Efecto de la simulación háptica en la autoeficacia académica de odontólogos en formación

La simulación es un recurso ampliamente utilizado en los procesos formativos en odontología, especialmente para adquirir destrezas motrices y potencialmente en el desarrollo de la autoeficacia. Objetivo: Evaluar el efecto de la simulación háptica en la autoeficacia académica de odontólogos en formación. Materiales y métodos: Este estudio se centró en estudiantes de un curso de anticipación disciplinar (n=134). Se aplicó la escala de autoeficacia general después de dos actividades de tallado con apresto tradicional, mediadas por una sesión de tallado con simulación háptica. Resultados: Al determinar el rol de las dimensiones de autoeficacia en dos actividades de simulación tradicional (ABT1 y ABT2), mediadas por la háptica se obtuvo un promedio de ABT1: x̄=3,27 (n=123) y de ABT2: x̄=3,20 (n=105). De los diez ítems de la escala, hubo diferencia estadística respecto a la disminución del grado de autoeficacia en el Nº1 (p=0,05) y Nº6 (p=0,01). Conclusiones: Se puede establecer que, al utilizar un simulador háptico de manera complementaria a las de apresto tradicional, la intervención influye en la autoeficacia, puesto que se adquiere mayor conciencia de las complejidades asociadas, debiendo desafiar su propia autorregulación para hacerles frente.

Simulation is a widely used resource in dental training processes, especially to acquire motor skills and potentially in the development of self-efficacy. Objective: To evaluate the effect of haptic simulation in the academic self-efficacy of dentists in training. Materials and methods: This study focused on students of a curricular anticipatory course (n=134). The general self-efficacy scale was applied after two carving activities with a traditional approach, complemented by a carving session with haptic simulation. Results: When determining the role of the self-efficacy dimensions in two traditional simulation activities (ABT1 and ABT2) complemented by haptics, we obtained an average of ABT1: x̄=3,27 (n=123) and ABT2: x̄=3,20 (n=105). Of the ten items of the scale, there was a statistical difference regarding the decrease in the degree of self-efficacy in Nº1 (p=0,05) and Nº6 (p=0,01). Conclusions: It can be established that complementing traditional training with a haptic simulator influences self-efficacy, since the students become more aware of the associated complexities, and need to challenge their own self-regulation to deal with them.

Técnicas de reproducción asistida en personas del mismo sexo y solas por opción: realidad en Chile 2021 / Assisted reproduction techniques in people of the same sex and alone by option: reality in Chile 2021

Resumen El concepto de familia ha cambiado con los años y la constitución de los hogares en Chile ya no es la misma que hace un siglo. Las familias diversas en nuestro país han existido durante toda la vida, pero el conocimiento de cómo se han constituido y la existencia de un catastro en Chile son escasos. El objetivo de esta revisión es mostrar cómo se han constituido las familias diversas en Chile, cómo ha sido el acceso de estas a las técnicas de reproducción asistida, cuál ha sido la política del Estado y las aseguradoras de salud (Fonasa e Isapres) en las coberturas, y qué ha pasado con la legislación a lo largo de los años que ha facilitado la constitución de nuevas familias. Por otra parte, se pretende mostrar cuáles son las barreras al acceso por parte de las familias diversas y la necesidad de una ley de reproducción asistida que permita el acceso a todas las personas independientemente de su estado civil, orientación sexual o identidad de género, y que proteja a todos los nacidos chilenos por igual.

Abstract The image of a typical family has changed in recent years, as the makeup of households in Chile is no longer the same as decades ago. While gender and sexual diverse families in our country have always existed, there is a scarcity of reliable data. We review the evolution of the makeup of these diverse families in Chile and their access to assisted reproduction techniques. We also review national policies and health insurance coverage by both governmental and private carriers (Fonasa and Isapres) and how changes in legislation over the years have facilitated the constitution of these families. We outline barriers to access assisted reproduction techniques and the need for further legislative action to guarantee access to all citizens regardless of their marital status, sexual orientation, or gender identity.

AMPs as Anti-biofilm Agents for Human Therapy and Prophylaxis.

