The practice of social protection policies in China: a systematic review on how left-behind children's mental health can be optimised.

AIMS: By discussing the mental health challenges faced by left-behind children, this article recommends or comments on existing social protection policies that can affect left-behind children's mental health at the micro-, meso- and macro-levels to holistically understand how a range of parties can jointly socially include left-behind children, a process which is conducive to the latter's mental health development. METHODS: J.H. carried out a systematic review by searching through the English bibliographical databases Google Scholar, Web of Science and Scopus, in addition to Chinese bibliographic databases CNKI, Wanfang Data and VIP Chinese Science and Technology Periodicals. Here J.H. searched for the words ('social protection' OR 'socially protected') AND ('mental health' OR 'psychological wellbeing' OR 'mental problems' OR 'psychological problems') AND ('left-behind children' OR 'LBC' OR 'leftover children') AND ('China' OR 'Chinese'). Publication dates of the search results were limited to between 2010 and 2022. RESULTS: One of the primary problems encountered by left-behind children is their inadequate home supervision. A further study indicates that parental migration serves as a crucial risk factor for child depression. State-level provision of insurance programmes helps curtail these children's encounters of mental health challenges. Moreover, an improvement in family and school protection is essential when optimising the protection system for left-behind rural Chinese children from poor villages. It is necessary for upper-level government units to re-structure their lower-level counterparts to improve the local administration. This allows lower-level government units to exploit preferential policies, refine relevant regulations and policies on child protection, and facilitate the establishment of social organisations where local policies can be successfully implemented to socially include and protect left-behind children in villages. CONCLUSIONS: At the meso-level, community environment construction should be emphasised. At macro- and meso-levels, government authorities and social organisations should encourage the marketisation of hiring professional surrogate parents. At the micro-level, migrant parents should proactively take an initiative to contact their left-behind children via telecommunications.

Rapid antigen test during a COVID-19 outbreak in a private hospital in Hong Kong.

INTRODUCTION: In response to two nosocomial clusters of coronavirus disease 2019 (COVID-19) in our hospital, we adopted a series of strict infection control measures, including regular rapid antigen test (RAT) screening for high-risk patients, visitors, and healthcare workers. We evaluated the diagnostic performance of a locally developed RAT, the INDICAID COVID-19 Rapid Antigen Test (Phase Scientific, Hong Kong), using respiratory samples from both symptomatic and asymptomatic individuals. METHODS: Real-time reverse-transcription polymerase chain reaction (rRT-PCR)-confirmed deep throat saliva (DTS) and pooled nasopharyngeal swab and throat swab (NPS/TS) samples collected from 1 November to 30 November 2020 were tested by INDICAID. Screening RATs were performed on asymptomatic healthcare workers during a 16-week period (1 December 2020 to 22 March 2021). RESULTS: In total, 20 rRT-PCR-confirmed samples (16 DTS, four pooled NPS/TS) were available for RAT. Using the original sample, RAT results were positive in 17/20 samples, indicating 85% sensitivity (95% confidence interval [CI]=62.11%-96.79%). Negative RAT results were associated with higher cycle threshold (Ct) values. For samples with Ct values <25, the sensitivity was 100%. Of the 49 801 RATs collected from healthcare workers, 33 false positives and one rRT-PCR-confirmed case were detected. The overall specificity was 99.93% (95% CI=99.91%-99.95%). The positive and negative predictive values were 2.94% (95% CI=2.11%-4.09%) and 100%, respectively. CONCLUSION: The INDICAID COVID-19 RAT demonstrated good sensitivity for specimens with high viral loads and satisfactory specificity for low-risk, asymptomatic healthcare workers.

Emerging dominance of summer rainfall driving High Arctic terrestrial-aquatic connectivity.

Hydrological transformations induced by climate warming are causing Arctic annual fluvial energy to shift from skewed (snowmelt-dominated) to multimodal (snowmelt- and rainfall-dominated) distributions. We integrated decade-long hydrometeorological and biogeochemical data from the High Arctic to show that shifts in the timing and magnitude of annual discharge patterns and stream power budgets are causing Arctic material transfer regimes to undergo fundamental changes. Increased late summer rainfall enhanced terrestrial-aquatic connectivity for dissolved and particulate material fluxes. Permafrost disturbances (<3% of the watersheds' areal extent) reduced watershed-scale dissolved organic carbon export, offsetting concurrent increased export in undisturbed watersheds. To overcome the watersheds' buffering capacity for transferring particulate material (30 ± 9 Watt), rainfall events had to increase by an order of magnitude, indicating the landscape is primed for accelerated geomorphological change when future rainfall magnitudes and consequent pluvial responses exceed the current buffering capacity of the terrestrial-aquatic continuum.

