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INTRODUCTION: Few studies have reported the response of high-molecular-weight (HMW) adiponectin to acute aerobic exercise. PURPOSE: The purpose of this study was to investigate the influence of acute aerobic exercise on HMW adiponectin in healthy men. METHODS: Eight healthy men (age, 24.9 +/- 1.8 yr; BMI, 21.9 +/- 0.5 kg x m) participated in this study. They performed two trials. Trial 1 [exercise trial (EX)] consisted of 60-min stationary cycle exercise (50% peak oxygen uptake) followed by 30-min rest. Trial 2 [control trial (CON)] was 90-min rest. Blood samples were drawn to assess hormones (catecholamine and insulin), metabolites (free fatty acid [FFA], glycerol, and glucose), and total and HMW adiponectin concentration. RESULTS: There were significant trial x group interactions in serum FFA and glycerol concentrations (P < 0.05). Serum FFA and glycerol concentrations were higher in EX than in CON (P < 0.05). There were significant trial x group interactions in plasma insulin and glucose concentration (P < 0.05). Plasma insulin and glucose concentrations were lower in EX than in CON (P < 0.05). Total adiponectin, HMW adiponectin concentration, and the ratio of HMW to total adiponectin concentration, however, were unchanged during aerobic exercise and postexercise. Also, those changes did not differ between EX and CON. CONCLUSION: Our results indicate that total adiponectin and HMW adiponectin concentrations are not regulated by the change of hormones or metabolites during acute moderate-intensity aerobic exercise and postexercise in healthy young men. [ABSTRACT FROM AUTHOR]

Leukotriene C4 synthase (LTC4S) is a glutathione S -transferase that mediates the biosynthesis of cysteinyl leukotriene C4 (LTC4). Cysteinyl leukotrienes (CysLTs) are lipid mediators that drive type 2 inflammation, bronchoconstriction, and itch. Thus, LTC4S represents an attractive drug target for the treatment of allergic inflammatory diseases, but to date, no LTC4S inhibitor has been tested in patients. Herein, we disclose the discovery and preclinical profiling of the highly selective, oral LTC4S inhibitor GJG057 (compound 1 ), which exhibits 20-fold improved potency (IC 50 = 44 nM) versus clinical candidate AZD9898 (IC 50 = 900 nM) in a human whole blood LTC4 release assay. GJG057 showed efficacy in a murine asthma exacerbation model as well as in a mastoparan-induced skin challenge PK/PD model and was profiled in GLP toxicology studies. Despite its promising properties, GJG057 was not progressed into clinical trials as an oral drug. Its potential as a topical drug is currently being evaluated.

Background: Infarct volume on diffusion-weighted imaging (DWI) is a promising imaging marker for clinical outcomes in patients with acute stroke treated with mechanical thrombectomy (MT), but its predictive value has not been well evaluated, especially in consecutive patients. The present study aimed to elucidate the relationship between infarct volume and its change and favorable functional outcomes in consecutive patients with acute stroke who underwent MT., Method: Of patients with consecutive acute stroke who underwent MT from September 2014 through December 2019, those who were pre-morbidly independent were enrolled. Infarct volume on DWI was measured at admission (DWI initial ) and 24 h after admission (DWI 24h ) with semi-automated imaging software. Infarct growth (IG) was calculated as the difference between DWI 24h and DWI initial . Factors associated with a favorable outcome (mRS score 0-2) 3 months after stroke onset were assessed by multivariable analyses. Model performance was evaluated with the C-statistic., Results: A total of 251 patients (165 male [66 %], median age 75 [IQR 67-81] years, median NIHSS score 15 [7-21]) were enrolled in the present study. Multivariable logistic regression analysis showed that DWI 24h (OR 0.74, 95 % CI 0.62-0.87 for every 10-mL increment) and IG (0.74, 0.62-0.88 for every 10-mL increment) were independently and negatively associated with a favorable outcome. These associations were observed in patients with diverse vessel occlusions. Adding DWI 24h or IG to the conventional predictors of favorable outcomes improved predictive accuracy (p < 0.05)., Conclusion: DWI infarct volume 24 h after admission and IG can be strong imaging predictors of favorable outcomes after MT., Competing Interests: Declaration of competing interest This work was partly supported by JSPS KAKENHI Grant Number JP23K19574, Research fund of Mitsukoshi Health and Welfare Foundation 2024, and Grants-in-aid for medical research from Kitsuokai., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Circulating