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With society's rising concern over resource expenditures, sustainable solutions are sought across industries. The pharmaceutical research & development (R&D) enterprise faces the dual challenge of navigating the complexity of human disease and a highly regulated environment, leading to extensive data generation to ensure patient-focused development of optimal therapeutics. Through innovative study designs, translational technologies, and model-informed approaches, clinical pharmacology as a discipline can meaningfully contribute to reducing drug development's carbon footprint and achieving sustainability goals.
The pet population is steadily increasing worldwide, and treats, which account for approximately 15% of the pet food market, are the fastest-growing segment of the pet food industry. However, the widespread use of antimicrobials in poultry farms may pose a direct risk to pets' health, leading to the emergence of antimicrobial resistance. For this reason, we sought to assess the possible presence of drug residues and antimicrobial-resistant bacteria in a limited cohort of 11 dehydrated chicken feet intended as dog treats purchased from the European market. Residues of nicarbazin (64%), 4-4' dinitrocarbanilide (64%), semicarbazide (91%), decoquinate (9%), cypermethrin (27%), dichlorvos (9%), pirimiphos-methyl (36%), piperonyl butoxide (18%), toltrazuril sulfone (9%), doxycycline (9%), lasalocid A (9%), monensin A (9%), and 37 bacterial strains belonging to the Staphylococcus genus (S. warneri, S. haemolyticus, S. pasteuri, and S. intermedius) were detected among all samples. S. warneri species was resistant to oxacillin, erythromycin, clindamycin, teicoplanin, and tetracycline (25%, 25%, 37.5%, 6.25%, and 6.25%, respectively), S. haemolyticus was also resistant to erythromycin, clindamycin, teicoplanin, and tetracycline (52.9%, 11.7%, 29.4%, and 35.2%, respectively), while S. pasteuri was resistant to both oxacillin and clindamycin (66.6% and 33.3%, respectively). No resistance was detected for S. intermedius. The detection of multiple residues further suggests the possibility of cumulative or synergistic toxic effects, especially with prolonged intake. In this sense, a One Health approach to mitigate risks associated with antimicrobial resistance and chemical exposure in pets and, in turn, in humans becomes mandatory.
The HLA-B*15:02 allele is related to a high risk of severe cutaneous adverse drug reactions (SCARs) in patients taking certain antiepileptic drugs. However, its prevalence in the Asian population and the number of drugs linked to SCARs due to the carriage of this variant are relatively underexplored. This study sought to address these knowledge gaps. The prevalence of the HLA-B*15:02 allele in Asian populations was estimated by using the data from the Allele Frequency Net Database. Weighted means, standard deviations, and 95% Confidence Interval (CI) were estimated for the study populations, and the chi-square test was used to assess the statistical significance of variability in allele frequencies across populations. Drugs associated with SCARs due to HLA-B*15:02 were identified from the clinical guidelines of the international pharmacogenomics (PGx) working groups. HLA-B*15:02 was most prevalent in South-East Asia (5.6% ± 3.1), followed by South Asia (2.1% ± 1.5), North-East Asia (0.6% ± 0.9), and West Asia (0.01% ± 0.05). This distribution was statistically significant (χ2 = 9712.5, df = 3, p < 0.001; χ 2 test). Country-wise, prevalence was the highest in the Philippines (22%; 95% CI, 11.53-35.96%), followed by Vietnam (13.5%; 95% CI, 8.77-19.61%), Indonesia (11.9% ± 1.5), Malaysia (10% ± 4.3), Hong Kong (9.3% ± 0.2), Thailand (8.4% ± 0.1), Singapore (8.1% ± 3.7), China (5.4% ± 5.4), Taiwan (4.4% ± 0.7), Sri Lanka (2.5%, single study), India (2.1% ± 1.5) and South Korea (1.5% ± 0.9). PharmGKB clinical annotations identified four drugs (carbamazepine, oxcarbazepine, lamotrigine, phenytoin) with strong evidence (Level 1 A) for HLA-B*15:02-related SCARs, though the majority of the evidence for lamotrigine came from the Han Chinese Population. International PGx working groups require or recommend preemptive HLA-B*15:02 genotyping for at least three drugs, i.e., carbamazepine, oxcarbazepine, and phenytoin. Considering the high prevalence of the HLA-B*15:02 in the Southeast and South Asians, and its association with drug-induced SCARs, pre-emptive HLA-B*15:02 testing may reduce SCARs substantially in this region.
