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Human beings are frequently exposed to a mixture of chemical pollutants through the ingestion of contaminated drinking water. The present study aimed to assess the ecological and human health risks associated with the contamination of cyanotoxins and heavy metals in a drinking water supply reservoir, the Tri An Reservoir (TAR), in Vietnam. Results demonstrated that the concentrations of individual heavy metals varied in the following order: iron (Fe) > lead (Pb) > arsenic (As) > zinc (Zn). Although the ecological potential risk of heavy metals was low during the study period, the concentration of Fe sometimes exceeded the Vietnamese standard for drinking water. Toxic cyanobacteria and microcystins (MCs) frequently occurred in the TAR with the highest density of 198.7 × 103 cells/mL and 7.8 µg/L, respectively, indicating a high risk of health impacts to humans. The results of the study indicate that exposure to heavy metals does not pose any non-carcinogenic health risks for both adults and children. However, the contamination of MCs in the surface water posed a serious disease enhancement to both adults and children through direct ingestion and dermal absorption.
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Agua Potable , Metales Pesados , Adulto , Niño , Humanos , Toxinas de Cianobacterias , Metales Pesados/toxicidad , Abastecimiento de Agua , Medición de RiesgoRESUMEN
AIM: Partnered Pharmacist Medication Charting (PPMC) in patients admitted under general medical units has been shown to reduce medication errors. The aim of this study is to evaluate the impact of the PPMC model on medication errors in patients admitted under cancer units in Victorian hospitals. METHODS: A prospective cohort study comparing cohorts before and after the introduction of PPMC was conducted. This included a 2-month pre-intervention phase and 3-month intervention phase. PPMC was implemented during the intervention phase as new model of care that enabled credentialed pharmacists to chart all admission medications, including pre-admission or new medications and cancer therapies, in collaboration with the admitting medical officer. The proportion of medication charts with at least one error was the primary outcome measure. RESULTS: Seven health services across Victoria were included in the study. The majority of health services were using paper-based prescribing systems for oncology. Of the 547 patients who received standard medical medication charting, 331 (60.5%) had at least one medication error identified compared to 18 out of 416 patients (4.3%) using the PPMC model (p < 0.001). The median (interquartile range) inpatient length of stay was 5 (2.9-10.6) days in pre-intervention and 4.9 (2.9-11) days in intervention (p = 0.88). In the intervention arm, 42 patients had cancer therapy charted by a pharmacist with no errors. CONCLUSIONS: PPMC was successfully scaled into cancer units as a collaborative medication safety strategy. The model was associated with significantly lower rates of medication errors, including cancer therapies. PPMC should be adopted more widely in cancer units in Australia.
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BACKGROUND: Motorized transport access and out-of-home activities are two potential correlates of Life-space mobility (LSM), a common research topic in mobility studies of older adults. These correlates remain mostly unexplored in previous literature and relating them with LSM can reveal directions for improving the LSM of older adults. METHODS: The associations between motorized transport access, out-of-home activities, and LSM were examined using data from 1,333 older adults (mean age = 70.63) living in 15 cities and towns in Japan. LSM was assessed using composite life-space assessment (LSA) scores. Motorized transport access was measured using dummies showing whether a person had car access (divided into five levels) and used public transport (bus and railway), and out-of-home activities were measured using the number of various activities that were conducted during the most recent weekday and weekend day. Generalized linear models were used to assess the associations. RESULTS: The sample was dominated by males (74.42%), with more than half of the sample had their own cars. On average, each respondent had four activities during two survey days, and shopping was the most common activity. The results showed that owning a car and using railway, as well as various activities were associated with increased composite LSA scores, whereas no cars or only shared cars in home were associated with decreased composite LSA scores. However, these associations differed between males and females. CONCLUSIONS: In this study, different levels of motorized transport access and different types of out-of-home activities were found to associate differently with composite LSA scores. Based on these findings, we suggest that policymakers should provide more transport access, pay more attention to the LSM of older adults with high clinics/hospital activities, and trigger more shopping and daily leisure activities for older adults to improve the LSM of this population.
