Triglycerides/HDL cholesterol ratio and type 2 diabetes incidence: Panasonic Cohort Study 10.

BACKGROUND: Previous studies have investigated the association between the ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) and the incidence of diabetes in adults and discovered that a high TG/HDL-C ratio was linked to an elevated risk of new-onset diabetes. However, the comparison of predicting diabetes development among lipid profiles including the TG/HDL-C ratio, and the ratio of TG/HDL-C cut-off value has received limited attention. We examined the relationship between diabetes onset and the TG/HDL-C ratio in addition to the applicable cut-off value for predicting diabetes onset. METHODS: This study included 120,613 participants from the health examination database at Panasonic Corporation from 2008 to 2017. Cox regression analysis employing multivariable models was used to investigate the association between lipid profiles, particularly the ratio of TG/HDL-C and the development of type 2 diabetes (T2D). The multivariable model was adjusted for age, sex, BMI, systolic blood pressure, plasma glucose levels after fasting, smoking status, and exercise habits. Areas under time-dependent receiver operating characteristic (ROC) curves (AUCs) were employed to assess the prediction performance and cut-off values of each indicator. A fasting plasma glucose level of 126 mg/dL, a self-reported history of diabetes, or usage of antidiabetic medicines were used to identify T2D. RESULTS: During the course of the study, 6,080 people developed T2D. The median follow-up duration was 6.0 (3-10) years. Multivariable analysis revealed that the ratio of TG/HDL-C (per unit, HR; 1.03 [95% CI 1.02-1.03]) was substantially linked to the risk of incident T2D. AUC and cut-off points for the ratio of TG/HDL-C for T2D development after 10 years were 0.679 and 2.1, respectively. Furthermore, the AUC of the ratio of TG/HDL-C was considerably larger compared to that of LDL-C, HDL-C, and TG alone (all P < 0.001). We discovered an interaction effect between sex, BMI, and lipid profiles in subgroup analysis. Females and participants having a BMI of < 25 kg/m2 showed a higher correlation between lipid profile levels and T2D onset. CONCLUSIONS: The ratio of TG/HDL-C was found to be a stronger predictor of T2D development within 10 years than LDL-C, HDL-C, or TG, indicating that it may be useful in future medical treatment support.

Distinct Profiles of Desensitization of µ-Opioid Receptors Caused by Remifentanil or Fentanyl: In Vitro Assay with Cells and Three-Dimensional Structural Analyses.

Remifentanil (REM) and fentanyl (FEN) are commonly used analgesics that act by activating a µ-opioid receptor (MOR). Although optimal concentrations of REM can be easily maintained during surgery, it is sometimes switched to FEN for optimal pain regulation. However, standards for this switching protocol remain unclear. Opioid anesthetic efficacy is decided in part by MOR desensitization; thus, in this study, we investigated the desensitization profiles of REM and FEN to MOR. The efficacy and potency during the 1st administration of REM or FEN in activating the MOR were almost equal. Similarly, in ß arrestin recruitment, which determines desensitization processes, they showed no significant differences. In contrast, the 2nd administration of FEN resulted in a stronger MOR desensitization potency than that of REM, whereas REM showed a higher internalization potency than FEN. These results suggest that different ß arrestin-mediated signaling caused by FEN or REM led to their distinct desensitization and internalization processes. Our three-dimensional analysis, with in silico binding of REM and FEN to MOR models, highlighted that REM and FEN bound to similar but distinct sites of MOR and led to distinct ß arrestin-mediated profiles, suggesting that distinct binding profiles to MOR may alter ß arrestin activity, which accounts for MOR desensitization and internalization.

Effect of remimazolam on the incidence of delirium after transcatheter aortic valve implantation under general anesthesia: a retrospective exploratory study.

PURPOSE: Delirium after transcatheter aortic valve implantation (TAVI) should be prevented because it is associated with worse patient outcomes. Perioperative administration of benzodiazepines is a risk factor for postoperative delirium; however, the association between remimazolam, a newer ultrashort-acting benzodiazepine for general anesthesia, and postoperative delirium remains unclear. This study aimed to evaluate whether remimazolam administration during TAVI under general anesthesia affected the incidence of postoperative delirium. METHODS: This single-center retrospective study recruited all adult patients who underwent transfemoral TAVI (TF-TAVI) under general anesthesia between March 2020 and May 2022. Patients were divided into the remimazolam (R) and propofol (P) groups according to the sedative used for anesthesia. In the R group, all patients received flumazenil after surgery. The primary endpoint was the incidence of delirium within 3 days after surgery. Factors associated with delirium after TF-TAVI were examined by multiple logistic regression analysis. RESULTS: Ninety-eight patients were included in the final analysis (R group, n = 40; P group, n = 58). The incidence of postoperative delirium was significantly lower in the R group than in the P group (8% vs. 26%, p = 0.032). Multiple logistic regression analysis revealed that remimazolam (odds ratio 0.17, 95% CI 0.04-0.80, p = 0.024) was independently associated with the incidence of postoperative delirium, even after adjustment for age, sex, preoperative cognitive function, history of stroke, and TF-TAVI approach. CONCLUSION: Remimazolam may benefit TF-TAVI in terms of postoperative delirium; however, its usefulness must be further evaluated in extensive prospective studies.

