Optimization of Orally Bioavailable Antileishmanial 2,4,5-Trisubstituted Benzamides.

Leishmaniasis, a neglected tropical disease caused by Leishmania species parasites, annually affects over 1 million individuals worldwide. Treatment options for leishmaniasis are limited due to high cost, severe adverse effects, poor efficacy, difficulty of use, and emerging drug resistance to all approved therapies. We discovered 2,4,5-trisubstituted benzamides (4) that possess potent antileishmanial activity but poor aqueous solubility. Herein, we disclose our optimization of the physicochemical and metabolic properties of 2,4,5-trisubstituted benzamide that retains potency. Extensive structure-activity and structure-property relationship studies allowed selection of early leads with suitable potency, microsomal stability, and improved solubility for progression. Early lead 79 exhibited an 80% oral bioavailability and potently blocked proliferation of Leishmania in murine models. These benzamide early leads are suitable for development as orally available antileishmanial drugs.

Population-specific facial traits and diagnosis accuracy of genetic and rare diseases in an admixed Colombian population.

Up to 40% of rare disorders (RD) present facial dysmorphologies, and visual assessment is commonly used for clinical diagnosis. Quantitative approaches are more objective, but mostly rely on European descent populations, disregarding diverse population ancestry. Here, we assessed the facial phenotypes of Down (DS), Morquio (MS), Noonan (NS) and Neurofibromatosis type 1 (NF1) syndromes in a Latino-American population, recording the coordinates of 18 landmarks in 2D images from 79 controls and 51 patients. We quantified facial differences using Euclidean Distance Matrix Analysis, and assessed the diagnostic accuracy of Face2Gene, an automatic deep-learning algorithm. Individuals diagnosed with DS and MS presented severe phenotypes, with 58.2% and 65.4% of significantly different facial traits. The phenotype was milder in NS (47.7%) and non-significant in NF1 (11.4%). Each syndrome presented a characteristic dysmorphology pattern, supporting the diagnostic potential of facial biomarkers. However, population-specific traits were detected in the Colombian population. Diagnostic accuracy was 100% in DS, moderate in NS (66.7%) but lower in comparison to a European population (100%), and below 10% in MS and NF1. Moreover, admixed individuals showed lower facial gestalt similarities. Our results underscore that incorporating populations with Amerindian, African and European ancestry is crucial to improve diagnostic methods of rare disorders.

Papel de la plasticidad celular en la regeneración intestinalinducida por lesiones / Role of cell plasticity in injury-induced intestinal regeneration

El sistema intestinal posee una capacidad regenerativa intrínseca y fisiológica que tiene lugar a partir de las células madreLgr5+ ubicadas en el fondo de las criptas intestinales, las cuales se diferencian hacia las células progenitoras secretoras y absortivas con sus respectivas células especializadas mediante la activación de señalizaciones intracelulares como Wnt, Hippo y Notch. Condiciones adversas como lesiones e infecciones tisulares inducen esta actividad regenerativa promovida por variados mecanismos que influyen en el microambiente celular. El sistema inmunológico detecta alteraciones en el tejido intestinal y, a través de la activación de células inmunocompetentes y la secreción de citoquinas proinflamatorias, favorece la desdiferenciación de células especializadas hacia células madre para desencadenar la respuesta regenerativa. En cuanto al sistema nervioso entérico, su influencia está sujeta a modificaciones en la microbiota y los hábitos alimenticios, y se encuentra determinada en gran parte, por las células gliales entéricas y la expresión de distintos marcadores de plasticidad, que permiten limitar la lesión y reparar el tejido. Por su parte, la epigenéticamodifica la expresión genética y consecuentemente, la capacidadregenerativa intestinal, variando de acuerdo a cada paciente porla influencia de factores externos como la dieta o el estadopsicobiológico. De esta forma, la respuesta regenerativa intestinalinducida por lesiones, integra múltiples mecanismos y poseeimportantes repercusiones clínicas en cuanto a EII, disbiosise incluso tumorogénesis; conocer los mecanismos que regulanesta actividad puede sentar las bases para la creación de terapias innovadoras en el mismo ámbito(AU)

