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Video de sección "Imágenes en ginecología y obstetricia" donde se muestra los componentes y los 7 pasos de acomplamiento para la cirugía ginecológica utilizando laparoscópica asistida por robot (HUGO RAS).

Video of the section "Imaging in gynecology and obstetrics" showing the components and the 7 steps for gynecological surgery using robotas sisted laparoscopic surgery (HUGO RAS).

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Bariatric surgery is a widely used intervention for significant weight loss, yet some patients face challenges with insufficient weight loss or weight regain post-surgery. To address this issue, adjunctive treatments like glucagon-like peptide-1 receptor agonists (GLP1-RAs) are being explored for their potential to enhance weight loss outcomes. This meta-analysis was conducted to evaluate the effectiveness of GLP1-RAs in improving weight loss after bariatric surgery compared to a placebo. By systematically reviewing and analyzing data from three randomized controlled trials (RCTs) involving 130 patients, we found that GLP1-RA therapy, particularly liraglutide (1.8-3 mg), significantly reduced mean BMI and body weight percentage at six months. Future studies should explore newer GLP1-RAs with weekly dosing and include longer follow-up periods to assess the durability of these outcomes.

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Dengue is a disease caused by a flavivirus (DENV) and transmitted by the bite of a mosquito, primarily the Aedes aegypti and Aedes albopictus species. Previous studies have demonstrated a relationship between the host gut microbiota and the evolution of dengue. It seems to be a bidirectional relationship, in which the DENV can affect the microbiota by inducing alterations related to intestinal permeability, leading to the release of molecules from microbiota dysbiosis that can influence the evolution of dengue. The role of angiotensin II (Ang II) in the microbiota/dengue relationship is not well understood, but it is known that the renin-angiotensin system (RAS) is present in the intestinal tract and interacts with the gut microbiota. The possible effect of Ang II on the microbiota/Ang II/dengue relationship can be summarised as follows: the presence of Ang II induced hypertension, the increase in angiotensinogen, chymase, and microRNAs during the disease, the induction of vascular dysfunction, the production of trimethylamine N-oxide and the brain/microbiota relationship, all of which are elements present in dengue that could be part of the microbiota/Ang II/dengue interactions. These findings suggest the potential use of Ang II synthesis blockers and the use of AT1 receptor antagonists as therapeutic drugs in dengue.

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The renin-angiotensin system (RAS)-a classical blood pressure regulator-largely contributes to healthy organ development and function. Besides, RAS activation promotes age-related changes and age-associated diseases, which are attenuated/abolished by RAS-blockade in several mammalian species. RAS-blockers also increase rodent lifespan. In previous work, we discussed how RAS-blockade downregulates mTOR and growth hormone/IGF-1 signaling, and stimulates AMPK activity (together with klotho, sirtuin, and vitamin D-receptor upregulation), and proposed that at least some of RAS-blockade's aging benefits are mediated through regulation of these intermediaries and their signaling to mitochondria. Here, we included RAS-blockade's impact on other aging regulatory pathways, that is, TGF-ß, NF-kB, PI3K, MAPK, PKC, Notch, and Wnt, all of which affect mitochondria. No direct evidence is available on RAS/RAS-blockade-aging regulatory pathway-mitochondria interactions. However, existing results allow to conjecture that RAS-blockers neutralize mitochondrial dysfunction by acting on the discussed pathways. The reviewed evidence led us to propose that the foundation is laid for conducting clinical trials aimed at testing whether angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB)-even at subclinical doses-offer the possibility to live longer and in better health. As ACEi and ARB are low cost and well-tolerated anti-hypertension therapies in use for over 35 years, investigating their administration to attenuate/prevent aging effects seems simple to implement.

