Paediatric Uveitis - the uniqueness in clinical presentation and the efficacy of biologics treatment.

AIMS: To evaluate unique clinical characteristics of paediatric uveitis in our locality and treatment outcomes especially the efficacy of biologics. METHODS: This was a retrospective cohort. RESULTS: 37 paediatric uveitis cases involving 67 eyes were included. Male-to-female ratio was 1:1.3. Mean age of uveitis onset was 11 ± 3.7 (4-18). 81.1% cases suffered from bilateral uveitis. 75.7% cases were chronic uveitis. Nearly half of the cases (40.5%) presented with anterior uveitis. The predominant diagnosis of uveitis in our cohort was idiopathic. Unlike studies from other populations, the associated systemic conditions in this mostly Chinese cohort were Behçet's disease (8.1%), tubulointerstitial nephritis and uveitis (8.1%) and HLA-B27 associated uveitis (8.1%). Steroid response was a common phenomenon, observed in 40.5% of cases. The most common complication was posterior synechiae (45.9%), followed by cataract (37.8%), glaucoma (27.0%), band keratopathy (18.9%) and macular oedema (13.5%). 3/37 patients encountered either first attack of uveitis or flare after receiving COVID-19 vaccine. 54.1% of patients required systemic steroid for disease control. The majority required steroid sparing immunotherapy, including Methotrexate (43.2%), Mycophenolate Mofetil (24.3%), Cyclosporine A (8.1%), Azathioprine (5.4%) and Tacrolimus (2.7%). Resistant cases required biologics including tumour necrosis factor alpha inhibitors (Adalimumab 32.4%, Infliximab 2.7%) and interleukin-6 inhibitors (Tocilizumab 2.7%). CONCLUSIONS: Clinical presentation of the local paediatric uveitis differs from previously described features in Caucasian and other populations. According to our experience as a tertiary eye centre, Behçet's disease, tubulointerstitial nephritis and uveitis and HLA-B27 associated uveitis were more often encountered than Juvenile Idiopathic Arthritis associated uveitis. Our report evaluated the efficacy of immunomodulatory therapy and biologics in controlling uveitis and reducing ocular complications.

HEART + score: integrating carotid ultrasound to chest pain assessment in the emergency department.

OBJECTIVES: The HEART score is a clinical decision tool that stratifies patients into categories of low, moderate, and high-risk of major adverse cardiac events in the emergency department (ED) but cannot identify underlying cardiovascular disease in patients without prior history. The presence of atherosclerosis can easily be detected at the bedside using carotid ultrasound. Plaque quantification is well established, and plaque composition can be assessed using ultrasound grayscale pixel distribution analysis. This study aimed to determine whether carotid plaque burden and/or composition correlated with risk of events and could improve the sensitivity of the HEART score in risk stratifying ED patients with chest pain. METHODS: The HEART score was calculated based on history, electrocardiogram, age, risk factors, and initial troponin in patients presenting to the ED with chest pain (n = 321). Focused carotid ultrasound was performed, and maximum plaque height and total plaque area were used to determine plaque burden (quantity). Plaque composition (% blood, fat, muscle, fibrous, calcium-like tissue) was assessed by pixel distribution analysis. RESULTS: Carotid plaque height and area increased with HEART score (p < 0.0001). Carotid plaque % fibrous and % calcium also increased with HEART score. The HEART score had a higher area under the curve (AUC = 0.84) in predicting 30-day events compared to the plaque variables alone (AUCs < 0.70). Integrating plaque quantity into the HEART score slightly increased test sensitivity (62-69%) for 30-day events and reclassified 11 moderate-risk participants to high-risk (score 7-10). CONCLUSION: Plaque burden with advanced composition features (fibrous and calcium) was associated with increased HEART score. Integrating plaque assessment into the HEART score identified subclinical atherosclerosis in moderate-risk patients.

