Search

Background: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. Methods: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP). Results: We did not find any variant associated with breast cancer-specific mortality at P < 5 × 10−8. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10−7, hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84–0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10−7, HR = 1.27, 95% CI = 1.16–1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster. Conclusions: We uncovered germline variants on chromosome 7 at BFDP

Resumen: El enfoque de Rehabilitación Basada en la Comunidad (RBC) repre senta una estrategia cuyo propósito es lograr la plena integración e inclusión de las personas en situación de discapacidad (PsSD) a nivel social. Considerando que la comunicación y el lenguaje humano representan herramientas de expresión del pensamiento, la Asociación Americana de Habla, Lenguaje y Audición (ASHA) insta a promover el desarrollo de una comunicación efectiva como un derecho humano accesible para todas las personas, en consideración de su dignidad inherente. Objetivo: conocer el quehacer de fonoaudiólogos(as) que se desempeñan en el contexto de RBC, en la Quinta Región de Valparaíso. Método: investigación de tipo cualita tiva, con enfoque fenomenológico. Se realizó una entrevista semiestructurada y posteriormente se procedió a realizar un análisis de contenido. Resultados: Los fonoaudiólogos(as) ejecutan acciones atingentes a los cinco pilares de la RBC y se observa la práctica de actos vinculados a la gestión del intersector. Conclusiones: Los pro fesionales adoptan la estrategia RBC incorporada en la visión de la institución en la que se encuentran insertos, adoptando un perfil orientado a la transdisciplina. Abstract: The Community Based Rehabilitation (CBR) approach represents a strategy whose purpose is to achieve full social integration and inclu sion of people with disabilities. Considering that communication and human language represent tools of expression of thought, the American Speech, Language and Hearing Association (ASHA) advo cates the development of effective communication promotion, as a human right accessible to all people, considering its inherent dignity. Objective: to analyze speech and language pathologist‘s CBR prac tices in the fifth region of Valparaíso. Method: qualitative research, with a phenomenological approach. A semi-structured interview was conducted followed by a content analysis. Results: speech and Language pathologists carry out actions related to the five CBR key components and also the practice of actions in accord to intersector. Conclusions: The professionals adopt the CBR approach incorporat ing the institutional vision of service in which they are inserted and adopting a profile oriented to transdisciplinary.

En su libro El sello del Espiritu derramado sobre la Carne (2018), el antropologo Rodrigo Moulian expone de manera novedosa aquello que hace del pentecostalismo una religion para la cual la corporalidad la distingue de otras formas religiosas presentes en America Latina. Para analizar esta contribucion antropologica vale la pena comenzar restableciendo el valor de la espontaneidad y la experiencia directa de relacion con la esfera de lo divino que caracterizaba al cristianismo primitivo y que la posterior intelectualizacion de la fe y con ella la especializacion –dicho esto ultimo en terminos de Weber– que acompano la pretension de tenencia de exclusividad en materia de tecnicas salvificas por parte de instituciones eclesiasticas termino diluyendo de manera drastica...

Resumen: La fonoaudiología chilena, en el contexto de la salud, concentra su práctica en el segundo y tercer nivel (hospitalario), existiendo una fuer te tradición biomédica en el área. Las orientaciones disciplinares y el contexto de la salud pública nacional invitan a fortalecer la atención primaria de la salud, desde un punto de vista preventivo y promotor. Objetivo: Describir las acciones del fonoaudiólogo en Atención Primaria de Salud (APS) en la Quinta Región de Valparaíso y revisar su pertinencia respecto al modelo propuesto por el Ministerio de Salud. Métodos: Estudio cualitativo con enfoque fenomenológico. Se aplicó una entrevista semiestructurada a fonoaudiólgos(as) que se desempeña ban en APS y la información recopilada fue sometida a análisis de contenido. Resultados: El contexto laboral de los fonoaudiólogos se circunscribe a convenios con programas que dan cobertura a un segmento específico de la población (infantil). Los fonoaudiólogos no cuentan con jornadas de trabajo completa en APS. Las acciones fonoaudiológicas se concentran en el diagnóstico, la habilitación y rehabilitación comunicativa. Conclusiones: La práctica fonoaudioló- gica no responde actualmente al modelo de APS chileno. Es necesario incorporar una visión biopsicosocial y comunitaria a la práctica fonoaudiológica, con el fin de dar respuesta a las necesidades de la salud pública nacional. Abstract: The Community Based Rehabilitation (CBR) approach represents a strategy whose purpose is to achieve full social integration and inclusion of people with disabilities. Considering that communica tion and human language represent tools of expression of thought, the American Speech, Language and Hearing Association (ASHA) advocates the development of effective communication promotion, as a human right accessible to all people, considering its inherent dignity. Objective: to analyze speech and language pathologist ‘s CBR practices in the fifth region of Valparaíso. Method: qualitative research, with a phenomenological approach. A semi-structured interview was conducted followed by a content analysis. Results: speech and Language pathologists carry out actions related to the five CBR key components and also the practice of actions in accord to intersector. Conclusions: The professionals adopt the CBR approach incorporating the institutional vision of service in which they are inserted and adopting a profile oriented to transdisciplinary.

Background Mesial temporal sclerosis (MTS) is commonly referred to as hippocampal sclerosis (HS), is the most common association with intractable temporal lobe epilepsy. The typical MRI features of hippocampal sclerosis, are unilateral volume loss and increased signal intensity on T2-weighted images. There is no sex or side preference and a proportion of cases are bilateral. Macroscopically the hippocampus is firm and shrunken. Microscopic findings include a characteristic pattern of neuronal loss and reactive gliosis that varies in severity from case to case. Mesial temporal sclerosis is an uncommon finding in children, but when it occurs, it is always associated with epilepsy. Mesial temporal sclerosis is the most frequent cause of drug-resistant temporal lobe epilepsy but has a satisfactory response to surgery, and is considered infrequent in children. Patient Characteristics: 13 year old girl, she was born at 41 week of gestation with an uneventful antenatal history. She was ventilated at birth and also treated for streptococcal meningitis. She developed seizures during this treatment period. She didn’t require antiepileptic at discharge. No developmental concerns. She presented with focal seizures at the age of 3 years. Had further seizures, about one or two a year, up to the age of 6 years. Eye deviation to right side, abnormal mouthing movements, disoriented, confused, vacant, lip smacking lasting for 10 min followed by headache and vomiting with post ictal phase for two hours. She remained seizure free for the past 6 years. She was not commenced on any medication. Investigations EEG at the age of 5 years shown clustered spike epileptiform discharges focal in the central, temporal and occipital area. MRI scan – MRI brain scan showed dilatation of the left temporal horn with left mesial temporal sclerosis. Conclusion This is a case of mesial temporal sclerosis with spontaneous remission of epilepsy. It is extremely unusual for mesial temporal sclerosis to be spontaneously seizure free. Pathophysiological mechanism of epilepsy in mesial temporal sclerosis is not fully understood. Further imaging and pathological studies comparing similar cases against the usual MTS with drug resistant epilepsy might lead to find clinically useful indicators.

Background The commonest cause of recurrent apnoea in early infancy is due to bronchiolitis especially when they present with other respiratory symptoms. Lumbar puncture is commonly performed in these babies to rule out the possibility of meningitis. Almost all these babies are also commenced on antibiotics and antiviral agents to cover meningitis until it is excluded. Aim To identify the incidence of meningitis in infants presenting with recurrent apnoea to a tertiary paediatric intensive care unit. Methods Prospective collection of data and retrospective review of case notes of all the infants intubated and ventilated because of recurrent apnoea. The study period was for three and a half years from October 2014 to February 2017. Results Sixty five infants were included in the study. Their mean age was 5 weeks (range: 3 weeks to 3 months). All of them had a non-bronchoscopic Broncho Alveolar Lavage (BAL) to identify respiratory pathogens and also had lumbar puncture to rule out meningitis. All the infants presented with a history of coryzal symptoms, poor feeding, respiratory distress and recurrent apnoea. The average highest peak CRP for this group was 73(interquartile range: 26–103). 39 babies (60%) received fluid resuscitation at presentation. PCR test was positive in the BAL for a viral pathogen in sixty infants (92%) and negative in five (8%). Two babies in the BAL positive group also had a positive PCR test for a virus in the CSF. One baby had enterovirus positive in both BAL and CSF and another baby was PCR positive for Rhinovirus in BAL and HHV6 in CSF. The CSF cell count was normal in both these infants. No infant had evidence of bacterial meningitis or a treatable cause of viral meningitis. Conclusion Our results show that there is a low incidence of possible viral meningitis in infants presenting with recurrent apnoea and other respiratory symptoms. None of the babies would have benefitted from antibiotics or antiviral agents.

