"Plant Golden" C. sativus: Qualitative and quantitative analysis of major components in stigmas and petals and their biological activity in vitro.

Crocus sativus L. (C. sativus) has its stigma as the main valuable part used. With extremely low production and high prices, stigma is considered a scarce resource. As a result, its petals, considered as by-products, are often discarded, leading to significant waste. We developed a UPLC-Q-Orbitrap HRMS method for qualitative analysis of stigmas and petals and a UHPLC-QQQ-MS/MS method for simultaneous quantification of 9 characteristic active compounds for the first time, and compared their biological activity in vitro. The results indicated that a total of 63 compounds were identified in the petals and stigmas. The content of flavonoids in the petals was significantly superior to that in the stigma, and the content of quercetin in the petals was 50 times higher than that in the stigma. The results of the in vitro evaluation of biological activity indicated that both the petals （•OH: IC50=39.70 mg/mL; DPPH: IC50=28.37 mg/mL; ABTS: IC50=0.9868 mg/mL）and stigma （•OH: IC50=34.41 mg/mL; DPPH: IC50=38.99 mg/mL; ABTS: IC50=3.194 mg/mL）demonstrated comparable antioxidant activities. However, the tyrosinase inhibitory activity in petals （IC50=21.17 mg/mL） was weaker than that in stigma（IC50=1.488 mg/mL）. This study provides a fast, reliable, and efficient analytical method that can be used for the quality assessment of petals as a natural resource and its related products in the food and pharmaceutical industries.

Use of invitations and reminders are associated with higher levels of Herpes zoster (shingles) vaccination uptake. A cross-sectional survey of general practices in Wales, and ecological analysis of uptake data, 2022.

In 2013, shingles vaccination was introduced in Wales as a routine immunisation programme for older adults. Invitation for this vaccination has historically been recommended but not mandated by vaccination policy. We surveyed general practices to investigate if invitations and reminders are associated with higher uptake of shingles vaccine. Using data from general practices, we calculated practice-level shingles vaccine uptake between 01/07/2021 and 31/06/2022 for registered patients aged 70-84 years. We distributed an online survey via email to all general practices in Wales on their use of vaccination invitations and reminders, method of invitations, and characteristics of their vaccination delivery. We used linear regression to calculate coefficients and 95 %CI to measure associations between invitations and vaccine uptake, adjusting for key demographics, with a multi-level component to account for similarities between general practices within the same health board. Survey response rate was 37 % (143/384). Median vaccine uptake for responding general practices was 57 % (IQR 50-68 %) compared to 58 % (IQR 48-68 %) nationally. General practices inviting all eligible patients (n = 95) had a 9 % (95 %CI 6-13 %) higher vaccination uptake compared to those inviting none or some (n = 48, p < 0.001). Of practices sending invitations, those who reminded all patients (n = 42) had a 6 % (95 %CI 1-11 %, p = 0.02) higher uptake compared to those that reminded none (n = 30). Practice size was associated with higher uptake, with small practices (n = 11, p = 0.02) having coverage 9 % (95 %CI 2-16 %) higher compared to the reference population (medium-sized practices, n = 78). General practices inviting and reminding all eligible patients for shingles vaccination have a higher uptake compared to those inviting and reminding only some or none. From September 2023, shingles vaccination policy in Wales has been updated to explicitly mandate effective universal call and recall mechanisms in general practices.

Near-source passive sampling for monitoring viral outbreaks within a university residential setting.

Wastewater-based epidemiology (WBE) has proven to be a powerful tool for the population-level monitoring of pathogens, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For assessment, several wastewater sampling regimes and methods of viral concentration have been investigated, mainly targeting SARS-CoV-2. However, the use of passive samplers in near-source environments for a range of viruses in wastewater is still under-investigated. To address this, near-source passive samples were taken at four locations targeting student hall of residence. These were chosen as an exemplar due to their high population density and perceived risk of disease transmission. Viruses investigated were SARS-CoV-2 and its variants of concern (VOCs), influenza viruses, and enteroviruses. Sampling was conducted either in the morning, where passive samplers were in place overnight (17 h) and during the day, with exposure of 7 h. We demonstrated the usefulness of near-source passive sampling for the detection of VOCs using quantitative polymerase chain reaction (qPCR) and next-generation sequencing (NGS). Furthermore, several outbreaks of influenza A and sporadic outbreaks of enteroviruses (some associated with enterovirus D68 and coxsackieviruses) were identified among the resident student population, providing evidence of the usefulness of near-source, in-sewer sampling for monitoring the health of high population density communities.

