Regulated inositol synthesis is critical for balanced metabolism and development in Drosophila melanogaster.

Myo-inositol is a precursor of the membrane phospholipid, phosphatidylinositol (PI). It is involved in many essential cellular processes including signal transduction, energy metabolism, endoplasmic reticulum stress, and osmoregulation. Inositol is synthesized from glucose-6-phosphate by myo-inositol-3-phosphate synthase (MIPSp). The Drosophila melanogaster Inos gene encodes MIPSp. Abnormalities in myo-inositol metabolism have been implicated in type 2 diabetes, cancer, and neurodegenerative disorders. Obesity and high blood (hemolymph) glucose are two hallmarks of diabetes, which can be induced in Drosophila melanogaster third-instar larvae by high-sucrose diets. This study shows that dietary inositol reduces the obese-like and high-hemolymph glucose phenotypes of third-instar larvae fed high-sucrose diets. Furthermore, this study demonstrates Inos mRNA regulation by dietary inositol; when more inositol is provided there is less Inos mRNA. Third-instar larvae with dysregulated high levels of Inos mRNA and MIPSp show dramatic reductions of the obese-like and high-hemolymph glucose phenotypes. These strains, however, also display developmental defects and pupal lethality. The few individuals that eclose die within two days with striking defects: structural alterations of the wings and legs, and heads lacking proboscises. This study is an exciting extension of the use of Drosophila melanogaster as a model organism for exploring the junction of development and metabolism.

Accurate, strong, and stable reporting of choroid plexus epithelial cells in transgenic mice using a human transthyretin BAC.

BACKGROUND: Choroid plexus epithelial cells express high levels of transthyretin, produce cerebrospinal fluid and many of its proteins, and make up the blood-cerebrospinal fluid barrier. Choroid plexus epithelial cells are vital to brain health and may be involved in neurological diseases. Transgenic mice containing fluorescent and luminescent reporters of these cells would facilitate their study in health and disease, but prior transgenic reporters lost expression over the early postnatal period. METHODS: Human bacterial artificial chromosomes in which the transthyretin coding sequence was replaced with DNA for tdTomato or luciferase 2 were used in pronuclear injections to produce transgenic mice. These mice were characterized by visualizing red fluorescence, immunostaining, real-time reverse transcription polymerase chain reaction, and luciferase enzyme assay. RESULTS: Reporters were faithfully expressed in cells that express transthyretin constitutively, including choroid plexus epithelial cells, retinal pigment epithelium, pancreatic islets, and liver. Expression of tdTomato in choroid plexus began at the appropriate embryonic age, being detectable by E11.5. Relative levels of tdTomato transcript in the liver and choroid plexus paralleled relative levels of transcripts for transthyretin. Expression remained robust over the first postnatal year, although choroid plexus transcripts of tdTomato declined slightly with age whereas transthyretin remained constant. TdTomato expression patterns were consistent across three founder lines, displayed no sex differences, and were stable across several generations. Two of the tdTomato lines were bred to homozygosity, and homozygous mice are healthy and fertile. The usefulness of tdTomato reporters in visualizing and analyzing live Transwell cultures was demonstrated. Luciferase activity was very high in homogenates of choroid plexus and continued to be expressed through adulthood. Luciferase also was detectable in eye and pancreas. CONCLUSIONS: Transgenic mice bearing fluorescent and luminescent reporters of transthyretin should prove useful for tracking transplanted choroid plexus epithelial cells, for purifying the cells, and for reporting their derivation from stem cells. They also should prove useful for studying transthyretin synthesis by other cell types, as transthyretin has been implicated in many functions and conditions, including clearance of ß-amyloid peptides associated with Alzheimer's disease, heat shock in neurons, processing of neuropeptides, nerve regeneration, astrocyte metabolism, and transthyretin amyloidosis.

