Redox-sensitive transient receptor potential channels in oxygen sensing and adaptation

Regulation of ion channels is central to the mechanisms that underlie immediate acute physiological responses to changes in the availability of molecular oxygen (O2). A group of cation-permeable channels that are formed by transient receptor potential (TRP) proteins have been characterized as exquisite sensors of redox reactive species and as efficient actuators of electric/ionic signals in vivo. In this review, we first discuss how redox-sensitive TRP channels such as TRPA1 have recently emerged as sensors of the relatively inert oxidant O2. With regard to the physiological significance of O2 sensor TRP channels, vagal TRPA1 channels are mainly discussed with respect to their role in respiratory regulation in comparison with canonical pathways in glomus cells of the carotid body, which is a well-established O2-sensing organ. TRPM7 channels are discussed regarding hypoxia-sensing function in ischemic cell death. Also, ubiquitous expression of TRPA1 and TRPM7 together with their physiological relevance in the body is examined. Finally, based upon these studies on TRP channels, we propose a hypothesis of “O2 remodeling.” The hypothesis is that cells detect deviation of O2 availability from appropriate levels via sensors and adjust local O2 environments in vivo by controlling supply and consumption of O2 via pathways comprising cellular signals and transcription factors downstream of sensors, which consequently optimize physiological functions. This new insight into O2 adaptation through ion channels, particularly TRPs, may foster a paradigm shift in our understanding in the biological significance of O2

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

TRPCチャネル制御機構とその腎臓チャネロパチーに対する関与の解明

京都大学0048新制・課程博士博士(工学)甲第22124号工博第4654号新制||工||1726(附属図書館)京都大学大学院工学研究科合成・生物化学専攻(主査)教授 森 泰生, 教授 跡見 晴幸, 教授 浜地 格学位規則第4条第1項該当Doctor of Philosophy (Engineering)Kyoto UniversityDGA

Validación externa de los sistemas de puntuación actuales y desarrollo de un nuevo sistema de puntuación para la predicción de la tasa libre de cálculos tras la cirugía intrarrenal retrógrada en pacientes con un diámetro acumulado del cálculo de 2-4 cm

Objective: Our primary aim is to perform the external validation of the current scoring systems in predicting stone-free status (SFS) after retrograde intrarenal surgery (RIRS) for renal stones 2-4 cm and develop a novel scoring system by re-examining possible predictive factors related to SFS.Methods: Patients who underwent RIRS due to renal stones with a cumulative stone diameter of 2-4 cm between January 2017 and March 2021 were retrospectively screened. Residual stones 2 cm. The SFS predictive ability of our new scoring system was higher in > 2 cm stones compared to the other scoring systems.Objetivo: Nuestro objetivo principal es realizar la validación externa de los sistemas de puntuación actuales para predecir el estado libre de cálculos (ELC) después de la cirugía intrarrenal retrógrada (CRIR) para cálculos renales de 2−4 cm y desarrollar un nuevo sistema de puntuación reexaminando los posibles factores predictivos relacionados con el ELC. Métodos: Se evaluaron retrospectivamente los pacientes que recibieron CRIR para el tratamiento de cálculos renales con diámetro acumulado de 2−4 cm, entre enero de 2017 y marzo de 2021. Los cálculos residuales ≤2 mm se definieron como clínicamente insignificantes, y estos casos se consideraron como ELC. Se examinaron los posibles factores predictivos relacionados con el ELC mediante el análisis de regresión logística multivariante. Se elaboró un nomograma y se creó un sistema de puntuación utilizando variables predictivas independientes. Mediante el análisis ROC se evaluó la capacidad de predicción de los sistemas de puntuación actuales y del recién desarrollado. Resultados: Los sistemas de puntuación existentes resultaron insuficientes para predecir el ELC (AUC 2 cm. Nuestro nuevo sistema de puntuación tuvo una capacidad predictiva del ELC mayor en cálculos de >2 cm, en comparación con los otros sistemas de puntuación

Validación externa de los sistemas de puntuación actuales y desarrollo de un nuevo sistema de puntuación para la predicción de la tasa libre de cálculos tras la cirugía intrarrenal retrógrada en pacientes con un diámetro acumulado del cálculo de 2-4 cm

Objective: Our primary aim is to perform the external validation of the current scoring systems in predicting stone-free status (SFS) after retrograde intrarenal surgery (RIRS) for renal stones 2-4 cm and develop a novel scoring system by re-examining possible predictive factors related to SFS. Methods: Patients who underwent RIRS due to renal stones with a cumulative stone diameter of 2-4 cm between January 2017 and March 2021 were retrospectively screened. Residual stones ≤2 mm were defined as clinically insignificant, and these cases were considered to have SFS. Possible predictive factors related to SFS were examined using the multivariate logistic regression analysis. A nomogram and a scoring system were developed using independent predictive variables. The prediction ability of the previous and the new scoring system were evaluated with the ROC analysis. Results: The existing scoring systems were found to be insufficient in predicting SFS (AUC 2 cm. The SFS predictive ability of our new scoring system was higher in >2 cm stones compared to the other scoring systems.Objetivo: Nuestro objetivo principal es realizar la validación externa de los sistemas de puntuación actuales para predecir el estado libre de cálculos (ELC) después de la cirugía intrarrenal retrógrada (CRIR) para cálculos renales de 2−4 cm y desarrollar un nuevo sistema de puntuación reexaminando los posibles factores predictivos relacionados con el ELC. Métodos: Se evaluaron retrospectivamente los pacientes que recibieron CRIR para el tratamiento de cálculos renales con diámetro acumulado de 2−4 cm, entre enero de 2017 y marzo de 2021. Los cálculos residuales ≤2 mm se definieron como clínicamente insignificantes, y estos casos se consideraron como ELC. Se examinaron los posibles factores predictivos relacionados con el ELC mediante el análisis de regresión logística multivariante. Se elaboró un nomograma y se creó un sistema de puntuación utilizando variables predictivas independientes. Mediante el análisis ROC se evaluó la capacidad de predicción de los sistemas de puntuación actuales y del recién desarrollado. Resultados: Los sistemas de puntuación existentes resultaron insuficientes para predecir el ELC (AUC 2 cm. Nuestro nuevo sistema de puntuación tuvo una capacidad predictiva del ELC mayor en cálculos de >2 cm, en comparación con los otros sistemas de puntuación