Epidemiological, mechanistic, and practical bases for assessment of cardiorespiratory fitness and muscle status in adults in healthcare settings.

Given their importance in predicting clinical outcomes, cardiorespiratory fitness (CRF) and muscle status can be considered new vital signs. However, they are not routinely evaluated in healthcare settings. Here, we present a comprehensive review of the epidemiological, mechanistic, and practical bases of the evaluation of CRF and muscle status in adults in primary healthcare settings. We highlight the importance of CRF and muscle status as predictors of morbidity and mortality, focusing on their association with cardiovascular and metabolic outcomes. Notably, adults in the best quartile of CRF and muscle status have as low as one-fourth the risk of developing some of the most common chronic metabolic and cardiovascular diseases than those in the poorest quartile. The physiological mechanisms that underlie these epidemiological associations are addressed. These mechanisms include the fact that both CRF and muscle status reflect an integrative response to the body function. Indeed, muscle plays an active role in the development of many diseases by regulating the body's metabolic rate and releasing myokines, which modulate metabolic and cardiovascular functions. We also go over the most relevant techniques for assessing peak oxygen uptake as a surrogate of CRF and muscle strength, mass, and quality as surrogates of muscle status in adults. Finally, a clinical case of a middle-aged adult is discussed to integrate and summarize the practical aspects of the information presented throughout. Their clinical importance, the ease with which we can assess CRF and muscle status using affordable techniques, and the availability of reference values, justify their routine evaluation in adults across primary healthcare settings.

In vivo absolute quantification of carnosine in the vastus lateralis muscle with 1H MRS using a surface coil and water as internal reference.

OBJECTIVE: To standardize a method for 1H MRS intramuscular absolute quantification of carnosine in the thigh, using a surface coil and water as internal reference. MATERIALS AND METHODS: Carnosine spectra were acquired in phantoms (5, 10, and 15 mM) as well as in the right gastrocnemius medialis (GM) and right vastus lateralis (VLM) muscles of young team sports athletes, using volume (VC) and surface (SC) coils on a 3 T scanner, with the same receiver gain. Water spectra were used as internal reference for the absolute quantification of carnosine. RESULTS: Phantom's experiments showed a maximum error of 7%, highlighting the validity of the measurements in the study setup. The carnosine concentrations (mmol/kg ww, mean ± SD) measured in the GM were 6.8 ± 2.2 with the VC (CcarVC) and 10.2 ± 3.0 with the SC (CcarSC) (P = 0.013; n = 9). Therefore, a correction was applied to these measurements (CcarVC = 0.6582*CcarSC), to make coils performance comparable (6.8 ± 2.2 for VC and 6.7 ± 2.0 for SC, P = 0.97). After that, only the SC was used to quantify carnosine in the VLM, where a concentration of 5.4 ± 1.5 (n = 30) was found, with significant differences between men (6.2 ± 1.3; n = 15) and women (4.6 ± 1.2; n = 15). The error in quantitation was 5.3-5.5% with both coils. CONCLUSION: The method using the SC and water as internal reference can be used to quantify carnosine in voluminous muscles and regions of the body in humans, where the VC is not suitable, such as the VLM.

Serum Levels of Myonectin Are Lower in Adults with Metabolic Syndrome and Are Negatively Correlated with Android Fat Mass.

Myonectin has shown beneficial effects on lipid regulation in murine models; therefore, it may have implications in the pathophysiology of metabolic syndrome (MS). We evaluated the relationship between serum myonectin and serum lipids, global and regional fat mass, intramuscular lipid content, and insulin resistance (IR) in adults with metabolic risk factors. This was a cross-sectional study in sedentary adults who were diagnosed with MS or without MS (NMS). Serum myonectin was quantified by enzyme-linked immunosorbent assay, lipid profile by conventional techniques, and free fatty acids (FFA) by gas chromatography. Body composition was assessed by dual-energy X-ray absorptiometry and intramuscular lipid content through proton nuclear magnetic resonance spectroscopy in the right vastus lateralis muscle. IR was estimated with the homeostatic model assessment (HOMA-IR). The MS (n = 61) and NMS (n = 29) groups were comparable in age (median (interquartile range): 51.0 (46.0-56.0) vs. 53.0 (45.5-57.5) years, p > 0.05) and sex (70.5% men vs. 72.4% women). MS subjects had lower serum levels of myonectin than NMS subjects (1.08 (0.87-1.35) vs. 1.09 (0.93-4.05) ng·mL-1, p < 0.05). Multiple linear regression models adjusted for age, sex, fat mass index and lean mass index showed that serum myonectin was negatively correlated with the android/gynoid fat mass ratio (R2 = 0.48, p < 0.01), but not with the lipid profile, FFA, intramuscular lipid content or HOMA-IR. In conclusion, serum myonectin is lower in subjects with MS. Myonectin negatively correlates with a component relevant to the pathophysiology of MS, such as the android/gynoid fat mass ratio, but not with other components such as FFA, intramuscular fat or IR.

