The Conventional and Breakthrough Tool for the Study of L-Glutamate Transporters.

In our recent report, we clarified the direct interaction between the excitatory amino acid transporter (EAAT) 1/2 and polyunsaturated fatty acids (PUFAs) by applying electrophysiological and molecular biological techniques to Xenopus oocytes. Xenopus oocytes have a long history of use in the scientific field, but they are still attractive experimental systems for neuropharmacological studies. We will therefore summarize the pharmacological significance, advantages (especially in the study of EAAT2), and experimental techniques that can be applied to Xenopus oocytes; our new findings concerning L-glutamate (L-Glu) transporters and PUFAs; and the significant outcomes of our data. The data obtained from electrophysiological and molecular biological studies of Xenopus oocytes have provided us with further important questions, such as whether or not some PUFAs can modulate EAATs as allosteric modulators and to what extent docosahexaenoic acid (DHA) affects neurotransmission and thereby affects brain functions. Xenopus oocytes have great advantages in the studies about the interactions between molecules and functional proteins, especially in the case when the expression levels of the proteins are small in cell culture systems without transfections. These are also proper to study the mechanisms underlying the interactions. Based on the data collected in Xenopus oocyte experiments, we can proceed to the next step, i.e., the physiological roles of the compounds and their significances. In the case of EAAT2, the effects on the neurotransmission should be examined by electrophysiological approach using acute brain slices. For new drug development, pharmacokinetics pharmacodynamics (PKPD) data and blood brain barrier (BBB) penetration data are also necessary. In order not to miss the promising candidate compounds at the primary stages of drug development, we should reconsider using Xenopus oocytes in the early phase of drug development.

Effect of using hypotension prediction index versus conventional goal-directed haemodynamic management to reduce intraoperative hypotension in non-cardiac surgery: A randomised controlled trial.

STUDY OBJECTIVE: It remains unclear whether it is the hypotension prediction index itself or goal-directed haemodynamic therapy that mitigates intraoperative hypotension. DESIGN: A single centre randomised controlled trial. SETTING: Sapporo Medical University Hospital. PATIENTS: A total of 64 adults patients undergoing major non-cardiac surgery under general anaesthesia. INTERVENTIONS: Patients were randomly assigned to either group receiving conventional goal-directed therapy (FloTrac group) or combination of the hypotension prediction index and conventional goal-directed therapy (HPI group). To investigate the independent utility of the index, the peak rates of arterial pressure and dynamic arterial elastance were not included in the treatment algorithm for the HPI group. MEASUREMENTS: The primary outcome was the time-weighted average of the areas under the threshold. Secondary outcomes were area under the threshold, the number of hypotension events, total duration of hypotension events, mean mean arterial pressure during the hypotension period, number of hypotension events with mean arterial pressure < 50 mmHg, amounts of fluids, blood products, blood loss, and urine output, frequency and amount of vasoactive agents, concentration of haemoglobin during the monitoring period, and 30-day mortality. MAIN RESULTS: The time-weighted average of the area below the threshold was lower in the HPI group than in the control group; 0.19 mmHg (interquartile range, 0.06-0.80 mmHg) vs. 0.66 mmHg (0.28-1.67 mmHg), with a median difference of -0.41 mmHg (95% confidence interval, -0.69 to -0.10 mmHg), p = 0.005. Norepinephrine was administered to 12 (40%) and 5 (17%) patients in the HPI and FloTrac groups, respectively (p = 0.045). No significant differences were observed in the volumes of fluid and blood products between the study groups. CONCLUSIONS: The current randomised controlled trial results suggest that using the hypotension prediction index independently lowered the cumulative amount of intraoperative hypotension during major non-cardiac surgery.

Apnea management during WATCHMAN device deployment with apneic oxygenation: A case report of three cases.

