported. This study aimed to investigate the antithrombotic effects of FJH-KO in carrageenan-induced thrombosis mouse models and human endothelial cells. Thrombosis was induced by carrageenan injection, whereas the mice received FJH-KO pretreatment. FJH-KO attenuated carrageenan-induced thrombus formation in mouse tissue vessels and prolonged tail bleeding. The inhibitory effect of FJH-KO was associated with decreased plasma levels of thromboxane B2, P-selectin, endothelin-1, ß-thromboglobulin, platelet factor 4, serotonin, TNF-α, IL-1ß, and IL-6. Meanwhile, FJH-KO induced plasma levels of prostacyclin I2 and plasminogen. In vitro, FJH-KO decreased the adhesion of THP-1 monocytes to human endothelial cells stimulated by TNF-α via eNOS activation and NO production. Furthermore, FJH-KO inhibited the expression of TNF-α-induced adhesion molecules such as ICAM-1 and VCAM-1 by suppressing the NF-κB signaling pathway. Taken together, our study demonstrates that FJH-KO protects against carrageenan-induced thrombosis by regulating endothelial cell activation and has potential as an antithrombotic agent.

Caveolin-1 mediates the utilization of extracellular proteins for survival in refractory gastric cancer.

Despite advances in cancer therapy, the clinical outcome of patients with gastric cancer remains poor, largely due to tumor heterogeneity. Thus, finding a hidden vulnerability of clinically refractory subtypes of gastric cancer is crucial. Here, we report that chemoresistant gastric cancer cells rely heavily on endocytosis, facilitated by caveolin-1, for survival. caveolin-1 was highly upregulated in the most malignant stem-like/EMT/mesenchymal (SEM)-type gastric cancer cells, allowing caveolin-1-mediated endocytosis and utilization of extracellular proteins via lysosomal degradation. Downregulation of caveolin-1 alone was sufficient to induce cell death in SEM-type gastric cancer cells, emphasizing its importance as a survival mechanism. Consistently, chloroquine, a lysosomal inhibitor, successfully blocked caveolin-1-mediated endocytosis, leading to the marked suppression of tumor growth in chemorefractory gastric cancer cells in vitro, including patient-derived organoids, and in vivo. Together, our findings suggest that caveolin-1-mediated endocytosis is a key metabolic pathway for gastric cancer survival and a potential therapeutic target.

Cohabitation as a determinant of adaptive and innate immune cell profiles: Findings from the Health and Retirement Study.

Introduction: Non-genetic factors are important but poorly understood determinants of immune profiles. Age and Cytomegalovirus (CMV) infection remain two well documented non-genetic determinants of the immune profile. Recently, one study identified cohabitation in the same household as an important determinant of immune profiles. Methods: We used immunophenotyping data from the Health and Retirement Study (HRS) to evaluate the association between cohabitation and the adaptive (subsets of T-cells, B-cells) and innate immune profiles (subsets of monocytes, natural killer cells and neutrophils). We compared adaptive and innate immune cell profiles using immunophenotyping data from 1184 same-household pairs (cohabitating partners) to 1184 non-household pairs to evaluate the association between cohabitation and adaptive immune cell profiles. We used data from 1737 same-household pairs and 1737 non-household pairs to evaluate the association between cohabitation and innate cell profiles. Household and non-household pairs were matched on age (±2years), educational background and race/ethnicity to minimize confounding due to these factors. The adaptive immune cells and innate immune cell profiles were compressed to two coordinates using multidimensional scaling (MDS). The Euclidean distances between same-household pairs were compared to the distances between non-household pairs for the adaptive and innate cell profiles separately using two sample independent t-tests. We also performed additional adjustment for age and BMI differences, CMV serostatus and smoking concordance/discordance status among household members. Results: For adaptive immune cell profiles, the mean Euclidean distance between same-household pairs was 4% lower than the non-household pairs (p = 0.03). When stratified by concordance for CMV serostatus among household pairs, the Euclidean distance was significantly lower by 8% in the same-household pairs as compared to non-household pairs among those who were discordant for CMV serostatus (p = 0.01) and among same-household pairs who were CMV seronegative (p = 0.02) after covariate adjustment. The mean Euclidian distance between same-household pairs was also 8% lower than non-household pairs for the innate immune cell profiles (p-value <0.0001) and this difference remained consistent across all strata of CMV infection. Discussion: This study confirms that cohabitation is associated with similarity in immune cell profiles. The differential effects of cohabitation on the adaptive and innate immune profiles suggest that further studies into the common environmental factors that influence individual immune cell subsets need to be evaluated in greater detail.

