Quantum circuits with many photons on a programmable nanophotonic chip.

Growing interest in quantum computing for practical applications has led to a surge in the availability of programmable machines for executing quantum algorithms1,2. Present-day photonic quantum computers3-7 have been limited either to non-deterministic operation, low photon numbers and rates, or fixed random gate sequences. Here we introduce a full-stack hardware-software system for executing many-photon quantum circuit operations using integrated nanophotonics: a programmable chip, operating at room temperature and interfaced with a fully automated control system. The system enables remote users to execute quantum algorithms that require up to eight modes of strongly squeezed vacuum initialized as two-mode squeezed states in single temporal modes, a fully general and programmable four-mode interferometer, and photon number-resolving readout on all outputs. Detection of multi-photon events with photon numbers and rates exceeding any previous programmable quantum optical demonstration is made possible by strong squeezing and high sampling rates. We verify the non-classicality of the device output, and use the platform to carry out proof-of-principle demonstrations of three quantum algorithms: Gaussian boson sampling, molecular vibronic spectra and graph similarity8. These demonstrations validate the platform as a launchpad for scaling photonic technologies for quantum information processing.

Ground-Based Mobile Measurements to Track Urban Methane Emissions from Natural Gas in 12 Cities across Eight Countries.

To mitigate methane emission from urban natural gas distribution systems, it is crucial to understand local leak rates and occurrence rates. To explore urban methane emissions in cities outside the U.S., where significant emissions were found previously, mobile measurements were performed in 12 cities across eight countries. The surveyed cities range from medium size, like Groningen, NL, to large size, like Toronto, CA, and London, UK. Furthermore, this survey spanned across European regions from Barcelona, ES, to Bucharest, RO. The joint analysis of all data allows us to focus on general emission behavior for cities with different infrastructure and environmental conditions. We find that all cities have a spectrum of small, medium, and large methane sources in their domain. The emission rates found follow a heavy-tailed distribution, and the top 10% of emitters account for 60-80% of total emissions, which implies that strategic repair planning could help reduce emissions quickly. Furthermore, we compare our findings with inventory estimates for urban natural gas-related methane emissions from this sector in Europe. While cities with larger reported emissions were found to generally also have larger observed emissions, we find clear discrepancies between observation-based and inventory-based emission estimates for our 12 cities.

FAS A-670G and Fas ligand IVS2nt A 124G polymorphisms are significantly increased in women with pre-eclampsia and may contribute to HELLP syndrome: a case-controlled study.

OBJECTIVE: We evaluated the association between the Fas-670A/G and the Fas ligand FasL IVS2nt 124 A/G polymorphisms and the risk of pre-eclampsia and its complications. DESIGN: A case-controlled study. SETTING: University Hospitals in most areas of Tunisia. POPULATION: We recruited 300 pregnant women who developed pre-eclampsia and 300 age-matched healthy pregnant women from the same hospital. METHODS: Genotyping of Fas-670A/G and the FasL IVS2nt 124A/G gene polymorphisms were conducted using polymerase chain reaction-restriction fragment length polymorphism among our cohort. MAIN OUTCOME MEASURES: Fisher's exact test was used to compare the statistical differences between groups for categorical variables and Student t tests were used for continuous variables. RESULTS: The frequency of the Fas-670G gene variant was significantly increased in women with pre-eclampsia (42%) compared with control women (30%; P < 0.001). Also, a statistically significant difference was obtained in the distribution of the FasL IVS2nt 124G gene variant when comparing women with pre-eclampsia (43%) with controls (30%; P < 0.001). Interestingly, we found that the carriage of Fas-670G was associated with increased liver enzymes, suggesting an increased prevalence of the haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, a pre-eclampsia complication. CONCLUSION: The Fas-670G and FasL IVS2nt 124G polymorphisms are associated with a higher risk of pre-eclampsia and its complications. TWEETABLE ABSTRACT: Polymorphisms in the Fas and FasL genes are associated with increased risk of pre-eclampsia and HELLP syndrome.

