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AIMS/HYPOTHESIS: Alterations in circadian rhythms increase the likelihood of developing type 2 diabetes and CVD. Circadian rhythms are controlled by several core clock genes, which are expressed in nearly every cell, including immune cells. Immune cells are key players in the pathophysiology of type 2 diabetes, and participate in the atherosclerotic process that underlies cardiovascular risk in these patients. The role of the core clock in the leukocytes of people with type 2 diabetes and the inflammatory process associated with it are unknown. We aimed to evaluate whether the molecular clock system is impaired in the leukocytes of type 2 diabetes patients and to explore the mechanism by which this alteration leads to an increased cardiovascular risk in this population. METHODS: This is an observational cross-sectional study performed in 25 participants with type 2 diabetes and 28 healthy control participants. Clinical and biochemical parameters were obtained. Peripheral blood leukocytes were isolated using magnetic bead technology. RNA and protein lysates were obtained to assess clock-related gene transcript and protein levels using real-time PCR and western blot, respectively. Luminex XMAP technology was used to assess levels of inflammatory markers. Leukocyte-endothelial interaction assays were performed by perfusing participants' leukocytes or THP-1 cells (with/without CLK8) over a HUVEC monolayer in a parallel flow chamber using a dynamic adhesion system. RESULTS: Participants with type 2 diabetes showed increased BMAL1 and NR1D1 mRNA levels and decreased protein levels of circadian locomotor output cycles kaput (CLOCK), cryptochrome 1 (CRY1), phosphorylated basic helix-loop-helix ARNT like 1 (p-BMAL1) and period circadian protein homologue 2 (PER2). Correlation studies revealed that these alterations in clock proteins were negatively associated with glucose, HbA1c, insulin and HOMA-IR levels and leukocyte cell counts. The leukocyte rolling velocity was reduced and rolling flux and adhesion were enhanced in individuals with type 2 diabetes compared with healthy participants. Interestingly, inhibition of CLOCK/BMAL1 activity in leukocytes using the CLOCK inhibitor CLK8 mimicked the effects of type 2 diabetes on leukocyte-endothelial interactions. CONCLUSIONS/INTERPRETATION: Our study demonstrates alterations in the molecular clock system in leukocytes of individuals with type 2 diabetes, manifested in increased mRNA levels and decreased protein levels of the core clock machinery. These alterations correlated with the impaired metabolic and proinflammatory profile of the participants with type 2 diabetes. Our findings support a causal role for decreased CLOCK/BMAL1 activity in the increased level of leukocyte-endothelial interactions. Overall, our data suggest that alterations in core clock proteins accelerate the inflammatory process, which may ultimately precipitate the onset of CVD in patients with type 2 diabetes.
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Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for 85% to 90% of all liver cancer cases. It is a hepatocyte-derived primary tumor, causing 550,000 deaths per year, ranking it as one of the most common cancers worldwide. The liver is a highly metabolic organ with multiple functions, including digestion, detoxification, breakdown of fats, and production of bile and cholesterol, in addition to storage of vitamins, glycogen, and minerals, and synthesizing plasma proteins and clotting factors. Due to these fundamental and diverse functions, the malignant transformation of hepatic cells can have a severe impact on the liver's metabolism. Furthermore, tumorigenesis is often accompanied by activation of the endoplasmic reticulum (ER) stress pathways, which are known to be highly intertwined with several metabolic pathways. Because HCC is characterized by changes in the metabolome and by an aberrant activation of the ER stress pathways, the aim of this review was to summarize the current knowledge that links ER stress and metabolism in HCC, thereby focusing on potential therapeutic targets.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Hepatócitos/metabolismo , Estresse do Retículo EndoplasmáticoRESUMO
