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1.
Phys Med Biol ; 69(14)2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38964312

RESUMO

Objective.To present a new set of lithium-ion cross-sections for (i) ionization and excitation processes down to 700 eV, and (ii) charge-exchange processes down to 1 keV u-1. To evaluate the impact of the use of these cross-sections on micro a nano dosimetric quantities in the context of boron neutron capture (BNC) applications/techniques.Approach.The Classical Trajectory Monte Carlo method was used to calculate Li ion charge-exchange cross sections in the energy range of 1 keV u-1to 10 MeV u-1. Partial Li ion charge states ionization and excitation cross-sections were calculated using a detailed charge screening factor. The cross-sections were implemented in Geant4-DNA v10.07 and simulations and verified using TOPAS-nBio by calculating stopping power and continuous slowing down approximation (CSDA) range against data from ICRU and SRIM. Further microdosimetric and nanodosimetric calculations were performed to quantify differences against other simulation approaches for low energy Li ions. These calculations were: lineal energy spectra (yf(y) andyd(y)), frequency mean lineal energyyF-, dose mean lineal energyyD-and ionization cluster size distribution analysis. Microdosimetric calculations were compared against a previous MC study that neglected charge-exchange and excitation processes. Nanodosimetric results were compared against pure ionization scaled cross-sections calculations.Main results.Calculated stopping power differences between ICRU and Geant4-DNA decreased from 33.78% to 6.9%. The CSDA range difference decreased from 621% to 34% when compared against SRIM calculations. Geant4-DNA/TOPAS calculated dose mean lineal energy differed by 128% from the previous Monte Carlo. Ionization cluster size frequency distributions for Li ions differed by 76%-344.11% for 21 keV and 2 MeV respectively. With a decrease in theN1within 9% at 10 keV and agreeing after the 100 keV. With the new set of cross-sections being able to better simulate low energy behaviors of Li ions.Significance.This work shows an increase in detail gained from the use of a more complete set of low energy cross-sections which include charge exchange processes. Significant differences to previous simulation results were found at the microdosimetric and nanodosimetric scales that suggest that Li ions cause less ionizations per path length traveled but with more energy deposits. Microdosimetry results suggest that the BNC's contribution to cellular death may be mainly due to alpha particle production when boron-based drugs are distributed in the cellular membrane and beyond and by Li when it is at the cell cytoplasm regions.


Assuntos
Terapia por Captura de Nêutron de Boro , Lítio , Método de Monte Carlo , Radiometria , Lítio/química , Terapia por Captura de Nêutron de Boro/métodos , Nanotecnologia , Elasticidade
2.
West J Emerg Med ; 25(4): 477-482, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39028233

RESUMO

Introduction: Methadone is a medically necessary and lifesaving medication for many patients with opioid use disorder. To adequately address these patients' needs, methadone should be offered in the hospital, but barriers exist that limit its continuation upon discharge. The code of federal regulations allows for methadone dosing as an inpatient as well as outpatient dispensing for up to three days to facilitate linkage to treatment. As a quality initiative, we created a new workflow for discharging patients on methadone to return to the emergency department (ED) for uninterrupted dosing. Methods: Our addiction medicine team changed hospital methadone policy to better allow hospitalization as a window of opportunity to start methadone. This necessitated the creation of a warm-handoff process to link patients to methadone clinics if that linkage could not happen immediately on discharge. Thus, our team created the "ED Bridge" process, which uses the "3-day rule" to dispense methadone from the ED post hospital discharge. We then followed every patient we directed through this workflow as an observational cohort for outcomes and trends. Results: Of the patients for whom ED bridge dosing was planned, 40.4% completed all bridge dosing and an additional 17.3% received at least one but not all bridge doses. Established methadone patients made up 38.1% of successful linkages, and 61.9% were patients who were newly started on methadone in the hospital. Conclusion: Improving methadone as a treatment option remains an ongoing issue for policymakers and advocates. Our ED bridge workflow allows us to expand access and continuation of methadone now using existing laws and regulations, and to better use hospitals as a point of entry into methadone treatment.