Efficacy of high-intensity interval- or continuous aerobic-training on insulin resistance and muscle function in adults with metabolic syndrome: a clinical trial.

PURPOSE: We carried out a randomized, clinical trial in adults of both sexes with metabolic syndrome (MS) to assess the efficacy of high-intensity, low-volume interval training (HIIT) compared to moderate-intensity continuous training (MICT) on insulin resistance (IR), muscle mass, muscle activation, and serum musclin. METHODS: Fasting glycemia, insulinemia, and glycated haemoglobin were determined by conventional methods, IR by Homeostatic model assessment (HOMA), lean mass by Dual-Energy X-ray Absorptiometry, muscle activation through carnosine by Proton Magnetic Resonance Spectroscopy, and musclin by Enzyme-Linked ImmunoSorbent Assay before and after a supervised, three-times/week, 12-week treadmill programme. HIIT (n = 29) consisted of six intervals with one-minute, high-intensity phases at 90% of peak oxygen consumption (VO2peak). MICT (n = 31) trained at 60% of VO2peak for 30 min. RESULTS: Patients had a mean age of 50.8 ± 6.0 years, body mass index of 30.6 ± 4.0 kg/m2, and VO2peak of 29.0 ± 6.3 mL.kg-1.min-1. Compared to MICT, HIIT was not superior at reducing Ln HOMA-IR (adjusted mean difference: 0.083 [95%CI - 0.092 to 0.257]), carnosine or musclin or at increasing thigh lean mass. HIIT increased carnosine by 0.66 mmol/kg.ww (95% CI 0.08-1.24) after intervention. Both interventions reduced IR, body fat percentage and increased total lean mass/height2 and VO2peak. Musclin showed a non-significant reduction with a small effect size after both interventions. CONCLUSION: Compared to MICT, HIIT is not superior at reducing IR, carnosine or musclin or at increasing skeletal muscle mass in adults with MS. Both training types improved IR, muscle mass and body composition. NCT03087721, March 22nd, 2017. TRIAL REGISTRATION NUMBER: NCT03087721. Registered March 22nd, 2017.

Effects of Low-Volume, High-Intensity Interval Training Compared with Continuous Training on Regional and Global Body Composition in Adults with Metabolic Syndrome: A post hoc Analysis of a Randomized Clinical Trial.

OBJECTIVE: The aim of this study was to compare the effects of low-volume, high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) on body composition in adults with metabolic syndrome (MS). METHODS: This is a post hoc analysis of the randomized clinical trial Intraining-MET. Sixty adults (40-60 years old) were randomized to an MICT (n = 31) or HIIT (n = 29) supervised programme 3 days/week for 12 weeks. MICT sessions were conducted for 36 min at 60% of peak oxygen consumption (VO2peak). HIIT sessions included 6 intervals at 90% VO2peak for 1 min, followed by 2 min at 50% VO2peak. Body composition was assessed with dual energy X-ray absorptiometry. RESULTS: Body weight did not change from pre- to post-training in either MICT (78.9 ± 15.6 kg; 77.7 ± 16.5 kg, p = 0.280) or HIIT groups (76.3 ± 13.4 kg; 76.3 ± 13.7 kg, p = 0.964). Body fat percentage and fat mass (FM) decreased post-training in the MICT (-0.9%; 95% confidence interval [CI]: -0.27 to -1.47 and -0.7 kg; 95% CI: -0.12 to -1.30) and HIIT groups (-1.0%; 95% CI: -0.32 to -1.68 and -0.8 kg; 95% CI: -0.17 to -1.47). Compared to the HIIT programme, MICT significantly reduced android FM (-0.14 kg; 95% CI: -0.02 to -0.26). Lean mass (LM) increased post-training in MICT (+0.7 kg; 95% CI: 0.01-1.41) and HIIT groups (+0.9 kg; 95% CI: 0.12-1.64), but only HIIT increased the trunk LM (+0.6 kg; 95% CI: 0.06-1.20). CONCLUSIONS: Both MICT and HIIT reduced FM without changing body weight in adults with MS. MICT had additional benefits by reducing the android FM, whereas HIIT seemed to increase LM. Given the characteristics of the post hoc analysis, further research is required to confirm these results.

[Predictive validity of a functional classification method in older adultsValidação preditiva de método de classificação funcional em idosos]. / Validación predictiva de un método de clasificación funcional en adultos mayores.

