Semiquantitative analysis of cerebral [18F]FDG-PET uptake in pediatric patients.

BACKGROUND: Glycolytic metabolism in the brain of pediatric patients, imaged with [18F]  fluorodeoxyglucose-positron emission tomography (FDG-PET) is incompletely characterized. OBJECTIVE: The purpose of the current study was to characterize [18F]FDG-PET brain uptake in a large sample of pediatric patients with non-central nervous system diseases as an alternative to healthy subjects to evaluate changes at different pediatric ages. MATERIALS AND METHODS: Seven hundred ninety-five [18F]FDG-PET examinations from children < 18 years of age without central nervous system diseases were included. Each brain image was spatially normalized, and the standardized uptake value (SUV) was obtained. The SUV and the SUV relative to different pseudo-references were explored as a function of age. RESULTS: At all evaluated ages, the occipital lobe showed the highest [18F]FDG uptake (0.27 ± 0.04 SUV/year), while the parietal lobe and brainstem had the lowest uptake (0.17 ± 0.02 SUV/year, for both regions). An increase [18F]FDG uptake was found for all brain regions until 12 years old, while no significant uptake differences were found between ages 13 (SUV = 5.39) to 17 years old (SUV = 5.52) (P < 0.0001 for the whole brain). A sex dependence was found in the SUVmean for the whole brain during adolescence (SUV 5.04-5.25 for males, 5.68-5.74 for females, P = 0.0264). Asymmetries in [18F]FDG uptake were found in the temporal and central regions during infancy. CONCLUSIONS: Brain glycolytic metabolism of [18F]FDG, measured through the SUVmean, increased with age until early adolescence (< 13 years old), showing differences across brain regions. Age, sex, and brain region influence [18F]FDG uptake, with significant hemispheric asymmetries for temporal and central regions.

Hospital outcomes in patients evaluated by rheumatology in a Colombian historical cohort

Introduction: Hospitalized patients with systemic autoimmune rheumatic diseases (SARDs) generate high impact in clinical terms. Objectives: To characterize the study population and estimate risk factors associated with the presence of adverse outcomes in hospitalized patients consulting rheumatology at Clínica Imbanaco between January 2013 and December 2019. Methods: We analyzed a historical cohort of hospitalized patients who were evaluated by rheumatology. The population was classified as follows: group 1, patients with new onset diagnosed SARDs; group 2, patients with known diagnosed SARDs; group 3, patients without diagnosed SARDs; and group 4, patients with unconfirmed suspicion of SARDs. A composite adverse outcome was defined if at least one of the following occurred: (1) hospital mortality, (2) admission to the intensive care unit, (3) hospital infection, or (4) readmission. Results: Information was collected from 327 hospitalization events (307 patients). The median age was 48 (34-63) years and 222 (72.3%) were women. The composite adverse outcome occurred in 136 (41.5%) hospitalization events. Group 2 had the highest number of adverse outcomes (61/128; 47.6%). The variables associated with the worst outcomes were cardiovascular diagnosis at admission (OR = 4.63; CI: 1.60-13.43; p = 0.005), longer hospital stay (OR = 1.04; CI: 1.01-1.07; p = 0.005), and a treating specialty other than internal medicine (OR = 2.79; CI: 1.26-6.17; p = 0.011). Male sex (OR = 0.29; CI: 0.12-0.66; p = 0.004), having special health coverage (OR = 0.39; CI: 0.15-.099; p = 0.047), and hemoglobin > 11.4 g/dL (OR = 0.82; CI: 0.69-0.99; p = 0.039) were the factors associated with lower odds of developing the composite outcome. Conclusions: In this historical cohort, the group of patients with known diagnosed SARDs presented a higher number in percentage terms of adverse outcomes. The most frequent adverse outcomes were admission to the ICU and hospital readmission.

