Time-Resolved Resonant Raman Spectroscopy of the Photoinduced Electron Transfer from Ruthenium(II) Trisbipyridine to Methyl Viologen.

We report the first time-resolved resonant Raman (TR3) spectra of photoinduced charge transfer from [Ru(bpy)3]2+ to methyl viologen, with observations of vibrational structure. The presence of singly charged methyl viologen in solution is noted by the appearance of several spectroscopic lines, which are visible in the spectra following subtraction of reagent molecules. Assignments are confirmed using both density functional theory (DFT) calculations and literature values and are shown to be consistent with transient absorption spectroscopy data. This presents proof-of-concept for the application of TR3 in mechanistic studies of photocatalytic systems.

Early Childhood Caries and Risk Factors in Vietnam.

OBJECTIVE: To investigate caries prevalence and examine its relationship with socioeconomic status and oral health behavior of Vietnamese kindergarten children. STUDY DESIGN: The study was carried out on 1,028 children aged 2-5 years in six kindergartens in Thua Thien Hue province, Vietnam. Information about socioeconomics and oral health behaviors was collected through a self-administered questionnaire, and oral health status by clinical dental examination. RESULTS: Clinical dental examination found that overall caries prevalence and mean dmft were 89.1% and 9.32. Caries prevalence and mean dmft increased greatly from two years to three years old, and gradually developed from three years to five years old. A logistic regression revealed that caries had an inverse relationship with mothers' educational level and a positive relationship with the habit of retaining food in the mouth for a long time in two-year-old children. Prolonged breastfeeding, more frequent sweets consumption, no thumb sucking habit, and higher modified debris index score were the risk factors for caries among three-to-five-year-old children. CONCLUSIONS: This study indicated a high prevalence of caries and related risk factors such as low mother's educational level and inappropriate oral health behavior among kindergarten children in Vietnam.

Three-dimensional ordered assembly of thin-shell Au/TiO2 hollow nanospheres for enhanced visible-light-driven photocatalysis.

An Au/TiO(2) nanostructure was constructed to obtain a highly efficient visible-light-driven photocatalyst. The design was based on a three-dimensional ordered assembly of thin-shell Au/TiO(2) hollow nanospheres (Au/TiO(2)-3 DHNSs). The designed photocatalysts exhibit not only a very high surface area but also photonic behavior and multiple light scattering, which significantly enhances visible-light absorption. Thus Au/TiO(2)-3 DHNSs exhibit a visible-light-driven photocatalytic activity that is several times higher than conventional Au/TiO(2) nanopowders.

Clinical efficacy and satisfaction of a digital wheeze detector in a multicentre randomised controlled trial: the WheezeScan study.

Introduction: Wheezing is common in preschool children and its clinical assessment often challenging for caretakers. This study aims to evaluate the impact of a novel digital wheeze detector (WheezeScan™) on disease control in a home care setting. Methods: A multicentre randomised open-label controlled trial was conducted in Berlin, Istanbul and London. Participants aged 4-84 months with a doctor's diagnosis of recurrent wheezing in the past 12 months were included. While the control group followed usual care, the intervention group received the WheezeScan™ for at-home use for 120 days. Parents completed questionnaires regarding their child's respiratory symptoms, disease-related and parental quality of life, and caretaker self-efficacy at baseline (T0), 90 days (T1) and 4 months (T2). Results: A total of 167 children, with a mean±sd age of 3.2±1.6 years, were enrolled in the study (intervention group n=87; control group n=80). There was no statistically significant difference in wheeze control assessed by TRACK (mean difference 3.8, 95% CI -2.3-9.9; p=0.2) at T1 between treatment groups (primary outcome). Children's and parental quality of life and parental self-efficacy were comparable between both groups at T1. The evaluation of device usability and perception showed that parents found it useful. Conclusion: In the current study population, the wheeze detector did not show significant impact on the home management of preschool wheezing. Hence, further research is needed to better understand how the perception and usage behaviour may influence the clinical impact of a digital support.

[Mechanisms of insulin resistance]. / Insuliiniresistenssin mekanismit.