Purpose Obesity is associated with both obstructive sleep apnea (OSA) and obesity hypoventilation. Differences in adipose tissue distribution are thought to underlie the development of both OSA and hypoventilation. We explored the relationships between the distribution of upper airway, neck, chest, abdominal and muscle fat in very obese individuals. Methods We conducted a cross-sectional cohort study of individuals presenting to a tertiary sleep clinic or for assessment for bariatric surgery. Individuals underwent magnetic resonance (MR) imaging of their upper airway, neck, chest, abdomen and thighs; respiratory polygraphy; 1 week of autotitrating CPAP; and morning arterial blood gas to determine carbon dioxide partial pressure and base excess. Results Fifty-three individuals were included, with mean age of 51.6 ± 8.4 years and mean BMI of 44.3 ± 7.9 kg/m2; there were 27 males (51%). Soft palate, tongue and lateral wall volumes were significantly associated with the AHI in univariable analyses (p Conclusions In very obese individuals, our results indicate that increased volumes of upper airway structures are associated with increased severity of OSA, as previously reported in less obese individuals. Increasingly large upper airway structures that reduce pharyngeal lumen size are likely to lead to OSA by increasing the collapsibility of the upper airway. However, we did not show any significant association between regional fat distribution and propensity for hypoventilation, in this population.

Background Preterm birth (PTB) is a multifactorial syndrome occurring before the 37th week of fullterm pregnancy [1]. Babies delivered preterm experience short-term and long-term complications affecting multiple organ systems, and serious maternal complications include hemorrhage and infection. Each year, an estimated 15 million babies are born preterm, and complications from prematurity are the leading cause of death among children up to 5 years of age [2]. With another increase in PTB rates over the last several years, the United States continues to have the highest incidence of any industrialized country [3]. Makena (a progesterone analog) is the only FDA approved medication available in the United States to reduce the risk of PTB. Its use is only indicated in women who are currently pregnant with one fetus and have unexpectedly delivered a baby preterm in the past [4]. Furthermore, Makena is very expensive and not used in mothers with multiple gestations or other risk factors, such as infection, preeclampsia and obesity. Consequently, physicians commonly prescribe supportive therapies, such as magnesium sulfate, to slow uterine contractions, and glucocorticoids to stimulate fetal lung maturity. Methods In this article, we review the full spectrum of in vivo models that investigators have developed to study PTB, including rodent, ruminant and non-human primate models. We evaluate the discrepancies among various models, the shortcomings of individual models and how well these models reflect various causes of PTB in humans. Results Recent studies reveal that infection is unessential in reproductive disorders linked to inflammation, and that infection and inflammation are two of many triggers of PTB [1, 5-6]. Despite such findings, many investigators continue recycling infectious- (using bacterium) and non-infectious-based models (using products of bacteria or individual cytokines). These models are inconsistent across laboratories, and produce variable degrees of maternal morbidity (inconsistent with human PTB). Conclusion The aim of this review is to encourage the reproductive science community to rethink the design of non-infectious PTB animal studies. While these models have strengthened our understanding of the mediators and triggers of PTB, we must develop improved models that are more consistent with the various factors associated with human PTB (Fig. 1). If we continue viewing PTB through one lens or dimension, Makena will remain the only FDA approved medication. In vivo PTB research requires multi-model, multifactorial approaches that account for the complexity of living animals within and between species.

Introduction In vitro model using continuous tumour cell lines is very common in the screening of new drugs in the treatment of cancer. However, the low number of commercially available cervical cancer cell lines (CCCL) poses a challenge to generate an effective and representative means of screening. There is thus a need to establish new CCCL to improve this process. Therefore, we aimed to establish and to characterise a CCCL from a Brazilian patient. Material and methods Following patient‘s consent (Ethics Committee HCB-985/2015), a biopsy sample was taken, fragmented and subjected to enzymatic digestion. The material was then cultured in a flask with keratinocyte medium and when cells reached sixth passage, they were submitted to immunocytochemistry to characterise its phenotype. To investigate the HPV status, PCR for GP5+/GP6 +sequences and the HPV test using COBAS were carried out. Short tandem repeat (STR) analysis from cell line and patient´s blood was done to confirm the patient origin. Following DNA isolation of cell line and patient‘s blood, whole-exome sequencing (WES) and copy number variation (CNV) assays were performed. Moreover, functional assays are being performed to evaluate its tumorigenic potential protein profile. Results and discussions Overall, 35 tissues were collected and attempted to be established in vitro . Only one (2,9%) of the cultures survived for more than 3 months. The successful cell line, named HCB-514, was derived from a stage IIB squamous cell carcinoma of a 30 years old patient, with no previous treatment. It continued to grow after freeze-thaw cycles and showed positive expression for AE1/AE3 cytokeratin, confirming its epithelial phenotype. The STR analysis of HCB-514 compared with the patient’s blood confirmed its lineage. The HCB-514 was HPV 16 positive. The WES identified 93 non-silent mutations, among them 11 (HPS-3, IRX2, XPO5, CBWD1, TGFBR1, CUBN, TRHDE, BRCA2, THBS1, TGM5, CCDC22) have potentially pathogenic. CNV revealed 44 somatic alteration, including 30 regions with gains (NF1, CCND1, MYC, TP53, DCC, MAP2K4, AURKA, IGF1R, PIK3CA, GAB2, NKX2-1, BCL2L2, C8orf4, BCL2L1, ZNF217, EGFR, NCOA3, SKP2, FADD, ORAOV1, EEF1A2, REL, TERT, AKT3, PRKCI, MAPK7, DCUN1D1, BIRC2, YAP1, MYCN) and 14 losses (FHIT, GPC5, IRS2, BRCA2, RB1, PDGFRA, CDK6, SHH, APC, FOXO1, MET, MITF, KDR, KIT). Conclusion The characterisation of a new cervical cancer cell line, HCB-514, will constitute an important in vitro tool for further biological and therapeutic studies of cervical cancer.

Background Preterm delivery accounts for 85% of perinatal morbidity and mortality. Although the consumption of a high-fat diet leads to exaggerated proinflammatory responses and, in pregnant women, increased rates of spontaneous preterm birth, the underlying mechanisms remain unclear. Objective We sought to elucidate the mechanisms by which maternal consumption of a high-fat diet leads to a dysregulated immune response and, subsequently, spontaneous preterm birth. Study Design We performed 16S ribosomal RNA sequencing of DNA extracted and amplified from stool samples and compared the gut microbiomes of lipopolysaccharide-induced pregnant mice that were maintained on a high-fat diet compared to a normal control diet. Next, we sequenced the uterine transcriptomes of the mice. To test the effect of dampening of the immune response on the microbiome, transcriptome, and risk of spontaneous preterm birth, we induced immune tolerance with repetitive subclinical doses (0.2 mg/kg/week for 8 weeks) of endotoxin and performed 16S ribosomal RNA and uterine transcriptome sequencing on these immunotolerized mice. Results High-fat diet potentiates lipopolysaccharide-induced preterm birth by affecting the maternal gut microbiome and uterine transcriptome and reduces antioxidant capacity in a murine model. High-fat diet consumption also increases the colonization of the gut by 5 immunogenic bacteria and decreases colonization by Lachnospiraceae_NK4A136_group. Uteri from high-fat diet mice had increased expression of genes that stimulate the inflammatory-oxidative stress axis, autophagy/apoptosis, and smooth muscle contraction. Repetitive endotoxin priming protects high-fat diet dams from spontaneous preterm birth, increases colonization of the gut by Lachnospiraceae_NK4A136_group, decreases levels of immunogenic bacteria in the gut microbiome, and reduces the number of dysregulated genes after high-fat diet consumption from 994 to 74. Conclusion High-fat diet-potentiated spontaneous preterm birth is mediated by increased inflammation, oxidative stress, and gut dysbiosis. The induction of immune tolerance via endotoxin priming reverses these effects and protects high-fat diet dams from spontaneous preterm birth. Based on this work, the role of immunomodulation as a novel therapeutic approach to prevent preterm birth among women who consume high-fat diets should be explored.

