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1.
Artigo em Inglês | MEDLINE | ID: mdl-39093376

RESUMO

BACKGROUND: County-level barriers (sociodemographic barriers, limited healthcare system resources, healthcare accessibility barriers, irregular healthcare seeking behaviors, low vaccination history) may impact individuals' reasons for receiving the COVID-19 vaccine. METHODS: This study linked data from REACH-US (Race-Related Experiences Associated with COVID-19 and Health in the United States), a nationally representative, online survey of 5475 adults living in the U.S (January-March 2021) to county-level barriers in the COVID-19 Vaccine Coverage Index. County-level vaccination barriers were measured using the COVID-19 Vaccine Coverage Index. Participants reported why they would or would not receive the COVID-19 vaccine in an open-ended item and their responses were coded using thematic analysis. Descriptive statistics and chi-square tests assessed whether reasons for COVID-19 vaccination intentions varied by county-level barriers and whether these distributions varied across racial/ethnic groups. RESULTS: Thematic analysis revealed twelve themes in participants' reasons why they would or would not receive the COVID-19 vaccine. Themes of societal responsibility (9.8% versus 7.7%), desire to return to normal (8.1% versus 4.7%), and trust in science/healthcare/government (7.7% versus 5.1%) were more frequently reported in counties with low/medium barriers (versus high/very high) (p-values < 0.05). Concerns of COVID-19 vaccine side effects/safety/development (25.3% versus 27.9%) and concerns of access/costs/availability/convenience (1.9% versus 3.6%) were less frequently reported in counties with low/medium barriers (versus high/very high) (p-values < 0.05). Trends in the prevalence of these themes varied across racial/ethnic groups (p-values < 0.05). CONCLUSIONS: Future pandemic responses should consider potential ways county-level barriers shape reasons for COVID-19 vaccination.

2.
Dis Model Mech ; 17(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38903015

RESUMO

Structural changes to the vocal fold (VF) epithelium, namely, loosened intercellular junctions, have been reported in VF benign lesions. The potential mechanisms responsible for the disruption of cell junctions do not address the contribution of resident microbial communities to this pathological phenomenon. In this study, we focused on determining the relationship between Streptococcus pseudopneumoniae (SP), a dominant bacterial species associated with benign lesions, and Streptococcus salivarius (SS), a commensal bacterium, with human VF epithelial cells in our three-dimensional model of the human VF mucosa. This experimental system enabled direct deposition of bacteria onto constructs at the air/liquid interface, allowing for the assessment of bacterium-host interactions at the cellular, molecular and ultrastructural levels. Our findings demonstrate that SP disrupts VF epithelial integrity and initiates inflammation via the exported products HtrA1 and pneumolysin. In contrast, SS attaches to the VF epithelium, reduces inflammation and induces Mmp2-mediated apical desquamation of infected cells to mitigate the impact of pathogens. In conclusion, this study highlights the complexity of microbial involvement in VF pathology and potential VF mucosal restoration in the presence of laryngeal commensals.


Assuntos
Streptococcus salivarius , Prega Vocal , Humanos , Prega Vocal/microbiologia , Prega Vocal/patologia , Streptococcus salivarius/fisiologia , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Mucosa/microbiologia , Mucosa/patologia , Inflamação/patologia , Inflamação/microbiologia , Streptococcus pneumoniae/fisiologia
3.
JAMA Netw Open ; 7(5): e2412880, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38819825

