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Purpose To describe the change in ventilatory practice in a tertiary paediatric intensive care unit (PICU) in the 5-year period after the introduction of high-flow nasal prong (HFNP) therapy in infants <24 months of age. Additionally, to identify the patient subgroups on HFNP requiring escalation of therapy to either other non-invasive or invasive ventilation, and to identify any adverse events associated with HFNP therapy. Methods The study was a retrospective chart review of infants <24 months of age admitted to our PICU for HFNP therapy. Data was also extracted from both the local database and the Australian New Zealand paediatric intensive care (ANZPIC) registry for all infants admitted with bronchiolitis. Results Between January 2005 and December 2009, a total of 298 infants <24 months of age received HFNP therapy. Overall, 36 infants (12%) required escalation to invasive ventilation. In the subgroup with a primary diagnosis of viral bronchiolitis ( n  = 167, 56%), only 6 (4%) required escalation to invasive ventilation. The rate of intubation in infants with viral bronchiolitis reduced from 37% to 7% over the observation period corresponding with an increase in the use of HFNP therapy. No adverse events were identified with the use of HFNP therapy. Conclusion HFNP therapy has dramatically changed ventilatory practice in infants <24 months of age in our institution, and appears to reduce the need for intubation in infants with viral bronchiolitis.

Ostracod shells are used extensively in paleontology, but we know little about their evolution, especially in ancient lakes. Lake Baikal (LB) is the world’s most important stronghold of Candonidae diversity. These crustaceans radiated here rapidly (12–5 Ma) and with an unprecedented morphological diversity. We reconstruct their molecular phylogeny with 46 species and two markers (18S and 16S rRNA), and use it to estimate the evolution of the shell shape and size with landmark-based geometric morphometrics (LBGM). High posterior probabilities support four major clades, which differ in node depth and morphospace clustering. After removing a significant allometry, the first three principal components (PCs) describe about 88% of total variability, suggesting a strong integration. Reconstructed ancestral shapes are similar for all four clades, indicating that diversification happened after colonization. Major evolutionary changes occurred from trapezoidal to elongated shapes. Sister species are separated in morphospace, by centroid size, or both, as well as by vertical and horizontal distributions in LB. Ostracod shell is a strongly integrated structure that exhibits high evolvability, with some extreme shapes, although mostly along the first PC. This is the first study that combines molecular phylogeny and LBGM for ostracods and for any LB group.

To investigate factors associated with survival after out-of-hospital cardiac arrest in Viet Nam. We did a multicentre prospective observational study of people (> 18 years) presenting with out-of-hospital cardiac arrest (not caused by trauma) to three tertiary hospitals in Viet Nam from February 2014 to December 2018. We collected data on characteristics, management and outcomes of patients with out-of-hospital cardiac arrest and compared these data by type of transportation to hospital and survival to hospital admission. We assessed factors associated with survival to admission to and discharge from hospital using logistic regression analysis. Of 590 eligible people with out-of-hospital cardiac arrest, 440 (74.6%) were male and the mean age was 56.1 years (standard deviation: 17.2). Only 24.2% (143/590) of these people survived to hospital admission and 14.1% (83/590) survived to hospital discharge. Most cardiac arrests (67.8%; 400/590) occurred at home, 79.4% (444/559) were witnessed by bystanders and 22.3% (124/555) were given cardiopulmonary resuscitation by a bystander. Only 8.6% (51/590) of the people were taken to hospital by the emergency medical services and 32.2% (49/152) received pre-hospital defibrillation. Pre-hospital defibrillation (odds ratio, OR: 3.90; 95% confidence interval, CI: 1.54-9.90) and return of spontaneous circulation in the emergency department (OR: 2.89; 95% CI: 1.03-8.12) were associated with survival to hospital admission. Hypothermia therapy during post-resuscitation care was associated with survival to discharge (OR: 5.44; 95% CI: 2.33-12.74). Improvements are needed in the emergency medical services in Viet Nam such as increasing bystander cardiopulmonary resuscitation and public access defibrillation, and improving ambulance and post-resuscitation care.

