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Background Terminally ill patients often experience exacerbations of diseases that render mainstream medicine ineffective in relieving symptoms, prompting attempts at complementary and alternative medicine (CAM). This study collected data from terminally ill patients and their relatives to determine differences between CAM use, behavioral patterns, and perceptions of health information about CAM. Methods A cross-sectional design using a self-administered questionnaire was adopted. Eight medical institutions in Taiwan with inpatient hospice palliative care units were chosen. Ninety-two terminally ill patients and 267 relatives met the inclusion criteria. The questions concerned the experience of CAM use, the kinds of products/services CAM provided, the purpose of CAM use, the source of CAM information, and the perceptions and attitudes toward CAM. Results Both terminally ill patients and their relatives have a high proportion of lifetime and one-year prevalence of CAM use (88.0% vs. 88.4%; p = 0.929). CAM use for musculoskeletal and neurological discomfort is higher among terminally ill patients than among their relatives. Relatives/friends are the most frequent sources of information on CAM (53.3% vs. 62.2%; p = 0.133). The percentage of terminally ill patients who discontinued mainstream medical treatment because of CAM use was higher than that of their relatives (18.5% vs. 9.3%; p = 0.026). More than half the terminally ill patients and their relatives had never been asked about CAM by medical staff (64.1% vs. 66.7%), nor had they informed medical professionals about the use of CAM products and services (63% vs. 66.9%). Random inquiries by medical professionals may be associated with increased disclosure of CAM use (terminally ill patients: odds ratio, 9.75; 95% confidence interval, 1.97–48.35 vs. relatives: odds ratio, 5.61; 95% confidence interval, 2.66–11.83). Conclusions The high prevalence and concealment of CAM use in terminally ill patients should be considered. Medical professionals should establish a friendly and barrier-free communication model, encourage patients to share CAM experiences, and provide evidence-based information on the use of CAM products and services, to reduce the potential damage caused by harmful use.

OBJECTIVE We assessed the effect of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on ischemic stroke prevention in the Asian population with type 2 diabetes (T2D) without established cardiovascular disease. RESEARCH DESIGN AND METHODS This retrospective cohort study examined data obtained from the Taiwan National Health Insurance Research Database for the period from 1998 to 2018. The follow-up ended upon the occurrence of hospitalization for ischemic stroke. The median follow-up period was 3 years. The effect of GLP-1RA exposure time on the development of hospitalization for ischemic stroke was assessed. RESULTS The GLP-1RA and non–GLP-1RA user groups both included 6,534 patients. Approximately 53% of the patients were women, and the mean age was 49 ± 12 years. The overall risk of ischemic stroke hospitalization for GLP-1RA users was not significantly lower than that for GLP-1RA nonusers (adjusted hazard ratio [HR] 0.69 [95% CI 0.47–1.00]; P = 0.0506), but GLP-1RA users with a >251-day supply during the study period had a significantly lower risk of ischemic stroke hospitalization than GLP-1RA nonusers (adjusted HR 0.28 [95% CI 0.11–0.71]). Higher cumulative dose of GLP-1 RAs (>1,784 mg) was associated with significantly lower risk of ischemic stroke hospitalization. The subgroup analyses defined by various baseline features did not reveal significant differences in the observed effect of GLP-1RAs. CONCLUSIONS Longer use and higher dose of GLP-1 RAs were associated with a decreased risk of hospitalization for ischemic stroke among Asian patients with T2D who did not have established atherosclerotic cardiovascular diseases, but who did have dyslipidemia or hypertension.

BackgroundAcute ST-elevation myocardial infarction (STEMI) elicits a robust cardiomyocyte death and inflammatory responses despite timely revascularization.ObjectivesThis phase 1, open-label, single-arm, first-in-human study aimed to assess the safety and efficacy of combined intracoronary (IC) and intravenous (IV) transplantation of umbilical cord-derived mesenchymal stem cells (UMSC01) for heart repair in STEMI patients with impaired left ventricular ejection fraction (LVEF 30-49%) following successful reperfusion by percutaneous coronary intervention.MethodsConsenting patients received the first dose of UMSC01 through IC injection 4-5 days after STEMI followed by the second dose of UMSC01 via IV infusion 2 days later. The primary endpoint was occurrence of any treatment-related adverse events and the secondary endpoint was changes of serum biomarkers and heart function by cardiac magnetic resonance imaging during a 12-month follow-up period.ResultsEight patients gave informed consents, of whom six completed the study. None of the subjects experienced treatment-related serious adverse events or major adverse cardiovascular events during IC or IV infusion of UMSC01 and during the follow-up period. The NT-proBNP level decreased (1362 ± 1801 vs. 109 ± 115 pg/mL, p = 0.0313), the LVEF increased (52.67 ± 12.75% vs. 62.47 ± 17.35%, p = 0.0246), and the wall motion score decreased (26.33 ± 5.57 vs. 22.33 ± 5.85, p = 0.0180) at the 12-month follow-up compared to the baseline values. The serial changes of LVEF were 0.67 ± 3.98, 8.09 ± 6.18, 9.04 ± 10.91, and 9.80 ± 7.56 at 1, 3, 6, and 12 months, respectively as compared to the baseline.ConclusionThis pilot study shows that combined IC and IV transplantation of UMSC01 in STEMI patients with impaired LVEF appears to be safe, feasible, and potentially beneficial in improving heart function. Further phase 2 studies are required to explore the effectiveness of dual-route transplantation of UMSC01 in STEMI patients.

