A preliminary retrospective evaluation of screening and diagnosis of ornithine transcarbamylase deficiency in high-risk patients at a referral center in Vietnam.

Introduction: To date, newborn screening (NBS) for proximal urea cycle disorders, including Ornithine transcarbamylase deficiency (OTCD), was not recommended due to the lack of appropriate tests and insufficient evidence of the benefits. This study aimed to investigate the potential of tandem mass spectrometry (MS/MS) for OTCD screening and its value in guiding further investigation to obtain a final diagnosis in high-risk patients. Methods: The study included patients with OTCD referred to the National Children's Hospital between April 2020 and November 2023. A retrospective evaluation of amino acid concentrations measured by MS/MS and their ratios in patients with early-onset and late-onset OTCD was conducted. Results: While all ten early-onset cases had glutamine concentrations above the upper limit, only five of them had citrulline concentrations below the lower limit of the reference interval. Only two late-onset cases had elevated glutamine levels, while all had citrulline within reference intervals. The Cit/Phe ratio was decreased, and the Gln/Cit and Met/Cit ratios were increased in all early-onset OTCD cases, while they were abnormal in only one late-onset case. Conclusions: The preliminary results suggest that hyperglutaminemia, in combination with low or normal citrulline concentrations and specific ratios (Gln/Cit, Met/Cit, and Cit/Phe), can serve as reliable markers for screening early-onset OTCD in high-risk patients. However, these markers proved less sensitive for detecting the late-onset form, even in symptomatic patients.

Alzheimer Disease: Treatment of Cognitive and Functional Symptoms.

Alzheimer disease is a progressive, neurodegenerative disorder characterized by the accumulation of amyloid beta plaques and hyperphosphorylated tau proteins. Alzheimer disease affects cognitive function, leading to memory loss and impairment in activities of daily living. Approximately 6.9 million people in the United States 65 years and older live with Alzheimer disease, a number expected to double by 2060. Although there is no cure for Alzheimer disease, treatments are available to manage symptoms. Tools such as the Diagnostic and Statistical Manual of Mental Disorders, 5th ed., criteria aid in identifying major neurocognitive disorders. The evaluation involves a comprehensive medical history, cognitive examinations, and collateral information. Nonpharmacologic interventions focus on psychosocial approaches, with music, sensory stimulation, and validation therapies showing some evidence of reducing responsive behaviors. Pharmacologic management, such as acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and the N-methyl-d-aspartate receptor antagonist memantine, targets symptom relief and disease progression. Vitamin E does not improve cognition but may mitigate functional decline. Brexpiprazole has been approved in the United States for treating agitation associated with Alzheimer disease. Anti-amyloid monoclonal antibody treatments are approved for mild cognitive impairment and mild Alzheimer disease, but they are controversial and safety concerns exist. Ineffective therapies include ginkgo biloba, nonsteroidal anti-inflammatory drugs, omega-3 fatty acids, and statins.

Impact of Drug Conjugation Site and Corona Chemistry on the Therapeutic Activity of Polymer Nanorod - Drug Conjugates.

Biocompatible rod-shaped nanoparticles of controlled length can be produced through the heat-induced "living" seeded crystallization-driven self-assembly (CDSA) of poly(2-isopropyl-2-oxazoline)-containing block copolymers. With a hydrophilic poly(2-methyl-2-oxazine) or poly(2-methyl-2-oxazoline) corona, these nanorods have proven non-cytotoxic, non-hemolytic, and ideal for use as a polymer-based drug delivery system. This study demonstrates a facile, one-pot method for the synthesis of mycophenolic acid (MPA)-conjugated block copolymer "unimers" for use in seeded CDSA. Through altering block order during sequential monomer addition cationic ring-opening polymerization (CROP), MPA is conjugated to either the chain end of the core-forming or corona-forming block. This allows bioactive polymer nanorods to be prepared with MPA positioned at either the periphery of the corona, or at the core-corona interface of the nanorod formed during seeded CDSA. In vitro, these nanorods arrest growth in human T and B lymphocytes, with reduced effect in "off-target" monocytes when compared with unconjugated MPA. Furthermore, the conjugation of MPA to the core-corona interface of the nanorods leads to a slower release and reduced cytostatic effect. This study offers a robust investigation into the effect of steric hindrance and corona chemistry on the therapeutic potential of drug-conjugated CDSA nanorods and demonstrates the potential of poly(2-oxazoline)/poly(2-oxazine)-based CDSA nanomaterials as effective drug delivery platforms.

