The intrinsic substrate specificity of the human tyrosine kinome.

Phosphorylation of proteins on tyrosine (Tyr) residues evolved in metazoan organisms as a mechanism of coordinating tissue growth1. Multicellular eukaryotes typically have more than 50 distinct protein Tyr kinases that catalyse the phosphorylation of thousands of Tyr residues throughout the proteome1-3. How a given Tyr kinase can phosphorylate a specific subset of proteins at unique Tyr sites is only partially understood4-7. Here we used combinatorial peptide arrays to profile the substrate sequence specificity of all human Tyr kinases. Globally, the Tyr kinases demonstrate considerable diversity in optimal patterns of residues surrounding the site of phosphorylation, revealing the functional organization of the human Tyr kinome by substrate motif preference. Using this information, Tyr kinases that are most compatible with phosphorylating any Tyr site can be identified. Analysis of mass spectrometry phosphoproteomic datasets using this compendium of kinase specificities accurately identifies specific Tyr kinases that are dysregulated in cells after stimulation with growth factors, treatment with anti-cancer drugs or expression of oncogenic variants. Furthermore, the topology of known Tyr signalling networks naturally emerged from a comparison of the sequence specificities of the Tyr kinases and the SH2 phosphotyrosine (pTyr)-binding domains. Finally we show that the intrinsic substrate specificity of Tyr kinases has remained fundamentally unchanged from worms to humans, suggesting that the fidelity between Tyr kinases and their protein substrate sequences has been maintained across hundreds of millions of years of evolution.

The impact of Aprepitant on Nausea and Vomiting following Laparoscopic Sleeve Gastrectomy: A Blinded Randomized Controlled Trial.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is associated with postoperative nausea and vomiting (PONV). We aimed to compare the effects of aprepitant on the incidence of PONV after LSG. METHODS: In this double-blind, randomized controlled trial, the case group received the standard care regimen for PONV (dexamethasone 10 mg, ondansetron 4 mg, and metoclopramide 10 mg) plus prophylactic oral aprepitant 80 mg 1 h preoperatively. The control group received standard care plus a placebo. Comparative analyses using the Rhodes index were performed at 0, 6, 12, and 24 h postoperatively. RESULTS: A total of 400 patients (201 in the aprepitant group and 199 in the placebo group) underwent LSG. The groups were homogeneous. The aprepitant group experienced less PONV: early, 69 (34.3%) vs. 103 (51.7%), p ≤ 0.001; 6 h, 67 (33.3%) vs. 131 (65.8%), p ≤ 0.001; 12 h, 41 (20.4%) vs. 115 (57.8%), p ≤ 0.001; and 24 h, 22 (10.9%) vs. 67 (33.7%), p ≤ 0.001. Fewer patients in the aprepitant group vomited: early, 3 (1.5%) vs. 5 (2.5%), p = 0.020; 6 h, 6 (3%) vs. 18 (9%), p = 0.020; 12 h, 2 (1%) vs. 17 (8.5%), p = 0.006; and 24 h, 1 (0.5%) vs. 6 (3%), p = 0.040. Patients in the aprepitant group required less additional PONV medication: early, 61 (30.3%) vs. 86 (43.2), p = 0.008; 6 h, 7 (3.5%) vs. 34 (17%), p = 0.001; 12 h, 6 (3%) vs. 31 (15.6%), p ≤ 0.001; and 24 h, 5 (2.5%) vs. 11 (5.5%), p ≤ 0.001. CONCLUSIONS: Prophylactic aprepitant improved PONV between 0 h (early) and 24 h postoperatively in patients undergoing LSG.

Potential predictors for surgical delay in patients with intertrochanteric fractures and their impact on hospitalization length, in a Latin American trauma center.

