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1.
Clin Pharmacol Drug Dev ; 13(9): 1051-1060, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38973337

RESUMO

Myocardial reperfusion injury (MRI) accounts for up to 50% of the final size in acute myocardial infarction and other conditions associated with ischemia-reperfusion. Currently, there is still no therapy to prevent MRI, but it is well known that oxidative stress has a key role in its mechanism. We previously reduced MRI in rats through a combined antioxidant therapy (CAT) of ascorbic acid, N-acetylcysteine, and deferoxamine. This study determines the safety and pharmacokinetics of CAT in a Phase I clinical trial. Healthy subjects (n = 18) were randomized 2:1 to CAT or placebo (NaCl 0.9% i.v.). Two different doses/infusion rates of CATs were tested in a single 90-minute intravenous infusion. Blood samples were collected at specific times for 180 minutes to measure plasma drug concentrations (ascorbic acid, N-acetylcysteine, and deferoxamine) and oxidative stress biomarkers. Adverse events were registered during infusion and followed for 30 days. Both CAT1 and CAT2 significantly increased the CAT drug concentrations compared to placebo (P < .05). Most of the pharmacokinetic parameters were similar between CAT1 and CAT2. In total, 6 adverse events were reported, all nonserious and observed in CAT1. The ferric-reducing ability of plasma (an antioxidant biomarker) increased in both CAT groups compared to placebo (P < .001). The CAT is safe in humans and a potential treatment for patients with acute myocardial infarction undergoing reperfusion therapy.


Assuntos
Acetilcisteína , Antioxidantes , Ácido Ascórbico , Desferroxamina , Traumatismo por Reperfusão Miocárdica , Estresse Oxidativo , Humanos , Antioxidantes/farmacocinética , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Antioxidantes/farmacologia , Masculino , Acetilcisteína/administração & dosagem , Acetilcisteína/farmacocinética , Acetilcisteína/efeitos adversos , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/farmacocinética , Ácido Ascórbico/efeitos adversos , Adulto , Estresse Oxidativo/efeitos dos fármacos , Feminino , Desferroxamina/farmacocinética , Desferroxamina/administração & dosagem , Desferroxamina/efeitos adversos , Voluntários Saudáveis , Adulto Jovem , Infusões Intravenosas , Pessoa de Meia-Idade , Método Duplo-Cego , Quimioterapia Combinada , Biomarcadores/sangue
2.
medRxiv ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38699295

RESUMO

BACKGROUND: Prediabetes has been associated with increased all-cause and cardiovascular mortality. However, no large-scale studies have been conducted in Mexico or Latin America examining these associations. METHODS: We analyzed data from 115,919 adults without diabetes (diagnosed or undiagnosed) aged 35-84 years who participated in the Mexico City Prospective Study between 1998 and 2004. Participants were followed until January 1st, 2021 for cause-specific mortality. We defined prediabetes according to the American Diabetes Association (ADA, HbA1c 5.7% to 6.4%) and the International Expert Committee (IEC, HbA1c 6.0-6.4%) definitions. Cox regression adjusted for confounders was used to estimate all-cause and cause-specific mortality rate ratios (RR) at ages 35-74 years associated with prediabetes. FINDINGS: During 2,085,392 person-years of follow-up (median in survivors 19 years), there were 6,810 deaths at ages 35-74, including 1,742 from cardiovascular disease, 892 from renal disease and 108 from acute diabetic crises. Of 110,405 participants aged 35-74 years at recruitment, 28,852 (26%) had ADA-defined prediabetes and 7,203 (7%) had IEC-defined prediabetes. Compared with those without prediabetes, individuals with prediabetes had higher risk of all-cause mortality at ages 35-74 years (RR 1.13, 95% CI 1.07-1.19 for ADA-defined prediabetes and RR 1.28, 1.18-1.39 for IEC-defined prediabetes), as well as increased risk of cardiovascular mortality (RR 1.22 [1.10-1.35] and 1.42 [1.22-1.65], respectively), renal mortality (RR 1.35 [1.08-1.68] and 1.69 [1.24-2.31], respectively), and death from an acute diabetic crisis (RR 2.63 [1.76-3.94] and 3.43 [2.09-5.62], respectively). RRs were larger at younger than at older ages, and similar for men compared to women. The absolute excess risk associated with ADA and IEC-defined prediabetes at ages 35-74 accounted for6% and 3% of cardiovascular deaths respectively, 10% and 5% of renal deaths respectively, and 31% and 14% of acute diabetic deaths respectively. INTERPRETATION: Prediabetes is a significant risk factor for all-cause, cardiovascular, renal, and acute diabetic deaths in Mexican adults. Identification and timely management of individuals with prediabetes for targeted risk reduction could contribute to reducing premature mortality from cardiometabolic causes in this population. FUNDING: Wellcome Trust, the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Cancer Research UK, British Heart Foundation, UK Medical Research Council. Instituto Nacional de Geriatría (Mexico City).