Although the past research results have provided many effective tools for evaluating public bus service quality, they still lack the concept of risk. This study assessed the quality risk for city bus service by constructing a quality risk assessment model that integrated Kano’s model, IPA, and FMEA. The online questionnaire was distributed to commuters who use BMTA’s bus service in Bangkok with 429 samples. This study analyzed the service quality attributes of bus services via Kano’s model, an IPA, and an FMEA. For the results of Kano’s model, this study identified nine one-dimensional and three attractive attributes. The results of the IPA showed that the safety of boarding and disembarking from the bus, the cleanliness of vehicles, and the punctuality of buses according to the schedule were the top three attributes that had a large gap between importance and satisfaction. According to the results of the FMEA, the safety of boarding and disembarking from the bus, the cleanliness of vehicles, and the punctuality of buses according to the schedule were the top three attributes that had a high service quality risk and considered a priority improvement. These attributes belonged to interaction with passengers, tangible service equipment, and operating management support dimensions. Therefore, the government should take action and improve service quality to make Bangkok commuters consider switching from driving cars to using a bus. Finally, this study provides practical improvement strategies for managers to improve passenger experiences and enhance the quality of bus services.

BackgroundHypertension (HTN) is the leading preventable risk factor for cardiovascular disease worldwide. Patients with HTN are at higher risk for heart failure (HF). The currently available therapeutic approaches for HTN do not always optimally control blood pressure or are not suitable for hypertensive patients who have a higher number of comorbidities. This study aimed to determine whether Chinese herbal medicine (CMH)-based interventions could reduce the risk of HF in hypertensive patients.MethodsThis retrospective study randomly selected 2 million enrollees from the National Health Insurance Research Database and identified 507,608 patients who were newly diagnosed with HTN in 2000–2017. After 1:1 frequency-matching by age, sex, index year, income, urbanization, duration of HTN, comorbidities and antihypertensive medications, we selected 8,912 eligible patients in each group. During 16 years of follow-up, 380 CHM users and 426 CHM non-users developed HF, representing incidence rates of 6.29 and 7.43 per 1,000 person-years, respectively.ResultsCHM users had significantly lower HF risk compared with CHM non-users (adjusted HR = 0.85, 95% CI 0.74–0.98). The markedly predominant effect was observed in those receiving CHM products for more than 180 days (adjusted HR = 0.65). The frequently prescribed formula, Jia-Wei-Xiao-Yao-San, and the single herbs Ge Gen, Huang Qi, Du Zhong, Huang Qin, and Chuan Xiong were significantly associated with lower risk of HF.ConclusionsThis population-based study revealed decreased HF risk in hypertensive patients with CHM use. These findings may provide a reference for HF prevention strategies and support the integration of CHM into clinical intervention programs that provide a favorable prognosis for hypertensive patients.

This work reports a study on employing lignin in the formation of a selective layer of thin-film composite (TFC) membranes for pervaporation desalination. The TFC membranes with lignin-based separation layers are fabricated using a solution-casting method. With a reduction of the separation layer thickness to about 0.47 μm, a water permeation flux of 18.5 kg h−1 m−2 and a salt rejection of above 99.95% have been recorded on the lignin based TFC membrane with a feeding solution of 3.5 wt% NaCl(aq) at 45 °C. The membrane also exhibits high stability in long-term operation tests and can be applied for operations on high salinity water (up to 15 wt% NaCl(aq)). While being applied to seawater desalination, the membrane exhibits a water permeation flux of about 20.4 kg h−1 m−2 and a salt rejection of above 99.95% at 45 °C. A membrane separation process, which uses sustainable materials for salty wastewater treatments and water resource generation, has been demonstrated.

In this study, the enhanced solubilization performance of a poorly soluble drug, beclomethasone dipropionate (BDP), was investigated using hydroxypropyl-β-cyclodextrin (HP-β-CD) and ethanol. The enhanced solubility of the drug was determined using the phase solubility method and correlated as a function of both HP-β-CD and ethanol concentrations. The effective progress of drug solubility originated from the formation of cyclodextrin and BDP inclusion complexes and increase in the lipophilicity of the medium, by aqueous ethanol, for hydrophobic BDP. BDP and HP-β-CD composite particles were produced using supercritical assisted atomization (SAA) with carbon dioxide as the spraying medium, 54.2% (w/w) aqueous ethanol as the solvent, and an optimal amount of the dispersion enhancer leucine. The effect of the mass ratio of HP-β-CD to BDP (Z) on the in vitro aerosolization and in vitro dissolution performance of BDP–HP-β-CD composite particles was evaluated. The aerosolization performance showed that the fine particles fraction (FPF) of the composite particles increased with increasing mass ratio. The water-soluble excipient (HP-β-CD) effectively enhance the dissolution rate of BDP from composite particles. This study suggests that BDP–HP-β-CD composite particles produced using SAA can be employed in immediate-release drug formulations for pulmonary delivery.

The activity of norovirus varies from season to season, and the effect of climate change on the incidence of norovirus outbreaks is a widely recognized yet poorly understood phenomenon. Investigation of the possible association between climatic factors and the incidence of norovirus is key to a better understanding of the epidemiology of norovirus and early prediction of norovirus outbreaks. In this study, clinical stool samples from acute gastroenteritis outbreaks were collected from January 2015 to June 2019 in Taiwan. Data analysis from our study indicated that more than half of the cases were reported in the winter and spring seasons, including those caused by norovirus of genotypes GII (genogroup II).2, GII.3, GII.6, and GII.17, and 45.1% of the patients who tested positive for norovirus were infected by the GII.4 norovirus in autumn. However, GII.6 norovirus accounted for a higher proportion of the cases reported in summer than any other strain. Temperature is a crucial factor influencing patterns of epidemic outbreaks caused by distinct genotypes of norovirus. The results of this study may help experts predict and issue early public warnings of norovirus transmission and understand the effect of climate change on norovirus outbreaks caused by different genotypes and occurring in different locations.

