Systematic review of existing literature regarding the prevalence of pediatric atopic dermatitis in Honduras.

Background: Atopic dermatitis (AD) is an inflammatory skin condition, often multifactorial in origin, and most commonly manifests during childhood. Although there remains a deficit in literature, current data suggest Honduras may have the highest prevalence and severity of AD among all Latin American countries. Objective: To assess the current prevalence of pediatric AD in Honduras and evaluate existing gaps in available literature to monitor disease burden. Methods: A comprehensive literature search was performed in March 2023. Articles were removed if they were published before 2007, were of the incorrect study design, or were focused on countries outside of Honduras. The articles were independently reviewed by 2 authors. Results: The initial literature search yielded 174 studies, of which 7 met inclusion criteria. AD prevalence rates in children in Honduras ranged from 0.7% to 40.0%. Limitations: Limitations include elements of study design, analytic methods, study populations, and limited articles. Conclusion: There appears to be a disproportionately higher prevalence and disease burden of pediatric AD in Honduras. Future research should acquire accurate data to further understand the prevalence, incidence, and severity of AD in Honduras.

Analysis of Diffusion Coefficients of Iron Monoboride and Diiron Boride Coating Formed on the Surface of AISI 420 Steel by Two Different Models: Experiments and Modelling.

In the present work, two mathematical diffusion models have been used to estimate the growth of the iron monoboride and diiron boride coating formed on AISI 420 steel. The boronizing of the steel was carried out with the solid diffusion packing method at a boronizing temperature of 1123 K-1273 K. Experimental results show the two-coating system consists of an outer monoboride and an inner diiron boride coating with a predominantly planar structure at the propagation front. The depth of the boride coating increases according to temperature and treatment time. A parabolic curve characterizes the propagation of the boride coatings. The two proposed mathematical models of mass transfer diffusion are founded on the solution corresponding to Fick's second fundamental law. The first is based on a linear boron concentration-penetration profile without time dependence, and the second model with time dependence (exact solution). For both models, the theoretical law of parabolic propagation and the average flux of boron atoms (Fick's first fundamental law) at the growth interfaces (monoboride/diiron boride and diiron boride/substrate) are considered to estimate the propagation of the boride coatings (monoboride and diiron boride). To validate the mathematical models, a programming code is written in the MATLAB program (adaptation 7.5) designed to simulate the growth of the boride coatings (monoboride and diiron boride). The following parameters are used as input data for this computer code: (the layer thicknesses of the FeB and Fe2B phases, the operating temperature, the boronizing time, initial formation time of the boride coating, the surface boron concentration limits, FeB/Fe2B and Fe2B/Fe growth interfaces, and the mass transfer diffusion coefficient of boron in the iron monoboride and diiron boride phases). The outputs of the computer code are the constants εFeB and εFe2B. The assessment of activation energies of AISI 420 steel for the two mathematical models of mass transfer is coincident (QFeB=221.9 kJ∙mol-1 and QFe2B=209.1 kJ∙mol-1). A numerical analysis was performed using a standard Taylor series for clarification of the proximity between the two models. SEM micrographs exhibited a strong propensity toward a flat-fronted composition at expansion interfaces of the iron monoboride and diiron boride coating, confirmed by XRD analysis. Tribological characterizations included the Vickers hardness test method, pin-on-disc, and Daimler-Benz Rockwell-C indentation adhesion tests. After thorough analysis, the energies were compared to the existing literature to validate our experiment. We found that our models and experimental results agreed. The diffusion models we utilized were crucial in gaining a deeper understanding of the boronizing behavior of AISI 420 steel, and they also allowed us to predict the thicknesses of the iron monoboride and diiron boride coating. These models provide helpful approaches for predicting the behavior of these steels.

Stalking Victimization and Emotional Consequences: A Cross-Cultural Comparison Between American and Spanish University Students.