Variants in the HCN1 gene cause a syndrome of childhood epilepsy and developmental disability with a broad phenotypic range. Many affected children manifest with early infantile epileptic encephalopathy (EIEE) and highly drug-resistant epilepsy. There are anecdotal reports that seizures in this syndrome are exacerbated by some anti-seizure medications (ASMs), including lamotrigine and lacosamide. However, the efficacy of most ASMs in this disorder is unknown. We sought to understand which ASMs were most effective. We compiled a registry of 10 children with HCN1 variants and refractory epilepsy via outreach to parent members of an online social affinity group, and from unsolicited parent outreach to us. Parents filled out an eight-page survey detailing their child's and parents' genetic testing results, child's developmental status, and response to ASMs. Outside medical records were provided that documented genetic testing results. Five of these variants had not been previously reported in the literature. Of these, there was phenotypic variability depending on where the variant mapped on the HCN1 ion channel structure, with variants mapping to an ion channel transmembrane domain causing more severe phenotypes. Subjects given lamotrigine or oxcarbazepine had exacerbated seizure frequency whereas those exposed to valproate or clobazam had improved seizure frequency, with two subjects becoming seizure-free. We report here five novel HCN1 variants. We also provide a novel survey of ASM efficacy. These trends in ASM efficacy are similar to what has been observed in Dravet syndrome, another EIEE, raising questions about potential common pathogenic mechanisms at a cellular level. We surveyed families whose children had been diagnosed with a rare epilepsy syndrome due to mutations in the HCN1 gene. In reviewing their genetic testing results, we discovered five new gene mutations (variants) that had not been previously reported. We also asked which anti-seizure medications had been most effective: they cited valproate and clobazam as most effective, while lamotrigine and oxcarbazepine made seizures worse.
Autoantibodies neutralizing type I interferon (AAN-I-IFN) have been found in at least 10-15% of critical COVID-19 pneumonia cases in various studies across North and Latin America, Oceania, Europe, and Asia. We sought to analyze the prevalence of AAN-I-IFN and describe the demographic, clinical, and laboratory characteristics in a Moroccan cohort of patients with life-threatening COVID-19. We performed a cross-sectional and multicenter study of patients hospitalized in different university hospitals and clinical centers in Casablanca between November 2020 and December 2021. Our cohort included 195 patients with proven SARS-CoV-2 infection, 164 (84.1%) of whom developed severe or critical COVID-19 disease requiring hospitalization, and 31 (15.9%) patients developed mild or moderate disease. Patients with moderate or mild COVID-19 did not exhibit detectable levels of AAN-I-IFNs. Among the 20 patients with AAN-I-IFN, most were men (n=16, 80%), and age ranged from 19 to 101 years. 13 (65%) patients with severe COVID-19 and 7 (35%) with critical COVID-19 had AAN-I-IFNs. Twelve patients (60%) had autoantibodies (auto-Abs) neutralizing both high and low concentrations of IFN-α2 and/or IFN-ω, five (25%) had auto-Abs neutralizing only low concentrations of IFN-α2 or IFN-ω, two (10%) had auto-Abs neutralizing IFN-β (1ng/mL) only, and one (5%) had auto-Abs neutralizing high and low concentrations of IFN-α2 and IFN-ω, as well as IFN-β at 1ng/mL, but none neutralized IFN-β at 10 ng/mL. Overall, AAN-I-IFNs were detected in 20/195 (10.3%) of Moroccan patients with life-threatening COVID-19 and in 20/164 (12.2%) patients with severe or critical disease, whereas none were detected in patients with mild or moderate COVID-19.
