Effects of Virtual Reality on Pain and Anxiety During Children's Circumcision: A Systematic Review and Meta-Analysis.

BACKGROUND: Circumcision-a common pediatric procedure-can cause significant pain and anxiety. Virtual reality has been proposed as a nonpharmacological intervention to alleviate these negative experiences. OBJECTIVE: This systematic review and meta-analysis was conducted to evaluate the effects of virtual reality interventions on pain and anxiety in children undergoing circumcision. METHODS: This study comprehensively searched PubMed, Embase, and Cochrane Library for articles published from database inception to October 2, 2023. Randomized controlled trials that investigated the effects of virtual reality interventions on pain and anxiety during circumcision in children were included. The Cochrane risk-of-bias tool was used to appraise the included studies. The primary outcomes were pain and anxiety scores. RESULTS: Three randomized controlled trials and four data sets involving a total of 224 children were included in our meta-analysis. Virtual reality interventions significantly reduced children's pain and anxiety scores. CONCLUSIONS: Virtual reality interventions are promising nonpharmacological strategies for alleviating children's pain and anxiety during circumcision. Pediatric healthcare professionals use virtual reality interventions to create a child-friendly and healthy healthcare environment.

Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions.

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.

Interpretable Predicting Creep Rupture Life of Superalloys: Enhanced by Domain-Specific Knowledge.

Evaluating and understanding the effect of manufacturing processes on the creep performance in superalloys poses a significant challenge due to the intricate composition involved. This study presents a machine-learning strategy capable of evaluating the effect of the heat treatment process on the creep performance of superalloys and predicting creep rupture life with high accuracy. This approach integrates classification and regression models with domain-specific knowledge. The physical constraints lead to significantly enhanced prediction accuracy of the classification and regression models. Moreover, the heat treatment process is evaluated as the most important descriptor by integrating machine learning with superalloy creep theory. The heat treatment design of Waspaloy alloy is used as the experimental validation. The improved heat treatment leads to a significant enhancement in creep performance (5.5 times higher than the previous study). The research provides novel insights for enhancing the precision of predicting creep rupture life in superalloys, with the potential to broaden its applicability to the study of the effects of heat treatment processes on other properties. Furthermore, it offers auxiliary support for the utilization of machine learning in the design of heat treatment processes of superalloys.

Trajectories of sleep quality and depressive symptoms in women from pregnancy to 3 months postpartum: a prospective cohort study.

Sleep quality and depression during pregnancy often affect women's adaptation to motherhood and are linked with adverse maternal and neonatal outcomes. Using a prospective cohort study comprising 190 pregnant women in central Taiwan, we investigated the trajectories of sleep quality and depressive symptoms and their associated predictors in perinatal women from pregnancy to postpartum. Sleep and depressive symptoms were assessed using the Pittsburgh Sleep Quality Index and the Edinburgh Postnatal Depression Scale, respectively, from mid-pregnancy to 3 months postpartum. We used group-based trajectory modelling and logistic regression modelling to analyse the data collected from the structured questionnaires. Pregnant women (50.5% primipara) with a mean (standard deviation) age of 32.3 (4.1) years were included. We identified three distinctive classes of sleep quality trajectories during the perinatal period: 'stable good' (18.4%), 'increasing poor' (48.9%), and 'stable poor' (32.6%). We further detected three stable trajectories of depressive symptoms: 'stable low' (36.3%), 'stable mild' (42.1%), and 'stable high' (21.6%). A significant association between sleep quality and depression trajectories was evident (p < 0.001). High fatigue symptoms and low social support predicted the high trajectories of poor sleep and depressive symptoms. Distinctive dynamic sleep quality and stable depression trajectories were characterised. Our findings revealed that both the sleep and depression trajectories were closely associated with one another, with common predictors of fatigue symptoms and social support. The early assessment of maternal sleep and depression status is important for identifying at-risk women and initiating interventions tailored to perinatal women to improve their sleep and mental health.

Relationships between stroke prevalence, health literacy, and oral health-related quality of life in middle-aged and older adults: a national survey study.