WATCHMAN is a percutaneous left atrial appendage closure device that is implanted in patients who are unsuitable for anticoagulation therapy for atrial fibrillation. During WATCHMAN implantation, inducing apnea in the patient is preferable to allow stable deployment. We present three cases in which apneic oxygenation was employed to maintain oxygenation during apnea, and oxygen reserve index (ORiTM) was measured to evaluate its safety and efficacy. Oxygen was administered continuously via the endotracheal tube during apnea. During all four apneic events in three patients (mean duration of 356 seconds), the ORi values maintained above 0.24, which is generally considered the threshold of partial pressure of arterial oxygen (PaO2) > 100 mmHg. Transcutaneous oxygen saturation and PaO2 remained above 99% and 300 mmHg, respectively. There were no respiratory or circulatory complications during or after the surgery.

Dexmedetomidine as a cardioprotective drug: a narrative review.

Dexmedetomidine (DEX), a highly selective alpha2-adrenoceptors agonist, is not only a sedative drug used during mechanical ventilation in the intensive care unit but also a cardio-protective drug against ischemia-reperfusion injury (IRI). Numerous preclinical in vivo and ex vivo studies, mostly evaluating the effect of DEX pretreatment in healthy rodents, have shown the efficacy of DEX in protecting the hearts from IRI. However, whether DEX can maintain its cardio-protective effect in hearts with comorbidities such as diabetes has not been fully elucidated. Multiple clinical trials have reported promising results, showing that pretreatment with DEX can attenuate cardiac damage in patients undergoing cardiac surgery. However, evidence of the post-treatment effects of DEX in clinical practice remains limited. In this narrative review, we summarize the previously reported evidence of DEX-induced cardio-protection against IRI and clarify the condition of the hearts and the timing of DEX administration that has not been tested. With further investigations evaluating these knowledge gaps, the use of DEX as a cardio-protective drug could be further facilitated in the management of patients undergoing cardiac surgery and might be considered in a broader area of clinical settings beyond cardiac surgery, including patients with acute myocardial infarction.

Neuroprotective Potential of L-Glutamate Transporters in Human Induced Pluripotent Stem Cell-Derived Neural Cells against Excitotoxicity.

Human induced pluripotent stem cell (hiPSC)-derived neural cells have started to be used in safety/toxicity tests at the preclinical stage of drug development. As previously reported, hiPSC-derived neurons exhibit greater tolerance to excitotoxicity than those of primary cultures of rodent neurons; however, the underlying mechanisms remain unknown. We here investigated the functions of L-glutamate (L-Glu) transporters, the most important machinery to maintain low extracellular L-Glu concentrations, in hiPSC-derived neural cells. We also clarified the contribution of respective L-Glu transporter subtypes. At 63 days in vitro (DIV), we detected neuronal circuit functions in hiPSC-derived neural cells by a microelectrode array system (MEA). At 63 DIV, exposure to 100 µM L-Glu for 24 h did not affect the viability of neural cells. 100 µM L-Glu in the medium decreased to almost 0 µM in 60 min. Pharmacological inhibition of excitatory amino acid transporter 1 (EAAT1) and EAAT2 suppressed almost 100% of L-Glu decrease. In the presence of this inhibitor, 100 µM L-Glu dramatically decreased cell viability. These results suggest that in hiPSC-derived neural cells, EAAT1 and EAAT2 are the predominant L-Glu transporters, and their uptake potentials are the reasons for the tolerance of hiPSC-derived neurons to excitotoxicity.

A Patient with Class III Obesity and a Body Mass Index of 70.1 kg/m² Requiring Pulmonary Artery Catheterization to Confirm the Diagnosis of Pulmonary Hypertension.