The intestinal system has an intrinsic and physiological regenerative capacity that takes place from the Lgr5+ stem cells located at the bottom of the intestinal crypts, which differentiate into secretory and absorptive progenitor cells with their specialized cells by activating intracellular signalslike Wnt, Hippo and Notch. Adverse conditions such asinjuries and tissue infections induce this regenerative activity promoted by various mechanisms that influence the cellular microenvironment. The immune system senses disturbances in the intestinal tissue and, through the activation of immunocompetent cells and the secretion of proinflammatorycytokines, favors the dedifferentiation of specialized cells intostem cells to trigger the regenerative response. Regarding theenteric nervous system, its influence is subject to modificationsin the microbiota and dietary habits, and is largely determinedby enteric glial cells and the expression of different plasticitymarkers, which enable to limit injuries and repair tissue. On the other hand, epigenetics modifies genetic expressionand, consequently, intestinal regenerative capacity, varying according to each patient due to the influence of external factors such as diet or psychobiological status. There fore, the intestinal regenerative response induced by lesions integrates multiple mechanisms and has important clinical repercussions in terms of IBD, dysbiosis, and even tumorigenesis; knowing themechanisms that regulate this activity can lay the foundations for the creation of innovative therapies in the same field (AU)

Intervention Research to Increase Pediatric Hearing Device Use: A Scoping Review.

PURPOSE: This study is a scoping review examining interventions to increase hearing device use for children. METHOD: Online databases were used to identify peer-reviewed journal articles published prior to November 1, 2021, yielding 1,288 after duplications were removed. Four articles met the inclusion criteria after articles were screened by title name and abstract and subsequent full-text screening of six articles. A qualitative analysis was conducted to identify features of the intervention studies related to the participants, design, intervention, key findings, and limitations. RESULTS: The included studies were published between 1982 and 2021, and in all four studies, the children used hearing aids. All four of the studies used a longitudinal design to address hearing aid use problems, with the timeframe ranging from approximately 1 month to 6 months and had variable success in increasing use time. None of the studies included a protocol, such as counseling skills, for addressing internal challenges that interfere with hearing aid use. CONCLUSIONS: Review of the limited research in this area found variable effectiveness for the interventions studied. There is an urgent need for research in this area to inform clinical practice and provide evidence-based interventions to address malleable factors that interfere with audibility for children who use hearing devices.

Viruela símica: revisión bibliográfica / Monkeypox: Bibliographic Review

La viruela símica es una enfermedad que ocurre en los monos, sin embargo también se han presentado casos en humanos desde 1970, transformándose en una zoonosis de origen viral, la sintomatología es similar a la viruela pero menos grave. Objetivo: Proporcionar información actualizada sobre la viruela símica, situación epidemiológica, sintomatología, letalidad, diagnóstico, tratamiento y medidas de prevención Materiales y métodos: Se realizó una búsqueda de literatura científica en las bases de datos Organización Mundial de la Salud, Google Académico y PubMed, se eligieron los descriptores o palabras relacionadas con la enfermedad y se realizó la búsqueda para la descripción de reportes de casos y brotes producidas por la viruela símica. Resultados: Desde que se reportó el primer caso en humanos, han existido brotes en el continente africano, fuera de éste, se han reportados varios casos y brotes en otros países, la mayoría en los Estados Unidos. El último evento se reporta en mayo de 2022 y es de preocupación mundial, debido a la aparición en varios países no endémicos. Conclusiones: La presencia de casos de viruela símica en humanos se ha mantenido desde su aparición, la ausencia de un tratamiento específico y vacunas autorizadas para su administración, podrían generar un aumento en la morbimortalidad(AU)

Monkeypox is a disease that occurs in monkeys, however there have also been cases in humans since 1970, becoming a zoonosis of viral origin, the symptoms are similar to smallpox but less severe. Objective: To provide updated information on monkeypox, epidemiological situation, symptomatology, lethality, diagnosis, treatment and prevention measures. Materials and methods: A search of scientific literature was carried out in the World Health Organization, Google Scholar and PubMed databases. , the descriptors or words related to the disease were chosen and the search was performed for the description of case reports and outbreaks caused by monkeypox. Results: Since the first human case was reported, there have been outbreaks on the African continent, outside of Africa, several cases and outbreaks have been reported in other countries, most in the United States. The last event is reported in May 2022 and is of global concern, due to the appearance in several non-endemic countries. Conclusions: The presence of cases of monkeypox in humans has been maintained since its appearance, the absence of a specific treatment and vaccines authorized for its administration, could generate an increase in morbidity and mortality(AU)

The stem rust effector protein AvrSr50 escapes Sr50 recognition by a substitution in a single surface-exposed residue.