Assuntos
Serviço Hospitalar de Emergência , Metadona , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides , Alta do Paciente , Metadona/administração & dosagem , Metadona/uso terapêutico , Humanos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Tratamento de Substituição de Opiáceos/métodos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Masculino , Feminino
3.
Braz J Biol ; 84: e279899, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38896728

RESUMO

It has been demonstrated that Lantana camara possesses several therapeutic properties that can be used to treat various human diseases, including dermatological and gastrointestinal conditions, tetanus, malaria, and tumours. In this investigation, every collected part of L. camara was extracted with absolute methanol to examine its antioxidant capacity using the DPPH assay and its anti-leukemia activity on two AML cell lines, MOLM-13 and MV4-11. In addition, anti-inflammatory effectiveness was evaluated. The results show that extracts from various sections of L. camara have a significant ability to neutralize free radicals, as indicated by their EC50 values. Most of the extracts had values less than 100 µg/ml, with the flower extract having an even lower value of less than 50 µg/ml. Experiments on two AML cell lines showed that the anti-leukemia effects of the extracts were remarkable, with the most potent impact belonging to the root extract (IC50 was 9.78 ± 0.61 and 12.48 ± 1.69 for MOLM-13 and MV4-11 cell lines). The antitumor effect of the extracts was determined to be time- and dose-dependent and did not correlate with antioxidant capacity. Furthermore, when BJ cells were exposed to L. camara root and leaf extracts, their migratory potential was dramatically reduced compared to untreated cells. The extracts demonstrated potential anti-inflammatory capabilities by lowering NO production in LPS-induced BJ cells.


Assuntos
Anti-Inflamatórios , Antioxidantes , Lantana , Extratos Vegetais , Humanos , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Lantana/química , Anti-Inflamatórios/farmacologia , Linhagem Celular Tumoral , Antineoplásicos Fitogênicos/farmacologia
4.
Int J Tuberc Lung Dis ; 28(6): 287-294, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822484

RESUMO

BACKGROUNDGiven the high prevalence of asthma-chronic obstructive pulmonary disease overlap (ACO) in Vietnam, there is an urgent need to establish a simplified strategy for categorising patients as either having asthma or chronic obstructive pulmonary disease (COPD). This classification would streamline the application of treatment recommendations outlined by the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD).METHODSPatients with obstructive lung function were classified as having COPD, asthma, or ACO based on GINA/GOLD guidelines. We hypothesised that ACO-like asthma (ACO-A) would present with positive skin prick tests (SPTs) or early onset of symptoms without a history of tuberculosis (TB), while those with ACO-like COPD (ACO-B) would exhibit negative SPTs and late onset of symptoms and/or a history of TB.RESULTSAmong 235 patients, the prevalence of asthma, ACO-A, ACO-B, and COPD was respectively 21%, 22%, 17%, and 40%. Allergic history, rhinitis, and childhood asthma were associated with ACO-A, while high cumulative smoking was correlated with ACO-B. Socio-economic and demographic parameters, medical history, clinical features, smoking habits, lung function, and para-clinical investigations significantly differed between "all asthma" (i.e., individuals with asthma combined with ACO-A) and "all COPD" (i.e., individuals with COPD combined with ACO-B).CONCLUSIONBased on SPTs, history of TB, and onset age, ACO patients may be defined as people with asthma or COPD..


Assuntos
Asma , Fenótipo , Doença Pulmonar Obstrutiva Crônica , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Prevalência , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Adulto , Asma/epidemiologia , Asma/diagnóstico , Vietnã/epidemiologia , Idoso , Testes Cutâneos , Síndrome de Sobreposição da Doença Pulmonar Obstrutiva Crônica e Asma/epidemiologia , Síndrome de Sobreposição da Doença Pulmonar Obstrutiva Crônica e Asma/diagnóstico
5.
bioRxiv ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38746426

RESUMO

In eukaryotes, the essential process of cellular respiration takes place in the cristae of mitochondria. The protein Mic60 is known to stabilize crista junctions; however, how the C-terminal Mitofilin domain of Mic60 mediates cristae-supported respiration remains elusive. Here, we used ancestral sequence reconstruction to generate Mitofilin ancestors up to and including the last opisthokont common ancestor (LOCA). We found that yeast-lineage derived Mitofilin ancestors as far back as the LOCA rescue respiration. By comparing Mitofilin ancestors with different respiratory phenotypes, we identify four residues that explain the difference between respiration functional yeast- and non-functional animal-derived common Mitofilin ancestors. Our results imply that Mitofilin-supported respiration in yeast stems from a conserved mechanism, and provide a foundation for investigating the divergence of candidate crista junction interactions present during the emergence of eukaryotes.

