Association between stroke and psychosis across four nationally representative psychiatric epidemiological studies.

BACKGROUND: Both stroke and psychosis are independently associated with high levels of disability. However, psychosis in the context of stroke has been under-researched. To date, there are no general population studies on their joint prevalence and association. AIMS: To estimate the joint prevalence of stroke and psychosis and their statistical association using nationally representative psychiatric epidemiology studies from two high-income countries (the UK and the USA) and two middle-income countries (Chile and Colombia) and, subsequently, in a combined-countries data-set. METHOD: Prevalences were calculated with 95% confidence intervals. Statistical associations between stroke and psychosis and between stroke and psychotic symptoms were tested using regression models. Overall estimates were calculated using an individual participant level meta-analysis on the combined-countries data-set. The analysis is available online as a computational notebook. RESULTS: The overall prevalence of probable psychosis in stroke was 3.81% (95% CI 2.34-5.82) and that of stroke in probable psychosis was 3.15% (95% CI 1.94-4.83). The odds ratio of the adjusted association between stroke and probable psychosis was 3.32 (95% CI 2.05-5.38). On the individual symptom level, paranoia, hallucinated voices and thought passivity delusion were associated with stroke in the unadjusted and adjusted analyses. CONCLUSIONS: Rates of association between psychosis and stroke suggest there is likely to be a high clinical need group who are under-researched and may be poorly served by existing services.

Remodelling the surface of thioredoxin from Escherichia coli by grafting an iron-binding site from the CyaY protein family.

In this work, we have designed and generated a Fe(III)-binding protein with thiol oxidoreductase activity. The consensus iron-binding motif EExxED from the frataxin protein family was grafted on a model peptide and on the surface of thioredoxin (TRX) from E. coli. We investigated metal interactions with a family of peptides containing the motif EExxED or altered versions obtained by removing negatively charged residues: EExxEx, xExxED, and xExxEx. The interaction of the metal ion with the peptides was studied by circular dichroism, and our results indicated that the motif EExxED retained its functional properties and also that this motif is able to bind Ga(III) and Al(III). The interaction of the grafted TRX with iron(III) was investigated by NMR, showing that the motif was functional in the context of the protein structure, and also the binding of two equivalents of Fe(III) per TRX molecule was stable in a non-chelating neutral buffer. Protein conformation, stability, and enzymatic activity were studied by applying experimental and computational approaches. Interestingly, the thiol oxidoreductase activity was modulated by interaction with Ga(III), a Fe(III) mimetic ion. Furthermore, the design of functional proteins with both functions, oxidoreductase activity and metal-ion binding ability, should consider the reorganisation of the electrostatic network. Similarly, studying the crosstalk and electrostatic balance among different metal-binding sites may be critical.

SM-COLSARSPROT: Highly Immunogenic Supramutational Synthetic Peptides Covering the World's Population.

Fifty ~20-amino acid (aa)-long peptides were selected from functionally relevant SARS-CoV-2 S, M, and E proteins for trial B-21 and another 53 common ones, plus some new ones derived from the virus' main genetic variants for complementary trial C-21. Peptide selection was based on tremendous SARS-CoV-2 genetic variability for analysing them concerning vast human immunogenetic polymorphism for developing the first supramutational, Colombian SARS-protection (SM-COLSARSPROT), peptide mixture. Specific physicochemical rules were followed, i.e., aa predilection for polyproline type II left-handed (PPIIL) formation, replacing ß-branched, aromatic aa, short-chain backbone H-bond-forming residues, π-π interactions (n→π* and π-CH), aa interaction with π systems, and molecular fragments able to interact with them, disrupting PPIIL propensity formation. All these modified structures had PPIIL formation propensity to enable target peptide interaction with human leukocyte antigen-DRß1* (HLA-DRß1*) molecules to mediate antigen presentation and induce an appropriate immune response. Such modified peptides were designed for human use; however, they induced high antibody titres against S, M, and E parental mutant peptides and neutralising antibodies when suitably modified and chemically synthesised for immunising 61 major histocompatibility complex class II (MHCII) DNA genotyped Aotus monkeys (matched with their corresponding HLA-DRß1* molecules), predicted to cover 77.5% to 83.1% of the world's population. Such chemically synthesised peptide mixture represents an extremely pure, stable, reliable, and cheap vaccine for COVID-19 pandemic control, providing a new approach for a logical, rational, and soundly established methodology for other vaccine development.

