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.

Baseline cardiac output and its alterations during ibuprofen treatment for patent ductus arteriosus in preterm infants.

BACKGROUND: Infants with hemodynamically significant patent ductus arteriosus (PDA) may physiologically compensate with a supranormal cardiac output (CO). As such, a supranormal CO may be a surrogate marker for a significant PDA or indicate a failed response to PDA closure by ibuprofen. Electrical cardiometry (EC) is an impedance-based monitor that can continuously and non-invasively assess CO (COEC). We aimed to trend COEC through ibuprofen treatment for PDA in preterm infants. METHODS: We reviewed our database of preterm infants receiving ibuprofen for PDA closure. Response to ibuprofen was defined as no ductal flow in echocardiography ≤24 h after treatment. Responders were compared with gestational age (GA) and postnatal age matched non-responders and their trends of COEC were compared. Both groups' baseline COEC were further compared to the reference infants without PDA. RESULTS: Eighteen infants (9 responders and 9 non-responders) with median (interquatile range) GA 27.5 (26.6-28.6) weeks, birthweight 1038 (854-1218) g and age 3.5 (3.0-4.0) days were studied. There were positive correlations between COEC and ductal diameter and left atrium/ aortic root ratio (r = 0.521 and 0.374, p < 0.001, respectively). Both responders and non-responders had significantly higher baseline COEC than the reference. Although there was no significant within-subject alteration of COEC during ibuprofen treatment, there was a between-subject difference indicating non-responders had generally higher COEC. CONCLUSIONS: The changes of COEC during pharmacological closure of PDA is less drastic compared to surgical closure. Infants with PDA had higher baseline COEC compared to those without PDA, and non-responders had higher COEC especially at baseline compared to responders.

Protective factors against preterm infants to develop significant patent ductus arteriosus.

BACKGROUND: Identifying preterm infants with a higher likelihood of spontaneous patent ductus arteriosus (PDA) closure would be desirable. This study aimed to examine daily PDA status during the first week of life for very low birthweight (VLBW, <1500 g) preterm infants and to develop a scoring system to predict spontaneous PDA closure. METHODS: We enrolled VLBW infants admitted between January 2016 and January 2017 and performed daily echocardiographic screening for PDA existence. Oxygen index (OI, mean airway pressure × fraction of inspired oxygen/partial pressure of arterial oxygen) was applied to represent the respiratory condition. RESULTS: A total of 215 VLBW infants were enrolled, and the accumulative incidence of spontaneous PDA closure by age 1 week was 80%, 70%, and 34% for infants born of gestational age (GA) ≥30, 28-29, and ≤27 weeks, respectively. Of these 215 infants, 184 infants entered the second phase to establish the scoring system. Infants with spontaneous PDA closure were more mature (GA 29.2 ± 2.3 vs. 26.9 ± 2.3 weeks, p < 0.001), had lower OI (2.8 ± 2.2 vs. 5.6 ± 5.3, p < 0.001) and were less likely to need endotracheal intubation (23% vs. 68%, p < 0.001). Using the receiver operating characteristics curve, OI <2.5 was determined favoring higher PDA closure incidence. The score was calculated based on the odds ratio generated in multiple regression: 4, 3 and 1 points for GA ≥30, 28-29 and ≤27 weeks, 2 and 1 points for OI <2.5 and ≥2.5, and 3 and 1 points for without and with endotracheal intubation. Using score ≥6 to predict PDA closure, the sensitivity and specificity were 0.77 and 0.72. CONCLUSION: A score made up of GA, OI and need for intubation was proposed to predict spontaneous PDA closure by age 1 week, which could be helpful to clinicians in the management of PDA in preterm infants.

Behavioral Model of Middle-Aged and Seniors for Bicycle Tourism.

This research centers on the behavioral tendency of the middle-aged and seniors in bicycle tourism at environmentally protected scenic areas and its relevant influence factors. The theory of planned behavior (TPB) is adopted as the basis of this study. The middle-aged and seniors are the subjects of this research. A questionnaire survey is conducted at environmentally protected national scenic areas in Taiwan. A total of 230 samples are drawn with a random sampling method, and 210 are valid. The findings indicate two things. First, when applying the TPB to different fields of the study, the level of predictability may vary. Another finding is that subjective norm shows a higher level of susceptibility to sport habit and predictability to behavioral intention than the other two constructs. With an empirical analysis, the study is able to provide middle-aged and senior participants and sport administration authorities with relevant suggestions for reference at the end of this paper.