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BACKGROUND: Transversus abdominis release (TAR) is an effective technique for treating large midline and off-midline hernias. Recent studies have demonstrated that robotic TAR (rTAR) is technically feasible and associated with improved outcomes compared to open surgery. There is no published experience to date describing abdominal wall reconstruction using the novel robotic platform HUGO RAS System (Medtronic®). METHODS: All consecutive patients who underwent a rTAR in our institution were included. Three of the four arm carts of the HUGO RAS System were used at any given time. Each arm configuration was defined by our team in conjunction with Medtronic® personnel. rTAR was performed as previously described. Upon completion of the TAR on one side, a redocking process with different, mirrored arms angles was performed to continue with the contralateral TAR. Operative variables and early morbidity were recorded. RESULTS: Ten patients were included in this study. The median BMI was 31 (21-40.6) kg/m2. The median height was 1.6 m (1.5-1.89 m). A trend of decreased operative time, console time, and redocking time was seen in these consecutive cases. No intraoperative events nor postoperative morbidity was reported. The median length of stay was 3 (1-6) days. CONCLUSION: Robotic TAR utilizing the HUGO RAS system is a feasible and safe procedure. The adoption of this procedure on this novel platform for the treatment of complex abdominal wall hernias has been successful for our team.

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Introducción: la información en cáncer en poblaciones indígenas colombianas es escasa; de ahí que el objetivo de este estudio sea conocer las perspectivas comunitarias y de los prestadores de servicios de salud acerca del cáncer de cuello uterino (CaCU) en mujeres indígenas del Amazonas colombiano. Materiales y métodos: estudio cualitativo, derivado de una investigación de métodos mixtos de triangula-ción convergente. Se realizaron 40 entrevistas semiestructuradas que incluían profesionales de la salud y actores clave comunitarios representados en curacas, médicos tradicionales o chamanes, parteras, pro-motores de salud, auxiliares de salud pública, líderes y lideresas, abuelos, abuelas y mujeres indígenas en general. Para el análisis se utilizó la técnica de análisis de contenido. Resultados: emergieron cuatro categorías:1) concepciones y factores de riesgo alrededor del cáncer en general y el CaCU, 2) prácticas de cuidado y de atención occidentales y ancestrales para el CaCU, 3) dificultades socioculturales y del sistema de salud para la prevención y atención del CaCU y 4) recomendaciones para el fortalecimiento de la de prevención del CaCU. Conclusión: los participantes reconocen la citología cervicouterina como una forma de prevenir el cáncer y aunque los participantes mencionaron algunos aspectos culturales y personales que podrían constituirse en una barrera para la prevención y control del CaCU, se hizo hinca-pié en los problemas estructurales del sistema de salud, la falta de integración cultural y las dificultades de acceso al tamizaje, diagnóstico y tratamiento.

Introduction: Information on cancer in Colombian indigenous populations is scarce, the objective of this study was to know the community and health care providers' perspectives on cervical cancer (CaCU) in indigenous women of the Colombian Amazon. Materials and methods: Qualitative study, derived from a mixed methods research of convergent triangulation, 40 semi-structured interviews were conducted, including health professionals and key community actors represented by curacas, traditional doctors or shamans, midwives, health promoters, public health assistants, leaders, grandfathers, grandmothers, and indigenous women in general. The content analysis technique was used for the analysis. Results:Four categories emerged: (a) conceptions and risk factors surrounding cancer in general and CaCU; (b) western and ancestral care and attention practices for CaCU; (c) sociocultural and health system diffi-culties for the prevention and attention of CaCU, and (d) recommendations for strengthening CaCU pre-vention. Conclusion: Participants recognize cervical cytology as a way to prevent cancer and although participants mentioned some cultural and personal aspects that could constitute a barrier to cervical cancer prevention and control, the greatest emphasis was given to structural problems of the health system, lack of cultural integration and difficulties of access to screening, diagnosis and treatment.