fatty acid-binding protein 4 (FABP4) influences cardiovascular disease and glucose metabolism. Acute aerobic exercise increases circulating FABP4 concentrations, but the factors underlying this effect in humans are unclear. We investigated the effect of exercise duration on circulating FABP4 concentrations in healthy men., Methods: This randomized crossover study enrolled healthy young men randomly assigned to two trials, short-duration (SE) and long-duration (LE) aerobic exercises trials. Both involved acute aerobic exercise followed by 60 min of bed rest. The exercise intensity was the same (40% peak oxygen uptake); however, the duration was 40 and 70 min for the SE and LE trials, respectively. Venous blood samples were collected to measure hormones, metabolites, and FABP4 concentrations., Results: Twelve healthy young men completed both trials. Changes in hormone levels did not differ significantly between the SE and LE trials (p > 0.05). However, the circulating FABP4 concentration increased significantly only in the LE trial immediately after exercise (p = 0.018). It increased significantly 30-60 min post-exercise in both the SE and LE trials (p < 0.018), with the extent of the increase being significantly higher in the LE trial than in the SE trial (p < 0.001). In each trial, the total incremental area under the curve of circulating FABP4 concentration was significantly positively correlated with body fat percentage (SE trial: r s  = 0.699, p = 0.019; LE trial: r s  = 0.643, p = 0.024)., Conclusion: Our findings suggest that exercise duration is associated with the magnitude of increased FABP4 secretion into the blood circulation. Body fat accumulation may also be involved in the magnitude of FABP4 secretion induced by acute aerobic exercise., Trial Registration: The study was pre-registered with the University Hospital Medical Information Network Center (UMIN), a clinical trial registration system (ID: UMIN000051068)., Competing Interests: Declarations. Ethics approval and consent to participate: The study conformed to the principles outlined in the Helsinki Declaration and was approved by the ethics committee of the National Institute of Fitness and Sports in Kanoya (Approval number: 22–1-72). The purpose, design, and risks of this study were explained to all the participants, and each participant provided written informed consent. Consent for publication: This is not applicable as the study does not have individual data. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background and Objective: Whether intracranial hemorrhage (ICH) detected using magnetic resonance imaging (MRI) affects the clinical outcomes of patients with large-vessel occlusion (LVO) treated with mechanical thrombectomy (MT) remains unclear. This study investigated the clinical features of ICH after MT detected solely by MRI., Methods: This was a retrospective analysis of patients with acute ischemic stroke and occlusion of the internal carotid artery or middle cerebral artery treated with MT between April 2011 and March 2021. Among 632 patients, patients diagnosed with no ICH using CT, with a pre-morbid modified Rankin Scale (mRS) score ≤ 2, and those who underwent MRI including T2* and computed tomography (CT) within 72 h from MT were enrolled. The main outcomes were the association between ICH detected solely by MRI and clinical outcomes at 90 days. Poor clinical outcomes were defined as mRS score > 2 at 90 days after onset., Results: Of the 246 patients, 29 (12%) had ICH on MRI (MRI-ICH(+)), and 217 (88%) were MRI-ICH(-). There was no significant difference between number of patients with MRI-ICH(+) experiencing poor (10 [12%]) and favorable (19 [12%]) outcomes. The mRS score at 90 days between patients with MRI-ICH (+) and MRI-ICH(-) was not significantly different (2 [1-4] vs. 2 [1-4], respectively). Higher age and lower ASPECTS were independent risk factors for poor outcomes, as shown by multivariate regression analysis. MRI-ICH(+) status was not associated with poor outcomes., Conclusions: ICH detected by MRI alone did not influence clinical outcomes in patients with LVO treated with MT., Competing Interests: Declaration of competing interest Kazumi Kimura received lecture fees from Bristol-Myers Squibb Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Bayer Healthcare Co., Ltd., and Daiichi Sankyo Co.; research funding from Nippon Boehringer Ingelheim Co., Ltd., Daiichi Sankyo Co., Pfizer Japan Inc., Medtronic Co., Ltd., and Teijin Pharma Ltd.; and personal funding from the 38th Mihara Cerebrovascular Disorder Research Promotion Fund, Ltd., (Copyright © 2023. Published by Elsevier B.V.)

