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Intermittent oil-water wetting can have a significant effect on the internal corrosion of steel pipelines. This paper presents a combined experimental and molecular modeling study of several influential factors on the surface properties and corrosion behavior of mild steel in CO2 environments. The influence of different model oils (LVT-200 and Aromatic-200) and select surface-active compounds (myristic acid, cyclohexane butyric acid, and oleic acid) on the corrosion behavior of carbon steel during intermittent oil-water wetting was determined by measuring the corrosion rate after intermittent wetting cycles. The interfacial tension measurements were performed to study the incorporation of the oil phase along with surface-active molecules in the protective layer formed on the specimen surface. Results showed that the interfacial tension for an aromatic oil-water interface is lower than that for an aliphatic oil-water interface. To understand this result, molecular dynamics simulations of oil-water interfaces were performed in the presence of surface-active molecules and different oils to analyze the structure of the layer formed at the interface. The simulations supported the hypothesis that aromatic molecules are less structured at the interface, which results in the incorporation of more water molecules into the protective layer formed at the steel surface, causing a higher corrosion rate. On the other hand, the simulations revealed that myristic acid in an aliphatic oil forms a well-aligned structure at the interface, devoid of any water molecules. This is in agreement with the hypothesis that the linear molecular structure of myristic acid favors the alignment of molecules at an aliphatic oil-water interface, resulting in a lower interfacial tension and more effective corrosion mitigation as compared to the other two nonlinear compounds tested. It is concluded that an important factor controlling the corrosion behavior is the molecular structure of the oil-water interface, which is adopted by the steel surface layer through the Langmuir-Blodgett process.
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Microplastics (MPs) and nanoplastics (NPs) in water pose a global threat to human health and the environment. To develop efficient removal strategies, it is crucial to understand how these particles behave as they aggregate. However, our knowledge of the process of aggregate formation from primary particles of different sizes is limited. In this study, we analyzed the growth kinetics and structures of aggregates formed by polystyrene MPs in mono- and bidisperse systems using in situ microscopy and image analysis. Our findings show that the scaling behavior of aggregate growth remains unaffected by the primary particle size distribution, but it does delay the onset of rapid aggregation. We also performed a structural analysis that reveals the power law dependence of aggregate fractal dimension (df) in both mono- and bidisperse systems, with mean df consistent with diffusion-limited cluster aggregation (DLCA) aggregates. Our results also suggest that the df of aggregates is insensitive to the shape anisotropy. We simulated molecular forces driving aggregation of polystyrene NPs of different sizes under high ionic strength conditions. These conditions represent salt concentration in ocean water and wastewater, where the DLVO theory does not apply. Our simulation results show that the aggregation tendency of the NPs increases with the ionic strength. The increase in the aggregation is caused by the depletion of clusters of ions from the NPs surface.
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Salt-induced colloidal aggregates can significantly influence contaminant fate and transport in natural and engineered systems. These aggregates' fractal dimensions (df), ranging from 1.4 to 2.2, depend on various system variables. However, the quantitative relationship between these variables and df of aggregates has not been fully explored, especially in predicting a wide range of df. Here, we developed a random forest model capable of predicting the complete range of aggregate df using just four simple physical and chemical parameters of the aggregating system as inputs. The model accurately predicts the df of aggregates formed by colloids of different sizes, ranging from nano to micro sizes, after being trained and tested on appropriate data sets. Ionic strength (IS) has the most significant influence on the df of aggregates formed by microsized particles followed by the relative hydrodynamic radius of aggregates (Rh/Rp), particle concentration (Cp), and primary particle radius (Rp). For aggregates formed by both nano- and microsized particles, IS still has a strong influence on the df, with the significance of Rp increasing. All four inputs are negatively correlated with predicting the df of aggregates. The predictions align well with the physical interpretations.
