Clinical and microbiological characteristics of bacterial infections in patients with cirrhosis. A prospective cohort study from Argentina and Uruguay.

INTRODUCTION AND OBJECTIVES: there is insufficient data regarding bacterial infections in patients with cirrhosis to support recommendations for empiric antibiotic treatments, particularly in Latin America. This study aimed to evaluate bacterial infection's clinical impact and microbiological characteristics, intending to serve as a platform to revise current practices. MATERIALS AND METHODS: multicenter prospective cohort study of patients with cirrhosis and bacterial infections from Argentina and Uruguay. Patient and infection-related information were collected, focusing on microbiology, antibiotic susceptibility patterns, and outcomes. RESULTS: 472 patients were included. Spontaneous bacterial infections and urinary tract infections (UTIs) were registered in 187 (39.6%) and 116 (24.6%) patients, respectively, representing the most common infections. Of the 256 culture-positive infections, 103 (40.2%) were caused by multidrug-resistant organisms (reaching 50% for UTI), and 181 (70.7%) received adequate initial antibiotic treatment. The coverage of cefepime and ceftriaxone was over 70% for the empirical treatment of community-acquired spontaneous infections, but ceftazidime´s coverage was only 40%. For all UTI cases and for healthcare-associated or nosocomial spontaneous bacterial infections, the lower-spectrum antibiotics that covered at least 70% of the isolations were imipenem and meropenem. During hospitalization, a second bacterial infection was diagnosed in 9.8% of patients, 23.9% required at least one organ support, and 19.5% died. CONCLUSIONS: short-term mortality of bacterial infections in patients with cirrhosis is very high, and a high percentage were caused by multidrug-resistant organisms, particularly in UTIs. The information provided might serve to adapt recommendations, particularly related to empirical antibiotic treatment in Argentina and Uruguay. The study was registered in Clinical Trials (NCT03919032).

Cannabis medicinal como recurso terapéutico: estudio preliminar / Medical cannabis as a therapeutic resource: preliminary study / Cannabis medicinal como recurso terapêutico: estudo preliminar

Introducción: los productos de Cannabis sativa L poseen una eficacia terapéutica conocida desde la Antigüedad, aunque su tipificación farmacológica data de mediados del siglo XX. Recientemente se regularizó su uso en Uruguay. Objetivo: analizar una experiencia clínico terapéutica preliminar con cannabis medicinal (CM) con alto contenido en cannabidiol (CBD). Método: estudio epidemiológico observacional y retrospectivo de una cohorte de 355 pacientes que concurrieron a consultar espontáneamente sobre CM en una clínica privada entre agosto de 2016 y diciembre de 2017. Durante la primera entrevista se recogieron datos demográficos, historia clínica, farmacológica, expectativas y experiencia previa con cannabis. Se indicó mayoritariamente cannabis con alto contenido en CBD (5,25% de CBD y 0,2% de tetrahidrocannabinol (THC)). En consultas siguientes, se investigó el acceso al CM y se valoró su respuesta y efectos adversos mediante escalas analógicas. Se utilizó estadística descriptiva. Resultados: en la cohorte estudiada predominaron mujeres con edad promedio de 67 años, de nivel educativo terciario. Las patologías de consulta fueron neurológicas (38%), enfermedades reumáticas o artro-degenerativas (37%), neoplasias (13%), psiquiátricas (4%) y misceláneas (8%). La mayoría de estos casos (60,6%) refirió mejoría de sus síntomas y solo 16,3% de la población estudiada presentó efectos adversos de grado leve. Los altos costos y la gestión dificultosa para conseguir el CM fueron causas para no iniciar o abandonar el tratamiento. Conclusiones: nuestro estudio preliminar refleja una respuesta terapéutica positiva y sin efectos adversos significativos al CM con alto contenido de CBD. El 60,6% de los pacientes tratados refirió mejoría de sus síntomas. Los factores decisivos para un tratamiento exitoso orientan a facilitar el acceso al CM, mejorando la gestión para su obtención y disminuyendo los costos para una mayor accesibilidad.

Introduction: Cannabis Sativa L. products are known to be therapeutically effective since ancient times, despite its pharmacological typification was made in the mid-20th century. Its use was recently regulated in Uruguay. Objective: to analyse a preliminary clinical-therapeutic experience with MC with high content of cannabidiol (CBD). Method: epidemiological, observational and retrospective study of a 355 patient cohort who spontaneously consulted to learn about CM at a private clinic, between August 2016 and December 2017. Demographic data, medical records, expectation and previous experience with cannabis were collected in the first interview. In most cases, cannabis with high content of CBD was prescribed (5,25 % CBD and 0,2% THC). In subsequent consultations, access to access to MC was invesrtigated and both response to it and adverse effects were studied by means of analogue scales. The study used descriptive statistics. Results: in the cohort studied, women with an average age of 67 years old and university studies prevailed. The following conditions motivated consultations: neurological (38%), rheumatic or bone degenerative diseases (37%), neoplasms (13%), psychiatric diseases (4%) and miscelánea (8%). In most cases (60,6%) patients stated symptoms improved and only 16,3% of the populaiton studied presented mild adverse effects. High costs and difficulties in accessing MC were the reasons for not starting or abandoning treatment. Conclusions: our preliminary study reflects the positive therapeutic response and non significant adverse effects to MC with high content of CBD. 60,6% of patients treated referred improvement in their symptoms. Decisive factors for a successful treatment point at the need to make access to MC easier by improving management to obtain it and reducing costs for a greater accessibility.

