Expression of a kinase inactive SLK is embryonic lethal and impairs cell migration in fibroblasts.

Kinases are known to have kinase activity independent functions. To gain further insights into potential kinase-independent functions of SLK/STK2, we have developed a kinase-dead allele, SLKK63R using in vivo CRISPR/Cas technology. Our studies show that blastocysts homozygote for SLKK63R do not develop into viable mice. However, heterozygotes are viable and fertile with no overt phenotypes. Analyses of mouse embryonic fibroblasts show that expression of SLKK63R results in a 50% decrease in kinase activity in heterozygotes. In contrast to previous studies, our data show that SLK does not form homodimers and that the kinase defective allele does not act in a dominant negative fashion. Expression of SLKK63R leads to altered Rac1 and RhoA activity, increased stress fiber formation and delayed focal adhesion turnover. Our data support a previously observed role for SLK in cell migration and suggest that at least 50% kinase activity is sufficient for embryonic development.

Connexin 40-Mediated Regulation of Systemic Circulation and Arterial Blood Pressure.

Vascular system is a complex network in which different cell types and vascular segments must work in concert to regulate blood flow distribution and arterial blood pressure. Although paracrine/autocrine signaling is involved in the regulation of vasomotor tone, direct intercellular communication via gap junctions plays a central role in the control and coordination of vascular function in the microvascular network. Gap junctions are made up by connexin (Cx) proteins, and among the four Cxs expressed in the cardiovascular system (Cx37, Cx40, Cx43, and Cx45), Cx40 has emerged as a critical signaling pathway in the vessel wall. This Cx is predominantly found in the endothelium, but it is involved in the development of the cardiovascular system and in the coordination of endothelial and smooth muscle cell function along the length of the vessels. In addition, Cx40 participates in the control of vasomotor tone through the transmission of electrical signals from the endothelium to the underlying smooth muscle and in the regulation of arterial blood pressure by renin-angiotensin system in afferent arterioles. In this review, we discuss the participation of Cx40-formed channels in the development of cardiovascular system, control and coordination of vascular function, and regulation of arterial blood pressure.

Accuracy, acceptability, and feasibility of diagnostic tests for the screening of Strongyloides stercoralis in the field (ESTRELLA): a cross-sectional study in Ecuador.

BACKGROUND: WHO recommends the implementation of control programmes for strongyloidiasis, a neglected tropical disease caused by Strongyloides stercoralis. Specific recommendations on the diagnostic test or tests to be used for such programmes have yet to be defined. The primary objective of this study was to estimate the accuracy of five tests for strongyloidiasis. Secondary objectives were to evaluate acceptability and feasibility of use in an endemic area. METHODS: The ESTRELLA study was a cross-sectional study for which we enrolled school-age children living in remote villages of Ecuador. Recruitment took place in two periods (Sept 9-19, 2021, and April 18-June 11, 2022). Children supplied one fresh stool sample and underwent blood collection via finger prick. Faecal tests were a modified Baermann method and an in-house real-time PCR test. Antibody assays were a recombinant antigen rapid diagnostic test; a crude antigen-based ELISA (Bordier ELISA); and an ELISA based on two recombinant antigens (Strongy Detect ELISA). A Bayesian latent class model was used to analyse the data. FINDINGS: 778 children were enrolled in the study and provided the required samples. Strongy Detect ELISA had the highest sensitivity at 83·5% (95% credible interval 73·8-91·8), while Bordier ELISA had the highest specificity (100%, 99·8-100). Bordier ELISA plus either PCR or Baermann had the best performance in terms of positive and negative predictive values. The procedures were well accepted by the target population. However, study staff found the Baermann method cumbersome and time-consuming and were concerned about the amount of plastic waste produced. INTERPRETATION: The combination of Bordier ELISA with either faecal test performed best in this study. Practical aspects (including costs, logistics, and local expertise) should, however, also be taken into consideration when selecting tests in different contexts. Acceptability might differ in other settings. FUNDING: Italian Ministry of Health. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Use of a "tablet pole" for the administration of ivermectin for strongyloidiasis in a field study in Ecuador.

