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1.
Artículo en Inglés | MEDLINE | ID: mdl-39058433

RESUMEN

Despite exercise intolerance being predictive of outcomes in pulmonary arterial hypertension (PAH), its underlying cardiac mechanisms are not well described. The aim of the study was to explore the biventricular response to exercise and its associations with cardiorespiratory fitness in children with PAH. Participants underwent incremental cardio-pulmonary exercise testing and simultaneous exercise echocardiography on a recumbent cycle ergometer. Linear mixed models were used to assess cardiac function variance and associations between cardiac and metabolic parameters during exercise. Eleven participants were included with a mean age 13.4 ±2.9 years. Right ventricle (RV) systolic pressure (RVsp) increased from a mean of 59 ±25 mmHg at rest to 130 ±40 mmHg at peak exercise (p<0.001), while RV fractional area change (RV-FAC) and RV free wall longitudinal strain (RVFW-Sl) worsened (35.2% vs 27%, p=0.09 and -16.6% vs -14.6%, p=0.1, respectively). At low and moderate intensity exercise, RVsp was positively associated with stroke volume and O2 pulse (p<0.1). At high intensity exercise RV-FAC, RVFW-Sl and left ventricular longitudinal strain were positively associated with oxygen uptake and O2 pulse (p<0.1), while stroke volume decreased towards peak (p=0.04). In children with PAH, the increase of pulmonary pressure alone does not limit peak exercise, but rather the concomitant reduced RV functional reserve, resulting in RV-PA uncoupling, worsening of inter-ventricular interaction and LV dysfunction. A better mechanistic understanding of PAH exercise physiopathology can inform stress testing and cardiac rehabilitation in this population.

2.
Cell Biochem Funct ; 42(3): e4012, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38584583

RESUMEN

Osteoarthritis (OA) is characterised by the deterioration of cartilage in the joints and pain. We hypothesise that semaphorin-3A (sema-3A), a chemorepellent for sensory nerves, plays a role in joint degradation and pain. We used the mechanical joint loading (MJL) model of OA to investigate sema-3A expression in the joint and examine its association with the development of OA and pain. We also analyse its effect on chondrocyte differentiation using the ATDC5 cell line. We demonstrate that sema-3A is present in most tissues in the healthy joint and its expression increases in highly innervated tissues, such as cruciate ligaments, synovial lining and subchondral bone, in loaded compared to nonloaded control joints. In contrast, sema-3A expression in cartilage was decreased in the severe OA induced by the application of high loads. There was a significant increase in circulating sema-3A, 6 weeks after MJL compared to the nonloaded mice. mRNA for sema-3A and its receptor Plexin A1 were upregulated in the dorsal root ganglia of mice submitted to MJL. These increases were supressed by zoledronate, an inhibitor of bone pain. Sema-3A was expressed at all stages of Chondrocyte maturation and, when added exogenously, stimulated expression of markers of chondrocyte differentiation. This indicates that sema-3A could affect joint tissues distinctively during the development of OA. In highly innervated joint tissues, sema-3A could control innervation and/or induce pain-associated neuronal changes. In cartilage, sema-3A could favour its degeneration by modifying chondrocyte differentiation.


Asunto(s)
Huesos , Semaforina-3A , Animales , Ratones , Huesos/metabolismo , Diferenciación Celular , Línea Celular , Dolor , Semaforina-3A/genética , Semaforina-3A/metabolismo
3.
J Clin Densitom ; 27(3): 101494, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38677082