Introdução: a informação sobre o câncer nas populações indígenas colombianas são escassas, o objetivo deste estudo foi conhecer as perspectivas da comunidade e dos prestadores de serviços de saúde sobre o câncer do colo do útero (CaCU), em mulheres indígenas da Amazônia colombiana. Materiais e méto-dos: estudo qualitativo, derivado de uma investigação de métodos mistos de triangulação convergente. Foram realizadas 40 entrevistas semiestruturadas que incluíram profissionais de saúde e principais atores comunitários representados em curacas, médicos tradicionais ou xamãs, parteiras, promotores de saúde, assistentes de saúde pública, lideranças, avôs, avós e mulheres indígenas em geral. Para a análise foi uti-lizada a técnica de análise de conteúdo. Resultados: emergiram quatro categorias, a) concepções e fatores de risco em torno do câncer em geral e do CaCU; b) cuidados e práticas de cuidado ocidentais e ancestrais para CaCU; c) dificuldades socioculturais e do sistema de saúde para a prevenção e cuidado do CaCU, e d) recomendações para fortalecer a prevenção de CaCU. Conclusão: as participantes reconhecem a citolo-gia cervical como forma de prevenção do câncer e embora as participantes tenham mencionado alguns aspectos culturais e pessoais que poderiam constituir uma barreira para a prevenção e controle do câncer do colo do útero, a maior ênfase foi dada aos problemas estruturais do sistema de saúde, a falta de integra-ção cultural e as dificuldades de acesso ao rastreio, ao diagnóstico e ao tratamento

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The renin-angiotensin system (RAS) is an important cascade of enzymes and peptides that regulates blood pressure, volume, and electrolytes. Within this complex system of reactions, its counter-regulatory axis has attracted attention, which has been associated with the pathophysiology of inflammatory and fibrotic diseases. This review article analyzes the impact of different components of the counter-regulatory axis of the RAS on different pathologies. Of these peptides, Angiotensin-(1-7), angiotensin-(1-9) and alamandine have been evaluated in a wide variety of in vitro and in vivo studies, where not only they counteract the actions of the classical axis, but also exhibit independent anti-inflammatory and fibrotic actions when binding to specific receptors, mainly in heart, kidney, and lung. Other functional peptides are also addressed, which despite no reports associated with inflammation and fibrosis to date were found, they could represent a potential target of study. Furthermore, the association of agonists of the counter-regulatory axis is analyzed, highlighting their contribution to the modulation of the inflammatory response counteracting the development of fibrotic events. This article shows an overview of the importance of the RAS in the resolution of inflammatory and fibrotic diseases, offering an understanding of the individual components as potential treatments.

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Introduction: Breast cancer (BC) is the leading cause of cancer-related deaths among women, with triple-negative breast cancer (TNBC) representing one of the most aggressive and treatment-resistant subtypes. In this study, we aimed to evaluate the antitumor potential of C14 and P8 molecules in both TNBC and radioresistant TNBC cells. These compounds were chosen for their ability to stabilize the complex formed by the overactivated form of K-Ras4BG13D and its membrane transporter (PDE6δ). Methods: The antitumor potential of C14 and P8 was assessed using TNBC cell lines, MDA-MB-231, and the radioresistant derivative MDA-MB-231RR, both carrying the K-Ras4B> G13D mutation. We investigated the compounds' effects on K-Ras signaling pathways, cell viability, and tumor growth in vivo. Results: Western blotting analysis determined the negative impact of C14 and P8 on the activation of mutant K-Ras signaling pathways in MDA-MB-231 and MDA-MB-231RR cells. Proliferation assays demonstrated their efficacy as cytotoxic agents against K-RasG13D mutant cancer cells and in inducing apoptosis. Clonogenic assays proven their ability to inhibit TNBC and radioresistant TNBC cell clonogenicity. In In vivo studies, C14 and P8 inhibited tumor growth and reduced proliferation, angiogenesis, and cell cycle progression markers. Discussion: These findings suggest that C14 and P8 could serve as promising adjuvant treatments for TNBC, particularly for non-responders to standard therapies. By targeting overactivated K-Ras and its membrane transporter, these compounds offer potential therapeutic benefits against TNBC, including its radioresistant form. Further research and clinical trials are warranted to validate their efficacy and safety as novel TNBC treatments.

