A field evaluation of the Hardy TB MODS Kit™ for the rapid phenotypic diagnosis of tuberculosis and multi-drug resistant tuberculosis.

BACKGROUND: Even though the WHO-endorsed, non-commercial MODS assay offers rapid, reliable TB liquid culture and phenotypic drug susceptibility testing (DST) at lower cost than any other diagnostic, uptake has been patchy. In part this reflects misperceptions about in-house assay quality assurance, but user convenience of one-stop procurement is also important. A commercial MODS kit was developed by Hardy Diagnostics (Santa Maria, CA, USA) with PATH (Seattle, WA, USA) to facilitate procurement, simplify procedures through readymade media, and enhance safety with a sealing silicone plate lid. Here we report the results from a large-scale field evaluation of the MODS kit in a government service laboratory. METHODS & FINDINGS: 2446 sputum samples were cultured in parallel in Lowenstein-Jensen (LJ), conventional MODS and in the MODS kit. MODS kit DST was compared with conventional MODS (direct) DST and proportion method (indirect) DST. 778 samples (31.8%) were Mycobacterium tuberculosis culture-positive. Compared to conventional MODS the sensitivity, specificity, positive, and negative predictive values (95% confidence intervals) of the MODS Kit were 99.3% (98.3-99.8%), 98.3% (97.5-98.8%), 95.8% (94.0-97.1%), and 99.7% (99.3-99.9%). Median (interquartile ranges) time to culture-positivity (and rifampicin and isoniazid DST) was 10 (9-13) days for conventional MODS and 8.5 (7-11) for MODS Kit (p<0.01). Direct rifampicin and isoniazid DST in MODS kit was almost universally concordant with conventional MODS (97.9% agreement, 665/679 evaluable samples) and reference indirect DST (97.9% agreement, 687/702 evaluable samples). CONCLUSIONS: MODS kit delivers performance indistinguishable from conventional MODS and offers a convenient, affordable alternative with enhanced safety from the sealing silicone lid. The availability in the marketplace of this platform, which conforms to European standards (CE-marked), readily repurposed for second-line DST in the near future, provides a fresh opportunity for improving equity of access to TB diagnosis and first and second-line DST in settings where the need is greatest

Residuos de 2,3-dihidro-2,2-dimetilbenzofuran-7-il metilcarbamato (carbofuran) en un suelo con y sin uso agricola

A fin de determinar la residualidad de carbofuran en un Molisol al cabo de un tiempo de aplicación, se realizó un estudio en macetas de 1 kg de suelo a las que se agregó 100 mg L-1 de carbofuran. El suelo utilizado provino de una selección de dos lotes adyacentes, con y sin laboreo. Se tomaron muestras a dos profundidades, según tratamientos: L1 = Lote con cultivo (0 - 20 cm), L2 = Lote con cultivo (20 - 40 cm), L3 = Lote sin laboreo (0 - 20 cm) y L4 = Lote sin laboreo (20 - 40 cm). El muestreo de suelo se hizo a los 0, 7, 30 y 60 días de aplicación del pesticida. Según la residualidad de carbofuran y el nivel de materia orgánica se encontraron diferencias significativas entre fechas, uso y profundidad. La correlación entre contenido de carbofuran y materia orgánica, resultó significativa para L1 y L2 (0.52) teniendo cuenta el uso y según profundidad para L1 y L3 (-0.60). Observandose persistencia en todos los tratamientos en las fechas en que se extrajeron las muestras, siendo mayor en los que poseían un mayor tenor de materia orgánica

CXCL1-CXCR1/2 signaling is induced in human temporal lobe epilepsy and contributes to seizures in a murine model of acquired epilepsy

Abstract CXCL1, a functional murine orthologue of the human chemokine CXCL8 (IL-8), and its CXCR1 and CXCR2 receptors were investigated in a murine model of acquired epilepsy developing following status epilepticus (SE) induced by intra-amygdala kainate. CXCL8 and its receptors were also studied in human temporal lobe epilepsy (TLE). The functional involvement of the chemokine in seizure generation and neuronal cell loss was assessed in mice using reparixin (formerly referred to as repertaxin), a non-competitive allosteric inhibitor of CXCR1/2 receptors. We found a significant increase in hippocampal CXCL1 level within 24 h of SE onset that lasted for at least 1 week. No changes were measured in blood. In analogy with human TLE, immunohistochemistry in epileptic mice showed that CXCL1 and its two receptors were increased in hippocampal neuronal cells. Additional expression of these molecules was found in glia in human TLE. Mice were treated with reparixin or vehicle during SE and for additional 6 days thereafter, using subcutaneous osmotic minipumps. Drug-treated mice showed a faster SE decay, a reduced incidence of acute symptomatic seizures during 48 h post-SE, and a delayed time to spontaneous seizures onset compared to vehicle controls. Upon reparixin discontinuation, mice developed spontaneous seizures similar to vehicle mice, as shown by EEG monitoring at 14 days and 2.5 months post-SE. In the same epileptic mice, reparixin reduced neuronal cell loss in the hippocampus vs vehicle-injected mice, as assessed by Nissl staining at completion of EEG monitoring. Reparixin administration for 2 weeks in mice with established chronic seizures, reduced by 2-fold on average seizure number vs pre-treatment baseline, and this effect was reversible upon drug discontinuation. No significant changes in seizure number were measured in vehicle-injected epileptic mice that were EEG monitored in parallel. Data show that CXCL1-IL-8 signaling is activated in experimental and human epilepsy and contributes to acute and chronic seizures in mice, therefore representing a potential new target to attain anti-ictogenic effects

