Tuberculosis patients face high treatment support costs in Colombia, 2021.

OBJECTIVE: To estimate the baseline to measure one of the three indicators of the World Health Organization (WHO) End TB strategy (2015-2035), measure the costs incurred by patients affected by tuberculosis (TB) during a treatment episode and estimate the proportion of households facing catastrophic costs (CC) and associated risk factors, in Colombia, 2021. MATERIAL AND METHODS: A nationally representative cross-sectional survey was conducted among participants on TB treatment in Colombia, using telephone interviews due to the exceptional context of the COVID-19 pandemic. The survey collected household costs (direct [medical and non-medical out-of-pocket expenses] and indirect) over an episode of TB, loss of time, coping measures, self-reported income, and asset ownership. Total costs were expressed as a proportion of annual household income and analyzed for risk factors of CC (defined as costs above 20% annual household income). RESULTS: The proportion of TB-affected households incurring in costs above 20% annual household income (CC) was 51.7% (95%CI: 45.4-58.0) overall, 51.3% (95%CI: 44.9-57.7) among patients with drug-sensitive (DS) TB, and 65.0% (95%CI: 48.0-82.0) among drug-resistant (DR). The average patient cost of a TB case in Colombia was $1,218 (95%CI 1,106-1,330) including $860.9 (95%CI 776.1-945.7) for non-medical costs, $339 (95%CI 257-421) for the indirect costs, and $18.1 (95%CI 11.9-24.4) for the medical costs. The factors that influenced the probability of facing CC were income quintile, job loss, DR-TB patient, and TB type. CONCLUSION: Main cost drivers for CC were non-medical out-of-pocket expenses and income loss (indirect costs). Current social protection programs ought to be expanded to mitigate the proportion of TB-affected households facing CC in Colombia, especially those with lower income levels.

Non-pharmacological interventions for autism spectrum disorder in children: an overview of systematic reviews.

OBJECTIVE: To assess the effectiveness of non-pharmacological interventions for the treatment of autism spectrum disorder (ASD) in children. DESIGN: Overview of systematic reviews (SRs). PARTICIPANTS: Children aged 12 years and under with ASD. SEARCH METHODS: In October 2021, we searched Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO and Epistemonikos placing no restrictions on language or date of publication. INTERVENTIONS: 17 non-pharmacological interventions compared with placebo, no-treatment (including waiting list) or other interventions (ie, usual care, as defined by the authors of each study). DATA COLLECTION AND ANALYSIS: We rated the methodological quality of the included SRs using A Measurement Tool to Assess Systematic Reviews (AMSTAR 2). We reported the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) certainty of the evidence (CoE) according to the analysis conducted by the authors of the included SRs. MAIN OUTCOME MEASURES: A multidisciplinary group of experts agreed on analysing nine critical outcomes evolving core and non-core ASD symptoms. PUBLIC AND PATIENT INVOLVEMENT STATEMENT: Organisations of parents of children with ASD participated in external revision of the final version of the report. RESULTS: We identified 52 reports that were within our scope, of which 48 were excluded for various reasons. After excluding less reliable SRs, we included four SRs. Non-pharmacological interventions (ie, Early Intensive Behavioural Intervention, Applied Behaviour Analysis, Picture Exchange Communication System and Naturalistic Developmental Behavioural Interventions) may have favourable effects on some core outcomes including language, social and functioning, play or daily living skills in children with ASD (with either no GRADE assessment, very low or low CoE). In addition, we identified a lack of report for other key outcomes in the included SRs (ie, restricted, repetitive behaviour; play and sensory processing). CONCLUSIONS: Synthesised evidence regarding the efficacy of non-pharmacological interventions for children with ASD is scarce. High-quality SRs addressing the variety of both non-pharmacological interventions and relevant outcomes are needed. PROSPERO REGISTRATION NUMBER: CRD42020206535.

Safety and efficacy of convalescent plasma for severe COVID-19: a randomized, single blinded, parallel, controlled clinical study.