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In this paper, the phototransistor behavior is investigated in the germanium-on-insulator (GeOI)-based junctionless nanowire (JL-NW) transistor under various light conditions. High responsivity and photosensitivity are attributed in the fully depleted regime within the visible and near-infrared bands. The impact of light is also investigated in detail on the electronic and transfer characteristics such as energy bandgap, carrier distribution, electrostatic potential, electric field, and generation and recombination rates. Further, the channel doping and thickness are tuned to optimize the optical responsivity. The significant tunability of responsivity is observed with increasing channel thickness. The device exhibits fast optical switching performance, which is further enhanced at higher input light power. Overall, at the nanoscale dimension, our proposed phototransistor demonstrates better detectivity with a significantly smaller illumination area. Thus, the GeOI-based JL-NW phototransistors can be used for imaging (visible wavelength range) and bioimaging (near-infrared wavelength range) applications in advanced technology nodes.
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COVID-19 vaccine hesitancy is a significant public health concern, particularly among parents who serve as gatekeepers for their child(ren)'s vaccination status. This study adds to the literature by examining COVID-19 vaccine decisions among parents living in a mid-size, lower-income, racially/ethnically diverse, community. Parents of children, < 18 years and enrolled in the public schools system, were invited to complete a questionnaire offered in English, Spanish, and Portuguese. The questionnaire included questions about their child(ren)'s vaccination status, as well as factors which, based on the literature, might impact parents' vaccination decisions. Parents (n = 277) were mostly Hispanic/Latinx, females, with a high school degree/GED as their highest level of education achieved, a mean age of 40 years, and an average of two children < 18 years. Four-fifths (78.6%) of parents reported being vaccinated against COVID-19, but only 40.8% reported having all of their children vaccinated; 14.8% had some of their children get the COVID-19 vaccine, and 44.4% had none of their children get the COVID-19 vaccine. In bivariate associations, parents' vaccination status, parents age, the CDC website as a COVID-19 information source, awareness of age eligibility for the COVID-19 vaccine, parents reporting knowing someone who does not want to vaccinate their child, and parents' perceived social norm score were associated with children's vaccination status. However, when multivariate analyses were conducted, only parents' age and perceived social norms increased parents' odds of choosing to vaccinate their child. These findings have implications for those promoting COVID-19 vaccination among parents in lower-income, diverse communities.
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Drugs are the imperial part of modern society, but along with their therapeutic effects, drugs can also cause adverse effects, which can be mild to morbid. Pharmacovigilance is the process of collection, detection, assessment, monitoring and prevention of adverse drug events in both clinical trials as well as in the post-marketing phase. The recent trends in increasing unknown adverse events, known as signals, have raised the need to develop an ideal system for monitoring and detecting the potential signals timely. The process of signal management comprises of techniques to identify individual case safety reports systematically. Automated signal detection is highly based upon the data mining of the spontaneous reporting system such as reports from health care professional, observational studies, medical literature or from social media. If a signal is not managed properly, it can become an identical risk associated with the drug which can be hazardous for the patient safety and may have fatal outcomes which may impact health care system adversely. Once a signal is detected quantitatively, it can be further processed by the signal management team for the qualitative analysis and further evaluations. The main components of automated signal detection are data extraction, data acquisition, data selection, and data analysis and data evaluation. This system must be developed in the correct format and context, which eventually emphasizes the quality of data collected and leads to the optimal decision-making based upon the scientific evaluation.
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Sistemas de Notificação de Reações Adversas a Medicamentos , Mineração de Dados , Bases de Dados Factuais , Processamento Eletrônico de Dados , Farmacovigilância , HumanosRESUMO
PURPOSE: To characterize diabetic macular edema (DME) incidence in fellow eyes of patients treated for DME in the study eye. METHODS: This post hoc analysis of VISTA/VIVID data evaluated fellow eyes without DME at baseline through Week 100. Diabetic macular edema presence in the fellow eye was inferred by investigator-reported DME adverse events and use of DME treatments. RESULTS: Over 100 weeks, 44.9%, 44.2%, and 42.9% of fellow eyes developed DME in the intravitreal aflibercept injection 2 mg every 4 weeks (n = 245), intravitreal aflibercept injection 2 mg every 8 weeks (n = 258), and laser control (n = 252) groups, respectively. Mean time to DME development in combined treatment groups was â¼6 months. Multivariable regression analysis confirmed patients with shorter diabetes duration (hazard ratio per 10-year decrease, 1.16; 95% confidence interval, 1.03-1.30; P = 0.0160) and thicker baseline study eye central subfield thickness (hazard ratio per 10- µ m increase, 1.01; 95% confidence interval, 1.01-1.02; P = 0.0002) were at higher risk of developing DME in the fellow eye. CONCLUSION: Among patients with DME in one eye at baseline, almost half developed DME in the fellow eye over 2 years. Shorter duration of diabetes and thicker study eye central subfield thickness were predictors of DME development in the fellow eye.