This paper entails a comparative study between a country that has criminalized stalking for almost three decades (the U.S.) and a nation that just recently outlawed the phenomenon (Spain). Employing a sample of American and Spanish university students, we examined the prevalence and types of stalking behaviors and victims' emotional responses to their victimization. We also explored whether experiencing a particular category of stalking behaviors (i.e., surveillance and approach stalking) triggers specific emotional responses similarly among American and Spanish victims. We found more than two-thirds (36%) of the Spanish students (n = 638) and almost half (48%) of the American students (n = 411) reported that they have experienced the unwanted or intrusive behaviors included in our study. We also found relative to Spanish victims, American victims were significantly more likely to encounter approach stalking and report feeling anxious, angry, depressed, sick, and suicidal as a result of their victimization. Implications of our findings and directions for future research are discussed.

Estrategias de afrontamiento formales en victimización por stalking: factores asociados a la denuncia policial / Formal coping strategies for victims of stalking: Factors associated with reporting to the police

Introducción: La tasa de denuncia policial del delito de acecho en España es baja. El presente trabajo pretende conocer qué factores influyen en la decisión de denunciar el hecho victimizante a instancias policiales, así como conocer los motivos de no denuncia. Material y métodos: Un total de 1.773 estudiantes universitarios españoles (71,9% mujeres y 27,4% varones; media de edad 21,35 años; DS=4,493) cumplimentaron una encuesta de victimización de conductas de acecho con el objetivo de conocer la tasa de prevalencia de victimización por acecho, la gravedad del comportamiento y la probabilidad de denuncia. Resultados: Seiscientos treinta y ocho estudiantes (35,6%) indicaron haber sido víctimas de acecho alguna vez en su vida (79,5% mujeres, media de edad=21,85; DS=5,340). Únicamente 35 víctimas (5,5%) denunció los hechos a la policía. El hecho de ser mujer, recibir amenazas con dañar a terceros, así como amenazas directas fueron las variables que más relación guardaban con denunciar la situación. En relación con aquellas víctimas que no denunciaron los hechos (386) más de la mitad lo justifican por pensar que la situación no era lo suficientemente importante como para poner en conocimiento a la policía. Conclusiones: El acecho es un fenómeno prevalente, no obstante, la tasa de denuncia a instancias policiales es baja. La gravedad de las conductas experimentadas incrementa la probabilidad de denuncia. En este sentido, es necesaria una concienciación previa sobre el fenómeno del acecho, para prevenir conductas graves y potenciar la visibilidad de este delito. (AU)

Introduction: The rate of reporting the crime of stalking to the police in Spain is low. The present study aims to determine the factors that influence the decision to report the victimizing event to the police, as well as the reasons for non-reporting. Methods: A total of 1,773 Spanish university students (71.9% female and 27.4% male; mean age 21.35 years; SD=4.493) completed a stalking victimization survey to determine the prevalence rate of stalking victimization, the severity of the behaviour and the likelihood of reporting. Results: 638 students (35.6%) reported having been victims of stalking at some time in their lives (79.5% female, mean age=21.85, SD=5.340). Only 35 victims (5.5%) reported the incident to the police. Being a woman, receiving threats of harm to third parties, as well as direct threats were the variables most related to reporting the situation. Of the victims who did not report the events (386), more than half considered that the situation was not important enough to report to the police. Conclusions: Stalking is a prevalent phenomenon, however, the rate of reporting to the police is low. The severity of the behaviours experienced increases the likelihood of reporting. Therefore, it is necessary to raise awareness of the phenomenon of stalking to prevent serious behaviours and enhance the visibility of this crime. (AU)

Retos forenses ante la cibercriminalidad social en menores / Forensic challenges presented by social cybercrime in minors

