Dispel some mist on circulating biopterins: measurement, physiological interval and pathophysiological implication.

BACKGROUND AND AIMS: Biopterins, including tetrahydrobiopterin (BH4), dihydrobiopterin (BH2), and biopterin (B), were crucial enzyme cofactors in vivo. Despite their recognized clinical significance, there remain notable research gaps and controversies surrounding experimental outcomes. This study aims to clarify the biopterins-related issues, including analytical art, physiological intervals, and pathophysiological implications. MATERIALS AND METHODS: A novel LC-MS/MS method was developed to comprehensively profile biopterins in plasma, utilizing chemical derivatization and cold-induced phase separation. Subsequently, apparently healthy individuals were enrolled to investigate the physiological ranges. And the relationships between biopterins and biochemical indicators were analyzed to explore the pathophysiological implications. RESULTS: The developed method was validated as reliable for detecting biopterins across the entire physiological range. Timely anti-oxidation was found to be essential for accurate assessment of biopterins. The observed overall mean ± SDs levels were 3.51 ± 0.94, 1.54 ± 0.48, 2.45 ± 0.84 and 5.05 ± 1.14 ng/mL for BH4, BH2, BH4/BH2 and total biopterins. The status of biopterins showed interesting correlations with age, gender, hyperuricemia and overweight. CONCLUSION: In conjunction with proper anti-oxidation, the newly developed method enables accurate determination of biopterins status in plasma. The observed physiological intervals and pathophysiological implications provide fundamental yet inspiring support for further clinical researches.

Ultrasonic aerosol agglomeration: Manipulation of particle deposition and its impact on air filter pressure drop.

Acoustic agglomeration is a technique that leverages on sound waves to promote the collision of aerosol particulate matter, thus leading to the formation of larger particle agglomerates. In this study, this acoustics-driven phenomenon is demonstrated for its usefulness as an aerosol pre-conditioning method to significantly enhance the efficiency of filtration systems in particle treatment processes. Specifically, favorable changes in pressure drop across the filters are observed as a result of receiving less particle mass, for which filters are shown to be able to have their operational life extended remarkably by more than 50%. The involved ultrasonic aerosol agglomeration mechanisms are unveiled through numerical simulations, and the effects of residence time, sound pressure level, and initial particle number concentration on agglomeration performances are experimentally investigated. In addition, validations and measurements of filter pressure drop are obtained through a series of experiments. This study provides a comprehensive overview to the design and performance characterization of acoustics-agglomeration-enhanced filtration systems, which could potentially derive energy savings for fan power in ventilation systems and be scaled up for applications in industrial plants for reducing carbon emissions.

Ultrahigh Passive Cooling Power in Hydrogel with Rationally Designed Optofluidic Properties.

The cooling power of a radiative cooler is more than halved in the tropics, e.g., Singapore, because of its harsh weather conditions including high humidity (84% on average), strong downward atmospheric radiation (∼40% higher than elsewhere), abundant rainfall, and intense solar radiation (up to 1200 W/m2 with ∼58% higher UV irradiation). So far, there has been no report of daytime radiative cooling that well achieves effective subambient cooling. Herein, through integrated passive cooling strategies in a hydrogel with desirable optofluidic properties, we demonstrate stable subambient (4-8 °C) cooling even under the strongest solar radiation in Singapore. The integrated passive cooler achieves an ultrahigh cooling power of ∼350 W/m2, 6-10 times higher than a radiative cooler in a tropical climate. An in situ study of radiative cooling with various hydration levels and ambient humidity is conducted to understand the interaction between radiation and evaporative cooling. This work provides insights for the design of an integrated cooler for various climates.

An RNA-Scaffold Protein Subunit Vaccine for Nasal Immunization.

