Embryonic development of the neotropical pit viper Bothrops atrox (Serpentes: Viperidae: Crotalinae), with emphasis on pit organ morphogenesis and its evolution in snakes.

BACKGROUND: Bothrops atrox is a pit viper with a loreal pit organ, and its embryological development remains undescribed. Here, we provide a comprehensive description of the embryology of B. atrox, focusing on the loreal pit organ and cephalic scales. RESULTS: We characterized 13 developmental stages of B. atrox based on external features consistent with the embryogenesis of previously described snake species. The loreal pit organ originates from the circumorbital region and migrates to its final position. In Crotalinae, the pit organ first becomes visible at stage 28, whereas in Pythonidae labial, pit organs appear at Stage 35. Pit organs evolved independently three times in Serpentes, encompassing Boidae, Pythonidae, and Crotalinae. Boidae lacks embryological information for pit organs. Furthermore, we observed that head scalation onset occurs at Stage 33 in B. atrox, with fusion of scales surrounding the loreal pit organ. CONCLUSIONS: The embryology of pit organs in Pythonidae and Boidae species remains poorly understood. Our detailed embryological descriptions are critical for proposing developmental scenarios for pit organs and guiding future research on these structures.

Molecular genetics of maternally-controlled cell divisions.

Forward genetic screens remain at the forefront of biology as an unbiased approach for discovering and elucidating gene function at the organismal and molecular level. Past mutagenesis screens targeting maternal-effect genes identified a broad spectrum of phenotypes ranging from defects in oocyte development to embryonic patterning. However, earlier vertebrate screens did not reach saturation, anticipated classes of phenotypes were not uncovered, and technological limitations made it difficult to pinpoint the causal gene. In this study, we performed a chemically-induced maternal-effect mutagenesis screen in zebrafish and identified eight distinct mutants specifically affecting the cleavage stage of development and one cleavage stage mutant that is also male sterile. The cleavage-stage phenotypes fell into three separate classes: developmental arrest proximal to the mid blastula transition (MBT), irregular cleavage, and cytokinesis mutants. We mapped each mutation to narrow genetic intervals and determined the molecular basis for two of the developmental arrest mutants, and a mutation causing male sterility and a maternal-effect mutant phenotype. One developmental arrest mutant gene encodes a maternal specific Stem Loop Binding Protein, which is required to maintain maternal histone levels. The other developmental arrest mutant encodes a maternal-specific subunit of the Minichromosome Maintenance Protein Complex, which is essential for maintaining normal chromosome integrity in the early blastomeres. Finally, we identify a hypomorphic allele of Polo-like kinase-1 (Plk-1), which results in a male sterile and maternal-effect phenotype. Collectively, these mutants expand our molecular-genetic understanding of the maternal regulation of early embryonic development in vertebrates.

Quantification of glycated hemoglobin and glucose in vivo using Raman spectroscopy and artificial neural networks.

Undiagnosed type 2 diabetes (T2D) remains a major public health concern. The global estimation of undiagnosed diabetes is about 46%, being this situation more critical in developing countries. Therefore, we proposed a non-invasive method to quantify glycated hemoglobin (HbA1c) and glucose in vivo. We developed a technique based on Raman spectroscopy, RReliefF as a feature selection method, and regression based on feed-forward artificial neural networks (FFNN). The spectra were obtained from the forearm, wrist, and index finger of 46 individuals. The use of FFNN allowed us to achieve an error in the predictive model of 0.69% for HbA1c and 30.12 mg/dL for glucose. Patients were classified according to HbA1c values into three categories: healthy, prediabetes, and T2D. The proposed method obtained a specificity and sensitivity of 87.50% and 80.77%, respectively. This work demonstrates the benefit of using artificial neural networks and feature selection techniques to enhance Raman spectra processing to determine glycated hemoglobin and glucose in patients with undiagnosed T2D.

Disordered Glucose Levels Are Associated with Xanthine Oxidase Activity in Overweight Type 2 Diabetic Women.

