RESUMEN
Osteomalacia is a pathological bone condition consisting in a deficient primary mineralization of the matrix, leading to an accumulation of osteoid tissue and reduced bone mechanical strength. The amounts, properties and organization of bone constituents at tissue level, are known to influence its mechanical properties. It is then important to investigate the relationship between mechanical behavior and tissue composition at this scale in order to provide a better understanding of bone fragility mechanisms associates with this pathology. Our purpose was to analyze the links between ultra-structural properties and the mechanical behavior of this pathological bone tissue (osteomalacia) at tissue level (mineral and osteoid separately, or global). Four bone biopsies were taken from patients with osteomalacia, and subsequently embedded, sectioned, and polished. Then nanoindentation tests were performed to determine local elastic modulus E, contact hardness Hc and true hardness H for both mineralized and organic bone phases and for the global bone. The creep of the bone was also studied using a special indentation procedure in order to assess visco-elasto-plastic (creep) bone behavior. This allowed a detailed study of the rheological models adapted to the bone and to calculate the parameters associated to a Burgers model. Ultra-structural parameters were measured by Fourier Transform InfraRed Microspectroscopy (FTIRM) on the same position as the indents. The use of rheological models confirmed a significant contribution from the organic phase on the viscous character of bone tissue. The elastic E and the elasto-plastic Hc deformation were correlated to both collagen maturity and Mineral/Matrix. The pure plastic deformation H was only correlated to the mineral phase. Our data show that mineral phase greatly affects mechanical variables (moduli and viscosities) and that organic phase (as illustrated in osteoid tissue) may play an important role in the creep behavior of bone. In conclusion, this study brings mechanical and physicochemical values for osteoid and mineral phases.
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Osteomalacia , Huesos , Análisis de Fourier , Dureza , Humanos , ViscosidadRESUMEN
Background. The Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) has been performing active influenza surveillance since 2009 (ClinicalTrials.gov identifier: NCT01517191). Influenza A and B viruses are identified and characterized using real-time reverse-transcriptase polymerase chain reaction (RT-PCR), and multiplex testing has been performed on a subset of patients to identify other respiratory virus aetiologies. Since both methods can identify influenza A and B, a direct comparison was performed.Methods. Validated real-time RT-PCRs from the World Health Organization (WHO) to identify influenza A and B viruses, characterize influenza A viruses into the H1N1 or H3N2 subtypes and describe influenza B viruses belonging to the Yamagata or Victoria lineages. In a subset of patients, the Seeplex RV15 One-Step ACE Detection assay (RV15) kit was also used for the detection of other respiratory viruses.Results. In total, 1111 nasopharyngeal swabs were tested by RV15 and real-time RT-PCRs for influenza A and B identification and characterization. For influenza A, RV15 showed 98.0â% sensitivity, 100â% specificity and 99.7â% accuracy. The performance characteristics of RV15 were similar for influenza A subtypes H1N1 and H3N2. For influenza B, RV15 had 99.2â% sensitivity, 100â% specificity and 99.8â% accuracy, with similar assay performance being shown for both the Yamagata and Victoria lineages.Conclusions. Overall, the detection of circulating subtypes of influenza A and lineages of influenza B by RV15 was similar to detection by real-time RT-PCR. Multiplex testing with RV15 allows for a more comprehensive respiratory virus surveillance in hospitalized adults, without significantly compromising the reliability of influenza A or B virus detection.