BACKGROUND Intensive care management of patients with morbid obesity has been linked to a higher mortality rate than that of the normal population and can be challenging. Obesity is a recognized risk factor for pulmonary hypertension, but it can prevent cardiac imaging. This report presents the case of a 28-year-old man with class III (morbid) obesity, a body mass index (BMI) of 70.1 kg/m², and heart failure, requiring pulmonary artery catheterization (PAC) to confirm the diagnosis of pulmonary hypertension. CASE REPORT A 28-year-old male patient with a a body mass index (BMI) of 70.1 kg/m² was admitted to the Intensive Care Unit (ICU) for the management of respiratory and cardiac failure. The patient had class III obesity (BMI >50 kg/m²) and heart failure. Due to the difficulties in evaluating hemodynamic status via echocardiography, a pulmonary artery catheter (PAC) was placed, revealing a mean pulmonary artery pressure of 49 mmHg, and a diagnosis of pulmonary hypertension was made. The alveolar partial pressures of oxygen and carbon dioxide were optimized by ventilatory management to reduce pulmonary vascular resistance. The patient was extubated on day 23 and was discharged from the ICU on day 28. CONCLUSIONS Pulmonary hypertension should be considered in the evaluation of obese patients. Using a PAC during the intensive care management of a patient with obesity could aid in the diagnosis of pulmonary hypertension as well as cardiac dysfunction, determine treatment strategies, and evaluate hemodynamic responses to various therapies.

Validity and Utility of Early Parameters in TEG6s Platelet Mapping to Assess the Coagulation Status During Cardiovascular Surgery With Cardiopulmonary Bypass.

Background The aim of this retrospective observational study was to explore the early predictive parameters for maximum amplitudein the kaolin with heparinase (HKH) assay (MAHKH) of TEG6s Platelet Mapping in cardiovascular surgery including cardiopulmonary bypass (CPB) period. The relationship between each parameter of the assay and laboratory data was also assessed. Methods We included the patients who underwent TEG6s Platelet Mapping during cardiovascular surgery under CPB between November 2021 and May 2022. The correlation between MAHKH and the early parameters was assessed. The association between each parameter of Platelet Mapping and a combination of fibrinogen concentration > 150 mg/dL and platelet count > 100,000µL was also evaluated by the receiver operating characteristic (ROC) curve. Results In 23 patients who underwent TEG6s Platelet Mapping during the study period, 62 HKH assay data including 59 pairs of data (HKH assay and laboratory data) were analyzed. K and angle, but not R, were significantly correlated with MAHKH (r [95% CI]: -0.90 [-0.94, -0.83], p < 0.0001 for K, and 0.87 [0.79, 0.92], p < 0.0001 for angle). Furthermore, ROC curves suggested that these parameters predicted a combination of fibrinogen concentration > 150 mg/dL and platelet count > 100,000/µL with high accuracy. Similar results were confirmed in the heparinized blood samples obtained during CPB. Conclusion These findings suggest that not only MAKHK but also K and angle, which are early parameters in the HKH assay, provide clinically significant information that will facilitate rapid decision-making regarding coagulation strategies during cardiovascular surgery including the CPB period.

Leucine 434 is essential for docosahexaenoic acid-induced augmentation of L-glutamate transporter current.

Astrocytic excitatory amino acid transporter 2 (EAAT2) plays a major role in removing the excitatory neurotransmitter L-glutamate (L-Glu) from synaptic clefts in the forebrain to prevent excitotoxicity. Polyunsaturated fatty acids such as docosahexaenoic acid (DHA, 22:6 n-3) enhance synaptic transmission, and their target molecules include EAATs. Here, we aimed to investigate the effect of DHA on EAAT2 and identify the key amino acid for DHA/EAAT2 interaction by electrophysiological recording of L-Glu-induced current in Xenopus oocytes transfected with EAATs, their chimeras, and single mutants. DHA transiently increased the amplitude of EAAT2 but tended to decrease that of excitatory amino acid transporter subtype 1 (EAAT1), another astrocytic EAAT. Single mutation of leucine (Leu) 434 to alanine (Ala) completely suppressed the augmentation by DHA, while mutation of EAAT1 Ala 435 (corresponding to EAAT2 Leu434) to Leu changed the effect from suppression to augmentation. Other polyunsaturated fatty acids (docosapentaenoic acid, eicosapentaenoic acid, arachidonic acid, and α-linolenic acid) similarly augmented the EAAT2 current and suppressed the EAAT1 current. Finally, our docking analysis suggested the most stable docking site is the lipid crevice of EAAT2, in close proximity to the L-Glu and sodium binding sites, suggesting that the DHA/Leu434 interaction might affect the elevator-like slide and/or the shapes of the other binding sites. Collectively, our results highlight a key molecular detail in the DHA-induced regulation of synaptic transmission involving EAATs.

