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.

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.

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.

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.

Suppression of SARS-CoV-2 infection in ex-vivo human lung tissues by targeting class III phosphoinositide 3-kinase.

The novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and caused the coronavirus disease 19 (COVID-19) pandemic due to its high transmissibility and early immunosuppression. Previous studies on other betacoronaviruses suggested that betacoronavirus infection is associated with the host autophagy pathway. However, it is unclear whether any components of autophagy or virophagy can be therapeutic targets for COVID-19 treatment. In this report, we examined the antiviral effect of four well-characterized small molecule inhibitors that target the key cellular factors involved in key steps of the autophagy pathway. They include small molecules targeting the ULK1/Atg1 complex involved in the induction stage of autophagy (ULK1 inhibitor SBI0206965), the ATG14/Beclin1/VPS34 complex involved in the nucleation step of autophagy (class III PI3-kinase inhibitor VPS34-IN1), and a widely-used autophagy inhibitor that persistently inhibits class I and temporary inhibits class III PI3-kinase (3-MA) and a clinically approved autophagy inhibitor that suppresses autophagy by inhibiting lysosomal acidification and prevents the formation of autophagolysosome (HCQ). Surprisingly, not all the tested autophagy inhibitors suppressed SARS-CoV-2 infection. We showed that inhibition of class III PI3-kinase involved in the initiation step of both canonical and noncanonical autophagy potently suppressed SARS-CoV-2 at a nano-molar level. In addition, this specific kinase inhibitor VPS34-IN1, and its bioavailable analogue VVPS34-IN1, potently inhibited SARS-CoV-2 infection in ex vivo human lung tissues. Taken together, class III PI3-kinase may be a possible target for COVID-19 therapeutic development.

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.

Dynamic Analysis of Particle Emissions from FDM 3D Printers through a Comparative Study of Chamber and Flow Tunnel Measurements.

Ultrafine particle emissions originating from fused deposition modeling (FDM) three-dimensional (3D) printers have received widespread attention recently. However, the obvious inconsistency and uncertainty in particle emission rates (PERs, #/min) measured by chamber systems still remain, owing to different measurement conditions and calculation models used. Here, a dynamic analysis of the size-resolved PER is conducted through a comparative study of chamber and flow tunnel measurements. Two models to resolve PER from the chamber and a model for flow tunnel measurements were examined. It was found that chamber measurements for different materials underestimated PER by up to an order of magnitude and overestimated particle diameters by up to 2.3 times, while the flow tunnel measurements provided more accurate results. Field measurements of the time-resolved particle size distribution (PSD) in a typical room environment could be predicted well by the flow tunnel measurements, while the chamber measurements could not represent the main PSD characteristics (e.g., particle diameter mode). Secondary aerosols (>30 nm) formed in chambers were not observed in field measurements. Flow tunnel measurements were adopted for the first time as a possible alternative for the study of 3D printer emissions to overcome the disadvantages in chamber methods and as a means to predict exposure levels.

Size-resolved dynamics of indoor and outdoor fluorescent biological aerosol particles in a bedroom: A one-month case study in Singapore.

This study evaluated the interrelations between indoor and outdoor bioaerosols in a bedroom under a living condition. Two wideband integrated bioaerosol sensors were utilized to measure indoor and outdoor particulate matter (PM) and fluorescent biological airborne particles (FBAPs), which were within a size range of 0.5-20 µm. Throughout this one-month case study, the median proportion of FBAPs in PM by number was 19% (5%; the interquartile range, hereafter) and 17% (3%) for indoors and outdoors, respectively, and those by mass were 78% (12%) and 55% (9%). According to the size-resolved data, FBAPs dominated above 2 and 3.5 µm indoors and outdoors, respectively. Comparing indoor upon outdoor ratios among occupancy and window conditions, the indoor FBAPs larger than 3.16 µm were dominated by indoor sources, while non-FBAPs were mainly from outdoors. The occupant dominated the indoor source of both FBAPs and non-FBAPs. Under awake and asleep, count- and mass-based mean emission rates were 45.9 and 18.7 × 106 #/h and 5.02 and 2.83 mg/h, respectively. Based on indoor activities and local outdoor air quality in Singapore, this study recommended opening the window when awake and closing it during sleep to lower indoor bioaerosol exposure.

