Mental telehealth in a public child and adolescent psychiatry unit during the pandemic: a qualitative implementation study. / Telesalud mental en una unidad pública de psiquiatría infanto-juvenil en pandemia: estudio cualitativo de implementación.

Background: The COVID-19 pandemic led to a prompt implementation of remote care, especially in mental health care. The evidence supporting this modality of care is still emerging, with few qualitative studies describing its implementation in Latin American countries. This study aims to understand the perspectives of therapists and patients regarding the use of telehealth in a child and adolescent mental health unit of a Chilean public service. Methods: This is a qualitative study. Two focus groups were defined with 14 professionals, and 16 in-depth interviews were conducted with users of an outpatient child and adolescent psychiatry unit. The data were analyzed using the grounded theory model. Results: In the group of therapists, four main categories emerged: background of mental telehealth, implementation, mental telehealth from the therapist's position, and projections. Three main categories emerged in the patient's group: implementation, evaluation of mental telehealth users, and projections. Conclusions: There are elements in common between the opinions of patients and therapists. Something to note within the patient's group is that, despite accepting remote care and recognizing its positive aspects, aside from the pandemic context, they prefer face-to-face or mixed care.

Antecedentes: La pandemia por COVID-19 generó una implementación súbita de las atenciones a distancia, especialmente en atenciones de salud mental. La evidencia que sustenta esta modalidad de atención es aún emergente, con escasos estudios cualitativos que representen su implementación en países latinoamericanos. El objetivo de este trabajo es conocer la perspectiva de terapeutas y de usuarios, respecto del uso de la telesalud en una unidad de salud mental infantil y de la adolescencia de un servicio público chileno. Métodos: Estudio cualitativo. Se establecieron dos grupos focales con 14 profesionales en total, y 16 entrevistas en profundidad con usuarios de una unidad ambulatoria de psiquiatría infanto juvenil.. Los datos se analizaron utilizando el modelo de teoría fundamentada. Resultados: En el grupo de terapeutas surgen cuatro categorías fundamentales; antecedentes de la telesalud mental, implementación, telesalud mental desde la posición del terapeuta y proyecciones. En el grupo de usuarios surgieron tres categorías principales: implementación, evaluación de los usuarios de la telesalud mental y proyecciones. Conclusiones: Existen elementos en común entre la opinión de los usuarios y terapeutas. Un elemento importante dentro del grupo de los usuarios es que, a pesar de aceptar la atención remota y reconocer aspectos positivos en esta, fuera del contexto de pandemia prefieren atenciones presenciales o mixtas.

Telesalud mental en una unidad pública de psiquiatría infanto-juvenil en pandemia: estudio cualitativo de implementación / Mental telehealth in a public child and adolescent psychiatry unit during the pandemic: a qualitative implementation study

Antecedentes La pandemia por COVID-19 generó una implementación súbita de las atenciones a distancia, especialmente en atenciones de salud mental. La evidencia que sustenta esta modalidad de atención es aún emergente, con escasos estudios cualitativos que representen su implementación en países latinoamericanos. El objetivo de este trabajo es conocer la perspectiva de terapeutas y de usuarios, respecto del uso de la telesalud en una unidad de salud mental infantil y de la adolescencia de un servicio público chileno. Métodos Estudio cualitativo. Se establecieron dos grupos focales con 14 profesionales en total, y 16 entrevistas en profundidad con usuarios de una unidad ambulatoria de psiquiatría infanto juvenil.. Los datos se analizaron utilizando el modelo de teoría fundamentada Resultados En el grupo de terapeutas surgen cuatro categorías fundamentales; antecedentes de la telesalud mental, implementación, telesalud mental desde la posición del terapeuta y proyecciones. En el grupo de usuarios surgieron tres categorías principales: implementación, evaluación de los usuarios de la telesalud mental y proyecciones. Conclusiones Existen elementos en común entre la opinión de los usuarios y terapeutas. Un elemento importante dentro del grupo de los usuarios es que, a pesar de aceptar la atención remota y reconocer aspectos positivos en esta, fuera del contexto de pandemia prefieren atenciones presenciales o mixtas.