Two weeks of high-fat feeding disturb lipid and cholesterol molecular markers.

Metabolic disorders are often associated with liver steatosis and increased plasma cholesterol levels. However, the link between excessive lipid accumulation and impairments in cholesterol metabolism remains uninvestigated in the liver. Short term of high-fat diet (HFD) was previously shown to promote excessive lipid accumulation prior to the development of metabolic disorders. The present study intended to characterize how increases in liver fat alter the expression of several key regulators of hepatic cholesterol metabolism in response to a short-term HFD. Wistar rats were randomly submitted either to HFD (n = 8) or a regular chow diet (n = 8) for 14 days. Increases in triglycerides were highly significant (P < 0.01) in the liver but marginal in the plasma of HFD rats. In contrast, the HFD resulted in higher (P < 0.01) cholesterol levels in plasma but not in liver samples. Gene expression of key markers involved in cholesterol uptake (LDL particles) including low-density lipoprotein receptor-related protein-1 (LRP-1) and protein convertase subtilisin/kexin type 9 (PCSK9) along with ATP-binding cassette, superfamily G, member 5 (ABCG5) involved in cholesterol exportation via bile ducts was found to be higher (P < 0.05) in response to the HFD. In contrast, expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), involved in cholesterol synthesis, was downregulated in the liver. The data support the concept that excessive accumulation of lipids promptly alters the expression of key genes regulating cholesterol metabolism in the liver. On a clinical point of view, this indicates that increases in plasma cholesterol occur after a short-term HFD.

Molecular insights into the normal operation, regulation, and multisystemic roles of K+-Cl- cotransporter 3 (KCC3).

Long before the molecular identity of the Na+-dependent K+-Cl- cotransporters was uncovered in the mid-nineties, a Na+-independent K+-Cl- cotransport system was also known to exist. It was initially observed in sheep and goat red blood cells where it was shown to be ouabain-insensitive and to increase in the presence of N-ethylmaleimide (NEM). After it was established between the early and mid-nineties, the expressed sequence tag (EST) databank was found to include a sequence that was highly homologous to those of the Na+-dependent K+-Cl- cotransporters. This sequence was eventually found to code for the Na+-independent K+-Cl- cotransport function that was described in red blood cells several years before. It was termed KCC1 and led to the discovery of three isoforms called KCC2, KCC3, and KCC4. Since then, it has become obvious that each one of these isoforms exhibits unique patterns of distribution and fulfills distinct physiological roles. Among them, KCC3 has been the subject of great attention in view of its important role in the nervous system and its association with a rare hereditary sensorimotor neuropathy (called Andermann syndrome) that affects many individuals in Quebec province (Canada). It was also found to play important roles in the cardiovascular system, the organ of Corti, and circulating blood cells. As will be seen in this review, however, there are still a number of uncertainties regarding the transport properties, structural organization, and regulation of KCC3. The same is true regarding the mechanisms by which KCC3 accomplishes its numerous functions in animal cells.

Analysis of genomic copy number variation in equine recurrent airway obstruction (heaves).

We explored the involvement of genomic copy number variants (CNVs) in susceptibility to recurrent airway obstruction (RAO), or heaves-an asthmalike inflammatory disease in horses. Analysis of 16 RAO-susceptible (cases) and six RAO-resistant (control) horses on a custom-made whole-genome 400K equine tiling array identified 245 CNV regions (CNVRs), 197 previously known and 48 new, distributed on all horse autosomes and the X chromosome. Among the new CNVRs, 30 were exclusively found in RAO cases and were further analyzed by quantitative PCR, including additional cases and controls. Suggestive association (P = 0.03; corrected P = 0.06) was found between RAO and a loss on chromosome 5 involving NME7, a gene necessary for ciliary functions in lungs and involved in primary ciliary dyskinesia in humans. The CNVR could be a potential marker for RAO susceptibility but needs further study in additional RAO cohorts. Other CNVRs were not associated with RAO, although several involved genes of interest, such as SPI2/SERPINA1 from the serpin gene family, which are associated with chronic obstructive pulmonary disease and asthma in humans. The SPI2/SERPINA1 CNVR showed striking variation among horses, but it was not significantly different between RAO cases and controls. The findings provide baseline information on the relationship between CNVs and RAO susceptibility. Discovery of new CNVs and the use of a larger population of RAO-affected and control horses are needed to shed more light on their significance in modulating this complex and heterogeneous disease.