OBJECTIVE: Evaluate the predictive validity of a functional classification (FC) method for the use of emergency services and hospitalization, mortality, and health care costs among older adults. METHODS: Retrospective cohort study that included 2 168 older adults in a chronic noncommunicable disease (CNCD) care program in Medellin, Colombia. Patients were stratified according to a FC method based on functional status, presence of risk factors, and control of comorbidity. During one year of follow-up, the predictive validity of the FC method was assessed for the studied outcomes. Discrimination and calibration were measured with the C-statistic and Hosmer-Lemeshow (HL) test, respectively. RESULTS: The average age was 74.6 ± 7.9 years; 40.8% (n = 884) were men and 7.7% (n = 168) died. The risk of death (odds ratio [OR]: 1.767; 3.411; 8.525), hospitalization (OR: 1.397; 2.172; 3.540) and high cost of health care (OR: 1.703; 2.369; 5.073) increased in proportion to a deterioration in functional classification (classes 2B, 3, and 4, respectively). The predictive model for the outcome of death showed good capacity for discrimination (C-statistic = 0.721) and calibration (HL statistic 10.200; P = 0.251). CONCLUSION: There is a dose-response relationship between deterioration in FC and a higher risk of death, hospitalization, and high cost. FC has predictive validity for the mortality rate and could be used to stratify older adults in CNCD care programs with a view to guiding interventions.

OBJETIVO: Avaliar a validade preditiva de um método de classificação funcional (CF) para a utilização de serviços de emergência e internação hospitalar, mortalidade e custos da atenção de saúde em idosos. MÉTODOS: Estudo de coorte retrospectivo com 2 168 idosos atendidos em um programa de atenção de doenças crônicas não transmissíveis (DCNT) em Medellín, Colômbia. Um método de CF foi usado para estratificar os participantes segundo o estado funcional, presença de fatores de risco e controle de comorbidades. No período de acompanhamento de um ano, a validade preditiva da CF foi avaliada para os desfechos de interesse. A capacidade discriminatória (estatística C) e a calibração (teste de Hosmer-Lemeshow [H-L]) do modelo foram avaliadas. RESULTADOS: A média de idade dos participantes do estudo foi 74,6 ± 7,9 anos, 40,8% (n = 884) eram do sexo masculino e 7,7% (n = 168) vieram a óbito. Houve aumento do risco de óbito (odds ratio [OR] 1,767; 3,411­8,525), internação hospitalar (OR 1,397; 2,172-3,540) e custo elevado da atenção de saúde (OR 1,703; 2,369­5,073) com o declínio funcional ­ classes funcionais 2B, 3 e 4, respectivamente. O modelo preditivo para o desfecho de óbito demonstrou boa capacidade discriminatória (estatística C = 0,721) e calibração (estatística H-L = 10,200; P = 0,251). CONCLUSÃO: Há uma relação de dose-resposta entre o declínio da CF e risco maior de óbito, internação hospitalar e custo elevado da atenção. A CF tem validade preditiva para a taxa de mortalidade e poderia ser utilizada na estratificação de idosos em programas de atenção de DCNT para ajudar a direcionar as medidas de intervenção.

Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors.

BACKGROUND: Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluorescent dyes were injected into animals developing metastatic lung nodules and analyzed by fluorescence/computer tomography imaging, quantitative neutron activation analysis and gold-enhanced optical microscopy. RESULTS: We determined that B16F10 cells preferentially take up their own EVs, when compared with colon adenocarcinoma, macrophage and kidney cell-derived EVs. In addition, we were able to detect the preferential accumulation of B16F10 EVs in small metastatic tumors located in lungs when compared with the rest of the organs, as well as their precise distribution between tumor vessels, alveolus and tumor nodules by histological analysis. Finally, we observed that tumor EVs can be used as effective vectors to increase gold nanoparticle delivery towards metastatic nodules. CONCLUSIONS: Our findings provide a valuable tool to study the distribution and interaction of EVs in mice and a novel strategy to improve the targeting of gold nanoparticles to cancer cells and metastatic nodules by using the natural properties of malignant EVs.

Pulse wave velocity reference values in 3,160 adults referred to a hypertension clinic for 24-hour ambulatory blood pressure monitoring.

Background: Carotid-femoral pulse wave velocity (PWV) is a direct measure of aortic stiffness used in the stratification of cardiovascular risk. Its clinical application in Latin America has been limited by the absence of reference values. The objective of this study was to establish PWV reference values among adults referred to a specialized cardiology center for 24-hour ambulatory blood pressure monitoring (ABPM) in Medellín, Colombia.Methods: A descriptive study of 3,160 records of adult (older than 18 years) patients without pharmacological treatment assessed for PWV using a Mobil-O-Graph® 24-hour PWA device (IEM, Stolberg, Germany) and 24-hour ABPM with hemodynamic parameters based on suspected hypertension or hypotension was conducted. Patient records were categorized by decade of age and sub-divided based on the following 24-hour ABPM categories: normal (< 130/80 mmHg), grade I hypertension (between 130-150/80-90 mmHg), and grade II hypertension (> 150/90 mmHg).Results: PWV increased with age (r = 0,894; p < 0,001) and blood pressure category (ρ = 0,081; p < 0,001); the age-related increase was more pronounced among the patients in the higher blood pressure categories. Measures of central tendency and dispersion regarding PWV are presented, and reference values are proposed from the 90th percentile based on the age and 24-hour ABPM categories.Conclusions: PWV is directly related to age and blood pressure and can be predicted using a simple equation that includes these two variables. To stratify the cardiovascular risk of patients and make clinical decisions, the 90th percentile based on the age and 24-hour ABPM categories is recommended as a cut-off.