RESUMO

Importance: Screening for lung cancer using low-dose computed tomography is associated with reduced lung cancer-specific mortality, but uptake is low in the US; understanding how patients make decisions to engage with lung cancer screening is critical for increasing uptake. Prior research has focused on individual-level psychosocial factors, but environmental factors (eg, historical contexts that include experiencing racism) and modifying factors-those that can be changed to make it easier or harder to undergo screening-also likely affect screening decisions. Objective: To investigate environmental, psychosocial, and modifying factors influencing lung cancer screening decision-making and develop a conceptual framework depicting relationships between these factors. Design, Setting, and Participants: This multimethod qualitative study was conducted from December 2021 to June 2022 using virtual semistructured interviews and 4 focus groups (3-4 participants per group). All participants met US Preventive Services Task Force eligibility criteria for lung cancer screening (ie, age 50-80 years, at least a 20 pack-year smoking history, and either currently smoke or quit within the past 15 years). Screening-eligible US participants were recruited using an online panel. Main Outcomes and Measures: Key factors influencing screening decisions (eg, knowledge, beliefs, barriers, and facilitators) were the main outcome. A theory-informed, iterative inductive-deductive approach was applied to analyze data and develop a conceptual framework summarizing results. Results: Among 34 total participants (interviews, 20 [59%]; focus groups, 14 [41%]), mean (SD) age was 59.1 (4.8) years and 20 (59%) identified as female. Half had a household income below $20 000 (17 [50%]). Participants emphasized historical and present-day racism as critical factors contributing to mistrust of health care practitioners and avoidance of medical procedures like screening. Participants reported that other factors, such as public transportation availability, also influenced decisions. Additionally, participants described psychosocial processes involved in decisions, such as perceived screening benefits, lung cancer risk appraisal, and fear of a cancer diagnosis or harmful encounters with practitioners. In addition, participants identified modifying factors (eg, insurance coverage) that could make receiving screening easier or harder. Conclusions and Relevance: In this qualitative study of patient lung cancer screening decisions, environmental, psychosocial, and modifying factors influenced screening decisions. The findings suggest that systems-level interventions, such as those that help practitioners understand and discuss patients' prior negative health care experiences, are needed to promote effective screening decision-making.


Assuntos
Tomada de Decisões , Detecção Precoce de Câncer , Neoplasias Pulmonares , Pesquisa Qualitativa , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/psicologia , Feminino , Masculino , Pessoa de Meia-Idade , Detecção Precoce de Câncer/psicologia , Detecção Precoce de Câncer/métodos , Idoso , Grupos Focais , Idoso de 80 Anos ou mais , Tomografia Computadorizada por Raios X/psicologia , Estados Unidos
4.
BMC Public Health ; 24(1): 1084, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641573

RESUMO

BACKGROUND: Trust in the healthcare system may impact adherence to recommended healthcare practices, including willingness to test for and vaccinate against COVID-19. This study examined racial/ethnic differences in the associations between trust in the U.S. healthcare system and willingness to test for and vaccinate against COVID-19 during the first year of the pandemic. METHODS: This cross-sectional study used data from the REACH-US study, a nationally representative online survey conducted among a diverse sample of U.S. adults from January 26, 2021-March 3, 2021 (N = 5,121). Multivariable logistic regression estimated the associations between trust in the U.S. healthcare system (measured as "Always", "Most of the time", "Sometimes/Almost Never", and "Never") and willingness to test for COVID-19, and willingness to receive the COVID-19 vaccine. Racial/ethnic differences in these associations were examined using interaction terms and multigroup analyses. RESULTS: Always trusting the U.S. healthcare system was highest among Hispanic/Latino Spanish Language Preference (24.9%) and Asian (16.7%) adults and lowest among Multiracial (8.7%) and Black/African American (10.7%) adults. Always trusting the U.S. healthcare system, compared to never, was associated with greater willingness to test for COVID-19 (AOR: 3.20, 95% CI: 2.38-4.30) and greater willingness to receive the COVID-19 vaccine (AOR: 2.68, 95% CI: 1.97-3.65). CONCLUSIONS: Trust in the U.S. healthcare system was associated with greater willingness to test for COVID-19 and receive the COVID-19 vaccine, however, trust in the U.S. healthcare system was lower among most marginalized racial/ethnic groups. Efforts to establish a more equitable healthcare system that increases trust may encourage COVID-19 preventive behaviors.


Assuntos
COVID-19 , Hispânico ou Latino , Adulto , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Estudos Transversais , Disparidades em Assistência à Saúde , Confiança , Vacinação , Brancos , Negro ou Afro-Americano , Asiático , Grupos Raciais
5.
Epidemiology ; 35(3): 377-388, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38567886

