Hypoabsorptive surgeries cause limb-dependent changes in the gut endocannabinoidome and microbiome in association with beneficial metabolic effects.

OBJECTIVE: To determine whether the metabolic benefits of hypoabsorptive surgeries are associated with changes in the gut endocannabinoidome (eCBome) and microbiome. METHODS: Biliopancreatic diversion with duodenal switch (BPD-DS) and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) were performed in diet-induced obese (DIO) male Wistar rats. Control groups fed a high-fat diet (HF) included sham-operated (SHAM HF) and SHAM HF-pair-weighed to BPD-DS (SHAM HF-PW). Body weight, fat mass gain, fecal energy loss, HOMA-IR, and gut-secreted hormone levels were measured. The levels of eCBome lipid mediators and prostaglandins were quantified in different intestinal segments by LC-MS/MS, while expression levels of genes encoding eCBome metabolic enzymes and receptors were determined by RT-qPCR. Metataxonomic (16S rRNA) analysis was performed on residual distal jejunum, proximal jejunum, and ileum contents. RESULTS: BPD-DS and SADI-S reduced fat gain and HOMA-IR, while increasing glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) levels in HF-fed rats. Both surgeries induced potent limb-dependent alterations in eCBome mediators and in gut microbial ecology. In response to BPD-DS and SADI-S, changes in gut microbiota were significantly correlated with those of eCBome mediators. Principal component analyses revealed connections between PYY, N-oleoylethanolamine (OEA), N-linoleoylethanolamine (LEA), Clostridium, and Enterobacteriaceae_g_2 in the proximal and distal jejunum and in the ileum. CONCLUSIONS: BPD-DS and SADI-S caused limb-dependent changes in the gut eCBome and microbiome. The present results indicate that these variables could significantly influence the beneficial metabolic outcome of hypoabsorptive bariatric surgeries.

Consistent gut bacterial and short-chain fatty acid signatures in hypoabsorptive bariatric surgeries correlate with metabolic benefits in rats.

OBJECTIVE: The study aimed at comparing how changes in the gut microbiota are associated to the beneficial effects of the most clinically efficient hypoabsorptive bariatric procedures, namely Roux-en-Y gastric bypass (RYGB), biliopancreatic diversion with duodenal switch (BPD-DS) and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S). METHODS: Diet-induced obese (DIO) male Wistar rats were divided into seven groups. In addition to the groups subjected to RYGB, BPD-DS and SADI-S, the following four control groups were included: SHAM-operated rats fed a high-fat diet (SHAM HF), SHAM fed a low-fat diet (SHAM LF), SHAM HF-pair-weighed to BPD-DS (SHAM HF-PW) and sleeve-gastrectomy (SG) rats. Body weight, food intake, glucose tolerance, insulin sensitivity/resistance, and L-cell secretion were assessed. The gut microbiota (16 S ribosomal RNA gene sequencing) as well as the fecal and cæcal contents of short-chain fatty acids (SCFAs) were also analyzed prior to, and after the surgeries. RESULTS: The present study demonstrates the beneficial effect of RYGB, BPD-DS and SADI-S on fat mass gain and glucose metabolism in DIO rats. These benefits were proportional to the effect of the surgeries on food digestibility (BPD-DS > SADI-S > RYGB). Notably, hypoabsorptive surgeries led to consonant microbial signatures characterized by decreased abundance of the Ruminococcaceae (Oscillospira and Ruminococcus), Oscillospiraceae (Oscillibacter) and Christensenellaceae, and increased abundance of the Clostridiaceae (Clostridium), Sutterellaceae (Sutterella) and Enterobacteriaceae. The gut bacteria following hypoabsorptive surgeries were associated with higher fecal levels of propionate, butyrate, isobutyrate and isovalerate. Increases in the fecal SCFAs were in turn positively and strongly correlated with the levels of peptide tyrosine-tyrosine (PYY) and with the beneficial effects of the surgery. CONCLUSION: The present study emphasizes the consistency with which the three major hypoabsorptive bariatric procedures RYGB, BPD-DS and SADI-S create a gut microbial environment capable of producing a SCFA profile favorable to the secretion of PYY and to beneficial metabolic effects.