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PURPOSE: RAS (KRAS/NRAS) mutational status on a tumor biopsy is mandatory to guide the best treatment in metastatic colorectal cancer (mCRC). Determining the RAS mutational status by tumor-tissue biopsy is essential in guiding the optimal treatment decision for mCRC. RAS mutations are negative predictive factors for the use of EGFR monoclonal antibodies. Cell-free DNA (cfDNA) analysis enables minimally invasive monitoring of tumor evolution. METHODS/PATIENTS: PERSEIDA was an observational, prospective study assessing cfDNA RAS, BRAF and EGFR mutations (using Idylla™) in first-line mCRC, RAS wild-type (baseline tumor-tissue biopsy) patients (cohort 2). Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression. RESULTS: 117 patients were included (103 received panitumumab + chemotherapy as first-line treatment). At baseline, 7 (6.8%) patients had RAS mutations, 4 (3.9%) BRAF mutations and no EGFR mutations were detected (cfDNA, panitumumab + chemotherapy subpopulation [panitumumab + Ch]). The baseline RAS mutational status concordance between tissue and liquid biopsies was 94.0% (93.2%, panitumumab + Ch). At 20 weeks, only one patient in the study (included in the panitumumab + Ch) had an emerging cfDNA RAS mutation. No emerging BRAF or EGFR mutations were reported. At disease progression, 6 patients had emergent mutations not present at baseline (RAS conversion rate: 13.3% [6/45]; 15.0% [6/40], panitumumab + Ch). CONCLUSIONS: The concordance rate between liquid and solid biopsies at baseline was very high, as previously reported, while our results suggest a considerable emergence of RAS mutations during disease progression. Thus, the dynamics of the genomic landscape in ctDNA may provide relevant information for the management of mCRC patients.

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The renin-angiotensin system (RAS) is an endocrine system composed of two main axes: the classical and the counterregulatory, very often displaying opposing effects. The classical axis, primarily mediated by angiotensin receptors type 1 (AT1R), is linked to obesity-associated metabolic effects. On the other hand, the counterregulatory axis appears to exert antiobesity effects through the activation of two receptors, the G protein-coupled receptor (MasR) and Mas-related receptor type D (MrgD). The local RAS in adipose organ has prompted extensive research into white adipose tissue and brown adipose tissue (BAT), with a key role in regulating the cellular and metabolic plasticity of these tissues. The MasR activation favors the brown plasticity signature in the adipose organ by improve the thermogenesis, adipogenesis, and lipolysis, decrease the inflammatory state, and overall energy homeostasis. The MrgD metabolic effects are related to the maintenance of BAT functionality, but the signaling remains unexplored. This review provides a summary of RAS counterregulatory actions triggered by Mas and MrgD receptors on adipose tissue plasticity. Focus on the effects related to the morphology and function of adipose tissue, especially from animal studies, will be given targeting new avenues for treatment of obesity-associated metabolic effects.