The validity, reliability and clinical utility of a performance-based executive function assessment in people with mild to moderate dementia.

Objective: Performance-based evaluation of executive function by using real-world daily living activities is an important area of study. This approach has been used extensively in evaluating patients after stroke or traumatic brain injury and patients with schizophrenia. Most important is the fact that until now, there has been no validated performance-based evaluation of executive function in people with dementia.Methods: To address that knowledge gap, this study recruited 80 patients diagnosed with dementia and 80 demographically matched healthy controls. The participants were administered tests for evaluating their performance-based executive function (Chinese Multiple Errands Test), their instrumental activities of daily living (Lawton Instrumental Activities of Daily Living Scale, Chinese Version), and their functional disability (Chinese Version of the Disability Assessment for Dementia), along with a cognitive screening test (Montreal Cognitive Assessment, Hong Kong Version) and a neuropsychological test of executive function (Trail-making Test).Results: The Chinese Multiple Errands Test demonstrated excellent inter-rater reliability, test-retest reliability and high internal consistency. Results revealed that the healthy controls out-performed the dementia patients in the performance-based executive function and cognitive screening, but not in the instrumental activities of daily living tests. Additionally, the performance efficiency scores of the older adults with dementia on the Chinese Multiple Errands Test correlated significantly with their performance results on the neuropsychological test of executive function and on the tests of functional disability and cognitive function.Conclusion: Our results indicated that the Chinese Multiple Errands Test is a reliable and valid instrument for assessing executive function in Chinese older people with dementia.

Gestational weight gain and risk of autism spectrum disorders in offspring: a systematic review and meta-analysis.

It has been revealed that gestational weight gain (GWG) influences the risk of autism spectrum disorder (ASD) in the offspring, but the findings are inconsistent. The current study aimed to evaluate the relationship between GWG and risk of ASD in offspring. Four electronic databases were searched up to August 28 2018 to identify observational studies reporting the association between GWG and risk of ASD in the offspring. Nine studies which met the inclusion criteria were included in the systematic review. Finally, five studies with a total of 3793 children with ASD were included in the meta-analysis. The-results indicated that excessive GWG might increase the risk of ASD in offspring (p = .0008, OR = 1.23, 95% confidence interval (CI) 1.09-1.38). More high quality cohort studies are needed to confirm this result. This research has the potential to inspire new research on ASD and promote efforts to design appropriate interventions against excessive GWG.Impact statementWhat is already known on this subject? It has been revealed that gestational weight gain (GWG) influences the risk of autism spectrum disorder (ASD) in the offspring, but the findings are inconsistent.What the results of this study add? This is the first systematic review and meta-analysis on the association between GWG and ASDs in offspring. This study suggested that excessive GWG was associated with higher risk of ASD in offspring.What the implications are of these findings for clinical practice and/or further research? More high quality cohort studies are needed to confirm this result. This research has the potential to inspire new research on ASD and promote efforts to design appropriate interventions against excessive GWG.

Clinical presentation, treatment and outcome of Takayasu's arteritis in southern Chinese: a multicenter retrospective study.

