Associations of diabetes status and glucose measures with outcomes after endovascular therapy in patients with acute ischemic stroke: an analysis of the nationwide TREAT-AIS registry.

Background: Hyperglycemia affects the outcomes of endovascular therapy (EVT) for acute ischemic stroke (AIS). This study compares the predictive ability of diabetes status and glucose measures on EVT outcomes using nationwide registry data. Methods: The study included 1,097 AIS patients who underwent EVT from the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke. The variables analyzed included diabetes status, admission glucose, glycated hemoglobin (HbA1c), admission glucose-to-HbA1c ratio (GAR), and outcomes such as 90-day poor functional outcome (modified Rankin Scale score ≥ 2) and symptomatic intracranial hemorrhage (SICH). Multivariable analyses investigated the independent effects of diabetes status and glucose measures on outcomes. A receiver operating characteristic (ROC) analysis was performed to compare their predictive abilities. Results: The multivariable analysis showed that individuals with known diabetes had a higher likelihood of poor functional outcomes (odds ratios [ORs] 2.10 to 2.58) and SICH (ORs 3.28 to 4.30) compared to those without diabetes. Higher quartiles of admission glucose and GAR were associated with poor functional outcomes and SICH. Higher quartiles of HbA1c were significantly associated with poor functional outcomes. However, patients in the second HbA1c quartile (5.6-5.8%) showed a non-significant tendency toward good functional outcomes compared to those in the lowest quartile (<5.6%). The ROC analysis indicated that diabetes status and admission glucose had higher predictive abilities for poor functional outcomes, while admission glucose and GAR were better predictors for SICH. Conclusion: In AIS patients undergoing EVT, diabetes status, admission glucose, and GAR were associated with 90-day poor functional outcomes and SICH. Admission glucose was likely the most suitable glucose measure for predicting outcomes after EVT.

Comparative study of Scleromitrion diffusum and Oldenlandia corymbosa: Microscopy, TLC, HPLC, and antioxidant activity.

Quality control of herbal medicines is crucial, especially the role of herbal drug identification. This is essential for preventing the misuse of herbs, which can affect efficacy or cause toxicity. Scleromitrion diffusum is a common herb, yet it is often mistaken for Oldenlandia corymbosa. This study analyzed the morphology, microscopy, thin-layer chromatography (TLC), and high-pressure liquid chromatography (HPLC) using two markers, asperuloside and scandoside methyl ester, to distinguish between S. diffusum and O. corymbosa with the analysis included 10 samples of S. diffusum and 10 samples of O. corymbosa collected from the Taiwan market. By quantifying the total polyphenols and flavonoids, we investigated the antioxidant activity, including the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging effect, 2,2'-azino-bis 3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+) scavenging effect, and reducing power to further elucidate the biological effects of the two herbs. The results of this study revealed notable differences in microscopy and suggested a TLC method for distinguishing between the two herbs in the market. In HPLC, the ratios of asperuloside and scandoside methyl ester differed between the two herbs. S. diffusum contained a higher asperuloside content. In contrast, O. corymbosa contained higher concentrations of scandoside methyl esters. With more total polyphenols and flavonoids in S. diffusum than those in O. corymbosa, the antioxidant activity of S. diffusum was superior to that of O. corymbosa. This study provides a comprehensive understanding for the identification and quality evaluation of S. diffusum in the market. RESEARCH HIGHLIGHTS: The study consolidates and clarifies the morphological and microscopic differences between Scleromitrion diffusum and Oldenlandia corymbosa - a common adulterant species of S. diffusum on the Taiwan markets. Using Asperuloside and Scandoside methyl ester as two chemical markers, the study proposes a TLC method for rapidly testing S. diffusum and O. corymbosa on the market. Through HPLC analysis, our results showed that S. diffusum and O. corymbosa had a clear difference in the ratio of two markers, Asperuloside and Scandoside methyl ester: Asperuloside/Scandoside methyl ester in S. diffusum is higher than that in O. corymbosa. Through phytochemicals contents, including total phenols content, flavonoids content, and antioxidant activity, including DPPH, ABTS•+ scavenging activity, and reducing power, S. diffusum showed slightly higher levels of phenols and flavonoids as well as a better antioxidant activity than O. corymbosa.

Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry.

BACKGROUND: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase). METHODS: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis. RESULTS: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40-0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88-3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0-2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28-2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43-1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata. CONCLUSIONS: Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy.

Induced pluripotent stem cell-derived exosomes attenuate vascular remodelling in pulmonary arterial hypertension by targeting HIF-1α and Runx2.

AIMS: Pulmonary arterial hypertension (PAH) is characterized by extensive pulmonary arterial remodelling. Although mesenchymal stem cell (MSC)-derived exosomes provide protective effects in PAH, MSCs exhibit limited senescence during in vitro expansion compared with the induced pluripotent stem cells (iPSCs). Moreover, the exact mechanism is not known. METHODS AND RESULTS: In this study, we used murine iPSCs generated from mouse embryonic fibroblasts with triple factor (Oct4, Klf4, and Sox2) transduction to determine the efficacy and action mechanism of iPSC-derived exosomes (iPSC-Exo) in attenuating PAH in rats with monocrotaline (MCT)-induced pulmonary hypertension. Both early and late iPSC-Exo treatment effectively prevented the wall thickening and muscularization of pulmonary arterioles, improved the right ventricular systolic pressure, and alleviated the right ventricular hypertrophy in MCT-induced PAH rats. Pulmonary artery smooth muscle cells (PASMC) derived from MCT-treated rats (MCT-PASMC) developed more proliferative and pro-migratory phenotypes, which were attenuated by the iPSC-Exo treatment. Moreover, the proliferation and migration of MCT-PASMC were reduced by iPSC-Exo with suppression of PCNA, cyclin D1, MMP-1, and MMP-10, which are mediated via the HIF-1α and P21-activated kinase 1/AKT/Runx2 pathways. CONCLUSION: IPSC-Exo are effective at reversing pulmonary hypertension by reducing pulmonary vascular remodelling and may provide an iPSC-free therapy for the treatment of PAH.

A non-invasive mouse model that recapitulates disuse-induced muscle atrophy in immobilized patients.

Disuse muscle atrophy occurs consequent to prolonged limb immobility or bed rest, which represents an unmet medical need. As existing animal models of limb immobilization often cause skin erosion, edema, and other untoward effects, we here report an alternative method via thermoplastic immobilization of hindlimbs in mice. While significant decreases in the weight and fiber size were noted after 7 days of immobilization, no apparent skin erosion or edema was found. To shed light onto the molecular mechanism underlying this muscle wasting, we performed the next-generation sequencing analysis of gastrocnemius muscles from immobilized versus non-mobilized legs. Among a total of 55,487 genes analyzed, 787 genes were differentially expressed (> fourfold; 454 and 333 genes up- and down-regulated, respectively), which included genes associated with muscle tissue development, muscle system process, protein digestion and absorption, and inflammation-related signaling. From a clinical perspective, this model may help understand the molecular/cellular mechanism that drives muscle disuse and identify therapeutic strategies for this debilitating disease.

The impact of end-stage kidney disease on mortality in patients after acute myocardial infarction: A nationwide study.

