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1.
J Community Genet ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39240499

RESUMO

Latinas are less likely to receive genetic counseling and genetic testing (GCT) compared to non-Latina Whites because of systemic and patient-level barriers. We developed and tested fotonovelas to increase awareness of GCT among Latinas at-risk of hereditary breast and ovarian cancer (HBOC). Content for the fotonovelas was drawn from an existing culturally targeted narrative video focused on improving GCT use among Latinas at-risk of HBOC. Using mixed methods, we interviewed cancer patients (n = 10) and their relatives (n = 10) to assess the preliminary efficacy of the fotonovelas through pre-and post-fotonovela items assessing self-rated knowledge of GCT and willingness to discuss cancer with family. Health workers (n = 10) provided feedback on the fotonovela content. McNemar's test was used to examine differences in the proportions of the outcomes pre- and post-fotonovelas. Interviews were transcribed and coded in Dedoose using a consensual qualitative research approach. Reading the fotonovelas increased self-rated knowledge of GCT by 22% (p = 0.16), from 50 to 60% in patients and from 63 to 100% among relatives. Analogously, reading the fotonovela increased willingness to talk about cancer with family by 33% (p = 0.02), from 70 to 100% in patients and from 38 to 75% in relatives. We identified six themes, some centered around the fotonovela's message, feedback, and perceived barriers to GCT. Overall, participants liked the use of fotonovelas to increase GCT awareness and cancer conversations with family. Fotonovelas could potentially be used as educational tools to increase GCT awareness and cancer conversations among Latino families at-risk of HBOC.

2.
J Clin Med ; 13(11)2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38892833

RESUMO

Optimizing pain management in spinal surgery is crucial for preventing adverse events due to delayed mobilization. Magnesium sulfate has potential benefits in spinal surgery because of its analgesic properties and modulation of neurotransmitters and autonomic nervous system. Existing evidence regarding the use of magnesium sulfate is partial and controversial, necessitating a comprehensive meta-analysis to evaluate its efficacy and safety. The aim of this study was to conduct a comprehensive meta-analysis to evaluate the efficacy and safety of magnesium sulfate in spinal surgery compared to other available options. This meta-analysis adhered to the PRISMA guidelines. Patients undergoing spinal surgery were included, with the intervention group receiving intravenous magnesium sulfate (MS) at various doses or combinations, whereas the comparison group received other alternatives or a placebo. The efficacy and safety outcomes were assessed. Data were collected from multiple databases and analyzed using Review Manager version 5.4. Heterogeneity was assessed and fixed- or random-effects models were applied. The meta-analysis included eight studies (n = 541). Magnesium sulfate demonstrated significant reductions in pain at 24 h (MD -0.20, 95% CI: -0.39 to -0.02) and opioid consumption (SMD -0.66, 95% CI: -0.95 to -0.38) compared to placebo. Additionally, a decrease in the use of muscle relaxants (SMD -0.91, 95% CI: -1.65 to -0.17) and remifentanil (SMD -1.52, 95% CI: -1.98 to -1.05) was observed. In contrast, an increase in extubation time (MD 2.42, 95% CI: 1.14 to 3.71) and verbal response (MD 1.85, 95% CI: 1.13 to 2.58) was observed compared to dexmedetomidine. In conclusion, magnesium sulfate administration in spinal surgery reduced pain and opioid consumption, and prolonged orientation and verbal response. No significant differences in blood pressure or heart rate were observed between the groups.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38276807

RESUMO

With Europe's ageing population and rising demand for palliative care, it is crucial to examine the use of palliative care among older adults during their last years of life and understand the factors influencing their access and end-of-life circumstances. This study employed a cohort of SHARE participants aged 65 years or older who had passed away between Wave 6 (2015) and Wave 7 (2017). Information on death circumstances, palliative care utilization, and associated variables were analysed. The study revealed that nearly 13.0% of individuals across these countries died under palliative care, with Slovenia having the lowest rate (0.3%) and France the highest (30.4%). Palliative care utilization in the last 30 days before death was observed in over 24.0% of participants, with the Czech Republic having the lowest rate (5.0%) and Greece the highest (48.8%). A higher risk of using or dying in palliative care was significantly associated with cognitive impairment (low verbal fluency), physical inactivity, and good to excellent self-perceived health. This work highlights the urgent need for enhanced global access to palliative care and advocates for the cross-country comparison of effective practices within Europe, tailored to the unique healthcare needs of older adults.


