[Suicide risk after bariatric surgery]. / Suicidio y cirugía bariátrica: un estudio de la evidencia.

Bariatric surgery is considered the most effective treatment for severe obesity and its benefits include improvement in medical comorbidities. However, a higher rate of suicides after this type of surgery has been reported. We performed a literature review on the subject, and concluded that the mentioned increase in suicide rates, compared to the general population, is probably caused by conditions that the patient had before surgery, especially psychiatric disorders such as depression or eating disorders. These are risk factors for suicide, and are more common in the population with indication for bariatric surgery. Therefore, it is necessary to thoroughly evaluate these patients before surgery searching for suicide risk factors, deriving them to a mental health professional if necessary and follow their mental health after surgery. Considering that the literature on the topic is inconsistent, further research is needed.

Quaternary origin and genetic divergence of the endemic cactus Mammillaria pectinifera in a changing landscape in the Tehuacán Valley, Mexico.

The endemic Mexican cactus, Mammillaria pectinifera, shows low dispersal capabilities and isolated populations within the highly dissected landscape of Tehuacán Valley. These characteristics can restrict gene flow and act upon the genetic divergence and speciation in arid plants. We conducted a phylogeographic study to determine if the origin, current distribution, and genetic structure of M. pectinifera were driven by Quaternary geomorphic processes. Sequences of the plastids psbA-trnH and trnT-trnL obtained from 66 individuals from seven populations were used to estimate genetic diversity. Population differentiation was assessed by an analysis of molecular variance. We applied a stepwise phylogenetic calibration test to determine whether species origin and genetic divergence among haplotypes were temporally concordant with recognizable episodes of geomorphic evolution. The combination of plastid markers yielded six haplotypes, with high levels of haplotype diversity (h = 0.622) and low nucleotide diversity (π = 0.00085). The populations were found to be genetically structured (F(ST) = 0.682; P < 0.00001), indicating that geographic isolation and limited dispersal were the primary causes of genetic population differentiation. The estimated origin and divergence time among haplotypes were 0.017-2.39 and 0.019-1.237 mya, respectively, which correlates with Pleistocene tectonics and erosion events, supporting a hypothesis of geomorphically-driven geographical isolation. Based on a Bayesian skyline plot, these populations showed long term demographic stability, indicating that persistence in confined habitats has been the main response of this species to landscape changes. We conclude that the origin and haplotype divergence of M. pectinifera were a response to local Quaternary geomorphic evolution.

A family of three mouse potassium channel genes with intronless coding regions.

To understand the molecular mechanisms responsible for generating physiologically diverse potassium channels in mammalian cells, mouse genomic clones have been isolated with a potassium channel complementary DNA, MBK1, that is homologous to the Drosophila potassium channel gene, Shaker. A family of three closely related potassium channel genes (MK1, MK2, and MK3) that are encoded at distinct genomic loci has been isolated. Sequence analysis reveals that the coding region of each of these three genes exists as a single uninterrupted exon in the mouse genome. This organization precludes the generation of multiple forms of the protein by alternative RNA splicing, a mechanism known to characterize the Drosophila potassium channel genes Shaker and Shab. Thus, mammals may use a different strategy for generating diverse K+ channels by encoding related genes at multiple distinct genomic loci, each of which produces only a single protein.

Conversion of a tumor-binding peptide identified by phage display to a functional chimeric T cell antigen receptor.

Adoptive transfer of ex vivo expanded tumor-specific T cells is a promising therapeutic modality for promoting or augmenting antitumor immunity. Several groups, including ours, are developing antigen receptor gene transfer strategies as a means of generating effector cells for adoptive therapy. Chimeric antigen receptors (CARs) have been described that use single-chain antibodies or cytokine ligands as tumor targeting domains. Here, we describe the capacity of a tumor-binding peptide identified by phage display combinatorial library screening to serve as a CAR targeting domain. A phage library-selected high-affinity 12-mer peptide (Bpep) specific for alpha(v) beta(6) integrin (alpha v beta6) was chosen for these studies. Primary human T cells were genetically modified to express the Bpep-CAR consisting of an alpha v beta6-specific peptide and human IgG4 hinge-Fc extracellular domain fused to the cytoplasmic tail of CD3-zeta. T cell expression of the Bpep-CAR was assessed by Western blot analysis, and trafficking of the Bpep-CAR to the cell surface was demonstrated by flow cytometry. Functionally, Bpep-CAR redirected cytotoxic T lymphocytes specifically kill integrin alpha v beta6+ ovarian tumor targets, and are activated for interferon gamma secretion. Our data suggest that large new repertoires of tumor-specific T cell antigen receptor transgenes might be available through merging combinatorial peptide libraries with CAR construct design.