Insulin resistance refers to an aberrant physiological response to insulin in its target tissues. Several signal transduction mechanisms sensing intracellular stress are activated in situations where energy supply exceeds the cells' energy requirements. This stress interferes with insulin-induced intracellular signal transduction and leads to an inflammatory state. The activation of inflammatory responses in peripheral tissues and central nervous system weakens the body's insulin sensitivity, glucose tolerance and predisposes to obesity. Insulin resistance is thus a crucial metabolic disorder in obesity, type 2 diabetes and cardiovascular diseases.

High Prevalence of Post-Traumatic Stress Disorder and Psychological Distress Among Healthcare Workers in COVID-19 Field Hospitals: A Cross-Sectional Study from Vietnam.

Objective: To evaluate the prevalence of post-traumatic stress disorder (PTSD) and other psychological disturbances in the Vietnamese healthcare workers (HCWs) at COVID-19 field hospitals. Methods: A cross-sectional study was conducted using the Impact of Event Scale-Revised (IES-R) to measure PTSD and the Depression Anxiety Stress scale (DASS) to measure other psychological disturbances. The anxiety about COVID-19 was evaluated by the fear of COVID-19 (FOC) scale. A self-developed questionnaire was used to assess work conditions and HCW's major concerns and preparedness. Ordinal logistic regression was used to identify factors associated with the severity of PTSD. A structural modeling equation (SEM) model was fitted to examine the correlation between PTSD and other psychological disturbances. Results: A total of 542 HCWs participated in this study. The prevalence of PTSD was 21.2%, most cases were mild. In the ordinal logistic regression analysis, a history of mental illness, poor preparedness, working in a condition with poor resources, a greater number of concerns, and greater fear of COVID-19 were independently associated with higher severity of PTSD. The prevalence of depression, anxiety, and stress was 46.8%, 38.3%, and 60.2, respectively. In the SEM model, PTSD and psychological disturbances had a strong correlation (standardized covariance 0.86). Conclusion: The prevalence of PTSD and other psychological disturbances was alarmingly high among HCWs who worked at COVID-19 field hospitals. The reported associated factors can be useful for policymakers and health authorities in the preparation for future pandemics.

Structural and enzyme activity studies demonstrate that aryl substituted 2,3-butadienamine analogs inactivate Arthrobacter globiformis amine oxidase (AGAO) by chemical derivatization of the 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor.

Copper amine oxidases (CAOs) are a family of redox active enzymes containing a 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor generated from post translational modification of an active site tyrosine residue. The Arthrobacter globiformis amine oxidase (AGAO) has been widely used as a model to guide the design and development of selective inhibitors of CAOs. In this study, two aryl 2,3-butadienamine analogs, racemic 5-phenoxy-2,3-pentadienylamine (POPDA) and racemic 6-phenyl-2,3-hexadienylamine (PHDA), were synthesized and evaluated as mechanism-based inactivators of AGAO. Crystal structures show that both compounds form a covalent adduct with the amino group of the substrate-reduced TPQ, and that the chemical structures of the rac-PHDA and rac-POPDA modified TPQ differ by the allenic carbon that is attached to the cofactor. A chemical mechanism accounting for the formation of the respective TPQ derivative is proposed. Under steady-state conditions, no recovery of enzyme activity is detected when AGAO pre-treated with rac-PHDA or rac-POPDA is diluted with excess amount of the benzylamine substrate (100-fold K(m)). Comparing the IC(50) values further reveals that the phenoxy substituent in POPDA offers an approximately 4-fold increase in inhibition potency, which can be attributed to a favourable binding interaction between the oxygen atom in the phenoxy group and the active site of AGAO as revealed by crystallographic studies. This hypothesis is corroborated by the observed >3-fold higher partition ratio of PHDA compared to POPDA. Taken together, the results presented in this study reveal the mechanism by which aryl 2,3-butadienamines act as mechanism-based inhibitors of AGAO, and the potency of enzyme inactivation could be fine-tuned by optimizing binding interaction between the aryl substituent and the enzyme active site.

Remote sensing of vital signs by medical radar time-series signal using cardiac peak extraction and adaptive peak detection algorithm: Performance validation on healthy adults and application to neonatal monitoring at an NICU.