RESUMEN

PURPOSE: Osteoporosis is a pressing public health concern among older adults, contributing to substantial mortality and morbidity rates. Low- to middle-income countries (LMICs) often grapple with limited access to dual-energy X-ray absorptiometry (DXA), the gold standard for early osteoporosis detection. This study aims to assess the performance of the FRAX® score as a population-wide screening tool for predicting osteoporosis risk, rather than fracture, in individuals aged 50 and above within an LMIC context. METHODS: This retrospective cohort study (n=864) assessed the performance of the FRAX® score for predicting osteoporosis risk using comparative c-statistics from Receiver Operating Characteristic (ROC) curves. Hazard ratios (HR) and 95 % confidence intervals (CI) were calculated, with p-values <0.05 indicating statistically significant. RESULTS: The 10-year FRAX® probability for hip fracture, calculated without bone mass density (BMD), exhibited significantly superior performance compared to the 10-year FRAX® probability for major fracture in predicting osteoporosis risk (AUROC: 0.71 versus 0.67, p<0.001). Within 2 to 10 years of follow-up, the 10-year FRAX® probability for hip fracture showed both greater predictive performance and net benefit in the decision curve compared to the FRAX® 10-year probability for major fracture. A newly established cutoff of 1.9 % yielded a negative predictive value of 92.9 % (95 %CI: 90.4-94.8 %) for the 10-year FRAX® probability for hip fracture. CONCLUSION: The 10-year FRAX® probability for hip fracture estimated without BMD emerges as an effective 10-year screening tool for identifying osteoporosis risk in aged 50 and older, especially when confronted with limited access to DXA scans in LMICs. MINI ABSTRACT: The Fracture Risk Assessment Tool score performance as an osteoporosis screening tool was assessed in areas with limited dual-energy X-ray access. The hip fracture probability showed better performance than major fracture probability within 2 to 10 years. The tool emerges as effective for screening osteoporosis risk in individuals over 50.


Asunto(s)
Absorciometría de Fotón , Densidad Ósea , Tamizaje Masivo , Osteoporosis , Fracturas Osteoporóticas , Humanos , Medición de Riesgo/métodos , Anciano , Femenino , Masculino , Estudios Retrospectivos , Osteoporosis/diagnóstico por imagen , Osteoporosis/complicaciones , Persona de Mediana Edad , Fracturas Osteoporóticas/epidemiología , Tamizaje Masivo/métodos , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/epidemiología , Curva ROC , Países en Desarrollo , Anciano de 80 o más Años , Configuración de Recursos Limitados
4.
Dermatol Online J ; 30(2)2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38959922

RESUMEN

Febrile ulceronecrotic Mucha-Habermann disease is a rare and severe variant of pityriasis lichenoides, characterized by sudden onset of generalized ulceronecrotic papules that rapidly coalesce into ulcers associated with high fever. Systemic manifestations such as intravascular disseminated coagulation and pulmonary, cardiac, gastrointestinal, and central nervous system involvement are common. Treatment is based on oral corticosteroids, immunosuppressive drugs such as methotrexate, and general supportive treatment. The present case describes a stepwise approach to a patient with Mucha-Habermann disease with insufficient response to methotrexate.


Asunto(s)
Metotrexato , Pitiriasis Liquenoide , Humanos , Fiebre/etiología , Herpes Simple , Inmunosupresores/uso terapéutico , Metotrexato/uso terapéutico , Pitiriasis Liquenoide/patología , Pitiriasis Liquenoide/tratamiento farmacológico , Úlcera Cutánea/etiología , Úlcera Cutánea/tratamiento farmacológico , Úlcera Cutánea/patología
5.
Rheumatology (Oxford) ; 62(7): 2621-2630, 2023 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-36398888

RESUMEN

OBJECTIVE: Class 3 semaphorins are reduced in the synovial tissue of RA patients and these proteins are involved in the pathogenesis of the disease. The aim of this study was to identify the transcription factors involved in the expression of class 3 semaphorins in the synovium of RA patients. METHODS: Protein and mRNA expression in synovial tissue from RA and individuals at risk (IAR) patients, human umbilical vein endothelial cells (HUVEC) and RA fibroblast-like synoviocytes (FLS) was determined by ELISA, immunoblotting and quantitative PCR. TCF-3, EBF-1 and HOXA5 expression was knocked down using siRNA. Cell viability, migration and invasion were determined using MTT, calcein, wound closure and invasion assays, respectively. RESULTS: mRNA expression of all class 3 semaphorins was significantly lower in the synovium of RA compared with IAR patients. In silico analysis suggested TCF-3, EBF-1 and HOXA5 as transcription factors involved in the expression of these semaphorins. TCF-3, EBF-1 and HOXA5 silencing significantly reduced the expression of several class 3 semaphorin members in FLS and HUVEC. Importantly, HOXA5 expression was significantly reduced in the synovium of RA compared with IAR patients and was negatively correlated with clinical disease parameters. Additionally, TNF-α down-regulated the HOXA5 expression in FLS and HUVEC. Finally, HOXA5 silencing enhanced the migratory and invasive capacities of FLS and the viability of HUVEC. CONCLUSION: HOXA5 expression is reduced during the progression of RA and could be a novel therapeutic strategy for modulating the hyperplasia of the synovium, through the regulation of class 3 semaphorins expression.


