Undiagnosed type 2 diabetes is common - intensified screening of established risk groups is imperative in Sweden: the SDPP cohort.

BACKGROUND: Undiagnosed type 2 diabetes (T2D) is a global problem. Current strategies for diagnosis in Sweden include screening individuals within primary healthcare who are of high risk, such as those with hypertension, obesity, prediabetes, family history of diabetes, or those who smoke daily. In this study, we aimed to estimate the proportion of individuals with undiagnosed T2D in Stockholm County and factors associated with T2D being diagnosed by healthcare. This information could improve strategies for detection. METHODS: We used data from the Stockholm Diabetes Prevention Programme (SDPP) cohort together with information from national and regional registers. Individuals without T2D aged 35-56 years at baseline were followed up after two ten-year periods. The proportion of diagnosed T2D was based on register information for 7664 individuals during period 1 and for 5148 during period 2. Undiagnosed T2D was assessed by oral glucose tolerance tests at the end of each period. With logistic regression, we analysed factors associated with being diagnosed among individuals with T2D. RESULTS: At the end of the first period, the proportion of individuals with T2D who had been diagnosed with T2D or not was similar (54.0% undiagnosed). At the end of the second period, the proportion of individuals with T2D was generally higher, but they were less likely to be undiagnosed (43.5%). The likelihood of being diagnosed was in adjusted analyses associated with overweight (OR=1.85; 95% CI 1.22-2.80), obesity (OR=2.73; 95% CI 1.76-4.23), higher fasting blood glucose (OR=2.11; 95% CI 1.67-2.66), and self-estimated poor general health (OR=2.42; 95% CI 1.07-5.45). Socioeconomic factors were not associated with being diagnosed among individuals with T2D. Most individuals (>71%) who developed T2D belonged to risk groups defined by having at least two of the prominent risk factors obesity, hypertension, daily smoking, prediabetes, or family history of T2D, including individuals with T2D who had not been diagnosed by healthcare. CONCLUSIONS: Nearly half of individuals who develop T2D during 10 years in Stockholm County are undiagnosed, emphasizing a need for intensified screening of T2D within primary healthcare. Screening can be targeted to individuals who have at least two prominent risk factors.

Simultaneous quantification of lead, cadmium and zinc in superficial marine sediments using a carbon-fiber microelectrode modified with bismuth film.

Marine sediments are a useful environmental assessment matrix as they naturally trap toxic substances of anthropogenic origin and thus have higher concentrations of these than the surrounding water. Therefore, developing methods for the sensitive, accurate, and inexpensive quantification of these substances is important, as the traditional techniques have various disadvantages. The current study evaluated the effectiveness of an in situ bismuth-modified carbon-fiber microelectrode (voltamperometric sensor) to simultaneously detect Pb, Cd, and Zn in marine sediments from Puerto Jeli in El Oro Province, Ecuador. This site is representative of the contamination levels present along the coast in this province. Differential pulse anodic stripping voltammetry was applied, and the resulting linear regression for the metal quantification ranged from 12 to 50 µg mL-1, with quantification limits for Pb(II), Cd(II), and Zn(II) of 18.69, 12.55, and 19.29 µg mL-1, respectively. Thus, the quantification with the sensor was successful. According to the preliminary results, Cd and Pb values exceeded the permissible limits established by Ecuador (Texto Unificado de la Legislación Secundaria del Ministerio del Ambiente) and the US Environmental Protection Agency, respectively.

Evaluation of a gold-nanoparticle-modified carbon-fiber microelectrode to quantify mercury in canned tuna sold in Ecuador.

Seafood consumption is the primary exposure route for trace metals like mercury. Accordingly, canned tuna meat has been focused on by researchers because of the potential bioaccumulation of high amounts of mercury. This study aimed to test a novel and reliable electroanalytical method employing a working electrode consisting of gold-nanoparticle-modified carbon microfibers to quantify total mercury in canned tuna samples. Determination was achieved via differential pulse anodic stripping voltammetry. The proposed method had a limit of detection of 3.9781 ± 0.0001 µg L-1 and a limit of quantification of 33.6634 ± 0.0001 µg L-1, with a sensitivity of 0.3275 nA µg L-1. The modified electrode was evaluated in samples taken from three canned tuna brands sold in the Sangolquí parish in Rumiñahui, Ecuador. These brands, coded A, B, and C, represent 47.92%, 27.08%, and 11.98% of all canned tuna sold in the Ecuadorian market, respectively. The resulting respective total mercury concentrations were 0.5999 ± 0.0001 mg kg-1; 0.9387 ± 0.0001 mg kg-1; and 0.3442 ± 0.0001 mg kg-1 for A, B, and C. Method accuracy was determined through the recovery percentages of ≥98%, which indicated acceptable accuracy for the final optimized method. Mean mercury concentrations for all samples did not represent a carcinogenic risk for consumers. However, the values obtained for potential no-carcinogenic risk and daily consumption rate suggest that consumers of tuna canned in water, particularly brand C, may be at risk.

