Effects of concurrent exercise on cardiometabolic status during perimenopause: the FLAMENCO Project.

OBJECTIVES: The aim of this study was to evaluate the influence of a 4-month concurrent exercise training program on cardiometabolic status in perimenopausal women. METHODS: The participants (n = 150) were randomized into counseling (n = 75) and exercise (n = 75) groups. The exercise group followed 4-month (3 days/week, 60 min/session) concurrent training. The counseling group attended conferences on a healthy lifestyle. We determined plasma glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, and C-reactive protein, and measured blood pressure and the resting heart rate. RESULTS: In the per-protocol analyses, the exercise group showed lower LDL-C concentrations than the counseling group when the model was further adjusted for the baseline values and diet (10.2 mg/dl; 95% confidence interval -19.4, -0.96; p = 0.031). Borderline significant total cholesterol and diastolic blood pressure were reduced in both groups with better results in exercise group (p = 0.068 and p = 0.090, respectively). CONCLUSION: The present findings suggest that the concurrent exercise training program could improve plasma glucose, lipid profile, CRP, and systolic and diastolic blood pressures in the exercise group. These results also suggest the importance of a healthy diet and active behavior during menopause, as improvements in both the exercise and the counseling group were observed. Future analysis should combine both interventions in search of better results.

Clay-Nanoarchitectures as Photocatalysts by In Situ Assembly of ZnO Nanoparticles and Clay Minerals.

ZnO-clay nanoarchitectures have been prepared by In Situ generation of ZnO nanoparticles from zinc acetylacetonate in isopropanol under reflux in the presence of organoclays. Two layered clays, a commercial Wyoming montmorillonite and a smectite from Gafsa (Tunisia), and a fibrous clay, sepiolite from Vallecas-Vicalvaro (Spain), modified with cetyltrimethylammonium ions were the organoclay substrates for assembling the formed nanoparticles. After a convenient thermal treatment, the organic matter is eliminated and the ZnO/clay nanoarchitectures consolidated. XRD, FE-SEM and TEM, among other characterization techniques confirmed the presence of the ZnO in wurtzite phase assembled to the clays in the final porous ZnO/clay nanoarchitectures. The activity as photocatalysts of the resulting materials was evaluated using ibuprofen as a model drug in view to explore the usefulness of these ZnO/clay nanoarchitectures in the removal of emergent pollutants in water.

Influence of the degree of adherence to the Mediterranean diet on the cardiometabolic risk in peri and menopausal women. The Flamenco project.

BACKGROUND AND AIMS: The Mediterranean diet (MD) has been associated with reduced morbidity from cardiovascular diseases in the general population. The aim of this study was to assess whether different degrees of adherence to the MD were associated with the cardiometabolic risk in peri and menopausal women. METHODS AND RESULTS: This cross-sectional study included 198 peri and menopausal women participating in the Flamenco project. Validated questionnaires were used to assess menopause health-related quality of life and degree of adherence to the MD (low, medium and high). The following cardiometabolic risk factors were assessed: fat mass percentage, waist circumference, blood pressure and resting heart rate, plasma markers (total cholesterol, high and low-density lipoprotein cholesterol [HDL-C and LDL-C, respectively], total cholesterol/HDL ratio, triglycerides, C-reactive protein and fasting glucose), Physical activity levels and smoking status. The degree of adherence to the MD among the study sample was 27%, 40% and 30% for low, medium and high adherence, respectively. After controlling for potential confounders, women with a high adherence to the MD showed lower plasma total cholesterol (p = 0.025), resting heart rate (p = 0.005), LDL-C (p = 0.019), triglycerides (p = 0.046) and C-reactive protein (p = 0.009) compared to those with a low adherence. Likewise women with high adherence to the MD showed lower total cholesterol/HDL-C ratio (p = 0.020) compared to those with a medium adherence. The high MD adherence group also showed lower clustered cardiometabolic risk (p = 0.004). Moreover, when analysing specific MD components, whole grain cereals, pulses (both p < 0.05) and red wine (p < 0.01) consumption were inversely associated with the clustered cardiometabolic risk. CONCLUSION: The present findings suggest that a high but not medium adherence to the MD is associated with a cardioprotective effect in peri and menopausal women. As a low percentage of the sample showed a high adherence to the MD, future research aimed at increasing the adherence to this dietary pattern for a better cardiometabolic status during peri and menopause is warranted.

