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Background: Lymphedema is a common breast cancer side effect, with an average incidence of 30%. The gold standard conservative treatment for lymphedema is complex decongestive therapy (CDT), which includes manual lymphatic drainage, compression therapy, skin care, and exercise. Lymphovenular anastomosis (LVA) is a microsurgical technique that intends to redirect excess lymphatic fluid to the venous circulation; this procedure is usually performed when conservative treatment fails. Therefore, the objective of this study is to evaluate the effectiveness of LVA and CDT for the treatment of breast cancer-related lymphedema (BCRL). Methods and Results: The search was performed in CENTRAL, MEDLINE, Embase, PsycINFO, SCOPUS, and LILACS. Inclusion criteria were (1) population: women with BCRL; (2) intervention: treated with LVA and CDT; and (3) outcome: primary outcome was lymphedema reduction. Secondary outcome was quality of life. Risk of bias and quality of study reporting were also assessed. The search found 3872 articles, with 5 articles meeting the PICO (population, intervention, comparison, outcomes) criteria, 4 pre-post studies, and one observational cohort study. The total sample included 2763 patients. Follow-up was variable. The follow-up varies from 7.8 to 120 months, with an average of 35 months. Lymphedema reduction was obtained in the five studies. Conclusion: The present systematic review suggests that for patients with lymphedema secondary to breast cancer, the combination of both treatments is effective in reducing the size of the limb and improving quality of life. Low-quality evidence was found for both limb circumference reduction and quality of life. Additional research effort is needed to reduce bias and improve the quality of evidence, in order to better inform clinical practice and enhance the care and well-being of patients with BCRL.
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Anastomose Cirúrgica , Linfedema Relacionado a Câncer de Mama , Neoplasias da Mama , Vasos Linfáticos , Qualidade de Vida , Humanos , Feminino , Anastomose Cirúrgica/métodos , Neoplasias da Mama/complicações , Neoplasias da Mama/cirurgia , Resultado do Tratamento , Vasos Linfáticos/cirurgia , Linfedema Relacionado a Câncer de Mama/terapia , Linfedema Relacionado a Câncer de Mama/etiologia , Linfedema Relacionado a Câncer de Mama/cirurgia , Drenagem Linfática Manual/métodos , Linfedema/etiologia , Linfedema/terapia , Linfedema/cirurgiaRESUMO
Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting over 50 million people worldwide in 2020 and this number will triple to 152 million by 2050. Much of the increase will be in developing countries like Colombia. In familial forms, highly penetrant mutations have been identified in three genes, APP, PSEN1, and PSEN2, supporting a role for amyloid-ß peptide. In sporadic forms, more than 30 risk genes involved in the lipid metabolism, the immune system, and synaptic functioning mechanisms. We used whole-exome sequencing (WES) to evaluate a family of 97 members, spanning three generations, with a familiar AD, and without mutations in APP, PSEN1, or PSEN2. We sequenced two affected and one unaffected member with the aim of identifying genetic variants that could explain the presence of the disease in the family and the candidate variants were validated in eleven members. We also built a structural model to try to determine the effect on protein function. WES analysis identified two rare variants in SORL1 and MTHFD1L genes segregating in the family with other potential risk variants in APOE, ABCA7, and CHAT, suggesting an oligogenic inheritance. Additionally, the structural 3D models of SORL1 and MTHFD1L variants shows that these variants produce polarity changes that favor hydrophobic interactions, resulting in local structural changes that could affect the protein function and may contribute to the development of the disease in this family.
