A novel validated assay to support the discovery of new anti-malarial gametocytocidal agents

Additional file 1. Graphical representation of the expression of 12 selected genes throughout the 30 days of gametocytogenesis. Y-axis shows the gene expression represented as (Ctgene−Ct18S rRNA)Ttime × −(Ctgene−Ct18S rRNA)T0, considering the time 0 as the basal expression. Although only the gametocytogenesis during 30 days is presented, similar results were obtained from day 0 to day 15 in both assays

El género, un factor determinante en el riesgo de somnolencia

Los trastornos del sueño constituyen un grupo muy numeroso y heterogéneo de procesos. La clasificación se ha ido modificando en este inicio del siglo xxi y agrupa más de 90 patologías. A nivel mundial se estima que la prevalencia de trastornos del sueño oscila entre 35 y 45% de la población adulta mayor de 18 a˜nos. Se ha considerado que en México la prevalencia sea similar a la internacional por lo que alrededor de 1 de cada 3 mexicanos tiene algún trastorno del sueño y la mayor parte de ellos, no recibe tratamiento médico ya sea por desconocimiento de estos problemas por parte del personal de salud o por insuficientes centros de atención de los mismos.Los trastornos del sueno constituyen un grupo numeroso y heterogéneo de procesos. A nivel mundial se estima que la prevalencia de trastornos del sueno oscila entre 35 y 45% de la población adulta mayor de 18 anos. Estudios previos realizados en la Cd de México han demostrado una somnolencia excesiva diurna en el 18%, de los cuales 19% fueron mujeres y 17% hombres por lo que el objetivo de este proyecto es detectar en una población adulta del valle de Toluca, el riesgo de somnolencia. Métodos: Se empleó un instrumento validado: escala de somnolencia de Epworth que tiene por objeto evaluar la magnitud de la somnolencia diurna frente a ocho situaciones de la vida diaria. Resultados: De los 227 sujetos analizados, se encontró que 76 de ellos (33.4%): 44 hombres (19.4% del total) y 27 mujeres (11.9% del total) tenían somnolencia excesiva. Se dividió a la población en dos grupos: mayores o iguales a 50 anos de edad y 49 años o menos. Al comparar el riesgo Hombre-Mujer se encontró un valor de O.R. de 4.1 en los hombres de 50 anos o más, mientras que en el género femenino fue de 1.0. Al establecer una separación con los sujetos que tenían entre 9 y 11 puntos de la escala de Epworth, se demostró que el riesgo seguía siendo elevado en OR = 4.0 Conclusiones: En la población estudiada el género masculino tiene un riesgo cuatro veces mayor que la mujer de presentar somnolencia excesiva diurna

A novel procedure for protein extraction from formalin-fixed paraffin-embedded tissues

Most of the archived pathological specimens in hospitals are kept as formalin-fixed paraffin-embedded tissues (FFPE) for long-term preservation. Up to now, these samples are only used for immunohistochemistry in a clinical routine as it is difficult to recover intact protein from these FFPE tissues. Here, we report a novel, short time-consuming and cost-effective method to extract full-length, non-degraded proteins from FFPE tissues. This procedure is combined with an effective and non-toxic deparaffinisation process and an extraction method based on antigen-retrieval, high concentration of SDS and high temperature. We have obtained enough intact protein to be detected by Western blotting analysis. This technique will allow utilising these stored FFPE tissues in several applications for protein analysis helping to advance the translational studies in cancer and other diseases

The “DrownSafe” project: assessing the feasibility of a puppet show in teaching drowning prevention to children and parents

Drowning remains a prominent global pediatric health concern, necessitating preventive measures such as educational initiatives for children and caregivers. In this study, we aimed to assess the feasibility and educational effectiveness of an interactive puppet show centered on teaching water safety to children and parents. A 30 min original theater performance, featuring two actors and three puppets (a girl, a crab, and a lifeguard), was conducted. Subsequently, 185 children (aged 4 to 8) and their 160 parents (134 mothers and 26 fathers) participated in this quasi-experimental study. Pre- and post-show tests were administered to evaluate knowledge and behaviors regarding aquatic environments. Prior to the puppet show, 78% of the children exhibited basic aquatic competency. Only 33% considered swimming alone risky. Following the intervention, 81.6% of the children changed their perception of the risks of solo beach activities, showing improved knowledge regarding contacting an emergency number (from 63.2% to 98.9%, p < 0.001). The intervention increased parents’ intention to visit lifeguard-patrolled beaches and improved their CPR knowledge with regard to drowning victims by 58.8%. In conclusion, a drowning prevention puppet show positively impacted children and parents, potentially enhancing safety behaviors during water-related leisure activities, warranting its consideration part of comprehensive drowning prevention strategies.Universidade de Vig

Medidas de la turbulencia atmosférica en los Observatorios de Canarias: técnica SCIDAR

