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BACKGROUND: Eosinophils play a key role in the asthma allergic response by releasing cytotoxic molecules such as eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) that generate epithelium damages. OBJECTIVE: We sought to identify genetic variants influencing ECP and EDN levels in asthma-ascertained families. METHODS: We performed univariate and bivariate genome-wide association analyses of ECP and EDN levels in 1018 subjects from the EGEA study with follow-up in 153 subjects from the Saguenay-Lac-Saint-Jean study and combined the results of these 2 studies through meta-analysis. We then conducted Bayesian statistical fine mapping together with quantitative trait locus and functional annotation analyses to identify the most likely functional genetic variants and candidate genes. RESULTS: We identified 5 genome-wide significant loci (P < 5 × 10<sup>-8</sup>) including 7 distinct signals associated with ECP and/or EDN levels. The genes targeted by our fine mapping and functional search include RNASE2 and RNASE3 (14q11), which encode EDN and ECP, respectively, and 4 other genes that regulate ECP and EDN levels. These 4 genes were JAK1 (1p31), a transcription factor that plays a key role in the immune response and acts as a potential therapeutic target for eosinophilic asthma; ARHGAP25 (2p13), which is involved in leukocyte recruitment to inflammatory sites; NDUFA4 (7p21), which encodes a component of the mitochondrial respiratory chain and is involved in cellular response to stress; and CTSL (9q22), which is involved in immune response, extracellular remodeling, and allergic inflammation. CONCLUSION: Analysis of specific phenotypes produced by eosinophils allows the identification of genes that play a major role in allergic response and inflammation, and offers potential therapeutic targets for asthma.
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Asma , Hipersensibilidad , Humanos , Eosinófilos , Estudio de Asociación del Genoma Completo , Teorema de Bayes , Neurotoxina Derivada del Eosinófilo/genética , Neurotoxina Derivada del Eosinófilo/metabolismo , Proteína Catiónica del Eosinófilo/genética , Proteína Catiónica del Eosinófilo/metabolismo , Hipersensibilidad/metabolismo , Inflamación/metabolismo , Proteínas en los Gránulos del Eosinófilo/genética , Proteínas en los Gránulos del Eosinófilo/metabolismo , Proteínas Sanguíneas/metabolismoRESUMEN
AIM: Chronic inflammation has been associated to the development of cardiometabolic dysfunctions. The use of an intravenous (IV) catheter is highly recommended for physiology testing. Yet, the presence of an IV catheter triggers local inflammation that does not reflect systemic inflammatory status. The aim of this study was to assess the effect of an IV catheter on serum concentrations of IL-6, IL-8 and hsCRP in a fasting state and after a high-fat meal known to trigger low-grade inflammation. METHODS: Twenty-two healthy subjects (7 men, 15 women) were included in this study. The trial included 2 visits. After an overnight fast, a venous catheter was inserted into an antecubital vein. A first blood sample was collected through this catheter at Tâ¯=â¯0â¯min. On each visit, participants were requested either to drink only water for the whole duration of the test (WO test), or to consume a high-fat meal (HFM). Blood samples were collected through the catheter at T60, T120, T180 and T300 min. Additional venous punctures were performed on the contralateral arm at T180 and T300 min. Serum inflammatory mediators were measured at each time point of both interventions. RESULTS: When serum was collected by venous punctures, IL-6 concentrations remained unchanged during both WO and HFM tests (Ptimeâ¯=â¯0.15 and Ptimeâ¯=â¯0.23, respectively), whereas the concentrations increased progressively over time when serum was collected through the catheter (Ptimeâ¯<â¯0.001). The high-fat meal had no additional effect on IL-6 levels (Pmealâ¯=â¯0.27) neither in serum collected by venous puncture nor in serum collected through the catheter. Serum IL-8 and hsCRP concentrations did not vary over time, and were influenced neither by the meal type nor by the blood collection method. CONCLUSION: The insertion of an indwelling catheter is associated with a local inflammatory response possibly mediated by IL-6 but not IL-8. This inflammatory response was not enhanced by a pro-inflammatory high-fat meal.