Model-based intersection optimization strategies that produce signal timings over a specified optimization horizon have been widely investigated for urban traffic signal control, and recent work in this area produced a scalable approach to real-time traffic control based on a decentralized schedule-driven optimization model. In this approach, a scheduling agent is associated with each intersection. Each agent senses the traffic approaching its intersection through local sensors and in real-time constructs a schedule that minimizes the cumulative wait time of vehicles approaching the intersection over the current look-ahead horizon. Intersections then exchange schedule information with their neighbors to achieve network level coordination. Although the approach is general and has demonstrated substantial success, its effectiveness in a given road network depends on the extent to which various parameters of the model, e.g, maximum green time, are adjusted to match that network's actual flow conditions over time. To address this problem, we propose a two-stage hierarchical structure that combines online planning and reinforcement learning. Reinforcement learning is applied to adjust the parameters of the model over a longer time-scale. On the other hand, online planning is used to compute the schedule for managing the traffic signals in the shorter term. We demonstrate how this hybrid approach outperforms the original approach in real-time traffic signal control problems.

Purpose:Previous studies have shown that metformin exhibits an anti-inflammatory effect and may decrease the risk of incidental diabetes. But the effect of metformin on incidental Sjögren's syndrome is unknown. The aim of the study was to examine the association between metformin exposure and Sjögren's syndrome in diabetic patients.Methods:The dataset in this retrospective cohort study was obtained from the National Health Insurance Research Database (2000–2013) in Taiwan. In total, 15,098 type 2 diabetic patients under metformin treatment and an equivalent number without metformin treatment matched for comparison were included. The primary endpoint was the incidence of Sjogren's syndrome. Univariate and multivariate Cox proportional hazards models were used for data analysis. A subgroup analysis and sensitivity test were also performed.Results:The incidence rate of Sjögren's syndrome in non-metformin controls was 40.83 per 100,000 person-years and 16.82 per 100,000 person-years in metformin users. The adjusted hazard ratio (aHR) in diabetic patients under metformin treatment was 0.46 (95% CI, 0.23 to 0.92). In subgroup analysis, men had a lower risk of developing Sjögren's syndrome than women [aHR = 0.15, 95% CI = (0.05, 0.41)]. After prescribing metformin to type 2 diabetic patients aged 60 years or more, those patients had a lower risk of developing Sjögren's syndrome [aHR = 0.34, 95% CI = (0.12, 0.96)].Conclusion:In this large population-based cohort study, metformin exposure was associated with a reduced risk of developing Sjögren's syndrome in type 2 diabetic patients.

In this work, a novel thermoresponsive switching transistor is developed through the rational design of active materials based on the typical field-effect transistor (FET) device configuration, where the active material is composed of a blend of a thermal expansion polymer and a polymeric semiconductor. Herein, polyethylene (PE) is employed as the thermal expansion polymer because of its high volume expansion coefficient near its melting point (90–130 °C), which similarly corresponds to the overheating point that would cause damage or cause fire in the devices. It is revealed that owing to the thermistor property of PE, the FET characteristics of the derived device will be largely decreased at high temperatures (100–120 °C). It is because the high volume expansion of PE at such high temperature (near its Tm) effectively increases the distance of the crystalline domains of poly(3-hexylthiophene-2,5-diyl) to result in a great inhibition of current. Besides, the performance of this device will recover back to its original value after cooling from 120 to 30 °C owing to the volume contraction of PE. The reversible FET characteristics with temperature manifest the good thermal sensitivity of the PE-based device. Our results demonstrate a facile and promising approach for the development of next-generation overheating shutdown switches for electrical circuits.

Background: Scabies is an infectious inflammatory skin disease. Cytokine-mediated inflammatory responses may be one of the pathological mechanisms underlying myocardial infarction. Objective: We explore the association between scabies and subsequent acute myocardial infarction (AMI) and all-cause mortality; Methods: We conducted a nationwide population-based study using data from the National Health Insurance Research Database (NHIRD) in Taiwan. Patients with scabies (n = 30,184) and 120,739 controls without scabies were included. The primary outcomes were incidental AMI and all-cause mortality. Using Cox proportional-hazards regression analysis, we estimated the risk of acute myocardial infarction for the study cohort; Results: The mean age of the study cohort was 51.81 ± 19.89 years. The adjusted sub-distribution hazard ratios (aSHRs) of AMI were 1.214 (95% CI, 1.068–1.381) after adjusting for demographic characteristics, income, OPD utility frequency, days in hospital, co-morbidities, and medication. The adjusted hazard ratio (aHR) of all-cause mortality after adjusting for age, gender, income, OPD utility frequency, days in hospital, co-morbidities, co-medication, and urbanization was 1.612 (95% CI, 1.557–1.669). Conclusions: Our study showed that patients with scabies infestations were at higher risk for subsequent AMI and all-cause mortality.

Background This study aimed to investigate the risk of Parkinson’s disease (PD) among patients with age-related macular degeneration (AMD) and its association with confounding comorbidities. Methods A population-based retrospective cohort study was conducted using Longitudinal Health Insurance Database 2000 (LHID2000). We established AMD and non-AMD cohorts from January 1, 2000 to December 31, 2012 to determine the diagnosis of PD. A total of 20,848 patients were enrolled, with 10,424 AMD patients and 10,424 controls matched for age, sex, and index year at a 1:1 ratio. The follow-up period was from the index date of AMD diagnosis to the diagnosis of PD, death, withdrawal from the insurance program, or end of 2013. Multivariable Cox regression analysis was performed to examine the hazard ratio (HR) and 95% confidence interval (CI) for the risk of PD between the AMD and non-AMD cohorts. Result After adjusting for potential confounders, there was a higher risk of developing PD in the AMD cohort than in the non-AMD cohort (adjusted HR = 1.35, 95% CI = 1.16–1.58). A significant association could be observed in both female (aHR = 1.42, 95% CI = 1.13–1.80) and male (aHR = 1.28, 95% CI = 1.05–1.57) patients, aged more than 60 years (60–69: aHR = 1.51, 95% CI = 1.09–2.09, 70–79: aHR = 1.30, 95% CI = 1.05–1.60; 80–100: aHR = 1.40, 95% CI = 1.01–1.95), and with more than one comorbidity (aHR = 1.40, 95% CI = 1.20–1.64). A significant association between increased risk of PD and AMD was observed among patients with comorbidities of osteoporosis (aHR = 1.68, 95% CI = 1.22–2.33), diabetes (aHR = 1.41, 95% CI = 1.12–1.78) and hypertension (aHR = 1.36, 95% CI = 1.15–1.62) and medications of statin (aHR = 1.42, 95% CI = 1.19–1.69) and calcium channel blocker (CCB) (aHR = 1.32, 95% CI = 1.11–1.58). The cumulative incidence of PD was significantly higher over the 12-year follow-up period in AMD cohort (log-rank test, p Conclusions Patients with AMD may exhibit a higher risk of PD than those without AMD.