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Actividades Cotidianas , Evaluación Geriátrica , Anciano , Femenino , Evaluación Geriátrica/métodos , Humanos , Japón , Masculino , Limitación de la Movilidad , Encuestas y CuestionariosRESUMEN
Tilapia Lake Virus (TiLV) is reported as a threat to tilapia aquaculture in 16 countries on four continents with outbreaks causing up to 90% mortality. This research is one of the first studies on TiLVs from Vietnam. We propagated successfully one TiLV isolate HB196-VN-2020 from a diseased tilapia sample using an E-11 cell line and evaluated its virulence in two different weights of red hybrid tilapia and three serial 10-fold diluted viral titers. Smaller fish (4.5 ± 1.98 g) were proved to be more susceptible to TiLV infection at the viral titre of 9.1 × 105 TCID50 fish-1 than larger fish (20.8 ± 7.5 g) with the mortalities of 92.5% and 12.5%, respectively. Reassortant detection analysis revealed seven potential reassortment events among 23 TiLV genomes, indicating the mixed infection of multiple TiLV isolates at the farms and the fish movement among different regions. Seven maximum likelihood phylogenetic trees based on the individual segments or the concatenated coding regions of some segments showed the genetically distant relationship of the Southern Vietnamese isolate RIA2-VN-2019 with the 21 reference isolates, and suggest the different origins of two Vietnamese TiLV isolates (RIA2-VN-2019 and HB196-VN-2020). However, additional sequences from various sampling locations and times are required to better understand the impacts of genetic diversity and reassortments on the evolution, migration and natural selection of TiLVs in Vietnam and other countries.
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Enfermedades de los Peces , Tilapia , Virus , Animales , Filogenia , Vietnam/epidemiologíaRESUMEN
We report the first time-resolved resonant Raman (TR3) spectra of photoinduced charge transfer from [Ru(bpy)3]2+ to methyl viologen, with observations of vibrational structure. The presence of singly charged methyl viologen in solution is noted by the appearance of several spectroscopic lines, which are visible in the spectra following subtraction of reagent molecules. Assignments are confirmed using both density functional theory (DFT) calculations and literature values and are shown to be consistent with transient absorption spectroscopy data. This presents proof-of-concept for the application of TR3 in mechanistic studies of photocatalytic systems.
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The Canadian Domestic Substances List (DSL) contains chemicals that have not been tested for genotoxicity as their use pre-dates regulatory requirements. In the present study, (quantitative) structure-activity relationships ((Q)SAR) model predictions and in vitro tests were conducted for genotoxicity assessment of 13 data-poor chemicals from the DSL (i.e. CAS numbers 19286-75-0, 13676-91-0, 2478-20-8, 6408-20-8, 74499-36-8, 26694-69-9, 29036-02-0, 120-24-1, 84696-48-9, 4051-63-2, 5718-26-3, 632-51-9, and 600-14-6). First, chemicals were screened by (Q)SAR models in Leadscope® and OASIS TIMES; two chemicals were excluded from (Q)SAR as they are complex mixtures. Six were flagged by (Q)SAR as potentially mutagenic and were subsequently confirmed as mutagens using the Ames assay. Of nine chemicals with clastogenic (Q)SAR flags, eight induced micronuclei in TK6 cells. Benchmark dose analysis was used to evaluate the potency of the chemicals. Four chemicals were bacterial mutagens with similar potencies. Three chemicals were more potent in micronuclei induction than the prototype alkylating agent methyl methanesulfonate and three were equipotent to the mutagenic carcinogen benzo[a]pyrene in the presence of rat liver S9. Overall, 11 of the 13 DSL chemicals demonstrated at least one type of genotoxicity in vitro. This study demonstrates the application of genotoxic potency analysis for prioritizing further investigations.