Vegetation community composition in wetlands created following oil sand mining in Alberta, Canada.

Reclaiming wetlands following open pit mining for industrial oil sand extraction is challenging due to the physical and chemical conditions of the post-mined landscape. The aim of our study was to examine and compare the influence of oil sands process water (OSPW) and material (fine fluid tails or FFT) on the plant community composition of created wetlands. Compared to created-unamended and natural wetlands, the created wetlands amended with OSPW and/or FFT (created-tailings wetlands) had significantly higher water salinity, conductivity, dissolved oxygen concentration and lower oxidative-reductive potential. Water chemistry parameters of created-unamended did not differ significantly from those of natural wetlands. The sediment of created wetlands had significantly less moisture, total nitrogen, and organic content than the natural wetlands. The application of OSPW/FFT in created wetlands will likely lead to initial vegetation composition atypical of natural regional wetlands. For the objective of reclaiming vegetation composition to the status of natural regional wetlands, unamended wetlands were the best reclamation option, based on the physical and chemical parameters measured. Despite being the favored reclamation option, created-unamended wetlands' physical and chemical characteristics remain atypical of natural wetlands. Most significantly, the basin morphometry of created wetlands was significantly different from that of naturally-formed wetlands in the region, and this appears to partly explain difference in vegetation composition. We also demonstrate that species richness alone is not a useful measure in wetland monitoring. Instead, plant community composition is a better indicator of wetland conditions.

Performance of wetland forbs transplanted into marshes amended with oil sands processed water.

Companies mining oil sands in Alberta (Canada) face the challenge of reclaiming wetlands under water use restrictions. Wetland reclamation after mining will generate marshes characterized by elevated salinity and residual hydrocarbons. Oil sands wetlands are also impoverished in forbs, suggesting that their establishment may be constrained by water chemistry. We transplanted skullcap, mint, and smartweed plants into experimental trenches that simulated two possible reclamation scenarios: wetlands amended with on-site freshwater or with oil sands processed water (OSPW). The main scientific question was is OSPW a suitable water amendment as freshwater for reclaiming wetland forb habitat? As a surrogate of plant health, we studied plant ecophysiology (gas exchange, leaf fluorescence), leaf chemistry, and plant growth. Results showed that there were no differences in skullcap mineral contents under either treatment; however, mint and smartweed plants subjected to OSPW had a significantly higher Na content than those under freshwater. Smartweed dark-adapted leaf fluorescence showed a reduced photochemistry in OSPW relative to plants in freshwater. Mint leaves exhibited lower stomatal conductance in OSPW than in freshwater, a condition that negatively affected transpiration and carboxylation. Skullcap plants grown in OSPW had lower net CO2 assimilation rates than those in freshwater but did not show any other ecophysiological difference between treatments. Mint plants experienced growth reductions (i.e., shoot height) in OSPW. Our results show, for the first time in the literature, that plants photosynthetic capacity was negatively affected by OSPW. Conditions in OSPW proved to be suitable for establishment as transplanted forbs showed 100 % survival after the first growing season. However, impaired physiological functions in plants subjected to OSPW indicated that OSPW amendment created a less hospitable habitat for wetland forbs than freshwater.

Do peat amendments to oil sands wet sediments affect Carex aquatilis biomass for reclamation success?