BACKGROUND: Convalescent plasma (CP) has been widely used to treat COVID-19 and is under study. However, the variability in the current clinical trials has averted its wide use in the current pandemic. We aimed to evaluate the safety and efficacy of CP in severe coronavirus disease 2019 (COVID-19) in the early stages of the disease. METHODS: A randomized controlled clinical study was conducted on 101 patients admitted to the hospital with confirmed severe COVID-19. Most participants had less than 14 days from symptoms onset and less than seven days from hospitalization. Fifty patients were assigned to receive CP plus standard therapy (ST), and 51 were assigned to receive ST alone. Participants in the CP arm received two doses of 250 mL each, transfused 24 h apart. All transfused plasma was obtained from "super donors" that fulfilled the following criteria: titers of anti-SARS-CoV-2 S1 IgG ≥ 1:3200 and IgA ≥ 1:800 antibodies. The effect of transfused anti-IFN antibodies and the SARS-CoV-2 variants at the entry of the study on the overall CP efficacy was evaluated. The primary outcomes were the reduction in viral load and the increase in IgG and IgA antibodies at 28 days of follow-up. The per-protocol analysis included 91 patients. RESULTS: An early but transient increase in IgG anti-S1-SARS-CoV-2 antibody levels at day 4 post-transfusion was observed (Estimated difference [ED], - 1.36; 95% CI, - 2.33 to - 0.39; P = 0.04). However, CP was not associated with viral load reduction in any of the points evaluated. Analysis of secondary outcomes revealed that those patients in the CP arm disclosed a shorter time to discharge (ED adjusted for mortality, 3.1 days; 95% CI, 0.20 to 5.94; P = 0.0361) or a reduction of 2 points on the WHO scale when compared with the ST group (HR adjusted for mortality, 1.6; 95% CI, 1.03 to 2.5; P = 0.0376). There were no benefits from CP on the rates of intensive care unit admission (HR, 0.82; 95% CI, 0.35 to 1.9; P = 0.6399), mechanical ventilation (HR, 0.66; 95% CI, 0.25 to 1.7; P = 0.4039), or mortality (HR, 3.2; 95% CI, 0.64 to 16; P = 0.1584). Anti-IFN antibodies and SARS-CoV-2 variants did not influence these results. CONCLUSION: CP was not associated with viral load reduction, despite the early increase in IgG anti-SARS-CoV-2 antibodies. However, CP is safe and could be a therapeutic option to reduce the hospital length of stay. Trial registration NCT04332835.

Targeting Induced Local Lesions in the Wheat DEMETER and DRE2 Genes, Responsible for Transcriptional Derepression of Wheat Gluten Proteins in the Developing Endosperm.

Wheat is a major source of energy and nutrition worldwide, but it is also a primary cause of frequent diet-induced health issues, specifically celiac disease, for which the only effective therapy so far is strict dietary abstinence from gluten-containing grains. Wheat gluten proteins are grouped into two major categories: high-molecular-weight glutenin subunits (HMWgs), vital for mixing and baking properties, and gliadins plus low-molecular-weight glutenin subunits (LMWgs) that contain the overwhelming majority of celiac-causing epitopes. We put forth a hypothesis that eliminating gliadins and LMWgs while retaining HMWgs might allow the development of reduced-immunogenicity wheat genotypes relevant to most gluten-sensitive individuals. This hypothesis stems from the knowledge that the molecular structures and regulatory mechanisms of the genes encoding the two groups of gluten proteins are quite different, and blocking one group's transcription, without affecting the other's, is possible. The genes for gliadins and LMWgs have to be de-methylated by 5-methylcytosine DNA glycosylase/lyase (DEMETER) and an iron-sulfur (Fe-S) cluster biogenesis enzyme (DRE2) early during endosperm development to permit their transcription. In this study, a TILLING (Targeting Induced Local Lesions IN Genomes) approach was undertaken to identify mutations in the homoeologous DEMETER (DME) and DRE2 genes in common and durum wheat. Lines with mutations in these genes were obtained that displayed reduced content of immunogenic gluten proteins while retaining essential baking properties. Although our data at first glance suggest new possibilities for treating celiac disease and are therefore of medical and agronomical interest, it also shows that inducing mutations in the DME and DRE2 genes analyzed here affected pollen viability and germination. Hence there is a need to develop other approaches in the future to overcome this undesired effect.

A Bitter-Sweet Story: Unraveling the Genes Involved in Quinolizidine Alkaloid Synthesis in Lupinus albus.

Alkaloids are part of a structurally diverse group of over 21,000 cyclic nitrogen-containing secondary metabolites that are found in over 20% of plant species. Lupinus albus are naturally containing quinolizidine alkaloid (QA) legumes, with wild accessions containing up to 11% of QA in seeds. Notwithstanding their clear advantages as a natural protecting system, lupin-breeding programs have selected against QA content without proper understanding of quinolizidine alkaloid biosynthetic pathway. This review summarizes the current status in this field, with focus on the utilization of natural mutations such as the one contained in pauper locus, and more recently the development of molecular markers, which along with the advent of sequencing technology, have facilitated the identification of candidate genes located in the pauper region. New insights for future research are provided, including the utilization of differentially expressed genes located on the pauper locus, as candidates for genome editing. Identification of the main genes involved in the biosynthesis of QA will enable precision breeding of low-alkaloid, high nutrition white lupin. This is important as plant based high quality protein for food and feed is an essential for sustainable agricultural productivity.