BACKGROUND: Establishment of efficient control programs for strongyloidiasis, the infection by Strongyloides stercoralis, is among the World Health Organization (WHO) targets for 2030. Ivermectin is a drug of choice for strongyloidiasis, but its weight-based administration can be unfeasible in remote areas. We evaluated a WHO tablet pole for administration of ivermectin in school-age children living in remote villages in Ecuador. METHODS: Children were enrolled in 16 villages in Esmeraldas Province of Ecuador, between July 2021 and June 2022. The pole identified four height intervals corresponding to ivermectin doses going from one to four tablets. For each child, we calculated the dose (µg/kg) administered with both weight-based and pole-based administration. Results were classified as follows: optimal dose, acceptable, overdose, underdose. Agreement between the two methods for estimating the number of tablets was assessed with Cohen's kappa coefficient. Estimations were reported with 95% confidence intervals (CIs). RESULTS: Total of 778 children (47.3% female) were enrolled, with median age of 9.59 years (interquartile range: 7.42‒11.22). Optimal dose was achieved for a higher proportion of children when assessed with weight (37.9%) than with pole (25.7%). Underdose and overdose were more frequent with the pole (8.3% and 19.2% children, respectively) than with the weight-based (3.7% and 6.0%, respectively) administration. Agreement between weight-based and pole-based administration was moderate: 0.56 (95% CI 0.51, 0.61). The two methods indicated the same number of tablets in 71.6% (95% CI 0.684, 0.748) cases. CONCLUSIONS: In our setting, the tablet pole could be a valid alternative. The tool needs further evaluation in different populations.

Estudio de cohorte para evaluar la asociación entre el tiempo de inicio de nutrición con días de ventilación mecánica invasiva en pacientes con choque séptico / Cohort study to evaluate the association between the start time of nutrition with days of invasive mechanical ventilation in patients with septic shock / Estudo de coorte para avaliar a associação entre o tempo de início da nutrição com os dias de ventilação mecânica invasiva em pacientes com choque séptico

Resumen: Introducción: estudio de cohorte para evaluar la asociación entre el tiempo de inicio de nutrición con los días de ventilación mecánica invasiva (VMI) en pacientes con choque séptico. La ventilación mecánica (VM) es un soporte que mantiene al paciente mientras la lesión estructural o funcional por la que se indicó se corrige. La sepsis es una causa de disfunción diafragmática que contribuye a insuficiencia respiratoria; sin embargo, se dispone de pocos datos sobre la interacción entre sepsis y VM prolongada. Actualmente, aunque la nutrición se ha establecido como un pilar de apoyo y tratamiento en pacientes críticamente enfermos, el impacto de esta intervención es poco clara. Objetivo: verificar la existencia de la asociación entre el tiempo de inicio de la nutrición y la duración de la VMI en pacientes con choque séptico. Material y métodos: se realizó un estudio de cohorte prolectivo en pacientes con choque séptico y VMI, se documentó el tiempo de inicio de la nutrición, esta decisión fue independiente del estudio. Se dio seguimiento diario con respecto a los días que requirieron VMI y el inicio de nutrición enteral o parenteral. La nutrición temprana es cuando se inicia en las primeras 48 horas del ingreso a terapia intensiva. Se empleó Stata para el análisis estadístico, en el cual se utilizaron pruebas χ2 y regresión logística. Resultados: se incluyeron 131 pacientes con choque séptico y VMI, a 110 pacientes se les inició nutrición temprana y a 21 nutrición tardía. La edad promedio fue de 69 años, 23% (31) del total de los pacientes tenía diabetes mellitus (DM), que se presentó con mayor frecuencia en el grupo de nutrición tardía. En cuanto a la gravedad, no se encontró diferencia entre ambos grupos. La duración promedio con ventilación fue de dos días, con mayor tiempo en el grupo de inicio tardío de la nutrición (dos días vs cinco días, p = 0.012). No obstante, al ajustar por regresión logística, no se encontró diferencia estadísticamente significativa (OR 0.13, IC 95% 0.14-1.17, p = 0.69). Conclusiones: aunque la nutrición se considera un pilar de apoyo necesario en todo paciente crítico, de acuerdo con nuestros resultados, el momento de inicio no afecta directamente los días de VMI.

Abstract: Introduction: cohort study to evaluate the association between the start time of nutrition with the days of invasive mechanical ventilation (IMV) in patients with septic shock. Mechanical ventilation (MV) is a support that maintains the patient while the structural or functional injury for which it was indicated is corrected. Sepsis is a cause of diaphragmatic dysfunction, contributing to respiratory failure; however, few data are available on the interaction between sepsis and prolonged MV. Currently, although nutrition has been established as a mainstay of support and treatment in critically ill patients, the impact of this intervention is unclear. Objective: to verify the existence of the association between the start time of nutrition and the duration of IMV in patients with septic shock. Material and methods: a prolective cohort study was carried out in patients with septic shock and IMV was documented at the start of nutrition, this decision being independent of the study. Daily follow-up was given regarding the days that required IMV and the start of enteral or parenteral nutrition. Early nutrition is when it is started within the first 48 hours of admission to intensive care. Stata was used for statistical analysis in which χ2 tests and logistic regression were used. Results: 131 patients with septic shock and IMV were included, 110 patients started early nutrition and 21 delayed nutrition. The average age was 69 years, 23% (31) of the total patients had diabetes mellitus (DM), presenting more frequently in the late nutrition group. Regarding severity, no difference was found between the two groups. The average duration with ventilation was two days, with a longer time in the late start of nutrition group (2 days vs 5 days, p = 0.012). However, when adjusting for logistic regression, no statistically significant difference was found (OR 0.13, CI 95% 0.14-1.17, p = 0.69). Conclusions: although nutrition is considered a necessary support pillar in all critical patients, according to our results, the start time does not directly affect the days of invasive mechanical ventilation.