Magnetic resonance imaging for assessment of the quadriceps tendon cross-sectional area as an adjunctive diagnostic parameter in patients with patellofemoral pain syndrome.

OBJECTIVES: In this study, we aimed to provide a more valuable diagnostic parameter and more equivocal assessment of the diagnostic potential of patellofemoral pain syndrome (PFPS) by comparing the quadriceps tendon cross-sectional area (QTCSA) with the quadriceps tendon thickness (QTT), a traditional measure of quadriceps tendon hypertrophy. PATIENTS AND METHODS: Between March 2014 and August 2020, a total of 30 patients with PFPS (16 males, 14 females; mean age, 30.4±11.2 years; range, 16 to 49 years) and 30 healthy individuals (19 males, 11 females; mean age: 30.8±13.8 years; range, 17 to 62 years) who underwent knee magnetic resonance imaging (MRI) were retrospectively analyzed. T1-weighted turbo spin-echo transverse MRI scans were obtained. The QTCSA was measured on the axial angled phases of the images by drawing outlines, and the QTT was measured at the most hypertrophied quadriceps tendon. RESULTS: The mean QTT and QTCSA in the patients with PFPS (6.33±0.80 mm and 155.77±36.60 mm2, respectively) were significantly higher than those in the control group (5.77±0.36 mm and 111.90±24.10 mm2, respectively; p<0.001, for both). The receiver operating characteristic curve was used to confirm the sensitivities and specificities for both the QTT and QTCSA as predictors of PFPS. The optimal diagnostic cut-off value for QTT was 5.98 mm, with a sensitivity of 66.7%, a specificity of 70.0%, and an area under the curve (AUC) of 0.75 (range, 0.62 to 0.88). The optimal diagnostic cut-off value for QTCSA was 121.04 mm2, with a sensitivity of 73.3%, a specificity of 70.0%, and an AUC of 0.83 (range, 0.74 to 0.93). CONCLUSION: Based on our study results, the QTCSA seems to be a more reliable diagnostic indicator for PFPS than QTT.

Lactic Acid Bacteria Isolated from Human Breast Milk Improve Colitis Induced by 2,4,6-Trinitrobenzene Sulfonic Acid by Inhibiting NF-κB Signaling in Mice.

Inflammatory bowel disease (IBD), a chronic inflammatory disease, results from dysregulation of the immune responses. Some lactic acid bacteria (LAB), including Lactobacillus, alleviate IBD through immunomodulation. In this study, the anti-colitis effect of LAB isolated from human breast milk was investigated in a mouse model induced acute colitis with 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS remarkably increased weight loss, colon shortening, and colonic mucosal proliferation, as well as the expression levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1ß. Oral administration of LAB isolated from human breast milk resulted in a reduction in TNBS-induced colon shortening, as well as induced cyclooxygenase (COX)-2, nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB). In addition, LAB suppressed inflammatory cytokines such as TNF-α, IL-6, and IL-1ß, and thus showed an effect of suppressing the level of inflammation induced by TNBS. Furthermore, LAB alleviated gut microbiota dysbiosis, and inhibited intestinal permeability by increasing the expression of intestinal tight junction protein including ZO-1. Collectively, these results suggest that LAB isolated from human breast milk can be used as a functional food for colitis treatment by regulating NF-κB signaling, gut microbiota and increasing expression of intestinal tight junction protein.

Cosmetic Open Rhinoplasty in Acute Nasal Bone Fracture With Pre-Existing Deformity.