Structural Modelling of KCNQ1 and KCNH2 Double Mutant Proteins, Identified in Two Severe Long QT Syndrome Cases, Reveals New Insights into Cardiac Channelopathies.

Congenital long QT syndrome (LQTS) is a cardiac channelopathy characterized by a prolongation of the QT interval and T-wave abnormalities, caused, in most cases, by mutations in KCNQ1, KCNH2, and SCN5A. Although the predominant pattern of LQTS inheritance is autosomal dominant, compound heterozygous mutations in genes encoding potassium channels have been reported, often with early disease onset and more severe phenotypes. Since the molecular mechanisms underlying severe phenotypes in carriers of compound heterozygous mutations are unknown, it is possible that these compound mutations lead to synergistic or additive alterations to channel structure and function. In this study, all-atom molecular dynamic simulations of KCNQ1 and hERG channels were carried out, including wild-type and channels with compound mutations found in two patients with severe LQTS phenotypes and limited family history of the disease. Because channels can likely incorporate different subunit combinations from different alleles, there are multiple possible configurations of ion channels in LQTS patients. This analysis allowed us to establish the structural impact of different configurations of mutant channels in the activated/open state. Our data suggest that channels with these mutations show moderate changes in folding energy (in most cases of stabilizing character) and changes in channel mobility and volume, differentiating them from each other and from WT. This would indicate possible alterations in K+ ion flow. Hetero-tetrameric mutant channels showed intermediate structural and volume alterations vis-à-vis homo-tetrameric channels. These findings support the hypothesis that hetero-tetrameric channels in patients with compound heterozygous mutations do not necessarily lead to synergistic structural alterations.

Factores relacionados con el resultado de los tratamientos endodónticos realizados en una institución universitaria con odontólogos en formación / Factors related to the result of endodontic treatments performed in a university institution with dentists in training / Fatores relacionados ao resultado de tratamentos endodônticos realizados em instituição universitária com dentistas em treinamento

Resumen Introducción y objetivo: el tratamiento endodóntico se realiza para tratar la enfermedad pulpoperiapical y puede tener un porcentaje de éxito de más del 90% en condiciones ideales para su realización. Dentro de los factores que condicionan la práctica clínica, se encuentran la anatomía interna del diente, las habilidades del operador, el conocimiento de la técnica, los instrumentos empleados y el tiempo operatorio. El éxito lo determina la supervivencia y la ausencia de signos clínicos y radiográficos en el seguimiento. Determinar los factores asociados al resultado del tratamiento de endodoncia, realizado por estudiantes de pregrado en odontología de una universidad colombiana. Materiales y métodos: estudio de cohorte retrospectivo con una cohorte expuesta y una no expuesta a la periodontitis apical. Se evaluaron clínica y radiográficamente todos los pacientes cuyo motivo de consulta fue endodoncia durante los años 2013-2014. Resultados: la media de edad de los pacientes fue 51,23 (DE = 14,23) con un mayor porcentaje de participación de mujeres (71,1%). En el diagnóstico inicial se encontró un 26% de dientes con Periodontitis apical. Se encontró asociación entre una mediana mayor de consultas y no presentar Periodontitis apical al final del tratamiento. En los análisis bivariados y multivariados se encontró asociación de la presencia de accidentes y endodoncia suboturada con la presencia de Periodontitis apical al final del tratamiento. Conclusión: seguir protocolos y guía de atención que permitan evitar los accidentes y conservar la adecuada longitud en la conformación y obturación pueden incrementar la frecuencia de éxito en los tratamientos.