3.
Microbiol Spectr ; 12(4): e0316523, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38441469

RESUMO

Trichoderma species are known for their mycoparasitic activity against phytopathogenic fungi that cause significant economic losses in agriculture. During mycoparasitism, Trichoderma spp. recognize molecules produced by the host fungus and release secondary metabolites and hydrolytic enzymes to kill and degrade the host's cell wall. Here, we explored the participation of the Trichoderma atroviride RNAi machinery in the interaction with six phytopathogenic fungi of economic importance. We determined that both Argonaute-3 and Dicer-2 play an essential role during mycoparasitism. Using an RNA-Seq approach, we identified that perception, detox, and cell wall degradation depend on the T. atroviride-RNAi when interacting with Alternaria alternata, Rhizoctonia solani AG2, and R. solani AG5. Furthermore, we constructed a gene co-expression network that provides evidence of two gene modules regulated by RNAi, which play crucial roles in essential processes during mycoparasitism. In addition, based on small RNA-seq, we conclude that siRNAs regulate amino acid and carbon metabolism and communication during the Trichoderma-host interaction. Interestingly, our data suggest that siRNAs might regulate allorecognition (het) and transport genes in a cross-species manner. Thus, these results reveal a fine-tuned regulation in T. atroviride dependent on siRNAs that is essential during the biocontrol of phytopathogenic fungi, showing a greater complexity of this process than previously established.IMPORTANCEThere is an increasing need for plant disease control without chemical pesticides to avoid environmental pollution and resistance, and the health risks associated with the application of pesticides are increasing. Employing Trichoderma species in agriculture to control fungal diseases is an alternative plant protection strategy that overcomes these issues without utilizing chemical fungicides. Therefore, understanding the biocontrol mechanisms used by Trichoderma species to antagonize other fungi is critical. Although there has been extensive research about the mechanisms involved in the mycoparasitic capability of Trichoderma species, there are still unsolved questions related to how Trichoderma regulates recognition, attack, and defense mechanisms during interaction with a fungal host. In this work, we report that the Argonaute and Dicer components of the RNAi machinery and the small RNAs they process are essential for gene regulation during mycoparasitism by Trichoderma atroviride.


Assuntos
Hypocreales , Praguicidas , Plantas , Comunicação , Regulação Fúngica da Expressão Gênica
5.
Podium (Pinar Río) ; 18(3)dic. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1521334

RESUMO

La práctica de taekwondo, en el confinamiento de la pandemia del COVID 19, guarda relación con los hábitos de vida saludables y autoconcepto físico. En tal sentido, se determinó como el objetivo de esta investigación identificar las relaciones que puedan producirse entre las respuestas al CAF (Cuestionario de autoconcepto físico) y hábitos de vida saludables de los practicantes de taekwondo a nivel nacional. Se implementó un diseño ex post facto de carácter retrospectivo y correlacional, donde las variables independientes no son susceptibles de manipulación, se utilizó un muestreo no probabilístico discrecional, cuya muestra la componen 423 deportistas de taekwondo entre 12 y 58 años. Los participantes cumplimentaron el Cuestionario de autoconcepto físico (CAF) y el Cuestionario de hábitos de vida saludables. Los resultados, comprueban la importancia de los entrenamientos en confinamiento de taekwondo como aporte de una vida saludable, en relación con su propia percepción del autoconcepto físico de los participantes. Se concluyó que la práctica del taekwondo en época de pandemia aportó significativamente en el cuidado y desarrollo de los hábitos de vida saludables.


A prática do Taekwondo, no confinamento da pandemia da COVID-19, está relacionada a hábitos de vida saudáveis e ao autoconceito físico. Nesse sentido, o objetivo desta pesquisa foi identificar as relações que podem ocorrer entre as respostas ao CAF (Questionário de Autoconceito Físico) e os hábitos de vida saudável dos praticantes de Taekwondo em nível nacional. Foi implementado um projeto retrospectivo e correlacional ex post facto, em que as variáveis independentes não são suscetíveis de manipulação. Foi utilizada uma amostragem não probabilística discreta, com uma amostra de 423 atletas de taekwondo entre 12 e 58 anos de idade. Os participantes preencheram o Questionário de Autoconceito Físico (CAF) e o Questionário de Hábitos de Estilo de Vida Saudável. Os resultados comprovam a importância do treinamento de confinamento do taekwondo como contribuição para um estilo de vida saudável, em relação à percepção dos próprios participantes sobre seu autoconceito físico. Concluiu-se que a prática do taekwondo em tempos de pandemia contribuiu significativamente para o cuidado e o desenvolvimento de hábitos de vida saudáveis.