A low-cost platform suitable for sequencing-based recovery of natural variation in understudied plants.

Genetic characterization of wild and cultivated plants provides valuable knowledge for conservation and agriculture. DNA sequencing technologies are improving, and costs are dropping. Yet analysis of many species is hindered because they grow in regions that lack infrastructure for advanced molecular biology. The authors developed and adapted low-cost methods that address these issues. Tissue was collected and stored in silica gel, avoiding the need for liquid nitrogen and freezers. The authors optimized low-cost, homemade DNA extraction to increase yields, reduce costs and produce DNA suitable for next-generation sequencing. The authors describe how to build a gel documentation system for DNA quantification. As a proof of principle, the authors used these methods to evaluate wild Berberis darwinii, native to Southern Chile.

Trastorno de estrés postraumático en menores internados por maltrato en cinco instituciones ICBF - Pereira / Post-traumatic stress disorder in abused children that are hospitalized in five ICBF institutions in Pereira

Resumen Introducción: El trastorno de estrés postraumático (TEPT) aparece después de la exposición a un evento amenazante e incluye síntomas de evitación e intrusión del recuerdo, hiper-alerta e hiperreactividad , alteraciones negativas cognitivas y alteraciones en el estado de ánimo. Puede aparecer en más del 50% de los niños afectados por desastres de origen natural o humano, como el maltrato, afectando gravemente su calidad de vida presente y futura. Objetivo: Determinar la prevalencia de TEPT en niños internados por maltrato en cinco instituciones de Pereira vinculadas al ICBF. Materiales y métodos: Se construyó, validó y utilizó una escala graduada a partir de los criterios sintomáticos del DSM-5 de TEPT adaptada a población escolar. Se aplicó mediante entrevista personal, previa educación lúdica a los niños sobre los conceptos pertinentes. Resultados y conclusiones: La población de estudio fueron 46 hombres y 47 mujeres institucionalizados en el ICBF, con una media de edad de 11.6 (desviación estándar 2.0) y un tiempo de estadía máximo en el rango inferior de menos de 6 meses con tendencia a la baja y una escolaridad por debajo de lo esperado para la edad . La causa principal de ingreso fue por maltrato intrafamiliar con un 49% , seguido por el abandono o pobreza extrema con un 41%. En cuanto a los criterios para TEPT, el 60 (64.5%) de los menores de edad institucionalizados por vulneración de derechos, cumplían todos los criterios y el 8 (8.6%) cumplían todos menos un criterio sintomático (TEPT subclínico), este alto porcentaje concuerda con la literatura mundial y nacional. Finalmente, el 21.5% no presentaban síntomas y el 5.4% no habían estado expuestos a eventos traumáticos. Los diferentes criterios sintomáticos tenían un nivel similar de intensidad.

Abstract Introduction: Post-traumatic stress disorder (PTSD) appears after being exposed to a threatening event; it includes symptoms of avoidance and intrusion of memories, an increase of arousal and reactivity, and negative alterations in cognitions and mood. It can appear in more than 50% of children affected by disasters caused by nature or human beings, such as abuse; these experiences can seriously affect the children's present and future quality of life. Objective: This descriptive research aims to determine the prevalence of PTSD in hospitalized children for mistreatment in five Pereira institutions linked to the ICBF. Materials and Methods: A graded scale was constructed, validated, and used based on the symptomatic DSM-5 criteria of PTSD and was adapted to the school population. It was applied through a personal interview after giving some playful education about the relevant concepts to the children. Results and conclusions: The standard population was composed of 46 boys and 47 girls that were part of the ICBF. The main range of age was 11.6 (standard deviation 2.0), the maximum stay time in place was the lowest (less than six months) with a decreasing tendency, and a schooling level below to the expected according to the age. The most common cause of hospitalization was inter-family violence (49%) and 41% for abandonment or extreme poverty. According to the PTSD criteria, 60 youngers (64.5%) were hospitalized for violation of rights, and eight children (8.6%) fit with all but one symptomatic standard (subclinical PTSD). This high percentage tallies with the ones found in the world literature and Colombia. Finally, 21.5% had no symptoms, and 5.4% had not been exposed to traumatic events. The different symptomatic criteria had a similar level of intensity.