BACKGROUND: Stroke may cause debilitating neurological deficiencies that result in motor, sensory, and cognitive deficits and poorer psychosocial functioning. Prior studies have provided some initial evidence for the significant roles of health literacy and poor oral health for old people. However, few studies have focused on the health literacy of individuals who had a stroke; therefore, the relationships between the health literacy and oral health-related quality of life (OHRQoL) among middle-aged and older adults who had a stroke are unknown. We aimed to assess the relationships between stroke prevalence, health literacy status, and OHRQoL in middle-aged and older adults. METHODS: We retrieved the data from The Taiwan Longitudinal Study on Aging, a population-based survey. For each eligible subject, we gathered data in 2015 on age, sex, level of education, marital status, health literacy, the activity daily living (ADL), stroke history and OHRQoL. We evaluated the respondents' health literacy by using a nine-item health literacy scale and categorized their health literacy level as low, medium, or high. OHRQoL was identified based on the Taiwan version of the Oral Health Impact Profile (OHIP-7T). RESULTS: The final study contained 7702 community-based dwelling elderly people (3630 male and 4072 female) were analysis in our study. Stroke history was reported in 4.3% of participants, 25.3% reported low health literacy, and 41.9% had at least one ADL disability. Furthermore, 11.3% of participants had depression, 8.3% had cognitive impairment, and 3.4% had poor OHRQoL. Age, health literacy, ADL disability, stroke history, and depression status were significantly associated with poor OHRQoL after sex and marital status was adjusted. Medium (odds ratio [OR] = 1.784, 95% confidence interval [CI] = 1.177, 2.702) to low health literacy (OR = 2.496, 95% CI = 1.628, 3.828) was significantly associated with poor OHRQoL. CONCLUSIONS: Base our study results, people with stroke history had poor OHRQoL. Lower health literacy and ADL disability were associated with worse QHRQoL. Further studies are necessary to define practical strategies for reducing the risk of stroke and oral health with constantly lower health literacy, thereby improving the quality of life and providing health care of older people.

Sleep and Its Disturbance in Parents of Children and Adolescents with Epilepsy: A Systematic Review and Meta-Analysis.

Sleep disturbances are commonly reported by parents of children and adolescents with epilepsy. However, evidence synthesis including quality and quantity of sleep in parents of children and adolescents with epilepsy is lacking. This systematic review and meta-analysis was conducted to quantify pooled mean estimates of parental sleep variables and to determine the prevalence of sleep disturbances in parents of children and adolescents with epilepsy. Five electronic databases, PubMed, Medline, Embase, PsychINFO, and CINAHL, were systematically searched from inception to September 2021. Eleven observational studies examining parents of pediatric patients aged <18 years with epilepsy using a quantitative measure of sleep duration, sleep quality, or sleep disturbance were reviewed. Our results showed that the pooled nocturnal sleep duration was 5.93 hours (95% CI: 4.64 to 7.21 hours). Overall sleep quality as estimated by the bias-adjusted pooled Pittsburgh Sleep Quality Index total score was 6.65 (95% CI: 5.98 to 7.33). Parents of children with epilepsy had significantly higher Pittsburgh Sleep Quality Index total scores compared to parents of healthy children (differences in means 1.84, 95% CI: 1.29 to 2.39). The pooled estimated prevalence of parental sleep disturbances was 58.1% (95% CI: 45.7% to 69.6%). Our findings demonstrate a high prevalence of sleep disturbances with poor sleep quality and substantial reductions in sleep time in parents of children and adolescents with epilepsy. Healthcare professionals in pediatric neurology clinics should proactively initiate screening for sleep disturbances in parents of children and adolescents with epilepsy and refer parents to a sleep specialist when necessary.