Stanozolol Decreases Bone Turnover Markers, Increases Mineralization, and Alters Femoral Geometry in Male Rats.

Stanozonol (ST) is a synthetic derivative of testosterone; it has anabolic/androgenic activity, increasing both the turnover of trabecular bone and the endocortical apposition of bone. The present study aimed to examine the effects of ST on bone status in rats by bone mineral content, markers of formation and resorption, bone density, and structural and microarchitectural parameters. Twenty male Wistar rats were randomly distributed into two experimental groups corresponding to placebo or ST administration, which consisted of weekly intramuscular injections of 10 mg/kg body weight of ST. Plasma parameters were analyzed by immunoassay. Bone mineral content was determined by spectrophotometry. Bone mineral density (BMD) and structural parameters were measured by peripheral quantitative computed tomography, and trabecular and cortical microarchitecture by micro-computed tomography. Plasma Ca, Mg, and alkaline phosphatase were higher, and urinary Ca excretion, corticosterone, and testosterone concentrations lower in the ST group. Femur Ca content was higher and P content was lower in the ST, whereas osteocalcin, aminoterminal propeptides of type I procollagen, and C-terminal telopeptides of type I collagen were lower. Total cross-sectional, trabecular, and cortical/subcortical areas were lower in the ST. No differences were observed on BMD and area parameters of the diaphysis as well as on trabecular and cortical microarchitecture. The use of ST increases bone mineralization, ash percentage, and Ca and Mg content in femur. In spite of an absence of changes in BMD, geometric metaphyseal changes were observed. We conclude that ST alters bone geometry, leads to low bone turnover, and thus may impair bone quality.

Interval aerobic training combined with strength-endurance exercise improves metabolic markers beyond caloric restriction in Zucker rats.

AIMS: To investigate the effects of interval aerobic training combined with strength-endurance exercise (IASE) and caloric restriction (CR) on body composition, glycaemic and lipid profile and inflammatory markers. METHODS AND RESULTS: Thirty-two Zucker diabetic fatty rats were randomised into 4 groups (sedentary + CR; sedentary + adlibitum; IASE + CR; and IASE + adlibitum). Training groups conducted an IASE programme in the same session, 5 days/week for 2 months. Body weight, fat and muscle mass and body water were measured using a body composition analyser. Plasma total, LDL and HDL cholesterol, phospholipids, triglycerides, insulin, adiponectin, tumour necrosis factor alpha, interleukin 1 and 10 were measured. Blood fasting and postprandial glucose were assessed. Body weight was lower in the CR compared to the adlibitum groups (p < 0.001). Fat mass was lower in the CR compared to the adlibitum (p < 0.05) and in the IASE compared to the sedentary groups (p < 0.001), but IASE increased lean mass (p < 0.001). Triglycerides were lower in the CR compared to the adlibitum groups (p < 0.001) whereas total and LDL-cholesterol and fasting glucose were reduced only in the IASE groups (all, p < 0.001). Phospholipids decreased in the CR compared to the adlibitum (p < 0.05) and the IASE compared to the sedentary groups (p < 0.001). The area under the curve after oral glucose tolerance test, insulin and homoeostatic model assessment were lower in the IASE and the CR compared to the sedentary and adlibitum groups, respectively (all, p < 0.001). Adiponectin was lower in the CR groups (p < 0.001). CONCLUSION: Overall, IASE as well as CR were both useful interventions, especially when combined. However, IASE showed greater improvements on body composition, inflammatory and glycaemic profile than CR did.

Association of physical fitness with health-related quality of life in early postmenopause.