RESUMO

BACKGROUND: Perceptions of the US healthcare system can impact individuals' healthcare utilization, including vaccination intentions. This study examined the association between perceived racial-ethnic inequities in COVID-19 healthcare and willingness to receive the COVID-19 vaccine. METHODS: This study used data from REACH-US, a nationally representative online survey of a large, diverse sample of U.S. adults (N=5145 January 26, 2021-March 3, 2021). Confirmatory factor and regression analyses examined a latent factor of perceived racial-ethnic inequities in COVID-19 healthcare, whether the factor was associated with willingness to receive the COVID-19 vaccine, and whether associations varied across racial-ethnic groups reported as probit estimates (B) and 95% confidence intervals (CIs). RESULTS: Perceived racial-ethnic inequities in COVID-19 healthcare were highest among Black/African American adults (mean latent factor score: 0.65 ± 0.43) and lowest among White adults (mean latent factor score: 0.04 ± 0.67). Black/African American (B = -0.08; 95% CI = -0.19, 0.03) and Native Hawaiian/Pacific Islander (B = -0.08; 95% CI = -0.23, 0.07) adults who perceived greater racial-ethnic inequities in COVID-19 healthcare were less willing than participants who perceived lower inequities. In contrast, American Indian/Alaska Native (B = 0.15; 95% CI = -0.01, 0.30), Asian (B = 0.20; 95% CI = 0.08, 0.31), Hispanic/Latino (English language preference) (B = 0.22; 95% CI = 0.01, 0.43), Multiracial (B = 0.23; 95% CI = 0.09, 0.36), and White (B = 0.31; 95% CI = 0.19, 0.43) adults who perceived greater racial-ethnic inequities in COVID-19 healthcare were more willing to receive the COVID-19 vaccine than participants perceiving higher inequities. CONCLUSIONS: Greater perceived racial-ethnic inequities in COVID-19 healthcare were associated with less willingness to receive the COVID-19 vaccine among Black/African American and Native Hawaiian/Pacific Islander adults.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Disparidades em Assistência à Saúde , Adulto , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Etnicidade , Estados Unidos/epidemiologia , Grupos Raciais
6.
Cells ; 13(4)2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38391962

RESUMO

Optimising drug delivery to tumours remains an obstacle to effective cancer treatment. A prerequisite for successful chemotherapy is that the drugs reach all tumour cells. The vascular network of tumours, extravasation across the capillary wall and penetration throughout the extracellular matrix limit the delivery of drugs. Ultrasound combined with microbubbles has been shown to improve the therapeutic response in preclinical and clinical studies. Most studies apply microbubbles designed as ultrasound contrast agents. Acoustic Cluster Therapy (ACT®) is a novel approach based on ultrasound-activated microbubbles, which have a diameter 5-10 times larger than regular contrast agent microbubbles. An advantage of using such large microbubbles is that they are in contact with a larger part of the capillary wall, and the oscillating microbubbles exert more effective biomechanical effects on the vessel wall. In accordance with this, ACT® has shown promising therapeutic results in combination with various drugs and drug-loaded nanoparticles. Knowledge of the mechanism and behaviour of drugs and microbubbles is needed to optimise ACT®. Real-time intravital microscopy (IVM) is a useful tool for such studies. This paper presents the experimental setup design for visualising ACT® microbubbles within the vasculature of tumours implanted in dorsal window (DW) chambers. It presents ultrasound setups, the integration and alignment of the ultrasound field with the optical system in live animal experiments, and the methodologies for visualisation and analysing the recordings. Dextran was used as a fluorescent marker to visualise the blood vessels and to trace drug extravasation and penetration into the extracellular matrix. The results reveal that the experimental setup successfully recorded the kinetics of extravasation and penetration distances into the extracellular matrix, offering a deeper understanding of ACT's mechanisms and potential in localised drug delivery.


Assuntos
Neoplasias , Animais , Ultrassonografia , Neoplasias/tratamento farmacológico , Acústica , Meios de Contraste , Microscopia Intravital
7.
PLoS One ; 19(2): e0290505, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38359055

RESUMO

Coral reefs are the most diverse ecosystem on the planet based on the abundance and diversity of phyla and higher taxa. However, it is still difficult to assess the diversity of lower taxa, especially at the species level. One tool for improving the identification of lower taxa are genetic markers that can distinguish cryptic species and assess species boundaries. Here, we present one such approach for an important and challenging group of reef-building corals. Porites corals are the main reef-builders of many coral reefs in the Indo-Pacific, owing to the massive growth forms of some species. The current number of valid Porites species is controversial, inflated with many synonymies, and often based on gross colony morphology although several morphospecies believed to be widespread and common can only be distinguished based on detailed microstructure analyses by taxonomic experts. Here, we test the suitability of multiple regions of mtDNA as genetic barcodes to identify suitable markers for species differentiation and unambiguous identification. Resulting sequencing data was further used for the first phylogenetic analysis of Guam's Porites species. We tested eight different mitochondrial markers and analyzed four in detail for 135 Porites specimens: mtDNA markers were amplified for 67 Porites specimens from Guam, representing 12 nominal Porites species, and combined with 69 mitochondrial genomes, mostly from Hawaii. The combination of all 4 markers distinguished 10 common and 7 uncommon Central-West Pacific Porites species. Most clades separate species along taxonomic boundaries, which is uncommon for Porites corals and testifies to the suitability of our multi-marker approach, and a combination of the two most promising barcodes distinguished 8/10 common species. These barcodes are thus suitable to distinguish virtually cryptic species in one of the most important and challenging coral genera. They offer a cheap, fast and reliable way to identify Porites species for species-level research, monitoring and conservation.