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Mediadores de Inflamación/sangre , Inflamación/sangre , Adulto , Catéteres , Dieta Alta en Grasa , Femenino , Humanos , Interleucina-6/sangre , Interleucina-8/sangre , MasculinoRESUMEN
INTRODUCTION: Intersectoral collaboration is a collaborative approach between the health sectors and other sectors to address the interdependent nature of the social determinants of health associated with chronic diseases such as diabetes. This scoping review aims to identify intersectoral health interventions implemented in primary care and community settings to improve the well-being and health of people living with type 2 diabetes. METHODS AND ANALYSIS: This protocol is developed by the Arksey and O'Malley (2005) framework for scoping reviews and the Levac et al methodological enhancement. MEDLINE, Embase, CINAHL, grey literature and the reference list of key studies will be searched to identify any study, published between 2000 and 2023, related to the concepts of intersectorality, diabetes and primary/community care. Two reviewers will independently screen all titles/abstracts, full-text studies and grey literature for inclusion and extract data. Eligible interventions will be classified by sector of action proposed by the Social Determinants of Health Map and the conceptual framework for people-centred and integrated health services and further sorted according to the actors involved. This work started in September 2023 and will take approximately 10 months to be completed. ETHICS AND DISSEMINATION: This review does not require ethical approval. The results will be disseminated through a peer-reviewed publication and presentations to stakeholders.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/terapia , Determinantes Sociales de la Salud , Colaboración Intersectorial , Proyectos de Investigación , Atención Primaria de Salud/organización & administración , Literatura de Revisión como AsuntoRESUMEN
Healthy diet and physical activity are associated with a lower cardiometabolic risk (CMR). Little is known about whether they interact to improve CMR. The purpose of the present study was to determine the synergistic associations of diet quality and physical activity energy expenditure (PAEE) on CMR factors. The present study was an a posteriori analysis of two cross-sectional studies on 124 inactive non-diabetic postmenopausal women with a BMI ≥ 27 kg/m². The following factors were measured: diet quality (assessed by the Canadian Healthy Eating Index (C-HEI) from a 3 d food record); PAEE (doubly labelled water); body composition (dual-energy X-ray absorptiometry, computed tomography scan); lipoprotein profile (total, HDL- and LDL-cholesterol (HDL-C and LDL-C), non-HDL-C, total cholesterol:HDL-C, TAG, apoA1, apoB, apoA1:apoB and LDL-C:apoB); insulin sensitivity (homeostasis model assessment of insulin resistance and hyperinsulinaemic-euglycaemic clamp); inflammatory markers (high-sensitivity C-reactive protein (hs-CRP), haptoglobin, orosomucoid, IL-6 and leucocyte count). The association of the interaction PAEE × C-HEI and CMR factors was evaluated by hierarchical regressions. Fat mass-adjusted ANCOVA determined the interaction between PAEE and the C-HEI. In hierarchical regressions, the interaction PAEE × C-HEI was a correlate of more favourable values of HDL-C, apoB, apoA1:apoB and LDL-C:apoB ratios, and hs-CRP, while only PAEE was a negative correlate of haptoglobin. Compared with those in the low-PAEE/low-C-HEI group, women in the high-PAEE/high-C-HEI group had 10 % higher HDL-C, 13 % lower apoB, 11 % larger LDL particles and 28 % lower hs-CRP concentrations (P< 0·05). PAEE and the C-HEI have a synergistic association with the CMR profile. These results support the integration of both diet quality and physical activity in the management of CMR.
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Enfermedades Cardiovasculares/complicaciones , Dieta , Ejercicio Físico , Estilo de Vida , Obesidad/complicaciones , Sobrepeso/complicaciones , Anciano , Índice de Masa Corporal , Peso Corporal , Enfermedades Cardiovasculares/fisiopatología , Estudios de Cohortes , Estudios Transversales , Metabolismo Energético , Femenino , Alimentos , Humanos , Inflamación , Persona de Mediana Edad , Actividad Motora , Obesidad/fisiopatología , Sobrepeso/fisiopatología , Posmenopausia , Factores de RiesgoRESUMEN
OBJECTIVE: To describe and evaluate the contribution of multiple coding approaches applied to a clinical conversation on deprescribing in primary care (PC). METHODS: Seven distinct coding approaches were applied to one audiotaped consultation. Only exchanges related to deprescribing a benzodiazepine (BZD) were coded for: content, interaction, arguments, connectors, transitions, orientation towards deprescribing and concordance with a deprescribing algorithm. A discursive map presents the unfolding of the exchanges. RESULTS: The deprescribing conversation was broken down into 31 utterances divided into three segments: opening (n = 6), development (n = 16) and closing (n = 9). The family physician dominated the last two segments and most of her utterances were favorable to BZD deprescribing while the patient's utterances were generally unfavorable in the first two segments. The number of distinct codes assigned to utterances varied according to the coding approach. The map illustrates how each utterance can be viewed through different lenses revealing the dynamics and complexity of the deprescribing conversation. CONCLUSION: This multidimensional methodological approach with its proposed way of presenting results, either quantitatively or qualitatively, and its map offer a comprehensive evaluation of the deprescribing process in this PC setting. PRACTICE IMPLICATIONS: This novel multidimensional coding approach has potential to be applied to a range of other topics in clinical communications.