Pathogen effectors are crucial players during plant colonisation and infection. Plant resistance mostly relies on effector recognition to activate defence responses. Understanding how effector proteins escape from plant surveillance is important for plant breeding and resistance deployment. Here we examined the role of genetic diversity of the stem rust (Puccinia graminis f. sp. tritici (Pgt)) AvrSr50 gene in determining recognition by the corresponding wheat Sr50 resistance gene. We solved the crystal structure of a natural variant of AvrSr50 and used site-directed mutagenesis and transient expression assays to dissect the molecular mechanisms explaining gain of virulence. We report that AvrSr50 can escape recognition by Sr50 through different mechanisms including DNA insertion, stop codon loss or by amino-acid variation involving a single substitution of the AvrSr50 surface-exposed residue Q121. We also report structural homology of AvrSr50 to cupin superfamily members and carbohydrate-binding modules indicating a potential role in binding sugar moieties. This study identifies key polymorphic sites present in AvrSr50 alleles from natural stem rust populations that play important roles to escape from Sr50 recognition. This constitutes an important step to better understand Pgt effector evolution and to monitor AvrSr50 variants in natural rust populations.

The burden of the most common rheumatic disease in Colombia.

BACKGROUND: Estimating the burden of rheumatic diseases (RDs) requires proper evaluation of its lethal and nonlethal consequences. In Colombia, it is possible to find local data and Global Burden of Disease (GBD) reports that collect information from varied contexts and apply complex statistical models, but no on-site estimations are available. METHODS: This was a descriptive study on the burden of RD based on occurrence and mortality data in the general population during 2015, including information and prevalence estimations from the Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) study. Disability-adjusted life years (DALYs) were estimated by combining measures of years of life lost (YLL) and years lived with disability (YLDs). For disability weight estimations among cases, different COPCORD responses were mapped using flowcharts to show the severity distribution according to GBD. All model parameters and results were validated through an expert consensus panel. RESULTS: Low back pain (LBP) was the RD with the greatest burden of disease, costing 606.05 (95% CI 502.76-716.58) DALYs per 100,000 inhabitants, followed by osteoarthritis (292.11; 95% CI 205.76-386.85) and rheumatoid arthritis (192.46, 95% CI 109.7-239.69). CONCLUSIONS: The burden of RD is as high in Colombia as in other countries of the region. The results offer an interesting tool for optimizing healthcare system design as well as for planning the distribution of human and economic resources to achieve early diagnosis and adequate care of these diseases.

Amino-Substituted 3-Aryl- and 3-Heteroarylquinolines as Potential Antileishmanial Agents.

Leishmaniasis, a disease caused by protozoa of the Leishmania species, afflicts roughly 12 million individuals worldwide. Most existing drugs for leishmaniasis are toxic, expensive, difficult to administer, and subject to drug resistance. We report a new class of antileishmanial leads, the 3-arylquinolines, that potently block proliferation of the intramacrophage amastigote form of Leishmania parasites with good selectivity relative to the host macrophages. Early lead 34 was rapidly acting and possessed good potency against L. mexicana (EC50 = 120 nM), 30-fold selectivity for the parasite relative to the macrophage (EC50 = 3.7 µM), and also blocked proliferation of Leishmania donovani parasites resistant to antimonial drugs. Finally, another early lead, 27, which exhibited reasonable in vivo tolerability, impaired disease progression during the dosing period in a murine model of cutaneous leishmaniasis. These results suggest that the arylquinolines provide a fruitful departure point for the development of new antileishmanial drugs.

Genomics accelerated isolation of a new stem rust avirulence gene-wheat resistance gene pair.

