-
Drug and Chemical Toxicology Jul 2024is a shrubby plant, often consumed by traditional populations in religious rituals. Previous studies have shown that this plant's infusion can inhibit the activity of...
is a shrubby plant, often consumed by traditional populations in religious rituals. Previous studies have shown that this plant's infusion can inhibit the activity of Acetylcholinesterase (AChE) in rats. Despite the therapeutic potential, there is a lack of research regarding its possible toxicological and genotoxic effects. Hence, this study aimed to analyze the chemical profile of the ethanol extract from leaves by LC-DAD-MS and assess its possible toxicity and genotoxicity in zebrafish (). Adult zebrafish (N = 9/group) were exposed at different concentrations and the LC was calculated. Frequencies of micronucleus (MN) and nuclear abnormalities (NA) were estimated for genotoxic effects, and degree of tissue changes (DTC) was used to assess the liver and gill histopathology. From the LC-DAD-MS analyses, the identified compounds included -fructosyl valine, ethyl hexoside, 5--caffeoylquinic acid, feruloylagmatime, roseoside, di-O-deoxyhexoyl-hexosyl quercetin, loiolide, and oleamide. The calculated values of LC did not vary significantly during the time of exposure. At the concentrations of 1.25, 2.5, 3.75, 5, 7.5, 10 and 15 mg/L, there was no genotoxicity, and only low to moderate toxicity for the tissues was observed, despite mortality of 100% at doses of 20-100 mg/L of ethanolic leaf extract. There were changes in cytoplasm of hepatocytes at 1.25 mg/L, and karyorrhexis, karyolysis and megalocytosis at 10 mg/L. In the gills, the alterations were primary lamellar hyperplasia in all concentrations, and at 10 mg/L, secondary lamellar edema and vascular hyperemia were common. Additionally, the chemical composition of was expanded.
PubMed: 38953234
DOI: 10.1080/01480545.2024.2367560 -
Blue Ribbon Committee II: Report of the Subcommittee on Faculty Development and Educational Support.Annals of Surgery Jul 2024The American College of Surgeons, American Board of Surgery, and the American Surgical Association have created a Blue Ribbon Committee II to evaluate the current status...
The American College of Surgeons, American Board of Surgery, and the American Surgical Association have created a Blue Ribbon Committee II to evaluate the current status of surgical education in the United States. As part of this endeavor, a subcommittee was formed to address issues pertinent to development of surgical faculty as teachers. This entailed multiple discussions among a group of experienced surgical educators, a review of the literature, and a delphi analysis of possible suggested improvements for faculty educational support, resulting in a final set of recommendations for improvement for future surgical faculty development. These recommendations include a task force to establish a validated system of compensation for faculty teaching, a task force to determine an accurate assessment of the value of surgical trainees to health systems, a review by the Surgical Residency Review Committee and the Association of Program Directors in Surgery of minimal faculty resources for program accreditation in the area of teaching learners, collaborative efforts across surgical specialties for the definition of a national curriculum for faculty, and development of a tool for evaluation of faculty teaching performance.
PubMed: 38953210
DOI: 10.1097/SLA.0000000000006435 -
Pediatric Blood & Cancer Jul 2024The molecular pathogenesis of acute myeloid leukemia (AML) was dramatically clarified over the latest two decades. Several important molecular markers were discovered in...
High DOCK1 expression identifies a distinct prognostic subgroup of pediatric acute myeloid leukemia: Results of the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 trial.
BACKGROUND
The molecular pathogenesis of acute myeloid leukemia (AML) was dramatically clarified over the latest two decades. Several important molecular markers were discovered in patients with AML that have helped to improve the risk stratification. However, developing new treatment strategies for relapsed/refractory acute myeloid leukemia (AML) is crucial due to its poor prognosis.
PROCEDURE
To overcome this difficulty, we performed an assay for transposase-accessible chromatin with sequencing (ATAC-seq) in 10 AML patients with various gene alterations. ATAC-seq is based on direct in vitro sequencing adaptor transposition into native chromatin, and is a rapid and sensitive method for integrative epigenomic analysis. ATAC-seq analysis revealed increased accessibility of the DOCK1 gene in patients with AML harboring poor prognostic factors. Following the ATAC-seq results, quantitative reverse transcription polymerase chain reaction was used to measure DOCK1 gene expression levels in 369 pediatric patients with de novo AML.