Introdução: A eficácia terapêutica dos produtos de Cannabis Sativa L. é conhecida desde a antiguidade, embora sua tipificação farmacológica tenha sido feita a meados do século XX. Seu uso no Uruguai foi regularizado recentemente. Objetivo: Analisar uma experiencia clínico-tera-pêutica preliminar com CM com alto teor de Cannabidiol (CBD). Métodos: Estudo epidemiológico observacional e retrospectivo de uma coorte de 355 pacientes que consultaram espontaneamente sobre CM em uma clínica privada no período agosto de 2016 - dezembro de 2017. Durante a primeira entrevista foram coletados dados demográficos, clínicos, farmacológicos, expectativas e experiencia previa com cannabis. Na maioria dos casos indicou-se cannabis com alto teor em CBD (5,25 % de CBD e 0,2 % de THC). Nas consultas seguintes, coletou-se informação sobre o acesso a CM e realizou-se uma avaliação da resposta e dos efeitos adversos utilizando escalas analógicas. Foram utilizados métodos de estadística descritiva. Resultados: Na coorte estudada predominaram mulheres com idade média de 67 anos, de nível educativo terciário. As razõoes de consulta foram patologias neurológicas (38%), enfermidades reumáticas ou artro-degenerativas (37%), neoplasias (13%), doenças psiquiátricas (4%) e outras (8%). A maioria dos casos (60.6 %) informou melhoria dos sintomas e somente 16.3 % da população estudada apresentou efeitos adversos leves. As causas para não iniciar ou abandonar o tratamento foram os altos custos e as dificuldades para a obtenção da CM. Conclusões: Este estudo preliminar mostra uma resposta terapêutica positiva e sem efeitos adversos significativos ao CM com alto teor de CBD. 60.6% dos pacientes tratados informou melhoria de sintomas. Os fatores decisivos para um tratamento exitoso mostram a necessidade de facilitar o acesso a CM melhorando a gestão para sua obtenção e diminuindo os custos para aumentar o acesso.

Molecular Dynamics Investigation of Polylysine Peptide Translocation through MoS2 Nanopores.

Solid-state nanopores (SSN) made of two-dimensional materials such as molybdenum disulfide (MoS2) have emerged as candidate devices for biomolecules sequencing. SSN sequencing is based on measuring the variations in ionic conductance as charged biomolecules translocate through nanometer-sized channels, in response to an external voltage applied across the membrane. Although several experiments on DNA translocation through SSNs have been performed in the past decade, translocation of proteins has been less studied, partly due to small protein size and detection limits. Moreover, the threading of proteins through nanopore channels is challenging, because proteins can exhibit neutral global charge and not be sensitive to the electric field. In this paper, we investigate the translocation of lysine residues and a model protein with polylysine tags through MoS2 nanoporous membranes using molecular dynamics simulations. Adding lysine tags to biological peptides is the method proposed here to promote the entrance of proteins through SSN. Specifically, we study the relationship existing between the translocation events and the ionic conductance signal drops. We show that individual lysine residues translocate easily through MoS2 nanopores, but the translocation speed is extremely fast, which leads to indiscernible ionic conductance drops. To reduce the translocation speed, we demonstrate that increasing the thickness of the membrane from single-layer to bilayer MoS2 reveals a stepwise process of translocation with discernible conductance drops that could be measured experimentally. Finally, a study of the threading of proteins with polylysine tags through MoS2 nanopores is presented. The addition of the positively charged tag to the neutral protein allows the threading and full translocation of the protein through the pore (at least two lysine residues are necessary in this case to observe translocation) and a similar sequence of translocation events is detected, independently of the tag length.

Origin and Migration of Olfactory Cajal-Retzius Cells.

Early telencephalic development involves the migration of diverse cell types that can be identified by specific molecular markers. Most prominent among them are Cajal-Retzius (CR) cells that emanate mainly from the cortical hem and to a lesser extent from rostrolateral, septal and caudo-medial regions. One additional territory proposed to give rise to CR cells that migrate dorsally into the neocortex lies at the ventral pallium, although contradictory results question this notion. With the use of a cell-permeable fluorescent tracer in cultured embryos, we identified novel migratory paths of putative CR cells and other populations that originate from the rostrolateral telencephalon at its olfactory region. Moreover, extensive labeling on the lateral telencephalon along its rostro-caudal extent failed to reveal a dorsally-migrating CR cell population from the ventral pallium at the stages analyzed. Hence, this work reveals a novel olfactory CR cell migration and supports the idea that the ventral pallium, where diverse types of neurons converge, does not actually generate CR cells.