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Deprescripciones , Comunicación , Femenino , Humanos , Atención Primaria de Salud , Grabación en CintaRESUMEN
Asthma affects 340 million people worldwide and varies in time. Twenty years ago, in Canada, the Saguenay-Lac-Saint-Jean asthma family cohort was created to study the genetic and environmental components of asthma. This study is a follow-up of 125 participants of this cohort to explore the appearance, persistence, and progression of asthma over 10-20 years. Participants answered a clinical standardized questionnaire. Lung function was assessed (forced expiratory volume in 1 s, forced vital capacity, bronchial reversibility, and methacholine bronchoprovocation), skin allergy testing was performed, blood samples were obtained (immunoglobulin E, white blood cell counts) and phenotypes were compared between recruitment and follow-up. From the participants without asthma at recruitment, 12% developed a phenotype of adult-onset asthma with the presence of risk factors, such as atopy, high body mass index, and exposure to smoking. A decrease of PC20 values in this group was observed and a decrease in the FEV1/FVC ratio in all groups. Also, 7% of individuals with asthma at recruitment developed chronic obstructive pulmonary disease, presenting risk factors at recruitment, such as moderate-to-severe bronchial hyperresponsiveness, exposure to smoking, and asthma. This study allowed a better interpretation of the evolution of asthma. Fine phenotypic characterization is the first step for meaningful genetic and epigenetic studies.
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Asma , Asma/genética , Canadá/epidemiología , Estudios de Seguimiento , Volumen Espiratorio Forzado , Humanos , Cloruro de MetacolinaRESUMEN
OBJECTIVE: This study documents the adoption of telehealth by various types of primary healthcare (PHC) providers working in teaching PHC clinics in Quebec during the COVID-19 pandemic. It also identifies the perceived advantages and disadvantages of telehealth. METHOD: A cross-sectional study was conducted between May and August 2020. The e-survey was completed by 48/50 teaching primary care clinics representing 603/1,357 (44%) PHC providers. RESULTS: Telephone use increased the most, becoming the principal virtual modality of consultation, during the pandemic. Video consultations increased, with variations by type of PHC provider: between 2% and 16% reported using it "sometimes." The main perceived advantages of telehealth were minimizing the patient's need to travel, improved efficiency and reduction in infection transmission risk. The main disadvantages were the lack of physical exam and difficulties connecting with some patients. CONCLUSION: The variation in telehealth adoption by type of PHC provider may inform strategies to maximize the potential of telehealth and help create guidelines for its use in more normal times.
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COVID-19/diagnóstico , COVID-19/terapia , Personal de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricos , Atención Primaria de Salud/organización & administración , Atención Primaria de Salud/estadística & datos numéricos , Telemedicina/organización & administración , Telemedicina/estadística & datos numéricos , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Quebec , SARS-CoV-2RESUMEN
BACKGROUND: This study reports the genetic features of four Caucasian males from the Saguenay-Lac-St-Jean region affected by partial agenesis of the corpus callosum (ACC) with hypotonia, epilepsy, developmental delay, microcephaly, hypoplasia, and autistic behavior. METHODS: We performed whole exome sequencing (WES) to identify new genes involved in this pathological phenotype. The regions of interest were subsequently sequenced for family members. RESULTS: Single-nucleotide variations (SNVs) and insertions or deletions were detected in genes potentially implicated in brain defects observed in these patients. One patient did not have mutations in genes related to ACC, but carried a de novo pathogenic mutation in Mucolipin-1 (MCOLN1) and was diagnosed with mucolipidosis type IV. Among the other probands, missense SNVs were observed in DCLK2 (Doublecortin Like Kinase 2), HERC2 (HECT And RLD Domain Containing E3 Ubiquitin Protein Ligase 2), and KCNH3 (Potassium channel, voltage-gated, subfamily H, member 3). One patient also carried a non-frameshift insertion in CACNA1A (Cav2.1(P/Q-type) calcium channels). CONCLUSION: Although no common genetic defect was observed in this study, we provide evidence for new avenues of investigation for ACC, such as molecular pathways involving HERC2, CACNA1A, KCNH3, and more importantly DCLK2. We also allowed to diagnose an individual with mucolipidosis type IV.