Background: Fatty acid-binding protein 4 (FABP4) has been associated with cardiovascular disease and diabetes. Acute aerobic exercise increases circulating FABP4 concentrations, but the underlying mechanisms remain unclear. The purpose of this study was to investigate the effects of inhibition of lipolysis by carbohydrate ingestion on circulating FABP4 concentrations during and after acute aerobic exercise in healthy men., Methods: Men aged between 20 and 40, with no exercise habits and no metabolic diseases, were recruited. In a randomized crossover design, the participants underwent a carbohydrate-ingestion exercise (CE) and a fasted exercise (FE) trial. The CE trial consisted of 40-min acute aerobic exercise with ingestion of carbohydrates and 60-min bed rest. The FE trial followed the same protocol as the CE trial but without carbohydrate ingestion. Venous blood samples were collected to measure hormones (adrenaline, noradrenaline, and insulin) metabolites (glycerol, free fatty acids, and glucose), and FABP4 concentrations. Ventilation and gas exchange were also collected to measure substrate oxidation., Results: Thirteen healthy men participated in and completed both the CE and FE trials. The insulin concentration was more than 4 times higher in the CE trial than in the FE trial (p < 0.004, effect size [ES] > 2.00). Free fatty acid concentrations were more than 4 times lower in the CE trial than in the FE trial (p < 0.02, ES > 2.04). However, there was no significant difference in the changes in circulating FABP4 concentrations between the CE and FE trials (p = 0.108), which did not change during aerobic exercise and significantly increased post-aerobic exercise in both trials (p < 0.002, ES > 1.212). Changes in FABP4 concentrations following aerobic exercise were not significantly correlated with changes in glycerol or free fatty acid concentrations during aerobic exercise., Conclusions: The results suggest that suppression of lipolysis and elevation of insulin are not strongly involved in increases in FABP4 secretion following acute aerobic exercise., (© 2024. The Author(s).)