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Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/epidemiologia , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Incidência , Inibidores da Angiogênese , Fotocoagulação a Laser , Fator A de Crescimento do Endotélio Vascular , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Injeções Intravítreas , Proteínas Recombinantes de Fusão/uso terapêuticoRESUMO
PURPOSE: To report the outcomes of the 0.18 mg fluocinolone acetonide insert (FAi) in the treatment of chronic (>6 months) postoperative cystoid macular edema after cataract surgery. METHODS: This was a retrospective consecutive case series of eyes with chronic postoperative cystoid macular edema treated with the FAi. Visual acuity, intraocular pressure, optical coherence tomography metrics, and supplemental therapies were extracted from the charts before and at 3, 6, 12, 18, and 21 months after FAi placement, when available. RESULTS: Nineteen eyes of 13 patients with chronic postoperative cystoid macular edema after cataract surgery underwent FAi placement with an average follow-up of 15.4 months. Ten eyes (52.6%) had a ≥2-line gain in visual acuity. Sixteen eyes (84.2%) had a ≥20% reduction in optical coherence tomography central subfield thickness. Eight eyes (42.1%) had complete resolution of CME. Improvements in central subfield thickness and visual acuity were sustained throughout individual follow-up. Compared with 18 eyes (94.7%) requiring local corticosteroid supplementation before FAi, only six eyes (31.6%) required supplementation after FAi. Similarly, of the 12 eyes (63.2%) that were on corticosteroid drops before FAi, only 3 (15.8%) required drops after FAi. CONCLUSION: Eyes with chronic postoperative cystoid macular edema after cataract surgery treated with the FAi had improved and sustained visual acuity and optical coherence tomography metrics, along with a reduction in supplemental treatment burden.
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Catarata , Edema Macular , Humanos , Fluocinolona Acetonida , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Glucocorticoides , Estudos Retrospectivos , Corpo Vítreo , Tomografia de Coerência ÓpticaRESUMO
With the advent of next-generation sequencing, large-scale initiatives for mining whole genomes and exomes have been employed to better understand global or population-level genetic architecture. India encompasses more than 17% of the world population with extensive genetic diversity, but is under-represented in the global sequencing datasets. This gave us the impetus to perform and analyze the whole genome sequencing of 1029 healthy Indian individuals under the pilot phase of the 'IndiGen' program. We generated a compendium of 55,898,122 single allelic genetic variants from geographically distinct Indian genomes and calculated the allele frequency, allele count, allele number, along with the number of heterozygous or homozygous individuals. In the present study, these variants were systematically annotated using publicly available population databases and can be accessed through a browsable online database named as 'IndiGenomes' http://clingen.igib.res.in/indigen/. The IndiGenomes database will help clinicians and researchers in exploring the genetic component underlying medical conditions. Till date, this is the most comprehensive genetic variant resource for the Indian population and is made freely available for academic utility. The resource has also been accessed extensively by the worldwide community since it's launch.