Transgene-enforced co-stimulation of CD4+ T cells leads to enhanced and sustained anti-tumor effector functioning.

Background The role of co-stimulation in CD4+ T cell activation by professional APC is well established, while less is known of the role co-stimulation plays when CD4+ T cells interact directly with tumor cells. Methods Through genetic engineering of human CD4+ T cells, we tested the hypothesis that integration of co-stimulatory signaling domains within a tumor-targeting chimeric Ag receptor (CAR), the IL-13Ralpha2-specific IL-13-zetakine (IL13zeta), would enhance CD4+ T cell mediated responses against tumors that fail to express ligands for co-stimulatory receptors. Results Compared with CD3zeta-mediated activation alone, CD4+ effector T cells expressing the IL13-CD28-41BBzeta CAR exhibited augmented/sustained MAPK and AKT activity, up-regulated Th1 cytokine production, and enhanced cytolytic potency against tumor targets. Moreover, upon recursive stimulation with tumor, the IL13-CD28-41BBzeta+ cells retained/recycled their lytic function, whereas IL-13zeta+ CD4+ cells became anergic/exhausted. These in vitro observations correlated with enhanced in vivo control of established orthotopic CNS glioma xenografts in immunodeficient mice mediated by adoptively transferred ex vivo-expanded CD4+ T cells expressing the co-stimulatory CAR. Discussion Together these studies demonstrate the importance of integrating co-stimulation with CD3zeta signaling events to activate fully CD4+ anti-tumor effector cells for sustained function in the tumor microenvironment.

Accuracy comparison of several common implicit solvent models and their implementations in the context of protein-ligand binding.

In this study several commonly used implicit solvent models are compared with respect to their accuracy of estimating solvation energies of small molecules and proteins, as well as desolvation penalty in protein-ligand binding. The test set consists of 19 small proteins, 104 small molecules, and 15 protein-ligand complexes. We compared predicted hydration energies of small molecules with their experimental values; the results of the solvation and desolvation energy calculations for small molecules, proteins and protein-ligand complexes in water were also compared with Thermodynamic Integration calculations based on TIP3P water model and Amber12 force field. The following implicit solvent (water) models considered here are: PCM (Polarized Continuum Model implemented in DISOLV and MCBHSOLV programs), GB (Generalized Born method implemented in DISOLV program, S-GB, and GBNSR6 stand-alone version), COSMO (COnductor-like Screening Model implemented in the DISOLV program and the MOPAC package) and the Poisson-Boltzmann model (implemented in the APBS program). Different parameterizations of the molecules were examined: we compared MMFF94 force field, Amber12 force field and the quantum-chemical semi-empirical PM7 method implemented in the MOPAC package. For small molecules, all of the implicit solvent models tested here yield high correlation coefficients (0.87-0.93) between the calculated solvation energies and the experimental values of hydration energies. For small molecules high correlation (0.82-0.97) with the explicit solvent energies is seen as well. On the other hand, estimated protein solvation energies and protein-ligand binding desolvation energies show substantial discrepancy (up to 10kcal/mol) with the explicit solvent reference. The correlation of polar protein solvation energies and protein-ligand desolvation energies with the corresponding explicit solvent results is 0.65-0.99 and 0.76-0.96 respectively, though this difference in correlations is caused more by different parameterization and less by methods and indicates the need for further improvement of implicit solvent models parameterization. Within the same parameterization, various implicit methods give practically the same correlation with results obtained in explicit solvent model for ligands and proteins: e.g. correlation values of polar ligand solvation energies and the corresponding energies in the frame of explicit solvent were 0.953-0.966 for the APBS program, the GBNSR6 program and all models used in the DISOLV program. The DISOLV program proved to be on a par with the other used programs in the case of proteins and ligands solvation energy calculation. However, the solution of the Poisson-Boltzmann equation (APBS program) and Generalized Born method (implemented in the GBNSR6 program) proved to be the most accurate in calculating the desolvation energies of complexes.

