Kairos study protocol: a multidisciplinary approach to the study of school timing and its effects on health, well-being and students' performance.

Recent evidence from chronobiology, chssronomedicine and chronopsychology shows that the organisation of social time (e.g., school schedules) generally does not respect biological time. This raises concerns about the impact of the constant mismatch between students' social and internal body clocks on their health, well-being and academic performance. The present paper describes a protocol used to investigate the problem of (de) synchronisation of biological times (chronotypes) in childhood and youth in relation to school times. It studies the effects of student chronotype vs. school schedule matches/mismatches on health behaviours (e.g., how many hours students sleep, when they sleep, eat, do physical activity, spend time outdoors in daylight) and learning (verbal expression, spatial structuring, operations) and whether alert-fatigue levels mediate this effect alignments/misalignments on learning (verbal expression, spatial structuring, operations) and their mediation by alert-fatigue levels. The novelty of our protocol lies in its multidisciplinary and mixed methodology approach to a relevant and complex issue. It draws on up-to-date knowledge from the areas of biology, medicine, psychology, pedagogy and sociology. The methods employed include a varied repertoire of techniques from hormonal analysis (cortisol and melatonin), continuous activity and light monitoring, self-registration of food intake, sleep timings, exercise and exposure to screens, alongside with systematic application of cognitive performance tests (e.g., memory, reasoning, calculation, attention) and self-reported well-being. This comprehensive and interdisciplinary protocol should support evidence-based education policy measures related to school time organisation. Appropriate and healthier school timetables will contribute to social change, healthier students and with more efficient learning. The results of studies using a similar methodology in other countries would ensure replication and comparability of results and contribute to knowledge to support policy making.

Long-Term Effects of Microfiltered Seawater and Resistance Training with Elastic Bands on Hepatic Parameters, Inflammation, Oxidative Stress, and Blood Pressure of Older Women: A 32-Week, Double-Blinded, Randomized, Placebo-Controlled Trial.

The bulk of research on microfiltered seawater (SW) is based on its short-term effects. However, the long-term physiological adaptations to combining SW and resistance training (RT) are unknown. This study aimed to analyse the impact of an RT program using elastic bands combined with SW intake on hepatic biomarkers, inflammation, oxidative stress, and blood pressure in post-menopausal women. Ninety-three women voluntarily participated (age: 70 ± 6.26 years; body mass index: 22.05 ± 3.20 kg/m2; Up-and-Go Test: 6.66 ± 1.01 s). RT consisted of six exercises (32 weeks, 2 days/week). Nonsignificant differences were reported for hepatic biomarkers except for a reduction in glutamic-pyruvic transaminase (GPT) in both RT groups (RT + SW: p = 0.003, ES = 0.51; RT + Placebo: p = 0.012, ES = 0.36). Concerning oxidative stress, vitamin D increased significantly in RT + SW (p = 0.008, ES = 0.25). Regarding inflammation, interleukin 6 significantly decreased (p = 0.003, ES = 0.69) in RT + SW. Finally, systolic blood pressure significantly decreased in both RT groups (RT + placebo: p < 0.001, ES = 0.79; RT + SW: p < 0.001, ES = 0.71) as did diastolic blood pressure in both SW groups (RT + SW: p = 0.002, ES = 0.51; CON + SW: p = 0.028, ES = 0.50). Therefore, RT + SW or SW alone are safe strategies in the long term with no influences on hepatic and oxidative stress biomarkers. Additionally, SW in combination with RT positively influences vitamin D levels, inflammation, and blood pressure in older women.

Multicomponent and power training with elastic bands improve metabolic and inflammatory parameters, body composition and anthropometry, and physical function in older women with metabolic syndrome: A 20-week randomized, controlled trial.

