Representações sociais sobre o planejamento reprodutivo entre mulheres em gravidez não planejada / Social representations of reproductive planning among women with unplanned pregnancies / Representaciones sociales sobre la planificación reproductiva de las mujeres con embarazo no planificado

Objetivo: conhecer as representações sociais sobre o planejamento reprodutivo entre mulheres em gravidez não planejada na Estratégia Saúde da Família. Método: estudo qualitativo, orientado pela Teoria das Representações Sociais, realizado com 15 gestantes, entre abril e maio de 2019. Utilizou-se a entrevista semiestruturada. Os dados foram organizados por meio do Discurso do Sujeito Coletivo, com auxílio do software DSCsoft©. Protocolo de pesquisa aprovado pelo Comitê de Ética em Pesquisa. Resultados: as representações sociais das mulheres em gravidez não planejada evidenciadas pelo Discurso do Sujeito Coletivo foram representadas por oito ideias centrais, a saber: "eu não me preveni, nem ele", "nós nos prevenimos", "eu comprava", "pegava no posto", "construir uma família", "ter esse acesso", "estou por fora" e "eu sei que é disponível". Conclusão: as representações sociais nos discursos das mulheres em gravidez não planejada estavam pautadas no desconhecimento acerca do planejamento reprodutivo, dos anticoncepcionais disponíveis e seu uso correto.

Objective: to understand the social representations of reproductive planning among women with unplanned pregnancies in the Family Health Strategy. Method: qualitative study, guided by the Theory of Social Representations, carried out with 15 pregnant women between April and May 2019. Semi-structured interviews were used. The data was organized using the Discourse of the Collective Subject, with the aid of DSCsoft© software. Research protocol approved by the Research Ethics Committee. Results: the social representations of women with unplanned pregnancies as evidenced by the Collective Subject Discourse were represented by eight central ideas, namely: "I didn't prevent myself, nor did he", "we prevented ourselves", "I would buy it", "I would get it at the health center", "build a family", "have this access", "I am not aware" and "I know it is available". Conclusion: the social representations in the women's speeches about unplanned pregnancies were based on a lack of knowledge about reproductive planning, the contraceptives available and their correct use.

Objetivo: conocer las representaciones sociales sobre la planificación reproductiva de las mujeres con embarazo no planificado en la Estrategia Salud de la Familia. Método: estudio cualitativo, basado en la Teoría de las Representaciones Sociales, realizado con 15 mujeres embarazadas, entre abril y mayo de 2019. Se utilizaron entrevistas semiestructuradas. Los datos fueron organizados mediante el Discurso del Sujeto Colectivo, con ayuda del software DSCsoft©. El protocolo de investigación fue aprobado por el Comité de Ética en Investigación. Resultados: las representaciones sociales de las mujeres con embarazo no planificado reveladas por el Discurso del Sujeto Colectivo fueron representadas por ocho ideas centrales, a saber: "yo no me cuidé y él tampoco", "nos cuidamos", "yo los compraba", "los buscaba en el centro de salud", "construir una familia", "tener acceso", "no participo" y "sé que está disponible". Conclusión: las representaciones sociales en los discursos de las mujeres con embarazo no planificado se basaron en la falta de conocimiento sobre la planificación reproductiva, en los anticonceptivos disponibles y su uso correcto.

Chemical characterization and antibacterial activities of Brazilian propolis extracts from Apis mellifera bees and stingless bees (Meliponini).

