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Abstract Parkinson’s disease (PD) is a debilitating neurodegenerative disorder and its rising global incidence highlights the need for the identification of modifiable risk factors. In a gene-based burden test of rare variants (8647 PD cases and 777,693 controls) we discovered a novel association between loss-of-function variants in ITSN1 and PD. This association was further supported with burden data from the Neurodegenerative Disease Knowledge Portal and the Accelerating Medicines Partnership Parkinson’s Disease Knowledge Platform. Our findings show that Rho GTPases and disruptions in synaptic vesicle transport may be involved in the pathogenesis of PD, pointing to the possibility of novel therapeutic approaches.

Background Growing evidence indicates an association between disordered eating and a range of mental health problems, including anxiety, depression and emotional dysregulation. Aims This study aimed to explore whether reducing risk factors for eating disorders, such as body dissatisfaction and low self-esteem, through school-based programmes can enhance adolescent mental health. Method We searched PubMed, PsycINFO, EMBASE and Web of Science from the date of inception to 15 October 2023. Data were synthesised by using a systematic narrative synthesis framework, and formal assessments were conducted to assess the quality of the included studies. Results After title/abstract screening and full-text assessment, 13 articles met the pre-specified inclusion criteria, comprising a total of 14 studies (n = 5853). Notably, three studies encompassed multiple programmes, leading to the identification of 17 eating disorder prevention programmes. Among these programmes, seven (41%) employed dissonance-based approaches. Topics covered in the programmes included psychoeducation, body acceptance, sociocultural issues, nutrition and physical activities, self-esteem and stress coping. Ten (59%) of the programmes were effective in improving adolescent mental health. Six of the 14 studies (43%) did not specify follow-up time, and quality assessments found the majority to be of either high (five studies, 36%) or fair (eight studies, 57%) quality. Conclusions The findings from the ten effective programmes consistently support the use of body acceptance strategies in improving the mental health of adolescent students. Brief interventions delivered by trained, non-licensed facilitators appear good for the sustainable implementation of in-school psychological services to support well-being among adolescents.

Abstract Essential tremor (ET) is a prevalent neurological disorder with a largely unknown underlying biology. In this genome-wide association study meta-analysis, comprising 16,480 ET cases and 1,936,173 controls from seven datasets, we identify 12 sequence variants at 11 loci. Evaluating mRNA expression, splicing, plasma protein levels, and coding effects, we highlight seven putative causal genes at these loci, including CA3 and CPLX1. CA3 encodes Carbonic Anhydrase III and carbonic anhydrase inhibitors have been shown to decrease tremors. CPLX1, encoding Complexin-1, regulates neurotransmitter release. Through gene-set enrichment analysis, we identify a significant association with specific cell types, including dopaminergic and GABAergic neurons, as well as biological processes like Rho GTPase signaling. Genetic correlation analyses reveals a positive association between ET and Parkinson’s disease, depression, and anxiety-related phenotypes. This research uncovers risk loci, enhancing our knowledge of the complex genetics of this common but poorly understood disorder, and highlights CA3 and CPLX1 as potential therapeutic targets.

Abstract This study aimed to establish sex- and age-specific reference values for motor performance (MP) in Hong Kong preschoolers aged 3–5 years old and examine the relationship between MP and BMI status. A cross-sectional study was conducted among 5579 preschoolers in Hong Kong. Three MP tests were administered, and height and weight information were collected. GAMLSS was used to compute the normative values of the motor tests. Boys outperformed girls in activities requiring muscle strength and power, while girls outperformed boys in activities requiring balance and coordination. The MP scores increased with age for both overarm beanbag throw and standing long jump for both sexes, while the one-leg balance scores showed larger differences between P50 and P95 in older preschoolers. Children with excessive weight performed worse in standing long jump and one-leg balance compared to their healthy weight peers. This study provides valuable information on the MP of preschoolers in Hong Kong, including sex- and age-specific reference values and the association between BMI status and MP scores. These findings can serve as a reference for future studies and clinical practice and highlight the importance of promoting motor skill development in preschoolers, particularly those who are overweight or obese.

Abstract Background Despite the preventive policies adopted, reduction in sexually transmitted infections (STIs) among men who have sex with men (MSM) has been limited. The risk of hepatitis C virus (HCV) infection has increased among the most vulnerable population groups, including MSM. The aim of this study was to estimate the prevalence of HCV infection and to assess risky practices among MSM from 12 Brazilian cities. Methods This study was carried out from June to December 2016 using respondent driven sampling (RDS). Participants completed a self-administered questionnaire to collect behavioral, socioeconomic, and demographic variables. In addition, the rapid diagnostic test (RDT) for HCV was offered. Positive results were sent to Instituto Adolfo Lutz for confirmation. Results A total of 4,176 participants were recruited and 23 samples were sent for confirmation. Of these, 16 were confirmed, resulting in a prevalence of 0.7% (95% CI: 0.3%—1.7%). The Southeast region showed a prevalence of 0.9% (95% CI: 0.3—2.6), followed by the South region, with 0.6% (95% CI: 0.2—2.1). The Northeast region had a prevalence of 0.3% (95% CI: 0.1—1.0) and the Midwest 0.1% (95% CI: 0.0—0.7). No positive cases were found in the North. Single men aged 40 years or older were the majority of participants exposed to HCV. High levels of alcohol consumption, illicit drug use, irregular condom use, in addition to infection with other STIs, were associated with exposure to HCV. Conclusions STIs continue to be important health problems in Brazil and globally. Many STIs are inapparent for many years until they bring more serious consequences. Extra investment in HCV is also warranted, given that it can be eliminated. Relying solely on clinical data to provide information about inapparent infection, especially in stigmatized populations, will make that goal more difficult to achieve. Surveillance studies, such as the one reported here need to be repeated over time to demonstrate trends and to provide information for evaluation, program and policies. Investments in the most vulnerable populations are critical to achieve the World Health Organization global health goals including the elimination of viral hepatitis by 2030.