Daily rhythms of metabolic function are supported by molecular circadian clock systems that are strongly regulated by feeding and fasting. Intermittent fasting diets have been associated with weight loss and improved metabolism. However, the effects of time-restricted eating (TRE) on glycemic parameters are still under debate. In this review, we aim to systematically analyze the effects of TRE on glycemic parameters. We searched on PubMed, EMBASE, and the Cochrane Library for controlled studies in which subjects followed TRE for at least 4 weeks. 20 studies were included in the qualitative systematic review, and 18 studies (n = 1169 subjects) were included in the meta-analysis. Overall, TRE had no significant effect on fasting glucose (Hedges's g = -0.08; 95% CI:-0.31,0.16; p = 0.52), but it did reduce HbA1c levels (Hedges's g = -0.27; 95% CI: -0.47, -0.06; p = 0.01). TRE significantly reduced fasting insulin (Hedges's g = -0.40; 95% CI: -0.73,-0.08; p = 0.01) and showed a tendency to decrease HOMA-IR (Hedges's g = -0.32; 95% CI:-0.66,0.02; p = 0.06). Interestingly, a cumulative analysis showed that the beneficial effects of TRE regarding glucose levels were less apparent as studies with later TRE windows (lTRE) were being included. Indeed, a subgroup analysis of the early TRE (eTRE) studies revealed that fasting glucose was significantly reduced by eTRE (Hedges's g = -0.38; 95% CI:-0.62, -0.14; p < 0.01). Our meta-analysis suggests that TRE can reduce HbA1c and insulin levels, and that timing of food intake is a crucial factor in the metabolic benefit of TRE, as only eTRE is capable of reducing fasting glucose levels in subjects with overweight or obesity.PROSPERO registration number CRD42023405946.
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Glucose , Controle Glicêmico , Humanos , Hemoglobinas Glicadas , Insulina , Ingestão de AlimentosRESUMO
INTRODUCTION: Sexually transmitted infections (STI) are currently on the increase worldwide. New molecular tools have been developed in the past few years in order to improve their diagnosis. An evaluation was carried out using a new commercially available real-time PCR assay, Anyplex™ II STI-7 (Seegene, Seoul, Korea), which detects seven major pathogens in a single reaction - Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum, and Ureaplasma parvum - and compared with conventional methods performed in our laboratory. MATERIALS AND METHODS: Two different populations were included, and 267 specimens from different sites of infection (urines, endocervical swabs, rectal swabs, vaginal swabs, urethral swabs and one inguinal adenopathy) were processed for both methods. RESULTS: The parameters of clinical performance were calculated for C. trachomatis, N. gonorrhoeae, and T. vaginalis, and the assay achieved sensitivities (SE) from 93.94% to 100%, and specificities (SP) from 96.55% to 100%, with negative predictive values (NPV) from 93.33% to 98.85%, and positive predictive values (PPV) from 96.88% to 100%, with a very good agreement (kappa index from 0.88 to 1). CONCLUSIONS: Anyplex™ II STI-7 is a good tool for the reliable diagnosis of STI. Its ease of use and processing allows it to be incorporated into the day to day laboratory work.