Thermodynamically driven salts and annealing processes developed the pure silk fibroin (SF) membranes from Bombyx mori cocoons. For more generation, the silk fibroin solution 5 wt% mixed the sodium chloride (NaCl) and polyethylene glycol (PEG). The top surface and cross-section of silk fibroin mixed with NaCl (SF/NaCl) showed pore in the surface membrane and hydrophilic property. The β-sheet content in the SF/NaCl membrane is higher than pure silk fibroin (SF) and the silk fibroin mixed with PEG (SF/PEG) membranes. Then cadmium (Cd), lead (Pb), and mercury (Hg) metals in water filtered pass through only SF/NaCl experimented. The pressure, pH, and temperature were effect by the flow rate efficiency of SF/NaCl membranes. The results showed that the highest % removal of Cd, Pb, and Hg were 45.36%, 61.43%, and 86.87%, respectively. The best condition of absorption capacity was 8.50, 6.42, and 41.14 mg/g for Cd, Pb, and Hg. As a natural biopolymer, SF/NaCl possibly apply for Hg removal for water treatment, its nontoxicity, excellent biocompatibility, and mechanical toughness.

Early integration of palliative care for terminally ill cancer and non-cancer patients improves quality of life. However, there are sparse data on results of palliative care consultation services (PCCS) between cancer and non-cancer patients. In this 9-year observational study, data were collected from the Hospice-Palliative Clinical Database (HPCD) of Taichung Veterans General Hospital (TCVGH). Terminally ill cancer and non-cancer patients who received PCCS during 2011 to 2019 were enrolled. Trend analysis was performed to evaluate differences in outcomes of PCCS, including duration of PCCS, the awareness of disease of patients and families before and after PCCS, status of PCCS termination, and DNR declaration before and after PCCS among cancer and non-cancer patients throughout study period. In total, 5223 cancer patients and 536 non-cancer patients received PCCS from 2011 to 2019. The number of people who received PCCS increased stably over the decade, both for cancer and non-cancer patients. The average duration of PCCS for cancer and non-cancer patients was 21.4 days and 18.4 days, respectively. Compared with non-cancer patients, cancer patients had longer duration of PCCS, less DNR declaration (82% vs. 98%, respectively), and more transfers to the palliative care unit (17% vs. 11%, respectively), or for palliative home care (12% vs.8%, respectively). Determinants of late referral to PCCS includes age (OR 0.992, 95% CI 0.987–0.996), DNR declaration after PCCS (OR 1.967, 95% CI 1.574–2.458), patients’ awareness after PCCS (OR 0.754, 95% CI 0.635–0.895), and status of PCCS termination. This 9-year observational study showed that the trend of PCCS among cancer and non-cancer patients had changed over the duration of the study, and early integration of PCCS to all patients is essential for both cancer and non-cancer patients.

Three-finger toxins (3FTXs) are the most clinically relevant components in cobra (genus Naja) venoms. Administration of the antivenom is the recommended treatment for the snakebite envenomings, while the efficacy to cross-neutralize the different cobra species is typically limited, which is presumably due to intra-specific variation of the 3FTXs composition in cobra venoms. Targeting the clinically relevant venom components has been considered as an important factor for novel antivenom design. Here, we used the recombinant type of long-chain α-neurotoxins (P01391), short-chain α-neurotoxins (P60770), and cardiotoxin A3 (P60301) to generate a new immunogen formulation and investigated the potency of the resulting antiserum against the venom lethality of three medially important cobras in Asia, including the Thai monocled cobra (Naja kaouthia), the Taiwan cobra (Naja atra), and the Thai spitting cobra (Naja Siamensis) snake species. With the fusion of protein disulfide isomerase and the low-temperature settings, the correct disulfide bonds were built on these recombinant 3FTXs (r3FTXs), which were confirmed by the circular dichroism spectra and tandem mass spectrometry. Immunization with r3FTX was able to induce the specific antibody response to the native 3FTXs in cobra venoms. Furthermore, the horse and rabbit antiserum raised by the r3FTX mixture is able to neutralize the venom lethality of the selected three medically important cobras. Thus, the study demonstrated that the r3FTXs are potential immunogens in the development of novel antivenom with broad neutralization activity for the therapeutic treatment of victims involving cobra snakes in countries.

Key to the effectiveness of schedule-driven approaches to real-time traffic control is an ability to accurately predict when sensed vehicles will arrive at and pass through the intersection. Prior work in schedule-driven traffic control has assumed a static vehicle arrival model. However, this static predictive model ignores the fact that the queue count and the incurred delay should vary as different partial signal timing schedules (i.e., different possible futures) are explored during the online planning process. In this paper, we propose an alternative arrival time model that incorporates queueing dynamics into this forward search process for a signal timing schedule, to more accurately capture how the intersection’s queues vary over time. As each search state is generated, an incremental queueing delay is dynamically projected for each vehicle. The resulting total queueing delay is then considered in addition to the cumulative delay caused by signal operations. We demonstrate the potential of this approach through microscopic traffic simulation of a real-world road network, showing a 10-15% reduction in average wait times over the schedule-driven traffic signal control system in heavy traffic scenarios.

