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1.
J Nucl Med Technol ; 52(2): 115-120, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839114

RESUMO

Brown fat can present challenges in patients with cancer who undergo 18F-FDG PET scans. Uptake of 18F-FDG by brown fat can obscure or appear similar to active oncologic lesions, causing clinical challenges in PET interpretation. Small, retrospective studies have reported environmental and pharmacologic interventions for suppressing brown fat uptake on PET; however, there is no clear consensus on best practices. We sought to characterize practice patterns for strategies to mitigate brown fat uptake of 18F-FDG during PET scanning. Methods: A survey was developed and distributed via e-mail LISTSERV to members of the Children's Oncology Group diagnostic imaging committee, the Society for Nuclear Medicine and Molecular Imaging pediatric imaging council, and the Society of Chiefs of Radiology at Children's Hospitals between April 2022 and February 2023. Responses were stored anonymously in REDCap, aggregated, and summarized using descriptive statistics. Results: Fifty-five complete responses were submitted: 51 (93%) faculty and fellow-level physicians, 2 (4%) technologists, and 2 (4%) respondents not reporting their rank. There were 43 unique institutions represented, including 5 (12%) outside the United States. Thirty-eight of 41 (93%) institutions that responded on environmental interventions reported using warm blankets in the infusion and scanning rooms. Less than a third (n = 13, 30%) of institutions reported use of a pharmacologic intervention, with propranolol (n = 5, 38%) being most common, followed by fentanyl (n = 4, 31%), diazepam (n = 2, 15%), and diazepam plus propranolol (n = 2, 15%). Selection criteria for pharmacologic intervention varied, with the most common criterion being brown fat uptake on a prior scan (n = 6, 45%). Conclusion: Clinical practices to mitigate brown fat uptake on pediatric 18F-FDG PET vary widely. Simple environmental interventions including warm blankets or increasing the temperature of the injection and scanning rooms were not universally reported. Less than a third of institutions use pharmacologic agents for brown fat mitigation.


Assuntos
Tecido Adiposo Marrom , Fluordesoxiglucose F18 , Hospitais Pediátricos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/metabolismo , Inquéritos e Questionários , Internacionalidade , Transporte Biológico , Criança
2.
Drug Metab Dispos ; 52(7): 582-596, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38697852

RESUMO

The International Consortium for Innovation and Quality in Pharmaceutical Development Transporter Working Group had a rare opportunity to analyze a crosspharma collation of in vitro data and assay methods for the evaluation of drug transporter substrate and inhibitor potential. Experiments were generally performed in accordance with regulatory guidelines. Discrepancies, such as not considering the impact of preincubation for inhibition and free or measured in vitro drug concentrations, may be due to the retrospective nature of the dataset and analysis. Lipophilicity was a frequent indicator of crosstransport inhibition (P-gp, BCRP, OATP1B, and OCT1), with high molecular weight (MW ≥500 Da) also common for OATP1B and BCRP inhibitors. A high level of overlap in in vitro inhibition across transporters was identified for BCRP, OATP1B1, and MATE1, suggesting that prediction of DDIs for these transporters will be common. In contrast, inhibition of OAT1 did not coincide with inhibition of any other transporter. Neutrals, bases, and compounds with intermediate-high lipophilicity tended to be P-gp and/or BCRP substrates, whereas compounds with MW <500 Da tended to be OAT3 substrates. Interestingly, the majority of in vitro inhibitors were not reported to be followed up with a clinical study by the submitting company, whereas those compounds identified as substrates generally were. Approaches to metabolite testing were generally found to be similar to parent testing, with metabolites generally being equally or less potent than parent compounds. However, examples where metabolites inhibited transporters in vitro were identified, supporting the regulatory requirement for in vitro testing of metabolites to enable integrated clinical DDI risk assessment. SIGNIFICANCE STATEMENT: A diverse dataset showed that transporter inhibition often correlated with lipophilicity and molecular weight (>500 Da). Overlapping transporter inhibition was identified, particularly that inhibition of BCRP, OATP1B1, and MATE1 was frequent if the compound inhibited other transporters. In contrast, inhibition of OAT1 did not correlate with the other drug transporters tested.