RéSUMé: OBJECTIFS: Le score HEART est un outil de décision clinique qui stratifie les patients en catégories de risque faible, modéré et élevé d'événements cardiaques indésirables majeurs à l'urgence (ED), mais ne peut pas identifier les maladies cardiovasculaires sous-jacentes chez les patients sans antécédents. La présence d'athérosclérose peut facilement être détectée au chevet du patient à l'aide de l'échographie carotide. La quantification de la plaque est bien établie et la composition de la plaque peut être évaluée à l'aide d'une analyse échographique de la distribution des pixels en niveaux de gris. Cette étude visait à déterminer si la charge et/ou la composition de la plaque carotidienne étaient corrélées avec le risque d'événements et pouvaient améliorer la sensibilité du score HEART chez les patients souffrant de douleurs thoraciques stratifiés. MéTHODES: Le score HEART a été calculé sur la base des antécédents, de l'électrocardiogramme, de l'âge, des facteurs de risque et de la troponine initiale chez les patients présentant une douleur thoracique à l'urgence (n = 321). L'échographie carotidienne focalisée a été effectuée, et la hauteur maximale de la plaque et la surface totale de la plaque ont été utilisées pour déterminer la charge de plaque (quantité). La composition de la plaque (% de sang, de graisse, de muscle, de tissu fibreux, de type calcique) a été évaluée par analyse de la distribution des pixels. RéSULTATS: La hauteur et la surface de la plaque carotide ont augmenté avec le score HEART (p<0,0001). Le pourcentage de plaque carotide fibreuse et le pourcentage de calcium ont également augmenté avec le score HEART. Le score HEART avait une zone plus élevée sous la courbe (ASC = 0,84) pour prédire les événements de 30 jours par rapport aux seules variables de la plaque (CCU < 0,70). L'intégration de la quantité de plaque dans le score HEART a légèrement augmenté la sensibilité au test (62 % à 69 %) pour les événements de 30 jours et a reclassé 11 participants à risque modéré à risque élevé (score de 7 à 10). CONCLUSION: La charge de plaque avec des caractéristiques de composition avancées (fibreuse et calcique) était associée à une augmentation du score HEART. Intégrer l'évaluation de la plaque dans le score HEART a identifié l'athérosclérose subclinique chez les patients à risque modéré.

Mechanisms underlying the relations between parents' perfectionistic tendencies and young children's mathematical abilities.

BACKGROUND: Parents' high academic expectations are positively associated with young children's mathematical abilities. However, minimal attention has been devoted to whether, and how, different ways of conveying the performance targets would result in different outcomes. AIMS: The current study investigated whether and how parents' perfectionistic strivings and concerns were associated with young children's mathematical abilities through home mathematical activities, children's approach motivation to learn mathematics, and children's avoidance motivation to learn mathematics. SAMPLE: Participants included 211 kindergarteners in Hong Kong and their parents. METHODS: Data were collected through individual child tests and parent questionnaires. RESULTS: Structural equation modelling revealed that parents' perfectionistic strivings had a direct positive link with children's mathematical abilities, an indirect link via approach motivation to learn mathematics, and an indirect link via home mathematical activities, and then approach motivation. Parents' perfectionistic concerns had a direct negative link with children's mathematical abilities, an indirect link via approach motivation to learn mathematics, and an indirect link via avoidance motivation to learn mathematics. CONCLUSIONS: Early childhood practitioners are recommended to raise parents' awareness of how to communicate high-performance targets to children in a constructive manner.

Comparative effectiveness of non-pharmacological interventions on sleep in individuals with chronic musculoskeletal pain: A systematic review with network meta-analysis.

This network meta-analysis aimed to estimate the comparative effectiveness of non-pharmacological interventions on sleep in individuals with chronic musculoskeletal pain. Seven databases were systematically searched up to February 2023. A random-effects network meta-analysis in a frequentist framework was performed to synthesize continuous data as standardized mean differences (SMD) along with a 95% confidence interval (95% CI). A total of 15,641 records were identified, and 107 randomized controlled trials involving 8,121 participants were included. Of 14 identified interventions, eight were significantly more effective than passive control in improving sleep quality at immediate post-intervention (SMDs = 0.67-0.74), with cognitive behavioral therapy (CBT) being the most effective treatment (SMD = 0.74, 95% CI: 0.45-1.03). Only CBT demonstrated sustained effects at short-term (SMD = 1.56; 95% CI: 0.62-2.49) and mid-term (SMD = 1.23; 95% CI: 0.44-2.03) follow-ups. Furthermore, CBT significantly improved subjective (SMD = 0.64; 95% CI: 0.25-1.03) and objective (SMD = 0.30; 95% CI: 0.01-0.59) sleep efficiency compared with passive control at immediate post-intervention. Our findings support CBT as the first-line treatment for improving sleep in individuals with chronic musculoskeletal pain, given its superior effectiveness across multiple sleep outcomes and its sustainable effects until mid-term follow-up. However, the certainty of evidence for these interventions in improving sleep quality was very low to low.

Associations between paraspinal muscle characteristics and spinal curvature in conservatively treated adolescent idiopathic scoliosis: a systematic review.