Neurodegenerative diseases (NDDs) present significant challenges due to limited treatment options, ethical concerns surrounding traditional animal models, and the time-consuming and costly process of using human-induced pluripotent stem cells (iPSCs). We addressed these issues by developing a 3D culture protocol for differentiating SH-SY5Y cells into glutamatergic neurons, enhancing physiological relevance with a 3D microarray culture plate. Our protocol optimized serum concentration and incorporated retinoic acid (RA) to improve differentiation. We analyzed the proportions of N-type and S-type cells, observing that RA in the maturation stage not only reduced cell proliferation but also enhanced the expression of MAP2 and VGLUT1, indicating effective neuronal differentiation. Our approach demonstrates the strong expression of glutamatergic neuron phenotypes in 3D SH-SY5Y neural spheroids, offering a promising tool for high-throughput NDD modeling and advancing drug discovery and therapeutic development. This method overcomes limitations associated with conventional 2D cultures and animal models, providing a more effective platform for NDD research.

Mirror movements are involuntary contralateral movements that mirror voluntary ones and are often associated with defects in midline crossing of the developing central nervous system. We studied two large families, one French Canadian and one Iranian, in which isolated congenital mirror movements were inherited as an autosomal dominant trait. We found that affected individuals carried protein-truncating mutations in DCC (deleted in colorectal carcinoma), a gene on chromosome 18q21.2 that encodes a receptor for netrin-1, a diffusible protein that helps guide axon growth across the midline. Functional analysis of the mutant DCC protein from the French Canadian family revealed a defect in netrin-1 binding. Thus, DCC has an important role in lateralization of the human nervous system.

Background: Vitamin D deficiency (VDD) is a global micronutrient issue that commonly occurs in pregnant women, leading to adverse health outcomes. We examined the role of sunlight-related factors and dietary vitamin D intake on vitamin D concentrations among pregnant women in different climate zones. Methods: We conducted a nationwide cross-sectional survey in Taiwan between June 2017 and February 2019. The data of 1502 pregnant women were collected, including sociodemographic information and characteristics related to pregnancy, diet, and sun exposure. Serum 25-hydroxyvitamin D concentrations were measured, and VDD was assessed as a concentration of less than 20 ng/mL. Logistic regression analyses were used to explore the factors associated with VDD. Furthermore, the area under the receiver operating characteristic (AUROC) curve was used to analyze the contribution of sunlight-related factors and dietary vitamin D intake to vitamin D status stratified by climate zones. Results: The prevalence of VDD was 30.1% and was the highest in the north. Sufficient intake of red meat (odds ratio (OR): 0.50, 95% confidence interval (CI): 0.32–0.75; p = 0.002), vitamin D and/or calcium supplements (OR: 0.51, 95% CI: 0.39–0.66; p < 0.001), sun exposure (OR: 0.75, 95% CI: 0.57–0.98; p = 0.034), and blood draw during sunny months (OR: 0.59, 95% CI: 0.46–0.77; p < 0.001) were associated with a lower likelihood of VDD. Additionally, in northern Taiwan, which is characterized by a subtropical climate, dietary vitamin D intake (AUROC: 0.580, 95% CI: 0.528–0.633) had a greater influence on vitamin D status than did sunlight-related factors (AUROC: 0.536, 95% CI: 0.508–0.589) with a z value = 51.98, p < 0.001. By contrast, sunlight-related factors (AUROC: 0.659, 95% CI: 0.618–0.700) were more important than dietary vitamin D intake (AUROC: 0.617, 95% CI, 0.575–0.660) among women living in tropical areas of Taiwan (z value = 54.02, p < 0.001). Conclusions: Dietary vitamin D intake was essential to alleviate VDD in the tropical region, whereas sunlight-related factors played a greater role in subtropical areas. Safe sunlight exposure and adequate dietary vitamin D intake should be promoted appropriately as a strategic healthcare program.

Molecular epidemiology and clinical impact of human rhinovirus (HRV) are not well documented in tropical regions. This study compared the clinical characteristics of HRV to other common viral infections and investigated the molecular epidemiology of HRV in hospitalized children with acute respiratory infections (ARIs) in Vietnam. From April 2010 to May 2011, 1082 nasopharyngeal swabs were screened for respiratory viruses by PCR. VP4/VP2 sequences of HRV were further characterized. HRV was the most commonly detected virus (30%), in which 70% were diagnosed as either pneumonia or bronchiolitis. Children with single HRV infections presented with significantly higher rate of hypoxia than those infected with respiratory syncytial virus or parainfluenza virus (PIV)-3 (12·4% vs. 3·8% and 0%, respectively, P < 0·05), higher rate of chest retraction than PIV-1 (57·3% vs. 34·5%, P = 0·028), higher rate of wheezing than influenza A (63·2% vs. 42·3%, P = 0·038). HRV-C did not differ to HRV-A clinically. The genetic diversity and changes of types over time were observed and may explain the year-round circulation of HRV. One novel HRV-A type was discovered which circulated locally for several years. In conclusion, HRV showed high genetic diversity and was associated with significant morbidity and severe ARIs in hospitalized children.