Background and Objective: Whether asymptomatic intracranial hemorrhage (ICH) affects the clinical outcomes in patients with acute large vessel occlusion treated with mechanical thrombectomy (MT) remains unclear. This study aimed to address this uncertainty., Methods: We retrospectively analyzed patients with acute ischemic stroke and internal carotid or middle cerebral (M1 segment) artery occlusion treated with MT between April 2011 and March 2021 at a single center. All patients had a premorbid modified Rankin scale (mRS) score ≤ 2 and an anterior circulation occlusion and underwent magnetic resonance imaging at admission. Asymptomatic ICH was defined as ICH without symptomatic ICH defined by the SITS-MOST criteria. A favorable outcome was defined as an mRS score ≤ 2 at 90 days after stroke onset., Results: Our study included 349 patients; 62% were men, the median age was 76 [67-83] years, and the median National Institutes of Health Stroke Scale (NIHSS) score was 15 [8-21]. As determined via computed tomography, 103 (30%) patients had ICH (20 symptomatic and 83 asymptomatic). The favorable outcome rate was significantly lower for asymptomatic vs. no ICH (30% vs. 67%, p < 0.01). In a multivariate regression analysis, a high NIHSS score (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02-1.10; p < 0.01) and low Alberta Stroke Program Early CT Score (OR, 0.78; 95% CI, 0.65-0.92; p < 0.01) were independent risk factors for ICH., Conclusions: Asymptomatic ICH is associated with poor clinical outcome at 90 days after stroke onset., Competing Interests: Declaration of competing interest Kazumi Kimura received lecture fees from Bristol-Myers Squibb Co. Ltd., Nippon Boehringer Ingelheim Co. Ltd., Bayer Healthcare Co. Ltd., and Daiichi Sankyo Co.; research funding from Nippon Boehringer Ingelheim Co. Ltd., Daiichi Sankyo Co., Pfizer Japan Inc., Medtronic Co. Ltd., and Teijin Pharma Ltd., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to investigate the association between changes in FABP4 concentration and hormone and metabolite levels during and after acute low- and moderate-intensity aerobic exercise in healthy men. Eleven healthy men (24.4±1.4 years) were administered three trials in random order: 1) low-intensity aerobic exercise trial (LE trial; acute exercise at 40% peak oxygen uptake [Vo 2 peak]+bed rest), 2) moderate-intensity aerobic exercise trial (ME trial: acute exercise at 60%Vo 2 peak+bed rest), and 3) bed rest (Con trial). Expired gas and venous blood samples were collected at baseline, and immediately, 30 and 60 min after exercise, and substrate oxidation and hormone, metabolite, and FABP4 concentrations were measured. FABP4 concentration did not increase during aerobic exercise in LE and ME trials (p>0.05). However, FABP4 concentration significantly increased after the acute aerobic exercise in both the LE and ME trials (p≤0.003). Increased FABP4 concentration after acute exercise was not correlated with adrenaline, noradrenaline, other hormone, and metabolite concentration changes. These findings suggest that FABP4 concentration increases after acute aerobic exercise independently of exercise intensity. Furthermore, increased FABP4 concentration after acute aerobic exercise may not be involved in the magnitude of adrenaline, noradrenaline, and lipolytic response., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

[Purpose] The square-touch exercise is an upper-extremity exercise program that can be performed in a seated position and includes cognitive tasks. It was designed to maintain and improve cognitive function in older people. This study aimed to investigate the effects of a three-month square-touch exercise program on the cognitive and upper-extremity functions in older females. [Participants and Methods] The participants were divided into an intervention group of 15 individuals with a mean age of 78.1 ± 5.9 years and a control group of 16 individuals with a mean age of 81.7 ± 6.3 years. The intervention group participated in the square-touch exercise program once a week for three months. The mini-mental state examination, trail-making test, peg test, and grip strength were measured before and after the intervention. [Results] The intervention group showed improved mini-mental state examination scores as well as significantly improved attention and calculation, which are sub-items of the mini-mental state examination. [Conclusion] The square-touch exercise program may be effective for maintaining and improving cognitive function in older females., Competing Interests: None., (2023©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Background/aims: Early initiation of enteral nutrition (EN) is recommended for acute stroke patients, but it is time-consuming. Reducing EN administration time without increasing the frequency of complications is a worthwhile goal. We aimed to determine whether this goal was feasible., Methods: Consecutive acute stroke patients with severe dysphagia within 72 h of hospital admission who received EN were retrospectively enrolled. Patients were classified into two groups (Rapid administration group: 100 mL/5 min on days 1-3 after stroke onset and 200 mL/30 min on days 4-7, Conventional administration group: 100 mL/h on days 1-3 and 200 mL/h on days 4-7)., Results: Among 118 consecutive acute stroke patients, 71 patients [median age, 77 (68-82) years; 37 (52%) males] were enrolled. The baseline clinical characteristics of the rapid administration group (45 patients) and the conventional administration group (26 patients) did not differ. The total duration of EN administration in the first week after stroke onset was significantly longer in the conventional vs. rapid administration group [21 (15-21) h vs. 6 (2-8) h, p < 0.01]. There were no significant differences in the frequency of diarrhea (42% vs. 42%, p = 1.00), vomiting (0% vs. 7%, p = 0.29), or pneumonia (15% vs. 7%, p = 0.41). There was also no difference in the percentage of patients with one or more complications (54% vs. 49%, p = 0.81)., Conclusions: Rapid administration of EN is safe and has the potential to decrease the time required for EN feeding., (Copyright © 2022. Published by Elsevier B.V.)