BackgroundEvidence supports the effectiveness of serious games in health education, but little is known about their effects on the psychosocial well-being of children in the general population. ObjectiveThis study aimed to investigate the potential of a mobile game–based safety education program in improving children’s safety and psychosocial outcomes. MethodsSafe City is a mobile roleplaying game specifically designed to educate children in Hong Kong about safety. This randomized controlled trial included 340 children in grades 4 through 6. Intervention arm participants (n=170) were instructed to play the Safe City mobile game for 4 weeks, whereas control arm participants (n=170) received a safety booklet. All participants completed a survey on safety knowledge and behaviors and psychosocial problems at baseline (T1), 1 month postintervention (T2), and 3 months postintervention (T3). Cumulative game scores and mini-game performance were analyzed as a proxy for the extent of exposure to the game. Outcome data were analyzed using 2-sample 2-tailed t tests to compare mean change from T1 to T2 and to T3 for intervention versus control arm participants. The association of game use with outcome changes postintervention was analyzed using generalized additive models. ResultsNo significant differences were found in mean changes between the intervention and control arms. However, use analyses showed that higher game scores were associated with improvements in safe behavior (P=.03) and internalizing problems (P=.01) at T3. Matching and Spot the Danger mini-game performance significantly predicted improvements in safety knowledge at T2 and T3. ConclusionsAnalysis of use has shown that playing the Safe City mobile game can result in significant improvements in safety knowledge and reductions in unsafe behavior and internalizing problems. These findings provide evidence for the positive impact of serious games on psychological and social well-being, highlighting the potential of technology-driven interventions to assist children in learning about safety and preventing injuries. Trial RegistrationClinicalTrials.org NCT04096196; https://clinicaltrials.gov/show/NCT04096196 International Registered Report Identifier (IRRID)RR2-10.2196/17756

Introduction: Vaccination against influenza is indicated in children at risk of complications or severe disease. The objective of this study was to describe the percentage of children aged less than 15 years with risk conditions vaccinated against influenza in the Community of Madrid, and to analyze the factors associated with adherence to vaccination throughout 3 vaccination campaigns. Materials and methods: Population-based cross-sectional observational study of children aged 6 months to 14 years with conditions that indicated influenza vaccination at the beginning of the 2018−2019 campaign. Electronic population registers were used. We described the percentage of children vaccinated in 3 consecutive campaigns, and assessed the association of adherence to vaccination with demographic and socioeconomic variables and risk conditions using bivariate and multivariate analysis. Results: The vaccination coverage was 15.6% in the 2018−2019 campaign. The adherence to vaccination was 65.9%. The variables associated with greater adherence were age greater than 2 years, especially in the 6−10 years group (aOR = 1.63; 95% CI, 1.43−1.85) and presenting more than one risk condition, especially 3 or more diseases (aOR = 1.80; 95% CI, 1.00−3.26). Diabetes mellitus was the disease associated most strongly with adherence (aOR = 2.15; 95% CI, 1.74–2.65). Adherence was lower in the immigrant population (aOR = 0.43; 95% CI, 0.36−0.51). We found no association between vaccination adherence and sex or socioeconomic status. Conclusions: Vaccination coverage and adherence were suboptimal. Adherence to vaccination against influenza is associated with demographic and clinical conditions. Strategies need to be established to increase vaccination in children, with greater involvement of professionals and education of parents. Resumen: Introducción: La vacunación antigripal está especialmente indicada en población infantil con riesgo de complicaciones o enfermedad grave. El objetivo de este estudio es describir el porcentaje de vacunación frente a la gripe en menores de 15 años con condiciones de riesgo en la Comunidad de Madrid, así como analizar los factores asociados a la adherencia vacunal a lo largo de tres campañas de vacunación. Material y métodos: Estudio observacional transversal de base poblacional de niños/as de 6 meses a 14 años y con condiciones de riesgo que fueran indicación de vacunación antigripal al inicio de la campaña 2018−2019. Se emplearon registros poblacionales electrónicos. Se describió el porcentaje de vacunados durante tres campañas consecutivas. Se analizó mediante análisis bivariado y multivariado la asociación de la adherencia vacunal con variables demográficas, socioeconómicas y condiciones de riesgo. Resultados: La cobertura vacunal fue del 15,6% en la campaña 2018−2019. La adherencia a la vacunación fue del 65,9%. Se asociaron a una mayor adherencia edad ≥3 años, fundamentalmente de 6−10 años (ORa = 1,63; IC 95% [1,43−1,85]) y presentar más de una condición de riesgo, especialmente ≥3 (ORa = 1,80; IC 95% [1,00–3,26]). Diabetes mellitus fue la enfermedad más asociada (ORa = 2,15; IC 95% [1,74−2,65]). Las personas extranjeras presentaron menor adherencia (ORa = 0,43; IC 95% [0,36−0,51]). No se encontraron diferencias en la adherencia según sexo ni nivel socioeconómico. Conclusiones: La adherencia y cobertura vacunal se encuentran en niveles subóptimos. La adherencia a la vacunación antigripal se asocia a características demográficas y clínicas. Es necesario establecer estrategias para incrementar la vacunación en población infantil, con mayor implicación de profesionales y formación de progenitores.