INTRODUCTION: The incidence of intertrochanteric fractures is increasing, and health institutions must know the profile of their patients. This paper describes the relationship between clinical characteristics and attention process with surgical delay and prolonged hospitalization length in patients with intertrochanteric fractures admitted to a Latin-American trauma center. MATERIALS AND METHODS: Retrospective, comparative, cross-sectional study. The medical records of patients admitted for intertrochanteric fracture between August 1st 2019 and May 31st 2021 were reviewed to extract data regarding clinical characteristics, causes of surgery delay, and hospitalization length. Regression models were used to distinguish potential predictor variables on surgical delay and hospitalization length. RESULTS: 362 cases with intertrochanteric fractures were surgically treated during the study period. The mean time from admission to surgery was 4.2 ± 3.8 days. in 33,1% of the cases the surgery was performed within the first 48 h. A history of coronary heart disease (CHD) and chronic kidney disease were potential predictors of surgery delay (p<0.005). Only CHD was independently associated with surgery delay (OR 5.267 [95%CI 1.201-23.100); p = 0.028). Hospitalization was extended in cases where surgery was performed after 48 h (10,1 ± 6,2 days vs 5,9 ± 3,0 days; p<0.001). The regression model showed that for each day passed from fracture to admission and each day from admission to surgery, the hospitalization duration increased by 3,7 and 4,4 days, respectively. DISCUSSION: Patients with intertrochanteric fractures have comorbidities that potentially delay their surgical treatment and prolong hospitalization duration. The efficient use of hospital resources and the proper early evaluation of cardiac pathologies conducted during admission, could positively impact the achievement of surgical treatment within the first 48 h after the fracture, reducing hospitalization duration.

Validity of a low-cost friction encoder for measuring velocity, force and power in flywheel exercise devices.

The purpose of this study was to investigate the validity of a low-cost friction encoder against a criterion measure (strain gauge combined with a linear encoder) for assessing velocity, force and power in flywheel exercise devices. Ten young and physically active volunteers performed two sets of 14 maximal squats on a flywheel inertial device (YoYo Technology, Stockholm, Sweden) with five minutes rest between each set. Two different resistances were used (0.075 kg · m2 for the first set; 0.025 kg · m2 for the second). Mean velocity (Vrep), force (Frep) and power (Prep) for each repetition were assessed simultaneously via a friction encoder (Chronojump, Barcelona, Spain), and with a strain gauge combined with a linear encoder (MuscleLab 6000, Ergotest Technology, Porsgrunn, Norway). Results are displayed as (Mean [CI 90%]). Compared to criterion measures, mean bias for the practical measures of Vrep, Frep and Prep were moderate (-0.95 [-0.99 to -0.92]), small (0.53 [0.50 to 0.56]) and moderate (-0.68 [-0.71 to -0.65]) respectively. The typical error of estimate (TEE) was small for all three parameters; Vrep (0.23 [0.20 to 0.25]), Frep (0.20 [0.18 to 0.22]) and Prep (0.18 [0.16 to 0.20]). Correlations with MuscleLab were nearly perfect for all measures in all load configurations. Based on these findings, the friction encoder provides valid measures of velocity, force and power in flywheel exercise devices. However, as error did exist between measures, the same testing protocol should be used when assessing changes in these parameters over time, or when aiming to perform inter-individual comparisons.

Features of Mpox infection: The analysis of the data submitted to the ID-IRI network.

Background: Mpox is a rare zoonotic disease caused by the Mpox virus. On May 21, 2022, WHO announced the emergence of confirmed Mpox cases in countries outside the endemic areas in Central and West Africa. Methods: This multicentre study was performed through the Infectious Diseases International Research Initiative network. Nineteen collaborating centres in 16 countries participated in the study. Consecutive cases with positive Mpoxv-DNA results by the polymerase chain reaction test were included in the study. Results: The mean age of 647 patients included in the study was 34.5.98.6% of cases were males, 95.3% were homosexual-bisexual, and 92.2% had a history of sexual contact. History of smallpox vaccination was present in 3.4% of cases. The median incubation period was 7.0 days. The most common symptoms and signs were rashes in 99.5%, lymphadenopathy in 65.1%, and fever in 54.9%. HIV infection was present in 93.8% of cases, and 17.8% were followed up in the hospital for further treatment. In the two weeks before the rash, prodromal symptoms occurred in 52.8% of cases. The incubation period was 3.5 days shorter in HIV-infected Mpox cases with CD4 count <200/µL, we disclosed the presence of lymphadenopathy, a characteristic finding for Mpox, accompanied the disease to a lesser extent in cases with smallpox vaccination. Conclusions: Mpox disseminates globally, not just in the endemic areas. Knowledge of clinical features, disease transmission kinetics, and rapid and effective implementation of public health measures are paramount, as reflected by our findings in this study.