IntroductionLeukotriene A4 hydrolase (LTA4H) is the final and rate limiting enzyme regulating the biosynthesis of leukotriene B4 (LTB4), a pro-inflammatory lipid mediator implicated in a large number of inflammatory pathologies. Inhibition of LTA4H not only prevents LTB4 biosynthesis but also induces a lipid mediator class-switch within the 5-lipoxygenase pathway, elevating biosynthesis of the anti-inflammatory lipid mediator Lipoxin A4. Ample preclinical evidence advocates LTA4H as attractive drug target for the treatment of chronic inflammatory diseases.Areas coveredThis review covers details about the biochemistry of LTA4H and describes its role in regulating pro- and anti-inflammatory mediator generation. It summarizes recent efforts in medicinal chemistry toward novel LTA4H inhibitors, recent clinical trials testing LTA4H inhibitors in pulmonary inflammatory diseases, and potential reasons for the discontinuation of former development programs.Expert opinionGiven the prominent role of LTB4 in initiating and perpetuating inflammation, LTA4H remains an appealing drug target. The reason former attempts targeting this enzyme have not met with success in the clinic can be attributed to compound-specific liabilities of first-generation inhibitors and/or choice of target indications to test this mode of action. A new generation of highly potent and selective LTA4H inhibitors is currently undergoing clinical testing in indications with a strong link to LTB4 biology.

Background and Purpose: We investigated whether the signal change on fluid-attenuated inversion recovery (FLAIR) can serve as a tissue clock that predicts the clinical outcome after endovascular thrombectomy (EVT), independently of the onset-to-admission time., Methods: Consecutive patients with acute stroke treated with EVT between September 2014 and December 2018 were enrolled. Based on the parenchymal signal change on FLAIR, patients were classified into FLAIR-negative and FLAIR-positive groups. The clinical characteristics, imaging findings, EVT parameters, and the intracranial hemorrhage defined as Heidelberg Bleeding Classification ≥1c hemorrhage (parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, and/or subdural hemorrhage) were compared between the 2 groups. A modified Rankin Scale score 0 to 1 at 3 months was considered to represent a good outcome., Results: Of the 227 patients with EVT during the study period, 140 patients (62%) were classified into the FLAIR-negative group and 87 (38%) were classified into the FLAIR-positive group. In the FLAIR-negative group, the patients were older (P=0.011), the onset-to-image time was shorter (P<0.001), the frequency of cardioembolic stroke was higher (P=0.006), and the rate of intravenous thrombolysis was higher (P<0.001) in comparison to the FLAIR-positive group. Although the rate of complete recanalization after EVT did not differ between the 2 groups (P=0.173), the frequency of both any-intracranial hemorrhage and Heidelberg Bleeding Classification ≥1c hemorrhage were higher in the FLAIR-positive group (P=0.004 and 0.011). At 3 months, the percentage of patients with a good outcome (FLAIR-negative, 41%; FLAIR-positive, 27%) was significantly related to the FLAIR signal change (P=0.047), while the onset-to-image time was not significant (P=0.271). A multivariate regression analysis showed that a FLAIR-negative status was independently associated with a good outcome (odds ratio, 2.10 [95% CI, 1.02–4.31], P=0.044)., Conclusions: A FLAIR-negative status may predict the clinical outcome more accurately than the onset-to-admission time, which may support the role of FLAIR as a tissue clock.