Introducción: Los pacientes hospitalizados con enfermedades reumáticas o autoinmunes sistémicas (ERAS) generan gran impacto en términos clínicos. Objetivos: Caracterizar a la población y estimar factores de riesgo asociados con la presencia de desenlaces adversos en pacientes evaluados hospitalariamente por reumatología en la Clínica Imbanaco durante los arios 2013-2019. Metodología: Se analizó una cohorte histórica de pacientes hospitalizados que fueron evaluados por reumatología. La población se clasificó así: grupo 1, pacientes con ERAS diagnosticada de novo; grupo 2, pacientes con ERAS diagnosticada conocida; grupo 3, pacientes sin ERAS diagnosticada; y grupo 4, pacientes con sospecha no confirmada de ERAS. Se definió un desenlace adverso compuesto si se presentó al menos uno de los siguientes casos: 1) mortalidad hospitalaria; 2) ingreso a la unidad de cuidado intensivo; 3) infección intrahospitalaria; 4) reingreso. Resultados: En un total de 327 eventos de hospitalización (307 pacientes), la mediana de edad fue 48 (34-63) años y 222 (72,3%) fueron mujeres. El desenlace adverso compuesto se presentó en 136 (41,5%) eventos. El grupo 2 tuvo mayor número de desenlaces adversos (61/128; 47,6%). Las variables asociadas con peores resultados fueron: diagnóstico inicial cardiovascular (OR = 4,63; IC: 1,60-13,43; p = 0,005), mayor estancia hospitalaria (OR = 1,04; IC: 1,01-1,07; p = 0,005) y tener una especialidad tratante diferente a medicina interna (OR = 2,79; IC: 1,266,17; p = 0,011). El sexo masculino (OR = 0,29; IC: 0,12-0,66; p = 0,004), pertenecer a un régimen especial de salud (OR = 0,39; IC: 0,15-0,99; p = 0,047) y tener hemoglobina > 11,4 g/dL (OR = 0,82; IC: 0,69-0,99; p = 0,039) fueron factores asociados con menor oportunidad de desarrollar el desenlace compuesto. Conclusiones: En esta cohorte histórica se encontró que porcentualmente el grupo de pacientes con ERAS diagnosticadas conocidas presentó mayor número de desenlaces adversos, entre los que se destacan para el mismo grupo, el ingreso a UCI y el reingreso hospitalario.

Effectiveness of Telemedicine Compared with Standard Care for Patients with Rheumatic Diseases: A Systematic Review.

Objective: The aim of this study was to systematically review the evidence on the effectiveness of telemedicine compared to standard care for patients with rheumatic diseases. Methods: A search was performed in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews; for the gray literature, GREYNET databases and a snowball search were used. MeSH or Emtree terms. Three authors independently selected systematic reviews, randomized controlled trail (RCTs), or non-RCTs with patients with autoimmune or inflammatory rheumatic diseases, where telemedicine was compared with standard care. Effectiveness was measured in terms of disease activity, quality of life, and functional activity. The patients' satisfaction was also measured. The risk of bias was assessed by the Cochrane collaboration tool for RCTs and AMSTAR II for systematic reviews. Results: Four RCTs, one cross-out study, and five systematic reviews were included. The studies were conducted with rheumatoid arthritis patients, and one study involved patients with systematic lupus erythematosus. The interventions mainly involved teleconsultation and telemonitoring, with patient-reported outcomes (PROs) being compared with standard care. Four studies measured the effectiveness of telemedicine using PROs, in which three of the RCTs did not find differences in the clinical outcomes, and one found that telemedicine improved the remission of diseases, functional impairment, and radiographic joint damage progression. Two studies measured patient satisfaction with telemedicine and standard care without a significant difference between the groups. Conclusions: Despite heterogeneity between studies, the findings were remarkably consistent in demonstrating that there was no significant difference between the telemedicine group and the control group in terms of PROs and patient satisfaction. Patients should be offered the option of telemedicine to manage their diseases as part of health-care support. Further research is needed on the effectiveness of telemedicine in the long term for patients with rheumatic diseases.

The repurposing of Tebipenem pivoxil as alternative therapy for severe gastrointestinal infections caused by extensively drug-resistant Shigella spp.

Background: Diarrhoea remains one of the leading causes of childhood mortality globally. Recent epidemiological studies conducted in low-middle income countries (LMICs) identified Shigella spp. as the first and second most predominant agent of dysentery and moderate diarrhoea, respectively. Antimicrobial therapy is often necessary for Shigella infections; however, we are reaching a crisis point with efficacious antimicrobials. The rapid emergence of resistance against existing antimicrobials in Shigella spp. poses a serious global health problem. Methods: Aiming to identify alternative antimicrobial chemicals with activity against antimicrobial resistant Shigella, we initiated a collaborative academia-industry drug discovery project, applying high-throughput phenotypic screening across broad chemical diversity and followed a lead compound through in vitro and in vivo characterisation. Results: We identified several known antimicrobial compound classes with antibacterial activity against Shigella. These compounds included the oral carbapenem Tebipenem, which was found to be highly potent against broadly susceptible Shigella and contemporary MDR variants for which we perform detailed pre-clinical testing. Additional in vitro screening demonstrated that Tebipenem had activity against a wide range of other non-Shigella enteric bacteria. Cognisant of the risk for the development of resistance against monotherapy, we identified synergistic behaviour of two different drug combinations incorporating Tebipenem. We found the orally bioavailable prodrug (Tebipenem pivoxil) had ideal pharmacokinetic properties for treating enteric pathogens and was effective in clearing the gut of infecting organisms when administered to Shigella-infected mice and gnotobiotic piglets. Conclusions: Our data highlight the emerging antimicrobial resistance crisis and shows that Tebipenem pivoxil (licenced for paediatric respiratory tract infections in Japan) should be accelerated into human trials and could be repurposed as an effective treatment for severe diarrhoea caused by MDR Shigella and other enteric pathogens in LMICs. Funding: Tres Cantos Open Lab Foundation (projects TC239 and TC246), the Bill and Melinda Gates Foundation (grant OPP1172483) and Wellcome (215515/Z/19/Z).