Background Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) gain attention as a potent cell source in regenerative medicine and drug discovery. With the necessity of the demands for experimental models to create a more physiologically relevant model of the heart in vitro we herein investigate a 3D culturing platform and a method for assessing rhythm in hiPSC-CMs. Methods The 3D cell culture PAMCELL™ plate is designed to enable cells to attach exclusively to adhesive patterned areas. These cell adhesive zones, named as micro-patterned pads, feature micron silica beads that are surface-modified with the well-known arginyl-glycyl-aspartic acid (RGD) peptide. RGD binding to the surface of hiPSC-CMs facilitates cell–cell attachment and the formation of uniform-size spheroids, which is controlled by the diameter of the micro-patterned pads. The assessment and evaluation of 3D hiPSC-CMs beating pattern are carried out using reflective properties of retroreflective Janus micro-particle (RJP). These RJPs are modified with an antibody targeting the gap junction protein found on the surface of hiPSC-CM spheroids. The signal assessment system comprises a camera attached to an optical microscope and a white light source. Results The 3D PAMCELL™ R100 culture plate efficiently generate approximately 350 uniform-sized hiPSC-CM spheroids in each well of a 96-well plate and supported a 20-day culture. Analysis of genes and protein expression levels reveal that iPSC-CM spheroids grown on PAMCELL™ R100 retain cardiac stem cell characteristics and functions, outperforming traditional 2D culture platform. Additionally, the RJPs enable monitoring and evaluation of in vitro beating properties of cardiomyocytes without using complex monitoring setup. The system demonstrates its capability to identify alteration in the rhythmic activity of cardiac cells when exposed to ion channel blockers, nifedipine and E4031. Conclusions The integration of the 3D culture method and RJPs in this study establishes a platform for evaluating the rhythmic properties of 3D hiPSC-CMs. This approach holds significant potential for identifying arrhythmias or other cardiac abnormalities, ultimately contributing to the development of more effective therapies for heart diseases. Graphical Abstract

This study sought to investigate the prevalence of osteoporosis and the role of sex hormone levels in the determination of bone mineral density (BMD) and osteoporosis in a Vietnamese population of women and men. The cross-sectional study involved 269 women and 222 men aged 13–83 years, who were randomly selected from urban and rural areas in northern Vietnam. Serum concentrations of estradiol and testosterone were analyzed, and BMD was measured by dual X-ray absorptiometry. We found that the prevalence of osteoporosis in postmenopausal women was 18, 17, and 37 % for the femoral neck, total hip, and lumbar spine, respectively. For men aged 50 years or older, the corresponding values were 8, 7, and 12 %. In men, the most important predictors of BMD for the femoral neck and total hip were age, body mass index, and serum levels of estradiol. For the BMD of the lumbar spine, testosterone also had a significant influence. Determinants of osteoporosis in men for the total hip and lumbar spine were age, weight, and serum concentrations of estradiol and testosterone. In postmenopausal women, age, weight, and residence (urban vs rural) were the most important predictors of BMD and osteoporosis. For all women (including those of reproductive age), serum levels of estradiol were also significant. These data suggest that the prevalence of osteoporosis in the Vietnamese population is high also in men, and that estradiol levels are essential for bone mass in both men and women. The results should have clinical implications and increase awareness of an important health issue within Vietnamese society.

Bone differentiation is crucial for skeletal development and maintenance. Its dysfunction can cause various pathological conditions such as rickets, osteoporosis, osteogenesis imperfecta, or Paget’s disease. Although traditional two-dimensional cell culture systems have contributed significantly to our understanding of bone biology, they fail to replicate the intricate biotic environment of bone tissue. Three-dimensional (3D) spheroid cell cultures have gained widespread popularity for addressing bone defects. This review highlights the advantages of employing 3D culture systems to investigate bone differentiation. It highlights their capacity to mimic the complex in vivo environment and crucial cellular interactions pivotal to bone homeostasis. The exploration of 3D culture models in bone research offers enhanced physiological relevance, improved predictive capabilities, and reduced reliance on animal models, which have contributed to the advancement of safer and more effective strategies for drug development. Studies have highlighted the transformative potential of 3D culture systems for expanding our understanding of bone biology and developing targeted therapeutic interventions for bone-related disorders. This review explores how 3D culture systems have demonstrated promise in unraveling the intricate mechanisms governing bone homeostasis and responses to pharmacological agents.