Assuntos
Envelhecimento , Cuidados Paliativos , Humanos , Idoso , Cuidados Paliativos/psicologia , Envelhecimento/psicologia , Europa (Continente)/epidemiologia , República Tcheca/epidemiologia , Instalações de Saúde
4.
Front Cell Infect Microbiol ; 13: 1268959, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37868350

RESUMO

Granulomas are important immunological structures in the host defense against the fungus Paracoccidioides brasiliensis, the main etiologic agent of Paracoccidioidomycosis (PCM), a granulomatous systemic mycosis endemic in Latin America. We have performed transcriptional and proteomic studies of yeasts present in the pulmonary granulomas of PCM aiming to identify relevant genes and proteins that act under stressing conditions. C57BL/6 mice were infected with 1x106 yeasts and after 8- and 12-weeks of infection, granulomatous lesions were obtained for extraction of fungal and murine RNAs and fungal proteins. Dual transcriptional profiling was done comparing lung cells and P. brasiliensis yeasts from granulomas with uninfected lung cells and the original yeast suspension used in the infection, respectively. Mouse transcripts indicated a lung malfunction, with low expression of genes related to muscle contraction and organization. In addition, an increased expression of transcripts related to the activity of neutrophils, eosinophils, macrophages, lymphocytes as well as an elevated expression of IL-1ß, TNF-α, IFN-γ, IL-17 transcripts were observed. The increased expression of transcripts for CTLA-4, PD-1 and arginase-1, provided evidence of immune regulatory mechanisms within the granulomatous lesions. Also, our results indicate iron as a key element for the granuloma to function, where a high number of transcripts related to fungal siderophores for iron uptake was observed, a mechanism of fungal virulence not previously described in granulomas. Furthermore, transcriptomics and proteomics analyzes indicated a low fungal activity within the granuloma, as demonstrated by the decreased expression of genes and proteins related to energy metabolism and cell cycle.


Assuntos
Paracoccidioides , Paracoccidioidomicose , Animais , Camundongos , Paracoccidioides/genética , Proteômica , Camundongos Endogâmicos C57BL , Ferro/metabolismo , Imunidade , Granuloma
5.
Commun Chem ; 6(1): 162, 2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37532884

RESUMO

Pyridoxal 5'-phosphate (PLP)-dependent enzymes utilize a vitamin B6-derived cofactor to perform a myriad of chemical transformations on amino acids and other small molecules. Some PLP-dependent enzymes, such as serine hydroxymethyltransferase (SHMT), are promising drug targets for the design of small-molecule antimicrobials and anticancer therapeutics, while others have been used to synthesize pharmaceutical building blocks. Understanding PLP-dependent catalysis and the reaction specificity is crucial to advance structure-assisted drug design and enzyme engineering. Here we report the direct determination of the protonation states in the active site of Thermus thermophilus SHMT (TthSHMT) in the internal aldimine state using room-temperature joint X-ray/neutron crystallography. Conserved active site architecture of the model enzyme TthSHMT and of human mitochondrial SHMT (hSHMT2) were compared by obtaining a room-temperature X-ray structure of hSHMT2, suggesting identical protonation states in the human enzyme. The amino acid substrate serine pathway through the TthSHMT active site cavity was tracked, revealing the peripheral and cationic binding sites that correspond to the pre-Michaelis and pseudo-Michaelis complexes, respectively. At the peripheral binding site, the substrate is bound in the zwitterionic form. By analyzing the observed protonation states, Glu53, but not His residues, is proposed as the general base catalyst, orchestrating the retro-aldol transformation of L-serine into glycine.

6.
J Food Sci ; 88(8): 3422-3434, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37326342

RESUMO

Garambullo (Myrtillocactus geometrizans) is endemic in México, and although popularly consumed locally, its nutritional characteristics and value have not been studied in details. The objective of this work was to investigate the bioactive compounds and antioxidant activity in garambullo fruit from different sites at three ripening stages. Fruit from the three ripening stages (red, purple, and dark purple) were investigated for their physicochemical characteristics, hydrophilic (phenolic compounds, betalains, and ascorbic acid), and lipophilic (carotenoids, tocopherols, and fatty acids) bioactive compounds, using spectrophotometry, gas chromatography (GC-FID), and high-pressure liquid chromatography coupled to mass spectrometry (HPLC/DAD-ESI-MS). The antioxidant capacity was measured with the 2,2'-diphenyl-1-picrylhydrazyl and the ferric-ion-reducing antioxidant power assays. The color components of the fruit, chroma and a* values increased, whereas lightness (L*) and b* significantly decreased during ripening. Five betacyanins and four betaxanthins were tentatively identified with HPLC/DAD-ESI-MS, and betacyanins were more abundant than betaxanthins. Betalains content and antioxidant capacity of hydrophilic extracts significantly increased during ripening. Ten phenolic compounds were identified, with ferulic acid being the most abundant. Tocopherols were low (0.023-0.033 mg/100 g fw). Five fatty acids were abundant, and linoleic acid was the most important. Phenolic compounds, ascorbic acid, total carotenoids, and fatty acids decreased during fruit ripening. Garambullo fruit is rich in phytochemical compounds of importance for human nutrition and health. PRACTICAL APPLICATION: The physicochemical and bioactive compounds characterization in garambullo fruit is important to establish maturation and harvesting indices, postharvest strategies to preserve fruit quality and prolong postharvest life, promote the consumption and utilization of the fruit, and the designing of proper functional foods. In addition, the knowledge on the bioactive components might be useful to include this fruit in personalized nutritional approaches for patients with risks of certain chronic diseases. The methodology used in this study could be useful for the study of other fruits, especially those from the Cactaceae family.