Assuntos
Antozoários , Animais , Antozoários/genética , Filogenia , Ecossistema , Recifes de Corais , DNA Mitocondrial
8.
Cancers (Basel) ; 15(22)2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-38001675

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) remains a challenging malignancy, mainly due to its resistance to chemotherapy and its complex tumour microenvironment characterised by stromal desmoplasia. There is a need for new strategies to improve the delivery of drugs and therapeutic response. Relevant preclinical tumour models are needed to test potential treatments. This paper compared orthotopic and subcutaneous PDAC tumour models and their suitability for drug delivery studies. A novel aspect was the broad range of tumour properties that were studied, including tumour growth, histopathology, functional vasculature, perfusion, immune cell infiltration, biomechanical characteristics, and especially the extensive analysis of the structure and the orientation of the collagen fibres in the two tumour models. The study unveiled new insights into how these factors impact the uptake of a fluorescent model drug, the macromolecule called 800CW. While the orthotopic model offered a more clinically relevant microenvironment, the subcutaneous model offered advantages for drug delivery studies, primarily due to its reproducibility, and it was characterised by a more efficient drug uptake facilitated by its collagen organisation and well-perfused vasculature. The tumour uptake seemed to be influenced mainly by the structural organisation and the alignment of the collagen fibres and perfusion. Recognising the diverse characteristics of these models and their multifaceted impacts on drug delivery is crucial for designing clinically relevant experiments and improving our understanding of pancreatic cancer biology.

9.
J Natl Cancer Inst Monogr ; 2023(62): 231-245, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37947336

RESUMO

PURPOSE: Structural racism could contribute to racial and ethnic disparities in cancer mortality via its broad effects on housing, economic opportunities, and health care. However, there has been limited focus on incorporating structural racism into simulation models designed to identify practice and policy strategies to support health equity. We reviewed studies evaluating structural racism and cancer mortality disparities to highlight opportunities, challenges, and future directions to capture this broad concept in simulation modeling research. METHODS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review Extension guidelines. Articles published between 2018 and 2023 were searched including terms related to race, ethnicity, cancer-specific and all-cause mortality, and structural racism. We included studies evaluating the effects of structural racism on racial and ethnic disparities in cancer mortality in the United States. RESULTS: A total of 8345 articles were identified, and 183 articles were included. Studies used different measures, data sources, and methods. For example, in 20 studies, racial residential segregation, one component of structural racism, was measured by indices of dissimilarity, concentration at the extremes, redlining, or isolation. Data sources included cancer registries, claims, or institutional data linked to area-level metrics from the US census or historical mortgage data. Segregation was associated with worse survival. Nine studies were location specific, and the segregation measures were developed for Black, Hispanic, and White residents. CONCLUSIONS: A range of measures and data sources are available to capture the effects of structural racism. We provide a set of recommendations for best practices for modelers to consider when incorporating the effects of structural racism into simulation models.


Assuntos
Neoplasias , Racismo Sistêmico , Humanos , Negro ou Afro-Americano , Disparidades nos Níveis de Saúde , Neoplasias/mortalidade , Neoplasias/terapia , Estados Unidos/epidemiologia , Hispânico ou Latino , Brancos
10.
MethodsX ; 11: 102440, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37885761

RESUMO

The Analytic Hierarchy Process (AHP) is a method that allows complex decisions to be made from impartiality, making it suitable for reaching a consensus among experts seeking to solve a problem. This method has been successfully applied in other investigations, and its use has been extended to several disciplines. This technical paper presents the lessons learned from a study that relied on the AHP method to determine priority aspects for sustainable neighborhoods. The research is developed in three replicable phases. In each of them, aspects that are recommended to be considered are detailed, for example, in the formulation of the hierarchical structure, selection of experts, expert survey design, and information processing for the determination of weights and levels of importance.•The utilization of software to apply the AHP method can help researchers to optimize time and resources.•Social networks proved to be more effective than conventional methods for identifying and contacting experts.•Subjective sustainability issues can be prioritized by expert consensus.