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Modelos Teóricos , Mutágenos/toxicidad , Animales , Línea Celular , Simulación por Computador , Cricetulus , Humanos , Pruebas de Mutagenicidad , Mutágenos/química , Relación Estructura-Actividad CuantitativaRESUMEN
Gels represent an increasingly important class of soft materials with applications ranging from regenerative medicine to commodity materials. However, gels typically exhibit relative mechanical weakness, which worsens under repeated strain. Here we report a new class of responsive gels with latent crosslinking moieties that exhibit strain-stiffening behavior. This property results from the lability of disulfides, initially isolated in a protected state, then activated to crosslink on-demand. The thiol groups are induced to form inter-chain crosslinks when subjected to mechanical compression, resulting in a gel that strengthens under strain. Molecular shielding design elements regulate the strain-sensitivity and spontaneous crosslinking tendencies of the polymer network. These strain-responsive gels represent a rational design of new advanced materials with on-demand stiffening properties and potential applications in elastomers, adhesives, foams, films, and fibers.
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PURPOSE: Our study aimed to investigate the association between prenatal exposure to reactive intermediate (RI)-inducing drugs and the initiation of psychotropic medications among children. METHODS: We designed a cohort study using a pharmacy prescription database. Pregnant women were considered exposed when they received a prescription of RI-inducing drugs. These drugs could be either used alone (RI+/FAA-) or combined with drugs exhibiting folic acid antagonism (FAA, RI+/FAA+). The reference group included pregnant women who did not receive any RI-inducing drugs or FAA drugs. RESULTS: We analyzed 4116 exposed and 30 422 reference pregnancies. The hazard ratio (HR) with 95% confidence interval (CI) was 1.27 (95%CI 1.15-1.41) for pregnancies exposed to RI-inducing drugs as a whole. Considering subgroups of RI-inducing drugs, prenatal exposure to both RI+/FAA+ and RI+/FAA- was associated with the children's initiation of psychotropic medications, HRs being 1.35 (95%CI 1.10-1.66) and 1.26 (1.13-1.41), respectively. The HRs were increased with prolonged exposure to RI-inducing drugs, especially in the first and second trimesters. In a detailed examination of the psychotropics, the incidences of receiving antimigraine preparations and psychostimulants were significantly increased for the exposed children, compared with the reference children. The incidences of receiving antipsychotics and hypnotics were also higher for the exposed children; however, the HRs did not reach significance after adjustment. CONCLUSIONS: We found a significantly increased incident use of psychotropic medications among children prenatally exposed to RI-inducing drugs, especially during the first and second trimesters. This suggests a detrimental effect during critical periods of brain development. Copyright © 2017 John Wiley & Sons, Ltd.
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Efectos Tardíos de la Exposición Prenatal/epidemiología , Medicamentos bajo Prescripción/administración & dosificación , Psicotrópicos/administración & dosificación , Adulto , Niño , Preescolar , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Embarazo , Trimestres del Embarazo , Medicamentos bajo Prescripción/efectos adversos , Factores de TiempoRESUMEN
Industrial vegetable oil production in Viet Nam depends on oil seeds and crude plant oils that are currently more than 90% imported. As the first step in investigating the feasibility of using microalgae to provide Viet Nam with a domestic source of oil for food and edible oil industries, fifty lipid-producing microalgae were isolated and characterized. The microalgae were isolated from water sources ranging from freshwater to brackish and marine waters from a wide geographic distribution in Viet Nam. Initial analyses showed that 20 of the 50 strains had good growth rates, produced high biomass and had high lipid content, ranging up to 50% of dry weight biomass. 18S rRNA gene sequence analyses of the 50 strains showed a great diversity in this assemblage of microalgae, comprising at least 38 species and representatives of 25 genera: Chlamydomonas, Poterioochromonas, Scenedesmus, Desmodesmus, Chlorella, Bracteacoccus, Monoraphidium, Selenastrum, Acutodesmus, Mychonastes, Ankistrodesmus, Kirchneriella, Raphidocelis, Dictyosphaerium, Coelastrella, Schizochlamydella, Oocystidium, Nannochloris, Auxenochlorella, Chlorosarcinopsis, Stichococcus, Picochlorum, Prasinoderma, Chlorococcum, and Marvania. Some of the species are closely related to well-known lipid producers such as Chlorella sorokiniana, but some other strains are not closely related to the strains found in public sequence databases and likely represent new species. Analysis of oil quality showed that fatty acid profiles of the microalgal strains were very diverse and strain-dependent. Fatty acids in the microalgal oils comprised saturated fatty acids (SFAs), poly-unsaturated fatty acids (PUFAs), and mono-unsaturated fatty acids (MUFAs). The main SFA was palmitic acid. MUFAs and PUFAs were dominated by oleic acid, and linoleic and linolenic acids, respectively. Some strains were especially rich in the essential fatty acid α-linolenic acid (ALA), which comprised more than 20% of the fatty acids in these strains. Other strains had fatty acid compositions similar to that of palm oil. Several strains have been selected on the basis of their suitable fatty acid profiles and high lipid content for further chemical and physical characterization, toxicity and organoleptic tests of their oils, and for scale-up.