Stem rust caused by the fungus Puccinia graminis f. sp. tritici (Pgt) is a devastating disease of the global staple crop wheat. Although this disease was largely controlled in the latter half of the twentieth century, new virulent strains of Pgt, such as Ug99, have recently evolved1,2. These strains have caused notable losses worldwide and their continued spread threatens global wheat production. Breeding for disease resistance provides the most cost-effective control of wheat rust diseases3. A number of rust resistance genes have been characterized in wheat and most encode immune receptors of the nucleotide-binding leucine-rich repeat (NLR) class4, which recognize pathogen effector proteins known as avirulence (Avr) proteins5. However, only two Avr genes have been identified in Pgt so far, AvrSr35 and AvrSr50 (refs. 6,7), and none in other cereal rusts8,9. The Sr27 resistance gene was first identified in a wheat line carrying an introgression of the 3R chromosome from Imperial rye10. Although not deployed widely in wheat, Sr27 is widespread in the artificial crop species Triticosecale (triticale), which is a wheat-rye hybrid and is a host for Pgt11,12. Sr27 is effective against Ug99 (ref. 13) and other recent Pgt strains14,15. Here, we identify both the Sr27 gene in wheat and the corresponding AvrSr27 gene in Pgt and show that virulence to Sr27 can arise experimentally and in the field through deletion mutations, copy number variation and expression level polymorphisms at the AvrSr27 locus.

Host-Feeding Patterns of the Mosquito Assemblage at Lomas Barbudal Biological Reserve, Guanacaste, Costa Rica.

Mosquito-borne pathogens have spread throughout tropical regions of the Western Hemisphere causing increased burden of disease in the region. Outbreaks of dengue fever, yellow fever, chikungunya, West Nile, and Zika have occurred over the past several years. Mosquito blood-feeding patterns need to be assayed to assist in determining which vertebrates could act as hosts of these mosquito-borne pathogens and which mosquito species could act as vectors. We conducted bloodmeal analyses of mosquitoes collected at Lomas Barbudal Biological Reserve, a dry tropical forest reserve in Costa Rica. Mosquitoes were collected using backpack aspirators and light, gravid, and resting traps, and then identified morphologically. Blood-fed mosquitoes underwent DNA extraction, PCR amplification, and sequencing of the vertebrate cytochrome b and cytochrome c oxidase 1 genes to identify vertebrate bloodmeal hosts. Several mosquitoes known to vector pathogens were found including Culex (Melanoconion) erraticus Dyar & Knab (Diptera: Culicidae), Cx. (Mel.) pedroi Sirivanakarn & Belkin, Aedes (Stegomyia) albopictus Skuse, Ae. (Ochlerotatus) scapularis Rondani, Ae. (Och.) serratus Theobald, and Ae. (Och.) taeniorhynchus Wiedemann. The most common bloodmeal hosts were basilisk lizards (Basiliscus vittatus) Wiegmann (Squamata: Corytophanidae) in Culex (Linnaeus) species and white-tailed deer (Odocoileus virginianus) Zimmermann (Artiodactyla: Cervidae) in Aedes (Meigen) species. These results show the diversity of mosquito species in a tropical dry deciduous forest and identify associations between mosquito vectors and potential pathogen reservoir hosts. Our study highlights the importance of understanding interactions between vector species and their hosts that could serve as predictors for the potential emergence or resurgence of mosquito-borne pathogens in Costa Rica.

Tactics of host manipulation by intracellular effectors from plant pathogenic fungi.

Fungal pathogens can secrete hundreds of effectors, some of which are known to promote host susceptibility. This biological complexity, together with the lack of genetic tools in some fungi, presents a substantial challenge to develop a broad picture of the mechanisms these pathogens use for host manipulation. Nevertheless, recent advances in understanding individual effector functions are beginning to flesh out our view of fungal pathogenesis. This review discusses some of the latest findings that illustrate how effectors from diverse species use similar strategies to modulate plant physiology to their advantage. We also summarize recent breakthroughs in the identification of effectors from challenging systems, like obligate biotrophs, and emerging concepts such as the 'iceberg model' to explain how the activation of plant immunity can be turned off by effectors with suppressive activity.