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Bases de Dados Genéticas , Variação Genética , Genoma Humano , Projeto Genoma Humano , Software , Adulto , Exoma , Feminino , Genética Populacional/estatística & dados numéricos , Humanos , Índia , Internet , Masculino , Anotação de Sequência Molecular , Sequenciamento Completo do GenomaRESUMO
Kojic acid is a fungal secondary metabolite commonly known as a tyrosinase inhibitor, that acts as a skin-whitening agent. Its applications are widely distributed in the area of cosmetics, medicine, food, and chemical synthesis. Renewable resources are the alternative feedstocks that can fulfill the demand for free sugars which are fermented for the production of kojic acid. This review highlights the current progress and importance of bioprocessing of kojic acid from various types of competitive and non-competitive renewable feedstocks. The bioprocessing advancements, secondary metabolic pathway networks, gene clusters and regulations, strain improvement, and process design have also been discussed. The importance of nitrogen sources, amino acids, ions, agitation, and pH has been summarized. Two fungal species Aspergillus flavus and Aspergillus oryzae are found to be extensively studied for kojic acid production due to their versatile substrate utilization and high titer ability. The potential of A. flavus to be a competitive industrial strain for large-scale production of kojic acid has been studied.
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Aspergillus oryzae , Pironas , Pironas/metabolismo , Aspergillus flavus/genética , Aspergillus flavus/metabolismo , Aminoácidos/metabolismo , Aspergillus oryzae/genéticaRESUMO
Rotavirus infection is highly prevalent in children, and the most severe effects are diarrhea and vomiting. It is well accepted that the enteric nervous system (ENS) is activated and plays an important role, but knowledge of how rotavirus activates nerves within ENS and to the vomiting center is lacking. Serotonin is released during rotavirus infection, and antagonists to the serotonin receptor subtype 3 (5-HT3 receptor) can attenuate rotavirus-induced diarrhea. In this study, we used a 5-HT3 receptor knockout (KO) mouse model to investigate the role of this receptor in rotavirus-induced diarrhea, motility, electrolyte secretion, inflammatory response, and vomiting reflex. The number of diarrhea days (P = 0.03) and the number of mice with diarrhea were lower in infected 5-HT3 receptor KO than wild-type pups. In vivo investigation of fluorescein isothiocyanate (FITC)-dextran transit time showed that intestinal motility was lower in the infected 5-HT3 receptor KO compared to wild-type mice (P = 0.0023). Ex vivo Ussing chamber measurements of potential difference across the intestinal epithelia showed no significant difference in electrolyte secretion between the two groups. Immediate early gene cFos expression level showed no difference in activation of the vomiting center in the brain. Cytokine analysis of the intestine indicated a low effect of inflammatory response in rotavirus-infected mice lacking the 5-HT3 receptor. Our findings indicate that the 5-HT3 receptor is involved in rotavirus-induced diarrhea via its effect on intestinal motility and that the vagus nerve signaling to the vomiting center occurs also in the absence of the 5-HT3 receptor. IMPORTANCE The mechanisms underlying rotavirus-induced diarrhea and vomiting are not yet fully understood. To better understand rotavirus pathophysiology, characterization of nerve signaling within the ENS and through vagal efferent nerves to the brain, which have been shown to be of great importance to the disease, is necessary. Serotonin (5-HT), a mediator of both diarrhea and vomiting, has been shown to be released from enterochromaffin cells in response to rotavirus infection and the rotavirus enterotoxin NSP4. Here, we investigated the role of the serotonin receptor 5-HT3, which is known to be involved in the nerve signals that regulate gut motility, intestinal secretion, and signal transduction through the vagus nerve to the brain. We show that the 5-HT3 receptor is involved in rotavirus-induced diarrhea by promoting intestinal motility. The findings shed light on new treatment possibilities for rotavirus diarrhea.