PURPOSE: This study aimed to explore the effects of 20 weeks of multicomponent or power training with elastic bands (EBs) on metabolic and inflammatory blood parameters, body composition, anthropometry, and physical function in older women with metabolic syndrome (MS). METHODS: Ninety participants were randomly assigned to a multicomponent (MCG; n = 30), power (PG; n = 30), or a control group (CG; n = 30). The MCG performed balance, slow-speed strength, and aerobic training, twice per week. The PG completed a high-speed resistance training program twice per week, composed of three to four sets of ten repetitions of six overall body exercises at a perceived rating of effort for the first repetition of 3-4 on the OMNI-Resistance Exercise Scale EB. MS-related variables (glucose, triglycerides, and waist circumference) and cardiometabolic risk factors (high-density lipoprotein [HDL], glycosylated hemoglobin, total cholesterol, low-density lipoprotein cholesterol [LDL], C-reactive protein, and anthropometric profile) were assessed. Physical function was evaluated through balance, strength, and mobility tests. RESULTS: An analysis of variance revealed that both training groups similarly improved most glycemic and lipidic profile parameters (p ≤ 0.006; d ≥ 0.46), body composition and anthropometry (p < 0.001; d ≥ 0.41), and physical function (p ≤ 0.005; d ≥ 0.69). Opposed to the PG, the MCG improved balance (p < 0.001; d = 0.96) and decreased the inflammatory status by downregulating C-reactive protein (p = 0.003; d = 0.47). On the other hand, the PG exhibited improvements in handgrip strength (p = 0.006; d = 0.48), while the MCG did not. CONCLUSION: Therefore, multicomponent and power training with EBs are plausible strategies for improving the cardiometabolic health status and physical function in older women with MS.

Traffic Density Exposure, Oxidative Stress Biomarkers and Plasma Metabolomics in a Population-Based Sample: The Hortega Study.

Exposure to traffic-related air pollution (TRAP) generates oxidative stress, with downstream effects at the metabolic level. Human studies of traffic density and metabolomic markers, however, are rare. The main objective of this study was to evaluate the cross-sectional association between traffic density in the street of residence with oxidative stress and metabolomic profiles measured in a population-based sample from Spain. We also explored in silico the potential biological implications of the findings. Secondarily, we assessed the contribution of oxidative stress to the association between exposure to traffic density and variation in plasma metabolite levels. Traffic density was defined as the average daily traffic volume over an entire year within a buffer of 50 m around the participants' residence. Plasma metabolomic profiles and urine oxidative stress biomarkers were measured in samples from 1181 Hortega Study participants by nuclear magnetic resonance spectroscopy and high-performance liquid chromatography, respectively. Traffic density was associated with 7 (out of 49) plasma metabolites, including amino acids, fatty acids, products of bacterial and energy metabolism and fluid balance metabolites. Regarding urine oxidative stress biomarkers, traffic associations were positive for GSSG/GSH% and negative for MDA. A total of 12 KEGG pathways were linked to traffic-related metabolites. In a protein network from genes included in over-represented pathways and 63 redox-related candidate genes, we observed relevant proteins from the glutathione cycle. GSSG/GSH% and MDA accounted for 14.6% and 12.2% of changes in isobutyrate and the CH2CH2CO fatty acid moiety, respectively, which is attributable to traffic exposure. At the population level, exposure to traffic density was associated with specific urine oxidative stress and plasma metabolites. Although our results support a role of oxidative stress as a biological intermediary of traffic-related metabolic alterations, with potential implications for the co-bacterial and lipid metabolism, additional mechanistic and prospective studies are needed to confirm our findings.

Genetic interaction in the association between oxidative stress and diabetes in the Spanish population.