The use of Enhanced Vegetation Index for assessing access to different types of green space in epidemiological studies.

BACKGROUND: Exposure to green space can protect against poor health through a variety of mechanisms. However, there is heterogeneity in methodological approaches to exposure assessments which makes creating effective policy recommendations challenging. OBJECTIVE: Critically evaluate the use of a satellite-derived exposure metric, the Enhanced Vegetation Index (EVI), for assessing access to different types of green space in epidemiological studies. METHODS: We used Landsat 5-8 (30 m resolution) to calculate average EVI for a 300 m radius surrounding 1.4 million households in Wales, UK for 2018. We calculated two additional measures using topographic vector data to represent access to green spaces within 300 m of household locations. The two topographic vector-based measures were total green space area stratified by type and average private garden size. We used linear regression models to test whether EVI could discriminate between publicly accessible and private green space and Pearson correlation to test associations between EVI and green space types. RESULTS: Mean EVI for a 300 m radius surrounding households in Wales was 0.28 (IQR = 0.12). Total green space area and average private garden size were significantly positively associated with corresponding EVI measures (ß = < 0.0001, 95% CI: 0.0000, 0.0000; ß = 0.0001, 95% CI: 0.0001, 0.0001 respectively). In urban areas, as average garden size increases by 1 m2, EVI increases by 0.0002. Therefore, in urban areas, to see a 0.1 unit increase in EVI index score, garden size would need to increase by 500 m2. The very small ß values represent no 'measurable real-world' associations. When stratified by type, we observed no strong associations between greenspace and EVI. IMPACT: It is a widely implemented assumption in epidiological studies that an increase in EVI is equivalent to an increase in greenness and/or green space. We used linear regression models to test associations between EVI and potential sources of green reflectance at a neighbourhood level using satellite imagery from 2018. We compared EVI measures with a 'gold standard' vector-based dataset that defines publicly accessible and private green spaces. We found that EVI should be interpreted with care as a greater EVI score does not necessarily mean greater access to publicly available green spaces in the hyperlocal environment.

Improved detection of aortic dissection in non-contrast-enhanced chest CT using an attention-based deep learning model.

Rationale and objectives: This study investigated the effects of implementing an attention-based deep learning model for the detection of aortic dissection (AD) using non-contrast-enhanced chest computed tomography (CT). Materials and methods: We analysed the records of 1300 patients who underwent contrast-enhanced chest CT at 2 medical centres between January 2015 and February 2023. We considered an internal cohort of 200 patients with AD and 200 patients without AD and an external test cohort of 40 patients with AD and 40 patients without AD. The internal cohort was divided into training and test sets, and a deep learning model was trained using 9600 CT images. A convolutional block attention module (CBAM) and a traditional deep learning architecture (namely, You Only Look Once version 5 [YOLOv5]) were combined into an attention-based model (i.e., YOLOv5-CBAM). Its performance was measured against the unmodified YOLOv5 model, and the accuracy, sensitivity, and specificity of the algorithm were evaluated by two independent radiologists. Results: The CBAM-based model outperformed the traditional deep learning model. In the external testing set, YOLOv5-CBAM achieved an area under the curve (AUC) of 0.938, accuracy of 91.5 %, sensitivity of 90.0 %, and specificity of 92.9 %, whereas the unmodified model achieved an AUC of 0.844, accuracy of 83.6 %, sensitivity of 71.2 %, and specificity of 96.0 %. The sensitivity results of the unmodified algorithms were not significantly different from those of the radiologists; however, the proposed YOLOv5-CBAM algorithm outperformed the unmodified algorithms in terms of detection. Conclusions: Incorporating the CBAM attention mechanism into a deep learning model can significantly improve AD detection in non-contrast-enhanced chest CT. This approach may aid radiologists in the timely and accurate diagnosis of AD, which is important for improving patient outcomes.