Características clínicas del síndrome de takotsubo: una serie de casos / Clinical characteristics of takotsubo syndrome: a series of cases

Resumen Introducción: El síndrome de takotsubo (STT) es una entidad de reciente reconocimiento que asemeja un síndrome coronario agudo. Su epidemiologia ha sido estudiada en diversas poblaciones del mundo. El desencadenante más frecuente es un evento estresante emocional. Objetivo: Describir las características clínicas de una serie de casos con STT. Material y métodos: Se realizó un estudio descriptivo y retrospectivo. Se evaluaron las variables de edad, sexo, características clínicas, factores de riesgo cardiovascular, factores desencadenantes, biomarcadores, hallazgos electrocardiográficos, ecocardiográficos y angiográficos en los expedientes clínicos de un grupo de casos de pacientes con STT. Resultados: Se incluyeron 19 casos de STT. Fueron 16 mujeres y 3 hombres, promedio de edad 62 ± 14 años; el principal factor de riesgo cardiovascular fue el sedentarismo, en 13 casos. El desencadenante emocional estuvo presente en la mayoría de los casos. El síntoma más frecuente fue el dolor torácico, ocho casos presentaron datos de choque e insuficiencia cardiaca. La variante más común por ecocardiograma fue el balonamiento apical en un 79%, al igual que por ventriculografía. La complicación más común fue choque cardiogénico. Conclusiones: Las características clínicas de nuestra población son similares a las descritas previamente en la literatura. El STT es una miocardiopatía transitoria y reversible con buen pronóstico.

Abstract Introduction: takotsubo syndrome (TTS) is a recently recognized entity that resembles an acute coronary syndrome. Its epidemiology has been studied in various populations around the world. The most frequent trigger is an emotional stressful event. Objective: To describe the clinical characteristics of a series of cases with TTS. Material and methods: A descriptive and retrospective study was carried out. The variables of age, gender, clinical characteristics, cardiovascular risk factors, triggering factors, biomarkers, electrocardiographic, echocardiographic, and angiographic findings in the clinical records of a group of cases of patients with TTS were evaluated. Results: 19 cases of TTS were included. There were 16 women and 3 men, the average age was 62 ± 14 years; the main cardiovascular risk factor was sedentary lifestyle in 13 cases. The emotional trigger was present in most cases. The most frequent symptom was chest pain, eight cases presented data of shoCKP and heart failure. The most common variant by echocardiography was apical ballooning in 79%, as well as by ventriculography. The most common complication was cardiogenic shoCKP. Conclusions: The clinical characteristics of our population are like those previously described in the literature. TTS is a transient and reversible cardiomyopathy with a good prognosis.

Clinical characteristics of takotsubo syndrome: a series of cases.

INTRODUCTION: takotsubo syndrome (TTS) is a recently recognized entity that resembles an acute coronary syndrome. Its epidemiology has been studied in various populations around the world. The most frequent trigger is an emotional stressful event. OBJECTIVE: To describe the clinical characteristics of a series of cases with TTS. MATERIAL AND METHODS: A descriptive and retrospective study was carried out. The variables of age, gender, clinical characteristics, cardiovascular risk factors, triggering factors, biomarkers, electrocardiographic, echocardiographic, and angiographic findings in the clinical records of a group of cases of patients with TTS were evaluated. RESULTS: 19 cases of TTS were included. There were 16 women and 3 men, the average age was 62 ± 14 years; the main cardiovascular risk factor was sedentary lifestyle in 13 cases. The emotional trigger was present in most cases. The most frequent symptom was chest pain, eight cases presented data of shoCKP and heart failure. The most common variant by echocardiography was apical ballooning in 79%, as well as by ventriculography. The most common complication was cardiogenic shoCKP. CONCLUSIONS: The clinical characteristics of our population are like those previously described in the literature. TTS is a transient and reversible cardiomyopathy with a good prognosis.