The aim of this study was to evaluate the physicochemical composition and antibacterial activity of Brazilian propolis extracts from different types, concentrations, and extraction solvents and from different regions in Brazil. A total of 21 samples were analyzed, comprising 14 samples from Apis mellifera (12 green, 1 brown, and 1 red) and 7 samples from stingless bees (3 mandaçaia, 2 jataí, 1 hebora, and 1 tubuna). The analyses performed were dry extract, total phenolic content (TPC) and antioxidant activity (DPPH and ABTS). The antibacterial activity was performed by Determination of Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC). The results showed that very low levels of phenolic compounds and antioxidant activity decreased the antimicrobial activity of the propolis extracts from tubuna and jataí. However, there was no correlation between the increase in propolis concentration in the extract, and the increase in antimicrobial activity. The highest TPC and antioxidant activity was obtained for green propolis extract made with 70% raw propolis that presented similar antibacterial activity to the samples formulated with 30% or less raw propolis. The aqueous propolis extract showed lower antimicrobial activity compared to the alcoholic extracts, indicating that ethanol is a better solvent for extracting the active compounds from propolis. It was observed that the MIC (0.06 to 0.2 mg/mL) and MBC (0.2 to 0.5 mg/mL) values for Gram-negative bacteria were higher compared to Gram-positive bacteria (MIC 0.001-0.2 mg/mL, and the MBC 0.02-0.5 mg/mL). The propolis extracts that exhibited the highest antimicrobial activities were from stingless bees hebora from the Distrito Federal (DF) and mandaçaia from Santa Catarina, showing comparable efficacy to samples 5, 6, and 7, which were the green propolis from the DF. Hence, these products can be considered an excellent source of bioactive compounds with the potential for utilization in both the pharmaceutical and food industries.

Nature portrayed in images in Dutch Brazil: Tracing the sources of the plant woodcuts in the Historia Naturalis Brasiliae (1648).

By the mid-seventeenth century, images of natural elements that originated in Dutch Brazil circulated in Europe. These were often included in art collections (the Libri Picturati) and natural history treatises (the Historia Naturalis Brasiliae and the India Utriesque re Naturale et Medica, 1658). The plant woodcut images in these books constituted (icono) type specimens and played a significant role in disseminating scientific botanical knowledge. We present a systematic analysis of their origins by cross-referencing the visual and textual sources related to Dutch Brazil. To do so, we used our previous botanical identifications of the portrayed plants, published sources, and digital archival material. The plant woodcuts accounted for 529 images, which corresponded to 426 taxa. We created a PDF booklet to visualize the (dis-) similarities of the woodcuts with the Libri Picturati and other visual sources. Substantial differences in the visual-making methodology exist between the two treatises (1648, 1658). In the first book, most of the images were available from Dutch Brazil and carved into the woodcuts, while most of these woodcuts were reused in the second one. The Indigenous Tupi-based plant names accompanying the images were crucial when arranging the sources, and portraying as much botanical information as possible was commonly the goal. Freshly picked, living plants, dried branches, fruits, and seeds were used to represent the megadiverse Brazilian flora, even when these belonged to species originating from other regions. Despite not being recognized for their contribution, Indigenous Brazilians and enslaved Africans were essential in the visual knowledge-making processes that later resulted in these natural history collections. As several sources remain lost and many histories yet untold, further archival studies and collaborative projects are pertinent to reveal the missing pieces of this conundrum.

Enhancing Human Health and Wellbeing through Sustainably and Equitably Unlocking a Healthy Ocean's Potential.

A healthy ocean is essential for human health, and yet the links between the ocean and human health are often overlooked. By providing new medicines, technologies, energy, foods, recreation, and inspiration, the ocean has the potential to enhance human health and wellbeing. However, climate change, pollution, biodiversity loss, and inequity threaten both ocean and human health. Sustainable realisation of the ocean's health benefits will require overcoming these challenges through equitable partnerships, enforcement of laws and treaties, robust monitoring, and use of metrics that assess both the ocean's natural capital and human wellbeing. Achieving this will require an explicit focus on human rights, equity, sustainability, and social justice. In addition to highlighting the potential unique role of the healthcare sector, we offer science-based recommendations to protect both ocean health and human health, and we highlight the unique potential of the healthcare sector tolead this effort.

High-Density Perfusion Cultures of the Marine Bacterium Rhodovulum sulfidophilum for the Biomanufacturing of Oligonucleotides.