Noninvasive camera-traps are commonly used to survey mammal communities in the Neotropics. This study used camera-traps to survey medium and large mammal diversity in the San Juan - La Selva Biological Corridor, Costa Rica. The connectivity of the corridor is affected by the spread of large-scale agriculture, cattle ranching, and a growing human presence. An occupancy modeling approach was used to estimate corridor species richness and species-specific detection probabilities in 16 forested sites within four different matrix-use categories: eco-lodge reserves, tree plantations/general reforestation, cattle ranches, and pineapple/agricultural plantations. Rarity had a highly negative effect (β = -1.96 ± 0.65 SE) on the ability to detect species presence. Corridor richness was estimated at 20.4 ± 0.66 species and was lower than that observed in protected areas in the Neotropics. Forest cover was significantly less at pineapple plantations than other land-use matrices. Richness estimates for different land-use matrices were highly variable with no significant differences; however, pineapple plantations exhibited the highest observed richness. Given the limited forest cover at those sites, we believe that this reflects the concentrated occurrence of medium and large mammals in small forest patches, particularly because the majority of pineapple plantation communities were generalist mesopredators. Fragmentation and connectivity will need to be addressed with reforestation and limitations on pineapple production for the region to function as an effective corridor. Occupancy modeling has only recently been applied to camera-trap data and our results suggest that this approach provides robust richness and detection probability estimates and should be further explored. Càmaras-trampa no invasivas son comúnmente utilizadas para estudiar las comunidades de mamíferos en los Neotrópicos. En éste estudio se utilizaron càmaras-trampa para estudiar la diversidad de mamíferos de tamaños medianos y grandes en el Corredor Biológico San Juan - La Selva en Costa Rica. La conectividad del corredor se ve afectada por la expansión de la agricultura a gran escala, la ganadería y continuo crecimiento poblacional humano. Se desarrolló un modelo de ocupación para estimar la riqueza de especies y especies específicas para el corredor, con probabilidades de detección en 16 localizaciones forestales en cuatro diferentes categorías de uso de la matriz: reservas eco-lodge, plantaciones de àrboles / reforestación general, ranchos ganaderos y piñas / plantaciones agrícolas. Rareza tenía un efecto altamente negativo (β = −1,96 ± 0,65 SE) en la capacidad de detectar la presencia de especies. La riqueza de especies en el corredor se estimó en 20,4 ± 0,66 especies y fue menor que la observada en las àreas protegidas en los Neotrópicos. La cubierta forestal fue significativamente menor en las plantaciones de piña que en otras matrices de uso de suelo. Las estimaciones de riqueza para matrices diferentes de uso del suelo fueron muy variables sin diferencias significativas. Sin embargo, las plantaciones de piña exhibieron la mayor riqueza de especies observadas. Dada a la cobertura forestal limitada en estos sitios, consideramos que lo antes mencionado refleja una incidencia concentrada de mamíferos medianos y grandes en pequeños parches de bosque, sobre todo porque la mayoría de las comunidades de las plantaciones de piña sumaron mesodepredadores generalistas. Por esta razón, tendràn que ser abordados con la reforestación y las limitaciones de la producción de piña para que la región bajo estudio pueda funcionar como un corredor eficaz. Modelos de ocupación se han aplicado recientemente a los datos de la càmara-trampa y nuestros resultados sugieren que éste enfoque proporciona un estimado robusto de riqueza de especies y sólida probabilidad de detección, lo cual propone estudiarse a cabalidad en el futuro. Universidad Nacional, Costa Rica University of Central Missouri, USA Selva Verde Lodge, Costa Rica Centro Científico Tropical, Costa Rica Instituto Internacional en Conservación y Manejo de Vida Silvestre

Baird's tapir Tapirus bairdii is categorized as Endangered on the IUCN Red List and is considered rare and locally extirpated from most of its historic range in Costa Rica. We conducted camera-trap and track surveys at 38 forested sites in and around the San Juan–La Selva Biological Corridor in the Northern Zone of Costa Rica. Cameras were set along established game trails and natural funnels and operated for 14–38 days per site. Additionally, we documented tapir tracks at many sites. We used survey photographs and track presence to create detection histories to estimate the habitat and survey-specific variables that influence the probability of detection and the probability of occurrence of Baird's tapir. The two major protected areas within and adjacent to the corridor were most positively associated with tapir occurrence, and forest cover and native and exotic tree plantations were also positively associated with tapirs’ use of sites. Although the Baird's tapir is rare, our findings suggest that it is more resilient and better able to use available habitat in the fragmented corridor than previously thought. This is most likely a consequence of increased forest cover from reforestation and tree plantations and limited hunting pressure. Given its charismatic nature we recommend that Baird's tapir could be used as a flagship species for the San Juan–La Selva Biological Corridor, to raise local awareness about conservation and increase economic growth from ecotourism.

RESUMEN El artículo propone una reflexión hermenéutico-histórica y jurídica con referencia al tema REFORMA Y AUTONOMÍA UNIVERSITARIA, contextualizado desde el pronunciamiento de Córdoba, más conocido como el Manifiesto que se gestó en esta ciudad argentina a comienzos del Siglo XX (1918), y su amplia repercusión se dio en Latinoamérica. En la Universidad de Nariño, desde el año 2008 se inició un proceso de Reforma del Alma Mater en sus Estatutos, en pleno ejercicio de su autonomía y democracia, como atributos reconocidos por el Estado y haciendo eco a los Diez Puntos enarbolados en ese movimiento en el país austral. Se destacan en especial el principio de la autonomía universitaria consagrado en la Constitución Política de Colombia, cuyo estudio e interpretación se lo ha hecho a la luz del Derecho Constitucional con base en la Ley 30 de 1992, el Estatuto General vigente y la normatividad expedida por el Honorable Consejo Superior a partir de la creación y conformación de la Asamblea Universitaria como mecanismo para agenciar dicho proceso, contando con la participación de todos los estamentos que conforman la Universidad (Docentes, Estudiantes, Empleados, Trabajadores, Jubilados); proceso de Reforma que ha dado como resultado la formulación del nuevo Proyecto Educativo Institucional (PEI) aprobado por los Consejos Académico y Superior, respectivamente; y se encuentra en la fase final de discusión para ser llevado a la Asamblea Universitaria el Proyecto de Estatuto General. Clasificación JEL: I21, I23 ABSTRACT This paper proposes a hermeneutic-historical and legal reflection on the subject REFORM AND UNIVERSITY AUTONOMY, contextualized from delivery of Cordoba, known as the Manifesto, which was conceived in that city of the Argentina province in the early twentieth century (1918), and its impact on Latin America, particularly at the University of Nariño, given that since 2008 began a process of reform of the Alma Mater in its Statutes, in full exercise of their autonomy and democracy, as attributes recognized by the state and which echo the Ten Points peaked in that movement in the southern country. It highlights, in particular, the principle of university autonomy, enshrined in the Political Constitution of the country, whose study and interpretation has been made in light of Constitutional Law, Law 30 of 1992, the current General Statute and regulations issued by the Honorable Superior Council from the creation and shaping of the University Assembly as a mechanism for brokering this process, with the participation of all sectors that make up the university (teachers, students, employees, workers, retirees)... which has led to the formulation of the new Institutional Educational Project (PEI) approved by the Academic and Superior Councils, respectively, and is in the final stages of discussion, to be taken to the University Assembly, the General Statute Draft. JEL Classification: I21, I23