LDL receptor and Pcsk9 transcripts are decreased in liver of ovariectomized rats: effects of exercise training.

The aim of this study was to determine the effects of ovariectomy in rats on hepatic gene expression of key molecules involved in cholesterol metabolism and to verify if exercise training may play a role in preventing hypercholesterolemia in Ovx rats. Sprague-Dawley rats were ovariectomized (Ovx) or sham-operated (Sham) and were either trained (Tr) on treadmill or kept sedentary (Sed) for 8 weeks. Rats were divided into 5 groups: Sham-Sed, Sham-Tr, Ovx-Sed, Ovx-Tr and Ovx with 17ß-estradiol supplementation (Ovx-E2). Ovx animals had significantly (p<0.05) higher body weight, adiposity, liver total cholesterol (TC) content and hypercholesterolemia compared to Sham rats. In contrast, gene expression of hepatic low-density lipoprotein receptor (LDL-R), LDL receptor-related protein (Lrp1), proprotein convertase subtilisin/kexin type 9 (Pcsk9), sterol regulatory element binding protein 2 (SREBP-2) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoA-r) were reduced (p<0.05) in Ovx compared to Sham rats. Hepatic mRNA levels of scavenger receptor class B member 1 (SR-B1) and ATP-binding cassette subfamily A member 1 (ABCA1) (hepatic and intestinal) were higher (p<0.05) in Ovx compared to Sham rats. All of these molecular changes were corrected in Ovx-E2. Exercise training, significantly reversed the effect of Ovx on adiposity, plasma triglyceride, TC and mRNA expression of SREBP-2 but had no effect on all other hepatic genes expression. These data indicate that hypercholesterolemia in Ovx rats is associated with a reduction of hepatic LDL-R and Lrp1 gene expression.

Loss of ovarian estrogens causes only mild deterioration of glucose homeostasis in female ZDF rats preventable by voluntary running exercise.

Studies on normoglycemic ovariectomized Sprague-Dawley rats have provided insights about the effects of estrogen deficiency on insulin resistance in lean individuals. It is not completely clear if subjects with pre-established obesity and insulin resistance are at greater risk of developing type 2 diabetes when ovarian estrogens are no longer secreted, and if physical activity can protect against this susceptibility. Contrasting with their male counterparts, obese and insulin resistant female ZDF (Zucker diabetic fatty) rats do not become hyperglycemic when fed a standard diet. The aim of the study was to evaluate the hypothesis that withdrawal of ovarian estrogens in insulin resistant female ZDF rats would trigger overt hyperglycemia, provided they remain physically inactive. Female ZDF rats underwent either an ovariectomy (OVX) or a simulated surgery (SHAM). Thereafter, OVX rats engaged either in voluntary wheel cage running (OVX-Active), or like the Sham rats, remained sedentary (OVX-Sed) for 6 weeks. Fasting glycemia, insulinemia, and glucose tolerance were not altered in OVX-Sed as compared to SHAM-Sed rats. However, OVX-Sed rats showed altered liver triglyceride and glycogen contents, increased pancreatic insulin content and reduced insulin-stimulated muscle pAKT as compared to SHAM-Sed rats. Physical activity in OVX rats lowered fasting glucose and insulin levels, improved glucose tolerance and insulin-stimulated skeletal muscle glucose uptake as compared to OVX-Sed rats. OVX-induced alterations in pancreatic insulin content and liver glycogen and triglyceride contents were significantly improved by physical activity. Loss of ovarian estrogens did not cause overt hyperglycemia in insulin-resistant female ZDF rats. Physical activity improved glucose homeostasis despite estrogen deficiency.