OBJECTIVE: To assess the association of different components of physical fitness with HRQoL in early postmenopause and to test which physical fitness components are independently associated with the physical and mental components of HRQoL. METHODS: The final sample comprised 67 early postmenopausal women. Physical fitness was assessed with the Senior Fitness Test battery (additionally including handgrip strength test), and HRQoL was evaluated with the Short-Form Health Survey-36 (SF-36). We also analyzed plasma gonadotropic hormones and estradiol. RESULTS: Overall, most of the fitness components were positively associated with HRQoL. Lower-body flexibility, upper-body muscle strength and cardiorespiratory fitness were the fitness components more strongly associated with HRQoL (r range from 0.28 to 0.56). Static balance was especially associated with mental health (r = -0.46, P < 0.001). Lower-body flexibility (assessed with the chair sit-and-reach test) and upper-body muscle strength (assessed with handgrip dynamometry) were independently associated with the SF-36 Physical Component Summary (both, P < 0.001). Upper-body muscle strength (P < 0.01) and cardiorespiratory fitness (assessed with the 6-min walk test, P < 0.05) were independently associated with the SF-36 Mental Component Summary. CONCLUSIONS: Higher physical fitness is associated with better HRQoL in early postmenopause. Lower-body flexibility and upper-body muscle strength were the most important independent fitness indicators, explaining ~30 % of HRQoL.

High-intensity Exercise Modifies the Effects of Stanozolol on Brain Oxidative Stress in Rats.

We analyzed the effects of high-intensity exercise (HIE) and anabolic androgenic steroids (AAS) on brain redox status. 40 male Wistar rats were randomly distributed in 4 experimental groups (n=10) with or without HIE and with or without weekly Stanozolol administration. Thiobarbituric acid-reactive substances (TBARs) and protein carbonyl content (PCC) were assessed. Total superoxide dismutase (tSOD), manganese superoxide dismutase (Mn-SOD), copper/zinc superoxide dismutase (CuZn-SOD) and catalase (CAT) activities were measured. Finally, protein expression levels of glutathione peroxidase (GPx), NAD(P)H dehydrogenase, Quinone 1 (NQO1), NF-E2-Related Factor 2 (Nrf2), glial fibrillary acidic protein (GFAP), nuclear factor kappa ß p65 (NF-κß) and signal transducer and activator of transcription 3 were determined. Brain PCC concentrations were lower in the HIE groups compared to the untrained controls, whereas CAT activity was higher (both, p<0.01). Both HIE and AAS groups exhibited higher expression levels of GFAP and GPx, but lower NQO1 levels (all, p<0.05). There were increased expression levels of NF-κß in the AAS groups (p<0.01). In addition, there was increased expression of Nrf2 in the HIE groups (p<0.001). HIE*AAS interactions were found on TBARs content and GFAP expression, with HIE downregulating and upregulating AAS-mediated increases in TBARs and GFAP, respectively (p<0.05). Overall, HIE appeared to reduce the AAS-mediated negative effect on brain redox status.

High-intensity exercise may compromise renal morphology in rats.

We investigated the renal effects of a high-intensity exercise (HIE) program based on strength training. 20 Wistar rats were randomly assigned to 2 experimental groups performing HIE or control over 12 weeks. Urinary volume, pH, citrate and calcium, and plasma urea, total proteins, creatinine, albumin, lactate dehydrogenase, creatine kinase (CK), calcium, magnesium, corticosterone and testosterone were measured. We also studied renal morphology with the Fibrosis HR(®) software. Plasma urea and CK concentrations were higher in the HIE compared to the control group (p < 0.05), whereas plasma creatinine was lower (p < 0.01). Plasma corticosterone was higher (p < 0.05) and testosterone lower (p < 0.01) in the HIE group. Except for the higher urinary volume found in the HIE group (p < 0.05), no differences between groups were observed in the rest of urinary parameters analyzed. Renal interstitial connective tissue was ~30% higher in the HIE group (p < 0.05). Glomerular tufts and mesangial areas were also higher in the HIE group (all, p < 0.05). No differences between groups were observed in the glomerular area. Overall, HIE promoted a worse morphological renal profile that might be associated with a higher risk for incidence of kidney disease in the long-term. The stress induced by the type of exercise performed could be on the basis of this worse morphological renal status.