The practice of Taekwondo, in the confinement of the COVID19 pandemic, is related to healthy lifestyle habits and physical self-concept. In this sense, the objective of this research was determined to identify the relationships that may occur between the responses to the CAF (Physical Self-Concept Questionnaire) and healthy lifestyle habits of Taekwondo practitioners nationwide. An ex post facto design of a retrospective and correlational nature was implemented, where the independent variables are not susceptible to manipulation, a discretionary non-probabilistic sampling was used, which sample is made up of 423 taekwondo athletes between 12 and 58 years old. The participants completed the Physical Self-Concept Questionnaire (CAF) and the Healthy Life Habits questionnaire. The results prove the importance of Taekwondo confinement training as a contribution to a healthy life, in relation to their own perception of the participants' physical self-concept. It was concluded that the practice of taekwondo during the pandemic contributed significantly to the care and development of healthy lifestyle habits.

6.
Nature ; 622(7984): 784-793, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37821707

RESUMO

The Mexico City Prospective Study is a prospective cohort of more than 150,000 adults recruited two decades ago from the urban districts of Coyoacán and Iztapalapa in Mexico City1. Here we generated genotype and exome-sequencing data for all individuals and whole-genome sequencing data for 9,950 selected individuals. We describe high levels of relatedness and substantial heterogeneity in ancestry composition across individuals. Most sequenced individuals had admixed Indigenous American, European and African ancestry, with extensive admixture from Indigenous populations in central, southern and southeastern Mexico. Indigenous Mexican segments of the genome had lower levels of coding variation but an excess of homozygous loss-of-function variants compared with segments of African and European origin. We estimated ancestry-specific allele frequencies at 142 million genomic variants, with an effective sample size of 91,856 for Indigenous Mexican ancestry at exome variants, all available through a public browser. Using whole-genome sequencing, we developed an imputation reference panel that outperforms existing panels at common variants in individuals with high proportions of central, southern and southeastern Indigenous Mexican ancestry. Our work illustrates the value of genetic studies in diverse populations and provides foundational imputation and allele frequency resources for future genetic studies in Mexico and in the United States, where the Hispanic/Latino population is predominantly of Mexican descent.


Assuntos
Sequenciamento do Exoma , Genoma Humano , Genótipo , Hispânico ou Latino , Adulto , Humanos , África/etnologia , América/etnologia , Europa (Continente)/etnologia , Frequência do Gene/genética , Genética Populacional , Genoma Humano/genética , Técnicas de Genotipagem , Hispânico ou Latino/genética , Homozigoto , Mutação com Perda de Função/genética , México , Estudos Prospectivos
7.
Lancet Public Health ; 8(9): e670-e679, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37633676

RESUMO

BACKGROUND: Social inequalities in adult mortality have been reported across diverse populations, but there is no large-scale prospective evidence from Mexico. We aimed to quantify social, including educational, inequalities in mortality among adults in Mexico City. METHODS: The Mexico City Prospective Study recruited 150 000 adults aged 35 years and older from two districts of Mexico City between 1998 and 2004. Participants were followed up until Jan 1, 2021 for cause-specific mortality. Cox regression analysis yielded rate ratios (RRs) for death at ages 35-74 years associated with education and examined, in exploratory analyses, the mediating effects of lifestyle and related risk factors. FINDINGS: Among 143 478 participants aged 35-74 years, there was a strong inverse association of education with premature death. Compared with participants with tertiary education, after adjustment for age and sex, those with no education had about twice the mortality rate (RR 1·84; 95% CI 1·71-1·98), equivalent to approximately 6 years lower life expectancy, with an RR of 1·78 (1·67-1·90) among participants with incomplete primary, 1·62 (1·53-1·72) with complete primary, and 1·34 (1·25-1·42) with secondary education. Education was most strongly associated with death from renal disease and acute diabetic crises (RR 3·65; 95% CI 3·05-4·38 for no education vs tertiary education) and from infectious diseases (2·67; 2·00-3·56), but there was an apparent higher rate of death from all specific causes studied with lower education, with the exception of cancer for which there was little association. Lifestyle factors (ie, smoking, alcohol drinking, and leisure time physical activity) and related physiological correlates (ie, adiposity, diabetes, and blood pressure) accounted for about four-fifths of the association of education with premature mortality. INTERPRETATION: In this Mexican population there were marked educational inequalities in premature adult mortality, which appeared to largely be accounted for by lifestyle and related risk factors. Effective interventions to reduce these risk factors could reduce inequalities and have a major impact on premature mortality. FUNDING: Wellcome Trust, the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Cancer Research UK, British Heart Foundation, and the UK Medical Research Council Population Health Research Unit.