Satiety quotient linked to food intake and changes in anthropometry during menopause: a MONET Study.

OBJECTIVES: It is unknown whether the satiety quotient (SQ) differs across the menopausal transition, and whether changes in SQ are related to changes in anthropometric/body composition variables. The objective of this study was to evaluate the changes in SQ and its association with energy intake and changes in anthropometric/body composition variables across the menopausal transition. METHODS: At baseline, 102 premenopausal women (aged 49.9 ± 1.9 years, body mass index 23.3 ± 2.2 kg/m(2)) took part in a 5-year observational, longitudinal study. Body composition (DXA), appetite (visual analog scales), energy and macronutrient intakes (ad libitum lunch and 7-day food diary) were assessed annually. The SQ (mm/100 kcal) was calculated at 60 and 180 min post-breakfast consumption. RESULTS: Overall, the SQ increased at years 3 and 4 (p = 0.01-0.0001), despite no significant differences between menopausal status groups. Lower fullness, prospective food consumption and mean SQ values predicted overall increases in lunch energy and macronutrient intakes (p = 0.04-0.01), whereas only prospective food consumption and fullness SQ predicted energy intake and carbohydrate intake, respectively, when assessed with food diaries (p = 0.01). Delta SQs were negatively correlated with changes in waist circumference (p = 0.03-0.02), whereas delta SQs were positively (p = 0.04) and negatively (p = 0.02) associated with delta fat mass between years 1 and 5, and years 4 and 5, respectively. CONCLUSION: These results suggest that variations in SQ across the menopausal transition are related to energy and macronutrient intakes and coincide with changes in body composition and waist circumference.

Red blood cell antigen portrait of self-identified black donors in Quebec.

OBJECTIVES: The goal of this study was to establish a red blood cell antigen portrait of self-identified Black donors for the province of Quebec, Canada. BACKGROUND: The demand for extensively phenotyped red blood cells is on the rise. A good example is the sickle cell patient cohort. To better answer their transfusion needs, Héma-Québec put forward great efforts to increase the recruitment of donors among cultural communities. MATERIALS AND METHODS: In October 2009, an optional question was added on the record of donation to indicate the donor's ethnicity. Self-identified Black donors were extensively phenotyped by the Immunohematology Laboratory, whereas the Research and Development team genotyped red blood cell antigens to complete the picture. RESULTS: Approximately 1500 self-identified Black donors have donated blood at least once since the beginning of the programme. Genotyping results predicted rare phenotypes: 18 S-s- (3 U-, 15 U+(w) ), 15 Js(a+b-), 5 Hy-, 3 Jo(a-), 34 hr(B) +(w) /- and 15 hr(B)-. CONCLUSION: These Black donors, with or without a rare phenotype, are precious to the patient cohort depending on blood transfusions and to our organisation as the blood provider for the whole province of Quebec.

The effects of gestational age on neonatal cholestasis: A retrospective cohort study.