Ponencia presentada en: 1er Encuentro sobre Meteorología y Atmósfera de Canarias, celebrado en el Puerto de la Cruz, los días 12,13 y 14 de noviembre de 2003. El encuentro estuvo organizado por el Centro Meteorológico Territorial en Canarias Occidental, con la colaboración del Observatorio Atmosférico de Izaña y del Grupo de Física de la Atmósfera de la Facultad de Física (Universidad de La Laguna)SCIDAR es una técnica que permite medir la turbulencia atmosférica (Ci (h)) ópticamente, así como la velocidad (V(h)) de esas capas turbulentas en función de la altura. El Instituto de Astrofísica de Canarias ha comenzado un programa de caracterización de la turbulencia atmosférica en los observatorios de lzaña (Tenerife) y Roque de los Muchachos (La Palma). En esta contribución describimos la técnica SCIDAR y su aplicación a diferentes problemas científicos: óptica adaptativa y comunicaciones ópticas; y presentamos resultados estadísticos de perfiles de turbulencia atmosférica obtenidos en el observatorio de lzaña (Tenerife), así como su evolución temporal

The Mutational Landscape of Acute Myeloid Leukaemia Predicts Responses and Outcomes in Elderly Patients from the PETHEMA-FLUGAZA Phase 3 Clinical Trial

Mutational profiling using a custom 43-gene next-generation sequencing panel revealed that patients with mutated DNMT3A or EZH2, or an increase in TET2 VAF and lower TP53 VAF showed a higher overall response. NRAS and TP53 variants were associated with shorter overall survival (OS), whereas only mutated BCOR was associated with a shorter relapse-free survival (RFS). Subgroup analyses of OS according to biological and genomic characteristics showed that patients with low-intermediate cytogenetic risk and mutated NRAS benefited from azacytidine therapy and patients with mutated TP53 showed a better RFS in the azacytidine arm. In conclusion, differential mutational profiling might anticipate the outcomes of first-line treatment choices (AZA or FLUGA) in older patients with AML. We sought to predict treatment responses and outcomes in older patients with newly diagnosed acute myeloid leukemia (AML) from our FLUGAZA phase III clinical trial (PETHEMA group) based on mutational status, comparing azacytidine (AZA) with fludarabine plus low-dose cytarabine (FLUGA). Mutational profiling using a custom 43-gene next-generation sequencing panel revealed differences in profiles between older and younger patients, and several prognostic markers that were useful in young patients were ineffective in older patients. We examined the associations between variables and overall responses at the end of the third cycle. Patients with mutated DNMT3A or EZH2 were shown to benefit from azacytidine in the treatment-adjusted subgroup analysis. An analysis of the associations with tumor burden using variant allele frequency (VAF) quantification showed that a higher overall response was associated with an increase in TET2 VAF (odds ratio (OR), 1.014; p = 0.030) and lower TP53 VAF (OR, 0.981; p = 0.003). In the treatment-adjusted multivariate survival analyses, only the NRAS (hazard ratio (HR), 1.9, p = 0.005) and TP53 (HR, 2.6, p = 9.8 × 10 −7) variants were associated with shorter overall survival (OS), whereas only mutated BCOR (HR, 3.6, p = 0.0003) was associated with a shorter relapse-free survival (RFS). Subgroup analyses of OS according to biological and genomic characteristics showed that patients with low-intermediate cytogenetic risk (HR, 1.51, p = 0.045) and mutated NRAS (HR, 3.66, p = 0.047) benefited from azacytidine therapy. In the subgroup analyses, patients with mutated TP53 (HR, 4.71, p = 0.009) showed a better RFS in the azacytidine arm. In conclusion, differential mutational profiling might anticipate the outcomes of first-line treatment choices (AZA or FLUGA) in older patients with AML. The study is registered at ClinicalTrials.gov as NCT0231913

A clinical method for mapping and quantifying blood stasis in the left ventricle

In patients at risk of intraventrcular thrombosis, the benefits of chronic anticoagulation therapy need to be balanced with the pro-hemorrhagic effects of therapy. Blood stasis in the cardiac chambers is a recognized risk factor for intracardiac thrombosis and potential cardiogenic embolic events. In this work, we present a novel flow image-based method to assess the location and extent of intraventricular stasis regions inside the left ventricle (LV) by digital processing flow-velocity images obtained either by phase-contrast magnetic resonance (PCMR) or 2D color-Doppler velocimetry (echo-CDV). This approach is based on quantifying the distribution of the blood Residence Time (TR) from time-resolved blood velocity fields in the LV. We tested the new method in illustrative examples of normal hearts, patients with dilated cardiomyopathy and one patient before and after the implantation of a left ventricular assist device (LVAD). The method allowed us to assess in-vivo the location and extent of the stasis regions in the LV. Original metrics were developed to integrate flow properties into simple scalars suitable for a robust and personalized assessment of the risk of thrombosis. From a clinical perspective, this work introduces the new paradigm that quantitative flow dynamics can provide the basis to obtain subclinical markers of intraventricular thrombosis risk. The early prediction of LV blood stasis may result in decrease strokes by appropriate use of anticoagulant therapy for the purpose of primary and secondary prevention. It may also have a significant impact on LVAD device design and operation set-up

Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care : a pragmatic, randomised, non-inferiority clinical trial (OB12)