Microbial cells show a strong natural tendency to adhere to surfaces and to colonize them by forming complex communities called biofilms. In this growth mode, biofilm-forming cells encase themselves inside a dense matrix which efficiently protects them against antimicrobial agents and effectors of the immune system. Moreover, at the physiological level, biofilms contain a very heterogeneous cell population including metabolically inactive organisms and persisters, which are highly tolerant to antibiotics. The majority of human infectious diseases are caused by biofilm-forming microorganisms which are responsible for pathologies such as cystic fibrosis, infective endocarditis, pneumonia, wound infections, dental caries, infections of indwelling devices, etc. AMPs are well suited to combat biofilms because of their potent bactericidal activity of broad spectrum (including resting cells and persisters) and their ability to first penetrate and then to disorganize these structures. In addition, AMPs frequently synergize with antimicrobial compounds and were recently reported to repress the molecular pathways leading to biofilm formation. Finally, there is a very active research to develop AMP-containing coatings that can prevent biofilm formation by killing microbial cells on contact or by locally releasing their active principle. In this chapter we will describe these strategies and discuss the perspectives of the use of AMPs as anti-biofilm agents for human therapy and prophylaxis.

Antibacterial action of synthetic antilipopolysaccharide peptides (SALP) involves neutralization of both membrane-bound and free toxins.

Increasing failure of conventional antibiotics to combat bacterial infections requires the urgent development of new antibacterial drugs; a promising class of new drugs based on antimicrobial peptides. Here, we studied the molecular interaction of polycationic synthetic antilipopolysaccharide peptides (SALPs) with various gram-negative and gram-positive bacteria, including resistant strains. The analysis of antimicrobial activity by conventional techniques and atomic force microscopy showed a strict dependence on amino acid (aa) sequences, with the type of amino acid, its position within the primary structure, and the sequence length being critical parameters. By monitoring lipopolysaccharide (LPS)- or bacteria-induced cytokine production in human mononuclear cells and whole blood, we found a direct link between the binding of the lead compound Pep19-2.5 to Salmonella enterica and the anti-inflammatory activity of the peptide. Thermodynamic analysis of Pep19-2.5 binding to the bacterial cell envelope showed an exothermic reaction with saturation characteristics, whereas small-angle X-ray scattering data indicated a direct attachment of Pep19-2.5 to the bacterial cell envelope. This binding preferentially takes place to the LPS outer monolayer, as evidenced by the change in the LPS acyl chain and phosphate vibrational bands seen by Fourier-transform infrared spectroscopy. We report here that the anti-inflammatory activity of Pep19-2.5 is not only connected with neutralization of cell-free bacterial toxins but also with a direct binding of the peptide to the outer leaflet of the bacterial outer membrane.

Inhibition of Lipopolysaccharide- and Lipoprotein-Induced Inflammation by Antitoxin Peptide Pep19-2.5.

The most potent cell wall-derived inflammatory toxins ("pathogenicity factors") of Gram-negative and -positive bacteria are lipopolysaccharides (LPS) (endotoxins) and lipoproteins (LP), respectively. Despite the fact that the former signals via toll-like receptor 4 (TLR4) and the latter via TLR2, the physico-chemistry of these compounds exhibits considerable similarity, an amphiphilic molecule with a polar and charged backbone and a lipid moiety. While the exterior portion of the LPS (i.e., the O-chain) represents the serologically relevant structure, the inner part, the lipid A, is responsible for one of the strongest inflammatory activities known. In the last years, we have demonstrated that antimicrobial peptides from the Pep19-2.5 family, which were designed to bind to LPS and LP, act as anti-inflammatory agents against sepsis and endotoxic shock caused by severe bacterial infections. We also showed that this anti-inflammatory activity requires specific interactions of the peptides with LPS and LP leading to exothermic reactions with saturation characteristics in calorimetry assays. Parallel to this, peptide-mediated neutralization of LPS and LP involves changes in various physical parameters, including both the gel to liquid crystalline phase transition of the acyl chains and the three-dimensional aggregate structures of the toxins. Furthermore, the effectivity of neutralization of pathogenicity factors by peptides was demonstrated in several in vivo models together with the finding that a peptide-based therapy sensitizes bacteria (also antimicrobial resistant) to antibiotics. Finally, a significant step in the understanding of the broad anti-inflammatory function of Pep19-2.5 was the demonstration that this compound is able to block the intracellular endotoxin signaling cascade.

Antimicrobial endotoxin-neutralizing peptides promote keratinocyte migration via P2X7 receptor activation and accelerate wound healing in vivo.