Desarrollo de un instrumento culturalmente pertinente para medir creencias en psicoterapia / Development of a culturally relevant instrument to measure beliefs in psychotherapy

El estudio de cómo los factores culturales se relacionan con la adherencia a psicoterapia es altamente relevante y sin embargo, en Chile no existen instrumentos que tomen en consideración tales factores. El objetivo de este estudio es ilustrar la construcción de un instrumento para medir variables culturales que se asocian a la adherencia a psicoterapia. Se utilizó una metodología mixta de tres etapas. Primero, se realizaron 32 entrevistas semiestructuradas con el objetivo de identificar creencias socialmente compartidas respecto de la psicoterapia. Luego, se desarrolló la Escala de Creencias en Psicoterapia (ECPSI) y se piloteó en una muestra de 109 personas. Finalmente, se exploró la estructura factorial y propiedades psicométricas de la nueva escala en 201 usuarias de centros de salud primaria de la Región de La Araucanía. Los resultados indican que la ECPSI es un instrumento adecuado psicométricamente y culturalmente pertinente a la sociedad Chilena.

The study of how cultural factors are related to adherence to psychotherapy is highly relevant, however in Chile there are no available measures that addresses these factors. In order to develop an instrument culturally relevant for measuring cultural factors associated with adherence to psychotherapy, a three-stage mixed methodology was used. First, 32 semi-structured interviews were conducted aiming to identifying socially shared beliefs about psychotherapy. Second, the Psychotherapy Beliefs Scale was developed and piloted with a sample of109 participants. Finally, the factorial structure, and the scale reliability were tested with a sample of 201 women recruited from several primary care health centers. The results obtained suggest that this scale is psychometrically sound and culturally relevant for measuring cultural beliefs associated with adherence to psychotherapy.

Analytical validation of COMSOL Multiphysics for theoretical models of Radiofrequency ablation including the Hyperbolic Bioheat transfer equation.

In this paper we outline our main findings about the differences between the use of the Bioheat Equation and the Hyperbolic Bioheat Equation in theoretical models for Radiofrequency (RF) ablation. At the moment, we have been working on the analytical approach to solve both equations, but more recently, we have considered numerical models based on the Finite Element Method (FEM). As a first step to use FEM, we conducted a comparative study between the temperature profiles obtained from the analytical solutions and those obtained from FEM. Regarding the differences between both methods, we obtain agreement in less than 5% of relative differences. Then FEM is a good alternative to model heating of biological tissues using BE and HBE in, for example, more complex and realistic geometries.

Theoretical modeling of RF ablation with internally cooled electrodes: comparative study of different thermal boundary conditions at the electrode-tissue interface.

Previous studies on computer modeling of RF ablation with cooled electrodes modeled the internal cooling circuit by setting surface temperature at the coolant temperature (i.e., Dirichlet condition, DC). Our objective was to compare the temperature profiles computed from different thermal boundary conditions at the electrode-tissue interface. We built an analytical one-dimensional model based on a spherical electrode. Four cases were considered: A) DC with uniform initial condition, B) DC with pre-cooling period, C) Boundary condition based on Newton's cooling law (NC) with uniform initial condition, and D) NC with a pre-cooling period. The results showed that for a long time (120 s), the profiles obtained with (Cases B and D) and without (Cases A and C) considering pre-cooling are very similar. However, for shorter times ( 30 s), Cases A and C overestimated the temperature at points away from the electrode-tissue interface. In the NC cases, this overestimation was more evident for higher values of the convective heat transfer coefficient (h). Finally, with NC, when h was increased the temperature profiles became more similar to those with DC. The results suggest that theoretical modeling of RF ablation with cooled electrodes should consider: 1) the modeling of a pre-cooling period, especially if one is interested in the thermal profiles registered at the beginning of RF application; and 2) NC rather than DC, especially for low flow in the internal circuit.

Thermal modeling for pulsed radiofrequency ablation: analytical study based on hyperbolic heat conduction.

