Which anthropometric measures best reflect neonatal adiposity?

BACKGROUND: Studying the determinants and the long-term consequences of fetal adipose accretion requires accurate assessment of neonatal body composition. In large epidemiological studies, in-depth body composition measurement methods are usually not feasible for cost and logistical reasons, and there is a need to identify anthropometric measures that adequately reflect neonatal adiposity. METHODS: In a multiethnic Asian mother-offspring cohort in Singapore, anthropometric measures (weight, length, abdominal circumference, skinfold thicknesses) were measured using standardized protocols in newborn infants, and anthropometric indices (weight/length, weight/length2 (body mass index, BMI), weight/length3 (ponderal index, PI)) derived. Neonatal total adiposity was measured using air displacement plethysmography (ADP) and abdominal adiposity using magnetic resonance imaging (MRI). Correlations of the anthropometric measures with ADP- and MRI-based adiposity were assessed using Pearson's correlation coefficients (rp), including in subsamples stratified by sex and ethnicity. RESULTS: Study neonates (n=251) had a mean (s.d.) age of 10.2 (2.5) days. Correlations between ADP-based fat mass (ADPFM) and anthropometric measures were moderate (rp range: 0.44-0.67), with the strongest being with weight/length, weight, BMI and sum of skinfolds (rp=0.67, 0.66, 0.62, 0.62, respectively, all P<0.01). All anthropometric measures except skinfold thicknesses correlated more strongly with ADP-based fat-free mass than ADPFM, indicating that skinfold measures may have more discriminative power in terms of neonatal total body adiposity. For MRI-based measures, weight and weight/length consistently showed strong positive correlations (rp⩾0.7) with abdominal adipose tissue compartments. These correlations were consistent in boys and girls, across different ethnic groups, and when conventional determinants of neonatal adiposity were adjusted for potential confounding. Abdominal circumference was not strongly associated with ADPFM or abdominal fat mass. CONCLUSIONS: Simple anthropometric measures (weight and weight/length) correlated strongly with neonatal adiposity, with some evidence for greater discriminative power for skinfold measures. These simple measures could be of value in large epidemiological studies.

Sixteen weeks of resistance training decrease plasma heat shock protein 72 (eHSP72) and increase muscle mass without affecting high sensitivity inflammatory markers' levels in sarcopenic men.

BACKGROUND: Sarcopenia has been associated with increased systemic inflammation and risk of physical disability in older adults. Recently, extracellular heat shock protein 72 (eHSP72) was proposed as a biomarker of sarcopenia but its response to interventions designed to increase muscle mass has never been evaluated. AIMS: The present study was designed to (1) assess eHSP72 levels following resistance training and, (2) determine whether changes in eHSP72 correlate to changes in muscle mass and inflammatory markers. METHODS: A total of 26 sarcopenic men participated in a 16-week resistance training program. The following variables were measured pre-post-intervention: plasma HSP72, serum high sensitivity (hs) inflammatory markers: interleukin-6 (hsIL-6), C-reactive protein (hsCRP), and tumor necrosis factor alpha (hsTNF-α), lean body mass (LBM) and appendicular muscle mass index (appMMI). RESULTS: eHSP72 was detected in 47 % of our participants and its level significantly decreased (P = 0.04) after the intervention, with a concomitant increase in several LBM variables and appMMI (all P < 0.035). Serum hsIL-6, hsCRP and hsTNF-α changes did not reach significance. Baseline hsIL-6 and hsCRP levels were negatively correlated with several LBM variables but solely baseline hsIL-6 was associated with changes in appLBM. No correlations were found between changes in measured variables. DISCUSSION: Attenuation of eHSP72 following resistance training in parallel with increase in LBM variables showed a concordance between the evolution of this biomarker and a clinical outcome relevant to sarcopenia. CONCLUSION: Nevertheless, the low bloodstream detection rate of eHSP72 in a sarcopenic otherwise healthy population might limit its use in clinical settings for now.

Colostrum whey down-regulates the expression of early and late inflammatory response genes induced by Escherichia coli and Salmonella enterica Typhimurium components in intestinal epithelial cells.