A case of a 107-year-old elderly COVID-19 patient infected with Omicron variant BA.5.1.3 in Hainan / 中国热带医学

@#Abstract: Objective　This article summarizes the clinical characteristics and diagnosis and treatment experience of an elderly patient infected with Omicron variant BA.5.1.3 of COVID-19 in Hainan Province. Methods　The clinical data and treatment of an elderly patient infected with Omicron variant BA.5.1.3 of COVID-19 admitted to Haikou designated hospital on August 15, 2022 were retrospectively analyzed. Results　A 107-year-old female patient was admitted to the hospital with "fever and cough for 1 day". Two of her family members have infected with COVID-19. The patient initially developed fever, accompanied by cough, expectoration, a little white sticky sputum, accompanied by sore throat, muscle pain, fatigue. Nucleic acid test was positive in throat swab, indicating Omicron variant BA.5.1.3 infection. The patient was diagnosed as mild COVID-19 and treated with antiviral therapy, Chinese medicine conditioning, anticoagulation, electrolyte disorder regulation and symptomatic treatment for 9 days. The patient's clinical symptoms were relieved, and she was cured and discharged after two negative nucleic acid tests. One week later, the patient recovered well. Conclusions　Omicron variant BA.5.1.3 is highly infectious, and comprehensive treatment such as antiviral treatment and traditional Chinese medicine treatment has achieved good efficacy. For elderly patients, attention should be paid to maintaining the stability of organ function and internal environment, which is helpful to improve the prognosis of patients.

Effects of an integrated childbirth education program to reduce fear of childbirth, anxiety, and depression, and improve dispositional mindfulness: A single-blind randomised controlled trial.

OBJECTIVE: To evaluate the effects of an integrated childbirth education intervention on reducing childbirth fear, anxiety, and depression, and improving dispositional mindfulness. DESIGN: A two-arm parallel, single-blind randomised controlled trial. SETTING: A teaching hospital in Northern Taiwan. PARTICIPANTS: Pregnant women ≥ 20 years of age with a singleton pregnancy (12-24 weeks gestation) and their support partners were recruited. All women included in the study had a score of ≥ 7 points on a fear of childbirth visual analogue scale. INTERVENTIONS: The intervention group (n = 53) received an 8-week course in a childbirth education programme, which included (1) childbirth education using simulation-based learning that highlighted coping with labour pain and (2) instruction in mindfulness breathing, body scans, stretching, sitting meditation, and mindfulness walking. Support partners were invited to participate. The control group (n = 53) received the usual standard prenatal care. MEASUREMENTS: The primary outcome of fear of childbirth was assessed using the Wijma Delivery Expectancy/Experience Questionnaire. The secondary outcomes of anxiety, depression, and dispositional mindfulness were assessed with the Edinburgh Postpartum Depression Scale, State-Trait Anxiety Inventory Scale, and the Mindful Attention Awareness Scale, respectively. Repeated data were collected at baseline, 36 weeks gestation, and 1 week postpartum. FINDINGS: Ninety-one mothers completed the study, with a mean age of 33.9 years (SD = 4.4), and most were primipara (n = 83). The baseline measurements did not differ between the groups. Compared with the control group, there were significant differences in all measures from baseline for the intervention group: the scores were significantly lower for fear of childbirth (mean difference (MD) =-14.8 ∼ -23.7, p < .01), symptoms of anxiety (MD =-7.4 ∼ -6.4, p < .01), and depression (MD =-3.7 ∼ -3.5, p < .01); the levels of dispositional mindfulness were significantly higher (MD =4.9 ∼ 5.7, p < .01) at 36 weeks gestation, and 1 week postpartum. CONCLUSION AND IMPLICATIONS FOR PRACTICE: The 8-week integrated childbirth education intervention was effective in reducing the fear of childbirth in pregnant women. The mindfulness techniques were easily learnt and applied by the participants. Using these techniques during pregnancy and labour enhanced participants' mental health and coping. The integrated childbirth education which includes pregnant women and their support partners could be easily taught by midwives in other contexts.

Health Literacy and Exercise to Treat Frailty in Community-Dwelling Older Adults: A National Survey Study.