Correlation between the hysteresis of the pressure-volume curve and the recruitment-to-inflation ratio in patients with coronavirus disease 2019.

BACKGROUND: Since the response to lung recruitment varies greatly among patients receiving mechanical ventilation, lung recruitability should be assessed before recruitment maneuvers. The pressure-volume curve (PV curve) and recruitment-to-inflation ratio (R/I ratio) can be used bedside for evaluating lung recruitability and individualing positive end-expiratory pressure (PEEP). Lung tissue recruitment on computed tomography has been correlated with normalized maximal distance (NMD) of the quasi-static PV curve. NMD is the maximal distance between the inspiratory and expiratory limb of the PV curve normalized to the maximal volume. However, the relationship between the different parameters of hysteresis of the quasi-static PV curve and R/I ratio for recruitability is unknown. METHODS: We analyzed the data of 33 patients with severe coronavirus disease 2019 (COVID-19) who received invasive mechanical ventilation. Respiratory waveform data were collected from the ventilator using proprietary acquisition software. We examined the relationship of the R/I ratio, quasi-static PV curve items such as NMD, and respiratory system compliance (Crs). RESULTS: The median R/I ratio was 0.90 [interquartile range (IQR), 0.70-1.15] and median NMD was 41.0 [IQR, 37.1-44.1]. The NMD correlated significantly with the R/I ratio (rho = 0.74, P < 0.001). Sub-analysis showed that the NMD and R/I ratio did not correlate with Crs at lower PEEP (- 0.057, P = 0.75; and rho = 0.15, P = 0.41, respectively). On the contrary, the ratio of Crs at higher PEEP to Crs at lower PEEP (Crs ratio (higher/lower)) moderately correlated with NMD and R/I ratio (rho = 0.64, P < 0.001; and rho = 0.67, P < 0.001, respectively). CONCLUSIONS: NMD of the quasi-static PV curve and R/I ratio for recruitability assessment are highly correlated. In addition, NMD and R/I ratio correlated with the Crs ratio (higher/lower). Therefore, NMD and R/I ratio could be potential indicators of recruitability that can be performed at the bedside.

Continuous renal replacement therapy using a cellulose triacetate hemofilter for severe coronavirus disease.

Background: In patients with severe coronavirus disease (COVID-19), the use of acrylonitrile hemofilters can reduce cytokine concentrations. However, acrylonitrile hemofilters can easily coagulate, and the effect of hemofilters on improvement in patient prognosis remains unclear. Therefore, we aimed to investigate the changes in serum cytokine concentrations, alleviation of organ damage, and improvement in patient prognosis with continuous renal replacement therapy (CRRT) using a cellulose triacetate (CTA) filter with excellent anticoagulation property in patients with severe COVID-19. Methods: This was a retrospective, single-center study conducted by the Advanced Critical Care Center in Sapporo Medical University Hospital, Japan. Seven patients with severe COVID-19 between March 01 and June 30, 2020, were included. The patients were under mechanical ventilation and received continuous blood purification therapy with a CTA filter. We summarized the CRRT status and patient prognosis and measured their serum cytokine (interleukin [IL]-1ß, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-α, and interferon-γ) and serum marker levels, before and after CRRT. In addition, we evaluated the changes in their respiratory status, hemodynamics, and organ dysfunction scores. The average age of the patients was 61.5 years, and five patients were male. Extracorporeal membrane oxygenation was used in five patients. The treatment outcome included three deaths. Results: The median CRRT duration was 7 days. The hemofilter was replaced once a day. After CRRT, the IL-6 concentration decreased from 393 to 85 pg/mL (p = 0.016), the Krebs von den Lungen-6 concentration decreased from 554 to 350 U/mL, and the PaO2/FiO2 ratio increased significantly from 90 to 248, and therefore, oxygenation improved. In addition, the norepinephrine dose and lactate level decreased, and the circulation tended to improve; however, the renal function and Sequential Organ Failure Assessment score did not change. Conclusions: The serum IL-6 level decreased, and the respiratory status improved upon CRRT using a CTA filter in patients with severe COVID-19.

