A Narrative Review on Diabetic Ketoacidosis in Children.

BACKGROUND: Diabetic ketoacidosis (DKA) is a life-threatening complication in children with diabetes mellitus. There are considerable differences in the management approaches for DKA between different countries. One of the main areas of differences between guidelines is the administration of fluid, with most guidelines adopting a restrictive approach. This is based on the concern over cerebral oedema, a lethal sequela allegedly to be caused by excessive fluid administration. However, in recent years, new clinical studies suggest that there is no causal relationship between intravenous fluid therapy and DKA-related cerebral injury. The British Society of Paediatric Endocrinology updated its guideline in 2020 to adopt a more permissive approach to fluid administration, which has sparked controversy among some paediatricians. OBJECTIVES: The purpose of this article is to provide a narrative review on the management of DKA. METHODS: A PubMed search was performed with clinical queries using the key term "diabetic ketoacidosis". The search strategy included randomized controlled trials, clinical trials, meta-analyses, observational studies, guidelines, and reviews. The search was restricted to English literature and the age range of 18 years and younger. Moreover, we reviewed and compared major guidelines. CONCLUSION: The management of DKA involves early recognition, accurate diagnosis, meticulous fluid and insulin treatment with close monitoring of blood glucose, ketones, electrolytes, renal function, and neurological status. There is still limited clinical evidence to support either a restrictive or permissive approach in the fluid management of paediatric DKA patients. Clinicians should exercise caution when applying different guidelines in their clinical practice, considering the specific circumstances of individual paediatric patients.

How People Process Different Types of Health Misinformation: Roles of Content Falsity and Evidence Type.

Emerging communication technologies have seen the proliferation of misleading claims, untruthful narratives, and conspiracies. To understand how people perceive and act on different types of misinformation, this study examines how health misinformation varying in falsity (fabrication versus misuse) and evidence type (statistical versus narrative) affects sharing and verification intentions. Using COVID-19 vaccines as cases, the results from an online experiment showed that misused misinformation was perceived as less false than fabricated misinformation and resulted in higher sharing intentions for the issue of vaccine efficacy. Misinformation with narrative evidence, as compared to that with statistical evidence, was perceived as less false and led to lower verification intentions. These findings can be explained by psychological processes such as counterarguing and narrative engagement. Our results can help practitioners develop dedicated misinformation literacy programs.

Cashless gambling: Qualitative analysis of consumer perspectives regarding the harm minimization potential of digital payment systems for electronic gaming machines.

OBJECTIVE: Land-based gambling venues remain predominantly cash-based despite broader consumer trends toward digital payments. Little prior literature directly investigates the role of payment methods in gambling; however, digital payment systems offer a key intervention point for gambling harm minimization. This study explores the perspectives of electronic gaming machine (EGM) gamblers regarding the concept of cashless gambling-the ability to gamble without using physical currency. METHOD: Twenty-six Australian EGM gamblers (10 females, 16 males; aged 24-76 years) participated in four online focus group discussions. Using content analysis and a pragmatic approach, data were organized thematically in relation to consumer perceptions about the benefits and risks of cashless gambling, factors potentially influencing uptake of cashless gambling, and recommendations about harm reduction features that could be incorporated into the system. RESULTS: Cashless gambling was perceived to present important opportunities for more useful and meaningful harm reduction measures based on the ability to track a user's complete gambling activity. However, participants reported reluctance toward adoption of cashless gambling, tending to perceive such systems as being overly restrictive and invasive, and potentially facilitating (over)spending, depending on design and implementation. Participants commonly perceived systems as offering little value to individuals who gamble without experiencing significant harms. CONCLUSIONS: Perceived irrelevance and privacy concerns appear to be major barriers to adoption of a cashless gambling system with strong harm reduction features. Our findings provide insights for policy makers considering the optimal design, implementation, and marketing of cashless gambling from a harm reduction perspective. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A case series of appendicitis and pseudo-appendicitis in a paediatric intensive care unit.

