Effect and mechanism of quercetin or quercetin-containing formulas against COVID-19: From bench to bedside.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global coronavirus disease 2019 (COVID-19) pandemic since 2019. Immunopathogenesis and thromboembolic events are central to its pathogenesis. Quercetin exhibits several beneficial activities against COVID-19, including antiviral, anti-inflammatory, immunomodulatory, antioxidative, and antithrombotic effects. Although several reviews have been published, these reviews are incomplete from the viewpoint of translational medicine. The authors comprehensively evaluated the evidence of quercetin against COVID-19, both basically and clinically, to apply quercetin and/or its derivatives in the future. The authors searched the PubMed, Embase, and the Cochrane Library databases without any restrictions. The search terms included COVID-19, SARS-CoV-2, quercetin, antiviral, anti-inflammatory, immunomodulatory, thrombosis, embolism, oxidative, and microbiota. The references of relevant articles were also reviewed. All authors independently screened and reviewed the quality of each included manuscript. The Cochrane Risk of Bias Tool, version 2 (RoB 2) was used to assess the quality of the included randomized controlled trials (RCTs). All selected studies were discussed monthly. The effectiveness of quercetin against COVID-19 is not solid due to methodological flaws in the clinical trials. High-quality studies are also required for quercetin-containing traditional Chinese medicines. The low bioavailability and highly variable pharmacokinetics of quercetin hinder its clinical applications. Its positive impact on immunomodulation through reverting dysbiosis of gut microbiota still lacks robust evidence. Quercetin against COVID-19 does not have tough clinical evidence. Strategies to improve its bioavailability and/or to develop its effective derivatives are needed. Well-designed RCTs are also crucial to confirm their effectiveness in the future.

Proton pump inhibitors reduce the survival of advanced lung cancer patients with therapy of gefitinib or erlotinib.

Gefitinib and erlotinib are the first-line tyrosine kinase inhibitors (TKI) for advanced non-small-cell lung cancer. However, co-administration of either drug with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) may reduce TKI's bioavailability. Therefore, we aimed to investigate the effects of these drug-drug interactions. We surveyed nationwide population-based databases between Jan 1, 2010, and Dec 30, 2018. Newly diagnosed patients with advanced lung adenocarcinoma who received first-line gefitinib or erlotinib were identified. Effects on overall survival (OS) and time to next treatment (TTNT) association between PPIs or H2RAs and co-administrated gefitinib or erlotinib were evaluated. PPIs or H2RAs users were defined if the period overlapped with TKIs by ≥ 20%. A total of 4340 gefitinib and 1635 erlotinib users were included. PPI group had the shortest median OS and TTNT compared to the H2RA and non-user groups (in gefitinib cohort: OS: 14.35 vs. 17.67 vs. 21.87 months; P < 0.0001, TTNT: 8.47 vs. 10.78 vs. 10.33 months; P < 0.0001); (in erlotinib cohort: OS: 16.97 vs. 20.07 vs. 23.92 months; P < 0.0001, TTNT: 9.06 vs. 11.85 vs. 10.90 months; P = 0.0808). Compared with the non-user group, the adjusted hazard ratio (aHR) of the PPI group in the gefitinib was 1.58 on OS (95% CI 1.42-1.76), 1.37 on TTNT (95% CI 1.24-1.52); in the erlotinib was 1.54 on OS (95% CI 1.30-1.82) and 1.19 on TTNT (95% CI 1.01-1.39). Concurrent use of PPIs with first-line gefitinib or erlotinib therapy was associated with a worse OS and TTNT in patients with lung adenocarcinoma harboring EGFR mutations.

Spine-like Joint Link Mechanism to Design Wearable Assistive Devices.

When we develop wearable assistive devices, comfort and support are two main issues that need to be considered. In conventional design approaches, the degree of freedom of the wearer's joint movements tends to be oversimplified. Accordingly, the wearer's motion becomes restrained and bone/ligament injuries might occur in case of an unexpected fall. To mitigate these issues, this paper proposes a novel joint link mechanism inspired by a human spine structure as well as functionalities. The key feature of the proposed spine-like joint link mechanism is that hemispherical blocks are concatenated via flexible synthetic fiber lines so that their concatenation stiffness can be adjusted according to a tensile force. This feature has a great potentiality for designing a wearable assistive device that can support aged people's sit-to-stand action or augment spinal motion by regulating the concatenation stiffness. In addition, the concatenated hemispherical blocks enable the wearer to move his/her joint with full freedom, which in turn increases the wearer's mobility and prevents joint misalignment. The experimental results with a testbed and a pilot wearer substantiated that the spine-like joint link mechanism can serve as a key component in the design of wearable assistive devices for better mobility.