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Background: SARS-CoV-2 binding to ACE2 is potentially associated with severe pneumonia due to COVID-19. The aim of the study was to test whether Mas-receptor activation by 20-hydroxyecdysone (BIO101) could restore the Renin-Angiotensin System equilibrium and limit the frequency of respiratory failure and mortality in adults hospitalized with severe COVID-19. Methods: Double-blind, randomized, placebo-controlled phase 2/3 trial. Randomization: 1:1 oral BIO101 (350 mg BID) or placebo, up to 28 days or until an endpoint was reached. Primary endpoint: mortality or respiratory failure requiring high-flow oxygen, mechanical ventilation, or extra-corporeal membrane oxygenation. Key secondary endpoint: hospital discharge following recovery (ClinicalTrials.gov Number, NCT04472728). Findings: Due to low recruitment the planned sample size of 310 was not reached and 238 patients were randomized between August 26, 2020 and March 8, 2022. In the modified ITT population (233 patients; 126 BIO101 and 107 placebo), respiratory failure or early death by day 28 was 11.4% lower in the BIO101 (13.5%) than in the placebo (24.3%) group, (p = 0.0426). At day 28, proportions of patients discharged following recovery were 80.1%, and 70.9% in the BIO101 and placebo group respectively, (adjusted difference 11.0%, 95% CI [-0.4%, 22.4%], p = 0.0586). Hazard Ratio for time to death over 90 days: 0.554 (95% CI [0.285, 1.077]), a 44.6% mortality reduction in the BIO101 group (not statistically significant). Treatment emergent adverse events of respiratory failure were more frequent in the placebo group. Interpretation: BIO101 significantly reduced the risk of death or respiratory failure supporting its use in adults hospitalized with severe respiratory symptoms due to COVID-19. Funding: Biophytis.

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PURPOSE: Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract, and its unique location within the small intestine presents difficulties in obtaining tissue samples from the lesions. This limitation hinders the research and development of effective clinical treatment methods. Circulating tumor DNA (ctDNA) analysis holds promise as an alternative approach for investigating SBA and guiding treatment decisions, thereby improving the prognosis of SBA. METHODS: Between January 2017 and August 2021, a total of 336 tissue or plasma samples were obtained and the corresponding mutation status in tissue or blood was evaluated with NGS. RESULTS AND CONCLUSIONS: The study found that in SBA tissues, the most commonly alternated genes were TP53, KRAS, and APC, and the most frequently affected pathways were RTK-RAS-MAPK, TP53, and WNT. Notably, the RTK-RAS-MAPK pathway was identified as a potential biomarker that could be targeted for treatment. Then, we validated the gene mutation profiling of ctDNA extracted from SBA patients exhibited the same characteristics as tissue samples for the first time. Subsequently, we applied ctDNA analysis on a terminal-stage patient who had shown no response to previous chemotherapy. After detecting alterations in the RTK-RAS-MAPK pathway in the ctDNA, the patient was treated with MEK + EGFR inhibitors and achieved a tumor shrinkage rate of 76.33%. Our study utilized the largest Chinese SBA cohort to uncover the molecular characteristics of this disease, which might facilitate clinical decision making for SBA patients.

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Obesity has emerged as a significant public health challenge. With the ongoing increase in life expectancy, the prevalence of obesity is steadily growing, particularly among older age demographics. The extension of life expectancy frequently results in additional years of vulnerability to chronic health issues associated with obesity in the elderly.The concept of SARS-CoV-2 directly infecting adipose tissue stems from the fact that both adipocytes and stromal vascular fraction cells express ACE2, the primary receptor facilitating SARS-CoV-2 entry. It is noteworthy that adipose tissue demonstrates ACE2 expression levels similar to those found in the lungs within the same individual. Additionally, ACE2 expression in the adipose tissue of obese individuals surpasses that in non-obese counterparts. Viral attachment to ACE2 has the potential to disturb the equilibrium of renin-angiotensin system homeostasis, leading to an exacerbated inflammatory response.Consequently, adipose tissue has been investigated as a potential site for active SARS-CoV-2 infection, suggesting its plausible role in virus persistence and contribution to both acute and long-term consequences associated with COVID-19.This review is dedicated to presenting current evidence concerning the presence of SARS-CoV-2 in the adipose tissue of elderly individuals infected with the virus. Both obesity and aging are circumstances that contribute to severe health challenges, heightening the risk of disease and mortality. We will particularly focus on examining the mechanisms implicated in the long-term consequences, with the intention of providing insights into potential strategies for mitigating the aftermath of the disease.