Assessing mitochondria-targeted acyl hydroquinones on the mitochondrial platelet function and cytotoxic activity: Role of the linker length.

INTRODUCTION: The use of triphenylphosphonium cation (TPP+) linked to phenolic compounds by alkyl chains has a significant relevance as a mitochondrial delivery strategy in biomedicine because it affects mitochondrial bioenergetics in models of noncommunicable diseases such as cancer and cardiovascular-related conditions. Studies indicate that a long alkyl chain (10-12 carbon) increases the mitochondrial accumulation of TPP+-linked drugs. In contrast, other studies show that these compounds are consistently toxic to micromolar concentrations (as observed in platelets). In the present study, we evaluated the in vitro effect of three series of triphenylphosphonium-linked acyl hydroquinones derivates on the metabolism and function of human platelets using 3-9 carbons for the alkyl linker. Those were assessed to determine the role of the length of the alkyl chain linker on platelet toxicity. METHODS: Human platelets were exposed in vitro to different concentrations (2-40 µM) of every compound; cellular viability, phosphatidylserine exposition, mitochondrial membrane potential (ΔΨm), intracellular calcium release, and intracellular ROS generation were assessed by flow cytometry. An in silico energetic profile was generated with Umbrella sampling molecular dynamics (MD). RESULTS AND CONCLUSIONS: There was an increase in cytotoxic activity directly related to the length of the acyl chain and lipophilicity, as seen by three techniques, and this was consistent with a decrease in ΔΨm. The in silico energetic profiles point out that the permeability of the mitochondrial membrane may be involved in the cytotoxicity of phosphonium salts. This information may be relevant for the design of new TPP+ -based drugs with a safe cardiovascular profile.

The Use of Triphenyl Phosphonium Cation Enhances the Mitochondrial Antiplatelet Effect of the Compound Magnolol.

Although platelets are anucleated cells, they have fully functional mitochondria, and currently, it is known that several processes that occur in the platelet require the action of mitochondria. There are plenty of mitochondrial-targeted compounds described in the literature related to cancer, however, only a small number of studies have approached their interaction with platelet mitochondria and/or their effects on platelet activity. Recent studies have shown that magnolia extract and mitochondria-targeted magnolol can inhibit mitochondrial respiration and cell proliferation in melanoma and oral cancer cells, respectively, and they can also induce ROS and mitophagy. In this study, the effect of triphenylphosphonium cation, linked by alkyl chains of different lengths, to the organic compound magnolol on human-washed platelets was evaluated. We demonstrated that the addition of triphenylphosphonium by a four-carbon linker to magnolol (MGN4) considerably enhanced the Magnolol antiplatelet effect by a 3-fold decrease in the IC50. Additionally, platelets exposed to MGN4 5 µM showed several differences from the control including increased basal respiration, collagen-induced respiration, ATP-independent respiration, and reduced ATP-dependent respiration and non-mitochondrial respiration.

Long-term air pollution exposure and Parkinson's disease mortality in a large pooled European cohort: An ELAPSE study.

BACKGROUND: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson's Disease (PD) remains limited. OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts. METHODS: Within the project 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (O3), as well as 8 PM2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders. RESULTS: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM2.5 (hazard ratio per 5 µg/m3: 1.25; 95% confidence interval: 1.01-1.55), NO2 (1.13; 0.95-1.34 per 10 µg/m3), and BC (1.12; 0.94-1.34 per 0.5 × 10-5m-1), and a negative association with O3 (0.74; 0.58-0.94 per 10 µg/m3). Associations of PM2.5, NO2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM2.5 remained robust when adjusted for NO2 (1.24; 0.95-1.62) or BC (1.28; 0.96-1.71), whereas associations with NO2 or BC attenuated to null. O3 associations remained negative, but no longer statistically significant in models with PM2.5. We detected suggestive positive associations with the potassium component of PM2.5. CONCLUSION: Long-term exposure to PM2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality.

In Vitro Effect of Mitochondria-Targeted Triphenylphosphonium-Based Compounds (Honokiol, Lonidamine, and Atovaquone) on the Platelet Function and Cytotoxic Activity.

