Identification of renin progenitors in the mouse bone marrow that give rise to B-cell leukaemia

cell of origin and triggering events for leukaemia are mostly unknown. Here we show that the bone marrow contains a progenitor that expresses renin throughout development and possesses a B-lymphocyte pedigree. This cell requires RBP-J to differentiate. Deletion of RBP-J in these renin-expressing progenitors enriches the precursor B-cell gene programme and constrains lymphocyte differentiation, facilitated by H3K4me3 activating marks in genes that control the pre-B stage. Mutant cells undergo neoplastic transformation, and mice develop a highly penetrant B-cell leukaemia with multi-organ infiltration and early death. These reninexpressing cells appear uniquely vulnerable as other conditional models of RBP-J deletion do not result in leukaemia. The discovery of these unique renin progenitors in the bone marrow and the model of leukaemia described herein may enhance our understanding of normal and neoplastic haematopoiesis.

Does bracing affect bone health in women with adolescent idiopathic scoliosis?

Purpose: Adolescent idiopathic scoliosis (AIS) is often associated with low bone mineral content and density (BMC, BMD). Bracing, used to manage spine curvature, may interfere with the growth-related BMC accrual, resulting in reduced bone strength into adulthood. The purpose of this study was to assess the effects of brace treatment on BMC in adult women, diagnosed with AIS and braced in early adolescence. Methods: Participants included women with AIS who: (i) underwent brace treatment (AIS-B, n = 15, 25.6 ± 5.8 yrs), (ii) underwent no treatment (AIS, n = 15, 24.0 ± 4.0 yrs), and (iii) a healthy comparison group (CON, n = 19, 23.5 ± 3.8 yrs). BMC and body composition were assessed using dual-energy X-ray absorptiometry. Differences between groups were examined using a oneway ANOVA or ANCOVA, as appropriate. Results: AIS-B underwent brace treatment 27.9 ± 21.6 months, for 18.0 ± 5.4 h/d. Femoral neck BMC was lower (p = 0.06) in AIS-B (4.54 ± 0.10 g) compared with AIS (4.89 ± 0.61 g) and CON (5.07 ± 0.58 g). Controlling for lean body mass, calcium and vitamin D daily intake, and strenuous physical activity, femoral neck BMC was statistically different (p = 0.02) between groups. A similar pattern was observed at other lower extremity sites (p < 0.05), but not in the spine or upper extremities. BMC and BMD did not correlate with duration of brace treatment, duration of daily brace wear, or overall physical activity. Conclusion: Young women with AIS, especially those who were treated with a brace, have significantly lower BMC in their lower limbs compared to women without AIS. However, the lack of a relationship between brace treatment duration during adolescence and BMC during young adulthood, suggests that the brace treatment is not the likely mechanism of the low BMC.

Efecto de la oxidación de lípidos en harina de subproductos de atún sobre el crecimiento del camarón blanco (Penaeus vannamei Bone) en condiciones de laboratorio

Tesis (Maestría en Ciencias con Especialidad en Recursos Alimenticiosy Produccisn Acumcola) UANL

Bone mineral density measurement and osteoporosis treatment after a fragility fracture in older adults: regional variation and determinants of use in Quebec

Affiliation: Pierre Dagenais : Hôpital Maisonneuve-Rosemont, Faculté de médecine, Université de Montréal

Dopamine Receptor Subtypes,IP3, cAMP and cGMP Functional Regulation in Parkinsonism Induced by Unilateral Infusion of Rotenone in Rats: Recovery with Bone Marrow Cells,Serotonin and GABA Supplementation