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Reação em Cadeia da Polimerase Multiplex/métodos , Infecções Sexualmente Transmissíveis/diagnóstico , Chlamydia trachomatis/isolamento & purificação , Estudos Transversais , Feminino , Humanos , Mycoplasma genitalium/isolamento & purificação , Mycoplasma hominis/isolamento & purificação , Neisseria gonorrhoeae/isolamento & purificação , Estudos Retrospectivos , Sensibilidade e Especificidade , Infecções Sexualmente Transmissíveis/microbiologia , Trichomonas vaginalis/isolamento & purificação , Ureaplasma/isolamento & purificação , Ureaplasma urealyticum/isolamento & purificaçãoRESUMO
Overloaded glucose levels in several metabolic diseases such as type 2 diabetes (T2D) can lead to mitochondrial dysfunction and enhanced production of reactive oxygen species (ROS). Oxidative stress and altered mitochondrial homeostasis, particularly in the cardiovascular system, contribute to the development of chronic comorbidities of diabetes. Diabetes-associated hyperglycemia and dyslipidemia can directly damage vascular vessels and lead to coronary artery disease or stroke, and indirectly damage other organs and lead to kidney dysfunction, known as diabetic nephropathy. The new diabetes treatments include Na+-glucose cotransporter 2 inhibitors (iSGLT2) and glucagon-like 1 peptide receptor agonists (GLP-1RA), among others. The iSGLT2 are oral anti-diabetic drugs, whereas GLP-1RA are preferably administered through subcutaneous injection, even though GLP-1RA oral formulations have recently become available. Both therapies are known to improve both carbohydrate and lipid metabolism, as well as to improve cardiovascular and cardiorenal outcomes in diabetic patients. In this review, we present an overview of current knowledge on the relationship between oxidative stress, mitochondrial dysfunction, and cardiovascular therapeutic benefits of iSGLT2 and GLP-1RA. We explore the benefits, limits and common features of the treatments and remark how both are an interesting target in the prevention of obesity, T2D and cardiovascular diseases, and emphasize the lack of a complete understanding of the underlying mechanism of action.
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Doenças Cardiovasculares , Sistema Cardiovascular , Diabetes Mellitus Tipo 2 , Doenças Mitocondriais , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Estresse Oxidativo , Glucose/farmacologia , Doenças Mitocondriais/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Hipoglicemiantes/farmacologiaRESUMO
Hepatocellular carcinoma (HCC) is characterized by a low and variable response to chemotherapeutic treatments. One contributing factor to the overall pharmacodynamics is the activation of endoplasmic reticulum (ER) stress pathways. This is a cellular stress mechanism that becomes activated when the cell's need for protein synthesis surpasses the ER's capacity to maintain accurate protein folding, and has been implicated in creating drug-resistance in several solid tumors. OBJECTIVE: To identify the role of ER-stress and lipid metabolism in mediating drug response in HCC. METHODS: By using a chemically-induced mouse model for HCC, we administered the ER-stress inhibitor 4µ8C and/or doxorubicin (DOX) twice weekly for three weeks post-tumor initiation. Histological analyses were performed alongside comprehensive molecular biology and lipidomics assessments of isolated liver samples. In vitro models, including HCC cells, spheroids, and patient-derived liver organoids were subjected to 4µ8C and/or DOX, enabling us to assess their synergistic effects on cellular viability, lipid metabolism, and oxygen consumption rate. RESULTS: We reveal a pivotal synergy between ER-stress modulation and drug response in HCC. The inhibition of ER-stress using 4µ8C not only enhances the cytotoxic effect of DOX, but also significantly reduces cellular lipid metabolism. This intricate interplay culminates in the deprivation of energy reserves essential for the sustenance of tumor cells. CONCLUSIONS: This study elucidates the interplay between lipid metabolism and ER-stress modulation in enhancing doxorubicin efficacy in HCC. This novel approach not only deepens our understanding of the disease, but also uncovers a promising avenue for therapeutic innovation. The long-term impact of our study could open the possibility of ER-stress inhibitors and/or lipase inhibitors as adjuvant treatments for HCC-patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Humanos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Metabolismo dos Lipídeos , Estresse do Retículo Endoplasmático , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Linhagem Celular TumoralRESUMO