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Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza B/aislamiento & purificación , Gripe Humana/virología , Técnicas de Diagnóstico Molecular/métodos , Reacción en Cadena de la Polimerasa Multiplex/métodos , Adulto , Canadá/epidemiología , Femenino , Hospitalización , Humanos , Virus de la Influenza A/clasificación , Virus de la Influenza A/genética , Virus de la Influenza B/clasificación , Virus de la Influenza B/genética , Gripe Humana/diagnóstico , Gripe Humana/epidemiología , Gripe Humana/terapia , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
Acceleration of remodeling activity after menopause leads to bone loss and fragility, however, whether this is associated with modifications of bone matrix quality has been less studied. The impact of variation in bone remodeling rate on bone matrix has been studied mainly in pathologies or anti-osteoporotic treatments. However, in healthy women this has been less studied. We analyzed, at the global level, bone matrix quality in bone biopsies from 3 groups of healthy women (20 per group): 1) before menopause (PreM), 2) 1â¯year after menopause (PostM, paired biopsies with preM), and 3) 14 (±9) years after menopause (LT-PostM). The mean degree of mineralization (DMB) and heterogeneity index (HI) of mineralization were assessed by X-ray microradiography on whole bone matrix; intrinsic properties (mineral/organic ratio, mineral maturity, mineral crystallinity, collagen maturity) were assessed by Fourier Transform Infrared microspectroscopy, microhardness by microindentation, both at a global level and calculated by mean of several measurements over the whole tissue area. In PostM compared to PreM (bone remodeling rate had doubled), mean DMB measured on the entire bone plane (whole bone matrix) of the sample was not different. HI was increased in trabecular bone indicating a higher heterogeneity of mineralization. However, in PostM, mineral/organic ratio (trabecular) and microhardness (cortical and trabecular) were decreased, whereas mineral/collagen maturation or crystal size/perfection were unchanged. Thus, in PostM, the local mineral content and microhardness were first affected. In LT-PostM (bone remodeling rate was 3 times higher), the mean DMB was still not different. However, the mineral/organic ratio, microhardness, mineral maturity, crystallinity all were lower compared to PreM and PostM, in both cortical and trabecular bone. Bone remodeling rate was negatively correlated with microhardness, DMB, mineral/organic and crystallinity. This suggests that increases in bone remodeling rates after menopause have a direct impact on bone quality by inducing the formation of more extensive "immature" bone areas, but the amount of immature bone does not cause modification of the global DMB.
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Densidad Ósea/fisiología , Matriz Ósea/metabolismo , Remodelación Ósea/fisiología , Calcificación Fisiológica/fisiología , Menopausia/metabolismo , Anciano , Femenino , Humanos , Persona de Mediana Edad , Espectroscopía Infrarroja por Transformada de Fourier , Salud de la MujerRESUMEN
BACKGROUND: Recent studies have demonstrated the possibility of negative associations between prior influenza vaccines and subsequent influenza vaccine effectiveness (VE), depending on season and strain. We investigated this association over 4 consecutive influenza seasons (2011-2012 through 2014-2015) in Canada. METHODS: Using a matched test-negative design, laboratory-confirmed influenza cases and matched test-negative controls admitted to hospitals were enrolled. Patients were stratified into 4 groups according to influenza vaccine history (not vaccinated current and prior season [referent], vaccinated prior season only, vaccinated current season only, and vaccinated both current and prior season). Conditional logistic regression was used to estimate VE; prior vaccine impact was assessed each season for overall effect and effect stratified by age (<65 years, ≥65 years) and type/subtype (A/H1N1, A/H3N2, influenza B). RESULTS: Overall, mainly nonsignificant associations were observed. Trends of nonsignificant decreased VE among patients repeatedly vaccinated in both prior and current season relative to the current season only were observed in the A/H3N2-dominant seasons of 2012-2013 and 2014-2015. Conversely, in 2011-2012, during which B viruses circulated, and in 2013-2014, when A/H1N1 circulated, being vaccinated in both seasons tended to result in a high VE in the current season against the dominant circulating subtype. CONCLUSIONS: Prior vaccine impact on subsequent VE among Canadian inpatients was mainly nonsignificant. Even in circumstances where we observed a trend of negative impact, being repeatedly vaccinated was still more effective than not receiving the current season's vaccine. These findings favor continuation of annual influenza vaccination recommendations, particularly in older adults. CLINICAL TRIALS REGISTRATION: NCT01517191.
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Hospitalización , Vacunas contra la Influenza/inmunología , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Estaciones del Año , Vacunación , Anciano , Anciano de 80 o más Años , Canadá/epidemiología , Estudios de Casos y Controles , Femenino , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/inmunología , Virus de la Influenza B/inmunología , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Vigilancia en Salud Pública , Factores de RiesgoRESUMEN
Primary hyperoxaluria is a rare genetic disorder characterized by oxalate overproduction, leading to kidney failure due to nephrocalcinosis, and is eventually responsible for systemic oxalosis. Bone impairment, secondary to oxalate deposits, is one of the many complications that may occur. Skeletal involvement can be difficult to diagnose because of lack of clinical symptoms and therefore needs to be confirmed by invasive testing, such as transiliac bone biopsy. If confirmed, bone oxalosis is the proof of disease severity and that combined liver-kidney transplantation should be performed.