Abstract Introduction and objetive: an endodontic treatment is performed to treat pulp-periapical disorders and may have a success rate of over 90% under ideal conditions. Among the factors that need to be considered, knowledge of the internal anatomy of the root, operator skills, selected technique, instruments involved and surgical time are the most important to determine the success of such treatment. Success implies the survival of the tooth in the oral cavity as well as the absence of clinical and radiographic signs and symptoms. The purpose of this work was to determine the factors associated to the success of an endodontic treatment performed by undergraduate dental students in a Colombian university. Materials and methods: a retrospective study with cohorts exposed and unexposed to apical periodontitis was carried out. Patients who consulted for endodontic treatment in 2013-2014 were invited to participate and were assessed both clinically and radiographically. Results: mean age was 51.23 (SD 14.23) years and higher percentage of female participation (71.1%) was observed. At initial diagnosis, 26% of teeth were diagnosed with apical periodontitis. An association between a high consultation mean and absence of apical periodontitis at the end of treatment was found. Bivariate and multivariate analyses showed an association between the presence of procedure accidents and under-filled root canal obturation with the presence of apical periodontitis at the end of treatment. Conclusion: success rate of endodontic treatments may be increased by carefully following protocols and attention guidelines to reduce the possibility of accidents and to keep an adequate length of the canal filling.

Resumo Introdução e objetivo: um tratamento endodôntico é realizado para tratar distúrbios pulpar-periapicais e pode ter uma taxa de sucesso superior a 90% em condições ideais. Entre os fatores que precisam ser considerados, o conhecimento da anatomia interna da raiz, as habilidades do operador, a técnica selecionada, os instrumentos envolvidos e o tempo cirúrgico são os mais importantes para determinar o sucesso desse tratamento. O sucesso implica a sobrevivência do dente na cavidade oral, bem como a ausência de sinais e sintomas clínicos e radiográficos. O objetivo deste trabalho foi determinar os fatores associados ao sucesso de um tratamento endodôntico realizado por estudantes de graduação em odontologia de uma universidade colombiana. Materiais e métodos: estudo retrospectivo com coortes expostas e não expostas à periodontite apical. Os pacientes que consultaram para tratamento endodôntico em 2013-2014 foram convidados a participar e foram avaliados clinicamente e radiograficamente. Resultados: a média de idade foi de 51,23 (DP 14,23) anos e maior percentual de participação feminina (71,1%). No diagnóstico inicial, 26% dos dentes foram diagnosticados com periodontite apical. Foi encontrada associação entre alta média de consulta e ausência de periodontite apical ao final do tratamento. As análises bivariadas e multivariadas mostraram associação entre a presença de acidentes do procedimento e a obturação do canal radicular com preenchimento insuficiente com a presença de periodontite apical ao final do tratamento. Conclusão: a taxa de sucesso dos tratamentos endodônticos pode ser aumentada seguindo-se cuidadosamente os protocolos e diretrizes de atenção para reduzir a possibilidade de acidentes e manter um comprimento adequado do preenchimento do canal.

Ichthyosis: case report in a Colombian man with genetic alterations in ABCA12 and HRNR genes.

BACKGROUND: Ichthyosis is a heterogeneous group of diseases caused by genetic disorders related to skin formation. They are characterized by generalized dry skin, scaling, hyperkeratosis and frequently associated with erythroderma. Among its different types, harlequin ichthyosis (HI) stands out due to its severity. HI is caused by mutations in the ABCA12 gene, which encodes essential proteins in epidermal lipid transport, and it helps maintain the homeostasis of the stratum corneum of the epidermis. However, due to the wide spectrum of genetic alterations that can cause ichthyosis, holistic medical care, and genetic studies are required to improve the diagnosis and outcomes of these diseases. CASE PRESENTATION: Here, we presented the case of a 19 years old male patient who was a premature infant and exhibited clinical features consistent with HI, including bright yellow hyperkeratotic plates with erythematous fissures that covered his entire body like a collodion baby. Currently, he exhibited erythroderma, photosensitivity, ectropion, auricular pavilion alterations, and musculoskeletal disorders, such as equinovarus feet, fingers, hands, and hypoplastic feet with contractures in flexion and marked difficulty in fine motor skills. In addition, he presented dyschromatopsia, Achilles reflex hyporeflexia, slight speech, dental alteration and deficient cognitive performance. After the genetic sequencing, variants were found in ABCA12 and HRNR which are related to several skin diseases, including ichthyosis. CONCLUSIONS: Although in clinical practice, ichthyosis is a common entity, a severe type of ichthyosis is presented, highlighting the importance of appropriate genetic diagnosis, given the broad spectrum of genetic alterations with similar phenotypic and clinical characteristics. These pathologies must be known to guarantee initial support measures to prevent complications and offer multidisciplinary management to those patients.