Antibody diversity is generated through stochastic rearrangement of the immunoglobulin heavy chain locus (Igh) involving the recombination of variable (V H ), diversity (D H ) and joining (J H ) gene segments. How coding elements within the Igh locus locate one another in the complex nuclear environment is not understood. Here, we sought to identify the molecular mechanisms and physical principles that govern V H- D H J H genomic encounters. We found that transcription imposed a local confinement that stabilized interactions between spatially proximal genomic elements. The loop anchor CTCF modestly constrained population-average chromatin motion, whereas cohesin-mediated loops established large-scale confinement and reinforced self-similarity of V H- D H J H motion across spatial and temporal scales. Quantitative scaling arguments for first-passage times revealed that encounter frequencies between remote V H- D H J H genomic regions are governed by the interplay of diffusivity and spatial proximity. Together, these findings show that the hierarchy of confinements imposed by transcription and loop extrusion provides the balance between stability and mobility required to regulate genomic encounter frequencies.
Chronic inflammation is a key driver of atherosclerotic cardiovascular disease. Notably, anti-inflammatory therapies have demonstrated efficacy in reducing cardiac events. We previously reported that TREM2 (triggering receptor expressed on myeloid cells 2) promotes foam cell formation in atherosclerosis. Elevated levels of soluble TREM2 (sTREM2) have been observed in the plasma of patients with atherosclerosis. This study sought to investigate the pathological role of sTREM2 in the progression of atherosclerosis, elucidate its underlying mechanistic pathways, and propose potential targeted therapeutic interventions. Plasma sTREM2 levels were measured in patients with carotid atherosclerosis and in apolipoprotein E-deficient (Apoe-/-) mice. To study the functional role of sTREM2, we administered recombinant sTREM2 to Apoe-/- mice and used macrophage-specific Hsp90ab1 knockout mice (Hsp90ab1Mac-KO). Mechanistic pathways were investigated using immunoprecipitation-mass spectrometry, and surface plasmon resonance imaging was used to identify sTREM2 antagonists. Plasma sTREM2 levels correlated with atherosclerotic burden in both humans and mice. Exogenous sTREM2 administration exacerbated plaque progression in Apoe-/- mice, an effect abolished in Hsp90ab1Mac-KO mice. Mechanistically, sTREM2 binds to HSP90β (heat shock protein 90 beta), enhancing its interaction with the IKKs (IκB kinase complex), thereby activating the IκBα/NF-κB P65 pathway. This activation potentiates monocyte adhesion and chemotaxis and enhances macrophage inflammatory activation signatures in atherosclerotic lesions-effects that were reversed on myeloid-specific Hsp90ab1 deletion. Additionally, we identified 3-bromopyruvate as a small-molecule antagonist that selectively disrupts the sTREM2/HSP90β interaction and attenuates atherosclerosis. sTREM2 promotes proatherogenic myeloid recruitment and macrophage inflammatory activation via HSP90β-dependent NF-κB activation. Genetic and pharmacological approaches establish the sTREM2/HSP90β axis as a druggable target, with 3-bromopyruvate demonstrating translational potential for atherosclerosis therapy.