INTRODUCCIÓN: El síndrome de takotsubo (STT) es una entidad de reciente reconocimiento que asemeja un síndrome coronario agudo. Su epidemiologia ha sido estudiada en diversas poblaciones del mundo. El desencadenante más frecuente es un evento estresante emocional. OBJETIVO: Describir las características clínicas de una serie de casos con STT. MATERIAL Y MÉTODOS: Se realizó un estudio descriptivo y retrospectivo. Se evaluaron las variables de edad, sexo, características clínicas, factores de riesgo cardiovascular, factores desencadenantes, biomarcadores, hallazgos electrocardiográficos, ecocardiográficos y angiográficos en los expedientes clínicos de un grupo de casos de pacientes con STT. RESULTADOS: Se incluyeron 19 casos de STT. Fueron 16 mujeres y 3 hombres, promedio de edad 62 ± 14 años; el principal factor de riesgo cardiovascular fue el sedentarismo, en 13 casos. El desencadenante emocional estuvo presente en la mayoría de los casos. El síntoma más frecuente fue el dolor torácico, ocho casos presentaron datos de choque e insuficiencia cardiaca. La variante más común por ecocardiograma fue el balonamiento apical en un 79%, al igual que por ventriculografía. La complicación más común fue choque cardiogénico. CONCLUSIONES: Las características clínicas de nuestra población son similares a las descritas previamente en la literatura. El STT es una miocardiopatía transitoria y reversible con buen pronóstico.

A novel application of entropy analysis for assessing changes in movement variability during cumulative tackles in young elite rugby league players.

The aim of this study was to identify between-position (forwards vs. backs) differences in movement variability in cumulative tackle events training during both attacking and defensive roles. Eleven elite adolescent male rugby league players volunteered to participate in this study (mean ± SD, age; 18.5 ± 0.5 years, height; 179.5 ± 5.0 cm, body mass; 88.3 ± 13.0 kg). Participants performed a drill encompassing four blocks of six tackling (i.e. tackling an opponent) and six tackled (i.e. being tackled by an opponent while carrying a ball) events (i.e. 48 total tackles) while wearing a micro-technological inertial measurement unit (WIMU, Realtrack Systems, Spain). The acceleration data were used to calculate sample entropy (SampEn) to analyse the movement variability during tackles performance. In tackling actions SampEn showed significant between-position differences in block 1 (p = 0.0001) and block 2 (p = 0.0003). Significant between-block differences were observed in backs (block 1 vs 3, p = 0,0021; and block 1 vs 4, p = 0,0001) but not in forwards. When being tackled, SampEn showed significant between-position differences in block 1 (p = 0.0007) and block 3 (p = 0.0118). Significant between-block differences were only observed for backs in block 1 vs 4 (p = 0,0025). Movement variability shows a progressive reduction with cumulative tackle events, especially in backs and when in the defensive role (tackling). Forwards present lower movement variability values in all blocks, particularly in the first block, both in the attacking and defensive role. Entropy measures can be used by practitioners as an alternative tool to analyse the temporal structure of variability of tackle actions and quantify the load of these actions according to playing position.

Physicomechanical and Morphological Characterization of Multi-Structured Potassium-Acrylate-Based Hydrogels.