The evaluation of different methods for kafirin extraction was made to obtain techno-functional concentrates from two sorghum cultivars. The concentrates were rheologically evaluated in a “dough-like” resin system to assess their potential as a gluten substitute. Under acidic extractions (ethanol 70%, pH 2.5), yields of 56.98% and 46.31% for white (WS) and red sorghum (RS) were obtained, with the highest purity for WS (74.54%). A characteristic electrophoretic pattern was obtained for kafirins, including fractions α1, α2, β and γ. The WS protein was used to prepare resins with lactic acid (LA) as a plasticizing agent, showing similar extensibility to zein (11.37 vs. 11.89 mm respectively) but below wheat gluten (42.61 mm). The microstructure of kafirin resins showed air encapsulation and alignment as fibers. This study allowed to explore new food-compatible extractions for kafirin and evaluate how they will perform rheologically at the kneading stage using a simple resin method.

Abstract Background The prevalence and consequences of child maltreatment are alarming, but evidence from studies with long follow-up intervals are limited. This study examined the long-term consequences of child maltreatment in relation to age of onset and follow-up interval. Methods The exposed group comprised 63 individuals (aged 13–34 years) with a first-time diagnosis of child maltreatment between 2001 and 2010, whereas the unexposed group comprised 63 individuals who were matched upon gender, age of onset, follow-up period, and poverty status at the index hospital admission but had no medical records of maltreatment in Hong Kong. The participants completed a set of questionnaires on executive functions and mental health and provided blood samples for measurement of IL-6 and IL-10 levels during a health assessment session. Results Compared with the unexposed group, the exposed group reported poorer maternal care during childhood (β = −4.64, p

Abstract There has been a lack of high-quality evidence concerning the association between childhood maltreatment and psychiatric diagnoses particularly for Axis II disorders. This study aimed to examine the association between childhood maltreatment exposure and Axis I and Axis II psychiatry disorders using electronic health records. In this study, the exposed group (n = 7473) comprised patients aged 0 to 19 years with a first-time record of maltreatment episode between January 1, 2001 and December 31, 2010, whereas the unexposed group (n = 26,834) comprised individuals of the same gender and age who were admitted into the same hospital in the same calendar year and month but had no records of maltreatment in the Hong Kong Clinical Data Analysis and Reporting System (CDARS). Data on their psychiatric diagnoses recorded from the date of admission to January 31, 2019 were extracted. A Cox proportional hazard regression model was fitted to estimate the hazard ratio (HR, plus 95% CIs) between childhood maltreatment exposure and psychiatric diagnoses, adjusting for age at index visit, sex, and government welfare recipient status. Results showed that childhood maltreatment exposure was significantly associated with subsequent diagnosis of conduct disorder/ oppositional defiant disorder (adjusted HR, 10.99 [95% CI 6.36, 19.01]), attention deficit hyperactivity disorder (ADHD) (7.28 [5.49, 9.65]), and personality disorders (5.36 [3.78, 7.59]). The risk of psychiatric disorders following childhood maltreatment did not vary by history of childhood sexual abuse, age at maltreatment exposure, and gender. Individuals with a history of childhood maltreatment are vulnerable to psychiatric disorders. Findings support the provision of integrated care within the primary health care setting to address the long-term medical and psychosocial needs of individuals with a history of childhood maltreatment.

Abstract The graded association between family socioeconomic status (SES) and physical fitness is evident, but little is known about the mechanism underlying this association. This study investigated the role of early-life activities as mediators of the longitudinal relationship between early-life SES and health-related physical fitness in 168 adolescents (51.2% boys; final mean age: 12.4 years old). In Wave 1 (2011–12), their parents completed questionnaires about family socioeconomic status (SES), parent–child activities, and child screen time. In Wave 2 (2014–15), participants’ physical activity levels were assessed through parent proxy-reports. In Wave 3 (2018–19), a direct assessment of handgrip strength, standing long-jump, and 6-min walk test (6MWT) performance was conducted. After controlling for demographic factors, results of mediation analyses revealed that (a) Wave 1 SES predicted Wave 3 long-jump and 6MWT performance; (b) child physical activity level in Wave 2 mediated the relation between Wave 1 SES and standing long-jump performance in Wave 3; and (c) recreational parent–child activities and child screen time in wave 1 mediated the relation between Wave 1 SES and 6MWT performance in Wave 3. Our findings suggest that the type and frequency of early-life activities play a role in the graded association between childhood SES and physical fitness in adolescence.

Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.