Assuntos
Indústria Farmacêutica , Proteínas de Membrana Transportadoras , Humanos , Indústria Farmacêutica/métodos , Proteínas de Membrana Transportadoras/metabolismo , Desenvolvimento de Medicamentos/métodos , Interações Medicamentosas/fisiologia , Preparações Farmacêuticas/metabolismo , Transporte Biológico/fisiologia , Inquéritos e Questionários , Animais
3.
Curr Protoc ; 4(4): e1021, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38619090

RESUMO

Intracellular bacterial pathogens implement a diverse array of strategies to target host cells and establish infection. For vacuolar pathogens, the process of pathogen-containing vacuole movement within host cells, termed intracellular trafficking, is central to both pathogen survival and infection progression. Typically a process mediated by secreted virulence factors that manipulate the host cytoskeletal machinery, internalized pathogen-containing vacuoles traffic to the site of replication to establish a unique replicative niche, and if applicable, traffic back toward the host cell periphery for cell-to-cell spread. As such, the intracellular positioning of pathogen-containing vacuoles represents a fundamental measure of infection progression. Here, we describe a fluorescence microscopy-based method to quantitatively assess bacterial intracellular positioning, using Salmonella enterica serovar Typhimurium infection of epithelial cells as a model. This experimental approach can be modified to study infection in diverse host cell types, and with a broad array of pathogens. The system can also be adapted to examine the kinetics of infection, identify secreted virulence factors that mediate host trafficking, investigate host factors that are targeted by the pathogen for trafficking, and assess functional domains within a virulence factor responsible for mediating the phenotype. Collectively, these tools can provide fundamental insight into the pathogenesis of a diverse array of intracellular bacterial pathogens, and new host factors that are hijacked to mediate infection. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Culture and preparation of host cells Alternate Protocol: Culture and preparation of host cells to assess host factor contribution to bacterial positioning Basic Protocol 2: Infection of epithelial cells with S. Typhimurium Basic Protocol 3: Fluorescence staining for analysis of bacterial positioning Basic Protocol 4: Fluorescence microscopy analysis of bacterial positioning.


Assuntos
Citoesqueleto , Vacúolos , Transporte Biológico , Células Epiteliais , Fatores de Virulência
4.
Biotechnol J ; 19(2): e2300390, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38375564

RESUMO

Organ-on-a-chip technology has shown great potential in disease modeling and drug evaluation. However, traditional organ-on-a-chip devices are mostly pump-dependent with low throughput, which makes it difficult to leverage their advantages. In this study, we have developed a generic, pump-free organ-on-a-chip platform consisting of a 32-unit chip and an adjustable rocker, facilitating high-throughput dynamic cell culture with straightforward operation. By utilizing the rocker to induce periodic fluid forces, we can achieve fluidic conditions similar to those obtained with traditional pump-based systems. Through constructing a gut-on-a-chip model, we observed remarkable enhancements in the expression of barrier-associated proteins and the spatial distribution of differentiated intestinal cells compared to static culture. Furthermore, RNA sequencing analysis unveiled enriched pathways associated with cell proliferation, lipid transport, and drug metabolism, indicating the ability of the platform to mimic critical physiological processes. Additionally, we tested seven drugs that represent a range of high, medium, and low in vivo permeability using this model and found a strong correlation between their Papp values and human Fa, demonstrating the capability of this model for drug absorption evaluation. Our findings highlight the potential of this pump-free organ-on-a-chip platform as a valuable tool for advancing drug development and enabling personalized medicine.