Usefulness and accuracy of a handheld ultrasound device for epidurssal landmark and depth assessment by anesthesiology residents.

PURPOSE: The aim of this study was to assess the usefulness and accuracy of a handheld ultrasound device (Accuro, Rivanna Medical, Charlottesville, VA, USA) for epidural landmark and depth assessment when epidural anesthesia is performed by residents. METHODS: Patients scheduled to receive epidural anesthesia were randomly assigned to the Accuro group (group A) or control group (group C). In group A, the depth to the epidural space and the appropriate place for epidural insertion according to Accuro was recorded. In group C, epidural anesthesia was performed using a conventional method. The following were recorded and compared between the groups: time from puncture of the Tuohy needle to loss of resistance, number of Tuohy needle redirects, and epidural-related complications. In group A, depth to the epidural space estimated by Accuro (Accuro Depth) and the actual depth measured with a marker on the needle (Needle Depth) were recorded and compared. RESULTS: Sixty patients were enrolled during the study period. There was no significant difference between the groups regarding the median or range of time required to locate the epidural space. The number of Tuohy needle redirects was 0 (0-3) in group A and 1.5 (0-7) in group C (P = 0.012). Accuro Depth was less than Needle Depth [mean difference, 0.85 cm (95% CI-1.10 to - 0.62), SD = 0.62]. CONCLUSIONS: Although there was no significant difference in time from Tuohy needle puncture to loss of resistance, Accuro reduced the number of Tuohy needle redirects and accurately indicated the depth to the epidural space. Accuro may be useful for identifying the needle insertion point and estimating depth to the epidural space when residents perform epidural anesthesia.

Sedentary behavior is associated with reduced cardiovagal baroreflex sensitivity in healthy adults.

Sedentary behavior is an established risk factor for cardiovascular disease; however, it remains unclear whether sedentary behavior is associated with the deterioration of arterial blood pressure regulation. The purpose of this study was to determine the association between the time spent in sedentary behavior and cardiovagal baroreflex sensitivity (cBRS) in healthy adults. We investigated the cross-sectional relationship between sedentary time and cBRS in 179 adults aged 22-81 years. Sedentary time was objectively measured using a triaxial accelerometer. cBRS was evaluated by the transfer function gain of beat-by-beat changes in systolic blood pressure and the R-R interval during 5 min of spontaneous resting. Glycemic, lipidemic, and vascular risk factors were measured as potential covariates of cBRS and sedentary behavior. Men had a longer sedentary time and lower cBRS than women (p = 0.001). In a simple correlation analysis, older age was negatively associated with cBRS and positively associated with sedentary time, but sedentary time was not correlated with cBRS. However, after adjustment for age and sex, a longer sedentary time was associated with a lower cBRS. Multiple linear regression analysis showed that sedentary time was independently associated with lower cBRS with adjustment for covariates (ß = -0.325, p = 0.002). A significant association was also confirmed when the analysis was performed separately in the younger and older groups. This finding suggests that high sedentary behavior may have an adverse effect on arterial blood pressure regulation.

Infectious sacroiliitis due to group A streptococcus infection during pregnancy: a case report.