BACKGROUND AND PURPOSE: Wound healing is a complex process that is essential to provide skin homeostasis. Infection with pathogenic bacteria such as Staphylococcus aureus can lead to chronic wounds, which are challenging to heal. Previously, we demonstrated that the antimicrobial endotoxin-neutralizing peptide Pep19-2.5 promotes artificial wound closure in keratinocytes. Here, we investigated the mechanism of peptide-induced cell migration and if Pep19-2.5 accelerates wound closure in vivo. EXPERIMENTAL APPROACH: Cell migration was examined in HaCaT keratinocytes and P2X7 receptor-overexpressing HEK293 cells using the wound healing scratch assay. The protein expression of phosphorylated ERK1/2, ATP release, calcium influx and mitochondrial ROS were analysed to characterize Pep19-2.5-mediated signalling. For in vivo studies, female BALB/c mice were wounded and infected with methicillin-resistant S. aureus (MRSA) or left non-infected and treated topically with Pep19-2.5 twice daily for 6 days. KEY RESULTS: Specific P2X7 receptor antagonists inhibited Pep19-2.5-induced cell migration and ERK1/2 phosphorylation in keratinocytes and P2X7 receptor-transfected HEK293 cells. ATP release was not increased by Pep19-2.5; however, ATP was required for cell migration. Pep19-2.5 increased cytosolic calcium and mitochondrial ROS, which were involved in peptide-induced migration and ERK1/2 phosphorylation. In both non-infected and MRSA-infected wounds, the wound diameter was reduced already at day 2 post-wounding in the Pep19-2.5-treated groups compared to vehicle, and remained decreased until day 6. CONCLUSIONS AND IMPLICATIONS: Our data suggest the potential application of Pep19-2.5 in the treatment of non-infected and S. aureus-infected wounds and provide insights into the mechanism involved in Pep19-2.5-induced wound healing.

Serum Estradiol Level at Intensive Care Unit Admission and Mortality in Critically Ill Patients.

CONTEXT: It has been observed that sex hormones may play a role in inflammatory processes and mortality of critically ill patients. AIMS: The aim was evaluated the relationship between serum estradiol level at Intensive Care Unit (ICU) admission and mortality of critically ill patients. SETTINGS AND DESIGN: This study was a prospective cohort conducted in one mixed ICU. SUBJECTS AND METHODS: In heterogeneous group of critically ill patients admitted to the ICU, we measured serum estradiol at admission time. STATISTICAL ANALYSIS USED: The discrimination to predict mortality of serum estradiol level was assessed by the receiver-operating curve (ROC) curve and its association with mortality by logistic regression analysis. RESULTS: We included 131 patients, 57.3% of which were male. The serum estradiol level measured at ICU admission was significantly higher in nonsurvivors than in survivors: 116 versus 67.2 pg/mL, respectively (P < 0.0001). The area under the ROC of serum estradiol level to predict mortality was 0.74 (P < 0.0001). Serum estradiol level ≥97.9 pg/mL had sensitivity of 60%, specificity of 90%, positive predictive value of 64%, negative predictive value of 88%, positive likelihood ratio of 6, and negative likelihood ratio of 0.44, for predicting mortality. In multivariate analysis, it had relative risk of 6.47 (P = 0.002) for ICU mortality. CONCLUSIONS: The serum estradiol level is elevated in critically ill patients, regardless of gender, especially in those who die. It has good discriminative capacity to predict mortality, and it is an independent risk factor for death in this group of patients.

Coupling killing to neutralization: combined therapy with ceftriaxone/Pep19-2.5 counteracts sepsis in rabbits.

Sepsis, which is induced by severe bacterial infections, is a major cause of death worldwide, and therapies combating the disease are urgently needed. Because many drugs have failed in clinical trials despite their efficacy in mouse models, the development of reliable animal models of sepsis is in great demand. Several studies have suggested that rabbits reflect sepsis-related symptoms more accurately than mice. In this study, we evaluated a rabbit model of acute sepsis caused by the intravenous inoculation of Salmonella enterica. The model reproduces numerous symptoms characteristic of human sepsis including hyperlactatemia, hyperglycemia, leukopenia, hypothermia and the hyperproduction of several pro-inflammatory cytokines. Hence, it was chosen to investigate the proposed ability of Pep19-2.5-an anti-endotoxic peptide with high affinity to lipopolysaccharide and lipoprotein-to attenuate sepsis-associated pathologies in combination with an antibiotic (ceftriaxone). We demonstrate that a combination of Pep19-2.5 and ceftriaxone administered intravenously to the rabbits (1) kills bacteria and eliminates bacteremia 30 min post challenge; (2) inhibits Toll-like receptor 4 agonists in serum 90 min post challenge; (3) reduces serum levels of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor α); and (4) reverts to hypothermia and gives rise to temperature values indistinguishable from basal levels 330 min post challenge. The two components of the combination displayed synergism in some of these activities, and Pep19-2.5 notably counteracted the endotoxin-inducing potential of ceftriaxone. Thus, the combination therapy of Pep19-2.5 and ceftriaxone holds promise as a candidate for human sepsis therapy.