Pathogenic invasion by Escherichia coli and Salmonellae remains a constant threat to the integrity of the intestinal epithelium and can rapidly induce inflammatory responses. At birth, colostrum consumption exerts numerous beneficial effects on the properties of intestinal epithelial cells and protects the gastrointestinal tract of newborns from pathogenic invasion. The present study aimed to investigate the effect of colostrum on the early and late inflammatory responses induced by pathogens. The short-term (2 h) and long-term (24 h) effects of exposure to heat-killed (HK) E. coli and Salmonella enterica Typhimurium on gene expression in the porcine intestinal epithelial cell (IPEC-J2) model were first evaluated by microarray and quantitative PCR analyses. Luciferase assays were performed using a NF-κB-luc reporter construct to investigate the effect of colostrum whey treatment on the activation of NF-κB induced by HK bacteria. Luciferase assays were also performed using NF-κB-luc, IL-8-luc and IL-6-luc reporter constructs in human colon adenocarcinoma Caco-2/15 cells exposed to dose-response stimulations with HK bacteria and colostrum whey. Bovine colostrum whey treatment decreased the expression of early and late inflammatory genes induced by HK bacteria in IPEC-J2, as well as the transcriptional activation of NF-κB-luc induced by HK bacteria. Unlike that with colostrum whey, treatment with other milk fractions failed to decrease the activation of NF-κB-luc induced by HK bacteria. Lastly, the reduction of the HK bacteria-induced activation of NF-κB-luc, IL-8-luc and IL-6-luc by colostrum whey was dose dependent. The results of the present study indicate that bovine colostrum may protect and preserve the integrity of the intestinal mucosal barrier in the host by controlling the expression levels of early and late inflammatory genes following invasion by enteric pathogens.

Disturbance in uniformly 13C-labelled DHA metabolism in elderly human subjects carrying the apoE ε4 allele.

Carrying the apoE ε4 allele (E4+ ) is the most important genetic risk for Alzheimer's disease. Unlike non-carriers (E4- ), E4+ seem not to be protected against Alzheimer's disease when consuming fish. We hypothesised that this may be linked to a disturbance in n-3 DHA metabolism in E4+. The aim of the present study was to evaluate [13C]DHA metabolism over 28 d in E4+ v. E4-. A total of forty participants (twenty-six women and fourteen men) received a single oral dose of 40 mg [13C]DHA, and its metabolism was monitored in blood and breath over 28 d. Of the participants, six were E4+ and thirty-four were E4-. In E4+, mean plasma [13C]DHA was 31% lower than that in E4-, and cumulative b-oxidation of [13C]DHA was higher than that in E4- 1­28 d post-dose (P ≤0·05). A genotype x time interaction was detected for cumulative b-oxidation of [13C]DHA (P ≤ 0·01). The whole-body half-life of [13C]DHA was 77% lower in E4+ compared with E4- (P ≤0·01). In E4+ and E4-, the percentage dose of [13C]DHA recovered/h as 13CO2 correlated with [13C]DHA concentration in plasma, but the slope of linear regression was 117% steeper in E4+ compared with E4- (P ≤ 0·05). These results indicate that DHA metabolism is disturbed in E4+, and may help explain why there is no association between DHA levels in plasma and cognition in E4+. However, whether E4+ disturbs the metabolism of 13C-labelled fatty acids other than DHA cannot be deduced from the present study.

Bioavailability and immunotoxicity of silver nanoparticles to the freshwater mussel Elliptio complanata.

The purpose of this study was to examine the effects of Ag nanoparticles (nAg) of two different sizes (20 and 80 nm) and Ag(+) on the immune system of the freshwater mussel Elliptio complanata. Mussels were exposed to increasing concentrations of nAg and dissolved Ag (AgNO3) for 48 h at 15°C and concentration of 0, 0.8, 4, or 20 µg/L. Immunocompetence was determined by hemocyte viability, phagocytosis, and cell cytotoxicity. Ag tissue loadings and levels of metallothioneins (MT), lipid peroxidation (LPO), and labile zinc (Zn) were also determined. Results revealed first that 20- and 80-nm nAg readily formed aggregates in freshwater. Ag was detected in soft tissues with each form of Ag with bioconcentration factors of 20, 9, and 7 for Ag(+), 20-nm nAg, and 80-nm nAg, respectively. Significant induction in phagocytosis and decreased cell cytotoxicity were observed. All forms of Ag were able to induce LPO in gills and digestive glands at concentrations below those from the initial fraction of dissolved Ag. The effects of nAg on MT levels in mussels were not discernible from those of dissolved Ag, but the 80-nm was 25-fold more potent than 20-nm nAg in inducing MT. Multivariate analysis revealed that the global responses of the 20- and 80-nm nAg were generally similar to those of dissolved Ag. Data also demonstrated that nAg are bioavailable for mussels where the immune system is a target during early exposure to nanoparticles.