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Ácidos Grasos/aislamiento & purificación , Lípidos/aislamiento & purificación , Microalgas/metabolismo , Aceites/aislamiento & purificación , Biomasa , Ácidos Grasos/química , Ácidos Grasos Insaturados/química , Ácidos Grasos Insaturados/aislamiento & purificación , Estudios de Factibilidad , Genes de ARNr , Lípidos/química , Microalgas/genética , Aceites/química , ARN Ribosómico 18S/genética , VietnamRESUMEN
Among mitotic kinases, Aurora kinases are the most widely studied, since their expression is restricted to mitosis. They play a key role in chromosome segregation and cell polyploidy. Aurora kinases are important therapeutic targets, and several research groups have directed their efforts toward the identification of kinase inhibitors. The aim of this study is to screen and characterize Aurora kinase inhibitors from natural substances extracted from plants that are used in the Vietnamese pharmacopoeia. We have characterized in vitro Derrone, extracted from Erythrina orientalis L. MURR, as a novel Aurora kinase inhibitor. This compound exhibited an ability to inhibit the phosphorylation of histone H3 at ser10 both in kinase assay and at the cellular level. The compound was more effective against Aurora kinase B, with a lower IC50 value as compared to Aurora A. Moreover, it impaired the mitotic spindle checkpoint and led to endoreduplication in cancer cells, a phenomenon caused by an Aurora B inhibitor. Interestingly, using the xCelligence system and real-time cell analysis (RTCA) software, we set up a comparison of cell proliferation profiles between cancer cells treated with Derrone and VX680-a well-known Aurora kinase inhibitor-and we found that these profiles exhibited considerable similarity in cell morphology, growth, and death. Additionally, Derrone significantly inhibited the formation and growth of MCF7 tumor spheroids.
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Antineoplásicos/farmacología , Aurora Quinasa A/antagonistas & inhibidores , Aurora Quinasa B/antagonistas & inhibidores , Flavonoides/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Aurora Quinasa A/metabolismo , Aurora Quinasa B/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Histonas/metabolismo , Humanos , Mitosis/efectos de los fármacos , Piperazinas/farmacología , Proteínas Recombinantes/metabolismoRESUMEN
AIMS: Accurate assessment of anaplastic lymphoma kinase (ALK) gene rearrangement in non-small-cell lung cancers (NSCLCs) is critical to identify patients who are likely to respond to crizotinib. The aim of this study was to evaluate the ALK/EML4 TriCheck FISH probe in a series of NSCLCs enriched for tumours with equivocal ALK status. METHODS AND RESULTS: ALK FISH was prospectively performed on 45 NSCLCs with the ALK/EML4 TriCheck probe (ZytoVision) and the Vysis ALK break-apart probe (Abbott Molecular). ALK immunohistochemistry was performed with 5A4 and D5F3 antibodies. Fourteen cases had equivocal ALK status, based on borderline or focal FISH positivity, an atypical FISH pattern, or discrepancy between ALK FISH and immunohistochemistry. Four of the 14 equivocal cases showed discordance between the two FISH probes. All other cases were concordant. The TriCheck probe showed that, of 31 unequivocal cases, 15 were ALK-rearranged, and 60% of these had EML4 as the translocation partner. Within the group of 14 equivocal cases, 12 showed rearrangement with the Tricheck probe; only one of these showed EML4 rearrangement. Of the six equivocal cases that received crizotinib, four showed clinical benefit. CONCLUSIONS: The ALK/EML4 TriCheck FISH probe may be useful for the detection of ALK rearrangements, especially in borderline or atypical cases, where an additional unique ALK FISH probe may provide further confirmation of rearrangement.