11.
Front Public Health ; 11: 1192748, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37900019

RESUMO

Background: County-level vaccination barriers (sociodemographic barriers, limited healthcare system resources, healthcare accessibility barriers, irregular healthcare seeking behaviors, history of low vaccination) may partially explain COVID-19 vaccination intentions among U.S. adults. This study examined whether county-level vaccination barriers varied across racial/ethnic groups in the U.S. and were associated with willingness to receive the COVID-19 vaccine. In addition, this study assessed whether these associations differed across racial/ethnic groups. Methods: This study used data from the REACH-US study, a large online survey of U.S. adults (N = 5,475) completed from January 2021-March 2021. County-level vaccination barriers were measured using the COVID-19 Vaccine Coverage Index. Ordinal logistic regression estimated associations between race/ethnicity and county-level vaccination barriers and between county-level vaccination barriers and willingness to receive the COVID-19 vaccine. Models adjusted for covariates (age, gender, income, education, political ideology, health insurance, high-risk chronic health condition). Multigroup analysis estimated whether associations between barriers and willingness to receive the COVID-19 vaccine differed across racial/ethnic groups. Results: American Indian/Alaska Native, Black/African American, Hispanic/Latino ELP [English Language Preference (ELP); Spanish Language Preference (SLP)], and Multiracial adults were more likely than White adults to live in counties with higher overall county-level vaccination barriers [Adjusted Odd Ratios (AORs):1.63-3.81]. Higher county-level vaccination barriers were generally associated with less willingness to receive the COVID-19 vaccine, yet associations were attenuated after adjusting for covariates. Trends differed across barriers and racial/ethnic groups. Higher sociodemographic barriers were associated with less willingness to receive the COVID-19 vaccine (AOR:0.78, 95% CI:0.64-0.94), whereas higher irregular care-seeking behavior was associated with greater willingness to receive the vaccine (AOR:1.20, 95% CI:1.04-1.39). Greater history of low vaccination was associated with less willingness to receive the COVID-19 vaccine among Black/African American adults (AOR:0.55, 95% CI:0.37-0.84), but greater willingness to receive the vaccine among American Indian/Alaska Native and Hispanic/Latino ELP adults (AOR:1.90, 95% CI:1.10-3.28; AOR:1.85, 95% CI:1.14-3.01). Discussion: Future public health emergency vaccination programs should include planning and coverage efforts that account for structural barriers to preventive healthcare and their intersection with sociodemographic factors. Addressing structural barriers to COVID-19 treatment and preventive services is essential for reducing morbidity and mortality in future infectious disease outbreaks.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Acessibilidade aos Serviços de Saúde , Adulto , Humanos , COVID-19/epidemiologia , COVID-19/etnologia , COVID-19/prevenção & controle , Tratamento Farmacológico da COVID-19 , Vacinas contra COVID-19/uso terapêutico , Etnicidade/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Cobertura Vacinal/estatística & dados numéricos , Hesitação Vacinal/psicologia , Hesitação Vacinal/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Fatores Raciais , Indígena Americano ou Nativo do Alasca/estatística & dados numéricos , Negro ou Afro-Americano/estatística & dados numéricos , Grupos Raciais/etnologia , Grupos Raciais/estatística & dados numéricos , Brancos/estatística & dados numéricos
13.
Int J Public Health ; 68: 1605624, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37205045

RESUMO

Objectives: The European Centre for Disease Control (ECDC) COVID-19 guidelines for non-pharmaceutical interventions (NPI) identify safety, hygiene and physical distancing measures to control SARS-Cov-2 transmission in schools. Because their implementation requires complicated changes, the guidelines also include "accompanying measures" of risk communication, health literacy and community engagement. Although these are considered crucial, their implementation is complex. This study aimed to co-define a community partnership that a) identifies systemic barriers and b) designs recommendations on how to implement the NPI to improve SARS-Cov-2 prevention in schools. Methods: We designed and piloted a System-Oriented Dialogue Model with the participation of 44 teachers and 868 students and their parents from six Spanish schools during 2021. The results were analysed using thematic analysis. Results: Participants identified 406 items addressing issues related to system characteristics, which is indicative of the complexity of the challenge. Using a thematic analysis, we defined 14 recommendations covering five categories. Conclusion: These findings could help in developing guidelines for initiating community engagement partnerships in schools to provide more integrated prevention interventions.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , Espanha , Instituições Acadêmicas , Estudantes
14.
Biomed Pharmacother ; 162: 114596, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36989728