Oxidative stress plays an important role in vascular complications observed in patients with obesity and Type 2 Diabetes (T2D). Xanthine oxidase (XO) breaks down purine nucleotides into uric acid and contributes to the production of reactive oxygen species (ROS). However, the relationship between XO activity and glucose homeostasis in T2D subjects with obesity is unclear. We hypothesized that disordered glucose levels are associated with serum XO activity in overweight women and men with T2D and without hyperuricemia. We studied serum XO activity in women and men with and without T2D. Our results show that serum XO activity was greater in T2D patients with body mass index (BMI) ≥ 25 kg/m2 than in those with BMI < 25 kg/m2 (p < 0.0001). Sex-based comparative analyses of overweight T2D patients showed that serum XO activity correlated with homeostasis model assessment of ß-cell function (HOMA-ß), fasting plasma glucose (FPG), and hemoglobin A1C in overweight T2D women but not in overweight T2D men. In addition, as compared to overweight T2D men, women had higher high-sensitivity C-reactive protein (hs-CRP) levels. However, overweight T2D men had higher XO activity and uric acid levels than women. Our results suggest that XO activity is higher in overweight T2D patients, especially in men, but is more sensitive to disordered glucose levels in overweight women with T2D.

The Hippo pathway effector Taz is required for cell morphogenesis and fertilization in zebrafish.

Hippo signaling is a critical pathway that integrates extrinsic and intrinsic mechanical cues to regulate organ size. Despite its essential role in organogenesis, little is known about its role in cell fate specification and differentiation. Here, we unravel a novel and unexpected role of the Hippo pathway effector Taz (wwtr1) in controlling the size, shape and fate of a unique cell in the zebrafish ovary. We show that wwtr1 mutant females are infertile. In teleosts, fertilization occurs through the micropyle, a funnel-like opening in the chorion, formed by a unique enlarged follicle cell, the micropylar cell (MC). We describe here, for the first time, the mechanism that underlies the differentiation of the MC. Our genetic analyses show that Taz is essential for MC fate acquisition and subsequent micropyle formation in zebrafish. We identify Taz as the first bona fide MC marker and show that Taz is specifically and strongly enriched in the MC precursor. Altogether, we performed the first genetic and molecular characterization of the MC and propose that Taz is a key regulator of MC fate.This article has an associated 'The people behind the papers' interview.

Development of a comprehensive Percutaneous Dilatational Tracheostomy process model for procedural training: A Delphi-based experts consensus.

BACKGROUND: Deconstructing a complex procedure improves skills learning, but no model has covered all relevant Percutaneous Dilatational Tracheostomy (PDT) procedural aspects. Moreover, the heterogeneity of techniques described may hinder trainees' competency acquisition. Our objective was to develop a PDT model for procedural training that includes a comprehensive step-by-step design. METHODS: Procedural descriptions were retrieved after a structured search in medical databases. Activities were extracted and the adherence to McKinley's dimensions of procedural competence was analyzed. We developed a comprehensive PDT model, which was further validated through a Delphi-based consensus of Spanish-speaking international experts. RESULTS: The 14 descriptions retrieved for analysis presented a median [interquartile range] of 18 [11-22] steps, covering 3 [2-4] of McKinley's dimensions. The Delphi panel's first model included all McKinley's dimensions, and was answered by 25 experts from nine countries, ending in the second round. The final model included 59 activities divided into six stages (51 from the initial model and eight proposed by experts) and performed by two operators (bronchoscopy and tracheostomy). CONCLUSIONS: We have presented a PDT model that includes necessary competence dimensions to be considered complete. The model was validated by an experts' consensus, allowing to improve procedural training to promote safer patient care.

Viral Infection Drives the Regulation of Feeding Behavior Related Genes in Salmo salar.

The feeding behavior in fish is a complex activity that relies on the ability of the brain to integrate multiple signals to produce appropriate responses in terms of food intake, energy expenditure, and metabolic activity. Upon stress cues including viral infection or mediators such as the proinflammatory cytokines, prostaglandins, and cortisol, both Pomc and Npy/Agrp neurons from the hypothalamus are stimulated, thus triggering a response that controls both energy storage and expenditure. However, how appetite modulators or neuro-immune cues link pathogenesis and energy homeostasis in fish remains poorly understood. Here, we provide the first evidence of a molecular linkage between inflammation and food intake in Salmon salar. We show that in vivo viral challenge with infectious pancreatic necrosis virus (IPNV) impacts food consumption by activating anorexic genes such as mc4r, crf, and pomcb and 5-HT in the brain of S. salar. At the molecular level, viral infection induces an overall reduction in lipid content in the liver, favoring the production of AA and EPA associated with the increment of elovl2 gene. In addition, infection upregulates leptin signaling and inhibits insulin signaling. These changes are accompanied by a robust inflammatory response represented by the increment of Il-1b, Il-6, Tnfa, and Pge2 as well as an increased cortisol level in vivo. Thus, we propose a model in which hypothalamic neurons respond to inflammatory cytokines and stress-related molecules and interact with appetite induction/inhibition. These findings provide evidence of crosstalk between pathogenesis-driven inflammation and hypothalamic-pituitary-adrenocortical axes in stress-induced food intake behavior in fish.