Hoy en día las TIC forman parte de las actividades cotidianas de gran parte de la población a nivel mundial. Los procesos de socialización de los menores y jóvenes a través de las TIC han suscitado una creciente atención y preocupación por parte de la comunidad científica y educativa. Muchas de las conductas que se llevan a cabo en el mundo físico se han trasladado al ciberespacio, dando paso a «nuevos» comportamientos y oportunidades delictivas, así como a procesos de victimización en parte distintos. En este nuevo contexto han emergido 3 fenómenos prevalentes de cibercriminalidad social ante los que se plantean nuevos retos forenses. En el presente artículo se llama la atención respecto de las consecuencias psicopatológicas de estos 3 fenómenos: cyberbullying, sexting y online grooming, y se pone de manifiesto la necesidad de contar con profesionales en el ámbito de las ciencias forenses que estén formados en los entornos tecnológicos en los que tienen lugar las nuevas formas de criminalidad. Y se abren nuevas perspectivas de mejora en las evaluaciones periciales por parte de expertos forenses de las consecuencias victimológicas y de los perfiles de quienes intervienen en los nuevos ciberdelitos

Nowadays, ICTs have become part of people's daily routines. Attention has been drawn to the way in which teenagers and young adults socialize through ICTs, especially in the scientific and educational communities. Many behaviours undertaken in the physical world have transferred to cyberspace including criminal behaviours and victimization processes. In this new context, there are three prevalent cybercriminal phenomena that pose forensic challenges. Throughout this paper, the psychopathological consequences of cyberbullying, sexting and online grooming will be analyzed. The growth of these types of behaviour has necessitated well-trained professionals from multidisciplinary forensic sciences, who are able to evaluate the victimological consequences and offenders' profile of the abovementioned phenomena

Axl-mediated activation of TBK1 drives epithelial plasticity in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is characterized by an activating mutation in KRAS. Direct inhibition of KRAS through pharmacological means remains a challenge; however, targeting key KRAS effectors has therapeutic potential. We investigated the contribution of TANK-binding kinase 1 (TBK1), a critical downstream effector of mutant active KRAS, to PDA progression. We report that TBK1 supports the growth and metastasis of KRAS-mutant PDA by driving an epithelial plasticity program in tumor cells that enhances invasive and metastatic capacity. Further, we identify that the receptor tyrosine kinase Axl induces TBK1 activity in a Ras-RalB-dependent manner. These findings demonstrate that TBK1 is central to an Axl-driven epithelial-mesenchymal transition in KRAS-mutant PDA and suggest that interruption of the Axl-TBK1 signaling cascade above or below KRAS has potential therapeutic efficacy in this recalcitrant disease.

Heterophilic antibodies in sera from individuals without loxoscelism cross-react with phospholipase D from the venom of Loxosceles and Sicarius spiders.

BACKGROUND: Loxoscelism is a severe human envenomation caused by Loxosceles spider venom. To the best of our knowledge, no study has evaluated the presence of antibodies against Loxosceles venom in loxoscelism patients without treatment with antivenom immunotherapy. We perform a comparative analysis for the presence of antibodies capable of recognizing Loxosceles venom in a group of patients diagnosed with loxoscelism and in a group of people without loxoscelism. METHODS: The detection of L. laeta venom, Sicarius venom and recombinant phospholipases D from Loxosceles (PLDs) in sera from people with loxoscelism (Group 1) and from healthy people with no history of loxoscelism (Group 2) was evaluated using immuno-dot blot, indirect ELISA, and Western blot. RESULTS: We found naturally heterophilic antibodies (IgG-type) in people without contact with Loxosceles spiders or any clinical history of loxoscelism. Either serum pools or single sera from Group 1 and Group 2 analyzed by dot blot tested positive for L. laeta venom. Indirect ELISA for venom recognition showed titles of 1:320 for Group 1 sera and 1:160 for Group 2 sera. Total IgG quantification showed no difference in sera from both groups. Pooled sera and purified IgG from sera of both groups revealed venom proteins between 25 and 32 kDa and the recombinant phospholipase D isoform 1 (rLlPLD1), specifically. Moreover, heterophile antibodies cross-react with PLDs from other Loxosceles species and the venom of Sicarius spider. CONCLUSIONS: People without contact with the spider venom produced heterophilic antibodies capable of generating a cross-reaction against the venom of L. laeta and Sicarius spiders. Their presence and possible interference should be considered in the development of immunoassays for Loxosceles venom detection.