The oil sands industries of Alberta (Canada) have reclamation objectives to return the mined landscape to equivalent pre-disturbance land capability. Industrial operators are charged with reclaiming a vast landscape of newly exposed sediments on saline-sodic marine-shales sediments. Incorporated in these sediments are by-products resulting from bitumen extraction (consolidated tailings (CT), tailings-sand (TS), and oil sands processed water (OSPW)). A sedge community dominated by Carex aquatilis was identified as a desirable and representative late-succession community for wet-meadow zones of oil sands-created marshes. However, the physical and chemical conditions, including high salinity and low nutrient content of CT and TS sediments suppress plant growth and performance. We experimentally tested the response of C. aquatilis to amendments with peat-mineral-mix (PM) on oil sand sediments (CT and TS). In a two factorial design experiment, we also tested the effects of OSPW on C. aquatilis. We assessed survival, below- and aboveground biomass, and physiology (chlorophyll a fluorescence). We demonstrated that PM amendments to oil sands sediments significantly increased C. aquatilis survival as well as below and aboveground biomass. The use of OSPW significantly reduced C. aquatilis belowground biomass and affected its physiological performance. Due to its tolerance and performance, we verified that C. aquatilis was a good candidate for use in reclaiming the wet-meadow zones of oil sands-created marshes. Ultimately, amending CT and TS with PM expedited the reclamation of the wetland to a C. aquatilis-community which was similar in gross structure to undisturbed wetlands of the region.

Duration of isolation and contagiousness in coronavirus disease 2019 (COVID-19) patients receiving tocilizumab and dexamethasone: A case series.

We describe 10 patients with severe coronavirus disease 2019 (COVID-19) who received tocilizumab and dexamethasone. We correlated isolation duration with cycle thresholds (Ct) values of nucleic acid amplification tests, clinical state and viral cultures. Isolation duration exceeded 21 days for 7 patients due to positive viral cultures or Ct values <30.

A central thermogenic-like mechanism in feeding regulation: an interplay between arcuate nucleus T3 and UCP2.

The active thyroid hormone, triiodothyronine (T3), regulates mitochondrial uncoupling protein activity and related thermogenesis in peripheral tissues. Type 2 deiodinase (DII), an enzyme that catalyzes active thyroid hormone production, and mitochondrial uncoupling protein 2 (UCP2) are also present in the hypothalamic arcuate nucleus, where their interaction and physiological significance have not been explored. Here, we report that DII-producing glial cells are in direct apposition to neurons coexpressing neuropeptide Y (NPY), agouti-related protein (AgRP), and UCP2. Fasting increased DII activity and local thyroid hormone production in the arcuate nucleus in parallel with increased GDP-regulated UCP2-dependent mitochondrial uncoupling. Fasting-induced T3-mediated UCP2 activation resulted in mitochondrial proliferation in NPY/AgRP neurons, an event that was critical for increased excitability of these orexigenic neurons and consequent rebound feeding following food deprivation. These results reveal a physiological role for a thyroid-hormone-regulated mitochondrial uncoupling in hypothalamic neuronal networks.

Acute injection of ASP in the third ventricle inhibits food intake and locomotor activity in rats.

Acylation-stimulating protein (ASP; also known as C3adesArg) stimulates triglyceride synthesis and glucose transport via interaction with its receptor C5L2, which is expressed peripherally (adipose tissue, muscle) and centrally. Previous studies have shown that ASP-deficient mice (C3KO) and C5L2-deficient mice (C5L2KO) are hyperphagic (59 to 229% increase, P < 0.0001), which is counterbalanced by increased energy expenditure measured as oxygen consumption (Vo(2)) and a lower RQ. The aim of the present study was to evaluate ASP's effect on food intake, energy expenditure, and neuropeptide expression. Male rats were surgically implanted with intracerebroventricular (icv) cannulas directed toward the third ventricle. After a 5-h fast, rats were injected, and food intake was assessed at 0.5, 1, 2, 4, 16, 24, and 48 h, with a 5- to 7-day washout period between each injection. Acute icv injections of ASP (0.3-1,065 pmol) had a time-dependent effect on decreasing food intake by 20 to 57% (P < 0.05). Decreases were detected by 30 min (maximum 57%, P < 0.01) and at the highest dose effects extended to 48 h (19%, P < 0.05, 24- to 48-h period). Daily body weight gain was decreased by 131% over the first 24 h and 29% over the second 24 h (P < 0.05). A conditioned taste aversion test indicated that there was no malaise. Furthermore, acute ASP injection affected energy substrate usage, demonstrated by decreased Vo(2) and RQ (P < 0.05; implicating greater fatty acid usage), with a 49% decrease in total activity over 24 h (P < 0.05). ASP administration also increased anorexic neuropeptide POMC expression (44%) in the arcuate nucleus, with no change in NPY. Altogether ASP may have central in addition to peripheral effects.

