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1.
N Engl J Med ; 386(16): 1505-1518, 2022 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-35213105

RESUMO

BACKGROUND: Black and Latinx patients bear a disproportionate burden of asthma. Efforts to reduce the disproportionate morbidity have been mostly unsuccessful, and guideline recommendations have not been based on studies in these populations. METHODS: In this pragmatic, open-label trial, we randomly assigned Black and Latinx adults with moderate-to-severe asthma to use a patient-activated, reliever-triggered inhaled glucocorticoid strategy (beclomethasone dipropionate, 80 µg) plus usual care (intervention) or to continue usual care. Participants had one instructional visit followed by 15 monthly questionnaires. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included monthly asthma control as measured with the Asthma Control Test (ACT; range, 5 [poor] to 25 [complete control]), quality of life as measured with the Asthma Symptom Utility Index (ASUI; range, 0 to 1, with lower scores indicating greater impairment), and participant-reported missed days of work, school, or usual activities. Safety was also assessed. RESULTS: Of 1201 adults (603 Black and 598 Latinx), 600 were assigned to the intervention group and 601 to the usual-care group. The annualized rate of severe asthma exacerbations was 0.69 (95% confidence interval [CI], 0.61 to 0.78) in the intervention group and 0.82 (95% CI, 0.73 to 0.92) in the usual-care group (hazard ratio, 0.85; 95% CI, 0.72 to 0.999; P = 0.048). ACT scores increased by 3.4 points (95% CI, 3.1 to 3.6) in the intervention group and by 2.5 points (95% CI, 2.3 to 2.8) in the usual-care group (difference, 0.9; 95% CI, 0.5 to 1.2); ASUI scores increased by 0.12 points (95% CI, 0.11 to 0.13) and 0.08 points (95% CI, 0.07 to 0.09), respectively (difference, 0.04; 95% CI, 0.02 to 0.05). The annualized rate of missed days was 13.4 in the intervention group and 16.8 in the usual-care group (rate ratio, 0.80; 95% CI, 0.67 to 0.95). Serious adverse events occurred in 12.2% of the participants, with an even distribution between the groups. CONCLUSIONS: Among Black and Latinx adults with moderate-to-severe asthma, provision of an inhaled glucocorticoid and one-time instruction on its use, added to usual care, led to a lower rate of severe asthma exacerbations. (Funded by the Patient-Centered Outcomes Research Institute and others; PREPARE ClinicalTrials.gov number, NCT02995733.).


Assuntos
Antiasmáticos , Asma , Beclometasona , Negro ou Afro-Americano , Glucocorticoides , Hispânico ou Latino , Administração por Inalação , Adulto , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/etnologia , Beclometasona/administração & dosagem , Beclometasona/efeitos adversos , Beclometasona/uso terapêutico , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Qualidade de Vida , Inquéritos e Questionários , Exacerbação dos Sintomas
2.
J Allergy Clin Immunol ; 153(2): 408-417, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38000696

RESUMO

BACKGROUND: Black adults are disproportionately affected by asthma and are often considered a homogeneous group in research studies despite cultural and ancestral differences. OBJECTIVE: We sought to determine if asthma morbidity differs across adults in Black ethnic subgroups. METHODS: Adults with moderate-severe asthma were recruited across the continental United States and Puerto Rico for the PREPARE (PeRson EmPowered Asthma RElief) trial. Using self-identifications, we categorized multiethnic Black (ME/B) participants (n = 226) as Black Latinx participants (n = 146) or Caribbean, continental African, or other Black participants (n = 80). African American (AA/B) participants (n = 518) were categorized as Black participants who identified their ethnicity as being American. Baseline characteristics and retrospective asthma morbidity measures (self-reported exacerbations requiring systemic corticosteroids [SCs], emergency department/urgent care [ED/UC] visits, hospitalizations) were compared across subgroups using multivariable regression. RESULTS: Compared with AA/B participants, ME/B participants were more likely to be younger, residing in the US Northeast, and Spanish speaking and to have lower body mass index, health literacy, and <1 comorbidity, but higher blood eosinophil counts. In a multivariable analysis, ME/B participants were significantly more likely to have ED/UC visits (incidence rate ratio [IRR] = 1.34, 95% CI = 1.04-1.72) and SC use (IRR = 1.27, 95% CI = 1.00-1.62) for asthma than AA/B participants. Of the ME/B subgroups, Puerto Rican Black Latinx participants (n = 120) were significantly more likely to have ED/UC visits (IRR = 1.64, 95% CI = 1.22-2.21) and SC use for asthma (IRR = 1.43, 95% CI = 1.06-1.92) than AA/B participants. There were no significant differences in hospitalizations for asthma among subgroups. CONCLUSIONS: ME/B adults, specifically Puerto Rican Black Latinx adults, have higher risk of ED/UC visits and SC use for asthma than other Black subgroups.