The objectives of this study were to model the temperature progress of a pulsed radiofrequency (RF) power during RF heating of biological tissue, and to employ the hyperbolic heat transfer equation (HHTE), which takes the thermal wave behavior into account, and compare the results to those obtained using the heat transfer equation based on Fourier theory (FHTE). A theoretical model was built based on an active spherical electrode completely embedded in the biological tissue, after which HHTE and FHTE were analytically solved. We found three typical waveforms for the temperature progress depending on the relations between the dimensionless duration of the RF pulse delta(a) and the expression square root of lambda(rho-1), with lambda as the dimensionless thermal relaxation time of the tissue and rho as the dimensionless position. In the case of a unique RF pulse, the temperature at any location was the result of the overlapping of two different heat sources delayed for a duration delta(a) (each heat source being produced by a RF pulse of limitless duration). The most remarkable feature in the HHTE analytical solution was the presence of temperature peaks traveling through the medium at a finite speed. These peaks not only occurred during the RF power switch-on period but also during switch off. Finally, a physical explanation for these temperature peaks is proposed based on the interaction of forward and reverse thermal waves. All-purpose analytical solutions for FHTE and HHTE were obtained during pulsed RF heating of biological tissues, which could be used for any value of pulsing frequency and duty cycle.

Analytical thermal-optic model for laser heating of biological tissue using the hyperbolic heat transfer equation.

In this paper, we solve in an analytical way the thermal-optic coupled problem associated with a 1D model of non-perfused homogeneous biological tissue irradiated by a laser beam. We consider a laser pulse duration of 200 micros and study the temperatures of areas very close to the point of laser beam application. We consider that these values of the temporal and spatial variables mean that the problem has to be solved by means of the hyperbolic heat conduction model instead of the classic or parabolic model. We therefore obtain the solution using both models and apply the temperature profiles obtained to a specific biological tissue for comparison. Finally, we theoretically study the effect of the thermal relaxation time on the temperature profiles in the tissue for both heating and cooling phases (i.e. during and after laser application).

Effect of the thermal wave in radiofrequency ablation modeling: an analytical study.

To date, all radiofrequency heating (RFH) theoretical models have employed Fourier's heat transfer equation (FHTE), which assumes infinite thermal energy propagation speed. Although this equation is probably suitable for modeling most RFH techniques, it may not be so for surgical procedures in which very short heating times are employed. In such cases, a non-Fourier model should be considered by using the hyperbolic heat transfer equation (HHTE). Our aim was to compare the temperature profiles obtained from the FHTE and HHTE for RFH modeling. We built a one-dimensional theoretical model based on a spherical electrode totally embedded and in close contact with biological tissue of infinite dimensions. We solved the electrical-thermal coupled problem analytically by including the power source in both equations. A comparison of the analytical solutions from the HHTE and FHTE showed that (1) for short times and locations close to the electrode surface, the HHTE produced temperatures higher than the FHTE, however, this trend became negligible for longer times, when both equations produced similar temperature profiles (HHTE always being higher than FHTE); (2) for points distant from the electrode surface and for very short times, the HHTE temperature was lower than the FHTE, however, after a delay time, this tendency inverted and the HHTE temperature increased to the maximum; (3) from a mathematical point of view, the HHTE solution showed cuspidal-type singularities, which were materialized as a temperature peak traveling through the medium at a finite speed. This peak rose at the electrode surface, and clearly reflected the wave nature of the thermal problem; (4) the differences between the FHTE and HHTE temperature profiles were smaller for the lower values of thermal relaxation time and locations further from the electrode surface.

Assessment of hyperbolic heat transfer equation in theoretical modeling for radiofrequency heating techniques.

Theoretical modeling is a technique widely used to study the electrical-thermal performance of different surgical procedures based on tissue heating by use of radiofrequency (RF) currents. Most models employ a parabolic heat transfer equation (PHTE) based on Fourier's theory, which assumes an infinite propagation speed of thermal energy. We recently proposed a one-dimensional model in which the electrical-thermal coupled problem was analytically solved by using a hyperbolic heat transfer equation (HHTE), i.e. by considering a non zero thermal relaxation time. In this study, we particularized this solution to three typical examples of RF heating of biological tissues: heating of the cornea for refractive surgery, cardiac ablation for eliminating arrhythmias, and hepatic ablation for destroying tumors. A comparison was made of the PHTE and HHTE solutions. The differences between their temperature profiles were found to be higher for lower times and shorter distances from the electrode surface. Our results therefore suggest that HHTE should be considered for RF heating of the cornea (which requires very small electrodes and a heating time of 0.6 s), and for rapid ablations in cardiac tissue (less than 30 s).