Assuntos
Dispositivos Lab-On-A-Chip , Sistemas Microfisiológicos , Humanos , Técnicas de Cultura de Células , Intestinos , Transporte Biológico
5.
PLoS One ; 19(2): e0298825, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38377073

RESUMO

COVID-19 vaccination has significantly decreased morbidity, hospitalizations, and death during the pandemic. However, disparities in vaccination uptake threatens to stymie the progress made in safeguarding the health of Americans. Using a nationally representative adult (≥18 years old) sample from the 2021 Medical Expenditure Panel Survey (MEPS), we aimed to explore disparities in COVID-19 vaccine and booster uptake by income levels. To reflect the nature of the survey, a weighted logistic regression analysis was used to explore factors associated with COVID-19 vaccine and booster uptake. A total of 241,645,704 (unweighted n = 21,554) adults were included in the analysis. Average (SD) age of the population was 49 (18) years old, and 51% were female. There were disparities in COVID-19 vaccine and booster uptake by income groups. All other income groups were less likely to receive COVID-19 vaccines and booster shot than those in the high-income group. Those in the poor income group had 55% lower odds of being vaccinated for COVID-19 (aOR = 0.45, p<0.01). Considering the female population only, women with lower incomes may have greater disparities in access to COVID-19 vaccines than do males with lower incomes. Disparities in COVID-19 vaccination by income may have even greater implications as the updated vaccines are rolled out in the US without the government covering the cost as before.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Masculino , Feminino , Humanos , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Adolescente , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Transversais , Gastos em Saúde , Transporte Biológico , Vacinação
6.
Sensors (Basel) ; 24(2)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38257579

RESUMO

Surgery is a common first-line treatment for many types of disease, including cancer. Mortality rates after general elective surgery have seen significant decreases whilst postoperative complications remain a frequent occurrence. Preoperative assessment tools are used to support patient risk stratification but do not always provide a precise and accessible assessment. Wearable sensors (WS) provide an accessible alternative that offers continuous monitoring in a non-clinical setting. They have shown consistent uptake across the perioperative period but there has been no review of WS as a preoperative assessment tool. This paper reviews the developments in WS research that have application to the preoperative period. Accelerometers were consistently employed as sensors in research and were frequently combined with photoplethysmography or electrocardiography sensors. Pre-processing methods were discussed and missing data was a common theme; this was dealt with in several ways, commonly by employing an extraction threshold or using imputation techniques. Research rarely processed raw data; commercial devices that employ internal proprietary algorithms with pre-calculated heart rate and step count were most commonly employed limiting further feature extraction. A range of machine learning models were used to predict outcomes including support vector machines, random forests and regression models. No individual model clearly outperformed others. Deep learning proved successful for predicting exercise testing outcomes but only within large sample-size studies. This review outlines the challenges of WS and provides recommendations for future research to develop WS as a viable preoperative assessment tool.


Assuntos
Algoritmos , Dispositivos Eletrônicos Vestíveis , Humanos , Transporte Biológico , Eletrocardiografia , Teste de Esforço
7.
J Subst Use Addict Treat ; 156: 209212, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37935350

RESUMO

INTRODUCTION: Medications for opioid use disorder (MOUD) are the most effective treatment for opioid use disorder (OUD) but remain underutilized. To reduce barriers to MOUD prescribing and increase treatment access, New Jersey's Medicaid program implemented the Office-Based Addiction Treatment (OBAT) Program in 2019, which increased reimbursement for office-based buprenorphine prescribing and established newly reimbursable patient navigation services in OBAT clinics. Using a mixed-methods design, this study aimed to describe stakeholder experiences with the OBAT program and to assess implementation and uptake of the program. METHODS: This study used a concurrent, triangulated mixed-methods design, which integrated complementary qualitative (semi-structured interviews) and quantitative (Medicaid claims) data to gain an in-depth understanding of the implementation of the OBAT program. We elicited stakeholder perspectives through interviews with 22 NJ Medicaid MOUD providers and 8 policy key informants, and examined trends in OBAT program utilization using 2019-2020 NJ Medicaid claims for 5380 Medicaid enrollees who used OBAT services. We used cross-case analysis (provider interviews) and a case study approach (key informant interviews) in analyzing qualitative data, and calculated descriptive statistics and trends for quantitative data. RESULTS: Provider enrollment and utilization of OBAT services increased steadily during the first two years of program implementation. Interviewees reported that enhanced reimbursements for office-based MOUD incentivized greater MOUD prescribing, while coverage of patient navigation services improved patient care. Despite increasing enrollment in the OBAT program, the proportion of primary care physicians in the state who enrolled in the program remained limited. Key barriers to enrollment included: requirements for a patient navigator; concerns about administrative burdens and reimbursement delays from Medicaid; lack of awareness of the program; and beliefs that patients with OUD were better served in comprehensive care settings. Patient navigation was highlighted as a critical and valuable element of the program, but navigator enrollment and reimbursement challenges may have prevented greater uptake of this service. CONCLUSIONS: Implementation of an OBAT model that enhanced reimbursement and provided coverage for patient navigation likely expanded access to MOUD in NJ. Results support initiatives like the OBAT program in improving access to MOUD, but program adaptations, where feasible, could improve uptake and utilization.