Assuntos
Asma , População Negra , Adulto , Humanos , Asma/complicações , Asma/epidemiologia , Asma/etnologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Hispânico ou Latino/etnologia , Hispânico ou Latino/estatística & dados numéricos , Morbidade , Estudos Retrospectivos , Estados Unidos/epidemiologia , Porto Rico/etnologia , Negro ou Afro-Americano/etnologia , Negro ou Afro-Americano/estatística & dados numéricos , População do Caribe/estatística & dados numéricos , África/etnologia , População Negra/etnologia , População Negra/estatística & dados numéricos
3.
Ann Allergy Asthma Immunol ; 131(5): 614-627.e2, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37490981

RESUMO

BACKGROUND: Black and Latinx adults experience disproportionate asthma-related morbidity and limited specialty care access. The severe acute respiratory syndrome coronavirus 2 pandemic expanded telehealth use. OBJECTIVE: To evaluate visit type (telehealth [TH] vs in-person [IP]) preferences and the impact of visit type on asthma outcomes among Black and Latinx adults with moderate-to-severe asthma. METHODS: For this PREPARE trial ancillary study, visit type preference was surveyed by e-mail or telephone post-trial. Emergency medical record data on visit types and asthma outcomes were available for a subset (March 2020 to April 2021). Characteristics associated with visit type preferences, and relationships between visit type and asthma outcomes (control [Asthma Control Test] and asthma-related quality of life [Asthma Symptom Utility Index]), were tested using multivariable regression. RESULTS: A total of 866 participants consented to be surveyed, with 847 respondents. Among the participants with asthma care experience with both visit types, 42.0% preferred TH for regular checkups, which associated with employment (odds ratio [OR] = 1.61; 95% confidence interval [CI], 1.09-2.39; P = .02), lower asthma medication adherence (OR = 1.06; 95% CI, 1.01-1.11; P = .03), and having more historical emergency department and urgent care asthma visits (OR = 1.10 for each additional visit; 95% CI, 1.02-1.18; P = .02), after adjustment. Emergency medical record data were available for 98 participants (62 TH, 36 IP). Those with TH visits were more likely Latinx, from the Southwest, employed, using inhaled corticosteroid-only controller therapy, with lower body mass index, and lower self-reported asthma medication adherence vs those with IP visits only. Both groups had comparable Asthma Control Test (18.4 vs 18.9, P = .52) and Asthma Symptom Utility Index (0.79 vs 0.84, P = .16) scores after adjustment. CONCLUSION: TH may be similarly efficacious as and often preferred over IP among Black and Latinx adults with moderate-to-severe asthma, especially for regular checkups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02995733.


Assuntos
Asma , Preferência do Paciente , Telemedicina , Adulto , Humanos , Corticosteroides/uso terapêutico , Asma/tratamento farmacológico , Asma/diagnóstico , Hispânico ou Latino , Qualidade de Vida , Negro ou Afro-Americano
4.
J Allergy Clin Immunol ; 150(5): 1106-1113.e10, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35779669

RESUMO

BACKGROUND: Hispanic/Latinx (HL) ethnicity encompasses racially and culturally diverse subgroups. Studies suggest that Puerto Ricans (PR) may bear greater asthma-related morbidity than Mexicans, but these were conducted in children or had limited clinical characterization. OBJECTIVES: This study sought to determine whether disparities in asthma morbidity exist among HL adult subgroups. METHODS: Adults with moderate-severe asthma were recruited from US clinics, including from Puerto Rico, for the Person Empowered Asthma Relief (PREPARE) trial. Considering the shared heritage between PR and other Caribbean HL (Cubans and Dominicans [C&D]), the investigators compared baseline self-reported clinical characteristics between Caribbean HL (CHL) (PR and C&D: n = 457) and other HLs (OHL) (Mexicans, Spaniards, Central/South Americans; n = 141), and between CHL subgroups (C&D [n = 56] and PR [n = 401]). This study compared asthma morbidity measures (self-reported exacerbations requiring systemic corticosteroids, emergency department/urgent care (ED/UC) visits, hospitalizations, health care utilization) through negative binomial regression. RESULTS: CHL compared to OHL were similar in age, body mass index, poverty status, blood eosinophils, and fractional exhaled nitric oxide but were prescribed more asthma controller therapies. Relative to OHL, CHL had significantly increased odds of asthma exacerbations (odds ratio [OR]: 1.84; 95% CI: 1.4-2.4), ED/UC visits (OR: 1.88; 95% CI: 1.4-2.5), hospitalization (OR: 1.98; 95% CI: 1.06-3.7), and health care utilization (OR: 1.91; 95% CI: 1.44-2.53). Of the CHL subgroups, PR had significantly increased odds of asthma exacerbations, ED/UC visits, hospitalizations, and health care utilization compared to OHL, whereas C&D only had increased odds of exacerbations compared to OHL. PR compared to C&D had greater odds of ED/UC and health care utilization. CONCLUSIONS: CHL adults, compared with OHL, adults reported nearly twice the asthma morbidity; these differences are primarily driven by PR. Novel interventions are needed to reduce morbidity in this highly impacted population.