6.
Toxicol Sci ; 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796678

RESUMO

Addressing human anatomical and physiological variability is a crucial component of human health risk assessment of chemicals. Experts have recommended probabilistic chemical risk assessment paradigms in which distributional adjustment factors are used to account for various sources of uncertainty and variability, including variability in the pharmacokinetic behavior of a given substance in different humans. In practice, convenient assumptions about the distribution forms of adjustment factors and human equivalent doses (HEDs) are often used. Parameters such as tissue volumes and blood flows are likewise often assumed to be lognormally or normally distributed without evaluating empirical data for consistency with these forms. In this work, we performed dosimetric extrapolations using physiologically based pharmacokinetic (PBPK) models for dichloromethane (DCM) and chloroform that incorporate uncertainty and variability to determine if the HEDs associated with such extrapolations are approximately lognormal and how they depend on the underlying distribution shapes chosen to represent model parameters. We accounted for uncertainty and variability in PBPK model parameters by randomly drawing their values from a variety of distribution types. We then performed reverse dosimetry to calculate HEDs based on animal points of departure (PODs) for each set of sampled parameters. Corresponding samples of HEDs were tested to determine the impact of input parameter distributions on their central tendencies, extreme percentiles, and degree of conformance to lognormality. This work demonstrates that the measurable attributes of human variability should be considered more carefully and that generalized assumptions about parameter distribution shapes may lead to inaccurate estimates of extreme percentiles of HEDs.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38748935

RESUMO

OBJECTIVE: Our primary aim was to identify radiomic ultrasound features that can distinguish benign from malignant adnexal masses with solid ultrasound morphology, and primary invasive from metastatic solid ovarian masses, and to develop ultrasound-based machine learning models that include radiomics features to discriminate between benign and malignant solid adnexal masses. Our secondary aim was to compare the diagnostic performance of our radiomics models with that of the ADNEX model and subjective assessment by an experienced ultrasound examiner. METHODS: This is a retrospective observational single center study. Patients with a histological diagnosis of an adnexal tumor with solid morphology at preoperative ultrasound examination performed between 2014 and 2021 were included. The patient cohort was split into training and validation sets with a ratio of 70:30 and with the same proportion of benign and malignant (borderline, primary invasive and metastatic) tumors in the two subsets. The extracted radiomic features belonged to two different families: intensity-based statistical features and textural features. Models to predict malignancy were built based on a random forest classifier, fine-tuned using 5-fold cross-validation over the training set, and tested on the held-out validation set. The variables used in model building were patient's age, and those radiomic features that were statistically significantly different between benign and malignant adnexal masses (Wilcoxon-Mann-Whitney Test with Benjamini-Hochberg correction for multiple comparisons) and assessed as not redundant based on the Pearson correlation coefficient. We describe discriminative ability as area under the receiver operating characteristics curve (AUC) and classification performance as sensitivity and specificity. RESULTS: 326 patients were identified and 775 preoperative ultrasound images were analyzed. 68 radiomic features were extracted, 52 differed statistically significantly between benign and malignant tumors in the training set, and 18 features were selected for inclusion in model building. The same 52 radiomic features differed statistically significantly between benign, primary invasive malignant and metastatic tumors. However, the values of the features manifested overlap between primary malignant and metastatic tumors and did not differ statistically significantly between them. In the validation set, 25/98 tumors (25.5%) were benign, 73/98 (74.5%) were malignant (6 borderline, 57 primary invasive, 10 metastases). In the validation set, a model including only radiomics features had an AUC of 0.80, and 78% sensitivity and 76% specificity at its optimal risk of malignancy cutoff (68% based on Youden's index). The corresponding results for a model including age and radiomics features were 0.79, 86% and 56% (cutoff 60% based on Youden's method), while those of the ADNEX model were 0.88, 99% and 64% (at 20% malignancy cutoff). Subjective assessment had sensitivity 99% and specificity 72%. CONCLUSIONS: Even though our radiomics models had discriminative ability inferior to that of the ADNEX model, our results are promising enough to justify continued development of radiomics analysis of ultrasound images of adnexal masses. This article is protected by copyright. All rights reserved.