The molecular basis underlying T cell specificity towards citrullinated epitopes presented by HLA-DR4.

CD4+ T cells recognising citrullinated self-epitopes presented by HLA-DRB1 bearing the shared susceptibility epitope (SE) are implicated in rheumatoid arthritis (RA). However, the underlying T cell receptor (TCR) determinants of epitope specificity towards distinct citrullinated peptide antigens, including vimentin-64cit59-71 and α-enolase-15cit10-22 remain unclear. Using HLA-DR4-tetramers, we examine the T cell repertoire in HLA-DR4 transgenic mice and observe biased TRAV6 TCR gene usage across these two citrullinated epitopes which matches with TCR bias previously observed towards the fibrinogen ß-74cit69-81 epitope. Moreover, shared TRAV26-1 gene usage is evident in four α-enolase-15cit10-22 reactive T cells in three human samples. Crystal structures of mouse TRAV6+ and human TRAV26-1+ TCR-HLA-DR4 complexes presenting vimentin-64cit59-71 and α-enolase-15cit10-22, respectively, show three-way interactions between the TCR, SE, citrulline, and the basis for the biased selection of TRAV genes. Position 2 of the citrullinated epitope is a key determinant underpinning TCR specificity. Accordingly, we provide a molecular basis of TCR specificity towards citrullinated epitopes.

Severity predictors for multisystemic inflammatory syndrome in children after SARS-CoV-2 infection in Vietnam.

Multisystemic inflammatory syndrome in children (MIS-C) might manifest in a broad spectrum of clinical scenarios, ranging from mild features to multi-organ dysfunction and mortality. However, this novel entity has a heterogenicity of data regarding prognostic factors associated with severe outcomes. The present study aimed to identify independent predictors for severity by using multivariate regression models. A total of 391 patients (255 boys and 136 girls) were admitted to Vietnam National Children's Hospital from January 2022 to June 2023. The median age was 85 (range: 2-188) months, and only 12 (3.1%) patients had comorbidities. 161 (41.2%) patients required PICU admission, and the median PICU LOS was 4 (2-7) days. We observed independent factors related to PICU admission, including CRP ≥ 50 (mg/L) (OR 2.52, 95% CI 1.39-4.56, p = 0.002), albumin ≤ 30 (g/L) (OR 3.18, 95% CI 1.63-6.02, p = 0.001), absolute lymphocyte count ≤ 2 (× 109/L) (OR 2.18, 95% CI 1.29-3.71, p = 0.004), ferritin ≥ 300 (ng/mL) (OR 2.35, 95% CI 1.38-4.01), p = 0.002), and LVEF < 60 (%) (OR 2.48, 95% CI 1.28-4.78, p = 0.007). Shock developed in 140 (35.8%) patients, especially for those decreased absolute lymphocyte ≤ 2 (× 109/L) (OR 2.48, 95% CI 1.10-5.61, p = 0.029), albumin ≤ 30 (g/L) (OR 2.53, 95% CI 1.22-5.24, p = 0.013), or LVEF < 60 (%) (OR 2.24, 95% CI 1.12-4.51, p = 0.022). In conclusion, our study emphasized that absolute lymphocyte count, serum albumin, CRP, and LVEF were independent predictors for MIS-C severity. Further well-designed investigations are required to validate their efficacy in predicting MIS-C severe cases, especially compared to other parameters. As MIS-C is a new entity and severe courses may progress aggressively, identifying high-risk patients optimizes clinicians' follow-up and management to improve disease outcomes.

REV1 coordinates a multi-faceted tolerance response to DNA alkylation damage and prevents chromosome shattering in Drosophila melanogaster.