BACKGROUND AND OBJECTIVE: Continuous monitoring of vital signs plays a pivotal role in neonatal intensive care units (NICUs). In this paper, we present a system for monitoring fully non-contact medical radar-based vital signs to measure the respiratory rate (RR), heart rate (HR), I:E ratio, and heart rate variability (HRV). In addition, we evaluated its performance in a physiological laboratory and examined its adaptability in an NICU. METHODS: A non-contact medical radar-based vital sign monitoring system that includes 24 GHz radar installed in an incubator was developed. To enable reliable monitoring, an advanced signal processing algorithm (i.e., a nonlinear filter to separate respiration and heartbeat signals from the output of radar), template matching to extract cardiac peaks, and an adaptive peak detection algorithm to estimate cardiac peaks in time-series were proposed and implemented in the system. Nine healthy subjects comprising five males and four females (24 ± 5 years) participated in the laboratory test. To evaluate the adaptability of the system in an NICU setting, we tested it with three hospitalized infants, including two neonates. RESULTS: The results indicate strong agreement in healthy subjects between the non-contact system and reference contact devices for RR, HR, and inter-beat interval (IBI) measurement, with correlation coefficients of 0.83, 0.96, and 0.94, respectively. As anticipated, the template matching and adaptive peak detection algorithms outperformed the conventional approach. These showed a more accurate IBI close to the reference Bland-Altman analysis (proposed: bias of -3 ms, and 95% limits of agreement ranging from -73 to 67 ms; conventional: bias of -11 ms, and 95% limits of agreement ranging from -229 to 207 ms). Moreover, in the NICU clinical setting, the IBI correlation coefficient and 95% limit of agreement in the conventional method are 0.31 and 91 ms. The corresponding values obtained using the proposed method are 0.93 and 21 ms. CONCLUSION: The proposed system introduces a novel approach for NICU monitoring using a non-contact medical radar sensor. The signal processing method combining cardiac peak extraction algorithm with the adaptive peak detection algorithm shows high adaptability in detecting IBI the time series in various application settings.

Proof-of-principle Experiment on 24 GHz Medical Radar for Non-contact Vital Signs Measurement.

Medical radar for non-contact vital signs measurement exhibits great potential in both clinical and home healthcare settings. Especially during the corona virus spreading time, non-contact sensing more clearly shows the advantages. Many previous studies have concentrated on medical radar-based healthcare applications, but pay less attention to the working principles. A clear understanding of medical radars at both the mathematical and physical levels is critically important for developing application-specific signal processing algorithms. Therefore, this study aims to re-define the operating principle of radar, and a proof-of-principle experiment was performed on both actuator and human subjects using 24 GHz Doppler radar system. Experimental results indicate that there is a difference in the radar output signals between the two cases, where the displacement is greater than and less than half of the wavelength. For the former situation, the displacement x = n.λ/2 (n ≥ 1), one peak of radar signals corresponds to n peaks of baseband signals. By contrast, for the latter situation, the displacement x < λ/2, one peak of radar signals corresponds to one peak of baseband signals. Strikingly, with human measurement on the dorsal side, the the number of respiration peaks are seen from the radar raw signals.

Effect of HIV, antiretrovirals, and genetics on methadone pharmacokinetics: Results from the methadone antiretroviral pharmacokinetics study.

BACKGROUND: Methadone treatment of opioid use disorder in HIV-infected individuals is complicated by drug-drug interactions. Genetic and other cofactors further contribute to interindividual variability in methadone pharmacokinetics. We used population pharmacokinetics to estimate the effect of drug-drug interactions, genetics, and other cofactors on methadone pharmacokinetics in a methadone maintained population in Vietnam. METHODS: Plasma R- and S-methadone levels were measured in 309 methadone maintained individuals just before and 2-5 h following methadone dosing. A linear one-compartment population pharmacokinetic model with first-order conditional estimation with interaction was used to evaluate methadone clearance (CL/F) and volume of distribution (V/F). The influence of covariates on parameter estimates was evaluated using stepwise covariate modeling. Covariates included HIV status, antiretroviral use (efavirenz or nevirapine), weight, BMI, age, methadone dose, and 8 single nucleotide polymorphisms in across the CYP2B6, ABCB1, and NR1I3 genes. RESULTS: Taking either efavirenz or nevirapine increased R-methadone CL/F 220%. Nevirapine and efavirenz increased S-methadone CL/F by 404% and 273%, respectively. Variants in NR1I3 increased R- and S-methadone CL/F by approximately 20% only in patients taking efavirenz. Different alleles in ABCB1 rs2032582 either increased or decreased R-methadone CL/F by 10%. The CYP 2B6*4 variant decreased S-methadone CL/F by 18%. HIV-infection increased R- and S-methadone CL/F and V/F by 24%-39%. CONCLUSIONS: The HIV antiretrovirals nevirapine and efavirenz significantly increase methadone clearance. Variants inNR1I3 increased the effect of efavirenz on methadone clearance. Other variants affecting methadone CL/F were also confirmed. To our knowledge, this is the first report of HIV itself affecting methadone pharmacokinetics.