Resumo: Introdução: estudo de coorte para avaliar a associação entre o tempo de início da nutrição com os dias de ventilação mecânica invasiva (VMI) em pacientes com choque séptico. A ventilação mecânica (VM) é um suporte que mantém o paciente enquanto se corrige a lesão estrutural ou funcional para a qual foi indicada. A sepse é a causa da disfunção diafragmática, contribuindo para a insuficiência respiratória; no entanto, poucos dados estão disponíveis sobre a interação entre sepse e VM prolongada. Atualmente, embora a nutrição tenha se estabelecido como pilar de suporte e tratamento em pacientes críticos, o impacto dessa intervenção não está claro. Objetivo: verificar a existência de associação entre o tempo de início da nutrição e a duração da VMI em pacientes com choque séptico. Material e métodos: foi realizado um estudo de coorte proletivo em pacientes com choque séptico e VMI, o tempo para iniciar a nutrição foi documentado, sendo esta decisão independente do estudo. Foi feito acompanhamento diário dos dias que necessitaram de VMI e início de nutrição enteral ou parenteral. A nutrição precoce é quando é iniciada nas primeiras 48 horas de internação na terapia intensiva. Utilizou-se o Stata para a análise estatística em que foram utilizados os testes χ2 e regressão logística. Resultados: foram incluídos 131 pacientes com choque séptico e VMI, 110 pacientes iniciaram nutrição precoce e 21 nutrição tardia. A média de idade foi de 69 anos, 23% (31) do total de pacientes apresentavam diabetes mellitus (DM), apresentando-se com maior frequência no grupo de nutrição retardada. Em relação à gravidade, não foi encontrada diferença entre os dois grupos. A duração média da ventilação foi de 2 dias, com maior tempo no grupo de nutrição de início tardio (2 dias vs 5 dias, p = 0.012). No entanto, ao ajustar por regressão logística, não foi encontrada diferença estatisticamente significativa OR 0.13, IC (0.14-1.17) p = 0.69. Conclusões: embora a nutrição seja considerada um pilar de suporte necessário em todos os pacientes críticos, de acordo com nossos resultados, o horário de início não afeta diretamente os dias de ventilação mecânica invasiva.

CdGAP promotes prostate cancer metastasis by regulating epithelial-to-mesenchymal transition, cell cycle progression, and apoptosis.

High mortality of prostate cancer patients is primarily due to metastasis. Understanding the mechanisms controlling metastatic processes remains essential to develop novel therapies designed to prevent the progression from localized disease to metastasis. CdGAP plays important roles in the control of cell adhesion, migration, and proliferation, which are central to cancer progression. Here we show that elevated CdGAP expression is associated with early biochemical recurrence and bone metastasis in prostate cancer patients. Knockdown of CdGAP in metastatic castration-resistant prostate cancer (CRPC) PC-3 and 22Rv1 cells reduces cell motility, invasion, and proliferation while inducing apoptosis in CdGAP-depleted PC-3 cells. Conversely, overexpression of CdGAP in DU-145, 22Rv1, and LNCaP cells increases cell migration and invasion. Using global gene expression approaches, we found that CdGAP regulates the expression of genes involved in epithelial-to-mesenchymal transition, apoptosis and cell cycle progression. Subcutaneous injection of CdGAP-depleted PC-3 cells into mice shows a delayed tumor initiation and attenuated tumor growth. Orthotopic injection of CdGAP-depleted PC-3 cells reduces distant metastasic burden. Collectively, these findings support a pro-oncogenic role of CdGAP in prostate tumorigenesis and unveil CdGAP as a potential biomarker and target for prostate cancer treatments.

Discovery of a dual Ras and ARF6 inhibitor from a GPCR endocytosis screen.

