Low-volume walking HIIT: Efficient strategy to improve physical capacity and reduce the risk of cardiovascular disease in older women with type 2 diabetes.

BACKGROUND AND AIMS: To compare the effect of a low-volume walking high-intensity interval training (HIIT) to moderate-intensity continuous training (MICT) on risk of cardiovascular diseases and physical capacity in older women with type 2 diabetes (T2D). METHODS: Thirty inactive older women with T2D were randomized into either HIIT (75 min/week) or MICT (150 min/week). Cardiovascular risk profile (lipid profile; waist circumference and fat mass; resting, post-exercise and ambulatory blood pressure [BP]; VO2 peak; UKPDS score; ABC's) and physical capacity were assessed before and after a 12-week intervention. RESULTS: While resting systolic and diastolic BP (all p ≤ 0.01) were reduced, ambulatory BP (p ≥ 0.49) and lipid profile (p ≥ 0.40) remained unchanged after the intervention. Although VO2 peak increased to a similar extent in both groups (p = 0.015), the distance covered during the 6MWT (p = 0.01) and grip strength (p = 0.02) increased to a greater extend in HIIT. The UKPDS risk score decreased in both groups after the intervention (p = 0.03) and 31% of the participants reached the ABC's compared to 24% at baseline. CONCLUSION: Low-volume walking HIIT is an efficient exercise intervention for older women with T2D as it improved some CVD risk factors and physical capacity. Nevertheless, neither low-volume HIIT nor MICT is sufficient to affect ambulatory blood pressure in T2D patients.

Muscle Mass Index and Animal Source of Dietary Protein Are Positively Associated with Insulin Resistance in Participants of the NuAge Study.

OBJECTIVES: Contribute evidence towards the complex interrelationships of body composition, insulin sensitivity and protein intake independently from adiposity in an older population. DESIGN: This is a cross-sectional analysis of an existing dataset in which a literature-supported model linking together the variables of interest is tested using path analysis. SETTING: The loss of muscle mass has been implicated in the development of insulin resistance. We propose to test associations of muscle mass with insulin sensitivity and their respective associations with animal and vegetable sources of protein intake, independently from adiposity. PARTICIPANTS: Non-diabetic participants aged 68-82 years from the NuAge study with all available measures (n=441) were included. MEASUREMENTS: A model considering age, sex, chronic diseases, physical activity; smoking and sources of protein intake influencing body composition components and insulin sensitivity was created and tested with Path Analysis for their independent associations. Muscle mass index (MMI; kg/height in m2) and % body fat were derived from DXA and BIA. Insulin resistance was estimated by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score and physical activity by the Physical Activity Scale for the Elderly (PASE) questionnaire. Protein intakes were obtained from three non-consecutive 24h-diet recalls. RESULTS: In the final model, direct positive associations were observed between HOMA-IR score and MMI (ß=0.42; 95%CI: 0.24; 0.6) and % body fat (ß=0.094; 95%CI: 0.07; 0.11). There were no direct associations between animal protein intake and MMI or with HOMA-IR. There was a significant direct negative association between plant protein intake and MMI (ß= -0.068; 95%CI: -0.13; -0.003) and significant indirect associations mediated through MMI and % body fat between HOMA-IR and animal protein intake (ß=0.0321; 95%CI: 0.01; 0.05), as well as plant protein intake (ß= -0.07; 95%CI: -0.1; 0.0). CONCLUSIONS: Our final model indicated that MMI and HOMA score were significantly positively associated. Protein intake sources were related to HOMA-IR score differently through MMI and % body fat, respectively.

Tissue-specific targeting of cell fate regulatory genes by E2f factors.