Loss of Tbk1 kinase activity protects mice from diet-induced metabolic dysfunction.

OBJECTIVE: TANK Binding Kinase 1 (TBK1) has been implicated in the regulation of metabolism through studies with the drug amlexanox, an inhibitor of the IκB kinase (IKK)-related kinases. Amlexanox induced weight loss, reduced fatty liver and insulin resistance in high fat diet (HFD) fed mice and has now progressed into clinical testing for the treatment and prevention of obesity and type 2 diabetes. However, since amlexanox is a dual IKKε/TBK1 inhibitor, the specific metabolic contribution of TBK1 is not clear. METHODS: To distinguish metabolic functions unique to TBK1, we examined the metabolic profile of global Tbk1 mutant mice challenged with an obesogenic diet and investigated potential mechanisms for the improved metabolic phenotype. RESULTS AND CONCLUSION: We report that systemic loss of TBK1 kinase function has an overall protective effect on metabolic readouts in mice on an obesogenic diet, which is mediated by loss of an inhibitory interaction between TBK1 and the insulin receptor.

Assessment of TANK-binding kinase 1 as a therapeutic target in cancer.

TANK-binding kinase 1 (TBK1) is central to multiple biological processes that promote tumorigenesis including cell division, autophagy, innate immune response and AKT-pro survival signaling. TBK1 is well studied and most known for its function in innate immunity. However, the serine threonine protein kinase received significant attention as a synthetic lethal partner and effector of the major oncogene, RAS. This review summarizes newly identified cancer promoting functions of TBK1 and evaluates the therapeutic potential of targeting TBK1 in cancer.

Small-Molecule Inhibition of Axl Targets Tumor Immune Suppression and Enhances Chemotherapy in Pancreatic Cancer.

Activation of the receptor tyrosine kinase Axl is associated with poor outcomes in pancreatic cancer (PDAC), where it coordinately mediates immune evasion and drug resistance. Here, we demonstrate that the selective Axl kinase inhibitor BGB324 targets the tumor-immune interface to blunt the aggressive traits of PDAC cells in vitro and enhance gemcitibine efficacy in vivo Axl signaling stimulates the TBK1-NFκB pathway and innate immune suppression in the tumor microenvironment. In tumor cells, BGB324 treatment drove epithelial differentiation, expression of nucleoside transporters affecting gemcitabine response, and an immune stimulatory microenvironment. Our results establish a preclinical mechanistic rationale for the clinical development of Axl inhibitors to improve the treatment of PDAC patients.Significance: These results establish a preclinical mechanistic rationale for the clinical development of AXL inhibitors to improve the treatment of PDAC patients. Cancer Res; 78(1); 246-55. ©2017 AACR.

Heterophilic antibodies in sera from individuals without loxoscelism cross-react with phospholipase D from the venom of Loxosceles and Sicarius spiders