Behavioural Fever Promotes an Inflammatory Reflex Circuit in Ectotherms.

BACKGROUND: The communication between the brain and the immune system is a cornerstone in animal physiology. This interaction is mediated by immune factors acting in both health and pathogenesis, but it is unclear how these systems molecularly and mechanistically communicate under changing environmental conditions. Behavioural fever is a well-conserved immune response that promotes dramatic changes in gene expression patterns during ectotherms' thermoregulatory adaptation, including those orchestrating inflammation. However, the molecular regulators activating the inflammatory reflex in ectotherms remain unidentified. METHODS: We revisited behavioural fever by providing groups of fish a thermal gradient environment during infection. Our novel experimental setup created temperature ranges in which fish freely moved between different thermal gradients: (1) wide thermoregulatory range; T° = 6.4 °C; and (2) restricted thermoregulatory range; T° = 1.4 °C. The fish behaviour was investigated during 5-days post-viral infection. Blood, spleen, and brain samples were collected to determine plasmatic pro- and anti-inflammatory cytokine levels. To characterize genes' functioning during behavioural fever, we performed a transcriptomic profiling of the fish spleen. We also measured the activity of neurotransmitters such as norepinephrine and acetylcholine in brain and peripheral tissues. RESULTS: We describe the first set of the neural components that control inflammatory modulation during behavioural fever. We identified a neuro-immune crosstalk as a potential mechanism promoting the fine regulation of inflammation. The development of behavioural fever upon viral infection triggers a robust inflammatory response in vivo, establishing an activation threshold after infection in several organs, including the brain. Thus, temperature shifts strongly impact on neural tissue, specifically on the inflammatory reflex network activation. At the molecular level, behavioural fever causes a significant increase in cholinergic neurotransmitters and their receptors' activity and key anti-inflammatory factors such as cytokine Il10 and Tgfß in target tissues. CONCLUSION: These results reveal a cholinergic neuronal-based mechanism underlying anti-inflammatory responses under induced fever. We performed the first molecular characterization of the behavioural fever response and inflammatory reflex activation in mobile ectotherms, identifying the role of key regulators of these processes. These findings provide genetic entry points for functional studies of the neural-immune adaptation to infection and its protective relevance in ectotherm organisms.

Control-flow analysis of procedural skills competencies in medical training through process mining.

BACKGROUND: Procedural skills are key to good clinical results, and training in them involves a significant amount of resources. Control-flow analysis (ie, the order in which a process is performed) can provide new information for those who train and plan procedural training. This study outlines the steps required for control-flow analysis using process mining techniques in training in an ultrasound-guided internal jugular central venous catheter placement using a simulation. METHODS: A reference process model was defined through a Delphi study, and execution data (event logs) were collected from video recordings from pretraining (PRE), post-training (POST) and expert (EXP) procedure executions. The analysis was performed to outline differences between the model and executions. We analysed rework (activity repetition), alignment-based fitness (conformance with the ideal model) and trace alignment analysis (visual ordering pattern similarities). RESULTS: Expert executions do not present repetition of activities (rework). The POST rework is lower than the PRE, concentrated in the steps of the venous puncture and guidewire placement. The adjustment to the ideal model measure as alignment-based fitness, expressed as a median (25th-75th percentile) of PRE 0.74 (0.68-0.78) is less than POST 0.82 (0.76-0.86) and EXP 0.87 (0.82-0.87). There are no significant differences between POST and EXP. The graphic analysis of alignment and executions shows a progressive increase in order from PRE to EXP executions. CONCLUSION: Process mining analysis is able to pinpoint more difficult steps, assess the concordance between reference mode and executions, and identify control-flow patterns in procedural training courses.