BACKGROUND: Group A streptococcus infection during pregnancy can be concerning. It may cause toxic shock syndrome, which can be fatal. Here, we report a rare case of a pregnant woman who developed infectious sacroiliitis due to group A streptococcus infection. To the best of our knowledge, this case is the first of its kind to be reported. CASE PRESENTATION: A 32-year-old multiparous Japanese woman presented with fever and right buttock pain at 28 weeks of gestation. Based on our clinical findings and investigations, she was diagnosed with group A streptococcus bacteremia and infectious sacroiliitis caused by group A streptococcus. A cardiotocography performed to assess the fetal status showed fetal tachycardia. To prevent the patient from progressing to toxic shock syndrome caused by group A streptococcus, we performed an emergency cesarean section. The patient and her infant had a good course after the cesarean section. CONCLUSION: A pregnant woman diagnosed with group A streptococcus infection needs to be monitored closely because a timely decision to deliver the fetus before rapid deterioration to toxic shock syndrome is crucial.

High-Pressure Synthesis of Transition-Metal Oxyhydrides with Double-Perovskite Structures.

We report on the high-pressure synthesis, crystal structure, and magnetic properties of four novel transition-metal oxyhydrides─Ba2NaVO3H3, Ba2NaVO2.4H3.6, Ba2NaCrO2.2H3.8, and Ba2NaTiO3H3─crystallizing in the double-perovskite structure. Notably, they have a higher hydride content in their anion sites (50%-63%) than known oxyhydrides with perovskite structures do (≤33%). Vanadium and chromium oxyhydrides exhibited Curie-Weiss magnetic susceptibilities with no magnetic ordering down to 2 K, which may be due to geometrical frustration in their face-centered lattices and weak magnetic interactions. Density functional theory calculations revealed that the transition metal-hydride bonding nature of the prepared oxyhydrides is more covalent than that observed for known perovskite oxyhydrides, as evidenced by the shorter bond lengths of the former. Remarkably, our double-perovskite oxyhydrides with a high hydride content may possess a bonding character intermediate between those of known oxyhydrides and hydrides.

Long-term light and moderate exercise intervention similarly prevent both hippocampal and glycemic dysfunction in presymptomatic type 2 diabetic rats.

A prediabetic population has an increased risk of cognitive decline and type 2 diabetes mellitus (T2DM). This study investigated whether the progression of memory dysfunction and dysregulated brain glycogen metabolism is prevented with 4 mo of exercise intervention from the presymptomatic stage in a T2DM rat model. Memory function and biochemical and molecular profiles were assessed in the presymptomatic stage of Otsuka-Long-Evans-Tokushima fatty (OLETF) rats, a T2DM model, with Long-Evans Tokushima (LETO) rats as genetic control. These rats were subjected to light- or moderate-intensity treadmill running for 4 mo with repetition of the same experiments. Significant hippocampal-dependent memory dysfunction was observed in the presymptomatic stage of OLETF rats, accompanied by downregulated levels of hippocampal monocarboxylate transporter 2 (MCT2), a neuronal lactate-transporter, without alteration in hippocampal glycogen levels. Four months of light or moderate exercise from the presymptomatic stage of T2DM normalized glycemic parameters and hippocampal molecular normalization through MCT2, glycogen, and brain-derived neurotrophic factor (BDNF) levels with the improvement of memory dysfunction in OLETF rats. A 4-mo exercise regimen from the presymptomatic stage of T2DM at a light and moderate intensities contributed to the prevention of the development of T2DM and the progression of cognitive decline with hippocampal lactate-transport and BDNF improvement.NEW & NOTEWORTHY Type 2 diabetes mellitus is an independent risk factor for hippocampal memory dysfunction, which would progress since the prediabetic stage. We found that 4 mo of exercise both at the light and moderate intensity prevented the progression of memory dysfunction with an improvement of hippocampal MCT2 expression in presymptomatic diabetes, implying that light intensity exercise could be a therapeutic approach, and the alteration of hippocampal MCT2 would be a therapeutic target of memory dysfunction from presymptomatic diabetes.

Exercise-Induced Adrenocorticotropic Hormone Response Is Cooperatively Regulated by Hypothalamic Arginine Vasopressin and Corticotrophin-Releasing Hormone.