Assuntos
Antioxidantes , Cactaceae , Humanos , Antioxidantes/análise , Frutas/química , Betacianinas/análise , Betaxantinas/análise , Cromatografia Gasosa-Espectrometria de Massas , Cactaceae/química , Betalaínas/análise , Ácido Ascórbico/análise , Fenóis/análise , Tocoferóis/análise , Carotenoides/análise , Extratos Vegetais/química
7.
J Genet Couns ; 32(5): 965-981, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37062905

RESUMO

Genetic counseling and testing (GCT) inform cancer management for persons at risk for hereditary breast and ovarian cancer (HBOC). Community-based organizations (CBOs) may play a role in identifying at-risk Latinx individuals to connect them to GCT but data are lacking. Two academic centers and their four CBO partners planned to implement a validated questionnaire for HBOC risk screening ("HBOC risk screening tool"). This study aimed to assess CBO's preferences for HBOC risk screening tools, as well as the barriers and facilitators anticipated for future implementation. Pre-implementation focus groups were conducted with CBO's staff. Discussions centered on current practices to identify and refer at-risk patients. During the discussion, staff were asked to select one out of five validated HBOC risk screening tools to implement and to discuss anticipated barriers/facilitators for implementation. The four focus groups were coded and qualitative analyzed following the Consolidated Framework for Implementation Research (CFIR) and Health Equity domains. All CBOs chose the Family History Screen 7 (FHS-7). Participants (N = 35) highlighted how the FHS-7 was easy to adapt to better fit the target population and changing guidelines. They had positive attitudes toward implementing the screening tool, stressed how the culture of the organization positioned them to reach the target population, and noted barriers in different CFIR domains (e.g., low knowledge about HBOC and GCT referrals; scarce available resources). Participants pointed to barriers related to health equity domains including limited access to GCT and follow-up care for uninsured and underinsured populations, challenges obtaining accurate family history, and immigration-related barriers. CBOs highlighted the importance of partnering with other stakeholders to overcome barriers. Findings emphasize the need to develop multi-level implementation strategies to overcome barriers and leverage facilitators. This study can inform the development of implementation toolkits for CBOs to implement HBOC screening tools to advance health equity.


Assuntos
Neoplasias da Mama , Equidade em Saúde , Neoplasias Ovarianas , Humanos , Feminino , Detecção Precoce de Câncer , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Pesquisa Qualitativa , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética
8.
Am J Clin Nutr ; 117(6): 1086-1095, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37084814

RESUMO

BACKGROUND: Low 25-hydroxyvitamin D (25[OH]D) concentrations (<30 ng/mL [<50 nmol/L]) have been associated with muscle weakness and impaired physical performance in observational studies. However, the effect of vitamin D supplementation on changes in muscle strength and physical performance in randomized controlled trials has been mixed. OBJECTIVES: To determine the effect of daily vitamin D supplementation on leg power, strength, and physical performance in low-functioning older adults with 25(OH)D concentrations of 18 to <30 ng/mL. METHODS: In this double-blind, randomized controlled trial, 136 low-functioning [Short Physical Performance Battery (SPPB) scores ≤10] adults aged 65-89 y with 25(OH)D concentrations of 18 to <30 ng/mL were randomly assigned to 2000 IU/d vitamin D3 or placebo for 12 mo. Lower-extremity leg power (primary outcome), leg and grip strength, SPPB, timed up and go (TUG), postural sway, and gait velocity and spatiotemporal parameters (secondary outcomes) were assessed at baseline, 4 and 12 mo. A subset (n = 37) also underwent a muscle biopsy at baseline and 4 mo and muscle fiber composition and contractile properties were assessed. RESULTS: Participants' mean ± SD age and SPPB scores at baseline were 73.4 ± 6.3 y and 7.8 ± 1.8, respectively. Mean ± SD 25(OH)D concentrations at baseline and 12 mo were 19.4 ± 4.2 ng/mL and 28.6 ± 6.7 ng/mL in the vitamin D group and 19.9 ± 4.9 ng/mL and 20.2 ± 5.0 ng/mL in the placebo group for a mean ± SE difference of 9.1 ± 1.1 ng/mL (P < 0.0001). However, there were no differences in change in leg power, leg or grip strength, SPPB score, TUG, postural sway, or gait velocity and spatiotemporal parameters by intervention group over 12 mo or muscle fiber composition and contractile properties over 4 mo. CONCLUSIONS: In low-functioning older adults with 25(OH)D concentrations of 18 to <30 ng/mL, randomization to 2000 IU/d vitamin D3 did not result in improvements in leg power, strength, or physical performance or muscle fiber composition and contractile properties. This trial was registered at clinicaltrials.gov as NCT02015611.