[Evaluation of the cost-effectiveness of an integral model of ambulatory treatment in patients with acute coronary syndrome: application of a probabilistic Markov modelAvaliação da relação custo-eficácia de um modelo integral de tratamento ambulatorial em pacientes com síndrome coronariana aguda: aplicação de um modelo probabilístico de Markov]. / Evaluación de la costo-efectividad de un modelo integral de tratamiento ambulatorio en pacientes con síndrome coronario agudo: aplicación de un modelo de Markov probabilístico.

OBJECTIVE: To evaluate the cost-effectiveness of an integral model of ambulatory treatment in patients who presented an acute coronary syndrome. METHODS: An economic evaluation was made from a quasi-experimental intervention study, which included 442 patients aged 30 to 70 years who presented an acute coronary syndrome. The intervention group (n = 165) received an integral model of ambulatory treatment based on managed care (disease management), while the control group (n = 277) received conventional cardiovascular rehabilitation. During one year of follow-up, the presentation of cardiovascular events and hospitalizations was evaluated. A probabilistic Markov model was developed. The study perspective was applied within the General System of Health Social Security in Colombia, including the direct health costs; the time horizon was 50 years with discounts of 3.42% for costs and effectiveness; and the measure of effectiveness was quality-adjusted life years (QALYs). A probabilistic and multivariate sensitivity analysis was performed using the Montecarlo simulation. RESULTS: During the year of follow-up, the direct costs related to the value paid were, on average, USD 2 577 for the control group and USD 2 245 for the intervention group. In the probabilistic sensitivity analysis, 91.3% of the simulations were located in the quadrant corresponding to incremental negative costs and positive incremental effectiveness (evaluated intervention at a lower cost, more effective). In the simulations, an average annual savings per patient of USD 1 215 per QALY was observed. CONCLUSIONS: The integral model of ambulatory treatment implemented in patients who suffered an acute coronary syndrome was found to be less expensive and more effective compared to conventional care. Considering it is a dominant alternative, it is recommended as a model of care in this population.

OBJETIVO: Avaliar a relação custo-eficácia de um modelo integral de tratamento ambulatorial em pacientes que apresentaram síndrome coronariana aguda. MÉTODOS: Uma avaliação econômica foi feita a partir de um estudo de intervenção quase experimental, que incluiu 442 pacientes com idade entre 30 a 70 anos que apresentaram síndrome coronariana aguda. O grupo de intervenção (n = 165) recebeu um modelo integral de tratamento ambulatorial com base em cuidados gerenciados (gerenciamento de doenças), enquanto o grupo controle (n = 277) recebeu reabilitação cardiovascular convencional. Durante um ano de acompanhamento, foi avaliada a apresentação de eventos cardiovasculares e hospitalizações. Um modelo probabilístico de Markov foi desenvolvido. A perspectiva do estudo foi aplicada no Sistema Geral de Segurança Social na Saúde da Colômbia, incluindo os custos diretos de saúde; o horizonte temporal foi de 50 anos com descontos de 3,42% em custos e efetividade; e a medida de eficácia foi os anos de vida ajustados pela qualidade (QALY). Uma análise de sensibilidade probabilística e multivariada foi realizada utilizando a simulação de Montecarlo. RESULTADOS: Durante o ano de acompanhamento, os custos diretos relacionados ao valor pago foram, em média, USD 2 577 para o grupo controle e USD 2 245 para o grupo de intervenção. Na análise de sensibilidade probabilística, foram localizadas 91,3% das simulações no quadrante correspondente a custos negativos incrementais e eficácia incremental positiva (intervenção avaliada a menor custo, mais efetiva). Nas simulações, observou-se uma economia anual média por paciente de US $ 1 215 por QALY. CONCLUSÕES: O modelo integral de tratamento ambulatorial implementado em pacientes que sofreram síndrome coronariana aguda foi considerado menos caro e mais eficaz em comparação com os cuidados convencionais. Por ser uma alternativa dominante, é recomendado como modelo de cuidados nesta população.

Down-regulation of the antisense mitochondrial non-coding RNAs (ncRNAs) is a unique vulnerability of cancer cells and a potential target for cancer therapy.

