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1.
Transpl Int ; 37: 12997, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39206136

RESUMEN

The quality assurance provided by preimplantation biopsy quantification of chronic damage may allow greater use of kidneys from expanded criteria donors, and thereby expand the deceased donor pool. Preimplantation biopsy may, however, identify additional acute or chronic pathologies not considered in the scoring of chronic damage, and these may influence the decision to implant or discard the kidney. This single-centre retrospective cohort study of a contemporary UK donor population systematically characterised the nature of additional findings in 1,046 preimplantation and implantation biopsies over an eight-year period. A diverse range of findings were identified in 111/1,046 (11%) organs; most frequently diabetic glomerulopathy, focal segmental glomerulosclerosis, (micro)thrombi, neutrophil casts, and immunoglobulin/complement staining. Seventy (63%) of these were transplanted, with subsequent biopsy in 41 (58%) cases confirming that 80% of the initial acute changes had spontaneously resolved, while there was no progression of diabetic glomerulopathy, and the lesions of focal segmental glomerulosclerosis were not identified. Over 75% of assessable grafts with additional histological findings at the time of transplant showed adequate function at one-year following transplant. In conclusion, most histological abnormalities that may be identified in addition to chronic scarring in preimplantation kidney biopsies would not preclude transplantation nor predict poor graft function.


Asunto(s)
Trasplante de Riñón , Riñón , Humanos , Estudios Retrospectivos , Biopsia , Femenino , Masculino , Adulto , Persona de Mediana Edad , Riñón/patología , Incidencia , Glomeruloesclerosis Focal y Segmentaria/patología , Reino Unido/epidemiología , Anciano , Donantes de Tejidos , Nefropatías Diabéticas/patología
2.
Climacteric ; 27(1): 104-112, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38197424

RESUMEN

Ischemic heart disease is the primary cause of cardiovascular disease (CVD) mortality in both men and women. Strategies targeting traditional modifiable risk factors are essential - including hypertension, smoking, dyslipidemia and diabetes mellitus - particularly for atherosclerosis, but additionally for stroke, heart failure and some arrhythmias. However, challenges related to education, screening and equitable access to effective preventative therapies persist, and are particularly problematic for women around the globe and those from lower socioeconomic groups. The association of female-specific risk factors (e.g. premature menopause, gestational hypertension, small for gestational age births) with CVD provides a potential window for targeted prevention strategies. However, further evidence for specific effective screening and interventions is urgently required. In addition to population-level factors involved in increasing the risk of suffering a CVD event, efforts are leveraging the enormous potential of blood-based 'omics', improved imaging biomarkers and increasingly complex bioinformatic analytic approaches to strive toward more personalized early disease detection and personalized preventative therapies. These novel tactics may be particularly relevant for women in whom traditional risk factors perform poorly. Here we discuss established and emerging approaches for improving risk assessment, early disease detection and effective preventative strategies to reduce the mammoth burden of CVD in women.


Asunto(s)
Enfermedades Cardiovasculares , Hipertensión , Masculino , Humanos , Femenino , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/etiología , Factores de Riesgo , Medición de Riesgo , Prevención Primaria
3.
Matern Child Health J ; 28(3): 438-469, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38372834

RESUMEN

INTRODUCTION/PURPOSE: Poverty-reduction efforts that seek to support households with children and enable healthy family functioning are vital to produce positive economic, health, developmental, and upward mobility outcomes. The Supplemental Nutrition Assistance Program (SNAP) is an effective poverty-reduction policy for individuals and families. This study investigated the non-nutritional effects that families experience when receiving SNAP benefits. METHODS: We conducted a scoping review using the PRISMA Guidelines and strategic search terms across seven databases from 01 January 2008 to 01 February 2023 (n=2456). Data extraction involved two researchers performing title-abstract reviews. Full-text articles were assessed for eligibility (n=103). Forty articles were included for data retrieval. RESULTS: SNAP positively impacts family health across the five categories of the Family Stress Model (Healthcare utilization for children and parents, Familial allocation of resources, Impact on child development and behavior, Mental health, and Abuse or neglect). DISCUSSION/CONCLUSION: SNAP is a highly effective program with growing evidence that it positively impacts family health and alleviates poverty. Four priority policy actions are discussed to overcome the unintentional barriers for SNAP: distributing benefits more than once a month; increasing SNAP benefits for recipients; softening the abrupt end of benefits when wages increase; and coordinating SNAP eligibility and enrollment with other programs.