The program impact pathway (PIP) theory represents the architecture and causal mechanisms by which a program achieves its intended outcomes. We sought to identify and analyze the main applications of PIPs in the public health nutrition field. This scoping review selected 24 studies in March 2024. Four objectives for applying PIPs were identified: to ascertain the processes and identify mediators; to identify critical quality control points; to guide data collection and define program evaluation indicators; to analyze the processes, adaptations, and fidelity of implementation. The analyses use five methodological steps: I) construct the initial PIP diagram; II) confirm/revise the PIP diagram; III) identify evaluation indicators; IV) compare the implementation process with the PIP diagram; and V) evaluate outcomes or impact based on PIP analysis. In conclusion, PIP analysis offers immense possibilities for application, and the interactive analysis methodology supports program managers in the implementation process. A teoria dos caminhos de impacto do programa (CIPs) representa a arquitetura e mecanismos causais pelos quais um programa alcança os resultados pretendidos. Buscou-se identificar as principais aplicações dos CIPs no campo da nutrição em saúde pública. A revisão de escopo selecionou 24 estudos em março de 2024. Foram identificados quatro objetivos da aplicação dos CIPs: conhecer os processos e identificar mediadores; identificar pontos críticos de controle da qualidade; guiar a coleta de dados e definir indicadores de avaliação dos programas; e analisar os processos, as adaptações e a fidelidade da implementação. As análises utilizam cinco etapas metodológicas: I) elaborar o diagrama inicial dos CIPs; II) confirmar/revisar o diagrama dos CIPs; III) identificar indicadores de avaliação; IV) comparar o processo de implementação com o diagrama dos CIPs; e V) avaliar desfechos ou impacto tendo como base análises dos CIPs. Em conclusão, a análise dos CIPs tem amplas possibilidades de aplicações e a metodologia de análise interativa apoia os gestores dos programas no processo de implementação. La teoría de las vías de impacto de los programas (VIPs) representa la arquitectura y los mecanismos causales mediante los cuales un programa alcanza los resultados previstos. Se buscó identificar las principales aplicaciones de las VIPs en el campo de la nutrición en salud pública. La revisión de alcance seleccionó 24 estudios en marzo de 2024. Se identificaron cuatro objetivos para la aplicación de las VIPs: conocer los procesos e identificar mediadores; identificar puntos críticos de control de calidad; orientar la recogida de datos y definir los indicadores de evaluación del programa; analizar los procesos, las adaptaciones y la fidelidad de la aplicación. Los análisis utilizan cinco pasos metodológicos: I) elaborar el diagrama inicial de las VIPs; II) confirmar/revisar el diagrama de las VIPs; III) identificar los indicadores de evaluación; IV) comparar el proceso de implementación con el diagrama de las VIPs; y V) evaluar los resultados o el impacto basándose en los análisis de las VIPs. En conclusión, el análisis de las VIPs tiene amplias posibilidades de aplicación y la metodología de análisis interactivo ayuda a los gestores de programas en el proceso de implementación.
Pharmacy calculations are a crucial skill set in patient care. In an effort to improve best practices in teaching, identifying student cognitive abilities may impact their performance is critical in identifying students needing additional support to reach competency in this area. This study sought to examine the relationship between growth mindset and math confidence on pharmacy student performance on a comprehensive, must-pass pharmaceutical calculations exam. This study was conducted in fall semesters between 2022 and 2024. 212 PharmD students completed the Dweck Mindset Instrument and an Attitudes in Mathematics scale prior to, and after, participation in a required pharmaceutical calculations course. At the end of the course, students took a comprehensive, must-pass calculations exam. Student growth mindset and attitudes towards mathematics were compared to their results on the comprehensive calculations exam. There was no meaningful change in Growth Mindset or Mathematics Attitude from pre-course to post-course. There was a significant correlation of Mathematics Attitude with calculations exam performance, but there was no correlation between student growth mindset and exam performance. Student confidence regarding mathematics did directly correlate with their performance on the calculations exam. Student belief that they can generally improve their abilities and knowledge (growth mindset) did not have an association with their performance on a high-stakes, calculations exam. Further research is needed to determine if math performance impacts their feelings on the subject of mathematics, or if vice versa.