Asunto(s)
Artritis Reumatoide , Semaforinas , Sinoviocitos , Humanos , Semaforinas/genética , Células Cultivadas , Membrana Sinovial/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Sinoviocitos/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patología , Factores de Transcripción/metabolismo , ARN Mensajero/metabolismo , Fibroblastos/metabolismo , Proliferación Celular , Proteínas de Homeodominio/metabolismo , Proteínas de Homeodominio/uso terapéutico
6.
Plant Cell Environ ; 46(11): 3445-3463, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37565511

RESUMEN

Nitric oxide (NO) and reactive oxygen are common factors in multiple plant responses to stress, and their involvement in hypoxia-triggered responses is key to ensure growth under adverse environmental conditions. Here, we analyse the regulatory functions exerted by hypoxia-, NO- and oxidative stress-inducible Arabidopsis gene coding for the VQ motif-containing protein 10 (VQ10). A hypermorphic vq10-H mutant allowed identifying VQ10-exerted regulation on root and shoot development as well as its role in regulating responses to NO and oxidative stress. Enhanced VQ10 expression in vq10-H plants led to enhanced elongation of the primary root, and increased root cell division and meristem size during early postgermination development. In shoots, VQ10 activation of cell division was counteracted by WRKY33-exerted repression, thus leading to a dwarf bushy phenotype in plants with enhanced VQ10 expression in a wrky33 knock-out background. Low number of differentially expressed genes were identified when vq10-H versus Col-0 plants were compared either under normoxia or hypoxia. vq10-H and VQ10ox plants displayed less tolerance to submergence but, in turn, were more tolerant to oxidative stress and less sensitive to NO than wild-type plants. VQ10 could be a node integrating redox-related regulation on development and stress responses.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Meristema , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Óxido Nítrico/metabolismo , Raíces de Plantas/metabolismo , Arabidopsis/metabolismo , Estrés Oxidativo , Regulación de la Expresión Génica de las Plantas
7.
J Clin Densitom ; 26(2): 101362, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36967321

RESUMEN

BACKGROUND: Thyroid dysfunction and osteoporosis are conditions strongly associated with aging, and the prevalence of both conditions is expected to increase in the coming decades. Thyroid hormones regulate bone metabolism, and the role of subclinical hypothyroidism on bone mineral density (BMD) is still controversial. Hence, this study aims to assess the association of subclinical hypothyroidism with femoral osteopenia and osteoporosis in individuals aged 50 years or older. METHODOLOGY: This retrospective cohort study was carried out with 864 outpatients having at least one result for TSH levels before the first record of dual-energy X-ray absorptiometry (DXA). The primary endpoints were osteopenia (-2.5 standard deviation (SD)

Asunto(s)
Enfermedades Óseas Metabólicas , Hipotiroidismo , Osteoporosis , Humanos , Absorciometría de Fotón , Densidad Ósea/fisiología , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Enfermedades Óseas Metabólicas/epidemiología , Hipotiroidismo/complicaciones , Hipotiroidismo/epidemiología , Osteoporosis/epidemiología , Estudios Retrospectivos , Tirotropina , Persona de Mediana Edad
8.
Vet Dermatol ; 34(6): 495-504, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37434336