Cell cycle proteins are important regulators of diverse cell fate decisions, and in this capacity have pivotal roles in neurogenesis and brain development. The mechanisms by which cell cycle regulation is integrated with cell fate control in the brain and other tissues are poorly understood, and an outstanding question is whether the cell cycle machinery regulates fate decisions directly or instead as a secondary consequence of proliferative control. Identification of the genes targeted by E2 promoter binding factor (E2f) transcription factors, effectors of the pRb/E2f cell cycle pathway, will provide essential insights into these mechanisms. We identified the promoter regions bound by three neurogenic E2f factors in neural precursor cells in a genome-wide manner. Through bioinformatic analyses and integration of published genomic data sets we uncovered hundreds of transcriptionally active E2f-bound promoters corresponding to genes that control cell fate processes, including key transcriptional regulators and members of the Notch, fibroblast growth factor, Wnt and Tgf-ß signaling pathways. We also demonstrate a striking enrichment of the CCCTC binding factor transcription factor (Ctcf) at E2f3-bound nervous system-related genes, suggesting a potential regulatory co-factor for E2f3 in controlling differentiation. Finally, we provide the first demonstration of extensive tissue specificity among E2f target genes in mammalian cells, whereby E2f3 promoter binding is well conserved between neural and muscle precursors at genes associated with cell cycle processes, but is tissue-specific at differentiation-associated genes. Our findings implicate the cell cycle pathway as a widespread regulator of cell fate genes, and suggest that E2f3 proteins control cell type-specific differentiation programs by regulating unique sets of target genes. This work significantly enhances our understanding of how the cell cycle machinery impacts cell fate and differentiation, and will importantly drive further discovery regarding the mechanisms of cell fate control and transcriptional regulation in the brain, as well as in other tissues.

Inverted duplication with deletion: first interstitial case suggesting a novel undescribed mechanism of formation.

Inverted duplications with terminal deletions are a well-defined family of complex rearrangements already observed for most of chromosome extremities. Several mechanisms have been suggested which could lead to their occurrence, either through non-homologous end joining, non-allelic homologous recombination, or more recently through an intrastrand fold-back mechanism. We describe here a patient with intellectual disability and pharmacoresistant epilepsy, for which array CGH analysis showed the first interstitial case of inverted duplication with deletion on chromosome 1p. Furthermore, SNP array analysis revealed an associated segmental isodisomy for the distal part of 1p, which led us to consider a replicative mechanism to explain this abnormality. This observation extends the range of this once telomeric rearrangement.

Factors related to psychosocial quality of life for children with cerebral palsy.

Background. Current health services interventions focus on the treatment of the musculoskeletal impairments of cerebral palsy (CP). The goal of this study was to explore whether the severity of physical symptoms correlates with psychosocial quality of life (QOL) among pediatric patients with CP. Methods. A sample of 53 caregivers of children with CP was surveyed and health status information was extracted from patient medical records. Descriptive analysis explored the association between the main outcome variable, psychosocial QOL (CP QOL-child), and patient demographics, comorbidity (e.g., visual, hearing and feeding impairments, language delays, and epilepsy), CP severity (GMFCS), and the receipt of family centered care (MPOC-20). Results. Child psychosocial QOL decreased with increasing comorbidity but was not associated with CP symptom severity or any measured demographic factors. Reporting high levels of family centered care (FCC) was associated with higher psychosocial QOL in univariate analysis but was not significant when controlling for comorbidities. Conclusion. There is no clear connection between symptom severity and psychosocial QOL in children with CP. Comorbidity however is strongly associated with psychosocial QOL. Focusing on reducing CP comorbidities could have a positive impact on psychosocial QOL.

Role of leptin in pregnancy: consequences of maternal obesity.

Maternal obesity is associated with increased risks of pregnancy complications. Excessive fat mass, common to obese women, has the potential to influence production and secretion of adipose tissue derived proteins called adipokines. The adipokine leptin is involved in the regulation of multiple aspects of maternal metabolic homeostasis. In addition, leptin has been shown to be important for placentation and maternal-fetal exchanges processes regulating growth and development. In later stages of a healthy pregnancy, central leptin resistance occurs to allow increased nutrient availability for the fetus. Disruption of the signaling capacity of leptin associated with obesity is emerging as a potential risk factor leading to pregnancy complications as a result of aberrant fuel partitioning in utero. In this review we discuss the influence of obesity on the roles of leptin and leptin resistance at the central and placental level.