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Agenesia del Cuerpo Calloso/genética , Discapacidades del Desarrollo/genética , Epilepsia/genética , Exoma , Microcefalia/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Agenesia del Cuerpo Calloso/patología , Canales de Calcio/genética , Discapacidades del Desarrollo/patología , Quinasas Similares a Doblecortina , Epilepsia/patología , Canales de Potasio Éter-A-Go-Go/genética , Humanos , Masculino , Microcefalia/patología , Proteínas del Tejido Nervioso/genética , Proteínas Serina-Treonina Quinasas/genética , Síndrome , Canales de Potencial de Receptor Transitorio/genética , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
BACKGROUND: Little is known about the initiation, style and content of patient and healthcare provider communication around deprescribing. We report the findings from a content analysis of audio-recorded discussions of proton pump inhibitor (PPI) and benzodiazepine deprescribing in primary care. METHODS: Participants were healthcare providers (n = 13) from primary care practices (n = 3) and patients aged ⩾65 (n = 24) who were chronic users of PPIs or benzodiazepines. The EMPOWER educational brochures were distributed prior to (n = 15) or after (n = 9) the patient's usual healthcare provider appointment. Conversations were audio-recorded and coded using MEDICODE to analyze who initiated different themes, whether they followed a monologue or dialogue style, and to what extent the thematic content addressed issues pertaining to: 'dosage/instructions,' 'medication action and efficacy,' 'risk/adverse effects,' 'attitudes/emotions,' 'adherence' and 'follow up.' Descriptive analysis of the conversations was performed with comparison between patients who received the EMPOWER brochure before or after their appointments. RESULTS: Patients were mostly women (67%) with a mean age of 74 ± 6âyears. For PPI users, prior education resulted in a greater proportion of themes initiated by patients (44% versus 17%) and maintaining dialogue-style conversations (48% versus 28%). Among benzodiazepine users, conversation initiation (52% versus 47%) and conversation style was similar between both groups. The content of deprescribing conversations for PPIs revealed that patients and their healthcare providers focused less on 'dosage/instructions,' and more on the 'medication action and efficacy' and the necessity for 'follow up.' Conversations about stopping benzodiazepines were more likely to stagnate on the 'if' rather than the 'how.' CONCLUSION: The initiation, style and content of the conversations varied between PPI and benzodiazepine users, suggesting that healthcare providers will need to tailor deprescribing conversations accordingly.
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Resistance training (RT) has been shown to decrease fat mass (FM), and increase fat-free mass (FFM), which can be a useful for weight loss maintenance. OBJECTIVE: To examine the effects of a 1-year RT intervention on weight loss maintenance following a 6-month dietary weight loss intervention. DESIGN: Following a 6-month dietary weight loss intervention (-6%⯱â¯5.8; 5.05â¯kg⯱â¯4.45), 70 postmenopausal women living with overweight or obesity were randomized to a control group (nâ¯=â¯34) or a RT group (nâ¯=â¯36) (3×/week first 6â¯months, 2×/week last 6â¯months, 70-80% of 1-repetition maximum). Body composition (DXA), abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) (CT scan), resting energy expenditure (EE) (indirect calorimetry), physical activity EE and total daily EE were measured (doubly-labelled water). RESULTS: A total of 54 participants completed the study (control group nâ¯=â¯29; RT group nâ¯=â¯25) and compliance to the RT program was on average 64%. Significant regains were noted for body weight 0.98 (3.71)â¯kg vs. 1.33 (3.94)â¯kg and FM regain 1.32 (2.69)â¯kg vs. 0.81 (3.26)â¯kg in control and RT groups after the 1-year weight maintenance phase. No group differences were noted. Resting EE and total daily EE did not change after the weight maintenance phase, and no differences were observed between groups. Both groups had significantly greater than predicted decrease in resting EE after the 6-month dietary intervention and at the end of the 1-year weight-loss maintenance phase. CONCLUSIONS: Our results suggest that a 1-year RT intervention following a 6-month dietary weight loss intervention does not improve weight loss maintenance, body composition or EE in post-menopausal women living with overweight or obesity.