RESUMO

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly affects the elderly. AD's main features have been related to cellular and molecular events, including the aberrant aggregation of the amyloid beta peptide (Aß), Ca2+ dyshomeostasis, and increased mitochondria-associated membranes (MAMs). Transglutaminase type 2 (TG2) is a ubiquitous enzyme whose primary role is the Ca2+-dependent proteins transamidation, including the Aß peptide. TG2 activity has been closely related to cellular damage and death. We detected increased TG2 levels in neuronal cells treated with Aß oligomers (AßOs) and hippocampal slices from J20 mice using cellular and molecular approaches. In this work, we characterized the capacity of TG2 to interact and promote Aß toxic aggregates (AßTG2). AßTG2 induced an acute increase in intracellular Ca2+, miniature currents, and hiperexcitability, consistent with an increased mitochondrial Ca2+ overload, IP3R-VDAC tethering, and mitochondria-endoplasmic reticulum contacts (MERCs). AßTG2 also decreased neuronal viability and excitatory postsynaptic currents, reinforcing the idea of synaptic failure associated with MAMs dysregulation mediated by TG2. Z-DON treatment, TG2 inhibitor, reduced calcium overload, mitochondrial membrane potential loss, and synaptic failure, indicating an involvement of TG2 in a toxic cycle which increases Aß aggregation, Ca2+ overload, and MAMs upregulation. These data provide novel information regarding the role TG2 plays in synaptic function and contribute additional evidence to support the further development of TG2 inhibitors as a disease-modifying strategy for AD.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Camundongos , Animais , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/metabolismo , Cálcio/metabolismo , Mitocôndrias/metabolismo , Retículo Endoplasmático/metabolismo , Homeostase
15.
Methods Enzymol ; 680: 439-459, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36710022

RESUMO

Many biotic and abiotic stimuli arrive locally on the plant. For example, attack by an insect or invasion by a fungal pathogen generally starts with a single leaf. However, the responses that are then elicited are often systemic, triggering effects throughout the entire plant body. One of the rapid signaling systems that helps coordinate these plant-wide response networks is changes in cytoplasmic Ca2+ that rapidly propagate throughout the plant. These Ca2+ signals are readily visualized using plants expressing green fluorescent protein-based Ca2+-sensitive bioreporters, such as those of the GCaMP and GECO families. Dissecting the underlying molecular machinery behind this systemic spread of information is often approached by imaging the Ca2+ response in mutants in candidate genes. Introducing the GFP sensor into the relevant genetic backgrounds and then selecting lines usable for imaging can be very time consuming. An alternative, more rapid approach to screening these candidates is through virus-induced gene silencing (VIGS), where target genes are suppressed in the wild-type bioreporter expressing plants. This chapter describes how to generate VIGS constructs targeted to candidate genes and then how to visualize wound-induced, systemic Ca2+ signaling in the VIGS suppressed plants.


Assuntos
Cálcio , Inativação Gênica , Humanos , Cálcio/metabolismo , Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Nicotiana/genética
16.
Brain Behav Immun ; 109: 144-161, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36702234

RESUMO

In the last two decades, microglia have emerged as key contributors to disease progression in many neurological disorders, not only by exerting their classical immunological functions but also as extremely dynamic cells with the ability to modulate synaptic and neural activity. This dynamic behavior, together with their heterogeneous roles and response to diverse perturbations in the brain parenchyma has raised the idea that microglia activation is more diverse than anticipated and that understanding the molecular mechanisms underlying microglial states is essential to unravel their role in health and disease from development to aging. The Ikzf1 (a.k.a. Ikaros) gene plays crucial roles in modulating the function and maturation of circulating monocytes and lymphocytes, but whether it regulates microglial functions and states is unknown. Using genetic tools, here we describe that Ikzf1 is specifically expressed in the adult microglia in brain regions such as cortex and hippocampus. By characterizing the Ikzf1 deficient mice, we observed that these mice displayed spatial learning deficits, impaired hippocampal CA3-CA1 long-term potentiation, and decreased spine density in pyramidal neurons of the CA1, which correlates with an increased expression of synaptic markers within microglia. Additionally, these Ikzf1 deficient microglia exhibited a severe abnormal morphology in the hippocampus, which is accompanied by astrogliosis, an aberrant composition of the inflammasome, and an altered expression of disease-associated microglia molecules. Interestingly, the lack of Ikzf1 induced changes on histone 3 acetylation and methylation levels in the hippocampus. Since the lack of Ikzf1 in mice appears to induce the internalization of synaptic markers within microglia, and severe gliosis we then analyzed hippocampal Ikzf1 levels in several models of neurological disorders. Ikzf1 levels were increased in the hippocampus of these neurological models, as well as in postmortem hippocampal samples from Alzheimer's disease patients. Finally, over-expressing Ikzf1 in cultured microglia made these cells hyporeactive upon treatment with lipopolysaccharide, and less phagocytic compared to control microglia. Altogether, these results suggest that altered Ikzf1 levels in the adult hippocampus are sufficient to induce synaptic plasticity and memory deficits via altering microglial state and function.