Uso de medicina complementaria y alternativa y su asociación con la relación médico-paciente en enfermos con artritis reumatoide / Association between physician-patient relationship and the use of complementary and alternative medicine in patients with rheumatoid arthritis

RESUMEN Introducción: El uso de medicina complementaria y alternativa (MCA) en pacientes con enfermedades reumáticas es prevalente pero la comunicación con el reumatólogo suele ser deficiente, lo cual afecta la relación médico-paciente (RMP). Objetivos: Evaluar la asociación entre el uso de MCA y la RMP en enfermos con artritis reumatoide. Como objetivos adicionales, describir la percepción del paciente sobre la comunicación con su reumatólogo respecto al uso de MCA y el patrón de uso de las diferentes modalidades terapéuticas. Materiales y métodos: Estudio descriptivo de corte transversal. El uso de MCA y la RMP se evaluaron mediante la autoaplicación de cuestionarios validados (I-CAM-Q y PDRQ-9 respectivamente). Resultados: Se incluyó a 246 pacientes ambulatorios de una institución de tercer nivel de atención. Se encontró asociación entre una mayor satisfacción con el tratamiento y el no usar MCA, y entre el hecho de informar al reumatólogo sobre el uso de MCA con un mayor grado de acuerdo con el médico sobre el origen de los síntomas y mayor satisfacción con el tratamiento. Las modalidades más frecuentemente utilizadas fueron: quiropraxia, acupuntura y productos herbales. El 78,5% afirmaron estar de acuerdo con comunicar el uso de este tipo de medicación al reumatólogo, sin embargo, solo el 31,3% lo notificó, por temor a represalias (54,4%). Conclusiones: Pese a la alta prevalencia de uso de MCA en nuestros pacientes, la mayoría no lo comunicó al reumatólogo. Se encontró asociación entre el uso de MCA y una menor satisfacción del paciente con el tratamiento y entre la comunicación médico-paciente sobre la práctica de MCA y una mejor satisfacción con el tratamiento.

ABSTRACT Introduction: Although complementary and alternative medicine (CAM) use among patients with rheumatic diseases is extensive, discussions regarding these treatments occur rarely in the rheumatology setting, directly affecting the physician-patient relationship (PPR). Objectives: The aim of this study was to evaluate the association between patient-physician relationship and complementary and alternative medicine use. As secondary objectives, to describe the patient's perspective towards CAM use and estimate the prevalence of CAM treatments used in patients with rheumatoid arthritis. Methods and materials: A descriptive cross-sectional survey was conducted, in which CAM use and physician-patient relationship were assessed by self-reported validated questionnaires (I-CAM-Q and PDRQ-9, respectively). Results: The study included a total of 246 outpatients of a tertiary care hospital. There were no significant differences between CAM users vs. non-users, or informers vs. non-informers in terms of physician-patient relationship measured by PDQR. The most frequent used CAM treatments were: chiropractice, acupuncture, and herbal products. A large majority (78.5%) of the patients expressed agreement to the discussion of CAM use with the rheumatologist, but only 31.3% of total CAM users did so because of fear of retaliation (54.4%). Conclusion: Despite the extensive practice of CAM among patients with rheumatoid arthritis, most patients did not discuss these treatments with their physicians. Associations were found between MCA use and a lower patient's treatment satisfaction and between physician-patient communication about CAM practice and a higher patient's treatment satisfaction.

A five-transgene cassette confers broad-spectrum resistance to a fungal rust pathogen in wheat.

Breeding wheat with durable resistance to the fungal pathogen Puccinia graminis f. sp. tritici (Pgt), a major threat to cereal production, is challenging due to the rapid evolution of pathogen virulence. Increased durability and broad-spectrum resistance can be achieved by introducing more than one resistance gene, but combining numerous unlinked genes by breeding is laborious. Here we generate polygenic Pgt resistance by introducing a transgene cassette of five resistance genes into bread wheat as a single locus and show that at least four of the five genes are functional. These wheat lines are resistant to aggressive and highly virulent Pgt isolates from around the world and show very high levels of resistance in the field. The simple monogenic inheritance of this multigene locus greatly simplifies its use in breeding. However, a new Pgt isolate with virulence to several genes at this locus suggests gene stacks will need strategic deployment to maintain their effectiveness.

The Impact of Deforestation, Urbanization, and Changing Land Use Patterns on the Ecology of Mosquito and Tick-Borne Diseases in Central America.