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Hibridación Fluorescente in Situ/métodos , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinasas Receptoras/genética , Quinasa de Linfoma Anaplásico , Estudios de Cohortes , Reordenamiento Génico , Humanos , InmunohistoquímicaRESUMEN
Importance: Empathy is an aspect of the patient-physician relationship that may be particularly important in patients with chronic pain. Objective: To measure the association of physician empathy with pain, function, and health-related quality of life (HRQOL) among patients with chronic low back pain. Design, Setting, and Participants: This cohort study included adult enrollees from the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation national pain research registry. Study dates were from April 1, 2016, to July 25, 2023, with up to 12 months of follow-up. Exposure: Physician empathy was assessed with the Consultation and Relational Empathy measure and dichotomized to yield very empathic physician and slightly empathic physician groups. Main Outcomes and Measures: Main outcomes were patient-reported pain, function, and HRQOL measured with a numerical rating scale for low back pain intensity, the Roland-Morris Disability Questionnaire for back-related disability, and the Patient-Reported Outcomes Measurement Information System for HRQOL deficits pertaining to anxiety, depression, fatigue, sleep disturbance, and pain interference. Data were collected at 5 quarterly encounters from registry enrollment through 12 months and analyzed with generalized estimating equations, including multivariable models to measure temporal trends and to adjust for baseline and longitudinal covariates. Results: Among the 1470 patients, the mean (SD) age was 53.1 (13.2) years, and 1093 (74.4%) were female. Patients completed 5943 encounters in which multivariable analyses demonstrated that greater physician empathy was inversely associated with pain intensity (ß = -0.014; 95% CI, -0.022 to -0.006; P < .001), back-related disability (ß = -0.062; 95% CI, -0.085 to -0.040; P < .001), and HRQOL deficits on each measure (eg, pain interference: ß = -0.080; 95% CI, -0.111 to -0.049; P < .001). Correspondingly, compared with the slightly empathic physician group, the very empathic physician group reported lower mean pain intensity (6.3; 95% CI, 6.1-6.5 vs 6.7; 95% CI, 6.5-6.9; P < .001), less mean back-related disability (14.9; 95% CI, 14.2-15.6 vs 16.8; 95% CI, 16.0-17.6; P < .001), and fewer HRQOL deficits on each measure (eg, fatigue: 57.3; 95% CI, 56.1-58.5 vs 60.4; 95% CI, 59.0-61.7; P < .001). All physician empathy group differences were clinically relevant, with Cohen d statistics ranging from 0.21 for pain intensity to 0.30 for back-related disability, fatigue, and pain interference. Physician empathy was associated with more favorable outcomes than non-pharmacological treatments, opioid therapy, and lumbar spine surgery. Conclusions and Relevance: In this cohort study of adult patients with chronic pain, physician empathy was associated with better outcomes over 12 months. Greater efforts to cultivate and improve physician empathy appear warranted.
