Adverse event comparison between glucagon-like peptide-1 receptor agonists and other antiobesity medications following bariatric surgery.

AIM: To compare the incidence of adverse events (AEs) related to antiobesity medications (AOMs; glucagon-like peptide-1 receptor agonists [GLP-1RAs] vs. non-GLP-1RAs) after bariatric surgery. METHODS: This single-centre retrospective cohort included patients (aged 16-65 years) who had undergone laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy (cohort entry date) and initiated AOMs. Participants were categorized as users of US Food and Drug Administration (FDA)-approved, off-label, or GLP-1RA AOMs if documented as receiving the medication on or after cohort entry date. Non-GLP-1RA AOMs were phentermine, orlistat, topiramate, canagliflozin, dapagliflozin, empagliflozin, naltrexone, bupropion/naltrexone and phentermine/topiramate. GLP-1RA AOMs included: semaglutide, dulaglutide, exenatide and liraglutide. The primary outcome was AE incidence. Logistic regression was used to determine the association of AOM exposure with AEs. RESULTS: We identified 599 patients meeting our inclusion criteria, 83% of whom were female. Their median (interquartile range [IQR]) age was 47.8 (40.9-55.4) years. The median duration of surgery to AOM exposure was 30 months. GLP-1RAs use was not associated with higher odds of AEs: adjusted odds ratio (aOR) 1.1 (95% confidence interval [CI] 0.5-2.6) and aOR 1.1 (95% CI 0.6-2.3) for GLP-1RA versus FDA-approved and off-label AOM use, respectively. AOM initiation ≥12 months after surgery was associated with lower risk of AEs compared to <12 months (aOR 0.01 [95% CI 0.0-0.01]; p < 0.001). CONCLUSION: Our results showed that GLP-1RA AOMs were not associated with an increased risk of AEs compared to non-GLP-1RA AOMs in patients who had previously undergone bariatric surgery. Prospective studies are needed to identify the optimal timeframe for GLP-1RA initiation.

Sex- and operation-dependent effects on 5-year weight loss results of bariatric surgery.

BACKGROUND: Weight loss response after bariatric surgery is highly variable, and several demographic factors are associated with differential responses to surgery. Preclinical studies demonstrate numerous sex-specific responses to bariatric surgery, but whether these responses are also operation dependent is unknown. OBJECTIVE: To examine sex-specific weight loss outcomes up to 5 years after laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). SETTING: Single center, university, United States. METHODS: Retrospective, observational cohort study including RYGB (n = 5057) and vertical SG (n = 2041) patients from a single, academic health center. Percentage total weight loss (TWL) over time was examined with generalized linear mixed models to determine the main and interaction effects of surgery type on weight loss by sex. RESULTS: TWL demonstrated a strong sex-by-procedure interaction, with women having a significant advantage with RYGB compared with SG (adjusted difference at 5 yr: 8.0% [95% CI: 7.5-8.5]; P < .001). Men also experienced greater TWL over time with RYGB or SG, but the difference was less and clinically insignificant (adjusted difference at 5 yr: 2.9% [2.0-3.8]; P < .001; P interaction between sex and procedure type = .0001). Overall, women had greater TWL than men, and RYGB patients had greater TWL than SG patients (adjusted difference at 5 yr: 3.1% [2.4-3.2] and 6.9% [6.5-7.3], respectively; both P < .0001). Patients with diabetes lost less weight compared with those without (adjusted difference at 5 yr: 3.0% [2.7-3.2]; P < .0001). CONCLUSIONS: Weight loss after bariatric surgery is sex- and procedure-dependent. There is an association suggesting a clinically insignificant difference in weight loss between RYGB and SG among male patients at both the 2- and 5-year postsurgery time points.

Do restinga cnemidophorine lizards run on empty along the Brazilian coast? / Os lagartos cnemidophorine de restinga correm no vazio ao longo da costa brasileira?

Abstract The number of individuals with empty stomachs in a population (i.e. the proportion of individuals "running on empty") can be used as a simple index of instantaneous energy balance of some organisms such as lizards and fishes. In this study, we aimed to analyze the proportion of empty stomachs in 16 populations of five cnemidophorine species (Glaucomastix abaetensis, Ameivula ocellifera, Glaucomastix littoralis, Contomastix lacertoides and Ameivula nativo) along approximately 5,000 km the Brazilian coast. A total of 550 individuals had their stomach contents removed and identified in the laboratory. Our results showed that the proportion of individuals "running on empty" varied from 0 to 11.1% among the different populations and species. These proportions are suggestive that the five studied species would be in an overall positive energy balance at the time of the study.