INTRODUCTION: Appendicitis is a common childhood condition that can be diagnostically challenging. Severe cases may necessitate support in the critical or intensive care unit. These "critical appendicitis diagnoses" have rarely been described. CASE DESCRIPTION: We retrospective reviewed the PICU database of the Hong Kong Children's Hospital and identified cases of suspected and confirmed appendicitis. Clinical features, radiologic findings and final diagnosis of each case were summarized and reported in this case series. We review six anonymized cases of appendicitis managed in a paediatric intensive care unit (PICU) to illustrate the different age spectrum and clinical manifestations of the condition. Rupture of the inflamed appendix, peritonitis and pancreatitis were some of the complications encountered. Crohn disease was found in one case as an underlying diagnosis. Also, one girl clinically diagnosed with appendicitis was found to be a case of ruptured hepatoblastoma with no appendicitis (i.e., pseudoappendicitis). CONCLUSION: Prompt diagnosis, surgical removal of the inflamed appendix, and use of appropriate antimicrobials when indicated are essential in reducing mortality and morbidity associated with severe appendicitis. Significant premorbid conditions such as acute myeloid leukemia, mitochondrial encephalopathy lactic acidosis syndrome (MELAS), inflammatory bowel disease and complications may be present in patients needing intensive care as is illustrated in the present cases. Pseudoappendicitis is an important differential diagnosis. Imaging is crucial and useful in establishing and confirming the diagnosis of appendicitis and pseudo-appendicitis in these PICU cases.

Diversifying Amino Acids and Peptides via Deaminative Reductive Cross-Couplings Leveraging High-Throughput Experimentation.

A deaminative reductive coupling of amino acid pyridinium salts with aryl bromides has been developed to enable efficient synthesis of noncanonical amino acids and diversification of peptides. This method transforms natural, commercially available lysine, ornithine, diaminobutanoic acid, and diaminopropanoic acid to aryl alanines and homologated derivatives with varying chain lengths. Attractive features include ability to transverse scales, tolerance of pharma-relevant (hetero)aryls and biorthogonal functional groups, and the applicability beyond monomeric amino acids to short and macrocyclic peptide substrates. The success of this work relied on high-throughput experimentation to identify complementary reaction conditions that proved critical for achieving the coupling of a broad scope of aryl bromides with a range of amino acid and peptide substrates including macrocyclic peptides.

Predicting COVID-19 vaccine hesitancy in Hong Kong: Vaccine knowledge, risks from coronavirus, and risks and benefits of vaccination.

Introduction: Hongkongers have had access to COVID-19 vaccines for about four months, but vaccination rate remains low (34.4% as of 4 July 2021). Given that vaccine uptake is vital, this study aimed to determine how vaccine-hesitant and vaccinated individuals differ. The study also examined why people choose to delay vaccination (within 1 month, within 2 months, within 3 months, 3 months or more). Material and Methods: A population-based online survey (N = 1654) was conducted between 22 and 30 June 2021, a month after the Hong Kong government announced "Say no to vaccine hesitancy" on its website. All adults aged 18 years and older were eligible to take part. The survey included sociodemographic details, perceived susceptibility to infection, and perceived vaccine efficacy and risks. A series of analyses of covariance was performed to inspect differences among the groups and multiple regression analyses were done to examine factors associated with COVID-19 vaccine hesitancy. Results: With a vaccine hesitancy rate of 30.3%, analyses revealed that sociodemographic factors, party identification and self-reported health status had no effects on the degrees of vaccine hesitancy. While vaccine knowledge, perceived susceptibility to infection, and vaccine efficacy and safety were positive correlates of vaccine uptake, risks from vaccination and vaccine efficacy were positive correlates of vaccine hesitancy. Conclusions: Hesitancy in Hong Kong is more about vaccine efficacy and safety, and less about infection risks. Specifically, respondents expressed concerns about the particular vaccines supplied, especially BioNTech's efficacy and risks from Sinovac. While higher risk motivates longer preparation for vaccine uptake, higher levels of benefits from BioNTech could reduce hesitancy.

Assessing Mechanisms Underlying the Sharing of Official and Unofficial Information during a Pandemic.

The COVID-19 disease outbreak has seen mixed information flows comprising top-down communication from health authorities to the public and citizen-to-citizen communication. This study aimed to identify mechanisms underlying the sharing of official versus unofficial information during the outbreak. Survey findings based on a nationally representative U.S. sample (N = 856) showed that individuals' predispositions affected their information consumption and affective experiences, leading to distinct types of information-sharing behaviors. While anger toward the U.S. government's outbreak response was directly associated with unofficial information sharing, anxiety was directly associated with official information sharing. These findings enhance our understanding of the propagation of different kinds of pandemic information and provide implications for public education on information verification based on source authoritativeness.

High-efficiency motor neuron differentiation from human pluripotent stem cells and the function of Islet-1.