Assuntos
Suplementos Nutricionais , Deficiência de Vitamina D , Humanos , Idoso , Vitamina D , Vitaminas , Colecalciferol , Força Muscular , Método Duplo-Cego , Desempenho Físico Funcional , Músculos , Deficiência de Vitamina D/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Transl Behav Med ; 13(5): 297-308, 2023 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-36694918

RESUMO

Telephone genetic counseling (TGC) is accepted as standard clinical care for people seeking hereditary cancer risk assessment. TGC has been shown to be non-inferior to in-person genetic counseling, but trials have been conducted with a predominantly highly educated, non-Hispanic White population. This article describes the process of culturally adapting a TGC protocol and visual aid booklet for Spanish-preferring Latina breast cancer survivors at risk for hereditary breast and ovarian cancers. The adaptation process included two phases. Phase 1 involved a review of the literature and recommendations from an expert team including community partners. Phase 2 included interviews and a pilot with the target population (n = 14) to collect feedback about the adapted protocol and booklet following steps from the Learner Verification and Revision Framework. We describe the adaptation process and report the main adaptations following the Framework for Reporting Adaptations and Modifications to Evidence-based Interventions (FRAME). Adaptations in Phase 1 were responsive to the target population needs and characteristics (e.g., delivered in Spanish at an appropriate health literacy level, addressing knowledge gaps, targeting cultural values). Phase 2 interviews were crucial to refine details (e.g., selecting words) and to add components to address GCT barriers (e.g., saliva sample video). Cultural adaptations to evidence-based TGC protocols can increase the fit and quality of care for historically underserved populations. As TGC visits become routine in clinical care, it is crucial to consider the needs of diverse communities to adequately promote equity and justice in cancer care.


This article describes the process of adapting a telephone genetic counseling protocol and visual aid booklet for Spanish-preferring Latina breast cancer survivors at increased risk for hereditary breast and ovarian cancer (HBOC). The cultural adaptation process followed two phases. In the first phase, the authors reviewed the literature and obtained insights from interdisciplinary experts. In the second phase, the authors received iterative feedback from fourteen Latina women who were breast cancer survivors, spoke Spanish as a first language, and met criteria to be considered at increased risk for HBOC. Revisions to the protocol and visual aid booklet were conducted iteratively following feedback from the expert team, after the first five women reviewed the booklet, after the second five women reviewed the booklet, and after the final four women completed the entire culturally adapted telephone genetic counseling protocol with the booklet. The final adaptations to the protocol and visual aid booklet were responsive to the target population's needs. Most adaptations made were regarding content. For example, simplifying the material presented, adding culturally relevant images, and developing a video explaining how to collect a saliva sample. Culturally adapting health interventions can improve health outcomes in historically marginalized populations and promote equity.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Neoplasias Ovarianas , Humanos , Feminino , Aconselhamento Genético/psicologia , Neoplasias da Mama/genética , Neoplasias da Mama/psicologia , Folhetos , Neoplasias Ovarianas/genética , Hispânico ou Latino/psicologia , Telefone , Literatura de Revisão como Assunto
10.
Prev Med ; 165(Pt B): 107213, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35995103