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Oxalato de Calcio/metabolismo , Hiperoxaluria Primaria/metabolismo , Ilion/patología , Nefrocalcinosis/metabolismo , Adulto , Biopsia , Densidad Ósea , Oxalato de Calcio/orina , Humanos , Hiperoxaluria Primaria/tratamiento farmacológico , Hiperoxaluria Primaria/genética , Hiperoxaluria Primaria/orina , Ilion/citología , Ilion/diagnóstico por imagen , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/terapia , Trasplante de Riñón , Masculino , Microrradiografía , Nefrocalcinosis/diagnóstico por imagen , Nefrocalcinosis/genética , Nefrocalcinosis/orina , Osteoblastos/patología , Piridoxina/uso terapéutico , Diálisis Renal , Transaminasas/genéticaRESUMEN
The T cell specific adapter protein (TSAd) is expressed in activated T cells and NK cells. While TSAd is beginning to emerge as a critical regulator of Lck and Itk activity in T cells, its role in NK cells has not yet been explored. Here we have examined susceptibility to virus infections in a murine model using various viral infection models. We report that TSAd-deficient mice display reduced clearance of murine cytomegalovirus (MCMV) that lack the viral MHC class I homologue m157, which is critical for Ly49H-mediated NK cell recognition of infected cells. In this infection model, NK cells contribute in the early stages of the disease, whereas CD8+ T cells are critical for viral clearance. We found that mice infected with MCMV Δm157 displayed reduced viral clearance in the spleen as well as reduced proliferation in spleen NK cells and CD8+ T cells in the absence of TSAd. Though no other immunophenotype was detected in the infection models tested, these data suggests that in the absence of the Ly49H ligand activation, NK cell and CD8+ T cell responses may be compromised in TSAd-deficient mice.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Muromegalovirus/genética , Proteínas Virales/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Antígeno CD11b/metabolismo , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Línea Celular , Proliferación Celular , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/veterinaria , Infecciones por Citomegalovirus/virología , Modelos Animales de Enfermedad , Citometría de Flujo , Genotipo , Humanos , Inmunofenotipificación , Células Asesinas Naturales/citología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Muromegalovirus/fisiología , Mutación , Bazo/citología , Bazo/inmunología , Bazo/virología , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismo , Carga Viral , Replicación ViralRESUMEN
During the 2013/14 influenza season in Canada, 631 of 654 hospitalisations for laboratory-confirmed influenza enrolled in sentinel hospitals were due to Influenza A. Of the 375 with known subtype, influenza A(H1N1) accounted for 357. Interim unmatched vaccine effectiveness adjusted for age and presence of one or more medical comorbidities was determined by test-negative case-control design to be 58.5% (90% confidence interval (CI): 43.9-69.3%) overall and 57.9% (90% CI: 37.7-71.5) for confirmed influenza A(H1N1).
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Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Evaluación de Resultado en la Atención de Salud , Vigilancia de Guardia , Adolescente , Adulto , Anciano , Canadá/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/virología , Laboratorios , Masculino , Persona de Mediana Edad , Estaciones del Año , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
The cabbage maggot, Delia radicum L., has a bimodal pattern of emergence caused by the presence in populations of early and late-emerging genotypes that differ in their pupal development time. These genotypes could also express different egg-laying strategies. To examine oviposition patterns between genotypes and, particularly, their response to temperature, the egg-laying activity of females and egg mortality from each genotype were evaluated at temperatures from 12 to 30°C. Several criteria were used to describe the oviposition pattern: longevity of females, preoviposition period, lifetime fecundity, number of oviposition bouts, duration and number of eggs for each oviposition bout, duration of an oviposition cycle, and time interval between oviposition bouts. All criteria were similar between genotypes, except the preoviposition period and time interval between oviposition bouts. The preoviposition period was 1-4 d longer for the early emerging genotype than for the late-emerging genotype at temperatures <25°C, but similar at temperatures ≥25°C. The time interval between oviposition bouts of early emerging genotype was a few hours longer than for the late-emerging genotype at all temperatures. All oviposition pattern criteria responded to temperature, except the duration of oviposition bouts (â6.5 d) and egg mortality (â11%). The duration of a bout could be a compromise between oogenesis duration and the risks associated with egg deposition. According to these results, early and late-emerging genotypes express similar egg-laying strategies for all temperatures tested.
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Dípteros/fisiología , Genotipo , Oviposición , Temperatura , Animales , Dípteros/genética , Femenino , Fertilidad/genética , Longevidad/genética , Masculino , Oviparidad/genéticaRESUMEN
OBJECTIVES: The goals of this study were: 1) to determine if high-fat diet (HFD) feeding in female mice would negatively impact biomechanical and histologic consequences on the Achilles tendon and quadriceps muscle; and 2) to investigate whether exercise and branched-chain amino acid (BCAA) supplementation would affect these parameters or attenuate any negative consequences resulting from HFD consumption. METHODS: We examined the effects of 16 weeks of 60% HFD feeding, voluntary exercise (free choice wheel running) and BCAA administration in female C57BL/6 mice. The Achilles tendons and quadriceps muscles were removed at the end of the experiment and assessed histologically and biomechanically. RESULTS: HFD feeding significantly decreased the Achilles tendon modulus without histological alterations. BCAA administration significantly decreased the stiffness of Achilles tendons in the exercised normal diet mice. Exercise partially ameliorated both the weight gain and glucose levels in the HFD-fed mice, led to a significant decrease in the maximum load of the Achilles tendon, and an increase in the average fibril diameter of the quadriceps femoris muscle. There were significant correlations between body weight and several biomechanical properties, demonstrating the importance of controlling obesity for maintaining healthy tendon properties. CONCLUSIONS: In summary, this study showed a significant impact of obesity and body weight on tendon biomechanical properties with limited effects of exercise and BCAAs. Cite this article: Bone Joint Res 2013;2:186-92.
RESUMEN
Breast cancer is one of the most common malignancies in human females in the world. One protein that has elevated enzymatic lipase activity in breast cancers in vitro is phospholipase D (PLD), which is also involved in cell migration. We demonstrate that the PLD2 isoform, which was analyzed directly in the tumors, is crucial for cell invasion that contributes critically to the growth and development of breast tumors and lung metastases in vivo. We used three complementary strategies in a SCID mouse model and also addressed the underlying molecular mechanism. First, the PLD2 gene was silenced in highly metastatic, aggressive breast cancer cells (MDA-MB-231) with lentivirus-based short hairpin RNA, which were xenotransplanted in SCID mice. The resulting mouse primary mammary tumors were reduced in size (65%, P<0.05) and their onset delayed when compared with control tumors. Second, we stably overexpressed PLD2 in low-invasive breast cancer cells (MCF-7) with a biscistronic MIEG retroviral vector and observed that these cells were converted into a highly aggressive phenotype, as primary tumors that formed following xenotransplantation were larger, grew faster and developed lung metastases more readily. Third, we implanted osmotic pumps into SCID xenotransplanted mice that delivered two different small-molecule inhibitors of PLD activity (5-fluoro-2-indolyl des-chlorohalopemide and N-[2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4,5]dec-8-yl)ethyl]-2-naphthalenecarboxamide). These inhibitors led to significant (>70%, P<0.05) inhibition of primary tumor growth, metastatic axillary tumors and lung metastases. In order to define the underlying mechanism, we determined that the machinery of PLD-induced cell invasion is mediated by phosphatidic acid, Wiscott-Aldrich Syndrome protein, growth receptor-bound protein 2 and Rac2 signaling events that ultimately affect actin polymerization and cell invasion. In summary, this study shows for the first time that PLD2 has a central role in the development, metastasis and level of aggressiveness of breast cancer, raising the possibility that PLD2 could be used as a new therapeutic target.