Identification of glycosyltransferases involved in cell wall synthesis of wheat endosperm.

Plant cell walls are complex structures critical for plant fitness and valuable for human nutrition as dietary fiber and for industrial uses such as biofuel production. The cell wall polysaccharides in wheat endosperm consist of two major polymers, arabinoxylans and beta-glucans, as well as other minor components. Most of these polysaccharides are synthesized in the Golgi apparatus but the mechanisms underlying their synthesis have yet to be fully elucidated and only a few of the enzymes involved have been characterized. To identify actors involved in the wheat endosperm cell wall formation, we used a subcellular fractionation strategy to isolate Golgi-enriched fractions from endosperm harvested during active cell wall deposition. The proteins extracted from these Golgi-enriched fractions were analyzed by LC-MS/MS. We report the identification of 1135 proteins among which 64 glycosyltransferases distributed in 17 families. Their potential function in cell wall synthesis is discussed. In addition, we identified 63 glycosylhydrolases, some of which may be involved in cell wall remodeling. Several glycosyltransferases were validated by showing that when expressed as fusion proteins with a fluorescent reporter, they indeed accumulate in the Golgi apparatus. Our results provide new candidates potentially involved in cell wall biogenesis in wheat endosperm.

3D position of pericentromeric heterochromatin within the nucleus of a patient with ICF syndrome.

ICF (immunodeficiency, centromeric region instability, facial anomalies) syndrome is a rare autosomal recessive disorder characterised by severe immunodeficiency, craniofacial anomalies and chromosome instability. Chromosome analyses from blood samples show a high frequency of decondensation of pericentromeric heterochromatin (PH) and rearrangements involving chromosomes 1 and 16. It is the first and, as far as we know, the only disease associated with a mutation in a DNA methyltransferase gene, DNMT3B, with significant hypomethylation of the classical satellite DNA, the major component of the juxtacentromeric heterochromatin. To better understand the complex links between the hypomethylation of the satellite DNA, the cytogenetic anomalies and the clinical features of ICF syndrome, we performed three-dimensional (3D) FISH on preserved cells from a patient with a suspected ICF phenotype. Analysis of DNMT3B did not reveal any mutation in our patient, making this case an ICF type 2. The results of 3D-FISH showed a statistically significant change in the intranuclear position of PH of chromosome 1 in cells of the patient as compared to normal cells. It is difficult to understand how a defect in the methylation pathway can be responsible for the various symptoms of this condition. From our observations we suggest a mechanistic link between the reorganisation of the nuclear architecture and the altered gene expression.

Effect of exercise combined with phytoestrogens on quality of life in postmenopausal women.

BACKGROUND: Postmenopausal women seem to favor alternative therapies such as exercise and phytoestrogens as a substitute for potentially harmful hormone replacement therapy. Based on previous research, we hypothesized that phytoestrogens combined with exercise could have a synergic effect on women's health. OBJECTIVE: To verify whether phytoestrogens enhance the response to mixed training regarding menopausal symptoms and quality of life in postmenopausal women. METHODS: From a pool of women participating in a 6-month randomized, controlled exercise study, 21 received a placebo (mean age 58.3 ± 5.4 years, body mass index 29.8 ± 5.1 kg/m(2)) and 19 received phytoestrogen supplements (mean age 60.1 ± 3.4 years; body mass index 30.3 ± 4.6 kg/m(2)). Body weight, fat mass and lean body mass (dual-energy X-ray absorptiometry) were assessed. Quality of life was estimated by the Short Form-36 (SF-36) and Perceived Stress Scale-10 (PSS-10) questionnaires, and menopausal symptoms by the Kupperman index. All measurements were performed before and after the intervention. RESULTS: Although the Kupperman index and PSS-10 remained unchanged in both groups, the SF-36 Physical Component Summary and almost all the SF-36 subscales (except for role-emotional and mental health) increased only in the exercise group taking phytoestrogens (0.001 < p < 0.04). CONCLUSION: While phytoestrogens combined with mixed exercise were not sufficient to improve menopausal symptoms, it seemed to be a better strategy than exercise alone to improve the general quality of life in postmenopausal women.