Effects of the attachment method of the stimulating electrodes Nihon-Kohden NM-345Y™ and changes in forearm position on stimulus current values during calibration in electromyography-based neuromuscular monitoring: a single-center experimental study.

PURPOSE: The traditionally recommended method for attaching electromyography (EMG) electrodes (NM-345Y™) during EMG-based neuromuscular monitoring developed by Nihon-Kohden may decrease the monitoring accuracy when forearm limb position changes. This study investigated methods for attaching stimulating electrodes that maintained stable EMG-based neuromuscular monitoring accuracy, regardless of forearm limb position changes. METHODS: This single-center experimental study recruited 28 healthy adults from October 2022 to December 2022. The NM-345Y™ was attached to the forearm using three patterns: Pattern N, electrodes attached according to the attachment pattern recommended by Nihon-Kohden; Pattern U, electrodes attached along the ulnar nerve identified using an ultrasound device; Pattern C, electrodes attached where the ulnar nerve crosses the line connecting the centers of the anode and cathode of the stimulating electrodes. The stimulus current values during calibration were measured at three forearm positions for each attachment pattern: supination 90 degrees; pronation 0 degrees; pronation 90 degrees. The differences in stimulus current values caused by forearm position changes were calculated as the difference between values at supination 90 degrees and pronation 0 degrees and between values at supination 90 degrees and pronation 90 degrees. RESULTS: Pattern C showed significantly smaller differences than Pattern N between the stimulus current values at supination 90 degrees and pronation 0 degrees (p = 0.018) and between the stimulus current values at supination 90 degrees and pronation 90 degrees (p = 0.008). CONCLUSION: Crossing the ulnar nerve with the line connecting the anode and cathode of the stimulating electrodes may stabilize EMG-based neuromuscular monitoring accuracy.

Low aspartate aminotransferase/alanine aminotransferase ratio is a predictor of diabetes incidence in Japanese people: Population-based Panasonic cohort study 5.

AIMS: The aim of this study was to calculate the cut-off values of liver enzymes to identify the risk of incident type 2 diabetes (DM) and to investigate the association between liver enzymes and incident DM in participants with or without obesity. MATERIALS AND METHODS: The long-term cohort study included 70,688 subjects who underwent medical health checkups in 2008. The cut-off values of alanine aminotransferase (ALT) and the aminotransferase (AST)/ALT ratio for incident DM were evaluated using the time-dependent receiver operating characteristic curves. The risk of incident type 2 DM was examined according to cut-off values of liver enzymes and the group with body mass index (BMI) ≥25 kg/m2 using Cox regression analyses. RESULTS: In total, 4181 of 70,688 subjects developed DM within 10 years. The area under the curve and cut-off values for the ALT and the AST/ALT ratio for incident type 2 DM at 10 years were 0.707 and 23 IU/L and 0.694 and 0.875, respectively. The risk of incident DM was higher in subjects with ALT ≥23 or AST/ALT ≤0.875 and BMI <25 kg/m2 than in those with ALT <23 IU/L or AST/ALT >0.875 and BMI ≥25 kg/m2 , respectively. CONCLUSIONS: The cut-off values of ALT and the AST/ALT ratio associated with the risk of incident type 2 DM were determined. Non-obese individuals with AST/ALT ≤0.875 had a higher risk of incident type 2 DM than obese individuals with AST/ALT >0.875.

Ultrasound-guided regional anesthesia in COVID-19 and future pandemics: infection control.