Does exercise reduce brain oxidative stress? A systematic review.

The aim of the present systematic review was to investigate the influence of different exercise programs on brain oxidative stress. A search of the literature was conducted up to 1 December 2012 across five databases: PUBMED, SCOPUS, SPORTS DISCUS, Web of Science, and The Cochrane Library. The search strategy used in the electronic databases mentioned was established as: (swim* OR exercise OR training) AND ("oxidative stress" AND brain) for each database. A methodological quality assessment valuation/estimation was additionally carried out in the final sample of studies. Of 1553 potentially eligible papers, 19 were included after inclusion and exclusion criteria. The methodological quality assessment showed a total score in the Quality Index between 40% and 80%, with a mean quality of 56.8%. Overall, regular moderate aerobic exercise appears to promote antioxidant capacity on brain. In contrast, anaerobic or high-intensity exercise, aerobic-exhausted exercise, or the combination of both types of training could deteriorate the antioxidant response. Future investigations should be focused on establishing a standardized exercise protocol, depending on the exercise metabolism wanted to test, which could enhance the objective knowledge in this topic.

Fitness testing as a discriminative tool for the diagnosis and monitoring of fibromyalgia.

We aimed to determine the ability of a set of physical fitness tests to discriminate between presence/absence of fibromyalgia (FM) and moderate/severe FM. The sample comprised 94 female FM patients (52 ± 8 years) and 66 healthy women (54 ± 6 years). We assessed physical fitness by means of the 30-s chair stand, handgrip strength, chair sit and reach, back scratch, blind flamingo, 8-feet up and go, and 6-min walking tests. Patients were classified as having moderate FM if the score in the Fibromyalgia Impact Questionnaire (FIQ) was <70 and as having severe FM if the FIQ was ≥70. FM patients and patients with severe FM performed worse in most of the fitness tests studied (P < 0.001). Except the back scratch test, all the tests were able to discriminate between presence and absence of FM [area under the curve (AUC) = 0.66 to 0.92; P ≤ 0.001], and four tests also discriminated FM severity (AUC = 0.62 to 0.66; P ≤ 0.05). The 30-s chair stand test showed the highest ability to discriminate FM presence and severity (AUC = 0.92, P < 0.001; and AUC = 0.66, P = 0.008, respectively), being the corresponding discriminating cutoffs 9 and 6 repetitions, respectively. Physical fitness in general, and particularly the 30-s chair stand test, is able to discriminate between women with FM from those without FM, as well as between those with moderate FM from their peers with severe FM.

AGING-ASSOCIATED COGNITIVE DECLINE IS REVERSED BY D-SERINE SUPPLEMENTATION.

Brain aging is a natural process that involves structural and functional changes that lead to cognitive decline, even in healthy subjects. This detriment has been associated with N-methyl-D-aspartate receptor (NMDAR) hypofunction due to a reduction in the brain levels of D-serine, the endogenous NMDAR co-agonist. However, it is not clear if D-serine supplementation could be used as an intervention to reduce or reverse age-related brain alterations. In the present work, we aimed to analyze the D-serine effect on aging-associated alterations in cellular and large-scale brain systems that could support cognitive flexibility in rats. We found that D-serine supplementation reverts the age-related decline in cognitive flexibility, frontal dendritic spine density, and partially restored large-scale functional connectivity without inducing nephrotoxicity; instead, D-serine restored the thickness of the renal epithelial cells that were affected by age. Our results suggest that D-serine could be used as a therapeutic target to reverse age-related brain alterations.SIGNIFICANT STATEMENTAge-related behavioral changes in cognitive performance occur as a physiological process of aging. Then, it is important to explore possible therapeutics to decrease, retard or reverse aging effects on the brain. NMDA receptor hypofunction contributes to the aging-associated cognitive decline. In the aged brain, there is a reduction in the brain levels of the NMDAR co-agonist, D-Serine. However, it is unclear if chronic D-serine supplementation could revert the age-detriment in brain functions. Our results show that D-serine supplementation reverts the age-associated decrease in cognitive flexibility, functional brain connectivity, and neuronal morphology. Our findings raise the possibility that restoring the brain levels of D-serine could be used as a therapeutic target to recover brain alterations associated with aging.