Assuntos
Hipocampo , Microglia , Camundongos , Animais , Microglia/metabolismo , Hipocampo/metabolismo , Plasticidade Neuronal/fisiologia , Potenciação de Longa Duração/fisiologia , Inflamação/metabolismo
17.
Postgrad Med ; 135(2): 128-140, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36227619

RESUMO

OBJECTIVES: To analyze the temporal trends of premature mortality from diabetes in Costa Rica in the period 2000-2020, at a national level and by province, and the effect of the COVID-19 pandemic on diabetes mortality during the year 2020. METHODS: We studied the temporal trends of mortality from diabetes in Costa Rica in the period between 2000 and 2020. Age-standardized mortality rates and corresponding 95% confidence intervals were calculated for each year, sex and province. RESULTS: We analyzed the data of 17,968 deceased persons. The mean age was 72.5 years (range 1 to 109 years), and 51.5% of the population (n = 9253) was younger than 75 years. In both men and women, we observed a significant decrease in mortality from 2000 to 2014, followed by the opposite trend from 2014 to 2020, with average yearly increases of 13.9% in men and 11.6% in women. CONCLUSIONS: Premature mortality from diabetes has been growing from 2014. The COVID-19 pandemic changed the mortality pattern, increasing premature diabetes deaths in Costa Rica in 2020.


Assuntos
COVID-19 , Diabetes Mellitus , Masculino , Humanos , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Costa Rica/epidemiologia , Mortalidade Prematura , Pandemias , COVID-19/epidemiologia , Diabetes Mellitus/epidemiologia
18.
BMC Public Health ; 22(1): 2458, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-36585651

RESUMO

College students are often reluctant to follow U.S. preventive guidelines to lower their risk of COVID-19 infection, despite an increased risk of transmission in college settings. Prior research suggested that college students who perceived greater COVID-19 severity and susceptibility (i.e., COVID-19 threat) were more likely to engage in COVID-19 preventive behaviors, yet there is limited research examining whether perceived COVID-19 threat, perceived U.S. healthcare system inequities, and personal experiences of healthcare discrimination collectively influence college students' COVID-19 preventive behaviors. This study identified latent classes of perceived COVID-19 threat, perceived U.S. healthcare system inequities, and personal experiences of healthcare discrimination, examined whether latent classes were associated with COVID-19 preventive behavioral intentions, and assessed whether latent class membership varied across racial/ethnic groups.Students from the University of Maryland, College Park (N = 432) completed the Weighing Factors in COVID-19 Health Decisions survey (December 2020-December 2021). Latent class analysis identified latent classes based on perceived COVID-19 threat, perceived U.S. healthcare system inequities, and personal experiences of healthcare discrimination. Regression analyses examined associations between the latent classes and COVID-19 preventive behavioral intentions (i.e., social distancing, mask-wearing, COVID-19 vaccination) and whether latent class membership varied across racial/ethnic groups.Students in Latent Class 1 (27.3% of the sample) had high perceived COVID-19 threat and U.S. healthcare system inequities and medium probability of experiencing personal healthcare discrimination. Students in Latent Class 1 had higher social distancing, mask-wearing, and vaccination intentions compared to other latent classes. Compared to Latent Class 4 (reference group), students in Latent Class 1 had higher odds of identifying as Hispanic or Latino, Non-Hispanic Asian, Non-Hispanic Black or African American, and Non-Hispanic Multiracial versus Non-Hispanic White.Latent classes of higher perceived COVID-19 threat, perceived U.S. healthcare system inequities, and personal experiences of healthcare discrimination were associated with higher COVID-19 preventive behavioral intentions and latent class membership varied across racial/ethnic groups. Interventions should emphasize the importance of COVID-19 preventive behaviors among students who perceive lower COVID-19 threat.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Intenção , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudantes , Disparidades em Assistência à Saúde
19.
J Am Heart Assoc ; 11(12): e024594, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35699190