In this work, a photo-polymerization route was used to obtain potassium acrylate-co-acrylamide hydrogels with enhanced mechanical properties, well-defined microstructures in the dry state, and unique meso- and macrostructures in the hydrated state. The properties of the hydrogels depended on the concentration of the crosslinking agent. Mechanical properties, swelling capacity, and morphology were analyzed, showing a well-defined transition at a critical concentration of the crosslinker. In terms of morphology, shape-evolving surface patterns appeared at different scales during swelling. These surface structures had a noticeable influence on the mechanical properties. Hydrogels with structures exhibited better mechanical properties compared to unstructured hydrogels. The critical crosslinking concentration reported in this work (using glycerol diacrylate) is a reference point for the future preparation of multistructured acrylic hydrogel with enhanced properties.

Low sensitivity of the COVID-19 antigen test (PANBIO™ COVID-19 Ag rapid test) to detect asymptomatic infections in health personnel of the National Institute of Respiratory Diseases.

Background: COVID-19 requires an early diagnosis to optimize management and limit transmission. SARS-CoV-2 is able to spread effectively. Infected asymptomatic individuals have been found to be contagious. RT-qPCR is the currently recommended laboratory method for diagnosing acute infection. However, rapid antigen detection (RAD) tests are not only fast, but require less specialized training. The possibility of using RAD tests to identify asymptomatic patients is attractive, as it could effectively contribute to minimizing the hospital spread of SARS-CoV-2. The objective of the study was to determine the performance of RAD vs. RT-qPCR for the detection of asymptomatic cases in INER health personnel. Methods: In order to follow WHO guidelines, generalized tests, a test station for health care workers was implemented on demand. A rapid test was carried out and a second sample was taken to be processed by RT-qPCR. With the results of both tests we conducted a retrospective study. Sensitivity, specificity, positive predictive value, negative predictive value and negative likelihood ratios were calculated. Results: A total of 1640 RAD tests were performed in health care workers (mean age was 39, 69, 47% with a self-reported comorbidity). Participants provided 1,640 valid RAD/RT-qPCR test pairs with 2% testing positive via RT-qPCR. 12 RAD samples were positive for SARS-CoV-2. Overall sensitivity of the PANBIO ™ COVID-19 Ag Rapid Test test was 35.2%. Conclusions: RADs are not recommended for the detection of asymptomatic cases due to low performance.

Efficacy and safety of intravenous immunoglobulin in patients with lupus nephritis: A systematic review of the literature.

INTRODUCTION AND OBJECTIVE: Intravenous immunoglobulin (IVIg) is an anti-inflammatory drug with an unclear role in the treatment of patients with lupus nephritis (LN). This systematic review evaluates the evidence for IVIg in the care of patients with LN. METHODOLOGY: A systematic search was done in the PubMed, EMBASE, BVS and OVID databases - All EBM Reviews following the PRISMA methodology (registration in PROSPERO CRD42021236662). The variables were extracted: indications for use, dosage, partial or complete response, adverse reactions, initiation of renal replacement therapy, reduction of proteinuria, and mortality. The quality assessment was done with the "The Joanna Briggs Institute (JBI) Critical Appraisal tools for use in Systematic Reviews Checklist". In addition, synthesis reports were prepared through the Synthesis Without Meta-analysis - SWiM guide. RESULTS: A total of 2328 articles were obtained (28 were considered for inclusion). When the studies were evaluated, IVIg therapy was found to be between 60% to 70% effective (except for patients with class V LN) with overall responses (complete + partial) even for patients who are refractory to first line treatment. Normalization (<0.5 g) of nephrotic proteinuria occurred in 24% of cases with infrequent adverse events and a mortality plus dialysis composite of 11.5% and 24.1% (most representative study). CONCLUSION: In patients with LN refractory to conventional treatment or co-infection situations, the reported data seem to demonstrate effectiveness of IVIg therapy. There are few adverse reactions and caution is exercised when using it on patients with class V NL. However, given the lack of controlled studies with long-term follow-up, these data should be interpreted cautiously thus encouraging the development of high-quality RCTs.

Clinical and Virological Features of Patients Hospitalized with Different Types of COVID-19 Vaccination in Mexico City.