Oxidative stress (OS) is a relevant intermediate mechanism involved in Type 2 Diabetes Mellitus (T2D) development. To date, the interaction between OS parameters and variations in genes related to T2D has not been analyzed. AIMS: To study the genetic interaction of genes potentially related to OS levels (redox homeostasis, renin-angiotensin-aldosterone system, endoplasmic stress response, dyslipidemia, obesity and metal transport) and OS and T2D risk in a general population from Spain (the Hortega Study) in relation to the risk of suffering from T2D. MATERIALS AND METHODS: One thousand five hundred and two adults from the University Hospital Rio Hortega area were studied and 900 single nucleotide polymorphisms (SNPs) from 272 candidate genes were analyzed. RESULTS: There were no differences in OS levels between cases and controls. Some polymorphisms were associated with T2D and with OS levels. Significant interactions were observed between OS levels and two polymorphisms in relation to T2D presence: rs196904 (ERN1 gene) and rs2410718 (COX7C gene); and between OS levels and haplotypes of the genes: SP2, HFF1A, ILI8R1, EIF2AK2, TXNRD2, PPARA, NDUFS2 and ERN1. CONCLUSIONS: Our results indicate that genetic variations of the studied genes are associated with OS levels and that their interaction with OS parameters may contribute to the risk of developing T2D in the Spanish general population. These data support the importance of analyzing the influence of OS levels and their interaction with genetic variations in order to establish their real impact in T2D risk. Further studies are required to identify the real relevance of interactions between genetic variations and OS levels and the mechanisms involved in them.

The role of oxidative stress, tumor and inflammatory markers in colorectal cancer patients: A one-year follow-up study.

Oxidative stress (OS) and inflammation are known to play an important role in colorectal cancer (CRC). This study analyzed tumor, inflammatory and OS markers in CRC patients and in a control group. In addition, the evolution of these markers was evaluated after one-year of follow-up treatment. This was a longitudinal and prospective, observational study in 80 CRC patients who were candidates for tumor resection surgery and/or chemo-radiotherapy treatment and a healthy control group (n = 60). Subsequently, catalase (CAT), reduced glutathione (GSH), oxidized glutathione (GSSG) and GSSG/GSH ratio in serum and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and F2-IsoProstanes (F2-IsoPs) in urine at 1, 6 and 12 months after treatment was analyzed. Tumor markers (CEA and CA 19.9), as well as inflammatory markers-leukocytes, neutrophils, neutrophil/lymphocyte (N/L) index, platelets, fibrinogen, C-reactive protein (CRP), and interleukin 6 (IL6)- were also analyzed. As expected, levels of CEA and CA 19.9 and markers of inflammation, except CRP, were significantly higher in CRC compared to the control group. Regarding OS markers, a decrease in CAT and GSH and an increase in GSSG, GSSG/GSH ratio, 8-oxodG and F2-IsoPs were found in CRC patients compared to healthy controls at baseline. After treatment, an improvement of their inflammation profile was accompanied by a progressive recovery of antioxidant enzyme activities and the decline of oxidative byproducts both in serum and urine. Based on the results obtained, we propose the assay of urinary 8-oxodG and F2-IsoPs, as well as serum CAT, GSH, GSSG as a marker for the evaluation of OS and the clinical follow-up of CRC patients.

Oxidative Stress and DNA Damage Markers in Colorectal Cancer.

Oxidative stress (OS) and inflammation are known to play an important role in chronic diseases, including cancer, and specifically colorectal cancer (CRC). The main objective of this study was to explore the diagnostic potential of OS markers in patients with CRC, which may translate into an early diagnosis of the disease. To do this, we compared results with those in a group of healthy controls and assessed whether there were significant differences. In addition, we explored possible correlations with the presence of tumors and tumor stage, with anemia and with inflammatory markers used in clinical practice. The study included 80 patients with CRC and 60 healthy controls. The following OS markers were analyzed: catalase (CAT), reduced glutathione (GSH) and oxidized glutathione (GSSG) in serum; and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and F2-isoprotanes in urine (F2-IsoPs). Tumor markers (CEA and CA 19.9), anemia markers (hemoglobin, hematocrit and medium corpuscular volume) and inflammatory markers (leukocytes, neutrophils, N/L index, platelets, fibrinogen, C-reactive protein, CRP and IL-6) were also determined. Comparison of means between patients and controls revealed highly significant differences for all OS markers, with an increase in the prooxidant markers GSSG, GSSG/GSH ratio, 8-oxodG and F2-IsoPs, and a decrease in the antioxidant markers CAT and GSH. Tumor and inflammatory markers (except CRP) correlated positively with GSSG, GSSG/GSH ratio, 8-oxodG and F2-IsoPs, and negatively with CAT and GSH. In view of the results obtained, OS markers may constitute a useful tool for the early diagnosis of CRC patients.

