RESUMO
BACKGROUND: Many promising artificial intelligence (AI) and computer-aided detection and diagnosis systems have been developed, but few have been successfully integrated into clinical practice. This is partially owing to a lack of user-centered design of AI-based computer-aided detection or diagnosis (AI-CAD) systems. OBJECTIVE: We aimed to assess the impact of different onboarding tutorials and levels of AI model explainability on radiologists' trust in AI and the use of AI recommendations in lung nodule assessment on computed tomography (CT) scans. METHODS: In total, 20 radiologists from 7 Dutch medical centers performed lung nodule assessment on CT scans under different conditions in a simulated use study as part of a 2×2 repeated-measures quasi-experimental design. Two types of AI onboarding tutorials (reflective vs informative) and 2 levels of AI output (black box vs explainable) were designed. The radiologists first received an onboarding tutorial that was either informative or reflective. Subsequently, each radiologist assessed 7 CT scans, first without AI recommendations. AI recommendations were shown to the radiologist, and they could adjust their initial assessment. Half of the participants received the recommendations via black box AI output and half received explainable AI output. Mental model and psychological trust were measured before onboarding, after onboarding, and after assessing the 7 CT scans. We recorded whether radiologists changed their assessment on found nodules, malignancy prediction, and follow-up advice for each CT assessment. In addition, we analyzed whether radiologists' trust in their assessments had changed based on the AI recommendations. RESULTS: Both variations of onboarding tutorials resulted in a significantly improved mental model of the AI-CAD system (informative P=.01 and reflective P=.01). After using AI-CAD, psychological trust significantly decreased for the group with explainable AI output (P=.02). On the basis of the AI recommendations, radiologists changed the number of reported nodules in 27 of 140 assessments, malignancy prediction in 32 of 140 assessments, and follow-up advice in 12 of 140 assessments. The changes were mostly an increased number of reported nodules, a higher estimated probability of malignancy, and earlier follow-up. The radiologists' confidence in their found nodules changed in 82 of 140 assessments, in their estimated probability of malignancy in 50 of 140 assessments, and in their follow-up advice in 28 of 140 assessments. These changes were predominantly increases in confidence. The number of changed assessments and radiologists' confidence did not significantly differ between the groups that received different onboarding tutorials and AI outputs. CONCLUSIONS: Onboarding tutorials help radiologists gain a better understanding of AI-CAD and facilitate the formation of a correct mental model. If AI explanations do not consistently substantiate the probability of malignancy across patient cases, radiologists' trust in the AI-CAD system can be impaired. Radiologists' confidence in their assessments was improved by using the AI recommendations.
RESUMO
The stability of monoclonal antibodies (mAbs) is vital for their therapeutic success. Sorbitol, a common mAb stabilizer used to prevent aggregation, was evaluated for any potential adverse effects on the chemical stability of mAb X. An LC-MS/MS based analysis focusing on the post-translational modifications (PTMs) of mAb X was conducted on samples that had undergone accelerated aging at 40°C. Along with PTMs that are known to affect mAbs' structure function and stability (such as deamidation and oxidation), a novel mAb PTM was discovered, the esterification of glutamic acid by sorbitol. Incubation of mAb X with a 1:1 ratio of unlabeled sorbitol and isotopically labeled sorbitol (13C6) further corroborated that the modification was the consequence of the esterification of glutamic acid by sorbitol. Levels of esterification varied across glutamic acid residues and correlated with incubation time and sorbitol concentration. After 4 weeks of accelerated stability with isotopically labeled sorbitol, it was found that 16% of the total mAb possesses an esterified glutamic acid. No esterification was observed at aspartic acid sites despite the free carboxylic acid side chain. This study unveils a unique modification of mAbs, emphasizing its potential significance for formulation and drug development.
