Adaptive thermogenesis is essential for survival, and therefore is tightly regulated by a central neural circuit. Here, we show that microRNA (miR)-33 in the brain is indispensable for adaptive ...thermogenesis. Cold stress increases miR-33 levels in the hypothalamus and miR-33
mice are unable to maintain body temperature in cold environments due to reduced sympathetic nerve activity and impaired brown adipose tissue (BAT) thermogenesis. Analysis of miR-33
dopamine-β-hydroxylase (DBH)-Cre mice indicates the importance of miR-33 in Dbh-positive cells. Mechanistically, miR-33 deficiency upregulates gamma-aminobutyric acid (GABA)
receptor subunit genes such as Gabrb2 and Gabra4. Knock-down of these genes in Dbh-positive neurons rescues the impaired cold-induced thermogenesis in miR-33
DBH-Cre mice. Conversely, increased gene dosage of miR-33 in mice enhances thermogenesis. Thus, miR-33 in the brain contributes to maintenance of BAT thermogenesis and whole-body metabolism via enhanced sympathetic nerve tone through suppressing GABAergic inhibitory neurotransmission. This miR-33-mediated neural mechanism may serve as a physiological adaptive defense mechanism for several stresses including cold stress.
A 47-year-old man had localized pulmonary edema (LPE) and a massive pulmonary embolism. The cause of LPE was believed to be a high blood supply to the spared pulmonary artery territories without a ...thrombus. The patient was successfully treated with unfractionated heparin and thrombolytic agents.
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A 47-year-old man had localized pulmonary edema (LPE) and a massive pulmonary embolism. The cause of LPE was believed to be a high blood supply to the spared pulmonary artery territories without a ...thrombus. The patient was successfully treated with unfractionated heparin and thrombolytic agents.
Pentazocine (PTZ) is a widely used drug for postoperative pain. It should be administered at appropriate dosing intervals not only because of its morphine-like side effects but also because frequent ...inappropriate dosing can lead to dependence. Although perioperative patients reportedly have nonnegligible effects on placebo drugs and postoperative wound healing, no pharmacokinetic (PK)/pharmacodynamic (PD) model has been established and simulated using real-world data for the perioperative period. This study aimed to perform PTZ modeling and simulation and to establish an indicator of the timing of drug efficacy evaluation in clinical practice. Participants were in-hospital orthopedic surgery patients who received 15 mg of PTZ within 48 h postoperatively. Pain severity was assessed using the numerical rating scale (NRS). A two-compartment model was selected for the population PK model and an indirect response model for the PK/PD model. Using these models, a virtual population of 1000 patients with Painbase NRS of 5 and 6 and body weights of 40, 80, and 120 kg were treated with single and multiple PTZ administrations (4, 8, and 24 h apart) of 15 mg. Simulation results indicate that its analgesic efficacy should be evaluated within 1 h after administration of 15 mg of PTZ. Additional doses should be considered every 8–12 h in postoperative patients with Painbase NRS of 5 weighing 40–80 kg. Simulation using the PK/PD model developed in this study may provide useful information for determining the analgesic effects and timing of the dosing interval after PTZ administration in perioperative patients.
Histopathological diagnosis of pancreatic ductal adenocarcinoma (PDAC) on endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) specimens has become the mainstay of preoperative pathological ...diagnosis. However, on EUS-FNB specimens, accurate histopathological evaluation is difficult due to low specimen volume with isolated cancer cells and high contamination of blood, inflammatory and digestive tract cells. In this study, we performed annotations for training sets by expert pancreatic pathologists and trained a deep learning model to assess PDAC on EUS-FNB of the pancreas in histopathological whole-slide images. We obtained a high receiver operator curve area under the curve of 0.984, accuracy of 0.9417, sensitivity of 0.9302 and specificity of 0.9706. Our model was able to accurately detect difficult cases of isolated and low volume cancer cells. If adopted as a supportive system in routine diagnosis of pancreatic EUS-FNB specimens, our model has the potential to aid pathologists diagnose difficult cases.
A 79-year-old woman was presented to our hospital complaining of vomiting, fever, and abdominal pain. Abdominal computed tomography scan showed a solid 17.5 cm wide air-filled structure in the lower ...abdomen attached to small bowels, free air, and portal venous gas. Emergency surgery for peritonitis due to perforated viscera was performed, and intra operative findings revealed a perforated tumor-lesion, the size of a child's head in the ileum approximately 100 cm from the ileo cecal junction with internal necrosis. Partial ileal resection with primary small bowel anastomosis was performed. The resected specimen showed a submucosal tumor protruding in a sac-like shape on the ileum's anti-mesenteric boarder while histopathological and immunohistological examination revealed a gastrointestinal stromal tumor. She developed prolonged jaundice because of constitutional jaundice and sepsis. The patient was discharged on postoperative day 16 and treated with imatinib as adjuvant therapy because of high risk of recurrence.
Abstract
Portable-type electrostatic-collection radon monitors (RAD7) are often used for in-situ measurements of radon in water. In this study, we evaluated the calibration factors and their ...uncertainties for two RAD7 monitors based on comparative measurements with the liquid scintillation counting method. In the first experiment, we found that both RAD7 monitors had relatively large uncertainties due to leakage of radon gas that bubbled from the gaps between the lids of the desiccant container and the glass vial. Therefore, for the second experiment, these gaps were closed as much as possible using parafilm and clay, respectively. As a result, the relative uncertainties for both RAD7 monitors were significantly decreased. Furthermore, we collected spring water samples to confirm the reliability of radon concentrations. After closing the leakage point, the uncertainty of radon concentrations in spring water we measured using the typical protocol of the RAD7 were significantly lower, which improves the measurement.
In this study, several interesting iterative sequences were investigated. First, we define the iterative sequences. We fix function f(n). An iterative sequence starts with a natural number n, and ...calculates the sequence f(n),f(f(n)), ...f(f(f(f(n))),... We then search for interesting features in this sequence. We study Kaprekar's routine, the digit factorial process, and the digit power process. The authors presented new variants of Kaprekar's routine.