Developing recombinant proteins as nasal vaccines for inducing systemic and mucosal immunity against respiratory viruses is promising. However, additional adjuvants are required to overcome the low immunogenicity of protein antigens. Here, a self-adjuvanted protein-RNA ribonucleoprotein vaccine was developed and found to be an effective nasal vaccine in mice and the SARS-CoV-2 infection model. The vaccine consisted of spike RBD (as an antigen), nucleoprotein (as an adaptor), and ssRNA (as an adjuvant and RNA scaffold). This combination robustly induced mucosal IgA, neutralizing antibodies and activated multifunctional T-cells, while also providing sterilizing immunity against live virus challenge. In addition, high-resolution scRNA-seq analysis highlighted airway-resident immune cells profile during prime-boost immunization. The vaccine also possesses modularity (antigen/adaptor/RNA scaffold) and can be made to target other viruses. This protein-RNA ribonucleoprotein vaccine is a novel and promising approach for developing safe and potent nasal vaccines to combat respiratory virus infections.

An interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models.

A pan-sarbecovirus or pan-betacoronavirus vaccine that can prevent current and potential future beta-coronavirus infections is important for fighting possible future pandemics. Here, we report a mucosal vaccine that cross-protects small animal models from sarbecoviruses including SARS-CoV-1, SARS-CoV-2 and its variants. The vaccine comprises a live-but-defective SARS-CoV-2 virus that is envelope deficient and has the orf8 segment replaced by interferon-beta, hence named Interferon Beta Integrated SARS-CoV-2 (IBIS) vaccine. Nasal vaccination with IBIS protected mice from lethal homotypic SARS-CoV-2 infection and hamsters from co-housing-mediated transmission of homotypic virus. Moreover, IBIS provided complete protection against heterotypic sarbecoviruses, including SARS-CoV-2 Delta and Omicron variants, and SARS-CoV-1 in both mice and hamsters. Besides inducing a strong lung CD8 + T cell response, IBIS specifically heightened the activation of mucosal virus-specific CD4 + T cells compared to the interferon-null vaccine. The direct production of interferon by IBIS also suppressed virus co-infection of SARS-CoV-2 in human cells, reducing the risk of genetic recombination when using as live vaccines. Altogether, IBIS is a next-generation pan-sarbecovirus vaccine and warrants further clinical investigations.

Experimental study on the impact of indoor air quality on creativity by Serious Brick Play method.

Companies are increasingly asking their employees to find creative solutions to their problems. However, the office environment may reduce an employee's creative potential. In this study, the role of indoor air quality parameters (PM2.5, TVOC, and CO2) in maintaining a creative environment (involving lateral thinking ability) was evaluated by Serious Brick Play (SBP), an adaptation of the LEGO Serious Play (LSP) framework. This study was conducted in a simulated office space with 92 participants over a period of 6 weeks. The SBP required participants to address a challenge by building using Lego bricks, and then describe the solution within a given timeframe. The creations and descriptions were then graded in terms of originality, fluency, and build. The results indicated that higher TVOC levels were significantly associated with lower-rated creative solutions. A 71.9% reduction in TVOC (from 1000 ppb), improves an individual's full creative potential by 11.5%. Thus, maintaining a low TVOC level will critically enhance creativity in offices.

Sub-hourly measurement datasets from 6 real buildings: Energy use and indoor climate.

The data presented here were collected independently for 6 real buildings by researchers of different institutions and gathered in the context of the IEA EBC Annex 81 Data-driven Smart Buildings, as a joint effort to compile a diverse range of datasets suitable for advanced control applications of indoor climate and energy use in buildings. The data were acquired by energy meters, both consumption and PV generation, and sensors of technical installation and indoor climate variables, such as temperature, flow rate, relative humidity, CO2 level, illuminance. Weather variables were either acquired by local sensors or obtained from a close by meteorological station. The data were collected either during normal operation of the building, with observation periods between 2 weeks and 2 months, or during experiments designed to excite the thermal mass of the building, with observation periods of approximately one week. The data have a time resolution varying between 1 min and 15 min; in some case the highest resolution data are also averaged at larger intervals, up to 30 min.

Five-year cardiovascular event risk in early rheumatoid arthritis patients who received treat-to-target management: a case-control study.