Assuntos
Mortalidade Prematura , Adulto , Humanos , Estudos Prospectivos , Causas de Morte , México/epidemiologia , Escolaridade
8.
J Educ Health Promot ; 12: 127, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37397106

RESUMO

BACKGROUND: There is a strong need for transformation in our assessment systems from one that evaluates performance based on levels of training to another that focuses on professional competence to meet the expected requirements for the practice of the profession. The aim of this study is to validate for the first time a Spanish version of a new tool for assessing the professional performance of residents by nurses newly developed in the Ottawa Hospital (O-RON). MATERIALS AND METHODS: After the author's written authorization, the original O-RON form was translated and cross-culturally adapted. Then we conducted a prospective observational study in two cardiology centers in the city of Buenos Aires. The validity of the tools was evaluated by the ability of the instrument to discriminate the level of experience of the residents according to their post-graduate year level. Data is expressed as percentages and frequencies of the qualifications obtained in the different questions. The chi-square test was used to assess the significance of the differences obtained. A generalizability test was used to evaluate reliability. Feasibility was defined as a minimum of 4 assessments per resident per evaluation round. Satisfaction of evaluators was assessed using a survey with a 10-point scale designed by the authors. RESULTS: A total of 838 evaluations were performed. Regarding validity, the 15-item form could significantly discriminate the experience of the residents according to their postgraduate year level (P < 0,005). Thirty evaluations per resident are required to obtain reliable results. The tool is feasible to implement and an average of 4.55 assessment per resident per evaluation round were achieved throughout the entire experience. This value remained stable during the 8 rounds (1st: 4.65; 2nd: 4.34; 3rd: 4.47; 4th: 6.17; 5th: 4.56; 6th: 4.08; 7th: 4.36; 8th: 3.91). The levels of satisfaction among the evaluators were acceptable. CONCLUSION: The Spanish version of the O-RON form can provide residents with a valuable source of feedback from the eyes of nurses on important aspects of their professional training. This tool, positively assessed by the raters, significantly discriminates residents' experience. Its implementation is feasible in our environment, and it is user-friendly, though it requires a considerable number of assessments to achieve high reliability.

9.
Front Cell Dev Biol ; 11: 1072315, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37051468

RESUMO

Introduction: Cardiovascular diseases, especially metabolic-related disorders, are progressively growing worldwide due to high-fat-containing foods, which promote a deleterious response at the cellular level, termed lipotoxicity, or lipotoxic stress. At the cardiac level, saturated fatty acids have been directly associated with cardiomyocyte lipotoxicity through various pathological mechanisms involving mitochondrial dysfunction, oxidative stress, and ceramide production, among others. However, integrative regulators connecting saturated fatty acid-derived lipotoxic stress to mitochondrial and cardiomyocyte dysfunction remain elusive. Methods: Here, we worked with a cardiomyocyte lipotoxicity model, which uses the saturated fatty acid myristate, which promotes cardiomyocyte hypertrophy and insulin desensitization. Results: Using this model, we detected an increase in the mitochondrial E3 ubiquitin ligase, MUL1, a mitochondrial protein involved in the regulation of growth factor signaling, cell death, and, notably, mitochondrial dynamics. In this context, myristate increased MUL1 levels and induced mitochondrial fragmentation, associated with the decrease of the mitochondrial fusion protein MFN2, and with the increase of the mitochondrial fission protein DRP1, two targets of MUL1. Silencing of MUL1 prevented myristate-induced mitochondrial fragmentation and cardiomyocyte hypertrophy. Discussion: These data establish a novel connection between cardiomyocytes and lipotoxic stress, characterized by hypertrophy and fragmentation of the mitochondrial network, and an increase of the mitochondrial E3 ubiquitin ligase MUL1.