A Collaborative Model to Implement Flexible, Accessible and Efficient Oncogenetic Services for Hereditary Breast and Ovarian Cancer: The C-MOnGene Study.

Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a collaborative oncogenetic model was recently developed and implemented at the CHU de Québec-Université Laval; Quebec; Canada. Here, we present the protocol of the C-MOnGene (Collaborative Model in OncoGenetics) study, funded to examine the context in which the model was implemented and document the lessons that can be learned to optimize the delivery of oncogenetic services. Within three years of implementation, the model allowed researchers to double the annual number of patients seen in genetic counseling. The average number of days between genetic counseling and disclosure of test results significantly decreased. Group counseling sessions improved participants' understanding of breast cancer risk and increased knowledge of breast cancer and genetics and a large majority of them reported to be overwhelmingly satisfied with the process. These quality and performance indicators suggest this oncogenetic model offers a flexible, patient-centered and efficient genetic counseling and testing for HBOC. By identifying the critical facilitating factors and barriers, our study will provide an evidence base for organizations interested in transitioning to an oncogenetic model integrated into oncology care; including teams that are not specialized but are trained in genetics.

Nephrotic syndrome following four-component meningococcal B vaccination: Epidemiologic investigation of a surveillance signal.

BACKGROUND: In May 2014, a mass vaccination campaign with four-component meningococcal serogroup B (4CMenB) vaccine was launched in a localized region of Quebec, Canada experiencing high invasive meningococcal B disease endemicity. Active post-marketing surveillance identified several cases of nephrotic syndrome (NS) among ∼49,000 vaccinated individuals aged 2 months to 20 years. We report the epidemiologic investigation of this potential vaccine safety signal. METHODS: Active vaccine safety surveillance was conducted electronically, with participants completing an online questionnaire prompted at 7 days after each dose and 6 months following the last dose. Additional NS cases were sought from provincial hospitalization and emergency room databases. RESULTS: In the year following the first dose of 4CMenB vaccination, four confirmed NS cases (three hospitalized) were identified among vaccinated children 2-5-years-old with onset several months post-vaccination. None had renal biopsy but given their age, and positive response to steroids, idiopathic NS was presumptively diagnosed. Among vaccinated children 1-9-years-old, the NS incidence in the year post-vaccination was 17.7 per 100,000 (1 per 5650 vaccinees) with an NS hospitalization rate (i.e. excluding the outpatient case) that was 3.6-fold higher (95%CI = 0.7-11.8; p = 0.12) than the rest of the province for the same period, and 8.3-fold greater (95%CI = 1.1-62.0; p = 0.039) than during the eight years preceding the immunization campaign in the affected region. CONCLUSION: Active safety surveillance identified an unexpected increase in NS incidence following 4CMenB vaccination. Further epidemiological investigation identified four vaccinated cases in total over a 12 month period of follow up. The greater risk in vaccinees had wide confidence intervals with he lower limit including or just above the nul value, an observation with no or marginal statistical significance. The temporal association with vaccination may be explained by other causes and/or chance clustering of a rare event unrelated to vaccination. To confirm or refute a potential link to vaccination, surveillance in other jurisdictions administering 4CMenB to children 1-9-years-old is needed.

Alterations of Gut Microbiota After Biliopancreatic Diversion with Duodenal Switch in Wistar Rats.