OBJECTIVES: This study explored whether the excess cardiovascular (CV) disease (CVD) risk in RA could be ameliorated by suppression of inflammation using a treat-to-target (T2T) approach. We compared the CV event (CVE) incidence among ERA patients managed by a T2T strategy with a CV risk factor-matched non-RA population and a historical RA cohort (HRA). METHODS: This was an observational study using the city-wide hospital data and the ERA registry. ERA patients received T2T management while HRA patients received routine care. Each ERA/HRA patient was matched to three non-RA controls according to age, gender and CV risk factors. Patients on antiplatelet/anticoagulant agents, with pre-existing CVD, chronic kidney disease or other autoimmune diseases were excluded. All subjects were followed for up to 5 years. The primary end point was the first occurrence of a CVE. RESULTS: The incidence of CVE in the ERA cohort (n = 261) and ERA controls were similar with a hazard ratio of 0.53 (95% CI 0.15, 1.79). In contrast, the incidence of CVE in the HRA cohort (n = 268) was significantly higher than that of the HRA controls with a hazard ratio of 1.9 (95% CI 1.16, 3.13). The incidence of CVE in the ERA cohort was significantly lower than that of the HRA cohort and the difference became insignificant after adjusting for inflammation, the use of methotrexate and traditional CV risk factors. CONCLUSION: ERA patients managed by a T2T strategy did not develop excess CVE compared with CV risk factor-matched controls over 5 years.

Diurnal trends of indoor and outdoor fluorescent biological aerosol particles in a tropical urban area.

We evaluated diurnal trends of size-resolved indoor and outdoor fluorescent biological airborne particles (FBAPs) and their contributions to particulate matter (PM) within 0.5-20 µm. After a ten-week continuous sampling via two identical wideband integrated bioaerosol sensors, we found that both indoor and outdoor diurnal trends of PM were driven by its bioaerosol component. Outdoors, the median [interquartile range] FBAP mass concentration peaked at 8.2 [5.8-9.9] µg/m3 around sunrise and showed a downtrend from 6:00 to 18:00 during the daytime and an uptrend during the night. The nighttime FBAP level was 1.8 [1.4-2.2] times higher than that during the daytime, and FBAPs accounted for 45 % and 56 % of PM during daytime and nighttime, respectively. Indoors, the rise in concentrations of FBAPs smaller than 1 µm coincided with the starting operation of the heating, ventilation, and air conditioning (HVAC) system at 6:00, and the concentration peaked at 8:00 and dropped to the daily average by noontime. This indicated that the starting operation of the HVAC system dislodged the overnight settled and accumulated fine bioaerosols into the indoor environment. For particles larger than 1 µm, the variation of mass concentration was driven by occupancy. Based on regression modeling, the contributions of indoor PM, non-FBAP, and FBAP sources to indoor mass concentrations were estimated to be 93 %, 67 %, and 97 % during the occupied period.

A nasal omicron vaccine booster elicits potent neutralizing antibody response against emerging SARS-CoV-2 variants.

SARS-CoV-2 has caused the COVID-19 pandemic since early 2020. As of January 2022, the worldwide spreading of SARS-CoV-2 leads to approximately 0.35 billion of human infections and five millions of deaths. Current vaccination is one of the effective ways to control SARS-CoV-2 transmission and reduce the disease severity. However, the antibody level against the immunogen significantly drops several months after the standard two-dose vaccination, and hence a third or fourth dose booster (the same immunogen) has been suggested to boost the antibody response. Here, we described an ultra-effective nasal vaccine booster that potently induced the extraordinary high-level of neutralizing antibody in pre-vaccinated mice. The vaccine booster is composed of a recombinant receptor binding domain of SARS-CoV-2 spike (either wild-type or omicron) fused with a domain of SARS-CoV-2 nucleoprotein. In the absence of adjuvants, a single intranasal administration of the booster in pre-vaccinated mice significantly induced systemic and mucosal antibody responses as evidenced by the elevation of the cross-variant neutralizing antibody and induction of IgA in bronchoalveolar lavage respectively. Most importantly, the single dose nasal vaccine booster (omicron version) potently enhanced the neutralizing activity against authentic SARS-CoV-2 omicron virus infection. Taken together, the induction of respiratory mucosal immunity and the enhancement of cross-variant neutralizing activity by the nasal vaccine booster warrants further clinical trials in humans.

The effects of not having continuous companion support during labour on pregnancy and neonatal outcomes during the COVID-19 pandemic.