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Dolor Crónico , Dolor de la Región Lumbar , Médicos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor Crónico/terapia , Estudios de Cohortes , Empatía , Fatiga , Calidad de Vida , AncianoRESUMEN
Purpose: To assess over 2 weeks, the effect of 3 different low concentrations of atropine on pupillary diameter and accommodative amplitude in children with myopia. Methods: Fifty-eight children with myopia [spherical equivalent (SE) of -0.50 diopters (D) or worse, astigmatism of less than or equal to 2.00 D] were randomly allocated to 3 groups receiving 0.01%, 0.02%, or 0.03% atropine eye drops, once nightly for 2 weeks. The primary outcome was the change from baseline in pupillary diameter and accommodative amplitude with each of the concentrations. Results: Fifty-seven participants (114 eyes), aged between 6 and 12 years, completed the 2-week trial (mean age 9.3 ± 1.7 years and mean SE -3.53 ± 1.79 D). After 2 weeks of use, all the 3 concentrations were found to have a statistically significant effect on both the pupillary diameter and accommodative amplitude. Accommodative amplitude reduced by an average of 5.23 D, 9.28 D, and 9.32 D, and photopic pupil size increased by an average of 0.95 ± 1.05 mm, 1.65 ± 0.93 mm, and 2.16 ± 0.88 mm with 0.01%, 0.02%, and 0.03%, respectively. Of the eyes, a total of 5.3% and 5.9% of the eyes on 0.02% and 0.03% atropine had a mean residual accommodative amplitude of <5 D. The percentage of eyes having a pupillary dilation >3 mm were 4.8%, 10.5%, and 23.5% for 0.01%, 0.02%, and 0.03% atropine, respectively. Conclusions: Low-dose atropine had an effect on pupillary diameter and accommodative amplitude. With the highest concentration assessed, that is, 0.03% nearly 1 of 4 eyes had pupillary dilation of >3 mm. Clinical Trial Registration number: NCT03699423.
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Acomodación Ocular , Atropina , Midriáticos , Miopía , Soluciones Oftálmicas , Pupila , Humanos , Atropina/administración & dosificación , Atropina/farmacología , Niño , Miopía/tratamiento farmacológico , Miopía/fisiopatología , Acomodación Ocular/efectos de los fármacos , Pupila/efectos de los fármacos , Masculino , Femenino , Soluciones Oftálmicas/administración & dosificación , Midriáticos/administración & dosificación , Midriáticos/farmacología , Midriáticos/uso terapéutico , Relación Dosis-Respuesta a DrogaRESUMEN
OBJECTIVES: To determine the associated pathogen during the 2023 conjunctivitis outbreak in Vietnam METHODS: RNA-sequencing was used to identify pathogens before and during the outbreak. RESULTS: 24 patients with infectious conjunctivitis between March and October 2023 from Hai Yen Vision Institute in Vietnam were swabbed. Coxsackievirus A24v was the most common pathogen identified. Phylogenetic analysis of these strains demonstrates similarities to the Coxsackievirus identified in the 2022 India outbreak. Human adenovirus D was also circulating. Ocular findings of tearing, purulence, and itching were common in this outbreak. CONCLUSIONS: Multiple viruses can co-circulate during conjunctivitis outbreaks. Hemorrhagic conjunctivitis, commonly associated with coxsackievirus conjunctivitis, was not a common clinical sign in this outbreak. Repeat genetic surveillance, with the notable inclusion of RNA virus detection strategies, is important for outbreak detection.
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Infecciones por Coxsackievirus , Brotes de Enfermedades , Filogenia , Humanos , Vietnam/epidemiología , Infecciones por Coxsackievirus/epidemiología , Infecciones por Coxsackievirus/virología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adulto Joven , Niño , Adolescente , Preescolar , Conjuntivitis Viral/epidemiología , Conjuntivitis Viral/virología , Conjuntivitis Hemorrágica Aguda/epidemiología , Conjuntivitis Hemorrágica Aguda/virologíaRESUMEN
Single-cell technology has allowed researchers to probe tissue complexity and dynamics at unprecedented depth in health and disease. However, the generation of high-dimensionality single-cell atlases and virtual three-dimensional tissues requires integrated reference maps that harmonize disparate experimental designs, analytical pipelines, and taxonomies. Here, we present a comprehensive single-cell transcriptome integration map of cardiac fibrosis, which underpins pathophysiology in most cardiovascular diseases. Our findings reveal similarity between cardiac fibroblast (CF) identities and dynamics in ischemic versus pressure overload models of cardiomyopathy. We also describe timelines for commitment of activated CFs to proliferation and myofibrogenesis, profibrotic and antifibrotic polarization of myofibroblasts and matrifibrocytes, and CF conservation across mouse and human healthy and diseased hearts. These insights have the potential to inform knowledge-based therapies.
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Fibroblastos , Fibrosis , Análisis de la Célula Individual , Transcriptoma , Animales , Análisis de la Célula Individual/métodos , Humanos , Fibroblastos/metabolismo , Ratones , Miocardio/metabolismo , Miocardio/patología , Miofibroblastos/metabolismo , Miofibroblastos/patología , Perfilación de la Expresión GénicaRESUMEN
Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ-TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo-YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription.
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Proteínas Adaptadoras Transductoras de Señales , Adipocitos , Tejido Adiposo , Metabolismo Energético , Vía de Señalización Hippo , Leptina , Proteínas Serina-Treonina Quinasas , Transducción de Señal , Proteínas Señalizadoras YAP , Animales , Leptina/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Ratones , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Señalizadoras YAP/metabolismo , Tejido Adiposo/metabolismo , Adipocitos/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ/metabolismo , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Transactivadores/metabolismo , Transactivadores/genéticaRESUMEN
Molecular studies are part of standard care for cancer patients. Bone, a common and sometimes sole site of metastasis, requires decalcification for morphological examination. Many commonly used decalcification agents contain strong acids that degrade nucleic acids. The paradigm shift in oncology, with biomarker targeted therapy and gene expression profiling analysis, requires sufficient nucleic acid recovery from bone biopsy specimens. We systematically studied the effects of a spectrum of decalcification agents on the quantity and quality of RNA and DNA recovered from bone biopsies. Multiple bone biopsies of similar size and cellularity were fixed in 10% neutral-buffered formalin, randomized to various decalcification agents for 2 hours then processed, and embedded. Tissue lysates were obtained from unstained sections and nucleic acid isolated. DNA and RNA were quantified. Assessment of DNA and RNA integrity was accomplished by comparison of the average cycle threshold by polymerase chain reaction of selected housekeeping genes for each agent. Results were then analyzed by 2-sample t test. There was a significant decrease in both DNA and RNA yield and integrity with strong acids (hydrochloric, nitric) vs 14% EDTA and formic acid. DNA yield was (mean nanograms) 6.15 vs 68.68 (P<.001) and RNA was (mean nanograms) 121.53 vs 288.89 (P=.003), respectively. DNA integrity (mean cycle threshold) was 35.79 vs 30.16 (P<.001), and RNA was 33.03 vs 26.5 (P<.001), respectively. Decalcification of bone biopsies with EDTA or formic acid agents was associated with a significant improvement in recovered nucleic acid quantity and quality.
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Huesos/efectos de los fármacos , ADN/efectos de los fármacos , Ácido Edético/farmacología , Formiatos/farmacología , ARN/efectos de los fármacos , Adulto , Biopsia , ADN/análisis , ADN/aislamiento & purificación , Técnica de Descalcificación , Formaldehído , Humanos , Masculino , Persona de Mediana Edad , Adhesión en Parafina , ARN/análisis , ARN/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa , Fijación del TejidoRESUMEN
PURPOSE: To evaluate myopia progression with highly aspherical lenslet (HAL) spectacles vs conventional single vision (SV) spectacles. DESIGN: Prospective, double-blind, single-center, randomized, cross-over trial. METHOD: A total of 119 Vietnamese children (7-13 years of age, spherical equivalent refractive error [SE] = -0.75 to -4.75D) were randomized to wear either HAL or SV, and after 6 months (stage 1) crossed over to the other lens for another 6 months (stage 2). At the end of stage 2, both groups wore HAL for a further 6 months. In the order that lenses were worn at each stage, group 1 was designated HSH (HAL-SV-HAL) and group 2 SHH (SV-HAL-HAL). The main outcome measures were a comparison between HAL and SV for change (Δ) in SE and axial length (AL) during each stage; and a comparison of ΔSE/AL with SV between HSH and SHH groups to determine whether myopia rebounded when switched from HAL to SV (HSH group). RESULTS: Myopia progressed more slowly with HAL than with SV during stages 1 and 2 (SEΔ stage 1: -0.21 vs -0.27D, P = .317, stage 2: -0.05 vs -0.32D, P < .001; ALΔ stage 1: 0.07 vs 0.14 mm, P = .004; stage 2: 0.04 vs 0.17 mm, P < .001). ΔSE/AL with SV was not different between the HSH and SHH groups (ΔSE -0.33 ± 0.27D vs -0.27 ± 0.42D, P = .208; ΔAL 0.17 ± 0.13mm vs 0.13 ± 0.15 mm, P = .092). An average of 14 hours per day of lens wear was reported with both lenses. CONCLUSIONS: In this cross-over trial, intergroup and intragroup comparisons indicate that HAL slows myopia. Children were compliant with lens wear, and data were not suggestive of rebound when patients were switched from HAL to SV.