Internalization and intracellular trafficking of G protein-coupled receptors (GPCRs) play pivotal roles in cell responsiveness. Dysregulation in receptor trafficking can lead to aberrant signaling and cell behavior. Here, using an endosomal BRET-based assay in a high-throughput screen with the prototypical GPCR angiotensin II type 1 receptor (AT1R), we sought to identify receptor trafficking inhibitors from a library of ~115,000 small molecules. We identified a novel dual Ras and ARF6 inhibitor, which we named Rasarfin, that blocks agonist-mediated internalization of AT1R and other GPCRs. Rasarfin also potently inhibits agonist-induced ERK1/2 signaling by GPCRs, and MAPK and Akt signaling by EGFR, as well as prevents cancer cell proliferation. In silico modeling and in vitro studies reveal a unique binding modality of Rasarfin within the SOS-binding domain of Ras. Our findings unveil a class of dual small G protein inhibitors for receptor trafficking and signaling, useful for the inhibition of oncogenic cellular responses.

Bioactive Molecules From Native Mexican Avocado Fruit (Persea americana var. drymifolia): A Review.

Avocado (Persea americana Mill.) is a tree native from central and eastern México that belongs to the Lauraceae family. Avocado has three botanical varieties known as Mexican (P. americana var. drymifolia), West Indian (P. americana var. americana), and Guatemalan (P. americana var. guatemalensis). It is an oil-rich fruit appreciated worldwide because of its nutritional value and the content of bioactive molecules. Several avocado molecules show attractive activities of interest in medicine. Avocado fatty acids have beneficial effects on cardiovascular disease risk factors. Besides, this fruit possesses a high content of carotenoids and phenolic compounds with possible antifungal, anti-cancer and antioxidant activities. Moreover, several metabolites have been reported with anti-inflammatory effects. Also, an unsaponifiable fraction of avocado in combination with soybean oil is used for the treatment of osteoarthritis. The Mexican variety is native from México and is characterized by the anise aroma in leaves and by small thin-skinned fruits of rich flavor and excellent quality. However, the study of the bioactive molecules of the fruit has not been addressed in detail. In this work, we achieved a literature review on the inflammatory, immunomodulatory and cytotoxic properties of long-chain fatty acids and derivatives from Mexican avocado seed. Also, the antioxidant and anti-inflammatory properties of the oil extracted from the avocado seed are referred. Finally, the antimicrobial, immunomodulatory, and cytotoxic activities of some antimicrobial peptides expressed in the fruit are reviewed.

[I promotori di salute come attori-protagonisti delle cure primarie nel controllo delle malattie comunicabili e non comunicabili e nell' empowerment delle comunità. Esperienza e risultati di lungo periodo in aree marginali in Ecuador dal 1980 al 2018.] / The community health promoters as protagonist actorsof primary health care and community empowerment:a long term field-report from 1980 to 2018.

. INTRODUCTION: Against the increasing recognition of the critical importance of a direct participation of community members to assure effective health care in peripheral areas of Middle and Low Income Countries (MLIC), representative field experiences of their essential role are only occasionally available. AIMS AND METHODS: We report a narrative, factual documentation of a spectrum of projects covering the basic and specific health needs of the disperse communities in Ecuador, a model MLIC, and discuss the broader implications of the role and performance of HPs over a long period, 1980-2018, in the project activation, implementation and monitoring. RESULTS: The role of 60 HPs, with the coordination of a small core group of professionals of the Centro de Epidemiologia Comunitaria y Medicina Tropical (CECOMET) is documented through their main achievements which include: infectious diseases and in particular Neglected Tropical Diseases (eradication of onchocerciasis and yaws; virtual elimination of malaria and of strongyloidiasis; identification and control of a new focus of Chagas Disease; control of tuberculosis), mother and child health, reproductive health, hypertension (as model of the emergence of non-transmissible, chronic diseases). The most effective and sustainable strategies and methods are discussed also in terms of their more general transferability, already partially tested in programs in Bolivia, Burkina Faso, undeserved areas of Argentina. CONCLUSIONS: The systematic availability of non-professional, trained HPs should be recommended as a sustainable and reliable component of health care strategies and interventions targeted to marginalized settings, to assure a concrete accessibility to the fundamental human right to life.

Mapping the Prevalence of Strongyloides stercoralis Infection in Ecuador: A Serosurvey.