Down-Regulation of CPEB4 Alleviates Preeclampsia through the Inhibition of Ferroptosis by PFKFB3.

Gestational diabetes mellitus (GDM) complicated with preeclampsia can lead to polyhydramnios, ketosis. Herein, we explored that CPEB4 in cancer progression of preeclampsia and its underlying mechanism. All the serum samples were collected from patients with preeclampsia. These was the induction of CPEB4 in patients with preeclampsia. The serum of CPEB4 mRNA expression was positive correlation with Proteinuria, systolic blood pressure and diastolic blood pressure in patients. The serum of CPEB4 mRNA expression was also negative correlation with body weight of infant in patients. The serum of CPEB4 mRNA expression also was negative correlation with GPX4 level and GSH activity level in patients. The serum of CPEB4 mRNA expression was positive correlation with iron content in patients. CPEB4 gene inhibited trophoblast cell proliferation. CPEB4 gene promoted trophoblast cell ferroptosis by mitochondrial damage. CPEB4 gene induced PFKFB3 expression by the inhibition of PFKFB3 Ubiquitination. PFKFB3 inhibitor reduced the effects of CPEB4 on cell proliferation and ferroptosis of trophoblast cell. Taken together, the CPEB4 promoted trophoblast cell ferroptosis through mitochondrial damage by the induction of PFKFB3 expression, CPEB4 as an represents a potential therapeutic strategy for the treatment of preeclampsia or various types of GDM.

Preparation, characterization and application of a composite bioflocculant.

Composite flocculant PAFS-PDM was prepared from Polymeric aluminium ferric sulphate (PAFS) and Poly (diallyl dimethyl ammonium chloride) (PDM) in this study. A bacterium was selected from the soil near the shale gas exploitation platform as a bioflocculant-producing bacterium, and polysaccharide was extracted and combined with PAFS-PDM to obtain composite bioflocculant (CBF) to treat shale gas fracturing flowback fluid. The prepared CBF was characterized and the results showed that the prepared PAFS-PDM contained aluminium-iron hydroxyl polymer, which was a cationic flocculant. By measuring the turbidity removal rate and chemical oxygen demand (COD) removal efficiency, the function mechanism of CBF on the shale gas fracturing flowback fluid was discussed. The results showed that CBF had a stable treatment effect on fracturing flowback fluid when the pH value was about 7.0. With the increase of dosage, the coagulation efficiency increased first and then decreased. When the dosage of the CBF was 2500 mg·L-1, the treatment effect of shale gas fracturing flowback fluid was the best, and COD removal rate reached 89.43%. Through Zeta potential analysis, it was concluded that one of the coagulation mechanisms was electrical neutralization. According to the characterization results, it could be concluded that both adsorption bridging and charge neutralization mechanisms played important roles in the treatment of shale gas fracturing flowback fluids.

Effect of mesenchymal stromal cells transplantation on the outcomes of patients with knee osteoarthritis: A systematic review and meta-analysis.

Cell therapy has been explored as a new regenerative treatment for osteoarthritis in the field of regenerative medicine. However, the efficacy of stem cell transplantation from different sources for the treatment of knee osteoarthritis (KOA) remains controversial. This study integrates and evaluates the previously published data of stem cell transplantation for KOA to explore the curative effect of different stem cells. We conducted a meta-analysis of randomized controlled trials on stem cell therapy for KOA. Measures of efficacy included Visual Analog Scale (VAS), Lequesne index, Lysholm Knee Scoring Scale (LKSS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Joint injury was evaluated through the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system. We analyzed 16 studies involving 875 KOA patients. The stem cell treatment showed significant VAS reduction from the third month onwards. Subgroup analysis suggested the most significant pain relief at different postoperative months came from adipose-derived and umbilical cord-derived stem cells. Autologous adipose tissue resulted in better pain alleviation compared with allogenic. However, autologous bone marrow stem cells did not show increased pain relief over allogeneic ones. Combination therapy (HA and/or PRP) showed no effect. Autologous adipose-derived stem cells demonstrate the most effective recovery of knee joint function. In WORMS assessment, there was no significant difference between the stem cell group and control. Stem cell transplantation proved safe and effective for KOA treatment. Different sources stem cells have a good effect on alleviating knee joint pain, restoring knee joint function, and minimizing patient trauma.