Introduction: Obtaining triphenylphosphonium salts derived from anticancer compounds to inhibit mitochondrial metabolism is of major interest due to their pivotal role in reactive oxygen species (ROS) production, calcium homeostasis, apoptosis, and cell proliferation. However, the use of this type of antitumor compound presents a risk of bleeding since the platelet activation is especially dependent on the mitochondrial function. In this study, we evaluated the in vitro effect of three triphenylphosphonium-based compounds, honokiol (HNK), lonidamine (LDN), and atovaquone (ATO), on the platelet function linked to the triphenylphosphonium cation by a lineal 10-carbon alkyl chain and also the decyltriphenylphosphonium salt (decylphos). Methods: Platelets obtained by phlebotomy from healthy donors were exposed in vitro to different concentrations (0.1-10 µM) of the three compounds; cellular viability, exposure of phosphatidylserine, the mitochondrial membrane potential (∆Ψm), intracellular calcium release, and intracellular ROS generation were measured. Platelet activation and aggregation were induced by agonists (adenosine diphosphate, thrombin receptor-activating peptide-6, convulxin, or phorbol-12-myristate-13-acetate) and were evaluated by flow cytometry and light transmission, respectively. Results: The three compounds showed a slight cytotoxic effect from 1 µM, and this was concomitant with a decrease in ∆Ψm and intracellular calcium increase. Only ATO produced a modest but significant increase in intra-platelet ROS. Also, the three compounds increased the exposure to phosphatidylserine in platelets expressed in platelets positive for annexin V. None of the compounds had an inhibitory effect on the aggregation or activation markers of platelets stimulated with three different agonists. Similar results were obtained with decylphos. Conclusion: Triphenylphosphonium derivatives showed slight platelet toxicity below 1 µM, probably associated with their effect on ∆Ψm and exposure to phosphatidylserine, but no significant effect on platelet activation and aggregation, making them an antitumoral alternative with a low risk of bleeding. However, future assays on animal models and human trials are required to evaluate if their effects with a low risk for hemostasis are replicated in vivo.

Antioxidant Capacity and Antiplatelet Activity of Aqueous Extracts of Common Bean (Phaseolus vulgaris L.) Obtained with Microwave and Ultrasound Assisted Extraction.

Phaseolus vulgaris L. has beneficial effects on several chronic non-communicable diseases (e.g., cardiovascular diseases) related to oxidative stress. This redox state may influence platelet activation and aggregation; which is crucial in thrombus formation. In this work, the antiplatelet and antioxidant potential of aqueous extracts obtained by green processes, microwave-assisted extraction and ultrasound-assisted extraction, from 25 landraces of common beans were investigated. Phenol content and antioxidant potential were determined using the Folin-Ciocalteu method, total monomeric anthocyanin and ORAC assay, respectively. The antiplatelet potential of the extracts was explored by turbidimetry. Microwave extraction showed higher phenol content and antioxidant activity in most extracts. Soja landrace extract obtained by microwave-assisted extraction showed higher phenol content and antioxidant activity (893.45 ± 87.30 mg GAE/g and 35,642.85 ± 2588.88 ORAC µmolTE/g, respectively). Although most of the extracts obtained by microwave-assisted extraction showed antiplatelet activity, the extract of Hallado Aleman landrace obtained by ultrasound-assisted extraction (IC50 = 0.152 ± 0.018 mg/mL) had the highest antiplatelet potential. The extraction method, MAE and UAE, influences the biological potential of the beans, specifically the antiplatelet activity and antioxidant activity. The functional value of this legume for direct consumption by the population was evidenced, as well as its inclusion in food formulations.

Using Distributed Lag Non-Linear Models to Estimate Exposure Lag-Response Associations between Long-Term Air Pollution Exposure and Incidence of Cardiovascular Disease.

Long-term air pollution exposure increases the risk for cardiovascular disease, but little is known about the temporal relationships between exposure and health outcomes. This study aims to estimate the exposure-lag response between air pollution exposure and risk for ischemic heart disease (IHD) and stroke incidence by applying distributed lag non-linear models (DLNMs). Annual mean concentrations of particles with aerodynamic diameter less than 2.5 µm (PM2.5) and black carbon (BC) were estimated for participants in five Swedish cohorts using dispersion models. Simultaneous estimates of exposure lags 1-10 years using DLNMs were compared with separate year specific (single lag) estimates and estimates for lag 1-5- and 6-10-years using moving average exposure. The DLNM estimated no exposure lag-response between PM2.5 total, BC, and IHD. However, for PM2.5 from local sources, a 20% risk increase per 1 µg/m3 for 1-year lag was estimated. A risk increase for stroke was suggested in relation to lags 2-4-year PM2.5 and BC, and also lags 8-9-years BC. No associations were shown in single lag models. Increased risk estimates for stroke in relation to lag 1-5- and 6-10-years BC moving averages were observed. Estimates generally supported a greater contribution to increased risk from exposure windows closer in time to incident IHD and incident stroke.