La intimidación entre iguales es una problemática compleja que comprende no solo a los protagonistas directos que son los alumnos, sino también a los docentes que interactúan permanentemente en las aulas y el centro educativo. Los objetivos planteados están orientados a identificar los factores predictores de la intimidación entre iguales, percibidos desde los diferentes roles desempeñados (docente, alumno), comparar la percepción de factores personales, familiares y socioeducativos de la intimidación en estudiantes y profesores de diferente género. El diseño de investigación es descriptivo comparativo, la muestra de estudiantes es de 606 y la de docentes 70, todos ellos provenientes de centros educativos estatales. Los resultados encontrados señalan diferencias significativas en la percepción de los factores predictores de la intimidación entre iguales según el rol desempeñado: docentes y estudiantes, desde la perspectiva de género se encontraron diferencias significativas en el factor personal y familiar y no se encontraron diferencias en el factor socioeducativo.

Despite intensive research into novel treatment strategies for cancer, it remains the second most common cause of death in industrialized populations. Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with dismal prognosis. Currently, surgical resection offers the best chance for extended survival, yet recurrence remains high and is associated with poor outcome. Systemic treatment has evolved from non-specific, cytotoxic chemotherapy to the use of cancer-targeting agents, profoundly changing treatment approaches in the metastatic and adjuvant settings. One promising approach, highlighted in this review, uses the inherent capacity of Salmonella to colonize and eliminate solid tumors.

Two new species of potamid freshwater crabs of the genus Ovitamon Ng & Takeda, 1992, are described from the islands of Mindoro and Panay, Philippines. The two new species can easily be distinguished from congeners by the morphologies of their carapaces and male first gonopods. Six species of Ovitamon are now known from the islands of central and western Philippines.

X-linked Charcot-Marie-Tooth disease (CMT) is the second most common cause of CMT, and is usually caused by mutations in the gap junction protein beta 1 (GJB1) gene. This gene has nerve specific P2 promoter that work synergistically with SOX10 and EGR2 genes to initiate transcription. Mutation in this region is known to cause Schwann cell dysfunction. A single large family of X linked peripheral neuropathy was identified in our practice. Next generation sequencing for targeted panel assay identified an upstream exon-splicing deletion identified extending from nucleotide c.-5413 to approximately - c.-49. This matches the sequence of 32 nucleotides at positions c.*218-*249 in the 3'UTR downstream of the GJB1 gene. The deleted fragment included the entire P2 promoter region. The deletion segregated with the disease. To our knowledge a deletion of the P2 promoter alone as a cause of CMT has not been reported previously.