Assuntos
Asma , Adulto , Criança , Humanos , Asma/tratamento farmacológico , Asma/mortalidade , Etnicidade , Morbidade , Porto Rico/epidemiologia
5.
J Allergy Clin Immunol ; 150(4): 841-849.e4, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35597370

RESUMO

BACKGROUND: Asthma disproportionately affects African American/Black (AA/B) and Hispanic/Latinx (H/L) patients and individuals with low socioeconomic status (SES), but the relationship between SES and asthma morbidity within these racial/ethnic groups is inadequately understood. OBJECTIVE: To determine the relationship between SES and asthma morbidity among AA/B and H/L adults with moderate to severe asthma using multidomain SES frameworks and mediation analyses. METHODS: We analyzed enrollment data from the PeRson EmPowered Asthma RElief randomized trial, evaluating inhaled corticosteroid supplementation to rescue therapy. We tested for direct and indirect relationships between SES and asthma morbidity using structural equation models. For SES, we used a latent variable defined by poverty, education, and unemployment. For asthma morbidity, we used self-reported asthma exacerbations in the year before enrollment (corticosteroid bursts, emergency room/urgent care visits, or hospitalizations), and Asthma Control Test scores. We tested for mediation via health literacy, perceived stress, and self-reported discrimination. All models adjusted for age, sex, body mass index, ethnicity, and comorbidities. RESULTS: Among 990 AA/B and H/L adults, low SES (latent variable) was directly associated with hospitalizations (ß = 0.24) and worse Asthma Control Test scores (ß = 0.20). Stress partially mediated the relationship between SES and increased emergency room/urgent care visits and worse asthma control (ß = 0.03 and = 0.05, respectively). Individual SES domains were directly associated with asthma morbidity. Stress mediated indirect associations between low educational attainment and unemployment with worse asthma control (ß = 0.05 and = 0.06, respectively). CONCLUSIONS: Lower SES is directly, and indirectly through stress, associated with asthma morbidity among AA/B and H/L adults. Identification of stressors and relevant management strategies may lessen asthma-related morbidity among these populations.


Assuntos
Asma , Classe Social , Corticosteroides , Adulto , Negro ou Afro-Americano , Asma/tratamento farmacológico , Asma/epidemiologia , Humanos , Morbidade
6.
Int J Mol Sci ; 24(9)2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37175690

RESUMO

Under low oxygen conditions (hypoxia), cells activate survival mechanisms including metabolic changes and angiogenesis, which are regulated by HIF-1. The estrogen-related receptor alpha (ERRα) is a transcription factor with important roles in the regulation of cellular metabolism that is overexpressed in hypoxia, suggesting that it plays a role in cell survival in this condition. This review enumerates and analyses the recent evidence that points to the role of ERRα as a regulator of hypoxic genes, both in cooperation with HIF-1 and through HIF-1- independent mechanisms, in invertebrate and vertebrate models and in physiological and pathological scenarios. ERRα's functions during hypoxia include two mechanisms: (1) direct ERRα/HIF-1 interaction, which enhances HIF-1's transcriptional activity; and (2) transcriptional activation by ERRα of genes that are classical HIF-1 targets, such as VEGF or glycolytic enzymes. ERRα is thus gaining recognition for its prominent role in the hypoxia response, both in the presence and absence of HIF-1. In some models, ERRα prepares cells for hypoxia, with important clinical/therapeutic implications.