Atención integral y manejo del paciente con hemofilia en el contexto de la pandemia de COVID-19 / Comprehensive care and patient management with hemophilia, in the context of COVID-19 pandemic

Resumen El espectro clínico de la hemofilia severa ha evolucionado a lo largo de la historia desde una condición catastrófica y altamente fatal a principios del siglo xx, hasta un trastorno crónico y «manejable¼ en las últimas décadas, gracias a los notables avances en el tratamiento alcanzados en los últimos 40 años, avances impulsados y reforzados por algunas experiencias catastróficas pasadas, como lo fue el desastre biológico en la década de 1980 debido a infecciones virales fatales transmitidas por trasfusión, como hepatitis y virus de la inmunodeficiencia humana/sida, a partir de lo cual la aparición de nuevos agentes infecciosos son una preocupación constante para la comunidad de hemofilia, como lo es actualmente el caso al que nos enfrentamos con la pandemia de enfermedad por coronavirus 2019, que ha creado una situación extremadamente desafiante para los miembros de la comunidad mundial de trastornos hemorrágicos. Ante esta pandemia han surgido interrogantes sobre la posibilidad de si los pacientes con hemofilia tendrán mayor riesgo de infección y si la deficiencia de factor y su tratamiento podrían influir en las manifestaciones de la infección, su curso natural, tratamiento y complicaciones; aunado a la preocupación de que parece claro que la pandemia actual tendrá consecuencias definitivas sobre el manejo de la hemofilia en todo el mundo. Tales interrogantes han dado lugar a la revisión de la literatura, guías, consensos de expertos, incluyendo las recomendaciones de la Federación Mundial de Hemofilia, en un intento de responder a dichas interrogantes, generando así tanto pautas para la atención como ampliando algunas de ellas, impulsando el desarrollo de nuevos protocolos de investigación.

Abstract The clinical spectrum of severe hemophilia has evolved throughout history from a catastrophic and highly fatal condition in the early 20th century to a chronic and “manageable” disorder in recent decades, thanks to the remarkable advances in treatment achieved. in the last 40 years, advances driven and reinforced by some past catastrophic experiences, such as the biological disaster in the 1980s due to fatal viral infections transmitted by transfusion, such as hepatitis and HIV/AIDS, from which, the appearance of new infectious agents are an ongoing concern for the hemophilia community, as is currently the case facing us with the coronavirus disease 2019 pandemic, which has created an extremely challenging situation for members of the global bleeding disorders community. Faced with this pandemic, questions have arisen regarding the possibility of whether patients with hemophilia will have a higher risk of infection and whether factor deficiency and its treatment could influence the manifestations of the infection, its natural course, treatment and complications; coupled with the concern that it seems clear that the current pandemic will have definitive consequences on the management of hemophilia around the world. Such questions have led to a review of the literature, guidelines, and expert consensus, including the recommendations of the World Federation of Hemophilia, in an attempt to answer these questions, thus generating both guidelines for care, and expanding some of them, promoting the development of new research protocols.

Características clínico-radiológicas de la hiperostosis esquelética idiopática difusa en 2 centros médicos de Cali, Colombia: reporte de 24 casos / Clinical and radiological characteristics of diffuse idiopathic skeletal hyperostosis in two medical centers in Cali, Colombia: Report of 24 cases