Interrelaciones entre el sentido de la vida, la actividad física, la red de apoyo social, la edad y el género en adultos mayores / Interrelationships between the meaning of life, physical activity, social support network, age, and gender in older adults

Resumen Introducción: los adultos mayores que asisten a los centros diurnos tienen la oportunidad de interactuar con sus pares y realizar actividades, lo cual podría incidir en su sentido de la vida. Objetivo: evidenciar las asociaciones entre el sentido de la vida, la actividad física, la red de apoyo social, la edad y el género en siete centros diurnos de la provincia de Heredia, Costa Rica. Metodología: el estudio es cuantitativo de corte transversal. Se eligieron siete centros diurnos de los cuales se seleccionó una muestra por conveniencia de 77 adultos mayores. Las variables investigadas fueron el sentido de la vida, la actividad física, la red de apoyo social, la edad y el género. Para la recolección de datos se utilizaron autoreportes y los investigadores ayudaron a aclarar dudas sobre las preguntas. Resultados: el 46 % de las personas mayores reportó una falta de sentido de la vida y un 36 % un nivel de actividad física baja. Se determinó una asociación significativa entre la red de apoyo social y el sentido de la vida (.= .911; p < .001), entre la edad y la red de apoyo social (.=.30 .=.048), y entre el apoyo social y el género femenino (.=-6.08, .=.010). Conclusiones: la red de apoyo social es un predictor del sentido de la vida, así como la edad y el género predicen la red de apoyo social; pero no la actividad física reportada sobre las variables investigadas.

Abstract Introduction. Older adults attending daycare centers are in an environment in which different variables are interrelated and could shape their meaning of life, among other aspects. Objective: To analyze the associations between the meaning of life, physical activity, social support network, age, and gender in seven-day centers in the province of Heredia, Costa Rica. Methodology: This is a cross-sectional quantitative study. Seventy-seven older adults were recruited from seven-day centers. The variables investigated were the meaning of life, physical activity, social support network, age, and gender. Self-reports were collected and researchers clarified any doubts. Results: 46% of the participants reported a meaningless life and 36% low levels of physical activity. Significant associations were found between social support network and meaning of life (. = .91; . <.001), age and social support network (. = .30 . = .048), and social support and female gender (. = -6.08, . = .010). Conclusions: The social support network is a predictor of the meaning of life and age and gender predict the social support network, but not the physical activity reported in the variables investigated.

Antiplatelet Activity of Isorhamnetin via Mitochondrial Regulation.

With the diet, we ingest nutrients capable of modulating platelet function, which plays a crucial role in developing cardiovascular events, one of the leading causes of mortality worldwide. Studies that demonstrate the antiplatelet and antithrombotic potential of bioactive compounds are vital to maintaining good cardiovascular health. In this work, we evaluate the flavonol isorhamnetin's antiplatelet effect on human platelets, using collagen, thrombin receptor activator peptide 6 (TRAP-6), and phorbol myristate acetate (PMA) as agonists. Isorhamnetin induced a significant inhibition on collagen- and TRAP-6-induced platelet aggregation, with half-maximum inhibitory concentration (IC50) values of 8.1 ± 2.6 and 16.1 ± 11.1 µM, respectively; while it did not show cytotoxic effect. Isorhamnetin reduced adenosine triphosphate levels (ATP) in platelets stimulated by collagen and TRAP-6. We also evidenced that isorhamnetin's antiplatelet activity was related to the inhibition of mitochondrial function without effect on reactive oxygen species (ROS) levels. Additionally, we investigated isorhamnetin's effect on thrombus formation in vitro under flow conditions on the damaged vessel wall. In this context, we demonstrate that isorhamnetin at 20 µM induced a significant inhibition on platelet deposition, confirming its antithrombotic effect. Our findings corroborate the antiplatelet and antithrombotic potential of isorhamnetin present in many foods of daily consumption.