Effectiveness of emotional freedom techniques with a recreational plastic expression program in postraumatic stress of school age children boarded for abuse-related trauma / Eficacia de un programa de técnicas de libertad emocional con expresión plástica recreativa en el estrés postraumático de escolares internados por maltrato

Abstract We present an experimentally controlled and randomized investigation with pre- and post-trial results, carried out on 47 children boarded for abuse-related trauma in four different shelters. A gradual scale was utilized based on the DSM-5 criteria for post-traumatic stress disorder (PTSD). The program included six sessions that implemented Emotional Freedom Techniques (EFT), together with recreational plastic expression. The Plastic Expression was appropriate, considering the under-developed verbal skills and the hypoactivation of the speech area under the PTSD, and it facilitated the approach of memories in a safe, group-oriented environment. The recreational usage brought along the comfort which in turn helped to counteract the avoidance present at the onset of the PTSD. The EFT gave way to a rapid decrease in the distress response and contributed to the immediate elaboration of memories. The program significantly decreased the level of the PTSD, facilitated learning of new and effective forms of coping, and contributed by opening the mind towards a personal life project.

Resumen Presentamos una investigación experimental controlada y aleatorizada con pre y pos-prueba, llevada a cabo en 47 niños internados por maltrato en cuatro centros de protección. Se utilizó una escala graduada según los criterios del DSM-5 para el trastorno de estrés postraumático (TEPT). El programa comprendió seis sesiones que implementaron Técnicas de Liberación Emocional (EFT) junto con expresión plástica recreativa. La Expresión Plástica fue apropiada, considerando las habilidades verbales en desarrollo y la hipoactivación del área del lenguaje del TEPT, y facilitó la aproximación a tos recuerdos en un entorno seguro y grupal. La recreación brindó bienestar que ayudó a contrarrestar la evitación que está en la génesis del TEPT. La EFT produjo una rápida disminución de la respuesta de alarma y contribuyó a la pronta elaboración del recuerdo. El Programa disminuyó significativamente el nivel del TEPT, facilitó el aprendizaje de nuevas formas eficaces de afrontamiento y aportó al pensamiento de un proyecto de vida personal.

Directed-Mutagenesis of Flavobacterium meningosepticum Prolyl-Oligopeptidase and a Glutamine-Specific Endopeptidase From Barley.

Wheat gluten proteins are the known cause of celiac disease. The repetitive tracts of proline and glutamine residues in these proteins make them exceptionally resilient to digestion in the gastrointestinal tract. These indigested peptides trigger immune reactions in susceptible individuals, which could be either an allergic reaction or celiac disease. Gluten exclusion diet is the only approved remedy for such disorders. Recently, a combination of a glutamine specific endoprotease from barley (EP-B2), and a prolyl endopeptidase from Flavobacterium meningosepticum (Fm-PEP), when expressed in the wheat endosperm, were shown to reasonably detoxify immunogenic gluten peptides under simulated gastrointestinal conditions. However useful, these "glutenases" are limited in application due to their denaturation at high temperatures, which most of the food processes require. Variants of these enzymes from thermophilic organisms exist, but cannot be applied directly due to their optimum activity at temperatures higher than 37°C. Though, these enzymes can serve as a reference to guide the evolution of peptidases of mesophilic origin toward thermostability. Therefore, a sequence guided site-saturation mutagenesis approach was used here to introduce mutations in the genes encoding Fm-PEP and EP-B2. A thermostable variant of Fm-PEP capable of surviving temperatures up to 90°C and EP-B2 variant with a thermostability of up 60°C were identified using this approach. However, the level of thermostability achieved is not sufficient; the present study has provided evidence that the thermostability of glutenases can be improved. And this pilot study has paved the way for more detailed structural studies in the future to obtain variants of Fm-PEP and EP-B2 that can survive temperatures ~100°C to allow their packing in grains and use of such grains in the food industry.

Biobancos y COVID-19: implicaciones éticas / Biobanks and COVID-19: Ethical implications / Biobanks e COVID-19: Implicações éticas

Propósito/Contexto: De acuerdo con los antecedentes de epidemias anteriores, y en el contexto de la emergencia actual por COVID19, se ha reconocido como prioritario el desarrollo de investigaciones y la creación de biobancos o biorepositorios, que permitan el acceso a muestras e información para comprender la enfermedad, formular intervenciones, evaluar la seguridad y eficacia de exámenes, pruebas de diagnóstico, tratamientos, vacunas y estrategias de manejo. Aunque la investigación durante eventos de importancia en salud pública es fundamental, los estudios con seres humanos durante las emergencias deben contar con mayores garantías éticas que en las situaciones ordinarias. Metodología/Enfoque: para esta revisión se realizó la búsqueda de literatura relacionada con normatividad y legislación, biobancos, colecciones de muestras, y su relevancia en el contexto de la pandemia. Discusión/Conclusiones/Contribuciones: En esta revisión incluimos algunas reflexiones sobre el establecimiento y uso de los biobancos en el contexto de la pandemia que aqueja al mundo actualmente.