Therapeutic oligonucleotides (ONs) are typically manufactured via solid-phase synthesis, characterized by limited scalability and huge environmental footprint, limiting their availability. Biomanufactured ONs have the potential to reduce the immunogenic side-effects, and to improve the sustainability of their chemical counterparts. Rhodovulum sulfidophilum was demonstrated a valuable host for the extracellular production of recombinant ONs. However, low viable cell densities and product titer were reported so far. In this work, perfusion cell cultures were established for the intensification of ON biomanufacturing. First, the perfusion conditions were simulated in 50mL spin tubes, selected as a scale-down model of the process, with the aim of optimizing the medium composition and process parameters. This optimization stage led to an increase in the cell density by 44% compared to the reference medium formulation. In addition, tests at increasing perfusion rates were conducted until achieving the maximum viable cell density (VCDmax), allowing the determination of the minimum cell-specific perfusion rate (CSPRmin) required to sustain the cell culture. Intriguingly, we discovered in this system also a maximum CSPR, above which growth inhibition starts. By leveraging this process optimization, we show for the first time the conduction of perfusion cultures of R. sulfidophilum in bench-scale bioreactors. This process development pipeline allowed stable cultures for more than 20 days and the continuous biomanufacturing of ONs, testifying the great potential of perfusion processes.

Clinical profile of Oropouche Fever in Bahia, Brazil: unexpected fatal cases / Perfil clínico de la fiebre de Oropouche en Bahía, Brasil: casos fatales inesperados

Oropouche virus (OROV) is an arbovirus transmitted to humans by mosquitoes, with the Culicoides paraensis mosquito species as its primary vector, causing Oropouche fever. Records of an outbreak in Brazil have so far been restricted to Central-North region of the country. However, an increase in the occurrence of cases of this disease has been observed in the state of Bahia, where the rapid spread of the OROV virus is configured as an outbreak in the South and East macro-regions of great concern for public health. This is a case-based study of acute OROV infection that led to the death of two young women without comorbidities amid an outbreak of the disease. The patient's biological samples were subjected to routine real-time PCR assays for the diagnosis of Oropouche fever and other pathologies. In addition, serological tests and metagenomics were performed during the laboratory investigation. This study shows the need for an active and efficient surveillance system to control the spread of this virus, as well as the importance of carrying out prospective studies to better clarify the natural history of this disease.

El virus Oropouche (OROV) es un arbovirus transmitido al ser humano por mosquitos, siendo el mosquito de la especie Culicoides paraensis su vector principal, causante de la fiebre de Oropouche. Los registros de un brote en Brasil hasta ahora se han restringido a la región Centro-Norte del país. Sin embargo, se ha observado un aumento en la ocurrencia de casos de esta enfermedad en el estado de Bahía, donde la rápida propagación del virus OROV se configura como un brote en las macrorregiones Sur y Este de gran preocupación para la salud pública. Se trata de un estudio de caso de infección aguda por OROV que provocó la muerte de dos mujeres jóvenes sin comorbilidades en medio de un brote de la enfermedad. Las muestras biológicas de la paciente fueron sometidas a ensayos rutinarios de PCR en tiempo real para el diagnóstico de la fiebre de Oropouche y otras patologías. Además, se realizaron pruebas serológicas y metagenómicas durante la investigación de laboratorio. Este estudio muestra la necesidad de un sistema de vigilancia activo y eficiente para controlar la propagación de este virus, así como la importancia de realizar estudios prospectivos para esclarecer mejor la historia natural de esta enfermedad.

Surgical approach with minimally invasive intervention in lusoria dysphagia.

The lusoria artery has a prevalence of 0.5-2% in the general population. The abnormal development of the aortic arch forms vascular rings around the trachea and esophagus, causing pressure on them and leading to characteristic symptoms such as chest pain, difficulty breathing, and/or swallowing. Conventionally, only the subclavian artery was severed to release the esophagus, as done in neonates. However, this can lead to long-term hypotrophy of the thoracic limb. The surgical intervention remains controversial, with limitations, and it is only to be performed when the patient presents with symptoms. In the following two cases, a two-stage minimally invasive approach is described: first, a left lateral minithoracotomy for lusoria artery sectioning, and second, a supraclavicular approach for reimplantation into the right carotid artery.