BACKGROUND: Reference guidelines for neonatal conjugated hyperbilirubinemia (cholestasis) management use a uniform approach regardless of gestational age (GA). We hypothesize that the clinical pattern of neonatal cholestasis is tightly related to GA. The aim of this study was to describe the effects of GA on neonatal cholestasis. METHODS: A retrospective 4-year cohort study in a 70-bed neonatal care unit. Neonates with conjugated bilirubin≥34.2µmol/L (2 mg/dL) were identified. The incidence, clinical characteristics, etiology, treatment, and prognosis were compared between infants <32 and≥32 weeks GA. RESULTS: Overall incidence of cholestasis was 4% (125/3402). It was >5 times higher and the mean duration was >1.5 times longer in neonates <32 weeks GA (10% versus 1.8%, p <0.01 and 49 versus 31 days, p <0.01, respectively). The onset of cholestasis was later in neonates <32 weeks (22 versus 10 days of life, p <0.001). This later onset of cholestasis was associated with parenteral nutrition, whereas the earlier onset was associated with other causes. Treatment using fish oil lipids was more frequently administrated to infants <32 weeks GA, whereas Ursodeoxycholic acid was administrated more frequently in≥32 weeks GA. Cholestasis resolved during hospitalization in 73% of <32 versus 38% in≥32 weeks GA infants (p <0.01). CONCLUSIONS: The incidence, clinical presentation, etiology, treatment, and clinical evolution of neonatal cholestasis were all significantly affected by GA. Our results support the use of a GA-oriented approach for the management of neonatal cholestasis.

Inflammatory stimuli differentially modulate the transcription of paracrine signaling molecules of equine bone marrow multipotent mesenchymal stromal cells.

OBJECTIVE: Osteoarthritis (OA) is a degenerative disease of joint tissues that causes articular cartilage erosion, osteophytosis and loss of function due to pain. Inflammation and inflammatory cytokines in synovial fluid (SF) contribute to OA progression. Intra-articular (IA) injections of multipotent mesenchymal stromal cells (MSCs) are employed to treat OA in both humans and animals. MSCs secrete paracrine pro-inflammatory and anabolic signaling molecules that promote tissue repair. The objective of this study was to investigate the effects of OASF on the gene expression of paracrine signaling molecules by MSCs. METHODS: The effects of Lipopolysaccharide (LPS) and interleukin (IL)-1ß as well as both normal (N) and osteoarthritis (OA) SF stimulations on the expression of paracrine pro-inflammatory (tumor necrosis factor (TNF)-α, IL-1ß, IL-8), modulatory (IL-6) and anabolic (vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ß1 and insulin-like growth factor (IGF)-1) signaling molecules by equine bone marrow multipotent mesenchymal stromal cells (eBM-MSCs) was investigated employing reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: In contrast with NSF, OASF significantly up-regulated the expression of VEGF in eBM-MSCs. Both NSF and OASF significantly down-regulated the expression of IL-1ß. LPS and IL-1ß significantly increased the expression of pro-inflammatory cytokines (TNF-α, IL-8 and IL-6; and IL-1ß and IL-8 respectively). DISCUSSION: We conclude that the transcription of paracrine signaling molecules in eBM-MSCs is modulated by SF. Furthermore, OA alters the properties of SF and the response of eBM-MSCs. Finally, the effects of LPS or IL-1ß stimulation are distinct to that observed following stimulations with OASF.

Ovariectomy stimulates hepatic fat and cholesterol accumulation in high-fat diet-fed rats.

This study was designed to determine how estrogens withdrawal during a high-fat (HF) diet regimen affects liver triacylglycerol (TAG) and cholesterol accumulation. Female Sprague-Dawley rats were submitted to a HF (42% energy as fat) or a standard (SD) diet for 6 weeks before being either ovariectomized (Ovx) or sham operated (Sham). Thereafter, Ovx and Sham rats were kept on the same diet for another 6 weeks leading to euthanasia. Liver TAG content was increased (p<0.01) in Ovx rats but not by the HF diet alone. However, the combination of HF diet and Ovx resulted in a greater liver TAG accumulation (p<0.06) than that observed in Ovx-SD/SD. Measurement of molecular markers of liver lipid metabolism revealed an increase in transcripts of markers of lipid oxidation (CPT-1 and PGC1; p<0.05) in rats fed the HF diet. This increase was, however, substantially less if HF fed rats were Ovx. Liver total cholesterol levels were increased (p<0.01) only in the Ovx-HF/HF rats while plasma cholesterol levels were increased in Ovx-SD/SD and in SHAM-HF/HF and Ovx-HF/HF rats. Transcripts of molecular markers of cholesterol metabolism suggest that biliary acids synthesis (CYP7a-1) was reduced in Ovx-SD/SD and Sham-HF/HF rats and even more so in Ovx-HF/HF rats. It is concluded that the effects of a HF diet on liver TAG accumulation are especially observed in Ovx rats possibly through a reduction in hepatic lipid oxidation. The combination of Ovx and HF diet also acts synergistically to favor liver cholesterol accumulation.

