Inyección local de toxina botulínica para la prevención de cicatrices hipertróficas y queloides: un protocolo para una revisión panorámica

Introducción: Las cicatrices hipertróficas (CH) y queloides (QU) corresponden al resultado de una cicatrización patológica en la piel, que afectan la calidad de vida de quienes las presentan. Su tratamiento considera diversas intervenciones, muchas de las cuales son de alto costo y/o poco predecibles. Entre ellas, la toxina botulínica (TB) podría tener un efecto a nivel preventivo, aunque los resúmenes de evidencia presentan resultados disímiles. Por esto, proponemos sintetizar la evidencia proveniente de revisiones sistemáticas (RS) y metaanálisis (MA) de ensayos clínicos aleatorizados (ECA) sobre los efectos de la inyección local de TB en la prevención de CH y QU en pacientes que recibieron o recibirán un trauma quirúrgico en la piel. Métodos y análisis: Revisión panorámica siguiendo la declaración PRIOR. Ejecutaremos la búsqueda en la base de datos Epistemonikos. Realizaremos la selección de estudios, extracción de datos y evaluación de la calidad de las RS por duplicado. Compararemos las revisiones a través de matrices de evidencia, incluyendo las RS que aborden una pregunta similar y los ECA incluidos en estas. Estimaremos la superposición entre revisiones mediante el método de área cubierta y área cubierta corregida. Ética y difusión: No se requiere aprobación ética. Esta revisión se publicará después de un proceso de revisión por pares. Sus resultados podrían ser utilizados por personal de salud para informar decisiones individuales y por tomadores de decisión de servicios de salud para guiar la asignación de recursos.

Introduction: Hypertrophic scars (HS) and keloids (KE) result from an aberrant reparative process in the skin, impacting the quality of life of those who are affected by them. Their treatment consists of different interventions, many of which are costly and/or have unpredictable results. Among them, botulinum toxin (BT) might have a preventive effect, although current evidence summaries show varying results. Therefore, we aim to synthesize the evidence coming from systematic reviews (SRs) and meta-analyses (MA) of randomized controlled trials (RCTs) on the effects of local injection of TB in the prevention of HS and KE formation in patients after a surgical wound of the skin. Methods and analysis: This will be an overview of SRs following PRIOR statement. We will conduct the search in Epistemonikos Database. Two reviewers will independently conduct the screening of articles for inclusion, quality appraisal and data extraction. We will compare the SRs using an evidence matrix, including SRs that address this topic, and the RCTs included in them. We will estimate the overlap between them using the covered area method and corrected covered area index. Ethics and dissemination: Ethics approval is not required. This review will be published after a peer-review process. The results will inform areas of future research and could be used by health personnel to make individual decisions, and by healthcare managers, administrators, and policymakers to guide resource allocation.

Characterization of biofilm formation by Exiguobacterium strains in response to arsenic exposure.

IMPORTANCE: In this work, we characterized the composition, structure, and functional potential for biofilm formation of Exiguobacterium strains isolated from the Salar de Huasco in Chile in the presence of arsenic, an abundant metalloid in the Salar that exists in different oxidation states. Our results showed that the Exiguobacterium strains tested exhibit a significant capacity to form biofilms when exposed to arsenic, which would contribute to their resistance to the metalloid. The results highlight the importance of biofilm formation and the presence of specific resistance mechanisms in the ability of microorganisms to survive and thrive under adverse conditions.

Laboratory mice with a wild microbiota generate strong allergic immune responses.

Allergic disorders are caused by a combination of hereditary and environmental factors. The hygiene hypothesis postulates that early-life microbial exposures impede the development of subsequent allergic disease. Recently developed "wildling" mice are genetically identical to standard laboratory specific pathogen-free (SPF) mice but are housed under seminatural conditions and have rich microbial exposures from birth. Thus, by comparing conventional SPF mice with wildlings, we can uncouple the impact of lifelong microbial exposures from genetic factors on the allergic immune response. We found that wildlings developed larger populations of antigen-experienced T cells than conventional SPF mice, which included interleukin-10-producing CD4 T cells specific for commensal Lactobacilli strains and allergy-promoting T helper 2 (TH2) cells. In models of airway exposure to house dust mite (HDM), recombinant interleukin-33, or Alternaria alternata, wildlings developed strong allergic inflammation, characterized by eosinophil recruitment, goblet cell metaplasia, and antigen-specific immunoglobulin G1 (IgG1) and IgE responses. Wildlings developed robust de novo TH2 cell responses to incoming allergens, whereas preexisting TH2 cells could also be recruited into the allergic immune response in a cytokine-driven and TCR-independent fashion. Thus, wildling mice, which experience diverse and lifelong microbial exposures, were not protected from developing pathological allergic immune responses. Instead, wildlings mounted robust allergic responses to incoming allergens, shedding new light on the hygiene hypothesis.

Encapsulation of Vitamins A and E as Spray-Dried Additives for the Feed Industry.