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Doença de Alzheimer , Idoso , Humanos , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Colômbia , Sequenciamento do Exoma , Predisposição Genética para Doença , Proteínas Relacionadas a Receptor de LDL/genética , Proteínas de Membrana Transportadoras/genética , Mutação , Presenilina-1/genéticaRESUMO
A whole-exome capture and next-generation sequencing was applied to an 11 y/o patient with a clinical history of congenital hypotonia, generalized motor and cognitive neurodevelopmental delay, and severe cognitive deficit, and without any identifiable Syndromic pattern, and to her parents, we disclosed a de novo heterozygous pathogenic mutation, c.697_699del p.Phe233del (rs786204835)(ACMG classification PS2, PM1, PM2, PP5), harbored in the PURA gene (MIM*600473) (5q31.3), associated with Autosomal Dominant Mental Retardation 31 (MIM # 616158). We used the significant improvement in the accuracy of protein structure prediction recently implemented in AlphaFold that incorporates novel neural network architectures and training procedures based on the evolutionary, physical, and geometric constraints of protein structures. The wild-type (WT) sequence and the mutated sequence, missing the Phe233, were reconstructed. The predicted local Distance Difference Test (lDDT) for the PURAwt and the PURA-Phe233del showed that the occurrence of the Phe233del affects between 220-320 amino acids. The distortion in the PURA structural conformation in the ~5 Å surrounding area after the p.Phe233del produces a conspicuous disruption of the repeat III, where the DNA and RNA helix unwinding capability occurs. PURA Protein-DNA docking corroborated these results in an in silico analysis that showed a loss of the contact of the PURA-Phe233del III repeat domain model with the DNA. Together, (i) the energetic and stereochemical, (ii) the hydropathic indexes and polarity surfaces, and (iii) the hybrid Quantum Mechanics-Molecular Mechanics (QM-MM) analyses of the PURA molecular models demarcate, at the atomic resolution, the specific surrounding region affected by these mutations and pave the way for future cell-based functional analysis. To the best of our knowledge, this is the first report of a de novo mutation underpinning a PURA syndrome in a Latin American patient and highlights the importance of predicting the molecular effects in protein structure using artificial intelligence algorithms and molecular and atomic resolution stereochemical analyses.
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Alzheimer's disease manifests itself in brain tissue by neuronal death, due to aggregation of ß-amyloid, produced by senile plaques, and hyperphosphorylation of the tau protein, which produces neurofibrillary tangles. One of the genetic markers of the disease is the gene that translates the presenilin-2 protein, which has mutations that favor the appearance of the disease and has no reported crystallographic structure. In view of this, protein modeling is performed using prediction and structural refinement tools followed by an energetic and stereochemical characterization for its validation. For the simulation, four reported mutations are chosen, which are Met239Ile, Met239Val, Ser130Leu, and Thr122Arg, all associated with various functional responses. From a theoretical analysis, a preliminary bioinformatic study is made to find the phosphorylation patterns in the protein and the hydropathic index according to the polarity and chemical environment. Molecular visualization was carried out with the Chimera 1.14 software, and the theoretical calculation with the hybrid quantum mechanics/molecular mechanics system from the semi-empirical method, with Spartan18 software and an AustinModel1 basis. These relationships allow for studying the system from a structural approach with the determination of small distance changes, potential surfaces, electrostatic maps, and angle changes, which favor the comparison between wild-type and mutant systems. With the results obtained, it is expected to complement experimental data reported in the literature from models that would allow us to understand the effects of the selected mutations.
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Alzheimer's disease pathology is characterized by ß-amyloid plaques and neurofibrillary tangles. Amyloid precursor protein is processed by ß and γ secretase, resulting in the production of ß-amyloid peptides with a length ranging from 38 to 43 amino acids. Presenilin 1 (PS1) is the catalytic unit of γ-secretase, and more than 200 PS1 pathogenic mutations have been identified as causative for Alzheimer's disease. A complete monocrystal structure of PS1 has not been determined so far due to the presence of two flexible domains. We have developed a complete structural model of PS1 using a computational approach with structure prediction software. Missing fragments Met1-Glut72 and Ser290-Glu375 were modeled and validated by their energetic and stereochemical characteristics. Then, with the complete structure of PS1, we defined that these fragments do not have a direct effect in the structure of the pore. Next, we used our hypothetical model for the analysis of the functional effects of PS1 mutations Ala246GLu, Leu248Pro, Leu248Arg, Leu250Val, Tyr256Ser, Ala260Val, and Val261Phe, localized in the catalytic pore. For this, we used a quantum mechanics/molecular mechanics (QM/MM) hybrid method, evaluating modifications in the topology, potential surface density, and electrostatic potential map of mutated PS1 proteins. We found that each mutation exerts changes resulting in structural modifications of the active site and in the shape of the pore. We suggest this as a valid approach for functional studies of PS1 in view of the possible impact in substrate processing and for the design of targeted therapeutic strategies.