Oxygen-sensing PHDs regulate bone homeostasis through the modulation of osteoprotegerin

The bone microenvironment is composed of niches that house cells across variable oxygen tensions. However, the contribution of oxygen gradients in regulating bone and blood homeostasis remains unknown. Here, we generated mice with either single or combined genetic inactivation of the critical oxygen-sensing prolyl hydroxylase (PHD) enzymes (PHD1–3) in osteoprogenitors. Hypoxia-inducible factor (HIF) activation associated with Phd2 and Phd3 inactivation drove bone accumulation by modulating osteoblastic/osteoclastic cross-talk through the direct regulation of osteoprotegerin (OPG). In contrast, combined inactivation of Phd1, Phd2, and Phd3 resulted in extreme HIF signaling, leading to polycythemia and excessive bone accumulation by overstimulating angiogenic–osteogenic coupling. Wealso demonstrate that genetic ablation of Phd2 and Phd3 was sufficient to protect ovariectomized mice against bone loss without disrupting hematopoietic homeostasis. Importantly,we identify OPG as a HIF target gene capable of directing osteoblast-mediated osteoclastogenesis to regulate bone homeostasis. Here, we show that coordinated activation of specific PHD isoforms fine-tunes the osteoblastic response to hypoxia, thereby directing two important aspects of bone physiology: cross-talk between osteoblasts and osteoclasts and angiogenic–osteogenic coupling

Accelerometer Cut-Points for Physical Activity Assessment in Adults with Mild to Moderate Huntington’s Disease: A Cross-Sectional Multicentre Study

Accelerometers can estimate the intensity, frequency, and duration of physical activity in healthy adults. Although thresholds to distinguish varying levels of activity intensity using the Actigraph wGT3X-B have been established for the general population, their accuracy for Huntington’s disease (HD) is unknown. We aimed to define and cross-validate accelerometer cut-points for different walking speeds in adults with mild to moderate HD. A cross-sectional, multicentre, case-control, observational study was conducted with a convenience sample of 13 symptomatic ambulatory HD participants. The accelerometer was placed around the right hip, and a heart monitor was fitted around the chest to monitor heart rate variability. Participants walked on a treadmill at three speeds with light, moderate and vigorous intensities. Correlation and receiver operation curve analyses were performed between the accelerometer magnitude vector with relative oxygen and heart rate. Optimal cut-points for walking speeds of 3.2 km/h were ≤2852; 5.2 km/h: >2852 to ≤4117, and in increments until their maximum velocity: >4117. Our results support the application of the disease-specific cut-points for quantifying physical activity in patients with mild to moderate HD and promoting healthy lifestyle interventions.The project leading to these results has received funding from “La Caixa” Foundation (ID100010434), under agreement FUI1-PI008

Case Report: Expanding the phenotypic spectrum of PURA syndrome in South America with the first presentation of concurrent vitiligo

Purine-rich element-binding protein A (PURα) regulates multiple cellular processes. Rare de novo mutations can lead to PURA syndrome, which manifests as a range of multisystem disturbances, including hypotonia, global developmental delay, swallowing disorders, apnea, seizures, visual impairments, and congenital heart defects. We report the case of a Colombian girl with no relevant medical history who was diagnosed with PURA syndrome at the age of 7, due to a heterozygous mutation located at 5q31.2, specifically the variant c.697_699del (p.Phe233del), in exon 1 of the PURA gene. This represents the first documented case of PURA syndrome in South America and the first association of the syndrome with vitiligo, thereby expanding the known phenotypic spectrum. In addition to enriching the literature concerning the phenotypic diversity of PURA syndrome, this report highlights, for the first time, the diagnostic challenges faced by developing countries like Colombia in diagnosing high-burden rare diseases such as PURA syndrome