Loxoscelism is a severe human envenomation caused by Loxosceles spider venom. To the best of our knowledge, no study has evaluated the presence of antibodies against Loxosceles venom in loxoscelism patients without treatment with antivenom immunotherapy. We perform a comparative analysis for the presence of antibodies capable of recognizing Loxosceles venom in a group of patients diagnosed with loxoscelism and in a group of people without loxoscelism. Methods The detection of L. laeta venom, Sicarius venom and recombinant phospholipases D from Loxosceles (PLDs) in sera from people with loxoscelism (Group 1) and from healthy people with no history of loxoscelism (Group 2) was evaluated using immuno-dot blot, indirect ELISA, and Western blot. Results We found naturally heterophilic antibodies (IgG-type) in people without contact with Loxosceles spiders or any clinical history of loxoscelism. Either serum pools or single sera from Group 1 and Group 2 analyzed by dot blot tested positive for L. laeta venom. Indirect ELISA for venom recognition showed titles of 1:320 for Group 1 sera and 1:160 for Group 2 sera. Total IgG quantification showed no difference in sera from both groups. Pooled sera and purified IgG from sera of both groups revealed venom proteins between 25 and 32 kDa and the recombinant phospholipase D isoform 1 (rLlPLD1), specifically. Moreover, heterophile antibodies cross-react with PLDs from other Loxosceles species and the venom of Sicarius spider. Conclusions People without contact with the spider venom produced heterophilic antibodies capable of generating a cross-reaction against the venom of L. laeta and Sicarius spiders. Their presence and possible interference should be considered in the development of immunoassays for Loxosceles venom detection.(AU)

Heterophilic antibodies in sera from individuals without loxoscelism cross-react with phospholipase D from the venom of Loxosceles and Sicarius spiders

Background Loxoscelism is a severe human envenomation caused by Loxosceles spider venom. To the best of our knowledge, no study has evaluated the presence of antibodies against Loxosceles venom in loxoscelism patients without treatment with antivenom immunotherapy. We perform a comparative analysis for the presence of antibodies capable of recognizing Loxosceles venom in a group of patients diagnosed with loxoscelism and in a group of people without loxoscelism. Methods The detection of L. laeta venom, Sicarius venom and recombinant phospholipases D from Loxosceles (PLDs) in sera from people with loxoscelism (Group 1) and from healthy people with no history of loxoscelism (Group 2) was evaluated using immuno-dot blot, indirect ELISA, and Western blot. Results We found naturally heterophilic antibodies (IgG-type) in people without contact with Loxosceles spiders or any clinical history of loxoscelism. Either serum pools or single sera from Group 1 and Group 2 analyzed by dot blot tested positive for L. laeta venom. Indirect ELISA for venom recognition showed titles of 1:320 for Group 1 sera and 1:160 for Group 2 sera. Total IgG quantification showed no difference in sera from both groups. Pooled sera and purified IgG from sera of both groups revealed venom proteins between 25 and 32 kDa and the recombinant phospholipase D isoform 1 (rLlPLD1), specifically. Moreover, heterophile antibodies cross-react with PLDs from other Loxosceles species and the venom of Sicarius spider. Conclusions People without contact with the spider venom produced heterophilic antibodies capable of generating a cross-reaction against the venom of L. laeta and Sicarius spiders. Their presence and possible interference should be considered in the development of immunoassays for Loxosceles venom detection.

Conocimientos de fibromialgia en médicos de atención primaria de la provincia de Chiclayo-Perú, 2016 / Knowledge on fibromyalgia among general practitioners, from Chiclayo-Peru, 2016

Objetivo. Describir los conocimientos en fibromialgia de los médicos de atención primaria de la provincia de Chiclayo durante el 2016. Materiales y métodos. Estudio descriptivo transversal, con un muestreo no probabilístico, tipo censal. Se evaluaron 145 médicos mediante un cuestionario de 14 preguntas, validado por expertos y con una prueba piloto. El análisis univariado y bivariado se realizó con STATA v. 13. Resultados. El acierto en las preguntas de diagnóstico fue del 41,1% y en las de tratamiento, del 65%. El 75,1% «habían visto pacientes con fibromialgia», previamente. La media de puntos dolorosos acertados fue de 2,2±2,8. Solo el 2,8% identificaron de 11 a más puntos dolorosos; el 54,5% respondieron que «el diagnóstico es clínico y los exámenes son para el diagnóstico diferencial». El 46,1% de los médicos del Ministerio de Salud del Perú (MINSA) y el 28,3% de los del Seguro Social de Salud (EsSalud) respondieron correctamente el ítem de criterios diagnósticos (p=0,021). El 65,7% respondieron que la psicoterapia, la pregabalina y el ejercicio aeróbico eran la tríada terapéutica más eficaz, sin diferencias entre MINSA y EsSalud, con un 61,5 y 68,6%, respectivamente (p=0,23). El 59,3% respondieron que los fármacos con utilidad demostrada son: pregabalina, duloxetina y amitriptilina. El 66,2% respondieron que la terapia física más eficaz es el ejercicio aeróbico. Conclusiones. El conocimiento en diagnóstico y tratamiento de la fibromialgia en médicos generales de Chiclayo es deficiente. Existen algunas diferencias en el conocimiento según la edad y el tipo de institución a la que pertenecen (AU)