Adherence to the Mediterranean Diet Has a Protective Role against Metabolic and DNA Damage Markers in Colorectal Cancer Patients.

Oxidative stress (OS) and inflammation have been related to colorectal cancer (CRC), but the influence of the Mediterranean diet (MD) on these parameters is unknown. Therefore, the aim of this study was to determine the association between adherence to the MD and markers of OS and DNA damage in CRC patients and to study the influence of adherence to the MD on metabolic and tumor-related factors. This prospective observational study included a total of 80 patients diagnosed with CRC. Adherence to the MD was estimated by the 14-item Mediterranean Diet Adherence Screener (MEDAS) questionnaire. The levels of OS markers (catalase, glutathione peroxidase, and glutathione system in serum; 8-oxo-7'8-dihydro-2'-deoxyguanosine and F2-isoprotanes in urine) and tumor and metabolic factors were determined. A total of 51.2% of our CRC patients showed a high adherence to the MD. These patients presented decreased levels of 8-oxodG, increased GPX and HDL-cholesterol levels, and a downward trend in the GSSG/GSH ratio with respect to patients with low adherence to the MD. In addition, a high adherence to the MD was associated with a lower histological grade of the tumor and a lower presence of synchronous adenomas. We conclude that a high adherence to the MD has a protective role against metabolic and oxidative DNA damage and improves antioxidant systems in CRC patients.

Biomonitoring of Phthalates, Bisphenols and Parabens in Children: Exposure, Predictors and Risk Assessment.

Exposure to emerging contaminants, such as phthalates, bisphenols and parabens in children has been associated with possible neurodevelopment and endocrine alterations. In the present study, the biomonitoring of biomarkers in children (5-12 years old) from the Valencia Region (Spain) have been implemented using urines from the BIOVAL program. More than 75% of the children studied (n = 562) were internally exposed (>LOQ) to bisphenols and parabens, and the whole population assessed (n = 557) were exposed to at least one phthalate. The geometric means (GM) of the concentrations of bisphenol A, methyl paraben and propyl paraben were 0.9, 1.4 and 0.39 ng/mL, respectively. Regarding phthalates, monoethyl phthalate GM was 55.0 ng/mL and diethyl hexyl phthalate (as the sum of five metabolites) GM was 60.6 ng/mL. Despite the studied population being widely exposed, the detection frequencies and concentrations were in general lower than in previous studies involving children in Spain and in other countries in recent years. Furthermore, the risk assessment study concluded that the internal exposure to phthalates, bisphenols and parabens is lower than the guidance values established, and, therefore, a health risk derived from the exposure to these compounds in the studied population is not expected.

Prevention of Teratogenesis in Pregnancies of Obese Rats by Vitamin E Supplementation.

Congenital malformations are a common adverse outcome in pregnancies complicated by pregestational obesity, although the underlying mechanisms are still unrevealed. Our aim was to study the effect of oxidative stress in obesity-induced teratogenesis. Wistar rats were fed a high-fat diet for 13 weeks, with (OE group) or without (O group) vitamin E supplementation. Then, rats were mated and sacrificed at day 11.5 of gestation. Embryos from O dams presented a 25.9 ± 3.5% rate of malformations (vs. 8.7 ± 3.4% in C rats), which was reduced in the OE group (11.5 ± 2.3%). Pregestational obesity induced hepatic protein and DNA oxidation and a decline in antioxidant enzymes. Importantly, glutathione content was also decreased, limiting the availability of this antioxidant in the embryos. Vitamin E supplementation efficiently maintained glutathione levels in the obese mothers, which could be used in their embryos to prevent oxidation-induced malformations. To test the effect of decreasing glutathione levels alone in a cell culture model of neuroepithelium, murine embryonic stem cells (ESC) were induced to form neuronal precursors and glutathione synthesis was inhibited with the gamma-glutamylcysteine synthesis inhibitor, buthionine sulfoximine (BSO). BSO inhibited the expression of Pax3, a gene required for neural tube closure that is also inhibited by oxidative stress. Taken together, our data indicate that obesity causes malformations through the depletion of maternal glutathione, thereby decreasing glutathione-dependent free radical scavenging in embryos, which can be prevented by vitamin E supplementation.