Data on the prevalence of strongyloidiasis in Ecuador are patchy. The aim of this study was to document the presence of Strongyloides stercoralis infection in rural communities of different provinces of Ecuador. We tested 1,418 serum samples stored at the biobank of the Central University of Ecuador, Quito, with an ELISA test for Strongyloides. The samples had been collected in eight different provinces of Ecuador. Two hundred ninety-four samples (20.7%) were positive, and Jipijapa, Manabí Province, was the site with the largest proportion of positive samples (66.7%). Further surveys aimed at estimating the prevalence of the infection should be carried out in areas where the infection seems highly prevalent, and ad hoc control measures should be adopted.

Community Epidemiology Approach to Parasitic Infection Screening in a Remote Community in Ecuador.

The Awa indigenous people of Ecuador live in remote areas and were included in health programs only recently. The first screening for parasitic infections in the Awa communities was implemented in the context of community epidemiology. During the site visits in each community, the health-care staff collected the samples for stool microscopy and serology for Strongyloides. A total of 705 individuals consented for the study, representing 40% of the Awa population living in the targeted communities; 184 (26%) participants supplied a stool sample. Giardia intestinalis was found in about 11% of samples. Prevalence of Ascaris lumbricoides and Trichuris trichiura was 54.9% and 36.9%, respectively. No hookworm eggs were found. In addition, Strongyloides stercoralis larvae were found in eight individuals (4.3%), whereas serology was positive in 22.7% of the individuals tested. The community-based approach resulted in an impressive participation. There was a high prevalence of parasites associated with relevant morbidity.

Polypharmacy and potential drug-drug interactions in an HIV-infected elderly population / Polifarmacia e interacciones farmacológicas potenciales en una población envejecida con infección por el VIH

Objective: Comorbidities associated with the ageing of the HIV+ population may require chronic treatment. Our aim is to determine the degree of polypharmacy and the number of potential drug-drug interactions, as well as the relationship between both variables in a HIV-infected population over the age of 65. Methods: Descriptive transversal study targeting HIV+ patients aged ≥65, attended in a Spanish hospital in 2014. The prevalence of polypharmacy (≥5 drugs) and potential drug-drug interactions were assessed, and also risk factors associated with such. Results: 265 subjects aged ≥65 years were identified, 197 of whom were on antiretroviral treatment and had data about their electronic prescription. 93% were polymedicated. The patients whose antiretroviral treatment included a non-nucleoside reverse transcriptase inhibitor (NNRTI) demonstrated a fourfold probability of being polymedicated. 65% of the patients showed at least one potential drug-drug interaction and 6.6% a severe potential drug-drug interaction. The risk of interaction was significantly associated with the number of prescribed drugs (incidence rate ratio per prescribed drug, CI 95%: 1.18 (1.14;1.22; p<0.0001) and with the use of protease inhibitors (PI) (incidence rate ratio, CI 95%: 1.65 (1.28;2.11; p=0.0001)). Conclusion: Polypharmacy has a high prevalence and is more common in patients treated with NNRTI. The number of potential drug-drug interactions increase with the number of prescribed drugs and is higher in those patients on PI (AU)

Objetivo: Las comorbilidades asociadas al envejecimiento de la población VIH+ pueden requerir tratamientos crónicos. Nuestro objetivo es determinar el grado de polifarmacia y el número de interacciones farmacológicas potenciales, así como la relación entre ambas variables en un grupo de población VIH+ mayor de 65 años. Métodos: Estudio descriptivo transversal en pacientes VIH+≥65 años atendidos en un hospital español en 2014. Se evaluó la prevalencia de polimedicación (≥5 fármacos) y se analizaron las interacciones farmacológicas potenciales y los factores de riesgo asociados a ellas. Resultados: Se identificaron 265 sujetos ≥65 años, de los cuales 197 recibían tratamiento antirretroviral y tenían datos en la receta electrónica. El 93% estaban polimedicados. Los pacientes cuyo tratamiento antirretroviral incluía un inhibidor de la transcriptasa inversa no nucleósido (ITINN) presentaban una probabilidad cuatro veces mayor de estar polimedicados. El 65% de los pacientes presentó al menos una interacción potencial y el 6,6% una interacción potencial grave. El riesgo de interacciones se asoció significativamente al número de fármacos prescritos (razón de tasas de incidencia por fármaco prescrito con IC 95%: 1,18 (1,14;1,22; p<0.0001)) y a los inhibidores de la proteasa (IP) (razón de tasas de incidencia IC 95%: 1,65 (1,28;2,11; p=0,0001)). Conclusión: La prevalencia de la polifarmacia es muy alta y más frecuente en los pacientes tratados con ITINN. El número de interacciones farmacológicas potenciales aumenta con el número de fármacos prescritos y es mayor en los pacientes tratados con IP (AU)

Polypharmacy and potential drug-drug interactions in an HIV-infected elderly population.