La arteria lusoria tiene una prevalencia del 0.5% al 2% en la población general. Se trata de un arco aórtico izquierdo con arteria subclavia derecha aberrante, resulta de la regresión del cuarto arco derecho y la aorta dorsal derecha proximal. La anormalidad del desarrollo del arco aórtico forma anillos vasculares alrededor de la tráquea y el esófago ocasionando una presión hacia ellos y dar clínica característica de dolor torácico, dificultad para la respiración y/o deglución. Tradicionalmente solo seccionábamos la subclavia para liberar el esófago como se realiza en la edad neonatal, sin embargo, esto puede condicionar hipotrofia del miembro torácico a largo plazo. La intervención quirúrgica sigue siendo controvertida, con limitaciones y se decide realizarse cuando el paciente presenta sintomatología. En este reporte de dos casos se describe un abordaje por incisiones mínimamente invasiva en dos tiempos: primero por mini toracotomía lateral izquierda para sección de la arteria lusoria; segundo abordaje supraclavicular para reimplantación en la carótida derecha.

RIM and RIM-binding protein localize synaptic CaV2 channels to differentially regulate transmission in neuronal circuits.

At chemical synapses, voltage-gated Ca2+-channels (VGCCs) translate electrical signals into a trigger for synaptic vesicle (SV) fusion. VGCCs and the Ca2+ microdomains they elicit must be located precisely to primed SVs, to evoke rapid transmitter release. Localization is mediated by Rab3 interacting molecule (RIM) and RIM-binding proteins (RIM-BPs), which interact and bind to the C-terminus of the CaV2 VGCC α-subunit. We studied this machinery at the mixed cholinergic/GABAergic neuromuscular junction (NMJ) of Caenorhabditis elegans hermaphrodites. rimb-1 mutants had mild synaptic defects, through loosening the anchoring of UNC-2/CaV2 and delaying the onset of SV fusion. UNC-10/RIM deletion much more severely affected transmission. Even though postsynaptic depolarization was reduced, rimb-1 mutants had increased cholinergic (but reduced GABAergic) transmission, to compensate for the delayed release. This did not occur when the excitation-inhibition balance was altered by removing GABA transmission. Further analyses of GABA defective mutants and GABAA or GABAB receptor deletions, as well as cholinergic rescue of RIMB-1, emphasized that GABA neurons may be more affected than cholinergic neurons. Thus RIMB-1 function differentially affects excitation/inhibition balance in the different motor neurons, and RIMB-1 thus may differentially regulate transmission in mixed circuits. Untethering the UNC-2/CaV2 channel by removing its C-terminal PDZ ligand exacerbated the rimb-1 defects, and similar phenotypes resulted from acute degradation of the CaV2 ß-subunit CCB-1. Therefore, untethering of the CaV2 complex is as severe as its elimination, yet does not abolish transmission, likely due to compensation by CaV1. Thus, robustness and flexibility of synaptic transmission emerges from VGCC regulation.Significance statement The machinery for chemical synaptic transmission is organized in a precise spatial arrangement in order to enable efficient and temporally accurate coupling of action potentials with the rise of the Ca2+ concentration through CaV2 P/Q-type voltage gated Ca2+ channels. This triggers the fusion of synaptic vesicles with the plasma membrane and the release of transmitters. Here, we analyzed the molecular and functional interplay of proteins of the active zone scaffold, RIM and RIM-binding protein (RIMB-1), with the CaV2 channel in the C. elegans neuromuscular junction, a tripartite synapse with cholinergic and GABAergic neuronal input. Our work shows a differential requirement of RIMB-1 in cholinergic vs. GABAergic neurons, that affects the regulation of excitation-inhibition balance at circuit, cellular and ultrastructural levels.

A rare occurrence of isolated superior mesenteric artery dissection, a case image report.

Isolated spontaneous superior mesenteric artery (SMA) dissection is relatively rare. Often found incidentally on cross-sectional imaging, often managed non-operatively. We present a patient who presented with chest pain and was found to have a SMA dissection.

Consenso mexicano de tirosinemia tipo 1.

