A working memory intervention for children with prenatal alcohol exposure: Pilot study.

Cogmed© is a computerized working memory training program designed to improve attention and working memory. We examined the short- and long-term impacts of a 25-session Cogmed© intervention on working memory and other cognitive and learning domains in children with prenatal alcohol exposure (PAE) and typically developing children. Participants included 38 children (4 - 13 years old) from Alberta, Canada in two groups: PAE (n = 20) and typically developing (n = 18). Significant improvements in areas of working memory and attentional control for both the PAE and the typically developing group were reported immediately after intervention completion (short-term impact). The gains on some measures were retained at five-week follow up (long-term impact). Preliminary findings indicate that computerized interventions may positively impact WM and attention control and that these changes may be maintained after a delay period.

Validation of the first-trimester machine learning model for predicting pre-eclampsia in an Asian population.

OBJECTIVES: To evaluate the performance of an artificial intelligence (AI) and machine learning (ML) model for first-trimester screening for pre-eclampsia in a large Asian population. METHODS: This was a secondary analysis of a multicenter prospective cohort study in 10 935 participants with singleton pregnancies attending for routine pregnancy care at 11-13+6 weeks of gestation in seven regions in Asia between December 2016 and June 2018. We applied the AI+ML model for the first-trimester prediction of preterm pre-eclampsia (<37 weeks), term pre-eclampsia (≥37 weeks), and any pre-eclampsia, which was derived and tested in a cohort of pregnant participants in the UK (Model 1). This model comprises maternal factors with measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor (PlGF). The model was further retrained with adjustments for analyzers used for biochemical testing (Model 2). Discrimination was assessed by area under the receiver operating characteristic curve (AUC). The Delong test was used to compare the AUC of Model 1, Model 2, and the Fetal Medicine Foundation (FMF) competing risk model. RESULTS: The predictive performance of Model 1 was significantly lower than that of the FMF competing risk model in the prediction of preterm pre-eclampsia (0.82, 95% confidence interval [CI] 0.77-0.87 vs. 0.86, 95% CI 0.811-0.91, P = 0.019), term pre-eclampsia (0.75, 95% CI 0.71-0.80 vs. 0.79, 95% CI 0.75-0.83, P = 0.006), and any pre-eclampsia (0.78, 95% CI 0.74-0.81 vs. 0.82, 95% CI 0.79-0.84, P < 0.001). Following the retraining of the data with adjustments for the PlGF analyzers, the performance of Model 2 for predicting preterm pre-eclampsia, term pre-eclampsia, and any pre-eclampsia was improved with the AUC values increased to 0.84 (95% CI 0.80-0.89), 0.77 (95% CI 0.73-0.81), and 0.80 (95% CI 0.76-0.83), respectively. There were no differences in AUCs between Model 2 and the FMF competing risk model in the prediction of preterm pre-eclampsia (P = 0.135) and term pre-eclampsia (P = 0.084). However, Model 2 was inferior to the FMF competing risk model in predicting any pre-eclampsia (P = 0.024). CONCLUSION: This study has demonstrated that following adjustment for the biochemical marker analyzers, the predictive performance of the AI+ML prediction model for pre-eclampsia in the first trimester was comparable to that of the FMF competing risk model in an Asian population.

Effectiveness of Cognitive Stimulation Therapy (CST) for mild to moderate dementia: A systematic literature review and meta-analysis of randomised control trials using the original CST protocol.

AIMS: We aimed to conduct a systematic literature review and meta-analysis to evaluate the efficacy of the original 14 session Cognitive Stimulation Therapy (CST) protocol in improving cognitive function and related outcomes in people with mild to moderate dementia. METHODS: Four databases were searched, up to May 2023, for randomized controlled trials of CST using the original protocol. Pre- and post-test means and measures of dispersion for intervention and control groups were extracted for each reported outcome and used to calculate effect sizes. Effect sizes were grouped by outcome and pooled in inverse variance weighted random effects models. RESULTS: Twelve studies were identified as meeting inclusion criteria. Of these, ten were given either a 'high' or 'medium' quality rating. The pooled results indicated that CST had a significant beneficial impact on global cognition, language, working memory, depression, neuropsychiatric symptoms, communication, self-reported quality of life and severity of dementia. CONCLUSIONS: CST as delivered in adherence to the original 14-session protocol is an efficacious treatment for mild to moderate dementia with improvements in cognition, affective symptoms and quality of life demonstrated from global trials.

Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother-child pairs.

Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother-child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.6 million mother-child pairs between 2001 and 2014 with follow-up until 2020. Children who were born to mothers with any type of diabetes during pregnancy had a higher risk of ADHD than unexposed children (pooled hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 1.08-1.24). Higher risks of ADHD were also observed for both GDM (pooled HR = 1.10, 95% CI = 1.04-1.17) and PGDM (pooled HR = 1.39, 95% CI = 1.25-1.55). However, siblings with discordant exposure to GDM in pregnancy had similar risks of ADHD (pooled HR = 1.05, 95% CI = 0.94-1.17), suggesting potential confounding by unmeasured, shared familial factors. Our findings indicate that there is a small-to-moderate association between MDM and ADHD, whereas the association between GDM and ADHD is unlikely to be causal. This finding contrast with previous studies, which reported substantially higher risk estimates, and underscores the need to reevaluate the precise roles of hyperglycemia and genetic factors in the relationship between MDM and ADHD.

Consistency of Feces Affects Defecatory Function.

Background/Aims: It is a common belief that constipated patients have hard feces that contributes to the difficulties defecating. To the best of our knowledge, no studies had been published on controlled evacuation of simulated feces with different consistencies. Methods: Twelve normal subjects were recruited for studies with the simulated feces device "Fecobionics" of different consistency (silicone shore 0A-40A corresponding to Bristol Stool Form Scale types 2-4). The subjects filled out questionnaires and had the balloon expulsion test (BET) and anorectal manometry (ARM) done for reference. The Fecobionics probes were inserted in rectum in random order with +20 minutes between insertions. The bag was filled to urge-to-defecate and evacuations took place in privacy. Non-parametric statistics with median and quartiles are provided. Results: One subject was excluded due to technical issues, and another had abnormal ARM-BET. The 4 females/6 males subjects were 23yrs (range 20-48). Most differences were observed between the 0A and 10A probe (duration, maximum bag pressure, duration x maximum bag pressure, and relaxation of the front pressure and the bend angle during evacuation), eg, the duration was 9 (8-12) seconds at 0A and 18 (12-21) seconds at 10A (P < 0.05), and maximum bag pressure was 107 (96-116) at 0A and 140 (117-162) cmH2O at 10A (P < 0.05). The bend angle before evacuation differed between the probes whereas only the 10A differed from 40A during defecation. The 10A was harder to evacuate than the 0A probe. Except for the bend angles, no further significant change was observed from 10A to 40A. Conclusion: Fecal consistency affects defecatory parameters.

The central role of natural killer cells in mediating acute myocarditis after mRNA COVID-19 vaccination.

BACKGROUND: Vaccine-related acute myocarditis is recognized as a rare and specific vaccine complication following mRNA-based COVID-19 vaccinations. The precise mechanisms remain unclear. We hypothesized that natural killer (NK) cells play a central role in its pathogenesis. METHODS: Samples from 60 adolescents with vaccine-related myocarditis were analyzed, including pro-inflammatory cytokines, cardiac troponin T, genotyping, and immunophenotyping of the corresponding activation subsets of NK cells, monocytes, and T cells. Results were compared with samples from 10 vaccinated individuals without myocarditis and 10 healthy controls. FINDINGS: Phenotypically, high levels of serum cytokines pivotal for NK cells, including interleukin-1ß (IL-1ß), interferon α2 (IFN-α2), IL-12, and IFN-γ, were observed in post-vaccination patients with myocarditis, who also had high percentage of CD57+ NK cells in blood, which in turn correlated positively with elevated levels of cardiac troponin T. Abundance of the CD57+ NK subset was particularly prominent in males and in those after the second dose of vaccination. Genotypically, killer cell immunoglobulin-like receptor (KIR) KIR2DL5B(-)/KIR2DS3(+)/KIR2DS5(-)/KIR2DS4del(+) was a risk haplotype, in addition to single-nucleotide polymorphisms related to the NK cell-specific expression quantitative trait loci DNAM-1 and FuT11, which also correlated with cardiac troponin T levels in post-vaccination patients with myocarditis. CONCLUSION: Collectively, these data suggest that NK cell activation by mRNA COVID-19 vaccine contributed to the pathogenesis of acute myocarditis in genetically and epidemiologically vulnerable subjects. FUNDING: This work was funded by the Hong Kong Collaborative Research Fund (CRF) 2020/21 and the CRF Coronavirus and Novel Infectious Diseases Research Exercises (reference no. C7149-20G).