When replication forks encounter damaged DNA, cells utilize damage tolerance mechanisms to allow replication to proceed. These include translesion synthesis at the fork, postreplication gap filling, and template switching via fork reversal or homologous recombination. The extent to which these different damage tolerance mechanisms are utilized depends on cell, tissue, and developmental context-specific cues, the last two of which are poorly understood. To address this gap, we have investigated damage tolerance responses in Drosophila melanogaster. We report that tolerance of DNA alkylation damage in rapidly dividing larval tissues depends heavily on translesion synthesis. Furthermore, we show that the REV1 protein plays a multi-faceted role in damage tolerance in Drosophila. Larvae lacking REV1 are hypersensitive to methyl methanesulfonate (MMS) and have highly elevated levels of γ-H2Av (Drosophila γ-H2AX) foci and chromosome aberrations in MMS-treated tissues. Loss of the REV1 C-terminal domain (CTD), which recruits multiple translesion polymerases to damage sites, sensitizes flies to MMS. In the absence of the REV1 CTD, DNA polymerases eta and zeta become critical for MMS tolerance. In addition, flies lacking REV3, the catalytic subunit of polymerase zeta, require the deoxycytidyl transferase activity of REV1 to tolerate MMS. Together, our results demonstrate that Drosophila prioritize the use of multiple translesion polymerases to tolerate alkylation damage and highlight the critical role of REV1 in the coordination of this response to prevent genome instability.

A structural basis of T cell cross-reactivity to native and spliced self-antigens presented by HLA-DQ8.

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that has a strong HLA association, where a number of self-epitopes have been implicated in disease pathogenesis. Human pancreatic islet-infiltrating CD4+ T cell clones not only respond to proinsulin C-peptide (PI40-54; GQVELGGGPGAGSLQ) but also cross-react with a hybrid insulin peptide (HIP; PI40-47-IAPP74-80; GQVELGGG-NAVEVLK) presented by HLA-DQ8. How T cell receptors recognize self-peptide and cross-react to HIPs is unclear. We investigated the cross-reactivity of the CD4+ T cell clones reactive to native PI40-54 epitope and multiple HIPs fused at the same N-terminus (PI40-54) to the degradation products of two highly expressed pancreatic islet proteins, neuropeptide Y (NPY68-74) and amyloid polypeptide (IAPP23-29 and IAPP74-80). We observed that five out of the seven selected SKW3 T cell lines expressing TCRs isolated from CD4+ T cells of people with T1D responded to multiple HIPs. Despite shared TRAV26-1-TRBV5-1 gene usage in some T cells, these clones cross-reacted to varying degrees with the PI40-54 and HIP epitopes. Crystal structures of two TRAV26-1+-TRBV5-1+ T cell receptors (TCRs) in complex with PI40-54 and HIPs bound to HLA-DQ8 revealed that the two TCRs had distinct mechanisms responsible for their differential recognition of the PI40-54 and HIP epitopes. Alanine scanning mutagenesis of the PI40-54 and HIPs determined that the P2, P7, and P8 residues in these epitopes were key determinants of TCR specificity. Accordingly, we provide a molecular basis for cross-reactivity towards native insulin and HIP epitopes presented by HLA-DQ8.

Linearity assessment: deviation from linearity and residual of linear regression approaches.

In this computer simulation study, we examine four different statistical approaches of linearity assessment, including two variants of deviation from linearity (individual (IDL) and averaged (AD)), along with detection capabilities of residuals of linear regression (individual and averaged). From the results of the simulation, the following broad suggestions are provided to laboratory practitioners when performing linearity assessment. A high imprecision can challenge linearity investigations by producing a high false positive rate or low power of detection. Therefore, the imprecision of the measurement procedure should be considered when interpreting linearity assessment results. In the presence of high imprecision, the results of linearity assessment should be interpreted with caution. Different linearity assessment approaches examined in this study performed well under different analytical scenarios. For optimal outcomes, a considered and tailored study design should be implemented. With the exception of specific scenarios, both ADL and IDL methods were suboptimal for the assessment of linearity compared. When imprecision is low (3 %), averaged residual of linear regression with triplicate measurements and a non-linearity acceptance limit of 5 % produces <5 % false positive rates and a high power for detection of non-linearity of >70 % across different types and degrees of non-linearity. Detection of departures from linearity are difficult to identify in practice and enhanced methods of detection need development.

Gene expression differences associated with intrinsic hindfoot muscle loss in the jerboa, Jaculus jaculus.