10.
Artigo em Inglês | MEDLINE | ID: mdl-36889802

RESUMO

INTRODUCTION: Although higher risks of infectious diseases among individuals with diabetes have long been recognized, the magnitude of these risks is poorly described, particularly in lower income settings. This study sought to assess the risk of death from infection associated with diabetes in Mexico. RESEARCH DESIGN AND METHODS: Between 1998 and 2004, a total of 159 755 adults ≥35 years were recruited from Mexico City and followed up until January 2021 for cause-specific mortality. Cox regression yielded adjusted rate ratios (RR) for death due to infection associated with previously diagnosed and undiagnosed (HbA1c ≥6.5%) diabetes and, among participants with previously diagnosed diabetes, with duration of diabetes and with HbA1c. RESULTS: Among 130 997 participants aged 35-74 and without other prior chronic diseases at recruitment, 12.3% had previously diagnosed diabetes, with a mean (SD) HbA1c of 9.1% (2.5%), and 4.9% had undiagnosed diabetes. During 2.1 million person-years of follow-up, 2030 deaths due to infectious causes were recorded at ages 35-74. Previously diagnosed diabetes was associated with an RR for death from infection of 4.48 (95% CI 4.05-4.95), compared with participants without diabetes, with notably strong associations with death from urinary tract (9.68 (7.07-13.3)) and skin, bone and connective tissue (9.19 (5.92-14.3)) infections and septicemia (8.37 (5.97-11.7)). In those with previously diagnosed diabetes, longer diabetes duration (1.03 (1.02-1.05) per 1 year) and higher HbA1c (1.12 (1.08-1.15) per 1.0%) were independently associated with higher risk of death due to infection. Even among participants with undiagnosed diabetes, the risk of death due to infection was nearly treble the risk of those without diabetes (2.69 (2.31-3.13)). CONCLUSIONS: In this study of Mexican adults, diabetes was common, frequently poorly controlled, and associated with much higher risks of death due to infection than observed previously, accounting for approximately one-third of all premature mortality due to infection.


Assuntos
Doenças Transmissíveis , Diabetes Mellitus , Adulto , Humanos , México/epidemiologia , Hemoglobinas Glicadas , Diabetes Mellitus/epidemiologia , Fatores de Tempo , Doenças Transmissíveis/epidemiologia
11.
J Am Heart Assoc ; 12(3): e028263, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-36695315

RESUMO

Background Body-mass index is the sum of fat mass index (FMI) and lean mass index (LMI), which vary by age, sex, and impact on disease outcomes. We investigated the separate and joint relevance of FMI and LMI with vascular-metabolic causes of death in Mexican adults. Methods and Results A total of 113 025 adults aged 35 to 74 years and free from diabetes or other chronic diseases when recruited into the Mexico City Prospective Study were followed for 19 years. Cox models estimated sex-specific death rate ratios from vascular-metabolic causes after adjustment for confounders and exclusion of the first 5 years of follow-up. To account for the strong correlation between FMI and LMI, additional models estimated rate ratios associated with "residual FMI" and "residual LMI" (ie, the residuals from linear regression analyses of FMI on LMI, or vice versa). In both sexes, higher FMI and LMI were associated with higher risks of vascular-metabolic mortality. For a given (ie, fixed) level of LMI, the rate ratio (95% CI) for vascular-metabolic mortality per 1 kg/m2 higher residual FMI strengthened and was higher in women (1.52 [1.38-1.68]) than in men (1.19 [1.13-1.25]). By contrast, for a given level of FMI, higher residual LMI was inversely associated with vascular-metabolic mortality (rate ratio per 1 kg/m2 0.67 [0.56-0.80] in women and 0.94 [0.90-0.98] in men). Conclusions In this study, higher residual FMI was more strongly associated with vascular-metabolic mortality in women than in men. Conversely, higher residual LMI was inversely associated with vascular-metabolic mortality, particularly in women.


Assuntos
Composição Corporal , Adulto , Masculino , Humanos , Feminino , Estudos Prospectivos , México/epidemiologia , Índice de Massa Corporal , Doença Crônica
12.
Commun Med (Lond) ; 2(1): 143, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376486

RESUMO

BACKGROUND: Adiposity is a major cause of morbidity and mortality in part due to effects on blood lipids. Nuclear magnetic resonance (NMR) spectroscopy provides direct information on >130 biomarkers mostly related to blood lipid particles. METHODS: Among 28,934 Mexican adults without chronic disease and not taking lipid-lowering therapy, we examine the cross-sectional relevance of body-mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and hip circumference (HC) to NMR-measured metabolic biomarkers. Confounder-adjusted associations between each adiposity measure and NMR biomarkers are estimated before and after mutual adjustment for other adiposity measures. RESULTS: Markers of general (ie, BMI), abdominal (ie, WC and WHR) and gluteo-femoral (ie, HC) adiposity all display similar and strong associations across the NMR-platform of biomarkers, particularly for biomarkers that increase cardiometabolic risk. Higher adiposity associates with higher levels of Apolipoprotein-B (about 0.35, 0.30, 0.35, and 0.25 SD higher Apolipoprotein-B per 2-SD higher BMI, WHR, WC, and HC, respectively), higher levels of very low-density lipoprotein particles (and the cholesterol, triglycerides, and phospholipids within these lipoproteins), higher levels of all fatty acids (particularly mono-unsaturated fatty acids) and multiple changes in other metabolic biomarkers including higher levels of branched-chain amino acids and the inflammation biomarker glycoprotein acetyls. Associations for general and abdominal adiposity are fairly independent of each other but, given general and abdominal adiposity, higher gluteo-femoral adiposity is associated with a strongly favourable cardiometabolic lipid profile. CONCLUSIONS: Our results provide insight to the lipidic and metabolomic signatures of different adiposity markers in a previously understudied population where adiposity is common but lipid-lowering therapy is not.