Oxidative Stress in Non-Dialysis-Dependent Chronic Kidney Disease Patients.

BACKGROUND: Cardiovascular complications are the leading cause of morbidity and mortality at any stage of chronic kidney disease (CKD). Moreover, the high rate of cardiovascular mortality observed in these patients is associated with an accelerated atherosclerosis process that likely starts at the early stages of CKD. Thus, traditional and non-traditional or uremic-related factors represent a link between CKD and cardiovascular risk. Among non-conventional risk factors, particular focus has been placed on anaemia, mineral and bone disorders, inflammation, malnutrition and oxidative stress and, in this regard, connections have been reported between oxidative stress and cardiovascular disease in dialysis patients. METHODS: We evaluated the oxidation process in different molecular lines (proteins, lipids and genetic material) in 155 non-dialysis patients at different stages of CKD and 45 healthy controls. To assess oxidative stress status, we analyzed oxidized glutathione (GSSG), reduced glutathione (GSH) and the oxidized/reduced glutathione ratio (GSSG/GSH) and other oxidation indicators, including malondialdehyde (MDA) and 8-oxo-2'-deoxyguanosine (8-oxo-dG). RESULTS: An active grade of oxidative stress was found from the early stages of CKD onwards, which affected all of the molecular lines studied. We observed a heightened oxidative state (indicated by a higher level of oxidized molecules together with decreased levels of antioxidant molecules) as kidney function declined. Furthermore, oxidative stress-related alterations were significantly greater in CKD patients than in the control group. CONCLUSIONS: CKD patients exhibit significantly higher oxidative stress than healthy individuals, and these alterations intensify as eGFR declines, showing significant differences between CKD stages. Thus, future research is warranted to provide clearer results in this area.

The Effectiveness of Glutathione Redox Status as a Possible Tumor Marker in Colorectal Cancer.

The role of oxidative stress (OS) in cancer is a matter of great interest due to the implication of reactive oxygen species (ROS) and their oxidation products in the initiation of tumorigenesis, its progression, and metastatic dissemination. Great efforts have been made to identify the mechanisms of ROS-induced carcinogenesis; however, the validation of OS byproducts as potential tumor markers (TMs) remains to be established. This interventional study included a total of 80 colorectal cancer (CRC) patients and 60 controls. By measuring reduced glutathione (GSH), its oxidized form (GSSG), and the glutathione redox state in terms of the GSSG/GSH ratio in the serum of CRC patients, we identified significant changes as compared to healthy subjects. These findings are compatible with the effectiveness of glutathione as a TM. The thiol redox state showed a significant increase towards oxidation in the CRC group and correlated significantly with both the tumor state and the clinical evolution. The sensitivity and specificity of serum glutathione levels are far above those of the classical TMs CEA and CA19.9. We conclude that the GSSG/GSH ratio is a simple assay which could be validated as a novel clinical TM for the diagnosis and monitoring of CRC.

A new 8-oxo-7,8-2'deoxyguanosine nanoporous anodic alumina aptasensor for colorectal cancer diagnosis in blood and urine.