RESUMEN

BACKGROUND: Antibacterial effect studies of commercial antiseptics typically have evaluated hair and not the skin. OBJECTIVES: To evaluate the antibacterial effects of mousse products on both canine skin and hair. ANIMALS: Fifteen short-haired and eight long-haired dogs without skin disease. MATERIALS AND METHODS: Five mousses were applied once: (1) 2% chlorhexidine and 2% miconazole; (2) 0.05% phytosphingosine; (3) 2% salicylic acid and 10% ethyl lactate; (4) 3% chlorhexidine and 0.5% climbazole; and (5) 2% chlorhexidine and 1% ketoconazole. Skin swabs and hair were collected from application sites before treatment, and at 1 h and at Day (D)2, D4, D8, D10 and D14 post-treatment. Skin swabs and hair were placed on Mueller-Hinton plates inoculated with Staphylococcus pseudintermedius inoculum suspension. Inhibition zones were measured after incubation. RESULTS: Inhibition was not noted with mousses 2 and 3. In mousse 5, inhibition zone sizes produced by swabs from long- and short-haired dogs were not significantly different (p = 0.105), and all swabs and hair produced inhibition until D14, regardless of hair length. By contrast, in mousse 1, inhibition zones produced by swabs from long-haired dogs were smaller than those from short-haired dogs (p < 0.001), and swabs from long-haired dogs produced a shorter duration of bacterial inhibition than hair. CONCLUSIONS AND CLINICAL RELEVANCE: The antibacterial effects of mousse 5 were not affected by hair length. Hair may be acceptable for evaluating effects on the skin in short-haired dogs. However, long hair may interfere with product distribution and duration of bacterial inhibition. Therefore, the evaluation of hair alone may overestimate clinically relevant antibacterial effects.


Asunto(s)
Clorhexidina , Enfermedades de los Perros , Perros , Animales , Clorhexidina/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Staphylococcus , Cabello , Bacterias , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/microbiología
9.
J Sep Sci ; 44(16): 3107-3116, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34081839

RESUMEN

A simple method for the analysis of 13 synthetic musk compounds and six ultraviolet filters in soil samples was developed using a modified dispersive solid-phase methodology known as "Quick, Easy, Cheap, Effective, Rugged and Safe," followed by gas chromatography-triple quadrupole mass spectrometry. The methodology was validated by assessing linearity ranges, detection limits, precision, and accuracy. The method detection limit ranged between 0.01 and 10.00 ng/g dry weight and accuracy from 81 to 122%. A good precision was achieved, with relative standard deviation <10%. The applicability of the methodology was tested using different types of soils. Both synthetic musks and ultraviolet filters were detected in all soil samples. The most frequently detected compounds were benzophenone, octocrylene, 2-ethylhexyl 4-dimethylaminobenzoate, 2-ethylhexyl 4-methoxycinnamate, and galaxolide. Higher levels were detected for benzophenone (maximum value of 158 ng/g dry weight) and octocrylene (137 ng/g dry weight). In comparison with conventional techniques, this method uses lower amounts of solvents and sorbents, producing less waste ("greener" technique) and comparable performances. In addition, it presents as main advantages the simplicity, speed (short extraction/cleaning time), low cost, and minimum handling of extracts, which can minimize the possibility of samples cross-contamination.

10.
Brain Inj ; 35(1): 72-81, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33307834

RESUMEN

Objective: To investigate the characteristics of head injury (HI) and its association with offending behaviour, psychological and neurobehavioral functioning, and cognitive performance in female prisoners.Methods: Using a cross-sectional design, female prisoners in the UK reporting a HI with a loss of consciousness (LOC) over ten minutes (n = 10) were compared with a group without a HI with LOC over ten minutes (n = 41) across a range of measures; including scores on standardized clinical questionnaires and performance-based cognitive assessments. Semi-structured clinical interviews assessed HI and forensic history, with forensic history triangulated against the prison database.Results: Domestic abuse was the most frequently reported cause of HI. The HI with LOC group had been to prison a greater number of times and had committed a greater number violent offences. No significant difference was found on self-reported psychological and neurobehavioral measures, or between the groups' cognitive functioning on neuropsychological tests.Conclusions: Psychosocial factors such as trauma may contribute to higher rates of violent offending and imprisonment in those with a HI with LOC. Domestic abuse is an important factor in HI amongst female prisoners. Forensic screening and interventions need to be designed, adapted and evaluated with consideration of trauma and HI.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Traumatismos Craneocerebrales , Prisioneros , Estudios Transversales , Femenino , Humanos , Violencia
11.
Neuropsychol Rehabil ; 30(5): 948-960, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30272531