OBJECTIVE: With the surge of confirmed cases of coronavirus disease 2019 (COVID-19) and its associated morbidities and mortalities, continuous companion support during labour was halted in all public hospitals in Hong Kong to prevent the spread of the virus in hospitals. The purpose of this retrospective study was to evaluate the effect of not having continuous companion support during labour on pregnancy and neonatal outcomes during the COVID-19 pandemic period in a regional hospital. STUDY DESIGN: We retrieved information on women without continuous companion support during the COVID-19 pandemic period from February 1, 2020 to May 15, 2020 and those with continuous companion support within the same period in 2019 in Queen Mary Hospital, Hong Kong. The pregnancy and neonatal outcomes were compared between the two groups. RESULTS: A total of 446 women with continuous companion support in 2019 and 340 women without continuous companion support in 2020 were included in the analysis. The rate of labour augmentation was significantly lower in women with continuous companion support than in those without continuous companion support (3.1% vs. 6.5%, respectively, p = 0.027). Babies born to women with continuous companion support were less likely to have Apgar scores <7 at 1 min than those born to women without continuous companion support (2.5% vs. 5.3%, respectively, p = 0.036). More women with continuous companion support had breastfeeding at the first hour of delivery than those without (86.3% vs. 80.6%, respectively, p = 0.030). There were no differences in other pregnancy and neonatal outcomes. The subgroup analysis with only Chinese women showed that the pregnancy and neonatal outcomes were not significantly different between the two groups. CONCLUSION: Women without continuous companion support during labour had an increased chance of labour augmentation and babies with an Apgar score <7 at 1 min, and a reduced immediate breastfeeding rate when compared with those with continuous companion support.

Intravenous Injection of Coronavirus Disease 2019 (COVID-19) mRNA Vaccine Can Induce Acute Myopericarditis in Mouse Model.

BACKGROUND: Post-vaccination myopericarditis is reported after immunization with coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines. The effect of inadvertent intravenous injection of this vaccine on the heart is unknown. METHODS: We compared the clinical manifestations, histopathological changes, tissue mRNA expression, and serum levels of cytokine/chemokine and troponin in Balb/c mice at different time points after intravenous (IV) or intramuscular (IM) vaccine injection with normal saline (NS) control. RESULTS: Although significant weight loss and higher serum cytokine/chemokine levels were found in IM group at 1-2 days post-injection (dpi), only IV group developed histopathological changes of myopericarditis as evidenced by cardiomyocyte degeneration, apoptosis, and necrosis with adjacent inflammatory cell infiltration and calcific deposits on visceral pericardium, although evidence of coronary artery or other cardiac pathologies was absent. Serum troponin level was significantly higher in IV group. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antigen expression by immunostaining was occasionally found in infiltrating immune cells of the heart or injection site, in cardiomyocytes and intracardiac vascular endothelial cells, but not skeletal myocytes. The histological changes of myopericarditis after the first IV-priming dose persisted for 2 weeks and were markedly aggravated by a second IM- or IV-booster dose. Cardiac tissue mRNA expression of interleukin (IL)-1ß, interferon (IFN)-ß, IL-6, and tumor necrosis factor (TNF)-α increased significantly from 1 dpi to 2 dpi in the IV group but not the IM group, compatible with presence of myopericarditis in the IV group. Ballooning degeneration of hepatocytes was consistently found in the IV group. All other organs appeared normal. CONCLUSIONS: This study provided in vivo evidence that inadvertent intravenous injection of COVID-19 mRNA vaccines may induce myopericarditis. Brief withdrawal of syringe plunger to exclude blood aspiration may be one possible way to reduce such risk.

COVID-19 related fear and depression of pregnant women and new mothers.

OBJECTIVE: To explore factors associated with depression and COVID-19 related fear among pregnant women and new mothers. DESIGN: A cross-sectional survey was conducted in China from July 2020 to July 2021. SAMPLE: A total of 3027 pregnant and new mothers were recruited. MEASUREMENT: Sociodemographic characteristics and the perceptions of the COVID-19 pandemic were collected. The Patient Health Questionnaire-9 (PHQ-9) and the Fear Scale was used to assess the depressive and fear level towards the COVID-19 pandemic, respectively. RESULTS: Approximately 17.2% of the participants had depression (PHQ-9 ≥10). In Hong Kong, participants who perceived that they have increased knowledge to prevent infection were less likely to have depression (adjusted odds ratio [aOR] = 0.83; 95% confidence interval [CI] = 0.74-0.94). There was no association between perceived severity if infected and severity of spread and the depression level in our sample. An inverse relationship was found between the COVID-19 related fear level and perceived knowledge to prevent infection (Beta-coefficient [ß] = -0.20; 95% CI = -0.38 to -0.02). CONCLUSION: Public health nurses need to promote accurate and up to date COVID-19 related information at clinical and community settings and implement effective screening for depression and fear symptoms to identify these high-risk groups to improve women's psychological well-being.