Key priorities in managing glucose control in older people with diabetes.

Older people with diabetes represent a major and increasing proportion of our elderly population and their care requires better organisation. Targets for risk factor control and pathways of care must be adjusted to the subject's general health status. It is thus advisable to screen for frailty. We have carried out a detailed literature review of the studies published on diabetes in older people since 1990. Studies were considered if they included groups or subgroups of diabetic patients > 65 years old. This review discusses the elaboration of general targets for care, the approach to risk factor control, the screening and the specific prevention or management of complications, the integration of geriatric concepts in diabetes care and the specificity of education with respect to frailty status.

A call to incorporate the prevention and treatment of geriatric disorders in the management of diabetes in the elderly.

The prevalence of type 2 diabetes increases with age. However, the management of diabetes in the elderly has received surprisingly little attention. Diabetes in the elderly is associated with a high risk of geriatric syndromes including malnutrition and sarcopenia, functional impairments, falls and fractures, incontinence, depression and dementia. Tight glycaemic control for the prevention of vascular complications is often of limited value in the elderly. However, glycaemic control and non-pharmacological therapy may prevent diabetes symptoms and delay geriatric syndromes. The prevention, screening and treatment of both conventional diabetic complications and geriatric syndromes should be integrated in a management plan to optimize the patients' overall health status and quality of life.

Effect of antioxidants combined to resistance training on BMD in elderly women: a pilot study.

SUMMARY: We determined the effect of antioxidants and resistance training on bone mineral density of postmenopausal women. After 6 months, we observed a significant decrease in the lumbar spine BMD of the placebo group while other groups remained stable. Antioxidants may offer protection against bone loss such as resistance training. INTRODUCTION: The purpose of this pilot study was to determine the effects of antioxidant supplements combined to resistance training on bone mineral density (BMD) in healthy elderly women. METHODS: Thirty-four postmenopausal women (66.1 +/- 3.3 years) were randomized in four groups (placebo, n = 7; antioxidants, n = 8; exercise and placebo, n = 11; and exercise and antioxidants, n = 8). The 6-month intervention consisted in antioxidant supplements (600 mg vitamin E and 1,000 mg vitamin C daily) or resistance exercise (3x/week). Femoral neck and lumbar spine BMD (DXA) and dietary intakes (3-day food record) were measured before and after the intervention. A repeated measure ANOVA and non-parametric Mann-Whitney U tests were used. RESULTS: We observed a significant decrease in the placebo group for lumbar spine BMD (pre, 1.01 +/- 0.17 g/cm(2); post, 1.00 +/- 0.16 g/cm(2); P < 0.05 respectively) while it remained stable in all other groups. No changes were observed for femoral neck BMD. CONCLUSIONS: Antioxidant vitamins may offer some protection against bone loss in the same extent as resistance exercise although combining both does not seem to produce additional effects. Our results suggest to further investigate the impact of antioxidant supplements on the prevention of osteoporosis.

Endopolygalacturonases reveal molecular features for processivity pattern and tolerance towards acetylated pectin.