Assuntos
Comportamento Aditivo , Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Estados Unidos , Humanos , Medicaid , Transporte Biológico , Buprenorfina/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico
8.
JAMA Health Forum ; 4(12): e234335, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38153810

RESUMO

This cross-sectional study uses Traditional Medicare and Medicare Advantage claims data to evaluate uptake of biosimilars relative to their reference products.


Assuntos
Medicamentos Biossimilares , Medicare Part C , Estados Unidos , Transporte Biológico
9.
Environ Sci Pollut Res Int ; 30(57): 120576-120589, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37945947

RESUMO

A promising approach forfacilitating China's shift towards renewable energy sources entails combining digital finance and green financing. The present research investigates the supply chains and reverse logistics of significant financial indices, including the S&P Green Bond Index, the MSCI Global Markets Index, and the S&P Global Renewable Energy Index. The analysis encompasses the period from the creation of these indices on September 28, 2008, through January 12, 2022. To minimize risk, portfolios have increasingly adopted diverse indices, such as the S&P Global Clean Energy Index and the S&P Green Bond Index. This study investigates the intricate relationship between green financing and digital finance, shedding light on their combined impact on the uptake of renewable energy in China. This study examines the role of digital financial technologies, including blockchain, mobile payment systems, and big data analytics, in enhancing the accessibility of green financing choices for renewable energy projects. A comprehensive analysis of existing literature and empirical research is conducted to achieve this objective. The results emphasize the significant progress in improving financial inclusion, risk management, and transparency by integrating green financing and digital finance. As mentioned earlier, the enhancements have significantly enhanced the level of trust and assurance among investors operating within the renewable energy industry. Moreover, the report highlights the crucial need for continuous governmental backing and financial investments in digital financial infrastructure to drive China towards a more environmentally friendly and sustainable energy framework.


Assuntos
Governo , Energia Renovável , China , Transporte Biológico , Pesquisa Empírica , Desenvolvimento Econômico
10.
J Vis Exp ; (201)2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37982512

RESUMO

The pancreatic islets of Langerhans, which are small 3D collections of specialized endocrine and supporting cells interspersed throughout the pancreas, have a central role in the control of glucose homeostasis through the secretion of insulin by beta cells, which lowers blood glucose, and glucagon by alpha cells, which raises blood glucose. Intracellular signaling pathways, including those mediated by cAMP, are key for regulated alpha and beta cell hormone secretion. The 3D islet structure, while essential for coordinated islet function, presents experimental challenges for mechanistic studies of the intracellular signaling pathways in primary human islet cells. To overcome these challenges and limitations, this protocol describes an integrated live-cell imaging and microfluidic platform using primary human pseudoislets generated from donors without diabetes that resemble native islets in their morphology, composition, and function. These pseudoislets are size-controlled through the dispersion and reaggregation process of primary human islet cells. In the dispersed state, islet cell gene expression can be manipulated; for example, biosensors such as the genetically encoded cAMP biosensor, cADDis, can be introduced. Once formed, pseudoislets expressing a genetically encoded biosensor, in combination with confocal microscopy and a microperifusion platform, allow for the synchronous assessment of fluorescent biosensor dynamics and alpha and beta cell hormone secretory profiles to provide more insight into cellular processes and function.