Assuntos
Neoplasias , Fatores de Transcrição , Humanos , Hipóxia Celular , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias/genética , Receptores de Estrogênio/metabolismo , Fatores de Transcrição/metabolismo , Receptor ERRalfa Relacionado ao Estrogênio
7.
Gac Med Mex ; 157(1): 84-89, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34125824

RESUMO

The first cases of COVID-19, caused by the virus called SARS-CoV-2, were recorded in Wuhan, China, in December 2019; however, its transmission ability caused for the infection to be practically present throughout the world six months later. The origin of the virus appears to be zoonotic; it has been proposed that it comes from a bat and that it may have had an intermediate host that led to its introduction in the human population. SARS-CoV-2 is an enveloped virus, with a positive single-stranded RNA genome, and it binds to the angiotensin-converting enzyme, present in susceptible cells, to infect the human respiratory system. Although other coronaviruses have been previously known, they have not had the same impact, and, therefore, research on pharmacological treatments is not sufficiently developed to face the current challenge. Almost since the beginning of the epidemic, several molecules have been proposed for the treatment of infection; however, there is not yet a drug available with sufficient effectiveness for treatment. This review describes SARS-CoV-2 main characteristics, its replicative cycle, its possible origin and some advances in the development of antiviral treatments.


Los primeros casos de COVID-19, causada por el virus denominado SARS-CoV-2, se registraron en Wuhan, China, en diciembre de 2019; sin embargo, su capacidad de transmisión ocasionó que seis meses después la infección prácticamente estuviera presente en todo el mundo. El origen del virus parece ser zoonótico; se propone que proviene del murciélago y podría haber tenido un hospedero intermediario que llevó a su introducción en la población humana. SARS-CoV-2 es un virus envuelto, con genoma de ARN de cadena sencilla en sentido positivo y se ancla a la enzima convertidora de angiotensina, presente en las células susceptibles para infectar el sistema respiratorio de los humanos. Aunque previamente se han conocido otros coronavirus, no han tenido el mismo impacto, por lo que la investigación en tratamientos farmacológicos no tiene el desarrollo suficiente para afrontar el reto actual. Casi desde el comienzo de la epidemia se han propuesto moléculas para el tratamiento de la infección, sin embargo, aún no se cuenta con un fármaco con suficiente efectividad terapéutica. En esta revisión se describen las características principales de SARS-CoV-2, su ciclo replicativo, su posible origen y algunos avances en el desarrollo de tratamientos antivirales.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19/virologia , SARS-CoV-2/fisiologia , SARS-CoV-2/ultraestrutura , Humanos
8.
J Nutr ; 150(2): 249-255, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31529091

RESUMO

BACKGROUND: Choline, an essential nutrient, is required for cell membranes, lipoprotein secretion, and methyl-group metabolism. Recently, it has been proposed that excess dietary choline consumption is metabolized to trimethylamine (TMA) by the gut microbiota; TMA is then oxidized to trimethylamine N-oxide (TMAO) in the liver. Epidemiological studies have clearly shown a positive correlation between plasma TMAO concentrations and cardiovascular events. Furthermore, some studies have shown an association between excess dietary choline, plasma TMAO concentrations, and atherosclerotic lesion size in apoE knockout (Apoe-/-) mice. OBJECTIVE: The aim of this study was to further investigate the relation between dietary choline and atherosclerosis in 2 atherogenic mouse models, the LDL receptor knockout (Ldlr-/-) and Apoe-/- mice. METHODS: Six feeding trials were performed in Ldlr-/- (40% high-fat diet) and Apoe-/- (unpurified diet) male mice, aged 8-10 wk. Mice randomly received control diet (0.1% choline), or choline- (1% choline), betaine- (0.1% choline and 0.9% betaine), or TMAO- (0.1% choline and 0.12% or 0.2% TMAO) supplemented diet for ≤28 wk. After the dietary intervention, the animals were killed and tissues and blood collected. Aortic atherosclerotic plaque area, plasma lipids, and choline metabolites were quantified. RESULTS: In Ldlr-/- mice, dietary supplementation for 8 wk with choline or TMAO increased plasma TMAO concentrations by 1.6- and 4-fold, respectively. After 16 wk, there was a 2-fold increase in plasma TMAO after dietary TMAO supplementation. In Apoe-/- mice, dietary supplementation with choline, betaine, or TMAO for 12 wk did not increase plasma TMAO concentrations. However, choline and TMAO supplementation for 28 wk significantly increased plasma TMAO concentrations by 1.8- and 1.5-fold, respectively. Contrary to predictions, atherosclerotic lesion size was not altered by any of the dietary interventions, irrespective of mouse model. CONCLUSIONS: In our study, high intakes of dietary choline or TMAO supplementation did not influence atherosclerosis development in Ldlr-/- or Apoe-/- male mice.