Health of unpaid carers in Wales, UK: a population data linkage study.

BACKGROUND: The population of unpaid carers in Wales increased to record. There is no systematic approach to record unpaid caring status, resulting in limited quantitative evidence on unpaid carers' health. The aim of this study is to: (i) create an e-cohort of unpaid carers by linking routinely collected health and administrative datasets in Wales, UK. (ii) investigate whether long-term health conditions and multimorbidity are more prevalent amongst unpaid carers than non-carers. METHODS: Unpaid carers were identified by linking primary care dataset, National Survey for Wales data with demographic characteristics in the Secure Anonymise Information Linkage Databank. The clinical codes identified in Cambridge Multimorbidity Score were used to explore the prevalence of long-term health conditions. RESULTS: A total of 91 220 unpaid carers in Wales were identified between 1 January 2010 and 1 March 2022. Unpaid carers were found at higher risk of managing 35 of 37 long-term health conditions and multimorbidity than non-carers, exacerbated amongst younger age groups and deprived communities. CONCLUSIONS: The creation of the first e-cohort of unpaid carers in Wales provides opportunities to perform rapid analysis to systematically understand health needs and evaluate initiatives in future. To better support unpaid carers, flexible approaches focusing on early identification and prevention is crucial.

Temperature-insensitive optical fiber strain sensor fabricated by two parallel connection Fabry-Perot interferometers with air-bubbles.

A strain sensor formed by a parallel connection of two Fabry-Perot interferometers (FPI) is proposed. The femtosecond laser is used to process a micro groove on the end face of a single-mode fiber (SMF), and then, it is welded with another SMF to form a small air bubble at the fusion point, fabricating an FPI. When the axial strain acts on the air bubble, the transverse length of the air bubble will change, causing the air cavity of the FPI to be easily deformed, and FPI can obtain high strain sensitivity. Three FPIs were manufactured with the air bubble sizes of 63, 78, and 93 µm, respectively, and the strain sensitivities of the three FPIs are 2.9, 2.0, and 1.5 pm/µÎµ, respectively. The experimental results show that the smaller the air bubble, the higher the strain sensitivity of FPI. Since the free spectral ranges of the three FPIs are relatively similar, we, respectively, paralleled them to form two Vernier effect strain sensors, and their sensitivities are -14.9 and -14.5 pm/µÎµ, respectively. Their sensitivities are increased by 5.1 times and 7.3 times, respectively. In addition, because three FPIs are composed of air cavities, they have very low temperature sensitivities. When they are connected in parallel, their resonance peak wavelength moves in the same direction with an increase in temperature, forming a reduced Vernier effect, and the temperature sensitivity amplification is very small. Therefore, the temperature cross-sensitivity of the sensor is extremely low and can be ignored.

High-sensitivity humidity and temperature sensor by cascading a polyimide coated long period fiber grating and a polydimethylsiloxane wrapped Mach-Zehnder interferometer.

Two different structures, long period fiber grating (LPFG) and a Mach-Zehnder interferometer (MZI), were cascaded to fabricate a sensor for sensing humidity and temperature simultaneously. Due to the humidity sensitive characteristic of polyimide (PI) and the temperature sensitive characteristic of polydimethylsiloxane (PDMS), the LPFG was coated with PI and the MZI was wrapped in PDMS to improve the humidity and temperature sensitivities, respectively. Humidity and temperature experiments and the stability and repeatability of the proposed sensors were performed. The sensor shows humidity and temperature sensitivities of ∼164 pm/%RH and 183 pm/°C in the humidity and temperature increasing experiments, respectively. Combining increasing, decreasing, and repeatable experiments of temperature and humidity, the proposed sensor shows stable performance in humidity sensitivity of ∼159 pm/%RH and temperature sensitivity of ∼175 pm/°C, with good linearity of ∼0.994. The structure of the proposed sensor has the advantages of low implementation cost, easy fabrication, and good stability.