RESUMO

The reinforcing characteristics of e-cigarettes could moderate the impact of reducing cigarette nicotine content. In this study, people who smoke daily were recruited from North Carolina and Pennsylvania (US) in 2018 and 2019. Within a randomized 2 × 2 × 2 factorial design, participants received investigational cigarettes and an e-cigarette for 12 weeks. Cigarette nicotine content was very low (0.4 mg/g of tobacco; VLNC) or normal (15.8 mg/g; NNC). E-liquids were 0.3% ("low") or 1.8% ("moderate") freebase nicotine, and available in tobacco flavors or tobacco, fruit, dessert and mint flavors. Study recruitment concluded before reaching the planned sample size (N = 480). Fifty participants were randomized and 32 completed the study. We found that randomization to VLNC, relative to NNC cigarettes, reduced self-reported cigarettes per day (CPD; mean difference: -12.96; 95% CI: -21.51, -4.41; p = 0.005); whereas e-liquid nicotine content and flavor availability did not have significant effects. The effect of cigarette nicotine content was larger in the moderate vs. low nicotine e-liquid groups and in the all flavors versus tobacco flavors e-liquid groups; tests of the interaction between e-liquid characteristics and cigarette nicotine content were not significant. Biomarkers of smoke exposure at Week 12 did not differ across conditions, which may reflect variability in adherence to only using VLNC cigarettes. In conclusion this study offers preliminary evidence that the extent to which cigarette nicotine reduction decreases smoking may depend on the reinforcing characteristics of alternative products, including the available nicotine contents and flavors of e-cigarettes.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Humanos , Nicotina , Uso de Tabaco , Biomarcadores
11.
Am J Respir Crit Care Med ; 206(9): 1140-1152, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35767663

RESUMO

Rationale: Sarcoidosis is a multisystemic inflammatory disease characterized by the formation of granulomas in response to persistent stimuli. The long pentraxin PTX3 (pentraxin 3) has emerged as a component of humoral innate immunity with essential functions in the resolution of inflammation, but its role during granuloma formation is unknown. Objectives: To evaluate PTX3 as a modulator of pathogenic signals involved in granuloma formation and inflammation in sarcoidosis. Methods: Peripheral blood mononuclear cells obtained from patients with sarcoidosis harboring loss-of-function genetic variants and gene-deleted mice were used to assess the role of PTX3 in experimental models of granuloma formation in vitro and in vivo. The identified mechanisms of granulomatous inflammation were further evaluated in tissue and BAL samples and correlated with the disease course. Measurements and Main Results: We have identified a molecular link between PTX3 deficiency and the pathogenic amplification of complement activation to promote granuloma formation. Mechanistically, PTX3 deficiency licensed the complement component C5a-mediated activation of the metabolic checkpoint kinase mTORC1 (mammalian target of rapamycin complex 1) and the reprogramming of macrophages toward increased glycolysis to foster their proliferation and aggregation. This process sustained the further recruitment of granuloma-promoting immune cells and the associated proinflammatory microenvironment and influenced the clinical course of the disease. Conclusions: Our results identify PTX3 as a pivotal molecule that regulates complement-mediated signaling cues in macrophages to restrain granulomatous inflammation and highlight the therapeutic potential of this signaling axis in targeting granuloma formation in sarcoidosis.


Assuntos
Proteína C-Reativa , Ativação de Macrófagos , Sarcoidose , Componente Amiloide P Sérico , Animais , Camundongos , Proteína C-Reativa/metabolismo , Proteínas do Sistema Complemento , Granuloma , Inflamação , Leucócitos Mononucleares/metabolismo , Componente Amiloide P Sérico/genética , Componente Amiloide P Sérico/metabolismo , Humanos
12.
J Genet Couns ; 30(2): 383-393, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33010199

RESUMO

Bilateral salpingo-oophorectomy (BSO) is a risk management approach with strong evidence of mortality reduction for women with germline mutations in the tumor suppressor genes BRCA1 and BRCA2 (BRCA1/2). Few studies to date have evaluated uptake of BSO in women from diverse racial and ethnic backgrounds who carry BRCA1/2 mutations. The objective of the UPTAKE study was to explore rates and predictors of risk-reducing BSO among Latinas affected and unaffected with breast cancer who had a deleterious BRCA1/2 mutation. We recruited 100 Latina women with deleterious BRCA1/2 mutations from community hospitals, academic health systems, community, and advocacy organizations. Women completed interviews in Spanish or English. We obtained copies of genetic test reports for participants who provided signed medical release. After performing threefold cross-validation LASSO for variable selection, we used multiple logistic regression to identify demographic and clinical predictors of BSO. Among 100 participants, 68 had undergone BSO at the time of interview. Of these 68, 35 were US-born (61% of all US-born participants) and 33 were not (77% of the non-US-born participants). Among Latinas with BRCA1/2 mutations, older age (p = 0.004), personal history of breast cancer (p = 0.003), higher income (p = 0.002), and not having a full-time job (p = 0.027) were identified as variables significantly associated with uptake of BSO. Results suggest a high rate of uptake of risk-reducing BSO among a sample of Latinas with BRCA1/2 mutations living in the US. We document factors associated with BSO uptake in a diverse sample of women. Relevant to genetic counseling, our findings identify possible targets for supporting Latinas' decision-making about BSO following receipt of a positive BRCA1/2 test.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama , Hispânico ou Latino , Neoplasias Ovarianas , Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Feminino , Predisposição Genética para Doença , Hispânico ou Latino/genética , Humanos , Mutação , Neoplasias Ovarianas/etnologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Ovariectomia , Salpingo-Ooforectomia
13.
J Genet Couns ; 30(3): 730-741, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33222313