Art therapy has gained increasing attention as an adjunctive intervention for cancer patients. This study sought to conduct the first network meta-analysis (NMA) to evaluate the effects of various art therapies on the psychological well-being and quality of life in cancer survivors, rank various interventions by efficacy, and provide evidence-based guidance for clinical practice. Web of Science, PubMed, Embase, and the Cochrane Library, were systematically searched for studies published up to September 3, 2025. Eligible studies were selected according to predefined criteria, and data were independently extracted by two researchers. Heterogeneity was assessed using the I² statistic, and fixed- or random-effects models were applied accordingly. A Bayesian NMA was conducted to compare interventions and rank their efficacy using the surface under the cumulative ranking curve (SUCRA). Publication bias was assessed using comparison-adjusted funnel plots and Egger's test. Network meta-regression was performed for outcomes with high heterogeneity. Analyses were conducted using R Studio v4.5.2 and STATA v15.0. Twenty-eight studies involving 2,542 cancer survivors were included. The NMA demonstrated that mandala painting therapy exhibited statistically significant efficacy in alleviating depression and enhancing quality of life. Regarding fatigue reduction, music therapy was superior to routine care (standardized mean difference [SMD] = -5.83, 95% credible interval [CrI]: -6.65, -5.02) and had the highest SUCRA ranking (96.4%). In terms of anxiety and pain relief, although music therapy had high SUCRA rankings (67.4% and 69.0%, respectively), pairwise comparisons did not show statistically significant differences. Mandala art therapy and music therapy may improve psychological well-being and quality of life among cancer survivors. However, because of the absence of closed loops in the evidence network, substantial clinical heterogeneity, and potential publication bias, SUCRA-based rankings should be interpreted cautiously. Further high-quality, multi-arm, standardized randomized controlled trials with lower risk of bias are needed to confirm these findings. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251149102.
Among Veterans with traumatic brain injury (TBI) who received a cognitive rehabilitation referral, we sought to describe rates of referral completion (ie, Veteran attends the initial encounter). Second, we examined nonclinical factors associated with referral completion. Veterans Health Administration (VHA). Veterans with 1) clinician-confirmed TBI determined using the Comprehensive TBI Evaluation database and 2) a cognitive rehabilitation referral, determined using a validated algorithm (n = 19,923 mild TBI [mTBI]; n = 3797 moderate-severe TBI). Retrospective cohort study of VHA medical record data. Modified Poisson regression was used to model the likelihood of completing a cognitive rehabilitation referral based on nonclinical predisposing (eg, age) and enabling (eg, homelessness) factors. All analyses were stratified by TBI severity (mTBI vs. moderate-severe TBI). Completed cognitive rehabilitation referrals (no/yes), identified in the VHA electronic medical record. Cognitive rehabilitation referrals are documented as "complete" when the Veteran attends an initial encounter with the provider who receives the referral. The proportion of Veterans who completed their cognitive rehabilitation referral was similar across severities, with 69% of Veterans with mTBI and 68% of Veterans with moderate-severe TBI completing the referral. Veterans with mTBI who were older, married, and those who identified as students/homemakers/volunteers or unemployed and not looking (vs. employed) were more likely to complete the referral. Among Veterans with moderate-severe TBI, history of homelessness was associated with a reduced likelihood of completing a cognitive rehabilitation referral. While most Veterans with TBI initiate cognitive rehabilitation after receipt of a referral, a notable portion do not, suggesting missed opportunities for beneficial services in this population. Furthermore, patient factors such as age, marital status, employment status, and history of homelessness were associated with referral completion. Findings lay the foundation for system-level strategies that facilitate engagement with cognitive rehabilitation among Veterans with TBI.