Purpose/Context. According to the history of previous epidemics, and in the context of the current emergency caused by COVID-19, it is a priority to carry out research and create biobanks or biorepositories. These allow accessing samples and information to understand the disease, formulate interventions, and evaluate the safety and efficacy of examinations, diagnostic tests, treatments, vaccines, and management strategies. Although research during significant public health emergencies is essential, studies on human beings in these cases must have higher ethical guarantees than ordinary situations. Method/Approach. This review includes literature related to regulations and legislation, biobanks, sample collections, and their relevance to the context of the pandemic. Results/Findings. Accelerated sample collection and the establishment of biobanks have been typical during this pandemic, which induces the adoption of sample management guidelines with major ethical, legal, and social differences among countries. Discussion/Conclusions/Contributions. This review comprises reflections on the establishment and use of biobanks during the pandemic that is currently afflicting the world.

Objetivo/Contexto. De acordo com os antecedentes de epidemias anteriores e no contexto da atual emergência causada pelo COVID-19, tem-se reconhecido como prioritário o desenvolvimento de pesquisas e a criação de biobancos ou bio-repositórios, que permitam o acesso a amostras e informações para entender a doença, formular intervenções, avaliar a segurança e eficácia dos exames, dos testes de diagnóstico, dos tratamentos, as vacinas e as estratégias de manejo. Embora a pesquisa durante eventos importantes em saúde pública seja essencial, os estudos com seres humanos em situações de emergência devem ter maiores garantias éticas do que em situações comuns. Metodologia/Abordagem. Para esta revisão, se efetuo a busca de literatura relacionada com o regulamento e legislação, biobancos, coletas de amostras e sua relevância no contexto da pandemia. Resultados/Descobertas. Achamos que, no contexto da pandemia, é comum a coleta acelerada de amostras e o estabelecimento de biobancos, o que induz à adoção de diretrizes para o tratamento dessas amostras, com diferenças importantes em aspectos éticos, legais e sociais entre os diferentes países. Discussão/Conclusões/Contribuições. Nesta revisão, incluímos algumas reflexões sobre o estabelecimento e o uso de biobancos no contexto da pandemia que atualmente afeta o mundo.

Gluten Detection Methods and Their Critical Role in Assuring Safe Diets for Celiac Patients.

Celiac disease, wheat sensitivity, and allergy represent three different reactions, which may occur in genetically predisposed individuals on the ingestion of wheat and derived products with various manifestations. Improvements in the disease diagnostics and understanding of disease etiology unveiled that these disorders are widespread around the globe affecting about 7% of the population. The only known treatment so far is a life-long gluten-free diet, which is almost impossible to follow because of the contamination of allegedly "gluten-free" products. Accidental contamination of inherently gluten-free products could take place at any level from field to shelf because of the ubiquity of these proteins/grains. Gluten contamination of allegedly "gluten-free" products is a constant threat to celiac patients and a major health concern. Several detection procedures have been proposed to determine the level of contamination in products for celiac patients. The present article aims to review the advantages and disadvantages of different gluten detection methods, with emphasis on the recent technology that allows identification of the immunogenic-gluten peptides without the use of antibodies. The possibility to detect gluten contamination by different approaches with similar or better detection efficiency in different raw and processed foods will guarantee the safety of the foods for celiac patients.

The Role of Orange Gene in Carotenoid Accumulation: Manipulating Chromoplasts Toward a Colored Future.