Influence of low-protein dietetic foods consumption on quality of life and levels of B vitamins and homocysteine in patients with chronic renal failure.

OBJECTIVE: The aim of the study was to determine whether the consumption of low protein dietetic foods improved the quality of life and nutritional status for vitamins B and homocysteine in patients with chronic renal failure. METHODOLOGY: This nutritional-intervention involved 28 men and 21 women, divided into two groups. The control-group consumed a low-protein diet prescribed, and the experimental-group consumed a diet in which some commonly used foods were replaced by low-protein dietetic foods. The study lasted 6 months. Food consumption was assessed by 24-h recall. Vitamin B6 as alphaEAST was measured in blood. Creatinine, urea, vitamin B12, folate and homocysteine were measured in plasma. The impact on the patients' quality of life from consuming the dietetic foods was assessed via the SF-36 questionnaire. RESULTS: After 6 months, the protein intake among the experimental-group had decreased by 40%, and the urea/creatinine ratio and alphaEAST activity were also lower. The results of the SF-36 questionnaire show that the patients in the experimental-group obtained higher scores in the categories of general health and physical status. CONCLUSIONS: The dietetic foods were very well accepted by all patients and their use allowed a better control of the protein intake, improved B6 status and a better quality of life.

Mediterranean diet, tobacco consumption and body composition during perimenopause. The FLAMENCO project.

OBJECTIVE: To study the association of the adherence to the Mediterranean diet (MD) and tobacco consumption with body composition during perimenopause. STUDY DESIGN AND METHODS: A cross-sectional study in 176 perimenopausal women from the FLAMENCO project. A food frequency questionnaire and the Mediterranean Diet Score were assessed. Body composition was measured using dual-energy X-ray absorptiometry. MAIN OUTCOMES MEASURES: Body mass index (BMI), fat mass (FM), ratio of gynecoid to total fat mass (G/T), ratio of android to gynecoid fat mass (A/G), visceral adipose tissue (VAT) and waist circumference (WC). RESULTS: Intake of whole-grain cereals was associated with lower WC, FM percentage, android FM, VAT and higher G/T (all p < 0.05). Intake of nuts was associated with lower BMI and FM percentage and intake of fruits with lower BMI, WC, total and android FM, FM percentage, A/G, VAT and higher G/T (all p < 0.05). Intake of pulses was associated with lower weight, BMI and android FM. Intake of whole dairy products was associated with lower weight, BMI, WC, total and android FM and VAT (all p < 0.05). Intake of olive oil was associated with lower WC and FM percentage (all p < 0.05). Intake of sweetened beverages was associated with higher weight, BMI, WC, FM percentage, android FM, VAT and total FM (all, p < 0.05). Smokers had a lower MD adherence (p < 0.05). Finally, a greater MD adherence was associated with higher G/T (p < 0.01) and lower A/G (p < 0.05). CONCLUSIONS: A higher MD adherence, avoiding tobacco, an increased consumption of whole-grain cereals, nuts, fruits, pulses, whole dairy products and olive oil, and a lower consumption of sweetened beverages might contribute to a healthier body composition during perimenopause.

Therapeutic management of a new case of LCAT deficiency with a multifactorial long-term approach based on high doses of angiotensin II receptor blockers (ARBs).