Estado del arte de la quinua en el mundo en 2013

Alimento de base de las poblaciones andinas desde hace milenios, la quinua se ha convertido hoy en un producto apreciado en el mercado internacional de alimentos dietéticos, orgánicos y equitativos. Este cambio lo iniciaron los mismos productores del Altiplano Sur de Bolivia hace aproximadamente unos 40 años. En medio de un desierto de altura, ellos lograron desarrollar una floreciente producción agrícola de exportación. Aunque cuentan con lucrativos nichos de mercado, los productores de quinua no son agricultores especializados, ni residen de forma permanente en la zona de producción. Estas son algunas de las paradojas que caracterizan la producción de quinua en el Altiplano Sur de Bolivia. Después de describir el origen, la diversidad y los rasgos biológicos del ecotipo Quinua Real en el cual se basa la producción de esta zona, se plantea la importancia de la quinua en los agrosistemas locales y, más allá, en los sistemas de actividades agrícolas y no agrícolas manejados por las familias del Altiplano Sur. Movilidad geográfica y pluriactividad forman parte del modo de vida ancestral de estas poblaciones y determinan hasta hoy en día las condiciones de uso de los recursos territoriales y la organización de los productores en el contexto del auge comercial de la quinua. La producción actual de quinua en la región presenta rasgos de vulnerabilidad agroecológica y social, así como capacidades adaptativas para enfrentarlos. Se resaltan como puntos clave para la sostenibilidad de los agrosistemas locales : i) la concertación de reglas comunales e individuales para el acceso y uso de la tierra en agrosistemas socialmente equitativos y equilibrados entre cultivo y ganadería, ii) las normas internacionales para el reconocimiento de la Quinua Real en los mercados de exportación, iii) una actualización continua de las reglas y normas para mantener la adaptabilidad de los agrosistemas locales a los cambios imprevisibles del contexto socio-ecológico a varias escalas de espacio y de tiempo

Krebs von den Lungen-6 glycoprotein circulating levels are not useful as prognostic marker in COVID-19 pneumonia : A large prospective cohort study

Altres ajuts: Departament de Salut, Generalitat de Catalunya (COVID-PoC BioCAT).Coronavirus disease 2019 (COVID-19) has rapidly expanded worldwide. Currently, there are no biomarkers to predict respiratory worsening in patients with mild to moderate COVID-19 pneumonia. Small studies explored the use of Krebs von de Lungen-6 circulating serum levels (sKL-6) as a prognostic biomarker of the worsening of COVID-19 pneumonia. We aimed at a large study to determine the prognostic value of sKL-6 in predicting evolving trends in COVID-19. We prospectively analyzed the characteristics of 836 patients with COVID-19 with mild lung disease on admission. sKL-6 was obtained in all patients at least at baseline and compared among patients with or without respiratory worsening. The receiver operating characteristic curve was used to find the optimal cutoff level. A total of 159 (19%) patients developed respiratory worsening during hospitalization. Baseline sKL-6 levels were not higher in patients who had respiratory worsening (median {IQR} 315.5 {209-469} vs. 306 {214-423} U/ml p = 0.38). The last sKL-6 and the change between baseline and last sKL-6 were higher in the respiratory worsening group (p = 0.02 and p < 0.0001, respectively). The best sKL-6 cutoff point for respiratory worsening was 497 U/ml (area under the curve 0.52; 23% sensitivity and 85% specificity). sKL-6 was not found to be an independent predictor of respiratory worsening. A conditional inference tree (CTREE) was not useful to discriminate patients at risk of worsening. We found that sKL-6 had a low sensibility to predict respiratory worsening in patients with mild-moderate COVID-19 pneumonia and may not be of use to assess the risk of present respiratory worsening in inpatients with COVID-19 pneumonia

Bariatric surgery and calcifediol treatment, Gordian knot of severe-obesity-related comorbidities treatment

BackgroundObesity (OB) is a chronic metabolic disease with important associated comorbidities and mortality. Vitamin D supplementation is frequently administered after bariatric surgery (BS), so as to reduce OB-related complications, maybe including chronic inflammation.AimThis study aimed to explore relations between vitamin D metabolites and components of the inflammasome machinery in OB before and after BS and their relations with the improvement of metabolic comorbidities.Patients and methodsEpidemiological/clinical/anthropometric/biochemical evaluation was performed in patients with OB at baseline and 6 months after BS. Evaluation of i) vitamin-D metabolites in plasma and ii) components of the inflammasome machinery and inflammatory-associated factors [NOD-like-receptors (NLRs), inflammasome-activation-components, cytokines and inflammation/apoptosis-related components, and cell-cycle and DNA-damage regulators] in peripheral blood mononuclear cells (PBMCs) was performed at baseline and 6 months after BS. Clinical and molecular correlations/associations were analyzed.ResultsSignificant correlations between vitamin D metabolites and inflammasome-machinery components were observed at baseline, and these correlations were significantly reduced 6 months after BS in parallel to a decrease in inflammation markers, fat mass, and body weight. Treatment with calcifediol remarkably increased 25OHD levels, despite 24,25(OH)2D3 remained stable after BS. Several inflammasome-machinery components were associated with improvement in metabolic comorbidities, especially hypertension and dyslipidemia.ConclusionThe beneficial effects of vitamin D on OB-related comorbidities after BS patients are associated with significant changes in the molecular expression of key inflammasome-machinery components. The expression profile of these inflammasome components can be dynamically modulated in PBMCs after BS and vitamin D supplementation, suggesting that this profile could likely serve as a sensor and early predictor of the reversal of OB-related complications after BS