Aging is a major challenge facing modern society and has attracted global attention. Studies have provided some initial evidence that health literacy plays a role in determining frailty; however, most of these studies have used small convenience samples of individuals recruited from geographically limited areas, thus limiting the generalizability of their findings. The present study explored the relationships among health literacy, exercise, and frailty in Taiwanese older adults by using the data of a national population-based survey. We retrieved data from the Taiwan Longitudinal Study on Aging, a population-based survey. We gathered the 2015 data on the age, sex, education level, marital status, exercise habits, and activities of daily living (ADLs) of each eligible respondent. We evaluated the respondents' health literacy by using a nine-item health literacy scale and categorized their health literacy level as low, medium, or high. Frailty was diagnosed according the Fried criteria. Our final sample consisted of 7702 community-dwelling older adults (3630 men and 4072 adults). Of these, 25.3% had low health literacy. The proportion of respondents who had two or more disabilities in terms of ADLs or instrumental ADLs was higher among the women (36.4% and 12.6%, respectively), and regular exercise was more common among the men (19.6%). Frailty was more prevalent among the women; the prevalence of frailty among the male and female respondents was 4.5% and 8.1%, respectively. High health literacy and regular exercise were protective factors for frailty. According to our results, poor health literacy is a risk factor for prefrailty and frailty, and regular exercise is significantly negatively associated with prefrailty and frailty. Additional studies are necessary to define practical strategies for reducing the risks of disability and death for older adults with low health literacy who do not exercise regularly, thereby improving their quality of life.

Discovery of the oncogenic MDM2, a direct binding target of berberine and a potential therapeutic, in multiple myeloma.

Recent studies have suggested the potency of berberine (BBR) for multiple cancer treatments, including multiple myeloma (MM). However, the direct target and underlying mechanism of BBR remain largely understood in MM. Here, we demonstrated that BBR inhibited cell proliferation and acted synergistically with bortezomib in MM.1S cells. BBR treatment induced MM cell cycle arrest by downregulating several cell cycle-related proteins. Murine double minute 2 (MDM2) as a BBR-binding protein was identified by surface plasmon resonance image (SPRi) analysis and molecular docking. Overexpression of MDM2 is associated with MM progression and a poor prognosis. Knockdown MDM2 by siRNA transfection can repress MM malignant progression and attenuate the BBR sensitivity to MM.1S cells. BBR treatment induced the degradation of MDM2 through the ubiquitin-proteasome system and reactivated P53/P21 in MM cells. Overall, our data has illustrated that MDM2, as a binding protein of BBR for the first time, may serve as a potential therapeutic option for MM.

Sex-Influenced Risk Factors for Cognitive Impairment Among Community-Dwelling Older Adults.

The current study aimed to explore sex-influenced risk factors for cognitive impairment among community-dwelling older adults in Taiwan. This cross-sectional study was a secondary analysis using a population-based design. We accessed and analyzed data from the Taiwan Longitudinal Study on Aging survey of 2011. Participants were older adults aged ≥55 years living in non-indigenous townships. A total of 3,392 community-dwelling older adults were included. Results showed that the prevalence of cognitive impairment in females and males was 15.3% and 5.7%, respectively. Having a low educational level and being single (i.e., single, widowed, or divorced) were risk factors for cognitive impairment in both sexes. Males who had more than two chronic diseases had a higher risk of cognitive impairment. Self-reported hearing loss and depression increased risk of cognitive impairment in older females. Older age, lower educational level, and single marital status were associated with cognitive impairment among community-dwelling older adults in Taiwan. The effects of self-reported hearing loss, depression, and chronic disease on cognitive impairment were influenced by sex. [Journal of Gerontological Nursing, 48(6), 19-25.].

Effects of Acupressure on Anxiety: A Systematic Review and Meta-Analysis.