The E-wave propagation index (EPI) has been proposed as a simple risk marker of left ventricular (LV) thrombus (LVT) formation. We sought to investigate the association between EPI and LVT in patients with heart failure with reduced ejection fraction (HFrEF). This was a retrospective cohort study on 768 patients with HFrEF. The EPI was measured as the velocity time integral of the transmitral E-wave divided by the LV length. The endpoint was LVT formation. Logistic regression was applied to investigate the association between EPI and LVT. Multivariable adjustments were made for age, mitral regurgitation, apical aneurysm, prior myocardial infarction, and LV ejection fraction (LVEF). Area under receiver operating characteristic curves was used to assess the optimal cut-off value for EPI. Of 768 HFrEF patients, 24 (3%) had developed LVT. The mean age was 66 years, 73% were men, and the mean LVEF was 28%. EPI was lower among those who had developed LVT (1.1 vs 1.3, p = 0.018), and EPI was significantly associated with LVT formation in univariable logistic regression (OR = 1.16 (1.0-1.3), per 0.1 decrease). This finding was unchanged after multivariable adjustments. The EPI provided an area under the curve of 0.68 with an optimal cutoff of 1.2. This cutoff had a sensitivity of 75%, specificity of 60%, positive predictive value of 6%, and negative predictive value of 99%. Patients with an EPI <1.2 had a four-fold increased risk of LVT (OR = 4.42 (1.73-11.25), p = 0.002). In patients with HFrEF, the EPI was independently associated with LVT formation. Additionally, an EPI > 1.2 indicates a low likelihood of developing LVT.
Human sapovirus (HuSaV) is a major cause of gastroenteritis but has long lacked a defined receptor. Here, we identify the scavenger receptor CD36 as essential for infection. Comparative transcriptomics identified CD36 as the key susceptibility factor. CRISPR knockout abolished replication, while ectopic expression restored permissiveness across diverse cells. Binding assays showed nanomolar affinity between CD36 and HuSaV particles. Infection also required the bile acid glycocholic acid, which promoted CD36 internalization and viral entry. In human intestinal organoids, CD36 knockout abrogated infection, confirming physiological relevance. Our findings establish CD36 as the long-sought HuSaV receptor, uncover a bile acid-assisted entry mechanism that confines infection to the intestine and point to opportunities for antiviral and vaccine development.
Background Metastatic colorectal cancer (CRC) remains a major cause of cancer mortality, yet how epigenetic states within the tumor microenvironment (TME) relate to metastatic progression has not been fully characterized. Although aberrant DNA methylation has been implicated in cancer progression, many studies do not account for immune and stromal cell composition, which can confound bulk methylation analyses. We sought to define DNA methylation patterns in primary colorectal tumors associated with lymph node and distant metastasis, while accounting for tumor microenvironment cellular composition. Methods We analyzed DNA methylation patterns from 57 patients with stage pT3 colorectal adenocarcinoma, comparing tumors with and without concurrent metastasis. Methylation cytometry deconvolution was performed to estimate immune, stromal, and tumor cell fractions. Differentially methylated positions associated with metastatic status were identified using covariate-adjusted epigenome-wide association analyses, with genomic context enrichment to assess regional methylation patterns. Genomic context enrichment and gene annotations were used to assess biological relevance. Methylation-expression correlations were assessed in an independent TCGA-COAD cohort to evaluate whether discovery loci correspond to differences in gene expression. Results Metastatic status was not associated with large-scale differences in inferred cellular composition. Epigenome-wide analyses identified hypomethylated loci mapped to genes involved in Wnt/β-catenin and PI3K/Akt signaling, epithelial-mesenchymal transition, and immune modulation, whereas hypermethylated loci tracked to genes related to adhesion, Wnt signaling, cytoskeletal organization, and interferon signaling. Genomic context enrichment revealed CpG island enrichment among hypermethylated DMPs in the distant metastasis contrast. Among metastasis-associated CpGs, 23 showed significant negative correlations between methylation and gene expression in TCGA-COAD (FDR < 0.05), predominantly at promoter-proximal CpG islands, supporting a relationship between promoter methylation and reduced gene expression. Two candidate CpGs showed directional concordance with significance in matched TCGA contrasts. Conclusions We identify distinct epigenetic alterations associated with metastatic progression in colorectal cancer that are largely independent of bulk immune and stromal composition. Integration of methylation-expression data supports a role for promoter hypermethylation in metastasis-associated gene silencing. These findings highlight potential methylation-based biomarkers of metastatic risk and may inform future precision oncology strategies in CRC.