The association of anxiety disorders and depression with facial scarring: population-based, data linkage, matched cohort analysis of 358 158 patients.

BACKGROUND: Estimates suggest that 1 in 100 people in the UK live with facial scarring. Despite this incidence, psychological support is limited. AIMS: The aim of this study was to strengthen the case for improving such support by determining the incidence and risk factors for anxiety and depression disorders in patients with facial scarring. METHOD: A matched cohort study was performed. Patients were identified via secondary care data sources, using clinical codes for conditions resulting in facial scarring. A diagnosis of anxiety or depression was determined by linkage with the patient's primary care general practice data. Incidence was calculated per 1000 person-years at risk (PYAR). Logistic regression was used to determine risk factors. RESULTS: Between 2009 and 2018, 179 079 patients met the study criteria and were identified as having a facial scar, and matched to 179 079 controls. The incidence of anxiety in the facial scarring group was 10.05 per 1000 PYAR compared with 7.48 per 1000 PYAR for controls. The incidence of depression in the facial scarring group was 16.28 per 1000 PYAR compared with 9.56 per 1000 PYAR for controls. Age at the time of scarring, previous history of anxiety or depression, female gender, socioeconomic status and classification of scarring increased the risk of both anxiety disorders and depression. CONCLUSIONS: There is a high burden of anxiety disorders and depression in this patient group. Risk of these mental health disorders is very much determined by factors apparent at the time of injury, supporting the need for psychological support.

Green-blue space exposure changes and impact on individual-level well-being and mental health: a population-wide dynamic longitudinal panel study with linked survey data.

Background: Cross-sectional evidence suggests that living near green and blue spaces benefits mental health; longitudinal evidence is limited. Objectives: To quantify the impact of changes in green and blue spaces on common mental health disorders, well-being and health service use. Design: A retrospective, dynamic longitudinal panel study. Setting: Wales, UK. Participants: An e-cohort comprising 99,682,902 observations of 2,801,483 adults (≥ 16 years) registered with a general practice in Wales (2008-2019). A 5312-strong 'National Survey for Wales (NSW) subgroup' was surveyed on well-being and visits to green and blue spaces. Main outcome measures: Common mental health disorders, general practice records; subjective well-being, Warwick-Edinburgh Mental Well-being Scale. Data sources: Common mental health disorder and use of general practice services were extracted quarterly from the Welsh Longitudinal General Practice Dataset. Annual ambient greenness exposure, enhanced vegetation index and access to green and blue spaces (2018) from planning and satellite data. Data were linked within the Secure Anonymised Information Linkage Databank. Methods: Multilevel regression models examined associations between exposure to green and blue spaces and common mental health disorders and use of general practice. For the National Survey for Wales subgroup, generalised linear models examined associations between exposure to green and blue spaces and subjective well-being and common mental health disorders. Results and conclusions: Our longitudinal analyses found no evidence that changes in green and blue spaces through time impacted on common mental health disorders. However, time-aggregated exposure to green and blue spaces contrasting differences between people were associated with subsequent common mental health disorders. Similarly, our cross-sectional findings add to growing evidence that residential green and blue spaces and visits are associated with well-being benefits: Greater ambient greenness (+ 1 enhanced vegetation index) was associated with lower likelihood of subsequently seeking care for a common mental health disorder [adjusted odds ratio (AOR) 0.80, 95% confidence interval, (CI) 0.80 to 0.81] and with well-being with a U-shaped relationship [Warwick-Edinburgh Mental Well-being Scale; enhanced vegetation index beta (adjusted) -10.15, 95% CI -17.13 to -3.17; EVI2 beta (quadratic term; adj.) 12.49, 95% CI 3.02 to 21.97]. Those who used green and blue spaces for leisure reported better well-being, with diminishing extra benefit with increasing time (Warwick-Edinburgh Mental Well-being Scale: time outdoors (hours) beta 0.88, 95% CI 0.53 to 1.24, time outdoors2 beta -0.06, 95% CI -0.11 to -0.01) and had 4% lower odds of seeking help for common mental health disorders (AOR 0.96, 95% CI 0.93 to 0.99). Those in urban areas benefited most from greater access to green and blue spaces (AOR 0.89, 95% CI 0.89 to 0.89). Those in material deprivation benefited most from leisure time outdoors (until approximately four hours per week; Warwick-Edinburgh Mental Well-being Scale: time outdoorsâ€…× in material deprivation: 1.41, 95% CI 0.39 to 2.43; time outdoors2 × in material deprivation -0.18, 95% CI -0.33 to -0.04) although well-being remained generally lower. Limitations: Longitudinal analyses were restricted by high baseline levels and limited temporal variation in ambient greenness in Wales. Changes in access to green and blue spaces could not be captured annually due to technical issues with national-level planning datasets. Future work: Further analyses could investigate mental health impacts in population subgroups potentially most sensitive to local changes in access to specific types of green and blue spaces. Deriving green and blue spaces changes from planning data is needed to overcome temporal uncertainties. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (Project number 16/07/07) and will be published in full in Public Health Research; Vol. 11, No. 10. Sarah Rodgers is part-funded by the NIHR Applied Research Collaboration North West Coast.