BackgroundInjury is an increasingly pressing global health issue. An effective surveillance system is required to monitor the trends and burden of injuries. ObjectiveThis study aimed to identify a set of valid and context-specific injury indicators to facilitate the establishment of an injury surveillance program in Hong Kong. MethodsThis development of indicators adopted a multiphased modified Delphi research design. A literature search was conducted on academic databases using injury-related search terms in various combinations. A list of potential indicators was sent to a panel of experts from various backgrounds to rate the validity and context-specificity of these indicators. Local hospital data on the selected core indicators were used to examine their applicability in the context of Hong Kong. ResultsWe reviewed 142 articles and identified 55 indicators, which were classified into 4 domains. On the basis of the ratings by the expert panel, 13 indicators were selected as core indicators because of their good validity and high relevance to the local context. Among these indicators, 10 were from the construct of health care service use, and 3 were from the construct of postdischarge outcomes. Regression analyses of local hospitalization data showed that the Hong Kong Safe Community certification status had no association with 5 core indicators (admission to intensive care unit, mortality rate, length of intensive care unit stay, need for a rehabilitation facility, and long-term behavioral and emotional outcomes), negative associations with 4 core indicators (operative intervention, infection rate, length of hospitalization, and disability-adjusted life years), and positive associations with the remaining 4 core indicators (attendance to accident and emergency department, discharge rate, suicide rate, and hospitalization rate after attending the accident and emergency department). These results confirmed the validity of the selected core indicators for the quantification of injury burden and evaluation of injury-related services, although some indicators may better measure the consequences of severe injuries. ConclusionsThis study developed a set of injury outcome indicators that would be useful for monitoring injury trends and burdens in Hong Kong.

Abstract Background Existing studies on health-related quality of life (HRQoL) mainly covered single growth stages of childhood or adolescence and did not report on the trends in the relationships of HRQoL with sleep duration, physical activity, and screen time. This study aimed to establish the population norm of HRQoL in children and adolescents aged 6–17 years and examine the associations of screen time, sleep duration, and physical activity with HRQoL in this population. Methods We conducted a large-scale cross-sectional population-based survey study of Hong Kong children and adolescents aged 6 to 17 years. A representative sample of students were interviewed to assess their HRQoL using PedsQL and EQ-5D-Y-5L. Multivariable homoscedastic Tobit regression with linear form or restricted cubic spline of predictors was used to analyze the associations between screen time, sleep duration, and HRQoL. Multiple imputation by chained equations was performed to deal with missing data. Results A total of 7555 respondents (mean age 11.5, SD 3.2; 55.1% female) were sampled. Their EQ VAS scores, PedsQL physical summary scores, and psychosocial summary scores were positively correlated with sleep duration and moderate/vigorous activity but was negatively correlated with screen time. Conclusions Children and adolescents who had longer exposure to screen, shorter sleep duration, and lower physical activity levels appeared to have poorer HRQoL as assessed by PedsQL and EQ-5D-Y-5L. Advice and guidance on screen time allocation for children and adolescents should be provided at the levels of school, community, and family.

Hepatitis B virus (HBV) is a global public health problem and requires specific prevention actions, particularly focusing on the key populations, such as men who have sex with men (MSM). We aimed at assessing the prevalence of HBV infection, among MSM, in a multicity study in Brazil. In 2016, we conducted a survey using a respondent-driven sampling methodology in 12 Brazilian cities. Rapid tests (RT) were performed on 3178 samples from those MSM. Positive results were tested for HBV DNA and sequenced. If negative for HBV DNA, samples were tested for serological markers. The prevalence rate of HBV exposure and clearance was 10.1% (95% CI: 8.1–12.6), and 1.1% (95%; CI: 0.6–2.1) were confirmed to be HBsAg-positive. Of those samples tested for anti-HBs (n = 1033), only 74.4% presented a serological profile analogous to that elicited by hepatitis B vaccination. Among HBsAg-positive samples (n = 29), 72.4% were HBV DNA-positive, and from these, 18 were sequenced. HBV genotypes A, F, and G were found in 55.5%, 38.9%, and 5.6%, respectively. This study indicates high prevalence rates of MSM HBV exposure and a low positivity index for the serological marker of HBV vaccine immunity. These findings may contribute to the discussion of strategies to prevent hepatitis B and reinforce the importance of promoting HBV vaccination in this key population.

Tumor Treating Fields (TTFields) were incorporated into the treatment of glioblastoma, the most malignant brain tumor, after showing an effect on progression-free and overall survival in a phase III clinical trial. The combination of TTFields and an antimitotic drug might further improve this approach. Here, we tested the combination of TTFields with AZD1152, an Aurora B kinase inhibitor, in primary cultures of newly diagnosed (ndGBM) and recurrent glioblastoma (rGBM). AZD1152 concentration was titrated for each cell line and 5–30 nM were used alone or in addition to TTFields (1.6 V/cm RMS; 200 kHz) applied for 72 h using the inovitro™ system. Cell morphological changes were visualized by conventional and confocal laser microscopy. The cytotoxic effects were determined by cell viability assays. Primary cultures of ndGBM and rGBM varied in p53 mutational status; ploidy; EGFR expression and MGMT-promoter methylation status. Nevertheless; in all primary cultures; a significant cytotoxic effect was found following TTFields treatment alone and in all but one, a significant effect after treatment with AZD1152 alone was also observed. Moreover, in all primary cultures the combined treatment had the most pronounced cytotoxic effect in parallel with morphological changes. The combined treatment of TTFields and AZD1152 led to a significant reduction in the number of ndGBM and rGBM cells compared to each treatment alone. Further evaluation of this approach, which has to be considered as a proof of concept, is warranted, before entering into early clinical trials.