Familial lecithin cholesterol acyltransferase (LCAT) deficiency (FLD) is characterized by the appearance of corneal opacity, anemia, proteinuria progressing to chronic renal failure and abnormalities in the composition of plasma lipoproteins. No established therapy currently exists for this condition. We report here a new case of FLD caused by two novel mutations in the LCAT gene in which, for the first time, aggressive therapy with angiotensin II receptor blockers and lipid-lowering drugs showed benefit in blood pressure, lipid abnormalities, proteinuria and also kidney function, probably delaying progression to renal failure.

[Vitamin B complex and homocysteine in chronic renal failure]. / Vitaminas B y homocisteína en la insuficiencia renal crónica.

Metabolic, biochemical, and hormonal changes occur in chronic renal failure usually associated with hyponutrition states. In predialysis patients, knowing the nutritional state about water-soluble vitamins such as thiamine, riboflavin, pyridoxine, cianocobalamine, and folic acid is becoming more and more important since some of the manifestations of chronic renal failure may be due to the deficiency of some of these water-soluble vitamins. The metabolic pathways in which most of these vitamins participate are interrelated and it is difficult to understand how the individual deficits of each vitamin affect renal pathology. This work aims at reviewing not only this issue but also the status of these water-soluble vitamins that different authors have found in groups of predialysis patients. On the other hand, the issue on the high prevalence of hyperhomocysteinemia in chronic renal failure as the main mortality risk factor due to cardiovascular pathologies as well as the implication of these vitamins in the metabolism of homocysteine, and consequently in plasma levels of this metabolite in predialysis patients is reviewed.

Antimicrobial management in nosocomial peritonitis: microbiota, drug and time.

Complicated intra-abdominal infection requires surgical treatment and broad-spectrum empiric antibiotic treatment used early. The rapid spread of multidrug-resistant bacteria has become a serious threat, especially in critical care units. The excessive use of carbapenems has led to carbapenemase-producing Enterobacteriaceae, leaving tigecycline and colistin as therapeutical options. The new antimicrobials, ceftazidime-avibactam and ceftolozane-tazobactam open new horizons in the treatment of multi-drug resistant Enterobacteriaceae. Candida peritonitis causes a high mortality in the critical patient. Diagnosis and early treatment are associated with a better prognosis, the administration of an echinocandin being of choice in these patients.

Sepiolite nanoplatform for the simultaneous assembly of magnetite and zinc oxide nanoparticles as photocatalyst for improving removal of organic pollutants.

Novel ternary ZnO/Fe3O4-sepiolite nanostructured materials were developed in a two-step procedure based on the incorporation of ZnO nanoparticles on a substrate composed by magnetite nanoparticles previously assembled to the sepiolite fibrous silicate (Fe3O4-sepiolite). The structural and morphological characterization shows that both, ZnO and Fe3O4 nanoparticles, were homogeneously dispersed on the surface of sepiolite. Therefore, the resulting material is characterized as a multifunctional nanoplatform simultaneously providing magnetic and photoactive properties. ZnO/Fe3O4-sepiolite materials exhibit superparamagnetic properties at room temperature, which is one of the sought properties in view to facilitate their recovery from the reaction medium after application as heterogeneous catalysts. ZnO/Fe3O4-sepiolite materials were tested as photocatalysts using methylene blue dye in water as model of a pollutant molecule, showing full decolorization after 2h of UV irradiation. Moreover, the photocatalytic activity of this nanoplataform may be maintained after reuse in several consecutive cycles of treatment. Remarkably, the ZnO/magnetite-sepiolite nanostructured material displays a similar activity as ZnO/sepiolite materials, but shows the additional advantage of easier recovery by means of a magnet which facilitates its reuse.

Effect of α-tocopherol megadoses on hematologic parameters and antioxidant capacity of rats in an ultraendurance probe.