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Diarreia/fisiopatologia , Sistema Nervoso Entérico/fisiopatologia , Motilidade Gastrointestinal/fisiologia , Receptores 5-HT3 de Serotonina/metabolismo , Infecções por Rotavirus/patologia , Vômito/fisiopatologia , Animais , Células Enterocromafins/metabolismo , Motilidade Gastrointestinal/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/virologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores 5-HT3 de Serotonina/genética , Rotavirus/fisiologia , Serotonina/metabolismo , Antagonistas do Receptor 5-HT3 de Serotonina/farmacologiaRESUMO
Asphaltene aggregation is critical to many natural and industrial processes, from groundwater contamination and remediation to petroleum utilization. Despite extensive research in the past few decades, the fundamental process of sulfur-rich asphaltene aggregation still remains not fully understood. In this work, we have investigated the particle-by-particle growth of aggregates formed with sulfur-rich asphaltene by a combined approach of in situ microscopy and molecular simulation. The experimental results show that aggregates assembled from sulfur-rich asphaltene have morphologies with time-dependent structural self-similarity, and their growth rates are aligned with a crossover behavior between classic reaction-limited aggregation and diffusion-limited aggregation. Although the particle size distribution predicted using the Smoluchowski equation deviates from the observations at the initial stage, it provides a reasonable prediction of aggregate size distribution at the later stage, even if the observed cluster coalescence has an important effect on the corresponding cluster size distribution. The simulation results show that aliphatic sulfur exerts nonmonotonic effects on asphaltene nanoaggregate formation depending on the asphaltene molecular structure. Specifically, aliphatic sulfur has a profound effect on the structure of rod-like nanoaggregates, especially when asphaltene molecules have small aromatic cores. Interactions between aliphatic sulfur and the side chain of neighboring molecules account for the repulsive forces that largely explain the polydispersity in the nanoaggregates and corresponding colloidal aggregates. These results can improve our current understanding of the complex process of sulfur-rich asphaltene aggregation and sheds light on designing efficient crude oil utilization and remediation technologies.
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Here, we report a three-step concise and stereoselective synthesis route to one of the most important phytocannabinoids, namely, (-)-cannabidiol (-CBD), from inexpensive and readily available starting material R-(+)-limonene. The synthesis involved the diastereoselective bifunctionalization of limonene, followed by effective elimination leading to the generation of key chiral p-mentha-2,8-dien-1-ol. The chiral p-mentha-2,8-dien-1-ol on coupling with olivetol under silver catalysis provided regiospecific (-)-CBD, contrary to reported ones which gave a mixture. The newly developed approach was further extended to its structural analogues cannabidiorcin and other tail/terpenyl-modified analogues. Moreover, its opposite isomer (+)-cannabidiol was also successfully synthesized from S-(-)-limonene.
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CanabidiolRESUMO
Novel machine learning models (MLMs) using the seasonal indexing approach that captures the variation in air quality caused due to meteorological changes have been used to provide short-term, real-time forecasts of PM2.5 concentration for one of the most polluted air quality control regions (AQCR) in the capital city of Delhi. Two MLMs-multi-linear regression and random forest-have been developed for using time series data for 1-h and 24-h average PM2.5 concentration. Short-term, real-time forecasts have been made using the developed models. Various model performance evaluation indices indicate satisfactory model performance. R2 values for the hourly and daily models varied between 0.95 and 0.72 and between 0.76 and 0.68 for the 1st to 5th h/day, respectively. The lagged values of PM2.5 concentration (persistence) and the hourly and daily indices are the most influential variables for the forecasts for immediate time steps. In contrast, seasonal indices become more important with the forecasting time horizon. The developed models can be used for making short-term, real-time air quality forecasts and issuing a warning when the pollution levels go beyond acceptable limits.
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Monitoramento Ambiental , Previsões , Aprendizado de Máquina , Material Particulado/análise , Estações do AnoRESUMO
A typical clinical symptom of human norovirus infection is projectile vomiting. Although norovirus RNA and viral particles have been detected in vomitus, infectivity has not yet been reported. We detected replication-competent norovirus in 25% of vomit samples with a 13-fold to 714-fold increase in genomic equivalents, confirming infectious norovirus.
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Infecções por Caliciviridae , Norovirus , Humanos , Intestinos , Norovirus/genéticaRESUMO
The plasma membrane of eukaryotic cells is known to be compositionally asymmetric. Certain phospholipids, such as sphingomyelin and phosphatidylcholine species, are predominantly localized in the outer leaflet, while phosphatidylethanolamine and phosphatidylserine species primarily reside in the inner leaflet. While phospholipid asymmetry between the membrane leaflets is well established, there is no consensus about cholesterol distribution between the two leaflets. We have performed a systematic study, via molecular simulations, of how the spatial distribution of cholesterol molecules in different "asymmetric" lipid bilayers are affected by the lipids' backbone, head-type, unsaturation, and chain-length by considering an asymmetric bilayer mimicking the plasma membrane lipids of red blood cells, as well as seventeen other asymmetric bilayers comprising of different lipid types. Our results reveal that the distribution of cholesterol in the leaflets is solely a function of the extent of ordering of the lipids within the leaflets. The ratio of the amount of cholesterol matches the ratio of lipid order in the two leaflets, thus providing a quantitative relationship between the two. These results are understood by the observation that asymmetric bilayers with equimolar amount of lipids in the two leaflets develop tensile and compressive stresses due to differences in the extent of lipid order. These stresses are alleviated by the transfer of cholesterol from the leaflet in compressive stress to the one in tensile stress. These findings are important in understanding the biology of the cell membrane, especially with regard to the composition of the membrane leaflets.