Objective. Knowledge about fibromyalgia in general practitioners in the province of Chiclayo, Peru, 2016. Materials and methods. Cross sectional descriptive study. Non-probability sampling, census type. In all, 145 physicians were evaluated through a questionnaire of 14 questions, validated by experts and a pilot. The analysis was performed using STATA v. 13. Results. Accuracy in questions involving diagnosis was 41.1% and in questions about treatment: 65%; 75.1% ‘had seen patients with fibromyalgia’ previously. The average on locating pain points was 2.2±2.8. Only 2.8% identified 11 or more painful points; 54.5% answered that ‘the diagnosis is clinical and exams are for the differential diagnosis’; 46.1% in Ministerio de Salud (MINSA) and 28.3% in Seguro Social de Salud (EsSalud) answered the item about diagnostic criteria (P=.021); 65.7% said that psychotherapy, pregabalin and aerobic exercise were the most effective therapeutic triad, with no differences between MINSA and EsSalud: 61.5% vs. 68.6% (P=.23); 59.3% responded that drugs that had proved to be useful were: Pregabalin, duloxetine and amitriptyline; 66.2% responded that the most effective physical therapy is aerobic exercise. Conclusions. Knowledge of the diagnosis and treatment of fibromyalgia by general doctors in Chiclayo is poor. There are some differences in knowledge depending on the age and type of institution to which each belongs (AU)

Knowledge on fibromyalgia among general practitioners, from Chiclayo-Peru, 2016. / Conocimientos de fibromialgia en médicos de atención primaria de la provincia de Chiclayo-Perú, 2016.

OBJECTIVE: Knowledge about fibromyalgia in general practitioners in the province of Chiclayo, Peru, 2016. MATERIALS AND METHODS: Cross sectional descriptive study. Non-probability sampling, census type. In all, 145 physicians were evaluated through a questionnaire of 14 questions, validated by experts and a pilot. The analysis was performed using STATA v. 13. RESULTS: Accuracy in questions involving diagnosis was 41.1% and in questions about treatment: 65%; 75.1% 'had seen patients with fibromyalgia' previously. The average on locating pain points was 2.2±2.8. Only 2.8% identified 11 or more painful points; 54.5% answered that 'the diagnosis is clinical and exams are for the differential diagnosis'; 46.1% in Ministerio de Salud (MINSA) and 28.3% in Seguro Social de Salud (EsSalud) answered the item about diagnostic criteria (P=.021); 65.7% said that psychotherapy, pregabalin and aerobic exercise were the most effective therapeutic triad, with no differences between MINSA and EsSalud: 61.5% vs. 68.6% (P=.23); 59.3% responded that drugs that had proved to be useful were: Pregabalin, duloxetine and amitriptyline; 66.2% responded that the most effective physical therapy is aerobic exercise. CONCLUSIONS: Knowledge of the diagnosis and treatment of fibromyalgia by general doctors in Chiclayo is poor. There are some differences in knowledge depending on the age and type of institution to which each belongs.

Inhibition by Seeds of Phalaris canariensis Extracts of Key Enzymes Linked to Obesity.