IGFBP-3 and TGF-ß inhibit growth in epithelial cells by stimulating type V TGF-ß receptor (TßR-V)-mediated tumor suppressor signaling.

The TGF-ß type V receptor (TßR-V) mediates growth inhibition by IGFBP-3 and TGF-ß in epithelial cells and loss of TßR-V expression in these cells leads to development of carcinoma. The mechanisms by which TßR-V mediates growth inhibition (tumor suppressor) signaling remain elusive. Previous studies revealed that IGFBP-3 and TGF-ß inhibit growth in epithelial cells by stimulating TßR-V-mediated IRS-1/2-dependent activation and cytoplasm-to-nucleus translocation of IGFBP-3- or TGF-ß-stimulated protein phosphatase (PPase), resulting in dephosphorylation of pRb-related proteins (p107, p130) or pRb, and growth arrest. To define the signaling, we characterized/identified the IGFBP-3- and TGF-ß-stimulated PPases in cell lysates and nucleus fractions in Mv1Lu cells treated with IGFBP-3 and TGF-ß, using a cell-free assay with 32P-labeled casein as a substrate. Both IGFBP-3- and TGF-ß-stimulated PPase activities in cell lysates are abolished when cells are co-treated with TGF-ß/IGFBP-3 antagonist or RAP (LRP-1/TßR-V antagonist). However, the IGFBP-3-stimulated PPase activity, but not TGF-ß-stimulated PPase activity, is sensitive to inhibition by okadaic acid (OA). In addition, OA or PP2Ac siRNA reverses IGFBP-3 growth inhibition, but not TGF-ß growth inhibition, in Mv1Lu and 32D cells. These suggest that IGFBP-3- and TGF-ß-stimulated PPases are identical to PP2A and PP1, respectively. By Western blot/phosphorimager/immunofluorescence-microscopy analyses, IGFBP-3 and TGF-ß stimulate TßR-V-mediated IRS-2-dependent activation and cytoplasm-to-nucleus translocation of PP2Ac and PP1c, resulting in dephosphorylation of p130/p107 and pRb, respectively, and growth arrest. Small molecule TGF-ß enhancers, which potentiate TGF-ß growth inhibition by enhancing TßR-I-TßR-II-mediated canonical signaling and thus activating TßR-V-mediated tumor suppressor signaling cascade (TßR-V/IRS-2/PP1/pRb), could be used to prevent and treat carcinoma.

Differential effects of body mass index on domain-specific cognitive outcomes after stroke.

Although the obesity paradox is an important modifiable factor in cardiovascular diseases, little research has been conducted to determine how it affects post-stroke cognitive function. We aimed to investigate the association between body mass index (BMI) and domain-specific cognitive outcomes, focusing on the subdivision of each frontal domain function in post-ischemic stroke survivors. A total of 335 ischemic stroke patients were included in the study after completion of the Korean-Mini Mental Status Examination (K-MMSE) and the vascular cognitive impairment harmonization standards neuropsychological protocol at 3 months after stroke. Frontal lobe functions were analyzed using semantic/phonemic fluency, processing speed, and mental set shifting. Our study participants were categorized into four groups according to BMI quartiles. The z-scores of K-MMSE at 3 months differed significantly between the groups after adjustment for initial stroke severity (p = 0.014). Global cognitive function in stroke survivors in the Q1 (the lowest quartile) BMI group was significantly lower than those in Q2 and Q4 (the highest quartile) BMI groups (K-MMSE z-scores, Q1: - 2.10 ± 3.40 vs. Q2: 0.71 ± 1.95 and Q4: - 1.21 ± 1.65). Controlled oral word association test findings indicated that phonemic and semantic word fluency was lower in Q4 BMI group participants than in Q2 BMI group participants (p = 0.016 and p = 0.023 respectively). BMI might differentially affect cognitive domains after ischemic stroke. Although being underweight may negatively affect global cognition post-stroke, obesity could induce frontal lobe dysfunctions, specifically phonemic and semantic word fluency.