Inhibition of TGFBIp expression reduces lymphangiogenesis and tumor metastasis.

Transforming growth factor-ß-induced protein (TGFBIp) is an extracellular matrix protein that has a role in a wide range of pathological conditions. However, the role of TGFBIp signaling in lymphangiogenesis is poorly understood. The purpose of this study was therefore to analyze the effects of TGFBIp on lymphangiogenesis and determine whether TGFBIp-related lymphangiogenesis is important for the metastasis of tumor cells. TGFBIp increased adhesion, migration, and morphologic differentiation of human lymphatic endothelial cells (LECs), consistent with an increase in lymphatic vessel sprouting in a three-dimensional lymphatic ring assay. TGFBIp also induced phosphorylation of intracellular signaling molecules SRC, FAK, AKT, JNK and ERK. TGFBIp-induced lymphatic vessel sprouting was inhibited by addition of anti-integrin ß3 antibody and pharmacologic inhibitors of FAK, AKT, JNK or ERK. TGFBIp increased both CCL21 expression in LECs, a chemokine that actively recruits tumor cells expressing the cognate chemokine receptors to lymphatic vessels and LEC permeability by inducing the dissociation of VE-cadherin junctions between LECs via the activation of SRC signaling. In vivo, inhibition of TGFBIp expression in SW620 cancer cells dramatically reduced tumor lymphangiogenesis and metastasis. Collectively, our findings demonstrate that TGFBIp is a lymphangiogenic factor contributing to tumor dissemination and represents a potential target to inhibit metastasis.

Differences in the incidence of apoptosis between in vivo and in vitro produced blastocysts of farm animal species: a comparative study.

The occurrence of pregnancies and births after embryo transfer (ET) of in vivo produced embryos is generally more successful compared to that of embryos produced in vitro. This difference in ET success has been observed when embryos of morphological equal (high) quality were used. The incidence of apoptosis has been suggested as an additional criterion to morphological embryo evaluation in order to assess embryo quality and effectively predict embryo viability. In this study, equine, porcine, ovine, caprine and bovine in vivo and in vitro produced morphologically selected high quality (grade-I) blastocysts were compared for the occurrence of apoptosis in blastomeres. The total number of cells per embryo and the number of cells with damaged plasma membranes, fragmented DNA and fragmented nuclei per embryo were assessed in selected blastocysts by combining Ethidium homodimer (EthD-1), terminal dUTP nick end labeling (TUNEL) and Hoechst 33342 staining. In general, the level of blastomere apoptosis was low. A higher level of apoptosis was observed in in vitro produced equine, porcine and bovine blastocysts compared to their in vivo counterparts. Interestingly, 4 of the initially selected 29 bovine in vitro produced blastocysts exhibited extensive signs of apoptosis affecting the inner cell mass (ICM), which is not compatible with a viable conceptus. Repeated occurrence of this observation may explain the lower ET outcome of in vitro produced bovine embryos compared to in vivo produced embryos. It is concluded that, although in morphologically high quality blastocysts of several farm animal species a significant difference exists in the percentages of apoptotic cells between in vivo and in vitro produced embryos, the incidence of apoptosis at the blastocyst stage is at such a low level that it cannot reflect the substantial differences in embryo viability that have been described between in vivo and in vitro produced blastocysts following ET.

An efficient microtest to study adherence of bacteria to mammalian cells.

A simple, fast and highly reproducible microtest was developed for in vitro adherence studies. A rat epithelial cell line was investigated for the adherence of clinical and subclinical ovine and bovine Staphylococcus aureus strains isolated from mastitis. Staphylococcus aureus strains differed in their ability to adhere to epithelial cells, the degree of adherence being dependent on the concentration of bacteria used in the test.

Thermostable xylanases produced at 37 degrees C and 45 degrees C by a thermotolerant Aspergillus strain.