Effect of exercise training and isoflavones on hepatic steatosis in overweight postmenopausal women.

OBJECTIVES: Postmenopausal women are particularly inclined to an increased risk of developing non-alcoholic hepatic steatosis. The purpose of this study was to investigate whether adding isoflavone supplementation to exercise training could reduce the risk. METHODS: In a 6-month, double-blind, randomized, controlled trial, 54 healthy overweight-to-obese (body mass index 28-40 kg/m2) postmenopausal women were randomly assigned to one of the following groups: (1) exercise and isoflavones (Ex-Iso; n = 26), (2) exercise and placebo (Ex-Pla; n = 28). Exercise training consisted of three weekly sessions of mixed training. We examined the plasma level of specific hepatic enzymes (alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, and alkaline phosphatase) as a reflection of fatty liver along with the calculation of the fatty liver index. All measures were obtained at baseline and after the 6-month intervention. RESULTS: Following the intervention, a lower fatty liver index (p <0.01; 29% in Ex-Iso, 18% in Ex-Pla) and plasma γ-glutamyltransferase (p <0.01; 22% in Ex-Iso, 16% in Ex-Pla) were observed in both groups, with a higher reduction in the Ex-Iso group. On the other hand, for all other hepatic enzymes, there was no change. CONCLUSIONS: Our results show that exercise training appears to bring favorable changes in the plasma level of hepatic enzymes, possibly due to the lowering of liver fat content. While postmenopausal women can benefit from this intervention to decrease the risk of developing non-alcoholic hepatic steatosis, it seems that the addition of isoflavones to exercise training provides some additional effects to those provided by exercise alone.

Liver fat accumulation may be dissociated from adiposity gain in ovariectomized rats.

OBJECTIVE: The purpose of the present study was to establish a model of rats prone and resistant to intra-abdominal fat accumulation in response to ovariectomy (Ovx-P and Ovx-R) and to determine its relationship with molecular biomarkers. DESIGN: Two experiments were conducted in which female rats were either sham-operated (Sham) or ovariectomized (Ovx). In the first experiment, ovariectomized rats were stratified into three tertiles based on intra-abdominal adipose tissue mass. To strengthen the Ovx-P/Ovx-R model, we conducted a second experiment in which the numbers of rats in each group were extended and in which different molecular markers were measured. At the end of a 6-8-week period, ovariectomized rats that displayed the lower abdominal fat accumulation (lower tertile) were labelled as Ovx-R and those in the upper tertile as Ovx-P. RESULTS: Ovx-R rats displayed similar abdominal fat gain to Sham rats whereas Ovx-P rats depicted abdominal fat mass twice as high as that of Sham and Ovx-R rats. Despite the difference in abdominal adiposity, liver fat content was ~50% higher (p < 0.01) in both Ovx-R and Ovx-P rats compared to Sham rats. In addition, both Ovx-R and Ovx-P rats depicted higher HOMA-IR scores (p < 0.05) and lower (p < 0.01) hepatic gene expression of leptin receptor-b and -e, microsomal transfer protein (MTP), and diacylglycerol acyltransferase-2 (DGAT-2) compared to Sham rats. CONCLUSION: The present findings indicate that estrogen withdrawal-induced hepatic steatosis and associated insulin resistance may be dissociated from abdominal fat accumulation and suggest that a decrease in leptin action through a down-regulation of leptin receptors and a decrease in very low density lipoprotein production through a down-regulation of MTP and DGAT-2 may be factors responsible for this observation in the absence of peripheral fat gain.

