Differences in the superspreading potentials of COVID-19 across contact settings.

BACKGROUND: Superspreading events (SSEs) played a critical role in fueling the COVID-19 outbreaks. Although it is well-known that COVID-19 epidemics exhibited substantial superspreading potential, little is known about the risk of observing SSEs in different contact settings. In this study, we aimed to assess the potential of superspreading in different contact settings in Japan. METHOD: Transmission cluster data from Japan was collected between January and July 2020. Infector-infectee transmission pairs were constructed based on the contact tracing history. We fitted the data to negative binomial models to estimate the effective reproduction number (R) and dispersion parameter (k). Other epidemiological issues relating to the superspreading potential were also calculated. RESULTS: The overall estimated R and k are 0.561 (95% CrI: 0.496, 0.640) and 0.221 (95% CrI: 0.186, 0.262), respectively. The transmission in community, healthcare facilities and school manifest relatively higher superspreading potentials, compared to other contact settings. We inferred that 13.14% (95% CrI: 11.55%, 14.87%) of the most infectious cases generated 80% of the total transmission events. The probabilities of observing superspreading events for entire population and community, household, health care facilities, school, workplace contact settings are 1.75% (95% CrI: 1.57%, 1.99%), 0.49% (95% CrI: 0.22%, 1.18%), 0.07% (95% CrI: 0.06%, 0.08%), 0.67% (95% CrI: 0.31%, 1.21%), 0.33% (95% CrI: 0.13%, 0.94%), 0.32% (95% CrI: 0.21%, 0.60%), respectively. CONCLUSION: The different potentials of superspreading in contact settings highlighted the need to continuously monitoring the transmissibility accompanied with the dispersion parameter, to timely identify high risk settings favoring the occurrence of SSEs.

Rapid spectroscopic gas sensing using optical linear chirp chain.

Spectroscopic gas analysis for monitoring transient events in fast processes requires high spectrum acquisition rate with low uncertainty; however, so far high-speed spectroscopic gas detection with sufficient spectral resolution and spectral span is still challenging. Here, we propose an innovative method based on optical linear chirp chain (OLCC) for rapid acquisition of high-resolution gas spectra with a rate up to the order of MHz with 100% duty cycle, spectral resolution at 10-MHz level and spectral span > 20 GHz. The OLCC is generated by high-speed optical modulation driven by a digital arbitrary waveform generator in combination with a four-wave-mixing process, exhibiting a highly linear frequency chirp (linearity error of ~10-4) and low level of residual amplitude modulation (<1%). An image denoising method based on nonlocal means algorithm is exploited to reduce the high-frequency noise while guaranteeing the response time and spectral resolution. We demonstrate this method by monitoring a fast charging process of acetylene gas into a vacuumized gas cell, clearly unfolding gas pressure oscillations at µs time scale. Our proposed OLCC-based spectroscopic method opens up prospects for the development of high-speed spectrometers and optical sensors.

Integrated strategy based on high-resolution mass spectrometry coupled with multiple data mining techniques for the metabolic profiling of Xanthoceras sorbifolia Bunge husks in rat plasma, urine, and feces.

An integrated strategy based on high-resolution mass spectrometry coupled with multiple data mining techniques was developed to screen the metabolites in rat biological fluids after the oral administration of Xanthoceras sorbifolia Bunge husks. Mass defect filtering, product ion filtering, and neutral loss filtering were applied to detect metabolites from the complex matrix. As a result, 55 metabolites were tentatively identified, among which 45 barrigenol-type triterpenoid metabolites were detected in the feces, and six flavonoids and four coumarins metabolites were in the urine. Moreover, eight prototype constituents in plasma, 36 in urine and 23 in feces were also discovered. Due to the poor bioavailability of barrigenol type triterpenoids, most of them were metabolized by intestinal flora. Phase I metabolic reactions such as deglycosylation, oxidation, demethylation, dehydrogenation, and internal hydrolysis were supposed to be their principal metabolic pathways. Coumarins were found in all the biosamples, whereas flavonoids were mainly in the urine. Unlike the saponins, they were mainly metabolized through phase II metabolic reactions like glucuronidation and sulfonation, which made them eliminated more easily by urine. This work suggested the metabolic profile of X. sorbifolia husks for the first time, which will be very valuable for its further development.