[Threshold value of f/Vt index for predicting successful weaning from mechanical ventilation in active smokers]. / Valor umbral del índice f/Vt para predecir retiro exitoso de la ventilación mecánica en fumadores activos.

BACKGROUND: Mechanical ventilation (MV) is used in 60-70 % of patients admitted to the intensive care unit (ICU). An f/Vt threshold value of 105 is a predictor of successful weaning from mechanical ventilation (WMV) in patients with asthma, cardiac surgery, pneumonia, sepsis, neurocritical, etc. However, there are no reports about the usefulness of the f/Vt value to predict successful WMV in patients with active smoking (AS). The purpose of this paper is to identify a threshold value for f/Vt to predict successful WMV in patients with AS. METHODS: Prospectively, 85 patients with AS and MV >24 hours admitted to de ICU were included. Demographic and clinical data were registered. The f/Vt value was measured with a Wright's spirometer, and the sensibility, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to predict a successful WMV. A p value <0.05 was considered statistically significant. RESULTS: The average of f/Vt was 68.69. Successful WMV was of 75.3 %. An f/Vt threshold value of 79.5 had sensibility of 76 %, specificity of 61 %, PPV of 85 %, and NPV of 46 % to predict successful WMV in this group of patients. CONCLUSIONS: An f/Vt threshold value of 79.5 is useful to predict successful WMV in patients with AS.

Introducción: la ventilación mecánica (VM) se utiliza en el 60-70 % de los ingresos a la unidad de cuidados intensivos (UCI). Un valor umbral del índice f/Vt de 105 es un predictor de éxito en el retiro de la ventilación mecánica (RVM) en pacientes con asma, cirugía cardiaca, neumonía, sepsis, neurocríticos, etc. Sin embargo, no existen reportes de la utilidad del índice f/Vt para predecir RVM exitoso en pacientes con tabaquismo activo (TA). El objetivo de este trabajo es identificar un valor umbral del índice f/Vt para predecir RVM exitoso en pacientes con TA. Métodos: se incluyeron prospectivamente 85 pacientes con TA y VM >24 horas, ingresados a la UCI. Se registraron variables demográficas y clínicas. Se midió el índice f/Vt con un espirómetro de Wright y se calculó su sensibilidad, especificidad, valor predictivo positivo (VPP) y valor predictivo negativo (VPN) para predecir RVM exitoso. Una p <0.05 se consideró estadísticamente significativa. Resultados: el promedio del índice f/Vt fue de 68.69. El RVM exitoso fue del 75.3 %. Un valor umbral del índice f/Vt de 79.5 tuvo sensibilidad de 76 %, especificidad de 61 %, VPP de 85 % y VPN de 46 % para predecir RVM exitoso en este grupo de enfermos. Conclusiones: el valor umbral del índice f/Vt de 79.5 es útil para predecir éxito en el RVM en pacientes con TA.

Lipoproteins/peptides are sepsis-inducing toxins from bacteria that can be neutralized by synthetic anti-endotoxin peptides.

Sepsis, a life-threatening syndrome with increasing incidence worldwide, is triggered by an overwhelming inflammation induced by microbial toxins released into the bloodstream during infection. A well-known sepsis-inducing factor is the membrane constituent of Gram-negative bacteria, lipopolysaccharide (LPS), signalling via Toll-like receptor-4. Although sepsis is caused in more than 50% cases by Gram-positive and mycoplasma cells, the causative compounds are still poorly described. In contradicting investigations lipoproteins/-peptides (LP), lipoteichoic acids (LTA), and peptidoglycans (PGN), were made responsible for eliciting this pathology. Here, we used human mononuclear cells from healthy donors to determine the cytokine-inducing activity of various LPs from different bacterial origin, synthetic and natural, and compared their activity with that of natural LTA and PGN. We demonstrate that LP are the most potent non-LPS pro-inflammatory toxins of the bacterial cell walls, signalling via Toll-like receptor-2, not only in vitro, but also when inoculated into mice: A synthetic LP caused sepsis-related pathological symptoms in a dose-response manner. Additionally, these mice produced pro-inflammatory cytokines characteristic of a septic reaction. Importantly, the recently designed polypeptide Aspidasept(®) which has been proven to efficiently neutralize LPS in vivo, inhibited cytokines induced by the various non-LPS compounds protecting animals from the pro-inflammatory activity of synthetic LP.