BACKGROUND CONTEXT: Children with adolescent idiopathic scoliosis (AIS) may show asymmetrical paraspinal muscle characteristics. PURPOSE: To summarize the evidence regarding: (1) the associations between various paraspinal muscle characteristics and spinal curvature; (2) whether paraspinal muscle properties significantly differed between children with and without AIS; and (3) whether baseline paraspinal muscle characteristics predicted curve progression. STUDY DESIGN/SETTING: Systematic literature review. METHODS: Five databases (CINAHL, Academic Search Premier, MEDLINE, Scopus, and PubMed) were searched from inception to May 2022. This protocol was registered in the PROSPERO database of systematic reviews CRD 42020171263. The Critical appraisal skills program, the Appraisal Tool for Cross-Sectional Studies and Quality In Prognosis Studies tool were used to evaluate the risk of bias of the included studies. The strength of evidence of each identified association was determined by the Grading of Recommendations Assessment, Development, and Evaluation System (GRADE). RESULTS: Of 1,530 identified citations, four cohort, 17 cross-sectional, and 23 case-control studies including 31 with low, nine with moderate and four with high risk of bias were included. Low to very low-strength evidence supported that the convex side of the curve had more type I muscle fibers, higher muscle volume and paraspinal muscle activity, while the concavity had more intramuscular fatty infiltration. Very low-strength evidence substantiated greater side-to-side surface electromyography signals during left trunk bending in prone lying, standing, and standing with perturbation between people with and without AIS. Also, low to very low-strength evidence supported that a larger side-to-side surface electromyography ratio at the lower end vertebra predicted curve progression. CONCLUSIONS: Our review highlights that paraspinal muscles on the concavity of the curve demonstrate consistent changes (ie, altered muscle-related gene expression, muscle atrophy, increased fatty infiltration, reduced type I fibers, and reduced muscle activity), which may be the cause or consequence.

The Commonwealth Fund Survey of Primary Care Physicians Reveals Challenges Experienced by Family Doctors and Emphasizes the Need for Interoperability of Health Information Technologies.

Electronic health information that is easily accessible and shareable among healthcare providers and their patients can provide substantial improvements in Canada's primary care system and population health outcomes. The Commonwealth Fund's (CMWF's) 2022 International Health Policy Survey of Primary Care Physicians (CIHI 2023) highlights the views and experiences of primary care doctors in 10 developed countries, including Canada. The survey covered various topics related to physician workload, the use of information technology and coordination of care. While the COVID-19 pandemic contributed to an increased physician workload that may have impacted the ability to efficiently coordinate care with other healthcare providers, Canadian family doctors did close the gap with other countries as 93% of family doctors are now using electronic medical records (EMRs) in their practices. The CMWF's 2022 survey revealed challenges faced by Canadian family doctors in their practices. However, international comparisons provide opportunities to learn from other countries and build on the implementation of EMRs as part of Canada's shared health priorities.

Examining the learning effects of concrete and abstract materials among university students using a two-dimensional approach.

BACKGROUND: The debate on using concrete versus abstract materials in learning mathematics has been longstanding. For decades, research has focused on the physical characteristics of materials when defining them as concrete or abstract. AIMS: This study extends the field by proposing a two-dimensional classification, which defines materials as concrete or abstract based on the two dimensions of representation, namely object (i.e., appearance) and language (i.e., label). SAMPLE: A total of 120 university students participated in the study. METHODS: Participants were randomly assigned to learn the concept of modular arithmetic with one of four types of learning materials: concrete object labelled with concrete language, concrete object labelled with abstract language, abstract object labelled with concrete language and abstract object labelled with abstract language. They were also divided into high and low maths anxiety groups. RESULTS: Results showed that the students who learnt with abstract objects, regardless of the level of maths anxiety, outperformed their peers who learnt with concrete objects. However, for students with low maths anxiety only, those who learnt with materials labelled with abstract language showed better far-transfer performance compared with those who learnt with materials labelled with concrete language. CONCLUSIONS: The findings offer a new direction in the conceptualization of concrete and abstract learning materials by specifying the dimensions of representation.

Correlation of urodynamic studies and somatosensory evoked potential and their prognostic value in children with closed spinal dysraphism.