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In this study, we evaluated the toxicological and antiproliferative effects of B. glabra Choisy bract extract (BGCE) in its free and loaded into liposomes forms administered to C. elegans mutants with let-60 gain-of-function (gf). Our results demonstrated that the concentration up to 75 µg CAE/mL of BGCE was safe for the worms. Notably, we developed BGCE-loaded liposomes to extend the pharmacological window up to 100 µg CAE/mL without toxicity. In addition, the extract and liposomes reduced the number and area of the multivulva formed in let-60 gf mutants. There was also an increase in the apoptotic signaling in the germline cells and increased longevity mediated through DAF-16 nuclear translocation with GST-4 activation in the treated animals. Our findings demonstrated that the BGCE-loaded liposomes possess antitumoral effects due to the activation of the apoptotic signaling and DAF-16 nuclear translocation.

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Artemia nauplii are widely used as fish larvae feed due to its beneficial nutritional characteristics for larval development; however, efficient feeding strategies are needed to balance its high costs. Therefore, we evaluated the effects of different densities of Artemia nauplii (100, 250, 500, 750, and 1000 nauplii/post-larvae) on the growth, survival, water quality, and myogenic gene expression of tambaqui (Colossoma macropomum) post-larvae cultivated in a recirculating aquaculture system. After 2 weeks of trial, there was a significant decrease in dissolved oxygen concentration with the increase in nauplii density, but it did not interfere with larval performance and survival. In the first week, larvae fed with fewer than 500 nauplii/post-larvae presented slower growth, while in the second week, larvae fed with 1000 nauplii/post-larvae had the highest final weight and length. Regression analysis suggests that the optimum feeding density of Artemia nauplii during the first week is 411 nauplii/post-larvae, while for the second week, the growth increased proportionally to the feeding densities. The relative expression of the myod, myog, and mstn genes was higher in larvae fed with fewer than 500 nauplii/post-larvae. Although low-growing larvae showed increased expression of myod and myog genes, responsible for muscle hyperplasia and hypertrophy, respectively, mstn expression may have played a significant inhibitory role in larval development. Further research is needed to better determine the effects of the live food on the zootechnical performance and the expression of the myogenic genes in the initial phase of the life cycle of the tambaqui post-larvae.

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Resumo Este trabalho apresenta uma revisão crítica das políticas e ações público-governamentais no que tange ao enfrentamento da epidemia HIV/AIDS no Brasil. Apoia-se principalmente sobre orientações, documentos, relatórios e boletins do Ministério da Saúde, analisados por uma ótica queer e desconstrucionista consciente e crítica no que concerne à inserção de sujeitos historicamente marginalizados em políticas e serviços públicos de saúde no país. Pretende-se discutir e relacionar a imbricação entre o biopoder, as necropolíticas e o microcosmo da teoria queer no que diz respeito especialmente a práticas sexuais dissidentes. Analisando o acesso e a equidade em saúde, e afunilando para dados qualitativos e quantitativos das atividades de promoção e prevenção em saúde realizadas pelos Centros de Acolhimento Temporários (CTAs) e pelas Redes de Atenção à Saúde (RAS), surge uma breve elaboração teórica sobre as temáticas mencionadas, embasadas por discussões que perpassam a obra foucaultiana e sua influência sobre Teoria Queer e análises biopolíticas. Indivíduos que são considerados população-chave nas bases de estratégias preventivas continuam sendo negligenciados pelas políticas públicas ou enfrentam dificuldades no acesso aos serviços de saúde. Essas grandes contradições podem estar contribuindo para o aumento significativo no número de novas infecções pelo HIV/AIDS entre segmentos demográficos mais suscetíveis e vulneráveis socioeconômica-política-culturalmente.