Awake vs. asleep motor mapping for glioma resection: a systematic review and meta-analysis.

BACKGROUND: Intraoperative stimulation (IS) mapping has become the preferred standard treatment for eloquent tumors as it permits a more accurate identification of functional areas, allowing surgeons to achieve higher extents of resection (EOR) and decrease postoperative morbidity. For lesions adjacent to the perirolandic area and descending motor tracts, mapping can be done with both awake craniotomy (AC) and under general anesthesia (GA). OBJECTIVE: We aimed to determine which anesthetic protocol-AC vs. GA-provides better patient outcomes by comparing EOR and postoperative morbidity for surgeries using IS mapping in gliomas located near or in motor areas of the brain. METHODS: A systematic literature search was carried out to identify relevant studies from 1983 to 2019. Seven databases were screened. A total of 2351 glioma patients from 17 studies were analyzed. RESULTS: A random-effects meta-analysis revealed a trend towards a higher mean EOR in AC [90.1% (95% C.I. 85.8-93.8)] than with GA [81.7% (95% C.I. 72.4-89.7)] (p = 0.06). Neurological deficits were divided by timing and severity for analysis. There was no significant difference in early neurological deficits [20.9% (95% C.I. 4.1-45.0) vs. 25.4% (95% C.I. 13.6-39.2)] (p = 0.74), late neurological deficits [17.1% (95% C.I. 0.0-50.0) vs. 3.8% (95% C.I. 1.1-7.6)] (p = 0.06), or in non-severe [28.4% (95% C.I. 0.0-88.5) vs. 20.1% (95% C.I. 7.1-32.2)] (p = 0.72), and severe morbidity [2.6% (95% C.I. 0.0-15.5) vs. 4.5% (95% C.I. 1.1-9.6)] (p = 0.89) between patients who underwent AC versus GA, respectively. CONCLUSION: Mapping during resection of gliomas located in or near the perirolandic area and descending motor tracts can be safely carried out with both AC and GA.

[Association between high vitamin B12 levels and one year mortality in older people admitted to the hospital]. / Asociación entre niveles de vitamina B-12 y mortalidad en pacientes hospitalizados adultos mayores.

BACKGROUND: Supplementation of vitamin B12 in older adults is a common practice to avoid vitamin B12 insufficiency. However, there is a paucity of information about the effects of cobalamin excess. AIM: To asses any potential effects of high levels vitamin B12 on mortality on adults aged ≥ 65 years admitted to an internal medicine service. MATERIAL AND METHODS: We Prospectively studied patients admitted to an internal medicine service of an academic hospital from September 2017 to September 2018, who were able to give their consent and answer questionnaires. We tabulated age, gender, medical history, comorbidity index (Charlson), frailty score (Fried scale), admission diagnosis and blood tests performed within 48 hours of admission. The primary outcome was death by any cause in less of 30 days or after one of year follow up, determined according to death certificates. RESULTS: We included 93 patients aged 65 to 94 years (53% males). Fifteen patients died during the year of follow up (five within 30 days of admission). Those who died had higher cobalamin levels than survivors (1080.07 ± 788.09 and 656.68 ± 497.33 pg/mL respectively, p = 0.02). Patients who died had also a significantly lower corrected serum calcium, sodium (p = 0.04) and a medical history of chronic liver disease (p = 0.03). In the multivariable analysis, only vitamin B12 preserved the association with mortality (p = 0.009). CONCLUSIONS: There was a significant association between high levels of cobalamin and all-cause mortality in this group of patients aged ≥ 65 years-old.

Split top: a maternal cathepsin B that regulates dorsoventral patterning and morphogenesis.