BACKGROUND: The biliopancreatic diversion with duodenal switch (BPD/DS) represents the most effective surgical procedure for the treatment of severe obesity and associated type 2 diabetes. The mechanisms whereby BPD/DS exerts its positive metabolic effects have however yet to be fully delineated. The objective of this study was to distinguish the effects of the two components of BPD/DS, namely the sleeve gastrectomy (SG) and the DS derivation, on gut microbiota, and to appraise whether changes in microbial composition are linked with surgery-induced metabolic benefits. METHODS: BPD/DS, DS, and SG were performed in Wistar rats fed a standard chow diet. Body weight and energy intake were measured daily during 8 weeks post-surgery, at which time glucagon-like peptide 1 (GLP-1), peptide tyrosine tyrosine (PYY), insulin, and glucose were measured. Fecal samples were collected prior to surgery and at 2 and 8 weeks post-surgery. Intraluminal contents of the alimentary, biliopancreatic, and common limbs (resulting from BPD/DS) were taken from the proximal portion of each limb. Fecal and small intestinal limb samples were analyzed by 16S ribosomal RNA gene sequencing. RESULTS: BPD/DS and DS led to lower digestible energy intake (P = 0.0007 and P = 0.0002, respectively), reduced weight gain (P < 0.0001) and body fat mass (P < 0.0001), improved glucose metabolism, and increased GLP-1 (P = 0.0437, SHAM versus DS) and PYY levels (P < 0.0001). These effects were associated with major alterations of both the fecal and small intestinal microbiota, as revealed by significant decrease in bacterial richness and diversity at 2 (P < 0.0001, Chao1 index; P < 0.0001, Shannon index) and 8 weeks (P = 0.0159, SHAM versus DS, Chao1 index; P = 0.0219, SHAM versus DS, P = 0.0472, SHAM versus BPD/DS, Shannon index) post-surgery in BPD/DS and DS, and increased proportions of Bifidobacteriales (a 60% increase in both groups) but reduced Clostridiales (a 50% decrease and a 90% decrease respectively), which were mostly accounted at the genus level by higher relative abundance of Bifidobacterium in both the fecal and intestinal limb samples, as well as reduced abundance of Peptostreptococcaceae and Clostridiaceae in the small intestine. Those effects were not seen in SG rats. CONCLUSION: The metabolic benefits following BPD/DS are seemingly due to the DS component of the surgery. Furthermore, BPD/DS causes marked alterations in fecal and small intestinal microbiota resulting in reduced bacterial diversity and richness. Our data further suggest that increased abundance of Bifidobacterium and reduced level of two Clostridiales species in the gut microbiota might contribute to the positive metabolic outcomes of BPD/DS.

Loss of UCP2 impairs cold-induced non-shivering thermogenesis by promoting a shift toward glucose utilization in brown adipose tissue.

Uncoupling protein 2 (UCP2) was discovered in 1997 and classified as an uncoupling protein largely based on its homology of sequence with UCP1. Since its discovery, the uncoupling function of UCP2 has been questioned and there is yet no consensus on the true function of this protein. UCP2 was first proposed to be a reactive oxygen species (ROS) regulator and an insulin secretion modulator. More recently, it was demonstrated as a regulator of the mitochondrial fatty acid oxidation, which prompted us to investigate its role in the metabolic and thermogenic functions of brown adipose tissue. We first investigated the role of UCP2 in affecting the glycolysis capacity by evaluating the extracellular flux in cells lacking UCP2. We thereafter investigated the role of UCP2 in BAT thermogenesis with positron emission tomography using the metabolic tracers [11C]-acetate (metabolic activity), 2-deoxy-2-[18F]-fluoro-d-glucose (18FDG, glucose uptake) and 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid [18FTHA, non-esterified fatty acid (NEFA) uptake]. The effect of the ß3-adrenoreceptor (ADRB3) selective agonist, CL316,243 (CL), on BAT 18FDG and 18FTHA uptakes, as well as 11C-acetate activity was assessed in UCP2KO and UCP2WT mice exposed at room temperature or adapted to cold. Our results suggest that despite the fact that UCP2 does not have the uncoupling potential of UCP1, its contribution to BAT thermogenesis and to the adaptation to cold exposure appears crucial. Notably, we found that the absence of UCP2 promoted a shift toward glucose utilization and increased glycolytic capacity in BAT, which conferred a better oxidative/thermogenic activity/capacity following an acute adrenergic stimulation. However, following cold exposure, a context of high-energy demand, BAT of UCP2KO mice failed to adapt and thermogenesis was impaired. We conclude that UCP2 regulates BAT thermogenesis by favouring the utilization of NEFA, a process required for the adaptation to cold.