INTRODUCTION: Tyrosinemia type 1 is a rare disease with autosomal recessive inheritance, featuring various clinical manifestations. These may encompass acute neonatal liver failure, neonatal cholestatic syndrome, chronic hepatitis, cirrhosis, hepatocellular carcinoma, and, alternatively, kidney disorders like renal tubular acidosis, Fanconi syndrome, hypophosphatemic rickets, among other alterations. Diagnosis relies on detecting toxic metabolites in the blood and urine, ideally confirmed through molecular testing. METHOD: A consensus was reached with experts in the field of inborn errors of metabolism (EIM), including eight pediatric gastroenterologists, two EIM specialists, two geneticists, three pediatric nutritionists specialized in EIM, and a pediatric surgeon specializing in transplants. Six working groups were tasked with formulating statements and justifications, and 32 statements were anonymously voted on using the Likert scale and the Delphi method. The first virtual vote achieved an 80% consensus, with the remaining 20% determined in person. RESULTS: The statements were categorized into epidemiology, clinical presentation, diagnosis, nutritional and medical treatment, and genetic counseling. CONCLUSIONS: This consensus serves as a valuable tool for primary care physicians, pediatricians, and pediatric gastroenterologists, aiding in the prompt diagnosis and treatment of this disease. Its impact on the morbidity and mortality of patients with tyrosinemia type 1 is substantial.

INTRODUCCIÓN: La tirosinemia tipo 1 es una enfermedad rara, con herencia autosómica recesiva, con múltiples manifestaciones clínicas, que pueden comprender desde falla hepática aguda neonatal, síndrome colestásico neonatal, hepatitis crónica, cirrosis o hepatocarcinoma, hasta alteraciones renales como acidosis tubular renal, síndrome de Fanconi o raquitismo hipofosfatémico, entre otras. El diagnóstico se basa en la presencia de metabolitos tóxicos en la sangre y la orina, idealmente con la confirmación molecular de la enfermedad. MÉTODO: Se realizó un consenso con expertos en el área de los errores innatos del metabolismo (EIM): ocho gastroenterólogos pediatras, dos médicos especialistas en EIM, dos genetistas, tres nutriólogas pediatras especializadas en EIM y un cirujano pediatra especialista en trasplantes. Se formaron seis mesas de trabajo encargadas de desarrollar los enunciados con sus justificaciones y fueron votados anónimamente 32 enunciados en una escala Likert con un método Delphi. La primera votación fue virtual, obteniendo consenso del 80% de los enunciados, y la segunda fue presencial, obteniendo el 20% restante. RESULTADOS: Los enunciados fueron divididos en epidemiología, cuadro clínico, diagnóstico, tratamiento nutricional y médico, y consejo genético. CONCLUSIONES: Este consenso constituye una valiosa herramienta para los médicos de atención primaria, pediatras y gastroenterólogos pediátricos, ya que ayuda a diagnosticar y tratar rápidamente esta enfermedad. Su impacto en la morbilidad y mortalidad de los pacientes con tirosinemia tipo 1 es sustancial.