Background The COVID-19 pandemic led to a prompt implementation of remote care, especially in mental health care. The evidence supporting this modality of care is still emerging, with few qualitative studies describing its implementation in Latin American countries. This study aims to understand the perspectives of therapists and patients regarding the use of telehealth in a child and adolescent mental health unit of a Chilean public service. Methods This is a qualitative study. Two focus groups were defined with 14 professionals, and 16 in-depth interviews were conducted with users of an outpatient child and adolescent psychiatry unit. The data were analyzed using the grounded theory model. Results In the group of therapists, four main categories emerged: background of mental telehealth, implementation, mental telehealth from the therapist's position, and projections. Three main categories emerged in the patient's group: implementation, evaluation of mental telehealth users, and projections. Conclusions There are elements in common between the opinions of patients and therapists. Something to note within the patient's group is that, despite accepting remote care and recognizing its positive aspects, aside from the pandemic context, they prefer face-to-face or mixed care.

CRISPR/Cas9-Mediated Disruption of the pcz1 Gene and Its Impact on Growth, Development, and Penicillin Production in Penicillium rubens.

Penicillium rubens is a filamentous fungus of great biotechnological importance due to its role as an industrial producer of the antibiotic penicillin. However, despite its significance, our understanding of the regulatory mechanisms governing biological processes in this fungus is still limited. In fungi, zinc finger proteins containing a Zn(II)2Cys6 domain are particularly interesting regulators. Although the P. rubens genome harbors many genes encoding proteins with this domain, only two of them have been investigated thus far. In this study, we employed CRISPR-Cas9 technology to disrupt the pcz1 gene, which encodes a Zn(II)2Cys6 protein in P. rubens. The disruption of pcz1 resulted in a decrease in the production of penicillin in P. rubens. This decrease in penicillin production was accompanied by the downregulation of the expression of pcbAB, pcbC and penDE genes, which form the biosynthetic gene cluster responsible for penicillin production. Moreover, the disruption of pcz1 also impacts on asexual development, leading to decreased growth and conidiation, as well as enhanced conidial germination. Collectively, our results indicate that pcz1 acts as a positive regulator of penicillin production, growth, and conidiation, while functioning as a negative regulator of conidial germination in P. rubens. To the best of our knowledge, this is the first report involving a gene encoding a Zn(II)2Cys6 protein in the regulation of penicillin biosynthesis in P. rubens.

Single nucleotide polymorphisms associated with wine fermentation and adaptation to nitrogen limitation in wild and domesticated yeast strains.

For more than 20 years, Saccharomyces cerevisiae has served as a model organism for genetic studies and molecular biology, as well as a platform for biotechnology (e.g., wine production). One of the important ecological niches of this yeast that has been extensively studied is wine fermentation, a complex microbiological process in which S. cerevisiae faces various stresses such as limited availability of nitrogen. Nitrogen deficiencies in grape juice impair fermentation rate and yeast biomass production, leading to sluggish or stuck fermentations, resulting in considerable economic losses for the wine industry. In the present work, we took advantage of the "1002 Yeast Genomes Project" population, the most complete catalogue of the genetic variation in the species and a powerful resource for genotype-phenotype correlations, to study the adaptation to nitrogen limitation in wild and domesticated yeast strains in the context of wine fermentation. We found that wild and domesticated yeast strains have different adaptations to nitrogen limitation, corroborating their different evolutionary trajectories. Using a combination of state-of-the-art bioinformatic (GWAS) and molecular biology (CRISPR-Cas9) methodologies, we validated that PNP1, RRT5 and PDR12 are implicated in wine fermentation, where RRT5 and PDR12 are also involved in yeast adaptation to nitrogen limitation. In addition, we validated SNPs in these genes leading to differences in fermentative capacities and adaptation to nitrogen limitation. Altogether, the mapped genetic variants have potential applications for the genetic improvement of industrial yeast strains.

Response to Comment on "Feasibility of Raman spectroscopy as a potential in vivo tool to screen for pre-diabetes and diabetes".

This letter aims to reply to Bratchenko and Bratchenko's comment on our paper "Feasibility of Raman spectroscopy as a potential in vivo tool to screen for pre-diabetes and diabetes." Our paper analyzed the feasibility of using in vivo Raman measurements combined with machine learning techniques to screen diabetic and prediabetic patients. We argued that this approach yields high overall accuracy (94.3%) while retaining a good capacity to distinguish between diabetic (area under the receiver-operating curve [AUC] = 0.86) and control classes (AUC = 0.97) and a moderate performance for the prediabetic class (AUC = 0.76). Bratchenko and Bratchenko's comment focuses on the possible overestimation of the proposed classification models and the absence of information on the age of participants. In this reply, we address their main concerns regarding our previous manuscript.