Establishment of CT diagnostic reference levels (DRLs) for a Singapore healthcare cluster.

INTRODUCTION: The use of computed tomography (CT) in healthcare institutions has increased rapidly in recent years. The Singapore Health Services (SingHealth) cluster of healthcare institutions has taken the first step in establishing a local cluster-wide CT Diagnostic Reference Levels (DRL) in Singapore. CT dose data from each institution were collected through two primary dosimetry metrics: volume CT dose index (CTDIvol measured in mGy) and dose-length product (DLP measured in mGy.cm). METHODS: Data from 19 CT scanners in seven institutions under one of Singapore healthcare cluster were retrospectively collected and analysed. The five common adult CT examinations analysed were CT Brain (non-contrast enhanced), CT Chest (IV contrast enhanced), CT Kidney-Ureter-Bladder (CT KUB, non-contrast enhanced), CT Pulmonary Angiogram (CT PA, IV contrast enhanced) and CT Abdomen-Pelvis (CT AP, IV contrast enhanced, single phase). Median CTDIvol and DLP values for the five CT examinations from each institution were derived, with the cluster DRLs determined as the 75th percentile of the distribution of the institution median dose values. RESULTS: A total of 2413 dose data points were collected over a six-month period from June to November 2020. The cluster CT DRLs for the five CT examinations were determined to be 47 mGy and 820 mGy.cm for CT Brain, 5.4 mGy and 225 mGy.cm for CT Chest, 6.7 mGy and 248 mGy.cm for CT PA, 4.6 mGy and 190 mGy.cm for CT KUB and 6.9 mGy and 349 mGy.cm for CT AP. CONCLUSION: The establishment of the cluster CT DRLs provided individual institutions with a better understanding if their CT doses are unusually high or low, while emphasising that these DRLs are not meant as hard dose limits or constraints to follow strictly.

Genes for prostaglandin synthesis, transport and inactivation are differentially expressed in human uterine tissues, and the prostaglandin F synthase AKR1B1 is induced in myometrial cells by inflammatory cytokines.

Prostaglandins (PGs) are important factors in the physiology of human parturition and the control of uterine contractility. We have characterized the expression of 15 genes from all stages of the PG pathway in human pregnant and non-pregnant (NP) myometrium and in other uterine tissues at delivery, and the results show patterns indicative of different capacities for PG synthesis and catabolism in each tissue. In placenta, the PG synthase expression profile favours production of PGD2, PGE2 and PGF2, with high levels of PG transporters and catabolic PG dehydrogenase suggesting rapid PG turnover. Choriodecidua is primed for PGE2, PGF2 and PGD2 production and high PG turnover, whereas amnion expresses genes for PGE2 synthesis with low levels of PG transporters and dehydrogenase. In umbilical cord, PGI2 synthase is highly expressed. In pregnant myometrium, PGI2, PGD2 and PGF2 synthases are highly expressed, whereas PG dehydrogenase is underexpressed. Myometrium from women with spontaneous or induced labour had higher expression of the PGH2 synthase PTGS2 than tissue from women not-in-labour. Myometrium from NP women had lower levels of PG synthases and higher levels of PG dehydrogenase than pregnant myometrium. Discriminant function analysis showed that expression of selected genes in myometrium could distinguish groups of women with different modes of labour from each other and from NP women. In cultured myometrial cells, there was a dose-dependent stimulatory effect of interleukin 1ß and tumour necrosis factor α on PTGS2, PTGES and AKR1B1 (PGF synthase) expression.

Analysing a family-centred preoperative intervention programme: a dismantling approach.