Assuntos
Anticorpos Monoclonais , Ácido Glutâmico , Sorbitol , Anticorpos Monoclonais/química , Estabilidade de Medicamentos , Esterificação , Ácido Glutâmico/química , Espectrometria de Massa com Cromatografia Líquida/métodos , Processamento de Proteína Pós-Traducional , Estabilidade Proteica , Sorbitol/química , Espectrometria de Massas em Tandem/métodosRESUMO
Background: There is limited evidence on association between air pollutants and hospital admissions, hospital cost and length of stay (LOS) among patients with diabetes mellitus (DM) and comorbid respiratory diseases (RD), especially in low- and middle-income countries (LMICs) with low levels of air pollution. Methods: Daily data on RD-DM patients were collected in Panzhihua from 2016 to 2020. A generalised additive model (GAM) was used to explore the effect of air pollutants on daily hospital admissions, LOS and hospital cost. Attributable risk was employed to estimate RD-DM's burden due to exceeding air pollution exposure, using both 0 microgrammes per cubic metre (µg/m3) and WHO's 2021 air quality guidelines as reference. Results: For each 10 ug/m3 increase of particles with an aerodynamic diameter <2.5 micron (µm) (PM2.5), particles with an aerodynamic diameter <10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3), the admissions of RD-DM patients increased by 7.25% (95% CI = 4.26 to 10.33), 5.59% (95% CI = 3.79 to 7.42), 10.10% (95% CI = 7.29 to 12.98), 12.33% (95% CI = 8.82 to 15.95) and -2.99% (95% CI = -4.08 to -1.90); per 1 milligramme per cubic metre (mg/m3) increase of carbon monoxide (CO) corresponded to a 25.77% (95% CI = 17.88 to 34.19) increment for admissions of RD-DM patients. For LOS and hospital cost, the six air pollutants showed similar effect. Given 0 µg/m3 as the reference, NO2 showed the maximum attributable fraction of 32.68% (95% CI = 25.12 to 39.42%), corresponding to an avoidable burden of 5661 (95% CI = 3611 to 5860) patients with RD-DM. Conclusions: There is an association between PM2.5, PM10, SO2, NO2, and CO with increased hospital admissions, LOS and hospital cost in patients with RD-DM. Disease burden of RD-DM may be improved by formulating policies related to air pollutants exposure reduction, especially in LMICs with low levels of air pollution.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Diabetes Mellitus , Doenças Respiratórias , Humanos , Tempo de Internação , Dióxido de Nitrogênio/análise , Custos Hospitalares , Poluição do Ar/efeitos adversos , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Diabetes Mellitus/epidemiologia , China/epidemiologia , Material Particulado/efeitos adversos , Material Particulado/análise , Hospitais , Doenças Respiratórias/epidemiologiaRESUMO
BACKGROUND: Pulmonary infection (PI) and urinary tract infection (UTI) have been the most common cause of hospitalization and most frequent infection respectively in older people with disability (OPWD). Long-term care insurance (LTCI) policy, intending to provide services to reduce the disease burden of OPWD, it remains unclear whether LTCI could reduce PI-, and UTI-related hospitalizations. This quasi-experimental study aimed to assess the influences of LTCI on all-cause, especially PI- and UTI-related hospitalizations among OPWD and the variation across sociodemographic characteristics. METHODS: 32,120 participants in the Chengdu Long-term Care Insurance cohort were considered the intervention group, and 2,704 not covered by the LTCI were in the control group. A total of 3,134,160 hospitalization records were collected between January 2014 and June 2021. A doubly robust difference-in-differences (DID) method was used to estimate the average treatment effect on the treated (ATT), indicating the average effect of LTCI on intervention group. RESULTS: The average monthly all-cause, PI-, and UTI-related hospitalization rates were 16.3%, 4.0% and 0.5% in the intervention group, respectively, and were 19.3%, 3.9% and 0.5% in the control group, respectively. Under LTCI, all-cause (ATT [95% CI]: 7.15% [6.41%, 7.88%]), PI- (3.25% [2.76%, 3.74%]), and UTI-related hospitalizations (0.46% [0.28%, 0.64%]) were decreased. The influences of LTCI became significant after 5 months since the LTCI implementation and remained stable over time. The impact was more pronounced among those with longer coverage. The overall reduction was stronger in those who were not married, lived alone, and resided in institutions. CONCLUSIONS: LTCI may reduce the occurrence of all-cause, PI-, and UTI-related hospitalizations in OPWD, with stronger influences observed over an extended period of implementation. The implementation of LTCI can play a role in reducing the burden of infectious diseases in OPWD and the care burden of families and society.
Assuntos
Pessoas com Deficiência , Infecções Urinárias , Humanos , Idoso , Seguro de Assistência de Longo Prazo , Hospitalização , Infecções Urinárias/epidemiologia , Assistência de Longa DuraçãoRESUMO
In this study, the toxicity effects on circulatory system and respiratory system, and the acute toxicity test of recombinant neorudin (EPR-hirudin, EH) in cynomolgus monkeys were evaluated to provide reference information for clinical studies. Eighteen cynomolgus monkeys were randomly divided into three groups for single intravenous administration of 3, 30 mg/kg EH and normal saline, respectively. The changes of respiratory frequency, respiratory intensity, blood pressure and electrocardiogram before and after administration were recorded. In acute toxicity test, six cynomolgus monkeys were intravenously received EH at a single dose of 171, 257, 385, 578, 867 and 1300 mg/kg respectively. The vital signs, hematology, serum biochemistry, coagulation indexes and electrocardiogram indexes of the animals were determined before administration and on the 7th and 14th day after administration. As the results showed that there were no significant abnormal changes in respiratory frequency, respiratory intensity, blood pressure or electrocardiogram in cynomolgus monkeys after receiving EH at 3 mg/kg and 30 mg/kg, and there was no statistical difference between the treated groups and normal saline group. In the acute toxicity test, no significant abnormalities were observed in vital signs, hematology, serum biochemistry, coagulation indexes and electrocardiogram indexes of six cynomolgus monkeys at day 7 and 14 after EH administration. Furthermore, autopsies of all cynomolgus monkeys showed no abnormalities. The results of toxicokinetics showed that AUClast of the drug increased in proportion to the EH dose in the range of 171-578 mg/kg, and increased in over proportion to the EH dose in the range of 578-1300 mg/kg. The variation of Cmax was basically consistent with AUClast. In a sum, A single intravenous injection of 3 and 30 mg/kg of EH did not affect the circulatory system and respiratory system in cynomolgus monkeys and the maximum tolerated dose of EH in cynomolgus monkey is over 1300 mg/kg (equivalent to 619-1300 times of the proposed clinical equivalent dose).