Efficient Edge-AI Models for Robust ECG Abnormality Detection on Resource-Constrained Hardware.

This study introduces two models, ConvLSTM2D-liquid time-constant network (CLTC) and ConvLSTM2D-closed-form continuous-time neural network (CCfC), designed for abnormality identification using electrocardiogram (ECG) data. Trained on the Telehealth Network of Minas Gerais (TNMG) subset dataset, both models were evaluated for their performance, generalizability capacity, and resilience. They demonstrated comparable results in terms of F1 scores and AUROC values. The CCfC model achieved slightly higher accuracy, while the CLTC model showed better handling of empty channels. Remarkably, the models were successfully deployed on a resource-constrained microcontroller, proving their suitability for edge device applications. Generalization capabilities were confirmed through the evaluation on the China Physiological Signal Challenge 2018 (CPSC) dataset. The models' efficient resource utilization, occupying 70.6% of memory and 9.4% of flash memory, makes them promising candidates for real-world healthcare applications. Overall, this research advances abnormality identification in ECG data, contributing to the progress of AI in healthcare.

The rectum, anal sphincter and puborectalis muscle show different contraction wave forms during prolonged measurement with a simulated feces.

Contractile patterns in rectum, puborectalis muscle and anal sphincter must be studied to understand defecation. Six subjects had contractile waveforms studied with Fecobionics. Symptom questionnaires, balloon expulsion test and anorectal manometry were done for reference. The Fecobionics bag was filled in rectum to urge-to-defecate volume and measurements were done for 4 h before the subjects attempted to evacuate the device. Pressures and bend angle (BA) variations were analyzed with Fast Fourier Transformation. Four normal subjects exhibited low frequency waves (< 0.06 Hz) for pressures and BA. The waves were uncoordinated between recordings, except for rear and bag pressures. Peak wave amplitudes occurred at 0.02-0.04 Hz. Pressures and the BA differed for peak 1 (p < 0.001) and peak 2 amplitudes (p < 0.005). The front pressure amplitude was bigger than the others (rear and BA, p < 0.05; bag, p < 0.005) for peak 1, and bigger than bag pressure (p < 0.005) and BA (p < 0.05) for peak 2. One subject was considered constipated with lower front pressure amplitudes compared to normal subjects and increased amplitudes for other parameters. The sixth subject was hyperreactive and differed from the other subjects. In conclusion, the rectum, anal sphincter and puborectalis muscle showed different contraction waves during prolonged measurements. The data call for larger studies to better understand normal defecation, feces-withholding patterns, and the implications on anorectal disorders.

Intimate Partner Violence Against Women Before, During, and After Pregnancy: A Meta-Analysis.

Intimate partner violence (IPV) against pregnant women negatively impacts women's and infants' health. Yet inconsistent results have been found regarding whether pregnancy increases or decreases the risk of IPV. To answer this question, we systematically searched for studies that provided data on IPV against women before pregnancy, during pregnancy, and after childbirth. Nineteen studies met our selection criteria. We meta-analyzed the nineteen studies for the pooled prevalence of IPV across the three periods and examined study characteristics that moderate the prevalence. Results showed the pooled prevalence estimates of IPV were 21.2% before pregnancy, 12.8% during pregnancy and 14.7% after childbirth. Although these findings suggest a reduction in IPV during pregnancy, our closer evaluation of the prevalence of IPV after childbirth revealed that the reduction does not appear to persist. The prevalence of IPV increased from 12.8% within the first year after childbirth to 24.0% beyond the first year. Taken together, we should not assume pregnancy protects women from IPV, as IPV tends to persist across a longer-term period. Future studies are needed to investigate if IPV transits into other less obvious types of violence during pregnancy. Moderator analyses showed the prevalence estimates significantly varied across countries by income levels and regions.

The relationship between social media use and psychosocial outcomes in older adults: A systematic review.