Differences between xylanases produced by Aspergillus FP-470 growing under normal (37 degrees C) and temperature stress conditions (45 degrees C) were evaluated. Fungal growth at 45 degrees C was seriously affected. However, the xylanase specific activity was 2.5 times higher than that produced at 37 degrees C. Optimum pH and temperature were 6.5, 80 degrees C and 4.3, 50 degrees C for the xylanases produced at 37 degrees C and 45 degrees C, respectively. Electrophoresis showed that a more complex xylanolytic system was produced at 37 degrees C. Stress induced by temperature produced a decrease in the number of extracellular xylanases released by fungi, but increased the production of some xylanases, possibly essential for growth under stress conditions.

Binding of a surface protein of Staphylococcus aureus to cultured ovine mammary gland epithelial cells.

Staphylococcus aureus is the most persistent pathogen causing ovine mastitis. This study investigated S. aureus binding to cultured epithelial cells obtained from the mammary gland. A staphylococcal 145kDa cell wall adhesin, originally isolated from a bovine mastitis strain, was detected in lysostaphin-solubilized ovine mastitis strains and in the encapsulated strain A. This adhesin was able to bind to cultured ovine mammary gland epithelial cells (MGEC) and to a rat intestinal epithelial cell line (RIE-1), exhibiting different electrophoretic mobilities that could be attributable to protein polymorphism. Inhibition assays using antibodies against 145kDa adhesin and against whole bacteria showed the specificity of the binding to cells. The role of this protein in adherence was assessed by adherence inhibition tests carried out in vitro with radiolabeled bacteria and cultured epithelial cells. Preincubation of bacteria with antibodies against adhesin 145kDa or against strain c195 resulted in a statistically significant decrease of adherence. These experiments suggest that adherence of S. aureus to MGEC may be critical for colonization.

Effect of slime on adherence of Staphylococcus aureus isolated from bovine and ovine mastitis.

The interactions between slime, Staphylococcus aureus and ovine mammary gland epithelial cells (MGEC) were studied in vitro. Suspensions of radiolabelled bacteria incubated with slime significantly increased the ability of S. aureus strains to adhere to a filter. When suspensions of radiolabelled bacteria were incubated with MGEC treated with trypsin, the ability of slime to improve S. aureus adherence was also shown, indicating that it was not dependent on cell membrane proteins. The interaction of radiolabelled bacteria with slime prior to the adherence test with MGEC demonstrated that the adherence process requires the interaction between slime and bacteria. This interaction is inhibited by anti-slime antibodies. This study provides evidence that a specific interaction between bacteria coated with slime and MGEC could be a critical part of mammary gland infection.

Factors influencing the degree of in vitro bacterial adhesion to ovine mammary gland epithelial cells.

Bacterial adhesion to mammary gland epithelial cells (EC) may play a role in the pathogenesis of mastitis. In vitro adherence systems have been developed to study mastitis in cattle but little has been done in sheep. In this work, a method is described for obtaining mammary gland cell preparations containing greater than or equal to 65% EC from live or dead ewes, using a Ficoll-Hypaque flotation method (cell viability = 70-90%). An in vitro adhesion assay procedure was also developed to study the interaction between EC and ovine mastitis bacterial strains. It was observed that, under the test conditions, adherence increased as the incubation time was prolonged from 30 to 120 min (P less than 0.05). Adhesion was greater at incubation temperature of 37 degrees C than at 22 degrees C (P less than 0.001). An acidic pH (5.9) was associated with an increase in adhesion, when compared with a higher pH (7.2; P less than 0.05). Tween 20, Tween 80 and bovine serum albumin helped to eliminate a background of unbound bacteria from the test slides, but they also inhibited adhesion to some strains. Strain differences in adhesion and in ability to form a background were also observed. Some of these findings may have in vivo implications.

Adherence of ruminant mastitis Staphylococcus aureus strains to epithelial cells from ovine mammary gland primary cultures and from a rat intestinal cell line.

Staphylococcus aureus isolated from mastitis (14 bovine and 11 ovine strains) exhibited an ability to adhere to epithelial primary cultures from ovine mammary gland and to a rat epithelial cell line, RIE-1. Strain differences in the degree of adherence were observed in both cases. These differences were maintained when comparing different epithelial sources (rat vs. ovine). RIE-1 cells can thus be used as a model for studying staphylococcal adherence to epithelial cells. Changes in bacterial adherence were observed according to the bacterial growth phase. The magnitude of these changes differed among strains. Bacterial cell surface hydrophobicity was not related to the degree of adherence to mammalian epithelial cells.