8.
Biofabrication ; 16(3)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38776895

RESUMO

Silk fibroin (SF) is a natural protein extracted fromBombyx morisilkworm thread. From its common use in the textile industry, it emerged as a biomaterial with promising biochemical and mechanical properties for applications in the field of tissue engineering and regenerative medicine. In this study, we evaluate for the first time the effects of SF on cardiac bioink formulations containing cardiac spheroids (CSs). First, we evaluate if the SF addition plays a role in the structural and elastic properties of hydrogels containing alginate (Alg) and gelatin (Gel). Then, we test the printability and durability of bioprinted SF-containing hydrogels. Finally, we evaluate whether the addition of SF controls cell viability and function of CSs in Alg-Gel hydrogels. Our findings show that the addition of 1% (w/v) SF to Alg-Gel hydrogels makes them more elastic without affecting cell viability. However, fractional shortening (FS%) of CSs in SF-Alg-Gel hydrogels increases without affecting their contraction frequency, suggesting an improvement in contractile function in the 3D cultures. Altogether, our findings support a promising pathway to bioengineer bioinks containing SF for cardiac applications, with the ability to control mechanical and cellular features in cardiac bioinks.


Assuntos
Alginatos , Elasticidade , Fibroínas , Gelatina , Hidrogéis , Miócitos Cardíacos , Alginatos/química , Alginatos/farmacologia , Fibroínas/química , Fibroínas/farmacologia , Gelatina/química , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Bioimpressão , Sobrevivência Celular/efeitos dos fármacos , Engenharia Tecidual , Tinta , Esferoides Celulares/citologia , Esferoides Celulares/efeitos dos fármacos , Ratos , Contração Miocárdica/efeitos dos fármacos
9.
Pediatr Res ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575694

RESUMO

BACKGROUND: Invasive bacterial infections (IBIs) in febrile infants are rare but potentially devastating. We aimed to derive and validate a predictive model for IBI among febrile infants age 7-60 days. METHODS: Data were abstracted retrospectively from electronic records of 37 emergency departments (EDs) for infants with a measured temperature >=100.4 F who underwent an ED evaluation with blood and urine cultures. Models to predict IBI were developed and validated respectively using a random 80/20 dataset split, including 10-fold cross-validation. We used precision recall curves as the classification metric. RESULTS: Of 4411 eligible infants with a mean age of 37 days, 29% had characteristics that would likely have excluded them from existing risk stratification protocols. There were 196 patients with IBI (4.4%), including 43 (1.0%) with bacterial meningitis. Analytic approaches varied in performance characteristics (precision recall range 0.04-0.29, area under the curve range 0.5-0.84), with the XGBoost model demonstrating the best performance (0.29, 0.84). The five most important variables were serum white blood count, maximum temperature, absolute neutrophil count, absolute band count, and age in days. CONCLUSION: A machine learning model (XGBoost) demonstrated the best performance in predicting a rare outcome among febrile infants, including those excluded from existing algorithms. IMPACT: Several models for the risk stratification of febrile infants have been developed. There is a need for a preferred comprehensive model free from limitations and algorithm exclusions that accurately predicts IBIs. This is the first study to derive an all-inclusive predictive model for febrile infants aged 7-60 days in a community ED sample with IBI as a primary outcome. This machine learning model demonstrates potential for clinical utility in predicting IBI.

10.
Perm J ; 28(1): 42-45, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38192218

RESUMO

Mpox is a viral zoonotic infection endemic to countries in Central and West Africa. The outbreak that began in May 2022 is novel for its global spread and transmission through sexual encounters. Research of this outbreak shows a high rate of concurrent sexually transmitted infections (STIs) in patients with mpox, highlighting the need to consider STIs in mpox management, and to raise awareness of historically high levels of STIs caused by inadequacies in sexual health care. It is critical to prioritize sexual health and address health disparities to control current transmission of infections and prevent future outbreaks.