RESUMEN Introducción: La hiperostosis esquelética idiopática difusa (DISH, por sus siglas en inglés) es una afección caracterizada por la calcificación y la osificación progresiva de los ligamentos y las entesis. La mayoría de los pacientes permanecen asintomáticos hasta etapas avanzadas de la enfermedad, donde la limitación y el dolor son característicos. Objetivo: Describir las características demográficas, clínicas y radiológicas de los pacientes con DISH evaluados en el Centro Médico Imbanaco de Cali y en la Clínica de Artritis Temprana, en Cali, Colombia. Materiales y métodos: Es un estudio descriptivo, de corte transversal. Se revisaron los registros de pacientes diagnosticados con DISH, seguidos entre enero de 2000 y octubre de 2018. El diagnóstico se confirmó según los criterios de Resnick-Niwayama. Se encontraron 24 pacientes, todos se incluyeron para el análisis final. Resultados y discusión: En esta serie se encontraron 20 varones y 4 mujeres. La mediana de edad al diagnóstico fue de 70,5 arios (RIQ: 61,3-73,8 arios), siendo menor en las mujeres (71,5 versus 60 años; p = 0,04). La mediana de tiempo de evolución de los síntomas fue de 5 años (RIQ: 3-10 años), la duración fue menor en el grupo de las mujeres (5 versus 4 años; p = 0,20). El 54,2% tenían sobrepeso y el 20,8% eran diabéticos. El síntoma principal fue la limitación cervical. Los segmentos vertebrales (C: cervical; T: torácico; L: lumbar) más afectados por la osificación del ligamento longitudinal anterior (LLA) fueron C5-C6, T8-T10 y L1-L3. La afección periférica predominó en las crestas ilíacas. Todos los pacientes realizaron terapia física y 3 fueron sometidos a cirugía cervical. El grado de limitación funcional fue valorado en 19 pacientes a través de los cuestionarios modified Health Assessment Questionnaire (mHAQ) y Bath Ankylosing Spondylitis Functional Index (BASFI). La mediana del puntaje de ambos cuestionarios fue 2 veces más alta en las mujeres. Conclusión: La DISH fue más frecuente en varones mayores de 65 años y se asoció con enfermedades metabólicas como la obesidad y la diabetes. Aunque las diferencias no fueron significativas, los resultados sugieren que las mujeres presentan un fenotipo grave de la enfermedad explicado por el inicio temprano y curso progresivo de los síntomas, así como mayor limitación funcional medida por mHAQ y BASFI.

ABSTRACT Introduction: Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterised by calcification and progressive ossification of ligaments and entheses. Most patients remain asymptomatic until advanced stages of the disease, where limitation and pain are characteristic. Objective: To describe the demographic, clinical, and radiological characteristics of patients with DISH evaluated in the Centro Médico Imbanaco and Clínica de Artritis Temprana, in Cali, Colombia. Materials and methods: A descriptive, cross-sectional study was conducted by reviewing the records of patients diagnosed with DISH between January 2000 and October 2018. The diagnosis was confirmed according to the Resnick-Niwayama criteria. A total of 24 patients were found, and all were included for the final analysis. Results and discussion: The series included 20 men and 4 women, with a median age at diagnosis of 70.5 years (IQR 61.3-73.8 years), beinglower in women (71.5 versus 60 years; P=.04). The median time of onset of the symptoms was 5 years (IQR 3-10 years), and the duration was shorter in women (5 versus 4 years; P=.20). It was observed that 54% were overweight and 20% were diabetic. The main symptom was cervical limitation. The most affected vertebral segments due to the ossification of the anterior longitudinal ligament (ALL) were C5-C6, T8-T10 and L1-L3 (cervical C; thoracic T; lumbar L). The peripheral involvement was mainly in the iliac crests. All patients received physiotherapy, and three of them underwent cervical surgery. The degree of functional limitation was assessed in 19 patients using the mHAQ (Modified Health Assessment Questionnaire) and BASFI (Functional Ankylosing Spondylitis Functional (BASFI) questionnaires. The median score of both questionnaires was 2 times higher in women Conclusion: Diffuse idiopathic skeletal hyperostosis was more frequent in men over 65 years of age, and was associated with metabolic conditions such as obesity and diabetes. Although the differences were not significant, the results suggest that women have a more severe phenotype of the disease, explained by the early onset and progressive course of symptoms, as well as greater functional limitation measured by mHAQ and BASFI.

Hakin-1, a New Specific Small-Molecule Inhibitor for the E3 Ubiquitin-Ligase Hakai, Inhibits Carcinoma Growth and Progression.