A Study on the Place Attachment of Golf Club Members.

The purpose of this study is to explore the members of golf clubs in the central region of Taiwan and find out whether their involvement in activities affects the degree of place attachment and to add the two factors of activity experience and experience value so as to develop a theoretical framework. A questionnaire survey was used to collect 534 samples from golf clubs in central Taiwan for analysis using the following research tools: the Activity Involvement scale, Place Attachment scale, and Likert psychological scale. The results of the study show that (1) activity involvement has a significant positive impact on place attachment, activity experience, and experience value; (2) activity experience has a significant positive impact on experience value; (3) experience value has a significant positive impact on place attachment. This result verifies the theory that activity involvement impacts place attachment. It is suggested that the relevant bodies should strengthen the incentives given in the activities and strengthen the value of the leisure experience so as to facilitate the development of related industries in the future.

Exploring Consumers' Interest in Choosing Sustainable Food.

In order for humans to achieve a healthier diet and maintain ecological balance, a new concept regarding sustainable food has been introduced. The aim of this study is, therefore, to explore consumers' interest in choosing sustainable food. The study utilized "Do Survey," an internet survey platform, to distribute questionnaires. Survey invitations were sent out in a snowball manner. Invitations were posted in multiple online communities and forwarded by various members to other sites; 333 valid responses were collected. The results show that family and friend support and health incentive are the two strongest predictors for sustainable food buying interest. Price accessibility, on the other hand, has no impact on interest. This is not to say that price accessibility does not influence behavior. It just means that it is not the factor that fosters interest. Once an individual is interested, she/he may still rely heavily on price accessibility in purchasing sustainable food.

Trajectory of vitamin D, micronutrient status and childhood growth in exclusively breastfed children.

This study aimed to compare the trajectory of serum 25(OH)D, micronutrient levels, and anthropometric measurements between exclusively breastfed and mixed-fed children. This is a prospective cohort study. Anthropometric measurements of the children were obtained during scheduled clinical visits. Tests for 25(OHD), ferritin, zinc and complete blood count were performed yearly until 3 years of age. Clinical records and questionnaires on dietary habits were obtained. The results showed that despite official recommendations on vitamin D/iron supplements for breastfed children, less than 10% of our exclusively breastfed children received regular supplements. Thus, after 1 year, the odds for having iron deficiency anemia and vitamin D insufficiency were 9 [95% CI, 4-19] and 6 [95% CI, 2-16], respectively. Longitudinal follow-up showed the prevalence of iron deficiency to decrease from 34% at 1 year to 2% at age 3 years. However, the prevalence of vitamin D insufficiency remained persistently high throughout the first three years of life (60% at 1 to 44% at 3 years). Very few children had zinc deficiency. Anthropometric measurements showed exclusively breastfed children to have lower mean z-scores for body weight and height when compared to mixed-fed children after 12 months. In conclusion, children who were exclusively breastfed for longer than 4 months without proper supplement were more likely to have transient iron deficiency anemia and persistent vitamin D insufficiency. Their growth became relatively slower after infancy. Whether this was associated with underlying inadequate serum vitamin D and iron level remains an important issue to be explored.

Risk factors and molecular epidemiology of Acinetobacter baumannii bacteremia in neonates.