BACKGROUND: This study aimed to evaluate the impact of end-stage kidney disease (ESKD) on mortality in patients with first-time acute myocardial infarction (AMI). METHODS: This was a retrospective nationwide cohort study. Patients diagnosed with first-time AMI between January 1, 2000, and December 31, 2012, were included. All patients were followed-up until death or December 31, 2012, whichever occurred first. A one-to-one propensity score matching technique was used to match patients with ESKD to those without ESKD of similar sex, age, comorbidities, and coronary intervention (including percutaneous coronary intervention [PCI] and coronary artery bypass grafting [CABG]). Kaplan-Meier cumulative survival curves were constructed to compare AMI patients with and without ESKD. RESULTS: A total of 186 112 patients were enrolled and 8056 patients with ESKD were identified. Propensity score matched 8056 patients without ESKD were included in the comparison. Overall, the 12-year mortality rate was significantly higher in patients with ESKD than in those without ESKD (log-rank p < 0.0001), including the sex, age, and PCI and CABG subgroups. In Cox proportional-hazard regression analysis, ESKD was an independent risk factor for mortality after patients suffered from first-time AMI (hazard ratio, 1.77; 95% CI, 1.70-1.84; p < 0.0001). A forest plot for subgroup analysis revealed that in AMI patients, ESKD had a higher impact on mortality in male; younger age; without comorbidities such as hypertension, diabetes mellitus, peripheral vascular disease, heart failure, cerebrovascular accident, and chronic obstructive pulmonary disease; and receiving PCI and CABG subgroups. CONCLUSION: ESKD significantly increases the mortality risk in patients with first-time AMI, including both sexes, different ages, and whether PCI or CABG was performed. In patients with AMI, ESKD has a high impact on mortality in male, younger age, without comorbidities, and those undergoing PCI and CABG.

Impact of a targeted temperature management quality improvement project on survival and neurologic outcomes in cardiac arrest patients.

BACKGROUND: Targeted temperature management (TTM) is recommended for postresuscitation care of patients with sudden cardiac arrest (SCA) and its implementation remains challenging. This study aimed to evaluate the newly designed Quality Improvement Project (QIP) to improve the quality of TTM and outcomes of patients with SCA. METHODS: Patients who experienced out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) with return of spontaneous circulation (ROSC) and were treated in our hospital between January 2017 and December 2019 were enrolled retrospectively. All included patients received QIP intervention initiated as follows: (1) Protocols and standard operating procedures were created for TTM; (2) shared decision-making was documented; (3) job training instruction was created; and 4) lean medical management was implemented. RESULTS: Among 248 included patients, the postintervention group (n = 104) had shorter duration of ROSC to TTM than the preintervention group (n = 144) (356 vs 540 minutes, p = 0.042); better survival rate (39.4% vs 27.1%, p = 0.04), and neurologic performance (25.0% vs 17.4%, p < 0.001). After propensity score matching (PSM), patients who received TTM (n = 48 ) had better neurologic performance than those without TTM (n = 48) (25.1% vs 18.8%, p < 0.001). OHCA (odds ratio [OR] = 2.705, 95% CI: 1.657-4.416), age >60 (OR = 2.154, 95% CI: 1.428-3.244), female (OR = 1.404, 95% CI: 1.005-1.962), and diabetes mellitus (OR = 1.429, 95% CI: 1.019-2.005) were negative predictors of survival; while TTM (OR = 0.431, 95% CI: 0.266-0.699) and bystander cardiopulmonary resuscitation (CPR) (OR=0.589, 95% CI: 0.35-0.99) were positive predictors. Age >60 (OR= 2.292, 95% CI: 1.58-3.323) and OHCA (OR= 2.928, 95% CI: 1.858-4.616) were negative predictors of favorable neurologic outcomes; while bystander CPR (OR=0.572, 95% CI: 0.355-0.922) and TTM (OR=0.457, 95% CI: 0.296-0.705) were positive predictors. CONCLUSION: A new QIP with defined protocols, documented shared decision-making, and medical management guidelines improves TTM execution, duration from ROSC to TTM , survival, and neurologic outcomes of cardiac arrest patients.

Impact of medications on outcomes in patients with acute myocardial infarction and chronic obstructive pulmonary disease: A nationwide cohort study.