The requirement of the E3 ubiquitin-ligase Hakai for the ubiquitination and subsequent degradation of E-cadherin has been associated with enhanced epithelial-to-mesenchymal transition (EMT), tumour progression and carcinoma metastasis. To date, most of the reported EMT-related inhibitors were not developed for anti-EMT purposes, but indirectly affect EMT. On the other hand, E3 ubiquitin-ligase enzymes have recently emerged as promising therapeutic targets, as their specific inhibition would prevent wider side effects. Given this background, a virtual screening was performed to identify novel specific inhibitors of Hakai, targeted against its phosphotyrosine-binding pocket, where phosphorylated-E-cadherin specifically binds. We selected a candidate inhibitor, Hakin-1, which showed an important effect on Hakai-induced ubiquitination. Hakin-1 also inhibited carcinoma growth and tumour progression both in vitro, in colorectal cancer cell lines, and in vivo, in a tumour xenograft mouse model, without apparent systemic toxicity in mice. Our results show for the first time that a small molecule putatively targeting the E3 ubiquitin-ligase Hakai inhibits Hakai-dependent ubiquitination of E-cadherin, having an impact on the EMT process. This represents an important step forward in a future development of an effective therapeutic drug to prevent or inhibit carcinoma tumour progression.

Recognition and Activation of the Plant AKT1 Potassium Channel by the Kinase CIPK23.

Plant growth largely depends on the maintenance of adequate intracellular levels of potassium (K+). The families of 10 Calcineurin B-Like (CBL) calcium sensors and 26 CBL-Interacting Protein Kinases (CIPKs) of Arabidopsis (Arabidopsis thaliana) decode the calcium signals elicited by environmental inputs to regulate different ion channels and transporters involved in the control of K+ fluxes by phosphorylation-dependent and -independent events. However, the detailed molecular mechanisms governing target specificity require investigation. Here, we show that the physical interaction between CIPK23 and the noncanonical ankyrin domain in the cytosolic side of the inward-rectifier K+ channel AKT1 regulates kinase docking and channel activation. Point mutations on this domain specifically alter binding to CIPK23, enhancing or impairing the ability of CIPK23 to regulate channel activity. Our data demonstrate the relevance of this protein-protein interaction that contributes to the formation of a complex between CIPK23/CBL1 and AKT1 in the membrane for the proper regulation of K+ transport.

Restrictive cardiomyopathy in a patient with systemic sclerosis and Fabry disease: a case-based review.

Systemic sclerosis (SSc) is a rare immune-mediated vasculopathy characterized by fibrosis of the skin and internal organs. Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene producing α-galactosidase-A enzyme (α-Gal A) deficiency. Being a systemic disease, cardiac involvement in FD has a high mortality rate due to heart failure and arrhythmia. The coexistence of these two entities has not been reported previously. We describe the case of a female patient with limited SSc (lcSSc), a diagnosis based on the presence of sclerodactyly, Raynaud phenomenon, microvascular involvement, and positive anti-centromere antibodies. On follow-up, she developed chest pain, a second-degree A-V block, and restrictive cardiomyopathy (without cardiovascular risk factors). Although heart involvement is common in these two entities, the abnormal thickening of lateral and inferior wall, the infiltration pattern and the conduction system disorders presented herein are more characteristic in a heterozygous female with a cardiac variant of FD. The diagnosis of FD was confirmed with high globotriaosylsphingosine (Lyso-Gb3) levels and identification of GLA gene mutation. The patient was treated with enzymatic replacement (agalsidase alpha) following mild improvement in ventricular mass at 6th month, without clinical deterioration. The related literature on SSc associated with FD is also reviewed.

Identification of Novel Trypanosoma cruzi Proteasome Inhibitors Using a Luminescence-Based High-Throughput Screening Assay.

Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, is a potentially life-threatening condition that has become a global issue. Current treatment is limited to two medicines that require prolonged dosing and are associated with multiple side effects, which often lead to treatment discontinuation and failure. One way to address these shortcomings is through target-based drug discovery on validated T. cruzi protein targets. One such target is the proteasome, which plays a crucial role in protein degradation and turnover through chymotrypsin-, trypsin-, and caspase-like catalytic activities. In order to initiate a proteasome drug discovery program, we isolated proteasomes from T. cruzi epimastigotes and characterized their activity using a commercially available glow-like luminescence-based assay. We developed a high-throughput biochemical assay for the chymotrypsin-like activity of the T. cruzi proteasome, which was found to be sensitive, specific, and robust but prone to luminescence technology interference. To mitigate this, we also developed a counterscreen assay that identifies potential interferers at the levels of both the luciferase enzyme reporter and the mechanism responsible for a glow-like response. Interestingly, we also found that the peptide substrate for chymotrypsin-like proteasome activity was not specific and was likely partially turned over by other catalytic sites of the protein. Finally, we utilized these biochemical tools to screen 18,098 compounds, exploring diverse drug-like chemical space, which allowed us to identify 39 hits that were active in the primary screening assay and inactive in the counterscreen assay.