Design and Evaluation of Digital Filters for Non-Contact Measuring of HRV using Medical Radar and Its Application in Bedside Patient Monitoring System.

A non-contact bedside monitoring system using medical radar is expected to be applied to clinical fields. Our previous studies have developed a monitoring system based on medical radar for measuring respiratory rate (RR) and heart rate (HR). Heart rate variability (HRV), which is essentially implemented in advanced monitoring system, such as prognosis prediction, is a more challenging biological information than the RR and HR. In this study, we designed a HRV measurement filter and proposed a method to evaluate the optimal cardiac signal extraction filter for HRV measurement. Because the cardiac component in the radar signal is much smaller than the respiratory component, it is necessary to extract the cardiac element from the radar output signal using digital filters. It depends on the characteristics of the filter whether the HRV information is kept in the extracted cardiac signal or not. A cardiac signal extraction filter that is not distorted in the time domain and does not miss the cardiac component must be adopted. Therefore, we focused on evaluating the interval between the R-peak of the electrocardiogram (ECG) and the radar-cardio peak of the cardiac signal measured by radar (R-radar interval). This is based on the fact that the time between heart depolarization and ventricular contraction is measured as the R-radar interval. A band-pass filter (BPF) with several bandwidths and a nonlinear filter, locally projective adaptive signal separation (LoPASS), were analyzed and compared. The optimal filter was quantitatively evaluated by analyzing the distribution and standard deviation of the R-radar intervals. The performance of this monitoring system was evaluated in elderly patient at the Yokohama Hospital, Japan.

Impact of School-Based Oral Health Education on Vietnamese Adolescents: A 6-Month Study.

We have evaluated the impact of a school-based intervention on oral health knowledge, behaviours, and oral health status of adolescents in Vietnam. This 6-month study included 462 adolescents aged 12 years from four selected schools in Hue City, Vietnam. The intervention group received a 15-min lecture by a dentist and hands-on session on mouth observation and toothbrushing skills. The control group did not engage in any educational activities during the follow-up period. Data were collected at baseline and 6 months through a survey questionnaire and clinical examination. The Debris Index was used for dental plaque; the Papillary, Marginal, Attached gingiva index for gingivitis; and the Decayed, Missing, and Filled Teeth index (World Health Organization modification) for dental caries. Difference-in-difference analysis was used to compare changes between the groups. After 6 months, the control tended to show decreased toothbrushing frequency and increased dental plaque accumulation. The participants in the intervention group showed improved oral health knowledge (p < 0.01), behavior (p < 0.05), and hygiene (p < 0.001) compared to the control group. However, the intervention did not improve dental caries and gingivitis. A single school-based oral health education program can help adolescents improve oral health knowledge and prevent the deterioration of short-term oral health behavior and hygiene.

Discovery of α-Glucosidase Inhibitors from Marine Microorganisms: Optimization of Culture Conditions and Medium Composition.

Various studies showed that the suppression of α-glucosidase activity can impede the glucose absorption in our body, and therefore, it can be used to treat type 2 diabetes. Hence, the compounds with anti-α-glucosidase have gained considerable attention because of their potential application in diabetes treatment. In previous literature studies, these anti-α-glucosidase compounds were extracted from plants and fungus. Less studies are being conducted to identify the anti-α-glucosidase compounds in the microbial community. In this study, 23 marine bacterial strains were screened for their potential to suppress the α-glucosidase activity. The highest inhibitory activity was exhibited by isolated L06 which was identified as Oceanimonas smirnovii EBL6. The cultivation conditions, such as temperature and pH, were optimized to increase the production of α-glucosidase inhibitors by Oceanimonas smirnovii EBL6 strain. The result findings showed that the highest yield of α-glucosidase inhibitors can be obtained at the culture time of 120 h, fermentation temperature of 30 °C, and pH 4.6. Under these conditions, the inhibitory activity of α-glucosidase can reach 81%. The IC50 of n-butanol extract was 13.89 µg/ml, while standard acarbose was 31.16 µg/ml. Overall, these findings suggest that Oceanimonas smirnovii produces α-glucosidase inhibitors and could been applied in the biochemical and medicinal fields in the future.