PURPOSE OF REVIEW: Infection control is inherent in ultrasound-guided regional anesthesia practice, because ultrasound transducer and coupling gel can be vectors for pathogen transmission. We reviewed the current standards and recommendations of ultrasound transducer cleaning, disinfection, and safe handling of ultrasound equipment. Based on the available data, we propose a set of practical recommendations applicable to coronavirus disease 2019 (COVID-19) pandemic and future epidemics. RECENT FINDINGS: Regional anesthesia is often preferred over general anesthesia for COVID-19 patients. Avoidance of general anesthesia reduces the need for aerosol generating procedures. Administration of ultrasound-guided regional anesthesia and surgery under regional anesthesia in COVID-19 patients requires careful infectious precautions to prevent the viral spread through the use equipment. SUMMARY: Ultrasound machine, transducer and coupling gel can serve as a vector for transmission of pathogens. In the era of COVID-19 pandemic, standardized strategies are recommended to minimize the risk of spread of COVID-19 to both patients and the healthcare providers.

A novel method for evaluating activity of transient receptor potential channels using a cellular dielectric spectroscopy.

Cellular dielectric spectroscopy (CDS) is a novel technology enabling pharmacological evaluation of multiple receptor types with a label-free cell-based assay. We evaluated activities of a family of ligand-gated channels, transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) channels by an electrical impedance-based biosensor (CellKey™ system) using CDS. Measures of both potency (EC50) and efficacy (Emax) of these agonists with CellKey™ were almost identical to those made using the traditional Ca2+ influx assay in TRPV1- or TRPA1-expressing cells, suggesting that CellKey™ is a simpler and easier means of evaluating TRP activities.

Course of the thoracic nerves around the umbilicus within the posterior layer of the rectus sheath: a cadaver study.

Rectus sheath block is used to anesthetize thoracic nerves around the umbilicus. However, the appropriate point for anesthetic injection during rectus sheath block has not been determined anatomically. Here, we examined the course of thoracic nerve T10 at the posterior layer of the rectus sheath and the anatomical relationship between the nerve and the rectus abdominis and transversus abdominis muscles in formalin-fixed adult cadavers. The cranio-caudal distance from a horizontal line running through the umbilicus to where the thoracic nerve T10 passes through the posterior layer of the rectus sheath was 33.8 ± 14.4 (mean ± standard deviation) mm, while that from the horizontal line running through the umbilicus to the position where the lateral edge of the rectus abdominis muscle and the medial border of the transversus abdominis muscle cross was 33.1 ± 17.1 mm. The position where the lateral edge of the rectus abdominis muscle and the medial border of the transversus abdominis muscle cross approximates the position where thoracic nerves T10 passes through the posterior layer of the rectus sheath. Our results identify effective landmarks to guide the performance of rectus sheath block.

Localized synovial sarcoma: A single institutional study of 191 patients with a minimum follow-up of 5 years for survivors.

PURPOSE: Factors affecting long-term outcomes of synovial sarcoma (SS) remain unknown. Here, we aimed to investigate the long-term oncological outcomes and prognostic factors in a large group of patients with surgically-treated localized SS. PATIENTS AND METHODS: Between 1980 and 2011, 191 patients (94 males and 97 females) were treated at a single hospital with a minimum follow-up of 5 years for survivors. The median age was 35 years (range, 3-80 years), and the median follow-up period was 83 months (range, 3-235 months). RESULTS: Disease-specific survival was 76.4% and 60.4% at 5 and 10 years, respectively. Local recurrence occurred in 23 patients at a median of 33 months (range, 6-158 months), and metastasis occurred in 73 patients at a median of 20 months (range, 2-166 months). In multivariate analysis, grade 3 tumors sized ≥5 cm were significantly associated with worse survival. Ten patients (5.2%) developed metastasis more than 5 years after surgery. CONCLUSION: Tumor size and grade govern prognosis in surgically-treated localized SS in long-term settings. If adequately treated patients have not developed metastases for 5 years after surgery, the risk of subsequently developing metastases was lower than previously reported.

Spinocerebellar ataxia type 31 associated with REM sleep behavior disorder: a case report.

BACKGROUND: Spinocerebellar ataxia type 31 (SCA 31) is a slowly progressive neurodegenerative disorder characterized by pure cerebellar ataxia. Unlike other CAG repeat diseases, sleep-related problems have not been reported in patients with SCA 31 so far. CASE PRESENTATION: A 67-year-old woman was admitted to our hospital with dysarthria and gait disturbance after onset age of 62 years. Neurological examination revealed pure cerebellar ataxia. Genetic analysis detected expansion of a TGGAA repeat in the coding region of the BEAN/TK2 gene on chromosome 16p22.1, confirming the diagnosis of SCA 31. One year later, her husband noticed the patient talking loudly during sleep once or twice a week. Overnight polysomnography showed rapid eye movement sleep without atonia. Cardiac scintigraphy with iodine-123-labeled meta-iodobenzylguanidine revealed a low heart/mediastinum ratio, indicating reduced uptake, and a high washout rate. CONCLUSION: To our knowledge, this is the first report of a patient with SCA 31 associated with rapid eye movement sleep behavior disorder (RBD). In the future, evaluation of autonomic function, assessment of the frequency of RBD, and performance of cardiac iodine-123-labeled meta-iodobenzylguanidine scintigraphy in a larger number of SCA 31 patients could be useful to resolve important issues regarding the mechanism of RBD.