Objectives: The research aim was to perform a systematic review and meta-analysis evaluating the ability of acupressure to reduce anxiety. Design: Randomized controlled trials were obtained through a search of electronic medical databases (four in English and one in Chinese) from inception to October 5, 2020. Two authors searched the databases, evaluated studies' methodological quality, and performed data extraction independently. The final studies for analysis were identified after discussion with the third author. Results: We obtained 27 studies for our systematic review and meta-analysis. Eight studies had a low overall risk of bias, and 13 had some bias concerns with methodological quality. According to the results, acupressure significantly reduced patient anxiety (standardized mean difference = 1.152; 95% confidence interval: 0.847-1.459, p < 0.001), and the study heterogeneity was high (Q = 299.74, p < 0.001, I2 = 91.333%). Two studies reported acupressure-associated adverse events. We also performed a sensitivity analysis by omitting one outlier study, which had the largest effect size; however, high heterogeneity remained (I2 = 87.816%). A subgroup analysis revealed significant differences between participant types (Q = 46.573, p < 0.001), levels of methodological quality (Q = 6.228, p = 0.044), and massage equipment (Q = 4.642, p = 0.031). Conclusions: Our meta-analysis suggests that acupressure can alleviate anxiety. Acupressure was more effective for inpatients and preoperative patients when finger massage was applied. In individuals with anxiety and a stable hemodynamic status, acupressure could be a promising treatment option. However, the substantial heterogeneity across studies means that any inference from the results should be performed cautiously.

Predicting exercise behaviors and intentions of Taiwanese urban high school students using the theory of planned behavior.

PURPOSE: This study applied the Theory of Planned Behavior to predict exercise behaviors and intentions of teenagers and analyzed sex differences. DESIGN AND METHODS: A prospective study design was employed to survey tenth-grade students in Taipei, Taiwan. The 951 participants reported their exercise attitudes, subjective norms, perceived behavioral control (PBC), and intentions, and their exercise behaviors were tracked 6 months later. RESULTS: Results revealed that 22.1% of all students and more male students than female students exercised for ≥30 min/day on 5 or more days/week. Hierarchical multiple regression analyses demonstrated that intentions, PBC, attitudes, and subjective norms explained 32.5% of the variation in exercise behavior (p < .001). Intentions, attitudes, and PBC were related to exercise behavior regardless of sex. Attitudes, subjective norms, and PBC explained 67.0% of the variation in intentions (p < .001). Attitudes and PBC were related to intentions regardless of sex. CONCLUSIONS: The findings support that the main constructs of the Theory of Planned Behavior can effectively predict regular exercise intentions and behaviors among adolescents. PRACTICE IMPLICATIONS: The results can serve as a reference for nurses and other healthcare professionals when formulating effective strategies to encourage adolescents to engage in exercise practices.

The Effect of Paternal Skin-to-Skin Care: A Systematic Review and Meta-analysis of Randomized Control Trials.

BACKGROUND: Research about skin-to-skin care (SSC) experiences in early period after birth has focused on mothers and infants. PURPOSE: The purpose of this study was to determine the outcomes of paternal skin-to-skin care (P-SSC) in both fathers and infants. METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed/MEDLINE, Embase, CINAHL, PsycInfo, Airiti Library, and Google Scholar were searched for randomized controlled trials (RCTs) that reported outcomes of P-SSC in both fathers and infants. We calculated pooled mean differences (MDs) and 95% confidence intervals (CIs) using RevMan 5.3 for the meta-analysis [PROSPERO: CRD42018106790]. RESULTS: Seven RCTs including a total of 552 participants were eligible for inclusion. Compared to the maternal skin-to-skin care (M-SSC), fathers in the P-SSC exhibited no significant differences in salivary oxytocin levels (MD: -0.35 pg/mL; 95% CI: -0.75, 0.05), salivary cortisol levels (MD: 0.25 µg/dL; 95% CI: -0.82, 1.33), or anxiety scores (MD: -0.17; 95% CI: -0.57, 0.22) during the period of SSC. Similarly, there were no significant differences in the salivary cortisol levels (MD: -0.11 µg/dL; 95% CI: -0.05, 0.28) among preterm infants between the 2 groups. However, the crying time was less among full-term infants in the P-SSC group compared with infants in the incubator care or cot care groups. IMPLICATIONS FOR PRACTICE AND RESEARCH: P-SSC had similar effects as M-SSC on stress-related outcomes during and after SSC among fathers and infants in the early stages after birth. We recommend that P-SSC be implemented in the early stages after birth. Further RCTs with a longitudinal design and large samples are needed to better understand the long-term effects of P-SSC on fathers and infants.

Impacts of tai chi exercise on functional fitness in community-dwelling older adults with mild degenerative knee osteoarthritis: a randomized controlled clinical trial.