The simultaneous reduction of nasal bone fracture and cosmetic rhinoplasty is a challenging procedure, because of fracture severity and skeletal instability. Our aim was to investigate the surgical strategy and outcomes of cosmetic rhinoplasty according to the pre-existing nasal deformity when performing simultaneous reduction of nasal bone fracture and cosmetic rhinoplasty. In total, 71 patients who underwent cosmetic rhinoplasty were included. All patients were categorized according to pre-existing deformity, dorsal hump and irregularities, and deviation of the nose, wide nose, and flat nasal dorsum. The authors performed individual maneuvers to correct each deformity. Autologous tissue was used in all maneuvers for graft. Photoanalysis was performed to measure the deviation, nasal length, radix height, dorsal height, tip projection, nasofrontal angle, and nasolabial angle. Subjective evaluation of the functional and esthetic problems was confirmed through rhinoplasty outcome evaluation. In the analysis of the photographs, most patients presented improved scores ( P <0.05). The scores of satisfaction were significantly higher in the postoperative state ( P <0.05). As a postoperative complication, 2 cases of deviated tip occurred due to septal instability and were successfully revised with septoplasty and columellar strut graft. The authors created a harmonious face by evaluating, categorizing, and treating each deformity of the nose in patients with nasal fractures according to our algorithm.

Latissimus Dorsi Muscle Sling for Reconstruction of Chronic Seroma Pocket in the Axillary Fossa.

Managing chronic axillary seroma after breast cancer surgery is troublesome because of the challenges in obliterating the seroma pocket and the possible injury to the axillary neurovascular bundles during the procedure. Using the muscle sling technique, we successfully managed an axillary chronic seroma patient after mastectomy with a latissimus dorsi musculocutaneous (LDMC) flap.A 64-year-old woman with right breast cancer underwent radical mastectomy with axillary lymph node dissection 17 years ago. A mass of chronic seroma was observed in the right axilla 1 year postoperatively and gradually increased in size. The refractory seroma was excised. The LDMC flap was designed to obliterate the pocket, rotated counterclockwise, and fixed to the upper boundary of the pectoralis major in a U-shaped sling. In this way, the direct suture of the flap to the vessels-crossing axillary apex could be avoided, and the flap's lymphatic-rich fat tissue promoted alternative lymphatic drainage that improved lymphedema.

Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal cancer treatment (ICON8): overall survival results from an open-label, randomised, controlled, phase 3 trial.

BACKGROUND: Standard-of-care first-line chemotherapy for epithelial ovarian cancer is carboplatin and paclitaxel administered once every 3 weeks. The JGOG 3016 trial reported significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly (ie, once every 3 weeks) carboplatin. However, this benefit was not observed in the previously reported progression-free survival results of ICON8. Here, we present the final coprimary outcomes of overall survival and updated progression-free survival analyses of ICON8. METHODS: In this open-label, randomised, controlled, phase 3 trial (ICON8), women aged 18 years or older with newly diagnosed stage IC-IV epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (here collectively termed ovarian cancer, as defined by International Federation of Gynecology and Obstetrics [FIGO] 1988 criteria) and an Eastern Cooperative Oncology Group performance status of 0-2 were recruited from 117 hospitals with oncology departments in the UK, Australia and New Zealand, Mexico, South Korea, and Ireland. Patients could enter the trial after immediate primary surgery (IPS) or with planned delayed primary surgery (DPS) during chemotherapy, or could have no planned surgery. Participants were randomly assigned (1:1:1), using the Medical Research Council Clinical Trials Unit at University College London randomisation line with stratification by Gynecologic Cancer Intergroup group, FIGO disease stage, and outcome and timing of surgery, to either 3-weekly carboplatin area under the curve (AUC)5 or AUC6 and 3-weekly paclitaxel 175 mg/m2 (control; group 1), 3-weekly carboplatin AUC5 or AUC6 and weekly paclitaxel 80 mg/m2 (group 2), or weekly carboplatin AUC2 and weekly paclitaxel 80 mg/m2 (group 3), all administered via intravenous infusion for a total of six 21-day cycles. Coprimary outcomes were progression-free survival and overall survival, with comparisons done between group 2 and group 1, and group 3 and group 1, in the intention-to-treat population. Safety was assessed in all patients who started at least one chemotherapy cycle. The trial is registered on ClinicalTrials.gov, NCT01654146, and ISRCTN registry, ISRCTN10356387, and is closed to accrual. FINDINGS: Between June 6, 2011, and Nov 28, 2014, 1566 patients were randomly assigned to group 1 (n=522), group 2 (n=523), or group 3 (n=521). The median age was 62 years (IQR 54-68), 1073 (69%) of 1566 patients had high-grade serous carcinoma, 1119 (71%) had stage IIIC-IV disease, and 745 (48%) had IPS. As of data cutoff (March 31, 2020), with a median follow-up of 69 months (IQR 61-75), no significant difference in overall survival was observed in either comparison: median overall survival of 47·4 months (95% CI 43·1-54·8) in group 1, 54·8 months (46·6-61·6) in group 2, and 53·4 months (49·2-59·6) in group 3 (group 2 vs group 1: hazard ratio 0·87 [97·5% CI 0·73-1·05]; group 3 vs group 1: 0·91 [0·76-1·09]). No significant difference was observed for progression-free survival in either comparison and evidence of non-proportional hazards was seen (p=0·037), with restricted mean survival time of 23·9 months (97·5% CI 22·1-25·6) in group 1, 25·3 months (23·6-27·1) in group 2, and 24·8 months (23·0-26·5) in group 3. The most common grade 3-4 adverse events were reduced neutrophil count (78 [15%] of 511 patients in group 1, 183 [36%] of 514 in group 2, and 154 [30%] of 513 in group 3), reduced white blood cell count (22 [4%] in group 1, 80 [16%] in group 2, and 71 [14%] in group 3), and anaemia (26 [5%] in group 1, 66 [13%] in group 2, and 24 [5%] in group 3). No new serious adverse events were reported. Seven treatment-related deaths were reported (two in group 1, four in group 2, and one in group 3). INTERPRETATION: In our cohort of predominantly European women with epithelial ovarian cancer, we found that first-line weekly dose-dense chemotherapy did not improve overall or progression-free survival compared with standard 3-weekly chemotherapy and should not be used as part of standard multimodality front-line therapy in this patient group. FUNDING: Cancer Research UK, Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, and Cancer Australia.