Development and Evaluation of a Prediction Model for Ascertaining Rheumatic Heart Disease Status in Administrative Data.

BACKGROUND: Previous research has raised substantial concerns regarding the validity of the International Statistical Classification of Diseases and Related Health Problems (ICD) codes (ICD-10 I05-I09) for rheumatic heart disease (RHD) due to likely misclassification of non-rheumatic valvular disease (non-rheumatic VHD) as RHD. There is currently no validated, quantitative approach for reliable case ascertainment of RHD in administrative hospital data. METHODS: A comprehensive dataset of validated Australian RHD cases was compiled and linked to inpatient hospital records with an RHD ICD code (2000-2018, n=7555). A prediction model was developed based on a generalized linear mixed model structure considering an extensive range of demographic and clinical variables. It was validated internally using randomly selected cross-validation samples and externally. Conditional optimal probability cutpoints were calculated, maximising discrimination separately for high-risk versus low-risk populations. RESULTS: The proposed model reduced the false-positive rate (FPR) from acute rheumatic fever (ARF) cases misclassified as RHD from 0.59 to 0.27; similarly for non-rheumatic VHD from 0.77 to 0.22. Overall, the model achieved strong discriminant capacity (AUC: 0.93) and maintained a similar robust performance during external validation (AUC: 0.88). It can also be used when only basic demographic and diagnosis data are available. CONCLUSION: This paper is the first to show that not only misclassification of non-rheumatic VHD but also of ARF as RHD yields substantial FPRs. Both sources of bias can be successfully addressed with the proposed model which provides an effective solution for reliable RHD case ascertainment from hospital data for epidemiological disease monitoring and policy evaluation.

Mercury distribution and speciation in two lagoons with different pollution and eutrophication conditions in Taiwan.

This study explored biogeochemical processes controlling the distribution of mercury (Hg) species in two lagoons with different pollution and eutrophication conditions in southwestern Taiwan. The eutrophication and pollution levels were higher in the Dapeng Bay than in the Chiku Lagoon, engendering a higher particulate Hg concentration and enrichment factor in the Dapeng Bay. The concentration range of total dissolved Hg (HgTD) and reactive Hg (HgR) was comparable between the lagoons, but the concentration of particulate Hg (HgP) was higher in the Dapeng Bay. HgR and HgTD abundance was primarily controlled by the availability of dissolved oxygen (DO) and biological absorption. In addition to pollution (which elevated HgP concentration), biological absorption and/or adsorption rather than lithogenic processes more likely regulated the HgP concentration. The effect of Hg pollution may superimpose on that of DO on the distributions of HgR and HgTD and may enhance HgP formation in the Dapeng Bay.

Intravesical prostatic protrusion does not compromise the therapeutic effects of Mirabegron in male patients with overactive bladder.

AIMS: Intravesical prostatic protrusion (IPP) is associated with the degree of benign prostatic obstruction. We evaluated the effects of Mirabegron, a selective ß3 adrenoceptor agonist, on overactive bladder (OAB) in male patients with different degrees of IPP. METHODS: About 185 male patients ≥40 years with lower urinary tract symptoms were recruited from a tertiary referral center. OAB was defined by the overactive bladder symptom score (OABSS) urgency score of ≥2 and sum score of ≥3. IPP was measured in the midsagittal section using transrectal ultrasound and patients were divided into IPP ≤5 mm and IPP >5 mm groups. Outcomes were assessed at the baseline, 4, and 12 weeks. RESULTS: About 104 patients (56.2%) were diagnosed with OAB and received Mirabegron (50 mg) daily use. Both IPP groups (≤5 and >5 mm) had similar baseline OABSS and International Prostate Symptom Scores (IPSS). Four-week Mirabegron usage was associated with significant decreases in both symptom score measurements, OABSS: IPP ≤5 mm -27.4% and IPP >5 mm -19.7% (P = .419) and IPSS: -32% and -22.5% (P = .202), respectively. Urgency, urge incontinence, and nocturia sub-scores were decreased in both groups, -26.3% and -27.4% (P = .690), 53.3% and 46.2% (P = .916), and 20.8% and 15.4% (P = .958). Effects were maintained at 12 weeks. We found no significant improvement in the frequency sub-score in either group. One patient stopped medication because of intolerable hypertension. Most frequent adverse event was increased residual urine (≥50 mL higher than baseline), IPP ≤5 mm 9.2% and IPP >5 mm 5.1% (P = .707), but no case had acute urinary retention. CONCLUSIONS: Mirabegron is an effective drug to treat male OAB regardless of IPP grade.