Clinical Profile of Levamisole-Adulterated Cocaine-Induced Vasculitis/Vasculopathy: A 30-Case Series.

OBJECTIVES: The aims of this study were to describe clinical and laboratory manifestations of patients with levamisole-adulterated cocaine-induced vasculitis/vasculopathy and to propose a skin classification according to the distribution and severity of lesions. METHODS: We report the characteristics of 30 patients admitted with levamisole-adulterated cocaine-induced vasculitis/vasculopathy in 4 high-complexity institutions in Colombia, from December 2010 to May 2017. We compare our findings with the main published series. RESULTS: Median age was 31 years (interquartile range, 27-38 years) with a male-to-female ratio of 5:1. Eighty-three percent of the patients had retiform purpura affecting the limbs, buttocks, face, or abdomen; 73% had ear necrosis, 50% cutaneous ulcers, 17% genital necrosis, 13% oral ulcers, and 10% digital necrosis. Cutaneous involvement was classified according to the frequency of the compromised corporal area, and purpuric lesions were stratified in 4 grades of severity. Anti-neutrophil cytoplasmic autoantibodies were positive in 85% of the cases, lupus anticoagulant in 73%, and antinuclear autoantibodies in 57%; rheumatoid factor was negative in all cases. We found nephritis in 17 cases (57%). Prednisolone was used in most of the patients (70%), with other immunosuppressive agents being used in a lower percentage. Improvement was observed in 93% of the patients, but symptoms recurred in 40%, attributed to relapses in consumption. End-stage chronic renal disease developed in 10% of the cases, and 1 patient died. CONCLUSIONS: Because of rising cocaine consumption and levamisole adulteration frequency, levamisole-adulterated cocaine-induced vasculitis/vasculopathy is becoming more common. Detailed characterization of skin involvement coupled with multiple antibody positivity is essential for a diagnosis. Renal involvement is frequent, clinically and histologically heterogeneous, and potentially serious.

Identification of Levels of Serum Amyloid A and Apolipoprotein A1 in Serum Proteomic Analysis of Neuropsychiatric Systemic Lupus Erythematosus Patients.

Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) has multiple pathogenic mechanisms that cause diverse manifestations and whose diagnosis is challenging because of the absence of appropriate diagnostic tests. In the present study the application of proteomics using two-dimensional electrophoresis (2D) and mass spectrometry (MS) allowed the comparison of the protein profile of the serum low and high abundance protein fractions of NPSLE patients (NPSLE group) and SLE without neuropsychiatric syndromes (SLE group), Neuropsychiatric syndromes not associated with SLE (NPnoSLE groups), and healthy controls (CTRL group). The gels obtained were digitalized and analyzed with the PDQuest software. The statistical analysis of the spots was performed using the nonparametric Kruskal Wallis and Dunn's multiple comparison tests. Two spots showed significant differences and were identified by MS. Spot 4009 was significantly lower in NPSLE with regard to NPnoSLE (p= 0,004) and was identified as apolipoprotein A1 (APOA1) (score 809-1132). Spot 8001 was significantly higher in NPSLE regarding CTRL and NPnoSLE (p= 0,01 y 0,03, respectively) and was identified as serum amyloid A (SAA) (score 725-2488). The proinflammatory high density lipoproteins (HDL) have been described in SLE. In this HDL the decrease of APOA1 is followed by an increase in SAA. This altered level of both proteins may be related to the inflammatory state that is characteristic of an autoimmune disease like SLE, but this is not specific for NPSLE.

A high throughput screen for next-generation leads targeting malaria parasite transmission.

Spread of parasite resistance to artemisinin threatens current frontline antimalarial therapies, highlighting the need for new drugs with alternative modes of action. Since only 0.2-1% of asexual parasites differentiate into sexual, transmission-competent forms, targeting this natural bottleneck provides a tangible route to interrupt disease transmission and mitigate resistance selection. Here we present a high-throughput screen of gametogenesis against a ~70,000 compound diversity library, identifying seventeen drug-like molecules that target transmission. Hit molecules possess varied activity profiles including male-specific, dual acting male-female and dual-asexual-sexual, with one promising N-((4-hydroxychroman-4-yl)methyl)-sulphonamide scaffold found to have sub-micromolar activity in vitro and in vivo efficacy. Development of leads with modes of action focussed on the sexual stages of malaria parasite development provide a previously unexplored base from which future therapeutics can be developed, capable of preventing parasite transmission through the population.

Optimal water networks in protein cavities with GAsol and 3D-RISM.