Encapsulated fat-soluble powders containing vitamin A (VA) and E (VE) were prepared as a feasible additive for extruded feed products. The effect of the encapsulating agents (Capsul-CAP®, sodium caseinate-SC) in combination with Tween 80 (TW) as an emulsifier and maltodextrin (MD) as a wall material on the physicochemical properties of emulsions and powders was evaluated. First, nanoemulsions containing MD:CAP:TW:VA/VE and MD:SC:TW:VA/VE were prepared and characterized. Then, powders were obtained by means of spray-drying and analyzed in terms of the product yield, encapsulation efficiency, moisture content, porosity, surface morphology, chemical structure, and thermal properties and thermo-oxidative/thermal stability. Results showed that although nanoemulsions were obtained for all the compositions, homogeneous microcapsules were found after the drying process. High product yield and encapsulation efficiency were obtained, and the presence of the vitamins was corroborated. The characteristics of the powders were mainly influenced by the encapsulating agent used and also by the type of vitamin. In general, the microcapsules remained thermally stable up to 170 °C and, therefore, the proposed encapsulation systems for vitamins A and E were suitable for the preparation of additives for the feed manufacturing through the extrusion process.

Sexual Selection and the Evolution of Male Reproductive Traits in Benthic Octopuses.

Competition between same-sex organisms, or intra-sexual selection, can occur before and after mating, and include processes such as sperm competition and cryptic female choice. One of the consequences of intra-sexual selection is that male reproductive traits tend to evolve and diverge at high rates. In benthic octopuses, females often mate with more than one male in a single reproductive event, opening the venue for intra-sexual selection at multiple levels. For instance, males transfer spermatophores through hectocotylus, and can remove the spermatophores left by other males. Considering the limited evidence on post-copula competition in benthic octopuses, and the potential to affect the evolution of reproductive traits within octopodids, we put this hypothesis to a test employing a phylogenetic comparative approach. We combined data on hectocotylized arm length (HAL), ligula length (LL), spermatophore length (SL) with a Bayesian molecular phylogeny of 87 species, to analyze how reproductive traits have diverged across lineages and covary with body size (mantle length; ML). First, additionally to ML, we estimated the phylogenetic signal (λ) and mode of evolution (κ) in each reproductive trait. Second, we performed phylogenetic regressions to quantify the association among reproductive traits and their co-variation with ML. This analysis allowed us to estimate the phenotypic change along a branch into the phylogeny, and whether selection may have played a role in the evolution and diversification of specific clades. Estimations of λ were always high (>0.75), indicating concordance between the traits and the topology of the phylogenetic tree. Low values of κ (<1.0) suggested that evolution depends on branch lengths. All reproductive traits exhibiting a positive relation with ML (ß > 0.5 in all cases). Overall, evolutionary rate models applied to the SL-ML regression suggested that octopuses of the family Megaleledonidae have evolved larger spermatophores than expected for their size. The regression HAL-ML indicated that HAL was more variable in Megaleledonidae than in the remaining clades, suggesting that the high divergence across species within this group might partially reflect intra-sexual selection. These results support the hypothesis that, at least in some lineages, sexual selection may account for the divergence in reproductive traits of male octopuses.

Cx43-Gap Junctions Accumulate at the Cytotoxic Immunological Synapse Enabling Cytotoxic T Lymphocyte Melanoma Cell Killing.

Upon tumor antigen recognition, cytotoxic T lymphocytes (CTLs) and target cells form specialized supramolecular structures, called cytotoxic immunological synapses, which are required for polarized delivery of cytotoxic granules. In previous reports, we described the accumulation of connexin 43 (Cx43)-formed gap junctions (GJs) at natural killer (NK) cell-tumor cell cytotoxic immunological synapse. In this report, we demonstrate the functional role of Cx43-GJs at the cytotoxic immunological synapse established between CTLs and melanoma cells during cytotoxicity. Using confocal microscopy, we evaluated Cx43 polarization to the contact site between CTLs isolated from pMEL-1 mice and B16F10 melanoma cells. We knocked down Cx43 expression in B16F10 cells and evaluated its role in the formation of functional GJs and the cytotoxic activity of CTLs, by calcein transfer and granzyme B activity assays, respectively. We found that Cx43 localizes at CTL/B16F10 intercellular contact sites via an antigen-dependent process. We also found that pMEL-1 CTLs but not wild-type naïve CD8+ T cells established functional GJs with B16F10 cells. Interestingly, we observed that Cx43-GJs were required for an efficient granzyme B activity in target B16F10 cells. Using an HLA-A2-restricted/MART-1-specific CD8+ T-cell clone, we confirmed these observations in human cells. Our results suggest that Cx43-channels are relevant components of cytotoxic immunological synapses and potentiate CTL-mediated tumor cell killing.

Fluorescence enzymatic assay for bacterial polyphosphate kinase 1 (PPK1) as a platform for screening antivirulence molecules.

