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Dyslexia is a developmental disability affecting the acquisition of reading and writing skills, and its developmental nature makes longitudinal research of great importance. This study therefore investigated the cognitive-linguistic profiles of the typical-functioning dyslexics and high-functioning dyslexics with longitudinal cohorts of Chinese-speaking adolescents diagnosed with childhood dyslexia. These two dyslexic groups of fifty students (with 25 typical-functioning dyslexics) were assessed in Grade 2 (Time 1) and in Grade 8 (Time 2), whereas 25 typically developing controls were assessed at Time 2. Students were administered measures of phonological awareness, morphological skills, visual-orthographic knowledge, rapid naming, verbal working memory, and literacy skills. Results showed that, at Time 2, both dyslexic groups performed less well than the control group on most of the measures. Deficits in rapid naming were particularly salient in both dyslexic groups. Comparing the two dyslexic groups, the typical-functioning dyslexics had more multiple deficits than the high-functioning dyslexics. Findings highlight the importance of rapid naming deficits as potential universal causes of dyslexia and the utility of targeting visual-orthographic knowledge and morphological skills in supporting the development of dyslexic adolescents.

This study aims to investigate the relation of syntactic and discourse skills to morphological skills, rapid naming, and working memory in Chinese adolescent readers with dyslexia and to examine their cognitive–linguistic profiles. Fifty-two dyslexic readers (mean age, 13;42) from grade 7 to 9 in Hong Kong high schools were compared with 52 typically developing readers of the same chronological age (mean age, 13;30) in the measures of word reading, 1-min word reading, reading comprehension, morpheme discrimination, morpheme production, morphosyntactic knowledge, sentence order knowledge, digit rapid naming, letter rapid naming, backward digit span, and non-word repetition. Results showed that dyslexic readers performed significantly worse than their peers on all the cognitive-linguistic tasks. Analyses of individual performance also revealed that over half of the dyslexic readers exhibited deficits in syntactic and discourse skills. Moreover, syntactic skills, morphological skills, and rapid naming best distinguished dyslexic from non-dyslexic readers. Findings underscore the significance of syntactic and discourse skills for understanding reading impairment in Chinese adolescent readers.

Patients who were referred to Veterans Affairs gastroenterology clinics with heartburn unresponsive to a proton-pump inhibitor had comprehensive evaluation for eligibility for a trial comparing Nissen fundoplication surgery with medical therapy. In the minority of patients who were confirmed to have PPI-refractory and reflux-related heartburn, surgery was more effective than medical treatment in controlling reflux symptoms.

In 2001, the World Health Assembly (WHA) passed the landmark WHA 54.19 resolution for global scale-up of mass administration of anthelmintic drugs for morbidity control of schistosomiasis and soil-transmitted helminthiasis, which affect more than 1·5 billion of the world's poorest people. Since then, more than a decade of research and experience has yielded crucial knowledge on the control and elimination of these helminthiases. However, the global strategy has remained largely unchanged since the original 2001 WHA resolution and associated WHO guidelines on preventive chemotherapy. In this Personal View, we highlight recent advances that, taken together, support a call to revise the global strategy and guidelines for preventive chemotherapy and complementary interventions against schistosomiasis and soil-transmitted helminthiasis. These advances include the development of guidance that is specific to goals of morbidity control and elimination of transmission. We quantify the result of forgoing this opportunity by computing the yearly disease burden, mortality, and lost economic productivity associated with maintaining the status quo. Without change, we estimate that the population of sub-Saharan Africa will probably lose 2·3 million disability-adjusted life-years and US$3·5 billion of economic productivity every year, which is comparable to recent acute epidemics, including the 2014 Ebola and 2015 Zika epidemics. We propose that the time is now to strengthen the global strategy to address the substantial disease burden of schistosomiasis and soil-transmitted helminthiasis.