RESUMEN

The aim of this study was to investigate the psychometric properties and screening accuracy of the Brain Injury Screening Index (BISI), a self-report questionnaire designed to identify a history of acquired brain injury. The study was conducted in a closed male prison in the UK. The purposive sample comprised 55 male prisoners who arrived at the establishment during the study. A repeated measures design was used, where the Brain Injury Screening Index (BISI) was administered on three occasions. Inter-rater reliability was poor to moderate, but test retest reliability was moderate to good. Medical records were not available for all participants, but the limited number obtained resulted in a sensitivity of .38 to .71 and specificity of .47 to .70 across the three screening administrations of the BISI. The limitations of the present findings are discussed in the context of the use of the tool in custodial environments. It is argued that these results suggest that, when used as recommended, the BISI has acceptable reliability and validity as an initial screen for identifying individuals who should receive support and a comprehensive neuropsychological assessment, and it merits further investigation and development.


Asunto(s)
Lesiones Encefálicas/diagnóstico , Criminales , Pruebas Neuropsicológicas/normas , Psicometría/normas , Autoinforme/normas , Adulto , Conmoción Encefálica/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Prisiones , Psicometría/instrumentación , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
12.
Neuropsychol Rehabil ; 30(7): 1318-1347, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30843470

RESUMEN

To evaluate the efficacy of neurobehavioural rehabilitation (NbR) programmes, services should employ valid, reliable assessment tools; the ability to detect change on repeated assessment is a particular requirement. The United Kingdom Rehabilitation Outcomes Collaborative (UKROC) requires neurorehabilitation services to collect data using a standardized basket of measures, but the responsiveness and usefulness of using these in the context of NbR remains unknown. Anonymous data collected at two assessments for 123 people were examined using multiple methods to determine responsiveness of four outcome measures routinely used in NbR (HoNOS-ABI, FIM + FAM UK, MPAI-4, SASNOS). Predictive validity of two measures of rehabilitation complexity (RCS-E, SRS) regarding the extent of difference scores on these outcome measures at reassessment was also determined. All four outcome measures demonstrated responsiveness, with higher levels for SASNOS and MPAI-4 when only participants categorized as "most likely to change" at first assessment were analyzed. Predictive validity of the RCS-E and SRS in estimating the extent of change was variable. SRS was only predictive of improvement on the MPAI-4 whilst RCS-E was not predictive at all. Recommendations are made regarding ideal characteristics of NbR outcome measures, along with the need to develop measures of rehabilitation complexity specifically conceptualized for these programmes.


Asunto(s)
Lesiones Encefálicas/rehabilitación , Rehabilitación Neurológica/normas , Evaluación de Resultado en la Atención de Salud/normas , Evaluación de Programas y Proyectos de Salud , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Reino Unido
13.
J Am Anim Hosp Assoc ; 56(2): 133-138, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31961218

RESUMEN

An ∼12 yr old castrated mixed-breed dog was evaluated for a 7 wk progressive history of intermittent hyporexia, lethargy, and erosive dermatitis. Initial examination revealed disseminated papules and macules coalescing to irregularly shaped and serpiginous plaques with widespread erosion progressing to ulceration. Skin histopathology revealed transepidermal keratinocyte apoptosis with lymphocyte satellitosis and lymphocytic and histiocytic interface infiltrate. Histopathology combined with clinical signs and history were compatible with the diagnosis of erythema multiforme major. Treatment was initiated with multidrug immunosuppression. Following 36 hr with no improvement, intravenous human immunoglobulin (0.45 mg/kg IV) was administered resulting in notable improvement in the dog's attitude and appetite within 2 hr and the dog's skin lesions within 48 hr. Following discharge, the dog improved daily with near complete resolution of dermatologic disease achieved 1 mo postdischarge. All immunosuppressive medications were ultimately discontinued 5 mo following presentation. This is the first report of a dog with erythema multiforme major that has been successfully treated with a combination of intravenous immunoglobulin and immunosuppression.