Inorganic polyphosphate (polyP) and its metabolic enzymes are important in several cellular processes related with virulence and antibiotic susceptibility. Accordingly, bacterial polyP synthesis has been proposed as a good target for designing novel antivirulence molecules as alternative to conventional antibiotics. In most pathogenic bacteria, polyphosphate kinase 1 (PPK1), in charge of polyP synthesis from ATP, is widely conserved. Current colorimetric and radioactive polyP synthesis enzymatic assays are not suitable for high-throughput screening of PPK1 inhibitors. Given the ability of polyP to modify the excitation-emission spectra of DAPI (4'-6-diamidino-2-phenylindole), a fluorescence assay was previously developed by using a purified recombinant PPK1 enzyme from Escherichia coli. In this work we have developed a suitable methodology for high-throughput measurement of E. coli PPK1 activity. This platform can be used for the screening putative antimicrobial molecules for related enteropathogenic bacteria.

Rol del terapeuta ocupacional en tratamiento de niños con delirium hospitalario infantil en unidades hospitalarias de Chile / Occupational therapist role in children treatment with hospital infantile delirium at hospital units of Chile

En los últimos años, a nivel mundial, se han incrementado los casos de niños que desarrollan Delirium Hospitalario Infantil (DHI) en diferentes unidades hospitalarias. Por esto, se han realizado investigaciones orientadas al diagnóstico de este cuadro, sin evidencia suficiente que justifique y respalde el abordaje de niños con DHI desde terapia ocupacional. En Chile no existen estudios en el área pediátrica, sin embargo, hay evidencia que sí justifica el abordaje de este cuadro desde terapia ocupacional en población adulta mayor, lo cual entrega un precedente de efectividad de este tratamiento en delirium hospitalario. Por ello, el objetivo de esta investigación es describir el rol del terapeuta ocupacional en el tratamiento del Delirium Hospitalario Infantil en Unidades Hospitalarias de Chile. Esta investigación se enmarca en una metodología cualitativa, diseño fenomenológico, con alcance exploratorio-descriptivo. Cuenta con un universo total de 8 terapeutas ocupacionales (TO) que trabajan actualmente en unidades hospitalarias pediátricas y que han abordado casos de niños con DHI, profesionales que debieron responder cuestionarios, entrevistas en profundidad o entrevista a experto, a modo de triangular los resultados obtenidos para el logro del objetivo. A través de esta investigación se invita a los TO que se desempeñan en el área a sistematizar sus experiencias, con el fin de generar protocolos de intervención para un cuadro de salud subdiagnosticado en población pediátrica, y que es de suma urgencia abordar de manera interdisciplinaria, para promover el menor impacto de la hospitalización en el desarrollo normal de estos niños.

In recent years, worldwide, there has been an increase in cases of children who develop Delirium Hospitalario Infantil (DHI) in different hospital units. Therefore, there have been research with the aim of diagnose this condition, although without adequate evidence to substantiate and sustain occupational therapy to attend children with delirium.In Chile, there are not studies in the pediatric area, however, there are evidence that validate the Occupational Therapy attend in elderly people, which provides a precedent to effectiveness of this treatment in hospital delirium. Thus, the objective of this study is to describe the role of occupational therapist in the treatment of the Hospital Infantile Delirium (HID) in hospital units of Chile.This study is framed in a qualitative methodology, phenomenological with exploratory-descriptive scope. It has a total universe of 8 occupational therapist currently working in pediatric hospital units and who have addressed cases of children with HID, professionals who had to answer questionnaires, in-depth interviews or expert interviews, in order to triangulate the results obtained for the achievement of the objective.Through this study, occupational therapist who work in the area are invited to systematize their experiences, in order to generate intervention protocols for an underdiagnosed health condition in pediatric population, and it is critical to approach them in an interdisciplinary manner, to promote a minor impact hospitalization on the normal development of these children.

Dictyostelium discoideum as a surrogate host-microbe model for antivirulence screening in Pseudomonas aeruginosa PAO1.

The interest of the pharmaceutical industry in developing new antibiotics is decreasing, as established screening systems which identify compounds that kill or inhibit the growth of bacteria can no longer be used. Consequently, antimicrobial screening using classical minimum inhibitory concentration (MIC) measurements is becoming obsolete. The discovery of antimicrobial agents that specifically target a bacterial pathogen without affecting the host and its beneficial bacteria is a promising strategy. However, few host-microbe models are available for in vivo screening of novel antivirulence molecules. Here we designed high-throughput developmental assays in the social amoeba Dictyostelium discoideum to measure Pseudomonas aeruginosa virulence and to screen for novel antivirulence molecules without side effects to the host and its beneficial bacteria Klebsiella aerogenes. Thirty compounds were evaluated that had been previously selected by virtual screening for inhibitors of P. aeruginosa PAO1 polyphosphate kinase 1 (PaPPK1) and diverse compounds with combined PPK1 inhibitory and antivirulence activities were identified. This approach demonstrates that D. discoideum is a suitable surrogate host for preliminary high-throughput screening of antivirulence agents and that PPK1 is a suitable target for developing novel antivirulence compounds that can be further validated in mammalian models.