Resumo O número de indivíduos com estômagos vazios em uma população (i.e. a proporção de indivíduos "correndo no vazio") pode ser usado como um índice simples do balanço energético instantâneo de organismos como lagartos e peixes. Este estudo teve como objetivo analisar a proporção de estômagos vazios em 16 populações pertencentes a cinco espécies de cnemidophorines (Glaucomastix abaetensis, Ameivula ocellifera, Glaucomastix littoralis, Contomastix lacertoides e Ameivula nativo) ao longo de cerca de 5,000 km da costa leste do Brasil. Um total de 550 indivíduos tiveram seus conteúdos estomacais removidos e analisados em laboratório. Nossos resultados mostraram que a proporção de indivíduos "correndo no vazio" variou entre 0 a 11.1% entre as diferentes populações e espécies. Essas proporções sugerem que as cinco espécies estudadas estariam em geral em um balanço energético positivo, quando da realização deste estudo.

Bile Acids, Their Receptors, and the Gut Microbiota.

Bile acids (BAs) are a family of hydroxylated steroids secreted by the liver that aid in the breakdown and absorption of dietary fats. BAs also function as nutrient and inflammatory signaling molecules, acting through cognate receptors, to coordinate host metabolism. Commensal bacteria in the gastrointestinal tract are functional modifiers of the BA pool, affecting composition and abundance. Deconjugation of host BAs creates a molecular network that inextricably links gut microtia with their host. In this review we highlight the roles of BAs in mediating this mutualistic relationship with a focus on those events that impact host physiology and metabolism.

Subgingival microbiota of dogs with healthy gingiva or early periodontal disease from different geographical locations.

BACKGROUND: Periodontal disease is the most common oral disease of dogs worldwide and results from a complex interplay between plaque bacteria, the host and environmental factors. Recent studies have enhanced our understanding of the associations between the plaque microbiota and canine periodontal disease. These studies, however, were limited in their geographical reach. Thus associations between the canine oral microbiota and geographical location were investigated by determining the composition of subgingival plaque samples from 587 dogs residing in the United Kingdom (UK), United States of America (USA), China and Thailand using 454-pyrosequencing. RESULTS: After quality filtering 6,944,757 sequence reads were obtained and clustering of these at ≥98% sequence resulted in 280 operational taxonomic units (OTUs) following exclusion of rare OTUs (present at < 0.05% in all four countries). The subgingival plaque from dog populations located in the UK, USA, China and Thailand had a similar composition although the abundance of certain taxa varied significantly among geographical locations. Exploration of the effect of clinical status and age revealed a marked similarity among the bacteria associated with increased age and those associated with gingivitis: Young dogs and those with no gingivitis were dominated by taxa from the phyla Bacteroidetes and Proteobacteria whereas older dogs and those with moderate gingivitis were dominated by members of the Firmicutes. The plaque microbiota of small breed dogs was found to significantly differ to medium and large breeds and was dominated by species belonging to the Firmicutes. CONCLUSIONS: The bacterial associations with health, gingivitis and periodontitis were conserved across dogs from the UK, USA, China and Thailand. These bacterial signatures of periodontal health and disease have potential as biomarkers for disease detection.

Do restinga cnemidophorine lizards run on empty along the Brazilian coast?

The number of individuals with empty stomachs in a population (i.e. the proportion of individuals "running on empty") can be used as a simple index of instantaneous energy balance of some organisms such as lizards and fishes. In this study, we aimed to analyze the proportion of empty stomachs in 16 populations of five cnemidophorine species (Glaucomastix abaetensis, Ameivula ocellifera, Glaucomastix littoralis, Contomastix lacertoides and Ameivula nativo) along approximately 5,000 km the Brazilian coast. A total of 550 individuals had their stomach contents removed and identified in the laboratory. Our results showed that the proportion of individuals "running on empty" varied from 0 to 11.1% among the different populations and species. These proportions are suggestive that the five studied species would be in an overall positive energy balance at the time of the study.

Symmetrically substituted dichlorophenes inhibit N-acyl-phosphatidylethanolamine phospholipase D.