Made available in DSpace on 2021-06-25T12:17:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-11-23 Villanova Univ, Dept Biol, Villanova, PA 19085 USA Museu Nacl Hist Nat & Ciencia, Lisbon, Portugal Univ Brasilia, Dept Zool, Inst Ciencias Biol, BR-70910900 Brasilia, DF, Brazil Smithsonian Inst, Natl Museum Nat Hist, Washington, DC 20560 USA Sorbonne Univ, Museum Natl Hist Nat, ISYEB, Paris, France Univ Nacl Tucuman, San Miguel De Tucuman, Argentina King Saud Univ, Riyadh, Saudi Arabia Cornell Univ, Ithaca, NY USA Univ Fed Sao Paulo, Diadema, Brazil Upper Austrian Museum, Ctr Biol, Linz, Austria Villanova Univ, Villanova, PA 19085 USA Univ Salzburg, Salzburg, Austria Plazi, Bern, Switzerland Univ Brasilia, Brasilia, DF, Brazil Univ Sao Paulo, Ribeirao Preto, Brazil Zool Forsch Museum A Koenig, Bonn, Germany Museu Paraense Emilio Goeldi, Belem, Para, Brazil Russian Acad Sci, St Petersburg, Russia Pontificia Univ Catolica Rio Grande do Sul, Porto Alegre, RS, Brazil Museo Reg Sci Nat, Turin, Italy Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil Royal Museum Cent Africa, Tervuren, Belgium Univ Nacl Autonoma Mexico, Mexico City, DF, Mexico Univ Innsbruck, Inst Ecol, Innsbruck, Austria Hasselt Univ, Hasselt, Belgium Univ Fed Pernambuco, Recife, PE, Brazil Univ Fed Espirito Santo, Vitoria, ES, Brazil Univ Nacl Misiones, Felix De Azara, Argentina Albany Museum, Grahamstown, South Africa Natl Museum, Bloemfontein, South Africa Senckenberg Nat Hist Sammlungen, Dresden, Germany Univ Estadual Paulista, Botucatu, SP, Brazil Stephen F Austin State Univ, Nacogdoches, TX 75962 USA Landesmuseum, Leonding, Austria Univ Camerino, Camerino, Italy Univ Fed ABC, Sao Bernardo, Brazil Univ Estadual Londrina, Museu Zool, Londrina, Parana, Brazil Senckenberg Res Inst, Frankfurt, Germany Museo Civ Storia Nat, Carmagnola, Italy Polskiej Akad Nauk, Muzeum & Inst Zool, Warsaw, Poland Museo Civ Storia Nat, Genoa, Italy Russian Acad Sci, Inst Zool, St Petersburg, Russia Univ Estadual Paulista, Sao Vicente, Brazil Sorbonne Univ, ISYEB, Museum Natl Hist Nat, Paris, France Port Elizabeth Museum, Port Elizabeth, South Africa Sam Noble Museum, Norman, OK USA Harvard Univ, Museum Comparat Zool, Cambridge, MA 02138 USA North West Univ, Potchefstroom, South Africa Museu Nacl, Rio De Janeiro, Brazil Nat Hist Museum, Basel, Switzerland Senckenberg Nat Kundemuseum, Gorlitz, Germany North Carolina Museum Nat Sci, Raleigh, NC USA Univ Rennes 1, Rennes, France Univ Sao Paulo, Museu Zool, Sao Paulo, SP, Brazil Amer Museum Nat Hist, New York, NY 10024 USA Univ Huddersfield, Huddersfield, W Yorkshire, England North Dakota State Univ, Fargo, ND USA Univ Sao Paulo, Sao Paulo, SP, Brazil Fac Sci Sfax, Sfax, Tunisia DPTC PC, Manaus, Amazonas, Brazil Louisiana State Univ, Museum Nat Sci, Baton Rouge, LA 70803 USA Zool Survey India, Kolkata, India Univ Tennessee, Chattanooga, TN USA Ohio State Univ, Columbus, OH 43210 USA Univ Luterana Brasil, Museu Ciencias Nat, Canoas, Brazil Univ Firenze, Florence, Italy Univ Ovidius Constanta, Constanta, Romania Univ Mississippi, Oxford, MS USA Royal Belgian Inst Nat Sci, Brussels, Belgium Univ New Mexico, Albuquerque, NM 87131 USA Inst Nacl de Pesquisas da Amazonia, Manaus, Amazonas, Brazil Univ Stellenbosch, Matieland, South Africa Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil CIBIO Ctr Invest Biodiversidade & Recursos Genet, Vairao, Portugal Museum Hist Nat, Geneva, Switzerland Univ Fed Mato Grosso, Cuiaba, Brazil Univ Austral Chile, Valdivia, Chile Univ Malaysia, Sarawak, Malaysia Indian Inst Sci, Bangalore, Karnataka, India Scottish Assoc Marine Sci, Oban, Argyll, Scotland Sam Houston State Univ, Huntsville, TX 77340 USA Museo Nacl Ciencias Nat, Madrid, Spain Sorbonne Univ, CR2P, Museum Natl Hist Nat, Paris, France Drexel Univ, Acad Nat Sci, Philadelphia, PA 19104 USA Univ Richmond, Richmond, VA 23173 USA Ctr Pesquisas Cacau, Itabuna, Brazil Univ Torino, Turin, Italy Soc Hist Nat Alcide dOrbigny, Aubiere, France Wolfden Sci Consulting, Murcia, Spain Univ Fed Rio de Janeiro, Macae, Brazil Univ Tennessee, Knoxville, TN USA Inst Humboldt, Villa De Leyva, Colombia Escuela Politec Nacl, Quito, Ecuador Calif Acad Sci, San Francisco, CA 94118 USA Museum Dept Hist Nat Var, Toulon, France Nat Environm & Wildlife Soc, Angul, India Univ Kansas, Lawrence, KS 66045 USA Kyoto Univ, Kyoto, Japan Consejo Nacl Invest Cient & Tecn, Museo Argentino Ciencias Nat Bernardino Rivadavia, Buenos Aires, DF, Argentina Univ Fed Paraiba, Joao Pessoa, Paraiba, Brazil Univ Fed Parana, Curitiba, Parana, Brazil Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil Nat Hist Museum Narodini Museum, Prague, Czech Republic Nat Hist Museum Zimbabwe, Bulawayo, Zimbabwe Ateneo Manila Univ, Quezon City, Philippines Pontificia Univ Javeriana, Bogota, Colombia RACINE, St Maugan, France Univ Paris 06, Sorbonne Univ Paris, ISYEB, Paris, France Ocean Univ China, Qingdao, Peoples R China Museo Nacl Hist Nat Paraguay, San Lorenzo, Paraguay Univ Carabobo, Valencia, Venezuela Natl Ctr Biol Sci, Bengaluru, India Univ Nebraska, Lincoln, NE USA CENAK Ctr Nat Kunde, Hamburg, Germany Ohio Hist Connect, Columbus, OH USA Univ Fed Amazonas, Manaus, Amazonas, Brazil Univ Malaga, Malaga, Spain Chinese Acad Sci, Qingdao, Shandong, Peoples R China Benemerita Univ Autonoma Puebla, Puebla, Mexico Natl Polytech Inst, Ctr Res & Adv Studies, Irapuato, Mexico Field Museum Nat Hist, Chicago, IL 60605 USA Univ Texas El Paso, El Paso, TX 79968 USA Univ Fed Lavras, Lavras, Brazil Nat Hist Museum, Vienna, Austria La Sierra Univ, Riverside, CA USA Univ San Francisco Quito, Quito, Ecuador Univ Hong Kong, Hong Kong, Peoples R China CUNY, New York, NY 10021 USA CAS, Inst Vertebrate Biol, Brno, Czech Republic Sorbonne Univ, MECADEV, Museum Natl Hist Nat, Paris, France Univ Estadual Paulista, Rio Claro, Brazil Zool Staatssammlung Munchen, Munich, Germany Univ Michigan, Dearborn, MI 48128 USA Smithsonian Inst, Natl Museum Nat Hist, Washington, DC USA Helmholtz Ctr Environm Res, Leipzig, Germany Santa Rosa Jr Coll, Santa Rosa, CA USA George Washington Univ, Washington, DC 20037 USA Inst Teknol Bandung, Bandung, Indonesia Earlham Coll, Richmond, IN USA Senckenberg Forschungsinst & Nat Museum, Frankfurt, Germany Univ Estadual Londrina, Londrina, Parana, Brazil Univ Koblenz Landau, Koblenz, Germany Nat Hist Museum, London, England Ditsong Natl Museum Nat Hist, Pretoria, South Africa Bombay Nat Hist Soc, Bombay, Maharashtra, India Philipps Univ Marburg, Marburg, Germany Hess Landesmuseum, Darmstadt, Germany Smithsonian Conservat Biol Inst, Washington, DC USA Univ Pannonia, Keszthely, Hungary Staatliches Museum Nat Kunde, Stuttgart, Germany UFT, Tocantins, Portugal Museum Nat Kunde, Berlin, Germany Nat Hist Riksmuseet, Stockholm, Sweden Hikarigaoka, Munakata, Japan Inst Agr & Environm Sci, Tartu, Estonia Univ Los Andes, Merida, Venezuela Bat Jungle, Monteverde, Costa Rica Texas A&M Univ, College Stn, TX USA Yale Univ, New Haven, CT USA Univ Estadual Paulista, Sao Jose Do Rio Preto, Brazil Museo Nacl Hist Nat, Montevideo, Uruguay Consejo Nacl Invest Cient & Tecn, Fdn Miguel Lillo, San Miguel De Tucuman, Argentina Roger Tory Peterson Inst Nat Hist, Jamestown, VA USA Univ Fed Reconcavo Bahia, Cruz Das Almas, Brazil South China Normal Univ, Guangzhou 510631, Guangdong, Peoples R China Museu Ciencias Tecnol PUCRS, Porto Alegre, RS, Brazil Univ Fed Tocantins, Porto Nacl, Brazil Univ Toronto, Scarborough, ON, Canada Univ Nacl Colombia, Inst Ciencias Nat, Bogota, Colombia Natl Museum Philippines, Manila, Philippines NOVA Univ Lisbon, Caparica, Portugal Royal Saskatchewan Museum, Regina, SK, Canada Deutsch Zentrum Marine Biodiversitatsforsch, Hamburg, Germany Ctr Invest Biol Noroeste, La Paz, Mexico Naturalis Biodivers Ctr, Leiden, Netherlands Univ Douala, Douala, Cameroon Vet & Farmaceut Univ Brno, Brno, Czech Republic Univ Swaziland, Kwaluseni, Eswatini Fundacao Oswaldo Cruz, Rio De Janeiro, Brazil Univ Claude Bernard, Lyon, France Museum Vertebrate Zool, Berkeley, CA USA Smithsonian Inst, Washington, DC 20560 USA Nat Hist Museum & Inst, Chiba, Japan Senckenberg Biodiversitat & Klima Forschunsgzentr, Frankfurt, Germany Marquette Univ, Milwaukee, WI 53233 USA Univ Firenze, Museo Storia Nat, Florence, Italy Univ Fed Bahia, Salvador, BA, Brazil Fed Univ ABC, Sao Bernardo, Brazil Univ Fed Goias, Goiania, Go, Brazil Univ Alaska Museum, Fairbanks, AK USA Egerton Univ, Egerton, Kenya Museo Hist Nat, Lima, Peru IKIAM Univ Reg Amazon, Tena, Ecuador Univ Hyogo, Sanda, Japan Inst Rech Dev, Paris, France Univ Sao Paulo, Piracicaba, Brazil Niedersachs Landesbetrieb Wasserwirtschaft Kusten, Hannover, Germany Univ Complutense Madrid, Madrid, Spain Consejo Nacl Invest Cient & Tecn, Ctr Nacl Patagon, Puerto Madryn, Argentina Roosevelt Univ, Coll Profess Studies, Chicago, IL 60605 USA Western Kentucky Univ, Bowling Green, KY 42101 USA Univ Naples Federico II, Naples, Italy Univ Fed Acre, Rio Branco, Acre, Brazil Univ Fed Santa Catarina, Florianopolis, SC, Brazil Inst Bio & Geociencias Noroeste Argentino, Salta, Argentina Inst Venezolano Invest Cient, Caracas, Venezuela Umweltbundesamt, Vienna, Austria Penclen, Plumelec, France CNRS MNHN UPMC, Ctr Rech Paleobiodivers & Paleoenvironm, Paris, France Staatl Museum Nat Kunde, Stuttgart, Germany Consejo Nacl Invest Cient & Tecn, Museo Argentino Ciencias Nat Bernardino Rivada, Buenos Aires, DF, Argentina Ctr Biol Gest Populat INRA, Montferrier Sur Lez, France Loyola Univ Chicago, Chicago, IL USA Pontificia Univ Catolica Rio do Sul, Porto Alegre, RS, Brazil Durban Museum Nat Sci, Durban, South Africa Univ Estado Amazonas, Manaus, Amazonas, Brazil Brigham Young Univ, Provo, UT 84602 USA Museo Hist Nat La Salle, Caracas, Venezuela Univ Vet Med Hannover, Hannover, Germany Australian Museum, Sydney, NSW, Australia Texas Tech Univ, Lubbock, TX 79409 USA Francis Marion Univ, Florence, SC USA Univ Washington, Seattle, WA 98195 USA Univ Connecticut, Groton, CT USA Fed Univ ABC, Santo Andre, SP, Brazil Univ Fed Uberlandia, Uberlandia, MG, Brazil Fed Univ Para, Belem, Para, Brazil Yale Peabody Museum, New Haven, CT USA Univ Texas Arlington, Arlington, TX 76019 USA Senckenberg Deutsch Entomol Inst, Muncheberg, Germany CSIRO, Natl Res Collect, Canberra, ACT, Australia Univ Venda, Thohoyandou, South Africa Univ Ulsan, Ulsan, South Korea Univ Estadual Sao Paulo, Botucatu, SP, Brazil Senckenberg Forsch Inst & Nat Museum, Frankfurt, Germany Ocean Univ China, Inst Marine Biodivers & Evolut, Qingdao, Shandong, Peoples R China Univ Fed Para, Altamira, Brazil Univ Estadual Paulista, Assis, Brazil UPMC, Ctr Rech Paleobiodiversite & Paleoenvironm, CNRS, MNHN, Paris, France Tech Univ Kaiserslautern, Kaiserslautern, Germany Charles Univ Prague, Dept Zool, Prague, Czech Republic Univ Nacl Expt los Llanos Occident Ezequiel Zamor, Guanare, Venezuela Long Isl Univ, Brooklyn, NY USA Univ Ryukyus, Okinawa, Japan Pontificia Univ Catolica Ecuador, Museo Zool, Escuela Ciencias Biol, Quito, Ecuador Indiana Univ Penn, Indiana, PA USA IRD, Dakar, Senegal State Museum Nat Hist Karlsruhe, Karlsruhe, Germany Univ Toulouse III Paul Sabatier, Toulouse, France Univ Ghent, Ghent, Belgium Univ Antwerp, Antwerp, Belgium Karlsruhe Inst Technol, Karlsruhe, Germany Ctr Cellular & Mol Biol, Hyderabad, India Univ Fed ABC, Santo Andre, Brazil Yale Peabody Museum Nat Hist, New Haven, CT USA Univ Innsbruck, Mondsee, Austria Bethune Cookman Univ, Daytona Beach, FL USA Natl Museum Nat & Sci, Tokyo, Japan Zool Garten Koln, Cologne, Germany Univ Estadual Paulista, Botucatu, SP, Brazil Univ Estadual Paulista, Sao Vicente, Brazil Univ Estadual Paulista, Rio Claro, Brazil Univ Estadual Paulista, Sao Jose Do Rio Preto, Brazil Univ Estadual Paulista, Assis, Brazil