Central America is a unique geographical region that connects North and South America, enclosed by the Caribbean Sea to the East, and the Pacific Ocean to the West. This region, encompassing Belize, Costa Rica, Guatemala, El Salvador, Honduras, Panama, and Nicaragua, is highly vulnerable to the emergence or resurgence of mosquito-borne and tick-borne diseases due to a combination of key ecological and socioeconomic determinants acting together, often in a synergistic fashion. Of particular interest are the effects of land use changes, such as deforestation-driven urbanization and forest degradation, on the incidence and prevalence of these diseases, which are not well understood. In recent years, parts of Central America have experienced social and economic improvements; however, the region still faces major challenges in developing effective strategies and significant investments in public health infrastructure to prevent and control these diseases. In this article, we review the current knowledge and potential impacts of deforestation, urbanization, and other land use changes on mosquito-borne and tick-borne disease transmission in Central America and how these anthropogenic drivers could affect the risk for disease emergence and resurgence in the region. These issues are addressed in the context of other interconnected environmental and social challenges.

Mesenchymal stromal cells represent a therapeutic option for systemic sclerosis patients / Células estromales mesenquimales representan una opción terapéutica en pacientes con esclerosis sistémica

ABSTRACT The mesenchymal stromal cells (MSCs) are hematopoietic stem cells with high capacity of differentiation to other cellular lineages, depending on the microenvironment in which they live as well as on the interaction and signaling pathways they establish with the extracellular matrix. Several properties have been described in these cells: proangiogenic, antifibrotic and immunomodulatory. These properties are being studied as a therapeutic approach for autoimmune diseases such as cutaneous systemic sclerosis (SSc). SSc is a systemic chronic disease, with an approximate prevalence of 35.6 cases per 100,000 inhabitants in North America and of 0.02% in Colombia in 2018. There are two different clinical variants, diffuse and localized. In both variants an important skin involvement and a rapidly deterioration of organs is present, which can overshadow the clinical prognosis and increase the mortality. Options for the treatment of advanced diffuse SSc are scarce mainly targeting symptomatic control with little impact on the progression and mortality. Therefore, there is an increasing interest in new therapies like advanced cellular therapy with hematopoietic stem cells and stromal mesenchymal cells. This article reviews the information related to the use of stromal mesenchymal cells in patients with this disease.

RESUMEN Las células mesenquimales estromales son células madre no hematopoyéticas pluripotenciales con alta capacidad de derivación a diferentes linajes celulares, dependiendo tanto del microambiente en el que se encuentren, como de la interacción y señalización que establezcan con la matriz extracelular del entorno, esto ha permitido describir un potencial proangiogénico, antifibrótico e inmunomodulador, que ha sido blanco de investigación en enfermedades autoinmunes como la esclerosis sistêmica cutánea. Considerando que la esclerosis sistêmica cutánea es una enfermedad inflamatoria crónica, con una prevalencia estimada de 35,6 casos por cada 100.000 habitantes en Norte América y de 0,02% en nuestro país para el 2018, se caracteriza por presentar dos variables clínicas principalmente; una variante limitada y una variante difusa, presentando en ambas un compromiso extenso de piel y órganos que puede ser rápidamente progresivo y deteriorar el pronóstico de los pacientes que la padecen aumentando su mortalidad. Debido a que las opciones terapéuticas en esta entidad son limitadas y buscan únicamente el control de síntomas, pero con poco impacto en progresión y mortalidad, terapias celulares avanzadas han surgido como nuevas opciones terapéuticas incluyendo el trasplante de células madre hematopoyéticas y las células mesenquimales estromales. A continuación, se revisará acerca de la utilidad y evidencia de células mesenquimales estromales en pacientes con esta enfermedad.

Comparison of quality of life in patients with musculoskeletal symptoms, those with other comorbidities, and healthy people, in a Colombian open population study / Comparación de la calidad de vida de pacientes con síntomas musculoesqueléticos, comorbilidades asociadas y personas sanas en un estudio abierto de población colombiano