N-Acyl-phosphatidylethanolamine phospholipase D (NAPE-PLD) (EC 3.1.4.4) catalyzes the final step in the biosynthesis of N-acyl-ethanolamides. Reduced NAPE-PLD expression and activity may contribute to obesity and inflammation, but a lack of effective NAPE-PLD inhibitors has been a major obstacle to elucidating the role of NAPE-PLD and N-acyl-ethanolamide biosynthesis in these processes. The endogenous bile acid lithocholic acid (LCA) inhibits NAPE-PLD activity (with an IC50 of 68 µm), but LCA is also a highly potent ligand for TGR5 (EC50 0.52 µm). Recently, the first selective small-molecule inhibitor of NAPE-PLD, ARN19874, has been reported (having an IC50 of 34 µm). To identify more potent inhibitors of NAPE-PLD, here we used a quenched fluorescent NAPE analog, PED-A1, as a substrate for recombinant mouse Nape-pld to screen a panel of bile acids and a library of experimental compounds (the Spectrum Collection). Muricholic acids and several other bile acids inhibited Nape-pld with potency similar to that of LCA. We identified 14 potent Nape-pld inhibitors in the Spectrum Collection, with the two most potent (IC50 = ∼2 µm) being symmetrically substituted dichlorophenes, i.e. hexachlorophene and bithionol. Structure-activity relationship assays using additional substituted dichlorophenes identified key moieties needed for Nape-pld inhibition. Both hexachlorophene and bithionol exhibited significant selectivity for Nape-pld compared with nontarget lipase activities such as Streptomyces chromofuscus PLD or serum lipase. Both also effectively inhibited NAPE-PLD activity in cultured HEK293 cells. We conclude that symmetrically substituted dichlorophenes potently inhibit NAPE-PLD in cultured cells and have significant selectivity for NAPE-PLD versus other tissue-associated lipases.

Lense-Thirring frame dragging induced by a fast-rotating white dwarf in a binary pulsar system.

Radio pulsars in short-period eccentric binary orbits can be used to study both gravitational dynamics and binary evolution. The binary system containing PSR J1141-6545 includes a massive white dwarf (WD) companion that formed before the gravitationally bound young radio pulsar. We observed a temporal evolution of the orbital inclination of this pulsar that we infer is caused by a combination of a Newtonian quadrupole moment and Lense-Thirring (LT) precession of the orbit resulting from rapid rotation of the WD. LT precession, an effect of relativistic frame dragging, is a prediction of general relativity. This detection is consistent with an evolutionary scenario in which the WD accreted matter from the pulsar progenitor, spinning up the WD to a period of <200 seconds.

Roux-en-Y gastric bypass surgery improves hepatic glucose metabolism and reduces plasma kisspeptin levels in morbidly obese patients with type 2 diabetes.

Roux-en-Y gastric bypass surgery (RYGB) is known to improve whole-body glucose metabolism in patients with type 2 diabetes (T2D), although the mechanisms are not entirely clear and are likely multifactorial. The aim of this study was to assess fasting hepatic glucose metabolism and other markers of metabolic activity before and after RYGB in patients with and without T2D. Methods: Metabolic characteristics of patients who are obese with T2D were compared with those without the disease (non-T2D) before and 1 and 6 mo after RYGB. Fasting plasma insulin and the insulin:glucagon ratio were markedly reduced as early as 1 mo after RYGB in both patients with T2D and without T2D. Despite this reduction, endogenous glucose production and fasting plasma glucose levels were lower in both groups after RYGB, with the reductions being much larger in T2D. Plasma kisspeptin, an inhibitor of insulin secretion, was reduced only in T2D after surgery. Improved hepatic glucose metabolism and lower plasma kisspeptin in T2D after RYGB may link improved hepatic function with enhanced insulin responsiveness after surgery.NEW & NOTEWORTHY Our manuscript is the first, to the best of our knowledge, to present data showing that Roux-en-Y gastric bypass surgery (RYGB) lowers fasting kisspeptin levels in patients who are obese with type 2 diabetes. This lowering of kisspeptin is important because it could link improvements in liver glucose metabolism after RYGB with increased insulin responsiveness also seen after surgery.

The prevalence of an elevated F cell population in a maternal and gynaecology cohort.