Asunto(s)
Enfermedades de los Perros/tratamiento farmacológico , Eritema Multiforme/veterinaria , Inmunoglobulinas/uso terapéutico , Inmunosupresores/uso terapéutico , Animales , Enfermedades de los Perros/patología , Perros , Eritema Multiforme/tratamiento farmacológico , Eritema Multiforme/patología , Humanos , Masculino
14.
Vet Dermatol ; 30(3): 183-e57, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30887651

RESUMEN

BACKGROUND: Topical therapy alone can be effective in the treatment of canine pyoderma. Topical products are commercially available as shampoos, sprays, wipes and mousses. To date, no studies have evaluated the efficacy of commercially available mousse products in the treatment of canine pyoderma. OBJECTIVE: To determine the residual antibacterial activity of canine hairs treated with mousse products containing different active ingredients. ANIMALS: Fifteen client-owned dogs with no history of dermatological disease. METHODS AND MATERIALS: Dogs were treated once with five mousse products [(i) 2% chlorhexidine and 1% ketoconazole, (ii) 2% chlorhexidine and 2% miconazole, (iii) 3% chlorhexidine and 0.5% climbazole, (iv) 2% salicylic acid 10% ethyl lactate and (v) phytosphingosine HCl 0.05%; control]. Hair samples were collected from each treatment area before application, one hour after application and on days 2, 4, 7, 10 and 14 post-treatment. Collected hairs were weighed and plated on Mueller-Hinton agar plates streaked with a Staphylococcus pseudintermedius isolate showing no antimicrobial resistance. Plates were incubated for 24 h and bacterial growth inhibition zones around the hairs were measured. RESULTS: Mousses 1, 2 and 3 created significant inhibition zones up to Day 10 when compared to pre-treatment samples. On Day 14, only mousse 3 produced a significant zone of inhibition when compared to the pre-treatment sample. Mousses 4 and 5 showed no statistical difference between any of the samples. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest that three of the mousse products had residual activity in inhibiting S. pseudintermedius growth in vitro for at least 10 days.


Asunto(s)
Antibacterianos/análisis , Residuos de Medicamentos/análisis , Preparaciones para el Cabello/química , Piodermia/veterinaria , Infecciones Cutáneas Estafilocócicas/veterinaria , Staphylococcus/efectos de los fármacos , Administración Tópica , Animales , Antibacterianos/administración & dosificación , Clorhexidina/administración & dosificación , Enfermedades de los Perros/tratamiento farmacológico , Perros , Cabello , Cetoconazol/administración & dosificación , Miconazol/administración & dosificación , Pruebas de Sensibilidad Microbiana , Mascotas , Piodermia/tratamiento farmacológico , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico
15.
Genet Med ; 20(10): 1196-1205, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29388947

RESUMEN

PURPOSE: Fresh-frozen (FF) tissue is the optimal source of DNA for whole-genome sequencing (WGS) of cancer patients. However, it is not always available, limiting the widespread application of WGS in clinical practice. We explored the viability of using formalin-fixed, paraffin-embedded (FFPE) tissues, available routinely for cancer patients, as a source of DNA for clinical WGS. METHODS: We conducted a prospective study using DNAs from matched FF, FFPE, and peripheral blood germ-line specimens collected from 52 cancer patients (156 samples) following routine diagnostic protocols. We compared somatic variants detected in FFPE and matching FF samples. RESULTS: We found the single-nucleotide variant agreement reached 71% across the genome and somatic copy-number alterations (CNAs) detection from FFPE samples was suboptimal (0.44 median correlation with FF) due to nonuniform coverage. CNA detection was improved significantly with lower reverse crosslinking temperature in FFPE DNA extraction (80 °C or 65 °C depending on the methods). Our final data showed somatic variant detection from FFPE for clinical decision making is possible. We detected 98% of clinically actionable variants (including 30/31 CNAs). CONCLUSION: We present the first prospective WGS study of cancer patients using FFPE specimens collected in a routine clinical environment proving WGS can be applied in the clinic.