La inclusión de personas con discapacidad en una escuela multideportiva: Efecto de las actitudes hacia la discapacidad en niños, niñas, jóvenes, padres, madres y personal de instrucción / The Inclusion of People with Disabilities in a Multi-Sport School: Effect of Attitudes on Children, Youth, Parents, and Instructors Towards Disability

Resumen: El propósito del estudio fue observar el efecto de un programa multideportivo inclusivo sobre las actitudes de niños, niñas, jóvenes, padres, madres y personal de instrucción hacia las personas con discapacidad. Metodología: 18 niños, 4 instructores y 11 padres (n=33), pertenecientes a un programa multideportivo (EDP) de la Escuela de Movimiento Humano y Calidad de Vida, de la Universidad Nacional. Los actores fueron expuestos a una intervención que consistió en la participación en sesiones multideportivo, al menos 2 horas a la semana de 3 disciplinas deportivas (disciplinas individuales y de conjunto) que variaban semana a semana para un total de 6 semanas. Se les evaluó el cuestionario de "Actitudes hacia las personas con discapacidad" previo y posterior a la intervención. Los resultados fueron explorados mediante un análisis de varianza mixto3(grupo)x2(medición) con un alfa establecido en p 0.05). Conclusiones: La inmersión de diferentes actores en un programa multideportivo inclusivo ha sido eficaz al modificar positivamente algunas dimensiones (VCL y CG) de la actitud hacia las personas con discapacidad. Otras dimensiones que requieren una mayor interacción y vínculo con este tipo de poblaciones (RND e IP) probablemente necesiten una intervención más prolongada.

Abstract This study aimed to observe children, youth, parents, and instructors' attitudes towards disability. The study intended to measure the effects of a multidisciplinary program of the Escuela Deportiva Pedagógica -EDP- (Pedagogical Sports School) of the School of Human Movement and Quality of Life, at the National University of Costa Rica. Methodology: thirty-three participants were incorporated into the study. Then, they were separated into three groups: four instructors, eleven parents, and eighteen children. The intervention consisted of participation in multisport sessions, at least two hours per week in three sport disciplines that varied from week to week over six weeks. All of them were given a questionnaire titled "Actitudes hacia las personas con discapacidad" (Attitudes towards people with disabilities). The questionnaire was applied both at the beginning and at the end of the intervention. A two-factor mixed ANOVA of 3 (groups) x 2 (measurements) with an alpha of 0.05 was used. Results: A significant interaction was found after the treatment in the dimension of "Valoración de las capacidades y limitaciones" -VCL- (Assessment of skills and limitations), F(2, 30) = 10.28, p 0.05).Conclusion:The results showed that the multidisciplinary programs of an inclusive nature positively modify attitudes (VCL and CG) towards the population with disabilities, but it is likely that some aspects related to attitude take longer to be changed (RND and IP).

Resumo: O objetivo do estudo foi observar o efeito de um programa poliesportivo inclusivo nas atitudes das crianças, jovens, pais, mães e instrutores em relação às pessoas com incapacidade. Metodologia: 18 crianças, 4 instrutores e 11 casais (n = 33) pertencentes a um programa poliesportivo (EDP) da Escola de Movimento Humano e Qualidade de Vida, da Universidade Nacional. Os atores foram expostos a uma intervenção que consistia em participar de sessões poliesportivas, pelo menos 2 horas por semana em 3 disciplinas esportivas (disciplinas individuais e em grupo) que variavam de semana para semana, durante um total de 6 semanas. O questionário "Atitudes em relação às pessoas com deficiência" foi avaliado antes e após a intervenção. Os resultados foram explorados por meio de uma análise mista de variância mista 3 (grupo) x2 (medicao) com alfa estabelecido em p 0,05). Conclusões: A imersão de diferentes atores em um programa poliesportivo inclusivo tem sido eficaz na modificação positiva de algumas dimensões (VCL e GC) da atitude em relação às pessoas com incapacidade. Outras dimensões que requerem maior interação e vinculação com esse tipo de população (RND e IP) provavelmente requerem uma intervenção mais longa.