Involvement of the Acyl-CoA binding domain containing 7 in the control of food intake and energy expenditure in mice.

Acyl-CoA binding domain-containing 7 (Acbd7) is a paralog gene of the diazepam-binding inhibitor/Acyl-CoA binding protein in which single nucleotide polymorphism has recently been associated with obesity in humans. In this report, we provide converging evidence indicating that a splice variant isoform of the Acbd7 mRNA is expressed and translated by some POMC and GABAergic-neurons in the hypothalamic arcuate nucleus (ARC). We have demonstrated that the ARC ACBD7 isoform was produced and processed into a bioactive peptide referred to as nonadecaneuropeptide (NDN) in response to catabolic signals. We have characterized NDN as a potent anorexigenic signal acting through an uncharacterized endozepine G protein-coupled receptor and subsequently via the melanocortin system. Our results suggest that ACBD7-producing neurons participate in the hypothalamic leptin signalling pathway. Taken together, these data suggest that ACBD7-producing neurons are involved in the hypothalamic control exerted on food intake and energy expenditure by the leptin-melanocortin pathway.

Malabsorption plays a major role in the effects of the biliopancreatic diversion with duodenal switch on energy metabolism in rats.

BACKGROUND: The mechanisms underlying the metabolic benefits of the biliopancreatic diversion with duodenal switch (BPD/DS) have not been clarified. The objective of this study was to investigate the metabolic roles of sleeve gastrectomy (SG) and duodenal switch (DS) as main surgical components of BPD/DS. METHODS: BPD/DS, SG, and DS surgeries were performed on chow-fed nonobese Wistar rats. Weight and energy intake were recorded during 8 postsurgical weeks. Glucagon-like peptide 1 (GLP-1), peptide tyrosine-tyrosine (PYY), glucose-dependent insulinotropic peptide, and ghrelin were measured pre- and postprandially at weeks 3 and 8, after surgery. Body composition, muscle, liver, and adipose tissue weights were measured. Gut morphometry and the presence and distribution of GLP-1 and PYY (L-cells) in the gut were determined using histochemical techniques. RESULTS: Compared with sham, BPD/DS and DS led to significant reductions in weight gain, percentage of fat, and adipose tissue weight. These effects were accompanied by a reduction in digestible energy intake associated with fecal energy loss due to DS. BPD/DS and DS produced intestinal hypertrophy, as well as higher plasma GLP-1 and PYY in both fasted and refed states. It is noteworthy that none of those alterations were observed after SG, which nonetheless led to transient postoperative reduction in gross energy intake and weight. Similar to BPD/DS, SG alone produced a reduced meal size and an enhanced postprandial depression of plasma ghrelin. CONCLUSION: BPD/DS results in metabolic benefits, which appear largely caused by food malabsorption due to DS. The elevation of anorectic GLP-1 and PYY are additional consequences of DS, which, together with malabsorption, could promote the metabolic benefits of BPD/DS.

Metabolic changes induced by the biliopancreatic diversion in diet-induced obesity in male rats: the contributions of sleeve gastrectomy and duodenal switch.