RESUMO

Background Hypertension and diabetes disproportionately affect older non-Hispanic Black and Hispanic adults in the United States. Chronic stress may partially explain these disparities. This study identified underlying stress profiles of older US adults, analyzed stress profiles in relation to hypertension and diabetes, examined the distribution of stress profiles by race and ethnicity, and assessed patterns of change in latent classes of stress over time. Methods and Results Latent class analysis was conducted with a nationally representative sample of older US adults who completed 3 waves of the HRS (Health and Retirement Study) (ie, 2010 [n=6863], 2014 [n=4995], and 2018 [n=3089]). Latent classes of stress in 2010 (ie, stress profiles) were identified using 15 indicators of unmet needs within 5 categories (ie, physiological, safety/security, belonging, esteem, and self-fulfillment). Hypertension and diabetes status were examined as outcomes of latent class membership at 3 time points, and race and ethnicity were examined in association with class membership, adjusting for sociodemographic covariates. Finally, a latent transition analysis examined the stability of latent class membership and racial and ethnic differences in the patterns of stress profiles experienced from 2010 to 2018. Five classes were identified: Generally Unmet Needs (13% of sample), Generally Met Needs (42% of sample), Unmet Self-Efficacy/Goal Needs (12% of sample), Unmet Financial Needs (20% of sample), and Unmet Social Belonging Needs (13% of sample). Compared with the Generally Met Needs class, the Generally Unmet Needs class had higher odds of hypertension (odds ratio [OR], 1.80; [95% CI, 1.35-2.39]) and diabetes (OR, 1.94; [95% CI, 1.45-2.59]), and the Unmet Financial Needs class had higher odds of diabetes (OR, 1.50; [95% CI, 1.10-2.05]). Non-Hispanic Black participants compared with non-Hispanic White participants had higher odds of being members of the Generally Unmet Needs, Unmet Self-Efficacy/Goal Needs, and Unmet Financial Needs classes (OR, 2.70; [95% CI, 1.59-4.58]; OR, 1.99; [95% CI, 1.15-3.43]; and OR, 4.74; [95% CI, 3.32-6.76], respectively). Class membership remained relatively stable over time, with 93% of participants remaining in Generally Met Needs and 78% of participants remaining in Generally Unmet Needs across time points. Compared with non-Hispanic White participants, non-Hispanic Black participants had lower odds of Generally Met Needs class membership at any time point (OR, 0.60; [95% CI, 0.42-0.84]) and had lower odds of moving into the Generally Met Needs class and higher odds of moving into the Unmet Financial Needs class from 2010 to 2014 (OR, 0.33; [95% CI, 0.13-0.86]; and OR, 3.02; [95% CI, 1.16-7.87], respectively). Conclusions Underlying classes of stress based on unmet needs were associated with hypertension and diabetes status. Racial and ethnic differences were observed for both latent class membership and transitions between classes over time. Latent classes of stress associated with unmet needs, hypertension, and diabetes and the ability to transition between classes may explain the perpetuation of racial and ethnic disparities in cardiovascular health. Interventions targeting unmet needs may be used to confront these disparities.


Assuntos
Diabetes Mellitus , Hipertensão , Adulto , Idoso , Diabetes Mellitus/epidemiologia , Etnicidade , Humanos , Hipertensão/epidemiologia , Análise de Classes Latentes , Pessoa de Meia-Idade , Aposentadoria , Estados Unidos/epidemiologia
20.
J Exp Soc Psychol ; 101: 104299, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35469190

RESUMO

Many people practiced COVID-19-related safety measures in the first year of the pandemic, but Republicans were less likely to engage in behaviors such as wearing masks or face coverings than Democrats, suggesting radical disparities in health practices split along political fault lines. We developed an "intervention tournament" which aimed to identify the framings that would promote mask wearing among a representative sample of Republicans and Democrats in the U.S. from Oct 14, 2020, to Jan 14, 2021 (N = 4931). Seven different conditions reflecting different moral values and factors specific to COVID-19-including protection from harm (self), protection from harm (community), patriotic duty, purity, reviving the economy, threat, and scientific evidence-were implemented to identify which framings would "win" in terms of promoting mask wearing compared to a baseline condition. We found that Republicans had significantly more negative attitudes toward masks, lower intentions to wear them, and were less likely to sign or share pledges on social media than Democrats, which was partially mediated by Republicans, compared to Democrats, perceiving that the threat of COVID-19 was lower. None of our framing conditions significantly affected Republicans' or Democrats' attitudes, intentions, or behaviors compared to the baseline condition, illustrating the difficulty in overcoming the strength of political polarization during COVID-19.

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