Impacto de COVID-19 en la enfermedad cardiovascular / Impact of COVID-19 on cardiovascular disease

Resumen La enfermedad por coronavirus-2019 (COVID-19) es una enfermedad infecciosa cuya sintomatología inicial, en la mayoría de las ocasiones, se manifiesta con compromiso del tracto respiratorio. El virus que causa dicha enfermedad se denomina síndrome respiratorio agudo severo por coronavirus 2 (SARS-CoV2). Si bien la manifestación grave más frecuente de la infección parece ser la neumonía, se han documentado diversas implicaciones cardiovasculares. Las personas que cursan con dicha infección y que tienen una enfermedad cardiovascular preexistente tienen un riesgo mayor de cuadros graves y mortalidad. Existen asociaciones directas o indirectas de la infección con injuria miocárdica, arritmias, enfermedad tromboembólica venosa y miocarditis. Los tratamientos en investigación pueden tener efectos adversos en el sistema eléctrico del corazón; además, algunos medicamentos de uso crónico (como los inhibidores del sistema renina angiotensina aldosterona) se les ha otorgado un polémico papel en la virulencia del microorganismo. La alta demanda en atención en salud que requieren los pacientes infectados por SARS-CoV 2 puede comprometer la asistencia de pacientes cardiovasculares sin dicha infección y dejar en riesgo de exposición al personal sanitario. Se presenta una revisión sobre los aspectos más llamativos donde estas dos condiciones interaccionan.

Abstract Coronavirus-2019 disease (COVID-19) is an infectious disease which initial symptoms, in most cases, manifest with respiratory tract compromise. The virus that causes said disease is called severe acute respiratory syndrome by coronavirus 2 (SARS-CoV 2), although the most frequent serious manifestation of the infection appears to be pneumonia, various implications have been documented from the cardiovascular point of view. People who have this infection and a pre-existing cardiovascular disease have an increased risk of severe symptoms and mortality. There are direct or indirect associations of the infection with myocardial injury, arrhythmias, venous thromboembolic disease and myocarditis. Investigational treatments may have adverse effects on the heart's electrical system. In addition, some medications of chronic use (such as renin angiotensin aldosterone systeminhibitors), have been given a controversial role in the virulence of the organism. The high demand in health care required by patients infected with SARS-CoV 2 can compromise the care of cardiovascular patients without said infection, in addition to leaving healthcare personal at risk of exposure. Therefore, a review is presented on the most striking aspects where these two conditions interact.

Mitoquinone (MitoQ) Inhibits Platelet Activation Steps by Reducing ROS Levels.

Platelet activation plays a key role in cardiovascular diseases. The generation of mitochondrial reactive oxygen species (ROS) has been described as a critical step required for platelet activation. For this reason, it is necessary to find new molecules with antiplatelet activity and identify their mechanisms of action. Mitoquinone (MitoQ) is a mitochondria-targeted antioxidant that reduces mitochondrial overproduction of ROS. In this work, the antiplatelet effect of MitoQ through platelet adhesion and spreading, secretion, and aggregation was evaluated. Thus MitoQ, in a non-toxic effect, decreased platelet adhesion and spreading on collagen surface, and expression of P-selectin and CD63, and inhibited platelet aggregation induced by collagen, convulxin, thrombin receptor activator peptide-6 (TRAP-6), and phorbol 12-myristate 13-acetate (PMA). As an antiplatelet mechanism, we showed that MitoQ produced mitochondrial depolarization and decreased ATP secretion. Additionally, in platelets stimulated with antimycin A and collagen MitoQ significantly decreased ROS production. Our findings showed, for the first time, an antiplatelet effect of MitoQ that is probably associated with its mitochondrial antioxidant effect.

Aneurisma de arteria pulmonar: un hallazgo incidental / Pulmonary artery aneurysm: an incidental finding

Resumen Los aneurismas de la arteria pulmonar son entidades infrecuentes y su tratamiento es tema de discusión. Desde el punto de vista etiológico pueden ser congénitos o adquiridos. Los primeros, generalmente se asocian a malformaciones cardiacas que producen hipertensión pulmonar, siendo el ductus arterioso la más frecuente. Otras anomalías incluyen defectos auriculares o ventriculares. Las causas adquiridas pueden ser idiopáticas o estar asociadas a infecciones (tuberculosis, sífilis), traumatismos o colagenopatías. Presentamos el caso de una mujer de 62 años, quien consultó por un cuadro clínico en el que se destacaba su sintomatología neurológica e infecciosa, con posterior progresión a un choque séptico y en quien los hallazgos de las imágenes mostraron un aneurisma gigante de la arteria pulmonar siendo este un hallazgo incidental y sin relación a la sintomatología de la paciente.