Carotenoids are isoprenoid pigments synthesized in plants, algae, and photosynthetic bacteria and fungus. Their role is essential in light capture, photoprotection, pollinator attraction, and phytohormone production. Furthermore, they can regulate plant development when they are processed as small signaling molecules. Due to their importance for human health, as promoters of the immune system and antioxidant activity, carotenoids have been used in the pharmaceutical, food, and nutraceutical industries. Regulation of carotenoid synthesis and accumulation has been extensively studied. Excellent work has been done unraveling the mode of action of phytoene synthase (PSY), a rate-limiting enzyme of carotenoid biosynthesis pathway, in model species and staple crops. Lately, interest has been turned to Orange protein and its interaction with PSY during carotenoid biosynthesis. Discovered as a dominant mutation in Brassica oleracea, Orange protein regulates carotenoid accumulation by posttranscriptionally regulating PSY, promoting the formation of carotenoid-sequestering structures, and also preventing carotenoid degradation. Furthermore, Orange protein contributes to homeostasis regulation, improving plant tolerance to abiotic stress. In this mini review, the focus is made on recent evidence that elucidates Orange protein mode of action and expression in different plant species. Additionally, strategies are proposed to modify Orange gene by utilization of genome editing techniques. A better understanding of carotenoid biosynthesis and accumulation will lead to a positive impact on the development of healthy food for a growing population.

Preoperative Bevacizumab for Tractional Retinal Detachment in Proliferative Diabetic Retinopathy: A Prospective Randomized Clinical Trial.

PURPOSE: To assess the effectiveness and safety of an intravitreal injection of 1.25 mg bevacizumab (IVB) as a preoperative adjunct to small-gauge pars plana vitrectomy (PPV) compared with PPV alone in eyes with tractional retinal detachment secondary to proliferative diabetic retinopathy. METHODS: This prospective, double-masked, randomized, multicenter, active-controlled clinical trial enrolled 224 eyes of 224 patients between November 2013 and July 2015. All eyes underwent a baseline examination including best-corrected visual acuity, color photos, optical coherence tomography, and fluorescein angiography. Data were collected on intraoperative bleeding, total surgical time, early (<1 month) postoperative vitreous hemorrhage, and mean change in best-corrected visual acuity at 12 months. P < .05 was considered statistically significant. RESULTS: A total of 214 patients (214 eyes) were randomized in a 1:1 ratio to PPV plus IVB ([study group] 102 eyes) or PPV plus sham ([control] 112 eyes). Iatrogenic retinal breaks were noted intraoperatively in 35 eyes (34.3%) in the study group, and 66 eyes (58.9%) in the control group (P = .001). Grade 2 intraoperative bleeding was noted in 32 (31.3%) eyes in the study group and 58 (51.7 %) eyes in the control group (P = .001). Endodiathermy was necessary in 28 (27.4 %) eyes in the study group, compared with 75 (66.9%) eyes in the control group (P = .0001). Mean surgical time was 71.3 ± 32.1 minutes in the study group and 83.6 ± 38.7 minutes in the control group (P = .061). CONCLUSION: Preoperative IVB seems to reduce intraoperative bleeding, improving surgical field visualization, and reducing intraoperative and postoperative complications. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Development of wheat genotypes expressing a glutamine-specific endoprotease from barley and a prolyl endopeptidase from Flavobacterium meningosepticum or Pyrococcus furiosus as a potential remedy to celiac disease.

Ubiquitous nature of prolamin proteins dubbed gluten from wheat and allied cereals imposes a major challenge in the treatment of celiac disease, an autoimmune disorder with no known treatment other than abstinence diet. Administration of hydrolytic glutenases as food supplement is an alternative to deliver the therapeutic agents directly to the small intestine, where sensitization of immune system and downstream reactions take place. The aim of the present research was to evaluate the capacity of wheat grain to express and store hydrolytic enzymes capable of gluten detoxification. For this purpose, wheat scutellar calli were biolistically transformed to generate plants expressing a combination of glutenase genes for prolamin detoxification. Digestion of prolamins with barley endoprotease B2 (EP-HvB2) combined with Flavobacterium meningosepticum prolyl endopeptidase (PE-FmPep) or Pyrococcus furiosus prolyl endopeptidase (PE-PfuPep) significantly reduced (up to 67%) the amount of the indigestible gluten peptides of all prolamin families tested. Seven of the 168 generated lines showed inheritance of transgene to the T2 generation. Reversed phase high-performance liquid chromatography of gluten extracts under simulated gastrointestinal conditions allowed the identification of five T2 lines that contained significantly reduced amounts of immunogenic, celiac disease-provoking gliadin peptides. These findings were complemented by the R5 ELISA test results where up to 72% reduction was observed in the content of immunogenic peptides. The developed wheat genotypes open new horizons for treating celiac disease by an intraluminal enzyme therapy without compromising their agronomical performance.