Sp1-Induced FNBP1 Drives Rigorous 3D Cell Motility in EMT-Type Gastric Cancer Cells.

Cancer is heterogeneous among patients, requiring a thorough understanding of molecular subtypes and the establishment of therapeutic strategies based on its behavior. Gastric cancer (GC) is adenocarcinoma with marked heterogeneity leading to different prognoses. As an effort, we previously identified a stem-like subtype, which is prone to metastasis, with the worst prognosis. Here, we propose FNBP1 as a key to high-level cell motility, present only in aggressive GC cells. FNBP1 is also up-regulated in both the GS subtype from the TCGA project and the EMT subtype from the ACRG study, which include high portions of diffuse histologic type. Ablation of FNBP1 in the EMT-type GC cell line brought changes in the cell periphery in transcriptomic analysis. Indeed, loss of FNBP1 resulted in the loss of invasive ability, especially in a three-dimensional culture system. Live imaging indicated active movement of actin in FNBP1-overexpressed cells cultured in an extracellular matrix dome. To find the transcription factor which drives FNBP1 expression in an EMT-type GC cell line, the FNBP1 promoter region and DNA binding motifs were analyzed. Interestingly, the Sp1 motif was abundant in the promoter, and pharmacological inhibition and knockdown of Sp1 down-regulated FNBP1 promoter activity and the transcription level, respectively. Taken together, our results propose Sp1-driven FNBP1 as a key molecule explaining aggressiveness in EMT-type GC cells.

Traction Applying Technique on Bicanalicular Crawford Silicone Tube to Overcome the Notching Deformity After Lacrimal Canalicular Repair.

ABSTRACT: Lower eyelid avulsion injury with lower canalicular laceration generally occur just medial to the punctum with insufficient skin remnant for repair causing tension on repair margins. The inevitable blinking force, along with the tension widens the repair margin, resulting in an aesthetically challenging notch at the medial lower lid. The authors attempted to minimize this notching deformity with a traction applying technique on bicanalicular silicone tube.Fifteen patients were enrolled and divided into 2 groups: the experimental group with 10 patients which received the traction technique, and the control group with 5 patients which the traction technique was omitted. Each end of the bicanalicular silicone tube was intubated through both puncta and the lacerated canaliculus. No canalicular anastomosis was performed. The tube ends were retrieved through the nostril, followed by medial canthal tendon, orbicularis oculi muscle, and skin repair. The tube ends were pulled to create a tension on the loop, until upper and lower puncta apposed each other, creating a dimple in the medial canthal area. The tube ends were tied and anchored at internal valve of the nostril to maintain the traction tension. Medial lower lid notching (>2 mm width), epiphora, and conjunctival injection were evaluated and compared in the 2 groups.Patients with traction technique showed symmetric medial canthal angle and minimized lower lid notching deformity when compared with the control group (P = 0.025). No conjunctival injections and epiphora were observed in either group. Symmetric and aesthetically satisfactory results were achieved by traction applying technique on bicanalicular silicone tube.