Assuntos
Apolipoproteínas E/genética , Aterosclerose/genética , Aterosclerose/prevenção & controle , Colina/administração & dosagem , Suplementos Nutricionais , Metilaminas/administração & dosagem , Receptores de LDL/genética , Animais , Aterosclerose/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
9.
Int J Mol Sci ; 21(6)2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32183317

RESUMO

Pesticides are used extensively in agriculture, and their residues in food must be monitored to prevent toxicity. The most abundant protein in cow's milk, ß-lactoglobulin (BLG), shows high affinity for diverse hydrophobic ligands in its central binding pocket, called the calyx. Several of the most frequently used pesticides are hydrophobic. To predict if BLG may be an unintended carrier for pesticides, we tested its ability to bind 555 pesticides and their isomers, for a total of 889 compounds, in a rigid docking screen. We focused on the analysis of 60 unique molecules belonging to the five pesticide classes defined by the World Health Organization, that docked into BLG's calyx with ΔGs ranging from -8.2 to -12 kcal mol-1, chosen by statistical criteria. These "potential ligands" were further analyzed using molecular dynamic simulations, and the binding energies were explored with Molecular Mechanics/Generalized Born/Surface Area (MMGBSA). Hydrophobic pyrethroid insecticides, like cypermethrin, were found to bind as deeply and tightly into the calyx as BLG's natural ligand, palmitate; while polar compounds, like paraquat, were expelled. Our results suggest that BLG could be a carrier for pesticides, in particular for pyrethroid insecticides, allowing for their accumulation in cow's milk beyond their solubility restrictions. This analysis opens possibilities for pesticide biosensor design based on BLG.


Assuntos
Lactoglobulinas/metabolismo , Leite/química , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/metabolismo , Animais , Bovinos , Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Piretrinas/metabolismo
10.
J Mol Evol ; 87(9-10): 327-342, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31701178

RESUMO

Twenty-nine DNA regions of plastid origin have been previously identified in the mitochondrial genome of Cucurbita pepo (pumpkin; Cucurbitaceae). Four of these regions harbor homolog sequences of rbcL, matK, rpl20-rps12 and trnL-trnF, which are widely used as molecular markers for phylogenetic and phylogeographic studies. We extracted the mitochondrial copies of these regions based on the mitochondrial genome of C. pepo and, along with published sequences for these plastome markers from 13 Cucurbita taxa, we performed phylogenetic molecular analyses to identify inter-organellar transfer events in the Cucurbita phylogeny and changes in their nucleotide substitution rates. Phylogenetic reconstruction and tree selection tests suggest that rpl20 and rbcL mitochondrial paralogs arose before Cucurbita diversification whereas the mitochondrial matK and trnL-trnF paralogs emerged most probably later, in the mesophytic Cucurbita clade. Nucleotide substitution rates increased one order of magnitude in all the mitochondrial paralogs compared to their original plastid sequences. Additionally, mitochondrial trnL-trnF sequences obtained by PCR from nine Cucurbita taxa revealed higher nucleotide diversity in the mitochondrial than in the plastid copies, likely related to the higher nucleotide substitution rates in the mitochondrial region and loss of functional constraints in its tRNA genes.


Assuntos
Cucurbita/genética , Genoma Mitocondrial/genética , Plastídeos/genética , Evolução Biológica , Evolução Molecular , Genes de Plantas/genética , Genoma de Planta/genética , Mitocôndrias/genética , Filogenia , Análise de Sequência de DNA
11.
Gac Med Mex ; 155(3): 276-283, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31219465

RESUMO

Neurodegenerative diseases are a group of heterogeneous diseases characterized by a gradual, progressive and selective decrease in nervous system functions. The etiology of these pathologies remains unknown; however, mitochondrial function has been proposed as a common factor that could be involved in the establishment of these diseases, owing to the high energy requirement neurons have in order to carry out their physiological functions. Mitochondria are extremely dynamic organelles that can change their morphology and function in response to different physiological stimuli and, for this reason, mitochondrial dynamics have started being studied as one of cell survival main regulators. This event comprises different processes, such as the generation of new mitochondria and their elimination when they are no longer functional, as well as mitochondrial fusion and fission processes and the traffic of these organelles within the cellular environment. All these processes are highly regulated, and their main purpose is optimal functionality of mitochondria and cellular homeostasis.


Las enfermedades neurodegenerativas son un grupo heterogéneo caracterizado por la disminución gradual, progresiva y selectiva de las funciones del sistema nervioso. La etiología de estas patologías aún se desconoce, sin embargo, se ha propuesto que la función mitocondrial pudiese estar participando en el establecimiento de estas enfermedades, debido al alto requerimiento energético que tienen las neuronas para realizar sus funciones fisiológicas. La mitocondria es un organelo dinámico que puede cambiar su morfología y función en respuesta a diferentes estímulos fisiológicos, por ello se ha empezado a estudiar a la dinámica mitocondrial como uno de los principales reguladores de la supervivencia celular. Este evento comprende diferentes procesos como la generación de nuevas mitocondrias y su eliminación cuando ya no son funcionales, así como los procesos de fusión y fisión mitocondrial y el tráfico de estos organelos en el entorno celular. Todos estos procesos son altamente regulados y tienen como finalidad la óptima funcionalidad de la mitocondria y la homeostasis celular.