BACKGROUND: Degenerative osteoarthritis (OA) often leads to pain and stiffness of the affected joints, which may affect the physical performance and decrease the quality of life of people with degenerative knee OA. Compared to traditional exercise, tai chi is a safe exercise with slow movements which can facilitate physical functioning and psychological well being, and might be suitable for improving the physical activities of older adults with knee OA. Therefore, this study investigated the impacts of tai chi exercise on the functional fitness of community-dwelling older adults with degenerative knee OA. METHODS: Sixty-eight community-dwelling older adults with knee OA were recruited from the local community to participate in this randomized controlled clinical trial. All subjects were randomly assigned to either an TCE group that practiced tai chi exercise (TCE) (n = 36) or a control group (CON) (n = 32) that received regular health education programs twice per week for 12 weeks. Outcome measurements were determined using functional fitness tests before and after the intervention, including a 30-s chair stand (number of repeats), 30-s arm-curl (number of repeats), 2-min step (number of steps), chair sit-and-reach (reaching distance, cm), back-scratch flexibility (distance between hands, cm), single-leg stand (time, s), functional reach (reaching distance, cm), 8-foot up-and-go (time, s), and 10-m walk tests (time, s). Pre-post comparisons of functional fitness were analyzed using the ANCOVA test with SPSS software version 18.0. RESULTS: Results revealed that participants' functional fitness in the TCE group had significantly higher adjusted mean post-tests scores than that in the CON group after the intervention, including the 8-foot up-and-go (s) (mean difference [MD]=-2.92 [-3.93, -1.91], p = 2.39*10- 7), 30-s arm curl (MD = 4.75 (2.76, 6.73), p = 1.11*10- 5), 2-min step (MD = 36.94 [23.53, 50.36], p = 7.08*10- 7), 30-s chair stand (MD = 4.66 [2.97, 6.36], p = 6.96*10- 7), functional-reach (MD = 5.86 [3.52, 8.20], p = 4.72*10- 6), single-leg stand with eyes closed (MD = 3.44 [1.92, 4.97], p = 2.74*10- 5), chair sit-and-reach (MD = 3.93 [1.72, 6.15], p = 0.001), and single-leg stand with eyes opened (MD = 17.07 [6.29, 27.85], p = 0.002), with large effect sizes (η²=0.14 ~ 0.34). CONCLUSIONS: Community-dwelling older adults with knee OA in the TCE group had better functional fitness performances after the 12-week tai chi intervention than those receiving only health education.

Whole genome deep sequencing analysis of viral quasispecies diversity and evolution in HBeAg seroconverters.

BACKGROUND & AIMS: We aimed to investigate how viral quasispecies of the HBV whole genome evolves and diversifies in response to HBeAg seroconversion and viral control utilising next-generation sequencing (NGS). METHODS: Fifty HBeAg-positive chronic hepatitis B patients, including 18 treatment-naïve and 32 interferon (IFN)-treated individuals, were recruited. Serial HBV whole genomes in serum were analysed by NGS to determine sequence characteristics and viral quasispecies. RESULTS: HBV quasispecies diversity, measured by nucleotide diversity, was negatively correlated with viral load and hepatitis activity. Spontaneous HBeAg seroconverters exhibited significantly greater viral quasispecies diversity than treatment-naïve non-seroconverters from >1 year before seroconversion (0.0112 vs. 0.0060, p <0.01) to >1 year after seroconversion (0.0103 vs. 0.0068, p <0.01). IFN-induced HBeAg seroconverters tended to have higher viral genetic diversity than non-seroconverters along with treatment. Particularly, the IFN responders, defined as IFN-induced HBeAg seroconversion with low viraemia, exhibited significantly greater genetic diversity of whole HBV genome at 6 months post-IFN treatment than IFN non-responders (0.0148 vs. 0.0106, p = 0.048). Moreover, spontaneous HBeAg seroconverters and IFN responders exhibited significantly higher evolutionary rates and more intra-host single-nucleotide variants. Interestingly, in spontaneous HBeAg seroconverters and IFN responders, there were distinct evolutionary patterns in the HBV genome. CONCLUSIONS: Higher HBV quasispecies diversity is associated with spontaneous HBeAg seroconversion and IFN-induced HBeAg seroconversion with low viraemia, conferring a favourable clinical outcome. LAY SUMMARY: HBeAg seroconversion is a landmark in the natural history of chronic HBV infection. Using next-generation sequencing, we found that the nucleotide diversity of HBV was negatively correlated with viral load and hepatitis activity. Patients undergoing HBeAg seroconversion had more diverse HBV genomes and a faster viral evolution rate. Our findings suggest HBeAg seroconversion is driven by host selection pressure, likely immune selection pressure.