INTRODUCTION: Somatosensory evoked potential (SSEP) and urodynamic studies (UD) are valuable tools for assessing patients with closed spinal dysraphism (CSD) before neurosurgical intervention. No studies have correlated their findings in this cohort and our aim is to study their correlation and prognostic value in pediatric patients with closed spinal dysraphism. METHODS: Retrospective review of all patients referred to a multidisciplinary clinic in a tertiary pediatric surgical center over a 17 years period between April 2004 to September 2021 was performed. Inclusion criteria were <18 years old, diagnosed with CSD, with SSEP and UD done within 1 year of each other. Demographics data collected include age at presentation/at referral/at neurosurgical operation, gender, symptoms at presentation and intra-operative diagnoses. Pre-operative SSEP and UD findings were documented. Primary outcome was UD results in the group with normal and abnormal SSEP. Secondary outcome was urological and bowel function outcome in 4 groups of patients (Group A-both normal SSEP and UD, Group B- abnormal SSEP only, Group C - abnormal UD only and Group D-both abnormal SSEP and UD). RESULTS: A total of 45 patients were included for analysis. Mean follow up time was 118.9 months (24-216 months, SD 55.8 months). SSEP was normal in 20 patients and abnormal in 25 patients. Baseline demographics, preoperative symptoms and imaging were similar between 2 groups. Primary outcome Patients with abnormal SSEP were more likely to have abnormal UD results with a statistically significant difference (84% vs 40%, p < 0.05). They have a significantly higher end-fill detrusor pressure (12% vs 0%, p < 0.05), abnormal bladder compliance (20% vs 0%, p < 0.05), abnormal cystometric capacity (48% vs 10%, p < 0.05), poor emptying efficiency (24% vs 5%, p < 0.05) and sphincter incompetence (8% vs 0%, p < 0.05). Secondary outcome When compared to Groups A to C, patients in group D were more likely to be on anti-cholinergic (33.3% vs 4.3%, p < 0.05), required clean intermittent catheterization (42.9% vs 4.3%, p < 0.05) and had intravesical botulinum injection (19% vs 0%, p < 0.05). All the patients who had augmentation cystoplasty were in this group as well. Bowel function in terms of regular enema use was also statistically significantly higher in this group (33.4% p < 0.05). CONCLUSION: Pre-operative SSEP and UD results correlate well in patients with closed spinal dysraphism. Patients with abnormal SSEP and UD preoperatively have higher risk of urological deterioration over time. Close monitoring in this group is warranted.

Case Report: Multiple autoimmune syndrome (MAS)-An unusual combination.

This is a case report of a Chinese adolescent boy who had multiple autoimmune syndrome (MAS) of a rare combination comprising type 1 diabetes, Hashimoto thyroiditis and childhood-onset systemic lupus erythematosus (SLE). He developed SLE within one year of symptom onset, presenting with necrotising histiocytic lymphadenitis and hepatitis. We highlight the importance for physicians to be aware of the need for continued surveillance for developing new autoimmune diseases in patients with multiple autoimmune diseases. It is also essential to remain vigilant for overlap syndrome as autoimmune diseases commonly share similar subphenotypes and non-specific autoantibodies. Long-term follow-up is warranted to define the final phenotype.

Potential mechanisms underlying the accelerated cognitive decline in people with chronic low back pain: A scoping review.

A growing body of evidence has shown that people with chronic low back pain (CLBP) demonstrate significantly greater declines in multiple cognitive domains than people who do not have CLBP. Given the high prevalence of CLBP in the ever-growing aging population that may be more vulnerable to cognitive decline, it is important to understand the mechanisms underlying the accelerated cognitive decline observed in this population, so that proper preventive or treatment approaches can be developed and implemented. The current scoping review summarizes what is known regarding the potential mechanisms underlying suboptimal cognitive performance and cognitive decline in people with CLBP and discusses future research directions. Five potential mechanisms were identified based on the findings from 34 included studies: (1) altered activity in the cortex and neural networks; (2) grey matter atrophy; (3) microglial activation and neuroinflammation; (4) comorbidities associated with CLBP; and (5) gut microbiota dysbiosis. Future studies should deepen the understanding of mechanisms underlying this association so that proper prevention and treatment strategies can be developed.

Motor Vehicle Collision and Acute Kidney Injury in Children.