OBJECTIVES: This study aimed to determine F cell prevalence in a cohort of maternal and gynaecology specimens using QuikQuant anti-HbF flow cytometry (FC) kit and to investigate if the presence of maternal F cells can lead to fetomaternal haemorrhage (FMH) overestimation. BACKGROUND: The gold standard to estimate FMH is the Kleihauer-Betke test (KBT). The KBT has proved to be insufficiently sensitive to detect low numbers of circulating fetal cells due to the presence of maternal F cells. At present, the prevalence of false positive KBT results due to raised maternal F cell population, defined as >5%, is poorly characterised. METHODS: A total of 120 specimens were tested for the presence of F cells and fetal cells by KBT and anti-HbF FC. The results calculated were compared to determine FMH overestimation. RESULTS: Of our cohort, 32% showed an elevated F cell population, of which 69% (27 of 39) were clinically significant according to KBT (>2 mL FMH). The mean FMH volumes by KBT and anti-HbF FC were 3·90 mL (0·20-35·40 mL) and 4·09 mL (0·20-9·70 mL), respectively. CONCLUSION: The study highlighted that an elevated F cell level could be found in the cohort tested, with an F cell level of >10% causing significant FMH overestimation by KBT.

Two-week administration of engineered Escherichia coli establishes persistent resistance to diet-induced obesity even without antibiotic pre-treatment.

Adverse alterations in the composition of the gut microbiota have been implicated in the development of obesity and a variety of chronic diseases. Re-engineering the gut microbiota to produce beneficial metabolites is a potential strategy for treating these chronic diseases. N-acyl-phosphatidylethanolamines (NAPEs) are a family of bioactive lipids with known anti-obesity properties. Previous studies showed that administration of Escherichia coli Nissle 1917 (EcN) engineered with Arabidopsis thaliana NAPE synthase to produce NAPEs imparted resistance to obesity induced by a high-fat diet that persisted after ending their administration. In prior studies, mice were pre-treated with ampicillin prior to administering engineered EcN for 8 weeks in drinking water. If use of antibiotics and long-term administration are required for beneficial effects, implementation of this strategy in humans might be problematic. Studies were therefore undertaken to determine if less onerous protocols could still impart persistent resistance and sustained NAPE biosynthesis. Administration of engineered EcN for only 2 weeks without pre-treatment with antibiotics sufficed to establish persistent resistance. Sustained NAPE biosynthesis by EcN was required as antibiotic treatment after administration of the engineered EcN markedly attenuated its effects. Finally, heterologous expression of human phospholipase A/acyltransferase-2 (PLAAT2) in EcN provided similar resistance to obesity as heterologous expression of A. thaliana NAPE synthase, confirming that NAPEs are the bioactive mediator of this resistance.

A single fast radio burst localized to a massive galaxy at cosmological distance.

Fast radio bursts (FRBs) are brief radio emissions from distant astronomical sources. Some are known to repeat, but most are single bursts. Nonrepeating FRB observations have had insufficient positional accuracy to localize them to an individual host galaxy. We report the interferometric localization of the single-pulse FRB 180924 to a position 4 kiloparsecs from the center of a luminous galaxy at redshift 0.3214. The burst has not been observed to repeat. The properties of the burst and its host are markedly different from those of the only other accurately localized FRB source. The integrated electron column density along the line of sight closely matches models of the intergalactic medium, indicating that some FRBs are clean probes of the baryonic component of the cosmic web.

Mars's Dayside Upper Ionospheric Composition Is Affected by Magnetic Field Conditions.

Previous observations have shown that electron density and temperature in the dayside ionosphere of Mars vary between strongly and weakly magnetized regions of the planet. Here we use data from the Neutral Gas and Ion Mass Spectrometer (NGIMS) on the Mars Atmosphere and Volatile EvolutioN (MAVEN) spacecraft to examine whether dayside ion densities and ionospheric composition also vary. We find that O+, O 2 + , and CO 2 + densities above ~200 km are greater in strongly magnetized regions than in weakly magnetized regions. Fractional abundances of ion species are also affected. The O + / O 2 + ratio at 300-km altitude increases from ~0.5 in strongly magnetized regions to ~0.8 in weakly magnetized regions. Consequently, the plasma reservoir available for escape is fundamentally different between strongly magnetized and weakly magnetized regions.