Control de la calidad y ensayos de rendimiento de CromoCen® SALM según la norma ISO 11133:2014/Amd. 1: 2018 / Quality control and performance testing of CromoCen® SALM according to ISO 11133: 2014 / Amd.1: 2018

Introducción: En Cuba, se desarrolló un medio de cultivo cromogénico y fluorogénico, para la detección, aislamiento y diferenciación de Salmonella de otras bacterias Gram negativas. El método que emplea el medio fue validado y su uso se adoptó en una norma cubana. El aseguramiento de la calidad y el control del rendimiento de los medios garantizan la confiabilidad de los resultados analíticos. La norma ISO 11133 establece criterios mínimos y métodos para evaluarlos. Objetivo: Evaluar los criterios de control de la calidad y de rendimiento de CromoCen® SALM, establecidos en la ISO 11133:2014/Amd.1:2018, para demostrar su fiabilidad para el análisis microbiológico de los alimentos de consumo humano. Métodos: Se evaluaron los indicadores de calidad físico-químicos de tres lotes y se definió un conjunto de ellos que caracteriza la calidad del medio antes y después de terminado, así como la consistencia entre lotes. Para el ensayo de rendimiento se seleccionaron 10 cepas de diferentes géneros. Se determinó la relación de productividad, el factor de selectividad y la electividad de CromoCen® SALM, según la ISO 11133. Resultados: La evaluación físico-química mostró una consistencia entre lotes en color, homogeneidad, apariencia del polvo y del medio preparado. Los valores de contenido de humedad y pH se encontraron dentro de los valores establecidos para este producto. La relación de productividad de CromoCen® SALM con respecto al agar triptona soya, fue superior al 50 por ciento, mientras que el factor de selectividad resultó de 4. Se demostró que en el medio de cultivo se puede diferenciar un grupo representativo de géneros microbianos de Salmonella. Conclusiones: CromoCen® SALM cumple con los requisitos de calidad establecidos para este tipo de productos, según la ISO 11133 vigente. La correcta formulación de los lotes, así como el cumplimiento de los requisitos de calidad aseguran el funcionamiento adecuado para lo que fue diseñado(AU)

Introduction: In Cuba, a new chromogenic and fluorogenic culture medium was developed for the detection, isolation and differentiation of Salmonella from other Gram negative bacteria. The method and medium were validated and their use was adopted as a Cuban standard. Quality assurance and control of media is essential and mandatory to ensure the reliability of the results of the analysis in which they are used. ISO 11133 establishes minimum criteria and methods to evaluate them. Objective: To evaluate the quality and performance criteria of CromoCen® SALM, as recommended in ISO 11133:2014/Amd.1:2018 to demonstrate its reliability for the microbiological analysis of food for human consumption. Methods: The physical-chemical quality indicators of three batches were evaluated and a group of them was defined to characterize its quality before and after finishing, as well to evaluate the consistency between batches. For the performance test, 12 strains of different genera were selected. The productivity ratio, the selectivity factor and the electivity of CromoCen® SALM were determined. Results: The physico-chemical evaluation showed a consistency between batches in color, homogeneity, appearance of the powder and of the prepared medium. The moisture content and pH values ranged within the established values for this product. The productivity ratio of CromoCen® SALM with respect to tryptone soy agar was greater than 50 percent, while the selectivity factor was 4. It was shown that in the culture medium a representative group of Salmonella microbial genera can be differentiated. Conclusions: CromoCen® SALM meets the quality requirements established for this type of products, according to the current ISO 11133 standard. The correct formulation of the batches, as well as the fulfillment of the quality requirements ensure the proper functionality and match the design purpose(AU)

Bispyrrolidinoindoline Epi(poly)thiodioxopiperazines (BPI-ETPs) and Simplified Mimetics: Structural Characterization, Bioactivities, and Total Synthesis.