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BACKGROUND: The anterolateral thigh flap (ALT) has proven over time to be one of the best reconstructive workhorses due to its versatility and reliability. Without preoperative imaging, vascular anomalies such as having no sizable perforator are sometimes encountered during dissection. We propose a technique, based on a modified version of the traditional myocutaneous ALT to allow harvest of the flap based on non-sizable perforators. This technique can also enable the splitting of a flap when only one sizable perforator is present. METHODS: A retrospective review of patients who received reconstruction with free ALT flap from 2013 to 2019 by the senior author HSS was performed and included all flaps in which non-sizable perforators were harvested. Data collected for analysis included patient demographics, flap size, defect location, inset type, and flap survival. SURGICAL TECHNIQUE: Despite detachment of the majority of skin paddle from the muscle, the flap is harvested with a sleeve of areolar tissue containing preferably more than one non-sizable perforator attached to a small muscular segment of the vastus lateralis containing the pedicle. RESULTS: A total of 349 ALT flaps were performed during the review period by senior author HSS, and 25 flaps were harvested with non-sizable perforator, 10 of which were to enable a split. There were no total losses and 6 partial losses; 2 were amenable to direct closure after debridement, 1 required skin graft, and 3 required a new flap for wound coverage. Incorporating more than one non-sizable perforator increases the reliability of the flap. This technique should be used with caution in patients with multiple underlying comorbidities and when a flow-through flap is required. We were able to achieve primary closure of all donor sites. CONCLUSIONS: It is possible to harvest the anterolateral thigh flap without sizable perforators by conversion to a modified version of the myocutaneous flap. In well-selected patients, using our technique, several non-sizable perforators can reliably perfuse an ALT without the need to use an alternative donor site. This maximizes the number of harvestable ALTs and increases the reconstructive potential by splitting previously "un-splitable" flaps.
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Neoplasias de Cabeça e Pescoço/cirurgia , Retalho Perfurante/irrigação sanguínea , Procedimentos de Cirurgia Plástica/métodos , Coxa da Perna/cirurgia , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Taiwan , Coxa da Perna/irrigação sanguíneaRESUMO
Objetivo: Se realizó un estudio prospectivo, observacional, de seguimiento de casos en el servicio de cirugía plástica del hospital El Tunal, Bogotá, Colombia, para evaluar la efectividad de un apósito de hidrofibra reforzada, con plata iónica al 1,2%, potenciado con ácido etilendiaminotetraacético (EDTA) y cloruro de bencetonio en pacientes con heridas de difícil cicatrización. Método: Se incluyeron 23 pacientes con heridas de diferentes etiologías, signos locales de infección, presencia de exudado e indicadores visuales o indirectos de biofilm. Los pacientes fueron divididos en tres grupos: heridas que requerían cicatrización por segunda intención (n=10) (grupo 1), heridas con absceso (n=4) (grupo 2) y heridas en las que se requería preparar el lecho para cobertura quirúrgica (n=9) (grupo 3). El seguimiento de cada caso duró tres meses. Resultados: El grupo 1 demostró una disminución de exudado, infección y signos indirectos de biofilm, así como una reducción significativa de la superficie de la herida con cierre total en ocho de los 10 casos pertenecientes a este grupo. El grupo 2 logró el control de exudado y cierre de la cavidad en un promedio de 21 días. El grupo 3 obtuvo adecuada preparación del lecho de la herida y alcanzó una cobertura quirúrgica en 15 días, en promedio. No se encontraron efectos adversos en los pacientes tratados. Conclusión: Los resultados muestran que el apósito estudiado es efectivo para controlar exudado, infección y signos indirectos de biofilm, así como para disminuir el tamaño de la herida, lograr el cierre de heridas con absceso y preparar el lecho para una cobertura quirúrgica definitiva.Objective: A prospective, observational, case-series study evaluated the efficacy of a hydrofiber dressing with ionic silver, ethylenediaminetetraacetic acid and benzethonium chloride in patients with hard-to-heal wounds at El Tunal hospital in Bogota, Colombia. Method: A total of 23 patients with wounds of different aetiologies, local signs of infection, exudate and biofilm were recruited. Patients were divided into three groups: wounds for secondary intention healing (group 1), abscesses (group 2) and wounds for surgical coverage (group 3). Patients were followed up for 3 months. Results: Group 1 showed a reduction in exudate and infection levels, and a decrease in indirect signs of biofilm. There was also a significant reduction in wound surface, with eight out of 10 patients in this group achieving complete wound closure. Group 2 obtained exudate control and wound closure in 21 days, on average. Group 3 demonstrated an adequate wound bed preparation for surgical coverage in 15 days, on average. No side effects were observed. Conclusion: The results showed that the hydrofiber dressing could be effective in controlling exudate and infection levels, and managing the indirect signs of biofilm, as well as reducing the wound surface, achieving wound closure in abscesses and performing wound bed preparation for surgical coverage.