Hallmarks of cancer are fundamental principles involved in cancer progression. We propose an additional generalized hallmark of malignant transformation corresponding to the differential expression of a family of mitochondrial ncRNAs (ncmtRNAs) that comprises sense and antisense members, all of which contain stem-loop structures. Normal proliferating cells express sense (SncmtRNA) and antisense (ASncmtRNA) transcripts. In contrast, the ASncmtRNAs are down-regulated in tumor cells regardless of tissue of origin. Here we show that knockdown of the low copy number of the ASncmtRNAs in several tumor cell lines induces cell death by apoptosis without affecting the viability of normal cells. In addition, knockdown of ASncmtRNAs potentiates apoptotic cell death by inhibiting survivin expression, a member of the inhibitor of apoptosis (IAP) family. Down-regulation of survivin is at the translational level and is probably mediated by microRNAs generated by dicing of the double-stranded stem of the ASncmtRNAs, as suggested by evidence presented here, in which the ASncmtRNAs are bound to Dicer and knockdown of the ASncmtRNAs reduces reporter luciferase activity in a vector carrying the 3'-UTR of survivin mRNA. Taken together, down-regulation of the ASncmtRNAs constitutes a vulnerability or Achilles' heel of cancer cells, suggesting that the ASncmtRNAs are promising targets for cancer therapy.

[Intervention with rumba and nutrition education to modify cardiovascular risk factors in adults with metabolic syndrome]. / Intervención con rumba y educación nutricional para modificar factores de riesgo cardiovascular en adultos con síndrome metabólico.

OBJECTIVE: Evaluate the effect of an intervention with rumba dance and nutrition education on the cardiovascular risk factors in a group of people with metabolic syndrome in a rural area of Colombia. METHODS: Controlled, randomized clinical trial that included 59 people between 30 and 60 years of age with metabolic syndrome. The intervention group (n = 30) participated in a 12-week exercise program of aerobic rumba (60 minutes, 3 days per week) and muscle-strengthening work (30 minutes, twice a week). Each week the group also received two hours of nutrition education. The control group (n = 29) continued with conventional care. An assessment was made of the effect on the cardiovascular risk factors (physiological, metabolic, anthropometric, and nutritional) in the intervention group. RESULTS: The intervention group showed a reduction in systolic blood pressure (-10.0 mmHg; CI95%: -14.3 to -5.6, P < 0.001), diastolic blood pressure (-4.8 mmHg; CI95%: -8.4 to -1.1, P < 0.05) and overall cardiovascular risk at 10 years (-1.5%; CI95%: -2.7 to -0.3, P < 0.05). Furthermore, there was an increase in peak oxygen con-sumption (1.7 ml O2∙kg-1∙min-1; CI95%: 0.1 to 3.3, P < 0.05) and muscular strength (P < 0.001). Positive changes were also observed in body composition, caloric intake, and consumption of macro and micronutrients (P < 0.05). No differences were detected between metabolic variables in the two groups or in inflammatory markers (P < 0.05). CONCLUSIONS: An exercise program with rumba and muscular strengthening, combined with nutrition education, favorably modifies cardiovascular risk factors in people with metabolic syndrome.

Knockdown of Antisense Noncoding Mitochondrial RNA Reduces Tumorigenicity of Patient-Derived Clear Cell Renal Carcinoma Cells in an Orthotopic Xenograft Mouse Model.

Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer and its treatment is hindered by a resistance to targeted therapies, immunotherapies and combinations of both. We have reported that the knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) with chemically modified antisense oligonucleotides induces proliferative arrest and apoptotic death in tumor cells from many human and mouse cancer types. These studies have been mostly performed in vitro and in vivo on commercially available cancer cell lines and have shown that in mouse models tumor growth is stunted by the treatment. The present work was performed on cells derived from primary and metastatic ccRCC tumors. We established primary cultures from primary and metastatic ccRCC tumors, which were subjected to knockdown of ASncmtRNAs in vitro and in vivo in an orthotopic xenograft model in NOD/SCID mice. We found that these primary ccRCC cells are affected in the same way as tumor cell lines and in the orthotopic model tumor growth was significantly reduced by the treatment. This study on patient-derived ccRCC tumor cells represents a model closer to actual patient ccRCC tumors and shows that knockdown of ASncmtRNAs poses a potential treatment option for these patients.

Efficacy of high-intensity interval training versus continuous training on serum myonectin and lipid outcomes in adults with metabolic syndrome: A post-hoc analysis of a clinical trial.