Abstract This work presents a critical review of public-governmental policies and actions regarding combating the HIV/AIDS epidemic in Brazil. It is mainly based on guidelines, documents, reports, and bulletins from the Ministry of Health, analyzed from a conscious and critical queer and deconstructionist perspective regarding the inclusion of historically marginalized subjects in public health policies and services in the country. It intends to discuss and relate the overlap between the biopower, the necropolitics, and the microcosm of queer theory with regards especially to dissident sexual practices. Analyzing access and equity in health and focusing on qualitative and quantitative data on health promotion and prevention activities carried out by Temporary Reception Centers (TRC)s and Health Care Networks (HCN), the basis for a brief theoretical elaboration on the themes mentioned emerges, based on discussions that permeate Foucault's work and its influence on Queer Theory and biopolitical analyses. Individuals who are considered a key population in the basis of preventive strategies continue to be neglected by public policies or face difficulties in accessing health services. These major contradictions may be contributing to the significant increase in the number of new HIV/AIDS infections among the most susceptible and socio-economically-politically-culturally vulnerable demographic segments.

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Resumen: El presente texto tiene como objetivo comprender creencias sociales sobre la paz y la negociación política en el marco del conflicto armado colombiano en 304 ciuda danos de 12 municipios del país, para determinar de qué manera algunas de ellas se constituyen en barreras psicosociales para la construcción de la paz y la recon ciliación en Colombia. Pudo concluirse que los participantes tienen un núcleo de creencias sociales en torno a la paz, referida como tranquilidad, armonía, orden, seguridad, ausencia de conflicto y serenidad interior, que enlaza con conceptos propios de la 'paz liberal' en tanto el Estado es quien mantendría este orden y seguridad; niegan a su vez, la posibilidad de disenso, contradicción, oposición, protesta y rebeldía, aun cuando este orden establecido produzca situaciones de injusticia y exclusión, puesto que primaría el mantenimiento de esta 'paz'. En este contexto quienes se oponen al Estado o al poder establecido serán considera dos enemigos y se legitima su señalamiento, estigmatización, exclusión y elimina ción; además, se cierran puertas para la negociación política con actores armados que enarbolen una contradicción a estos sistemas sociales, puesto que, son consi derados 'delincuentes' y portadores de maldad, al alterar la tranquilidad, la se guridad y la armonía, configurándose así unas barreras psicosociales para la paz.

Abstract: The objective of this text is to understand social beliefs about peace and politi cal negotiation in the context of the Colombian armed conflict in 304 citizens of 12 municipalities in the country, in order to determine how some of them cons titute psychosocial barriers to peace building and reconciliation in Colombia. It was possible to conclude that the participants have a core of social beliefs about peace, referred to as tranquility, harmony, order, security, absence of conflict, and inner serenity, which is linked to concepts of 'liberal peace' insofar as the State is the one who would maintain this order and security. They deny, in turn, the possibility of dissent, contradiction, opposition, protest, and rebellion, even when this established order produces situations of injustice and exclusion, since the maintenan ce of this 'peace' would take precedence. In this context, those who oppose the State or the es tablished power are considered enemies, and they are legitimized to be singled out, stigmatized, excluded, and eliminated. Furthermore, the doors are closed to political negotiation with armed stakeholders who contradict these social systems, since they are considered 'criminals' and bea rers of evil, by altering tranquility, security, and harmony; thus creating psychosocial barriers to peace.

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PURPOSE: Evaluate overall survival (OS), RAS, BRAF, and MSI frequencies in patients with metastatic colorectal cancer (mCRC), refractory to chemotherapy, and finally treated with cetuximab. METHODS: A retrospective cohort study to evaluate 211 mCRC patients with wild-type KRAS treated with cetuximab. BRAF V600E, KRAS, NRAS gene mutations, and MSI status were identified using PCR techniques in a population of pre-treated patients who were refractory to fluoropyrimidines, oxaliplatin, and irinotecan. In addition, we evaluated the mutation frequency of the BRAF and NRAS genes and the MSI status of this population. Uni- and multivariate analyses were performed for independent prognostic factors of OS. RESULTS: The median OS was 10.4 months, 6.6 months for patients with right and 11.5 months for left colon cancers (p = 0.02). The frequencies of mutations were BRAF at 3.9% (median OS of 4.9 months), NRAS at 3.38% (median OS of 6.9 months), and MSI-High status at 3.3% (median OS of 4.6 months). The OS, NRAS, and MSI frequencies were similar to those found in other studies that evaluated cetuximab in poly-treated patients and were associated with lower survival rates in univariate analyses. The frequency of BRAF mutations was lower than that found in previous studies. The only variable that remained significant for OS in the multivariate model was tumour laterality, with patients with right colon cancer presenting a worse prognosis (HR = 2.81). CONCLUSION: Although BRAF, NRAS mutations, and MSI-High status were associated with shorter OS in univariate analyses, only tumour laterality remained an independent prognostic factor in the multivariate analysis.