RESULTS
High DOCK1 expression was detected in 132 (37%) patients. The overall survival (OS) and event-free survival (EFS) among patients with high DOCK1 expression were significantly worse than those patients with low DOCK1 expression (3-year EFS: 34% vs. 60%, p < .001 and 3-year OS: 60% vs. 80%, p < .001). To investigate the significance of high DOCK1 gene expression, we transduced DOCK1 into MOLM14 cells, and revealed that cytarabine in combination with DOCK1 inhibitor reduced the viability of these leukemic cells.
CONCLUSIONS
Our results indicate that a DOCK1 inhibitor might reinforce the effects of cytarabine and other anti-cancer agents in patients with AML with high DOCK1 expression.
PubMed: 38953149
DOI: 10.1002/pbc.31151 -
Zhonghua Yi Xue Za Zhi Jul 2024An effective infectious disease surveillance and early warning system is a crucial component of public health safety and is essential for preventing and controlling...
An effective infectious disease surveillance and early warning system is a crucial component of public health safety and is essential for preventing and controlling outbreaks of infectious diseases. Enhancing surveillance and early warning capabilities is an urgent priority for advancing high-quality disease prevention and control efforts. Combining the research findings and practical experiences of experts in epidemiology, clinical medicine, disease prevention and control, data science, and computer science, and following multiple rounds of expert discussions, we have developed a consensus on the key technologies for a multi-point trigger intelligent surveillance and early warning system for infectious diseases. This consensus primarily covers the related concepts and definitions of the multi-point trigger intelligent surveillance and early warning system for infectious diseases, the key technical framework, sources, acquisition, and governance of multi-channel warning data, classification of early warning methods, multi-point trigger intelligent surveillance and early warning paths, multi-point trigger warning and comprehensive assessment, response to warning signals, and evaluation of early warning effectiveness. It aims to provide technical references for the construction and application of a multi-point trigger intelligent surveillance and early warning system for infectious diseases.
PubMed: 38953126
DOI: 10.3760/cma.j.cn112137-20240612-01317 -
Pediatrics Jul 2024This study assessed the state of pediatric medical device (PMD) development by comparing PMD clinical trials to pediatric trials evaluating drugs and biologics, from...
OBJECTIVES
This study assessed the state of pediatric medical device (PMD) development by comparing PMD clinical trials to pediatric trials evaluating drugs and biologics, from 1999 to 2022.
METHODS
The site https://www.clinicaltrials.gov was used to identify and quantify both PMD clinical trials and pediatric trials for drugs and biologics. Clinical specialty was also assessed. The institutions included were the 7 children's hospitals primarily affiliated with the Food and Drug Administration (FDA) Pediatric Device Consortia (PDC) grant program between 2018 and 2023. For a national comparison, an additional search assessed PMD trials across all US medical institutions.
RESULTS
A total of 243 PMD clinical trials were identified at the FDA-PDC institutions on the basis of the year of initiation; the average number of PMD trials initiated per year per institution was 1.5 from 1999 to 2022. However, PMD trials significantly increased during the period 2014 to 2022 compared with 1999 to 2013 (P < .001); the rate of initiation of drug and biologic pediatric trials demonstrated no significant differences between these time periods. A national survey of all institutions initiating PMD trials, and drugs and biologics trials, identified 1885 PMD trials out of a total 12 943. A comparable trend was noted in the national survey with initiation of PMD trials increasing significantly from 2014 to 2022 (P < .001), compared with 1999 to 2013, whereas the rate of initiation of drug and biologic trials during these periods did not demonstrate a significant change.
CONCLUSIONS
Although pediatric clinical trial initiation for drugs and biologics remained stable from 1999 to 2022, the rate of new PMD trials significantly increased during the period 2014 to 2022 at FDA-PDC institutions and nationally.