Coronavirus disease 2019 (COVID-19) vaccines effectively protect against severe disease and death. However, the impact of the vaccine used, viral variants, and host factors on disease severity remain poorly understood. This work aimed to compare COVID-19 clinical presentations and outcomes in vaccinated and unvaccinated patients in Mexico City. From March to September 2021, clinical, demographic characteristics, and viral variants were obtained from 1014 individuals with a documented SARS-CoV-2 infection. We compared unvaccinated, partially vaccinated, and fully vaccinated patients, stratifying by age groups. We also fitted multivariate statistical models to evaluate the impact of vaccination status, SARS-CoV-2 lineages, vaccine types, and clinical parameters. Most hospitalized patients were unvaccinated. In patients over 61 years old, mortality was significantly higher in unvaccinated compared to fully vaccinated individuals. In patients aged 31 to 60 years, vaccinated patients were more likely to be outpatients (46%) than unvaccinated individuals (6.1%). We found immune disease and age above 61 years old to be risk factors, while full vaccination was found to be the most protective factor against in-hospital death. This study suggests that vaccination is essential to reduce mortality in a comorbid population such as that of Mexico.

Vitamin D and its Possible Relationship to Neuroprotection in COVID-19: Evidence in the Literature.

Vitamin D is a hormone involved in the regulation of important biological processes such as signal transduction, immune response, metabolic regulation and also in the nervous and vascular systems. To date, coronavirus disease 2019 (COVID-19) infection does not have a specific treatment. However, various drugs have been proposed, including those that attenuate the intense inflammatory response, and recently, the use of vitamin D, in clinical trials, as part of the treatment of COVID-19 has provided promising results. It has been observed in some clinical studies that the use of cholecalciferol (vitamin D3) and its two metabolites the circulating form, calcidiol or calcifediol (25-hydroxycalciferol, 25-(OH)-D), and the active form, calcitriol (1,25-(OH)2-D), in different doses, improve the clinical manifestations, prognosis, and survival of patients infected with COVID-19 probably because of its anti-inflammatory, antiviral and lung-protective action. In relation to the central nervous system (CNS) it has been shown, in clinical studies, that vitamin D is beneficial in some neurological and psychiatric conditions because of its anti-inflammatory and antioxidant properties, modulation of neurotransmitters actions, and regulation of calcium homeostasis between other mechanisms. It has been shown that COVID-19 infection induces CNS complications such as headache, anosmia, ageusia, neuropathy, encephalitis, stroke, thrombosis, cerebral hemorrhages, cytotoxic lesions, and psychiatric conditions and it has been proposed that the use of dietary supplements, as vitamin and minerals, can be adjuvants in this disease. In this review, the evidence of the possible role of vitamin D, and its metabolites, as a protector against the neurological manifestations of COVID-19 was summarized.

Glomerulopatía por C3: algoritmo diagnóstico en gestantes

La enfermedad glomerular comprende un grupo heterogéneo de entidades que se caracterizan por la pérdida de la arquitectura o función del glomérulo secundario a proceso inflamatorio del mismo de etiología autoinmune, infecciosa, paraneoplásica, que puede ser identificada con estudios de histopatología. Su reconocimiento durante la gestación representa un reto diagnóstico por la sobreposición de cambios fisiológicos, el debut de enfermedades autoinmunitarias o de enfermedades genéticas, entre otros. La presentación clínica suele encajar en grupos sindromáticos específicos, sin embargo, es frecuente que sean clínicamente indistinguibles o sobrepuestos. El debut de la enfermedad renal con curso clínico de rápida instauración y de evolución desfavorable con respecto a la función renal, hace mandatorio un estudio completo desde el abordaje clínico hasta la interpretación de los hallazgos histopatológicos, encaminado en la distinción de causas primarias y secundarias. Si bien las glomerulonefritis primarias no son las más frecuentes en la gestación, la identificación certera del diagnóstico y su adecuada clasificación permite el manejo dirigido y óptimo de las mismas. Se presentan los casos clínicos de dos gestantes con enfermedad glomerular primaria, con discrepancia en su diagnóstico, enfatizando en sus manifestaciones durante el curso de la gestación, el algoritmo diagnóstico utilizado, el tratamiento inicial y de mantenimiento utilizado. Se resalta la utilidad de la biopsia renal, específicamente la inmunofluorencia para aclarar el mismo.