The trial was financed by Ministerio de Sanidad y Consumo Español through their call for independent clinical research, Orden Ministerial SAS/2377, 2010 (EC10-115, EC10-116, EC10-117, EC10-119, EC10-122); CAIBER—Spanish Clinical Research Network, Instituto de Salud Carlos III (ISCIII) (CAI08/010044); and Gerencia Asistencial de Atención Primaria de Madrid. This study is also supported by the Spanish Clinical Research Network (SCReN), funded by ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, project number PT13/0002/0007, within the National Research Program I+D+I 2013-2016 and co-funded with European Union ERDF funds (European Regional Development Fund). This project received a grant for the translation and publication of this article from the Foundation for Biomedical Research and Innovation in Primary Care (FIIBAP) Call 2017 for grants to promote research programs.Objectives To compare the effectiveness of oral versus intramuscular (IM) vitamin B12 (VB12) in patients aged ≥65 years with VB12 deficiency. Design Pragmatic, randomised, non-inferiority, multicentre trial in 22 primary healthcare centres in Madrid (Spain). Participants 283 patients ≥65 years with VB12 deficiency were randomly assigned to oral (n=140) or IM (n=143) treatment arm. Interventions The IM arm received 1 mg VB12 on alternate days in weeks 1–2, 1 mg/week in weeks 3–8 and 1 mg/month in weeks 9–52. The oral arm received 1 mg/day in weeks 1–8 and 1 mg/week in weeks 9–52. Main outcomes Serum VB12 concentration normalisation (≥211 pg/mL) at 8, 26 and 52 weeks. Non-inferiority would be declared if the difference between arms is 10% or less. Secondary outcomes included symptoms, adverse events, adherence to treatment, quality of life, patient preferences and satisfaction. Results The follow-up period (52 weeks) was completed by 229 patients (80.9%). At week 8, the percentage of patients in each arm who achieved normal B12 levels was well above 90%; the differences in this percentage between the oral and IM arm were −0.7% (133 out of 135 vs 129 out of 130; 95% CI: −3.2 to 1.8; p>0.999) by per-protocol (PPT) analysis and 4.8% (133 out of 140 vs 129 out of 143; 95% CI: −1.3 to 10.9; p=0.124) by intention-to-treat (ITT) analysis. At week 52, the percentage of patients who achieved normal B12 levels was 73.6% in the oral arm and 80.4% in the IM arm; these differences were −6.3% (103 out of 112 vs 115 out of 117; 95% CI: −11.9 to −0.1; p=0.025) and −6.8% (103 out of 140 vs 115 out of 143; 95% CI: −16.6 to 2.9; p=0.171), respectively. Factors affecting the success rate at week 52 were age, OR=0.95 (95% CI: 0.91 to 0.99) and having reached VB12 levels ≥281 pg/mL at week 8, OR=8.1 (95% CI: 2.4 to 27.3). Under a Bayesian framework, non-inferiority probabilities (Δ>−10%) at week 52 were 0.036 (PPT) and 0.060 (ITT). Quality of life and adverse effects were comparable across groups. 83.4% of patients preferred the oral route. Conclusions Oral administration was no less effective than IM administration at 8 weeks. Although differences were found between administration routes at week 52, the probability that the differences were below the non-inferiority threshold was very low.Publisher PDFPeer reviewe

Impact of measurable residual disease by decentralized flow cytometry: a PETHEMA real-world study in 1076 patients with acute myeloid leukemia

The role of decentralized assessment of measurable residual disease (MRD) for risk stratification in acute myeloid leukemia (AML) remains largely unknown, and so it does which methodological aspects are critical to empower the evaluation of MRD with prognostic significance, particularly if using multiparameter flow cytometry (MFC). We analyzed 1076 AML patients in first remission after induction chemotherapy, in whom MRD was evaluated by MFC in local laboratories of 60 Hospitals participating in the PETHEMA registry. We also conducted a survey on technical aspects of MRD testing to determine the impact of methodological heterogeneity in the prognostic value of MFC. Our results confirmed the recommended cutoff of 0.1% to discriminate patients with significantly different cumulative-incidence of relapse (-CIR- HR:0.71, P < 0.001) and overall survival (HR: 0.73, P = 0.001), but uncovered the limited prognostic value of MFC based MRD in multivariate and recursive partitioning models including other clinical, genetic and treatment related factors. Virtually all aspects related with methodological, interpretation, and reporting of MFC based MRD testing impacted in its ability to discriminate patients with different CIR. Thus, this study demonstrated that “real-world” assessment of MRD using MFC is prognostic in patients at first remission, and urges greater standardization for improved risk-stratification toward clinical decisions in AML.This study was supported by the Centro de Investigación Biomédica en Red – Área de Oncología - del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369, CB16/12/00233, CB16/12/00284 and CB16/12/00400), Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS No. PI16/01661, PI16/00517 and PI18/01946), Gerencia Regional de Salud de CyL (GRS 1346/A/16) and the Plan de Investigación de la Universidad de Navarra (PIUNA 2014-18). This study was supported internationally by the Cancer Research UK, FCAECC and AIRC under the Accelerator Award Program EDITOR

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica