Exenatide Improves Glucose Homeostasis and Prolongs Survival in a Murine Model of Dilated Cardiomyopathy

There is growing awareness of secondary insulin resistance and alterations in myocardial glucose utilization in congestive heart failure. Whether therapies that directly target these changes would be beneficial is unclear. We previously demonstrated that acute blockade of the insulin responsive facilitative glucose transporter GLUT4 precipitates acute decompensated heart failure in mice with advanced dilated cardiomyopathy. Our current objective was to determine whether pharmacologic enhancement of insulin sensitivity and myocardial glucose uptake preserves cardiac function and survival in the setting of primary heart failure.The GLP-1 agonist exenatide was administered twice daily to a murine model of dilated cardiomyopathy (TG9) starting at 56 days of life. TG9 mice develop congestive heart failure and secondary insulin resistance in a highly predictable manner with death by 12 weeks of age. Glucose homeostasis was assessed by measuring glucose tolerance at 8 and 10 weeks and tissue 2-deoxyglucose uptake at 75 days. Exenatide treatment improved glucose tolerance, myocardial GLUT4 expression and 2-deoxyglucose uptake, cardiac contractility, and survival over control vehicle-treated TG9 mice. Phosphorylation of AMP kinase and AKT was also increased in exenatide-treated animals. Total myocardial GLUT1 levels were not different between groups. Exenatide also abrogated the detrimental effect of the GLUT4 antagonist ritonavir on survival in TG9 mice.In heart failure secondary insulin resistance is maladaptive and myocardial glucose uptake is suboptimal. An incretin-based therapy, which addresses these changes, appears beneficial

Morphology and morphometry of the human sublingual glands in mouth floor enlargements of edentulous patients

Asymptomatic mouth floor enlargements may be observed in edentulous patients. These masses, which protrude from the mouth floor, may complicate the fitting of dentures and require surgery. Whether this "entity" may be considered an anatomical variation of the mouth floor or represent specific alterations in the sublingual gland is not known. OBJECTIVE: The aim of this work is to investigate the morphological and morphometric aspects of the sublingual glands of edentulous patients with mouth floor enlargements and compare the glands of these patients with the sublingual glands of human cadavers. MATERIAL AND METHODS: Microscopic evaluation was performed on human sublingual glands from edentulous patients with mouth floor enlargements (n=20) and edentulous cadavers (n=20). The patients and cadavers were of similar ages. The data were compared using Mann-Whitney U, Fisher's exact and Student's t tests (p<0.05). RESULTS: Acinar atrophy, duct-like structures, mononuclear infiltrates, replacement of parenchyma with fibrous/adipose tissue, mucous extravasation and oncocytosis were similar between the groups (p>0.05). Only the variables "autolysis" and "congested blood vessels" presented statistical difference between groups (p=0.014; p=0.043). The morphometric study revealed that the volume densities of acini, ducts, stroma and adipose tissue were similar between the groups (p>0.05). CONCLUSION: The microscopic characteristics of the sublingual glands in mouth floor enlargements in edentulous patients correspond to characteristics associated with the normal aging process. The glands are not pathological and represent an age-related alteration that occurs with or without the presence of the mouth floor enlargements

Characterization of complex networks: A survey of measurements

Each complex network (or class of networks) presents specific topological features which characterize its connectivity and highly influence the dynamics of processes executed on the network. The analysis, discrimination, and synthesis of complex networks therefore rely on the use of measurements capable of expressing the most relevant topological features. This article presents a survey of such measurements. It includes general considerations about complex network characterization, a brief review of the principal models, and the presentation of the main existing measurements. Important related issues covered in this work comprise the representation of the evolution of complex networks in terms of trajectories in several measurement spaces, the analysis of the correlations between some of the most traditional measurements, perturbation analysis, as well as the use of multivariate statistics for feature selection and network classification. Depending on the network and the analysis task one has in mind, a specific set of features may be chosen. It is hoped that the present survey will help the proper application and interpretation of measurements.Comment: A working manuscript with 78 pages, 32 figures. Suggestions of measurements for inclusion are welcomed by the author

Risk factors in patient safety: minimally invasive surgery versus conventional surgery

Background This study aimed to identify the frequency of events in the different patient safety risk domains during minimally invasive surgery (MIS) and conventional surgery (CS). Methods A convenience sample of gynecologic MIS and CS was observed. Events were observed and categorized into one of the predefined patient safety risk domains. Results A total of 53 procedures were observed: 26 CS and 27 MIS procedures. The general characteristics were comparable between the two groups. A large number of environmental events were observed, averaging one every 2.5 min. Technical events and events of an organizational nature occurred more often in MIS (P < 0.01) than in CS (P < 0.01). The relative risk for the occurrence of one or more technical events in MIS compared with CS was 1.7, and the risk for two or more technical events was 4.1. A time out according to protocol showed no relationship to the occurrence of the different types of patient safety-related events. Conclusion The technological complexity inherent in MIS makes this type of surgery more prone to technology-related problems than CS, even in a specially designed minimally invasive surgical suite. A regular time-out procedure developed for CS lacks the attention necessary for the complex technology used in MIS and therefore is insufficient for MIS procedures briefing. Incorporating a specially designed technology checklist in a regular briefing protocol could be a solution to decrease the number of events in MIS.Biomechanical EngineeringMechanical, Maritime and Materials Engineerin

A new prozostrodontian cynodont (Therapsida) from the Late Triassic Riograndia Assemblage Zone (Santa Maria Supersequence) of Southern Brazil

We report here on a new prozostrodontian cynodont, Botucaraitherium belarminoi gen. et sp. nov., from the Late Triassic Riograndia Assemblage Zone (AZ) of the Candelária Sequence (Santa Maria Supersequence), collected in the Botucaraí Hill Site, Candelária Municipality, state of Rio Grande do Sul, Brazil. The new taxon is based on a single specimen (holotype MMACR-PV-003-T) which includes the left lower jaw, without postdentary bones, bearing the root of the last incisor, canine and four postcanines plus one partial crown inside the dentary, not erupted, and two maxillary fragments, one with a broken canine and another with one postcanine. The features of the lower jaw and lower/upper postcanines resemble those of the prozostrodontians Prozostrodon brasiliensis from the older Hyperodapedon AZ and Brasilodon quadrangularis and Brasilitherium riograndensis from the same Riograndia AZ. The inclusion of Botucaraitherium within a broad phylogenetic analysis, positioned it as a more derived taxon than tritylodontids, being the sister-taxon of Brasilodon, Brasilitherium plus Mammaliaformes. Although the new taxon is based on few cranial elements, it represents a additional faunal component of the Triassic Riograndia AZ of southern Brazil, in which small-sized derived non-mammaliaform cynodonts, closely related to the origin of mammaliaforms, were ecologically well succeed and taxonomically diverseNós reportamos aqui um novo cinodonte prozostrodonte, Botucaraitherium belarminoi gen. et sp. nov., do Triássico Tardio da Zona de Assembleia (ZA) de Riograndia da Sequência Candelária (Supersequência Santa Maria), coletado no afl oramento Sítio Botucaraí, no município de Candelária, Rio Grande do Sul, Brasil. O novo táxon está baseado em um único espécime (holótipo MMACR-PV- 003-T) o qual inclui a mandíbula esquerda, sem os ossos pós-dentários, com a raiz do último incisivo preservada, o canino e quatro dentes pós-caninos, além de uma coroa parcial, não erupcionada, do quinto pós-canino, e dois fragmentos maxilares, um com um canino quebrado, e outro portando apenas um dente pós-canino. As feições mandibulares e dentárias assemelham-se àquelas dos cinodontes prozostrodontes Prozostrodon brasiliensis da ZA de Hyperodapedon, mais antiga, e de Brasilodon quadrangularis e Brasilitherium riograndensis da mesma ZA de Riograndia. A inclusão de Botucaraitherium em uma ampla análise filogenética posicionou-o como um táxon mais derivado do que os tritilodontídeos, sendo o táxon-irmão de Brasilodon, Brasilitherium e mais Mammaliaformes. Apesar de o novo táxon ser baseado em poucos elementos cranianos, ele representa um componente faunístico adicional na ZA de Riograndia do Triássico sul-brasileiro, na qual os cinodontes não-mamaliaformes de pequeno tamanho, intimamente relacionados à origem dos mamíferos, foram ecologicamente bem sucedidos e taxonomicamente diverso

Blood Feeding and Insulin-like Peptide 3 Stimulate Proliferation of Hemocytes in the Mosquito Aedes aegypti

All vector mosquito species must feed on the blood of a vertebrate host to produce eggs. Multiple cycles of blood feeding also promote frequent contacts with hosts, which enhance the risk of exposure to infectious agents and disease transmission. Blood feeding triggers the release of insulin-like peptides (ILPs) from the brain of the mosquito Aedes aegypti, which regulate blood meal digestion and egg formation. In turn, hemocytes serve as the most important constitutive defense in mosquitoes against pathogens that enter the hemocoel. Prior studies indicated that blood feeding stimulates hemocytes to increase in abundance, but how this increase in abundance is regulated is unknown. Here, we determined that phagocytic granulocytes and oenocytoids express the A. aegypti insulin receptor (AaMIR). We then showed that: 1) decapitation of mosquitoes after blood feeding inhibited hemocyte proliferation, 2) a single dose of insulin-like peptide 3 (ILP3) sufficient to stimulate egg production rescued proliferation, and 3) knockdown of the AaMIR inhibited ILP3 rescue activity. Infection studies indicated that increased hemocyte abundance enhanced clearance of the bacterium Escherichia coli at lower levels of infection. Surprisingly, however, non-blood fed females better survived intermediate and high levels of E. coli infection than blood fed females. Taken together, our results reveal a previously unrecognized role for the insulin signaling pathway in regulating hemocyte proliferation. Our results also indicate that blood feeding enhances resistance to E. coli at lower levels of infection but reduces tolerance at higher levels of infection