Efficient derivation of large-scale motor neurons (MNs) from human pluripotent stem cells is central to the understanding of MN development, modelling of MN disorders in vitro and development of cell-replacement therapies. Here we develop a method for rapid (20 days) and highly efficient (~70%) differentiation of mature and functional MNs from human pluripotent stem cells by tightly modulating neural patterning temporally at a previously undefined primitive neural progenitor stage. This method also allows high-yield (>250%) MN production in chemically defined adherent cultures. Furthermore, we show that Islet-1 is essential for formation of mature and functional human MNs, but, unlike its mouse counterpart, does not regulate cell survival or suppress the V2a interneuron fate. Together, our discoveries improve the strategy for MN derivation, advance our understanding of human neural specification and MN development, and provide invaluable tools for human developmental studies, drug discovery and regenerative medicine.

Giving and Receiving Emotional Support Online: Communication Competence as a Moderator of Psychosocial Benefits for Women with Breast Cancer.

This study examines the moderating role of emotional communication competence in the relationship between computer-mediated social support (CMSS) group participation, specifically giving and receiving emotional support, and psychological health outcomes. Data were collected as part of randomized clinical trials for women diagnosed with breast cancer within the last 2 months. Expression and reception of emotional support was assessed by tracking and coding the 18,064 messages that 236 patients posted and read in CMSS groups. The final data used in the analysis was created by merging (a) computer-aided content analysis of discussion posts, (b) action log data analysis of system usage, and (c) baseline and six-month surveys collected to assess change. Results of this study demonstrate that emotional communication competence moderates the effects of expression and reception of emotional support on psychological quality of life and breast cancer-related concerns in both desired and undesired ways. Giving and receiving emotional support in CMSS groups has positive effects on emotional well-being for breast cancer patients with higher emotional communication, while the same exchanges have detrimental impacts on emotional well-being for those with lower emotional communication competence. The theoretical and practical implications for future research are discussed.

It is out of my hands: how deferring control to God can decrease quality of life for breast cancer patients.

OBJECTIVE: This paper seeks to contribute to the understanding of how and why religion affects psychosocial health outcomes. We propose a theoretical model predicting that when women with breast cancer defer control to God they will experience fewer breast cancer related concerns. Deferring control to God, however, should also reduce the likelihood that they take a proactive coping approach, which will be exacerbated by lowered breast cancer concerns. We therefore predict that this passive coping style will ultimately result in lower levels of quality of life. METHODS: Data were collected as part of a randomized clinical trial funded by the National Cancer Institute. A total of 192 women with breast cancer participated in a computer-mediated social support group. Deferring control to God statements were captured by using computer-aided content analysis of discussion posts. Psychosocial outcomes were measured using longitudinal survey data. Analysis was performed using structural equation modeling. RESULTS: The results of our analysis largely confirm our mediation model for which we find significant model fit. As predicted, deferring control to God leads to lower levels of breast cancer concerns but also to more passive coping styles. Ultimately, deferring control to God can lead to lower levels of quality of life. CONCLUSIONS: Our study demonstrates how and why religious coping can lead to both positive and negative psychosocial health outcomes. Health care practitioners should encourage patients who are relying on religion to keep their end of the bargain and maintain an active coping style.

High-efficiency induction of neural conversion in human ESCs and human induced pluripotent stem cells with a single chemical inhibitor of transforming growth factor beta superfamily receptors.

Chemical compounds have emerged as powerful tools for modulating ESC functions and deriving induced pluripotent stem cells (iPSCs), but documentation of compound-induced efficient directed differentiation in human ESCs (hESCs) and human iPSC (hiPSCs) is limited. By screening a collection of chemical compounds, we identified compound C (also denoted as dorsomorphin), a protein kinase inhibitor, as a potent regulator of hESC and hiPSC fate decisions. Compound C suppresses mesoderm, endoderm, and trophoectoderm differentiation and induces rapid and high-efficiency neural conversion in both hESCs and hiPSCs, 88.7% and 70.4%, respectively. Interestingly, compound C is ineffective in inducing neural conversion in mouse ESCs (mESCs). Large-scale kinase assay revealed that compound C targets at least seven transforming growth factor beta (TGF-ß) superfamily receptors, including both type I and type II receptors, and thereby blocks both the Activin and bone morphogenesis protein (BMP) signaling pathways in hESCs. Dual inhibition of Activin and BMP signaling accounts for the effects of compound C on hESC differentiation and neural conversion. We also identified muscle segment homeobox gene 2 (MSX2) as a downstream target gene of compound C and a key signaling intermediate of the BMP pathway in hESCs. Our findings provide a single-step cost-effective method for efficient derivation of neural progenitor cells in adherent culture from human pluripotent stem cells. Therefore, it will be uniquely suitable for the production of neural progenitor cells in large scale and should facilitate the use of stem cells in drug screening and regenerative medicine and study of early human neural development.