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SINOPSIS: Objetivo: Se realizó un estudio prospectivo, observacional, de seguimiento de casos en el servicio de cirugía plástica del hospital El Tunal, Bogotá, Colombia, para evaluar la efectividad de un apósito de hidrofibra reforzada, con plata iónica al 1,2%, potenciado con ácido etilendiaminotetraacético (EDTA) y cloruro de bencetonio en pacientes con heridas de difícil cicatrización. Método: Se incluyeron 23 pacientes con heridas de diferentes etiologías, signos locales de infección, presencia de exudado e indicadores visuales o indirectos de biofilm. Los pacientes fueron divididos en tres grupos: heridas que requerían cicatrización por segunda intención (n=10) (grupo 1), heridas con absceso (n=4) (grupo 2) y heridas en las que se requería preparar el lecho para cobertura quirúrgica (n=9) (grupo 3). El seguimiento de cada caso duró tres meses. Resultados: El grupo 1 demostró una disminución de exudado, infección y signos indirectos de biofilm, así como una reducción significativa de la superficie de la herida con cierre total en ocho de los 10 casos pertenecientes a este grupo. El grupo 2 logró el control de exudado y cierre de la cavidad en un promedio de 21 días. El grupo 3 obtuvo adecuada preparación del lecho de la herida y alcanzó una cobertura quirúrgica en 15 días, en promedio. No se encontraron efectos adversos en los pacientes tratados. Conclusión: Los resultados muestran que el apósito estudiado es efectivo para controlar exudado, infección y signos indirectos de biofilm, así como para disminuir el tamaño de la herida, lograr el cierre de heridas con absceso y preparar el lecho para una cobertura quirúrgica definitiva. ABSTRACT: Objective: A prospective, observational, case-series study evaluated the efficacy of a hydrofiber dressing with ionic silver, ethylenediaminetetraacetic acid and benzethonium chloride in patients with hard-to-heal wounds at El Tunal hospital in Bogota, Colombia. Method: A total of 23 patients with wounds of different aetiologies, local signs of infection, exudate and biofilm were recruited. Patients were divided into three groups: wounds for secondary intention healing (group 1), abscesses (group 2) and wounds for surgical coverage (group 3). Patients were followed up for 3 months. Results: Group 1 showed a reduction in exudate and infection levels, and a decrease in indirect signs of biofilm. There was also a significant reduction in wound surface, with eight out of 10 patients in this group achieving complete wound closure. Group 2 obtained exudate control and wound closure in 21 days, on average. Group 3 demonstrated an adequate wound bed preparation for surgical coverage in 15 days, on average. No side effects were observed. Conclusion: The results showed that the hydrofiber dressing could be effective in controlling exudate and infection levels, and managing the indirect signs of biofilm, as well as reducing the wound surface, achieving wound closure in abscesses and performing wound bed preparation for surgical coverage.