We investigated whether people who live near or visit green (parks, woodlands) and blue (riversides, beaches) spaces have fewer common mental health disorders (anxiety or depression), and better well-being. We considered whether changes in the amount of green and blue space around the home affected people's mental health. We assessed the availability of local green and blue spaces. Annual exposure and access to local green and blue spaces were extracted from planning and satellite data. We linked these data to anonymised health records of 2,801,483 adults registered with a general practice from 2008 to 2019, and to survey answers about leisure visits to natural environments and well-being. We found: people who lived in greener and bluer areas were less likely to seek help for a common mental health disorder than those in less green or blue areas, with those living in the most deprived areas benefiting the most people who used green and blue spaces for leisure, especially those with the greatest levels of deprivation, had better well-being and were less likely to seek help for common mental health disorders no evidence that changing amounts of green and blue space affected how likely people were to seek help for common mental health disorders; this may be because we found mostly small changes in green and blue space, and we may not have allowed enough time between moving home and recording mental health. We found evidence for relationships between green and blue space and mental health. However, some analyses were restricted due to lack of data on changes in green and blue spaces. An important finding was that people in deprived communities appear to benefit the most. Provision of green and blue spaces could be a strategy to improve the mental health of people living in disadvantaged areas.

Ambient greenness, access to local green spaces, and subsequent mental health: a 10-year longitudinal dynamic panel study of 2·3 million adults in Wales.