This study was aimed to analyze the effect of two different megadoses of α-tocopherol (vit E) in the antioxidant activity and red and white blood series of Wistar rats after a 180-min ultraendurance probe. Three groups of 10 rats were analyzed; VEAG: acute administration of a megadoses of 5,000 IU/kg of vit E the day before the probe; VECG: chronic administration of 1,000 IU/kg/day of vit E for 6 days before the probe; CG: placebo administration. VEAG presented white cells, red blood cells, hematocrit, hemoglobin values significantly higher than CG and VECG (p < 0.05). The mean corpuscular hemoglobin and lymphocytes concentrations were significantly higher in the VECG than in the other two groups (p < 0.05). Similarly, VEAG presented a significantly higher vit E blood concentration than VECG and CG (p < 0.05), and VECG than CG (p < 0.05). Finally, we found a significantly positive correlation between trolox equivalent antioxidant capacity (TEAC) and red blood cells concentration (r = 0.374) and a significantly inverse correlation between TEAC and blood lactate concentration (r = -0.365). Our findings suggest that acute vit E megadoses could protect against transitory sport anemia symptoms and increase the white blood cell count in comparison with the chronic dose and control groups after an ultraendurance probe.

High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients.

Gaucher disease (GD), the most prevalent lysosome storage disorder, presents an autosomal recessive mode of inheritance. It is a paradigm for therapeutic intervention in medical genetics due to the existence of effective enzyme replacement therapy. We report here the analysis of GD in 262 unrelated Brazilian patients, carried out in order to establish the frequency of the most common mutations and to provide prognostic information based on genotype-phenotype correlations. Among 247 type 1 GD patients, mutation N370S was detected in 47% of all the alleles, but N370S/N370S homozygosity was found in only 10% of the patients, a much lower frequency than expected, suggesting that most individuals presenting this genotype may not receive medical attention. Recombinant alleles were detected at a high frequency: 44% of the chromosomes bearing mutation L444P had other mutations derived from the pseudogene sequence, present in 25% of patients. Three neuronopathic type 2 patients were homozygous for L444P, all presenting additional mutations (E326K or recombinant alleles) that probably lead to the more severe phenotypes. Six children, classified as type 1 GD patients, had a L444P/L444P genotype, showing that neuronopathic symptoms may only manifest later in life. This would indicate the need for a higher treatment dose during enzyme replacement therapy. Finally, mutation G377S was present in 4 homozygous type 1 patients and also in compound heterozygosity in 5 (42%) type 3 patients. These findings indicate that G377S cannot be unambiguously classified as mild and suggest an allele-dose effect for this mutation.

The associations between physical fitness and cardiometabolic risk and body-size phenotypes in perimenopausal women.

OBJECTIVE: To study the association between physical fitness and body-size phenotypes, and to test which aspects of physical fitness show the greatest independent association with cardiometabolic risk in perimenopausal women. STUDY DESIGN: This cross-sectional study involved 228 women aged 53±5years from southern Spain. MAIN OUTCOME MEASUREMENTS: Physical fitness was assessed by means of the Senior Fitness Test Battery (additionally including handgrip strength and timed up-and-go tests). Anthropometry, resting heart rate, blood pressure and plasma markers of lipid, glycaemic and inflammatory status were measured by standard procedures. The harmonized definition of the 'metabolically healthy but obese' (MHO) phenotype was employed to classify individuals. RESULTS: The overall prevalence of the MHO phenotype was 13% but was 43% among the obese women. Apart from traditional markers, metabolically healthy non-obese women had lower levels of C-reactive protein than women with the other phenotypes (p<0.001), and levels of glycosylated haemoglobin were lower in MHO women than in metabolically abnormal non-obese women (overall p=0.004). Most of the components of physical fitness differed with body-size phenotypes. The 6-min walk and the back-scratch tests presented the most robust differences (both p<0.001). Moreover, the women's performance on the back-scratch (ß=0.32; p<0.001) and the 6-min walk (ß=0.22; p=0.003) tests was independently associated with the clustered cardiometabolic risk. The back-scratch test explained 10% of the variability (step 1, p<0.001), and the final model, which also included the 6-min walk test (step 2, p=0.003), explained 14% of the variability. CONCLUSION: Low upper-body flexibility was the most important fitness indicator of cardiometabolic risk in perimenopausal women, but cardiorespiratory fitness also played an important role.