Assuntos
Mpox , Saúde Sexual , Infecções Sexualmente Transmissíveis , Humanos , Infecções Sexualmente Transmissíveis/epidemiologia
11.
Nat Commun ; 15(1): 250, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38177118

RESUMO

Baculoviruses are insect-infecting pathogens with wide applications as biological pesticides, in vitro protein production vehicles and gene therapy tools. Its cylindrical nucleocapsid, which encapsulates and protects the circular double-stranded viral DNA encoding proteins for viral replication and entry, is formed by the highly conserved major capsid protein VP39. The mechanism for VP39 assembly remains unknown. We use electron cryomicroscopy to determine a 3.2 Å helical reconstruction of an infectious nucleocapsid of Autographa californica multiple nucleopolyhedrovirus, revealing how dimers of VP39 assemble into a 14-stranded helical tube. We show that VP39 comprises a distinct protein fold conserved across baculoviruses, which includes a Zinc finger domain and a stabilizing intra-dimer sling. Analysis of sample polymorphism shows that VP39 assembles in several closely-related helical geometries. This VP39 reconstruction reveals general principles for baculoviral nucleocapsid assembly.


Assuntos
Baculoviridae , Nucleocapsídeo , Animais , Baculoviridae/genética , Baculoviridae/metabolismo , Spodoptera , Nucleocapsídeo/genética , Nucleocapsídeo/metabolismo , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Proteínas do Nucleocapsídeo/genética , Proteínas do Nucleocapsídeo/metabolismo
12.
J Invest Dermatol ; 144(1): 116-124.e4, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37478901

RESUMO

Cutibacterium acnes is a commensal bacterium on the skin that is generally well-tolerated, but different strain types have been hypothesized to contribute to the disease acne vulgaris. To understand how some strain types might contribute to skin inflammation, we generated a repository of C. acnes isolates from skin swabs of healthy subjects and subjects with acne and assessed their strain-level identity and capacity to stimulate cytokine release. Phylotype II K-type strains were more frequent on healthy and nonlesional skin of subjects with acne than those isolated from lesions. Phylotype IA-1 C-type strains were increased on lesional skin compared with those on healthy skin. The capacity to induce cytokines from cultured monocyte-derived dendritic cells was opposite to this action on sebocytes and keratinocytes and did not correlate with the strain types associated with the disease. Whole-genome sequencing revealed a linear plasmid in high-inflammatory isolates within similar strain types that had different proinflammatory responses. Single-cell RNA sequencing of mouse skin after intradermal injection showed that strains containing this plasmid induced a higher inflammatory response in dermal fibroblasts. These findings revealed that C. acnes strain type is insufficient to predict inflammation and that carriage of a plasmid could contribute to disease.


Assuntos
Acne Vulgar , Dermatite , Animais , Camundongos , Humanos , Pele/microbiologia , Acne Vulgar/microbiologia , Propionibacterium acnes/genética , Plasmídeos/genética , Inflamação , Citocinas/genética
13.
Br J Soc Psychol ; 63(1): 20-36, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37358078

RESUMO

The present research aimed to examine how perceivers' system-justifying beliefs moderate the way they evaluate high- versus low-status targets on assertiveness and competence. In three experimental studies, we manipulated a target's hierarchical position within his company's organization. Participants rated the target on traits reflecting assertiveness and competence. Their system-justifying beliefs were assessed in an ostensibly unrelated study. Results consistently showed that participants inferred assertiveness from the target's hierarchical position regardless of system justification, whereas the relationship between social status and competence was consistently moderated by system-justifying beliefs: only participants high in system justification ascribed more competence to the high-status target than to the low-status target. These findings are in line with the hypothesis suggesting that inferring competence from high-status positions could rely on the tendency to justify social inequalities, whereas inferring assertiveness would not.


Assuntos
Assertividade , Hierarquia Social , Humanos
14.
Perm J ; 28(1): 81-85, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38073307

RESUMO

Atrial fibrillation (AF) is an arrhythmia characterized by disorganized atrial activity with an associated unevenly irregular ventricular response on an electrocardiogram. It is the most common sustained arrhythmia, with a lifetime risk of 25% in patients older than 40 years old. The incidence of AF increases with age and is associated with an increased risk for heart failure, stroke, adverse cardiac events, and dementia. The 2 main aims of AF treatment include anticoagulation for thromboembolism prophylaxis as well as rate vs rhythm control. The focus of this article will be on the treatment strategies in managing AF. Rate control refers to the use of atrioventricular nodal blocking medications, including beta blockers and calcium channel blockers, to maintain a goal heart rate. Rhythm control, on the other hand, refers to a treatment strategy focused on the use of antiarrhythmic drugs (AAD), cardioversion, and ablation to restore and to maintain a patient in sinus rhythm. Currently, the ideal treatment strategy remains greatly debated. Thus, we hope to compare the risks and benefits of rate to rhythm control to highlight how patients with AF are managed here at Kaiser Permanente Northern California.


Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Humanos , Adulto , Fibrilação Atrial/complicações , Fibrilação Atrial/terapia , Antiarrítmicos/uso terapêutico , Frequência Cardíaca , Cardioversão Elétrica , Insuficiência Cardíaca/induzido quimicamente
15.
Ann Oncol ; 35(2): 183-189, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37992871

RESUMO

BACKGROUND: Predicting relapse and overall survival (OS) in early-stage non-small-cell lung cancer (NSCLC) patients remains challenging. Therefore, we hypothesized that detection of circulating tumor DNA (ctDNA) can identify patients with increased risk of relapse and that integrating radiological tumor volume measurement along with ctDNA detectability improves prediction of outcome. PATIENTS AND METHODS: We analyzed 366 serial plasma samples from 85 patients who underwent surgical resections and assessed ctDNA using a next-generation sequencing liquid biopsy assay, and measured tumor volume using a computed tomography-based three-dimensional annotation. RESULTS: Our results showed that patients with detectable ctDNA at baseline or after treatment and patients who did not clear ctDNA after treatment had a significantly worse clinical outcome. Integrating radiological analysis allowed the stratification in risk groups prognostic of clinical outcome as confirmed in an independent cohort of 32 patients. CONCLUSIONS: Our findings suggest ctDNA and radiological monitoring could be valuable tools for guiding follow-up care and treatment decisions for early-stage NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , DNA Tumoral Circulante , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , DNA Tumoral Circulante/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Carga Tumoral , Mutação , Recidiva , Biomarcadores Tumorais/genética
16.
Aust Vet J ; 102(3): 67-73, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37875328

RESUMO

Classical swine fever virus (CSFV) identification has witnessed significant advancements with the development of rapid reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assays. However, conventional RT-LAMP assays for CSFV diagnosis are hindered by a laborious RNA extraction step. Moreover, the need for thermal incubators and expensive micropipettes has limited their application in field settings. Addressing these challenges, our study presents a groundbreaking solution-an electro-free and point-of-care (POC) tool known as the field-LAMP assay-for the rapid clinical detection of CSFV. By eliminating the RNA extraction requirement, advancing the colorimetric read-out and lyophilized reaction reagents, our field-LAMP assay streamlines the diagnostic process, saving valuable time and effort. This novel approach also overcomes the dependency on electric-dependent thermal incubators and expensive micropipettes, making it practical and accessible for use in the field. The successful development of the field-LAMP assay marks a significant milestone in CSFV detection. This electro-free and POC tool offers several advantages, including its ability to deliver rapid results without compromising accuracy, facilitating prompt response and containment measures.


Assuntos
Vírus da Febre Suína Clássica , Peste Suína Clássica , Doenças dos Suínos , Suínos , Animais , RNA , Sensibilidade e Especificidade , Peste Suína Clássica/diagnóstico , RNA Viral , Doenças dos Suínos/diagnóstico
17.
bioRxiv ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-37986829

RESUMO

Prominin-1 (Prom1) is a five-transmembrane-pass integral membrane protein that associates with curved regions of the plasma membrane. Prom1 interacts with membrane cholesterol and actively remodels the plasma membrane. Membrane bending activity is particularly evident in photoreceptors, where Prom1 loss-of-function mutations cause failure of outer segment homeostasis, leading to cone-rod retinal dystrophy (CRRD). The Tweety Homology (Ttyh) protein family has been proposed to be homologous to Prominin, but it is not known whether Ttyh proteins have an analogous membrane-bending function. Here, we characterize the membrane-bending activity of human Prom1 and Ttyh1 in native bilayer membranes. We find that Prom1 and Ttyh1 both induce formation of extracellular vesicles (EVs) in cultured mammalian cells and that the EVs produced are biophysically similar. Ttyh1 is more abundant in EV membranes than Prom1 and produces EVs with membranes that are more tubulated than Prom1 EVs. We further show that Prom1 interacts more stably with membrane cholesterol than Ttyh1 and that this may contribute to membrane bending inhibition in Prom1 EVs. Intriguingly, a loss-of-function mutation in Prom1 associated with CRRD induces particularly stable cholesterol binding. These experiments provide mechanistic insight into Prominin function in CRRD and suggest that Prom and Ttyh belong to a single family of functionally related membrane-bending, EV-generating proteins.