In the present study, the effects of 5-HT, GABA and Bone Marrow Cells infused intranigrally to substantia nigra individually and in combinations on unilateral rotenone infused Parkinsonism induced rats. Scatchard analysis of DA, DA D1 and D2 receptors in the corpus striatum, cerebral cortex, cerebellum, brain stem and hippocampus showed a significant increase in the Brain regions of rotenone infused rat compared to control. Real Time PCR amplification of DA D1, D2, Bax and ubiquitin carboxy-terminal hydrolase were up regulated in the brain regions of rotenone infused rats compared to control. Gene expression studies of -Synuclien, cGMP and Cyclic AMP response element-binding protein showed a significant down regulation in Rotenone infused rats compared to control. Behavioural studies were carried out to confirm the biochemical and molecular studies.Our study demonstrated that BMC administration alone cannot reverse the above said molecular changes occurring in PD rat. 5-HT and GABA acting through their specific receptors in combination with bone marrow cells play a crucial role in the functional recovery of PD rats. 5-HT, GABA and Bone marrow cells treated PD rats showed significant reversal to control in DA receptor binding and gene expression. 5-HT and GABA have co-mitogenic property. Proliferation and differentiation of cells re-establishing the connections in Parkinson's disease facilitates the functional recovery. Thus, it is evident that 5-HT and GABA along with BMC to rotenone infused rats renders protection against oxidative, related motor and cognitive deficits which makes them clinically significant for cellbased therapy. The BMC transformed to neurons when co-transplanted with 5-HT and GABA which was confirmed with PKH2GL and nestin. These newly formed neurons have functional significance in the therapeutic recovery of Parkinson’s disease.

Bone marrow cells differentiation to neurons in the rat brain using Serotonin and GABA:Their role on glutamate receptors, IP3, cAMP and cGMP functional regulation in unilateral Parkinsonism induced by 6-hydroxydopamine

Parkinson's disease is a chronic progressive neurodegenerative movement disorder characterized by a profound and selective loss of nigrostriatal dopaminergic neurons. Our findings demonstrated that glutamatergic system is impaired during PD. The evaluations of these damages have important implications in understanding the molecular mechanism underlying motor, cognitive and memory deficits in PD. Our results showed a significant increase of glutamate content in the brain regions of 6- OHDA infused rat compared to control. This increased glutamate content caused an increase in glutamatergic and NMDA receptors function. Glutamate receptor subtypes- NMDAR1, NMDA2B and mGluR5 have differential regulatory role in different brain regions during PD. The second messenger studies confirmed that the changes in the receptor levels alter the IP3, cAMP and cGMP content. The alteration in the second messengers level increased the expression of pro-apoptotic factors - Bax and TNF-α, intercellular protein - α-synuclein and reduced the expression of transcription factor - CREB. These neurofunctional variations are the key contributors to motor and cognitive abnormalities associated with PD. Nestin and GFAP expression study confirmed that 5-HT and GABA induced the differentiation and proliferation of the BMC to neurons and glial cells in the SNpc of rats. We also observed that activated astrocytes are playing a crucial role in the proliferation of transplanted BMC which makes them significant for stem cell-based therapy. Our molecular and behavioural results showed that 5-HT and GABA along with BMC potentiates a restorative effect by reversing the alterations in glutamate receptor binding, gene expression and behaviour abnormality that occur during PD. The therapeutic significance in Parkinson’s disease is of prominence.

Apatite-Polymer Composites for the Controlled Dual Delivery of BMP-2 and BMP-6 for Bone Tissue Engineering

The release of growth factors from tissue engineering scaffolds provides signals that influence the migration, differentiation, and proliferation of cells. The incorporation of a drug delivery platform that is capable of tunable release will give tissue engineers greater versatility in the direction of tissue regeneration. We have prepared a novel composite of two biomaterials with proven track records - apatite and poly(lactic-co-glycolic acid) (PLGA) – as a drug delivery platform with promising controlled release properties. These composites have been tested in the delivery of a model protein, bovine serum albumin (BSA), as well as therapeutic proteins, recombinant human bone morphogenetic protein-2 (rhBMP-2) and rhBMP-6. The controlled release strategy is based on the use of a polymer with acidic degradation products to control the dissolution of the basic apatitic component, resulting in protein release. Therefore, any parameter that affects either polymer degradation or apatite dissolution can be used to control protein release. We have modified the protein release profile systematically by varying the polymer molecular weight, polymer hydrophobicity, apatite loading, apatite particle size, and other material and processing parameters. Biologically active rhBMP-2 was released from these composite microparticles over 100 days, in contrast to conventional collagen sponge carriers, which were depleted in approximately 2 weeks. The released rhBMP-2 was able to induce elevated alkaline phosphatase and osteocalcin expression in pluripotent murine embryonic fibroblasts. To augment tissue engineering scaffolds with tunable and sustained protein release capabilities, these composite microparticles can be dispersed in the scaffolds in different combinations to obtain a superposition of the release profiles. We have loaded rhBMP-2 into composite microparticles with a fast release profile, and rhBMP-6 into slow-releasing composite microparticles. An equi-mixture of these two sets of composite particles was then injected into a collagen sponge, allowing for dual release of the proteins from the collagenous scaffold. The ability of these BMP-loaded scaffolds to induce osteoblastic differentiation in vitro and ectopic bone formation in a rat model is being investigated. We anticipate that these apatite-polymer composite microparticles can be extended to the delivery of other signalling molecules, and can be incorporated into other types of tissue engineering scaffolds.