Impact of an Education Program for Caregivers of Patients with Alzheimer's Disease on Treatment Discontinuation and Compliance in Korea.

BACKGROUND AND PURPOSE: Reportedly 30-50% of patients being treated for chronic illnesses do not adhere to their medication regimen. We assessed the impact of a nurse-led education program for caregivers of Korean de novo Alzheimer's disease patients who had newly been prescribed donepezil. METHODS: This multicenter study analyzed 93 participants in a caregiver education group and 92 participants in a caregiver no-education group. At every visit up to the end of the study (1 year), caregivers in the education group were given educational brochures regarding Alzheimer's disease and the efficacy and adverse events of donepezil treatment. The primary endpoint was the discontinuation rate of donepezil treatment during the 1-year observation period. The secondary endpoints included the effect of education on compliance with donepezil treatment assessed at each visit using a clinician rating scale (CRS) and visual analog scale (VAS), and changes from baseline in cognitive assessment tests. RESULTS: The donepezil discontinuation rates at 1 year were 5.38% (5/93) and 6.52% (6/92) in the caregiver education and no-education groups, respectively (p=0.742). No significant between-group differences in donepezil compliance rates on the CRS and VAS were observed, but significant changes were observed in some cognitive tests from baseline to the end of the study. CONCLUSIONS: Caregiver education had no significant effect on treatment discontinuation, but this may have been due to the low severity of cognitive impairment among the included population at baseline. In addition, the low discontinuation rates meant that no significant difference in treatment compliance was observed.

Discontinuation Rate of Newly Prescribed Donepezil in Alzheimer's Disease Patients in Asia.

BACKGROUND AND PURPOSE: The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer's disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. METHODS: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50-90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation, treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). RESULTS: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test-Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. CONCLUSIONS: In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Caregiving, care burden and awareness of caregivers and patients with dementia in Asian locations: a secondary analysis.

BACKGROUND: This study investigated the differences in caregiver activity, caregiver burden, and awareness of both caregivers and patients with Alzheimer's disease (AD) across different Asian locations. METHODS: This was a secondary analysis of a multi-national cohort study that aimed to assess caregiver activity and caregiver burden using the Caregiver Activity Scale (CAS) and Zarit Burden Interview (ZBI), respectively. Patients' awareness of their dementia diagnosis was assessed by asking the following yes/no question: "Do you have dementia?" Caregivers' awareness of the patient's dementia diagnosis was assessed by asking the following yes/no question: "Does your patient have dementia?" RESULTS: In total, 524 caregivers of patients with AD from China, Hong Kong, South Korea, the Philippines, Singapore, Thailand, and Taiwan participated. The CAS and ZBI score were significantly different across most locations (p < 0.001 and p = 0.033, respectively). Overall, 56.6% of caregivers and 37.5% of patients had awareness of the dementia diagnosis, and the proportion of patients and caregivers with awareness were also different between each location (all, p < 0.001). CONCLUSIONS: Caregiving, caregiver burden, and the awareness of caregivers and patients were different across many Asian locations. With understanding of cultural differences, further public education on dementia could help increase the awareness of patients and caregivers and reduce caregiver burden. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02262975 . Registered 13 October 2014.

Content Analysis of Korean Videos Regarding Restless Legs Syndrome on YouTube.

OBJECTIVE: To evaluate the accuracy and quality of Korean videos associated with restless legs syndrome (RLS) on YouTube. METHODS: A YouTube search was performed on April 1, 2020 using the term "restless legs syndrome" in the Korean language. Two reviewers coded the source, content, and demographics of the included videos. Video quality was assessed using the modified DISCERN (mDISCERN) instrument. RESULTS: Among the 80 videos analyzed, 44 (55.0%) were reliable, and 36 (45.0%) were misleading. There was a trend toward a higher number of mean daily views in the misleading videos than in the reliable videos. Most of the misleading videos (72.2%) advocated complementary and alternative medicine as a primary treatment for RLS. Although the reliable videos had higher mDISCERN scores than the misleading videos, the overall quality of the reliable videos was low. CONCLUSION: Many Korean videos regarding RLS on YouTube involve a risk of exposure to misinformation and are of unsatisfactory quality.