A b s t r a c t Purpose: To describe health-related QOL (HRQOL) in patients with musculoskeletal symptoms, compared to a population with other comorbidities, and a healthy population. Methods: A cross-sectional study was carried out on an open population involved in a community-oriented program for control of rheumatic diseases (COPCORD) study in Colombia, using EQ-5D-3L for estimating QOL, and the health assessment questionnaire disability index (HAQ-DI) for functional capacity. Results: Out of the total 4020 individuals evaluated, 2274 had rheumatic diseases, 642 had non-rheumatic diseases, and 1104 were healthy subjects. Spondyloarthritis (SpA) and rheumatoid arthritis (RA) patients had more complaints regarding pain/discomfort and mobility. As for daily activities, the diseases that mostly affected them were systemic lupus erythematosus (SLE) and RA. RA and fibromyalgia (FM) patients had the worst scores as regards anxiety/depression and self-care dimensions. FM patients had the lowest QOL measured by EQ-VAS (57.7 ± 26.2). The most frequent non-rheumatic diseases were cardiovascular and mental disorders, with 20% of these patients having a moderate level of pain/discomfort and anxiety/depression. The rheumatic patients reported a decrease in functional capacity (HAQ: 0.49), in contrast to the healthy population (0.01), and the population having other diseases (0.06). Conclusion: Rheumatic disease patients in Colombia had the worst QOL compared to the healthy population and patients with other comorbidities. Rheumatic patients had greater functional limitations, even more so when having comorbidities. This study revealed potential factors of interest requiring the attention of public health authorities, and for improving patients' QOL.

RESUMEN Objetivo: Describir la calidad de vida relacionada con la salud en pacientes con síntomas musculoesqueléticos, en comparación con pacientes con enfermedades no reumáticas y una población sana. Métodos: Se realizó un estudio transversal en comunidad abierta, en personas involucradas en un programa orientado a la comunidad para el control de enfermedades reumáticas (COP-CORD) en Colombia, utilizando el EQ-5D-3L para estimar la calidad de vida y el cuestionario de evaluación de la salud (HAQ- DI) para la capacidad funcional. Resultados: Se evaluaron 4.020 individuos; 2.274 tenían enfermedades reumáticas, 642 tenían enfermedades no reumáticas y 1.104 eran sujetos sanos. Los pacientes con espondiloartritis (SpA) y artritis reumatoide (AR) tuvieron mayores quejas con respecto al dolor/malestar y la movilidad. En cuanto a las actividades diarias, los enfermos con lupus eritematoso sistémico (LES) y AR fueron los más afectados. Los pacientes con AR y fibromialgia (FM) tuvieron las peores puntuaciones en ansiedad/depresión en las dimensiones de cuidado personal. Los pacientes con FM tuvieron la calidad de vida más baja medida por EQ-VAS (57,7 ± 26,2). Las enfermedades no reumáticas más frecuentes fueron los trastornos cardiovasculares y mentales; el 20% de estos pacientes tenía un nivel moderado de dolor/malestar y ansiedad/depresión. Los pacientes reumáticos reportaron una disminución de la capacidad funcional (HAQ: 0,49); en contraste con la población sana (0,01) y la población con otras enfermedades (0,06). Conclusión: Los pacientes con enfermedades reumáticas en Colombia tuvieron la peor calidad de vida en comparación con la población sana y los pacientes con otras enfermedades. Los pacientes reumáticos tuvieron una mayor limitación funcional, incluso más que los que tenían otras enfermedades. Este estudio reveló posibles factores relacionados con las enfermedades reumáticas que requieren la atención de las autoridades de salud pública con el objetivo de mejorar la calidad de vida de los pacientes.

Carcinoma de pulmón como disparador de una respuesta autoinmune: un desafío médico / Lung cancer acting as a trigger of autoimmunity: a medical challenge

RESUMEN Existe una relación compleja, dinámica y bidireccional entre la autoinmunidad y el cáncer. Si bien los mecanismos carcinogénicos y fisiopatológicos de las enfermedades autoinmunes no están claramente dilucidados, existe una base inmunológica común relacionada con la expresión de autoantígenos por parte de las células tumorales que desencadenan una respuesta antitumoral, facilitando el desarrollo de síndromes paraneoplásicos reumáticos y enfermedades autoinmunes reumáticas en población genéticamente susceptible. Se presenta un caso de un hombre que debutó con un síndrome pulmón riñón y se diagnosticó cáncer de pulmón y lupus eritematoso sistémico de forma simultánea.

A B S T R A C T There is a complex, dynamic, and bidirectional connection between autoimmunity and cancer. The underlying mechanisms of carcinogenesis and physiopathological aspects of autoimmune diseases are not fully understood. However, there is a common immunological base related to expression of autoantigens by tumour cells that cause an anti-cancer immune response, thereby, triggering the development of paraneoplastic rheumatic syndromes and autoimmune rheumatic diseases in a genetically predisposed population. The case is reported of a 57 year-old man presenting with pulmonary renal syndrome, and who was diagnosed lung cancer and systemic lupus erythematosus at the same time.