Vertebrate animals that run or jump across sparsely vegetated habitats, such as horses and jerboas, have reduced the number of distal limb bones, and many have lost most or all distal limb muscle. We previously showed that nascent muscles are present in the jerboa hindfoot at birth and that these myofibers are rapidly and completely lost soon after by a process that shares features with pathological skeletal muscle atrophy. Here, we apply an intra- and interspecies differential RNA-Seq approach, comparing jerboa and mouse muscles, to identify gene expression differences associated with the initiation and progression of jerboa hindfoot muscle loss. We show evidence for reduced hepatocyte growth factor and fibroblast growth factor signaling and an imbalance in nitric oxide signaling; all are pathways that are necessary for skeletal muscle development and regeneration. We also find evidence for phagosome formation, which hints at how myofibers may be removed by autophagy or by nonprofessional phagocytes without evidence for cell death or immune cell activation. Last, we show significant overlap between genes associated with jerboa hindfoot muscle loss and genes that are differentially expressed in a variety of human muscle pathologies and rodent models of muscle loss disorders. All together, these data provide molecular insight into the process of evolutionary and developmental muscle loss in jerboa hindfeet.

Compact machine learning model for the accurate prediction of first 24-hour survival of mechanically ventilated patients.

Background: The field of machine learning has been evolving and applied in medical applications. We utilised a public dataset, MIMIC-III, to develop compact models that can accurately predict the outcome of mechanically ventilated patients in the first 24 h of first-time hospital admission. Methods: 67 predictive features, grouped into 6 categories, were selected for the classification and prediction task. 4 tree-based algorithms (Decision Tree, Bagging, eXtreme Gradient Boosting and Random Forest), and 5 non-tree-based algorithms (Logistic Regression, K-Nearest Neighbour, Linear Discriminant Analysis, Support Vector Machine and Naïve Bayes), were employed to predict the outcome of 18,883 mechanically ventilated patients. 5 scenarios were crafted to mirror the target population as per existing literature. S1.1 reflected an imbalanced situation, with significantly fewer mortality cases than survival ones, and both the training and test sets played similar target class distributions. S1.2 and S2.2 featured balanced classes; however, instances from the majority class were removed from the test set and/or the training set. S1.3 and S 2.3 generated additional instances of the minority class via the Synthetic Minority Over-sampling Technique. Standard evaluation metrics were used to determine the best-performing models for each scenario. With the best performers, Autofeat, an automated feature engineering library, was used to eliminate less important features per scenario. Results: Tree-based models generally outperformed the non-tree-based ones. Moreover, XGB consistently yielded the highest AUC score (between 0.91 and 0.97), while exhibiting relatively high Sensitivity (between 0.58 and 0.88) on 4 scenarios (1.2, 2.2, 1.3, and 2.3). After reducing a significant number of predictors, the selected calibrated ML models were still able to achieve similar AUC and MCC scores across those scenarios. The calibration curves of the XGB and BG models, both prior to and post dimension reduction in Scenario 2.2, showed better alignment to the perfect calibration line than curves produced from other algorithms. Conclusion: This study demonstrated that dimension-reduced models can perform well and are able to retain the important features for the classification tasks. Deploying a compact machine learning model into production helps reduce costs in terms of computational resources and monitoring changes in input data over time.

Ampicillin detection using absorbance biosensors utilizing Mn-doped ZnS capped with chitosan micromaterials.

The detection of ampicillin plays a crucial role in managing and monitoring its usage and resistance. This study introduces a simple and effective biosensor for ampicillin detection, utilizing the unique absorbance features of Mn-doped ZnS capped by chitosan micromaterials in conjunction with ß-lactamase activity. The biosensors can detect ampicillin concentrations from 13.1 to 72.2 µM, with a minimum detection limit of 2.93 µM for sensors based on 300 mg/L of the sensing material. In addition, these sensors show high specificity for ampicillin over other antibiotics such as penicillin, tetracycline, amoxicillin, cephalexin, and a non-antibiotic-glucose. This specificity is demonstrated by an enhancing effect when beta-lactamase is used, as opposed to a quenching effect observed at 340 nm in the absorbance spectrum when no beta-lactamase is present. This research highlights the potential of affordable chitosan-capped Mn-doped ZnS micromaterials for detecting ampicillin through simple absorbance measurements, which could improve the monitoring of antibiotics in both clinical and environmental settings.