Assuntos
Sistema Cardiovascular , Hirudinas , Sistema Respiratório , Testes de Toxicidade Aguda , Animais , Sistema Cardiovascular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Hirudinas/administração & dosagem , Hirudinas/toxicidade , Infusões Intravenosas , Injeções Intravenosas , Macaca fascicularis , Sistema Respiratório/efeitos dos fármacos , Solução Salina/administração & dosagemRESUMO
Ocean acidification has emerged as a major challenge affecting the development of the marine aquaculture. Seasonal variations of seawater pH and aragonite saturation (Ωarag) were investigated in the Muping Marine Ranch, Yantai. The results showed that the seasonal variations of pH and Ωarag were distinct. The temperature exerted opposite effects on pH and Ωarag and played a dominant role in pH variation, while limited role in Ωarag. The air-sea exchange had a syntropic effect on pH and Ωarag but less impact on their seasonal variations. Biological activities affected seasonal variations of surface seawater pH and Ωarag, but they largely canceled each other out with other non-temperature effects; while bottom seawater Ωarag was mainly controlled by biological respiration in summer. This study demonstrates that pH is primarily controlled by seasonal temperature changes, whereas Ωarag would be a better indicator for ocean acidification caused by non-temperature processes.
Assuntos
Carbonato de Cálcio , Água do Mar , Concentração de Íons de Hidrogênio , Estações do Ano , Carbonato de Cálcio/análise , China , Dióxido de Carbono/análiseRESUMO
Background: The associations of ambient air pollution with hospital admissions (HAs) for overall and specific causes of cardiovascular diseases (CVDs), as well as related morbidity and economic burdens remain understudied, especially in low-pollution areas of low- and middle-income countries (LMICs). We evaluated the short-term effects of exposure to PM2.5 (particles with an aerodynamic diameter ≤2.5 µm), PM10 (particles with an aerodynamic diameter ≤10 µm), and SO2 (sulfur dioxide) on HAs for CVDs in Panzhihua, China, during 2016-2020, and calculated corresponding attributable risks and economic burden. Methods: We used a generalized additive model (GAM) while controlling for time trends, meteorological conditions, holidays, and days of the week to estimate the associations. The cost of illness (COI) method was adopted to further assess corresponding hospitalization costs and productivity losses. Results: A total of 27 660 HAs for CVDs were included in this study. PM10 and SO2 were significantly associated with elevated risks of CVDs hospitalizations. Each 10 µg/m3 increase in PM10 and SO2 at lag06 corresponded to an increase of 2.48% (95% confidence interval (CI) = 0.92%-4.06%), and 5.50% (95% CI = 3.09%-7.97%) in risk of HAs for CVDs, respectively. The risk estimates of PM10 and SO2 on CVD hospitalizations were generally robust after adjustment for other pollutants in two-pollutant models. We found stronger associations between air pollution (PM10 and SO2) and CVDs in cool seasons than in warm seasons. For specific causes of CVDs, significant associations of PM10 and SO2 exposure with cerebrovascular disease and ischaemic heart disease were observed. Using 0 µg/m3 as the reference concentrations, 11.91% (95%CI = 4.64%-18.56%) and 15.71% (95%CI = 9.30%-21.60%) of HAs for CVDs could be attributable to PM10 and SO2, respectively. During the study period, PM10 and SO2 brought 144.34 million Yuan economic losses for overall CVDs, accounting for 0.028% of local GDP. Conclusions: Our results suggest that PM10 and SO2 exposure might be an important trigger of HAs for CVDs and accounted for substantial morbidity and economic burden.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Doenças Cardiovasculares , Humanos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Material Particulado/toxicidade , Material Particulado/análise , Doenças Cardiovasculares/epidemiologia , Poluição do Ar/efeitos adversos , Hospitalização , China/epidemiologia , Hospitais , Exposição AmbientalRESUMO
This article aims to discuss how to give full play to the comparative advantages of the rural ecological environment and realize the endogenous development of rural society and economy in China. First, based on the ecological economy theory of "lucid waters and lush mountains are golden and silver mountains" (the "two mountains" theory), we integrated the theories and methods of ecology, economics, and geography disciplines to examine the transformation of "ecological advantages" into "economic development" from a comprehensive perspective. Second, based on the matching relationship between the division of major function zones and the classification of ecological services, we creatively constructed a theoretical framework for the endogenous development of rural areas. Third, accounting indicators and methods for rural ecological products' biophysical quantity and monetary value are established. Finally, we conducted an empirical study of Nanshi Village in central China as a case. The results showed that: The benefits provided by ecosystems to the development of human society would be underestimated if it is measured only by the provisioning services; the per capita Gross Ecosystem Product (GEP) of the case area was three times the per capita disposable income of rural permanent residents in the same period. Taking advantage of the rural ecological environment to promote the actual transformation of the potential value of ecological products is the feasible path for rural revitalization. One of the implications of this study is that it links the rural ecological and environmental advantages with social and economic development from the perspective of ecological economics and provides decision-making support for this case and other similar rural ecological industry revitalization practices.