Abstract Aneurysms of the pulmonary artery are rare entities and their treatment is a matter of discussion. From the etiological point of view, they can be congenital or acquired. Those in the first group are generally associated with cardiac malformations that generate pulmonary hypertension, with the ductus arteriosus being the most frequent. Other abnormalities include atrial or ventricular defects. The acquired causes may be idiopathic or associated with infections (tuberculosis, syphilis), trauma, or collagen disease. We present the case of a 62-year-old woman, which consulted for a clinical condition where neurological and infectious symptoms stood out, with subsequent progression to a state of septic shock, and in whom the imaging finding showed a giant pulmonary artery aneurysm. this being an incidental finding and unrelated to the patient's symptoms.

Polypharmacy Is Associated with Frailty, Nutritional Risk and Chronic Disease in Chilean Older Adults: Remarks from PIEI-ES Study.

AIM: To analyze the relationship between polypharmacy and variables as frailty and other chronic comorbidities in Chilean older adults. DESIGN: Cross-sectional study. PARTICIPANTS: One thousand two hundred and five older adults aged 65 and older. METHODS: The presence or absence of frailty syndrome was determined according to Fried criteria. Data collection was made through questionnaires conducted by an interview. RESULTS: The prevalence of polypharmacy was 37.59%. The prevalence of hyperpolypharmacy was 2%. Increased prevalence of frailty was demonstrated regarding the progression of the state of polypharmacy. When analyzing the contribution of frailty respect polypharmacy condition, frail state, nutritional risk and obesity are founded as a factor associated with polypharmacy. Regarding chronic disease, hypertension (OR: 8.039, p<0.0001), type 2 diabetes (OR: 4.001, p<0.0001) and respiratory diseases (OR: 2.930, p<0.0001) were associated to polypharmacy. It was found a strong and significant positive correlation between polypharmacy prevalence and frailty score (polypharmacy condition, Spearman R: 0.89, p=0.033; hyperpolypharmacy condition, Spearman R: 0.94, p=0.016). When analyzing the contribution of the polypharmacy to the presence of frailty, polypharmacy condition (OR: 1.510, p<0.05), cognitive impairment (OR: 3.887, p<0.001), obesity (OR: 1.560, p<0.01) and nutritional risk (OR: 2.590, p<0.001) are associated to frailty. CONCLUSION: Frailty and chronic conditions as nutritional risk, obesity, hypertension, type 2 diabetes and respiratory disease are an important risk factor for the development of polypharmacy in Chilean older adults. Likewise, polypharmacy condition was observed to be a risk factor for frailty, demonstrating the bidirectional relationship between both conditions. Frailty syndrome evaluation in Chilean older adults could be an important alternative for polypharmacy prevention.

Platelet Activation Is Triggered by Factors Secreted by Senescent Endothelial HMEC-1 Cells In Vitro.

Aging is one of the main risk factors for the development of chronic diseases, with both the vascular endothelium and platelets becoming functionally altered. Cellular senescence is a form of permanent cell cycle arrest initially described in primary cells propagated in vitro, although it can also be induced by anticancer drugs and other stressful stimuli. Attesting for the complexity of the senescent phenotype, senescent cells synthesize and secrete a wide variety of bioactive molecules. This "senescence-associated secretory phenotype" (SASP) endows senescent cells with the ability to modify the tissue microenvironment in ways that may be relevant to the development of various physiological and pathological processes. So far, however, the direct role of factors secreted by senescent endothelial cells on platelet function remains unknown. In the present work, we explore the effects of SASP factors derived from senescent endothelial cells on platelet function. To this end, we took advantage of a model in which immortalized endothelial cells (HMEC-1) were induced to senesce following exposure to doxorubicin, a chemotherapeutic drug widely used in the clinic. Our results indicate that (1) low concentrations of doxorubicin induce senescence in HMEC-1 cells; (2) senescent HMEC-1 cells upregulate the expression of selected components of the SASP and (3) the media conditioned by senescent endothelial cells are capable of inducing platelet activation and aggregation. These results suggest that factors secreted by senescent endothelial cells in vivo could have a relevant role in the platelet activation observed in the elderly or in patients undergoing therapeutic stress.

Reorganization of perineuronal nets in the medial Preoptic Area during the reproductive cycle in female rats.