Obesity increases the risk of multiple diseases, in part due to alterations in how the body breaks down carbohydrates and fats, which is reflected in molecules that circulate in blood. In obesity, disease risk may vary depending on whether fat accumulates in the body overall (i.e. total adiposity), in the middle of the body (i.e. abdominal adiposity) or around the hips (i.e. gluteo-femoral adiposity). Here, we show that in a population of Mexican adults higher total and abdominal adiposity relate adversely, while higher gluteo-femoral adiposity relates favourably, to numerous molecules in blood that are linked to type 2 diabetes and heart disease. These findings provide insight on the processes that link the accumulation of fat across the body with disease risk in a population where obesity rates are high.

14.
Nat Prod Bioprospect ; 12(1): 20, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35641706

RESUMO

From aerial parts of Austroeupatorium inulifolium was isolated the ent-nor-furano triol labdane austroeupatol 1. The compound 1 was treated with IBX showing an unexpected selectivity at the potentially oxidizable sites of the substrate yielding the 2-oxoaustroeupatol (2) and 2,19-dioxoaustroeupatol (3). The treatment of 2 with sodium periodate yields a heterocyclic derivative (ε-caprolactone derivate 4) formed by oxidative cleavage and unexpected intramolecular attack of the hydroxymethylene (C-19) oxygen to the ketonic carbon (C-2). A plausible mechanistic pathway for the obtention of compound 4 is proposed.

15.
Eur J Prev Cardiol ; 29(5): 730-738, 2022 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33693634

RESUMO

AIMS: Results of previous studies of abdominal adiposity and risk of vascular-metabolic mortality in Hispanic populations have been conflicting. We report results from a large prospective study of Mexican adults with high levels of abdominal adiposity. METHODS AND RESULTS: A total of 159 755 adults aged ≥35 years from Mexico City were enrolled in a prospective study and followed for 16 years. Cox regression, adjusted for confounders, yielded mortality rate ratios (RRs) associated with three markers of abdominal adiposity (waist circumference, waist-hip ratio, and waist-height ratio) and one marker of gluteo-femoral adiposity (hip circumference) for cause-specific mortality before age 75 years. To reduce reverse causality, deaths in the first 5 years of follow-up and participants with diabetes or other prior chronic disease were excluded. Among 113 163 participants without prior disease and aged 35-74 years at recruitment, all adiposity markers were positively associated with vascular-metabolic mortality. Comparing the top versus bottom tenth of the sex-specific distributions, the vascular-metabolic mortality RRs at ages 40-74 years were 2.32 [95% confidence interval (CI) 1.84-2.94] for waist circumference, 2.22 (1.71-2.88) for the waist-hip ratio, 2.63 (2.06-3.36) for the waist-height ratio, and 1.58 (1.29-1.93) for hip circumference. The RRs corresponding to each standard deviation (SD) higher usual levels of these adiposity markers were 1.34 (95% CI 1.27-1.41), 1.31 (1.23-1.39), 1.38 (1.31-1.45), and 1.18 (1.13-1.24), respectively. For the markers of abdominal adiposity, the RRs did not change much after further adjustment for other adiposity markers, but for hip circumference the association was reversed; given body mass index and waist circumference, the RR for vascular-metabolic mortality for each one SD higher usual hip circumference was 0.80 (0.75-0.86). CONCLUSIONS: In this study of Mexican adults, abdominal adiposity (and in particular the waist-height ratio) was strongly and positively associated with vascular-metabolic mortality. For a given amount of general and abdominal adiposity, however, higher hip circumference was associated with lower vascular-metabolic mortality.