La Lepra: una enfermedad vigente / Leprosy: an ongoing disease

El libro resalta que la lepra continúa siendo una enfermedad presente en Colombia y que aún constituye un problema de salud pública importante por los costos sociales, económicos y de sufrimiento humano que conlleva. Sabiendo que la literatura sobre el tema es escasa en nuestro medio, este libro surge como una herramienta de consulta creada para médicos y otros profesionales de salud, con la certeza de que es preciso mejorar la oportunidad del diagnóstico. Siendo fundamental que, durante su proceso formativo, todos los profesionales de la salud adquieran conocimientos sobre dicha enfermedad, que cada día se hace más visible por sus secuelas y diagnóstico tardío.

The book highlights the fact that leprosy continues to be a disease present in Colombia and that it is still a major public health problem due to the social, economic and human suffering costs it entails. Knowing that the literature on the subject is scarce in our country, this book is intended as a reference tool for doctors and other health professionals, in the knowledge that it is necessary to improve the timeliness of diagnosis. It is essential that, during their training process, all health professionals acquire knowledge about this disease, which is becoming more and more visible every day due to its sequelae and late diagnosis.

Development and characterization of InDel markers for Lupinus luteus L. (Fabaceae) and cross-species amplification in other Lupin species

Background: Strong artificial selection and/or natural bottle necks may limit genetic variation in domesticated species. Lupinus luteus, an orphan temperate crop, has suffered diversity reductions during its bitter/sweet alkaloid domestication history, limiting breeding efforts and making molecular marker development a difficult task. The main goal of this research was to generate new polymorphic insertion­deletion (InDel) markers to aid yellow lupin genetics and breeding. By combining genomic reduction libraries and next generation sequencing, several polymorphic InDel markers were developed for L. luteus L. Results: A total of 118 InDel in silico polymorphic markers were identified. Eighteen InDel primer sets were evaluated in a diverse L. luteus core collection, where amplified between 2­3 alleles per locus. Observed heterozygosity (HO; 0.0648 to 0.5564) and polymorphic information content (PIC; 0.06 to 0.48) estimations revealed a moderate level of genetic variation across L. luteus accessions. In addition, ten and nine InDel loci amplified successfully Lupinus hispanicus Boiss & Reut, and Lupinus mutabilis Sweet, respectively, two L. luteus close relatives. PCA analysis identified two L. luteus clusters, most likely explained by the domestication species history. Conclusion: The development of InDel markers will facilitate the study of genetic diversity across L. luteus populations, as well as among closely related species.

Tuberculosis por Mycobacterium bovis en trabajadores de fincas en saneamiento para tuberculosis bovina, de Antioquia, Boyacá y Cundinamarca / Tuberculosis caused by Mycobacterium bovis in workers of bovine tuberculosis sanitation farms in Antioquia, Boyacá and Cundinamarca

RESUMEN Objetivo Realizar la vigilancia epidemiológica clásica y molecular de la tuberculosis (TB) humana causada por Mycobacterium bovis en manipuladores de la cadena de producción bovina en fincas con bovinos PPD positivos de los Departamentos de Antioquia, Boyacá y Cundinamarca en un periodo de un año. Métodos Se visitaron las fincas ganaderas, con bovinos o bufalinos PPD positivos de los departamentos de estudio según información del Programa Nacional de Tuberculosis bovina del ICA. Se recolectó la información socio-demográfica y a los factores de riesgo para adquirir TB asociados a la ocupación a través de una encuesta aplicada a todos los trabajadores de las fincas visitadas. Se recolectaron muestras de esputo luego de haber obtenido un consentimiento informado. Los esputos fueron sometidos a pruebas microbiológicas y moleculares para la identificación de los miembros del complejo M. tuberculosis. Resultados Se visitaron 33 fincas ganaderas y se recolectó información para 164 trabajadores de la cadena de producción bovina. Se identificaron como posibles factores de riesgo para el desarrollo de TB la permanencia en la finca PPD positiva por más de un año, desconocimiento de la enfermedad y presencia de posibles reservorios como perros y gatos. No se encontraron casos de TB por M. bovis ni por M. tuberculosis en los trabajadores de las fincas visitadas. Conclusión No se documentaron casos de la enfermedad por este agente zoonótico en los departamentos de Antioquia, Boyacá y Cundinamarca.(AU)