El objetivo de la presente investigación, fue determinar el perfil del lenguaje oral de niños con Trastornos del Espectro Autista (TEA), comparándolos con el de niños con neurodesarrollo típico. El estudio tuvo un diseño no experimental, transaccional y descriptivo, mientras que la selección de los sujetos, se realizó por conveniencia, haciendo uso de criterios de inclusión-exclusión. La recolección de los datos se efectuó con diversos instrumentos que exploraban los componentes léxico, semántico, sintáctico y pragmático del lenguaje. Los resultados mostraron un desempeño significativamente mejor en los niños con neurodesarrollo típico, con respecto a los niños con TEA, en catorce de los diecisiete aspectos del lenguaje explorados. No se encontraron diferencias significativas en la comprensión oral de narraciones entre los seis y doce años; y tampoco en el vocabulario expresivo y análisis-síntesis verbal a la edad de cinco años., The aim of this research was to establish the profile of the oral language of children with Autism Spectrum Disorders (ASD), compared with children with typical neurodevelopment. The study had a non-experimental, descriptive and transeccional design, whereas the selection of subjects was made for convenience, using inclusion-exclusion criteria. The data collection was performed with several instruments which explored the lexical, semantic, syntactic and pragmatic components of language. The results showed significantly better performance in children with typical neurodevelopment, regarding children with ASD, in fourteen of the seventeen explored aspects of language. No significant differences in the understanding of oral narratives between six and twelve were found, nor in expressive vocabulary and verbal analysis-synthesis at the age of five.

Despite the clinical success of anti-PD1 antibody (α-PD1) therapy, the immune mechanisms contributing to the antineoplastic response remain unclear. Here, we describe novel aspects of the immune response involved in α-PD1-induced antitumor effects using an orthotopic Kras (G12D)/p53(R172H)/Pdx1-Cre (KPC) model of pancreatic ductal adenocarcinoma (PDA). We found that positive therapeutic outcome involved both the innate and adaptive arms of the immune system. Adoptive transfer of total splenocytes after short-term (3 d) but not long-term (28 d) PD1 blockade significantly extended survival of non-treated tumor-bearing recipient mice. This protective effect appeared to be mostly mediated by T cells, as adoptive transfer of purified natural killer (NK) cells and/or granulocyte receptor 1 (Gr1)(+) cells or splenocytes depleted of Gr1(+) cells and NK cells did not exhibit transferrable antitumor activity following short-term PD1 blockade. Nevertheless, splenic and tumor-derived CD11b(+)Gr1(+) cells and NK cells showed significant persistence of α-PD1 bound to these cells in the treated primary recipient mice. We observed that short-term inhibition of PD1 signaling modulated the profiles of multifunctional cytokines in the tumor immune-infiltrate, including downregulation of vascular endothelial growth factor A (VEGF-A). Altogether, the data suggest that systemic blockade of PD1 results in rapid modulation of antitumor immunity that differs in the tumor microenvironment (TME) when compared to the spleen. These results demonstrate a key role for early immune-mediated events in controlling tumor progression in response to α-PD1 treatment and warrant further investigation into the mechanisms governing responses to the therapy at the innate-adaptive immune interface.

Industrial applications of embedded materials have been increased in the recent years as the study of their mechanical properties. A particular interest is their homogeneousness which will determine a significant improvement or decay in the possible application. The optical system proposed here can show the internal micro structure and the internal displacements along a scanned volume through consecutives 2D tomographic and optical phase images. The volumetric information is retrieved by means of a liner stage which avoids the use of expensive tilting devices. Results show the response of homogeneous and in-homogeneous PMMA samples during controlled tests in order to find the simplest one which determines the sample’s condition.

Pancreatic ductal adenocarcinoma (PDAC) is predicted to have the second highest incidence of fatalities among all solid tumor malignancies worldwide. Despite three decades of research focused on treating PDAC, the five-year survival rate is less than 6%, thus leaving much room for improvement. Historically, PDAC has been difficult to treat due to the absence of early detection methods resulting in clinical disease that is significantly advanced and characterized by immunosuppression, an extreme form of fibrosis known as desmoplasia, and metastasis to vital organs [1]. Current chemotherapeutic combinations, such as gemcitabine with Abraxane, have been shown to extend patient survival; however, they only do so by two to three months [2]. The newly released irinotecan liposome injection tested in pancreatic cancer patients is, at best, equal in efficacy to gemcitabine with Abraxane [3-5]. The low efficacy and high toxicity of chemotherapy has lead to innovative new strategies using immunotherapeutic approaches for treatment of PDAC. For example, the whole pancreatic cancer cell vaccine expressing human macrophage-colony stimulating factor (GM-CSF), known as GVAX, combined with a Listeriabased vaccine expressing the PDAC antigen mesothelian (CRS-207) shows promise in extending survival evidenced by both pre-clinical and preliminary clinical data [6]. Furthermore, antibody therapies targeting CTLA-4 and PD-1 have shown great benefit toward enhancing antitumor immunity resulting in tumor regression and extension of survival in other solid tumor models [7]. Despite these successes, there is a growing consensus that a “multipronged” approach to induce anti-tumor immunity and simultaneously targeting immune suppression and desmoplasia will have the greatest effect in eliminating PDAC. However, balancing such aggressive approaches with minimal toxicity to the patient will prove to be an incredibly daunting task.