CONTEXT: Obesity and its associated diseases are an increasing problem around the world. One hyperglycemic remedy is reduction of glucose absorption performed by suppressing digestion of carbohydrates and lipids through the use of inhibitors. Phalaris canariensis (P canariensis) is a species belonging to the Graminaceae family and is used in traditional medicine in Mexico for treatment of diabetes and obesity. OBJECTIVE: The aim of the study was to evaluate the effects of different extracts of the seeds of P canariensis on enzymes metabolizing fat and carbohydrates, obtained using 3 solvents. DESIGN: The seeds of P canariensis were extracted using hexane (ALH), chloroform (ALC), and methanol (ALM) and were investigated for their antiobesity potential. SETTING: This research was conducted in the Laboratory of Research of Natural Products in the School of Chemical Engineering at the National Polytechnic Institute and in the Research Laboratory of Enzymology in the National School of Biological Sciences. OUTCOME MEASURES: Different concentrations of the extracts were used to study the inhibition of enzymatic activity by porcine pancreatic α-amylase, with carbose as a positive control. The inhibitory activity of α-glucosidase was determined using the standard method with bovine serum albumin (BSA). Pancreatic lipase (PL) activity was measured by absorbance at 412 nm, and the data obtained were compared with orlistat. The PL activity was assessed using a second method measuring the rate of release of oleic acid from triolein. Lipoprotein lipase (LPL) activity was measured by released (3H)-oleic acid. Lipolytic activity in cultured, mouse, 3T3-Ll adipocytes was used as a measure of hormone-sensitive lipase activity. The inhibitory activity of rat intestinal sucrase was determined by measuring the glucose released. A Caco-2 cell assay determined the content of free glucose. RESULTS: The ALH extract of P canariensis showed potent inhibitory activity with IC50 values of 2.13 and 1.25 mg/mL as compared with α-amylase and α-glucosidase, respectively, and produced inhibition in rat intestinal sucrose. Further, the ALM extract showed significantly inhibitory effects against PL, LPL, and lipolysis of 3T3-LI adipocytes. CONCLUSIONS: The results provide evidence for the effects of the seeds of P canariensis for a retarded absorption of carbohydrates and lipids through the inhibition of enzymes that are related to obesity and diabetes mellitus type 2.

Comprehensive Ex Vivo Transposon Mutagenesis Identifies Genes That Promote Growth Factor Independence and Leukemogenesis.

Aberrant signaling through cytokine receptors and their downstream signaling pathways is a major oncogenic mechanism underlying hematopoietic malignancies. To better understand how these pathways become pathologically activated and to potentially identify new drivers of hematopoietic cancers, we developed a high-throughput functional screening approach using ex vivo mutagenesis with the Sleeping Beauty transposon. We analyzed over 1,100 transposon-mutagenized pools of Ba/F3 cells, an IL3-dependent pro-B-cell line, which acquired cytokine independence and tumor-forming ability. Recurrent transposon insertions could be mapped to genes in the JAK/STAT and MAPK pathways, confirming the ability of this strategy to identify known oncogenic components of cytokine signaling pathways. In addition, recurrent insertions were identified in a large set of genes that have been found to be mutated in leukemia or associated with survival, but were not previously linked to the JAK/STAT or MAPK pathways nor shown to functionally contribute to leukemogenesis. Forced expression of these novel genes resulted in IL3-independent growth in vitro and tumorigenesis in vivo, validating this mutagenesis-based approach for identifying new genes that promote cytokine signaling and leukemogenesis. Therefore, our findings provide a broadly applicable approach for classifying functionally relevant genes in diverse malignancies and offer new insights into the impact of cytokine signaling on leukemia development.

A new reduced-order observer for the synchronization of nonlinear chaotic systems: An application to secure communications.

This paper deals with the master-slave synchronization scheme for partially known nonlinear chaotic systems, where the unknown dynamics is considered as the master system and we propose the slave system structure which estimates the unknown states. It introduced a new reduced order observer, using the concept of Algebraic Observability; we applied the results to a Sundarapandian chaotic system, and by means of some numerical simulations we show the effectiveness of the suggested approach. Finally, the proposed observer is utilized for encryption, where encryption key is the master system and decryption key is the slave system.