Asunto(s)
Variaciones en el Número de Copia de ADN/genética , Genoma Humano/genética , Neoplasias/genética , Secuenciación Completa del Genoma/métodos , Toma de Decisiones , Femenino , Humanos , Masculino , Neoplasias/sangre , Neoplasias/patología , Adhesión en Parafina , Polimorfismo de Nucleótido Simple/genética
16.
J Head Trauma Rehabil ; 33(5): E33-E41, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29194177

RESUMEN

OBJECTIVE: To evaluate the effectiveness of an automated interactive prompting technology in supporting the morning routine of persons with acquired brain injury. The morning routine included maintaining personal hygiene and dressing. SETTING: An inpatient neurorehabilitation hospital. PARTICIPANTS: Persons with acquired brain injury who required prompting when following their morning routine (n = 24), but were not limited by physical disability or dysphasia, took part in the study. Participants (67% with traumatic brain injury) had impairment on indices of memory and executive function. DESIGN: A randomized control trial evaluated the effect of an automated interactive micro-prompting device on the number of prompts by trained staff required for successful completion of the morning routine. MAIN MEASURES: Study-specific checklists assessed sequence performance, errors, and verbal prompts required over baseline, rehabilitation as usual, intervention, and return to baseline conditions. RESULTS: The intervention significantly reduced the support required to complete the task compared with usual rehabilitation. CONCLUSIONS: Micro-prompting technology is an effective assistive technology for cognition, which reduces support needs in people with significant cognitive impairments.


Asunto(s)
Actividades Cotidianas , Lesiones Encefálicas/rehabilitación , Personas con Discapacidad , Dispositivos de Autoayuda , Programas Informáticos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad
17.
Neuropsychol Rehabil ; 28(4): 633-648, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27398837

RESUMEN

Deficits in social cognition following acquired brain injury (ABI) have been found to be both prevalent and disabling. Despite this, relatively little attention has been given to identifying the characteristics of such deficits in a systematic way. We describe the development of self and informant versions of a new questionnaire designed to measure the changes in social cognition that may occur following ABI, the Brain Injury Rehabilitation Trust (BIRT) Social Cognition Questionnaire (BSCQ). Seventy-two participants (Mean age = 36 years, SD = 12), with different forms of ABI (76% traumatic brain injury, 8% cerebrovascular accident, 15% other) and who were on average 20 months post-injury (SD = 16), took part in the study. The measure demonstrates excellent psychometric properties, including high test-retest (.94) and split-half (.92) reliability, high internal consistency (Cronbach's alpha = .92), and good concurrent validity. The questionnaire measures characteristics that are distinguishable from measures of cognitive ability. There was moderate overlap between self-report and informant versions of the questionnaire (r = .50), but the informant version had the strongest predictive value of outcome, measured with the Mayo-Portland Adaptability Inventory III, one year later. The potential uses of the measure in relation to theory and practice are discussed. The results suggest that the BSCQ is a useful screening tool for those with ABI.


Asunto(s)
Lesiones Encefálicas/diagnóstico , Lesiones Encefálicas/psicología , Cognición , Pruebas Neuropsicológicas , Conducta Social , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Adulto Joven
18.
Vet Anaesth Analg ; 44(5): 1068-1075, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29037801

RESUMEN

OBJECTIVES: 1) To determine which peripheral artery commonly used for invasive arterial blood pressure (IBP) monitoring yields the least bias when compared with noninvasive blood pressure (NIBP) values obtained at the antebrachium of the dog, and 2) to identify and describe differences in systolic (SAP), mean (MAP) and diastolic arterial pressures (DAP) among different anatomical locations. STUDY DESIGN: Prospective experimental study. ANIMALS: Twenty adult hound dogs weighing 24.5 ± 1.1 kg (mean ± standard deviation). METHODS: Four peripheral arteries-dorsal pedal, median caudal, intermediate auricular and superficial palmar arteries-were catheterized with 20 gauge, 3.8 cm catheters. One NIBP cuff was placed in the middle third of the antebrachium. Four sets of IBP and NIBP measurements were simultaneously collected every 2 minutes. A linear mixed model was performed to analyze the collected data. RESULTS: IBP values varied depending on the arterial catheterization site. The difference was greater for SAP. NIBP measured at the antebrachium had the best agreement with IBP measured at the median caudal artery. CONCLUSION AND CLINICAL RELEVANCE: IBP varies among anatomical locations. The smallest bias and narrowest limits of agreement were obtained at the median caudal artery, providing the best overall agreement with the equipment studied. The median caudal artery may be the preferable anatomical location for clinical comparison studies between IBP and NIBP in dogs when the cuff is on the antebrachium.