Carboplatin Enhances the Activity of Human Transient Receptor Potential Ankyrin 1 through the Cyclic AMP-Protein Kinase A-A-Kinase Anchoring Protein (AKAP) Pathways.

Carboplatin, an anticancer drug, often causes chemotherapy-induced peripheral neuropathy (PN). Transient receptor potential ankyrin 1 (TRPA1), a non-selective cation channel, is a polymodal nociceptor expressed in sensory neurons. TRPA1 is not only involved in pain transmission, but also in allodynia or hyperalgesia development. However, the effects of TRPA1 on carboplatin-induced PN is unclear. We revealed that carboplatin induced mechanical allodynia and cold hyperalgesia, and the pains observed in carboplatin-induced PN models were significantly suppressed by the TRPA1 antagonist HC-030031 without a change in the level of TRPA1 protein. In cells expressing human TRPA, carboplatin had no effects on changes in intracellular Ca2+ concentration ([Ca2+]i); however, carboplatin pretreatment enhanced the increase in [Ca2+]i induced by the TRPA1 agonist, allyl isothiocyanate (AITC). These effects were suppressed by an inhibitor of protein kinase A (PKA). The PKA activator forskolin enhanced AITC-induced increase in [Ca2+]i and carboplatin itself increased intracellular cyclic adenosine monophosphate (cAMP) levels. Moreover, inhibition of A-kinase anchoring protein (AKAP) significantly decreased the carboplatin-induced enhancement of [Ca2+]i induced by AITC and improved carboplatin-induced mechanical allodynia and cold hyperalgesia. These results suggested that carboplatin induced mechanical allodynia and cold hyperalgesia by increasing sensitivity to TRPA1 via the cAMP-PKA-AKAP pathway.

Anesthesia for peroral endoscopic myotomy in Japan.

PURPOSE OF REVIEW: Peroral endoscopic myotomy (POEM) was developed in Japan as a less invasive treatment for esophageal achalasia requiring general anesthesia under positive pressure ventilation. In 2018, the Japan Gastroenterological Endoscopy Society published the first guidelines describing the standard care for POEM. Based on these guidelines, we discuss the typical approach to anesthesia during POEM for the management of esophageal achalasia in Japan. RECENT FINDINGS: Prior cleansing of the esophagus is essential to prevent both aspiration during induction of anesthesia and contamination of the mediastinum and thoracic/abdominal cavity by esophageal remnants after endoscopic resection of the esophageal mucosa. Although rare, adverse events related to intraoperative carbon dioxide insufflation occur. These are treated through percutaneous needle decompression and insertion of a chest drainage tube for pneumoperitoneum and pneumothorax, respectively. Caution should be exercised regarding the development of subcutaneous emphysema and its involvement in airway obstruction. SUMMARY: Prevention of aspiration pneumonia and adverse events related to the insufflation of carbon dioxide is essential in the management of esophageal achalasia through POEM. Close cooperation between gastrointestinal endoscopic surgeons and anesthesiologists is indispensable in POEM.

Intestinal fatty acid-binding protein levels in patients with chronic renal failure.

BACKGROUND: Intestinal fatty acid-binding protein (I-FABP), a biomarker of enterocyte injury, has been reported to be a diagnostic marker of intestinal ischemia and a prognostic marker in critically ill patients. However, the kinetics of I-FABP in renal failure patients is unknown. We sought to identify I-FABP levels in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) on hemodialysis (HD) and to identify the manner in which the I-FABP levels change. MATERIALS AND METHODS: Adult patients who were admitted for elective cardiac surgery with either normal renal function (NRF), CKD, or ESKD on HD were enrolled. Serum I-FABP levels in NRF and CKD patients and in ESKD patients before and after HD were determined. RESULTS: A total of 124 patients were evaluated: 47 NRF, 53 CKD, and 24 ESKD. The I-FABP levels of the CKD patients and pre-HD ESKD patients were significantly higher than those of the NRF patients (P = 0.018 and P <0.001, respectively). I-FABP levels were significantly negatively correlated with the estimated glomerular filtration rate in NRF and CKD patients (Spearman's ρ = -0.313, P = 0.002). In addition, I-FABP levels in ESKD patients were significantly lower after HD than those before HD (P <0.001). CONCLUSIONS: I-FABP levels in CKD and pre-HD ESKD patients were significantly higher than those in NRF patients. In addition, I-FABP was significantly eliminated by HD in patients with ESKD. Clinicians and researchers should consider this aspect of I-FABP when using it as a diagnostic and prognostic marker in patients with renal insufficiency.