A rapid in vivo screen for pancreatic ductal adenocarcinoma therapeutics.

Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer-related deaths in the United States, and is projected to be second by 2025. It has the worst survival rate among all major cancers. Two pressing needs for extending life expectancy of affected individuals are the development of new approaches to identify improved therapeutics, addressed herein, and the identification of early markers. PDA advances through a complex series of intercellular and physiological interactions that drive cancer progression in response to organ stress, organ failure, malnutrition, and infiltrating immune and stromal cells. Candidate drugs identified in organ culture or cell-based screens must be validated in preclinical models such as KIC (p48(Cre);LSL-Kras(G12D);Cdkn2a(f/f)) mice, a genetically engineered model of PDA in which large aggressive tumors develop by 4 weeks of age. We report a rapid, systematic and robust in vivo screen for effective drug combinations to treat Kras-dependent PDA. Kras mutations occur early in tumor progression in over 90% of human PDA cases. Protein kinase and G-protein coupled receptor (GPCR) signaling activates Kras. Regulators of G-protein signaling (RGS) proteins are coincidence detectors that can be induced by multiple inputs to feedback-regulate GPCR signaling. We crossed Rgs16::GFP bacterial artificial chromosome (BAC) transgenic mice with KIC mice and show that the Rgs16::GFP transgene is a Kras(G12D)-dependent marker of all stages of PDA, and increases proportionally to tumor burden in KIC mice. RNA sequencing (RNA-Seq) analysis of cultured primary PDA cells reveals characteristics of embryonic progenitors of pancreatic ducts and endocrine cells, and extraordinarily high expression of the receptor tyrosine kinase Axl, an emerging cancer drug target. In proof-of-principle drug screens, we find that weanling KIC mice with PDA treated for 2 weeks with gemcitabine (with or without Abraxane) plus inhibitors of Axl signaling (warfarin and BGB324) have fewer tumor initiation sites and reduced tumor size compared with the standard-of-care treatment. Rgs16::GFP is therefore an in vivo reporter of PDA progression and sensitivity to new chemotherapeutic drug regimens such as Axl-targeted agents. This screening strategy can potentially be applied to identify improved therapeutics for other cancers.

Ameliorative Effect of Hexane Extract of Phalaris canariensis on High Fat Diet-Induced Obese and Streptozotocin-Induced Diabetic Mice.

Obesity is one of the major factors to increase various disorders like diabetes. The present paper emphasizes study related to the antiobesity effect of Phalaris canariensis seeds hexane extract (Al-H) in high-fat diet- (HFD-) induced obese CD1 mice and in streptozotocin-induced mild diabetic (MD) and severely diabetic (SD) mice.AL-H was orally administered to MD and SD mice at a dose of 400 mg/kg once a day for 30 days, and a set of biochemical parameters were studied: glucose, cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, ALP, SGOT, SGPT, glucose-6-phosphatase, glucokinase, hexokinase, SOD, CAT, GSH, GPX activities, and the effect on insulin level. HS-H significantly reduced the intake of food and water and body weight loss as well as levels of blood glucose, serum cholesterol, triglyceride, lipoprotein, oxidative stress, showed a protective hepatic effect, and increased HDL-cholesterol, serum insulin in diabetic mice. The mice fed on the high-fat diet and treated with AL-H showed inhibitory activity on the lipid metabolism decreasing body weight and weight of the liver and visceral adipose tissues and cholesterol and triglycerides in the liver. We conclude that AL-H can efficiently reduce serum glucose and inhibit insulin resistance, lipid abnormalities, and oxidative stress in MD and SD mice. Our results demonstrate an antiobesity effect reducing lipid droplet accumulation in the liver, indicating that its therapeutic properties may be due to the interaction plant components soluble in the hexane extract, with any of the multiple targets involved in obesity and diabetes pathogenesis.