Assuntos
Mitocôndrias/patologia , Doenças Neurodegenerativas/fisiopatologia , Animais , Sobrevivência Celular/fisiologia , Homeostase , Humanos , Neurônios/metabolismo
12.
Tumour Biol ; 39(5): 1010428317698391, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28468591

RESUMO

Cancer is among the leading causes of death worldwide, and the number of new cases continues to rise. Despite recent advances in diagnosis and therapeutic strategies, millions of cancer-related deaths occur, indicating the need for better therapies and diagnostic strategies. Mitochondria and metabolic alterations have been recognized as important for cancer progression. However, a more precise understanding of how to manipulate mitochondria-related processes for cancer therapy remains to be established. Mitochondria are highly dynamic organelles which continually fuse and divide in response to diverse stimuli. Participation in the aforementioned processes requires a precise regulation at many levels that allows the cell to couple mitochondrial activity to nutrient availability, biosynthetic demands, proliferation rates, and external stimuli. The many functions of these organelles are intimately linked to their morphology. Recent evidence suggests an important link between mitochondrial morphology and disease, including neurodegenerative, inflammatory diseases and cancer. Here, we review recent advances in the understanding of mitochondrial dynamics with a special focus on its relationship to tumor progression.


Assuntos
Mitocôndrias/genética , Dinâmica Mitocondrial/genética , Neoplasias/genética , Humanos , Mitocôndrias/metabolismo , Neoplasias/patologia
13.
Sensors (Basel) ; 14(9): 15880-99, 2014 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-25166501

RESUMO

This paper presents a new micropower analog lock-in amplifier (LIA) suitable for battery-operated applications thanks to its reduced size and power consumption as well as its operation with single-supply voltage. The proposed LIA was designed in a 0.18 µm CMOS process with a single supply voltage of 1.8 V. Experimental results show a variable DC gain ranging from 24.7 to 42 dB, power consumption of 417 µW and integration area of 0.013 mm2. The LIA performance was demonstrated by measuring carbon monoxide concentrations as low as 1 ppm in dry N2. The experimental results show that the response to CO of the sensing system can be considerably improved by means of the proposed LIA.


Assuntos
Amplificadores Eletrônicos , Dióxido de Carbono/análise , Condutometria/instrumentação , Fontes de Energia Elétrica , Gases/análise , Transferência de Energia , Desenho de Equipamento , Análise de Falha de Equipamento , Integração de Sistemas
14.
Vaccines (Basel) ; 11(11)2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-38006008

RESUMO

During 2020-2023, Mexico had a large COVID-19 emergency with >331,000 adult deaths and one of the highest excess mortalities worldwide. Age at COVID-19 death has been lower in Mexico than in high-income countries, presumably because of the young demographics and high prevalence of chronic metabolic diseases in young and middle-aged adults. SARS-CoV-2 vaccination covered 85% of adults with at least one dose and 50% with booster(s) up to April 2022. No new vaccination efforts or updated boosters were introduced until October 2023; thus, we explored the public health impact of massive SARS-CoV-2 vaccination against ancestral strains and asked whether their real-world protection has persisted through time. We compared three periods with respect to vaccine roll-outs: before, during and after vaccine introduction in a national retrospective cohort of >7.5 million COVID-19 cases. The main findings were that after vaccination, COVID-19 mortality decreased, age at COVID-19 death increased by 5-10 years, both in populations with and without comorbidities; obesity stopped being a significant risk factor for COVID-19 death and protection against severe disease persisted for a year after boosters, including at ages 60-79 and 80+. Middle-aged adults had the highest protection from vaccines/hybrid immunity and they more than halved their proportions in COVID-19 deaths.

15.
Viruses ; 15(6)2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37376630

RESUMO

Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and hepatitis B virus (HBV) can be transmitted by blood transfusion. Most transmission occurs during the acute viremic phase (AVP), before antibody development. To reduce transmission risk, individual donor nucleic acid testing (ID-NAT) is used. In Puebla, Mexico, serological tests and ID-NAT have been applied to screen blood donors and detect individuals in AVP. In the present study, 106,125 blood donors' data in two periods (2012-2015 and 2017-2019) were analyzed. The residual risk (RR) values were calculated considering ID-NAT results. The RR for HIV was 14 in 1 million donations or 1 in 71,428, the RR for HVC was 6.8 in 1 million donations or 1 in 147,058 and, for HBV, it was 156 in 1 million donations, or 1 in 6410. Previously, it was predicted that the transmission RR of these viruses would be reduced in Mexico through better screening with NAT. The use of ID-NAT has, indeed, increased the safety of blood reserves for HIV and HCV. However, more research is needed to determine why the residual risk of HBV did not decrease as much over the study period. ID-NAT is an important complementary tool for blood donor screening that should be implemented.