Endopolygalacturonases (EndoPGs) hydrolyse the 1-4 linkages between two alpha-d-galacturonic acids (GalA) of the smooth homogalacturonan regions of pectin. GalA may be methyl-esterified on the carboxylic group and acetyl-esterified on the hydroxylic groups. EndoPG activity most often decreases with such increasing degree of substitution. In this paper, we used bioinformatics and molecular modelling technics to explain the tolerance profile at the molecular scale and processivity scheme of three endoPGs with respect to acetylated pectin substrate; the first two enzymes originate from Aspergillus niger (AnPGI and AnPGII) and the third from Fusarium moniliforme (FmPG). Partly acetylated and methylated homogalacturonan fragments in complex with the three PGs were successively modelled in silico. The amino acid residues involved in substrate binding were identified for each enzyme. Similarly, the docking pattern of the differently decorated oligomers in the catalytic groove was individually characterized for each enzyme. This work shows full agreement with our previous extensive mass spectrometry analysis of the hydrolytic products that established distinct tolerance profiles for the three endoPGs and earlier work that ascertained processivity, specifically for AnPGI. In our previous work, AnPGI was shown to be the most powerful enzyme among the three enzymes with an enhanced tolerance towards O2- and O3-acetylated substrates. We report here amino acids of AnPGI that are unique in binding the pectin backbone and that are identified as possibly crucial for its specificity, namely S191(An)(PGI)/D240(An)(PGI). Similarly, topologically equivalent residues in AnPGII and FmPG were identified that could impede such binding; S234(An)(PGII)/S91(An)(PGII) and S245(Fm)(PG)/V89(Fm)(PG). In addition, we report here, from normal mode analysis computed on AnPG1, a shear bending motion of 15 A of amplitude that fully accredits the processive action pattern for this enzyme, with D240(An)(PGI) and R96(An)(PGI) working as crampons to favour the sliding of the substrate. Conversely, the same method clearly evidences a hinge binding motion for AnPGII and FmPG that should only authorize one hydrolytic event per enzyme/substrate encounter.

Effects of Maghnian bentonite on physical properties of sandy soils under semi-arid Mediterranean climate.

This research has for object to study the influence of clay addition, i.e., Maghnian bentonite, like deposit clay, in the physical properties of sandy materials from Mostaganem plateau (North-West Algeria) submitted to salinity and sodicity. The first result was to show that the clay content changes drastically the physical properties of clay-sand mixtures. Important differences were observed as a function of the sand particle size distribution. At given clay content, the saturated Hydraulic Conductivity (HCs) was lower when the sand size was small and spread. For the coarse sand the salinity was maintained, even for high clay contents, a significant hydraulic conductivity. One of the main characteristics of Maghnia clay is the presence of calcium carbonates in the natural material. In comparison to that of Mostaganem clay of other deposit, it appears less sensitive to sodicity. An important aspect is the initial state of the clay when used in addition to sands, i.e., disturbance, conditions of preparation of sand clay mixtures and presence of associated components such as carbonates. Maghnia clay appeared to be adapted to the improvement of sandy soils, not because its mineralogical characteristics, but for its natural cationic form and obviously the presence of calcite in it.

Laparoscopic splenectomy for splenic masses.

BACKGROUND: This study aimed to evaluate the perioperative outcomes and pathology of patients undergoing laparoscopic splenectomy for splenic masses. METHODS: The records for 174 patients who underwent laparoscopic splenectomy from May 1994 to August 2006 were reviewed. Patient demographics, preoperative imaging, American Society of Anesthesiologists (ASA) score, body mass index (BMI), estimated blood loss (EBL), operative time, spleen size, complications, hospital length of stay (LOS), pathology, and mortality were extracted from the records. Data are expressed as means +/- standard deviation. Statistical significance (p < 0.05) was determined using a two-tailed t-test and Fisher's exact test. RESULTS: A splenic mass was diagnosed preoperatively for 18 patients (10.3%) (7 males and 11 females). The mean patient age was 51.4 +/- 13.7 years. The mean ASA was 2.3 +/- 0.8, and the mean BMI was 27.3 +/- 5.8 kg/m(2). Computed tomography scans demonstrated splenic masses in all the patients. The mean mass size was 4.3 +/- 3.3 cm (range, 1.0-11.0 cm), and the mean spleen length was 14.6 +/- 7.5 cm (range, 5.5-40.2 cm). Total laparoscopic splenectomy was completed for 15 patients, and hand-assisted splenectomy was performed for 3 patients (2 converted). The mean operative time was 128.3 +/- 38.5 min, and the mean EBL was 110 +/- 137.5 ml. There were no intraoperative complications or 30-day mortalities. The postoperative complication rate was 11.1%, and the mean LOS was 1.9 +/- 1.0 days. The pathology for six patients (33.3%) was malignant (5 lymphomas and 1 adenocarcinoma). There were three false-positive positron emission tomography (PET) scans. Compared with 73 patients undergoing laparoscopic splenectomy for idiopathic thrombocytopenic purpura, there was no significant difference in mean EBL, operative time, conversion rate, complication rate, LOS, or 30-day mortality rate (p > 0.05). CONCLUSIONS: Laparoscopic splenectomy is appropriate for patients whose indication for surgery is splenic mass. Suspicious splenic masses should be removed due to the relatively high incidence of malignant pathology, most commonly lymphoma.