BACKGROUND: Myonectin is a myokine with potential effects on the lipid metabolism; however, its regulation by exercise in humans remains unclear. We aimed to compare the efficacy of high-intensity interval training low-volume (HIIT) versus moderate-intensity continuous training (MICT) on serum myonectin, serum lipids, appendicular fat and lean mass, and intramuscular lipids in humans. METHODS: Secondary analysis of a controlled, randomized, clinical trial in adults of both sexes with metabolic syndrome, who underwent a supervised, three-times/week, 12-week treadmill program. HIIT (n = 29) consisted of six intervals with one-minute, high-intensity phases at 90% of peak oxygen consumption (VO2peak) for a total of 22 min. MICT (n = 31) trained at 60% of VO2peak for 36 min. Serum myonectin was measured using a human enzyme-linked immunosorbent assay. Lipid profile was determined by enzymatic methods and free fatty acids (FFA) were measured by gas chromatography. Fat and lean mass were assessed by dual-energy X-ray absorptiometry. Intramuscular lipids were measured through proton magnetic resonance spectroscopy. RESULTS: Subjects had a mean age of 50.8±6.0 years and body mass index of 30.6±4.0 kg/m2. Compared to MICT, HIIT was not superior at increasing serum myonectin (p = 0.661) or linoleic acid (p = 0.263), reducing palmitic (p = 0.286) or stearic acid (p = 0.350), or improving lipid profile (all p>0.05), appendicular fat mass index -AFMI- (p = 0.713) or appendicular lean mass percentage -ALM- (p = 0.810). Compared to baseline, only HIIT significantly increased myonectin (p = 0.042), with a large effect size, although both interventions reduced AFMI and increased ALM with a large effect size. Lipid profile, FFA and intramuscular lipids did not change in any intervention group (p>0.05). CONCLUSIONS: Compared to MICT, HIIT low volume did not demonstrate superiority in improving serum lipids. The fact that both training types reduced AFMI without paralleled significant changes in serum myonectin suggests that this myokine may have a minor effect on short-middle-term exercise-induced fat mobilization.

Sympathovagal quotient and resting-state functional connectivity of control networks are related to gut Ruminococcaceae abundance in healthy men.

INTRODUCTION: Heart rate variability (HRV), brain resting-state functional connectivity (rsFC), and gut microbiota (GM) are three recognized indicators of health status, whose relationship has not been characterized. We aimed to identify the GM genera and families related to HRV and rsFC, the interaction effect of HRV and rsFC on GM taxa abundance, and the mediation effect of diet on these relationships. METHODS: Eighty-eight healthy, young Colombian men were included in this cross-sectional study. HRV metrics were extracted from 24-hour Holter monitoring data and the resting functional connectivity strength (FCS) of 15 networks were derived from functional magnetic resonance imaging. Gut microbiota composition was assessed using the sequences of the V3-V4 regions of the 16 S rRNA gene, and diet was evaluated using a food frequency questionnaire. Multivariate linear regression analyses were performed to evaluate the correlations between the independent variables (HRV metrics and FCS) and the dependent variables (GM taxa abundance or alpha diversity indexes). Mediation analyses were used to test the role of diet in the relationship between HRV and GM. RESULTS: The sympathovagal quotient (SQ) and the FCS of control networks were positively correlated with the abundance of the gut Ruminococcaceae family and an unclassified Ruminococcaceae genus (Ruminococcaceae_unc). Additionally, the interaction between the FCS of the control network and SQ reduced the individual main effects on the Ruminococcaceae_unc abundance. Finally, reduced habitual fiber intake partially mediated the relationship between SQ and this genus. CONCLUSION: Two indicators of self-regulation, HRV and the rsFC of control networks, are related to the abundance of gut microbiota taxa in healthy men. However, only HRV is related to habitual dietary intake; thus, HRV could serve as a marker of food choice and GM composition in the future.

Expression of mitochondrial non-coding RNAs (ncRNAs) is modulated by high risk human papillomavirus (HPV) oncogenes.

The study of RNA and DNA oncogenic viruses has proved invaluable in the discovery of key cellular pathways that are rendered dysfunctional during cancer progression. An example is high risk human papillomavirus (HPV), the etiological agent of cervical cancer. The role of HPV oncogenes in cellular immortalization and transformation has been extensively investigated. We reported the differential expression of a family of human mitochondrial non-coding RNAs (ncRNAs) between normal and cancer cells. Normal cells express a sense mitochondrial ncRNA (SncmtRNA) that seems to be required for cell proliferation and two antisense transcripts (ASncmtRNAs). In contrast, the ASncmtRNAs are down-regulated in cancer cells. To shed some light on the mechanisms that trigger down-regulation of the ASncmtRNAs, we studied human keratinocytes (HFK) immortalized with HPV. Here we show that immortalization of HFK with HPV-16 or 18 causes down-regulation of the ASncmtRNAs and induces the expression of a new sense transcript named SncmtRNA-2. Transduction of HFK with both E6 and E7 is sufficient to induce expression of SncmtRNA-2. Moreover, E2 oncogene is involved in down-regulation of the ASncmtRNAs. Knockdown of E2 in immortalized cells reestablishes in a reversible manner the expression of the ASncmtRNAs, suggesting that endogenous cellular factors(s) could play functions analogous to E2 during non-HPV-induced oncogenesis.