Pembrolizumab-induced Stevens-Johnson syndrome/Toxic Epidermal Necrolysis in a Vietnamese patient with nonsmall-cell lung cancer.

Chemoimmunotherapy is an effective therapy for an individual with nonsmall-cell lung cancer (NSCLC) without anaplastic lymphoma kinase or epidermal growth factor receptor mutations. However, it can also be related to adverse cutaneous reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with high morbidities and mortality rates. We present a case of a 65-year-old male with NSCLC who underwent first-line chemotherapy with paclitaxel, carboplatin, and pembrolizumab, which was later followed by a second cycle of the same therapies. The patient developed a fever and rash 12 days after the second cycle. Pembrolizumab was strongly suspected as the culprit medication because cutaneous reactions to this drug have been frequently reported and threw other medications used as less likely candidates. This is the first case reported in Vietnam of SJS/TEN related to pembrolizumab and contributes to our knowledge of severe skin reactions associated with immune checkpoint inhibitors.

Multisite Pragmatic Cluster-Randomized Controlled Trial of the CONCERN Early Warning System.

Importance: Late predictions of hospitalized patient deterioration, resulting from early warning systems (EWS) with limited data sources and/or a care team's lack of shared situational awareness, contribute to delays in clinical interventions. The COmmunicating Narrative Concerns Entered by RNs (CONCERN) Early Warning System (EWS) uses real-time nursing surveillance documentation patterns in its machine learning algorithm to identify patients' deterioration risk up to 42 hours earlier than other EWSs. Objective: To test our a priori hypothesis that patients with care teams informed by the CONCERN EWS intervention have a lower mortality rate and shorter length of stay (LOS) than the patients with teams not informed by CONCERN EWS. Design: One-year multisite, pragmatic controlled clinical trial with cluster-randomization of acute and intensive care units to intervention or usual-care groups. Setting: Two large U.S. health systems. Participants: Adult patients admitted to acute and intensive care units, excluding those on hospice/palliative/comfort care, or with Do Not Resuscitate/Do Not Intubate orders. Intervention: The CONCERN EWS intervention calculates patient deterioration risk based on nurses' concern levels measured by surveillance documentation patterns, and it displays the categorical risk score (low, increased, high) in the electronic health record (EHR) for care team members. Main Outcomes and Measures: Primary outcomes: in-hospital mortality, LOS; survival analysis was used. Secondary outcomes: cardiopulmonary arrest, sepsis, unanticipated ICU transfers, 30-day hospital readmission. Results: A total of 60 893 hospital encounters (33 024 intervention and 27 869 usual-care) were included. Both groups had similar patient age, race, ethnicity, and illness severity distributions. Patients in the intervention group had a 35.6% decreased risk of death (adjusted hazard ratio [HR], 0.644; 95% confidence interval [CI], 0.532-0.778; P<.0001), 11.2% decreased LOS (adjusted incidence rate ratio, 0.914; 95% CI, 0.902-0.926; P<.0001), 7.5% decreased risk of sepsis (adjusted HR, 0.925; 95% CI, 0.861-0.993; P=.0317), and 24.9% increased risk of unanticipated ICU transfer (adjusted HR, 1.249; 95% CI, 1.093-1.426; P=.0011) compared with patients in the usual-care group. Conclusions and Relevance: A hospital-wide EWS based on nursing surveillance patterns decreased in-hospital mortality, sepsis, and LOS when integrated into the care team's EHR workflow. Trial Registration: ClinicalTrials.gov Identifier: NCT03911687.

Complete genome sequence of a Salmonella enterica strain of serovar Agona associated with an outbreak in France.

We report here the complete genome of one Salmonella Agona strain isolated in 2017 from a dried milk powder in France.

Dual-channel fluorescent sensors based on chitosan-coated Mn-doped ZnS micromaterials to detect ampicillin.