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Composición Corporal/fisiología , Mantenimiento del Peso Corporal/fisiología , Metabolismo Energético/fisiología , Obesidad/fisiopatología , Sobrepeso/fisiopatología , Entrenamiento de Fuerza/estadística & datos numéricos , Pérdida de Peso , Ejercicio Físico , Femenino , Humanos , Grasa Intraabdominal , Persona de Mediana Edad , Obesidad/dietoterapia , Sobrepeso/dietoterapia , Cooperación del Paciente/estadística & datos numéricos , PosmenopausiaAsunto(s)
Derecho Penal , Infecciones por VIH/transmisión , Canadá , Homicidio , Humanos , Masculino , Delitos SexualesRESUMEN
CONTEXT: A subpopulation of obese individuals remains insulin sensitive (ISO). They represent a unique human model to investigate factors underlying insulin resistance (IR) without the confounding effect of major differences in weight/adiposity. Altered fatty-acid (FA) metabolism in sc adipose tissue (SAT) contributes to obesity-associated IR. OBJECTIVE: To test the hypothesis that ISO and body mass index-matched insulin-resistant obese (IRO) patients demonstrate differential SAT expression profiles of genes involved in glycerolipid-FA metabolism and that weight loss-induced improvement of IR ameliorates these changes. DESIGN AND SETTING: A cross-sectional and longitudinal study. PATIENTS AND INTERVENTION: Thirty-eight nondiabetic obese women were stratified into ISO (n = 25) or IRO (n = 13) groups based on hyperinsulinemic-euglycemic clamp results. Subjects were studied before and after a 6-month hypocaloric diet intervention. MAIN OUTCOME MEASURES: mRNA (quantitative RT-PCR) and protein (mass spectrometry and immunoblots) levels were measured in SAT biopsies. RESULTS: Despite having age, body mass index, and fat mass similar to ISO individuals, IRO patients had lower insulin sensitivity and glucose tolerance (P < .05). Baseline SAT mRNA and protein levels of genes involved in both the synthesis and lipolysis of glycerolipid-FAs were higher in IRO individuals (P < .05), even when groups were matched for visceral adipose tissue content. The dietary intervention resulted in approximately 6% weight loss in both the IRO and ISO groups (P < .05) but only ameliorated insulin sensitivity in IRO individuals (P < .05). Likewise, the intervention reduced the expression of most glycerolipid-FA metabolism genes (P < .05), with expression levels in IRO individuals being restored to ISO levels. CONCLUSIONS: Increased SAT expression of genes involved in both the synthesis and hydrolysis of glycerolipid-FAs is closely associated with IR in obese women. The results suggest that enhanced glycerolipid-FA cycling in SAT contributes to obesity-associated IR.
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Ácidos Grasos/genética , Ácidos Grasos/metabolismo , Glucolípidos/genética , Glucolípidos/metabolismo , Resistencia a la Insulina/genética , Obesidad/genética , Obesidad/metabolismo , Grasa Subcutánea/metabolismo , Anciano , Estudios de Cohortes , Estudios Transversales , Dieta Reductora , Femenino , Expresión Génica , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Obesidad/dietoterapia , Posmenopausia/genéticaRESUMEN
Introduction. Subcutaneous fat (ScF) and visceral fat (VF) measurements using CT scan are expensive and may imply significant radiation doses. Cross-sectional studies using CT scan showed that ScF and VF are significantly correlated with abdominal fat measured by DXA (AF-DXA). The association has not been studied after a weight loss. Objective. To determine (1) the associations between AF-DXA and ScF and VF before and after weight loss and (2) the associations between their changes. Methods. 137 overweight/obese postmenopausal women were divided in two groups (1-caloric restriction or 2-caloric restriction + resistance training). AF was assessed using DXA and CT scan. Results. Correlations between AF-DXA and ScF (before: r = 0.87, after; r = 0.87; P < .01) and, AF-DXA and VF (before: r = 0.61, after; r = 0.69; P < .01) are not different before and after the weight loss. Correlations between delta AF-DXA and delta ScF (r = 0.72; P < .01) or delta VF (r = 0.51; P < .01) were found. Conclusion. The use of AF-DXA as a surrogate for VF after weight loss is questionable, but may be interesting for ScF.