Within the 2,5-dioxopiperazine-containing natural products generated by "head-to-tail" cyclization of peptides, those derived from tryptophan allow further structural diversification due to the rich chemical reactivity of the indole heterocycle, which can generate tetracyclic fragments of hexahydropyrrolo[2,3-b]indole or pyrrolidinoindoline skeleton fused to the 2,5-dioxopiperazine. Even more complex are the dimeric bispyrrolidinoindoline epi(poly)thiodioxopiperazines (BPI-ETPs), since they feature transannular (poly)sulfide bridges connecting C3 and C6 of their 2,5-dioxopiperazine rings. Homo- and heterodimers composed of diastereomeric epi(poly)thiodioxopiperazines increase the complexity of the family. Furthermore, putative biogenetically generated downstream metabolites with C11 and C11'-hydroxylated cores, as well as deoxygenated and/or oxidized side chain counterparts, have also been described. The isolation of these complex polycyclic tryptophan-derived alkaloids from the classical sources, their structural characterization, the description of the relevant biological activities and putative biogenetic routes, and the synthetic efforts to generate and confirm their structures and also to prepare and further evaluate structurally simple analogs will be reported.

Prevalence of Alzheimer's disease in rural and urban areas in Cuba and factors influencing on its occurrence: epidemiological cross-sectional protocol.

INTRODUCTION: According to the World Alzheimer's Report 2019, around 50 million people suffer from dementia, worldwide. Observational analysis revealed the existence of particular factors associated with the onset and progression of Alzheimer's disease (AD). There are no international homogeneous principles for the early detection and evaluation of memory impairment and possible AD. This work aimed at (1) determining the prevalence of possible AD in the elderly residing in urban and rural regions in Cuba and (2) identifying the main factors that could significantly influence on its occurrence. METHODS AND ANALYSIS: The study includes four neuropsychological tests (Clock Drawing Test, Mini-Mental Status Examination, Short Portable Mental Status Questionnaire, Cognitive and Non-Cognitive Alzheimer's Disease Assessment Scale) and two scales (Clinical Dementia Rating and Global Deterioration Scale). Moreover, the protocol includes a survey with demographic and socioeconomic information, educational level, occupation, health, neuropsychological status of subjects, familial pathological history, comorbidities and lifestyles. The study will comprise a total of 1092 subjects aged ≥60, of both genders, and from every ethnic group settled in rural and urban areas. PRIMARY OUTCOMES: prevalence of possible AD. SECONDARY OUTCOMES: correlation among risk and protective factors and AD, and comparison of the performance of neuropsychological tests and scales. ETHICS AND DISSEMINATION: This research met the ethical codes of the Declaration of Helsinki. The Scientific Research Council of the Promoting Research Institute and the Ethics Committee of the Health Authorities approved the protocol. The proper written informed consent is also incorporated. The results of the survey will be published in scientific papers and shared with the Health Authorities of each municipality.

Genetically modified organisms: adapting regulatory frameworks for evolving genome editing technologies.

Genetic modification of living organisms has been a prosperous activity for research and development of agricultural, industrial and biomedical applications. Three decades have passed since the first genetically modified products, obtained by transgenesis, become available to the market. The regulatory frameworks across the world have not been able to keep up to date with new technologies, monitoring and safety concerns. New genome editing techniques are opening new avenues to genetic modification development and uses, putting pressure on these frameworks. Here we discuss the implications of definitions of living/genetically modified organisms, the evolving genome editing tools to obtain them and how the regulatory frameworks around the world have taken these technologies into account, with a focus on agricultural crops. Finally, we expand this review beyond commercial crops to address living modified organism uses in food industry, biomedical applications and climate change-oriented solutions.

Identification of Dynamic Patterns of Personal Positions in a Patient Diagnosed With Borderline Personality Disorder and the Therapist During Change Episodes of the Psychotherapy.

Personal positions and voices of a patient diagnosed with borderline personality disorder (BPD) and the therapist during long-term psychotherapy were studied aiming to find differences in the patterns formed in these aspects of subjectivity according to the level of elaboration of the change episodes achieved by the patient. This case study considered a stage of qualitative analysis where change episodes of the patient were traced through the Change Episodes Model. Later, through the Model of Analysis of Discursive Positioning in Psychotherapy (MAPP), the voices and personal positions of the patient and her therapist were identified in each of the change episodes. In the stage of quantitative analysis, dynamic patterns in the voices and personal positions were established, accounting for hypothetical attractors using the Space State Grid (SSG) technique in each of the three different levels of subjective elaboration that constitute the change episodes. The results established differentiated dynamic patterns in the change episodes, coherent with the patient's change process, and formation of propositive/reflective specific patterns as the patient evolved in the three different levels of subjective elaboration. The above suggests that a subjective transformation process is displayed, and this is manifested in the different voices and personal positions that emerged as the change episodes evolve. The identified dynamic patterns can be considered nonlinear and emergent subjective exchanges between the patient and the therapist throughout the psychotherapy.