Aerosols from speaking can linger in the air for up to nine hours.

Airborne transmission of respiratory diseases has been under intense spotlight in the context of coronavirus disease 2019 (COVID-19) where continued resurgence is linked to the relaxation of social interaction measures. To understand the role of speech aerosols in the spread of COVID-19 globally, the lifetime and size distribution of the aerosols are studied through a combination of light scattering observation and aerosol sampling. It was found that aerosols from speaking suspended in stagnant air for up to 9 h with a half-life of 87.2 min. The half-life of the aerosols declined with the increase in air change per hour from 28 to 40 min (1 h-1), 10-14 min (4 h-1), to 4-6 min (9 h-1). The speech aerosols in the size range of about 0.3-2 µm (after dehydration) witnessed the longest lifetime compared to larger aerosols (2-10 µm). These results suggest that speech aerosols have the potential to transmit respiratory viruses across long duration (hours), and long-distance (over social distance) through the airborne route. These findings are important for researchers and engineers to simulate the airborne dispersion of viruses in indoor environments and to design new ventilation systems in the future.

International survey on fear and childbirth experience in pregnancy and the postpartum period during the COVID-19 pandemic: study protocol.

INTRODUCTION: The COVID-19 pandemic has caused unprecedented disruptions around the world. Adding to the existing stress surrounding pregnancy and childbirth, the threat of infection and social isolation policies may negatively impact pregnant women and new mothers. Literature on the effect of COVID-19 on fear during pregnancy and childbirth experience is limited. As the COVID-19 pandemic continues to affect the global population, it is important to understand how it has impacted pregnant women and new mothers' experiences worldwide to inform perinatal care and interventions. METHODS AND ANALYSIS: This multicountry study involving China and Canada targets to recruit 1000 pregnant women and new mothers who gave birth since 2020 in each participating country. Participants will be recruited online in the local language through mothers' groups, antenatal and postnatal clinics and hospital wards. All questionnaires will be completed online. Participants' level of fear, depression and childbirth experience will be assessed along with other sociodemographic, medical and COVID-related measures. Regression models will be used to compare the outcomes among the participating countries. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the institutional review boards of the participating countries. Findings will be disseminated in peer-reviewed journals and academic conferences. Results from this study may guide the formulation of future health guidelines and policies in the face of a pandemic.

Accurate measurement of colorectal polyps using computer-aided analysis.

INTRODUCTION: As we know, the majority of colorectal cancers are thought to evolve from colorectal adenomas. In this study, we explored the use of Computer-aided diagnosis (CAD) in the detection of colorectal polyps and the estimation of their sizes, which is important for the diagnosis and management of colorectal cancer. MATERIALS AND METHODS: As the distance between colonoscopy and lesion increases, magnification tends to decrease. Therefore, the size of colorectal polyps can be calculated by taking into account the captured image and the shooting distance. In this study, the fitting curve of the magnification of electronic colonoscopy was obtained by simulating intestinal tract and polyps in vitro. Then, the distance was artificially controlled in the endoscopic operation, and the image was taken at a preset distance. The CAD system was then trained on the overall shape of colorectal polyps. Image segmentation was employed to accurately identify colorectal polyps. Finally, on the basis of the magnification factor, the real value of polyps was predicted from the shooting distance and the segmentation image size. RESULTS: The CAD system can automatically calculate the range of colorectal polyps and calculate the true size of the colorectal polyps according to the magnification of the corresponding distance. CONCLUSIONS: In this study, we developed a method of accurately estimating the size of colorectal polyps. This approach is compatible with many devices, which would expand its range of applications. This method has the potential for application in other areas of clinical diagnosis.