BACKGROUND: Acinetobacter baumannii infections in neonates are not uncommon but rarely studied. METHODS: Clinical and molecular epidemiology of 40 patients with A. baumannii bacteremia in the neonatal intensive care units (NICUs) of a medical center from 2004 to 2014 was analyzed. RESULTS: Multi-drug resistance was found in only 3 isolates (7.5%). Sequence types (STs) of A. baumannii defined by multilocus sequencing typing were diverse, and 72.4% identified isolates belonged to novel STs. Majority of the isolates were susceptible to antibiotics tested. Among the 3 imipenem-resistant A. baumannii (IRAB) isolates, 2 (66.7%) belonged to ST684, a novel ST. All of the 3 isolates were susceptible to tigecycline and colistin. The predominant mechanism of imipenem resistance in these neonatal isolates is ISAba1-blaOXA-80, which has never been reported in Asia before. Most infected newborns were premature (95%), with very low birth weight (70% < 1500 g), prolonged intubation, usage of percutaneous central venous catheter (65%) and long-term usage of total parenteral nutrition or intravenous lipid (95%). IRAB infection, inappropriate initial therapy, 1-minute Apgar score and early onset infection within the first 10 days of life were found to correlate with mortality by log-rank test. Prior use of imipenem for at least 5 days and use of high frequency oscillation ventilation (HFOV) were statistically significant risk factors for acquiring IRAB infections. CONCLUSIONS: To reduce mortality of IRAB infection, it is crucial to consider giving effective agents, such as colistin, in 2 days for high risk neonates who has been given imipenem or used HFOV.

Infant anemia is associated with reduced TLR-stimulated cytokine responses and increased nasopharyngeal colonization with Moxarella catarrhalis.

Anemia is a major public health problem in young children. Reports on the role of anemia on infectious diseases remained controversial. We aim to investigate the effect of anemia on innate immunity, nasopharyngeal bacterial colonization, and subsequent infectious outcome. Blood tests were examined at the age of 12 months. TLR-induced cytokine production was assessed by ELISA. Bacteria from nasopharyngeal specimens were identified with traditional culture. Clinical infectious diseases were followed yearly until 3 years of age. Result showed that of the 423 infants, 72 had hemoglobin level ≤ 11 g/dL, among which 55% had normal iron level. There was significant association between hemoglobin level and TLR1-2, and 4 induced IL-6 (p = 0.04, 0.02) and that of TLR4 stimulated TNF-α response (p = 0.04). Children with anemia had higher nasopharyngeal colonization with Moxarella catarrhalis. Clinical analysis did not show anemia to be associated with infectious morbidity. However, children who developed LRTIs had mean lower ferritin levels. We speculated that iron might be the key factor related to infectious morbidity. Thus, to investigate the role of anemia in infectious diseases, it is important to first consider the prevalence of iron deficit, since the incidence of iron deficiency-induced anemia may vary among different regions.

Electrical Cardiometry to Monitor Cardiac Output in Preterm Infants with Patent Ductus Arteriosus: A Comparison with Echocardiography.

BACKGROUND: Electrical cardiometry (EC) is an impedance-based monitoring that provides noninvasive cardiac output (CO) assessment. Through comparison to transthoracic echocardiography (Echo), the accuracy of EC has been verified. However, left-to-right patent ductus arteriosus (PDA) shunting is a concern because PDA shunts aortic flow to the pulmonary artery and may interfere with EC in measuring CO. OBJECTIVE: To determine the agreement between EC and Echo in preterm infants with a hemodynamically significant PDA (hsPDA). METHODS: We reviewed our hemodynamic database in which simultaneous CO measurements by Echo and EC (Aesculon®) were recorded. Preterm infants with left-to-right shunting hsPDA were enrolled. RESULTS: A total of 105 paired measurements in 36 preterm infants were compared. Infants' median (range) age and weight at measurement were 27+2 weeks (24+0-33+1) and 1,015 g (518-1,880), with mean (95% CI) ductal diameter 2.11 mm (1.99-2.22) or 2.15 mm/kg (2.00-2.30). Mean COEC and COEcho were 252 ± 32 and 258 ± 45 mL/kg/min, respectively, which demonstrated a moderate correlation and without a significant between-measurement difference. Bland-Altman analysis showed a bias, limits of agreement, and error percentage of -5.3 mL/kg/min, -78.3 to 67.7 mL/kg/min, and 28.6%, respectively. There was a trend of increased bias and error percentage of infants with high CO ≥280 mL/kg/min and supported with high-frequency ventilator. CONCLUSIONS: EC and Echo have a wide but clinically acceptable agreement in measuring CO in preterm infants with hsPDA. However, for infants with high CO or ventilated by high-frequency ventilation, interpretation of COEC should be approached with caution.