OBJECTIVE: Type 2 diabetes (T2D) is linked to metabolic, mitochondrial and inflammatory alterations, atherosclerosis development and cardiovascular diseases (CVDs). The aim was to investigate the potential therapeutic benefits of GLP-1 receptor agonists (GLP-1 RA) on oxidative stress, mitochondrial respiration, leukocyte-endothelial interactions, inflammation and carotid intima-media thickness (CIMT) in T2D patients. RESEARCH DESIGN AND METHODS: Type 2 diabetic patients (255) and control subjects (175) were recruited, paired by age and sex, and separated into two groups: without GLP-1 RA treatment (196) and treated with GLP-1 RA (59). Peripheral blood polymorphonuclear leukocytes (PMNs) were isolated to measure reactive oxygen species (ROS) production by flow cytometry and oxygen consumption with a Clark electrode. PMNs were also used to assess leukocyte-endothelial interactions. Circulating levels of adhesion molecules and inflammatory markers were quantified by Luminex's technology, and CIMT was measured as surrogate marker of atherosclerosis. RESULTS: Treatment with GLP-1 RA reduced ROS production and recovered mitochondrial membrane potential, oxygen consumption and MPO levels. The velocity of leukocytes rolling over endothelial cells increased in PMNs from GLP-1 RA-treated patients, whereas rolling and adhesion were diminished. ICAM-1, VCAM-1, IL-6, TNFα and IL-12 protein levels also decreased in the GLP-1 RA-treated group, while IL-10 increased. CIMT was lower in GLP-1 RA-treated T2D patients than in T2D patients without GLP-1 RA treatment. CONCLUSIONS: GLP-1 RA treatment improves the redox state and mitochondrial respiration, and reduces leukocyte-endothelial interactions, inflammation and CIMT in T2D patients, thereby potentially diminishing the risk of atherosclerosis and CVDs.
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Aterosclerose , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Células Endoteliais , Receptor do Peptídeo Semelhante ao Glucagon 1 , Espessura Intima-Media Carotídea , Espécies Reativas de Oxigênio , Aterosclerose/tratamento farmacológico , Inflamação/tratamento farmacológico , Leucócitos , Endotélio , Peptídeo 1 Semelhante ao GlucagonRESUMO
Gold-ceria nanoparticles (Au/CeO2) are known to have antioxidant properties. However, whether these nanoparticles can provide benefits in type 2 diabetes mellitus (T2D) remains unknown. This work aimed to study the effects of Au/CeO2 nanoparticles at different rates of gold purity (10, 4.4, 1.79 and 0.82) on leukocyte-endothelium interactions and inflammation in T2D patients. Anthropometric and metabolic parameters, leukocyte-endothelium interactions, ROS production and NF-κB expression were assessed in 57 T2D patients and 51 healthy subjects. T2D patients displayed higher Body Mass Index (BMI) and characteristic alterations in carbohydrate and lipid metabolism. ROS production was increased in leukocytes of T2D patients and decreased by Au/CeO2 at 0.82% gold. Interestingly, Au/CeO2 0.82% modulated leukocyte-endothelium interactions (the first step in the atherosclerotic process) by increasing leukocyte rolling velocity and decreasing rolling flux and adhesion in T2D. A static adhesion assay also revealed diminished leukocyte-endothelium interactions by Au/CeO2 0.82% treatment. NF-κB (p65) levels increased in T2D patients and were reduced by Au/CeO2 treatment. Cell proliferation, viability, and apoptosis assays demonstrated no toxicity produced by Au/CeO2 nanoparticles. These results demonstrate that Au/CeO2 nanoparticles at 0.82% exert antioxidant and anti-inflammatory actions in the leukocyte-endothelium interaction of T2D patients, suggesting a protective role against the appearance of atherosclerosis and cardiovascular diseases when this condition exists.
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OBJECTIVES: Onco-haematological patients are prone to develop infections, and antibiotic prophylaxis may lead to negative blood cultures. Thus, the microbiological diagnosis and subsequent administration of a targeted antimicrobial therapy is often difficult. The goal of this study was to evaluate the usefulness of IRIDICA (PCR/ESI-MS technology) for the molecular diagnosis of bloodstream infections in this patient group. METHODS: A total of 463 whole blood specimens from different sepsis episodes in 429 patients were analysed using the PCR/ESI-MS platform, comparing the results with those of blood culture and other clinically relevant information. RESULTS: The sensitivity of PCR/ESI-MS by specimen (excluding polymicrobial infections, n = 25) in comparison with blood culture was 64.3% overall, 69.0% in oncological patients, and 59.3% in haematological patients. When comparing with a clinical infection criterion, overall sensitivity rose to 74.7%, being higher in oncological patients (80.0%) than in haematological patients (67.7%). Thirty-one microorganisms isolated by culture were not detected by IRIDICA, whereas 42 clinically relevant pathogens not isolated by culture were detected moleculary. CONCLUSIONS: PCR/ESI-MS offers a reliable identification of pathogens directly from whole blood. While additional studies are needed to confirm our findings, the system showed a lower sensitivity in onco-haematological patients in comparison with previously reported results in patients from the Intensive Care Unit.