Resultados en psicoterapia individual de adultos desde la perspectiva de los Sistemas Dinámicos: una revisión sistemática / Adult individual psychotherapy results from the Dynamic Systems perspective: a systematic review

Resumen: Existe un variado número de investigaciones que emplea nociones de la perspectiva de sistemas dinámicos (SD) para describir procesos de cambio en psicoterapia, conceptualizándolo como un sistema no lineal autoorganizado que presenta procesos emergentes y variaciones estructurales. Se realizó una revisión sistemática de la investigación en psicoterapia individual con pacientes adultos abordada desde esta perspectiva. La revisión se sustentó en la metodología PRISMA rastreando los principales conceptos de la perspectiva SD aplicados a la psicoterapia individual de adultos (entre 1997 y 2019), en los idiomas inglés y español, utilizando las bases de datos electrónicas PsycINFO y ProQuest. La selección final incluyó 34 estudios, tanto estudios de caso como estudios naturalistas, que abordaron diferentes variables de proceso y resultado de la psicoterapia. Los resultados resaltan la forma en que dichos conceptos ayudan a comprender el cambio de los pacientes como un proceso no lineal, destacando sus características de autoorganización, transiciones desde estados que generan sufrimiento psicológico a estados más saludables, y la formación de patrones emergentes en diferentes etapas de la psicoterapia. Se discuten algunos aspectos derivados (p.e. rol de la alianza, y de las intervenciones clínicas) que pueden ser abordados en el trabajo terapéutico.

Abstract: There is a diverse body of research that utilizes notions of the dynamical systems (DS) perspective to describe change processes in psychotherapy, understanding it as a non-linear self-organized system that presents emergent processes and structural variations. A systematic review of research in individual psychotherapy with adult patients addressed from this perspective has been carried out. The review was carried out supported by the PRISMA methodology tracking the main concepts of the DS perspective applied to individual psychotherapy of adults (between 1997 and 2019), in English and Spanish, using the electronic databases PsycINFO and ProQuest. The final selection included 34 studies, both case studies and naturalistic studies, covering different process and outcome variables of psychotherapy. The results highlight how such concepts help to understand patients' change as a nonlinear process, emphasizing its self-organizing characteristics, transitions from states that generate psychological distress to healthier states, and the formation of emergent patterns at different stages of psychotherapy. Some related aspects (e.g. role of the alliance, and of clinical interventions) that can be considered in the therapeutic work are discussed.

Feasibility of Raman spectroscopy as a potential in vivo tool to screen for pre-diabetes and diabetes.

In this article, we investigated the feasibility of using Raman spectroscopy and multivariate analysis method to noninvasively screen for prediabetes and diabetes in vivo. Raman measurements were performed on the skin from 56 patients with diabetes, 19 prediabetic patients and 32 healthy volunteers. These spectra were collected along with reference values provided by the standard glycated hemoglobin (HbA1c) assay. A multiclass principal component analysis and support vector machine (PCA-SVM) model was created from the labeled Raman spectra and was validated through a two-layer cross-validation scheme. Classification accuracy of the model was 94.3% with an area under the receiver operating characteristic curve AUC of 0.76 (0.65-0.84) for the prediabetic group, 0.86 (0.71-0.93) for the diabetic group and 0.97(0.93-0.99) for the control group. Our results suggest the feasibility of using Raman spectroscopy for the classification of prediabetes and diabetes in vivo.

Yeast as a biological platform for vitamin D production: A promising alternative to help reduce vitamin D deficiency in humans.

Vitamin D is an important human hormone, known primarily to be involved in the intestinal absorption of calcium and phosphate, but it is also involved in various nonskeletal processes (molecular, cellular, immune, and neuronal). One of the main health problems nowadays is the vitamin D deficiency of the human population due to lack of sun exposure, with estimates of one billion people worldwide with vitamin D deficiency, and the consequent need for clinical intervention (i.e., prescription of pharmacological vitamin D supplements). An alternative to reduce vitamin D deficiency is to produce good dietary sources of it, a scenario in which the yeast Saccharomyces cerevisiae seems to be a promising alternative. This review focuses on the potential use of yeast as a biological platform to produce vitamin D, summarizing both the biological aspects of vitamin D (synthesis, ecology and evolution, metabolism, and bioequivalence) and the work done to produce it in yeast (both for vitamin D2 and for vitamin D3 ), highlighting existing challenges and potential solutions.