Transcriptome analysis of osteoblasts in an ovariectomized mouse model in response to physical exercise.

OBJECTIVES: Osteoporosis is a metabolic disease resulting in progressive loss of bone mass as measured by bone mineral density (BMD). Physical exercise has a positive effect on increasing or maintaining BMD in postmenopausal women. The contribution of exercise to the regulation of osteogenesis in osteoblasts remains unclear. We therefore investigated the effect of exercise on osteoblasts in ovariectomized mice. METHODS: We compared the activity of differentially expressed genes of osteoblasts in ovariectomized mice that undertook exercise (OVX+T) with those that did not (OVX), using microarray and bioinformatics. RESULTS: Many inflammatory pathways were significantly downregulated in the osteoblasts after exercise. Meanwhile, IBSP and SLc13A5 gene expressions were upregulated in the OVX+T group. Furthermore, in in vitro assay, IBSP and SLc13A5 mRNAs were also upregulated during the osteogenic differentiation of MC3T3-E1 and 7F2 cells. CONCLUSION: These findings suggest that exercise may not only reduce the inflammatory environment in ovariectomized mice, indirectly suppressing the overactivated osteoclasts, but may also directly activate osteogenesis-related genes in osteoblasts. Exercise may thus prevent the bone loss caused by oestrogen deficiency through mediating the imbalance between the bone resorptive activity of osteoclasts and the bone formation activity of osteoblasts.Cite this article: W-B. Hsu, W-H. Hsu, J-S. Hung, W-J. Shen, R. W-W. Hsu. Transcriptome analysis of osteoblasts in an ovariectomized mouse model in response to physical exercise. Bone Joint Res 2018;7:601-608. DOI: 10.1302/2046-3758.711.BJR-2018-0075.R2.

Ability of computed tomography to predict right heart strain on an echocardiogram in patients with acute pulmonary embolus.

Patients with submassive pulmonary embolism (PE) resulting in right heart strain (RHS) have an increased risk of mortality compared to those with a preserved right ventricular function. This study aimed to investigate the predictive value of computed tomography pulmonary angiogram (CTPA) findings of right heart strain in patients with computed tomography (CT)-proven PE for the diagnosis of right heart strain by echocardiogram (ECHO). The institutional review board (IRB) approved retrospective chart review of the adult emergency department patients diagnosed with an acute PE between 2012 and 2016. A total of 128 patients diagnosed with RHS by CT who had received an ECHO during their hospitalization were included in the study. Descriptive statistics were run for the variables of interest. The majority of patients (101 patients) with reported findings of RHS on CT had similar findings on ECHO. In our cohort, a finding of enlarged right atrium (RA) on CT was 100% predictive of RHS diagnosis on ECHO, whereas having interventricular septal bowing alone on CT was the least predictive of RHS on subsequent ECHO (61%). The 2 remaining subgroups: right ventricle (RV) enlargement alone and RV enlargement with either interventricular septal bowing/hepatic vein blood reflux or both lies somewhere in between, with 80% of these patients showing strain on ECHO. We found that signs of RHS on CT are predictive of strain on an ECHO (78%) and RA enlargement in any combination was the most predictive finding of RHS on ECHO (100%). Future prospective randomized investigations are needed to confirm such findings.

Altered oesophageal mechanosensitivity of secondary peristalsis as a pathophysiological marker in patients with globus sensation.