Abstract Quantification of injury burden is vital for injury prevention, as it provides a guide for setting policies and priorities. This study generated a set of Hong Kong specific disability weights (DWs) derived from patient experiences and hospital records. Patients were recruited from the Accident and Emergency Department (AED) of three major trauma centers in Hong Kong between September 2014 and December 2015 and subsequently interviewed with a focus on health-related quality of life at most three times over a 12-month period. These patient-reported data were then used for estimation of DWs. The burden of injury was determined using the mortality and inpatient data from 2001 to 2012 and then compared with those reported in the UK Burden of Injury (UKBOI) and global burden of diseases (GBD) studies. There were 22,856 mortality cases and 817,953 morbidity cases caused by injuries, in total contributing to 1,027,641 disability-adjusted life years (DALYs) in the 12-year study timeframe. Estimates for DALYs per 100,000 in Hong Kong amounted to 1192, compared with 2924 in UKBOI and 3459 in GBD. Our findings support the use of multiple data sources including patient-reported data and hospital records for estimation of injury burden.

Nowadays, dairy products, especially fermented products such as yogurt, fromage frais, sour cream and custard, are among the most studied foods through tribological analysis due to their semi-solid appearance and close relationship with attributes like smoothness, creaminess and astringency. In tribology, dairy products are used to provide information about the friction coefficient (CoF) generated between tongue, palate, and teeth through the construction of a Stribeck curve. This provides important information about the relationship between friction, food composition, and sensory attributes and can be influenced by many factors, such as the type of surface, tribometer, and whether saliva interaction is contemplated. This work will review the most recent and relevant information on tribological studies, challenges, opportunity areas, saliva interactions with dairy proteins, and their relation to dairy product sensory.

Compounds with either ionone or chalcone skeletons present many biological properties including anticancer activity. Here we have prepared eight terpenoid-like chalcones in order to assess whether hybrid compounds with both structural frameworks could exhibit enhanced pharmacological profile. The terpenoid-like chalcones were synthesized by means of Claisen–Schmidt condensation reaction, using either α- or β-ionone with substituted benzaldehydes. The structure of six derivatives was elucidated by single crystal X-ray diffraction technique for the first time. Cyclohexene ring adopts half-chair conformation in α-ionone-derived chalcone with quaternary carbon at the flap, while twist puckering was observed in β-ionone terpenoid-like chalcones. All prepared compounds were tested for their cytotoxic activity against three cancer cell lines, namely SF-295, HCT-116 and OVCAR-8, which allowed us to establish some structure–activity relationships. Terpenoid-like chalcones with nitro substituted phenyl rings, regardless of its position and ionone type, were the most active chalcones among all that tested. The IC50 values do also reveal a trend of decrease in cytotoxic activity with weak electron-withdrawing groups at phenyl ring. Keywords: Claisen–Schmidt condensation, Crystal structure, X-ray diffraction, Cytotoxic activity, Antitumor compounds

The immune response must balance the pro-inflammatory, cell-mediated cytotoxicity with the anti-inflammatory and wound repair response. Epigenetic mechanisms mediate this balance and limit host immunity from inducing exuberant collateral damage to host tissue after severe and chronic infections. However, following treatment for these infections, including sepsis, pneumonia, hepatitis B, hepatitis C, HIV, tuberculosis (TB) or schistosomiasis, detrimental epigenetic scars persist, and result in long-lasting immune suppression. This is hypothesized to be one of the contributing mechanisms explaining why survivors of infection have increased all-cause mortality and increased rates of unrelated secondary infections. The mechanisms that induce epigenetic-mediated immune suppression have been demonstrated in-vitro and in animal models. Modulation of the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR), nuclear factor of activated T cells (NFAT) or nuclear receptor (NR4A) pathways is able to block or reverse the development of detrimental epigenetic scars. Similarly, drugs that directly modify epigenetic enzymes, such as those that inhibit histone deacetylases (HDAC) inhibitors, DNA hypomethylating agents or modifiers of the Nucleosome Remodeling and DNA methylation (NuRD) complex or Polycomb Repressive Complex (PRC) have demonstrated capacity to restore host immunity in the setting of cancer-, LCMV- or murine sepsis-induced epigenetic-mediated immune suppression. A third clinically feasible strategy for reversing detrimental epigenetic scars includes bioengineering approaches to either directly reverse the detrimental epigenetic marks or to modify the epigenetic enzymes or transcription factors that induce detrimental epigenetic scars. Each of these approaches, alone or in combination, have ablated or reversed detrimental epigenetic marks in in-vitro or in animal models; translational studies are now required to evaluate clinical applicability.

Objectives Data linkage of cohort-based data and electronic health records (EHRs) has been practised in many countries, but in Hong Kong there is still a lack of such research. To expand the use of multisource data, we aimed to identify a feasible way of linking two cohorts with EHRs in Hong Kong.Methods Participants in the ‘Children of 1997’ birth cohort and the Chinese Early Development Instrument (CEDI) cohort were separated into several batches. The Hong Kong Identity Card Numbers (HKIDs) of each batch were then uploaded to the Hong Kong Clinical Data Analysis and Reporting System (CDARS) to retrieve EHRs. Within the same batch, each participant has a unique combination of date of birth and sex which can then be used for exact matching, as no HKID will be returned from CDARS. Raw data collected for the two cohorts were checked for the mismatched cases. After the matching, we conducted a simple descriptive analysis of attention deficit hyperactivity disorder (ADHD) information collected in the CEDI cohort via the Strengths and Weaknesses of ADHD Symptoms and Normal Behaviour Scale (SWAN) and EHRs.Results In total, 3473 and 910 HKIDs in the birth cohort and CEDI cohort were separated into 44 and 5 batches, respectively, and then submitted to the CDARS, with 100% and 97% being valid HKIDs respectively. The match rates were confirmed to be 100% and 99.75% after checking the cohort data. From our illustration using the ADHD information in the CEDI cohort, 36 (4.47%) individuals had ADHD–Combined score over the clinical cut-off in the SWAN survey, and 68 (8.31%) individuals had ADHD records in EHRs.Conclusions Using date of birth and sex as identifiable variables, we were able to link the cohort data and EHRs with high match rates. This method will assist in the generation of databases for future multidisciplinary research using both cohort data and EHRs.