Serum Homocysteine Is Associated With HDL Only in Stroke Patients With Small Vessel Occlusion.

Background: Although controversial, homocysteine (Hcy) and lipid parameters have been associated with particular stroke subtypes. However, there are limited studies concerning the relationship between Hcy and lipid levels in acute ischemic stroke (AIS). We evaluated the impact of Hcy levels on lipid profiles in terms of specific stroke subtypes. Methods: A total of 2,324 patients with first-ever AIS were recruited from two hospitals in South Korea. The exclusion criteria were as follows: (a) pre-stroke modified Rankin scale (mRS) ≥ 1, (b) undetermined or other stroke etiology, and (c) absence of Hcy data. Among the 1,580 eligible patients, the Hcy level was divided into tertile groups. Logistic regression was used to assess association of Hcy levels with lipid levels by stroke subtypes. Results: Significant downward trends in total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were only observed in patients with small vessel occlusion (SVO) as Hcy increased. In logistic regression analysis, while in patients with SVO subtype, the highest level of Hcy tertiles (OR = 1.648, 95% CI = 1.047-2.594) was associated with the lower HDL level (≤40 mg/dL), the significance disappeared in patients with LAA and CE subtypes. Conclusion: Although our study does not demonstrate causal relationship, we suggest that Hcy might play a mediating role between HDL and SVO stroke development. To clarify the role of Hcy on AIS, this study will provide academic support for designing future research.

Timing of Transfusion, not Hemoglobin Variability, is Associated with 3-Month Outcomes in Acute Ischemic Stroke.

Objectives: This study aimed to investigate whether transfusions and hemoglobin variability affects the outcome of stroke after an acute ischemic stroke (AIS). METHODS: We studied consecutive patients with AIS admitted in three tertiary hospitals who received red blood cell (RBC) transfusion (RBCT) during admission. Hemoglobin variability was assessed by minimum, maximum, range, median absolute deviation, and mean absolute change in hemoglobin level. Timing of RBCT was grouped into two categories: admission to 48 h (early) or more than 48 h (late) after hospitalization. Late RBCT was entered into multivariable logistic regression model. Poor outcome at three months was defined as a modified Rankin Scale score ≥3. RESULTS: Of 2698 patients, 132 patients (4.9%) received a median of 400 mL (interquartile range: 400-840 mL) of packed RBCs. One-hundred-and-two patients (77.3%) had poor outcomes. The most common cause of RBCT was gastrointestinal bleeding (27.3%). The type of anemia was not associated with the timing of RBCT. Late RBCT was associated with poor outcome (odd ratio (OR), 3.55; 95% confidence interval (CI), 1.43-8.79; p-value = 0.006) in the univariable model. After adjusting for age, sex, Charlson comorbidity index, and stroke severity, late RBCT was a significant predictor (OR, 3.37; 95% CI, 1.14-9.99; p-value = 0.028) of poor outcome at three months. In the area under the receiver operating characteristics curve comparison, addition of hemoglobin variability indices did not improve the performance of the multivariable logistic model. CONCLUSION: Late RBCT, rather than hemoglobin variability indices, is a predictor for poor outcome in patients with AIS.

Impact of 25-Hydroxyvitamin D on the Prognosis of Acute Ischemic Stroke: Machine Learning Approach.