BACKGROUND: Various inhaled bronchodilators have been associated with cardiovascular safety concerns. This study aimed to investigate the long-term impact of chronic obstructive pulmonary disease (COPD) and the safety of COPD medications in patients after their first acute myocardial infarction (AMI). METHODS: This nationwide cohort study was conducted using data from the Taiwan National Health Insurance Research Database. Patients hospitalized between 2000 and 2012 with a primary diagnosis of first AMI were included and divided into three cohorts (AMI, ST-elevation myocardial infarction [STEMI], and non-STEMI [NSTEMI]). Each cohort was propensity score matched (1:1) with patients without COPD. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) with 95% CIs. RESULTS: A total of 186 112 patients with AMI were enrolled, and COPD was diagnosed in 13 065 (7%) patients. Kaplan-Meier curves showed that patients with COPD had a higher mortality risk than those without COPD in all cohorts (AMI, STEMI, and NSTEMI). The HR of mortality in AMI, STEMI, and NSTEMI patients with COPD was 1.12 (95% CI, 1.09-1.14), 1.20 (95% CI, 1.14-1.25), and 1.07 (95% CI, 1.04-1.10), respectively. Short-acting inhaled bronchodilators and corticosteroids increased mortality risk in all three cohorts. However, long-acting inhaled bronchodilators reduced mortality risk in patients with AMI (long-acting beta-agonist [LABA]: HR, 0.87; 95% CI, 0.81-0.94; long-acting muscarinic antagonist [LAMA]: HR, 0.82; 95% CI, 0.69-0.96) and NSTEMI (LABA: HR, 0.89; 95% CI, 0.83-0.97; LAMA: HR, 0.80; 95% CI, 0.68-0.96). CONCLUSION: This study demonstrated that AMI patients with COPD had higher mortality rates than those without COPD. Using inhaled short-acting bronchodilators and corticosteroids reduced survival, whereas long-acting bronchodilators provided survival benefits in AMI and NSTEMI patients. Therefore, appropriate COPD medication for acute AMI is crucial.

Outcome of endovascular thrombectomy in patients with end-stage renal disease undergoing dialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) are often excluded from clinical trials of endovascular thrombectomy (EVT). This study investigated the outcome in these patients. METHODS: From September 2014 to July 2021, all patients undergoing EVT for anterior circulation stroke in two stroke centers in Taiwan were included. They were divided into no renal dysfunction (non-RD, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2), RD (eGFR <60 mL/min/1.73 m2 but no dialysis), and ESRD undergoing dialysis (ESRD-dialysis). The clinical features and outcomes were compared. RESULTS: Of 482 patients included, there were 20 ESRD-dialysis, 110 RD, and 352 non-RD patients. The Alberta Stroke Program Early CT Score (ASPECTS), National Institutes of Health Stroke Scale (NIHSS), use of intravenous thrombolysis, EVT-related time metrics, and successful recanalization rates were comparable among the three groups. However, the ESRD-dialysis patients had more symptomatic intracerebral hemorrhage (ICH, 15% vs 3.6% vs 3.7%), more contrast-induced encephalopathy (15% vs 1.8% vs 0.9%), and a higher mortality at 90 days (35% vs 18% vs 11%) than the other groups. Multivariable analysis revealed that ESRD-dialysis was associated with a less favorable outcome (OR 0.21, 95% CI 0.04 to 0.77) and more severe disability or mortality (modified Rankin Scale 5 or 6; OR 13.1, 95% CI 3.93 to 48.1) at 90 days. In the ESRD-dialysis group, the patients with premorbid functional dependence had a significantly higher mortality than those without (75% vs 8.3%; P=0.004). CONCLUSION: ESRD-dialysis patients were associated with symptomatic ICH and less favorable outcome at 90 days. Patients with premorbid functional dependency had an excessively high mortality.

Eat Better to Look Better: The Relationship between Food Availability, UV Brightness of the Major Claw, and Mating Success of the Fiddler Crab Austruca lactea.