Background This study investigates the relationships between resilience dimensions, coping strategies, and prior disaster experience, focusing on disaster preparedness and avoidance behaviors in Taiwan. Methods A total of 550 participants were surveyed, with 57.82% being female and the majority aged between 21 and 40 years. Using confirmatory factor analysis (CFA) and path analysis, we examined six resilience dimensions, which include problem-solving, social support, negative emotion regulation, stable interpersonal relationships, assertiveness, and self-regulation, as predictors of disaster preparedness and avoidance behaviors. Results The models accounted for 41.83–44.83% of the variance in preparedness and 5.43–10.74% of the variance in denial/avoidance. Across all models, problem-solving, assertiveness, and living with family consistently predicted higher preparedness, while income consistently predicted lower denial and avoidance behaviors. Notably, flood experience significantly moderated the relationship between social support and denial/avoidance (β = 0.21, p  = .017), indicating that participants with stronger social support who had experienced floods were more likely to engage in denial and avoidance behaviors. Additionally, flood experience negatively moderated the relationship between negative emotion regulation and both preparedness (β = − 0.18, p  = .035) and denial/avoidance (β = − 0.23, p  = .030), suggesting that individuals with higher emotional regulation were less likely to prepare or deny disaster risks after flood exposure. Conclusion These findings highlight the importance of addressing individual resilience capacities and the complexities of prior disaster experiences in disaster preparedness interventions, with particular attention to vulnerable populations.

IL-37 is a member of the IL-1 family with profound anti-inflammatory functions. Nold and colleagues identify the receptor for IL-37 and clarify the molecular nature of the anti-inflammatory pathway induced by this cytokine. Interleukin 37 (IL-37) and IL-1R8 (SIGIRR or TIR8) are anti-inflammatory orphan members of the IL-1 ligand family and IL-1 receptor family, respectively. Here we demonstrate formation and function of the endogenous ligand-receptor complex IL-37–IL-1R8–IL-18Rα. The tripartite complex assembled rapidly on the surface of peripheral blood mononuclear cells upon stimulation with lipopolysaccharide. Silencing of IL-1R8 or IL-18Rα impaired the anti-inflammatory activity of IL-37. Whereas mice with transgenic expression of IL-37 (IL-37tg mice) with intact IL-1R8 were protected from endotoxemia, IL-1R8-deficient IL-37tg mice were not. Proteomic and transcriptomic investigations revealed that IL-37 used IL-1R8 to harness the anti-inflammatory properties of the signaling molecules Mer, PTEN, STAT3 and p62(dok) and to inhibit the kinases Fyn and TAK1 and the transcription factor NF-κB, as well as mitogen-activated protein kinases. Furthermore, IL-37–IL-1R8 exerted a pseudo-starvational effect on the metabolic checkpoint kinase mTOR. IL-37 thus bound to IL-18Rα and exploited IL-1R8 to activate a multifaceted intracellular anti-inflammatory program.

Cannabis use in pregnancy is associated with adverse perinatal outcomes, which are likely mediated by the placenta. However, the underlying mechanisms and specific vasoactive effects of cannabis on the placenta are unknown. Our objective was to determine the impact of chronic prenatal delta-tetrahydrocannabinol (THC, main psychoactive component of cannabis) exposure on placental function and development in a rhesus macaque model using advanced imaging. Animals were divided into two groups, control (CON, n = 5) and THC-exposed (THC, n = 5). THC-exposed animals received a THC edible daily pre-conception and throughout pregnancy. Animals underwent serial ultrasound and MRI at gestational days 85 (G85), G110, G135 and G155 (full term is ~ G168). Animals underwent cesarean delivery and placental collection at G155 for histologic and RNA-Seq analysis. THC-exposed pregnancies had significantly decreased amniotic fluid volume (p < 0.001), placental perfusion (p < 0.05), and fetal oxygen availability (p < 0.05), all indicators of placental insufficiency. Placental histological analysis demonstrated evidence of ischemic injury with microinfarctions present in THC-exposed animals only. Bulk RNA-seq demonstrated that THC alters the placental transcriptome and pathway analysis suggests dysregulated vasculature development and angiogenesis pathways. The longer-term consequences of these adverse placental findings are unknown, but they suggest that use of THC during pregnancy may deleteriously impact offspring development.

Mutations in the LRBA gene (encoding the lipopolysaccharide-responsive and beige-like anchor protein) cause a syndrome of autoimmunity, lymphoproliferation, and humoral immune deficiency. The biological role of LRBA in immunologic disease is unknown. We found that patients with LRBA deficiency manifested a dramatic and sustained improvement in response to abatacept, a CTLA4 (cytotoxic T lymphocyte antigen-4)–immunoglobulin fusion drug. Clinical responses and homology of LRBA to proteins controlling intracellular trafficking led us to hypothesize that it regulates CTLA4, a potent inhibitory immune receptor. We found that LRBA colocalized with CTLA4 in endosomal vesicles and that LRBA deficiency or knockdown increased CTLA4 turnover, which resulted in reduced levels of CTLA4 protein in FoxP3+ regulatory and activated conventional T cells. In LRBA-deficient cells, inhibition of lysosome degradation with chloroquine prevented CTLA4 loss. These findings elucidate a mechanism for CTLA4 trafficking and control of immune responses and suggest therapies for diseases involving the CTLA4 pathway.