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Anti-Infecciosos Locais/administração & dosagem , Bandagens , Carboximetilcelulose Sódica/administração & dosagem , Infecção dos Ferimentos/prevenção & controle , Adulto , Benzetônio/administração & dosagem , Ácido Edético/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Prata/administração & dosagem , Resultado do Tratamento , Infecção dos Ferimentos/patologia , Adulto JovemRESUMO
Metformin used as a first-line drug to treat Type 2 Diabetes Mellitus is transported via organic cation channels to soft tissues. Mutations in the SLC22A1 gene, such as Gly401Ser, Ser189Leu, and Arg206Cys, may affect the drug's therapeutic effect on these patients. This study aims at proposing a potential structural model for drug interactions with the hOCT1 transporter, as well as the impact of these mutations at both topological and electronic structure levels on the channel's surface, from a chemical point of view with, in addition to exploring the frequency distribution. To chemically understand metformin diffusion, we used an open model from the protein model database, with ID PM0080367, viewed through UCSF Chimera. The effect of the mutations was assessed using computational hybrid Quantum Mechanics/Molecular Mechanics, based on the Austin Model 1 semi-empirical method using Spartan 18' software. The results demonstrate coupling energy for metformin with amino acids F, W, H and Y, because of the interaction between the metformin dication and the electron cloud of π orbitals. The mutations analyzed showed changes in the chemical polarity and topology of the structure. The proposed diffusion model is a possible approach to the interaction mechanism between metformin and its transporter, as well as the impacts of variants, suggesting structural changes in the action of the drug. Metformin efficacy considerably varies from one patient to another; this may be largely attributed to the presence of mutations on the SLC22A1 gene. This study aims at proposing a potential structural model for metformin-hOCT1 (SLC22A1) transporter interaction, as well as the identification of the effect of mutations G401S (rs34130495), S189L (rs34104736), and R206C (616C > T) of the SLC22A1 gene at the topological and electronic structure levels on the channel surfaces, from a chemical viewpoint. Our results demonstrated that the coupling energies for metformin with aromatic amino acids F, W, H and Y, because of the interaction between the metformin dication and the electron cloud of π orbitals. Changes in the chemical environment's polarity and the structure's topology were reported in the mutations assessed. The diffusion model proposed is a potential approach for the mechanism of interaction of metformin with its transporter and the effects of variants on the efficacy of the drug in the treatment of type 2 diabetes. The assessment of the frequency of these mutations in a sample of Colombian type 2 diabetes patients suggests that different SLC22A1 gene variants might be involved in reduced OCT1 activity in the Colombian population since none of these mutations were detected.
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INTRODUCCIÓN: Ante la alta frecuencia de transfusiones alogénicas en cirugía cardiaca, que exponen a los pacientes a los riesgos asociados a la transfusión, surge la transfusión autóloga como una alternativa. OBJETIVO: Comparar el uso de hemocomponentes con transfusión autóloga frente a transfusión alogénica en pacientes sometidos a cirugía cardiaca con derivación cardiopulmonar. MATERIAL Y MÉTODOS: Estudio de cohorte prospectiva analítica de 26 pacientes sometidos a cirugía cardiaca con derivación cardiopulmonar, que se dividieron en dos grupos: grupo de estudio (n = 13), en el que se realizó transfusión autóloga, y grupo de control (n = 13), en el que solo se realizó transfusión alogénica. Se comparó la cantidad de hemocomponentes alogénicos transfundidos. RESULTADOS: En el grupo de transfusión autóloga se obtuvo: concentrados eritrocitarios por predepósito, 520.83 ml; plasma fresco congelado, 416.67 ml; concentrados eritrocitarios por hemodilución normovolémica, 334.38 ml; aféresis plaquetaria, 31.38 ml; y recuperado celular, 800.12 ml. En promedio, del grupo autólogo se transfundieron: concentrados eritrocitarios, 1329.23 ml; plasma fresco congelado, 303.38 ml; y plaquetas, 29.46 ml. El grupo de transfusión autóloga no requirió transfusión alogénica. En el grupo de transfusión alogénica se transfundieron, en el transquirúrgico: concentrados eritrocitarios, 807.89 ml; plasma fresco congelado, 676.92 ml; y concentrados plaquetarios, 500 ml. CONCLUSIONES: Con el uso de transfusión autóloga se evita la transfusión de productos alogénicos en cirugía cardiaca. BACKGROUND: Given the high frequency of allogeneic transfusion in cardiac surgery procedures, which expose the patient to the risks associated with transfusion, autologous transfusion arises as an alternative. OBJECTIVE: Compare the use of autologous transfusion versus allogeneic transfusion in patients undergoing cardiac surgery with cardiopulmonary bypass. MATERIAL AND METHODS: A prospective analytical cohort study of 26 patients undergoing cardiac surgery with cardiopulmonary bypass was carried out. They were divided into two groups: the study group (n = 13) in which autologous transfusion was performed and in the control group (n = 13) only allogenic transfusion was performed. The amount of allogeneic hemocomponents transfused was compared. RESULTS: In the autologous transfusion group, erythrocyte concentrates were obtained on average 520.83 ml, fresh frozen plasma 416.67 ml, erythrocyte concentrates by normovolemic hemodilution 334.38 ml, platelet aferesis of 31.38 ml, cell saver of 800.12 ml, on average, transfused. From the autologous group: erythrocyte concentrates 1329.23 ml, fresh frozen plasma 303.38, platelets of 29.46 ml. The autologous transfusion group did not require allogeneic transfusion. In the allogeneic transfusion group transfused 807.89 ml of erythrocyte concentrates, fresh frozen plasma of 676.92 and platelet concentrates of 500 ml. CONCLUSIONS: The use of autologous transfusion prevents the transfusion of allogeneic products in cardiac surgical procedures.