Glomerular disease involves a heterogeneous group of entities that are characterized by loss of the architecture and function of the glomerulus and this can be caused by immunity, infectious and paraneoplastic etiologies. The aforementioned can be identified in histopathological studies. The recognition of this entity during pregnancy represents a diagnostic challenge due to the superposition of physiological changes, the development of autoimmune diseases and / or genetic disease, among others. Clinical manifestations can be into specific syndromic groups; however we can find indistinguishable manifestations and overlapping of this. When the disease is present its common to find rapidly establishment and unfavorable evolution about renal function. With this it's necessary to complete studies involving the initial clinical approach until histopathological findings with the goal to find primary and secondary causes. As it's known primary glomerulonephritis is not the most frequent in pregnancy, the accuracy in the diagnosis and the proper classification allows the direct and soon management. In this case report we describe 2 pregnant women with primary glomerular disease with discrepancy in their diagnosis. We talk about manifestations during pregnancy, the algorithm used in the diagnosis and finally the initial treatment and the maintenance used in these patients.

Atypical hemolytic uremic syndrome in the Colombian Caribbean: its particular characteristics.

INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is a rare and genetically mediated systemic disease most often caused by uncontrolled and chronic complement activation that leads to systemic thrombotic microangiopathy, renal and extra-renal damage. MATERIALS AND METHODS: This is descriptive, retrospective and multicenter study, which reports demographic, clinical, laboratory, and genetic characteristics, as well as their treatment response and outcome of 20 aHUS patients diagnosed between 2014 and 2018. RESULTS: Most patients were female adults (75%) and 30% were associated to pregnancy/postpartum, 15% to autoimmune disease, and 65% to infections. Gastrointestinal involvement (75%) was the most frequent extra-renal organ damage. Antenatal mortality and mortality rate were 5% and 10%, respectively. 25% of the patients progressed to end-stage renal disease. In 4/8 of patients treated within 1 week of presentation, eculizumab treatment restored multi-organ function after 4 weeks of treatment. CFH (37%) and CFI (25%) mutations were the most frequent. CONCLUSION: This is the first series of aHUS cases of Colombian Caribbean region which reports the clinical and epidemiological characteristics of this condition in this region.

Genetic Analysis of SARS-CoV-2 Variants in Mexico during the First Year of the COVID-19 Pandemic.

During the first year of the SARS-CoV-2 pandemic in Mexico, more than two million people were infected. In this study, we analyzed full genome sequences from 27 February 2020 to 28 February 2021 to characterize the geographical and temporal distribution of SARS-CoV-2 lineages and identify the most common circulating lineages during this period. We defined six different geographical regions with particular dynamics of lineage circulation. The Northeast and Northwest regions were the ones that exhibited the highest lineage diversity, while the Central south and South/Southeast regions presented less diversity with predominance of a certain lineage. Additionally, by late February 2021, lineage B.1.1.519 represented more than 89% of all circulating lineages in the country.

Detection of Cytokines and Collectins in Bronchoalveolar Fluid Samples of Patients Infected with Histoplasma capsulatum and Pneumocystis jirovecii.