Background Many patients experience bilateral knee osteoarthritis and require bilateral total knee replacement (TKR). Same-stage, bilateral TKR is proposed to be a cost-effective and safe solution compared to two-stage, but conflicting results in the literature are reported. We aim to compare the costs, safety, and rehabilitation performance of patients in same-stage versus two-stage, bilateral TKR with our centre’s perioperative protocol. Materials and methods We retrospectively reviewed 175 patients (95 same-stage, 80 two-stage) who had undergone bilateral TKR in our centre. Patient selection for same-stage, bilateral TKR was strictly protocol-driven and required fulfilment of all criteria, including age < 75 years, American Society of Anesthesiologists (ASA) grade 1 or 2, body mass index (BMI) < 40, and having non-complex arthritis. All patients followed a standardised pre-operative, intra-operative, and post-operative Enhanced Recovery After Surgery (ERAS) protocol. The cost, safety profiles, and rehabilitation outcomes were compared between the same-stage and two-stage groups. Results The same-stage, bilateral TKR reduced the length of hospital stays by 5.71 days per patient, decreased the operation time by 27.4 min, saved 3.34 (18.6%) physiotherapy sessions, and 3.78 (51.5%) occupational therapy sessions. The same-stage group experienced a higher haemoglobin drop but no significant difference in transfusion percentage, transfusion volume, complication rate, and readmission rate. The two-stage subgroup with anaesthetic risk, age, and BMI similar to the same-stage group showed the same results. Same-stage, bilateral TKR patients experienced no significant difference in final post-operative pain levels and rehabilitation outcomes as two-stage TKR patients. Conclusion This study showed that same-stage, bilateral TKR can reduce costs, with similar safety profiles and rehabilitation outcomes compared to the two-stage, bilateral TKR.

This is a prospective study to establish prediction models that map the refined Scoliosis Research Society 22-item (SRS-22r) onto EuroQoL-5 dimension 5-level (EQ-5D-5L) utility scores in adolescent idiopathic scoliosis (AIS) patients. Comparison of treatment outcomes in AIS can be determined by cost-utility analysis. However, the mainstay spine-specific health-related quality of life outcome measure, the SRS-22r questionnaire does not provide utility assessment. In this study, AIS patients were prospectively recruited to complete both the EQ-5D-5L and SRS-22r questionnaires by trained interviewers. Ordinary least squares regression was undertaken to develop mapping models, which the validity and robustness were assessed by using the 10-fold cross-validation procedure. EQ-5D-5L utility scores were regressed on demographics, Cobb angle, curve types, treatment modalities, and five domains of the SRS-22r questionnaire. Three models were developed using stepwise selection method. EQ-5D-5L scores were regressed on 1) main effects of SRS-22r subscale scores, 2) as per 1 plus squared and interaction terms, and 3) as per 2 plus demographic and clinical characteristics. Model goodness-of-fit was assessed using R-square, adjusted R-square, and information criteria; whereas the predictive performance was evaluated using root mean square error (RMSE), mean absolute error (MAE), and the proportion of absolute error within the threshold of 0.05 and 0.10. A total of 227 AIS patients with mean age of 15.6 years were recruited. The EQ-5D-5L scores were predicted by four domains of SRS-22r (main effects of 'Function', 'Pain', 'Appearance' and 'Mental Health', and squared term of 'Function' and 'Pain'), and Cobb angle in Model 3 with the best goodness-of-fit (R-square/adjusted R-square: 62.1%/60.9%). Three models demonstrated an acceptance predictive performance in error analysis applying 10-fold cross-validation to three models where RMSE and MAE were between 0.063-0.065 and between 0.039-0.044, respectively. Model 3 was therefore recommended out of three mapping models established in this paper. To our knowledge, this is the first study to map a spine-specific health-related quality of life measure onto EQ-5D-5L for AIS patients. With the consideration and incorporation of demographic and clinical characteristics, over 60% variance explained by mapping model 3 enabled the satisfactory prediction of EQ-5D-5L utility scores from existing SRS-22r data for health economic appraisal of different treatment options.