The global threat of antibiotic resistance has increased the importance of the detection of antibiotics. Conventional methods to detect antibiotics are time-consuming and require expensive specialized equipment. Here, we present a simple and rapid biosensor for detecting ampicillin, a commonly used antibiotic. Our method is based on the fluorescent properties of chitosan-coated Mn-doped ZnS micromaterials combined with the ß-lactamase enzyme. The biosensors exhibited the highest sensitivity in a linear working range of 13.1-72.2 pM with a limit of detection of 8.24 pM in deionized water. In addition, due to the biological specificity of ß-lactamase, the proposed sensors have demonstrated high selectivity over penicillin, tetracycline, and glucose through the enhancing and quenching effects at wavelengths of 510 nm and 614 nm, respectively. These proposed sensors also showed promising results when tested in various matrices, including tap water, bottled water, and milk. Our work reports for the first time the cost-effective (Mn:ZnS)Chitosan micromaterial was used for ampicillin detection. The results will facilitate the monitoring of antibiotics in clinical and environmental contexts.

The therapeutic landscape for COVID-19 and post-COVID-19 medications from genetic profiling of the Vietnamese population and a predictive model of drug-drug interaction for comorbid COVID-19 patients.

Despite the raised awareness of the role of pharmacogenomic (PGx) in personalized medicines for COVID-19, data for COVID-19 drugs is extremely scarce and not even a publication on this topic for post-COVID-19 medications to date. In the current study, we investigated the genetic variations associated with COVID-19 and post-COVID-19 therapies by using whole genome sequencing data of the 1000 Vietnamese Genomes Project (1KVG) in comparison with other populations retrieved from the 1000 Genomes Project Phase 3 (1KGP3) and the Genome Aggregation Database (gnomAD). Moreover, we also evaluated the risk of drug interactions in comorbid COVID-19 and post-COVID-19 patients based on pharmacogenomic profiles of drugs using a computational approach. For COVID-19 therapies, variants related to the response of two causal treatment agents (tolicizumab and ritonavir) and antithrombotic drugs are common in the Vietnamese cohort. Regarding post-COVID-19, drugs for mental manipulations possess the highest number of clinical annotated variants carried by Vietnamese individuals. Among the superpopulations, East Asian populations shared the most similar genetic structure with the Vietnamese population, whereas the African population showed the most difference. Comorbid patients are at an increased drug-drug interaction (DDI) risk when suffering from COVID-19 and after recovering as well due to a large number of potential DDIs which have been identified. Our results presented the population-specific understanding of the pharmacogenomic aspect of COVID-19 and post-COVID-19 therapy to optimize therapeutic outcomes and promote personalized medicine strategy. We also partly clarified the higher risk in COVID-19 patients with underlying conditions by assessing the potential drug interactions.

Depression in Final-Year Medical Students in Ho Chi Minh City, Vietnam: The Role of Career-Choice Motivation.

OBJECTIVES: Depression in medical students is concerning, potentially fueled by many stressors including career choice-relating stress. Choosing Medicine is a life-long commitment, and low intrinsic motivation or excessive dependence on family can complicate this decision and adding stress throughout their training. This stress intensifies in the final year, as students lacking personal drive struggle to see themselves continuing the career. Given limited studies on this crucial topic in Asia and Vietnam, we explored direct linkage between career choice motivation and depression in final-year medical students. METHODS: A cross-sectional study was conducted with 569 final-year students between June and July 2020. The Vietnamese Patient Health Questionnaire 9 (PHQ-9) and 16-item CCM questionnaire were used as survey tools. Univariate analysis was used for descriptive statistics (absolute and relative frequency, mean (M), standard deviation (SD). Multinomial logistic regression models were used to explore the relationship between variables using STATA 5.1. RESULTS: The depression among participants was about 24.6% (PHQ-9 cut-off ≥ 12). No difference in gender was found regarding depression. The most acknowledged motivator is securing employment (M = 4.14, SD = 1.02) and the least is parental wishes (M = 3.17, SD = 1.32). Familial influence on career choice significantly increased odds of having "moderately-severe depression" (OR = 1.17, 95% CI 1.04-1.32) and "severe depression" (OR = 1.36, 95% CI 1.10-1.68), whereas, career-choice motivators including satisfaction (OR = .76, 95% CI .60-.97), self-competence (OR = .80, 95% CI .66-.97) and career success (OR = .84, 95% CI .71-.99) were found to be protective factors for depression. CONCLUSIONS: Roughly a quarter of final-year medical students encountered depression. Occupational security ranked as the primary motivator, with parental wish being the least. Familial influence heightened depression risk, while career prospects, satisfaction and self-efficacy acted as protective factors. Medical career paths should align with intrinsic motivations and personal interests for better mental health outcomes.