Background and Purpose: Vitamin D is a predictor of poor outcome for cardiovascular disease. We evaluated whether serum 25-hydroxyvitamin D level was associated with poor outcome in patients with acute ischemic stroke (AIS) using machine learning approach. Materials and Methods: We studied a total of 328 patients within 7 days of AIS onset. Serum 25-hydroxyvitamin D level was obtained within 24 h of hospital admission. Poor outcome was defined as modified Rankin Scale score of 3-6. Logistic regression and extreme gradient boosting algorithm were used to assess association of 25-hydroxyvitamin D with poor outcome. Prediction performances were compared with area under ROC curve and F1 score. Results: Mean age of patients was 67.6 ± 13.3 years. Of 328 patients, 59.1% were men. Median 25-hydroxyvitamin D level was 10.4 (interquartile range, 7.1-14.8) ng/mL and 47.2% of patients were 25-hydroxyvitamin D-deficient (<10 ng/mL). Serum 25-hydroxyvitamin D deficiency was a predictor for poor outcome in multivariable logistic regression analysis (odds ratio, 3.38; 95% confidence interval, 1.24-9.18, p = 0.017). Stroke severity, age, and 25-hydroxyvitamin D level were also significant predictors in extreme gradient boosting classification algorithm. Performance of extreme gradient boosting algorithm was comparable to those of logistic regression (AUROC, 0.805 vs. 0.746, p = 0.11). Conclusions: 25-hydroxyvitamin D deficiency was highly prevalent in Korea and low 25-hydroxyvitamin D level was associated with poor outcome in patients with AIS. The machine learning approach of extreme gradient boosting was also useful to assess stroke prognosis along with logistic regression analysis.

Is colistin-associated acute kidney injury clinically important in adults? A systematic review and meta-analysis.

Colistin is the last-resort antimicrobial agent against infections caused by multidrug-resistance Gram-negative bacteria (MDR-GNB). However, a differing risk of colistin-associated acute kidney injury (CA-AKI) has been demonstrated without affecting mortality, thus the association and its importance needs to be questioned. To assess the impact of this adverse effect, a meta-analysis comparing colistin with other antibiotics in treating MDR-GNB infections was conducted. The PubMed, Embase and Cochrane Library electronic databases were searched up to 31 December 2018 for cohort studies and randomised controlled trials with at least two arms with one arm containing colistin-based treatment. The primary endpoint was the incidence of AKI. The secondary endpoint was 30-day all-cause mortality. A total of 34 studies, including 26 regarding colistin-based therapy versus other antibiotics and 9 regarding colistin monotherapy versus combination therapy, were included. The incidence of CA-AKI was 32.3%. Colistin was associated with an 82% higher incidence of AKI than other antibiotics [odd ratio (OR) = 1.82, 95% confidence interval (CI) 1.13-2.92; P = 0.01]. Most CA-AKI events were mild and reversible without a higher rate of mortality or the requirement for renal replacement therapy (RRT). Only 1.0% of patients required RRT for > 4 weeks. Compared with colistin monotherapy, combination therapy was associated with a significantly lower incidence of AKI (OR = 1.46, 95% CI 1.10-1.94; P = 0.009), particularly in combination with a carbapenem (OR = 1.97, 95% CI 1.30-2.99; P = 0.001). In conclusion, CA-AKI might not be an important limitation of colistin in MDR-GNB therapy.

Unraveling the Molecular Mechanism of Traditional Chinese Medicine: Formulas Against Acute Airway Viral Infections as Examples.

Herbal medicine, including traditional Chinese medicine (TCM), is widely used worldwide. Herbs and TCM formulas contain numerous active molecules. Basically, they are a kind of cocktail therapy. Herb-drug, herb-food, herb-herb, herb-microbiome, and herb-disease interactions are complex. There is potential for both benefit and harm, so only after understanding more of their mechanisms and clinical effects can herbal medicine and TCM be helpful to users. Many pharmacologic studies have been performed to unravel the molecular mechanisms; however, basic and clinical studies of good validity are still not enough to translate experimental results into clinical understanding and to provide tough evidence for better use of herbal medicines. There are still issues regarding the conflicting pharmacologic effects, pharmacokinetics, drug interactions, adverse and clinical effects of herbal medicine and TCM. Understanding study validation, pharmacologic effects, drug interactions, indications and clinical effects, adverse effects and limitations, can all help clinicians in providing adequate suggestions to patients. At present, it would be better to use herbs and TCM formulas according to their traditional indications matching the disease pathophysiology and their molecular mechanisms. To unravel the molecular mechanisms and understand the benefits and harms of herbal medicine and TCM, there is still much work to be done.

Optimal Regimen of N-Acetylcysteine on Chromium-Induced Renal Cell Damage.