Natural extracellular nanovesicles and photodynamic molecules: is there a future for drug delivery?

Photodynamic molecules represent an alternative approach for cancer therapy for their property (i) to be photo-reactive; (ii) to be not-toxic for target cells in absence of light; (iii) to accumulate specifically into tumour tissues; (iv) to be activable by a light beam only at the tumour site and (v) to exert cytotoxic activity against tumour cells. However, to date their clinical use is limited by the side effects elicited by systemic administration. Extracellular vesicles are endogenous nanosized-carriers that have been recently introduced as a natural delivery system for therapeutic molecules. We have recently shown the ability of human exosomes to deliver photodynamic molecules. Therefore, this review focussed on extracellular vesicles as a novel strategy for the delivery of photodynamic molecules at cancer sites. This completely new approach may enhance the delivery and decrease the toxicity of photodynamic molecules, therefore, represent the future for photodynamic therapy for cancer treatment.

Deep and superficial circumflex iliac arteries and their relationship to the ultrasound-guided femoral nerve block procedure: A cadaver study.

The in-plane lateral to medial approach is a standard technique for ultrasound-guided femoral nerve block (USG-FNB). The first bifurcation of the femoral artery, which consists of the deep artery of the thigh (DAT) or occasionally the lateral circumflex femoral artery (LCFA), is regarded as the distal border for this procedure. We sometimes detect arteries along the estimated needle trajectory for USG-FNB. The superficial (SCIA) and deep (DCIA) circumflex iliac arteries run laterally parallel to the inguinal ligament from the femoral or external iliac artery. The relationship between the SCIA and DCIA and other anatomical structures related to USG-FNB around the femoral triangle region was studied by gross anatomical examination of 100 formalin-fixed adult cadavers. At least one SCIA and one DCIA were identified around each femoral triangle; 81.8% of SCIA and 58% of DCIA originated from the femoral artery. All DCIA coursed between the fascia lata and fascia iliaca and 80% of SCIA penetrated the fascia lata. In 94% of femoral triangles, at least one arterial branch heading towards the lateral part of the thigh originated from the femoral artery from the level of the inguinal ligament to the first bifurcation of the femoral artery. The presence of SCIA and DCIA should be considered during USG-FNB using the in-plane lateral to medial approach to avoid inadvertently injuring them, as they are occasionally located along the presumed needle trajectory superficial to the fascia iliaca. Clin. Anat. 30:413-420, 2017. © 2017 Wiley Periodicals, Inc.

Epidermal Growth Factor-dependent Activation of the Extracellular Signal-regulated Kinase Pathway by DJ-1 Protein through Its Direct Binding to c-Raf Protein.

DJ-1 is an oncogene and also a causative gene for familial Parkinson disease. DJ-1 has various functions, and the oxidative status of cysteine at position 106 (Cys-106) is crucial for determination of the activation level of DJ-1. Although DJ-1 requires activated Ras for its oncogenic activity and although it activates the extracellular signal-regulated kinase (ERK) pathway, a cell growth pathway downstream of Ras, the precise mechanism underlying activation of the ERK pathway by DJ-1 is still not known. In this study, we found that DJ-1 directly bound to the kinase domain of c-Raf but not to Ras and that Cys-106 mutant DJ-1 bound to c-Raf more weakly than did wild-type DJ-1. Co-localization of DJ-1 with c-Raf in the cytoplasm was enhanced in epidermal growth factor (EGF)-treated cells. Knockdown of DJ-1 expression attenuated the phosphorylation level of c-Raf in EGF-treated cells, resulting in reduced activation of MEK and ERK1/2. Although EGF-treated DJ-1 knock-out cells also showed attenuated c-Raf activation, reintroduction of wild-type DJ-1, but not C106S DJ-1, into DJ-1 knock-out cells restored c-Raf activation in a DJ-1 binding activity in a c-Raf-dependent manner. DJ-1 was not responsible for activation of c-Raf in phorbol myristate acetate-treated cells. Furthermore, DJ-1 stimulated self-phosphorylation activity of c-Raf in vitro, but DJ-1 was not a target for Raf kinase. Oxidation of Cys-106 in DJ-1 was not affected by EGF treatment. These findings showed that DJ-1 is a positive regulator of the EGF/Ras/ERK pathway through targeting c-Raf.