Association between low-dose aspirin and the risk of gastric cancer and adenoma according to a family history of gastric cancer.

This study aimed to evaluate the association between low-dose aspirin use and the risk of GC and gastric adenoma according to a family history of GC. We conducted a population-based study of 7,596,003 participants screened for GC between 2013 and 2014. Aspirin users and non-users were matched in a 1:1 ratio through propensity score matching (PSM). After PSM, 51,818 participants with a family history of GC and 359,840 without a family history of GC were analyzed (mean follow-up periods: 4.9 ± 0.8 and 4.8 ± 0.8 years, respectively). In patients with a family history of GC, aspirin use was significantly associated with a reduced risk of GC (adjusted hazard ratio [aHR]=0.80; 95 % confidence interval [CI]=0.65-0.995) and gastric adenoma (aHR=0.81; 95% CI=0.69-0.94). In those without a family history of GC, aspirin use was associated with a reduced risk of gastric adenoma (aHR = 0.92; 95 % CI = 0.86-0.98), but not with that of GC (aHR = 0.99; 95 % CI = 0.90-1.08). Low-dose aspirin use was associated with a reduced risk of gastric adenoma, regardless of a family history of GC, and may play a role in the early stages of gastric carcinogenesis. However, the association between aspirin and GC was only observed in those with a family history of GC.

MiRNA research-The potential for understanding the multiple facets of anorexia nervosa.

Anorexia nervosa (AN) has a multifaceted and complex pathology, yet major gaps remain in our understanding of factors involved in AN pathology. MicroRNAs (miRNAs) play a regulatory role in translating genes into proteins and help understand and treat diseases. An extensive literature review on miRNAs with AN and comorbidities has uncovered a significant lack in miRNA research. To demonstrate the importance of understanding miRNA deregulation, we surveyed the literature on depression and obesity providing examples of relevant miRNAs. For AN, no miRNA sequencing or array studies have been found, unlike other psychiatric disorders. For depression and obesity, screenings and mechanistic studies were conducted, leading to clinical studies to improve understanding of their regulatory influences. MiRNAs are promising targets for studying AN due to their role as signaling molecules, involvement in psychiatric-metabolic axes, and potential as biomarkers. These characteristics offer valuable insights into the disease's etiology and potential new treatment options. The first miRNA-based treatment for rare metabolic disorders has been approved by the FDA and it is expected that these advancements will increase in the next decade. MiRNA research in AN is essential to examine its role in the development, manifestation, and progression of the disease. PUBLIC SIGNIFICANCE: The current understanding of the development and treatment of AN is insufficient. miRNAs are short regulatory sequences that influence the translation of genes into proteins. They are the subject of research in various diseases, including both metabolic and psychiatric disorders. Studying miRNAs in AN may elucidate their causal and regulatory role, uncover potential biomarkers, and allow for future targeted treatments.

Conveying the pathogenesis of type 1 diabetes to the blind, low-vision and diverse needs communities through sensory stimulation.

To educate members of the blind, low-vision and diverse needs communities on the pathogenesis of the chronic autoimmune disease, type 1 diabetes, members of our team with research expertise in immune-mediated diseases, participated in the 2023 Monash Sensory Science (MSS) Exhibition. Using QR code linked audio commentary, participants were guided through tactile displays demonstrating normal insulin action in the regulation of blood glucose levels and its vital role in providing energy to tissues, followed by displays describing the various stages of the immune system's aberrant attack and the eventual complete destruction of the insulin producing beta-cells of the pancreatic islets in type 1 diabetes. These models conveyed to the participants the huge effect that this autoimmune-mediated disease has on the quality of life of affected individuals including the subsequent lifelong reliance on insulin injections to maintain glucose homeostasis. This MSS Exhibition provided a unique opportunity for our researchers to engage with under-represented members of the community and to raise awareness about such a debilitating and common autoimmune disease.