Motivation: Water molecules in protein binding sites play essential roles in biological processes. The popular 3D-RISM prediction method can calculate the solvent density distribution within minutes, but is difficult to convert it into explicit water molecules. Results: We present GAsol, a tool that is capable of finding the network of water molecules that best fits a particular 3D-RISM density distribution in a fast and accurate manner and that outperforms other available tools by finding the globally optimal solution thanks to its genetic algorithm. Availability and implementation: https://github.com/accsc/GAsol. BSD 3-clauses license. Contact: alvaro.x.cortes@gsk.com. Supplementary information: Supplementary data are available at Bioinformatics online.

Comportamiento de los embarazos de mujeres con enfermedades reumáticas en la Clínica de Artritis Temprana de Cali: 2011-2017 / Behavior of pregnancies in women with rheumatic diseases in Cali early arthritis Clinic: 2011-2017

Introducción y objetivo: La respuesta inmune en el embarazo varía de acuerdo a la enfermedad reumática presente. Describir los embarazos de mujeres con enfermedades reumáticas en una Clínica de Artritis Temprana. Métodos: Estudio descriptivo. Se revisaron registros de pacientes embarazadas atendidas desde agosto/2011 hasta noviembre/2017. Se encontraron 42 pacientes, 14 sin una entidad reumática definida (solo ANA positivos: se excluyeron). Veintiocho presentaban una enfermedad reumática autoinmune y tuvieron 29 embarazos (2 gemelares). Se escogieron para el análisis final. Solo tres se perdieron. Resultados: El promedio de edad fue 28.2 años. Los diagnósticos fueron: lupus eritematoso sistémico (13), artritis reumatoide (6), síndrome antifosfolipídico (2), anemia hemolítica autoinmune (2), artritis idiopática juvenil (2),

Aplicación de un programa de intervención para mejorar la comprensión táctica en fútbol sala: un estudio en contexto educativo / A aplicação de um programa de intervenção para melhorar a compreensão tática em futsal: um estudo realizado no contexto educacional / Application of an intervention program to improve tactical understanding in indoor football: a study conducted in an educational context

El objetivo del presente estudio fue analizar el efecto de un programa de Enseñanza Comprensiva sobre la toma de decisiones y ejecución del pase y de la conducción en el fútbol sala en un contexto educativo. Participaron 21 alumnos con edades comprendidas entre los 12 y los 14 años. Las variables independientes fueron el programa de intervención basado en el modelo Teaching Games for Understanding (TGFU) y la experiencia en fútbol sala federado. Las variables de toma de decisiones y ejecución fueron evaluadas a través del instrumento de observación Game Performance Evaluation Tool (GPET). Los resultados mostraron una mejoría significativa en la toma de decisión del pase en el grupo sin experiencia tras la aplicación del programa. Sin embargo, en el grupo con experiencia no fueron encontradas diferencias en ninguna de las variables. Los resultados destacan la necesidad de establecer adaptaciones e individualizar las tareas de aprendizaje en el contexto educativo, en función del nivel de habilidad de los alumnos.

The purpose of the study was to analyse the effects of a Comprehensive Teaching Programme on decision-making and execution, pass and dribbling actions in indoor football within an educational context. Participants were 21 students aged 12-14. Independent variables were the intervention program based on the “Teaching Games for Understanding (TGfU)” model and the experience in federated indoor football. Decisionmaking and execution variables were assessed through the observation instrument “Game Performance Evaluation Tool (GPET)”. The results show significant improvement in decision making for pass after the application of the program to the unexperienced group; however, those differences were not found in the experienced group. The results point out the need to adjust and individualize learning tasks in the educational context, depending on students’ skill level.

O objetivo deste estudo foi analisar o efeito de um Programa de Ensino Compreensivo na tomada de decisões e execução do passe e das ações de drible em futsal num contexto educativo. Participaram 21 alunos com idades entre 12 e 14 anos. As variáveis independentes foram o programa de intervenção baseado no modelo Teaching Games for Understanding (TGFU) e a experiência no futsal federado. As variáveis de tomada de decisão e de execução, foram avaliadas através do instrumento de observação Game Performance Evaluation Tool (GPET). Os resultados mostraram uma melhoria significativa na tomada de decisão do passe no grupo sem experiência após a aplicação do programa. No entanto, no grupo com experiência não foram encontradas diferenças em nenhuma das variáveis. Os resultados destacam a necessidade de estabelecer adaptações e individualizar as tarefas de aprendizagem no contexto educativo, em função do nível de habilidade dos alunos.

Potential application of a bioemulsifier-producing actinobacterium for treatment of vinasse.