Generating antitumor responses through the inhibition of tumor-derived immune suppression represents a promising strategy in the development of cancer immunotherapeutics. Here, we present a strategy incorporating delivery of the bacterium Salmonella typhimurium (ST), naturally tropic for the hypoxic tumor environment, transformed with a small hairpin RNA (shRNA) plasmid against the immunosuppressive molecule indoleamine 2,3-dioxygenase 1 (shIDO). When systemically delivered into mice, shIDO silences host IDO expression and leads to massive intratumoral cell death that is associated with significant tumor infiltration by polymorphonuclear neutrophils (PMN). shIDO-ST treatment causes tumor cell death independently of host IDO and adaptive immunity, which may have important implications for use in immunosuppressed patients with cancer. Furthermore, shIDO-ST treatment increases reactive oxygen species (ROS) produced by infiltrating PMNs and, conversely, PMN immunodepletion abrogates tumor control. Silencing of host IDO significantly enhances S. typhimurium colonization, suggesting that IDO expression within the tumor controls the immune response to S. typhimurium. In summary, we present a novel approach to cancer treatment that involves the specific silencing of tumor-derived IDO that allows for the recruitment of ROS-producing PMNs, which may act primarily to clear S. typhimurium infection, but in the process also induces apoptosis of surrounding tumor tissue resulting in a vigorous antitumor effect. Cancer Res; 72(24); 6447–56. ©2012 AACR.

Purpose: Recently, we showed that intratumoral delivery of low-dose, immunostimulatory CpG oligodeoxynucleotides conjugated with carbon nanotubes (CNT-CpG) was more effective than free CpG and not only eradicated intracranial (i.c.) gliomas but also induced antitumor immunity that protected mice from subsequent i.c. or systemic tumor rechallenge. Here, we examined whether the same “intracerebral immunotherapy” strategy could be applied to the treatment of metastatic brain tumors. Experimental Design: Mice with both i.c. and s.c. melanomas were injected intratumorally with CNT-CpG into either location. Antitumor responses were assessed by flow cytometry, bioluminescent imaging, and animal survival. Results: When given s.c., CNT-CpG response was mostly local, and it only modestly inhibited the growth of i.c. melanomas. However, i.c. CNT-CpG abrogated the growth of not only brain but also s.c. tumors. Furthermore, compared with s.c. injections, i.c. CNT-CpG elicited a stronger inflammatory response that resulted in more potent antitumor cytotoxicity and improved in vivo trafficking of effector cells into both i.c. and s.c. tumors. To investigate factors that accounted for these observations, CNT-CpG biodistribution and cellular inflammatory responses were examined in both tumor locations. Intracranial melanomas retained the CNT-CpG particles longer and were infiltrated by Toll-like receptor (TLR-9)–positive microglia. In contrast, myeloid-derived suppressive cells were more abundant in s.c. tumors. Although depletion of these cells before s.c. CNT-CpG therapy enhanced its cytotoxic responses, antitumor responses to brain melanomas were unchanged. Conclusions: These findings suggest that intracerebral CNT-CpG immunotherapy is more effective than systemic therapy in generating antitumor responses that target both brain and systemic melanomas. Clin Cancer Res; 18(20); 5628–38. ©2012 AACR.

Roadside point counts are often used to estimate trends of bird populations. The use of aural counts of birds without adjustment for detection probability, however, can lead to incorrect population trend estimates. We compared precision of estimates of density and detectability of whistling northern bobwhites (Colinus virginianus) using distance sampling, independent double-observer, and removal methods from roadside surveys. Two observers independently recorded each whistling bird heard, distance from the observer, and time of first detection at 362 call-count stops in Ohio. We examined models that included covariates for year and observer effects for each method and distance from observer effects for the double-observer and removal methods using Akaike's Information Criterion (AIC). The best model of detectability from distance sampling included observer and year effects. The best models from the removal and double-observer techniques included observer and distance effects. All 3 methods provid...

Este artículo presenta la automatización de una secadora de café para laboratorio controlada por medio de dos microcontroladores y equipada con motores DC, sensores de temperatura, humedad relativa, celdas de carga, sensores ópticos, pantalla de cristal líquido, teclado, alarma y comunicación serial con el computador. Se integró el proceso de secado y los sistemas mecánicos requeridos con los componentes electrónicos. El resultado fue una secadora de café con un proceso de secado automatizado junto a dos aplicaciones en Labview que permiten desplegar, registrar y graficar la información captada durante su funcionamiento.

Survivin is overexpressed by 70-80% of pancreatic cancers, and is associated with resistance to chemotherapy and a poor prognosis. Gemcitabine has been a standard treatment for patients with advanced pancreatic cancer for a decade. Recent reports have demonstrated that gemcitabine treatment attenuates the tumor-suppressive environment by eliminating CD11b(+)/Gr-1(+) myeloid-derived suppressor cells (MDSCs). We hypothesize that a cancer vaccine targeting survivin can achieve enhanced efficacy when combined with gemcitabine. In this study, we tested this hypothesis using modified vaccinia Ankara (MVA) expressing full-length murine survivin. The poorly immunogenic mouse pancreas adenocarcinoma cell line, Pan02, which expresses murine survivin and is syngeneic to C57BL/6, was used for this study. Immunization with MVA-survivin resulted in a modest therapeutic antitumor effect on established Pan02 tumors. When administered with gemcitabine, MVA-survivin immunization resulted in significant tumor regression and prolonged survival. The enhanced vaccine efficacy was associated with decreased CD11b(+)/Gr-1(+) MDSCs. To analyze the survivin-specific immune response to MVA-survivin immunization, we utilized a peptide library of 15mers with 11 residues overlapping from full-length murine survivin. Splenocytes from mice immunized with MVA-survivin produced intracellular γ-interferon in response to in vitro stimulation with the overlapping peptide library. Increased survivin-specific CD8(+) T cells that specifically recognized the Pan02 tumor line were seen in mice treated with MVA-survivin and gemcitabine. These data suggest that vaccination with MVA-survivin in combination with gemcitabine represents an attractive strategy to overcome tumor-induced peripheral immune tolerance, and this effect has potential for clinical benefit in pancreatic cancer.

Integration of exogenous DNA into modified vaccinia Ankara (MVA) is often accomplished using mapped deletion sites in the viral genome. Since MVA has a large capacity (≥ 30 kb) for foreign gene inserts and a limited number of unique integration sites, development of additional integration sites is needed to take full advantage of the extraordinary capacity for foreign gene insertion. In this report, we evaluate an alternative insertion site known as intergenic region 3 (IGR3). Recombinant MVA carrying the cytomegalovirus pp65 gene in IGR3 (rMVA-pp65-IGR3) demonstrated expression and genetic stability of the insert gene upon passage. Immunization of transgenic HLA-A2 mice with rMVA-pp65-IGR3 induced robust antigen-specific immune responses. Moreover, rMVA-pp65-IGR3-infected human EBV-transformed B cell lines were able to stimulate high levels of pp65-specific memory T cell responses in human PBMCs. These data support the usage of IGR3 for the development of highly immunogenic rMVA vaccines for clinical or veterinary use.