Assuntos
Infecções por HIV , HIV-1 , Hepatite B , Hepatite C , Humanos , Vírus da Hepatite B/genética , Hepacivirus/genética , Bancos de Sangue , México/epidemiologia , Centros de Atenção Terciária , HIV-1/genética , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Doadores de Sangue , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Viremia/diagnóstico , Doença Iatrogênica , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Técnicas de Amplificação de Ácido Nucleico/métodos
16.
Arch Med Res ; 54(3): 197-210, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36990888

RESUMO

BACKGROUND AND AIMS: Mexico is among the countries with the highest estimated excess mortality rates due to the COVID-19 pandemic, with more than half of reported deaths occurring in adults younger than 65 years old. Although this behavior is presumably influenced by the young demographics and the high prevalence of metabolic diseases, the underlying mechanisms have not been determined. METHODS: The age-stratified case fatality rate (CFR) was estimated in a prospective cohort with 245 hospitalized COVID-19 cases, followed through time, for the period October 2020-September 2021. Cellular and inflammatory parameters were exhaustively investigated in blood samples by laboratory test, multiparametric flow cytometry and multiplex immunoassays. RESULTS: The CFR was 35.51%, with 55.2% of deaths recorded in middle-aged adults. On admission, hematological cell differentiation, physiological stress and inflammation parameters, showed distinctive profiles of potential prognostic value in patients under 65 at 7 days follow-up. Pre-existing metabolic conditions were identified as risk factors of poor outcomes. Chronic kidney disease (CKD), as single comorbidity or in combination with diabetes, had the highest risk for COVID-19 fatality. Of note, fatal outcomes in middle-aged patients were marked from admission by an inflammatory landscape and emergency myeloid hematopoiesis at the expense of functional lymphoid innate cells for antiviral immunosurveillance, including NK and dendritic cell subsets. CONCLUSIONS: Comorbidities increased the development of imbalanced myeloid phenotype, rendering middle-aged individuals unable to effectively control SARS-CoV-2. A predictive signature of high-risk outcomes at day 7 of disease evolution as a tool for their early stratification in vulnerable populations is proposed.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Pandemias , Estudos Prospectivos , Comorbidade , Hematopoese
17.
Rev Med Chil ; 140(12): 1571-9, 2012 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-23677230

RESUMO

BACKGROUND: The Chilean population has inadequate lifestyles and high prevalence of chronic diseases. AIM: To analyze eating behaviors, nutritional status and history of previous diseases, in students of higher education. MATERIAL AND METHODS: Cross-sectional study in students of 54 higher education centers across the country. They answered a survey about dietary habits, physical activity, smoking, previous diseases and opinion of their nutritional condition. Weight and height were measured under standardized conditions and nutritional status classified according to body mass index. RESULTS: We studied 6,823 students aged 17 to 29 years. Forty seven percent did not have breakfast and 35% did not have lunch every day. A low proportion had a daily consumption of vegetables (51.2%), fruits (39.4%) and dairy products (57.5%). There was a high frequency of soft drinks, chips, cakes and sweets consumption. Seventy six percent were sedentary, 40.3% smokers and 27.4% overweight or obese. The latter had a significantly higher frequency of diabetes, hypertension and hypercholesterolemia. There was a poor agreement between actual nutritional status and self-perception, especially in males (Kappa index 0.38). Recipients of a food scholarship provided by the Ministry of Education ate lunch usually with a higher frequency (p < 0.05). CONCLUSIONS: A high prevalence of inadequate eating and physical activity patterns in these young subjects with good educational level was observed. The food scholarship has some positive effects, although differences in socioeconomic levels limited comparisons.


Assuntos
Qualidade dos Alimentos , Estilo de Vida , Atividade Motora/fisiologia , Estado Nutricional , Autoimagem , Fumar/epidemiologia , Estudantes/estatística & dados numéricos , Adolescente , Adulto , Análise de Variância , Índice de Massa Corporal , Chile/epidemiologia , Estudos Transversais , Escolaridade , Bolsas de Estudo/estatística & dados numéricos , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Universidades , Adulto Jovem
18.
Rev Med Inst Mex Seguro Soc ; 60(6): 599-601, 2022 Oct 25.
Artigo em Espanhol | MEDLINE | ID: mdl-36282675

RESUMO

The Revista Médica del IMSS faces the challenge of maintaining the visibility of its articles within the science communication process through indexing in bibliographic databases that make the scientific articles published available to readers, thanks to automation and constant development of information search and retrieval systems. Indexing represents the main means by which a reader will consult your articles regardless of their geographic location, their educational specialization, their affiliation, and even their native language. Likewise, it allows the generation of bibliometric indicators, which are used to evaluate scientific production.