Assuntos
Células Secretoras de Insulina , Ilhotas Pancreáticas , Humanos , Glicemia , Transporte Biológico , Insulina , Corantes
11.
PLoS One ; 18(10): e0289541, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37796981

RESUMO

Understanding factors that influence those who are initially COVID-19 vaccine hesitant to accept vaccination is valuable for the development of vaccine promotion strategies. Using Ipsos KnowledgePanel®, we conducted a national survey of adults aged 18 and older in the United States. We created a questionnaire to examine factors associated with COVID-19 vaccine uptake over a longitudinal period ("Wave 1" in April 2021 and "Wave 2" in February 2022), and utilized weighted data provided by Ipsos to make the data nationally representative. Overall, 1189 individuals participated in the Wave 1 survey, and 843 participants completed the Wave 2 survey (71.6% retention rate). Those who intended to be vaccinated as soon as possible ("ASAP") were overwhelmingly vaccinated by Wave 2 (96%, 95% CI: 92% to 100%). Of those who initially wished to delay vaccination until there was more experience with it ("Wait and See"), 57% (95% CI: 47% to 67%) were vaccinated at Wave 2. Within the "Wait and See" cohort, those with income <$50,000 and those who had never received the influenza vaccine were significantly less likely to be vaccinated at Wave 2. Among those who initially indicated that they would not receive a COVID-19 vaccine ("Non-Acceptors"), 28% (95% CI: 21% to 36%) were vaccinated at Wave 2. Those who believed COVID-19 was not a major problem in their community were significantly less likely to be vaccinated, while those with more favorable attitudes toward vaccines in general and public health strategies to decrease the impact of COVID-19 were significantly more likely to be vaccinated. Overall, barriers to vaccine uptake for the "Wait and See" cohort appear to be more practical, whereas barriers for the "Non-Acceptor" cohort seem to be more ideological. These findings will help target interventions to improve uptake of COVID-19 boosters and future novel vaccines.


Assuntos
COVID-19 , Vacinas contra Influenza , Adulto , Humanos , Vacinas contra COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Transporte Biológico , Vacinação
12.
PLoS One ; 18(9): e0279214, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37682898

RESUMO

BACKGROUND: Autism is a normal part of cognitive diversity, resulting in communication and sensory processing differences, which can become disabling in a neurotypical world. Autistic people have an increased likelihood of physical and mental co-occurring conditions and die earlier than neurotypical peers. Inaccessible healthcare may contribute to this. Autism Health Passports (AHPs) are paper-based or digital tools which can be used to describe healthcare accessibility needs; they are recommended in UK clinical guidance. However, questions remained as to the theoretical underpinnings and effectiveness of AHPs. METHODS: We undertook a systematic literature search identifying studies focused on AHPs for adults (aged over 16 years) from five databases. Included literature was subjected to realist evaluation. Data were extracted using a standardised form, developed by the research team, which considered research design, study quality for realist review and the Context, Mechanisms and Outcomes (CMOs) associated with each AHP tool. FINDINGS: 162 unique records were identified, and 13 items were included in the review. Only one item was considered high quality. Contextual factors focused on the inaccessibility of healthcare to Autistic patients and staff lack of confidence and training in supporting Autistic needs. Interventions were heterogeneous, with most sources reporting few details as to how they had been developed. The most frequently included contents were communication preferences. Mechanisms were often not stated or were inferred by the reviewers and lacked specificity. Outcomes were included in four studies and were primarily focused on AHP uptake, rather than Outcomes which measured impact. CONCLUSION: There is insufficient evidence to conclude that AHPs reduce the health inequalities experienced by Autistic people. Using an AHP tool alone in a healthcare Context that does not meet Autistic needs, without the inclusion of the local Autistic community developing the tool, and a wider intervention to reduce known barriers to health inequality, may mean that AHPs do not trigger any Mechanisms, and thus cannot affect Outcomes.