RESUMO

This paper presents a process evaluation of a culturally targeted narrative video about hereditary breast and ovarian cancer (HBOC) for Latina women at risk for HBOC. Spanish-speaking Latina women at risk for HBOC participated in a single arm study (n = 40). Participants watched the video developed by the authors and responded to surveys. We used mixed methods to assess theoretical constructs that are hypothesized mediators of narrative interventions (i.e., transportation or engagement, identification with characters, emotions) and implementation outcomes (e.g., acceptability). Descriptive statistics summarized theoretical constructs and implementation outcomes. We conducted Mann-Whitney U tests to assess the differences in theoretical and implementation outcomes between participants who were affected versus. unaffected and participants with different levels of education and health literacy. We used the consensual qualitative research framework to analyze qualitative data. Participants' mean age was 47.1 years (SD = 9.48). Most participants were high school graduates or less (62.5%). Acceptability of the video was extremely high (Md = 10.0, IQR = 0.2, scale 1-10). Most (82.5%) suggested video dissemination be through social media. Participants were highly engaged (Md = 5.7, IQR = 1.5, scale 1-7), strongly identified with the main character (Md = 8.7, IQR = 2.6, scale 1-10), and reported experiencing mostly positive emotions (Md = 9.5, IQR = 2.8, scale 1-10). Participants with low health literacy and affected participants reported a significantly higher identification with the main character (p<.05). Qualitative data reinforced the quantitative findings. Women reported gaining knowledge, correcting misconceptions, and feeling empowered. Our culturally targeted video is highly acceptable and targets mechanisms of behavior change for narrative interventions. The video is easily disseminable and can be used as an education tool for patients including affected and unaffected women and patients with different education and health literacy levels. Future studies should test the impact of the video in enhancing genetic counseling and testing uptake.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Neoplasias da Mama/genética , Feminino , Aconselhamento Genético , Hispânico ou Latino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Inquéritos e Questionários
14.
PLoS One ; 15(10): e0240079, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33022015

RESUMO

The Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) pandemic represents a global challenge. SARS-CoV-2's ability to replicate in host cells relies on the action of its non-structural proteins, like its main protease (Mpro). This cysteine protease acts by processing the viruses' precursor polyproteins. As proteases, together with polymerases, are main targets of antiviral drug design, we here have performed biochemical high throughput screening (HTS) with recombinantly expressed SARS-CoV-2 Mpro. A fluorescent assay was used to identify inhibitors in a compound library containing known drugs, bioactive molecules and natural products. These screens led to the identification of 13 inhibitors with IC50 values ranging from 0.2 µM to 23 µM. The screens confirmed several known SARS-CoV Mpro inhibitors as inhibitors of SARS-CoV-2 Mpro, such as the organo-mercuric compounds thimerosal and phenylmercuric acetate. Benzophenone derivatives could also be identified among the most potent screening hits. Additionally, Evans blue, a sulfonic acid-containing dye, could be identified as an Mpro inhibitor. The obtained compounds could be of interest as lead compounds for the development of future SARS-CoV-2 drugs.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/enzimologia , Infecções por Coronavirus/virologia , Avaliação Pré-Clínica de Medicamentos/métodos , Pneumonia Viral/virologia , Inibidores de Proteases/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , COVID-19 , Proteases 3C de Coronavírus , Cisteína Endopeptidases/química , Desenho de Fármacos , Escherichia coli/genética , Concentração Inibidora 50 , Modelos Moleculares , Pandemias , SARS-CoV-2 , Proteínas não Estruturais Virais/química
15.
Rev. chil. nutr ; 47(4): 604-611, ago. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1138595

RESUMO

RESUMEN La relevancia que tiene la medición de la fuerza de agarre (FA) se ha incrementado en los últimos años como marcador del estado nutricional, por su relación con la morbilidad y mortalidad y por su creciente aplicación clínica y epidemiológica. Estudios de FA en adultos jóvenes sanos, revelan que se asocia positivamente con variables antropométricas y de composición corporal, mismas que se vincularían con la promoción de la salud en esta población. El objetivo de este estudio fue determinar la correlación entre la FA con variables de antropometría, composición corporal medida por bioimpedancia eléctrica y con la realización de ejercicio, para evaluar su utilidad como indicador del estado nutricional en jóvenes universitarias. Los resultados mostraron que en las estudiantes universitarias la FA se correlacionó positiva y significativamente con variables antropométricas (talla), y de composición corporal (masa muscular). Los profesionales de la salud requieren promover entre este grupo de población la reducción de los factores de riesgo como la baja fuerza muscular a través de la promoción de un estilo de vida activo y en específico de la realización de ejercicio físico de fuerza.