BACKGROUND: The goal of this project was to identify key effective components of ADVANCE, a family-centred preoperative intervention programme, through the use of a dismantling approach. ADVANCE was previously demonstrated to be more effective than parental presence and just as effective as midazolam in reducing children's preoperative anxiety. The total programme, however, may be difficult to implement in hospitals across the country. METHODS: Subjects in this follow-up dismantling report were 96 children aged 2-10 who were part of the original study and who underwent anaesthesia and surgery. Baseline characteristics, parental adherence to the components of ADVANCE, and child and parent anxiety were assessed. RESULTS: We found that greater parental adherence to the ADVANCE intervention was associated with lower child anxiety before surgery. The two components of ADVANCE that emerged as having a significant impact on children's anxiety were practising with the anaesthesia mask at home and parental planning and use of distraction in the preoperative holding area. In fact, not only did children experience significantly less preoperative anxiety when their parents were adherent to mask practise and use of distraction, their anxiety tended to remain stable and relatively low throughout the preoperative period. CONCLUSIONS: Shaping and exposure (i.e. practise with the anaesthesia mask) and parental use of distraction in the surgical setting are two beneficial components that could be included in preoperative preparation programmes that will be designed in the future.

Short-term physiological effects of a xenobiotic mixture on the freshwater mussel Elliptio complanata exposed to municipal effluents.

The aim of this study was to investigate the short-term effects of tertiary-treated municipal effluents on the freshwater mussel Elliptio complanata. Caged mussels were immersed during 2 weeks in a river located North of Montreal Island, upstream/downstream the outfall and in one reference site located at the beginning of the Rivière des Prairies. A selection of biomarkers was analyzed to depict changes on various physiological systems: general physiology (mussel viability, condition index and gonado-somatic index), immune status (hemocyte viability, cellularity, phagocytosis efficiency, NK-like cytotoxic activity and lysozyme activity), inflammation (cyclo-oxygenase activity), detoxification (glutathione-S-transferases activity) and vitellogenesis (alkali-labile phosphate level). The analysis of total and fecal coliform counts in water and of heterotrophic bacteria levels in mussel tissues showed that the bacteriological quality of the water strongly decreased from the reference site to the downstream site. This was correlated with a significant loss of weight and an increase of mussel mortality. Cellularity and phagocytosis efficiency were significantly increased in the downstream site compared to the reference site. Though not statistically significant, lysozyme activity was also increased. NK-like cytotoxicity, activity of the pro-inflammatory enzyme COX and the levels of ALP and MT were not significantly changed. Conversely, the municipal effluents induced a significant increase of GST activity in downstream site, indicating a stimulation of detoxification metabolism. Altogether, these results confirm that a short-term exposure to a mixture of bacterial and chemical compounds released by the wastewater treatment plant La Pinière induces adverse physiological effects in E. complanata, as observed with the modulation of immune response and induction of detoxification metabolism.

Intravaginal dehydroepiandrosterone (prasterone), a highly efficient treatment of dyspareunia.

OBJECTIVE: To examine the effect of intravaginal dehydroepiandrosterone (DHEA) on pain at sexual activity (dyspareunia) identified as the most bothersome symptom of vaginal atrophy in postmenopausal women at both screening and day 1. METHODS: This prospective, randomized, double-blind and placebo-controlled phase III clinical trial studied the effect of prasterone (DHEA) applied locally in the vagina on the severity of dyspareunia in 114 postmenopausal women who had identified dyspareunia as their most bothersome symptom of vaginal atrophy, while meeting the criteria for superficial cells ≤ 5% and pH > 5.0 at both screening and day 1. RESULTS: At the standard duration of 12 weeks of treatment, increasing doses of 0.25%, 0.5% and 1.0% DHEA decreased the percentage of parabasal cells by 48.6  ±â€Š 6.78%, 42.4  ±  7.36% and 54.9  ±â€Š 6.60% (p < 0.0001 vs. placebo for all) with no change with placebo (p = 0.769). The effects on superficial cells and pH were also highly significant compared to placebo at all DHEA doses. The severity score of pain at sexual activity decreased by 0.5, 1.4, 1.6 and 1.4 units in the placebo and 0.25%, 0.5% and 1.0% DHEA groups, respectively, with the p value of differences from placebo ranging from 0.0017 to < 0.0001. CONCLUSIONS: Intravaginal DHEA, through local estrogen and androgen formation, causes a rapid and highly efficient effect on pain at sexual activity without systemic exposure of the other tissues, thus avoiding the recently reported systemic effects of estrogens.