Assuntos
Transtorno Autístico , Adulto , Idoso , Humanos , Transporte Biológico , Comunicação , Bases de Dados Factuais , Disparidades nos Níveis de Saúde
13.
PLoS One ; 18(9): e0292054, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37733812

RESUMO

BACKGROUND: Maternal mortality continues to be a pressing concern in global health, presenting an enduring and unmet challenge for healthcare systems worldwide. Utilization of institutional delivery services has been established as a proven intervention to mitigate life-threatening risks for both mothers and newborns. Exploring the determinants of institutional delivery is crucial to improve and enhance maternal and newborn safety. This study aimed to assess the contextual and individual factors associated with institutional delivery in Nepal. METHODS: This study utilized that data form Nepal Multiple Indicator Survey 2019, which included a sample of 1,932 women who had given birth within the two years prior to the survey. A multilevel logistic regression analysis was performed to determine the significant external environment, contextual and individual predictors of institutional delivery. RESULTS: The women from Madhesh province [Adjusted Odds Ratio (aOR): 0.32, 95% Confidence Interval (CI): 0.17-0.61], as compared to Bagmati province, women from rural areas (aOR: 0.55, 95% CI: 0.39-0.78) as compared to urban areas, and women from a relatively less-advantaged ethnic groups (aOR: 0.52, 95% CI: 0.35-0.76) as compared to the relatively advantaged ethnic groups were less likely to deliver in health institutions. Similarly, women from the poorest (aOR: 0.09, 95% CI: 0.04-0.22) and second wealth groups (aOR: 0.29, 95% CI: 0.13-0.64) were less likely to attend institute for delivery compared to women from the richest household. Women with formal education (aOR: 1.65, 95% CI: 1.16-2.35) were more likely to deliver in an institution over uneducated women. Moreover, the uptake of institutional delivery increased by 59% (aOR: 1.59, 95% CI: 1.43-1.75) for each additional ANC visit. CONCLUSION: The findings highlight the importance of stepping up efforts to achieve universal health care from the standpoint of long-term government investment, focusing particularly on illiterate women in rural areas, poorer households, and socially disadvantaged groups. Expanding the benefits of maternal benefit schemes targeting the women from the poorest households in the communities is recommended.


Assuntos
Academias e Institutos , Etnicidade , Recém-Nascido , Humanos , Feminino , Nepal , Transporte Biológico , Mães
14.
BMJ Open Ophthalmol ; 8(Suppl 2): A17-A18, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37604539

RESUMO

PURPOSE: Descemet membrane endothelial keratoplasty (DMEK) preparation is technically demanding and is a limiting factor for uptake of this kind of surgery. Supply methods that simplify the procedure for surgeons are key to increasing uptake. In this talk logistics and outcomes of Eye bank prepared DMEK tissue will be presented. METHODS: Laboratory studies of two different shipping protocols for DMEK (endothelium trifolded inwards and endothelium rolled outwards) will be presented. Clinical outcomes and complications of patients underwent to DMEK surgery with Eye bank prepared or surgeon prepared tissue will be presented. A Cost analysis of eye bank versus surgeon prepared endothelial grafts will be also part of the presentation. RESULTS: There was no difference in endothelial cell viability between surgeon or eye bank prepared tissue. Surgeon-stripped DMEK grafts in the laboratory investigation showed significantly higher elastic modulus and adhesion force compared to prestripped and preloaded tissues (p<0.0001). In the clinical data, rebubbling rates of 48%, 40% and 15% were observed in preloaded, prestripped and surgeon-stripped DMEK grafts, respectively. The cost analysis showed that eye bank prepared tissues had higher surgical expenses compared to those prepared by the surgeon, while the post-operative care expenses were similar between the two groups CONCLUSION: The Eye bank prepared tissues are a valid alternative to Surgeon prepared tissue, however need to be highlighted that with current method there is a decreased adhesion forces and elastic modulus in eye bank prepared tissues that may contribute to increased rebubbling rates.