Metabolomics Strategy Using High Resolution Mass Spectrometry Reveals Novel Biomarkers and Pain-Relief Effect of Traditional Chinese Medicine Prescription Wu-Zhu-Yu Decoction Acting on Headache Modelling Rats.

Headache is a common episodic or chronic neurologic disorder. Treatment options and diagnosis are restricted by an incomplete understanding of disease pathology and the lack of diagnostic markers. Wu-Zhu-Yu decoction (WZYD), a traditional Chinese medicine (TCM) formula containing four TCM herbs, is commonly used in the treatment of headache in China. To deeply understand more about headache and investigate the pain-relief mechanism of WZYD, a comprehensive metabolomics study combined with multivariate data processing strategy was carried out. An LC-high resolution mass spectrometry-based metabolomics approach was applied to characterize metabolic biomarker candidates. Multiple pattern recognition including principal component analysis-discriminant analysis, partial least squares-discriminant analysis and hierarchical cluster analysis were used to determine groups and confirm important variables. A total of 17 potential biomarkers were characterized and related metabolic pathways were identified. The study demonstrated that the established metabolomics strategy is a powerful approach for investigating the mechanism of headache attack and WZYD. In addition, the approach may highlight biomarkers and metabolic pathways and can capture subtle metabolite changes from headache, which may lead to an improved mechanism understanding of central nervous system diseases and TCM treatment.

Qualitative screening of absorbed indoloquinazoline alkaloids and their metabolites in rat plasma after the oral administration of Wu-Zhu-Yu decoction by high-resolution mass spectrometry with multiple data mining algorithms.

A rapid and sensitive liquid chromatography with high-resolution mass spectrometry method with multiple data processing algorithms was developed and applied for the metabolite profiling of evodiamine and its analogous alkaloids in rat plasma after the administration of Wu-Zhu-Yu decoction. All samples were purified using hydrophilic-lipophilic balanced solid-phase extraction cartridges and analyzed by a Sciex TripleTOF 5600(+) mass spectrometer with a 35 min liquid chromatography gradient elution. High-resolution full-scan mass spectrometry and information-dependent acquisition tandem mass spectrometry data were analyzed using multiple data processing approaches. The results indicated that the detected eight prototype alkaloids could be metabolized to 58 metabolites through both phase I and phase II reactions. Oxidation was demonstrated to be the principle metabolic pathway of the parent compounds. The study contributes to the understanding of the absorption and metabolism of the alkaloids in Wu-Zhu-Yu decoction and provides a detailed analysis of scientific data.

Post pandemic fatigue: what are effective strategies?

Recurrent updates in non-pharmaceutical interventions (NPIs) aim to control successive waves of the coronavirus disease 2019 (COVID-19) but are often met with low adherence by the public. This study evaluated the effectiveness of gathering restrictions and quarantine policies based on a modified Susceptible-Exposed-Infectious-Hospitalized-Recovered (SEIHR) model by incorporating cross-boundary travellers with or without quarantine to study the transmission dynamics of COVID-19 with data spanning a nine-month period during 2020 in Hong Kong. The asymptotic stability of equilibria reveals that the model exhibits the phenomenon of backward bifurcation, which in this study is a co-existence between a stable disease-free equilibrium (DFE) and an endemic equilibrium (EE). Even if the basic reproduction number ([Formula: see text]) is less than unity, this disease cannot be eliminated. The effect of each parameter on the overall dynamics was assessed using Partial Rank Correlation Coefficients (PRCCs). Transmission rates (i.e., [Formula: see text] and [Formula: see text]), effective contact ratio [Formula: see text] between symptomatic individuals and quarantined people, and transfer rate [Formula: see text] related to infection during quarantine were identified to be the most sensitive parameters. The effective contact ratios between the infectors and susceptible individuals in late July were found to be over twice as high as that in March of 2020, reflecting pandemic fatigue and the potential existence of infection during quarantine.

Validation of posttraumatic stress disorder (PTSD) and complex PTSD in Chinese children as per the ICD-11 proposals using the International trauma questionnaire.