Many factors affect male fiddler crab courting and female choice during underground mating, including claw-waving patterns, claw-waving frequency, hood structures, burrow quality, and visible and ultraviolet signals of the major claw. Under food-limited conditions, fiddler crabs decrease their investments in reproduction-e.g., lower their claw-waving frequency. However, the effect of food availability on the visible or ultraviolet signals important for courtship success is unknown, not only for fiddler crabs, but for crustaceans in general. This is the first study to explore the influence of food availability on the early stages of female choice in Austruca lactea. In the present study, we tested (1) the effect of food availability on the UV brightness of A. lactea's major claw and burrow quality and (2) the correlation between A. lactea courtship success and the UV brightness of its major claw. Our results showed that higher food availability increased the UV brightness of the major claw and enhanced the male's burrow quality. The UV component to the signal is important for courtship success. The males with a UV component of signal on their major claw had a higher courtship success. This is an indication that food availability may affect the attractiveness of male fiddler crabs.

Development of a traditional Chinese medicine-based agent for the treatment of cancer cachexia.

BACKGROUND: Despite recent advances in understanding the pathophysiology of cancer cachexia, prevention/treatment of this debilitating disease remains an unmet medical need. METHODS: We developed an integrated, multi-tiered strategy involving both in vitro and in vivo muscle atrophy platforms to identify traditional Chinese medicine (TCM)-based anti-cachectic agents. In the initial screening, we used inflammatory cytokine-induced atrophy of C2C12 myotubes as a phenotypic screening platform to assess the protective effects of TCMs. The selected TCMs were then evaluated for their abilities to protect Caenorhabditis elegans from age-related reduction of mobility and contractility, followed by the C-26 colon adenocarcinoma mouse model of cachexia to confirm the anti-muscle atrophy effects (body/skeletal muscle weights, fibre size distribution, grip strengths, and serum IL-6). Transcriptome analysis, quantitative real-time polymerase chain reaction, and immunoblotting were performed to gain understanding of the potential mechanism(s) by which effective TCM protected against C26 tumour-induced muscle atrophy. RESULTS: Of 29 widely used TCMs, Dioscorea radix (DR) and Mu Dan Pi (MDP) showed a complete protection (all P values, 0.0002) vis-à-vis C26 conditioned medium control in the myotube atrophy platform. MDP exhibited a unique ability to ameliorate age-associated decreases in worm mobility, accompanied by improved total body contractions, relative to control (P < 0.0001 and <0.01, respectively), which, however, was not noted with DR. This differential in vivo protective effect between MDP and DR was also confirmed in the C-26 mouse model. MDP at 1000 mg/kg (MDP-H) was effective in protecting body weight loss (P < 0.05) in C-26 tumour-bearing mice without changing food or water intake, accompanied by the restoration of the fibre size distribution of hindleg skeletal muscles (P < 0.0001) and the forelimb grip strength (P < 0.05). MDP-treated C-26-tumour-bearing mice were alert, showed normal posture and better body conditions, and exhibited lower serum IL-6 levels (P = 0.06) relative to vehicle control. This decreased serum IL-6 was associated with the in vitro suppressive effect of MDP (25 and 50 µg/mL) on IL-6 secretion into culture medium by C26 cells. RNA-seq analysis, followed by quantitative real-time polymerase chain reaction and/or immunoblotting, shows that MDP's anti-cachectic effect was attributable to its ability to reverse the C-26 tumour-induced re-programming of muscle homoeostasis-associated gene expression, including that of two cachexia drivers (MuRF1 and Atrogin-1), in skeletal muscles. CONCLUSIONS: All these findings suggest the translational potential of MDP to foster new strategies for the prevention and/or treatment of cachexia. The protective effect of MDP on other types of muscle atrophy such as sarcopenia might warrant investigations.

A Study on the Outcome of Targeted Temperature Management Comparing Cardiac Arrest Patients Who Received Bystander Cardiopulmonary Resuscitation With Those Who Did Not, Using the Nationwide TIMECARD Multicenter Registry.