Internalización del estigma en personas LGB: Análisis de su impacto sobre la salud mental y la búsqueda de ayuda psicoterapéutica en Chile / Internalization of stigma in LGB people: Analysis of its impact on mental health and psychotherapeutic support in Chile

Resumen Antecedentes Estudios señalan que la internalización de creencias, prejuicios y actitudes existentes en la sociedad sobre las personas de la diversidad sexual afectan fuertemente su salud mental y podrían constituirse en una barrera de acceso a la ayuda psicológica y terapéutica en personas LGB. Objetivo Determinar la asociación entre los niveles de internalización de estigma sexual (ESI) en personas autoidentificadas como lesbianas, gay y bisexuales (LGB) con la presencia de malestar subjetivo, sintomatología depresiva y ansiosa, suicidalidad, y asistencia a psicoterapia. Método Un cuestionario aplicado de manera online que incluía preguntas sobre haber asistido o estar asistiendo a psicoterapia, además de escalas que evaluaban estigma sexual internalizado, malestar-bienestar subjetivo, depresión y suicidalidad fue respondido por 669 personas cisgenero autoidentificadas como lesbianas, gay y bisexuales. Resultados Los resultados muestran una asociación positiva entre el nivel de ESI en personas LGB con sus niveles de malestar subjetivo, sintomatología depresiva y ansiosa, y suicidalidad, y una asociación negativa con estar asistiendo o haber asistido a psicoterapia. Conclusiones Se discuten las implicancias de los resultados presentados para el desarrollo de intervenciones psicoterapéuticas culturalmente competentes para pacientes pertenecientes a la diversidad sexual y de género.

Abstract Background Studies indicate that the internalization of beliefs, prejudices and attitudes existing in society about sexual minorities strongly affect their mental health and could constitute a barrier to access to psychological and therapeutic support in LGB people. Objective To determine the association between levels of internalized sexual stigma (ISS) in self-identified lesbian, gay and bisexual (LGB) people with the presence of subjective distress, depressive and anxious symptoms, suicidality, and psychotherapy attendance. Methods An online questionnaire including questions on having attended or attending psychotherapy, as well as scales assessing internalized sexual stigma, subjective distress-subjective well-being, depression, and suicidality was completed by 669 cisgender self-identified lesbian, gay, and bisexual individuals. Results The results show a positive association between the level of ISS in LGB people with their levels of subjective distress, depressive and anxious symptomatology, and suicidality, and a negative association with being attending or having attended psychotherapy. Conclusions The implications of the results presented for the development of culturally competent psychotherapeutic interventions for patients belonging to sexual and gender diversity are discussed.

Sparks of psychotherapeutic change: How therapists understand moments of meetings' contribution to change in psychotherapy.

OBJECTIVE: : This study describes therapists' experience of moments of meeting with their patients in psychotherapy, and how these moments relate to the patient's change process. METHOD: 13 in-depth interviews conducted with therapists from different theoretical backgrounds were analyzed using Grounded Theory. RESULTS: Four categories were established: (1) Characteristics of moments of meeting, (2) Triggers of moments of meeting (3) Enabling conditions, and (4) Main effects of moments of meeting. A conceptual model was developed around an axial phenomenon that provides understanding on how moments of meeting contribute to the change process in psychotherapy, through the construction of shared relational knowing. DISCUSSION: : The value of moments of meeting for the therapeutic process is discussed and reflected upon, as well as their effect on changes regarding implicit relational knowing.

An alternative, zeaxanthin epoxidase-independent abscisic acid biosynthetic pathway in plants.