Selection, purification, and evaluation of acarbose-an α-glucosidase inhibitor from Actinoplanes sp.

Actinoplanes sp. A1094 strain had been selected for its high production of acarbose from 20 different strains of Actinoplanes sp. can be found in wild. The content for glucosidase inhibitor of acarbose concentration was recorded at 1.12 g/L. The conducted analysis of 16S rRNA sequence of Actinoplanes sp. A1094 showed 99% similar identity to the corresponding sequence of Actinoplanes hulinensis. Acarbose was purified from Actinoplanes hulinensis 1094 with a yield of 8.48%, purity of 98% and further identified by LC/MS and NMR methods (C25H43NO18; m/z: 645.6 g/mol). The purified acarbose was used to evaluate the hypoglycemia in streptozotocin (STZ)-induced diabetic mice model. The purified acarbose reduced postprandial blood glucose level in comparison with Glucobay® as medication for control type 2 diabetes in a combination therapy. Notably, the outcomes of native acarbose on fasting blood glucose levels in mice resemble akin to the commercial product and the acarbose accumulating fermentation and metabolic engineering from the cell gene in which would reduce in production cost. Therefore, acarbose from Actinoplanes hulinensis 1094 could be potentially used to make products for the treatment of type II diabetes.

Late Pleistocene-Holocene sedimentary evolution in the coastal zone of the Red River Delta.

The Red River Delta is considered one of the largest megadelta systems in Asia. The formation of this delta has been controlled by the continent-ocean interaction and sea-level fluctuation during the Cenozoic. In this study, we present a new sequence stratigraphic framework of the Red River Delta based on borehole lithofacies analysis and high resolution seismic data. The Late Pleistocene-Holocene sediments in the coastal zone of the Red River Delta were subdivided into three systems tracts: (1) the lowstand systems tract (LST) is characterized by a Late Pleistocene alluvial silty sand facies complex (arLSTQ1 3b); (2) the transgressive systems tract (TST) is illustrated by the coastal marsh facies complex and the lagoonal greenish-gray clay facies of Early-Middle Holocene (amt, mtTSTQ2 1-2); and (3) the highstand systems tract (HST) is composed of the Middle-Late Holocene deltaic clayish silt facies complex (amhHSTQ2 2-3). The boundaries between these three systems tracts are not isochronous, namely: (1) The LST-HST boundary has been associated with the Würm 2 Glaciation, which occurred at ~40-18 Ka.; (2) The TST-LST boundary is identified by a transgressive erosion surface, whose age ranges from ~12-5 Ka.; and (3) the HST-TST boundary is an unconformity between the submarine deltaic facies complex and the Middle Holocene marine flooding plain.

Identifying Developmental Language Disorder in Vietnamese Children.

Purpose Developmental language disorder (DLD), defined by low language performance despite otherwise normal development, can negatively impact children's social and academic outcomes. This study is the 1st to examine DLD in Vietnamese. To lay the foundation, we identified cases of DLD in Vietnam and explored language-specific characteristics of the disorder. Method Teacher ratings of 1,250 kindergarteners living in Hanoi, Vietnam, were used to recruit children with and without risk for DLD. One hundred four children completed direct measures of vocabulary and language sampling, and their parents completed in-depth surveys. We examined convergence and divergence across tasks to identify measures that could serve as reliable indicators of risk. Then, we compared performance on direct language measures across ability levels. Results There were positive associations between teacher and parent report and between report and direct language measures. Three groups were identified based on convergence across measures: DLD, some risk for DLD, and no risk. The DLD group performed lowest on measures of receptive and expressive vocabulary, mean length of utterance, and grammaticality. Although children with DLD exhibited a greater number of errors, the types of errors found were similar across DLD and No Risk groups. Conclusions Similar to rates found globally, 7% of the kindergarten population in Vietnam exhibited risk for DLD. Results highlight the importance of parent and teacher report and the value of multiple measures to identify DLD. We discuss potential clinical markers for DLD in the Vietnamese language and outline future directions.