Effects of aerobic exercise, resistance exercise or both, on patient-reported health status and well-being in type 2 diabetes mellitus: a randomised trial.

AIMS/HYPOTHESIS: The Diabetes Aerobic and Resistance Exercise (DARE) study showed that aerobic and resistance exercise training each improved glycaemic control and that a combination of both was superior to either type alone in patients with type 2 diabetes mellitus. Here we report effects on patient-reported health status and well-being in the DARE Trial. METHODS: We randomised 218 inactive participants with type 2 diabetes mellitus in parallel to 22 weeks of aerobic exercise (n = 51), resistance exercise (n = 58), combined aerobic and resistance exercise (n = 57) or no exercise (control; n = 52). Intervention allocation was managed by a central office. Outcomes included health status as assessed by the physical and mental component scores of the Medical Outcomes Trust Short-Form 36-item version (SF-36) and well-being as measured by the Well-Being Questionnaire 12-item version (WBQ-12); these were measured at the Ottawa Hospital. RESULTS: Using a p value of 0.0125 for statistical significance due to multiple comparisons, mixed model analyses indicated that resistance exercise led to clinically but not statistically significant improvements in the SF-36 physical component score compared with aerobic exercise (Delta = 2.7 points; p = 0.048) and control (i.e. no exercise; Delta = 3.3 points; p = 0.015). For mental component scores, there were clinically important improvements favouring no (control) compared with resistance (Delta = 7.6 points; p < 0.001) and combined (Delta = 7.2 points; p < 0.001) exercise. No effects on WBQ-12 scores were noted. Overall, 59/218 (27%) of participants included in this analysis sustained an adverse event during the course of the study, including 16 participants in the combined exercise group, 19 participants in the resistance exercise group, 16 participants in the aerobic exercise group, and eight participants in the control group. All participants were included in the intent-to-treat analyses. The trial is now closed to follow-up. CONCLUSIONS/INTERPRETATION: Resistance exercise was better than aerobic or no exercise for improving physical health status in these patients. No exercise was superior to resistance or combined exercise for improving mental health status. Well-being was unchanged by intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT00195884 FUNDING: This study was funded by the Canadian Institutes of Health Research (grant MCT-44155) and the Canadian Diabetes Association (The Lillian Hollefriend Grant).

Immunocompetence and alterations in hepatic gene expression in rainbow trout exposed to CdS/CdTe quantum dots.

Cadmium (Cd) tellurium quantum dots (QDs) are long-lived fluorescent nanocrystals that have the ability to produce potentially toxic reactive oxygen species at the surface of the nanoparticle and release toxic cadmium ions. The purpose of this study was to examine the sublethal effects of CdS/CdTe QDs and dissolved Cd on the immune system of rainbow trout. Changes in hepatic gene expression were also monitored to provide insight on the mode of action of both forms of cadmium. Oncorhynchus mykiss fish were exposed to increasing concentrations of CdS/CdTe or dissolved Cd (CdSO(4)) for 48 h at 15 degrees C. The anterior head kidney was analyzed for leukocyte count, viability and phagocytic activity. The livers were harvested and prepared for gene expression analysis using a DNA microarray comprised of 207 stress-related genes. An analysis of total Cd in the aquarium water revealed that the nominal concentrations corresponded well to the actual concentrations and that a small proportion (0.4%) of Cd in the QDs was found in the dissolved fraction. Exposure to QDs led to significant reductions in leukocyte counts, viability and both resting and active phagocytic activity. On a mass concentration basis, QDs were more potent than dissolved Cd in suppressing immunocompetence in rainbow trout. The analysis revealed that both forms of Cd were strong inducers of metallothionein and CP2K1 gene expressions, which are respectively involved in metal detoxification processes and xenobiotic transformation/inflammation conditions. The analysis revealed different modes of action for each form of Cd. For QDs, 25 genes specific to QDs and related to the immune endpoints were found. The genes were involved in inflammation, xenobiotic biotransformation and endocrine system (including the induction of vitellogenin and its receptor). The effect for dissolved Cd was narrower than for QDs, with 9 genes specific to dissolved Cd being strongly correlated with the observed effects on immunocompetence. The involved genes were binding and transport of various solutes (urea, sodium, potassium) and the complement system. The present study revealed that each form of Cd produced a different pattern of gene expression and lowered fish immunocompetence.