PubMed: 38953121
DOI: 10.1542/peds.2023-063466 -
Frontiers in Immunology 2024Schistosomiasis (SM) is a parasitic disease caused by . SM causes chronic inflammation induced by parasitic eggs, with collagen/fibrosis deposition in the granuloma...
INTRODUCTION
Schistosomiasis (SM) is a parasitic disease caused by . SM causes chronic inflammation induced by parasitic eggs, with collagen/fibrosis deposition in the granuloma process in the liver, spleen, central nervous system, kidneys, and lungs. Pulmonary arterial hypertension (PAH) is a clinical manifestation characterized by high pressure in the pulmonary circulation and right ventricular overload. This study investigated the production of functional autoantibodies (fAABs) against the second loop of the G-protein-coupled receptor (GPCR) in the presence of hepatic and PAH forms of human SM.
METHODS
Uninfected and infected individuals presenting acute and chronic manifestations (e.g., hepatointestinal, hepato-splenic without PAH, and hepato-splenic with PAH) of SM were clinically evaluated and their blood was collected to identify fAABs/GPCRs capable of recognizing endothelin 1, angiotensin II, and a-1 adrenergic receptor. Human serum was analyzed in rat cardiomyocytes cultured in the presence of the receptor antagonists urapidil, losartan, and BQ123.
RESULTS
The fAABs/GPCRs from chronic hepatic and PAH SM individuals, but not from acute SM individuals, recognized the three receptors. In the presence of the antagonists, there was a reduction in beating rate changes in cultured cardiomyocytes. In addition, binding sites on the extracellular domain functionality of fAABs were identified, and IgG1 and/or IgG3 antibodies were found to be related to fAABs.
CONCLUSION
Our data suggest that fAABs against GPCR play an essential role in vascular activity in chronic SM (hepatic and PAH) and might be involved in the development of hypertensive forms of SM.
Topics: Autoantibodies; Humans; Animals; Receptors, G-Protein-Coupled; Rats; Male; Female; Adult; Hypertension, Pulmonary; Middle Aged; Myocytes, Cardiac; Schistosomiasis mansoni; Schistosoma mansoni; Schistosomiasis
PubMed: 38953035
DOI: 10.3389/fimmu.2024.1404384 -
Western Pacific Surveillance and... 2024On 12 September 2022, a 10-year-old female in Paracelis municipality, Mountain Province, the Philippines, without travel history outside the municipality, experienced...
On 12 September 2022, a 10-year-old female in Paracelis municipality, Mountain Province, the Philippines, without travel history outside the municipality, experienced acute onset of fever and a change in mental status with disorientation, an altered level of consciousness and new onset of seizures. She was hospitalized at the district hospital from 1 to 3 October 2022, before being transferred to the regional hospital. As diphtheria was originally suspected, the investigation team reviewed records and reports and interviewed key informants to gather additional information and organize case finding and contact tracing. The patient's condition was laboratory-confirmed for Japanese encephalitis virus infection. An environmental survey was carried out at the patient's residence to check for the presence of vectors and contributing factors. Exemplifying inadequate vaccination coverage for Japanese encephalitis virus in Mountain Province, the patient had not been vaccinated against the disease. It is recommended that vaccination campaigns be immediately implemented in the affected area and the surveillance system be strengthened for early detection and prompt response to the emergence of cases and outbreaks. Overall, the investigation highlighted the importance of strong surveillance and response systems for early detection and control of diseases, such as Japanese encephalitis virus. It also underscores the need for comprehensive vaccination programmes to prevent outbreaks and protect vulnerable populations.
Topics: Humans; Philippines; Female; Encephalitis, Japanese; Child; Encephalitis Virus, Japanese
PubMed: 38953004
DOI: 10.5365/wpsar.2024.15.2.1049 -
Network Neuroscience (Cambridge, Mass.) 2024Canonical correlation analysis (CCA) and partial least squares correlation (PLS) detect linear associations between two data matrices by computing latent variables (LVs)...