The p53 gene product is overexpressed in approximately 50% of cancers, making it an ideal target for cancer immunotherapy. We previously demonstrated that a modified vaccinia Ankara (MVA) vaccine expressing human p53 (MVA-p53) was moderately active when given as a homologous prime/boost in a human p53 knock in (Hupki) mouse model. We needed to improve upon the inefficient homologous boosting approach, because development of neutralizing immunity to the vaccine viral vector backbone suppresses its immunogenicity. To enhance specificity, we examined the combination of 2 different vaccine vectors provided in sequence as a heterologous prime/boost. Hupki mice were evaluated as a human p53 tolerant model to explore the capacity of heterologous p53 immunization to reject human p53-expressing tumors. We employed attenuated recombinant Listeria monocytogenes expressing human p53 (LmddA-LLO-p53) in addition to MVA-p53. Heterologous p53 immunization resulted in a significant increase in p53-specific CD8 and CD4 T cells compared with homologous single vector p53 immunization. Heterologous p53 immunization induced protection against tumor growth but had only a modest effect on established tumors. To enhance the immune response we used synthetic double-strand RNA (polyinsosinic:polycytidylic acid) and unmethylated CpG-containing oligodeoxynucleotide to activate the innate immune system via Toll-like receptors. Treatment of established tumor-bearing Hupki mice with polyinsosinic:polycytidylic acid and CpG-oligodeoxynucleotide in combination with heterologous p53 immunization resulted in enhanced tumor rejection relative to treatment with either agent alone. These results suggest that heterologous prime/boost immunization and Toll-like receptor stimulation increases the efficacy of a cancer vaccine, targeting a tolerized tumor antigen.

Introduction EGFR alterations (overexpression and mutations) are frequent events in non-small cell lung cancer (NSCLC). In the last years, second-generation EGFR-targeted therapies, such as afatinib such as allitinib were designed, having a potent irreversible inhibitor action of EGFR and other ErbB family members. Besides the EGFR mutation status, there are no predictive biomarkers of response to this new generation of inhibitors.On this context, the aim of our study was to compare the cytotoxic effects of two irreversible anti-EGFR inhibitors in a panel of NSCLC cell line and assess the impact of KRAS mutations in the response to these agents. Material and methods Total of 15 NSCLC cell lines were used. Cytotoxicity was assessed by (MTS). According to GI50 score, cell lines were classified into three groups: higly sensitive (HS), moderate sensitive (MS) and resistant (R). Mutational status of EGFR, KRAS, BRAF and PIK3CA was determined by direct sequencing. Sensitive H292 cell line was transfected with KRAS mutations (p.G12D and p.G12S), then profile of MAPK phospho-protein was assessed by RPPA. Subsequently, cytotoxicity, colony formation, migration and invasion were measured. In vivo chorioallantoic membrane assay (CAM) was used to evaluate the impact of KRAS mutations on tumour proliferation. Results and discussions We found 2 cell lines with EGFR and 5 with KRAS mutations. GI50 score show that 2 cell lines treated with afatinib and 7 treated with allitinib exhibited a HS phenotype. We observed IC50 values of 0.95±0.17 µM for H292 wild-type, a six times increase (6.56±0.23 µM) in the H292-KRAS-G12D and an eight times increase (8.47±0.15 µM) in the H292-KRAS-G12S cells. Protein array of KRAS mutant cell lines exhibited an AKT, CREB, HSP27, JNK and TOR activation. In addition, colony formation, migration and invasion potential were increased. Cam assay revealed increased tumour perimeter in KRAS mutant cell lines. Conclusion We demonstrated that allitinb is most potent anti-EGFR agent. Importantly KRAS mutations increase aggressive behaviour and can constitute a potential predictive biomarker of therapy response. Activation of intracellular protein, revelled by array represent a potential target for therapies combination. In additional, KRAS mutant cell lines increased the proliferative potential measured by CAM in vivo model.

Problem Complications from prematurity are the leading cause of death among children under 5 years of age. Although clinical studies have shown a positive correlation between maternal high-fat diet (HFD) and preterm birth (PTB), the underlying mechanisms remain to be elucidated. Furthermore, it remains unclear how fatty acid type influences the effects of bacterial endotoxins. Method of study HTR-8/SVneo trophoblasts were cultured in either 0.5 mmol L-1 palmitic acid (PA) or linoleic acid (LA) in the absence or presence of 100 μg mL-1 of lipopolysaccharide (LPS) or lipoteichoic acid (LTA). Murine placental explants were cultured in either 2 mmol L-1 PA or LA, and cell viability, total antioxidant capacity (TAC), lipid peroxidation, H2 O2 , heme oxygenase-1 (HO-1), and nuclear erythroid 2-related factor 2 (Nrf-2) and nuclear factor-kappa light-chain enhancer of activated B cells (NF-κB) transcription factor activity assays were assessed. Results Palmitic acid significantly (i) increased cell death, (ii) decreased TAC, and (iii) increased lipid peroxidation; but did not significantly increase HO-1. In contrast, LA maintained cell viability and significantly increased TAC and HO-1. In addition, incubating placental explants with PA significantly increased NF-κB activity. Co-incubating cells with PA and LPS or LTA significantly potentiated H2 O2 production and increased lipid peroxidation. Co-incubating cells with PA and LTA synergistically impaired TAC, and LTA decreased TAC more so than LPS. Co-incubation with PA/LA and LPS/LTA decreased HO-1 levels compared to treatment with either fatty acid alone. Conclusion Our findings suggest that saturated and unsaturated fats differentially regulate placental viability, antioxidant capacity, and inflammation and the actions of gram-positive and gram-negative endotoxins.

An ideal human immunodeficiency virus type 1 (HIV-1) vaccine would elicit potent cellular and humoral immune responses that recognize diverse strains of the virus. In the present study, combined methodologies (flow cytometry, Vβ repertoire analysis, and complementarity-determining region 3 sequencing) were used to determine the clonality of CD8+T lymphocytes taking part in the recognition of variant epitope peptides elicited in Mamu-A*01-positive rhesus monkeys immunized with vaccines encoding diverse HIV-1 envelopes (Envs). Monkeys immunized with clade B Envs generated CD8+T lymphocytes that cross-recognized both clade B- and clade C-p41A epitope peptides using a large degree of diversity in Vβ gene usage. However, with two monkeys immunized with clade C Env, one monkey exhibited p41A-specific cytotoxic T-lymphocytes (CTL) with the capacity for cross-recognition of variant epitopes, while the other monkey did not. These studies demonstrate that the cross-reactive potential of variant p41A epitope peptide-specific CTL populations can differ between monkeys that share the same restricting major histocompatibility complex class I molecule and receive the same vaccine immunogens.

[Guinotellus melvillensis Serene, 1971, is a rare euxanthine crab (Brachyura, Xanthidae) described from only a single juvenile male specimen devoid of pereiopods, and has never been reported since. Thirteen additional specimens, all adults, have since been discovered, allowing us to make a complete description of its adult morphology. The affinities of this unique, monotypic genus are also discussed. Guinotellus melvillensis Serene, 1971, est un crabe Euxanthinae rare (Brachyura, Xanthidae) qui a ete decrit a partir d'un unique specimen juvenile mâle depourvu de pereiopodes, et qui n'a jamais ete signale depuis. Treize specimens, tous adultes, ont ete decouverts, nous permettant de faire une description complete de la morphologie de l'adulte. Les affinites de ce genre monotypique, unique, sont aussi discutees., Guinotellus melvillensis Serene, 1971, is a rare euxanthine crab (Brachyura, Xanthidae) described from only a single juvenile male specimen devoid of pereiopods, and has never been reported since. Thirteen additional specimens, all adults, have since been discovered, allowing us to make a complete description of its adult morphology. The affinities of this unique, monotypic genus are also discussed. Guinotellus melvillensis Serene, 1971, est un crabe Euxanthinae rare (Brachyura, Xanthidae) qui a ete decrit a partir d'un unique specimen juvenile mâle depourvu de pereiopodes, et qui n'a jamais ete signale depuis. Treize specimens, tous adultes, ont ete decouverts, nous permettant de faire une description complete de la morphologie de l'adulte. Les affinites de ce genre monotypique, unique, sont aussi discutees.]