Combined viral quasispecies diversity and hepatitis B core-related antigen predict off-nucleos(t)ide analog durability in HBeAg-negative patients.

BACKGROUND: Viral quasispecies dynamics between pre- and post-nucleos(t)ide analog (NA) therapy remains unclear. AIM: This study aimed to investigate the HBV quasispecies evolution and its relationship with durability of off-therapy responses in HBeAg-negative chronic hepatitis B (CHB) patients who stopped NA therapy. METHODS: Fifty-four HBeAg-negative CHB patients who stopped NAs, including 19 virological controllers (VC) who maintained serum HBV DNA < 2000 IU/mL beyond 1-year off-therapy, and 35 virological relapsers (VR) experiencing virological relapse within 1-year off-therapy were recruited. Viral quasispecies was analyzed by deep sequencing. Hepatitis B core-related antigen (HBcrAg) and HBsAg were also measured. RESULTS: VC had significantly higher baseline viral quasispecies diversity of the precore/core gene, measured by nucleotide diversity, than VR. Low baseline viral nucleotide diversity (< 0.01) and high HBcrAg (≧ 2.0 KU/mL), but not HBsAg, at end of treatment (EOT) were significantly associated with higher risk of 1-year virological relapse (hazard ratio [HR] 6.09 and 3.31, respectively). Combination of low baseline viral nucleotide diversity and high HBcrAg at EOT could identify patients at high risk (HR 15.82). Further analysis of the evolution of HBV whole genome showed that HBV nucleotide diversity negatively correlated with serum HBV DNA levels. Notably, the viral quasispecies diversity between pre- and post-NA treatment remained relatively unchanged. CONCLUSION: Higher baseline HBV quasispecies diversity associates with more durable off-therapy viral suppression in HBeAg-negative CHB patients. Combination of baseline viral nucleotide diversity and HBcrAg at EOT can identify patients at high risk for virological relapse after stopping NAs.

Effects of Parental Education on Screen Time, Sleep Disturbances, and Psychosocial Adaptation Among Asian Preschoolers: A Randomized Controlled Study.

PURPOSE: A recent increase in screen time during early childhood has adversely affected the sleep and psychosocial health of children; however, limited information is available regarding effective interventions to reduce the screen time among them. This study aimed to investigate the effect of a parental educational program on screen use, sleep quality, and psychosocial adaptation among preschoolers. DESIGN AND METHODS: A clustered randomized controlled study with a parallel-group design was conducted. Preschoolers with a screen time of ≥2 h/day and their parents were recruited. In total, 14 kindergartens containing 129 parent-child dyads were randomly allocated to either the experimental group (receiving parental education, N = 63 dyads) or the control group (daily activities, N = 66 dyads). Data were collected before and after the intervention. A screen time questionnaire, the Children's Sleep Habits Questionnaire, and the Pediatric Symptom checklist-17 were provided to the participants. A linear mixed-model analysis was performed to examine the efficacy of the intervention. RESULTS: After the intervention, the screen time of children in the experimental group was significantly reduced (effect size: 0.83, p < .001), and they presented improved sleep quality (effect size: 0.57, p = .01) and attention score (effect size: 0.77, p = .02) for psychosocial adaptation. CONCLUSIONS: Parental education is an effective intervention for reducing screen time and improving sleep quality and attention among preschoolers. PRACTICE IMPLICATIONS: Healthcare professionals should consider implementing parental educational programs to reduce screen time, and thus improve the sleep quality and psychosocial health of preschoolers.