Active Versus Passive Drainage Systems for Subdural Hematomas: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Chronic subdural hematoma (CSDH) management involves various surgical techniques, with drainage systems playing a pivotal role. While passive drainage (PD) and active drainage (AD) are both used, their efficacy remains contentious. Some studies favor PD for lower recurrence rates, while others suggest AD superiority. A systematic review and meta-analysis were conducted to address this controversy, aiming to provide clarity on optimal drainage modalities post-CSDH evacuation. METHODS: This systematic review and meta-analysis followed preferred reporting items for systematic reviews guidelines, searching PubMed, Embase, and Web of Science until February 2024. Inclusion criteria focused on studies comparing active vs PD for subdural hematomas. Data extraction involved independent researchers, and statistical analysis was conducted using R software. The assessment of risk of bias was performed using the Risk of Bias in Non-Randomized Studies of Interventions framework and the Risk Of Bias 2 tool. RESULTS: In this meta-analysis, involving 1949 patients with AD and 1346 with PD, no significant differences were observed in recurrence rates between the active (13.6%) and passive (16.4%) drainage groups (risk ratio [RR] = 0.87; 95% CI: 0.58-1.31). Similarly, for complications, infection, hemorrhage, and mortality, no significant disparities were found between the 2 drainage modalities. Complication rates were 7.5% for active and 12.6% for PD (RR = 0.74; 95% CI: 0.36-1.52). Infection rates were available for 635 patients of the active group, counting for 2% and 2.6%, respectively (RR = 0.98; 95% CI: 0.24-4.01). Hemorrhage rates were also available for 635 patients of the active group, counting for 1.1% and 2.2%, respectively (RR = 0.44; 95% CI: 0.11-1.81). Mortality rates were 2.7% and 2.5%, respectively (RR = 0.94; 95% CI: 0.61-1.46). CONCLUSION: Our study found no significant difference between passive and AD for managing complications, recurrence, infection, hemorrhage, or mortality in CSDH cases. Further large-scale randomized trials are needed for clarity.

Genome drafts of Pseudogracilibacillus spp. from soil and sediment of Mount Makiling, a dormant volcano in the Philippines.

We present the draft whole-genome sequences of Pseudogracilibacillus spp. isolated from the soils and sediments of Sipit Creek located at Mount Makiling, a dormant volcano in the southern part of Luzon Island, Philippines. This Pseudogracilibacillus spp. genome report extends the body of knowledge on a lesser-known genus of Bacillaceae.

Optimization of enzymatic production of anti-skin aging biopeptides from white sorghum [Sorghum bicolor (L) Moench] grain.

Recently, kafirins from white sorghum [Sorghum bicolor (L) Moench] grain have shown promise as a source of biopeptides with anti-skin aging effects (anti-inflammatory, antioxidant, and inhibition of photoaging-associated enzymes). This study employed response surface methodology (RSM) to optimize the extraction and enzymatic hydrolysis of kafirins (KAF) for the production of peptides with anti-skin aging properties. The optimization of conditions (reaction time and enzyme/substrate ratio) for liquefaction with α-amylase and hydrolysis of KAF with alcalase was performed using 32 complete factorial designs. Subsequently, ultrafiltered peptide extracts were obtained with molecular weights of 1-3 kDa (KAF-UF3) and lower than 1 kDa (KAF-UF1), which mainly contain hydrophobic amino acids (proline, leucine, isoleucine, phenylalanine, and valine) and peptide fractions with molecular weights of 0.69, 1.14, and 1.87 kDa. Consequently, the peptide extracts protected immortalized human keratinocytes (HaCaT cells) from ultraviolet B radiation (UVB)-induced damage by preventing the decrease and/or restoring the activity of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)]. Furthermore, KAF-UF3 and KAF-UF1 inhibited (20-29%) elastase and collagenase overactivity in UVB-exposed murine fibroblasts (3T3 cells). Thus, KAF-UF3 and KAF-UF1 exhibited behavior similar to that observed with glutathione (GSH), suggesting their potential as functional peptide ingredients in skincare products.

Localized pemphigus vulgaris on scalp: an atypical presentation.

We present two middle-aged patients with pruritic, crusted scalp erosions. Skin biopsy showed epidermal acantholysis with IgG and C3 intercellular deposits on direct immunofluorescence, leading to the diagnosis of localized pemphigus vulgaris. Resolution of the lesions without relapse occurred after low doses of oral prednisone and intralesional triamcinolone acetonide.

Epidemiology of sarcoptic mange in free-ranging vicuñas (Vicugna vicugna): a cross-sectional study in Andean highland communities in Peru.