Vitamin D is essential for human health. However, it is not clear if vitamin D supplementation is necessary for all pregnant women. This study examines the relative importance of dietary patterns and vitamin D supplementation frequency in determining serum 25-hydroxyvitamin D (25(OH)D) and ferritin concentrations among pregnant women in Hong Kong, China. A total of 572 healthy women were recruited from antenatal clinics at 25–35 weeks pregnant. Participants completed an electronic version of the food frequency questionnaire and a web questionnaire on supplement use. Their blood samples were tested for serum 25(OH)D and ferritin. The associations of dietary patterns and vitamin D supplementation frequency with serum 25(OH)D and ferritin concentrations were analyzed using moderated hierarchical regression. Two dietary patterns were identified. The adequate dietary intake was characterized by the high probability of meeting recommended daily food group servings, whereas the inadequate dietary intake was characterized by inadequate consumption of vegetables, fruits, meat, fish, and eggs, or alternatives. The association between adequate dietary intake and serum ferritin concentrations was independent of vitamin D supplementation frequency (β = 0.05, p = 0.035), but dietary patterns interacted with vitamin D supplementation frequency to determine serum 25(OH)D concentrations (β = −13.22, p = 0.014). The current study presents evidence on the relative importance of dietary patterns and vitamin D supplementation in maintaining sufficient vitamin D and iron in pregnancy. Antenatal nutrition counselling services should be provided to pregnant women who show signs of inadequate dietary intake.

The evidence as to whether caffeine consumption is beneficial or harmful to human health has been mixed. This study aimed to examine the effect of 25-hydroxyvitamin D (25(OH)D) concentration on the association between caffeine consumption and mineral metabolism in pregnant women. This is a cross-sectional study involving pregnant women at their 25th to 35th gestational week recruited at antenatal clinics in the period of July 2019 to December 2020. Peripheral blood samples were collected to determine their total 25(OH)D, albumin, alkaline phosphatase (ALP), calcium, phosphate, and ferritin level in serum. Questionnaires on demographics and dietary intake were also administered. Among 181 pregnant women recruited (Average age = 32.9 years), 50 (27.6%) of them were found to be vitamin D insufficient (25(OH)D concentration < 75 nmol/L), and 131 (72.4%) were vitamin D sufficient (25(OH)D concentration ≥ 75 nmol/L). Adjusted regression models identified an association between higher caffeine intake and lower ALP level only among vitamin D-sufficient pregnant women (β = −0.24, p = 0.006), but not in those with insufficient vitamin D (β = −0.02, p = 0.912). The findings provide new insights into 25(OH)D concentration as a potential modifier of the health effects of caffeine consumption during pregnancy.

Haematological and immunological data of children with COVID-19 infection is lacking. Between 21st January and 20th March 2020, 244 children who were confirmed to have COVID-19 infection and admitted to the Wuhan Children's Hospital, China were retrospectively reviewed. 193 children were considered as symptomatic, which was defined as having either the presence of clinical symptoms or the presence of CT thorax abnormalities. Their haematological and immunological profiles, including complete blood counts, lymphocyte subsets (T, B and NK cell counts), immunoglobulin (Ig) profiles (IgG, IgA and IgM) and cytokine profiles were analysed and compared between the symptomatic and asymptomatic groups. The median values and the interquartile ranges were calculated. Comparison was made using the Mann–Whitney U test. Children with symptomatic COVID-19 infection had significantly lower haemoglobin levels, but higher absolute lymphocyte and monocyte counts, IgG and IgA levels, as well as interleukin 6 (IL-6), IL-10, tumour necrosis factor alpha and interferon gamma levels. The obtained data will be utilized for further studies in comparing children and adults with COVID-19 infections in other parts of the world and with different severity .

Abstract The objectives of this study were to (a) investigate the spray drift potential of dicamba (3,6‐dichloro‐2‐methoxybenzoic acid) formulations with different nozzles in a low‐speed wind tunnel and (b) evaluate the effects of sublethal rates of dicamba‐containing formulations on non–dicamba‐tolerant (DT) soybean [Glycine max (L.) Merr.] cultivars. The dicamba formulations used were diglycolamine (DGA), N,N‐Bis‐(3‐aminopropyl)methylamine, and diglycolamine with VaporGrip (DGAvg). The wind tunnel drift study was conducted with these three dicamba formulations, two nozzle types (AIXR110015 and TTI110015), and five downwind distances from the nozzle (1, 2, 4, 8, and 12 m). The dicamba rate was 560 g ae ha−1, simulating a 140 L ha−1 carrier volume. The soybean exposure study was conducted in two experimental runs with three sublethal dicamba rates (0.112, 0.56, and 5.6 g ae ha−1), the three dicamba formulations aforementioned, and five non‐DT soybean cultivars (Asgrow A3253, Asgrow AG2636, Credenz CZ2601LL, DynaGro 39RY25, and Hoegemeyer 2511NRR). Applications were made using a spray chamber with a single AI9502EVS even nozzle that delivered 140 L ha−1. During applications, soybean plants were at three‐leaf growth stage. Dicamba formulations had different drift deposition across the AIXR and TTI nozzles. The soybean cultivars had different levels of sensitivity to dicamba and depended on rate vs. formulation interaction. The DGA caused greater biomass reduction on soybean cultivars compared with DGAvg, especially for Credenz CZ2601LL, which was one of the most dicamba‐sensitive cultivars along with Hoegemeyer 2511NRR. Additional care must be taken to mitigate off‐target movement from dicamba applications with these cultivars nearby.