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Neoplasias de la Mama/patología , Fosfolipasa D/metabolismo , Animales , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Neoplasias Pulmonares/secundario , Células MCF-7 , Ratones , Ratones SCID , Invasividad Neoplásica , Metástasis de la Neoplasia , Trasplante de Neoplasias , Ácidos Fosfatidicos/biosíntesis , Fosfolipasa D/antagonistas & inhibidores , Fosfolipasa D/genética , Isoformas de Proteínas/metabolismo , Interferencia de ARN , ARN Interferente Pequeño , Transducción de SeñalRESUMEN
UNLABELLED: In paired biopsies of osteoporotic women treated with either strontium ranelate or a placebo for 36 months, characteristics of bone apatite crystals were not influenced by the presence of strontium. The mean rate of substitutions of calcium by strontium ions was 4.5 %. INTRODUCTION: The potential effect of strontium (Sr) on bone apatite crystals was investigated in paired biopsies of osteoporotic women treated with either strontium ranelate (SrRan) or a placebo for 36 months. METHODS: In ten paired biopsies, crystallinity, apparent length and width/thickness of crystals, interplanar distances, and lattice parameters of unit cells were assessed by X-ray diffraction and selected area electron diffraction. RESULTS: All these parameters, reflecting crystal and unit cell characteristics, were not influenced by the presence of Sr and were similar in SrRan and placebo groups after 36 months of treatment. The mean rate of substitutions of calcium by Sr ions was 4.5 %. CONCLUSION: Overall, the quality of bone apatite crystals was maintained after 36 months of treatment with SrRan.
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Apatitas/metabolismo , Conservadores de la Densidad Ósea/farmacología , Huesos/efectos de los fármacos , Compuestos Organometálicos/farmacología , Osteoporosis Posmenopáusica/metabolismo , Tiofenos/farmacología , Anciano , Anciano de 80 o más Años , Biopsia , Conservadores de la Densidad Ósea/uso terapéutico , Huesos/metabolismo , Huesos/patología , Cristalización , Método Doble Ciego , Femenino , Humanos , Ilion/efectos de los fármacos , Ilion/metabolismo , Ilion/patología , Compuestos Organometálicos/uso terapéutico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Osteoporosis Posmenopáusica/patología , Tiofenos/uso terapéutico , Difracción de Rayos X/métodosRESUMEN
Bone is a complex and structured material; its mechanical behavior results from an interaction between the properties of each level of its structural hierarchy. The degree of mineralization of bone (bone density measured at tissue level) and the characteristics of the mineral deposited (apatite crystals) are major determinants of bone strength. Bone remodeling activity acts as a regulator of the degree of mineralization and of the distribution of mineral at the tissue level, directly impacting bone mechanical properties. Recent findings have highlighted the need to understand the underlying process occurring at the nanostructure level that may be independent of bone remodeling itself. A more global comprehension of bone qualities will need further works designed to characterize what are the consequences on whole bone strength of changes at nano- or microstructure levels relative to each other.
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Densidad Ósea/fisiología , Remodelación Ósea/fisiología , Envejecimiento/fisiología , Apatitas/análisis , Enfermedades Óseas/patología , Enfermedades Óseas/fisiopatología , Huesos/química , Huesos/ultraestructura , Cristalización , Femenino , Humanos , Masculino , Osteoporosis Posmenopáusica/patología , Osteoporosis Posmenopáusica/fisiopatologíaRESUMEN
The paper tries to answer two questions: the safety of the injection of gadolinium during breastfeeding; the value of a breast MRI in the nursing mother if breast cancer is suspected. Recent Anglo-Saxon publications are in favour of continued breastfeeding following the injection of gadolinium. In fact, only a minute quantity of contrast product passes into the mother's milk, much less than the threshold recommended in paediatrics in the infant. However, a suspension of lactation for 24h after the injection of gadolinium chelate is still recommended in France. The literature is poor as regards the contribution of the MRI during lactation, although the data indicates that the MRI is contributory, in spite of the physiological changes in the breast during this period. In fact, all of the lesions have been visualised and correctly classified according to the BI-RADS classification by the ACR(1). However, the semiology is specific and has to be known.