INTRODUCTION: Exercise becomes a stress when performed at an intensity above the lactate threshold (LT) because at that point the plasma adrenocorticotropic hormone (ACTH), a marker of stress response, increases. It is possible that the exercise-induced ACTH response is regulated at least by arginine vasopressin (AVP) and possibly by corticotropin-releasing hormone (CRH), but this remains unclear. To clarify the involvement of these factors, it is useful to intervene pharmacologically in the regulatory mechanisms, with a physiologically acceptable exercise model. METHODS: We used a special stress model of treadmill running (aerobic exercise) for male Wistar rats, which mimic the human physiological response, where plasma ACTH levels increase at just above the LT for 30 min. Animals were administered the AVP V1b receptor antagonist SSR149415 (SSR) and/or the CRH type 1 receptor antagonist CP154526 (CP) intraperitoneally before the exercise, which allowed the monitoring of exercise-induced ACTH response. Immunohistochemical evaluation of activated AVP and CRH neurons with exercise was performed for the animals' hypothalami. RESULTS: A single injection of either antagonist, SSR or CP, resulted in inhibited ACTH levels after exercise stress. Moreover, the combined injection of SSR and CP strongly suppressed ACTH secretion during treadmill running to a greater extent than each alone. The running-exercise-induced activation of both AVP and CRH neurons in the hypothalamus was also confirmed. CONCLUSION: These results lead us to hypothesize that AVP and CRH are cooperatively involved in exercise-induced ACTH response just above the LT. This may also reflect the stress response with moderate-intensity exercise in humans.

Sedentary behavior and estimated nephron number in middle-aged and older adults with or without chronic kidney disease.

BACKGROUND: Excessive sedentary behavior may contribute to the pathogenesis of chronic kidney disease (CKD). The nephron index is a novel methodology for non-invasively estimating the number of functional nephrons, under the assumption that serum fibroblast growth factor 23 (FGF23) concentrations should correlate with phosphate excretion per nephron. The purpose of this study was to investigate the cross-sectional associations between daily sedentary time and the nephron index in middle-aged and older adults with or without CKD. METHODS: The daily time spent in sedentary behavior was assessed using a tri-axial accelerometer in 294 participants (182 non-CKD adults and 112 CKD patients). The nephron index value was calculated by measuring blood and spot urine phosphate and creatinine, together with serum FGF23 concentrations and estimated glomerular filtration rate. RESULTS: We observed that advancing age and CKD were associated with a progressive decrease in the nephron index value. Additionally, CKD patients with more sedentary time also had a greater nephron index decrease compared to those with less sedentary time (P < 0.05). Multiple linear regression analysis confirmed the independent association between sedentary time and the nephron index after adjusting for age, sex, presence of CKD, overweight/obesity, medication use, and total wear time (ß = -0.13, P = 0.035). CONCLUSIONS: These cross-sectional findings suggest that age- or CKD-related decreases in the estimated nephron number (that is, the nephron index) may be accelerated by increased sedentary behavior.

Differences in exercise capacity and physiological responses in Wistar rats among breeders.

In animal experiments aimed at extrapolation to humans, it is essential to ensure the reproducibility of experiments and universality between animals and humans. However, among animals with the same generic name but from different breeders, which is to say different stocks, even resting physiological conditions, such as genetics, do not coincide, and, therefore, exercise capacity and physiological responses may also vary. To address this issue, we examined the differences in exercise capacity and exercise-induced metabolic and endocrine responses among stocks of Wistar rats using an established treadmill running model for rodents, which mimics physiological responses in humans. Wistar rats from four breeders were acclimated to treadmill running and then had a catheter inserted into their external jugular veins. Subsequently, the rats were subjected to an incremental treadmill running test (IRT). We found that there were significant differences in the exercise capacity among Wistar rats from different breeders. Additionally, the dynamics of blood lactate, glucose, and adrenocorticotropic hormone levels during the IRT were found to vary among the Wistar rats from different breeders; only one stock showed human-type exercise-induced physiological responses. These results indicate that Wistar rats could have different capacities for and physiological responses to the same exercise depending on their stocks. Thus, the selection of the stock of experimental animals may affect the validity of the results when verifying exercise effects.