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OBJECTIVE: Large inter-individual variations exist in changes in inflammation and insulin resistance (IR) in response to hypocaloric-interventions in obese subjects that are not explained by weight-loss per se. We identified the number of serum apoB-lipoproteins (serum apoB) as the primary predictor of inflammatory markers in post-menopausal overweight/obese women. As apoB-lipoproteins are related to inflammation and inflammation promotes IR, we hypothesized that the reduction in inflammation and IR following hypocaloric-interventions is associated with the reduction in serum apoB. METHODS/RESULTS: After a 6-month hypocaloric-dietary-intervention in 56 overweight/obese post-menopausal women, there was a significant reduction in weight, total, subcutaneous abdominal and visceral abdominal fat mass, apoB, Lp(a), hsCRP, orosomucoid, haptoglobin and IR (increased M(clamp)) and an increase in LDL-C/apoB ratio. In regression analysis, % change in apoB was the primary predictor of % changes in hsCRP (R(2)=0.22), orosomucoid (R(2)=0.35), haptoglobin (R(2)=0.43) and M(clamp) (R(2)=0.17). When the study population was split around baseline median apoB (0.97g/L), women who were above median apoB (N=27) had significant reduction in apoB (-17%), hsCRP (-24%), orosomucoid (-8%), haptoglobin (-18%) and IR (M(clamp) +14%). On the other hand, women below median apoB (N=29) had no significant changes in these parameters despite equivalent reduction in weight and fat depots in the two groups. CONCLUSION: Reduction in apoB associated strongly and independently with the reduction in inflammatory markers and IR following a hypocaloric-diet in overweight/obese women. We hypothesize that the elevated apoB phenotype may be key therapeutic target to reduce obesity-associated inflammation and IR maximally by hypocaloric-dietary-interventions.
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Apolipoproteínas B/sangre , Inflamación/sangre , Resistencia a la Insulina , Obesidad/complicaciones , Anciano , Antropometría , Canadá , Complicaciones de la Diabetes/diagnóstico , Diabetes Mellitus Tipo 2/patología , Dieta Reductora , Femenino , Humanos , Persona de Mediana Edad , Fenotipo , Posmenopausia , Factores de RiesgoRESUMEN
Early in life, premature neonates are at risk of oxidant stress. They often require total parenteral nutrition (TPN), which is, however, contaminated with oxidation products. Coadministration of parenteral multivitamins (MVP) with a lipid emulsion (LIP) prevents lipid peroxidation. We hypothesized that LIP+MVP induces a lower oxidant load compared to preparations in which MVP is administered with an amino acid solution (AA+MVP). The aim of this study was to compare markers of oxidant stress in premature neonates receiving LIP+MVP, either exposed to or protected from light, or AA+MVP. Antioxidant vitamins, the redox potential of glutathione, isoprostane, and dityrosine were measured in urine or blood sampled on days 7 and 10 from babies requiring low (<0.25) vs high (≥0.25) fractional inspired O(2). Oxygen supplementation induced a more oxidized redox potential and increased dityrosine with AA+MVP only. Adding MVP in the lipid rather than the amino acid moiety of TPN protects against the oxidant stress associated with O(2) supplementation. Photoprotection added no benefit. Blood transfusions were found to produce a pronounced oxidant load masking the beneficial effect of LIP+MVP. The impact of these findings relates to a strong association between a more oxidized redox potential and later bronchopulmonary dysplasia, a clinical marker of oxidant stress.