Background: This research sought to determine the math proficiency of pharmacy technicians and the potential causes for the technicians' feelings of deficiency when attending continuing pharmacy education activity (CPE) and performing pharmaceutical calculations. Methods: To investigate these questions, the following questionnaire and test methods were utilized. Pharmacy technicians attending a 2-hour CPE activity completed a pre-activity survey assessing demographics, attitudes toward solving math problems, and sample calculation problems. Subsequently, the post-activity evaluation included additional calculation problems for comparison. Results: Our research found that most participants were nationally certified (82% of participants), but that most had not completed or were unsure if they had completed a formalized training program (58% of participants). Pre-survey data revealed participants perceiving low confidence in their pharmaceutical mathematical capability, as well as their over-reliance on rote memorization as their biggest barriers to solving pharmacy calculations. Baseline performance on calculation problems averaged 32% correct, with technicians finding the greatest difficulty in percentage strength, pediatric dosing, and alligation problems. Post-activity scores improved to an average of 66% correct across these areas. Conclusion: This in-person CPE activity improved pharmacy technicians' calculation skills. Although many pharmacy technicians struggle with pharmaceutical math problems, the reasons for these issues can be attributed to low confidence and lack of training rather than inability. Future CPE activities can continue to be focused on improving knowledge of underlying math concepts.
Oral health care is a crucial part of nursing for pediatric patients. General pediatric nurses need appropriate knowledge to provide effective preventive care, yet oral health is often overlooked and insufficiently integrated into daily practice. To assess the oral health knowledge, attitudes, and practices of nurses caring for pediatric patients in Dubai. A cross-sectional study using a validated questionnaire gathered socio-demographic data and assessed pediatric dental knowledge and attitudes. A 5-point Likert scale evaluated opinions on preventing children's oral diseases and willingness to pursue further oral health education. Knowledge and attitude scores were calculated; Mann-Whitney U and Kruskal-Wallis tests assessed associations. Among 125 nurses, the mean knowledge score was 69.5%. Female nurses and those over 30 years had significantly higher scores (p < 0.05). Most nurses performed oral care screenings for hospitalized children, but over half rarely assessed orthodontic appliances or preventive programs for children with special health care needs. Only 33.6% recognized xylitol's anticaries role, and 63.2% knew the recommended age for a first dental visit. Despite 57.6% perceiving nursing-led oral care as ineffective, 86.9% requested hands-on training, and 84.2% sought further education. Pediatric nurses in Dubai demonstrate adequate theoretical oral health knowledge but notable practice gaps. Structured training programs and integration of oral health into pediatric nursing protocols could enhance preventive practices, strengthen early detection and referral, and help reduce the high prevalence of early childhood caries in the UAE.
Adolescents are the age cohort most likely to attend an emergency department (ED) for suicide crisis, often accompanied by a parent. Parents report feeling as though they are not appropriately supported to provide the critical life sustaining care their adolescent child needs after discharge from the ED. This study sought to understand what support parents need during and after the ED presentation. Semi-structured, online interviews were conducted with 20 parents of adolescents (12-18 years) who had attended an Australian ED for suicide crisis. Reflexive thematic analysis indicated there were three domains of support parents' desired: (1) information about, and active involvement in, the emergency department care, (2) information about how to keep their adolescent child safe and support recovery, and (3) tools to support parents' own wellbeing. These findings provide a preliminary indication of the support parents need and what resources may need to be developed to educate and support parents, which could be integrated into the ED procedures. Improving the way in which parents are supported to care for their adolescent child may help reduce recurrent adolescent suicide attempts and improve parental wellbeing so they can more effectively care for their adolescent child. Parents who had lived experience of attending the ED with their suicidal adolescent were involved in this study as peer researchers. These peer researchers helped devise the interview guide, conducted interviews with participants, and contributed to the analysis and the writing of this paper.