CCMG guidelines: prenatal and postnatal diagnostic testing for uniparental disomy.

The aim of this statement is to provide clinicians, cytogeneticists and molecular geneticists of the Canadian College of Medical Geneticists (CCMG) a comprehensive review of the role of UPD in constitutional genetic diagnosis and to provide a guideline as to when investigation for UPD is recommended. Members of the CCMG Cytogenetics, Molecular Genetics, Clinical Practice, and Prenatal Diagnosis committees reviewed the relevant literature on uniparental disomy (UPD) in constitutional genetic diagnosis (May 2010). Guidelines were developed for UPD testing in Canada. The guidelines were circulated for comment to the CCMG members at large and following appropriate modification, approved by the CCMG Board of Directors (July 2010).

Hepatic VLDL-TG production and MTP gene expression are decreased in ovariectomized rats: effects of exercise training.

The present study was designed to investigate the effects of estrogen withdrawal and exercise training on hepatic very low density lipoprotein-triglyceride (VLDL-TG) production and on expression of genes involved in hepatic VLDL synthesis in response to lipid infusion. Female Sprague-Dawley rats underwent ovariectomy (Ovx), sham surgery (Sham), and Ovx with 17ß-estradiol supplementation (OvxE2) before being subdivided into sedentary (Sed) and trained (Tr) groups for 8 weeks. Exercise training consisted of continuous running on a rodent treadmill 5 times/wk. At the end of the 8-week period, all rats in the fasted state were intravenously infused with a 20% solution of Intralipid for 3-h followed by an injection of Triton WR-1339 to block lipoprotein lipase activity. Plasma TG accumulation was subsequently measured during 90 min to estimate VLDL-TG production. An additional control group consisting of Sham-Sed rats was infused with saline (0.9% NaCl). Estrogen withdrawal resulted in higher (p<0.01) liver fat accumulation concomitantly with lower (p<0.01) VLDL-TG production and lower mRNA and protein content of hepatic microsomal triglyceride transfer protein (MTP). All of these effects in Ovx rats were corrected with estrogen supplementation. Training in Ovx rats reduced (p<0.01) liver fat accumulation and further reduced (p<0.01) hepatic VLDL-TG production along with gene expression of MTP and diacylglycerol acyltransferase-2 (DGAT-2). It is concluded that VLDL-TG synthesis and/or secretion is decreased in Ovx rats probably via MTP regulation and that this decrease may constitute one of the factors involved in hepatic fat accumulation. The training effect on reducing VLDL production was independent of the estrogenic status.

Assessing the impact of non-dilating the eye on full-field electroretinogram and standard flash response.

We investigated the possibility of performing electroretinography (ERG) in non-pharmacologically dilated eyes using brighter flash (time-integrated) luminance. Photopic (N = 26; background 25.5 cd·m(-2), white LED flashes) and scotopic ERG (N = 23, green LED flashes) luminance response functions were obtained simultaneously in a dilated (DE) and non-dilated eye (NDE). In the NDE, photopic V (max) b-wave amplitude was reduced by 14% (P < 0.0001), implicit time prolonged (P < 0.0001), and retinal sensitivity (log K) decreased by 0.38 log units (P < 0.0001) with no effect on a-wave. Using a xenon strobe light (N = 6) to increase flash luminance, V (max) remained lower by about 12% in the NDE (P = 0.02). V (max) with LED and xenon was achieved at 3.9 ± 1.0 cd·s·m(-2) and 3.3 ± 0.81 cd·s·m(-2) in the DE and 10.6 ± 1.2 cd·s·m(-2) and 12.3 ± 1.90 cd·s·m(-2) in the NDE, that is an increase of 0.43 and 0.57 log unit (P < 0.0001), respectively. Increasing background luminance by 0.50 log units (80 cd·m(-2), N = 4) resulted in implicit time normalization but not V (max) amplitude. Rod V (max) was decreased by 7% in NDE (P < 0.05) and sensitivity reduced by 0.40 log units (P < 0.0001), but our data suggest that the luminance may have not been sufficient to reach V (max) in all participants in the NDE and that the sensitivity change may have been due to an inadequate inter-stimulus interval. For the photopic ERG, increasing flash luminance is not sufficient to compensate for the smaller pupil size, whereas for the scotopic ERG, more data are needed to establish proper inter-stimulus interval to perform recordings in a non-pharmacologically dilated.