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Colesterol , Bicamadas Lipídicas , Lipídeos de Membrana , Fosfatidilcolinas , FosfolipídeosRESUMO
PURPOSE: To characterize the true position of in-the-bag intraocular lenses (IOLs) relative to the limbus using ultrasound biomicroscopy and estimate scleral-sutured IOL positioning. METHODS: This prospective single-center study included 70 eyes of 41 patients with in-the-bag posterior chamber IOLs. Four vertical ultrasound biomicroscopy captures were performed in each eye in the superior, inferior, nasal, and temporal quadrants. Postoperative biometric data were collected. The primary outcome was the vertical distance of the in-the-bag IOL from the sclerocorneal limbus. Secondary outcomes included anterior shift and refractive change of a theoretical scleral-sutured IOL using sclerotomies at 2.5 mm and 3 mm posterior to the limbus. RESULTS: A total of 265 ultrasound biomicroscopy images were analyzed, including 64 superior, 69 inferior, 66 nasal, and 66 temporal. The true in-the-bag IOL position measured as distance posterior to the sclerocorneal limbus was 4.23 ± 0.56 mm superiorly, 4.22 ± 0.46 mm inferiorly, 3.95 ± 0.48 mm nasally, and 3.86 ± 0.52 mm temporally. The anterior shift of a theoretical scleral-sutured IOL was 0.60 mm for a 3-mm sclerotomy and 0.93 mm for a 2.5-mm sclerotomy, resulting in a theoretical myopic shift of 0.45 diopter (D) and 0.79 D, respectively, assuming a 15-D IOL. Larger biometric measurements correlated with a more posterior in-the-bag position. CONCLUSION: True in-the-bag IOL position was found to be more posterior than estimates of scleral-sutured IOLs. Additional corrections in scleral-sutured IOL calculations may improve refractive outcomes.
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Implante de Lente Intraocular/métodos , Lentes Intraoculares , Miopia/cirurgia , Refração Ocular/fisiologia , Esclera/cirurgia , Técnicas de Sutura , Idoso , Feminino , Seguimentos , Humanos , Limbo da Córnea/cirurgia , Masculino , Microscopia Acústica , Miopia/diagnóstico , Miopia/fisiopatologia , Estudos Prospectivos , Desenho de Prótese , Acuidade VisualRESUMO
The provision of sanitation services for fast-growing urban populations is one of the world's urgent challenges. Hutong neighborhoods in Beijing, capital of China, cannot be rebuilt due to the protection of historical heritage, while residents still need to keep the habit of defecating in public toilets. One hundred public toilets with non-sewered sanitation in the Hutong neighborhoods of Beijing were visited to investigate the actual operating status in response to the "toilet revolution" campaign. The fault tree approach was used to identify the barriers toward a decent and environment-friendly public toilet and evaluate potential risks from the malfunction of various components. Four subsystems are defined and elaborated to calculate the fault possibility. These subsystems are environment- and user-friendly, regarded as ancillary facilities, and used for fecal sludge (FS) management. Statistical analysis of targeted cases indicated that fault probabilities of environmental considerations, user-friendly considerations, ancillary facilities, FS management are calculated as 0.79, 0.96, 0.96, and 0, respectively. The subsystems were weighted using a Delphi method concept. Results showed that the well operation ratio of Beijing Hutong public toilets is only 32%, and the sanitation service value chain can be further optimized. This study also provides references for other countries, which are dedicated to promoting urban sanitation and public health.