OBJECTIVE: Secondary peristalsis is important for clearance of retained food bolus and refluxate from the oesophagus. We aimed to investigate whether patients with globus sensation have altered physiological characteristics of secondary peristalsis. DESIGN: Prospective case-controlled study SETTING: Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan. PARTICIPANTS: Seventeen globus patients and 18 healthy controls. MAIN OUTCOME MEASURES: After a baseline recording of primary peristalsis, secondary peristalsis was stimulated with slow and rapid mid-oesophageal injections of air. Distension thresholds and peristaltic activities of secondary peristalsis were analysed and compared between the patients and healthy controls. RESULTS: The threshold volume for generating secondary peristalsis during slow air distension did not differ between the patient and control groups (P = .55). The threshold volume for generating secondary peristalsis during rapid air distension was significantly greater in patients with globus than healthy controls (7.0 ± 0.9 vs 5.0 ± 0.3 mL, P = .04). Secondary peristalsis was triggered less frequently in globus patients as compared with healthy control after rapid air distension (40% [30%-65%] vs 60% [60%-83%], P = .001). There was no difference in any of peristaltic parameters for primary and secondary peristalsis between the groups. CONCLUSIONS: Our work identifies functional defects of oesophageal secondary peristalsis in patients with globus sensation and such defects are characterised with defective triggering of secondary peristalsis during rapid air distension. Whether current findings have therapeutic implication in the management of patients with globus sensation warrants further investigation.

Associations between cardiovascular disease and its risk factors with hearing loss-A cross-sectional analysis.

OBJECTIVES: To investigate the relationship between hearing loss and cardiovascular disease risk factors. DESIGN: Cross-sectional study. METHODS: Participants were recruited between May 2010 and December 2015 and answered a health and risk factor questionnaire. Physical and biochemical assessments were performed. SETTING: A community-based population. PARTICIPANTS: A total of 5107 participants born within the years 1946-1964 enrolled in the Busselton Healthy Ageing Study. MAIN OUTCOME MEASURES: Hearing was assessed behaviourally through the best ear pure-tone average (500, 1000, 2000, 4000 Hz), low-frequency average (250, 500, 1000 Hz) and high-frequency average (4000, 8000 Hz). Self-reported hearing loss, tinnitus and hyperacusis were assessed via questionnaire. Cardiovascular risk factors were assessed via a patient-completed questionnaire and objective measurements including blood pressure, body mass index, waist circumference, lipid profile and glycated haemoglobin. RESULTS: Of the participants, 54% were female, with the mean age of 58 years (range 45-69 years). Age, sex and family history of hearing loss were consistently strong determinants of hearing loss outcomes. After adjusting for these, obesity, current smoking, peripheral arterial disease and history of cardiovascular disease were significantly associated with pure-tone, low-frequency and high-frequency hearing loss. In addition, high blood pressure, triglyceride and glycated haemoglobin were significantly associated with low-frequency hearing loss. There was a graded association between hearing loss and Framingham Risk Score for cardiovascular risk (P<0.001). CONCLUSIONS: Established cardiovascular disease and individual and combined cardiovascular disease risk factors were found to be associated with hearing loss. Future research should prospectively investigate whether targeting cardiovascular disease can prevent hearing loss.

Physiological augmentation of esophageal distension pressure and peristalsis during conditions of increased esophageal emptying resistance.

BACKGROUND: Abdominal compression has been implemented as a provocative maneuver in high-resolution impedance manometry (HRIM) to "challenge" normal esophageal physiology with the aim of revealing abnormal motor patterns which may explain symptoms. In this study, we measured the effects of abdominal compression on esophageal functioning utilizing novel pressure-impedance parameters and attempted to identify differences between healthy controls and globus patients. METHODS: Twenty-two healthy volunteers (aged 23-32 years, 41% female) and 22 globus patients (aged 23-72 years, 68% female) were evaluated with HRIM using a 3.2-mm water perfused manometric and impedance catheter. All participants received 10 × 5 mL liquid swallows; healthy controls also received 10 × 5 mL liquid swallows with abdominal compression created using an inflatable cuff. All swallows were analyzed to assess esophageal pressure topography (EPT) and pressure-flow metrics, indicative of distension pressure, flow timing and bolus clearance were derived. KEY RESULTS: The effect of abdominal compression was shown as a greater contractile vigor of the distal esophagus by EPT and higher distension pressure based on pressure-flow metrics. Age and body mass index also increased contractile vigor and distension pressure. Globus patients were similar to controls. CONCLUSIONS AND INTERFERENCES: Intrabolus pressure and contractile vigor are indicative of the physiological modulation of bolus transport mechanisms. Provocative testing by abdominal compression induces changes in these esophageal bolus dynamics.