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Neoplasias de la Mama/diagnóstico , Lactancia , Imagen por Resonancia Magnética , Complicaciones Neoplásicas del Embarazo/diagnóstico , Trastornos Puerperales/diagnóstico , Adulto , Biopsia , Mama/patología , Lactancia Materna , Neoplasias de la Mama/patología , Medios de Contraste/administración & dosificación , Medios de Contraste/farmacocinética , Femenino , Gadolinio/efectos adversos , Gadolinio/farmacocinética , Humanos , Metástasis Linfática/patología , Leche Humana/química , Leche Humana/metabolismo , Embarazo , Complicaciones Neoplásicas del Embarazo/patología , Trastornos Puerperales/patología , Sensibilidad y Especificidad , Ultrasonografía MamariaRESUMEN
Edaphic factors such as soil temperature and moisture influence soil-dwelling insects, whose most vulnerable stages typically are eggs and young larvae. In this study, the survival of eggs and first-instar larvae of the cabbage maggot, Delia radicum L., was measured under laboratory conditions after exposure to a range of soil temperatures and moistures. When eggs were exposed to constant temperature (20-29°C) and humidity (5-200% [wt:wt]), temperature had no significant effect on survival, whereas humidity <25% [wt:wt] caused egg mortality. The gradual exposure of eggs to high temperatures resulted in low mortality below 33°C, but <5% of eggs survived at 40°C. When first-instar larvae were exposed to constant temperature (17-29°C) and humidity (5-100% [wt:wt]), both factors as well as their interaction had a significant effect on larval survival, which was nil at 5% (wt:wt) for all temperatures but increased from 21.9 to 42.8% at 17°C and from 34.1 to 55.0% at 29°C, for soil moisture contents of 15% and 100% (wt:wt), respectively. Eggs of D. radicum are resistant to low soil moisture and high temperature conditions. Larval survival tends to increase with an increase in soil temperature and moisture. It is suggested that soil temperature be integrated into insect development simulation models instead of air temperature, to build more effective models for cabbage maggot management.
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Dípteros/crecimiento & desarrollo , Control de Insectos/métodos , Suelo/química , Animales , Brassica napus , Dípteros/fisiología , Monitoreo del Ambiente , Humedad , Larva/crecimiento & desarrollo , Larva/fisiología , Óvulo/crecimiento & desarrollo , Óvulo/fisiología , Quebec , TemperaturaRESUMEN
In pre- and post-immunisation sera from children (17-120 months-old) and adults (20-59 years-old) immunised with 2010/11 trivalent inactivated influenza vaccine, we assessed age-related patterns of sero-susceptibility and vaccine-induced cross-reactive antibodies to a representative swine H3N2 (swH3N2) and a related ancestral human H3N2 (A/Sydney/5/1997) influenza virus. Few children but a greater proportion of adults showed pre-immunisation haemagglutination inhibition titres ≥40 to either virus. Titres increased with age among children but decreased in adults. Fewer than 20% showed a four-fold rise in antibody titres to either virus following immunisation. Further investigation is warranted to guide ongoing risk assessment and response to emerging swine H3N2 viruses.
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Anticuerpos Antivirales/metabolismo , Subtipo H3N2 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/epidemiología , Gripe Humana/inmunología , Adulto , Secuencia de Aminoácidos , Animales , Anticuerpos Antivirales/biosíntesis , Canadá/epidemiología , Niño , Preescolar , Reacciones Cruzadas/inmunología , Femenino , Humanos , Lactante , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Porcinos , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/uso terapéutico , Adulto JovenRESUMEN
Described for the first time in 2001, human metapneumovirus (hMPV) has become one of the main viral pathogens responsible for acute respiratory tract infections in children but also in the elderly and immuno-compromised patients. The pathogen most closely related to hMPV is human respiratory syncytial virus (hRSV), the most common cause of bronchiolitis and pneumonia in young children. hMPV has been classified into two main viral groups A and B and has a seasonal distribution in temperate countries with most cases occurring in winter and spring. Given the difficulties encountered in culturing hMPV in vitro, diagnosis is generally achieved using real-time polymerase chain reaction. Like other Paramyxoviridae, hMPV has a negative-sense single-stranded RNA genome that includes 8 genes coding for 9 different proteins. The genomic organization and functions of surface attachment and fusion glycoproteins are relatively similar to those of hRSV. Although many groups have studied the viral life cycle of hMPV, many questions remain unanswered concerning the exact roles of the viral proteins in the attachment, fusion and replication of hMPV. To date, there remains no approved modality to combat hMPV infections. The majority of treatments that have been tested on hMPV have already demonstrated activity against hRSV infections. Some innovative approaches based on RNA interference and on fusion inhibitors have shown efficacy in vitro and in animal studies and could be beneficial in treating human hMPV disease. Difficulties faced inducing a durable immune response represent the biggest challenge in the development of an effective hMPV vaccine. Several strategies, such as the use of live-attenuated viruses generated by reverse genetics or recombinant proteins, have been tested in animals with encouraging results.