RhoE controls myoblast alignment prior fusion through RhoA and ROCK.

Differentiation of skeletal myoblasts into multinucleated myotubes is a multi-step process orchestrated by several signaling pathways. The Rho small G protein family plays critical roles both during myogenesis induction and myoblast fusion. We report here that in C2C12 myoblasts, expression of RhoE, an atypical member of this family, increases until the onset of myoblast fusion before resuming its basal level once fusion has occurred. We show that RhoE accumulates in elongated, aligned myoblasts prior to fusion and that its expression is also increased during injury-induced skeletal muscle regeneration. Moreover, although RhoE is not required for myogenesis induction, it is essential for myoblast elongation and alignment before fusion and for M-cadherin expression and accumulation at the cell-cell contact sites. Myoblasts lacking RhoE present with defective p190RhoGAP activation and RhoA inhibition at the onset of myoblast fusion. RhoE interacts also with the RhoA effector Rho-associated kinase (ROCK)I whose activity must be downregulated to allow myoblast fusion. Consistently, we show that pharmacological inactivation of RhoA or ROCK restores myoblast fusion in RhoE-deficient myoblasts. RhoE physiological upregulation before myoblast fusion is responsible for the decrease in RhoA and ROCKI activities, which are required for the fusion process. Therefore, we conclude that RhoE is an essential regulator of myoblast fusion.

Impact of a checklist used by pharmacists on hospital antimicrobial use: a patient-level interrupted time series study.

BACKGROUND: Antimicrobial misuse leading to drug resistance is a growing concern for clinicians. Improving antimicrobial stewardship programmes through development of new tools could be part of the solution. AIM: To evaluate antimicrobial use in hospitalized patients after implementation of an antimicrobial checklist for ward-based clinical pharmacists. METHODS: A checklist based on quality indicators of optimal antimicrobial use was implemented to standardize hospital pharmacists' assessments of antimicrobial therapy. Antimicrobial use metrics from adults hospitalized during the control and intervention periods were assessed in an interrupted time series analysis of individual patient data. The primary endpoint was days of therapy (DOT) for all antimicrobials per 1000 days present for included patients. Secondary endpoints were the DOT of extended-spectrum antimicrobials (DOT-ES), length of therapy of all antimicrobials (LOT) and the number of pharmacist interventions. FINDINGS: One-thousand six-hundred and nineteen patients were included: 800 and 819 in the pre- and post-checklist implementation periods, respectively. As indicated by the point estimates and their 95% confidence intervals (CIs), there were no changes in trend for DOT, DOT-ES or LOT. A change in level was not found for the DOT, while a change of -118 DOT-ES [-209,-28] and -51 LOT [-97,-4] was documented. Furthermore, pharmacists' interventions regarding antimicrobials increased by 18.7% (14.0, 23.5) and progress notes by 32.3% (27.8, 36.8). CONCLUSION: An antimicrobial checklist used by ward-based clinical pharmacists did not decrease DOT for all antimicrobials, but decreased DOT-ES and LOT upon its implementation.

Hypertrophy and hyperplasia of abdominal adipose tissues in women.

OBJECTIVE: To examine the expression of selected transcription factors involved in adipogenesis and genes related to lipid metabolism in abdominal subcutaneous and omental fat tissue. RESEARCH DESIGN AND METHODS: We obtained subcutaneous and omental adipose tissue samples from 40 women undergoing abdominal hysterectomies (age: 47+/-5 years; BMI 27.9+/-5.3 kg/m(2)). We measured isolated adipocyte size and metabolism, and detailed measures of body fat accumulation and body fat distribution were obtained (dual-energy X-ray absorptiometry and computed tomography, respectively). RESULTS: Adipocyte size of both subcutaneous and omental fat were increased with higher body fat mass values, with similar regression slopes in each compartment. In contrast, with higher body fat mass values, fat accumulation was progressively higher in the subcutaneous than in the visceral fat compartment, suggesting hyperplasia in the subcutaneous fat compartment. Messenger RNA levels of CEBPalpha, PPARgamma2, SREBP1c and genes related to lipid metabolism (LPL, FABP4, DGAT1, DGAT2, PLIN and HSL) were significantly higher in subcutaneous than in omental fat tissue (P< or =0.001 for all). Only subcutaneous expression of these genes tracked with obesity levels as reflected by significant positive associations between subcutaneous fat CEBPalpha, SREBP1c and DGAT2 expression and total body fat mass (r=0.37, r=0.41, r=0.57, respectively, P< or =0,05), fat percentage (r=0.40, r=0.39, r=058, respectively, P< or =0,05) and subcutaneous adipose tissue area (r=0.36, r=0.38, r=0.58, respectively, P< or =0,05). Omental adipose tissue expression levels of these genes were not significantly related to adiposity measures. CONCLUSIONS: These results show that in obese women, hyperplasia is predominant in the subcutaneous fat depot, whereas fat cell hypertrophy is observed both in the omental and subcutaneous compartments.