Assuntos
Adiposidade , Obesidade Abdominal , Adulto , Biomarcadores , Índice de Massa Corporal , Feminino , Humanos , Masculino , México/epidemiologia , Obesidade/complicações , Obesidade Abdominal/complicações , Obesidade Abdominal/diagnóstico , Estudos Prospectivos , Fatores de Risco , Circunferência da Cintura , Relação Cintura-Quadril
16.
Animals (Basel) ; 11(12)2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34944120

RESUMO

Tropical dry forests (TDFs) are affected by land-use changes. These modifications impact their composition and arboreal structure, as well as the availability of food for several bird groups. In this study, we evaluated the foraging preferences in zoochorous trees of fruit-eating birds during the dry season of the year in three successional stages (early, intermediate, and mature) of TDFs in southern Mexico. The fruits of these trees are important in the diet of several birds during the dry season, a period during which food resources are significantly reduced in TDFs. We estimated foliar cover (FC) and foliage height diversity (FHD) of zoochorous trees in 123 circular plots. These variables were recognized as proxies of food availability and tree productivity. Foraging preferences were evaluated at the community level, by frugivore type, and by bird species. We evaluated the effect of the structural variables and the fruit size of zoochorous plants on fruit removal by birds and related the bird body mass and fruit size removed in the successional gradient. A total of 14 zoochorous tree species and 23 fruit-eating bird species were recorded along the successional gradient. Intermediate and mature stages showed greater fruit removal. The birds removed mainly B. longipes fruits across the three successional stages. The FHD and fruit size were important drivers in the selection of zoochorous trees and fruit removal by fruit-eating birds. Fruit size and bird body mass were positively related along the successional gradient. The results suggest that fruit removal by fruit-eating birds in the successional gradient can promote the demographic dynamics of several zoochorous tree species, especially of Bursera spp. along the TDFs.

17.
FASEB J ; 35(10): e21933, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34555201

RESUMO

In obesity, skeletal muscle mitochondrial activity changes to cope with increased nutrient availability. Autophagy has been proposed as an essential mechanism involved in the regulation of mitochondrial metabolism. Still, the contribution of autophagy to mitochondrial adaptations in skeletal muscle during obesity is unknown. Here, we show that in response to high-fat diet (HFD) feeding, distinct skeletal muscles in mice exhibit differentially regulated autophagy that may modulate mitochondrial activity. We observed that after 4 and 40 weeks of high-fat diet feeding, OXPHOS subunits and mitochondrial DNA content increased in the oxidative soleus muscle. However, in gastrocnemius muscle, which has a mixed fiber-type composition, the mitochondrial mass increased only after 40 weeks of HFD feeding. Interestingly, fatty acid-supported mitochondrial respiration was enhanced in gastrocnemius, but not in soleus muscle after a 4-week HFD feeding. This increased metabolic profile in gastrocnemius was paralleled by preserving autophagy flux, while autophagy flux in soleus was reduced. To determine the role of autophagy in this differential response, we used an autophagy-deficient mouse model with partial deletion of Atg7 specifically in skeletal muscle (SkM-Atg7+/- mice). We observed that Atg7 reduction resulted in diminished autophagic flux in skeletal muscle, alongside blunting the HFD-induced increase in fatty acid-supported mitochondrial respiration observed in gastrocnemius. Remarkably, SkM-Atg7+/- mice did not present increased mitochondria accumulation. Altogether, our results show that HFD triggers specific mitochondrial adaptations in skeletal muscles with different fiber type compositions, and that Atg7-mediated autophagy modulates mitochondrial respiratory capacity but not its content in response to an obesogenic diet.


Assuntos
Autofagia , Dieta Hiperlipídica , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/citologia , Animais , Proteína 7 Relacionada à Autofagia/deficiência , Proteína 7 Relacionada à Autofagia/genética , Respiração Celular , Ácidos Graxos/metabolismo , Masculino , Camundongos , Obesidade/genética , Obesidade/metabolismo , Obesidade/prevenção & controle , Oxirredução
18.
J Diabetes Res ; 2021: 7365075, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34426789

RESUMO

INTRODUCTION: The present study evaluated the quality of medical care for patients diagnosed with diabetes mellitus (DM), hypertension (HBP), and both pathologies (DM+HBP) within a public health system in Mexico. METHODS: 45,498 patients were included from 2012 to 2015. All information was taken from the electronic medical record database. Each patient record was compared against the standard to test the quality of medical care. RESULTS: Glycemia with hypertension goals reached 29.6% in DM+HBP, 48.6% in DM, and 53.2% in HBP. The goals of serum lipids were reached by 3% in DM+HBP, 5% in DM, and 0.2% in HBP. Glycemia, hypertension, and LDL cholesterol reached 0.04%. 15% of patients had an undiagnosed disease. Clinical follow-up examinations reached 20% for foot examination and clinical eye examination. Specialty referrals reached 1% in angiology or cardiology. CONCLUSION: Goals for glycemic and hypertension reached 50% in the overall population, while serum lipids, clinical follow-up examinations, and referral to a specialist were deficient. Patients who had both diseases had more consultations, better control for hypertension and lipids, but inferior glycemic control. Overall, quality care for DM and/or HBP has not been met according to the standards.