The cytosolic metalloenzyme leukotriene A 4 hydrolase (LTA4H) is the final and rate-limiting enzyme in the biosynthesis of pro-inflammatory leukotriene B 4 (LTB 4 ). Preclinical studies have validated this enzyme as an attractive drug target in chronic inflammatory diseases. Despite several attempts, no LTA4H inhibitor has reached the market, yet. Herein, we disclose the discovery and preclinical profile of LYS006, a highly potent and selective LTA4H inhibitor. A focused fragment screen identified hits that could be cocrystallized with LTA4H and inspired a fragment merging. Further optimization led to chiral amino acids and ultimately to LYS006, a picomolar LTA4H inhibitor with exquisite whole blood potency and long-lasting pharmacodynamic effects. Due to its high selectivity and its ability to fully suppress LTB 4 generation at low exposures in vivo , LYS006 has the potential for a best-in-class LTA4H inhibitor and is currently investigated in phase II clinical trials in inflammatory acne, hidradenitis suppurativa, ulcerative colitis, and NASH.

Background: Circulating fatty acid-binding protein 4 (FABP4) is a marker for various diseases. It would be highly useful to have simple and less invasive techniques for the assessment of FABP4 concentrations in the clinical research setting. The purpose of the present study was to assess the concordance of circulating FABP4 concentrations in venous and capillary blood both at rest and immediately after acute exercise in healthy young males., Results: Thirty-eight healthy young male adults aged from 19 to 25 years (mean age, 20.8 ± 1.2 years) were recruited. Paired blood samples were taken from the cubital vein (venous) and fingertip (capillary) blood at rest (resting state) and immediately after incremental exercise (exercising state). Blood samples were analyzed to determine the circulating FABP4 concentration using an enzyme-linked immunosorbent assay. Pearson's correlation coefficients for circulating FABP4 concentrations between venous and capillary blood samples indicated a strong positive correlation in both the resting and exercising state (resting state: r = 0.982, exercising state: r = 0.989, both p < 0.001). The mean FABP4 concentration was similar between venous and capillary blood in the resting state (p = 0.178), whereas it was significantly higher in capillary blood than in venous blood in the exercising state (p < 0.001). Furthermore, Bland-Altman plots showed a non-significant bias (- 0.07 ± 0.61 ng/mL, p = 0.453) in the resting state, whereas a significant bias (- 0.45 ± 0.61 ng/mL, p < 0.001) was observed in the exercising state., Conclusions: These results indicate that capillary blood sampling can slightly overestimate circulating FABP4 concentrations under a physiologically dynamic state. However, the association between the venous and capillary blood in terms of FABP4 concentration was very strong, suggesting that capillary blood sampling can detect changes in FABP4 concentration in both physiologically steady and dynamic states.

[Purpose] To determine the potential factors for difference in metabolic profiles between metabolically healthy obesity and metabolically unhealthy obesity, we investigated the difference in abdominal fat volume, metabolic characteristics, and physical activity levels between metabolically healthy obesity and metabolically unhealthy obesity identified with cardiovascular disease risk factors in Japanese males. [Participants and Methods] Of 305 volunteers recruited, 130 obese males (age: 46.9 ± 8.9 years; body mass index: 29.6 ± 3.5 kg/m 2 ) met the criteria for the study. They were divided into two groups; metabolically healthy obesity and metabolically unhealthy obesity according to cardiovascular disease risk factors including low-density lipoprotein cholesterol. Abdominal fat volumes were measured using magnetic resonance imaging. Cardiovascular disease risk factors and metabolic characteristics were evaluated by blood pressure and blood parameters. Physical activity levels were measured using an accelerometer. [Results] Despite the fact that metabolically healthy obesity had a more favorable metabolic profile than the metabolically unhealthy obesity, no significant differences in visceral and subcutaneous fat volumes were found between the two groups. Moreover, the metabolically healthy obesity had a significantly greater physical activity expenditure and moderate-to-vigorous physical activity level than the metabolically unhealthy obesity. [Conclusion] A more favorable metabolic profile in metabolically healthy obesity may be associated with physical activity level rather than abdominal fat volumes in Japanese males., Competing Interests: The authors declared that they have no competing interests., (2021©by the Society of Physical Therapy Science. Published by IPEC Inc.)