Therapeutical Administration of Peptide Pep19-2.5 and Ibuprofen Reduces Inflammation and Prevents Lethal Sepsis.

Sepsis is still a major cause of death and many efforts have been made to improve the physical condition of sepsis patients and to reduce the high mortality rate associated with this disease. While achievements were implemented in the intensive care treatment, all attempts within the field of novel therapeutics have failed. As a consequence new medications and improved patient stratification as well as a thoughtful management of the support therapies are urgently needed. In this study, we investigated the simultaneous administration of ibuprofen as a commonly used nonsteroidal anti-inflammatory drug (NSAID) and Pep19-2.5 (Aspidasept), a newly developed antimicrobial peptide. Here, we show a synergistic therapeutic effect of combined Pep19-2.5-ibuprofen treatment in an endotoxemia mouse model of sepsis. In vivo protection correlates with a reduction in plasma levels of both tumor necrosis factor α and prostaglandin E, as a likely consequence of Pep19-2.5 and ibuprofen-dependent blockade of TLR4 and COX pro-inflammatory cascades, respectively. This finding is further characterised and confirmed in a transcriptome analysis of LPS-stimulated human monocytes. The transcriptome analyses showed that Pep19-2.5 and ibuprofen exerted a synergistic global effect both on the number of regulated genes as well as on associated gene ontology and pathway expression. Overall, ibuprofen potentiated the anti-inflammatory activity of Pep19-2.5 both in vivo and in vitro, suggesting that NSAIDs could be useful to supplement future anti-sepsis therapies.

Translocación del tercio medio facial en un paciente en edad infantil. Fijación con un nuevo sistema de placas y pines reabsorbibles / Mid-facial translocation in children using a new system of absorbable plates and pins. A case report

La translocación del tercio medio facial, técnica consistente en la movilización del esqueleto centrofacial pediculado a los tejidos blandos, ha demostrado permitir un amplio acceso para el abordaje de lesiones situadas en las regiones faciales profundas y la región central de la base del cráneo. Uno de los principales inconvenientes que presentaba este abordaje en niños era la fijación del esqueleto con placas y tornillos de titanio, ya que podía interferir en el crecimiento del hueso en desarrollo. Todo ello planteaba el problema de una segunda intervención para la retirada del material, aumentando, de forma significativa, la morbilidad del procedimiento. Como solución al problema se comercializa, a partir de la década de 1980, el material de osteosíntesis reabsorbible. Presentamos a una paciente de 13 años de edad diagnosticada de un cordoma localizado en el clivus. Como abordaje, se realiza una translocación bilateral del tercio medio facial y se utiliza, para la fijación del esqueleto facial, un nuevo sistema de placas y tornillos reabsorbibles basado en ultrasonidos (Sonic Weld®. KLS Martin, LP, Jacksonville, Florida, USA). Se describen los principales abordajes a las regiones faciales profundas y centromediales de la base del cráneo, las principales variantes de la translocación del tercio medio facial, la técnica de aplicación del nuevo sistema Sonic Weld® y sus diferencias principales respecto a los sistemas reabsorbibles tradicionales(AU)

Mid-facial translocation, which involves mobilization of the central facial skeletal structures together with soft tissue pedicles, provides generous access to the anterior and central regions of the skull base. One of the drawbacks of this approach in children is skeletal fixation with titanium osteosynthesis plates and screws, which may affect the growth of developing bone. Consequently, a second intervention is required to remove titanium osteosynthesis material, which increases the morbidity of the procedure. Absorbable osteosynthesis material has been marketed since the 1980s as a solution to this problem. We report the case of a 13-year-old female patient diagnosed of chordoma of the clivus. A bilateral mid-facial approach was used with a new system of absorbable plates and pins affixed ultrasonically (SonicWeld®. KLS Martin, LP, Jacksonville, Florida, USA). The primary approaches to tumors located in the deep facial regions and skull base, the main variations of the mid-facial translocation technique, application of the new SonicWeld® absorbable system, and the main differences compared to traditional absorbable plates and screws are reviewed(AU)