The mechanisms underlying the body weight and fat loss after the biliopancreatic diversion with duodenal switch (BPD/DS) remain to be fully delineated. The aim of this study was to examine the contributions of the two main components of BPD/DS, namely sleeve gastrectomy (SG) and duodenal switch (DS), on energy balance changes in rats rendered obese with a high-fat (HF) diet. Three different bariatric procedures (BPD/DS, SG, and DS) and three sham surgeries were performed in male Wistar rats. Sham-operated animals fed HF were either fed ad libitum (Sham HF) or pair weighed (Sham HF PW) by food restriction to the BPD/DS rats. A group of sham-operated rats was kept on standard chow and served as normal diet control (Sham Chow). All three bariatric surgeries resulted in a transient reduction in food intake. SG per se induced a delay in body weight gain. BPD/DS and DS led to a noticeable gut malabsorption and a reduction in body weight and fat gains along with significant elevations in plasma levels of glucagon-like peptide-1(7-36) and peptide YY. BPD/DS and DS elevated energy expenditure above that of Sham HF PW during the dark phase. However, they reduced the volume, oxidative metabolism, and expression of thermogenic genes in interscapular brown adipose tissue. Altogether the results of this study suggest that the DS component of the BPD/DS, which led to a reduction in digestible energy intake while sustaining energy expenditure, plays a key role in the improvement in the metabolic profile led by BPD/DS in rats fed a HF diet.

The PVH as a site of CB1-mediated stimulation of thermogenesis by MC4R agonism in male rats.

The present study was designed to investigate the involvement of the cannabinoid receptor 1 (CB1) in the stimulating effects of the melanocortin-4 receptor (MC4R) agonism on whole-body and brown adipose tissue (BAT) thermogenesis. In a first series of experiments, whole-body and BAT thermogenesis were investigated in rats infused in the third ventricle of the brain with the MC4R agonist melanotan II (MTII) and the CB1 agonist δ9-tetrahydrocannabinol (δ(9)-THC) or the CB1 antagonist AM251. Whole-body thermogenesis was measured by indirect calorimetry and BAT thermogenesis assessed from interscapular BAT (iBAT) temperature. δ(9)-THC blunted the effects of MTII on energy expenditure and iBAT temperature, whereas AM251 tended to potentiate the MTII effects. δ(9)-THC also blocked the stimulating effect of MTII on (14)C-bromopalmitate and (3)H-deoxyglucose uptakes in iBAT. Additionally, δ(9)-THC attenuated the stimulating effect of MTII on the expression of peroxisome proliferator-activated receptor-γ coactivator 1-α (Pgc1α), type II iodothyronine deiodinase (Dio2), carnitine palmitoyltransferase 1B (Cpt1b), and uncoupling protein 1 (Ucp1). In a second series of experiments, we addressed the involvement of the paraventricular hypothalamic nucleus (PVH) in the CB1-mediated effects of MTII on iBAT thermogenesis, which were assessed following the infusion of MTII in the PVH and δ(9)-THC or AM251 in the fourth ventricle of the brain. We demonstrated the ability of δ(9)-THC to blunt MTII-induced iBAT temperature elevation. δ(9)-THC also blocked the PVH effect of MTII on (14)C-bromopalmitate uptake as well as on Pgc1α and Dio2 expression in iBAT. Altogether the results of this study demonstrate the involvement of the PVH in the CB1-mediated stimulating effects of the MC4R agonist MTII on whole-body and BAT thermogenesis.

A randomized, controlled trial of bedside versus conference-room case presentation in a pediatric intensive care unit.