Background and Purpose: Targeted temperature management (TTM) is associated with decreased mortality and improved neurological function after cardiac arrest. Additionally, studies have shown that bystander cardiopulmonary resuscitation (BCPR) doubled the survival of patients with out-of-hospital cardiac arrest (OHCA) compared to patients who received no BPCR (no-BCPR). However, the outcome benefits of BCPR on patients who received TTM are not fully understood. Therefore, this study aimed to investigate the outcome differences between BCPR and no-BCPR in patients who received TTM after cardiac arrest. Methods: The Taiwan Network of Targeted Temperature Management for Cardiac Arrest (TIMECARD) multicenter registry established a study cohort and a database for patients receiving TTM between January 2013 and September 2019. A total of 580 patients were enrolled and divided into 376 and 204 patients in the BCPR and no-BCPR groups, respectively. Results: Compared to the no-BCPR group, the BCPR group had a better hospital discharge and survival rate (42.25 vs. 31.86%, P = 0.0305). The BCPR group also had a better neurological outcome at hospital discharge. It had a higher average GCS score (11.3 vs. 8.31, P < 0.0001) and a lower average Glasgow-Pittsburgh cerebral performance category (CPC) scale score (2.14 vs. 2.98, P < 0.0001). After undertaking a multiple logistic regression analysis, it was found that BCPR was a significant positive predictor for in-hospital survival (OR = 0.66, 95% CI: 0.45-0.97, P = 0.0363). Conclusions: This study demonstrated that BCPR had a positive survival and neurological impact on the return of spontaneous circulation (ROSC) in patients receiving TTM after cardiac arrest.

General Use of Chinese Herbal Products among Female Patients with Mastitis in Taiwan.

Objectives: Little information is available regarding the use of Chinese herbal medicine to treat mastitis. This study evaluated the prescription patterns of Chinese herbal medicine products in women with mastitis in Taiwan. Design: This is a population-based cross-sectional study. Setting. 8,531 women aged 20-49 years, who received a diagnosis of mastitis between 2004 and 2013, were identified from the Longitudinal Health Insurance Database in Taiwan. We collected data on demographic characteristics, including age, monthly insurance premium, and urbanization level. The ten most Chinese herbal medicines prescribed for mastitis were assessed, including frequency, percentage, average daily dose, and average duration of prescription. Main outcome measures. We analysed the ten most single Chinese herbs and Chinese herbal formulae prescribed for mastitis. Results: Overall, 437 (5.1%) women received Chinese herbal medicine to treat mastitis. Mai Men Dong (Ophiopogon japonicus (Thunb.) Ker Gawl.; 22.3%), Pu Gong Yin (Taraxacum mongolicum Hand.-Mazz.; 7.8%), and Wang Bu Liu Xing (Vaccaria hispanica (Mill.) Rauschert; 3.5%) were three of the most commonly prescribed single Chinese herbs for mastitis. Xian-Fang-Huo-Ming-Yin (18.2%), Jia-Wei-Xiao-Yao-San (9.1%), and Chai-Hu-Shu-Gan-San (8.4%) were three of the most commonly prescribed Chinese herbal formulae. Conclusion: Xian-Fang-Huo-Ming-Yin can clear heat, detoxify body, alleviate swelling, activate blood, and relieve pain. It was the most frequently prescribed Chinese herbal formula in patients with mastitis.

An Empirical Approach to Analyzing the Effects of Stress on Individual Creativity in Business Problem-Solving: Emphasis on the Electrocardiogram, Electroencephalogram Methodology.