Asunto(s)
Arterias/fisiología , Determinación de la Presión Sanguínea/veterinaria , Perros/fisiología , Animales , Presión Sanguínea/fisiología , Determinación de la Presión Sanguínea/instrumentación , Determinación de la Presión Sanguínea/métodos , Arteria Carótida Externa/fisiología , Femenino , Pie/irrigación sanguínea , Masculino , Reproducibilidad de los Resultados , Cola (estructura animal)/irrigación sanguínea
19.
Vet Anaesth Analg ; 43(2): 199-203, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26451748

RESUMEN

OBJECTIVES: To compare two commonly used oscillometric technologies for obtaining noninvasive blood pressure (NIBP) measurements and to determine if there is a difference in agreement between these systems and invasive blood pressure (IBP) measurements. STUDY DESIGN: Prospective, experimental study. ANIMALS: Twenty adult laboratory dogs. METHODS: Each dog was anesthetized and its median caudal artery catheterized for IBP monitoring. An NIBP cuff was placed in the middle third of the antebrachium and attached to either monitor-1 or monitor-2. Four pairs of concurrent NIBP and IBP measurements were recorded with each monitor. Agreement between IBP and NIBP measurements was explored using Bland-Altman analysis, as well as the American College of Veterinary Internal Medicine (ACVIM) and Association for the Advancement of Medical Instrumentation (AAMI) guidelines for the validation of NIBP devices. RESULTS: Both NIBP technologies produced results that met the ACVIM and AAMI guidelines for the validation of NIBP devices. For monitor-1, analyses of agreement showed biases of 0.2 mmHg [95% limits of agreement (LoA) -11.8 to 12.3 mmHg] in systolic arterial pressure (SAP) values, -2.6 mmHg (95% LoA -14.4 to 9.1 mmHg) in diastolic arterial pressure (DAP) values, and -2.5 mmHg (95% LoA -12.7 to 7.3 mmHg) in mean arterial pressure (MAP) values. For monitor-2, analyses of agreement showed biases of 3.4 mmHg (95% LoA -8.7 to 15.5 mmHg) in SAP values, 2.2 mmHg (95% LoA -6.6 to 10.9 mmHg) in DAP values, and 1.6 mmHg (95% LoA -5.9 to 8.9 mmHg) in MAP values. CONCLUSIONS AND CLINICAL RELEVANCE: Multi-function monitors can contain components from various manufacturers. Clinicians should consider whether these have been validated in the species to be monitored. Both of the technologies studied here seem appropriate for use in dogs.


Asunto(s)
Presión Arterial , Determinación de la Presión Sanguínea/veterinaria , Perros , Animales , Determinación de la Presión Sanguínea/métodos , Femenino , Masculino , Oscilometría/veterinaria , Estudios Prospectivos , Especificidad de la Especie
20.
Neuropsychol Rehabil ; 25(5): 763-79, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25351687

RESUMEN

This study employed a correlational and group comparison design to investigate whether self-report of traumatic brain injury (TBI) in a sample of male prisoners screened using the Brain Injury Screening Index (BISI) was associated with impaired cognitive performance on standardised questionnaires and neuropsychological tests. A total of 139 male prisoners who reported having suffered a TBI in the BISI were interviewed, and completed further questionnaires and neuropsychological assessments. Their results were compared to 50 prisoners who had no reported history of TBI. The results of the screening questionnaire correlated with responses in a follow-up interview, with self-report questionnaires of neurobehavioural disorder (.31 to .50) and neuropsychological measures (-.24 to -.45). The "TBI Index", an indicator summarising the number and severity of self-reported injuries in a single score, also correlated well with scores on formal neuropsychological tests (-.20 to -.42). Self-report of traumatic brain injury among prisoners is consistently associated with measurable neuropsychological and neurobehavioural disability. The implications of these findings for current practice in identifying and referring individuals to specialist services are considered.


Asunto(s)
Lesiones Encefálicas/psicología , Prisioneros/psicología , Adulto , Humanos , Masculino , Pruebas Neuropsicológicas , Autoinforme , Encuestas y Cuestionarios , Reino Unido
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