We describe here our efforts to develop a PET tracer for imaging GluN2A-containing NMDA receptors, based on a 5H-thiazolo[3,2-α]pyrimidin-5-one scaffold. The metabolic stability and overall properties could be optimized satisfactorily, although binding affinities remained a limiting factor for in vivo imaging. We nevertheless identified 7-(((2-fluoroethyl)(3-fluorophenyl)amino)-methyl)-3-(2-(hydroxymethyl)cyclopropyl)-2-methyl-5H-thiazolo-[3,2-α]pyrimidin-5-one ([ 18 F]7b) as a radioligand providing good-quality images in autoradiographic studies, as well as a tritiated derivative, 2-(7-(((2-fluoroethyl)(4-fluorophenyl)amino)methyl)-2-methyl-5-oxo-5H-thiazolo[3,2-α]pyrimidin-3-yl)cyclopropane-1-carbonitrile ([ 3 H 2 ]15b), which was used for the successful development of a radioligand binding assay. These are valuable new tools for the study of GluN2A-containing NMDA receptors, and for the optimization of allosteric modulators binding to the pharmacophore located at the dimer interface of the GluN1-GluN2A ligand-binding domain., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Assays drive drug discovery from the exploratory phases to the clinical testing of drug candidates. As such, numerous assay technologies and methodologies have arisen to support drug discovery efforts. Robust identification and characterization of tractable chemical matter requires biochemical, biophysical, and cellular approaches and often benefits from high-throughput methods. To increase throughput, efforts have been made to provide assays in miniaturized volumes which can be arrayed in microtiter plates to support the testing of as many as 100,000 samples/day. Alongside these efforts has been the growth of microtiter plate-free formats with encoded libraries that can support the screening of billions of compounds, a hunt for new drug modalities, as well as emphasis on more disease relevant formats using complex cell models of disease states. This review will focus on recent developments in high-throughput assay technologies applied to identify starting points for drug discovery. We also provide recommendations on strategies for implementing various assay types to select high quality leads for drug development.

[Purpose] Square-stepping exercise is recommended for elderly people, as it has a positive effect on cognitive and physical functions; however, few studies have examined the exercise intensity of square-stepping exercise. Therefore, we aimed to examine the exercise intensity of square-stepping exercise in community-dwelling late elderly females. [Participants and Methods] Study 1: The participants, constituting 12 community-dwelling late elderly females (age: 78.7 ± 3.8 years), performed the three target step patterns. Exhaled gas, heart rate, and rating of perceived exertion using the Borg Scale were measured during square-stepping exercise. Study 2: Participants were 57 community-dwelling elderly females (81.2 ± 4.3 years old). The exercise intensity, heart rate, and rating of perceived exertion using the Borg Scale during square-stepping exercise were measured. [Results] Study 1: The average METs of the 3 target step patterns was 3.6 ± 0.7, and the %heart rate reserve and rating of perceived exertion were 54.3 ± 20.0% and 11.4 ± 1.9%, respectively. Study 2: The average METs during the square-stepping exercise program was 2.1 ± 0.2, and the %heart rate reserve and rating of perceived exertion were 19.6 ± 10.2% and 11.3 ± 1.4%, respectively. [Conclusion] Square-stepping exercise was confirmed to be a low to moderate intensity exercise program and is expected to improve health and physical fitness., (2020©by the Society of Physical Therapy Science. Published by IPEC Inc.)