Enhancement of resistance in mice treated with Lactobacillus casei: effect on Trichinella spiralis infection.

The ability of viable Lactobacillus casei, administered by an intraperitoneal route, to induce resistance in mice against Trichinella spiralis infection was tested. The percent reduction of adult worms in the intestine 5 days after T. spiralis infection observed in L. casei-treated animals, compared with those of the control group, fluctuated between 70.9 and 88.5%; reductions of larvae per gram of muscle tissue, evaluated at 30 days after infection, varied from 46.6 to 84.4% in L. casei-treated mice compared with controls. At 5 days after infection, intestinal villus height was shorter in T. spiralis-infected animals than in L. casei-treated or uninfected mice. There were fewer mast cells/crypt unit in L. casei-treated and uninfected mice than in T. spiralis-infected animals. Lactobacilli-treated mice showed twice as many mononuclear cells/crypt unit as T. spiralis-infected animals. The IFN-gamma serum level was higher in L. casei-treated animals at the time of worm challenge as compared with T. spiralis-infected or uninfected mice. The results indicate that: (1) L. casei increased resistance that acted against T. spiralis infection in mice, (2) this resistance apparently was directed against adult worms in the intestine.

Relationship quality of aggressive children and their siblings: a multiinformant, multimeasure investigation.

Sibling influence on the learning and enactment of aggressive behavior has been consistently demonstrated in studies of sibling relationships. Available evidence suggests that, compared with nonaggressive children's sibling interactions, the sibling interactions of aggressive children are marked by more frequent, intense, and prolonged aggressive behaviors. Although research on normative and aggressive children's sibling interactions has increased recently, a number of limitations in this literature were addressed in this study by: (1) including both an aggressive and nonaggressive comparison group, (2) examining both positive and negative features of sibling relationships, (3) employing a multimethod/multiinformant approach to data collection, and (4) utilizing an improved self-report method. In support of our hypotheses and consistent with previous research, results showed that aggressive children's sibling relationships were marked by higher levels of observed conflict and lower levels of self-reported positive features. When gender was examined, results showed that older brother/younger sister dyads were characterized by higher levels of negative features and lower levels of positive features.

Suicidio y cirugía bariátrica: un estudio de la evidencia / Suicide risk after bariatric surgery

Bariatric surgery is considered the most effective treatment for severe obesity and its benefits include improvement in medical comorbidities. However, a higher rate of suicides after this type of surgery has been reported. We performed a literature review on the subject, and concluded that the mentioned increase in suicide rates, compared to the general population, is probably caused by conditions that the patient had before surgery, especially psychiatric disorders such as depression or eating disorders. These are risk factors for suicide, and are more common in the population with indication for bariatric surgery. Therefore, it is necessary to thoroughly evaluate these patients before surgery searching for suicide risk factors, deriving them to a mental health professional if necessary and follow their mental health after surgery. Considering that the literature on the topic is inconsistent, further research is needed.

Phyllodes tumor of the prostate.

A 67-year-old man presented with gross hematuria. Magnetic resonance imaging showed a 900-mL cystic mass, in continuity to the basal left side of the prostate, that laterally compressed the bladder. The patient underwent tumor resection, and the histologic diagnosis was benign cystic Phyllodes tumor of the prostate. Phyllodes tumor of the prostate is a rare tumor composed of hyperplastic and neoplastic glandular-stromal proliferation. The tumor grade has an effect on the prognosis, although if not completely resected, even low-grade tumors can recur, metastasize, or differentiate into sarcoma.

Trastorno esquizoafectivo: ¿Cuánto de esquizofrenia? ¿Cuánto de bipolar? / Schizoaffective disorder: How much belongs to schizophrenia? How much belongs to bipolar disorder?