OBJECTIVE: Our study aimed to determine the prevalence of acute kidney injury (AKI) in pediatric patients who sustained trauma due to motor vehicle collision (MVC) and identify factors associated with its development. METHODS: We retrospectively reviewed the clinical information and laboratory tests of pediatric patients who were admitted because of MVC from January 2014 to April 2021. The occurrence of AKI was our primary outcome, which was defined by the Kidney Disease Improving Global Outcomes criteria. A serum creatine kinase (CK) level of 1000 IU/L or greater was defined as rhabdomyolysis. RESULTS: Sixty-four patients (median age, 9.6 years) were included in the study. Twenty three of the patients (35.9%) developed AKI: stage 1 AKI in 18 (78.3%) and stage 2 AKI in 5 (21.7%) patients. Acute kidney injury patients had higher injury severity scores (no AKI: 5.0; stage 1 AKI: 10.5; stage 2 AKI: 26.0). Rhabdomyolysis was present in 21.1% of the patients and was associated with the overall AKI risk (odds ratio [OR], 7.3; 95% confidence interval [CI], 1.6-32.6) and stage 2 AKI (OR, 15.0; 95% CI, 1.4-163.2). Blood tests from AKI patients showed lower serum bicarbonate and base excess, higher leukocyte and CK levels on admission, and a higher peak CK in the first 72 hours of admission. Intubation in emergency department (OR, 11.1; 95% CI, 1.2-102.1) and surgical interventions (OR, 3.2; 95% CI, 1.0-9.8) were associated with AKI. Acute kidney injury patients required longer stay in pediatric intensive care unit (median 1.0 vs 2.3 days, P < 0.001) and hospital (median 4.1 vs 7.0 days, P = 0.010). CONCLUSIONS: Approximately one third of pediatric patients who sustained trauma from MVC developed AKI. Initial blood results, including higher CK and leukocyte count, and lower bicarbonate and base excess, were associated with the development of AKI. Rhabdomyolysis occurred in approximately one fifth of the patients and was significantly associated with AKI.

Target-rate effect in continuous visual search.

From infrared body temperature surveillance to lifeguarding, real-life visual search is usually continuous and comes with rare targets. Previous research has examined realistic search tasks involving separate slides (such as baggage screening and radiography), but search tasks that require continuous monitoring have generally received less attention. In this study, we investigated whether continuous visual search would display a target-rate effect similar to the low-prevalence effect (LPE) in regular visual search. We designed a continuous detection task for a target feature (e.g., a green color) among items of continuously and gradually changing features (e.g., other colors). In four experiments, we demonstrated target-rate effects in terms of slower hit response times (RTs) and higher miss rates when targets were rare. Similar to regular search, target-rate effects were also observed for relative frequencies across two target features. Taken together, these results suggest a target-rate effect in continuous visual search, and its behavioral characteristics are generally similar to those of the LPE in regular visual search.

The roles of different executive functioning skills in young children's mental computation and applied mathematical problem-solving.

This study investigated the relationships of four executive functioning skills (including verbal working memory, spatial working memory, inhibitory control, and cognitive flexibility) with young children's mental computation and applied mathematical problem-solving. Two hundred and twenty-five Chinese kindergarteners were tested with a battery of general cognitive, executive functioning and mathematics skills. Results showed that when children's age, gender, non-verbal intelligence, and listening comprehension skills were controlled, verbal working memory and cognitive flexibility were significant correlates of mental computation, whereas verbal working memory, spatial working memory, and cognitive flexibility were significant correlates of applied mathematical problem-solving. Inhibitory control was not significantly associated with the two domains of mathematics under investigation. The findings highlight the differential roles of different executive functioning skills in early mathematical skills and offer practical implication for helping young children in learning complex mathematical skills.

Surface salt bridges contribute to the extreme thermal stability of an FN3-like domain from a thermophilic bacterium.

This study uses differential scanning calorimetry, X-ray crystallography, and molecular dynamics simulations to investigate the structural basis for the high thermal stability (melting temperature 97.5°C) of a FN3-like protein domain from thermophilic bacteria Thermoanaerobacter tengcongensis (FN3tt). FN3tt adopts a typical FN3 fold with a three-stranded beta sheet packing against a four-stranded beta sheet. We identified three solvent exposed arginine residues (R23, R25, and R72), which stabilize the protein through salt bridge interactions with glutamic acid residues on adjacent strands. Alanine mutation of the three arginine residues reduced melting temperature by up to 22°C. Crystal structures of the wild type (WT) and a thermally destabilized (∆Tm -19.7°C) triple mutant (R23L/R25T/R72I) were found to be nearly identical, suggesting that the destabilization is due to interactions of the arginine residues. Molecular dynamics simulations showed that the salt bridge interactions in the WT were stable and provided a dynamical explanation for the cooperativity observed between R23 and R25 based on calorimetry measurements. In addition, folding free energy changes computed using free energy perturbation molecular dynamics simulations showed high correlation with melting temperature changes. This work is another example of surface salt bridges contributing to the enhanced thermal stability of thermophilic proteins. The molecular dynamics simulation methods employed in this study may be broadly useful for in silico surface charge engineering of proteins.