BACKGROUND: Living in greener areas, or close to green and blue spaces (GBS; eg, parks, lakes, or beaches), is associated with better mental health, but longitudinal evidence when GBS exposures precede outcomes is less available. We aimed to analyse the effect of living in or moving to areas with more green space or better access to GBS on subsequent adult mental health over time, while explicitly considering health inequalities. METHODS: A cohort of the people in Wales, UK (≥16 years; n=2 341 591) was constructed from electronic health record data sources from Jan 1, 2008 to Oct 31, 2019, comprising 19 141 896 person-years of follow-up. Household ambient greenness (Enhanced Vegetation Index [EVI]), access to GBS (counts, distance to nearest), and common mental health disorders (CMD, based on a validated algorithm combining current diagnoses or symptoms of anxiety or depression [treated or untreated in the preceding 1-year period], or treatment of historical diagnoses from before the current cohort [up to 8 years previously, to 2000], where diagnosis preceded treatment) were record-linked. Cumulative exposure values were created for each adult, censoring for CMD, migration out of Wales, death, or end of cohort. Exposure and CMD associations were evaluated using multivariate logistic regression, stratified by area-level deprivation. FINDINGS: After adjustment, exposure to greater ambient greenness over time (+0·1 increased EVI on a 0-1 scale) was associated with lower odds of subsequent CMD (adjusted odds ratio 0·80, 95% CI 0·80-0·81), where CMD was based on a combination of current diagnoses or symptoms (treated or untreated in the preceding 1-year period), or treatments. Ten percentile points more access to GBS was associated with lower odds of a later CMD (0·93, 0·93-0·93). Every additional 360 m to the nearest GBS was associated with higher odds of CMD (1·05, 1·04-1·05). We found that positive effects of GBS on mental health appeared to be greater in more deprived quintiles. INTERPRETATION: Ambient exposure is associated with the greatest reduced risk of CMD, particularly for those who live in deprived communities. These findings support authorities responsible for GBS, who are attempting to engage planners and policy makers, to ensure GBS meets residents' needs. FUNDING: National Institute for Health and Care Research Public Health Research programme.

Increased reports of severe myocarditis associated with enterovirus infection in neonates, United Kingdom, 27 June 2022 to 26 April 2023.

Enteroviruses are a common cause of seasonal childhood infections. The vast majority of enterovirus infections are mild and self-limiting, although neonates can sometimes develop severe disease. Myocarditis is a rare complication of enterovirus infection. Between June 2022 and April 2023, twenty cases of severe neonatal enteroviral myocarditis caused by coxsackie B viruses were reported in the United Kingdom. Sixteen required critical care support and two died. Enterovirus PCR on whole blood was the most sensitive diagnostic test. We describe the initial public health investigation into this cluster and aim to raise awareness among paediatricians, laboratories and public health specialists.

Visiting nature is associated with lower socioeconomic inequalities in well-being in Wales.

Natural environments can promote well-being through multiple mechanisms. Many studies have investigated relationships between residential green/blue space (GBS) and well-being, fewer explore relationships with actual use of GBS. We used a nationally representative survey, the National Survey for Wales, anonymously linked with spatial GBS data to investigate associations of well-being with both residential GBS and time in nature (N = 7631). Both residential GBS and time spent in nature were associated with subjective well-being. Higher green-ness was associated with lower well-being, counter to hypotheses (predicting the Warwick and Edinburgh Mental Well-Being Scale (WEMWBS): Enhanced vegetation index ß = - 1.84, 95% confidence interval (CI) - 3.63, - 0.05) but time spent in nature was associated with higher well-being (four hours a week in nature vs. none ß = 3.57, 95% CI 3.02, 4.13). There was no clear association between nearest GBS proximity and well-being. In support of the equigenesis theory, time spent in nature was associated with smaller socioeconomic inequalities in well-being. The difference in WEMWBS (possible range 14-70) between those who did and did not live in material deprivation was 7.7 points for those spending no time in nature, and less at 4.5 points for those spending time in nature up to 1 h per week. Facilitating access and making it easier for people to spend time in nature may be one way to reduce socioeconomic inequalities in well-being.

Effects of the COVID-19 pandemic on the mental health of clinically extremely vulnerable children and children living with clinically extremely vulnerable people in Wales: a data linkage study.