ABSTRACT Objective To perform classic and molecular epidemiological surveillance of human tuberculosis caused by Mycobacterium bovis in bovine supply chains at farms with PPD positive bovines in the departments of Antioquia, Boyacá and Cundinamarca during a one-year period. Methods Livestock farms with PPD positive bovines or buffalos were visited in the study departments according to information obtained in the "Programa Nacional de Tuberculosis bovina" (National program on bovine Tuberculosis) released by ICA (Colombian Agriculture and Livestock Institute). Data on socio-demographic information and tuberculosis risk factors associated to the occupation were collected through a survey applied to all workers at the visited farms. Sputum samples were obtained after informed consent. The sputa underwent microbiological and molecular testing to identify members of the M. tuberculosis complex. Results Thirty-three livestock farms were visited and information of 164 workers from the bovine supply chain was collected. Staying in a PPD positive farm for more than a year, ignorance about the disease and the presence of possible vectors, like dogs and cats, were identified as possible risk factors for developing tuberculosis. No cases of tuberculosis caused by M. bovis or M. tuberculosis in workers of the visited farms were found. Conclusion No cases of the disease caused by this zoonotic agent were documented in the departments of Antioquia, Boyacá and Cundinamarca.(AU)

[Skin reaction to carbamazepine or DRESS syndrome: a case presentation]. / Reacción cutánea al tratamiento con carbamazepina o síndrome DRESS: presentación de un caso.

Carbamazepine is a frequently used drug that can produce adverse reactions like vertigo, somnolence and severe skin reactions like Drug Rash with Eosinophilia and Systemic Symptoms Syndrome (DRESS Syndrome). This syndrome is characterized by a late-appearing, slow-progressing cutaneous eruption accompanied by atypical lymphocytes, eosinophilia, and systemic symptoms such as fever, lymphadenopathy, hepatic compromise, and renal dysfunction that can be severe enough to cause death. We present a case that aims to highlight the importance of an early diagnosis of DRESS syndrome to adjust therapy and improve survival. The patient is a female patient prescribed carbamazepine for trigeminal neuralgia who presented with skin lesions, which were initially attributed to a hypersensitivity reaction. The lesions worsened in spite of treatment and systemic symptoms ensued. A diagnosis of DRESS syndrome was proposed and steroid treatment was initiated with rapid improvement.

La carbamazepina es un medicamento de empleo habitual que puede producir efectos secundarios y en algunos casos reacciones adversas como vértigos, somnolencia y reacciones cutáneas que pueden ser severas como el síndrome DRESS (Drug Rash with Eosinophilia and Systemic Symptoms). Se caracteriza por erupción cutánea tardía y lenta progresión, linfocitos atípicos con eosinofilia y síntomas sistémicos como fiebre, adenopatías, hepatopatía y trastornos renales, pudiendo llegar a la muerte del paciente. Se presenta un caso para destacar la importancia del diagnóstico temprano del síndrome DRESS, que garantice un manejo adecuado para la supervivencia del paciente. Es una paciente bajo tratamiento con carbamazepina para neuralgia del trigémino, que al tiempo comienza con lesiones cutáneas que se interpretan como reacción de hipersensibilidad. Al no mejorar con tratamiento inicial y empeorar el cuadro cutáneo, acompañándose de síntomas generales, se realizan análisis complementarios y se plantea el diagnóstico de síndrome DRESS que se resuelve definitivamente con esteroides.

[Tuberculosis caused by Mycobacterium bovis in workers of bovine tuberculosis sanitation farms in Antioquia, Boyacá and Cundinamarca]. / Tuberculosis por Mycobacterium bovis en trabajadores de fincas en saneamiento para tuberculosis bovina, de Antioquia, Boyacá y Cundinamarca.

OBJECTIVE: To perform classic and molecular epidemiological surveillance of human tuberculosis caused by Mycobacterium bovis in bovine supply chains at farms with PPD positive bovines in the departments of Antioquia, Boyacá and Cundinamarca during a one-year period. METHODS: Livestock farms with PPD positive bovines or buffalos were visited in the study departments according to information obtained in the "Programa Nacional de Tuberculosis bovina" (National program on bovine Tuberculosis) released by ICA (Colombian Agriculture and Livestock Institute). Data on socio-demographic information and tuberculosis risk factors associated to the occupation were collected through a survey applied to all workers at the visited farms. Sputum samples were obtained after informed consent. The sputa underwent microbiological and molecular testing to identify members of the M. tuberculosis complex. RESULTS: Thirty-three livestock farms were visited and information of 164 workers from the bovine supply chain was collected. Staying in a PPD positive farm for more than a year, ignorance about the disease and the presence of possible vectors, like dogs and cats, were identified as possible risk factors for developing tuberculosis. No cases of tuberculosis caused by M. bovis or M. tuberculosis in workers of the visited farms were found. CONCLUSION: No cases of the disease caused by this zoonotic agent were documented in the departments of Antioquia, Boyacá and Cundinamarca.