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Neoplasias Hematológicas/complicações , Técnicas de Diagnóstico Molecular , Reação em Cadeia da Polimerase , Sepse/diagnóstico , Espectrometria de Massas por Ionização por Electrospray , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/complicações , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular/instrumentação , Técnicas de Diagnóstico Molecular/métodos , Estudos Prospectivos , Sensibilidade e Especificidade , Sepse/complicações , Sepse/microbiologia , Espectrometria de Massas por Ionização por Electrospray/instrumentação , Espectrometria de Massas por Ionização por Electrospray/métodos , Adulto JovemRESUMO
Urinary tract infections (UTI) are highly prevalent in nosocomial and community settings, and their diagnosis is costly and time-consuming. Screening methods represent an important advance towards the final UTI diagnosis, diminishing inappropriate treatment or clinical complications. Automated analyzers have been developed and commercialized to screen and rule out negative urine samples. The aim of this study was to evaluate two of these automated analyzers (SediMax, an automatic sediment analyzer and UF-1000i a flow cytometer) to predict negative urine cultures. A total of 1934 urine samples were analyzed. A very strong correlation for white blood cells (WBC) (rs: 0.928) and a strong correlation for bacteria (BAC) (rs: 0.693) were obtained. We also calculated optimal cut-off points for both autoanalyzers: 18 WBC/µL and 97 BAC/µL for SediMax (sensitivity=96.25%, specificity=63.04%, negative predictive value=97.97%), and 40 WBC/µL and 460 BAC/µL for UF-1000i (sensitivity=98.13%, specificity=79.16%, negative predictive value=99.18%). The use of SediMax and UF-1000i resulted in a 46.33% and 57.19% reduction of all samples cultured, respectively. In conclusion, both analyzers are good UTI screening tools in our setting.
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Citometria de Fluxo/instrumentação , Microscopia , Urinálise/métodos , Infecções Urinárias/diagnóstico , Infecções Urinárias/urina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Rapid identification of the etiological agent in bloodstream infections is of vital importance for the early administration of the most appropriate antibiotic therapy. Molecular methods may offer an advantage to current culture-based microbiological diagnosis. The goal of this study was to evaluate the performance of IRIDICA, a platform based on universal genetic amplification followed by mass spectrometry (PCR/ESI-MS) for the molecular diagnosis of sepsis-related pathogens directly from the patient's blood. METHODS: A total of 410 whole blood specimens from patients admitted to Emergency Room (ER) and Intensive Care Unit (ICU) with clinical suspicion of sepsis were tested with the IRIDICA BAC BSI Assay (broad identification of bacteria and Candida spp.). Microorganisms grown in culture and detected by IRIDICA were compared considering blood culture as gold standard. When discrepancies were found, clinical records and results from other cultures were taken into consideration (clinical infection criterion). RESULTS: The overall positive and negative agreement of IRIDICA with blood culture in the analysis by specimen was 74.8% and 78.6%, respectively, rising to 76.9% and 87.2% respectively, when compared with the clinical infection criterion. Interestingly, IRIDICA detected 41 clinically significant microorganisms missed by culture, most of them from patients under antimicrobial treatment. Of special interest were the detections of one Mycoplasma hominis and two Mycobacterium simiae in immunocompromised patients. When ICU patients were analyzed separately, sensitivity, specificity, positive and negative predictive values compared with blood culture were 83.3%, 78.6%, 33.9% and 97.3% respectively, and 90.5%, 87.2%, 64.4% and 97.3% respectively, in comparison with the clinical infection criterion. CONCLUSIONS: IRIDICA is a promising technology that offers an early and reliable identification of a wide variety of pathogens directly from the patient's blood within 6h, which brings the opportunity to improve management of septic patients, especially for those critically ill admitted to the ICU.