Nontraumatic anterior spinal artery syndrome (ASAS) is an extremely rare clinical condition in pediatric populations with a mostly unknown underlying etiology. Here we discuss the case of a previously healthy 14-year-old girl presenting with sudden onset acute flaccid paralysis to the emergency department. A spinal STIR/DWI MRI revealed hyperintensities extending from cervical vertebrae C3-6, consistent with the diagnosis of ASAS. In order to determine any precipitating causes of ASAS, we also extensively investigated established potential risk factors for ASAS in our patient and noticed that she had a marked folate deficiency requiring folic acid supplementation to prevent future episodes of ASAS as well as to repair the patient’s injured spinal cord. Interestingly, the patient did not display elevated levels of homocysteine nor did she possess the three pathogenic MTHFR mutations characteristic of ASAS. Although her folate deficiency did not cause responsive hyperhomocysteinemia, and she did not have pathogenic MTHFR mutations that impair the function of methylenetetrahydrofolate reductase in folate cycle, we suggest that isolated folate deficiency may play a role in adolescent cases of ASAS that, once identified, would require prompt identification and early intervention to improve the prognosis of these patients.

We conducted this study to determine the effect of metformin use on the risk of new-onset chronic urticaria in patients with type 2 diabetes (T2D). In total, 24,987 pairs of metformin users and nonusers were identified with propensity score-matching from Taiwan’s National Health Insurance Research Database from 1 January 2000, to 31 December 2017. Multivariable Cox proportional hazards models were used to compare the risks of chronic urticaria development, severe chronic urticaria, and hospitalization for chronic urticaria between metformin users and nonusers. Compared with metformin nonuse, the aHRs (95% CI) for metformin use in chronic urticaria development, severe chronic urticaria, and hospitalization for chronic urticaria were 1.56 (1.39–1.74), 0.40 (0.12–1.30), and 1.45 (0.82–2.56), respectively. The cumulative incidence of chronic urticaria development was significantly higher in metformin users than in nonusers (p < 0.0001). A longer average cumulative duration of metformin use was associated with higher risks of new-onset and hospitalization for chronic urticaria than metformin nonuse. This nationwide cohort study showed that metformin use was associated with a significantly higher risk of chronic urticaria development. A longer average cumulative duration of metformin use was associated with a higher risk of outcomes. More prospective studies are needed to verify our results.

The prevalence of end-stage renal disease (ESRD) and the number of patients undergoing dialysis in Taiwan are high. Since September 2009, the National Health Insurance has started to provide hospice care to patients with renal failure in Taiwan. Therefore, it is necessary to understand the use of hospice and nonhospice care in patients with ESRD on dialysis. We aim to understand trends in patients with ESRD receiving hospice and nonhospice care as well as medical care efforts during the last month of their lives (2009-2013).The cohort study was conducted using 1 million randomly selected samples from the Taiwan Health Insurance Research Database for millions of people in Taiwan in 2009-2013. Descriptive statistics were presented to summarize the characteristics of data. To compare differences between cohorts, Chi-square tests and Student'sWe recruited 770 ESRD patients who underwent hemodialysis; among them, 154 patients received hospice care. Patients who received hospice care had a significantly longer survival time after removal of mechanical ventilator (20 vs. 0 days) and after discontinuation of dialysis (2 vs. 0 days) compared with those who did not receive hospice care. Patients who received hospice care had more pain control (61.04% vs. 17.37%,Our results suggest that the addition of hospice care may permit patients a longer life-support-free survival time. In addition, despite a more frequent symptomatic controlling agent use, hospice care significantly reduced the overall medical expenditure.

Rice blast is a serious threat to global rice production. Large-scale and long-term cultivation of rice varieties with a single blast resistance gene usually leads to breakdown of resistance. To effectively control rice blast in Taiwan, marker-assisted backcrossing was conducted to develop monogenic lines carrying different blast resistance genes in the genetic background of an elite japonica rice cultivar, Kaohsiung 145 (KH145). Eleven International Rice Research Institute (IRRI)-bred blast-resistant lines (IRBLs) showing broad-spectrum resistance to local Pyricularia oryzae isolates were used as resistance donors. Sequencing analysis revealed that the recurrent parent, KH145, does not carry known resistance alleles at the target Pi2/9, Pik, Pita, and Ptr loci. For each IRBL × KH145 cross, we screened 21 to 370 (average of 108) plants per generation from the BC1F1 to BC3F1/BC4F1 generation. A total of 1,499 BC3F2/BC4F2 lines carrying homozygous resistance alleles were selected and self-crossed for four to six successive generations. The derived lines were also evaluated for background genotype using genotyping by sequencing, for blast resistance under artificial inoculation and natural infection conditions, and for agronomic performance in multiple field trials. In Chiayi and Taitung blast nurseries in 2018 to 2020, Pi2, Pi9, and Ptr conferred high resistance, Pi20 and Pik-h moderate resistance, and Pi1, Pi7, Pik-p, and Pik susceptibility to leaf blast; only Pi2, Pi9, and Ptr conferred effective resistance against panicle blast. The monogenic lines showed agronomic traits, yield, and grain quality similar to those of KH145, suggesting the potential of growing a mixture of lines to achieve durable resistance in the field.