Sarcoptic mange or scabies is a contagious parasitic skin disease that affects a wide range of domestic and wildlife species. A cross-sectional study was carried out to determine the prevalence, molecular identification, and characteristics of sarcoptic mange in vicuñas. A total of 3,274 vicuñas were examined. Following ritual harvesting events ("chaccus") in 13 Andean communities. The presence of mange mites was determined by the skin scraping technique and confirmed by PCR analysis using specific primers for the ITS2 gene of Sarcoptes scabiei. The presence of mange mites was also confirmed by microscopy using samples taken from wallows. A data collection form was used to register the characteristics of the vicuñas sampled. The prevalence of sarcoptic mange was 4.9% (95% CI: 4.1 - 5.6%). All samples from wallows tested positive (9/9). Importantly, the presence of the species S. scabiei was molecularly confirmed. Adult females with regular body condition were more susceptible to sarcoptic mange, although the lesions were mild. This study confirms the presence of S. scabiei in semi-captive vicuñas and points to the possible role of wallows in the dissemination of Sarcoptes mites.

Precision oncology and systemic targeted therapy in Pseudomyxoma Peritonei.

PURPOSE: Pseudomyxoma peritonei (PMP) is a rare and poorly understood malignant condition characterized by the accumulation of intra-abdominal mucin produced from peritoneal metastases. Currently, cytoreductive surgery remains the mainstay of treatment but disease recurrence and death after relapse frequently occur in PMP patients. New therapeutic strategies are therefore urgently needed for these patients. EXPERIMENTAL DESIGN: A total of 120 PMP samples from 50 patients were processed to generate a collection of 50 patient-derived organoids (PDO) and xenograft (PDX) models. Whole exome sequencing (WES), immunohistochemistry analyses and in vitro and in vivo drug efficacy studies were performed. RESULTS: In this study, we have generated a collection of PMP preclinical models and identified druggable targets, including BRAFV600E, KRASG12C and KRASG12D,that could also be detected in intra-abdominal mucin biopsies of PMP patients using droplet digital PCR. Preclinical models preserved the histopathological markers from the original patient sample. The BRAFV600E inhibitor encorafenib reduced cell viability of BRAFV600E PMP-PDO models. Proof-of-concept in vivo experiments showed that a systemic treatment with encorafenib significantly reduced tumor growth and prolonged survival in subcutaneous and orthotopic BRAFV600E-PMP-PDX mouse models. CONCLUSIONS: Our study demonstrates for the first time that systemic targeted therapies can effectively control PMP tumors. BRAF signaling pathway inhibition represents a new therapeutic opportunity for BRAFV600E PMP patients who have a poor prognosis. Importantly, our present data and collection of preclinical models pave the way for evaluating the efficacy of other systemic targeted therapies toward extending the promise of precision oncology to PMP patients.

[Endoscopic-percutaneous rendezvous procedure for the management of difficult biliary tract: experience in an endoscopic center in Lima-Peru]. / Procedimiento endoscópico-percutáneo de rendezvous para el manejo de vía biliar difícil: experiencia en un centro endoscópico de Lima-Perú.

OBJECTIVES: Biliary access refractory to conventional cannulation techniques is a challenging clinical scenario for most endoscopists. The endoscopic-percutaneous rendezvous technique is an optimal alternative with high success rates and low complication rates in expert hands, however its routine use in the West, mainly in Latin America, is still limited. The aim of our study was to evaluate the feasibility, efficacy and safety of endoscopic-percutaneous rendezvous in the management of difficult biliary tract in an endoscopic center in Peru. MATERIALS AND METHODS: Descriptive study - case series type that included 21 patients, with diagnosis of difficult bile duct, all treated by endoscopic-percutaneous rendezvous between July 2017 to July 2020. We evaluated: age, gender, number of previous failed endoscopic retrograde cholangiopancreatography, associated endoscopic findings, rate of successful cannulation, rate of successful resolution of difficult choledocholithiasis, adverse events and procedure-related mortality. RESULTS: The rate of successful cannulation was 100% (21/21). There were 12 cases (57.1%) of difficult choledocholithiasis of which there was a successful resolution rate of 91.6% (11/12). The overall adverse event rate was 4.7% (1/21), which was one case of post-sphincteroplasty gastrointestinal bleeding that was successfully resolved endoscopically only. CONCLUSIONS: Endoscopic-percutaneous rendezvous performed by expert hands is feasible, safe and clinically effective for the management of the difficult bile duct in Latin America.