Background: Given that the validity of applying complex posttraumatic stress disorder (CPTSD) in nonclinical children remains unclear. Objectives: The current study aimed to explore the factor structure, discriminant validity, and risk factors of ICD-11 posttraumatic stress disorder (PTSD) and CPTSD using the International Trauma Questionnaire. Methods: A total of 3478 trauma-exposed Chinese children aged 9-12 years were included in this study. All participants were assessed for PTSD and CPTSD using the International Trauma Questionnaire (ITQ). Confirmatory factor analysis (CFA) was conducted to explore the factor structure of CPTSD in a sample of Chinese children. Latent class analysis (LCA) was employed to evaluate the discriminant validity of CPTSD symptoms. Multinomial logistic regression analyses determined associations between the different classes and traumatic events. Results: The CFA results showed that the first-order six-factor model was identified as the best-fitting model in Chinese children aged 9-12 years. Four different classes, CPTSD symptoms, PTSD symptoms, disturbances in self-organization (DSO) symptoms, and a low symptom class were found by LCA. Both prolonged interpersonal trauma and other types of trauma were risk factors for the CPTSD class and the PTSD class. Conclusions: The results of this study partially support the factorial validity and strongly support the discriminant validity of the ICD-11 proposals for PTSD and CPTSD in Chinese children, supporting the conceptualization of PTSD and CPTSD as sibling diagnoses based on the ICD-11. However, findings suggest the need for careful consideration of identified trauma types in the ICD-11 proposals.

Antecedentes: Dado que la validez de aplicar el diagnóstico de Trastorno de estrés postraumático complejo (TEPT-C) en población infantil no clínica es incierto.Objetivos: el presente estudio está dirigido a explorar la estructura de factores, validez de discriminación y factores de riesgo del TEPT y TEPT-C de la CIE-11 usando el Cuestionario Internacional de Trauma.Método: Un total de 3478 niños chinos expuestos a un evento traumático de 9 a 12 años de edad fueron incluidos en este estudio. Todos los participantes fueron evaluados para TEPT y TEPT-C usando el Cuestionario Internacional de Trauma (ITQ por sus siglas en inglés). Se realizó un análisis factorial confirmatorio (CFA por sus siglas en inglés) para explorar la estructura factorial del TEPT-C en una muestra de niños chinos. Se realizó un análisis de clases latentes (LCA) para evaluar la validez de discriminación de los síntomas de TEPT-C. Se realizó una regresión logística multinomial para determinar la asociación entre las diferentes clases y los eventos traumáticos.Resultados: Los resultados del CFA mostraron que el modelo de seis-factores de primer-orden fue identificado como el modelo más acertado en niños chinos de 9 a 12 años de edad. El LCA encontró cuatro clases diferentes, síntomas de TEPT-C, síntomas de TEPT, alteraciones en la auto-organización (DSO por sus siglas en inglés) y una clase de síntomas baja. Tanto el trauma interpersonal prolongado y otros tipos de trauma fueron factores de riesgo para las clases de TEPT y de TEPT-C.Conclusiones: Los resultados de este estudio apoyan parcialmente la validez factorial y apoyan contundentemente la validez discriminatoria de las propuestas del CIE-11 para TEPT y TEPT-C en niños chinos, apoyando la conceptualización del TEPT y el TEPT-C como diagnósticos hermanos basados en el CIE-11. Sin embargo, los hallazgos sugieren la necesidad de una consideración cuidadosa de los tipos de trauma identificados en las propuestas del CIE-11.

Spatial variations of soil phosphorus forms and the risks of phosphorus release in the water-level fluctuation zone in a tributary of the Three Gorges Reservoir.

The dynamics of soil phosphorus (P) in the water-level fluctuation zone (WLFZ) generally poses a great threat to the ecology of dam-formed reservoirs worldwide. Our study explored the spatial variations of soil P forms and the risks of P release in the WLFZ in a tributary of the Three Gorges Reservoir (TGR) in the upper reaches of the Yangtze River, China. Soil samples from multiple altitudes (145, 155 and 165 m) in the WLFZ, upland soils (175 m) as well as reservoir sediment samples were collected along seven transects in a tributary of the TGR (Pengxi River) in August 2016. Hedley's fractionation method was used to characterize the P forms, and the physical and chemical properties of the samples were determined. The distributions of the total P (TP) across the transects decreased in the order of sediments (675.9 ±â€¯124.8 mg/kg), upland soil (658.9 ±â€¯191.1 mg/kg), and WLFZ soil (613.9 ±â€¯100.7 mg/kg). Similar distributions of the bioavailable P (Bio-P) were observed. Longitudinally, the TP and Bio-P of the WLFZ soil gradually decreased from the estuary to the upstream of the tributary. The spatial variations of P in the WLFZ soil in the tributary of the TGR was influenced by the soil particle size distribution (PSD) that, in turn, was a result of joint effects of the anti-seasonal hydrological regime, rainfall erosion and mainstream backwater. Long-term flooding increased P release from soil and decreased the soil degree of P saturation (DPS) throughout the WLFZ, especially in the lower portion of the WLFZ. According to Water-P, molar Al:Fe ratio and DPS, the current risk of soil P release throughout the WLFZ are very low. Monitoring should be prioritized at an altitude of 165 m and in the estuary of the WLFZ considering the high DPS and/or low Al:Fe ratio in these areas.