18.
Clin Ter ; 174(6): 518-524, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38048115

RESUMO

Objective: The impact of establishing a pulmonary embolism response team (PERT) in patients with pulmonary embolism (PE) has been proven in many developed countries. However, the efficacy of a PERT largely depends on expertise and infrastructure. This study explored the benefit of establishing a PERT in developing countries with limited healthcare resources by comparing the outcomes of patients with acute PE before and after PERT establishment at University Medical Center Ho Chi Minh City in Vietnam. Methods: We conducted a single-center observational study from January 1, 2019, to August 1, 2021. All patients with PE confirmed on computed tomography were included. Patients admitted before PERT establishment were treated by cardiologists alone, while those hospitalized after PERT establishment were managed by the PERT. Results: A total of 130 patients were included (pre-PERT estab-lishment: 51 patients; post-PERT establishment: 79 patients). The demographic characteristics, severity of PE, and clinical and laboratory findings were similar between the two groups. The post-PERT establishment group had a lower incidence rate of major and clinically relevant nonmajor bleeding (11.3% vs. 31.4%, p = 0.005) and required more interventional therapies (16.5% vs. 3.9%, p = 0.046) than did the pre-PERT establishment group. The in-hospital mortality rate decreased in the post-PERT establishment group compared with that in the pre-PERT establishment group (8.9% vs. 21.6%, p = 0.041). Conclusions: Involvement of the PERT in PE management was associated with improved outcomes of patients with PE, including reduced bleeding and mortality rates in a resource-constrained hospital.


Assuntos
Países em Desenvolvimento , Embolia Pulmonar , Humanos , Mortalidade Hospitalar , Hospitalização , Hospitais , Embolia Pulmonar/terapia
19.
Phys Rev Lett ; 131(17): 178001, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37955497

RESUMO

We study the effects of irradiating water with 3 MeV protons at high doses by observing the motion of charged polystyrene beads outside the proton beam. By single-particle tracking, we measure a radial velocity of the order of microns per second. Combining electrokinetic theory with simulations of the beam-generated reaction products and their outward diffusion, we find that the bead motion is due to electrophoresis in the electric field induced by the mobility contrast of cations and anions. This work sheds light on the perturbation of biological systems by high-dose radiations and paves the way for the manipulation of colloid or macromolecular dispersions by radiation-induced diffusiophoresis.

20.
Eur Rev Med Pharmacol Sci ; 27(16): 7720-7727, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37667950

RESUMO

OBJECTIVE: This study aimed to determine the rate of salvage chemotherapy and review associated factors in invasive mole patients treated by primary or delayed hysterectomy. PATIENTS AND METHODS: This study was carried out at the Tu Du Hospital, where a total of 189 patients were diagnosed with invasive mole based on histologic examination by hysterectomy between 01/2016 to 12/2020. We used the life table method to estimate the cumulative rate. We applied the Cox proportional hazard model to determine the factors associated with the need for salvage chemotherapy. RESULTS: At 12-month follow-up, 47 patients had required salvage chemotherapy. The incidence was 24.87% (95% CI: 18.88-31.66). Applying the multivariate model, prophylactic chemotherapy (HR = 2.75, 95% Cl: 1.20-6.30) and two weeks postoperative hCG value greater than 1,900 mIU/mL (HR = 4.30, 95% Cl: 2.08-8.87) increased the risk of requiring salvage chemotherapy. Postoperative chemotherapy decreased the risk of requiring salvage chemotherapy (HR = 0.43, 95% Cl: 0.22-0.83). CONCLUSIONS: Hysterectomy can be considered safe and effective in treating invasive mole patients. Although patients were treated by hysterectomy, 24.87% of patients needed salvage chemotherapy to achieve remission. This study affirms the malignant nature of invasive mole, a subtype of gestational trophoblastic neoplasia (GTN). It is not purely a local invasion of molar villi. Postoperative chemotherapy plays an essential role in reducing the risk of requiring salvage chemotherapy.


Assuntos
Mola Hidatiforme Invasiva , Neoplasias Uterinas , Feminino , Gravidez , Humanos , Vietnã , Duodeno , Histerectomia , Neoplasias Uterinas/cirurgia
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