The vertebrate embryonic dorsoventral axis is established and patterned by Wnt and bone morphogenetic protein (BMP) signaling pathways, respectively. Whereas Wnt signaling establishes the dorsal side of the embryo and induces the dorsal organizer, a BMP signaling gradient patterns tissues along the dorsoventral axis. Early Wnt signaling is provided maternally, whereas BMP ligand expression in the zebrafish is zygotic, but regulated by maternal factors. Concomitant with BMP activity patterning dorsoventral axial tissues, the embryo also undergoes dramatic morphogenetic processes, including the cell movements of gastrulation, epiboly and dorsal convergence. Although the zygotic regulation of these cell migration processes is increasingly understood, far less is known of the maternal regulators of these processes. Similarly, the maternal regulation of dorsoventral patterning, and in particular the maternal control of ventral tissue specification, is poorly understood. We identified split top, a recessive maternal-effect zebrafish mutant that disrupts embryonic patterning upstream of endogenous BMP signaling. Embryos from split top mutant females exhibit a dorsalized embryonic axis, which can be rescued by BMP misexpression or by derepressing endogenous BMP signaling. In addition to dorsoventral patterning defects, split top mutants display morphogenesis defects that are both BMP dependent and independent. These morphogenesis defects include incomplete dorsal convergence, delayed epiboly progression and an early lysis phenotype during gastrula stages. The latter two morphogenesis defects are associated with disruption of the actin and microtubule cytoskeleton within the yolk cell and defects in the outer enveloping cell layer, which are both known mediators of epiboly movements. Through chromosomal mapping and RNA sequencing analysis, we identified the lysosomal endopeptidase cathepsin Ba (ctsba) as the gene deficient in split top embryos. Our results identify a novel role for Ctsba in morphogenesis and expand our understanding of the maternal regulation of dorsoventral patterning.

Validation of a non-laboratorial questionnaire to identify Metabolic Syndrome among a population in central Mexico.

OBJECTIVE: To determine the reliability of a non-laboratorial questionnaire, the Encuesta de Identificación de Sujetos Metabólicamente Comprometidos en Fase-I (ESF-I) for identifying Metabolic Syndrome among a population in central Mexico. METHODS: Clinical and biochemical parameters were collected for 232 participants from 1 June 2012 - 31 August 2013. Three definitions of Metabolic Syndrome (Harmonizing, National Cholesterol Education Program Expert Panel and Adult Treatment Panel III [ATPIII], and International Diabetes Federation [IDF]) were used to allocate subjects to either the normal or Metabolic Syndrome positive (MetS+) group. The predictability of the questionnaire was determined by the Area-Under-the-Receiver-Operating Characteristic curve (AUC). Youden's index was calculated and the highest score was considered the optimal cutoff value. Cohen´s kappa (κ) was calculated to determine the level of agreement between the ESF-I questionnaire (max score: 15 based on 15 items) and Metabolic Syndrome. RESULTS: From 53.8% - 60.7% of the participants were determined to be MetS+. The average questionnaire score was significantly higher in the MetS+ group for each definition (4.0 vs. 8.0, P < 0.05). The ESF-I questionnaire was predictive for the Harmonizing definition (AUC = 0.841, 95%CI: 0.790 - 0.892), the ATPIII definition (AUC = 0.827, 95%CI: 0.774 - 0.880), and the IDF definition (AUC = 0.836, 95%CI: 0.785 - 0.887). A cutoff value of 7 was determined for each definition; therefore, the cohort was re-categorized based on questionnaire results. There was a strong agreement between the ESF-I questionnaire and MetS (Harmonizing: accuracy = 77.6%, κ = 0.554; ATPIII: accuracy = 74.1%, κ = 0.489; IDF: accuracy = 74.6%, κ = 0.495, P < 0.001). CONCLUSION: The ESF-I questionnaire can identify MetS+ patients, and therefore, lead to earlier diagnoses, reduced number of consultations, and lower costs with easier application.

Differential effects of the methylenetetrahydrofolate reductase polymorphisms (C677T and A1298C) on hematological malignancies among Latinos: a meta-analysis.

Our objective was to determine the association between the methylenetetrahydrofolate reductase polymorphisms (C677T and A1298C) and the risk of developing acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), acute myeloid leukemia (AML), and multiple myelomas (MM) in Latinos. PubMed, SCOPUS, EBSCO, LILACS, and other Latin-specific databases were searched for case-control studies that investigated the association between these polymorphisms and hematologic malignancies until November 2017. Genotype distributions were extracted and either fixed-effects or random-effects models were used to calculate the pooled crude odds ratios (ORs) for the heterozygous, homozygous, dominant, recessive, and allelic genetic models. No publication bias was detected by the Begg-Mazumdar's test and Egger's test. From 290 publications, we identified 15 studies on the C677T polymorphism and 13 studies on the A1298C polymorphism. We observed a significant decrease in risk for the C677T polymorphism (OR range=0.54-0.75, p<0.01) and a significant increase in risk for the A1298C polymorphism (OR range=1.28-2.52, p<0.05) in developing ALL for all genetic models. No associations were determined for CML, AML, or MM for either polymorphism. This meta-analysis demonstrated that the A1298C polymorphism was associated with an increased risk of developing ALL, whereas the C677T polymorphism was associated with a decreased risk (protective factor) in the Latino population.