TRP-independent inhibition of the phospholipase C pathway by natural sensory ligands.

Menthol, cinnamaldehyde, and camphor are activators for temperature-sensitive transient receptor potential ion channels (thermoTRPs). Here we found that these three compounds inhibit the phospholipase C (PLC) signaling. P2Y purinoceptor-mediated or histamine receptor-mediated cytosolic calcium mobilization through the PLC pathway was significantly suppressed by menthol, cinnamaldehyde, and camphor. Experiments using a fluorescent pleckstrin homology domain of PLCdelta1 and IP1 accumulation assays demonstrated that direct inhibition of PLC activity occurred upon the addition of the sensory compounds. P2Y receptor-mediated PLC activation is part of the mechanism of platelet aggregation. The three compounds inhibited ADP-induced platelet aggregation. Calcium influx studies showed that thermoTRPs do not function in platelets, suggesting that the anti-aggregation effect is independent of thermoTRP activity. These results suggest that menthol, cinnamaldehyde, and camphor are able to modify PLC signaling and that those effects may lead to changes in cellular functions. This study also identifies new types of compounds that could potentially modulate platelet-related pathological events.

Key considerations in reimbursement decision-making for multiple sclerosis drugs in Australia.

BACKGROUND: In Australia, the Pharmaceutical Benefits Advisory Committee (PBAC) advises on the reimbursement of drugs to be subsidised through the Pharmaceutical Benefits Scheme (PBS). This study aims to provide insights into the PBAC process and key considerations regarding the reimbursement of MS drugs in Australia. METHODS: The factors considered by the PBAC and its advice on whether to reimburse a drug are documented in public summary documents (PSDs). Qualitative content analysis of PSDs was conducted for all MS drugs considered by the PBAC between January 2006 and January 2018. Key issues identified by the PBAC were extracted and categorised. Common issues were identified and compared between drugs indicated for MS. RESULTS: A total of 23 submissions were evaluated relating to 13 MS drugs. Eight were recommended for reimbursement; an approval rate of 35% per submission and 62% per drug. Approval rates were higher for disease modifying treatments (73% per drug) than for symptomatic drugs (0% for nabiximols and fampridine submissions). The most frequently discussed issues in PSDs, irrespective of PBAC decision, were: (1) the validity of the indirect comparisons formed (n = 11); (2) the validity of the approach to obtain utilities (n = 6); (3) the lack of appropriate/long-term safety data (n = 8); and (4) the time horizon used in the economic models (n = 3). CONCLUSION: A small but important number of issues have been consistently identified by the PBAC in relation to submissions for reimbursement of MS drugs. Drug developers and clinical trial investigators who are aware of these issues will be able to anticipate data requirements for reimbursement decision-making and thus potentially improve the evidence submitted for listing of MS drugs in Australia.

Probing heme coordination states of inducible nitric oxide synthase with a ReI(imidazole-alkyl-nitroarginine) sensitizer-wire.

Mammalian inducible nitric oxide synthase (iNOS) catalyzes the production of l-citrulline and nitric oxide (NO) from L-arginine and O2. The Soret peak in the spectrum of the iNOS heme domain (iNOSoxy) shifts from 423 to 390 nm upon addition of a sensitizer-wire, [ReI-imidazole-(CH2)8-nitroarginine]+, or [ReC8argNO2]+, owing to partial displacement of the water ligand in the active site. From analysis of competitive binding experiments with imidazole, the dissociation constant (Kd) for [ReC8argNO2]+-iNOSoxy was determined to be 3.0+/-0.1 microM, confirming that the sensitizer-wire binds with higher affinity than both L-arginine (Kd=22+/-5 microM) and imidazole (Kd=14+/-3 microM). Laser excitation (355 nm) of [ReC8argNO2]+-iNOSoxy triggers electron transfer to the active site of the enzyme, producing a ferroheme in less than approximately 1 micros.