Thinning of Calvarial Bone by Skull Growth in a Pediatric Patient After Skull Grinding Injury.

ABSTRACT: Several treatment options have been suggested for the treatment of scalp defects that occur following head trauma. Growth changes should be considered, especially for children. The authors report a case of delayed cranial bone absorption after successful free latissimus dorsi flap coverage following skull grinding injury in a pediatric patient.A 3-year-old patient was referred to the reconstructive surgery department because of a 7 × 8 cm-sized scalp defect in the temporoparietal area due to dragging and grinding injury. Debridement and free latissimus dorsi musculocutaneous flap coverage with split-thickness skin graft were performed. The operation was successful and antibiotics were administered for 4 weeks to prevent the occurrence of osteomyelitis (OM). The patient was discharged after confirming the absence of OM via magnetic resonance imaging.Thinning of cranial bone was observed in the skull series taken one year postoperatively. The size gradually increased, but no significant changes in size occurred after 5 years of patient's age. Magnetic resonance imaging was performed used to confirm the occurrence of OM and no specific findings were observed. It is well-known fact that the cranium grows to 90% of its adult capacity by the age of 5. In this regard, we believe that the current case and the demonstrated cranial thinning is due to bone absorption associated with the growth.In the pediatric population, injuries involving the cranial vault should be considered in the context of bone resorption due to skull growth, which may lead to cranial bone thinning. Reconstructive surgeons should closely observe the presence or absence of skull defects through long-term follow-ups.

Antihelical Auricular Reconstruction With Adipoperichondrial Turnover Flap and Full-thickness Skin Graft.

ABSTRACT: Reconstruction of the antihelical area can be challenging because the cartilage can be easily exposed due to the thin overlying soft tissue, and it has a lack of tissue mobility. Skin graft can be hesitant to perform in antihelical defects where the bare cartilage is exposed.A 70-year-old male with squamous cell carcinoma of the antihelix of the left ear was referred to our department for surgical excision. Wide excision with tumor-free margins resulted in a defect of 2.0 × 1.0 cm with exposed bare cartilage. The authors covered the defect using adipoperichondrial turnover flap from cephalic portion of the earlobe followed by full thickness skin graft. The skin graft took well with no complication. Aesthetic result was satisfactory with no auricular deformity.This adipoperichondrial turnover flap is simple, easy, can be performed in one stage, and produces good esthetic results with no disfiguration of the ear shape.

Sasa quelpaertensis Leaf Extract Ameliorates Dyslipidemia, Insulin Resistance, and Hepatic Lipid Accumulation in High-Fructose-Diet-Fed Rats.

BACKGROUND: Increased dietary fructose consumption is closely associated with lipid and glucose metabolic disorders. Sasa quelpaertensis Nakai possesses various health-promoting properties, but there has been no research on its protective effect against fructose-induced metabolic dysfunction. In this study, we investigated the effects of S. quelpaertensis leaf extract (SQE) on metabolic dysfunction in high-fructose-diet-fed rats. METHODS: Animals were fed a 46% carbohydrate diet, a 60% high-fructose diet, or a 60% high-fructose diet with SQE (500 mg/kg of body weight (BW)/day) in drinking water for 16 weeks. Serum biochemical parameters were measured and the effects of SQE on hepatic histology, protein expression, and transcriptome profiles were investigated. RESULTS: SQE improved dyslipidemia and insulin resistance induced in high-fructose-diet-fed rats. SQE ameliorated the lipid accumulation and inflammatory response in liver tissues by modulating the expressions of key proteins related to lipid metabolism and antioxidant response. SQE significantly enriched the genes related to the metabolic pathway, namely, the tumor necrosis factor (TNF) signaling pathway and the PI3K-Akt signaling pathway. CONCLUSIONS: SQE could effectively prevent dyslipidemia, insulin resistance, and hepatic lipid accumulation by regulation of metabolism-related gene expressions, suggesting its role as a functional ingredient to prevent lifestyle-related metabolic disorders.