La Revista Médica del IMSS enfrenta el reto de mantener la visibilidad de sus artículos dentro del proceso de comunicación de la ciencia a través de la indización en bases de datos bibliográficas, las cuales ponen al alcance de los lectores los artículos científicos que publica gracias a la automatización y desarrollo constante de los sistemas de búsqueda y recuperación de información. La indización representa el principal medio por el cual un lector consultará sus artículos, independientemente de su ubicación geográfica, la especialización de su formación, su afiliación e, incluso, su idioma natal. Así también, permite la generación de indicadores bibliométricos, los cuales son usados para evaluar la producción científica.


Assuntos
Bibliometria , Comunicação , Humanos , Bases de Dados Bibliográficas
19.
Front Public Health ; 10: 1010256, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36176536

RESUMO

Mexico, one of the countries severely affected by COVID-19, accumulated more than 5. 1 all-cause excess deaths/1,000 inhabitants and 2.5 COVID-19 confirmed deaths/1,000 inhabitants, in 2 years. In this scenario of high SARS-CoV-2 circulation, we analyzed the effectiveness of the country's vaccination strategy that used 7 different vaccines from around the world, and focused on vaccinating the oldest population first. We analyzed the national dataset published by Mexican health authorities, as a retrospective cohort, separating cases, hospitalizations, deaths and excess deaths by wave and age group. We explored if the vaccination strategy was effective to limit severe COVID-19 during the active outbreaks caused by Delta and Omicron variants. Vaccination of the eldest third of the population reduced COVID-19 hospitalizations, deaths and excess deaths by 46-55% in the third wave driven by Delta SARS-CoV-2. These adverse outcomes dropped 74-85% by the fourth wave driven by Omicron, when all adults had access to vaccines. Vaccine access for the pregnant resulted in 85-90% decrease in COVID-19 fatalities in pregnant individuals and 80% decrease in infants 0 years old by the Omicron wave. In contrast, in the rest of the pediatric population that did not access vaccination before the period analyzed, COVID-19 hospitalizations increased >40% during the Delta and Omicron waves. Our analysis suggests that the vaccination strategy in Mexico has been successful to limit population mortality and decrease severe COVID-19, but children in Mexico still need access to SARS-CoV-2 vaccines to limit severe COVID-19, in particular those 1-4 years old.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , México/epidemiologia , Estudos Retrospectivos , Vacinação
20.
J Natl Med Assoc ; 114(2): 182-192, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35090746

RESUMO

PURPOSE: To describe the socioeconomic and healthcare-related effects of the COVID-19 pandemic, and willingness to receive a free COVID-19 vaccine, among African American/Black (AA/B) and Hispanic/Latinx (H/L) adults with asthma currently enrolled in a large trial. METHODS: The present analysis is a sub-study of the PeRson EmPowered Asthma RElief (PREPARE) study, a pragmatic study of 1201 AA/B and H/L adults with asthma. A monthly questionnaire was completed by a subset of PREPARE participants (n = 325) during May-August, 2020. The 5-item questionnaire assessed self-reported impact of COVID-19 on respondents' ability to obtain asthma medications, medical care quality, employment, income and ability to pay bills; and willingness to get a free COVID-19 vaccine. Bivariate analysis and multivariate logistic regression were performed to investigate factors associated with vaccine hesitancy. RESULTS: Of 325 survey respondents (25% AA/B, 75% H/L), the majority reported no impact of COVID-19 on medical care or ability to get asthma medications. Approximately half of employed respondents experienced a lower level of employment or job loss, and approximately half reported having difficulty paying bills during the pandemic. Thirty-five percent of respondents reported unwillingness and 31% reported being somewhat likely to receive a free COVID-19 vaccine. AA/B race/ethnicity and poorer reported physical health were associated with a higher likelihood of COVID-19 vaccine hesitancy. CONCLUSION: AA/B and H/L adults with asthma may experience changes in the quality of their asthma care and increased socioeconomic stressors as a result of the COVID-19 pandemic and may be hesitant or unwilling to receive a COVID-19 vaccine.


Assuntos
Asma , COVID-19 , Adulto , Negro ou Afro-Americano , Asma/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Hispânico ou Latino , Humanos , Pandemias/prevenção & controle , Fatores Socioeconômicos
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