Classic Prescription, Kai-Xin-San, Ameliorates Alzheimer's Disease as an Effective Multitarget Treatment: From Neurotransmitter to Protein Signaling Pathway.

Alzheimer's disease (AD) is a widespread neurodegenerative disease caused by complicated disease-causing factors. Unsatisfactorily, curative effects of approved anti-AD drugs were not good enough due to their actions on single-target, which led to desperate requirements for more effective drug therapies involved in multiple pathomechanisms of AD. The anti-AD effect with multiple action targets of Kai-Xin-San (KXS), a classic prescription initially recorded in Bei Ji Qian Jin Yao Fang and applied in the treatment of dementia for thousands of years, was deciphered with modern biological methods in our study. Aß 25-35 and D-gal-induced AD rats and Aß 25-35-induced PC12 cells were applied to establish AD models. KXS could significantly improve cognition impairment by decreasing neurotransmitter loss and enhancing the expression of PI3K/Akt. For the first time, KXS was confirmed to improve the expression of PI3K/Akt by neurotransmitter 5-HT. Thereinto, PI3K/Akt could further inhibit Tau hyperphosphorylation as well as the apoptosis induced by oxidative stress and neuroinflammation. Moreover, all above-mentioned effects were verified and blocked by PI3K inhibitor, LY294002, in Aß 25-35-induced PC12 cells, suggesting the precise regulative role of KXS in the PI3K/Akt pathway. The utilization and mechanism elaboration of KXS have been proposed and dissected in the combination of animal, molecular, and protein strategies. Our results demonstrated that KXS could ameliorate AD by regulating neurotransmitter and PI3K/Akt signal pathway as an effective multitarget treatment so that the potential value of this classic prescription could be explored from a novel perspective.

A time-of-flight mass spectrometry based strategy to fast screen triterpenoids in Xanthoceras sorbifolia Bunge husks for bioactive substances against Alzheimer's disease.

Xanthoceras sorbifolia Bunge is a folk medicine in China. Recently, the triterpenoids in its husks have attracted more and more attention for potential prevention against Alzheimer's disease. However, current studies on its bioactive substances were still insufficient. To reveal more bioactive substances, an efficient and practical strategy based on high resolution mass spectra coupled with multiple data mining techniques was developed to characterize the barrigenol type triterpenoids in the husks and dosed rat plasma. A total of 50 barrigenol type triterpenoids were identified in the husks, and 6 of these were detected in the rat plasma, which were regarded as bioactive candidates. To find the real bioactive substances, the neuroprotective effect of the candidates was further tested by calculating the PC12 cell viability against amyloid-ß-induced cytotoxicity. As a result, three out of the six candidates exhibited obvious neuroprotction against amyloid-ß-induced cytotoxicity on PC12 cells, indicating their potential to be bioactive substances against Alzheimer's disease. This study will be a valuable reference of the bioactive substances in Xanthoceras sorbifolia Bunge husks against Alzheimer's disease and the provided strategy can also be applied to the exploration of the effective constituents in other medicines.

Two novel dual GLP-1/GIP receptor agonists are neuroprotective in the MPTP mouse model of Parkinson's disease.