To study the clinical presentation, treatment and outcome of southern Chinese patients with Takayasu's arteritis (TA). This is a retrospective chart review study of 78 patients managed in 14 public hospitals in Hong Kong between the years 2000 and 2010. Patients were identified from the hospital registry using the ICD-10 diagnostic code of the disease. The classification of TA was based on the American College of Rheumatology (ACR) or modified Ichikawa's criteria. Demographic data, clinical presentation, angiographic findings, pattern of vascular involvement (Numano's classification), treatment and outcome of these patients were presented. 78 patients were studied (82% women, age at presentation 34.2 ± 14 years). The estimated point prevalence of TA was 11/million population. The commonest initial manifestations were hypertension (62%) and vascular ischemic symptoms (38%). Systemic symptoms occurred in nine (12%) patients only. The proportion of patients fulfilling the angiographic subtypes of the Numano's classification was: types I (13%), IIa (4%), IIb (12%), III (12%), IV (20%) and V (39%), respectively. Thirty-two patients (41%) were treated with high-dose glucocorticoids (GCs) and 22 patients (28%) received additional non-GC immunosuppressive drugs. Vascular complications occurred in 26 (33%) patients and revascularization surgery was performed in 23(29%) patients. Three (4%) patients died of vascular complication at a median of 8 years after disease onset. TA is rare in southern Chinese patients of Hong Kong. Most patients present with ischemic symptoms during the stenotic phase of the disease. Although mortality is low, a significant proportion of patients developed vascular stenosis that required surgical interventions. More awareness of TA as a differential diagnosis of non-specific systemic symptoms with elevated inflammatory markers in younger patients is needed for earlier diagnosis.

Leukotriene signaling via ALOX5 and cysteinyl leukotriene receptor 1 is dispensable for in vitro growth of CD34+CD38- stem and progenitor cells in chronic myeloid leukemia.

Tyrosine kinase inhibitors targeting the BCR-ABL oncoprotein in chronic myeloid leukemia (CML) are remarkably effective inducing deep molecular remission in most patients. However, they are less effective to eradicate the leukemic stem cells (LSC), resulting in disease persistence. Therefore, there is great need to develop novel therapeutic strategies to specifically target the LSC. In an experimental mouse CML model system, the leukotriene pathway, and specifically, the expression ALOX5, encoding 5-lipoxygenase (5-LO), has been reported as a critical regulator of the LSC. Based on these results, the 5-LO inhibitor zileuton has been introduced in clinical trials as a therapeutic option to target the LSC although its effect on primary human CML LSC has not been studied. We have here by using multiplex single cell PCR analyzed the expression of the mediators of the leukotriene pathway in bone marrow (BM) BCR-ABL+CD34+CD38- cells at diagnosis, and found low or undetectable expression of ALOX5. In line with this, zileuton did not exert significant overall growth inhibition in the long-term culture-initiating cell (LTC-IC) and colony (CFU-C) assays of BM CD34+CD38- cells from 7 CML patients. The majority of the single leukemic BCR-ABL+CD34+CD38- cells expressed cysteinyl leukotriene receptors CYSLT1 and CYSLT2. However, montelukast, an inhibitor of CYSLT1, also failed to significantly suppress CFU-C and LTC-IC growth. These findings indicate that targeting ALOX5 or CYSLT1 signaling with leukotriene antagonists, introduced into the clinical practice primarily as prophylaxis and treatment for asthma, may not be a promising pharmacological strategy to eradicate persisting LSC in CML patients.

Suppression of Type I Interferon Production by Human T-Cell Leukemia Virus Type 1 Oncoprotein Tax through Inhibition of IRF3 Phosphorylation.