MHCBI: a pipeline for calculating peptide-MHC binding energy using semi-empirical quantum mechanical methods with explicit/implicit solvent models.

Experimentally estimating peptide-major histocompatibility complex (pMHC) binding affinity has been quite challenging due to the many receptors and the many potential ligands implicated in it. We have thus proposed a straightforward computational methodology considering the different mechanisms involved in pMHC binding to facilitate studying such receptor-ligand interactions. We have developed a pipeline using semi-empirical quantum mechanical methods for calculating pMHC class I and II molecules' binding energy (BE). This pipeline can systematize the methodology for calculating pMHC system BE, enabling the rational design of T-cell epitopes to be used as pharmaceuticals and vaccines.

Exploring the conformational transition between the fully folded and locally unfolded substates of Escherichia coli thiol peroxidase.

Thiol peroxidase from Escherichia coli (EcTPx) is a peroxiredoxin that catalyzes the reduction of different hydroperoxides. During the catalytic cycle of EcTPx, the peroxidatic cysteine (CP) is oxidized to a sulfenic acid by peroxide, then the resolving cysteine (CR) condenses with the sulfenic acid of CP to form a disulfide bond, which is finally reduced by thioredoxin. Purified EcTPx as dithiol and disulfide behaves as a monomer under near physiological conditions. Although secondary structure rearrangements are present when comparing different redox states of the enzyme, no significant differences in unfolding free energies are observed under reducing and oxidizing conditions. A conformational change denominated fully folded (FF) to locally unfolded (LU) transition, involving a partial unfolding of αH2 and αH3, must occur to enable the formation of the disulfide bond since the catalytic cysteines are 12 Å apart in the FF conformation of EcTPx. To explore this process, the FF → LU and LU → FF transitions were studied using conventional molecular dynamics simulations and an enhanced conformational sampling technique for different oxidation and protonation states of the active site cysteine residues CP and CR. Our results suggest that the FF → LU transition has a higher associated energy barrier than the refolding LU → FF process in agreement with the relatively low experimental turnover number of EcTPx. Furthermore, in silico designed single-point mutants of αH3 enhanced locally unfolding events, suggesting that the native FF interactions in the active site are not evolutionarily optimized to fully speed-up the conformational transition of wild-type EcTPx.

Assessing Peptide Binding to MHC II: An Accurate Semiempirical Quantum Mechanics Based Proposal.

Estimating peptide-major histocompatibility complex (pMHC) binding using structural computational methods has an impact on understanding overall immune function triggering adaptive immune responses in MHC class II molecules. We developed a strategy for optimizing pMHC structure interacting with water molecules and for calculating the binding energy of receptor + ligand systems, such as HLA-DR1 + HA, HLA-DR1 + CLIP, HLA-DR2 + MBP, and HLA-DR3 + CLIP, as well as a monosubstitution panel. Taking pMHC's structural properties, we assumed that ΔH ≫ -TΔS would generate a linear model for estimating relative free energy change, using three semiempirical quantum methods (PM6, PM7, and FMO-SCC-DFTB3) along with the implicit solvent models, and considering proteins in neutral and charged states. Likewise, we confirmed our approach's effectiveness in calculating binding energies having high correlation with experimental data and low root-mean-square error (<2 kcal/mol). All in all, our pipeline differentiates weak from strong peptide binders as a reliable method for studying pMHC interactions.