OBJECTIVE: Comorbidities associated with the ageing of the HIV+ population may require chronic treatment. Our aim is to determine the degree of polypharmacy and the number of potential drug-drug interactions, as well as the relationship between both variables in a HIV-infected population over the age of 65. METHODS: Descriptive transversal study targeting HIV+ patients aged ≥65, attended in a Spanish hospital in 2014. The prevalence of polypharmacy (≥5 drugs) and potential drug-drug interactions were assessed, and also risk factors associated with such. RESULTS: 265 subjects aged ≥65 years were identified, 197 of whom were on antiretroviral treatment and had data about their electronic prescription. 93% were polymedicated. The patients whose antiretroviral treatment included a non-nucleoside reverse transcriptase inhibitor (NNRTI) demonstrated a fourfold probability of being polymedicated. 65% of the patients showed at least one potential drug-drug interaction and 6.6% a severe potential drug-drug interaction. The risk of interaction was significantly associated with the number of prescribed drugs (incidence rate ratio per prescribed drug, CI 95%: 1.18 (1.14;1.22; p<0.0001) and with the use of protease inhibitors (PI) (incidence rate ratio, CI 95%: 1.65 (1.28;2.11; p=0.0001)). CONCLUSION: Polypharmacy has a high prevalence and is more common in patients treated with NNRTI. The number of potential drug-drug interactions increase with the number of prescribed drugs and is higher in those patients on PI.

Objetivo: Las comorbilidades asociadas al envejecimiento de la población VIH+ pueden requerir tratamientos crónicos. Nuestro objetivo es determinar el grado de polifarmacia y el número de interacciones farmacológicas potenciales, así como la relación entre ambas variables en un grupo de población VIH+ mayor de 65 años.Métodos: Estudio descriptivo transversal en pacientes VIH+≥65 años atendidos en un hospital español en 2014. Se evaluó la prevalencia de polimedicación (≥5 fármacos) y se analizaron las interacciones farmacológicas potenciales y los factores de riesgo asociados a ellas.Resultados: Se identificaron 265 sujetos ≥65 años, de los cuales 197 recibían tratamiento antirretroviral y tenían datos en la receta electrónica. El 93% estaban polimedicados. Los pacientes cuyo tratamiento antirretroviral incluía un inhibidor de la transcriptasa inversa no nucleósido (ITINN) presentaban una probabilidad cuatro veces mayor de estar polimedicados. El 65% de los pacientes presentó al menos una interacción potencial y el 6,6% una interacción potencial grave. El riesgo de interacciones se asoció significativamente al número de fármacos prescritos (razón de tasas de incidencia por fármaco prescrito con IC 95%: 1,18 (1,14;1,22; p<0.0001)) y a los inhibidores de la proteasa (IP) (razón de tasas de incidencia IC 95%: 1,65 (1,28;2,11; p=0,0001)).Conclusión: La prevalencia de la polifarmacia es muy alta y más frecuente en los pacientes tratados con ITINN. El número de interacciones farmacológicas potenciales aumenta con el número de fármacos prescritos y es mayor en los pacientes tratados con IP.

Diabetic concentrations of metformin inhibit platelet-mediated ovarian cancer cell progression.

Clinical studies have suggested a survival benefit in ovarian cancer patients with type 2 diabetes mellitus taking metformin, however the mechanism by which diabetic concentrations of metformin could deliver this effect is still poorly understood. Platelets not only represent an important reservoir of growth factors and angiogenic regulators, they are also known to participate in the tumor microenvironment implicated in tumor growth and dissemination. Herein, we investigated if diabetic concentrations of metformin could impinge upon the previously reported observation that platelet induces an increase in the tube forming capacity of endothelial cells (angiogenesis) and upon ovarian cancer cell aggressiveness. We demonstrate that metformin inhibits the increase in angiogenesis brought about by platelets in a mechanism that did not alter endothelial cell migration. In ovarian cancer cell lines and primary cultured cancer cells isolated from the ascitic fluid of ovarian cancer patients, we assessed the effect of combinations of platelets and metformin upon angiogenesis, migration, invasion and cancer sphere formation. The enhancement of each of these parameters by platelets was abrogated by the present of metformin in the vast majority of cancer cell cultures tested. Neither metformin nor platelets altered proliferation; however, metformin inhibited the increase in phosphorylation of focal adhesion kinase induced by platelets. We present the first evidence suggesting that concentrations of metformin present in diabetic patients may reduce the actions of platelets upon both endothelial cells and cancer cell survival and dissemination.

Converging on a theory of language through multiple methods.