Assuntos
Anti-Hipertensivos/uso terapêutico , Diabetes Mellitus/terapia , Controle Glicêmico , Hipertensão/terapia , Hipolipemiantes/uso terapêutico , Atenção Primária à Saúde , Indicadores de Qualidade em Assistência à Saúde , Adulto , Idoso , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Dieta Saudável , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Hipoglicemiantes/uso terapêutico , Lipídeos/sangue , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Encaminhamento e Consulta , Estudos Retrospectivos , Resultado do Tratamento
19.
J Clin Endocrinol Metab ; 106(10): 2828-2839, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34216216

RESUMO

CONTEXT: Chronic kidney disease (CKD) and diabetes are associated with dyslipidemia, metabolic abnormalities, and atherosclerotic risk. Nuclear magnetic resonance (NMR) spectroscopy provides much more detail on lipoproteins than traditional assays. METHODS: In about 38 000 participants from the Mexico City Prospective Study, aged 35 to 84 years and not using lipid-lowering medication, NMR spectroscopy quantified plasma concentrations of lipoprotein particles, their lipidic compositions, and other metabolic measures. Linear regression related low estimated glomerular filtration rate (eGFR; <60 mL/min/1.73 m2) to each NMR measure after adjustment for confounders and for multiplicity. Analyses were done separately for those with and without diabetes. RESULTS: Among the 38 081 participants (mean age 52 years, 64% women), low eGFR was present for 4.8% (306/6403) of those with diabetes and 1.2% (365/31 678) of those without diabetes. Among both those with and without diabetes, low eGFR was significantly associated with higher levels of 58 NMR measures, including apolipoprotein B (Apo-B), the particle numbers of most Apo-B containing lipoproteins, the cholesterol and triglycerides carried in these lipoproteins, several fatty acids, total cholines and phosphatidylcholine, citrate, glutamine, phenylalanine, ß-OH-butyrate, and the inflammatory measure glycoprotein-A, and significantly lower levels of 13 NMR measures, including medium and small high-density lipoprotein particle measures, very low-density lipoprotein particle size, the ratio of saturated:total fatty acids, valine, tyrosine, and aceto-acetate. CONCLUSIONS: In this Mexican population with high levels of adiposity and diabetes, low kidney function was associated with widespread alterations in lipidic and metabolic profiles, both in those with and without diabetes. These alterations may help explain the higher atherosclerotic risk experienced by people with CKD.


Assuntos
Testes de Função Renal , Lipídeos/sangue , Lipoproteínas/sangue , Espectroscopia de Ressonância Magnética , Insuficiência Renal Crônica/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas B/sangue , Aterosclerose/etnologia , Aterosclerose/etiologia , Colesterol/sangue , Colina/sangue , Diabetes Mellitus/sangue , Diabetes Mellitus/etnologia , Ácidos Graxos/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Modelos Lineares , Masculino , México , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/etnologia , Triglicerídeos
20.
J Pak Med Assoc ; 71(2(A)): 449-455, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33819226

RESUMO

Objective: Describing the results of a User-Centered Design workshop using Challenge Based Learning or CBL, where students from Chilean industrial design and health degrees, developed solutions to resolve health problems among the elderly. METHODS: It was a pre-experimental study; 45 university students took part in a workshop: 39 from Industrial Design, 3 from Speech Therapy, 2 from Medical Technology and 1 from Medicine. In this workshop, the students, using CBL in disciplinary heterogeneous groups, faced a 3-week challenge to develop products to overcome a health problem for an elderly person. Once the product was presented, the professors and students assessed the conceptual proposals, using a semantic differential. The students also evaluated the workshop with a perception survey. RESULTS: Both the students and professors positively evaluated the usefulness and functionality of the conceptual proposals; although, the industrial design students were more critical about these aspects. The originality of proposals evaluated was the worst. Regarding the workshop, all students (100%) felt that instructions were clear as were the three moments of design, with problem definition stage best evaluated. Conclusion: The CBL is shown to be an educational tool that allows training professionals in product design and in developing health technology that is suitable for the users' needs. Regarding the process, heterogeneous make-up of the groups and clear external guide appear as essential for CBL to work well.


Assuntos
Aprendizagem , Estudantes , Idoso , Chile , Humanos , Inquéritos e Questionários
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