Introduction: Schizoaffective Disorder represents a controversial clinical entity, in regard to nosology and classification criteria. It has been considered as a variant of Schizophrenia, as a mixed entity between Schizophrenia and Bipolar Disorder and as a Bipolar Disorder subtype Method: Classificatory, clinical issues, neuropsychology and genetics research contributions are reviewed. Discussion and Conclusion: Schizoaffective Disorder concept at present time, differs from its original description, maintaining lack of definitive clarity with respect to its nosology. Considering neurocognitive impairment within its course, Schizoaffective Disorder looks much closer to affective psychosis than to Schizophrenia. From genetic research field emerges data that challenge the classic dichotomist distinction between affective psychosis and Schizophrenia established by E. Kraepelin, raising again the question about thinking in psychosis as a continuum in which Schizoaffective Disorder could represent an intermediate state...

Introducción: El Trastorno Esquizoafectivo constituye un área de controversias respecto a su nosología y criterios para su clasificación. Ha sido considerado como una variante de la Esquizofrenia, un cuadro mixto en el cual coexisten la Esquizofrenia y el Trastorno Bipolar y como un subtipo del Trastorno Bipolar. Método: Se revisan aspectos diagnósticos, clasificatorios y características psicopatológicas del trastorno en su concepción actual y aportes desde la perspectiva de la investigación neuropsicológica y la genética. Discusión y Conclusiones: El concepto actual de Trastorno Esquizoafectivo, difiere de su descripción original manteniéndose la falta de claridad definitiva respecto a su nosología. Tomando en consideración las alteraciones neurocognitivas que acompañan su evolución, el Trastorno Esquizoafectivo guardaría una mayor afinidad con las psicosis afectivas que con la Esquizofrenia. Desde la investigación genética surgen datos que cuestionan la distinción dicotómica clásica entre las psicosis afectivas y la Esquizofrenia establecida por E. Kraepelin, replanteándose la formulación de la psicosis en un continuum del cual el Trastorno Esquizoafectivo podría representar un estadio intermedio...

Comparación de valores de temperatura obtenidos con termómetro ótico digital y con termómetros axilar y rectal de mercurio en menores de 5 años / Comparison of body temperature measurements obtained with otic digital thermometer and mercury axillary and rectal thermometers in children under the age of five

Introducción: En los últimos años han aparecido nuevos métodos para medir la temperatura en niños, como el termómetro digital ótico. Siendo este un método más rápido para medir la temperatura y por lo tanto ideal para el servicio de urgencias, es necesario conocer su confiabilidad. Objetivo: Comparar los valores de temperatura corporal que entrega el termómetro ótico digital con los termómetros de mercurio axilar y rectal. Pacientes y Método: Se efectuó la medición de la temperatura en 50 pacientes menores de 5 años elegidos al azar, que consultaron en el Servicio de Urgencia del Hospital de Niños y Cunas de Viña del Mar. Se les midió la temperatura con un termómetro digital ótico al lado izquierdo y derecho, y las temperaturas axilar derecha y rectal con termómetros de mercurio. EL análisis de los resultados se efectuó en el grupo estudiado, separado en dos grupos, menores y mayores de 6 meses. Resultados: Los resultados entre ambos subgrupos fueron los mismos. La temperatura media rectal obtenida fue 0,414°C más alta que la media ótica derecha (p < 0,001) y 0,438°C más alta que la temperatura media ótica izquierda (p < 0,001). Conclusión: El termómetro ótico digital entrega una temperatura significativamente más baja que la que entregan los termómetros de mercurio axilar y rectal.

Background: In recent years, otic thermometers to measure body temperature in children have become increasingly popular as they reflect changes in body temperature sooner than other thermometers. The have become valuable assets in hospital emergency rooms; however, their accuracy and reliability need further studies. Objective: To compare corporal temperature readings between an otic thermometer and mercury axillary and rectal thermometers. Patients and Method: 50 patients under the age of 5, who were treated at the emergency room of our hospital, were randomly chosen to participate in this study. Temperature was measured on their right and left ears using an otic thermometer, and their rectal and right axillary temperature was taken using mercury thermometers. Patients were separated into 2 subgroups for comparison, children under and over 6 months old. Results: The results between the 2 subgroups were very similar. The average temperature obtained by rectal thermometers was 0.414°C higher than the average right-ear temperature (p < 0.001) and 0.438°c higher than the average left-ear temperature (p < 0.001). Conclusion: The otic thermometer's reading is significantly lower than the one obtained using mercury rectal and axillary thermometers.