Chromium (Cr) is a well-known heavy metal that can cause renal damage. The production of reactive oxygen species (ROS) due to chromium-induced toxicity induces cell dysfunction, apoptosis, and death. N-acetylcysteine (NAC) is an antioxidant used as an antidote for chromium-induced toxicity. However, the optimal regimen and protective mechanisms of NAC are not fully understood in human renal cells. Our results showed that exposure to 10 µM K2Cr2O7, a toxic Cr(VI) compound, induced apoptosis and production of intracellular ROS in the human proximal tubular epithelial cell line HK-2. Supplements of 600 or 1000 µg/mL NAC inhibited intracellular ROS in HK-2 cells exposed to Cr(VI) and significantly increased cell viability within 2 h of Cr(VI)-induced cytotoxicity. Moreover, Cr(VI) induced the expression of apoptosis markers, including cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerase, cleaved-caspase 8, and cleaved-caspase 9, and altered the expression ratio of Bax/Bcl-xL. Expression of apoptosis markers within 2 h of Cr(VI)-induced cytotoxicity in cells treated with 600 µg/mL NAC was significantly suppressed. However, delayed treatment with NAC at 4 h and 8 h after exposure to Cr did not suppress the activation of apoptotic pathways. In summary, our study reports the optimum timing and dose of NAC for the protection of human renal proximal tubular cells from Cr(VI)-induced cell death. The NAC treatment strategy described could be applied in clinical practice to suppress renal cell apoptosis, which in turn could rescue renal function.

Two-month breathing-based walking improves anxiety, depression, dyspnoea and quality of life in chronic obstructive pulmonary disease: A randomised controlled study.

AIMS AND OBJECTIVES: To examine the effects of the two-month breathing-based walking intervention and its follow-up on anxiety, depression, dyspnoea and quality of life in patients with chronic obstructive pulmonary disease. BACKGROUND: Mind-body-related exercises improve bio-psychological symptoms and quality of life in chronic diseases, but these improvements are not proven for chronic obstructive pulmonary disease. DESIGN: This was a randomised controlled study and applied the Consolidated Standards of Reporting Trials (CONSORT) statement. METHODS: Outpatients diagnosed with chronic obstructive pulmonary disease were recruited from a medical centre in Taiwan and randomly assigned to two groups. The walking group (n = 42) received breathing, meditation and walking for two months, and the control group (n = 42) did not. Data from the outcomes of anxiety, depression, dyspnoea and quality of life were collected at baseline and in Month 1, Month 2 and Month 3. Clinical trial registration was done (ClinicalTrials.gov.: NCT03388489). FINDINGS: The results showed significant changes in anxiety, depression, dyspnoea and quality of life in the walking group across three months, compared to those in the control group and at baseline. CONCLUSION: This breathing-based walking intervention is promising to achieve bio-psychological well-being for patients with chronic obstructive pulmonary disease. RELEVANCE TO CLINICAL PRACTICE: This breathing-based walking, as a mind-body exercise, could serve as an evidence-based nursing care that contributes to improving anxiety, depression, dyspnoea and quality of life in stable chronic obstructive pulmonary disease outpatients. The feasibility and acceptability of the breathing-based walking were met the requirement of the chronic obstructive pulmonary disease outpatients, which could be considered as home-based exercise.

The use of chemical probes to detect the proteomics of renal tubular injury induced by maleic acid.

Maleic acid (MA), an industrial raw material, was found to be illegally added to edible starch-based food products in Taiwan in 2013, a practice unheard of in most of the world. MA has been associated with renal dysfunction in many experimental animal studies. In this study, we developed chemical probes to investigate protein-protein interactions between MA and renal proteins. In the fabrication of the MA probes, we used silicon dioxide (SiO2) modified with a silanized linker (3-aminopropyl triethoxyslane, APTES) to generate MA with APTES-SiO2 particles. The probes were then incubated with the cell lysates of normal human kidney cell lines (HK-2) and subjected to MS/MS for identifying several MA-related proteins, including nucleophosmin, neutral alpha-glucosidase AB, translocon-associated protein subunit alpha, elongation factor 1-gamma, 60S acidic ribosomal protein P0-like, and heat shock protein (HSP 90-alpha and beta). Based on our findings, we believed that the probe can potentially be used to identify and detect the target proteins and help characterize a network of MA protein-protein interactions.