Assuming that linguistic representation has been studied only by linguists using grammaticality judgments, Branigan & Pickering (B&P) present structural priming as a novel alternative. We show that their assumptions are incorrect for cognitive-functional linguistics, exposing converging perspectives on form/meaning pairings between generativists and cognitive-functional linguists that we hope will spark the cross-disciplinary discussion necessary to produce a cognitively plausible model of linguistic representation.

Comparison of S. stercoralis Serology Performed on Dried Blood Spots and on Conventional Serum Samples.

Background: Dried blood spots (DBS) are used for epidemiological surveys on infectious diseases in settings where limited resources are available. In fact, DBS can help to overcome logistic difficulties for the collection, transport and storage of biological specimens. Objective: To evaluate the accuracy of Strongyloides stercoralis serology performed on DBS. Methods: A survey was proposed to children attending a school in the village of Borbon, Ecuador, and to their parents/guardians. Each participant gave consent to the collection of both serum and DBS specimens. DBS absorbed on filter papers were analyzed with a commercially available ELISA test for S. stercoralis antibodies, as well as with standard serology. The agreement between the two methods was assessed through the Cohen's kappa coefficient. Results: The study sample was composed of 174 children and 61 adults, for a total of 235 serum and 235 DBS samples. The serology was positive in 31/235 (13%) serum samples, and in 27/235 (11%) DBS: 4 samples resulted discordant (positive at standard serology). Cohen's kappa coefficient was 0.921 (95% CI 0.845 - 0.998), indicating a high rate of concordance. Conclusion: DBS are suitable for in field-surveys requiring serological testing for S. stercoralis.

Mass Administration of Ivermectin for the Elimination of Onchocerciasis Significantly Reduced and Maintained Low the Prevalence of Strongyloides stercoralis in Esmeraldas, Ecuador.

OBJECTIVES: To evaluate the effect of ivermectin mass drug administration on strongyloidiasis and other soil transmitted helminthiases. METHODS: We conducted a retrospective analysis of data collected in Esmeraldas (Ecuador) during surveys conducted in areas where ivermectin was annually administered to the entire population for the control of onchocerciasis. Data from 5 surveys, conducted between 1990 (before the start of the distribution of ivermectin) and 2013 (six years after the interruption of the intervention) were analyzed. The surveys also comprised areas where ivermectin was not distributed because onchocerciasis was not endemic. Different laboratory techniques were used in the different surveys (direct fecal smear, formol-ether concentration, IFAT and IVD ELISA for Strongyloides stercoralis). RESULTS: In the areas where ivermectin was distributed the strongyloidiasis prevalence fell from 6.8% in 1990 to zero in 1996 and 1999. In 2013 prevalence in children was zero with stool examination and 1.3% with serology, in adult 0.7% and 2.7%. In areas not covered by ivermectin distribution the prevalence was 23.5% and 16.1% in 1996 and 1999, respectively. In 2013 the prevalence was 0.6% with fecal exam and 9.3% with serology in children and 2.3% and 17.9% in adults. Regarding other soil transmitted helminthiases: in areas where ivermectin was distributed the prevalence of T. trichiura was significantly reduced, while A. lumbricoides and hookworms were seemingly unaffected. CONCLUSIONS: Periodic mass distribution of ivermectin had a significant impact on the prevalence of strongyloidiasis, less on trichuriasis and apparently no effect on ascariasis and hookworm infections.

Seroprevalencia de marcadores de infecciones transmisibles por vía transfusional en banco de sangre de Colombia / Seroprevalence of markers of transfusion transmissible infections in blood bank in Colombia / Soroprevalencia de marcadores de infecções transmissiveis por via transfusional em banco de sangue da Colômbia

OBJETIVO: Determinar la seroprevalencia de marcadores de infecciones transmisibles por vía transfusional. MÉTODOS: Estudio transversal con fuente de información secundaria, basada en los resultados de pruebas biológicas en los donantes de un banco de sangre de Medellín, Colombia, de 2007 a 2010. Se determinó la seroprevalencia de los marcadores de infección y se compararon según sexo y tipo de donante a través de análisis de frecuencias, chi cuadrado, Fisher y razones de prevalencia. RESULTADOS: La población de base estuvo conformada por 65.535 donantes de los cuales, 3,3% presentaran al menos una prueba biológica positiva. El marcador más prevalente en las pruebas del banco de sangre fue sífilis (1,2%), seguido de tripanosomiasis (1,0%), virus de la hepatitis C (VHC) (0,6%), virus de la inmunodeficiencia humana (VIH) (0,5%) y virus de la hepatitis B (VHB) (0,2%). Con base en el laboratorio de referencia se halló una prevalencia de 0,6% para sífilis, 0,1% para VHB y 0% para VHC, VIH y Chagas. Se hallaron diferencias estadísticas en la prevalencia de VHB y sífilis según sexo y tipo de donante. CONCLUSIONES: Los resultados son coherentes con las prevalencias dadas por la Organización Panamericana de la Salud (OPS) y se pueden correlacionar con la prevalencia mundial de las infecciones transmisibles por via transfusional. Los resultados hallados en las pruebas del banco de sangre posibilitan la disminución del riesgo transfusional pero limitan la optimización de recursos al excluir donantes clasificados como falsos positivos.