Effects of physiological concentrations of heavy metals both individually and in mixtures on the viability and function of peripheral blood human leukocytes in vitro.

Among environmental contaminants recognized for their toxicity and global distribution, heavy metals are elements known to exert serious ecological consequences. Published experiments on the immunotoxic effects of metals such as methylmercury (MeHg), cadmium (Cd), and lead (Pb) were often conducted at concentrations higher than those present in the environment or those in human blood. In the present study the in vitro effects on human blood of environmentally relevant concentrations of MeHg (33-200 mug/L), Cd (3.1-16 mug/L), and Pb (75-207 mug/L) were assessed individually and in mixtures on the viability and immune competence of peripheral blood leukocytes (PBLs). At MeHg concentrations of 120 and 200 mug/L both lymphocyte proliferation, as measured by [(3)H]thymidine incorporation, and natural killer (NK) cytotoxity activity, as determined by dioctadecyloacarbocyanine, were suppressed. Our results showed an increase of intracellular thiols in lymphocytes and in monocytes at all the concentrations of metals tested. A decrease in the level of metallothionein (MT) was seen in monocytes in presence of Hg at concentration of 120 mug/L and higher. For lymphocytes, a significant increase of MT in groups containing the lower concentrations of Cd, and Hg was noted. In summary, it appears that Hg represents the most toxic metal at environmentally relevant concentrations on human peripheral mononuclear cells. The effects of Hg exposure were greater on lymphocytes and NK cells than on monocytes.

A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer's disease.

INTRODUCTION: Deteriorating brain glucose metabolism precedes the clinical onset of Alzheimer's disease (AD) and appears to contribute to its etiology. Ketone bodies, mainly ß-hydroxybutyrate and acetoacetate, are the primary alternative brain fuel to glucose. Some reports suggest that brain ketone metabolism is unchanged in AD but, to our knowledge, no such data are available for MCI. OBJECTIVE: To compare brain energy metabolism (glucose and acetoacetate) and some brain morphological characteristics in cognitively healthy older adult controls (CTL), mild cognitive impairment (MCI) and early AD. METHODS: 24 CTL, 20 MCI and 19AD of similar age and metabolic phenotype underwent a dual-tracer PET and MRI protocol. The uptake rate constants and cerebral metabolic rate of glucose (KGlu, CMRGlu) and acetoacetate (KAcAc, CMRAcAc) were evaluated with PET using [18F]-fluorodeoxyglucose ([18F]-FDG), a glucose analogue, and [11C]-acetoacetate ([11C]-AcAc), a ketone PET tracer. Regional brain volume and cortical thickness were evaluated by T1-weighted MRI. RESULTS: In AD compared to CTL, CMRGlu was ~11% lower in the frontal, parietal, temporal lobes and in the cingulate gyrus (p<0.05). KGlu was ~15% lower in these same regions and also in subcortical regions. In MCI compared to CTL, ~7% glucose hypometabolism was present in the cingulate gyrus. Neither regional nor whole brain CMRAcAc or KAcAc were significantly different between CTL and MCI or AD. Reduced gray matter volume and cortical thinning were widespread in AD compared to CTL, whereas, in MCI compared to CTL, volumes were reduced only in the temporal cortex and cortical thinning was most apparent in temporal and cingulate regions. DISCUSSION: This quantitative kinetic PET and MRI imaging protocol for brain glucose and acetoacetate metabolism confirms that the brain undergoes structural atrophy and lower brain energy metabolism in MCI and AD and demonstrates that the deterioration in brain energy metabolism is specific to glucose. These results suggest that a ketogenic intervention to increase energy availability for the brain is warranted in an attempt to delay further cognitive decline by compensating for the brain glucose deficit in MCI and AD.