Humerus bone

Photograph of an adult humerus bone.

Morbilidad laboral en el sector agrícola en trabajadores afiliados a una administradora de riesgos laborales (ARL) de Colombia, durante el periodo 2011-2012.

Este estudio muestra la prevalencia por enfermedad laboral de un grupo de trabajadores afiliados a una ARL en Colombia. Compara la morbilidad laboral entre dos grupo de trabajadores expuestos y no expuestos al trabajo agrícola y al interior del grupo de trabajadores agrícolas agrupados en las actividades de corte de caña, cultivo de banano y flores. Se realizó un estudio descriptivo de tipo transversal durante el periodo 2011-2012, mediante la revisión de una base de datos de morbilidad laboral. Se realizó un análisis uni-variado y Bi-variado y se comparó la morbilidad con datos sociodemográficos, grupos de trabajadores agrícolas y no agrícolas, y actividad productiva del sector agrícola. Se revisaron 3129 diagnósticos de enfermedad profesional durante el periodo de estudio, 433 diagnósticos fueron trabajadores agrícolas y 2696 pertenecieron a otros grupos de trabajadores. Los desórdenes Osteomusculares fueron los diagnósticos más prevalentes en el grupo Agro 92% y No Agro 86% y en las actividades de corte de caña, cultivo de banano y flores. Entre el grupo Agrícola y no agrícola se encontraron diferencias significativas en los siguientes diagnósticos: Síndrome del túnel del carpo, Síndrome de manguito rotador, Otras sinovitis y tenosinovitis, Lumbago no Especificado, Hipoacusia Neurosensorial Bilateral y epicondilitis lateral; de igual manera se encontraron diferencias entre las actividades de corte de caña y cultivo de banano y flores en los diagnósticos de: Epicondilitis, Sinovitis, Síndrome del túnel del Carpo y Trastorno lumbar. El factor de riesgo más prevalente en el grupo agrícola fue el Ergonómico con el 92.8% de los casos

Prevalencia de síntomas sugestivos del síndrome del túnel del carpo en trabajadores administrativos y asistenciales en IPS de Cundinamarca (Tocancipá, Sopo, Zipaquirá) en 2013

Este artículo muestra un estudio descriptivo transversal a través del cuestionario Boston respecto de los síntomas sugestivos del Síndrome del Túnel del Carpo (STC) en trabajadores asistenciales y administrativos de una IPS con sede en Cundinamarca.

Validación diagnóstica del test neural 1 para el síndrome de túnel del carpo

El objetivo de este estudio fue realizar una prueba de validez diagnostica del test neural 1 para el diagnóstico del Síndrome de Túnel del Carpo (STC) utilizando como prueba de referencia o de oro el test de conducción nerviosa. En este estudio participaron 115 sujetos, 230 manos con sospecha clínica de STC quienes fueron evaluados con el test de conducción nerviosa y el test neural 1. Se encontró una sensibilidad del 93.0% (IC 95%:88,21-96,79) y una especificidad del 6,67% (IC 95%:0,0-33,59), razón de verosimilitud positiva fue de 1,00 y razón de verosimilitud negativa de 1,05. Valor predictivo positivo de 86,9% y un valor predictivo negativo de 12,5%. Se concluye que el test neural 1 es una prueba clínica de alta sensibilidad y baja especificidad de gran utilidad para el monitoreo e identificación del STC. Es un procedimiento para el diagnóstico clínico de bajo costo que puede incluirse en los exámenes de rutina de los trabajadores como complemento a las pruebas clínicas sugeridas por las Gatiso para dar mayor precisión a la identificación temprana del STC. Se sugiere combinarla con otros test de mayor especificidad para ser aplicada en trabajadores en condiciones de riesgo o que presenten síntomas en miembros superiores y realizar otros estudios en donde participen sujetos sin diagnóstico clínico del STC.