Zika virus (ZIKV) can persist for months in semen and sperm. Here, the authors show that germ cells, compared to other cell types in the reproductive tract, are most susceptible to ZIKV and produce high levels of progeny virus, which coincides with decreased expression of the interferon-stimulated gene Ifi44l.

Abstract Background Tumor Treating Fields (TTFields) are an anti-neoplastic treatment modality delivered via application of alternating electric fields using insulated transducer arrays placed directly on the skin in the region surrounding the tumor. A Phase 3 clinical trial has demonstrated the effectiveness of continuous TTFields application in patients with glioblastoma during maintenance treatment with Temozolomide. The goal of this study was to evaluate the efficacy of combining TTFields with radiation treatment (RT) in glioma cells. We also examined the effect of TTFields transducer arrays on RT distribution in a phantom model and the impact on rat skin toxicity. Methods The efficacy of TTFields application after induction of DNA damage by RT or bleomycin was tested in U-118 MG and LN-18 glioma cells. The alkaline comet assay was used to measure repair of DNA lesions. Repair of DNA double strand breaks (DSBs) were assessed by analyzing γH2AX or Rad51 foci. DNA damage and repair signaled by the activation pattern of phospho-ATM (pS1981) and phospho-DNA-PKcs (pS2056) was evaluated by immunoblotting. The absorption of the RT energy by transducer arrays was measured by applying RT through arrays placed on a solid-state phantom. Skin toxicities were tested in rats irradiated daily through the arrays with 2Gy (total dose of 20Gy). Results TTFields synergistically enhanced the efficacy of RT in glioma cells. Application of TTFields to irradiated cells impaired repair of irradiation- or chemically-induced DNA damage, possibly by blocking homologous recombination repair. Transducer arrays presence caused a minor reduction in RT intensity at 20 mm and 60 mm below the arrays, but led to a significant increase in RT dosage at the phantom surface jeopardizing the “skin sparing effect”. Nevertheless, transducer arrays placed on the rat skin during RT did not lead to additional skin reactions. Conclusions Administration of TTFields after RT increases glioma cells treatment efficacy possibly by inhibition of DNA damage repair. These preclinical results support the application of TTFields therapy immediately after RT as a viable regimen to enhance RT outcome. Phantom measurements and animal models imply that it may be possible to leave the transducer arrays in place during RT without increasing skin toxicities.

Early childbearing is associated with high maternal stress and family violence. However, the long-term effects of rapid repeat pregnancy (RRP) in young motherhood on child outcomes remain largely unknown. This study examined the pathways between maternal RRP at young ages and child psychosocial problems and emergency room visits in later years. A total of 232 Chinese mother-child dyads provided baseline data in 2015 (Time 1; T1) and follow-up data 6 years later in 2021 (Time 2; T2). At T1, mothers completed questionnaires about child physical abuse frequency and family cohesion and reported their own stress levels. At T2, mothers were re-surveyed with the same questionnaires about child physical abuse frequency and family cohesion. Children's psychosocial problems were assessed through parent proxy-reports and records of emergency room visits were retrieved from hospital databases. After adjusting for demographic information, maternal history of RRP was associated with child physical abuse at T1 ([beta] = 0.15, p < 0.05) and in turn linked to child physical abuse recurrence ([beta] = 0.22, p < 0.01) and emergency room visits at T2 ([beta] = 0.22, p < 0.001). Improved family cohesion over time did not break the link between maternal RRP and child physical abuse recurrence. Poor family dynamics can lead to child physical abuse recurrence and worsen developmental outcomes in children, particularly when coupled with other risk factors such as maternal RRP at young ages. Early interventions to enhance support and reduce vulnerabilities are important for preventing child physical abuse in at-risk families.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, the implementation of social distancing and home confinement measures may elevate the risk of vitamin D deficiency particularly for infants. This study aimed to quantify changes in vitamin D level among infants and toddlers in Hong Kong after the COVID-19 outbreak. Methods: We recruited 303 infants and toddlers aged 2–24 months by stratified random sampling from 1 June 2019 to November 30, 2020. Regression models were used to estimate the effect of time on infants’ serum 25-hydroxyvitamin D (25(OH)D) level overall and by age groups before and after the outbreak. Interrupted time series (ITS) analysis was performed to examine the sustained effect of COVID-19 on their serum 25(OH)D level. Results: The ITS results showed no immediate reduction in serum 25(OH)D level among infants, but a decreasing trend was observed in the subsequent months post-outbreak at a monthly decline rate of −6.32 nmol/L. When analyzed by age group, the magnitude of post-outbreak reduction in 25(OH)D was stronger among younger infants (aged 2–6 months). Conclusion: Guidelines and recommendations should be given to pregnant women and mothers to ensure sufficient vitamin D level in their infants during the COVID-19 period.