Invarianza factorial del Launay-Slade Hallucinations Scale entre hombres y mujeres colombianos / Factorial invariance of the Launay-Slade Hallucinations Scale among Colombian male and female

Resumen Introducción: La Launay-Slade Hallucinations Scale (LSHS) es una de las pruebas más utilizadas en el estudio de las alucinaciones. Su estructura factorial ha sido descrita en diversas culturas, tanto en población general como población clínica. No obstante, pocos estudios han aportado evidencia de la equivalencia factorial con relación al sexo de los evaluados. El objetivo de esta investigación fue realizar un análisis de invarianza de medición y estructural de la LSHS-R en una muestra incidental de hombres y mujeres de población general colombiana. Método: Estudio instrumental en el cual participaron 350 habitantes de la ciudad de Medellín (Colombia), en su mayoría mujeres (64,3%), de edad promedio 28,62 años. Se realizaron análisis descriptivos de los ítems antes de realizar el análisis de invarianza de medición e invarianza estructural entre las muestras de hombres y mujeres. Resultados: El modelo de dos dimensiones reportado previamente en población colombiana presentaba los mejores índices de ajuste empírico para hombres y mujeres. Posteriormente, fue obtenida evidencia de invarianza configuracional, métrica y fuerte (invarianza de medición), además de igualdad de covarianzas y medias latentes (invarianza estructural) entre hombres y mujeres. Por otro lado, la LSHS-R presenta índices de confiabilidad aceptables. Conclusiones: La estructura de dos dimensiones de la LSHS-R así como la relación entre factores son estadísticamente equivalentes entre hombres y mujeres.

Introduction: The Launay-Slade Hallucinations Scale (LSHS) is one of the most used tests in the hallucinations study. Its factorial structure has been described in different cultures, in the general and the clinical population. However, few studies have provided evidence of factorial equivalence regarding the sex. The aim of this investigation was to perform a measurement and structural invariance analysis of LSHS-R in an incidental sample of men and women of Colombian general population. Method: This instrumental study involving 350 inhabitants of the city of Medellín (Colombia), mostly women (64.3%), with an average age of 28.62 years. Descriptive analyzes of the items were performed before performing the analysis of invariance of measurement and structural invariance between the samples of men and women. Results: The previously reported two-dimensional model in the Colombian population, presented the best empirical adjustment indexes for men and women. Later, was obtained evidence of configurational, metric and strong invariance (measurement invariance), as well as equality of covariances and latent means (structural invariance), between men and women. On the other hand, the LSHS-R has acceptable reliability indexes. Conclusions: The two-dimensional structure of LSHS-R as well as the relationship between factors are statistically equivalent between men and women.

Armed conflict and mental health in Colombia.

Although significant progress has been made in the peace process, Colombia still experiences high levels of ongoing violence and a legacy of more than five decades of armed conflict. Epidemiological studies show markedly raised levels of mental health problems in people affected by the conflict, with internally displaced people being a large and important group with unmet needs. Provision of mental health services is uneven and subject to significant underinvestment. Priority mental health treatment for victims of the conflict is now established in law, although the effectiveness of these programmes has yet to be established.

Validation of the Spanish-language Cardiff Anomalous Perception Scale.

The Cardiff Anomalous Perceptions Scale (CAPS) is a psychometric measure of hallucinatory experience. It has been widely used in English and used in initial studies in Spanish but a full validation study has not yet been published. We report a validation study of the Spanish-language CAPS, conducted in both Spain and Colombia to cover both European and Latin American Spanish. The Spanish-language version of the CAPS was produced through back translation with slight modifications made for local dialects. In Spain, 329 non-clinical participants completed the CAPS along with 40 patients with psychosis. In Colombia, 190 non-clinical participants completed the CAPS along with 21 patients with psychosis. Participants completed other psychometric scales measuring psychosis-like experience to additionally test convergent and divergent validity. The Spanish-language CAPS was found to have good internal reliability. Test-retest reliability was slightly below the cut-off, although could only be tested in the Spanish non-clinical sample. The scale showed solid construct validity and a principal components analysis broadly replicated previously reported three component factor structures for the CAPS.