Perineuronal nets (PNNs) are aggregations of extracellular matrix associated with specific neuronal populations in the central nervous system, suggested to play key roles in neural development, synaptogenesis and experience-dependent synaptic plasticity. Pregnancy and lactation are characterized by a dramatic increase in neuroplasticity. However, dynamic changes in the extracellular matrix associated with maternal circuits have been mostly overlooked. We analyzed the structure of PNNs in an essential nucleus of the maternal circuit, the medial preoptic area (mPOA), during the reproductive cycle of rats, using the Wisteria floribunda (WFA) label. PNNs associated to neurons in the mPOA start to assemble halfway through gestation and become highly organized prior to parturition, fading through the postpartum period. This high expression of PNNs during pregnancy appears to be mediated by the influence of estrogen, progesterone and prolactin, since a hormonal simulated-gestation treatment induced the expression of PNNs in ovariectomized females. We found that PNNs associated neurons in the mPOA express estrogen receptor α and progesterone receptors, supporting a putative role of reproductive hormones in the signaling mechanisms that trigger the assembly of PNNs in the mPOA. This is the first report of PNNs presence and remodeling in mPOA during adulthood induced by physiological variables.

Synthesis of antiplatelet ortho-carbonyl hydroquinones with differential action on platelet aggregation stimulated by collagen or TRAP-6.

Cardiovascular diseases are the leading cause of death in the world. Platelets have a major role in cardiovascular events as they bind to the damaged endothelium activating and forming thrombi. Although some hydroquinone scaffold-containing compounds have known antiplatelet activities, currently there is a lack of evidence on the antiplatelet activity of hydroquinones carrying electron attractor groups. In this work, we evaluate the antiplatelet effect of a series of ortho-carbonyl hydroquinone derivatives on cytotoxicity and function of human platelets, using collagen and thrombin receptor activator peptide 6 (TRAP-6) as agonists. Our structure-activity relationship study shows that gem-diethyl/methyl substitutions and the addition/modifications of the third ring of ortho-carbonyl hydroquinone scaffold influence on the selective index (IC50 TRAP-6/IC50 Collagen) and the inhibitory capacity of platelet aggregation. Compounds 3 and 8 inhibit agonist-induced platelet aggregation in a non-competitive manner with IC50 values of 1.77 ± 2.09 µM (collagen) and 11.88 ± 4.59 µM (TRAP-6), respectively and show no cytotoxicity. Both compounds do not affect intracellular calcium levels and mitochondrial bioenergetics. Consistently, they reduce the expression of P-selectin, activation of glycoprotein IIb/IIIa, and release of adenosine triphosphate and CD63 from platelet. Our findings may be used for further development of new drugs in platelet-related thrombosis diseases.

The Effect of Smartphone Apps Versus Supervised Exercise on Physical Activity, Cardiorespiratory Fitness, and Body Composition Among Individuals With Mild-to-Moderate Mobility Disability: Randomized Controlled Trial.

BACKGROUND: Adequate levels of physical activity (PA) and good cardiorespiratory fitness (CRF) are associated with profound health benefits for individuals with mobility disability (MD). Despite the vast amount of research published in the field of PA interventions, little attention has been given to individuals with MD. OBJECTIVE: The aim of this study was to examine the efficacy of an app-based versus a supervised exercise and health coaching program to support adults with MD to increase levels of PA, CRF, and improve body composition. METHODS: Participants with self-perceived MD, aged 18 to 45 years, were included in this 12-week parallel-group randomized controlled trial and allocated at random to an app-based intervention, using commercially available apps-the Swedish Military training app (FMTK), the Acupedo walking app, and the LogMyFood food photography app-or a supervised exercise and health coaching intervention, including 1 weekly supervised exercise session and healthy lifestyle coaching. The primary outcome was the level of moderate-to-vigorous PA (MVPA) measured with accelerometers. Secondary outcomes included CRF measured by a submaximal test performed on a stationary bicycle and body composition measured by bioelectrical impedance. All outcomes were measured at baseline, 6 weeks, and 12 weeks. Linear mixed-effect models were used to assess the between-group differences, as well as the within-group changes through time, in each intervention group. RESULTS: A total of 110 participants with MD were randomized to an app-based intervention (n=55) or a supervised exercise and health intervention (n=55). The mean age of participants was 34.9 years (SD 6.1), and 81.8% (90/110) of the participants were women. CRF showed a moderate increase in both groups after 12 weeks-1.07 (95% CI -0.14 to 2.27) mL/kg/min increase in the app-based group and 1.76 (95% CI 0.70 to 2.83) mLkg/min increase in the supervised exercise group. However, the intention-to-treat analysis showed no significant differences between the groups in MVPA or CRF after 12 weeks. Waist circumference was significantly lower in the app-based intervention group. CONCLUSIONS: Commercially available apps increased levels of CRF and improved body composition over 12 weeks to the same extent as supervised exercise sessions, showing that both are equally effective. However, neither the app-based intervention nor the supervised exercise intervention increased MVPA. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 22387524; http://isrctn.com/ISRCTN22387524.