Type 2 diabetes mellitus (T2DM) is a risk factors for developing Parkinson's disease (PD). Insulin desensitization is observed in the brains of PD patients, which may be an underlying mechanism that promotes neurodegeneration. Incretin hormones are growth factors that can re-sensitize insulin signalling. We have previously shown that analogues of the incretins GLP-1 or GIP have neuroprotective effects in the MPTP mouse model of PD. Novel dual GLP-1/GIP receptor agonists have been developed as treatments for T2DM. We have tested 3 novel dual receptor agonists DA-JC1, DA-JC4 and DA-CH5 in comparison with the GLP-1 analogue liraglutide (all drugs at 25 nmol/kg ip once-daily for 6 days) in the MPTP mouse model of PD (4 × 25 mg/kg ip). In the Rotarod and grip strength assessment, DA-CH5 performed best in reversing the MPTP-induced motor impairment. Dopamine synthesis as indicated by levels of tyrosine hydroxylase was much reduced by MPTP in the substantia nigra and striatum, and DA-CH5 was the best drug to reverse this. Pro-inflammatory cytokines were best reduced by DA-CH5, while expression levels of the neuroprotective growth factor Glial-Derived Neurotrophic Factor (GDNF) was most increased by DA-JC4. Synapses were protected best by DA-JC4 and DA-CH5. Both DA-JC1 and liraglutide showed inferior effects. These results show that a combination of GLP-1 and GIP receptor activation is more efficient compared to single GLP-1 receptor activation. We conclude that dual agonists are a promising novel treatment for PD. The GLP-1 mimetic exendin-4 has previously shown disease modifying effects in two clinical trials in Parkinson patients.

Development of an ultra-fast liquid chromatography-tandem mass spectrometry method for simultaneous determination of seven flavonoids in rat plasma: Application to a comparative pharmacokinetic investigation of Ginkgo biloba extract and single pure ginkgo flavonoids after oral administration.

For deeper pharmacokinetic investigation and further curative application of ginkgo flavonoids, a delicate, efficient and precise UFLC-MS/MS technique for synchronous quantitation of seven flavonoids, apigenin, luteolin, naringenin, quercetin, diosmetin, kaempferol and isorhamnetin in rat plasma has been established. After mixing with the internal standard (IS) linarin, bio-samples were pretreated via ethyl acetate for liquid-liquid extraction, then isolated at 0.2ml/min flow rate on a Venusil MP C18 chromatographic column (100mm×2.1mm, 3µm) by means of gradient elution. 0.1% formic acid-water and methanol system was used as the mobile phase. Mass spectrometric inspection was conducted on a 4000Q UFLC-MS/MS system with turbo ion spray source in patterns of negative ion and multiple reaction-monitoring (MRM). All calibration curves proved favorable linearity (R2≥0.9918) in linear ranges. Intra-day and inter-day precisions didn't exceed 14.0% for all the analytes, and the accuracy was within 6.9%. Extraction recoveries of analytes and IS were less than ±15.0% of nominal concentrations. This method has been under thorough and firm verification for a comparative pharmacokinetic research after gavage between Ginkgo biloba extract and single pure ginkgo flavonoids. The results demonstrated that there're evident pharmacokinetic discrepancies, and possible structural influences were innovatively proposed. Generally, substitution with 3-hydroxylation, a double bond in ring C, ring B methoxylation often confer longer onset period. The existence of ring B catechol group gives rise to faster clearance.

A novel GLP-1/GIP dual agonist is more effective than liraglutide in reducing inflammation and enhancing GDNF release in the MPTP mouse model of Parkinson's disease.

Type 2 diabetes mellitus (T2DM) is one of the risk factors for Parkinson's disease (PD). Insulin desensitisation has been observed in the brains of patients, which may promote neurodegeneration. Incretins are a family of growth factors that can re-sensitise insulin signalling. We have previously shown that mimetics of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP) mouse model of PD. Recently, dual GLP-1/GIP receptor agonists have been developed. We therefore tested the novel dual agonist DA3-CH in comparison with the best GLP-1 analogue currently on the market, liraglutide (both drugs 25nmol/kg ip once-daily for 7 days) in the MPTP mouse model of PD (25mg/kg ip once-daily for 7 days). In the Rotarod and grip strength assessment, DA3-CH was superior to liraglutide in reversing the MPTP-induced motor impairment. Dopamine synthesis as indicated by levels of tyrosine hydroxylase was much reduced by MPTP in the substantia nigra and striatum, and DA3-CH reversed this while liragutide only partially reversed this. The chronic inflammation response as shown in increased levels of activated microglia and astrocytes was reduced by both drugs. Importantly, expression levels of the neuroprotective growth factor Glial Derived Neurotrophic Factor (GDNF) was much enhanced by both DA3-CH and liragutide. The results demonstrate that the combination of GLP-1 and GIP receptor activation is superior to single GLP-1 receptor activation alone. Therefore, new dual agonists may be a promising treatment for PD. The GLP-1 receptor agonist exendin-4 has already shown disease modifying effects in clinical trials in PD patients.