Upregulation of CYP17A1 by Sp1-mediated DNA demethylation confers temozolomide resistance through DHEA-mediated protection in glioma.

Steroidogenesis-mediated production of neurosteroids is important for brain homeostasis. Cytochrome P450 17A1 (CYP17A1), which converts pregnenolone to dehydroepiandrosterone (DHEA) in endocrine organs and the brain, is required for prostate cancer progression and acquired chemotherapeutic resistance. However, whether CYP17A1-mediated DHEA synthesis is involved in brain tumor malignancy, especially in glioma, the most prevalent brain tumor, is unknown. To investigate the role of CYP17A1 in glioma, we determined that CYP17A1 expression is significantly increased in gliomas, which secrete more DHEA than normal astrocytes. We found that as gliomas became more malignant, both CYP17A1 and DHEA were significantly upregulated in temozolomide (TMZ)-resistant cells and highly invasive cells. In particular, the increase of CYP17A1 was caused by Sp1-mediated DNA demethylation, whereby Sp1 competed with DNMT3a for binding to the CYP17A1 promoter in TMZ-resistant glioma cells. CYP17A1 was required for the development of glioma cell invasiveness and resistance to TMZ-induced cytotoxicity. In addition, DHEA markedly attenuated TMZ-induced DNA damage and apoptosis. Together, our results suggest that components of the Sp1-CYP17A1-DHEA axis, which promotes the development of TMZ resistance, may serve as potential biomarkers and therapeutic targets in recurrent glioma.

Hypoxic lung cancer-secreted exosomal miR-23a increased angiogenesis and vascular permeability by targeting prolyl hydroxylase and tight junction protein ZO-1.

Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions. Exosomal miR-23a directly suppressed its target prolyl hydroxylase 1 and 2 (PHD1 and 2), leading to the accumulation of hypoxia-inducible factor-1 α (HIF-1 α) in endothelial cells. Consequently, hypoxic lung cancer cells enhanced angiogenesis by exosomes derived from hypoxic cancer under both normoxic and hypoxic conditions. In addition, exosomal miR-23a also inhibits tight junction protein ZO-1, thereby increasing vascular permeability and cancer transendothelial migration. Inhibition of miR-23a by inhibitor administration decreased angiogenesis and tumour growth in a mouse model. Furthermore, elevated levels of circulating miR-23a are found in the sera of lung cancer patients, and miR-23a levels are positively correlated with proangiogenic activities. Taken together, our study reveals the clinical relevance and prognostic value of cancer-derived exosomal miR-23a under hypoxic conditions, and investigates a unique intercellular communication, mediated by cancer-derived exosomes, which modulates tumour vasculature.

EGF-mediated inhibition of ubiquitin-specific peptidase 24 expression has a crucial role in tumorigenesis.

In this study, several cancer-related proteins (Bax, p300, E2F4 and securin) have been proven to be substrates of ubiquitin-specific peptidase 24 (USP24), and relevance has been shown between USP24 and its substrates in samples from clinical lung cancer patients. Silencing USP24 increases the cancer formation by inhibiting cellular apoptosis and increasing cellular proliferation. Epidermal growth factor (EGF) treatment, and the KrasG12D and EGFRL858R mutations decrease USP24 protein stability via EGF- or CDK1-mediated phosphorylation at Ser1616, Ser2047 and Ser2604. Knockdown of USP24 decreases Bax and p300 levels, and reduces Ku70 acetylation, thereby preventing cancer cell apoptosis. In addition, knockdown of USP24 increases cell cycle progression by enhancing the G1-S transition and metaphase-anaphase transition. The molecular mechanism involves a decrease in the USP24 level, which reduces the expression of E2F4 and its partner TFDP1, and thus increases the G1/S transition. In conclusion, the USP24 level was decreased during the early stage of cancer and the mitotic stage of the cell cycle to regulate its substrates p300, Bax, E2F4 and securin, resulting in decreased cell apoptosis and increased cell cycle progression and, thus, cancer formation.