Regrowth of the psoas tendon after arthroscopic tenotomy: a magnetic resonance imaging study.

PURPOSE: The purpose of this study was to evaluate whether the psoas tendon regenerates after arthroscopic tenotomy through the central compartment of the hip in patients with internal snapping hip. METHODS: Twenty-seven patients with a snapping hip, aged 18 to 54 years (mean, 37.47 years), underwent arthroscopic tenotomy through the central compartment of the hip; all patients had symptomatic femoroacetabular impingement as well. The degree of regeneration was evaluated by preoperative and postoperative measurements of the tendon perimeter with a magnetic resonance imaging protocol in patients with more than 6 months' follow-up. In addition, function was assessed preoperatively and postoperatively with the Western Ontario and McMaster Universities Osteoarthritis Index score. Postoperative active flexion force was graded clinically between 1 and 5 with the Medical Research Council score. RESULTS: Eight patients had less than 6 months' follow-up, and they were excluded. The remaining 19 patients were evaluated after a mean follow-up period of 23.16 months (SD, 12.95 months). Tendon regeneration occurred in all patients. Compared with preoperative measurement, the psoas tendon circumference had recovered by 84.3% on average (55.44 ± 5.68 mm v 46.71 ± 6.05 mm, P < .001). Pain improved in all patients, and the mean Western Ontario and McMaster Universities Osteoarthritis Index score fell from 49 ± 15.9 points to 10.74 ± 11.35 points (P < .001). Muscle force recovered completely in all cases. CONCLUSIONS: There is a process of tissular repair after psoas tenotomy, and the findings on magnetic resonance imaging suggest that tendon tissue regrowth occurs. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Hemodynamic profiles of arterial hypertension with ambulatory blood pressure monitoring.

Blood pressure (BP) measurements obtained during a twenty-four-hour ambulatory blood pressure monitoring (24 h ABPM) have not been reliably applied to extract arterial hemodynamics. We aimed to describe the hemodynamic profiles of different hypertension (HT) subtypes derived from a new method for total arterial compliance (Ct) estimation in a large group of individuals undergoing 24 h ABPM. A cross-sectional study was conducted, which included patients with suspected HT. Cardiac output, Ct, and total peripheral resistance (TPR) were derived through a two-element Windkessel model without having a pressure waveform. Arterial hemodynamics were analyzed according to HT subtypes in 7434 individuals (5523 untreated HT and 1950 normotensive controls [N]). The individuals mean age was 46.2 ± 13.0 years; 54.8% were male, and 22.1% were obese. In isolated diastolic hypertension (IDH), the cardiac index (CI) was greater than that in normotensive (N) controls (CI: IDH vs. N mean difference 0.10 L/m/m2; CI 95% 0.08 to 0.12; p value <0.001), with no significant clinical difference in Ct. Isolated systolic hypertension (ISH) and divergent systolic-diastolic hypertension (D-SDH) had lower Ct values than nondivergent HT subtype (Ct: divergent vs. nondivergent mean difference -0.20 mL/mmHg; CI 95% -0.21 to -0.19 mL/mmHg; p value <0.001). Additionally, D-SDH displayed the highest TPR (TPR: D-SDH vs. N mean difference 169.8 dyn*s/cm-5; CI 95% 149.3 to 190.3 dyn*s/cm-5; p value <0.001). A new method is provided for the simultaneous assessment of arterial hemodynamics with 24 h ABPM as a single diagnostic tool, which allows a comprehensive assessment of arterial function for hypertension subtypes. Main hemodynamic findings in arterial HT subtypes with regard to Ct and TPR. The 24 h ABPM profile reflects the state of Ct and TPR. Younger individuals with IDH present with a normal Ct and frequently increased CO. Patients with ND-SDH maintain an adequate Ct with a higher TPR, while subjects with D-SDH present with a reduced Ct, high PP and high TPR. Finally, the ISH subtype occurs in older individuals with significantly reduced Ct, high PP and a variable TPR proportional to the degree of arterial stiffness and MAP values. There was an observed increase in PP with age in relation to the changes in Ct (see also text). SBP: systolic blood pressure; DBP: diastolic blood pressure; MAP: mean arterial pressure; PP: pulse pressure; N: normotension; HT: hypertension; IDH: isolated diastolic hypertension; ND-SDH: nondivergent systole-diastolic hypertension; D-SDH: divergent systolic-diastolic hypertension; ISH: isolated systolic hypertension; Ct: total arterial compliance; TPR: total peripheral resistance; CO: cardiac output; 24 h ABPM: 24 h ambulatory blood pressure monitoring.