Circadian variation in the electroretinogram and the presence of central melatonin.

The light/dark cycle is the most important circadian clock synchronizer for mammals and humans. Circadian rhythms of dopamine and melatonin production in the retina have been reported to follow the light and dark cycle, but their impact on rod and cone functioning is not clear. The purpose of this study was to assess diurnal variations (morning vs. evening) in retinal function as measured with the photopic and scotopic electroretinogram (ERG). We also tried to correlate our results with the presence or absence of melatonin secretion in the saliva. Photopic and scotopic luminance-response functions were obtained in 29 participants at 11:00 (when melatonin should not be present) and 23:00 (when melatonin should be present). From the luminance-response function, Vmax, log K and slope parameters were derived. In scotopic condition, a significant increase of 6% in Vmax amplitude was observed in evening compared to morning (P = 0.03) along with a prolonged b-wave implicit time of 8% (P = 0.01) and an increase in rod sensitivity in evening compared to morning (P = 0.02). As expected, these changes in rod function were accompanied by a higher concentration of melatonin in saliva samples in the evening (P = 0.01). In photopic condition, only a prolonged a-wave implicit time of 5% was observed in evening when compared to morning (P = 0.02). Our findings suggest that the rod system is favored during night time, when circulating melatonin is present. Although statistically significant changes were observed, the day vs. night difference observed in the present study appears to be too small to impact significantly upon clinical assessment of retinal function.

Comparison between several insulin sensitivity indices and metabolic risk factors in overweight and obese postmenopausal women: a MONET study.

BACKGROUND AND AIMS: The purpose of this study was to compare the relationship of several insulin sensitivity indices with cardiometabolic risk factors in overweight and obese postmenopausal women. METHODS AND RESULTS: This was a cross-sectional study involving 137 overweight and obese postmenopausal women (age: 57.7+/-4.8 yrs; body mass index: 32.4+/-4.6 kg/m(2); body fat: 38.6+/-9.2 kg). Insulin sensitivity was determined by the euglycaemic-hyperinsulinemic (EH) clamp technique as well as by oral glucose tolerance test (OGTT) derived indices (Stumvoll, Matsuda and SI(is)) and fasting surrogate indices (HOMA, QUICKI). Cardiometabolic risk factors included: body composition and visceral fat that were measured using dual energy X-ray absorptiometry and computed tomography, respectively. Peak oxygen consumption, lower body muscle strength (using weight training equipment), physical activity energy expenditure (doubly labeled water), plasma lipids and C-reactive protein were also measured. Correlations of insulin sensitivity indices with metabolic risk factors showed some similarities, however, a wide range of variations were also observed. Furthermore, our results showed that visceral fat was the primary predictor for surrogate and OGTT indices, explaining 15-28% of the variance and the triglycerides/HDL-C ratio was the primary predictor for the EH clamp indices, explaining 15-17% of the variance. CONCLUSION: The present study indicates that the different methods of measuring and/or expressing insulin sensitivity display variations for associations with cardiometabolic risk factors. Therefore, interpretations of relationships between insulin sensitivity indices and cardiometabolic risk factors should take into account the method used to estimate and express insulin sensitivity.