Many applications of magnetic nanoparticles (MNPs) require accumulation at target organs that can be challenging to achieve and to characterize. Magnetic Particle Imaging (MPI) enables sensitive and quantitative detection of MNPs, however the proximity of target signals to high accumulation organs hinders accurate quantification due to signal spillover effects. Specifically, we sought to systematically evaluate MPI quantification strategies under conditions mimicking pre-clinical animal studies and account for spillover. We developed an anatomically accurate 3D-printed mouse phantom with a fillable liver cavity, brain and lung ports and a hind flank cavity. By emulating high liver MNP uptake alongside low MNP concentrations in target locations at varying distances, we compared quantification from threshold-based and constant-volume segmentations, as well as a subtraction approach, both for 2D and 3D MPI scans. Thresholding was reliable for isolated high-signal regions but overestimated signal near the liver or at low signal-to-noise ratios. Constant-volume segmentation improved signal separation, and subtraction strategies mitigated spillover overestimation, enhancing the limit of quantification. With the subtraction approach we were able to quantify as low a signal as 0.05 and 0.25 % of the total dose in the phantom in the brain/lung and hind flank of the mouse phantom with 3D MPI, respectively. These results underscore the importance of accounting for superimposed signals in quantitative MPI and highlight anatomically correct phantoms as essential tools for refining biodistribution assessment methods in nanomedicine using MPI.
Hypertension (HTN) is a common and complex disorder influenced by multiple genetic and environmental factor, where the underlying mechanisms of its etiology remain incompletely understood although the identification of several contributing elements. This research sought to evaluate the possible relationship between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and With-No-Lysine Kinase 1 (WNK1) genes and susceptibility to hypertension. Genomic DNA was extracted from blood samples collected from 220 individuals with hypertension and 220 normotensive controls. Genotyping of MTHFR (rs1801133 and rs1801131) and WNK1 (AluYb8) polymorphisms was performed using direct PCR and PCR-RFLP techniques. The resulting data were subjected to appropriate statistical analyses. A statistically significant association was identified between the rs1801131 polymorphism of the MTHFR gene and susceptibility to hypertension (p = 0.0006). This association remained significant under the codominant, dominant, and recessive genetic models, with all p-values < 0.016. Furthermore, the CC haplotype of the MTHFR gene showed a significant association with hypertension (OR = 2.02, p = 1e-04). These findings indicate that the MTHFR rs1801131 polymorphism is significantly associated with hypertension susceptibility and may represent a potential genetic marker. This highlights its relevance for future studies exploring genotype-driven risk assessment and personalized approaches to hypertension management.
Idiosyncratic drug reactions (IDRs) and, in particular, idiosyncratic drug-induced liver injury (iDILI) represent a significant risk for drug development. There are multiple lines of evidence that such reactions are mediated by the adaptive immune system. The idiosyncratic nature of adaptive immune responses makes it difficult to develop biomarkers to predict the risk that drug candidates will cause such adverse reactions. However, an adaptive immune response requires an innate immune response to activate antigen presenting cells such as macrophages, and the innate immune response to drugs should not be idiosyncratic. We had previously shown that clozapine and nevirapine produce a marked innate immune response in rodents. We sought to extend these studies to additional drugs that cause IDRs; namely, amodiaquine, carbamazepine, isoniazid, and ximelagatran. Ximelagatran was specifically chosen because, unlike the others, it does not appear to form a reactive metabolite. Amodiaquine and carbamazepine also produced changes associated with an innate immune response such as an increase in serum corticosterone and GDF-15 and changes in hepatic mRNA for Dusp1, Gadd45b and Cebpd. These changes resolved within hours. Not surprisingly, ximelagatran did not produce significant changes. However, it was surprising that isoniazid produced few such changes. There is evidence that ximelagatran can directly activate macrophages, and it is plausible that isoniazid can also directly activate macrophages. It is likely that changes in hepatic mRNA consistent with a stress/innate immune response would represent biomarkers of iDILI risk; however, some drugs may directly activate macrophages without the need of factors released from the liver.