Assuntos
Transplante de Córnea , Humanos , Bancos de Olhos , Transporte Biológico , Sobrevivência Celular , Custos e Análise de Custo
15.
J Labelled Comp Radiopharm ; 66(11): 345-352, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37408511

RESUMO

Positron emission tomography (PET) using O-(2-[18 F]fluoroethyl)-L-tyrosine ([18 F]FET) has shown great success in differentiating tumor recurrence from necrosis. In this study, we are reporting the experience of synthesis [18 F]FET by varying the concentration of TET precursor in different chemistry modules. TET precursor (2-10 mg) was used for the synthesis of [18 F]FET in an automated (MX Tracerlab) module (n = 6) and semiautomated (FX2N Tracerlab) module (n = 19). The quality control was performed for all the preparations. For human imaging, 220 ± 50 MBq of [18 F]FET was briefly injected into the patient to acquire PET-MR images. The radiochemical purity was greater than 95% for the final product in both modules. The decay corrected average yield was 10.7 ± 4.7% (10 mg, n = 3) and 8.2 ± 2.6% (2 mg, n = 3) with automated chemistry module and 36.7 ± 7.3% (8-10 mg, n = 12), 26.4 ± 3.1% (5-7 mg, n = 4), and 35.1 ± 3.8% (2-4 mg, n = 3) with semiautomated chemistry modules. The PET imaging showed uptake at the lesion site (SUVmax = 7.5 ± 2.6) and concordance with the MR image. The [18 F]FET was produced with a higher radiochemical yield with 2.0 mg of the precursor with substantial yield and is suitable for brain tumor imaging.


Assuntos
Neoplasias Encefálicas , Tirosina , Humanos , Neoplasias Encefálicas/patologia , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Transporte Biológico , Imageamento por Ressonância Magnética
16.
Biopharm Drug Dispos ; 44(4): 292-300, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37083940

RESUMO

Whilst the reproducibility of models in the area of systems biology and quantitative systems pharmacology has been the focus of attention lately, the concept of 'reusability' is not addressed. With the advent of the 'Model Master File' dominating some regulatory discussions on pharmaceutical applications of physiologically-based pharmacokinetic (PBPK) models, reusability becomes a vital aspect of confidence in their use. Herein, we define 'reusability' specifically in the context of PBPK models and investigate the influence of open versus non-open source-code (NOSC) nature of the software on the extent of 'reusability'. Original articles (n = 145) that were associated with the development of novel PBPK models were identified as source models and citations to these reports, which involved further PBPK model development, were explored (n > 1800) for reuse cases of the source PBPK model whether in full or partial form. The nature of source-code was a major determinant of external reusability for PBPK models (>50% of the NOSC models as opposed <25% of open source-code [OSC]). Full reusability of the models was not common and mostly involved internal reuse of the OSC model (by the group who had previously developed the original model). The results were stratified by the software utilised (various), organisations involved (academia, industry, regulatory), and type of reusability (full vs. partial). The clear link between external reuse of models and NOSC PBPK software might stem from many elements related to quality and trust that require further investigation, and challenges the unfounded notion that OSC models are associated with higher uptake for reuse.