IFN-γ and IL-33 modulate mesenchymal stem cells function targeting Th1/Th17 axis in a murine skin transplantation model.

The immune regulatory properties of IL-33 have indicated that this cytokine has the capacity to target several immune cells under a variety of immunological responses, including overt inflammation and tolerance. Due to its versatile mechanistics, we sought to investigate the role of IL-33 on mesenchymal stem cells (MSC), a population of cells with recognizable modulatory functions. Our data indicates that IL-33 does not affect the expression of classical MSC markers such as CD29, CD44 and CD73, or the lack of CD45, CD11b and CD117. Also, we found that IL-33 greatly induces iNOS expression and stimulates the secretion of TGF-ß and IL-6. Next, we decided to test IFN-γ/IL-33-treated MSC using a skin transplantation model. Our data indicate that allogeneic skin-grafted animals treated with IFN-γ/IL-33-modulated MSC reject as controls. Complementing this finding, we observed that ex vivo re-stimulated draining lymph nodes (dLN) cells from these mice secrete lower amounts of IFN-γ and a slightly higher amount of IL-17. Beside a reduction in CD4+ and CD8+ T cells number, we preliminarily found an increment in the frequencies of CD4+Foxp3+IL-17+ T cells. Altogether, our data propose that IL-33 and IFN-γ modulate MSC phenotype and function, most likely targeting Th1/Th17 axis.

Propofol pharmacokinetic and pharmacodynamic profile and its electroencephalographic interaction with remifentanil in children.

BACKGROUND: Propofol and remifentanil are commonly combined during total intravenous anesthesia. The impact of remifentanil in this relationship is poorly quantified in children. Derivation of an integrated pharmacokinetic and pharmacodynamic propofol model, containing remifentanil pharmacodynamic interaction information, enables propofol effect-site target-controlled infusion in children with a better prediction of its hypnotic effect when both drugs are combined. AIMS: We designed this study to derive an integrated propofol pharmacokinetic-pharmacodynamic model in children and to describe the pharmacodynamic interaction between propofol and remifentanil on the electroencephalographic bispectral index effect. METHODS: Thirty children (mean age: 5.45 years, range 1.3-11.9; mean weight: 23.5 kg, range 8.5-61) scheduled for elective surgery with general anesthesia were studied. After sevoflurane induction, maintenance of anesthesia was based on propofol and remifentanil. Blood samples to measure propofol concentration were collected during anesthesia maintenance and up to 6 hours in the postoperative period. Bispectral index data were continuously recorded throughout the study. A pharmacokinetic-pharmacodynamic model was developed using population modeling. The Greco model was used to examine the pharmacokinetic-pharmacodynamic interaction between propofol and remifentanil for BIS response RESULTS: Propofol pharmacokinetic data from a previous study in 53 children were pooled with current data and simultaneously analyzed. Propofol pharmacokinetics were adequately described by a three-compartment distribution model with first-order elimination. Theory-based allometric relationships based on TBW improved the model fit. The Greco model supported an additive interaction between propofol and remifentanil. Remifentanil showed only a minor effect in BIS response. CONCLUSION: We have developed an integrated propofol pharmacokinetic-pharmacodynamic model that can describe the pharmacodynamic interaction between propofol and remifentanil for BIS response. An additive interaction was supported by our modeling analysis.

Triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) index as a reference criterion of risk for metabolic syndrome (MetS) and low insulin sensitivity in apparently healthy subjects.