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Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Genetic factors associated with immune response contribute to infection development and disease. M. leprae has the capacity to invade Schwann cells in the peripheral nervous system and cause neuropathy. However, while the responsible molecular mechanisms remain to be fully unveiled, they have begun being elucidated. We studied genetic variants Myelin Protein Zero (MPZ), a major structural component of the myelin sheath, and Mannose Binding Lectin 2 (MBL2), a protein involved in immune response, in 112 family groups of 114 leprosy patients using PCR-RFLP, aiming to calculate the association and allelic transmission of variants associated in first, second and third-degree relatives. Polymorphisms found in MPZ and MBL2 showed association with leprosy. Different probabilities for allelic transmission were found for first and second-degree relatives, a fact that is important to take into account when evaluating risk in contacts of leprosy patients. Structural analysis allows the study of putative amino acids and their possible effect on protein structure and function, as well as on the assembly of a protein homotetramer. Our results suggest that the identified MPZ and MBL2 gene mutations are associated with leprosy in a Colombian population, which correlates with MPZ and MBL2 protein function, and increase the risk of M. leprae infection in leprosy-patients' family members. Additionally, structural analyses were carried out specifically for MPZ protein using information available in databases, and analyzing the substitutions in wildtype and mutant protein. The results show significant structural changes, which may be associated to infection and pathogenicity.
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Hanseníase , Lectina de Ligação a Manose , Proteína P0 da Mielina , Adulto , Colômbia , Feminino , Humanos , Hanseníase/genética , Hanseníase/imunologia , Masculino , Lectina de Ligação a Manose/química , Lectina de Ligação a Manose/genética , Lectina de Ligação a Manose/imunologia , Pessoa de Meia-Idade , Modelos Moleculares , Proteína P0 da Mielina/química , Proteína P0 da Mielina/genética , Proteína P0 da Mielina/imunologia , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Antecedentes: El análisis de los factores multicausales, tanto internos como externos a la institución, que afectan la motivación académica, cobra relevancia en una facultad que busca la cualificación de la formación que brinda. Materiales y métodos: Se realizó un estudio de corte transversal con una población de 559 estudiantes inscritos en la Facultad de Medicina de la Universidad de Manizales (Manizales, Colombia), en el año 2010, de primero a décimo semestre, con una muestra representativa de 210 estudiantes. Se empleó una encuesta anónima para identificar algunos factores personales y sociales que puedan ser desmotivantes o incluso constituirse en factor asociado para deserción académica. Resultados: Como factores que inciden en la desmotivación académica, sólo 52,7% de los estudiantes respondieron que sienten apoyo institucional, 75,2% refieren algun tipo de maltrato y 52,4% se han sentido acosados sexualmente; 79,5% presentan estrés, en su mayoría moderado. Conclusiones: Se concluye que entre los factores que afectan la motivación académica e inciden en que cerca de la mitad de los estudiantes haya contemplado la posibilidad de abandonar sus estudios se encuentra el no percibir respaldo institucional, el acoso y el estrés. Cerca de la mitad de la población no percibe apoyo institucional, las tres cuartas partes manifestaron percibir algún tipo de maltrato y cerca de la mitad refiere haber sido víctimas de al menos un tipo de acoso, con mayor frecuencia verbal e indirecto; un alto número se ven sometidos a niveles moderados de estrés...