FXR acetylation is normally dynamically regulated by p300 and SIRT1 but constitutively elevated in metabolic disease states.

The nuclear bile acid receptor FXR is critical for regulation of lipid and glucose metabolism. Here, we report that FXR is a target of SIRT1, a deacetylase that mediates nutritional and hormonal modulation of hepatic metabolism. Lysine 217 of FXR is the major acetylation site targeted by p300 and SIRT1. Acetylation of FXR increases its stability but inhibits heterodimerization with RXRalpha, DNA binding, and transactivation activity. Downregulation of hepatic SIRT1 increased FXR acetylation with deleterious metabolic outcomes. Surprisingly, in mouse models of metabolic disease, FXR interaction with SIRT1 and p300 was dramatically altered, FXR acetylation levels were elevated, and overexpression of SIRT1 or resveratrol treatment reduced acetylated FXR levels. Our data demonstrate that FXR acetylation is normally dynamically regulated by p300 and SIRT1 but is constitutively elevated in metabolic disease states. Small molecules that inhibit FXR acetylation by targeting SIRT1 or p300 may be promising therapeutic agents for metabolic disorders.

Cytoplasmic inclusion cistron of Soybean mosaic virus serves as a virulence determinant on Rsv3-genotype soybean and a symptom determinant.

Soybean mosaic virus (SMV; Potyvirus, Potyviridae) is one of the most widespread viruses of soybean globally. Three dominant resistance genes (Rsv1, Rsv3 and Rsv4) differentially confer resistance against SMV. Rsv1 confers extreme resistance and the resistance mechanism of Rsv4 is associated with late susceptibility. Here, we show that Rsv3 restricts the accumulation of SMV strain G7 to the inoculated leaves, whereas, SMV-N, an isolate of SMV strain G2, establishes systemic infection. This observation suggests that the resistance mechanism of Rsv3 differs phenotypically from those of Rsv1 and Rsv4. To identify virulence determinant(s) of SMV on an Rsv3-genotype soybean, chimeras were constructed by exchanging fragments between avirulent SMV-G7 and the virulent SMV-N. Analyses of the chimeras showed that both the N- and C-terminal regions of the cytoplasmic inclusion (CI) cistron are required for Rsv3-mediated resistance. Interestingly, the N-terminal region of CI is also involved in severe symptom induction in soybean.

The p300 acetylase is critical for ligand-activated farnesoid X receptor (FXR) induction of SHP.

The primary bile acid receptor farnesoid X receptor (FXR) maintains lipid and glucose homeostasis by regulating expression of numerous bile acid-responsive genes, including an orphan nuclear receptor and metabolic regulator SHP. Using SHP as a model gene, we studied how FXR activity is regulated by p300 acetylase. FXR interaction with p300 and their recruitment to the SHP promoter and acetylated histone levels at the promoter were increased by FXR agonists in mouse liver and HepG2 cells. In contrast, p300 recruitment and acetylated histones at the promoter were not detected in FXR-null mice. p300 directly interacted with and acetylated FXR in vitro. Overexpression of p300 wild type increased, whereas a catalytically inactive p300 mutant decreased, acetylated FXR levels and FXR transactivation in cells. While similar results were observed with a related acetylase, CBP, GCN5 did not enhance FXR transactivation, and its recruitment to the promoter was not increased by FXR agonists, suggesting functional specificity of acetylases in FXR signaling. Down-regulation of p300 by siRNA decreased acetylated FXR and acetylated histone levels, and occupancy of FXR at the promoter, resulting in substantial inhibition of SHP expression. These results indicate that p300 acts as a critical coactivator of FXR induction of SHP by acetylating histones at the promoter and FXR itself. Surprisingly, p300 down-regulation altered expression of other metabolic FXR target genes involved in lipoprotein and glucose metabolism, such that beneficial lipid and glucose profiles would be expected. These unexpected findings suggest that inhibition of hepatic p300 activity may be beneficial for treating metabolic diseases.