Fascial layers influence the spread of injectate during ultrasound-guided infraclavicular brachial plexus block: a cadaver study.

BACKGROUND: Fascial layers of the neurovascular sheath containing the brachial plexus influence distribution of local anaesthetic, hence increasing the risk of block failure when performing infraclavicular brachial plexus block (ICB). METHODS: Ultrasound-guided infraclavicular brachial plexus block was performed on cadavers using a single injection technique with dye (20-30 ml). After injection, we carried out consecutive dissection of the neurovascular bundle to study dye injectate spread and identify the presence of fascial layers. Ultrasound video images (scout scan and injection) and recordings of dissections were evaluated by independent experts (regional anaesthetists and anatomists). RESULTS: Well defined fascial layers were identified at dissection in seven out of 12 infraclavicular spaces studied. These fascial layers impeded the spread of dye injectate substantially in six cases and partially in one case. No fascial layers were identified at dissection in five cases, in each of which the spread of injectate was complete throughout the neurovascular bundle. The sensitivity and specificity of ultrasonography and haptic sensation for detection of fascial layers were poor. CONCLUSIONS: When fascial layers are present in the neurovascular sheath, they impede the spread of injectate during infraclavicular brachial plexus block. Ultrasound detection of these fascial layers is unreliable in cadavers. These findings support the use of greater volumes of injectate or a multiple injection technique when performing this block.

Effectiveness of CHA2DS2-VASc based decision support on stroke prevention in atrial fibrillation: A cluster randomised trial in general practice.

BACKGROUND: Guidelines on atrial fibrillation (AF) recommend the CHA2DS2-VASc rule for anticoagulant decision-making, but underuse exists. We studied the impact of an automated decision support on stroke prevention in patients with AF in a cluster randomised trial in general practice. METHODS: Intervention practices were provided with a CHA2DS2-VASc based anticoagulant treatment recommendation. Reference practices provided care as usual. The primary outcome was incidence of ischaemic stroke, transient ischaemic attack (TIA) and/or thromboembolism (TE). Secondary outcomes were bleeding and the proportion of patients on guideline recommended anticoagulant treatment. RESULTS: In total, 1129 AF patients were included in the 19 intervention practices and 1226 AF patients in the 19 reference practices. The median age was 77 (interquartile range (IQR) 68-75) years, the median CHA2DS2-VASc score was 3.0 (IQR 2.0-5.0). Underuse of anticoagulants in patients with CHA2DS2-VASc score ≥ 2 was 6.6%. After a median follow-up of 2.7 years (IQR 2.3-3.0), the incidence rate per 100 person-years of ischaemic stroke/TIA/TE was 1.96 in the intervention group and 1.42 in the reference group (hazard ratio (HR) 1.3, 95% C.I. 0.8-2.1). No difference was observed in the rate of bleeding (0.79 versus 0.82), or in the underuse (7.2% versus 8.2%) or overuse (8.0% versus 7.9%) of anticoagulation. CONCLUSIONS: In this study in patients with AF in general practice, underuse of anticoagulants was relatively low. Providing practitioners with CHA2DS2-VASc based decision support did not result in a reduction in stroke incidence, affect bleeding risk or anticoagulant over- or underuse.

Language development in deaf or hard-of-hearing children with additional disabilities: type matters!

BACKGROUND: This study examined language development in young children with hearing loss and different types of additional disabilities (ADs). METHOD: A population-based cohort of 67 children who were enrolled in the Longitudinal Outcomes of Children with Hearing Impairment study took part. Language ability was directly assessed at 3 and 5 years of age using the Preschool Language Scale, Fourth Edition and the Peabody Picture Vocabulary Test, Fourth Edition. Standard scores were used to enable comparison with age-based expectations for typically developing children. RESULTS: Analysis of variance showed that, across the total cohort, children's language scores remained stable over the 2-year period. However, this overall stability masked a significant difference between children with different types of ADs; in particular, children with autism, cerebral palsy and/or developmental delay showed a decline in standard scores, whereas children with other disabilities showed a relative improvement. In addition, larger improvements in receptive vocabulary were associated with use of oral communication only. CONCLUSIONS: The results suggest that type of AD can be used to gauge expected language development in the population of children with hearing loss and ADs when formal assessment of cognitive ability is not feasible.

HIV and viral hepatitis coinfection analysis using surveillance data from 15 US states and two cities.

Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.