OBJECTIVES: Case presentation and teaching performed at the bedside are declining. Patients' preference between bedside case presentation and conference-room case presentation is divergent in the literature. Residents seem to prefer the conference room. The objective of this study was to ascertain whether there was a difference of satisfaction and comfort between bedside case presentation and conference-room case presentation for the parents of patients hospitalized in the PICU and for the residents in training in the PICU. METHODS: Every child hospitalized in the PICU who had 2 consecutive morning rounds, performed in the presence of the same resident, attending pediatrician, and parent, was eligible for the study. The study began with the first patient's case presentation after admission in the PICU. Randomization was on the first case presentation: bedside or conference room. On the second day, the other type of case presentation was performed. After each round, the parents and the resident filled out a questionnaire. RESULTS: Twenty-seven parents of 22 patients answered both questionnaires, and 21 questionnaires were answered by residents. Parents' satisfaction was significantly higher during bedside case presentation (96 vs 92, answers reported on a 100-mm linear scale), they preferred bedside case presentation (95 vs 15), and they were more comfortable attending bedside teaching (89 vs 19). There was no difference in the residents' satisfaction nor in their comfort giving the actual case presentation. Residents, on the other hand, were significantly more comfortable asking questions (84 vs 69) and being asked questions (85 vs 67) during conference-room case presentation. A total of 81% of the parents wished that the next case presentation would take place at the bedside. CONCLUSIONS: This study demonstrates the feasibility of a clinical case presentation performed at the bedside in the PICU context that seems to satisfy parents without causing too much discomfort to residents. Thus, bedside case presentation could be a very good teaching strategy in university hospitals.

Differences in response to corticotropin-releasing factor after short- and long-term consumption of a high-fat diet.

We previously reported an exaggerated endocrine and weight loss response to stress in rats fed a high-fat (HF) diet for 5 days. Others report blunted stress-induced anxiety in rats made obese on a HF diet. Experiments described here tested whether sensitivity to stress-related peptides was changed in obese and nonobese HF-fed rats. Third ventricle infusion of corticotropin-releasing factor (CRF) in rats made obese on HF diet (40% kcal fat) produced an exaggerated hypophagia, which is thought to be mediated by CRF(2) receptors. Obese rats responded to a lower dose of CRF for a longer time than rats fed a low-fat (LF) diet (12% kcal fat). CRF-induced release of corticosterone, which is thought to be mediated by CRF(1) receptors, was not exaggerated in obese HF-fed rats. In contrast, rats fed HF diet for 5 days showed the same food intake and corticosterone response to CRF as LF-fed rats. CRF mRNA expression in the paraventricular nucleus of the hypothalamus was stimulated by mild stress (ip saline injection and placement in a novel cage) in LF-fed rats but not in rats fed HF diet for 5 days because of a nonsignificant increase in expression in nonstressed HF-fed rats. In addition, nonstressed levels of urocortin (UCN) I mRNA expression in the Edinger-Westphal nucleus were significantly inhibited in HF-fed rats. These data suggest that rats that have become obese on a HF diet show a change in responsiveness to stress peptides, whereas the increased stress response in nonobese HF-fed rats may be associated with changes in basal CRF and UCN I mRNA expression.

Implication of an AGT haplotype in a multigene association study with pregnancy hypertension.

Several association studies of candidate genes for preeclampsia and essential hypertension have led to discordant results, partly because of small sample sizes. Using a large population-based sample of pregnant women, we conducted an association study of 10 polymorphisms in 9 genes and aimed (1) to validate 10 published associations with preeclampsia or essential hypertension, (2) to investigate candidate polymorphisms previously associated with preeclampsia for association with essential hypertension and similarly with polymorphisms previously associated with essential hypertension. From a prospective sample of 3391 nulliparous French Canadian pregnant women, we identified 180 cases of preeclampsia, 203 cases of essential hypertension that were matched with normotensive control subjects (n=310 and 357, respectively). Polymorphisms were genotyped by allele-specific PCR. Among our candidate polymorphisms, the Met allele of Thr174Met of AGT was associated with preeclampsia (P=0.0033). Haplotype analysis revealed that the A-Met-Thr (G1035A-Thr174Met-Met235Thr) haplotype was associated with a 2.1-fold increased risk of preeclampsia (95% CI, 1.4 to 3.4; P=0.0008). In conclusion, we observed a strong association between a specific AGT haplotype and preeclampsia in our population, without replicating previous published associations with either preeclampsia or essential hypertension. Our data support a role for AGT in genetic susceptibility to preeclampsia.