Histoplasmosis and pneumocystosis co-infections have been reported mainly in immunocompromised humans and in wild animals. The immunological response to each fungal infection has been described primarily using animal models; however, the host response to concomitant infection is unknown. The present work aimed to evaluate the pulmonary immunological response of patients with pneumonia caused either by Histoplasma capsulatum, Pneumocystis jirovecii, or their co-infection. We analyzed the pulmonary collectin and cytokine patterns of 131 bronchoalveolar lavage samples, which included HIV and non-HIV patients infected with H. capsulatum, P. jirovecii, or both fungi, as well as healthy volunteers and HIV patients without the studied fungal infections. Our results showed an increased production of the surfactant protein-A (SP-A) in non-HIV patients with H. capsulatum infection, contrasting with HIV patients (p < 0.05). Significant differences in median values of SP-A, IL-1ß, TNF-α, IFN-γ, IL-18, IL-17A, IL-33, IL-13, and CXCL8 were found among all the groups studied, suggesting that these cytokines play a role in the local inflammatory processes of histoplasmosis and pneumocystosis. Interestingly, non-HIV patients with co-infection and pneumocystosis alone showed lower levels of SP-A, IL-1ß, TNF-α, IFN-γ, IL-18, IL-17A, and IL-23 than histoplasmosis patients, suggesting an immunomodulatory ability of P. jirovecii over H. capsulatum response.

Organic or conventional production system and nutrient rate affect the nematode community in carrot production.

Organic and conventional production are common in horticulture crops and each system may exert a different influence on the soil ecosystem, particularly the nematode community. Crop nutrient rate is an important choice in both production systems. The objectives of this study were to assess the impacts of (i) organic and conventional production systems and (ii) nutrient rate in both systems on the nematode community in carrot production. To investigate these objectives, field studies in organic and conventional production - which included fumigation with 1,3-dichloropropene - were conducted in North-Central Florida. In both production systems, nutrient rate treatments were 168, 224, 280, 336, and 392 kg N/ha. Poultry litter was the nitrogen source in organic production whereas synthetic, inorganic fertilizer was used in conventional production. All nematode trophic groups were consistently more abundant in organic than conventional production. The nematode community was more diverse and had greater trophic structure in organic production. Greater rates of organic nutrients increased enrichment opportunists (bacterivores and fungivores), but inconsistently across years. Conventional production had similar results except that only moderate nutrient rates increased fungivore abundances. Extreme enrichment opportunists (Rhabditis spp.) drove bacterivore trends in organic production whereas moderate enrichment opportunists (Cephalobus spp.) drove trends in conventional production. Nutrient rates did not affect omnivore-predators, herbivores, nematode community diversity, or structure in either system. In summary, type of production system, organic or conventional, exerts a strong influence on the nematode community, but nutrient rate has less consistent effects in horticulture production.

A bioinformatics pipeline for Mycobacterium tuberculosis sequencing that cleans contaminant reads from sputum samples.

Next-Generation Sequencing (NGS) is widely used to investigate genomic variation. In several studies, the genetic variation of Mycobacterium tuberculosis has been analyzed in sputum samples without previous culture, using target enrichment methodologies for NGS. Alignments obtained by different programs generally map the sequences under default parameters, and from these results, it is assumed that only Mycobacterium reads will be obtained. However, variants of interest microorganism in clinical samples can be confused with a vast collection of reads from other bacteria, viruses, and human DNA. Currently, there are no standardized pipelines, and the cleaning success is never verified since there is a lack of rigorous controls to identify and remove reads from other sputum-microorganisms genetically similar to M. tuberculosis. Therefore, we designed a bioinformatic pipeline to process NGS data from sputum samples, including several filters and quality control points to identify and eliminate non-M. tuberculosis reads to obtain a reliable genetic variant report. Our proposal uses the SURPI software as a taxonomic classifier to filter input sequences and perform a mapping that provides the highest percentage of Mycobacterium reads, minimizing the reads from other microorganisms. We then use the filtered sequences to perform variant calling with the GATK software, ensuring the mapping quality, realignment, recalibration, hard-filtering, and post-filter to increase the reliability of the reported variants. Using default mapping parameters, we identified reads of contaminant bacteria, such as Streptococcus, Rhotia, Actinomyces, and Veillonella. Our final mapping strategy allowed a sequence identity of 97.8% between the input reads and the whole M. tuberculosis reference genome H37Rv using a genomic edit distance of three, thus removing 98.8% of the off-target sequences with a Mycobacterium reads loss of 1.7%. Finally, more than 200 unreliable genetic variants were removed during the variant calling, increasing the report's reliability.