Body composition measurement in young children using quantitative magnetic resonance: a comparison with air displacement plethysmography.

BACKGROUND: Quantitative magnetic resonance (QMR) has been increasingly used to measure human body composition, but its use and validation in children is limited. OBJECTIVE: We compared body composition measurement by QMR and air displacement plethysmography (ADP) in preschool children from Singapore's multi-ethnic Asian population (n = 152; mean ± SD age: 5.0 ± 0.1 years). METHODS: Agreements between QMR-based and ADP-based fat mass and fat mass index (FMI) were assessed using intraclass correlation coefficient (ICC), reduced major axis regression and Bland-Altman plot analyses. Analyses were stratified for the child's sex. RESULTS: Substantial agreement was observed between QMR-based and ADP-based fat mass (ICC: 0.85) and FMI (ICC: 0.82). Reduced major axis regression analysis suggested that QMR measurements were generally lower than ADP measurements. Bland-Altman analysis similarly revealed that QMR-based fat mass were (mean difference [95% limits of agreement]) -0.5 (-2.1 to +1.1) kg lower than ADP-based fat mass and QMR-based FMI were -0.4 (-1.8 to +0.9) kg/m2 lower than ADP-based FMI. Stratification by offspring sex revealed better agreement of QMR and ADP measurements in girls than in boys. CONCLUSIONS: QMR-based fat mass and FMI showed substantial agreement with, but was generally lower than, ADP-based measures in young Asian children.

[Sensory and motor clinical presentation of congenital retraction syndromes: Stilling-Duane and Brown syndrome]. / Aspects cliniques sensoriels et moteurs des syndromes de rétractions congénitaux : syndrome de Stilling-Duane et syndrome de Brown.

INTRODUCTION: Congenital Brown syndrome and Stilling-Duane syndrome, two rare causes of strabismus are caused by fibrosis of one or more extraocular muscles. This series aims to report the clinical sensory and motor features of patients with Brown or Stilling-Duane syndrome. METHODS: Seventeen patients' records were retrospectively assessed for: the ocular deviation in primary position and in the 9 positions of gaze, head tilt, visual acuity and binocular vision. RESULTS: Eleven patients with Stilling-Duane syndrome had a mean age of 12 years, and monocular involvement, most frequently of type I. The ocular deviation was variable; 16 patients had an abnormal head position, while 50 % presented with amblyopia, and only 37 % achieved fusion in the compensatory head posture. Six patients presented with congenital Brown syndrome at mean age of 6 years. Three had a moderate form, 3 had a severe form with vertical deviation in primary position, compensatory head position, amblyopia and binocular vision impairment. DISCUSSION: The motility impairments depend highly on the identified syndrome, its classification and its severity. Therefore, these two retraction syndromes present some common features. Strabismus in primary position may lead to amblyopia and binocular vision impairment. CONCLUSION: Clinical motility and sensory assessment is essential, though difficult, to establish the diagnosis and the management of patients with retraction syndromes.

Incomplete cytokinesis/binucleation in mammals: The powerful system of hepatocytes.

Polyploidy, the state of having greater than a diploid DNA content (tetraploid, octoploid, etc.) is a characteristic feature of mammalian hepatocytes and accompanies late fetal development and postnatal maturation of the liver. During the weaning period, diploid hepatocytes can engage either into normal cell division cycle giving rise to two diploid hepatocytes or follow a scheduled division program characterized by incomplete cytokinesis. In that case, diploid hepatocytes undergo mitosis, but do not form a contractile ring. Indeed, cleavage-plane specification is never established, because of the deficiencies of actin cytoskeleton reorganization. Furthermore, microtubules fail both to contact the cortex and to deliver their molecular signal, preventing localization and activation of RhoA. Therefore, cytokinesis aborts and a binucleate tetraploid liver cell is generated, which subsequently plays a pivotal role in liver progressive polyploidization. In this chapter, we describe detailed protocols to monitor hepatocyte proliferation and cytokinesis process by in situ and dynamic ex vivo approaches.