In this study, experiments were conducted on 30 subjects by means of electrocardiogram (ECG) and electroencephalogram (EEG) methodologies as well as a money game to examine the effects of stress on creativity in business problem-solving. The study explained the relationship between creativity and human physiological response using the biopsychosocial model of challenge and threat. The subjects were asked to perform a cognitive mapping task. Based on the brain wave theory, we identified the types of brain waves and locations of brain activities that occurred during the creative problem-solving process in a business environment and studied the effects of stress on creativity. The results of the experiments showed significant differences in creativity in business problem-solving depending on whether or not stress was triggered. Differences were found in the time domain (SDNN, RMSSD) and frequency domain (HF, LF/HF ratio) of heart rates, a physiological stress indicator, between the stress group and the no-stress group. A brain wave analysis confirmed that alpha waves increased in the frontal lobe of the brain during creative business problem-solving but decreased when the subjects were under stress, during which beta waves in the brain increased. This study seeks to examine creativity in business problem-solving by studying the effects of stress on human physiological response and cognitive functions in the hope of providing a new and objective interpretation of existing research results.

Combining Serial and Parallel Functionality in Functional Lung Avoidance Radiation Therapy.

PURPOSE: Functional lung avoidance (FLA) radiation therapy (RT) aims to minimize post-RT pulmonary toxicity by preferentially avoiding dose to high-functioning lung (HFL) regions. A common limitation is that FLA approaches do not consider the conducting architecture for gas exchange. We previously proposed the functionally weighted airway sparing (FWAS) method to spare airways connected to HFL regions, showing that it is possible to substantially reduce risk of radiation-induced airway injury. Here, we compare the performance of FLA and FWAS and propose a novel method combining both approaches. METHODS: We used breath-hold computed tomography (BHCT) and simulation 4-dimensional computed tomography (4DCT) from 12 lung stereotactic ablative radiation therapy patients. Four planning strategies were examined: (1) Conventional: no sparing other than clinical dose-volume constraints; (2) FLA: using a 4DCT-based ventilation map to delineate the HFL, plans were optimized to reduce mean dose and V13.50 in HFL; (3) FWAS: we autosegemented 11 to 13 generations of individual airways from each patient's BHCT and assigned priorities based on the relative contribution of each airway to total ventilation. We used these priorities in the optimization along with airway dose constraints, estimated as a function of airway diameter and 5% probability of collapse; and (4) FLA + FWAS: we combined information from the 2 strategies. We prioritized clinical dose constraints for organs at risk and planning target volume in all plans. We performed the evaluation in terms of ventilation preservation accounting for radiation-induced damage to both lung parenchyma and airways. RESULTS: We observed average ventilation preservation for FLA, FWAS, and FLA + FWAS as 3%, 8.5%, and 14.5% higher, respectively, than for Conventional plans for patients with ventilation preservation in Conventional plans <90%. Generalized estimated equations showed that all improvements were statistically significant (P ≤ .036). We observed no clinically relevant improvements in outcomes of the sparing techniques in patients with ventilation preservation in Conventional plans ≥90%. CONCLUSIONS: These initial results suggest that it is crucial to consider the parallel and the serial nature of the lung to improve post-radiation therapy lung function and, consequently, quality of life for patients.

Calycosin, a Common Dietary Isoflavonoid, Suppresses Melanogenesis through the Downregulation of PKA/CREB and p38 MAPK Signaling Pathways.

Calycosin, a bioactive isoflavonoid isolated from root extracts of Astragalus membranaceus, has been reported to inhibit melanogenesis, the mechanism of which remains undefined. In this study, we interrogated the mechanistic basis by which calycosin inhibits melanin production in two model systems, i.e., B16F10 melanoma cells and zebrafish embryos. Calycosin was effective in protecting B16F10 cells from α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis and tyrosinase activity. This anti-melanogenic effect was accompanied by decreased expression levels of microphthalmia-associated transcription factor (MITF), a key protein controlling melanin synthesis, and its target genes tyrosinase and tyrosinase-related protein-2 (TRP-2) in calycosin-treated cells. Mechanistically, we obtained the first evidence that calycosin-mediated MITF downregulation was attributable to its ability to block signaling pathways mediated by cAMP response element-binding protein (CREB) and p38 MAP kinase. The protein kinase A (PKA) inhibitor H-89 and p38 inhibitor SB203580 validated the premise that calycosin inhibits melanin synthesis and tyrosinase activity by regulating the PKA/CREB and p38 MAPK signaling pathways. Moreover, the in vivo anti-melanogenic efficacy of calycosin was manifested by its ability to suppress body pigmentation and tyrosinase activity in zebrafish embryos. Together, these data suggested the translational potential of calycosin to be developed as skin-lightening cosmeceuticals.