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In filamentous fungi, the hypha orientation is essential for polarized growth and morphogenesis. The ability to re-orient tip growth in response to environmental cues is critical for the colony survival. Therefore, hyphal tip orientation and tip extension are distinct mechanisms that operate in parallel during filamentous growth. In yeast, the axial growth orientation requires a pathway regulated by Rsr1p/Bud1p, a Ras-like GTPase protein, which determines the axial budding pattern. However, in filamentous fungi the function of the Rsr1/Bud1p gene (krev-1 homolog) has not been completely characterized. In this work, we characterized the phenotype of a homokaryon mutant Bud1p orthologous in Neurospora crassa (△bud-1) and tagged BUD-1 with the green fluorescent protein (GFP) to determine its localization and cell dynamics under confocal microscopy. During spore germination BUD-1 was localized at specific points along the plasma membrane and during germ tube emergence it was located at the tip of the germ tubes. In mature hyphae BUD-1 continued to be located at the cell tip and was also present at sites of branch emergence and at the time of septum formation. The △bud-1 mutant showed a delayed germination, and the orientation of hyphae was somewhat disrupted. Also, the hypha diameter was reduced approximately 37 % with respect to the wild type. The lack of BUD-1 affected the Spitzenkörper (Spk) formation, trajectory, the localization of polarisome components BNI-1 and SPA-2, and the actin cytoskeleton polarization. The results presented here suggest that BUD-1 participates in the establishment of a new polarity axis. It may also mediate the delivery of secretory vesicles for the efficient construction of new plasma membrane and cell wall.

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BACKGROUND: The PanaMa trial demonstrated significant benefit in progression-free survival with the addition of panitumumab (Pmab) to fluorouracil and folinic acid (FU/FA) as maintenance therapy following first-line induction therapy with FOLFOX/Pmab in patients with RAS wild-type metastatic colorectal cancer. Here, we report health-related quality of life (HRQOL) analyses from the PanaMa trial. METHODS: HRQOL outcomes were evaluated using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) at every cycle of therapy until disease progression/death. HRQOL outcomes were mean and individual changes in EORTC QLQ-C30 from baselines (before induction therapy and before maintenance therapy) to each cycle of treatment. Comparative analyses were performed by randomisation status and treatment arm for induction- and maintenance-therapy, respectively. The trial is registered with clinicaltrials.gov (NCT01991873). RESULTS: At least one HRQOL questionnaire was completed by a total of 349/377 (93%) patients who received induction therapy, and by 237/248 (96%) patients who were randomised and received maintenance therapy. During induction therapy, most HRQOL dimensions remained stable or showed improvement, while appetite loss and diarrhoea significantly deteriorated. During maintenance therapy, HRQOL dimensions remained stable, while those that deteriorated during induction therapy showed significant improvement, without significant differences between the treatment arms. CONCLUSION: Maintenance therapy improves HRQOL dimensions that initially deteriorated during induction therapy while stabilising HRQOL in other dimensions. The addition of Pmab to FU/FA as maintenance therapy in patients with RAS wild-type metastatic colorectal cancer prolongs progression-free survival without negative impact on HRQOL.

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