Abscisic acid (ABA) is an important carotenoid-derived phytohormone that plays essential roles in plant response to biotic and abiotic stresses as well as in various physiological and developmental processes. In Arabidopsis, ABA biosynthesis starts with the epoxidation of zeaxanthin by the ABA DEFICIENT 1 (ABA1) enzyme, leading to epoxycarotenoids; e.g., violaxanthin. The oxidative cleavage of 9-cis-epoxycarotenoids, a key regulatory step catalyzed by 9-CIS-EPOXYCAROTENOID DIOXYGENASE, forms xanthoxin, which is converted in further reactions mediated by ABA DEFICIENT 2 (ABA2), ABA DEFICIENT 3 (ABA3), and ABSCISIC ALDEHYDE OXIDASE 3 (AAO3) into ABA. By combining genetic and biochemical approaches, we unravel here an ABA1-independent ABA biosynthetic pathway starting upstream of zeaxanthin. We identified the carotenoid cleavage products (i.e., apocarotenoids, ß-apo-11-carotenal, 9-cis-ß-apo-11-carotenal, 3-OH-ß-apo-11-carotenal, and 9-cis-3-OH-ß-apo-11-carotenal) as intermediates of this ABA1-independent ABA biosynthetic pathway. Using labeled compounds, we showed that ß-apo-11-carotenal, 9-cis-ß-apo-11-carotenal, and 3-OH-ß-apo-11-carotenal are successively converted into 9-cis-3-OH-ß-apo-11-carotenal, xanthoxin, and finally into ABA in both Arabidopsis and rice. When applied to Arabidopsis, these ß-apo-11-carotenoids exert ABA biological functions, such as maintaining seed dormancy and inducing the expression of ABA-responsive genes. Moreover, the transcriptomic analysis revealed a high overlap of differentially expressed genes regulated by ß-apo-11-carotenoids and ABA, suggesting that ß-apo-11-carotenoids exert ABA-independent regulatory activities. Taken together, our study identifies a biological function for the common plant metabolites, ß-apo-11-carotenoids, extends our knowledge about ABA biosynthesis, and provides new insights into plant apocarotenoid metabolic networks.

Genetically modified organisms: adapting regulatory frameworks for evolving genome editing technologies

Genetic modification of living organisms has been a prosperous activity for research and development of agricultural, industrial and biomedical applications. Three decades have passed since the first genetically modified products, obtained by transgenesis, become available to the market. The regulatory frameworks across the world have not been able to keep up to date with new technologies, monitoring and safety concerns. New genome editing techniques are opening new avenues to genetic modification development and uses, putting pressure on these frameworks. Here we discuss the implications of definitions of living/genetically modified organisms, the evolving genome editing tools to obtain them and how the regulatory frameworks around the world have taken these technologies into account, with a focus on agricultural crops. Finally, we expand this review beyond commercial crops to address living modified organism uses in food industry, biomedical applications and climate change-oriented solutions.

Perspectiva ética de la priorización de vacunación contra el COVID-19 en Chile

The SARS-CoV-2 pandemic has generated an important health and economic impact on the world. Vaccines emerge as an intervention that can contribute to the control of the pandemic. Vaccines were approved for emergency use in the United States, Europe, as well as in Chile, however, they will not be immediately available, creating the need to prioritize vaccine distribution. The World Health Organization (WHO) and other international agencies established ethical frameworks to guide the distribution of the COVID-19 vaccine globally. In Chile, the Advisory Council on Vaccines and Immunizations (CAVEI) and the COVID-19 Advisory Council of the Ministry of Health (MINSAL) recommended the groups to prioritize vaccination, based on the available evidence stating that this information could change over time. In this article, we propose a reference framework of ethical principles and values to support the decision-making of prioritization and distribution of vaccines in Chile. We propose three timeless values: maximizing benefits, prioritizing the most vulnerable, reciprocity, and two transversal bioethics principles: justice and transparency. This reference framework contributes to the vaccination plan communication, the decision-making by the authorities and supports the prioritization strategy's valúes framework. With an explicit values framework we can expect better communication or priorities, a greater acceptance of SARS-CoV-2 vaccination plan by the community and an increased vaccination coverage to protect the population.

Palladium-Catalyzed Aminocyclization-Coupling Cascades: Preparation of Dehydrotryptophan Derivatives and Computational Study.

Dehydrotryptophan derivatives have been prepared by palladium-catalyzed aminocyclization-Heck-type coupling cascades starting from o-alkynylaniline derivatives and methyl α-aminoacrylate. Aryl, alkyl (primary, secondary, and tertiary), and alkenyl substituents have been introduced at the indole C-2 position. Further variations at the indole benzene ring, as well as the C-2-unsubstituted case, have all been demonstrated. In the case of C-2 aryl substitution, the preparation of the o-alkynylaniline substrate by Sonogashira coupling and the subsequent cyclization-coupling cascade have been performed in a one-pot protocol with a single catalyst. DFT calculations have revealed significant differences in the reaction profiles of these reactions relative to those involving methyl acrylate or methacrylate, and between the reactions of the free anilines and their corresponding carbamates. Those calculations suggest that the nature of the alkene and of the acid HX released in the HX/alkene exchange step that precedes C-C bond formation could be responsible for the experimentally observed differences in reaction efficiencies.