Inverse Modulation of Aurora Kinase A and Topoisomerase IIα in Normal and Tumor Breast Cells upon Knockdown of Mitochondrial ASncmtRNA.

Breast cancer is currently the most diagnosed form of cancer and the leading cause of death by cancer among females worldwide. We described the family of long non-coding mitochondrial RNAs (ncmtRNAs), comprised of sense (SncmtRNA) and antisense (ASncmtRNA) members. Knockdown of ASncmtRNAs using antisense oligonucleotides (ASOs) induces proliferative arrest and apoptotic death of tumor cells, but not normal cells, from various tissue origins. In order to study the mechanisms underlying this selectivity, in this study we performed RNAseq in MDA-MB-231 breast cancer cells transfected with ASncmtRNA-specific ASO or control-ASO, or left untransfected. Bioinformatic analysis yielded several differentially expressed cell-cycle-related genes, from which we selected Aurora kinase A (AURKA) and topoisomerase IIα (TOP2A) for RT-qPCR and western blot validation in MDA-MB-231 and MCF7 breast cancer cells, as well as normal breast epithelial cells (HMEC). We observed no clear differences regarding mRNA levels but both proteins were downregulated in tumor cells and upregulated in normal cells. Since these proteins play a role in genomic integrity, this inverse effect of ASncmtRNA knockdown could account for tumor cell downfall whilst protecting normal cells, suggesting this approach could be used for genomic protection under cancer treatment regimens or other scenarios.

Unraveling the Genetic Threads of History: mtDNA HVS-I Analysis Reveals the Ancient Past of the Aburra Valley.

This article presents a comprehensive genetic study focused on pre-Hispanic individuals who inhabited the Aburrá Valley in Antioquia, Colombia, between the tenth and seventeenth centuries AD. Employing a genetic approach, the study analyzed maternal lineages using DNA samples obtained from skeletal remains. The results illuminate a remarkable degree of biological diversity within these populations and provide insights into their genetic connections with other ancient and indigenous groups across the American continent. The findings strongly support the widely accepted hypothesis that the migration of the first American settlers occurred through Beringia, a land bridge connecting Siberia to North America during the last Ice Age. Subsequently, these early settlers journeyed southward, crossing the North American ice cap. Of particular note, the study unveils the presence of ancestral lineages from Asian populations, which played a pivotal role in populating the Americas. The implications of these results extend beyond delineating migratory routes and settlement patterns of ancient populations. They also enrich our understanding of the genetic diversity inherent in indigenous populations of the region. By revealing the genetic heritage of pre-Hispanic individuals from the Aburrá Valley, this study offers valuable insights into the history of human migration and settlement in the Americas. Furthermore, it enhances our comprehension of the intricate genetic tapestry that characterizes indigenous communities in the area.

Determination of the differential expression of mitochondrial long non-coding RNAs as a noninvasive diagnosis of bladder cancer.

BACKGROUND: Bladder cancer is a significant cause of morbidity and mortality with a high recurrence rate. Early detection of bladder cancer is essential in order to remove the tumor, to preserve the organ and to avoid metastasis. The aim of this study was to analyze the differential expression of mitochondrial non-coding RNAs (sense and antisense) in cells isolated from voided urine of patients with bladder cancer as a noninvasive diagnostic assay. METHODS: The differential expression of the sense (SncmtRNA) and the antisense (ASncmtRNAs) transcripts in cells isolated from voided urine was determined by fluorescent in situ hybridization. The test uses a multiprobe mixture labeled with different fluorophores and takes about 1 hour to complete. We examined the expression of these transcripts in cells isolated from urine of 24 patients with bladder cancer and from 15 healthy donors. RESULTS: This study indicates that the SncmtRNA and the ASncmtRNAs are stable in cells present in urine. The test reveals that the expression pattern of the mitochondrial transcripts can discriminate between normal and tumor cells. The analysis of 24 urine samples from patients with bladder cancer revealed expression of the SncmtRNA and down-regulation of the ASncmtRNAs. Exfoliated cells recovered from the urine of healthy donors do not express these mitochondrial transcripts. This is the first report showing that the differential expression of these mitochondrial transcripts can detect tumor cells in the urine of patients with low and high grade bladder cancer. CONCLUSION: This pilot study indicates that fluorescent in situ hybridization of cells from urine of patients with different grades of bladder cancer confirmed the tumor origin of these cells. Samples from the 24 patients with bladder cancer contain cells that express the SncmtRNA and down-regulate the ASncmtRNAs. In contrast, the hybridization of the few exfoliated cells recovered from healthy donors revealed no expression of these mitochondrial transcripts. This assay can be explored as a non-invasive diagnostic tool for bladder cancer.