UNLABELLED: Infection with human T-cell leukemia virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and tropical spastic paraparesis. Type I interferons (IFNs) are key effectors of the innate antiviral response, and IFN-α combined with the nucleoside reverse transcriptase inhibitor zidovudine is considered the standard first-line therapy for ATL. HTLV-1 oncoprotein Tax is known to suppress innate IFN production and response but the underlying mechanisms remain to be fully established. In this study, we report on the suppression of type I IFN production by HTLV-1 Tax through interaction with and inhibition of TBK1 kinase that phosphorylates IRF3. Induced transcription of IFN-ß was severely impaired in HTLV-1-transformed ATL cells and freshly infected T lymphocytes. The ability to suppress IRF3 activation was ascribed to Tax. The expression of Tax alone sufficiently repressed the induction of IFN production by RIG-I plus PACT, cGAMP synthase plus STING, TBK1, IKKε, IRF3, and IRF7, but not by IRF3-5D, a dominant-active phosphomimetic mutant. This suggests that Tax perturbs IFN production at the step of IRF3 phosphorylation. Tax mutants deficient for CREB or NF-κB activation were fully competent in the suppression of IFN production. Coimmunoprecipitation experiments confirmed the association of Tax with TBK1, IKKε, STING, and IRF3.In vitrokinase assay indicated an inhibitory effect of Tax on TBK1-mediated phosphorylation of IRF3. Taken together, our findings suggested a new mechanism by which HTLV-1 oncoprotein Tax circumvents the production of type I IFNs in infected cells. Our findings have implications in therapeutic intervention of ATL. IMPORTANCE: Human T-cell leukemia virus type 1 (HTLV-1) is the cause of adult T-cell leukemia (ATL), an aggressive and fatal blood cancer, as well as another chronic disabling disease of the spinal cord. Treatments are unsatisfactory, and options are limited. A combination of antiviral cellular protein alpha interferon and zidovudine, which is an inhibitor of a viral enzyme called reverse transcriptase, has been recommended as the standard first-line therapy for ATL. Exactly how HTLV-1 interacts with the cellular machinery for interferon production and action is not well understood. Our work sheds light on the mechanism of action for the inhibition of interferon production by an HTLV-1 oncogenic protein called Tax. Our findings might help to improve interferon-based anti-HTLV-1 and anti-ATL therapy.

Pregnancy-associated plasma protein A (PAPP-A) to predict adverse fetal outcomes in Chinese: What is the optimal cutoff value?

A low level of PAPP-A predicts adverse fetal outcomes. As Chinese pregnant women have a higher level of PAPP-A, the predictive performance of PAPP-A and its optimal cutoff value might be different. This study aims to establish a PAPP-A cutoff value in the Chinese population that identifies adverse fetal outcomes. We retrospectively analysed 4936 spontaneous singleton pregnancies of Chinese women who underwent first-trimester combined Down's screening in our unit from March 2010 to January 2014 and had delivery information available. A composite adverse fetal outcome encompassed intrauterine fetal loss (including miscarriages and stillbirths), and live births either before 32 weeks or weighing less than -2 standard deviation (SD) for gestation. The area under the curve of the receiver-operator characteristic curve for prediction of the composite adverse outcome using PAPP-A was 0.626 (95% CI =0.612-0.640, p < 0.0001). PAPP-A ≤ 0.23 multiples of median (MoM) identified 0.6% of Chinese pregnant women to be at significant risk of adverse fetal outcome (positive likelihood ratio 11.2, positive predictive value 21.4%) despite a low sensitivity (5.1%, 95% CI =1.9-10.8). The negative predictive value was high (97.7%). The commonly used cutoff of 0.4 MoM was associated with a positive likelihood ratio of 3.7 only. A prospective study is warranted.

A Risk Assessment Scheme of Infection Transmission Indoors Incorporating the Impact of Resuspension.

A new risk assessment scheme was developed to quantify the impact of resuspension to infection transmission indoors. Airborne and surface pathogenic particle concentration models including the effect of two major resuspension scenarios (airflow-induced particle resuspension [AIPR] and walking-induced particle resuspension [WIPR]) were derived based on two-compartment mass balance models and validated against experimental data found in the literature. The inhalation exposure to pathogenic particles was estimated using the derived airborne concentration model, and subsequently incorporated into a dose-response model to assess the infection risk. Using the proposed risk assessment scheme, the influences of resuspension towards indoor infection transmission were examined by two hypothetical case studies. In the case of AIPR, the infection risk increased from 0 to 0.54 during 0-0.5 hours and from 0.54 to 0.57 during 0.5-4 hours. In the case of WIPR, the infection risk increased from 0 to 0.87 during 0-0.5 hours and from 0.87 to 1 during 0.5-4 hours. Sensitivity analysis was conducted based on the design-of-experiments method and showed that the factors that are related to the inspiratory rate of viable pathogens and pathogen virulence have the most significant effect on the infection probability under the occurrence of AIPR and WIPR. The risk assessment scheme could serve as an effective tool for the risk assessment of infection transmission indoors.