Calidad de las historias clínicas de los practicantes de un consultorio psicológico de una universidad colombiana / Quality of the clinical notes of internship students in a psychology clinic of a Colombian university

INTRODUCCIÓN: Las prácticas académicas en los programas de psicología en Colombia constituyen una parte fundamental del currículo. Los consultorios psicológicos universitarios son un escenario en el cual se desarrolla esta actividad en el campo de la psicología clínica, por lo que se hace necesario revisar la información que se recauda allí, con vistas a supervisar la calidad de dichas prácticas. MÉTODO: Estudio exploratorio retrospectivo en el cual se analizaron los motivos de consulta, los diagnósticos, las estrategias de evaluación e intervención, las metas terapéuticas y los datos sociodemográficos de 708 historias clínicas diligenciadas entre 1999 y 2012 por estudiantes de últimos semestres en periodo de prácticas en una universidad colombiana. RESULTADOS: Se encontró que los diagnósticos están referidos en su mayoría a estresores psicosociales, más que a psicopatologías, y tanto las herramientas de diagnóstico como las estrategias de intervención no son coherentes con el diagnóstico registrado en la historia clínica. CONCLUSIONES: Es evidente la necesidad de fortalecer la formación básica en psicología clínica, en cuanto a sus métodos y alcances, de forma que se brinde una atención a los usuarios que tenga bases científicas, así como establecer protocolos de control para la supervisión de estudiantes en prácticas clínicas en la formación de pregrado

INTRODUCTION: Academic internships in psychology programs in Colombia are a fundamental part of the curriculum. University Psychological Services are a scenario in which this activity is developed in the field of clinical psychology, making it necessary to review the information collected there in order to monitor the quality of such practices. METHOD: A retrospective exploratory study in which the reasons for consultation, diagnoses, strategies of evaluation and intervention, therapeutic goals and sociodemographic data of 708 medical records were analysed, between 1999 and 2012, by students in the final semesters of the internship period in a Colombian university. RESULTS: It was found that the diagnoses mostly referred to psychosocial stressors rather than psychopathologies. The diagnostic tools and intervention strategies are not consistent with the diagnosis recorded in the clinical notes. CONCLUSIONS: The need to strengthen basic training in clinical psychology is evident, in terms of its methods and scope, in order to provide users with a scientific basis, as well as to establish control protocols for the supervision of students in Clinical internships in undergraduate training

Perception of risk as a mediator between personality and perception of health: test of a model.

BACKGROUND: This research article addresses the relationships among personality, risk perception, and health perception. The personality construct has been one of the main topics of research in psychology throughout history and is understood as the set of traits or cognitive, affective and behavioral characteristics that an individual possesses. Important relationships have been found that show the impact of personality on people's health as well as the impact of health conditions on the configuration of personality. This research investigates the perception of risk as a mediating trait between personality and perception of health. MATERIALS AND METHODS: To achieve this, a cross-sectional study was conducted in which 398 Colombians from all regions of the country were evaluated. The NEO Five Factor Inventory (NEO-FFI), The General Health Questionnaire (GHQ-12) and Health Risk Perception Test (HRPT) tests were used. RESULTS: The data were analyzed with multiple regression and path analysis. The findings using multiple regression show that neuroticism and the personal meaning of risk affect the perception of health; however, using path analysis, model fit with the proposed model was not achieved with no mediator effect of perception of risk. CONCLUSION: It is necessary to focus on relationships between neuroticism and perception of health in future research.

Structural variability of E. coli thioredoxin captured in the crystal structures of single-point mutants.

Thioredoxin is a ubiquitous small protein that catalyzes redox reactions of protein thiols. Additionally, thioredoxin from E. coli (EcTRX) is a widely-used model for structure-function studies. In a previous paper, we characterized several single-point mutants of the C-terminal helix (CTH) that alter global stability of EcTRX. However, spectroscopic signatures and enzymatic activity for some of these mutants were found essentially unaffected. A comprehensive structural characterization at the atomic level of these near-invariant mutants can provide detailed information about structural variability of EcTRX. We address this point through the determination of the crystal structures of four point-mutants, whose mutations occurs within or near the CTH, namely L94A, E101G, N106A and L107A. These structures are mostly unaffected compared with the wild-type variant. Notably, the E101G mutant presents a large region with two alternative traces for the backbone of the same chain. It represents a significant shift in backbone positions. Enzymatic activity measurements and conformational dynamics studies monitored by NMR and molecular dynamic simulations show that E101G mutation results in a small effect in the structural features of the protein. We hypothesize that these alternative conformations represent samples of the native-state ensemble of EcTRX, specifically the magnitude and location of conformational heterogeneity.