Risk of acquiring Ascaris lumbricoides infection in an endemically infected rural community in Venezuela.

Soil-transmitted helminths, such as Ascaris lumbricoides, are the most prevalent parasites globally. Optimal anthelmintic treatment for A. lumbricoides in endemically infected communities is challenged by several host-related and environmental factors influencing infection acquisition. We assessed the risk of A. lumbricoides (re)infection after treatment in a Venezuelan rural community. Individual merthiolate-iodine-formaldehyde-fixed faecal samples were collected from 224 persons before a single-dose pyrantel treatment and at 1, 3, 6, 9 and 15 months after treatment. Effects of age, sex and socioeconomic status (SES) on A. lumbricoides prevalence, eggs/gram faeces (EPG) and infection (re)acquisition were assessed using both generalised linear mixed-effects models and survival analysis. Pre-treatment A. lumbricoides prevalence was 39.7%. Higher prevalence was associated with younger age and lower SES. Higher EPG values were observed among young children. Median time to A. lumbricoides infection was six months after treatment: at 1, 3, 6, 9 and 15 months post-treatment, cumulative incidence was 6.7%, 18.9%, 34.6%, 42.2%, and 52.6%, respectively. Younger age, lower SES, and pre-treatment A. lumbricoides infection status showed significantly elevated hazard ratios. Mass drug administration protocols would benefit from considering these factors in selective treatment strategies and possibly more than just annual or biannual treatments in the target population.

Multicriteria Decision Analysis for Updating of Quality Indicators for Inflammatory Bowel Disease Comprehensive Care Units in Spain.

BACKGROUND AND AIMS: Management of inflammatory bowel disease [IBD] is complex and IBD Comprehensive Care Units [ICCUs] facilitate the delivery of quality care to IBD patients. The objective of this study was to update the existing set of quality indicators [QIs] for ICCUs, based on a nationwide quality certification programme carried out in Spain, from a multi-stakeholder perspective and using multicriteria decision analysis [MCDA] methodology. METHODS: An MCDA comprising three different phases was conducted. In phase 1, a systematic literature review was performed, and after validation by a scientific committee comprising 11 experts, a preliminary set of QIs was developed. In phase 2, a larger group of 49 experts determined the relevance and relative importance of each QI by prioritising and weighing the preliminary set. Finally in phase 3, the scientific committee reviewed the results and made a final selection via a deliberative process. RESULTS: The final set comprised 67 QIs, classified as Structure [23 QIs], Process [35 QIs] and Outcome [9 QIs], which were ranked according to their relative importance. Multidisciplinary management was the most important requirement in ICCUs, followed by continuity of care, standardisation of clinical care and, especially, the incorporation of patients' reported outcomes. CONCLUSIONS: This updated set of QIs comprises a weighted and prioritised set of items that represent the essential minimum of criteria for ensuring appropriate quality of care in the management of IBD patients.

Ten-Second Electrophysiology: Evaluation of the 3DEP Platform for high-speed, high-accuracy cell analysis.

Electrical correlates of the physiological state of a cell, such as membrane conductance and capacitance, as well as cytoplasm conductivity, contain vital information about cellular function, ion transport across the membrane, and propagation of electrical signals. They are, however, difficult to measure; gold-standard techniques are typically unable to measure more than a few cells per day, making widespread adoption difficult and limiting statistical reproducibility. We have developed a dielectrophoretic platform using a disposable 3D electrode geometry that accurately (r2 > 0.99) measures mean electrical properties of populations of ~20,000 cells, by taking parallel ensemble measurements of cells at 20 frequencies up to 45 MHz, in (typically) ten seconds. This allows acquisition of ultra-high-resolution (100-point) DEP spectra in under two minutes. Data acquired from a wide range of cells - from platelets to large cardiac cells - benchmark well with patch-clamp-data. These advantages are collectively demonstrated in a longitudinal (same-animal) study of rapidly-changing phenomena such as ultradian (2-3 hour) rhythmicity in whole blood samples of the common vole (Microtus arvalis), taken from 10 µl tail-nick blood samples and avoiding sacrifice of the animal that is typically required in these studies.

Accurate quantification of apoptosis progression and toxicity using a dielectrophoretic approach.

A loss of ability of cells to undergo apoptosis (programmed cell death, whereby the cell ceases to function and destroys itself) is commonly associated with cancer, and many anti-cancer interventions aim to restart the process. Consequently, the accurate quantification of apoptosis is essential in understanding the function and performance of new anti-cancer drugs. Dielectrophoresis has previously been demonstrated to detect apoptosis more rapidly than other methods, and is low-cost, label-free and rapid, but has previously been unable to accurately quantify cells through the apoptotic process because cells in late apoptosis disintegrate, making cell tracking impossible. In this paper we use a novel method based on light absorbance and multi-population tracking to quantify the progress of apoptosis, benchmarking against conventional assays including MTT, trypan blue and Annexin-V. Analyses are performed on suspension and adherent cells, and using two apoptosis-inducing agents. IC50 measurements compared favourably to MTT and were superior to trypan blue, whilst also detecting apoptotic progression faster than Annexin-V.

Direct binding of arsenic trioxide to AMPK and generation of inhibitory effects on acute myeloid leukemia precursors.

Arsenic trioxide (As2O3) exhibits potent antineoplastic effects and is used extensively in clinical oncology for the treatment of a subset of patients with acute myeloid leukemia (AML). Although As2O3 is known to regulate activation of several signaling cascades, the key events, accounting for its antileukemic properties, remain to be defined. We provide evidence that arsenic can directly bind to cysteine 299 in AMPKα and inhibit its activity. This inhibition of AMPK by arsenic is required in part for its cytotoxic effects on primitive leukemic progenitors from patients with AML, while concomitant treatment with an AMPK activator antagonizes in vivo the arsenic-induced antileukemic effects in a xenograft AML mouse model. A consequence of AMPK inhibition is activation of the mTOR pathway as a negative regulatory feedback loop. However, when AMPK expression is lost, arsenic-dependent activation of the kinase RSK downstream of MAPK activity compensates the generation of regulatory feedback signals through phosphorylation of downstream mTOR targets. Thus, therapeutic regimens with As2O3 will need to include inhibitors of both the mTOR and RSK pathways in combination to prevent engagement of negative feedback loops and maximize antineoplastic responses.

Utilidad Clínica de las pruebas de susceptibilidad antimicótica / Clinic utility of testing

El objetivo primario de virtualmente todas las pruebas de susceptibilidad antimicrobiana in vitro es ayudar a predecir el efecto del agente antimicrobiano de interés en el resultado terapéutico de la infección que es causada por un patógeno especifíco. Esto es válido para cualquiera de las pruebas de susceptibilidad in vitro llevadas a cabo taanto para el cuidado de pacientes, como para el desarrollo o ensayo de nuevos fármacos o para el de estudios epidemiológicos. Los resultados obtenidos de una prueba in vitro es un simple, bien definido y altamente artificial sistema con limitaciones intrísecas útil para predicir el resultado en un proceso biológico complejo representado por una infección clínica; sólo se ha logrado una correlación modesta entre el resultado de la prueba in vitro y el resultado clínico, a pesar de décadas de experiencia con la estandarización de estos métodos.