Assuntos
Conservação dos Recursos Naturais , Ecossistema , China , Conservação dos Recursos Naturais/métodos , Desenvolvimento Econômico , Humanos , População RuralRESUMO
OBJECTIVE: To assess urban-rural disparities in the association between long-term exposure to high altitude and malnutrition among children under 5 years old. DESIGN: A three-stage, stratified, cluster sampling was used to randomly select eligible individuals from July to October 2020. The data of participants, including demographic characteristics, altitude of residence, and nutritional status, were collected via questionnaire and physical examination. SETTING: Tibet, China. PARTICIPANTS: Children under 5 years old in Tibet. RESULTS: Totally, 1975 children under 5 years old were included in this study. We found that an additional 1000 m increase in altitude was associated with decreased Z-scores of height-for-age (ß = -0·23, 95 % CI: -0·38, -0·08), Z-scores of weight-for-age (ß = -0·24, 95 % CI: -0·39, -0·10). The OR for stunting and underweight were 2·03 (95 % CI: 1·51 to 2·73) and 2·04 (95 % CI: 1·38 to 3·02) per 1000 m increase in altitude, respectively; and OR increased rapidly at an altitude above 3500 m. The effects of long-term exposure to high altitudes on the prevalence of underweight in rural children were higher than that in urban children (P < 0·05). CONCLUSIONS: High-altitude exposure is tightly associated with malnutrition among children under 5 years old. Improving children's nutrition is urgently needed in areas above 3500 m, especially in rural ones.
RESUMO
Importance: Few studies have prospectively assessed SARS-CoV-2 community infection in children aged 0 to 4 years. Information about SARS-CoV-2 incidence and clinical and virological features in young children could help guide prevention and mitigation strategies. Objective: To assess SARS-CoV-2 incidence, clinical and virological features, and symptoms in a prospective household cohort and to compare viral load by age group, symptoms, and SARS-CoV-2 lineage in young children, older children, and adults. Design, Setting, and Participants: This prospective cohort study enrolled 690 participants from 175 Maryland households with 1 or more children aged 0 to 4 years between November 24, 2020, and October 15, 2021. For 8 months after enrollment, participants completed weekly symptom questionnaires and submitted self-collected nasal swabs for SARS-CoV-2 qualitative real-time reverse transcriptase polymerase chain reaction (RT-PCR) testing, quantitative RT-PCR testing, and viral lineage determination. For the analyses, SARS-CoV-2 Alpha and Delta lineages were considered variants of interest or concern. Sera collected at enrollment and at approximately 4 months and 8 months after enrollment were assayed for SARS-CoV-2 spike and nucleocapsid protein antibodies. Main Outcomes and Measures: Incidence, clinical and virological characteristics, and symptoms of SARS-CoV-2 infection by age group and correlations between (1) highest detected viral load and symptom frequency and (2) highest detected viral load and SARS-CoV-2 lineage. Results: Among 690 participants (355 [51.4%] female and 335 [48.6%] male), 256 individuals (37.1%) were children aged 0 to 4 years, 100 (14.5%) were children aged 5 to 17 years, and 334 (48.4%) were adults aged 18 to 74 years. A total of 15 participants (2.2%) were Asian, 24 (3.5%) were Black, 603 (87.4%) were White, 43 (6.2%) were multiracial, and 5 (0.7%) were of other races; 33 participants (4.8%) were Hispanic, and 657 (95.2%) were non-Hispanic. Overall, 54 participants (7.8%) had SARS-CoV-2 infection during the surveillance period, including 22 of 256 children (8.6%) aged 0 to 4 years, 11 of 100 children (11.0%) aged 5 to 17 years, and 21 of 334 adults (6.3%). Incidence rates per 1000 person-weeks were 2.25 (95% CI, 1.28-3.65) infections among children aged 0 to 4 years, 3.48 (95% CI, 1.59-6.61) infections among children aged 5 to 17 years, and 1.08 (95% CI, 0.52-1.98) infections among adults. Children aged 0 to 17 years with SARS-CoV-2 infection were more frequently asymptomatic (11 of 30 individuals [36.7%]) compared with adults (3 of 21 individuals [14.3%]), with children aged 0 to 4 years most frequently asymptomatic (7 of 19 individuals [36.8%]). The highest detected viral load did not differ between asymptomatic vs symptomatic individuals overall (median [IQR], 2.8 [1.5-3.3] log10 copies/mL vs 2.8 [1.8-4.4] log10 copies/mL) or by age group (median [IQR] for ages 0-4 years, 2.7 [2.4-4.4] log10 copies/mL; ages 5-17 years: 2.4 [1.1-4.0] log10 copies/mL; ages 18-74 years: 2.9 [1.9-4.6] log10 copies/mL). The number of symptoms was significantly correlated with viral load among adults (R = 0.69; P < .001) but not children (ages 0-4 years: R = 0.02; P = .91; ages 5-17 years: R = 0.18; P = .58). The highest detected viral load was greater among those with Delta variant infections (median [IQR], 4.4 [3.9-5.1] log10 copies/mL) than those with infections from variants not of interest or concern (median [IQR], 1.9 [1.1-3.6] log10 copies/mL; P = .009) or those with Alpha variant infections (median [IQR], 2.6 [2.3-3.4] log10 copies/mL; P = .006). Conclusions and Relevance: In this study, SARS-CoV-2 infections were frequently asymptomatic among children aged 0 to 4 years; the presence and number of symptoms did not correlate with viral load. These findings suggest that symptom screening may be insufficient to prevent outbreaks involving young children.
Assuntos
COVID-19 , Adolescente , Adulto , COVID-19/diagnóstico , COVID-19/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , SARS-CoV-2 , Carga ViralRESUMO
BACKGROUND: There are prominent geographic disparities in the life expectancy (LE) of older US adults between the states with the highest (leading states) and lowest (lagging states) LE and their causes remain poorly understood. Heart failure (HF) has been proposed as a major contributor to these disparities. This study aims to investigate geographic disparities in HF outcomes between the leading and lagging states. METHODS: The study was a secondary data analysis of HF outcomes in older US adults aged 65+, using Center for Disease Control and Prevention sponsored Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database and a nationally representative 5% sample of Medicare beneficiaries over 2000-2017. Empiric estimates of death certificate-based mortality from HF as underlying cause of death (CBM-UCD)/multiple cause of death (CBM-MCD); HF incidence-based mortality (IBM); HF incidence, prevalence, and survival were compared between the leading and lagging states. Cox regression was used to investigate the effect of residence in the lagging states on HF incidence and survival. RESULTS: Between 2000 and 2017, HF mortality rates (per 100,000) were higher in the lagging states (CBM-UCD: 188.5-248.6; CBM-MCD: 749.4-965.9; IBM: 2656.0-2978.4) than that in the leading states (CBM-UCD: 79.4-95.6; CBM-MCD: 441.4-574.1; IBM: 1839.5-2138.1). Compared to their leading counterparts, lagging states had higher HF incidence (2.9-3.9% vs. 2.2-2.9%), prevalence (15.6-17.2% vs. 11.3-13.0%), and pre-existing prevalence at age 65 (5.3-7.3% vs. 2.8-4.1%). The most recent rates of one- (77.1% vs. 80.4%), three- (59.0% vs. 60.7%) and five-year (45.8% vs. 49.8%) survival were lower in the lagging states. A greater risk of HF incidence (Adjusted Hazards Ratio, AHR [95%CI]: 1.29 [1.29-1.30]) and death after HF diagnosis (AHR: 1.12 [1.11-1.13]) was observed for populations in the lagging states. The study also observed recent increases in CBMs and HF incidence, and declines in HF prevalence, prevalence at age 65 and survival with a decade-long plateau stage in IBM in both leading and lagging states. CONCLUSION: There are substantial geographic disparities in HF mortality, incidence, prevalence, and survival across the U.S.: HF incidence, prevalence at age 65 (age of Medicare enrollment), and survival of patients with HF contributed most to these disparities. The geographic disparities and the recent increase in incidence and decline in survival underscore the importance of HF prevention strategies.
Assuntos
Insuficiência Cardíaca , Medicare , Adulto , Idoso , Insuficiência Cardíaca/epidemiologia , Humanos , Incidência , Pessoa de Meia-Idade , Prevalência , Estados Unidos/epidemiologiaRESUMO
An appropriate animal wound model is urgently needed to assess wound dressings, cell therapies, and pharmaceutical agents. Minipig was selected owing to similarities with humans in body size, weight, and physiological status. Different wound sizes (0.07-100 cm2) were created at varying distances but fail to adequately distinguish the efficacy of various interventions. We aimed to resolve potential drawbacks by developing a systematic wound healing system. No significant variations in dorsal wound closure and contraction were observed within the thoracolumbar region between boundaries of both armpits and the paravertebral region above rib tips; therefore, Lanyu pigs appear suitable for constructing a reliable dorsal wound array. Blood flow signals interfered with inter-wound distances Ë 4 cm; a distance > 4 cm is therefore recommended. Wound sizes ≥ 4 cm × 4 cm allowed optimal differentiation of interventions. Partial- (0.23 cm) and full-thickness (0.6 cm) wounds showed complete re-epithelialization on days 13 and 18 and strongest blood flow signals at days 4 and 11, respectively. Given histological and tensile strength assessments, tissue healing resembling normal skin was observed at least after 6 months. We established some golden standards for minimum wound size and distance between adjacent wounds for effectively differentiating interventions in considering 3R principles.
Assuntos
Modelos Animais , Porco Miniatura , Cicatrização , Animais , Feminino , SuínosRESUMO
Lung epithelial cells and fibroblasts play key roles in pulmonary fibrosis and are involved in fibrotic signaling and production of the extracellular matrix (ECM), respectively. Recently, 3D airway models consisting of both cell types have been developed to evaluate the fibrotic responses while facilitating cell-cell crosstalk. This study aimed to evaluate the fibrotic responses in these models using different fibrogenic agents, which are known as key events in adverse outcome pathways of pulmonary fibrosis. We quantified cell injury and several sequential steps in fibrogenesis, including inflammation, the epithelial-mesenchymal transition (EMT), fibroblast activation, and ECM accumulation, using two different 3D airway models, the EpiAirway™-full thickness (Epi/FT) and MucilAir™-human fibroblast (Mucil/HF) models. In the Epi/FT model, fibrogenic agents induced the expression of inflammation and EMT-associated markers, while in the Mucil/HF model, they induced fibroblast activation and ECM accumulation. Using this information, we conducted gene ontology term network analysis. In the Epi/FT model, the terms associated with cell migration and response to stimulus made up a large part of the network. In the Mucil/HF model, the terms associated with ECM organization and cell differentiation and proliferation constituted a great part of the network. Collectively, our data suggest that polyhexamethyleneguanidine phosphate and bleomycin induce different responses in the two 3D airway models. While Epi/FT was associated with inflammatory/EMT-associated responses, Mucil/HF was associated with fibroblast-associated responses. This study will provide an important basis for selecting proper 3D airway models and fibrogenic agents to further research or screen chemicals causing inhalation toxicity.
Assuntos
Técnicas de Cultura de Células em Três Dimensões/métodos , Células Epiteliais/fisiologia , Fibroblastos/fisiologia , Fibrose/induzido quimicamente , Sistema Respiratório/citologia , Antineoplásicos/toxicidade , Biomarcadores , Bleomicina/toxicidade , Citocinas/genética , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Guanidinas/toxicidade , Humanos , Fator de Crescimento Transformador betaRESUMO
Background: There are substantial geographic disparities in the life expectancy (LE) across the U.S. with myocardial infarction (MI) contributing significantly to the differences between the states with highest (leading) and lowest (lagging) LE. This study aimed to systematically investigate the epidemiology of geographic disparities in MI among older adults. Methods: Data on MI outcomes among adults aged 65+ were derived from the Center for Disease Control and Prevention-sponsored Wide-Ranging Online Data for Epidemiologic Research database and a 5% sample of Medicare Beneficiaries for 2000-2017. Death certificate-based mortality from MI as underlying/multiple cause of death (CBM-UCD/CBM-MCD), incidence-based mortality (IBM), incidence, prevalence, prevalence at age 65, and 1-, 3-, and 5-year survival, and remaining LE at age 65 were estimated and compared between the leading and lagging states. Cox model was used to investigate the effect of residence in the lagging states on MI incidence and survival. Results: Between 2000 and 2017, MI mortality was higher in the lagging than in the leading states (per 100,000, CBM-UCD: 236.7-583.7 vs. 128.2-357.6, CBM-MCD: 322.7-707.7 vs. 182.4-437.7, IBM: 1330.5-1518.9 vs. 1003.3-1197.0). Compared to the leading states, lagging states had higher MI incidence (1.1-2.0% vs. 0.9-1.8%), prevalence (10.2-13.1% vs. 8.3-11.9%), pre-existing prevalence (2.5-5.1% vs. 1.4-3.6%), and lower survival (70.4 vs. 77.2% for 1-year, 63.2 vs. 67.2% for 3-year, and 52.1 vs. 58.7% for 5-year), and lower remaining LE at age 65 among MI patients (years, 8.8-10.9 vs. 9.9-12.8). Cox model results showed that the lagging states had greater risk of MI incidence [Adjusted hazards ratio, AHR (95% Confidence Interval, CI): 1.18 (1.16, 1.19)] and death after MI diagnosis [1.22 (1.21, 1.24)]. Study results also showed alarming declines in survival and remaining LE at age 65 among MI patients. Conclusion: There are substantial geographic disparities in MI outcomes, with lagging states having higher MI mortality, incidence, and prevalence, lower survival and remaining LE at age 65. Disparities in MI mortality in a great extent could be due to between-the-state differences in MI incidence, prevalence at age 65 and survival. Observed declines in survival and remaining LE require an urgent analysis of contributing factors that must be addressed.
RESUMO
The increasing amount of municipal sludge in China requires safe and effective management to protect human health and ensure environmental sustainability. Pyrolysis is a thermochemical process that decomposes organic matter at elevated temperature and under anaerobic conditions, and it has attracted an increasing attention in sludge treatment in the recent years. However, comprehensive environmental and economic assessment of sludge pyrolysis in China's context is rare, due to the small quantities of full-scale sludge pyrolysis plant. In this paper, we applied our design and operation parameters of full-scale sludge pyrolysis plants to generate the material and energy consumptions of the pyrolysis system under various of conditions, including sludge organic content and moisture content, system size, system energy distribution, and whether or not heat substitution is applied. Life cycle assessment and techno-economic assessment were then applied to investigate the environmental and economic performance of the system. Our results demonstrate the significant environmental and economic impacts associated with sludge properties and system size. Generally, sludge with higher organic content and lower moisture content requires less natural gas consumption, which leads to a simultaneous improvement of the system environmental and economic performance. The system economic performance is more sensitive to the system size, and centralized sludge handling using a larger pyrolysis system is more economic favorable. In the most ideal case, the average global warming potential and minimum sludge handling price of sludge pyrolysis could be as low as -32.5 kg CO2-Eq/t DS and 188.8 $/t DS, respectively. Based on these results, we discussed the pathways that could be taken to further optimize the environmental and economic performances of the pyrolysis system.
Assuntos
Pirólise , Esgotos , China , Temperatura Alta , HumanosRESUMO
OBJECTIVE: To establish a risk assessment and prediction system for early osteonecrosis of the femoral head (ONFH) in order to predict the collapse risk. METHODS: The risk assessment system for early necrosis and collapse of femoral head was established based on the combination of Steinberg stage, ABC typing and the proportion of the proximal sclerotic rim. Firstly, Steinberg stage system was applied. ABC typing was applied to predict risk in stage I, type C was risk free, type B was low risk, type A and type BC were medium risk, type A-C and type AB were high risk. The classification of proximal sclerotic rim was first applied when the Steinberg stage was â ¡-â ¢, and type 2 was expected to be low risk. If the classification of proximal sclerotic rimwas type 1, then the ABC typing was applied, type C was risk-free, type B was low risk, type A and type BC were medium risk, type A-C and type AB were high risk. According to this prediction system, the collapse risk of femoral head in 188 cases(301 hips) were predicted by retrospective analysis. All the hips were enrolled at the out-patient department of orthopedic in Guang'anmen Hospital attached to China Academy of Chinese Medical Science. The consistency of the prediction results of three doctors and one doctor at different times were evaluated. RESULTS: Among them, 136 cases were male, 52 were female. 75 cases were single hip, 113 were double hip. The age of the patients wa 19 to 64(42.61±12.07) years. The natural course of disease was 0.33 to 5.00(3.62±1.93) years. 206 hips in 301 hips had collapsed, with a collapse rate of 68.44%. In the risk-free group, none hip had collapsed, with a collapse rate of 0%. In the low-risk group, 9 hip in 91 hips had collapsed, with a collapse rate of 9.89%. In the medium-risk group, 12 hip in 19 hips had collapsed, with a collapse rate of 63.16%. And in the high risk group, 185 hips in 190 hips had collapsed, with a collapse rate of 97.37%. They were significantly differences in their collapse rate (P=0.00) in the following order:high-risk group> medium-risk > low-risk group > risk-free group. The prediction value of the system was high (AUC=0.95, P=0.00). The results predicted by different doctors were consistent (ICC=0.94, P=0.00), and the results predicted by the same doctor at two different times were consistent (Kappa coefficient =0.90, P=0.00). CONCLUSION: The risk assessment and prediction system for early ONFH selects different methods to predict the risk of collapse according to the imaging characteristics of different stages, which is combines with the comprehensive assessment of multiple risk factors. The system is applicable to a wide range, simple operation and convenient for clinical application.
Assuntos
Necrose da Cabeça do Fêmur , Cabeça do Fêmur , Adulto , China , Feminino , Cabeça do Fêmur/diagnóstico por imagem , Necrose da Cabeça do Fêmur/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Self-rated health (SRH) has been frequently used in population health surveys. However, most of these studies only focus on specific factors that might directly affect SRH, so only partial or confounding information about the determinants of SRH is potentially obtained. Conducted in an older Tibetan population in a Chinese plateau area, the aim of our study is to assess interrelationships between various factors affecting SRH based on the conceptual framework for determinants of health. METHODS: Between May 2018 and September 2019, 2707 Tibetans aged 50 years or older were recruited as part of the China Multi-Ethnic Cohort Study (CMEC) from the Chengguan District of Lhasa city in Tibet. The information included SRH and variables based on the conceptual framework for determinants of health (i.e., socioeconomic status, health behaviors, physical health, mental health, and chronic diseases). Structural equation modeling (SEM) was used to estimate the direct and indirect effects of multiple factors in the conceptual framework. RESULTS: Among all participants, 5.54% rated their health excellent, 51.16% very good, 33.58% good, 9.12% fairly poor and 0.59% poor. Physical health (ß = - 0.23, P < 0.001), health behaviors (ß = - 0.44, P < 0.001), socioeconomic status (ß = - 0.29, P < 0.001), chronic diseases (ß = - 0.32, P < 0.001) and gender (ß = 0.19, P < 0.001) were directly associated with SRH. Socioeconomic status, physical health and gender affected SRH both directly and indirectly. In addition, there are potential complete mediator effects in which age and mental health affect SRH through mediators, such as physical health, health behaviors and chronic diseases. CONCLUSIONS: The findings suggested that interventions targeting behavioral changes, health and chronic disease management should be attached to improve SRH among older populations in plateau areas without ignoring gender and socioeconomic disparities.
Assuntos
Comportamentos Relacionados com a Saúde , Nível de Saúde , China/epidemiologia , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , TibetRESUMO
BACKGROUND: After the first COVID-19 case detected on 8 December 2019 in Wuhan, the Provincial Capital of Hubei, the epidemic quickly spread throughout the whole country of China. Low developmental levels are often associated with infectious disease epidemic, this study attempted to test this notion with COVID-19 data. METHODS: Data by province from 8 December 2019 to 16 February 2020 were analysed using regression method. Outcomes were days from the first COVID-19 case in the origin of Hubei Province to the date when case was first detected in a destination province, and cumulative number of confirmed cases. Provincial gross domestic products (GDPs) were used to predict the outcomes while considering spatial distance and population density. RESULTS: Of the total 70 548 COVID-19 cases in all 31 provinces, 58 182 (82.5%) were detected in Hubei and 12 366 (17.5%) in other destination provinces. Regression analysis of data from the 30 provinces indicated that GDP was negatively associated with days of virus spreading (ß=-0.2950, p<0.10) and positively associated with cumulative cases (ß=97.8709, p<0.01) after controlling for spatial distance. The relationships were reversed with ß=0.1287 (p<0.01) for days and ß=-54.3756 (p<0.01) for cumulative cases after weighing in population density and controlling for spatial distance. CONCLUSION: Higher levels of developmental is a risk factor for cross-province spread of COVID-19. This study adds new data to literature regarding the role of economic growth in facilitating spatial spreading of infectious diseases, and provides timely data informing antiepidemic strategies and developmental plan to balance economic growth and people's health.
Assuntos
COVID-19 , Desenvolvimento Econômico , COVID-19/epidemiologia , China/epidemiologia , Desenvolvimento Econômico/estatística & dados numéricos , HumanosRESUMO
INTRODUCTION: Enhanced recovery after surgery (ERAS) protocols are a series of perioperative care to optimize preoperative preparation, prevent postoperative complications, minimize stress, and speedup recovery. Tympanoplasty and mastoidectomy are common surgical procedures for chronic suppurative otitis media. OBJECTIVE: To compare the efficacy and safety between ERAS and conventional recovery after surgery in the perioperative period of chronic suppurative otitis media. METHODS: From April 2018 to February 2019, a total of 84 patients scheduled for tympanoplasty and/or mastoidectomy due to chronic suppurative otitis media were involved and randomly divided into the ERAS group and the control group. The patients' preoperative anxiety, postoperative pain, and comfort level were determined by comparing the results of Self-Rating Anxiety Scale (SAS), Visual Analog Scale (VAS) and General Comfort Questionnaire (GCQ). The postoperative complications, postoperative hospital stay, and hospitalization cost were calculated. RESULTS: The ERAS group showed a lower SAS score (30 [28-31.5] vs 35 [30-43], P < .05], a higher GCQ score (88 [84-100] vs 83 [78.25-92.25], P < .05), and a lower VAS score (0 [0-0] vs 1 [0-2], P < .05] after surgery. No significant difference (P > .05) was observed between the ERAS group and the control group in postoperative complications, postoperative hospitalization time, and hospitalization cost, respectively. CONCLUSION: Enhanced recovery after surgery can reduce pain and improve comfort in the perioperative period of chronic suppurative otitis media.