Backgrounds Early integration of palliative care for terminally ill non-cancer patients improves quality of life. However, there are scanty data on Palliative Care Consultation Service (PCCS) among non-cancer patients. Methods In this 9-year observational study Data were collected from the Hospice-Palliative Clinical Database (HPCD) of Taichung Veterans General Hospital (TCVGH). Terminally ill non-cancer patients with 9 categories of diagnoses who received PCCS during 2011 to 2019 were enrolled. Trend analysis was performed to evaluate differences in categories of diagnosis throughout study period, duration of PCCS, patient outcomes, DNR declaration, awareness of disease by patients and families before and after PCCS. Results In total, 536 non-cancer patients received PCCS from 2011 to 2019 with an average age of 70.7 years. The average duration of PCCS was 18.4 days. The distributions of age, gender, patient outcomes, family’s awareness of disease before PCCS, and patient’s awareness of disease after PCCS were significantly different among the diagnoses. Organic brain disease and Chronic kidney disease (CKD) were the most prevalent diagnoses in patients receiving PCCS in 2019. For DNR declaration, the percentage of patients signing DNR before PCCS remained high throughout the study period (92.8% in 2019). Patient outcomes varied according to the disease diagnoses. Conclusion This 9-year observational study showed that the trend of PCCS among non-cancer patients had changed over the duration of the study. An increasing number of terminally ill non-cancer patients received PCCS during late life, thereby increasing the awareness of disease for both patients and families, which would tend to better prepare terminally ill patients for end-of-life as they may consider DNR consent. Early integration of PCCS into ordinary care for terminally non-cancer patients is essential for better quality of life.

Purpose: Subconjunctival hemorrhage (SCH) is usually a benign ocular disorder that causes painless, redness under the conjunctiva. However, since SCH and acute coronary syndrome (ACS) share many vascular risk factors, studies have suggested that these two disorders may be significantly associated with each other, and evaluate the concomitance of ACS in patients with SCH.Methods: This population-based cohort study, enrolled 35,260 Taiwanese patients, and used the Taiwan National Health Insurance Research Database to identify patients with ACS and SCH. Outcomes were compared between the with and without SCH groups. The study population was followed until the date of ACS onset, the date of withdrawal, death, or December 31st 2013, whichever came first.Results: Of the 85,925 patients identified with SCH between 1996 and 2013, 68,295 were excluded based on the study's exclusion criteria, and a total of 17,630 patients with SCH who were diagnosed by ophthalmologists between 2000 and 2012 were eligible for analysis. After 1:1 propensity score matching for 5-year age groups, gender, and the index year, the results showed that SCH was more common in the 40–59 age group (53.82%) and females (58.66%). As for the ACS-related risk factors, patients with diabetes mellitus (aHR = 1.58, 95% CI = [1.38, 1.81]), hypertension (aHR = 1.71, 95% CI = [1.49, 1.96]) and patients taking aspirin (aHR = 1.67, 95% CI = [1.47, 1.90]) had a notably higher risk of ACS. However, it was found that there were no significant differences in the occurrence of ACS between the non-SCH and SCH patients.Conclusion: This results of this study regarding the risk factors and epidemiology of SCH and ACS were in keeping with previously reported findings. However, the results revealed no significant association between SCH and ACS.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the key tobacco-specific nitrosamines that plays an important role in human lung carcinogenesis. Repeated dose inhalation toxicity data on NNK, particularly relevant to cigarette smoking, however, is surprisingly limited. Hence, there is a lack of direct information available on the carcinogenic and potential non-carcinogenic effects of NNK via inhalational route exposure. In the present study, the subchronic inhalation toxicity of NNK was evaluated in Sprague Dawley rats. Both sexes (9-10 weeks age; 23 rats/sex/group) were exposed by nose-only inhalation to air, vehicle control (75% propylene glycol), or 0.2, 0.8, 3.2, or 7.8 mg/kg body weight (BW)/day of NNK (NNK aerosol concentrations: 0, 0, 0.0066, 0.026, 0.11, or 0.26 mg/L air) for 1 h/day for 90 consecutive days. Toxicity was evaluated by assessing body weights; food consumption; clinical pathology; histopathology; organ weights; blood, urine, and tissue levels of NNK, its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and their glucuronides (reported as total NNK, tNNK, and total NNAL, tNNAL, respectively); tissue levels of the DNA adduct O

The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5 × 10−5, 5 × 10−3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9–10 weeks age) via nose-only inhalation (INH) exposure for 1 h. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal injection (IP) and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated time points and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 h post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the TK and genotoxicity of NNK.

Objective This study aimed to investigate the risk of Alzheimer’s disease among patients with age-related macular degeneration and its association with confounding comorbidities. Method This was a population-based, retrospective cohort study. By accessing data from the National Health Insurance Research Database of Taiwan, we identified 10,578 patients aged 50–100 years who were newly diagnosed with age-related macular degeneration between 2000 and 2012 and 10,578 non- age-related macular degeneration individuals. The comorbidities assessed were osteoporosis, diabetes, cirrhosis, cerebrovascular disease, chronic kidney disease, hypertension, hyperlipidemia, coronary artery disease, and chronic obstructive pulmonary disease. Results Patients with age-related macular degeneration had a 1.23-fold increased risk of their condition advancing to Alzheimer’s disease (aHR = 1.23, 95% CI = 1.04–1.46). The younger patients were diagnosed with age-related macular degeneration, the more likely patients got Alzheimer’s disease (50–64 age group: aHR = 1.97, 95% CI = 1.04–3.73; 65–79 age group: aHR = 1.27, 95% CI = 1.02–1.58; 80–100 age group: aHR = 1.06, 95% CI = 0.78–1.45). In addition, there were significantly higher risks of Alzheimer’s disease for patients with cirrhosis (aHR = 1.50, 95% CI = 1.09–2.06) in the age-related macular degeneration cohort than in the non-age-related macular degeneration cohort. Conclusion Patients with age-related macular degeneration may exhibit a higher risk of Alzheimer’s disease than people without age-related macular degeneration.

Employing crosslinkable polybenzoxazine (PBz) as the precursor, thermosetting resin based porous membranes possessing interconnected pores are prepared and applied for organic solvent phase microfiltration. The effects of the used solvents and additives on formation of interconnected pores in the obtained membranes are studied. Employing a solvent or an additive, which could build up hydrogen bonding based networks in the PBz solution, favors the formation of interconnected pores in the resulting membranes, as the polymer-solvent and polymer-additive networks could retard the mass transfers to result in a delayed demixing mechanism in the phase separation processes. 2-Pyrrolidone and lignin is an effective solvent and additive for formation of crosslinked PBz with interconnected pores. The crosslinked PBz/lignin membrane shows a high resistance to solvents, a high surface hydrophobicity with a water contact angle of about 141°, a high porosity of 70%, and a small pore size of 0.55 ± 0.05 μm. While being applied to a gravity-driven separation on a surfactant-stabilized water-in-toluene emulsion, the membrane demonstrates a flux of 278 ± 21 Lm−2h−1 and a water content of 474 ± 3 ppm of the permeated toluene, which is close to the natural solubility of water in toluene (411 ppm). This work has explored a new class of thermosetting resin based membrane with interconnected pores suitable for organic solvent microfiltration.