OBJECTIVE: To determine the seroprevalence of markers of transfusion transmissible infections in donors of a blood bank in Medellin, Colombia, beteween 2007 and 2010. METHODS: A cross-sectional secondary data source, based on the results of biological testing of donors to a blood bank in Medellin. We determined the seroprevalence of markers of infection and were compared by sex and type of donor through frequency analysis, chi square, Fisher and prevalence ratios. RESULTS: The base population was 65,535 donors, and 3.3% had at least one positive biological test. The most prevalent marker in the blood bank testing was syphilis (1,2%), followed by trypanosomiasis (1,0%), hepatitis C virus (HCV) (0,6%), human immunodeficiency virus (HIV) 0,5% and hepatitis B virus (HBV) (0,2%). Based on the reference laboratory found a prevalence of 0.6% for syphilis, 0,1% for (HBV) and 0% for (HCV), (HIV) and Chagas. We found statistical differences in the prevalence of (HBV) and syphilis by sex and type of donor. CONCLUSIONS: The results are consistent with the prevalences given by Pan American Health Organization and can be correlated with the global prevalence of transfusion-transmitted infections. The results founds by the blood bank lead to a transfusion risk reduction but limit the optimization of resources by excluding donors classified as false positives.

OBJETIVO: Determinar a soroprevalência de marcadores de infecções transmissíveis por transfusão. MÉTODOS: Estudo transversal com fonte de informação secundária, com base nos resultados dos testes biológicos em doadores de um banco de sangue em Medellín, Colômbia, de 2007 a 2010. Determinou-se a soroprevalência de marcadores de infecção, que foram comparados por sexo e tipo de doador por meio da análise de frequência, qui-quadrado, Fisher e taxas de prevalência. RESULTADOS: A população base foi formada por 65.535 doadores, dos quais 3,3% tinham pelo menos um teste biológico positivo. O marcador mais prevalente nos testes do banco de sangue foi a sífilis (1,2%), seguido pela tripanossomíase (1,0%), vírus da hepatite C (VHC) (0,6%), vírus da imunodeficiência humana (HIV) (0,5%) e vírus da hepatites B (VHB) (0,2%). Com base no laboratório de referência, detectou-se prevalência de 0,6% para sífilis, 0,1% para VHB e 0% para VHC, VIH e Chagas. Foram encontradas diferenças estatísticas na prevalência de VHB e sífilis por sexo e tipo de doador. CONCLUSÕES: Os resultados são consistentes com as prevalências informadas pela Organização Panamericana de Saúde e podem ser correlacionadas com a prevalência mundial das infecções transmitidas por transfusão. Os resultados dos testes do banco de sangue possibilitam a redução do risco de transfusão, mas limitam a otimização dos recursos ao excluir os doadores classificados como falsos positivos.

Cost comparison of 2 mass vaccination campaigns against influenza A H1N1 in New York City.

Objectives. We estimated and compared total costs and costs per dose administered for 2 influenza A 2009 monovalent vaccine campaigns in New York City: an elementary school-located campaign targeting enrolled children aged 4 years and older, and a community-based points-of-dispensing campaign for anyone aged 4 years and older. Methods. We determined costs from invoices or we estimated costs. We obtained vaccination data from the Citywide Immunization Registry and reports from the community points of dispensing. Results. The school campaign delivered approximately 202,089 vaccines for $17.9 million and $88 per dose. The community campaign delivered 49,986 vaccines for $7.6 million and $151 per dose. At projected capacity, the school campaign could have delivered 371,827 doses at $53 each or $13 each when we excluded the value of in-kind resources. The community points of dispensing could have administered 174,000 doses at $51 each or $24 each when we excluded the value of in-kind resources. Conclusions. The school campaign delivered vaccines at a lower cost per dose than did the community campaign. Had demand been higher, both campaigns may have delivered vaccine at lower, more comparable cost per dose.