Assuntos
Modelos Biológicos , Software , Reprodutibilidade dos Testes , Transporte Biológico , Farmacocinética , Simulação por Computador
17.
Chemosphere ; 329: 138649, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37043889

RESUMO

Novel Quantitative Structure-Activity Relationship (QSAR) models of compounds' placenta (PL) permeability expressed as their log FM (fetus-to-mother blood concentration) values or binary PL1/0 (crossing/non-crossing) score were generated using a number of statistical tools: Multiple Linear Regression, Boosted Trees, Principal Component Analysis and Artificial Neural Networks, on the basis of molecular descriptors calculated by Mordred software and selected using Partial Least Squares (PLS) analysis. It was established that the most important predictor of both log FM and the binary PL1/0 score is Lipinski - a binary variable reflecting the compounds' ability to satisfy the criteria of drug-likeness according to the Lipinski's "Rule of 5". The quantitative (log FM) and qualitative (PL1/0) models of PL permeability were applied to 345 pesticides from different chemical families (triazines, carbamates, pyrethroids, organochlorine, organophosphorus and miscellaneous compounds). The ability of studied pesticides to cross the placenta was assessed; the basic physico-chemical parameters responsible for good or poor placenta transport of pesticides were identified and the relationships between the pesticides' PL permeability, blood-brain barrier (BBB) transfer and gastro-intestinal (GI) absorption were investigated. It was found (on the basis of logistic regression analysis) that the probability of a compound crossing the placenta (PL1) is inversely correlated with its lipophilicity and molar refractivity and positively correlated with the total count of oxygen and nitrogen atoms.


Assuntos
Praguicidas , Gravidez , Feminino , Humanos , Praguicidas/toxicidade , Barreira Hematoencefálica , Relação Quantitativa Estrutura-Atividade , Transporte Biológico , Placenta
18.
Eur J Cell Biol ; 102(2): 151309, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36933283

RESUMO

The study of endomembrane trafficking is crucial for understanding how cells and whole organisms function. Moreover, there is a special interest in investigating endomembrane trafficking in plants, given its role in transport and accumulation of seed storage proteins and in secretion of cell wall material, arguably the two most essential commodities obtained from crops. The mechanisms of anterograde transport in the biosynthetic and endocytic pathways of plants have been thoroughly discussed in recent reviews, but, comparatively, retrograde trafficking pathways have received less attention. Retrograde trafficking is essential to recover membranes, retrieve proteins that have escaped from their intended localization, maintain homeostasis in maturing compartments, and recycle trafficking machinery for its reuse in anterograde transport reactions. Here, we review the current understanding on retrograde trafficking pathways in the endomembrane system of plants, discussing their integration with anterograde transport routes, describing conserved and plant-specific retrieval mechanisms at play, highlighting contentious issues and identifying open questions for future research.


Assuntos
Plantas , Transporte Biológico , Plantas/metabolismo , Transporte Proteico
19.
Artigo em Inglês | MEDLINE | ID: mdl-36767930

RESUMO

Moral hazard remains one of the major challenges of health insurance administration. This paper recursively analyzed the effect of health insurance on the willingness to take COVID-19 vaccines in Nigeria. The data comprised 1892 unvaccinated respondents in the 2021/2022 National Longitudinal Phone Survey (NLPS). The data were analyzed with Coban's recursive probit regression and decomposition approaches. The results revealed that 5.87% were health insured, and 7.93% were willing to take COVID-19 vaccines. Health insurance uptake significantly increased (p < 0.05) with an adult being the decision-maker on vaccination, requiring family planning, and urban residence, while it reduced with loss of jobs and residence in the southeast and southwest zones. In addition, health insurance significantly (p < 0.01) increased the willingness to take COVID-19 vaccines, along with each adult, all adults, and households' heads being the major vaccination decision-makers, loss of jobs, and support for making COVID-19 vaccines compulsory. The average treatment effects (ATEs) and average treatment effect on the treated (ATET) of health insurance were significant (p < 0.01), with positive impacts on willingness to be vaccinated. It was concluded that policy reforms to promote access to health insurance would enhance COVID-19 vaccination in Nigeria. In addition, hesitancy toward COVID-19 vaccines can be reduced by targeting adults and household heads with adequate information, while health insurance uptake should target southern states and rural areas.


Assuntos
COVID-19 , Vacinas , Adulto , Humanos , Vacinas contra COVID-19 , Nigéria , COVID-19/epidemiologia , COVID-19/prevenção & controle , Seguro Saúde , Transporte Biológico , Vacinação
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