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Sangue/microbiologia , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase/métodos , Sepse/sangue , Sepse/diagnóstico , Espectrometria de Massas por Ionização por Electrospray/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Serviço Hospitalar de Emergência , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Sepse/microbiologia , Adulto JovemRESUMO
El objetivo principal de esta investigación consistió en el análisis de la eficacia de las técnicas de control de la impulsividad para la prevención de la adicción a videojuegos añadidas a un programa de prevención previamente validado (PrevTec 3.1). Los resultados se tomaron en cuatro momentos: línea base, pre-test (primera sesión), post-test (última sesión) y seguimiento (a los tres meses). Los resultados indican que, mientras los grupos que permanecen en lista de espera no presentan cambios ni en el patrón de uso ni en la dependencia de videojuegos, aquellos en los que se aplica el programa sí que experimentan un descenso significativo. Las dos modalidades del programa de prevención son eficaces en la reducción de las variables analizadas, pero los resultados se mantienen más consistentes durante el seguimiento a quienes se entrenaron las técnicas de control de la impulsividad.
The main objective of this research has been the analysis of the effectiveness of some impulsivity control techniques to prevent videogame addiction. It has compared the results obtained with a prevention program that it had been already validated with the same program in which additional impulsiveness control techniques were added. Four periods were selected for the analysis: baseline, pre-test, post-test and follow-up. Two experimental conditions were designed: a) conventional prevention program, and b) program with impulsiveness control techniques. Results were compared with a group control (waiting list). Results indicate that, while groups that remain on waiting list do not present changes in pattern of use, those which the program was applied decrease significantly. The two modalities of prevention program were effective in the reduction of the analyzed variables, but the changes produced by the implementation of impulsive control techniques were more consistent and lasting in time.
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Humanos , Masculino , Feminino , Criança , Adolescente , Comportamento Aditivo/prevenção & controle , Jogos de Vídeo/psicologia , Análise de Variância , Seguimentos , Comportamento Impulsivo , Inquéritos e Questionários , Resultado do Tratamento , Jogos de Vídeo/efeitos adversosRESUMO
Resumen El objetivo del presente trabajo es validar en población peruana, el Test de Dependencia de Videojuegos (TDV) (Chóliz & Marco, 2011). Los resultados obtenidos demuestran que se trata de una herramienta confiable y válida. Se encontró una sola estructura factorial, en lugar de cuatro dimensiones, como plantearon los autores del TDV. Este factor podría denominarse genéricamente: adicción a videojuegos, y podría servir como evidencia de la existencia de este trastorno, que coincidiría con el denominado 'Trastorno de Juego por Internet', que aparece en la Sección III del DSM-5. Los resultados hallados se discuten en relación a lo planteado por Chóliz y Marco (2011), en lo que se refiere a las diferencias en cuanto a sexo, edad y la estructura interna del instrumento.
Abstract The objective of this work is the validation of the Test of Dependence of Videogames (TDV) (Chóliz & Marco, 2011) in Peruvian population. The results show that it is a reliable and valid tool. We found a single factorial structure, rather than four dimensions as the authors of the TDV raised. This factor could be generically called: 'Addiction to video games', and could serve as evidence of the existence of this disorder, which would coincide with the so-called "Disorder online Game" listed in Section III of the DSM-5. The results found are discussed in relation to Chóliz & Marco (2011) in terms of differences in sex, age and the internal structure of the instrument.