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Aparelho Sanitário , Pequim , China , Humanos , Saneamento , BanheirosRESUMO
Necessity to develop the efficient targeted delivery of highly potent immunosuppressant for IBD in order to avoid surgical procedure, led to fabrication and evaluation of its anti-inflammatory potential. Previously formulated cyclosporine A (Cyp A) into enteric coated capsules was further evaluated for its site-specificity in the treatment of TNBS induced colitis. Contact angle measurement studies showed excellent spreadability of the developed formulation over the hydrophilic biological tissue substrate. HET-CAM study demonstrates that the formulation prepared is nonirritant to the highly vascular tissues and hence can be used for the immunological sensitive tissues like inflamed intestine in IBD. Further the developed formulation has been characterized for site specificity to distal parts of intestine by pharmacokinetic studies. The appearance of drug in systemic circulation at approximately 5 hours in New Zealand strain of rabbits confirms drug delivery at distal parts of intestine. Significant reduced levels of TNF-α, IL-6 and IL-10 in drug treated animals signifies inhibition of inflammatory reactions at the TNBS treated site. Simultaneously, the change in body weight of same group of animals was observed for 15 days. Results showed a marginal recovery of body weight in Cyp A treated TNBS induced colitis animals. In conclusion, all in vitro and in vivo results confirm the successful site specific delivery and anti-inflammatory efficacy of developed formulation of Cyp A in TNBS induced colitis in New Zealand rabbits.
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Colite , Ciclosporina , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Modelos Animais de Doenças , Coelhos , Ácido Trinitrobenzenossulfônico/uso terapêutico , Fator de Necrose Tumoral alfa/química , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
Human adenovirus 41 (HAdV-41) causes acute gastroenteritis in young children. The main characteristics of HAdV-41 infection are diarrhea and vomiting. Nevertheless, the precise mechanism of HAdV-41-induced diarrhea is unknown, as a suitable small-animal model has not been described. In this study, we used the human midgut carcinoid cell line GOT1 to investigate the effect of HAdV-41 infection and the individual HAdV-41 capsid proteins on serotonin release by enterochromaffin cells and on enteric glia cell (EGC) activation. We first determined that HAdV-41 could infect the enterochromaffin cells. Immunofluorescence staining revealed that the cells expressed HAdV-41-specific coxsackievirus and adenovirus receptor (CAR); flow cytometry analysis supported these findings. HAdV-41 infection of the enterochromaffin cells induced serotonin secretion dose dependently. In contrast, control infection with HAdV-5 did not induce serotonin secretion in the cells. Confocal microscopy studies of enterochromaffin cells infected with HAdV-41 revealed decreased serotonin immunofluorescence compared to that in uninfected cells. Incubation of the enterochromaffin cells with purified HAdV-41 short fiber knob and hexon proteins increased the serotonin levels in the harvested cell supernatant significantly. HAdV-41 infection could also activate EGCs, as shown in the significantly altered expression of glia fibrillary acidic protein (GFAP) in EGCs incubated with HAdV-41. The EGCs were also activated by serotonin alone, as shown in the significantly increased GFAP staining intensity. Likewise, EGCs were activated by the cell supernatant of HAdV-41-infected enterochromaffin cells.IMPORTANCE The nonenveloped human adenovirus 41 causes diarrhea, vomiting, dehydration, and low-grade fever mainly in children under 2 years of age. Even though acute gastroenteritis is well described, how human adenovirus 41 causes diarrhea is unknown. In our study, we analyzed the effect of human adenovirus 41 infection on human enterochromaffin cells and found it stimulates serotonin secretion in the cells, which is involved in regulation of intestinal secretion and gut motility and can also activate enteric glia cells, which are found in close proximity to enterochromaffin cells in vivo This disruption of gut barrier homeostasis as maintained by these cells following human adenovirus 41 infection might be a mechanism in enteric adenovirus pathogenesis in humans and could indicate a possible serotonin-dependent cross talk between human adenovirus 41, enterochromaffin cells, and enteric glia cells.