Many important human diseases, and especially cancer, have been related to the overproduction of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG). This molecule is a product of oxidative stress processes over nucleophilic bases in DNA. In this work, an aptasensor for the rapid, selective and accurate detection of this oncomarker is presented. The aptasensor consists of a nanoporous anodic alumina material loaded with a dye and is functionalized with an aptamer-based "molecular gate". In the presence of target 8-oxo-dG, the capping aptamer displaces from the surface due to the high affinity of the analyte with the capping aptamer, thus inducing delivery of the preloaded fluorescent dye. In contrast, in the absence of 8-oxo-dG, a poor payload delivery is accomplished. This aptamer-based nanodevice has great sensitivity for 8-oxo-dG, resulting in a LOD of 1 nM and a detection time of ca. 60 min. Moreover, the aptasensor is able to accurately detect 8-oxo-dG in unmodified urine and serum without pre-concentration treatments. This diagnostic tool is validated in a set of 38 urine and serum samples from patients diagnosed of colorectal cancer and control patients. These samples are also analyzed using a standardized and specific ELISA kit. The aptasensor displays excellent sensitivity (95.83/100%) and specificity (80/100%) for 8-oxo-dG detection in serum and urine samples, respectively. Our results may serve as a basis for the development of generalized fluorogenic diagnostic platforms for the easy diagnosis of cancer in biofluids as well as for monitoring therapeutic treatments and detection of relapses without the use of expensive equipment or trained personnel.

Urinary levels of sirtuin-1 associated with disease activity in lupus nephritis.

Identifying new markers of disease flares in lupus nephritis (LN) that facilitate patient stratification and prognosis is important. Therefore, the aim of the present study was to analyze whether urinary SIRT1 expression was altered in LN and whether SIRT1 values in urine could be valuable biomarker of disease activity. In a cohort study, urinary pellets from 40 patients diagnosed with systemic lupus erythematosus (SLE) were analyzed. Clinical measures of lupus activity were assessed. The expression of SIRT1 was quantified by quantitative PCR (qRT-PCR) and immunoblot, then compared between patients with active lupus nephritis, in remission and healthy controls. Association with lupus activity and renal histological features was also analyzed. A significant increase in SIRT1 mRNA levels in patients with active LN was observed compared with those in remission (P=0.02) or healthy controls (P=0.009). In addition, SIRT-1 protein levels were also augmented in LN group than remission (P=0.029) and controls (P=0.001). A strong association was found between SIRT1 expression with anti-dsDNA in SLE and in patients with LN. In addition, histological features in LN biopsies were related with SIRT1, increasing its expression in proliferative forms. Finally, SIRT1 expression values showed a strong discriminatory power of renal injury in SLE. Our study demonstrated an altered urinary expression of SIRT1 and a strong association with disease activity in LN patients, being a valuable marker of renal injury. These results showed the role of the SIRT1 pathway in the SLE pathogenesis.

Effects of the Ser326Cys Polymorphism in the DNA Repair OGG1 Gene on Cancer, Cardiovascular, and All-Cause Mortality in the PREDIMED Study: Modulation by Diet.

BACKGROUND: Oxidatively induced DNA damage, an important factor in cancer etiology, is repaired by oxyguanine glycosylase 1 (OGG1). The lower repair capacity genotype (homozygote Cys326Cys) in the OGG1-rs1052133 (Ser326Cys) polymorphism has been associated with cancer risk. However, no information is available in relation to cancer mortality, other causes of death, and modulation by diet. OBJECTIVE: Our aim was to evaluate the association of the OGG1-rs1052133 with total, cancer, and cardiovascular disease (CVD) mortality and to analyze its modulation by the Mediterranean diet, focusing especially on total vegetable intake as one of the main characteristics of this diet. DESIGN: Secondary analysis in the PREDIMED (Prevención con Dieta Mediterránea) trial is a randomized, controlled trial conducted in Spain from 2003 to 2010. PARTICIPANTS/SETTING: Study participants (n=7,170) were at high risk for CVD and were aged 55 to 80 years. INTERVENTION: Participants were randomly allocated to two groups with a Mediterranean diet intervention or a control diet. Vegetable intake was measured at baseline. MAIN OUTCOME MEASURES: Main outcomes were all-cause, cancer, and CVD mortality after a median follow-up of 4.8 years. STATISTICAL ANALYSES: Multivariable-adjusted Cox regression models were fitted. RESULTS: Three hundred eighteen deaths were detected (cancer, n=127; CVD, n=81; and other, n=110). Cys326Cys individuals (prevalence 4.2%) presented higher total mortality rates than Ser326-carriers (P=0.009). The multivariable-adjusted hazard ratio for Cys326Cys vs Ser326-carriers was 1.69 (95% CI 1.09 to 2.62; P=0.018). This association was greater for CVD mortality (P=0.001). No relationship was detected for cancer mortality in the whole population (hazard ratio 1.07; 95% CI 0.47 to 2.45; P=0.867), but a significant age interaction (P=0.048) was observed, as Cys326Cys was associated with cancer mortality in participants <66.5 years (P=0.029). Recessive effects limited our ability to investigate Cys326Cys×diet interactions for cancer mortality. No statistically significant interactions for total or CVD mortality were found for the Mediterranean diet intervention. However, significant protective interactions for CVD mortality were found for vegetable intake (hazard ratio interaction per standard deviation 0.42; 95% CI 0.18 to 0.98; P=0.046). CONCLUSIONS: In this population, the Cys326Cys-OGG1 genotype was associated with all-cause mortality, mainly CVD instead of cancer mortality. Additional studies are needed to provide further evidence on its dietary modulation.