OBJECTIVES: To determine whether clinically extremely vulnerable (CEV) children or children living with a CEV person in Wales were at greater risk of presenting with anxiety or depression in primary or secondary care during the COVID-19 pandemic compared with children in the general population and to compare patterns of anxiety and depression during the pandemic (23 March 2020-31 January 2021, referred to as 2020/2021) and before the pandemic (23 March 2019-31 January 2020, referred to as 2019/2020), between CEV children and the general population. DESIGN: Population-based cross-sectional cohort study using anonymised, linked, routinely collected health and administrative data held in the Secure Anonymised Information Linkage Databank. CEV individuals were identified using the COVID-19 shielded patient list. SETTING: Primary and secondary healthcare settings covering 80% of the population of Wales. PARTICIPANTS: Children aged 2-17 in Wales: CEV (3769); living with a CEV person (20 033); or neither (415 009). PRIMARY OUTCOME MEASURE: First record of anxiety or depression in primary or secondary healthcare in 2019/2020 and 2020/2021, identified using Read and International Classification of Diseases V.10 codes. RESULTS: A Cox regression model adjusted for demographics and history of anxiety or depression revealed that only CEV children were at greater risk of presenting with anxiety or depression during the pandemic compared with the general population (HR=2.27, 95% CI=1.94 to 2.66, p<0.001). Compared with the general population, the risk among CEV children was higher in 2020/2021 (risk ratio 3.04) compared with 2019/2020 (risk ratio 1.90). In 2020/2021, the period prevalence of anxiety or depression increased slightly among CEV children, but declined among the general population. CONCLUSIONS: Differences in the period prevalence of recorded anxiety or depression in healthcare between CEV children and the general population were largely driven by a reduction in presentations to healthcare services by children in the general population during the pandemic.

Echinomycin as a promising therapeutic agent against KSHV-related malignancies.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), which preferentially arise in immunocompromised patients while lack of effective therapeutic options. Oncoproteins Myc and hypoxia-inducible factor-1α (HIF1α) have been found closely related to KSHV infection, replication and oncogenesis. However, the strategies of dual targeting these two oncoproteins have never been developed and tested for treatments of KSHV-related malignancies. In the current study, we report that treatment of echinomycin dramatically regresses cell growth both in vitro-cultured KSHV + tumor cells and in vivo KS or PEL xenograft mice models, through simultaneously inhibiting Myc and HIF1α expression. Echinomycin treatment also induces viral lytic gene expression whereas not increasing infectious virions production from KSHV + tumor cells. Our comparative transcriptomic analysis has identified a bunch of new Echinomycin-regulated, Myc- and HIF1α-related genes contributed to KSHV pathogenesis, including KDM4B and Tau, which are required for the survival of KSHV + tumor cells with functional validation. These data together reveal that dual targeting Myc and HIF1α such as using Echinomycin may represent a new and promising option for treatments of these virus-associated malignancies.

Ultra-sensitive temperature and pressure sensor based on PDMS-based FPI and Vernier effect.

An ultra-sensitive sensor, based on two Fabry-Perot interferometers (FPIs), has been realized for temperature and pressure sensing. A polydimethylsiloxane (PDMS)-based FPI1 was used as a sensing cavity, and a closed capillary-based FPI2 was used as a reference cavity for its insensitivity to both temperature and pressure. The two FPIs were connected in series to obtain a cascaded FPIs sensor, showing a clear spectral envelope. The temperature and pressure sensitivities of the proposed sensor reach up to 16.51 nm/°C and 100.18 nm/MPa, which are 25.4 and 21.6 times, respectively, larger than these of the PDMS-based FPI1, showing a great Vernier effect.

Role of Histamine and Related Signaling in Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis and Oncogenesis.

Although Kaposi's sarcoma-associated herpesvirus (KSHV) has been reported to cause several human cancers including Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), the mechanisms of KSHV-induced tumorigenesis, especially virus-host interaction network, are still not completely understood, which therefore hinders the development of effective therapies. Histamine, together with its receptors, plays an important role in various allergic diseases by regulating different inflammation and immune responses. Our previous data showed that antagonists targeting histamine receptors effectively repressed KSHV lytic replication. In the current study, we determined that histamine treatment increased cell proliferation and anchorage-independent growth abilities of KSHV-infected cells. Furthermore, histamine treatment affected the expression of some inflammatory factors from KSHV-infected cells. For clinical relevance, several histamine receptors were highly expressed in AIDS-KS tissues when compared to normal skin tissues. We determined that histamine treatment promoted KSHV-infected lymphoma progression in immunocompromised mice models. Therefore, besides viral replication, our data indicate that the histamine and related signaling are also involved in other functions of KSHV pathogenesis and oncogenesis.