Opioid-free anesthesia with a mixture of dexmedetomidine, ketamine, and lidocaine in one syringe for surgery in obese patients.

Recently, there has been a trend toward minimizing opioid use in obese patients to prevent opioid-related postoperative complications. Moreover, the use of opioid-free anesthesia has received growing interest. This case series reports the use of simple opioid-free anesthesia consisting of a mixture of dexmedetomidine, ketamine, and lidocaine in an obese male patient undergoing laparoscopic bariatric surgery and an obese pregnant woman undergoing cesarean section. These cases indicate that opioid-free anesthesia can be safely administered to obese patients and provides effective pain control without any postoperative adverse outcomes.

Radio-frequency-transmitting hexagonal boron nitride-based anti- and de-icing heating system.

Anti- and de-icing heating systems are used to both prevent the accumulation of ice and to remove it and thus avoid damage. Typically, anti- and de-icing heating systems employ carbon-based materials, metal frames, and bulky ceramic structures. These structures generally lead to the loss of radio-frequency (RF) signals and are also relatively heavy. Therefore, RF equipment such as radar domes (radomes) and antennas require anti- and de-icing systems with high RF transmittance for normal operation. In this work, we fabricated a fluorine-doped tin oxide (FTO) wave pattern covered with hexagonal boron nitride (h-BN) layers (i.e., an h-BN/FTO wave pattern) on a glass substrate for use as an RF-transmitting heating system for anti- and de-icing. The FTO wave pattern and h-BN layer act as the heating element and heat spreader, respectively. The h-BN layer showed a transmittance of approximately 90% for RF waves on glass (X band: 8.2-12.4 GHz) (the 10% loss was attributable to the glass substrate). The differences in the temperatures of the FTO-patterned and non-patterned areas for the h-BN(3.6 nm)/FTO and FTO wave pattern were 19.3 and 25.5 °C, respectively. This means that the h-BN layer improved the heat-spreading performance by 6.2 °C. Furthermore, a de-icing test was performed using the h-BN(3.6 nm)/FTO wave pattern by applying a voltage of 40 V at -20 °C. The ice on the non-patterned area melted within 1 min while that on the FTO-patterned area melted within 30 s. These results suggest that the fabricated h-BN(3.6 nm)/FTO wave pattern for RF-transmitting heating systems is suitable for use with the radomes of drones, unmanned aerial vehicles, aircraft, and spaceships in extremely cold environments.

Hemodynamic changes following accidental infiltration of a high dose of vasopressin.

Vasopressin local infiltration is useful in gynecological surgery because it can reduce hemorrhage. Depending on the activities of the sympathetic system and the renin-angiotensin system, reactions to vasopressin may differ and predicting its systemic effects is difficult. Because life-threatening complications can occur, infiltration with vasopressin should be administered with caution. A 42-year-old female patient was diagnosed with uterine leiomyomas. During a robot-assisted laparoscopic myomectomy, 50 U of vasopressin, which is ten-times the recommended dose, was accidentally infiltrated. Subsequently, bradycardia with a heart rate of 25 bpm occurred, which recovered within 3 minutes. Peripheral perfusion indices and the diameter of the radial and brachial arteries also decreased markedly and recovered within 1 hour. The surgery was concluded without additional events. The patient was discharged 2 days later with no abnormal findings. Because vasopressin infiltration can cause life-threatening complications, it is necessary to determine the extent of patient reactions to vasopressin using measures such as the peripheral perfusion index or radial and brachial artery diameters. These measures may also help to predict the occurrence of complications.

ATM mediated-p53 signaling pathway forms a novel axis for senescence control.

Previously, we uncovered a novel mechanism in which senescence is controlled by mitochondrial functional recovery upon Ataxia-telangiectasia mutated (ATM) inhibition. However, it remains elusive how ATM controls signaling pathways to achieve restorative effect. In this study, we performed microarray and found that p53 pathway was differentially expressed upon ATM inhibition. We found that ATM inhibition yields senescence amelioration through p53-dependent manner. The restorative effect was also afforded by direct p53 inhibition. Furthermore, mitochondrial metabolic reprogramming via p53 inhibition was a prerequisite for senescence amelioration. Taken together, our data indicated that p53 pathway functions as potential target for ATM-mediated senescence amelioration.