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Aminoácidos/administración & dosificación , Biomarcadores , Emulsiones Grasas Intravenosas/administración & dosificación , Nacimiento Prematuro/diagnóstico , Vitaminas/administración & dosificación , Adulto , Biomarcadores/sangre , Biomarcadores/orina , Displasia Broncopulmonar/etiología , Displasia Broncopulmonar/prevención & control , Femenino , Humanos , Oxigenoterapia Hiperbárica/efectos adversos , Recien Nacido con Peso al Nacer Extremadamente Bajo , Recién Nacido , Infusiones Parenterales , Estrés Oxidativo/efectos de los fármacos , Embarazo , Nacimiento Prematuro/metabolismo , Nacimiento Prematuro/terapiaRESUMEN
BACKGROUND: Caloric restriction is recommended for the treatment of obesity, but it is generally characterized by large interindividual variability in responses. The factors affecting the magnitude of weight loss remain poorly understood. Epigenetic factors (ie, heritable but reversible changes to genomic function that regulate gene expression independently of DNA sequence) may explain some of the interindividual variability seen in weight-loss responses. OBJECTIVE: The objective was to determine whether epigenetics and gene expression changes may play a role in weight-loss responsiveness. DESIGN: Overweight/obese postmenopausal women were recruited for a standard 6-mo caloric restriction intervention. Abdominal subcutaneous adipose tissue biopsy samples were collected before (n = 14) and after (n = 14) intervention, and the epigenomic and transcriptomic profiles of the high and low responders to dieting, on the basis of changes in percentage body fat, were compared by using microarray analysis. RESULTS: Significant DNA methylation differences at 35 loci were found between the high and low responders before dieting, with 3 regions showing differential methylation after intervention. Some of these regions contained genes known to be involved in weight control and insulin secretion, whereas others were localized in known imprinted genomic regions. Differences in gene expression profiles were observed only after dieting, with 644 genes being differentially expressed between the 2 groups. These included genes likely to be involved in metabolic pathways related to angiogenesis and cerebellar long-term depression. CONCLUSIONS: These data show that both DNA methylation and gene expression are responsive to caloric restriction and provide new insights about the molecular pathways involved in body weight loss as well as methylation regulation during adulthood.
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Restricción Calórica , Epigénesis Genética , Obesidad/genética , Grasa Subcutánea/metabolismo , Transcripción Genética , Anciano , Antropometría , Metilación de ADN , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Humanos , Persona de Mediana Edad , Obesidad/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN/química , ARN/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estadísticas no ParamétricasRESUMEN
CONTEXT: Recent studies in humans and mice suggest the implication of the cysteine proteases cathepsins S, L, and K in vascular and metabolic complications of obesity. OBJECTIVE: Our objective was to identify clinically relevant forms of cathepsin in human obesity. DESIGN AND SETTING: We conducted a prospective study on two independent cohorts. PARTICIPANTS AND INTERVENTIONS: The first cohort includes 45 obese women eligible for gastric surgery (age, 39 +/- 1.6 yr; body mass index, 47 +/- 0.99 kg/m(2)) and 17 nonobese women (age, 38 +/- 1.8 yr; body mass index, 21 +/- 0.44 kg/m(2)). The second cohort comprises 29 obese women (age, 57 +/- 0.8 yr; body mass index, 34 +/- 0.69 kg/m(2)) undergoing 6 months of medically supervised caloric restriction. MAIN OUTCOMES: Cathepsin S, L, and K mRNA levels were determined in surgical adipose tissue biopsies. The proteins were measured in conditioned medium of adipose tissue explants and in circulation. RESULTS: Obese subjects had a 2-fold increase in cathepsin S mRNA in adipose tissue as compared with normal-weight subjects and an increased rate (1.5-fold) of cathepsin S release in adipose tissue explants. Cathepsin S circulating concentrations were increased with obesity (+30%) and reduced after weight reduction (P < 0.05 for both). By contrast, cathepsin L was unaffected in adipose tissue and serum; cathepsin K was undetectable in circulation and unchanged in adipose tissue. CONCLUSION: In humans, cathepsin S is more influenced than cathepsins L and K by changes in energy balance in adipose tissue and circulation. This opens new avenues to explore whether selective inhibition of this protease could reduce cardiovascular risk and ameliorate metabolic status in obese subjects.