A series of thin-film composite (TFC) polyamide membranes was fabricated through interfacial polymerization on a modified polyacrylonitrile (mPAN) substrate, where an aqueous solution of diamine was reacted with an organic solution of diacyl chloride. Various monomers were used: two different diamines [1,3-diamino-2-propanol (DAPL) and hydrazine] and two different diacyl chlorides [succinyl chloride (SCC) and trans-5-norbornene-2,3-dicarbonyl chloride]. Combining these monomers resulted in a new polyamide layer. We investigated the effect of the monomer chemical structure and interfacial polymerization conditions on the membrane pervaporation performance in dehydrating an aqueous solution of ethanol. According to field emission scanning electron microscopy, DAPL-SCC provided the thinnest polyamide layer, which was also confirmed through positron annihilation lifetime spectroscopy. The results were used to correlate the variation in the membrane microstructure with the pervaporation performance of the fabricated TFC polyamide membranes. Both microstructural characteristics and surface properties affected the pervaporation performance. DAPL-SCC/mPAN membranes with lower free-volume sizes and suitable hydrophilicity were evaluated to deliver the highest water concentration in permeate and the lowest permeation flux (on the basis of the pervaporative dehydration of an aqueous solution of 90 wt% ethanol at 25 °C).

This work reports the utilization of lignin, a renewable and biomass-based material, as an effective modifying agent for thermally stable and hydrophobic membranes based on crosslinked polybenzoxazine (CRPBz) to significantly enhance their permeation fluxes in pervaporation dehydration tests. Lignin could involve in the crosslinking reaction of polybenzoxazine so as to be chemically embedded in the polymer networks. In addition to the inherent hydrophilicity of lignin, lignin could release the hydrophilic groups (phenol and tertiary amine) of crosslinked polybenzoxazine with formation of hydrogen bonding with crosslinked polybenzoxazine, consequently to significantly enhance the hydrophilicity and water permeation fluxes of the studied membranes. With feeding a 70 wt% tetrahydrofuran aqueous solution at 25 °C, lignin modification increases the permeation flux of the CRPBz based membrane from 237 g m−2 h−1 to 490 g m−2 h−1 and separation factor from 11,920 to 19,440. Lignin modification significantly enhances the water permeation flux of the membrane without scarifying separation ability. A 3.4-folds of pervaporation separation index (PSI, the product of permeation flux and separation factor) has been demonstrated with the lignin modification. Similar performance has also been recorded on the tests on a 70 wt% isopropanol aqueous solution. The effect of lignin has been attributed to increase the membrane hydrophilicity for facilitating water permeation. The results demonstrate the wide application scopes of the lignin-modified CRPBz based membranes in pervaporation dehydration based on their high stability and hydrophilicity.

Zwitterion augmented forward osmosis (FO) membranes were fabricated having polyamide active layer on the polysulfone support to improve the overall performance and antifouling characteristics. FTIR and XPS were employed in evidencing the incorporation of zwitterion in terms of functional groups and relative compositions of hetero atoms. AFM, SEM, water contact angle and zeta potential measurement are used to characterize the zwitterion augmented surface in terms of surface morphology, surface charge and hydrophilicity/hydrophobicity. Augmentation of zwitterion was found to enhance the hydrophilicity and surface roughness resulting the enhancement in the water permeability. The anionic moiety of the zwitterion was exposed outside, while the cationic moieties of the zwitterion mostly retained towards the core as suggested by negative zeta potential and protein absorption. Incorporation of zwitterion was found to enhance the antifouling property of the membrane as evident from static and dynamic test. The relative composition of zwitterion on active membrane surface was optimized by investigating the tradeoff between water permeability and reverse salt flux.

Graphene oxide quantum dots (GOQDs), a carbon-based nanomaterial resembling the structure of graphene oxide but with a smaller size of

Background This study aimed to investigate skin condition, quality of life, and psychological impact of breast cancer patients after radiation therapy. We designed and administered a questionnaire to breast cancer survivors for better understanding the skin sequelae after radiation therapy. Methods This study performed an anonymous online survey. Invitation join was posted in Facebook groups for Breast Cancer. Content of the questionnaire included basic information and a three-point scale on the degree of skin dryness, sweating, hotness sensation, itchy sensation, presence of pigment deposition, history of severe skin disorder, psychological impact, and quality of life after radiotherapy. Categorical variables were summarized using counts and percentages, and then Mantel–Haenszel chi-square tests, multiple correspondence analysis, Wald chi-square statistics, and logistic regression analyses were performed; P Results In total, 421 breast cancer survivors completed the questionnaire. Among them, 331 (78.62%) reported rarely sweating; 340 (80.76%) reported dry skin; 184 (43.71%) reported itchy skin in addition to dry skin; 336 (79.81%) had severe or mild skin color deposition; and 76 (18.05%) had eczema or contact dermatitis. Dry skin problems were caused by absent sweating and skin dryness in the irradiated skin area, post-RT severe skin disorders, and skin color deposition. Compared with patients sweating normally in the radiation field, patients with absent sweating and hotness sensation in the radiation field had a higher risk of depression. Conclusions This study showed that breast cancer patients after whole breast radiotherapy may experience skin dryness, hypersensitivity and hyper pigmentation in the irradiated skin area. These “radiation-irritated skin” lesions may induce depressive psychological status and impact the quality of life in breast cancer patients after whole breast radiotherapy.