Diabetes and education in the elderly.

Diabetes mellitus (DM) in the elderly is a chronic disease where self management is a key aspect. This includes lifestyle modification (diet and exercise), medication compliance and hypoglycaemia management. Education is an important part of this process and the specific needs of the older population with DM have been underlined. The literature has shown that education through a multidisciplinary approach may improve the glycaemic control in selected elderly patients with DM. This article will focus on the evidences from the medical literature and the multiple challenges of teaching in this population.

Passive electrostatic recycling spectrometer of desk-top size for charged particles of low kinetic energy.

A passive electrostatic recycling spectrometer for charged particles is described and demonstrated to store electrons with typical kinetic energies of tens of eV. The design of the charged particle optics and the basic operating characteristics of the storage ring are discussed. The storage lifetime achieved is approximately 50 micros, which is target gas pressure limited and corresponds to approximately 200 orbits of the 0.65 m orbital circumference. The storage ring also has controllable energy dispersive elements enabling it to operate as a spectroscopic device.

The metabolic syndrome.

The metabolic syndrome (MS) is a cluster of metabolic abnormalities leading to increased risk for cardiovascular diseases and diabetes type 2. Its prevalence is increasing with aging. There exists actually an epidemic of MS. Visceral obesity and the resulting insulin resistance (IR) are the major determinant in the development of the MS. Abdominal obesity results in a low grade inflammation via the adipose tissue and macrophages secreted adipokines. This inflammation, via the generated pro-inflammatory molecules, interferes with the normal insulin signalling and thus contributes to the etiopathogenesis of the MS. Large clinical studies showed that CRP is increased in obese subjects and concomitantly to the number of existing component of the MS. Treatment of the MS is aimed to improve the IR by lifestyle changes including exercise and diet alone or in combination with medication targeting the individual components but having also anti-inflammatory actions. More research is needed to bring new therapies to be able to decrease the incidence and prevalence of the MS among the population and thus increasing their quality of life.

Action pattern of Fusarium moniliforme endopolygalacturonase towards pectin fragments: Comprehension and prediction.

The structures of complexes of Fusarium moniliforme endopolygalacturonase (endoPG) with non-methylated or partly methylated homogalacturonan fragments were modeled to identify the residues involved in substrate binding and to correlate the cleavage pattern with the experimental productive modes. The conformational space of the complex was extensively explored and malto- to hexo-oligogalacturonates were modeled in the active cleft. To select the most highly probable productive complex for each oligomer between DP2 and 6, four energetic criteria were defined. Noteworthingly, the results were in accordance with the experimental results showing the mode of action of this enzyme towards un-methyl-esterified oligogalacturonates. Furthermore, the amino-acid residues involved in the binding were confirmed by similar studies performed on other endoPGs. Then, the oligomers were gradually methyl-esterified at one or more positions and similar docking experiments were carried out. Markedly, the docking energies were not significantly modified by the methyl-esterification of the substrate and it is likely that the methyl-esterification of the substrate does not alter the mode of action of the enzyme. Finally, 1D sequence and 3D structure of the endopolygalacturonase of Aspergillus niger II, known to be strictly non-tolerant to methylesters, were compared with the sequence and structure of the tolerant F. moniliforme endopolygalacturonase to get to a structural comprehension of the tolerant-or not-behaviour of endoPGs with methyl-esterified pectins.