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Tejido Adiposo/metabolismo , Catepsinas/metabolismo , Metabolismo Energético/fisiología , Obesidad/metabolismo , Adipocitos/metabolismo , Adulto , Anciano , Anastomosis en-Y de Roux , Animales , Índice de Masa Corporal , Restricción Calórica , Catepsinas/biosíntesis , Catepsinas/genética , Células Cultivadas , Estudios de Cohortes , Cistatina C/metabolismo , Femenino , Humanos , Leptina/sangre , Ratones , Ratones Obesos , Persona de Mediana Edad , Obesidad/sangre , Posmenopausia/metabolismo , Quebec , ARN/biosíntesis , ARN/genética , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Pérdida de PesoRESUMEN
Sarcopenia is believed to be associated with disability and metabolic complications. The objective of this study was to examine the metabolic and quality-of-life profile of sarcopenic overweight and obese postmenopausal women. In this cross-sectional study of 136 healthy overweight and obese postmenopausal women, 9 class I sarcopenic women were identified. Class I sarcopenia was defined as an appendicular lean body mass index (ALBMI) Asunto(s)
Atrofia Muscular/metabolismo
, Obesidad/metabolismo
, Sobrepeso/metabolismo
, Posmenopausia/metabolismo
, Calidad de Vida
, Anciano
, Glucemia/metabolismo
, Presión Sanguínea
, Índice de Masa Corporal
, Estudios Transversales
, Femenino
, Humanos
, Mediadores de Inflamación/sangre
, Insulina/sangre
, Resistencia a la Insulina
, Lípidos/sangre
, Persona de Mediana Edad
, Fuerza Muscular
, Atrofia Muscular/fisiopatología
, Atrofia Muscular/psicología
, Obesidad/fisiopatología
, Obesidad/psicología
, Sobrepeso/fisiopatología
, Sobrepeso/psicología
, Aptitud Física
, Posmenopausia/psicología
, Encuestas y Cuestionarios
RESUMEN
OBJECTIVE: To evaluate the validity of a new lipid-based index (Disse index) in assessing insulin sensitivity (IS) compared with the hyperinsulinemic-euglycemic (HIEG) clamp in overweight and obese, non-diabetic, postmenopausal women, before and after a weight loss intervention. RESEARCH DESIGN AND METHODS: Association between Disse index and the HIEG clamp was evaluated in 86 non-diabetic postmenopausal overweight and obese women before and after weight loss. Percentage changes (%Delta) were calculated for several fasting indices and compared with %Delta of HIEG clamp. RESULTS: We observed a strong correlation between Disse index and HIEG clamp (r=0.69, P<0.001). This association was higher than those of homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI), and McAuley indices while no significant difference was observed with Revised-QUICKI. Percent change of Disse index (pre- versus post-weight loss program) was significantly correlated with %Delta of HIEG clamp (r=0.34, P<0.01). This correlation was similar to those observed for the other indices tested. CONCLUSIONS: We validated the reliability of Disse index in assessing IS in non-diabetic post-menopausal overweight and obese women, before and after weight loss intervention. Disse index may be useful not only for insulin resistant diagnostics in this type of population, but also for the IS follow-up after a weight-loss program and weight stabilization. The presence of lipid elements in this fasting index improves the estimation of IS in overweight and obese non-diabetic post-menopausal women and could add more information about peripheral IS.
Asunto(s)
Técnicas de Diagnóstico Endocrino/normas , Resistencia a la Insulina , Obesidad/metabolismo , Sobrepeso/metabolismo , Posmenopausia/metabolismo , Pérdida de Peso , HDL-Colesterol/sangre , Diabetes Mellitus , Dieta Reductora , Ayuno , Ácidos Grasos no Esterificados/sangre , Femenino , Técnica de Clampeo de la Glucosa , Homeostasis/fisiología , Humanos , Lipólisis , Persona de Mediana Edad , Obesidad/dietoterapia , Sobrepeso/dietoterapia , Reproducibilidad de los Resultados , Triglicéridos/sangreRESUMEN
BACKGROUND: Ghrelin levels are decreased upon food intake, but the impact of specific diet-derived macronutrients on its regulation remains unclear. In addition, because of ghrelin's association with body weight regulation, it is important to understand the mechanisms regulating its levels in obese individuals. OBJECTIVE: To examine the effect of specific macronutrients on ghrelin levels in overweight and obese postmenopausal women. METHODS: Thirty-five subjects underwent a euglycemic/hyperinsulinemic clamp (EHC) to examine glucose disposal and total ghrelin (TotG) and acylated ghrelin (AG) levels. Macronutrient intake was evaluated with a 3-day food questionnaire. RESULTS: Under fasting conditions, positive associations were observed between fiber intake and TotG and AG levels. Fasting AG also correlated positively with the intake of total energy, as well as monounsaturated and polyunsaturated lipids. Importantly, fiber consumption explained up to 26 and 23% of the variation in TotG and AG respectively. During the EHC, TotG levels were significantly reduced at all times, while AG was decreased at 60 min only. TotG area under the curve (AUC) values were positively associated with fiber and polyunsaturated lipid intake, while AG AUC values correlated positively with fiber, total energy, carbohydrate, and lipid intake. Interestingly, fiber intake explained up to 21% of the variation in TotG AUC, while total energy intake predicted up to 21% of the variation in the AG AUC. CONCLUSION: The present study suggests that fiber intake is an important regulator of ghrelin levels both in fasting and in hyperinsulinemic conditions. Overall, these results reinforce the importance of the intimate association between eating habits and gastrointestinal hormonal regulation.