Hypoalbuminemia on admission in COVID-19 infection: An early predictor of mortality and adverse events. A retrospective observational study.

OBJECTIVES: Hypoalbuminemia is a negative acute phase reactant which has been associated with inflammatory response and poor outcome in infectious diseases. The aim of this study was to analyze the value of hypoalbuminemia on admission as a predictor of mortality and adverse events in COVID-19 patients. METHODS: We analyzed retrospective data from a cohort of 609 consecutive patients, with confirmed diagnosis of COVID-19, discharged from hospital (deceased or alive). Demographic characteristics, previous comorbidities, symptoms and laboratory findings on admission were collected. Comorbidities were assessed by Charlson-Age Comorbidity Index. RESULTS: Hypoalbuminemia on admission (<34 g/L) was more frequent in nonsurvivors than survivors (65.6% vs. 38%, p < 0.001) and was significantly associated with the development of sepsis, macrophage activation syndrome, acute heart failure, acute respiratory distress syndrome and acute kidney injury, regardless of Charlson-Age Comorbidity Index. Hypoalbuminemia was a predictor of mortality in multivariable Cox regression analysis (HR 1.537, 95% CI 1.050-2.250, p = 0.027), independently of Charlson-Age Index, gender, lymphocyte count <800/µL, creatinine, high-sensitivity C- reactive protein >8 mg/L, lactate dehydrogenase >250 U/L, bilateral infiltration on chest X-ray and q-SOFA ≥2. CONCLUSIONS: Hypoalbuminemia was an early predictor of in-hospital mortality in COVID-19, regardless of age, comorbidity and inflammatory markers. It also had significant association with severe adverse events, independently of Charlson-Age Comorbidity Index. Our results suggest that serum albumin determination on admission may help to identify patients with SARS-CoV-2 infection at high risk of developing potential life-threatening conditions and death.

OBJETIVOS: La hipoalbuminemia es un reactante de fase aguda negativo que ha sido asociado a la respuesta inflamatoria y mal resultado en enfermedades infecciosas. El objetivo de este estudio fue analizar el valor de la hipoalbuminemia en el momento del ingreso, como factor predictivo de mortalidad y episodios adversos en los pacientes de COVID-19. MÉTODOS: Analizamos los datos retrospectivos de una cohorte de 609 pacientes consecutivos, con diagnóstico confirmado de COVID-19, que abandonaron el hospital (fallecidos o vivos). Se recopilaron las características demográficas, comorbilidades previas, síntomas y hallazgos de laboratorio en el momento del ingreso. Las comorbilidades se asociaron al índice de comorbilidad de Charlson-Age. RESULTADOS: La hipoalbuminemia en el momento del ingreso (< 34 g/l) fue más frecuente en los no supervivientes que en los supervivientes (65,6 vs. 38%; p < 0,001) y estuvo significativamente asociada a desarrollo de sepsis, síndrome de activación macrofágica, insuficiencia cardiaca aguda, síndrome de distrés respiratorio agudo e insuficiencia renal aguda, independientemente del índice de comorbilidad de Charlson-Age. La hipoalbuminemia fue un factor predictivo de la mortalidad en el análisis multivariable de regresión de Cox (HR: 1,537; IC 95%: 1,050-2,250; p = 0,027), independientemente del índice de Charlson-Age, sexo, recuento linfocítico < 800/µl, creatinina, proteína C reactiva de alta sensibilidad > 8 mg/l, lactato deshidrogenasa > 250 U/l, infiltración bilateral en la placa de tórax y q-SOFA ≥ 2. CONCLUSIONES: La hipoalbuminemia fue un factor predictivo temprano de la mortalidad intrahospitalaria en la COVID-19, independientemente de la edad, de la comorbilidad y de los marcadores inflamatorios. También tuvo una asociación significativa con episodios adversos graves, independientemente del índice de comorbilidad de Charlson-Age. Nuestros resultados sugieren que determinar la albúmina sérica en el momento del ingreso podría ayudar a identificar a los pacientes con infección por SARS-CoV-2 con alto riesgo de desarrollar situaciones potencialmente mortales y muerte.