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Miopía , Oftalmología , Niño , Humanos , Recién Nacido , Lactante , Refracción Ocular , Anteojos , Estudios ProspectivosRESUMEN
Purpose: Conjunctivitis epidemics and pandemics remain a global burden. This study aims to comprehensively identify pathogens associated with conjunctivitis in Vietnam. Methods: Patients with acute conjunctivitis presented to an outpatient clinic in Ho Chi Minh City, Vietnam, were enrolled from September 2022 to March 2023. Swabs were obtained from conjunctiva and anterior nares of all patients. Unbiased RNA deep sequencing (RNA-seq) was used to identify any replicating pathogens in the samples. Results: Samples from 35 patients were analyzed. A pathogen was identified in 80% of the patients. 72% (95% confidence interval: 54% to 85%) were infected with either HAdV-D or HAdV-B. RNA viruses detected were rhinoviruses and human coronavirus 229E. Bacteria etiologies included Streptococcus pneumoniae, Hemophilus influenza, and Pseudomonas spp. One patient had co-infection of rhinovirus A and HAdV-B. Vittaforma corneae, a fungus, was identified in one patient. Corneal sub-epithelial infiltrates, pseudomembranes, or pre-auricular lymphadenopathy were not reported in any patient. Conclusions: Human adenoviruses are the common circulating pathogens associated with infectious conjunctivitis in Vietnam. HAdV species, however, appear to vary between geographic locations within Vietnam. Other under-recognized pathogens identified in this study, such as RNA viruses, suggest broader pathogen surveillance may be beneficial.
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Introduction: The development of organic manure from livestock excreta is a useful source for sustainable crop production in environment-friendly agriculture. Organic manure increases soil microbial activity and organic matter (OM) supply. The excessive use of chemical fertilizers (CFs) leads to air and water pollution caused by toxic chemicals and gases, and soil quality degradation via nutrient imbalance due to supplying specific chemical components. Thus, the use of organic manure will serve as a long-term supply of various nutrients in soil via OM decomposition reaction as well as the maintenance of environment. Methods: In this study, we aimed to analyze the diverse effects of Hanwoo manure (HM) on plant growth, feed quality, and soil bacterial communities in comparison with CFs, commercial poultry manure (CM), and the combined use of chemical fertilizer and Hanwoo manure (HM+CF). We analyzed the contents of crude matter (protein, fat, fiber, and ash), P, acid detergent fiber (ADF), and neutral detergent fiber (NDF) through feed quality analysis, and the contents or activities of total phenol, total flavonoid, ABTS, nitrite scavenging, and reducing power via the antioxidant assay. Furthermore, the soil microbial communities were determined using 16S rRNA sequencing. We compared the soil bacteria among different soil samples by using amplicon sequence variant (ASV) analysis. Results and discussion: We observed increased OM in the soil of the HM group compared to that of the CF and non-treated groups over a period of two years. Moreover, HM+CF treatment enormously improved plant growth. Organic manure, especially HM, caused an increase in the content of crude ash and phosphorus in plants. There were no significant differences in total polyphenol, total flavonoid, ABTS, nitrite scavenging, and reducing power in plants between HM and CF groups. Finally, we detected 13 soil bacteria (Acidibacter, Algisphaera, Cystobacter, Microvirga, Ohtaekwangia, Panacagrimonas, Pseudarthrobacter, Reryanella, Rhodoligotrophos, Solirubrobacter, Stenotrophobacter, Tellurimicrobium, and Thermomarinilinea) that were considerably correlated with OM and available phosphorus, and three considerably correlated bacteria were specifically distributed in CF or organic manure. The results suggest that HM is a valuable source of organic manure that can replace CF for sustainable crop production.