The Effect of Moderate- Versus High-Intensity Resistance Training on Systemic Redox State and DNA Damage in Healthy Older Women.

This study investigated effects of a 16-week progressive resistance training program (RTP) with elastic bands at two different intensities on systemic redox state, DNA damage, and physical function in healthy older women. METHODS: Participants were randomly assigned to the high-intensity group (HIGH; n = 39), moderate-intensity group (MOD; n = 31), or control group (CG; n = 23). The exercise groups performed an RTP twice a week with three to four sets of 6 (HIGH) or 15 (MOD) repetitions of six overall body exercises at a perceived exertion rate of 8-9 on the OMNI-Resistance Exercise Scale for use with elastic bands. Thiol redox state was determined by reduced glutathione (GSH), oxidized glutathione (GSSG), and GSSG/GSH in blood mononuclear cells. Degree of DNA damage was assessed by presence of the oxidized DNA base molecule 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG) in urine. Physical function monitoring was based on the arm curl, chair stand, up and go, and 6-min walk tests. RESULTS: The HIGH group showed a significant increase in 8-OHdG (+71.07%, effect size [ES] = 1.12) and a significant decrease in GSH (-10.91, ES = -0.69), while the MOD group showed a significant decrease in 8-OHdG levels (-25.66%, ES = -0.69) with no changes in thiol redox state. GSH levels differed significantly between the HIGH and CG groups posttest. The exercise groups showed significant improvements in physical function with no differences between groups. CONCLUSION: RTP at a moderate rather than high intensity may be a better strategy to reduce DNA damage in healthy older women while also increasing independence.

PAI-1 levels are related to insulin resistance and carotid atherosclerosis in subjects with familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCH) is a primary atherogenic dyslipidemia with insulin resistance and increased cardiovascular risk. Plasminogen activator inhibitor type 1 (PAI-1) and myeloperoxidase (MPO) activity are associated with proinflammatory and atherothrombotic risk. Our aim was to study the role played by PAI-1 and MPO activity in the carotid atherosclerosis prevalence in FCH subjects. 36 FCH unrelated subjects (17 women) were matched by age and body weight with 36 healthy normolipidemic subjects (19 female). Blood lipids, glucose, insulin, insulin resistance (homeostasis model assessment (HOMA)), MPO, and PAI-1 were determined in both groups. Carotid intima media thickness (IMT) was measured by the same investigator by standardized protocol. No differences in age, body mass index (BMI) or waist circumference were observed between the two groups. HOMA and PAI-1 values were higher in the FCH group, reaching statistical significance in those subjects with insulin resistance. In addition, PAI-1 values correlated significantly with metabolic syndrome components and carotid IMT. It is known that the elevated cardiovascular risk that characterizes FCH is frequently associated with insulin resistance. We have detected that two known proinflammatory and proatherothrombotic factors (MPO and PAI-1) are significantly elevated in FCH subjects with insulin resistance. These results could partly explain the high cardiovascular risk present in FCH subjects.