Vinasse is a complex effluent created during production of ethyl alcohol, which can present serious pollution hazard in areas where it is discharged. A variety of technologies, many based upon recovery of the effluent via microbial pathways, are continually being evaluated in order to mitigate the pollution potential of vinasse. The present work reports on initial advances related to the effectiveness of the actinobacterium Streptomyces sp. MC1 for vinasse treatment. Alternative use of raw vinasse as a substrate for producing metabolites of biotechnological interest such as bioemulsifiers, was also evaluated. The strain was able to grow at very high vinasse concentrations (until 50% v/v) and remove over 50% of the biodegradable organic matter in a time period as short as 4 d. Potentially toxic metals such as Mn, Fe, Zn, As, and Pb were also effectively removed during bacterial growth. Decrease in the pollution potential of treated vinasse compared to raw effluent, was reflected in a significant increase in the vigour index of Lactuca sativa (letucce) used as bioremediation indicator. Finally, significant bioemulsifier production was detected when this strain was incubated in a vinasse-based culture medium. These results represent the first advances on the recovery and re-valuation of an actual effluent, by using an actinobacterium from our collection of cultures.

Estudio comparativo de la eficacia de los glucocorticoides, mineralocorticoides y vasodilatadores en la recuperación auditiva de pacientes que padecen hipoacusia neurosensorial idiopática de localización coclear. Ensayo clínico preliminar / A comparative study on efficacy of glucocorticoids, mineralocorticoids and vasoactive drugs on reversing hearing loss in patients suffering idiopathic sensorineural cochlear hypoacusis. A preliminary clinical trial

Introducción y objetivos: La hipoacusia neurosensorial (HNS) puede conducir a causar grave deterioro auditivo. Su recuperación funcional parece relacionarse con el control de la homeostasis iónica coclear experimentalmente dependiente de los mineralocorticoides. El objetivo de este trabajo es valorar la eficacia terapéutica comparando 2 modalidades de corticoides frente a los vasodilatadores en pacientes con HNS idopática coclear (HNSIC). Material y métodos: El ensayo dura 3 meses, se realiza en 70 pacientes asignados aleatoriamente en 4 grupos: grupo control, sin medicación, formado por 14 pacientes (8 varones y 6 mujeres); grupo tratado con vasodilatadores formado por 21 pacientes (11 hombres y 10 mujeres); grupo sometido a terapia glucocorticoidea formado por 16 pacientes (10 varones y 6 mujeres); y grupo sometido a terapia mineralocorticoidea formado por 19 pacientes (11 varones y 8 mujeres). La valoración del nivel de pérdida auditiva y su topografía se estiman mediante audiometría tonal liminal (ATL) y potenciales auditivos de tronco cerebral (PEATC). Resultados: Encontramos mejor respuesta al tratamiento con los mineralocorticoides que con los glucocorticoides, siendo la respuesta más pobre para los vasodilatadores. Esta respuesta es mayor en las mujeres que en los hombres, y en general observamos mejor respuesta por parte del oído izquierdo, con independencia del sexo del paciente. Conclusiones: Las ganancias auditivas son significativamente mayores con los mineralocorticoides, seguidas por los glucocorticoides, mientras que con los vasodilatadores las respuestas son pobres y no significativas (AU)

Introduction and objectives: Sensory neural hearing loss (SNHL) is a disorder characterised by an important deterioration of the auditory function. Re-establishing normal ion homeostasis of the endolymph could be related to hearing recovery and it might be mediated by mineralocorticoids. The main purpose of this preliminary, randomized controlled clinical trial was assessing the recovery of idiopathic sensory neural cochlear hearing loss (SNHL) by comparing the efficacy of 2 types of steroids versus vasodilators. Material and methods: The 3-month intervention involved 70 patients, allocated into 4 different groups: a control with no medication, consisting of 14 patients (8 men and 6 women); a vasodilator group of 21 patients (11 men and 10 women); a glucocorticoid group with 16 patients (10 men and 6 women); and a mineralocorticoid therapy group, consisting of 19 patients (11 men and 8 women). The level of hearing loss and its topography were estimated using Liminal Tone Audiometry (LTA) and Auditory Brainstem Response (ABR). Results: Our research found overall greater efficacy of mineralocorticoids versus glucocorticoids and vasodilators. There was better response in women than in men and it was higher from the left ear, regardless of patient gender. Conclusions: The hearing gain was significantly superior in the mineralocorticoid group, followed by the glucocorticoid group. However, the responses to vasodilators were lesser and of low statistical significance (AU)