Optimal dosage and early intervention of L-ascorbic acid inhibiting K2Cr2O7-induced renal tubular cell damage.

Chromium poisoning can cause renal failure and death. Chromium intoxication may be managed using L-ascorbic acid (vitamin C) therapy. However, the evidence supporting the effectiveness of this treatment is insufficient, and the mechanism of action has not been clarified in renal cells. In this study, our results showed that the optimal regimen of L-ascorbic acid therapy in human epithelial renal proximal tubule cells, HK-2 cells, was 30 µg/mL. Supplementation of L-ascorbic acid with 30 µg/mL and within 8 h of chromium intoxication (K2Cr2O7, Cr6+) was effective to inhibit renal tubular cell damage by blocking generation of free radicals, cell apoptosis, and autophagy. Intracellular chromium concentrations were estimated using electrothermal atomic absorption spectrometry. Treatment of L-ascorbic acid within 8 h of chromium intoxication significantly decreased the entry of chromium into the cells. Moreover, concomitant administration of L-ascorbic acid with repeatedly dosing at 8-hourly intervals had a better protective effect at lower concentration of L-ascorbic acid when compared to single dosing of L-ascorbic acid at an early time point of chromium intoxication. These findings might help physicians develop effective therapy strategies in renal failure.

Effects of glycemic variability and hyperglycemia in acute ischemic stroke on post-stroke cognitive impairments.

AIMS: We aimed to investigate the effect of glycemic variability in the acute stage of stroke on the development of post-stroke cognitive impairment (PSCI). METHODS: Patients who underwent blood glucose tests at least five times within 7 days after acute ischemic stroke were included. Factors related to glycemic variability (standard deviation (SD), coefficient of variance (CV), and mean absolute glucose (MAG)) were calculated; neuropsychological assessments were administered 3 months after stroke. PSCI was defined as a score of less than -2 SDs for age-, sex-, and education-adjusted means in at least one cognitive domain. RESULTS: A total of 354 patients were enrolled. PSCI was identified in 74 (20.9%) subjects. In the diabetic group (n = 87), MAG was a significant predictor for PSCI (adjusted OR, 1.94; 95% CI, 1.11-3.42); however, it was not significant in the non-diabetic group, although PSCI exhibited an increasing tendency within higher SD and MAG tertiles. Moreover, hyperglycemia demonstrated a detrimental effect on PSCI, regardless of diabetes status; this effect did not appear in poorly-controlled diabetic patients with HbA1c ≥ 8.0%. CONCLUSIONS: Glycemic variability and hyperglycemia during acute ischemic stroke were identified as novel predictors for PSCI. Although this result is not evidence of a causal relationship, our study suggests that monitoring glycemic index and controlling its variability during the acute phase of ischemic stroke may help to prevent poor cognitive outcomes.

Comparison of the montreal cognitive assessment and the mini-mental state examination as screening tests in hemodialysis patients without symptoms.

Cognitive impairment in end-stage renal disease patients is associated with an increased risk of mortality. We examined the cognitive function in hemodialysis (HD) patients and compared the Korean versions of the Montreal Cognitive Assessment (K-MoCA) and of the Mini-Mental State Examination (K-MMSE) to identify the better cognitive screening instrument in these patients. Thirty patients undergoing hemodialysis and 30 matched reference group of apparently healthy control were included. All subjects underwent the K-MoCA, K-MMSE and a neuropsychological test battery to measure attention, visuospatial function, language, memory and executive function. All cognitive data were converted to z-scores with appropriate age and education level prior to group comparisons. Cognitive performance 1.0 SD below the mean was defined as modest cognitve impairment while 1.5 below the mean was defined as severe cognitive impairment. Modest cognitive impairment in memory plus other cognitive domains was detected in 27 patients (90%) while severe cognitive impairment in memory plus other cognitive domains was detected in 23 (77%) patients. Total scores in the K-MoCA were significantly lower in HD patients than in the reference group. However, no significant group difference was found in the K-MMSE. The K-MMSE ROC AUC (95% confidence interval) was 0.72 (0.59-0.85) and K-MoCA ROC AUC was 0.77 (0.65-0.89). Cognitive impairment is common but under-diagnosed in this population. The K-MoCA seems to be more sensitive than the K-MMSE in HD patients.