AIM: To evaluate if the TG/HDL-C index can be considered as a reference criterion of MetS and low insulin sensitivity in apparently healthy subjects. METHODS: The subjects were Mexican mestizos who resided in Puebla City, Mexico, who were anthropometrically, biochemically, and clinically characterized. The TG/HDL-C index was calculated by dividing triglyceride (TG) levels by HDL-C levels. MetS was diagnosed by the Third Report from the Adult Treatment Panel-National Cholesterol Education Program (ATP-III NCEP) criteria, while insulin sensitivity was evaluated by the Quantitative Insulin sensitivity Check Index (QUICKI). RESULTS: The study included 813 subjects, with an average age of 38.6 ± 12.1 years, of which 564 were women and 249 men. An association was found between high TG/HDL-C index and low insulin sensitivity (Odds ratio [OR]: 4.09; p < 0.01) and with MetS (OR: 15.29; p < 0.01). A correlation was found between the TG/HDL-C index and QUICKI (rho: -0.4989; p < 0.01) and with MetS (rho: 0.6581; p < 0.01). CONCLUSION: The results indicate that the TG/HDL-C index is associated with low insulin sensitivity and MetS in apparently healthy subjects, suggesting this index as a reference criterion of risk for low insulin sensitivity and MetS.

Propofol concentration to induce general anesthesia in children aged 3-11 years with the Kataria effect-site model.

BACKGROUND: The propofol pharmacokinetic model derived by Kataria et al. was recently modified to perform effect-site target-controlled infusion (TCI). Effect-site concentration (Ce) targets to induce general anesthesia with this model in children have not been described. The aim of this study was to identify propofol Ce targets associated with success rates of 50% (Ce50) and 95% (Ce95) among children 3-11 years of age. METHODS: Forty-two children were assigned to one of seven groups of six patients each according to propofol target Ce. After fentanyl administration propofol TCI was started with an assigned Ce target. A successful response was defined as loss of eyelash reflex and bispectral index < 50, 45 s after reaching the assigned Ce. Logistic regression analysis was performed to calculate propofol Ce50 and Ce95. RESULTS: Twenty-eight children had a successful response with the assigned propofol Ce. In these patients, a significant decrease in mean arterial blood pressure (79-59, P < 0.0001) and in heart rate (95-83, P < 0.0001) was observed. Propofol Ce and age showed a statistically significant effect in the logistic regression model. The overall calculated propofol Ce50 and Ce95 were 3.8 µg·ml(-1) (95% CI: 3.1-4.4 µg·ml(-1) ) and 6.1 µg·ml(-1) (95% CI: 4.6-7.6 µg·ml(-1) ), respectively. CONCLUSION: Our results identified useful propofol targets to be used with the Kataria effect-site model to induce anesthesia in children between 3 and 11 years. The recommended targets should be reduced progressively with increasing age most probably due to PK model misspecifications.

Dexmedetomidine-ketamine combination and caudal block for superficial lower abdominal and genital surgery in children.

BACKGROUND: The use of dexmedetomidine-ketamine combination to perform different diagnostic and surgical pediatric procedures has increased. The optimal ketamine dose to combine with dexmedetomidine has not been determined. The goal of this study was to determine the ED50 and ED95 of ketamine, which in combination with, dexmedetomidine (1 µg · kg(-1)) provides an adequate anesthetic effect to perform a caudal block and then the ensuing superficial lower abdominal or genital surgery. MATERIAL AND METHODS: Twenty-five patients, aged 1-8 years, scheduled for superficial lower abdominal or genital surgery, were studied. All patients received an intravenous dose of dexmedetomidine 1 µg · kg(-1) and a random dose of ketamine from 1 mg · kg(-1) to 2 mg · kg(-1). After ketamine administration, a caudal block was performed and then surgery was initiated. Hemodynamics, respiratory variables, sedation level, and postoperative complications were recorded. The ED50 and ED95 of ketamine were calculated using logistic regression analysis. RESULTS: The ED50 and ED95 of ketamine to perform a caudal block were 1.53 (1.29-1.76) mg · kg(-1) and 2.25 (1.63-2.88) mg · kg(-1), respectively. The ED50 and ED95 of ketamine to perform a caudal block and to complete the entire procedure were 1.76 (1.57-1.95) mg · kg(-1), and 2.21 (1.77-2.64) mg · kg(-1), respectively. Three patients presented mild, self-limited, intraoperative bradycardia. CONCLUSIONS: These results suggest that adding ketamine 2 mg · kg(-1) to dexmedetomidine 1 µg · kg(-1) should produce an effective anesthetic level to perform a caudal block and the ensuing superficial lower abdominal or genital surgery in children.