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Bronquiolitis Viral , Metapneumovirus , Neumonía Viral , Adulto , Animales , Antivirales/uso terapéutico , Investigación Biomédica/tendencias , Bronquiolitis Viral/tratamiento farmacológico , Bronquiolitis Viral/epidemiología , Bronquiolitis Viral/fisiopatología , Bronquiolitis Viral/virología , Línea Celular , Niño , Preescolar , Humanos , Metapneumovirus/genética , Metapneumovirus/aislamiento & purificación , Metapneumovirus/patogenicidad , Ratones , Infecciones por Paramyxoviridae/epidemiología , Infecciones por Paramyxoviridae/fisiopatología , Infecciones por Paramyxoviridae/virología , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , Neumonía Viral/fisiopatología , Neumonía Viral/virología , Vacunas Virales/uso terapéuticoRESUMEN
Bone is a multiscale composite material made of both a type I collagen matrix and a poorly crystalline apatite mineral phase. Due to remodeling activity, cortical bone is made of Bone Structural Units (BSUs) called osteons. Since osteon represents a fundamental level of structural hierarchy, it is important to investigate the relationship between mechanical behavior and tissue composition at this scale for a better understanding of the mechanisms of bone fragility. The aim of this study is to analyze the links between ultrastructural properties and the mechanical behavior of bone tissue at the scale of osteon. Iliac bone biopsies were taken from untreated postmenopausal osteoporotic women, embedded, sectioned and microradiographed to assess the degree of mineralization of bone (DMB). On each section, BSUs of known DMB were indented with relatively high load (~500 mN) to determine local elastic modulus (E), contact hardness (H(c)) and true hardness (H) of several bone lamellae. Crystallinity and collagen maturity were measured by Fourier Transform InfraRed Microspectroscopy (FTIRM) on the same BSUs. Inter-relationships between mechanical properties and ultrastructural components were analyzed using multiple regression analysis. This study showed that elastic deformation was only explained by DMB whereas plastic deformation was more correlated with collagen maturity. Contact hardness, reflecting both elastic and plastic behaviors, was correlated with both DMB and collagen maturity. No relationship was found between crystallinity and mechanical properties at the osteon level.
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Colágeno Tipo I/metabolismo , Ilion/metabolismo , Ensayo de Materiales/instrumentación , Fenómenos Mecánicos , Microtecnología/instrumentación , Minerales/metabolismo , Anciano , Fenómenos Biomecánicos , Densidad Ósea , Elasticidad , Femenino , Dureza , Humanos , Ilion/fisiopatología , Ilion/ultraestructura , Osteoporosis Posmenopáusica/metabolismo , Osteoporosis Posmenopáusica/patología , Osteoporosis Posmenopáusica/fisiopatología , Análisis de RegresiónRESUMEN
Despite systemic prophylaxis, infection rates after orthopedic surgery can reach more than 1%. A new HAP/TCP bone substitute loaded with 125 mg of gentamicin was designed for prophylactic use. Its aim was to enhance the efficacy of systemic prophylactic treatments by increasing the local antibiotic concentration. The release rate of gentamicin from the bone substitute was investigated after implantation in the femoral condyle of five sheep. In order to investigate the local and systemic gentamicin concentrations, synovial fluids and blood samples were assessed over a 5-day period. The mean gentamicin concentration peak in blood was 4.2 µg/ml and the mean local concentration in synovial fluids during the first 8 h was 305 µg/ml. After 48 h, the concentrations in blood and synovial fluids were less than 0.5 µg/ml. No remaining gentamicin was detected in bone substitutes explanted after 8 days of implantation. The gentamicin release rate from the bone substitutes assessed corresponds to the recommendations for the prophylactic use of antibiotics: high local concentration but limited in time (less than 48 h) not to select antibiotic-resistant bacterial strains. Our results indicated that this implant should be an effective prophylactic tool in orthopedic surgery in combination with systemic prophylaxis.