Prevalencia de patologías osteomusculares del miembro superior y su relación con factores ocupacionales en trabajadores de una empresa de flores. Bogotá 2015

Antecedentes: Las patologías osteomusculares del miembro superior son una importante causa de morbilidad laboral a nivel mundial y en nuestro país, particularmente en el sector de la floricultura. Del desarrollo de estos desórdenes se derivan importantes costos derivados del ausentismo laboral, incapacidades y secuelas. Objetivo: determinar la prevalencia de patología osteomuscular de miembro superior con calificación de origen de enfermedad laboral, en los trabajadores con diagnóstico de patología musculo esquelética de miembro superior y su relación con algunos factores ocupacionales y demográficos. Metodología: Estudio de corte transversal en el que se revisaron datos secundarios procedentes de una base de datos del servicio de salud ocupacional entre enero y mayo de 2015, correspondiente a 465 operarios (no administrativos) a término indefinido de una empresa floricultora de Bogotá, incluyendo únicamente aquellos trabajadores con patologías osteomusculares de miembro superior, que contaban con la clasificación en el diagnóstico ya sea como enfermedad laboral o enfermedad común y mayores de edad. Se excluyeron 19 trabajadores, quienes habían sido reubicados en nuevos sitios de trabajo y no se contó con la información para determinar su actividad antes de realizar el cambio. Se evaluaron las siguientes variables: sexo, edad, antigüedad y el cargo desempeñados por los operarios. La relación entre variables se realizó con la prueba de chi2 de Pearson. Se midió la magnitud de la asociación por medio de OR con sus respectivos intervalos de confianza del 95%. Resultados: Se incluyó a 373 operarios a término fijo, con una media de edad de 39 años (DE=5.55) y una media de antigüedad en el cargo de 6 años (DE=1.15). El 82.84% correspondió al sexo femenino. La prevalencia de enfermedad laboral osteomuscular de miembro superior fue del 54,4%. En el análisis de relación entre la calificación de la enfermedad, y demás variables (sexo, antigüedad en el cargo, edad, actividad desempeñada, localización de la lesión); se encontró que: estar entre los 40 a 49 años (OR= 1,7; IC-95%:1,12 – 2,79), diagnóstico de síndrome de manguito (OR= 4.45; IC-95%: 2.48 – 8.23) y el síndrome de túnel de carpo (OR= 4.22; IC-95%: 2.45 – 7.41) se asociaron a enfermedad laboral. Conclusiones: La prevalencia de enfermedad laboral de patología osteomuscular de miembro superior en los operarios de un cultivo de flores de la Sabana de Bogotá es del (54,4%). Se encontró una mayor asociación con el síndrome del manguito rotador y enfermedad laboral. No se encontró asociación entre la enfermedad laboral y la actividad desempeñada, el tiempo de exposición, ni con el sexo del trabajador.

The role of glutamate receptors in cholesteatoma induced bone resorption

This paper discusses a study examining a new model of cholesteatoma induced bone resorption in mice using autologous implantation of pinna dermis to the surface of the skull and the role of glutamate receptors in reducing the number of osteoclasts.

Bone-conducted tones masked by air-conducted noise

This paper presents a study designed to develop and evaluate a method for obtaining monaural thresholds for bone-conducted signals masked by air-conducted noises.

The role of integrin avB3 in bone remodeling

This paper examines the role of the avB3 integrin in osteoclastic resorption using a model of a localized inflammatory bone loss.