MMP-10 from M1 macrophages promotes pulmonary vascular remodeling and pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by muscularized pulmonary blood vessels, leading to right heart hypertrophy and cardiac failure. However, state-of-the-art therapeutics fail to target the ongoing remodeling process. Here, this study shows that matrix metalloproteinases (MMP)-1 and MMP-10 levels are increased in the medial layer of vessel wall, serum, and M1-polarized macrophages from patients with PAH and the lungs of monocrotaline- and hypoxia-induced PAH rodent models. MMP-10 regulates the malignant phenotype of pulmonary artery smooth muscle cells (PASMCs). The overexpression of active MMP-10 promotes PASMC proliferation and migration via upregulation of cyclin D1 and proliferating cell nuclear antigen, suggesting that MMP-10 produced by infiltrating macrophages contributes to vascular remodeling. Furthermore, inhibition of STAT1 inhibits hypoxia-induced MMP-10 but not MMP-1 expression in M1-polarized macrophages from patients with PAH. In conclusion, circulating MMP-10 could be used as a potential targeted therapy for PAH.

Functional Outcomes and Physical Performance of Knee Osteoarthritis Patients After Ultrasound-Guided Genicular Nerve Radiofrequency Ablation.

OBJECTIVE: To elucidate the effectiveness of ultrasound-guided genicular nerve radiofrequency ablation in alleviating pain as well as its effects on functional outcomes, quality of life and physical performance in knee osteoarthritis patients. DESIGN: Prospective observational study. SETTING: Patients were recruited within one community hospital. SUBJECTS: Patients with knee osteoarthritis. METHODS: The subjects underwent ultrasound-guided radiofrequency ablation of genicular nerves after showing a positive response to a diagnostic block. Outcome assessments were performed at baseline and at 2 and 12 weeks posttreatments using the 36-item Short Form Health Survey (SF-36), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and a physical performance evaluation including balance tests, quadriceps muscle strength test, two-minute walking test and knee joint proprioception test. RESULTS: Thirteen out of 38 patients were eligible for genicular nerve radiofrequency ablation. There were significant improvements from baseline to posttreatment in the numeric rating scale score, physical health domain score of SF-36, and pain and stiffness domain scores of the WOMAC. Regarding physical performance, the step test result significantly improved over the 12 weeks of follow-up. On the other hand, no significant deteriorations in the single leg stance test, isokinetic quadriceps muscle strength test, knee joint proprioception test or two-minute walking test results were observed after radiofrequency ablation of genicular nerves. CONCLUSIONS: Radiofrequency ablation of genicular nerves may significantly alleviate pain and improve functional outcomes in knee osteoarthritis patients. More importantly, static balance control and quadriceps muscle strength were preserved and there was a change of proprioception in the good direction.

Pulmonary arterial hypertension in the elderly population.

Pulmonary arterial hypertension (PAH) was a disease predominantly affecting young females about 40 years ago; however, it has been increasingly diagnosed in elderly individuals. Few studies have investigated the features of elderly patients with PAH. This review provides an overview of the characteristics of elderly patients with PAH compared to young patients. The examination of the changing demographics of the population with PAH revealed that the mean age has increased over the years. In addition, the investigation into the diagnostic challenges in elderly patients with PAH revealed the difficulty in differentiating PAH from pulmonary hypertension secondary to diastolic heart failure. Moreover, it was noted that elderly patients underwent combination drug regimens less frequently and exhibited poorer treatment responses than young patients. Finally, it was found that elderly PAH patients experienced poorer survival than young patients. The differences among five survival prediction models and their applicability in predicting the prognosis of PAH patients are discussed.