Recent evidence suggests that breastfeeding may increase the risk of vitamin D deficiency in offspring. However, it is unclear whether increased risk results from breastfeeding alone, or whether it is associated together with other risk factors. This study surveyed 208 infant–mother dyads recruited by stratified random sampling in different districts of Hong Kong. Mothers were asked to complete a questionnaire on their demographics, history of risk behavior, and feeding practices. Peripheral blood samples were collected from infants to determine their vitamin D status. Among all infant participants, 70 were vitamin D insufficient or deficient. Being breastfed, being a girl, having a multiparous mother, and the use of sun cream were found to be the strongest risk factors for vitamin D insufficiency during infancy (all p < 0.05), after mutual adjustment. The cumulative risk model displayed a dose–response pattern between the number of risk factors and the risk of vitamin D insufficiency during this period. Our findings indicate the risk profile of infants with insufficient vitamin D. Guidelines and recommendations on healthy diet and lifestyle should be provided to mothers during the early stage of pregnancy to increase the likelihood of adequate levels of vitamin D in their offspring.

Everyday conversation requires listeners to quickly recognize verbal actions, so-called speech acts, from the underspecified linguistic code and prepare a relevant response within the tight time constraints of turn-taking. The goal of this study was to determine the time-course of speech act recognition by investigating oscillatory EEG activity during comprehension of spoken dialog. Participants listened to short, spoken dialogs with target utterances that delivered three distinct speech acts (Answers, Declinations, Pre-offers). The targets were identical across conditions at lexico-syntactic and phonetic/prosodic levels but differed in the pragmatic interpretation of the speech act performed. Speech act comprehension was associated with reduced power in the alpha/beta bands just prior to Declination speech acts, relative to Answers and Pre-offers. In addition, we observed reduced power in the theta band during the beginning of Declinations, relative to Answers. Based on the role of alpha and beta desynchronization in anticipatory processes, the results are taken to indicate that anticipation plays a role in speech act recognition. Anticipation of speech acts could be critical for efficient turn-taking, allowing interactants to quickly recognize speech acts and respond within the tight time frame characteristic of conversation. The results show that anticipatory processes can be triggered by the characteristics of the interaction, including the speech act type.

ABSTRACT Studies on age and growth of fish populations have direct application in fisheries and contribute for policies of conservation. Our aim was update information on the Micropogonias furnieri growth parameters based on sagittae otoliths annulis readings, and we expected that the studied population from Southeast Brazil can reach more longevity than the reported in the available literature. We examined 286 individuals between August-2010 and July-2011 from Ubatuba Bay, SP. The Total Length ranged 200-480 mm. The determined growth parameters were: Males, L∞ =523.4mm, k = 0.05×year-1, t0 = -8.78 year; Females L∞ = 573.5mm, k = 0.06 × year-1, t0 = -7.49 year. The MI and % of edge type evidenced the formation of one ring per year during autumn/winter, coinciding with low temperature and low growth rate. These results differed from those reported for the Vazzoler’s Population I (summer), and we detected higher longevity (45-48 years) as compared with the recorded in the available information.

The buffy coat is obtained routinely for disseminated histoplamosis (DH) diagnosis in Ceará, Brazil. The aim of this study is to describe the accuracy of staining smears for Histoplasma in the buffy coat of AIDS-patients with DH. From 2012−2013, all results of stained buffy coat smears and culture for fungi performed at São José Hospital were recorded. In total, 489 buffy coats of 361 patients were studied; 19/361 (5.3%; 95%CI = 2.9−7.6%) had positive direct examination stained smears for Histoplasma and 61/361 (16.9%; 95%CI = 13.0−20.8%) had growth in culture. For those with positive Histoplasma cultures, the CD4 count was significantly lower (139.3 vs. 191.7cells/µL; p = 0.014) than others, and death was 18%. The sensitivity and specificity of stained smears was 25.9% and 100%, respectively. A second test, performed up to 36 days from the first one, increased the sensitivity of stained smears to 32.2%. Stained smears of buffy coat have low accuracy; nonetheless, they are easy to perform and can give a quick diagnosis in low-resource endemic areas. Despite the decrease in mortality, it is not yet to the low levels observed in areas that have better and more efficient methods.

The ability to recognize speech acts (verbal actions) in conversation is critical for everyday interaction. However, utterances are often underspecified for the speech act they perform, requiring listeners to rely on the context to recognize the action. The goal of this study was to investigate the time-course of auditory speech act recognition in action-underspecified utterances and explore how sequential context (the prior action) impacts this process. We hypothesized that speech acts are recognized early in the utterance to allow for quick transitions between turns in conversation. Event-related potentials (ERPs) were recorded while participants listened to spoken dialogues and performed an action categorization task. The dialogues contained target utterances that each of which could deliver three distinct speech acts depending on the prior turn. The targets were identical across conditions, but differed in the type of speech act performed and how it fit into the larger action sequence. The ERP results show an early effect of action type, reflected by frontal positivities as early as 200 ms after target utterance onset. This indicates that speech act recognition begins early in the turn when the utterance has only been partially processed. Providing further support for early speech act recognition, actions in highly constraining contexts did not elicit an ERP effect to the utterance-final word. We take this to show that listeners can recognize the action before the final word through predictions at the speech act level. However, additional processing based on the complete utterance is required in more complex actions, as reflected by a posterior negativity at the final word when the speech act is in a less constraining context and a new action sequence is initiated. These findings demonstrate that sentence comprehension in conversational contexts crucially involves recognition of verbal action which begins as soon as it can.