ABSTRACT The relevance of measuring handgrip strength (HGS) has increased in recent years as a marker of nutritional status, due to its relationship with morbidity and mortality and its increasing clinical and epidemiological application. HGS studies in healthy young adults reveal that it is positively associated with anthropometric and body composition variables, the same indicators used for health promotion among young university students. The objective of this study was to determine the correlation between the HGS with anthropometry variables, body composition measured by electrical bioimpedance and with exercise performance, to evaluate its usefulness as an indicator of nutritional status in college students. The results showed that the HGS of female college students was positively and significantly correlated with anthropometric variables (height), and body composition (muscle mass). Among this population group, health professionals need to promote the reduction of risk factors such as low muscle strength through the promotion of an active lifestyle and, specifically, strength exercises.


Assuntos
Adolescente , Adulto , Composição Corporal , Antropometria , Estado Nutricional , Exercício Físico , Saúde , Fatores de Risco
16.
Nat Commun ; 11(1): 2282, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385235

RESUMO

In response to infection, macrophages adapt their metabolism rapidly to enhance glycolysis and fuel specialized antimicrobial effector functions. Here we show that fungal melanin is an essential molecule required for the metabolic rewiring of macrophages during infection with the fungal pathogen Aspergillus fumigatus. Using pharmacological and genetic tools, we reveal a molecular link between calcium sequestration by melanin inside the phagosome and induction of glycolysis required for efficient innate immune responses. By remodeling the intracellular calcium machinery and impairing signaling via calmodulin, melanin drives an immunometabolic signaling axis towards glycolysis with activation of hypoxia-inducible factor 1 subunit alpha (HIF-1α) and phagosomal recruitment of mammalian target of rapamycin (mTOR). These data demonstrate a pivotal mechanism in the immunometabolic regulation of macrophages during fungal infection and highlight the metabolic repurposing of immune cells as a potential therapeutic strategy.


Assuntos
Aspergillus fumigatus/imunologia , Imunidade , Macrófagos/imunologia , Macrófagos/microbiologia , Melaninas/metabolismo , Fagossomos/metabolismo , Animais , Sinalização do Cálcio , Glucose/metabolismo , Glicólise , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Lactatos/metabolismo , Camundongos Endogâmicos C57BL , Serina-Treonina Quinases TOR/metabolismo , Transcriptoma/genética
17.
Nat Commun ; 11(1): 2395, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409656

RESUMO

Pollen tubes are highly polarized tip-growing cells that depend on cytosolic pH gradients for signaling and growth. Autoinhibited plasma membrane proton (H+) ATPases (AHAs) have been proposed to energize pollen tube growth and underlie cell polarity, however, mechanistic evidence for this is lacking. Here we report that the combined loss of AHA6, AHA8, and AHA9 in Arabidopsis thaliana delays pollen germination and causes pollen tube growth defects, leading to drastically reduced fertility. Pollen tubes of aha mutants had reduced extracellular proton (H+) and anion fluxes, reduced cytosolic pH, reduced tip-to-shank proton gradients, and defects in actin organization. Furthermore, mutant pollen tubes had less negative membrane potentials, substantiating a mechanistic role for AHAs in pollen tube growth through plasma membrane hyperpolarization. Our findings define AHAs as energy transducers that sustain the ionic circuit defining the spatial and temporal profiles of cytosolic pH, thereby controlling downstream pH-dependent mechanisms essential for pollen tube elongation, and thus plant fertility.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Tubo Polínico/crescimento & desenvolvimento , Polinização/fisiologia , ATPases Translocadoras de Prótons/metabolismo , Proteínas de Arabidopsis/genética , Membrana Celular/metabolismo , Polaridade Celular/fisiologia , Citosol/metabolismo , Técnicas de Silenciamento de Genes , Germinação/fisiologia , Concentração de Íons de Hidrogênio , Potenciais da Membrana/fisiologia , Mutação , Plantas Geneticamente Modificadas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , ATPases Translocadoras de Prótons/genética , Análise Espaço-Temporal
18.
J Community Genet ; 11(1): 85-99, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31104207