Canonical correlation analysis (CCA) and partial least squares correlation (PLS) detect linear associations between two data matrices by computing latent variables (LVs) having maximal correlation (CCA) or covariance (PLS). This study compared the similarity and generalizability of CCA- and PLS-derived brain-behavior relationships. Data were accessed from the baseline Adolescent Brain Cognitive Development (ABCD) dataset ( > 9,000, 9-11 years). The brain matrix consisted of cortical thickness estimates from the Desikan-Killiany atlas. Two phenotypic scales were examined separately as the behavioral matrix; the Child Behavioral Checklist (CBCL) subscale scores and NIH Toolbox performance scores. Resampling methods were used to assess significance and generalizability of LVs. LV for the CBCL brain relationships was found to be significant, yet not consistently stable or reproducible, across CCA and PLS models (singular value: CCA = .13, PLS = .39, < .001). LV for the NIH brain relationships showed similar relationships between CCA and PLS and was found to be stable and reproducible (singular value: CCA = .21, PLS = .43, < .001). The current study suggests that stability and reproducibility of brain-behavior relationships identified by CCA and PLS are influenced by the statistical characteristics of the phenotypic measure used when applied to a large population-based pediatric sample.
PubMed: 38952810
DOI: 10.1162/netn_a_00363 -
Ecology and Evolution Jul 2024Drylands are unique among terrestrial ecosystems in that they have a significant proportion of primary production facilitated by non-vascular plants such as colonial...
Drylands are unique among terrestrial ecosystems in that they have a significant proportion of primary production facilitated by non-vascular plants such as colonial cyanobacteria, moss, and lichens, i.e., biocrusts, which occur on and in the surface soil. Biocrusts inhabit all continents, including Antarctica, an increasingly dynamic continent on the precipice of change. Here, we describe in-situ field surveying and sampling, remote sensing, and modeling approaches to assess the habitat suitability of biocrusts in the Lake Fryxell basin of Taylor Valley, Antarctica, which is the main site of the McMurdo Dry Valleys Long-Term Ecological Research Program. Soils suitable for the development of biocrusts are typically wetter, less alkaline, and less saline compared to unvegetated soils. Using random forest models, we show that gravimetric water content, electrical conductivity, and snow frequency are the top predictors of biocrust presence and biomass. Areas most suitable for the growth of dense biocrusts are soils associated with seasonal snow patches. Using geospatial data to extrapolate our habitat suitability model to the whole basin predicts that biocrusts are present in 2.7 × 10 m and contain 11-72 Mg of aboveground carbon, based on the 90% probability of occurrence. Our study illustrates the synergistic effect of combining field and remote sensing data for understanding the distribution and biomass of biocrusts, a foundational community in the carbon balance of this region. Extreme weather events and changing climate conditions in this region, especially those influencing snow accumulation and persistence, could have significant effects on the future distribution and abundance of biocrusts and therefore soil organic carbon storage in the McMurdo Dry Valleys.
PubMed: 38952663
DOI: 10.1002/ece3.11649 -
Cureus Jun 2024The global population is aging, with those aged 65 years or over increasing in number and accounting for a growing share of the population. There are increasing demands... (Review)
Review
The global population is aging, with those aged 65 years or over increasing in number and accounting for a growing share of the population. There are increasing demands for geriatric care which makes the development and delivery of effective geriatric team training a priority. Training in geriatrics is complex because of the multiplicity of medical, psychosocial, and functional issues in elderly individuals which need to be addressed by a multidisciplinary approach using interprofessional education (IPE). Problem-based learning, a student-centered educational model that brings several natural strengths to IPE, is a unique curriculum replacing the traditional lecture-based learning model. This model enhances physician competency after graduation, mainly in psychosocial and teamwork issues that are fundamentally essential for geriatrics. IPE has been shown to have a substantial positive impact on team collaboration, individual development, and healthcare improvement. In this paper, we summarize the current findings from recent studies on training professionals from different healthcare disciplines to deliver care for the elderly in collaborative practice. We also discuss if an interprofessional problem-based geriatric team program in geriatrics is a promising solution to enhance professional collaboration and quality of patient care.
PubMed: 38952581
DOI: 10.7759/cureus.63055