Asunto(s)
Sustitutos de Huesos/farmacocinética , Fosfatos de Calcio/química , Durapatita/química , Gentamicinas/administración & dosificación , Animales , Sustitutos de Huesos/administración & dosificación , Inmunoensayo , Músculos/metabolismo , Equipo Ortopédico , Ortopedia , Porosidad , Ovinos , Líquido Sinovial/metabolismo , Factores de TiempoRESUMEN
A randomized placebo-controlled double-blind trial of a nasally administered inactivated trivalent influenza vaccine formulated with partially purified meningococcal outer membrane proteins (OMP-TIV) was conducted in 1349 healthy adults aged 18-64 years. Subjects received either vaccine containing 15 µg of haemagglutinin (HA) of each of three influenza strains for the 2003-2004 season on days 0 and 14, or 30 µg on day 0 and saline placebo on day 14, or placebo on days 0 and 14. Vaccination was well tolerated, with similar reactogenicity as placebo. Compared to placebo, statistically significant increases in mean serum haemagglutinin inhibition reciprocal titers and salivary secretory IgA to all 3 antigens were seen on day 28 for both vaccine dose groups. The incidence of culture-positive influenza and fever >37.8°C and cough and one or more of sore throat, runny nose or nasal congestion, muscle or joint ache, headache, fatigue, or chills or culture positive influenza and at least two of these symptoms was low (16/1349; 1.2%). In the intent-to-immunize population too few febrile culture-confirmed illness events (n=4) occurred to perform analysis. Fever occurred infrequently, even in the presence of positive cultures and disabling multi-symptom disease. In participants receiving all doses of either vaccine regimen the incidence of culture-confirmed influenza with respiratory symptoms and with or without fever was 0.77% (7/904) vs. 2.03% (9/443) in placebo recipients (p=0.045, Fisher's exact test; relative risk reduction 62%), despite circulation of a drift variant A/H3N2 that was poorly matched to vaccine. An OMP-TIV vaccine was well tolerated and reduced risk of symptomatic culture confirmed influenza. Vaccine efficacy will need to be validated in a season with a higher attack rate.
Asunto(s)
Vacunas contra la Influenza/efectos adversos , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/aislamiento & purificación , Adolescente , Adulto , Anticuerpos Antivirales/sangre , Proteínas de la Membrana Bacteriana Externa/administración & dosificación , Proteínas de la Membrana Bacteriana Externa/aislamiento & purificación , Método Doble Ciego , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Inmunidad Mucosa , Inmunización Secundaria/métodos , Inmunoglobulina A Secretora/análisis , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/patología , Masculino , Persona de Mediana Edad , Neisseria meningitidis/química , Placebos/administración & dosificación , Saliva/inmunología , Factores de Tiempo , Vacunación/métodos , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/efectos adversos , Vacunas de Productos Inactivados/inmunología , Adulto JovenRESUMEN
It is well known that increasing the ambient temperature increases the metabolic rate and consequently, the foraging rate of most insects. However, temperature experienced during the immature stages of insects affects their adult size (an inverse relationship). Because body size is generally correlated to foraging success, we hypothesized that temperature indirectly influences the foraging efficiency of adult insects through developmental effects. We first investigated the role of parasitoid: host body size ratio on the handling time of Aphidius colemani (Viereck) (Hymenoptera: Braconidae), then tested the prediction that increasing temperature during immature development increases the handling time of adults. As expected, parasitoids took longer to handle large aphids than small aphids. However, large parasitoids did not have shorter handling times than small parasitoids except when attacking large (adult) aphids. Developmental temperature had the predicted effect on parasitoids: Individuals reared at 25°C were smaller than those insects reared at 15°C. Parasitoids reared at 15°C had similar short handling times for both first instar and adult aphids, whereas parasitoids reared at 25°C took longer to handle adult aphids than first instar aphids. The size-mediated effect of temperature through development on parasitoid efficiency was opposite to the more familiar direct effect of temperature through metabolic rate. We conclude that the net effect of temperature on foraging insects will depend on its relative influence on immature and adult stages.