Association of significant risk perception with the use of complementary and alternative medicine: A cross-sectional study in Hispanic patients with rheumatoid arthritis.

BACKGROUND: Risk perception (RP) describes patient´s judgment of the likelihood of experiencing something unpleasant, and has been associated to the adoption of health behaviors. Current rheumatoid arthritis (RA) guidelines recommend early and intensive treatment, although patients also commonly use Complementary and Alternative Medicine (CAM). We aimed to investigate if significant RP was associated to CAM use in Hispanic RA outpatients and to describe additional associated factors. METHODS: Between March and August 2019, 266 consecutive outpatients were invited to a face-to-face interview to collect socio-demographic and RA-related information, to assess comorbidity and the following patient-reported-outcomes: pain, overall-disease and treatment adherence with visual analogue scales, disease activity with RAPID-3, RP with a validated questionnaire, and CAM use with a translated and cross-culturally adapted for Argentina version of the International CAM questionnaire. Medical records were reviewed to corroborate the data provided by the patients. CAM use definition was restricted to "in the last 3 months". Significant RP was defined based on published cut-off. Multiple logistic regression analysis was used to investigate factors associated to CAM use. The study received IRB approval. RESULTS: There were 246 patients included, primarily middle-aged women, with substantial disease duration, moderate disease activity and 70 patients (28.5%) had significant RP. Two hundreds patients (81.3%) were CAM users. Significant RP (OR: 2.388, 95%CI: 1.044-5.464, p = 0.039) and access to Federal health care system (OR: 2.916, 95%CI: 1.081-7.866, p = 0.035) were associated to CAM use. CONCLUSIONS: Patient´s perception of RA-related negative consequences was associated to recent CAM use in Hispanic RA outpatients.

TLR expression in peripheral monocyte subsets of patients with idiopathic inflammatory myopathies: association with clinical and immunological features.

BACKGROUND: Monocytes and toll-like receptors (TLR) have been found in the inflammatory infiltrate of muscle biopsies in patients with idiopathic inflammatory myopathies (IIM), suggesting an important role of these cells in the pathogenesis of myositis. The monocyte subsets, their TLR expression in peripheral blood and their relationship with the clinical characteristics of patients with IIM has not been addressed. METHODS: We recruited 45 patients with IIM diagnosis and 15 age and sex-adjusted healthy controls. We assessed the disease activity and damage, performed a nailfold capillaroscopy and registered the cardio-pulmonary parameters from the medical charts. Monocyte subsets, their expression of TLR2 and TLR4 and the serum Th1/Th2/Th17 cytokines levels were evaluated by flow cytometry. We expressed quantitative variables as medians and interquartile ranges (IQR) or minimum and maximum (min-max). Differences between groups were assessed with Mann-Whitney U and the Kruskal-Wallis tests. Correlation between quantitative variables was assessed with Spearman Rho. RESULTS: Twenty-nine patients were women (64.4%) and 32 (71.1%) had dermatomyositis. In comparison to healthy controls, patients with active IIM had a higher percentage of intermediate monocytes and lower amounts of classical monocytes. Patients with IIM had a higher expression of TLR4 in all their monocyte subsets, regardless of disease activity and prednisone treatment. Serum IL-6 correlated with the TLR2 expression in every monocyte subset and the expression of TLR2 in intermediate monocytes was higher among patients with dysphagia. Subjects with nailfold capillaroscopy abnormalities had a higher amount of TLR2+ classical and non-classical monocytes and those with interstitial lung disease (ILD) had a higher percentage of TLR4+ non-classical monocytes. The classical and intermediate monocytes from patients with anti Mi2 antibodies had a higher expression of TLR4. The percentage of intermediate monocytes and the expression of TLR4 in all monocyte subsets showed a good diagnostic capacity in patients with IIM. CONCLUSION: Patients with IIM have a differential pool of monocyte subsets with an enhanced expression of TLR2 and TLR4, which correlates with disease activity and distinctive clinical features including dysphagia, ILD, vasculopathy, and pro-inflammatory cytokines. These immunological features might be useful as a potential diagnostic tool as well as novel disease activity biomarkers in IIM.