OBJECTIVES: Social isolation and loneliness are prevalent in older adults and are detrimental to physical and mental health. Social media use has been shown to be effective in maintaining social connections and improving older adults' psychosocial outcomes. This study aimed to systematically review and synthesize current research on this topic. DESIGN: Searches were conducted in November 2021 (and updated in October 2023) in PsycINFO, PubMed, and CINAHL. Inclusion criteria: (1) participants ≥ 65 years (mean, median, or minimum age) and (2) reported impact of social media use on psychosocial outcomes (including loneliness, depression, anxiety, social connectedness, wellbeing, life satisfaction, and quality of life). Quality appraisal tools were utilized, and results were synthesized using narrative synthesis. RESULTS: Sixty-four papers met inclusion criteria, including cross-sectional (n = 38), observational longitudinal (n = 6), interventional (n = 9), mixed-methods (n = 4), and qualitative (n = 7) studies. Participant numbers ranged from 6 to 16,925. While associations between social media use and positive psychosocial outcomes were generally reported in cross-sectional studies, the impact of social media use over time from longitudinal studies was mixed and inconclusive. CONCLUSIONS: While social media use is associated with positive psychosocial outcomes, casual conclusions cannot be drawn. Few longitudinal and randomized controlled trial studies existed, and these reported mixed findings. Large variations in study methodology including participants, measurement of social media use, and outcome measures contributed to the inconsistencies of findings. Addressing this heterogeneity through standardized approaches and more rigorous research may enhance understanding.

Seeing through a robot's eyes: A cross-sectional exploratory study in developing a robotic screening technology for autism.

The present exploratory cross-sectional case-control study sought to develop a reliable and scalable screening tool for autism using a social robot. The robot HUMANE, installed with computer vision and linked with recognition technology, detected the direction of eye gaze of children. Children aged 3-8 (M = 5.52; N = 199) participated, 87 of whom had been confirmed with autism, 55 of whom were suspected to have autism, and 57 of whom were not considered to cause any concern for having autism. Before a session, a human experimenter instructed HUMANE to narrate a story to a child. HUMANE prompted the child to return his/her eye gaze to the robot if the child looked away, and praised the child when it re-established its eye gaze quickly after a prompt. The reliability of eye gaze detection was checked across all pairs of human raters and HUMANE and reached 0.90, indicating excellent interrater agreement. Using the pre-specified reference standard (Autism Spectrum Quotient), the sensitivity and specificity of the index tests (i.e., the number of robot prompts and duration of inattentiveness) reached 0.88 or above and the Diagnostic Odds Ratios were beyond 190. These results show that social robots may detect atypical eye patterns, suggesting a potential future for screening autism using social robots.

Natural history of infants with vitamin D deficiency in Hong Kong.

BACKGROUND AND OBJECTIVES: The usual recommended intake of vitamin D for healthy infants is 400 international unit (IU) daily. However, a high dose of vitamin D at 2000-3000 IU daily is needed for those with vitamin D deficiency (VDD). This study aimed to assess the natural history of a group of healthy infants with VDD and the associated factors for persistent VDD. METHODS AND STUDY DESIGN: Healthy infants detected to have VDD (25OHD <25 nmol/L) in a population study were followed, and their demographics and clinical data were collected. RESULTS: One hundred and thirty-one subjects (boys = 66%) were included. Their first serum 25OHD was taken at a median age of 87.5 days. None were treated with high-dose vitamin D supplements, but some have been given vitamin D at 400 IU daily. They were assessed again at the median age of 252.5 days when 15 remained to have VDD and 26 were in the insufficient range (25 - 49.9nmol/L). All persistent VDD children were on exclusive breastfeeding. Exclusive breastfeeding and no vitamin D supplementation were significant risk factors for persistent vitamin D insufficiency (<50nmol/L). CONCLUSIONS: Persistent VDD is common among infants exclusively breastfeeding and those who did not receive vitamin D supplementation.

Levothyroxine Treatment Among Pregnant Women and Risk of Seizure in Children: A Population-Based Cohort Study.