RESUMO

Disparities for genetic cancer risk assessment (GCRA) for hereditary breast and ovarian cancer (HBOC) persist between Latina and non-Hispanic Whites. There are few tested culturally targeted interventions. We developed a culturally targeted video to enhance GCRA uptake in at-risk Latinas. Interviews with healthcare providers (n = 20) and at-risk Latinas (n = 20) were conducted as formative research to inform the development of the video. Findings from the formative research, health behavior conceptual models, and evidence-based risk communication strategies informed the messages for the script. Then, we conducted a focus group with at-risk Latinas (n = 7) to obtain feedback for final refinement of the script. The final video was piloted for acceptability and potential dissemination in a sample of Latino community health workers (CHWs) (n = 31). Providers and at-risk Latinas suggested using simple language and visual aids to facilitate comprehension. Participants in the focus group identified areas for further clarification (e.g., cost). The result was an 18-min video that illustrates "Rosa's" story. Rosa learns about HBOC risk factors and overcomes barriers to attend genetic counseling. CHWs reported high overall satisfaction with the video (M = 9.61, SD = .88, range 1-10). A culturally targeted video has the potential to reach underserved populations with low literacy and English proficiency.

19.
J Genet Couns ; 29(4): 505-517, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31883202

RESUMO

Disparities in genetic cancer risk assessment (GCRA) uptake persist between Latinas and Non-Hispanic Whites. This study utilized a mental model approach to interview 20 Latinas (10 affected, 10 unaffected) at increased risk for hereditary breast and ovarian cancer (HBOC). Participants were asked about their knowledge and perceptions of GCRA, HBOC, risk, benefits, motivators, barriers, challenges, and experiences with GCRA. Using the Consensual Qualitative Analysis Framework, two authors independently coded the interviews and applied the final codes upon consensus. Additionally, interviews were coded to identify whether participants spontaneously brought up certain topics without a prompt. Findings identified multiple barriers and facilitators to GCRA uptake in this population, including patient level psychosocial/cultural factors (e.g., limited knowledge, worry about relatives' risk) and healthcare system factors (e.g., receiving no referrals). There were notable differences in awareness and knowledge between affected and unaffected women (e.g., genetic testing awareness), as well as knowledge gaps that were evident in both groups (e.g., age of diagnosis as a risk factor). To reduce disparities in GCRA uptake, interventions should address identified facilitators and barriers. Differences in knowledge and awareness between affected and unaffected women support the development of targeted interventions that address specific knowledge gaps. This study was registered in ClinicalTrials.gov (NCT03075540) by Alejandra Hurtado de Mendoza, Ph.D.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Testes Genéticos , Hispânico ou Latino/psicologia , Neoplasias Ovarianas/genética , Adulto , Estudos de Casos e Controles , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Conhecimento , Pessoa de Meia-Idade , Motivação , Medição de Risco
20.
Digestion ; 101(2): 137-143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30759428

RESUMO

BACKGROUND: Chronic pancreatitis (CP), pancreatic cancer (PCa), and autoimmune pancreatitis (AIP) often present as a pancreatic mass. Accurate diagnosis is not always possible; up to 8% of surgical procedures are performed in benign pancreatic masses presumed to be malignant. OBJECTIVES: We aimed to compare clinical and imaging characteristics of resected focal type 2 AIP, CP, and PCa and identify factors that could improve preoperative differential diagnosis. METHODS: Charts from patients that underwent pancreatic resection under suspicion of PCa between 2000 and 2014 were reviewed. Clinical and imaging data were recorded. Subjects were grouped as type 2 AIP, CP, and PCa. RESULTS: We included 79 cases; 41 men, mean age of 57.3 years/old ± 15.6 SD. Pathology report was type 2 AIP (20%), CP (10%), and PCa (70%). According to international consensus criteria for AIP 11 cases were deemed probable type 2 and 5 as unspecific pancreatic mass. A nondilated main pancreatic duct (MPD) was associated with AIP (OR 9.3; 95% CI 3.05-28.7), p < 0.001; obstructive jaundice (OR 28.5; 95% CI 8.18-79.5); and a dilated MPD (OR 5.21; 95% CI 1.9-14.6) suggested malignancy. CONCLUSIONS: In the setting of undetermined pancreatic focal mass, a nondilated MPD suggests the diagnosis of type 2 AIP.


Assuntos
Pancreatite Autoimune/diagnóstico , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico , Pancreatite Crônica/diagnóstico , Idoso , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/patologia , Ductos Pancreáticos/patologia , Estudos Retrospectivos
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