With rapid advancement in water filtration materials, several efforts have been made to fabricate electrospun nanofiber membranes (ENMs). ENMs play a crucial role in different areas of water treatment due to their several advantageous properties such as high specific surface area, high interconnected porosity, controllable thickness, mechanical robustness, and wettability. In the broad field of water purification, ENMs have shown tremendous potential in terms of permeability, rejection, energy efficiency, resistance to fouling, reusability and mechanical robustness as compared to the traditional phase inversion membranes. Upon various chemical and physical modifications of ENMs, they have exhibited great potential for emerging applications in environment, energy and health sectors. This review firstly presents an overview of the limiting factors influencing the morphology of electrospun nanofibers. Secondly, it presents recent advancements in electrospinning processes, which helps to not only overcome drawbacks associated with the conventional electrospinning but also to produce nanofibers of different morphology and orientation with an increased rate of production. Thirdly, it presents a brief discussion about the recent progress of the ENMs for removal of various pollutants from aqueous system through major areas of membrane separation. Finally, this review concludes with the challenges and future directions in this vast and fast growing area.

Additional file 1.

The purpose of this study was to explore the association between myasthenia gravis (MG) and the risk of atrial fibrillation (AF) in an Asian population. The risk was analyzed in a cohort of 5528 patients with history of MG and 5528 individuals without MG using a hospitalization claim dataset. Both groups were matched by age, sex, index year and baseline comorbidities as an original analysis. A Cox proportional hazard model was used to estimate the hazard ratio and 95% confidence interval of AF after adjusting for demographic and relevant clinical covariates. The adjusted hazard ratio of the MG group compared with that of the non-MG group was 1.03 (95% confidence interval, 0.76-1.38) for AF. A stratified analysis showed that compared with the propensity score matched non-MG group, there was no increased risk of developing AF based on age categories, gender, or comorbidities. Different time follow-up periods results showed no increased risk of AF compared with the non-MG group. Overall, in the Taiwanese cohort, MG is not associated with an increased risk of AF.

Background and Objectives: Iron-deficiency anemia (IDA) could predispose the afflicted individuals to various infections and musculoskeletal disorders. This study attempted to investigate the association between IDA and septic arthritis (SA), a musculoskeletal disease. Materials and Methods: We investigated all the eligible subjects in the Taiwanese longitudinal health insurance database (LHID) between 2000 and 2012. Subjects with the diagnosis of IDA (International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM): 280) were allocated to the IDA cohort. The control subjects were randomly matched to every subject with IDA coding by age and sex at the 1:4 ratio. All of the recruited subjects were followed since the index date to the onset of SA (ICD-9-CM: 711.0), withdrawal from the insurance (including death), or 31 December 2013. Results: The cumulative incidence of SA was assessed. We showed that the cumulative incidence of SA was higher in the IDA cohort than in the control cohort (p-value < 0.0001). After adjustment of the comorbidities, the IDA patients had a 2.53-fold risk of SA compared to control subjects (aHR = 2.53, 95% CI = 1.89–3.38). Conclusions: IDA was associated with an increased risk of SA.

To ascertain the direct effects of water stress upon wheat plants (Triticum aestivum L.) and how these effects, in turn, influence the population growth of the bird cherry-oat aphid (Rhopalosiphum padi L.), we conducted a physiological analysis of wheat seedlings grown under three different watering regimes and subsequently determined the population parameters of the aphid using the age-stage, two-sex life table. A significantly higher content of free amino acids and soluble sugars were observed in wheat seedlings exposed to drought stress compared to seedlings that were well-watered and those that were grown under waterlogged conditions. Extended phloem salivation and stylet penetration with shorter duration of sustained ingestion from phloem was observed in an electrical penetration graph (EPG) of R. padi on drought-stressed wheat seedlings. This suggested that the aphid’s feeding activity, as well as nutrient intake, were impeded. The significantly higher percentage of essential amino acids found in wheat seedlings grown under waterlogged conditions promoted significantly higher fecundity and intrinsic rate of increase in R. padi populations compared to aphids fed on drought-treated or well-watered wheat seedlings. Our findings suggest that wheat seedling responses to water stress involve changes in sap composition that are responsible for altering the aphids’ nutrient intake and consequently affect their population growth. From a grower’s perspective, extending wheat cultivation in a rice–wheat rotation paddy field during the winter season may not be economically profitable if the fields are chronically waterlogged, since this may potentially lead to a higher infestation of cereal aphids.

Norovirus is the leading cause of food-borne disease outbreaks. We conducted this study to examine the incidence and molecular characteristics of norovirus genogroup I infections from acute gastroenteritis outbreaks in Taiwan. Between January 2015 and June 2019, 2121 acute gastroenteritis clusters were reported to Taiwan CDC, of which 351 (16.5%) clusters were positive for NoV GI, and GI.3 was the most prevalent (36.8%) during the study period. The GI.3 infections were significantly higher than non-GI.3 infections in the age groups of 0–5 and 6–18 years. The phylogenetic analysis of the MCC tree revealed that VP1 genes were divided into 3 groups: the GI.P3-GI.3 strains in Taiwan were genetically close to Japan and the GI.Pd-GI.3 strains were segregated into 2 other groups which were genetically closely related to China. In addition, 7 GI.Pd-GI.3 recombinants were identified circulating in Taiwan between 2018 and 2019, and the prevalence of GI.Pd-GI.3 should be monitored to assess whether this could become the new predominant strains in neighboring Asian countries or other parts of the world. Both GI.P3-GI.3 and GI.Pd-GI.3 strains cocirculate, the recombination among these two lineages occurs frequently, contributing to the genetic diversity and multiple occurrences of different norovirus lineages, and their rapid evolution makes future control more difficult. Continued surveillance and timely interventions are critical to understand the complexity of norovirus gene variation and to monitor the new emerging norovirus strains.