INTRODUCTION AND OBJECTIVE: The risk of seizure in offspring following prenatal exposure to levothyroxine is not well investigated. This study aimed to evaluate the association between levothyroxine treatment among pregnant women and the risk of seizure in their offspring. METHODS: This population-based cohort study included all pregnant women who delivered a live birth between January 2001 to January 2018, with a follow-up to December 2020, using data from the Hong Kong Clinical Data Analysis and Reporting System. Propensity score fine-stratification weighted hazard ratios (wHR) with 95% confidence intervals (CIs) were presented to assess the association between maternal levothyroxine use during pregnancy and seizures in children. RESULTS: Among 528,343 included mother-child pairs, 3044 children were prenatally exposed to levothyroxine at any time during the pregnancy period. A significantly increased risk of seizure was observed in children of the prenatally exposed group compared with the prenatally unexposed group (wHR 1.12, 95% CI 1.02-1.22). An increased risk of seizure was observed when comparing the prenatally exposed group with euthyroid mothers who had no history of thyroid-related diagnosis or prescriptions (wHR 1.12, 95% CI 1.02-1.23). However, no significant difference was observed between the prenatally exposed group and those previously exposed to levothyroxine but had stopped during pregnancy (wHR 0.97, 95% CI 0.66-1.44). No significant difference was observed in the sibling-matched analysis either (wHR 1.23, 95% CI 0.76-2.01). CONCLUSION: The observed increased risk of seizure in children born from mothers exposed to levothyroxine during pregnancy might be due to residual confounding by maternal thyroid disease. The findings support the current guidelines on the safe use of levothyroxine treatment during pregnancy.

Inhibition of PLK4 remodels histone methylation and activates the immune response via the cGAS-STING pathway in TP53-mutated AML.

Acute myeloid leukemia (AML) with TP53 mutation is one of the most lethal cancers and portends an extremely poor prognosis. Based on in silico analyses of druggable genes and differential gene expression in TP53-mutated AML, we identified pololike kinase 4 (PLK4) as a novel therapeutic target and examined its expression, regulation, pathogenetic mechanisms, and therapeutic potential in TP53-mutated AML. PLK4 expression was suppressed by activated p53 signaling in TP53 wild-type AML and was increased in TP53-mutated AML cell lines and primary samples. Short-term PLK4 inhibition induced DNA damage and apoptosis in TP53 wild-type AML. Prolonged PLK4 inhibition suppressed the growth of TP53-mutated AML and was associated with DNA damage, apoptosis, senescence, polyploidy, and defective cytokinesis. A hitherto undescribed PLK4/PRMT5/EZH2/H3K27me3 axis was demonstrated in both TP53 wild-type and mutated AML, resulting in histone modification through PLK4-induced PRMT5 phosphorylation. In TP53-mutated AML, combined effects of histone modification and polyploidy activated the cGAS-STING pathway, leading to secretion of cytokines and chemokines and activation of macrophages and T cells upon coculture with AML cells. In vivo, PLK4 inhibition also induced cytokine and chemokine expression in mouse recipients, and its combination with anti-CD47 antibody, which inhibited the "don't-eat-me" signal in macrophages, synergistically reduced leukemic burden and prolonged animal survival. The study shed important light on the pathogenetic role of PLK4 and might lead to novel therapeutic strategies in TP53-mutated AML.

Influenza vaccine uptake and associated factors in adult patients with type 2 diabetes in a general outpatient clinic in Hong Kong.

BACKGROUND AND OBJECTIVES: This study examined the uptake of influenza vaccine (Vaxigrip Tetra, Sanofi-Aventis) among local patients with type 2 diabetes (T2D) and their intention to receive future flu vaccines. We also explored associations between factors pertinent to the Health Belief Model (HBM) and vaccination behaviour. Based on these findings, targeted strategies to improve flu vaccine uptake are proposed. METHOD: In all, 499 patients with diabetes were recruited from a government general outpatient clinic (GOPC) in Hong Kong between 1 and 14 March 2021. A cross-sectional, questionnaire-based study to investigate vaccination behaviours and the HBM was conducted. A self-reported questionnaire that included sociodemographic data of participants' and patients' knowledge and perceptions related to flu vaccines based on the HBM framework was used. Study subjects aged <18 years and those who were unable to provide consent or had contraindications to flu vaccine were excluded from the study. RESULTS: Among the study sample, the reported flu vaccine uptake rate was 42% during 2020. Results from multivariate logistic analyses revealed a positive correlation between the likelihood of vaccination and factors pertinent to the HBM, such as knowledge that flu vaccine is required annually, not considering side effects from flu vaccine uptake and having better access to flu vaccine. DISCUSSION: The rate of flu vaccine uptake in our study population was suboptimal. Given the significance of influenza among patients with T2D, various public health interventions should be used to promote annual flu vaccine uptake.