Asunto(s)
Asistencia Alimentaria , Pobreza , Niño , Humanos , Composición Familiar , Abastecimiento de Alimentos , Conductas Relacionadas con la Salud , Estado de Salud
4.
J Cutan Pathol ; 47(10): 970-975, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32483824

RESUMEN

Primary superficial Ewing sarcoma (psES) cases are exceedingly rare, with fewer than 150 cases reported in the literature. Small case series have suggested differences between psES and Ewing sarcoma (ES) of bone or deep soft tissues: psES appears to have a more indolent course and a higher 5-year overall survival rate. PsES is more common in older adolescent females as opposed to younger males in their peak growth velocity years in bone or deep soft tissue ES. We present a case report of a 17-year-old female with a relatively static nodule on her left thigh for 4 years. Morphologic, immunohistochemical, and molecular evaluations confirmed ES. Patient underwent a gross-total resection and a shortened course of adjuvant chemotherapy without radiation. Cancer gene panel testing found three gene abnormalities (in addition to EWSR1-FLI1 fusion): CCND1 copy number gain, ELF3 copy number loss, and TNFRSF14 copy number loss. To our knowledge, this is the first published case report of psES to include genomic sequencing and the first to report ELF3 and TNFRSF14 abnormalities in ES. Larger series of psES cases with genomic profiling are needed to elucidate a possible genetic etiology for its more indolent clinical course and favorable outcomes.


Asunto(s)
Proteínas de Unión al ADN/genética , Proteínas Proto-Oncogénicas c-ets/genética , Miembro 14 de Receptores del Factor de Necrosis Tumoral/genética , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/genética , Factores de Transcripción/genética , Adolescente , Quimioterapia Adyuvante/métodos , Ciclina D1/genética , Variaciones en el Número de Copia de ADN , Femenino , Humanos , Inmunohistoquímica/métodos , Imagen por Resonancia Magnética/métodos , Proteína Proto-Oncogénica c-fli-1/genética , Proteína EWS de Unión a ARN/genética , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/cirugía , Neoplasias Cutáneas/patología , Resultado del Tratamiento , Ultrasonografía Doppler en Color/métodos
5.
Br J Dermatol ; 178(6): 1331-1340, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29315488

RESUMEN

BACKGROUND: Incontinence-associated dermatitis (IAD) is a specific type of irritant contact dermatitis with different severity levels. An internationally accepted instrument to assess the severity of IAD in adults, with established diagnostic accuracy, agreement and reliability, is needed to support clinical practice and research. OBJECTIVES: To design the Ghent Global IAD Categorization Tool (GLOBIAD) and evaluate its psychometric properties. METHODS: The design was based on expert consultation using a three-round Delphi procedure with 34 experts from 13 countries. The instrument was tested using IAD photographs, which reflected different severity levels, in a sample of 823 healthcare professionals from 30 countries. Measures for diagnostic accuracy (sensitivity and specificity), agreement, interrater reliability (multirater Fleiss kappa) and intrarater reliability (Cohen's kappa) were assessed. RESULTS: The GLOBIAD consists of two categories based on the presence of persistent redness (category 1) and skin loss (category 2), both of which are subdivided based on the presence of clinical signs of infection. The agreement for differentiating between category 1 and category 2 was 0·86 [95% confidence interval (CI) 0·86-0·87], with a sensitivity of 90% and a specificity of 84%. The overall agreement was 0·55 (95% CI 0·55-0·56). The Fleiss kappa for differentiating between category 1 and category 2 was 0·65 (95% CI 0·65-0·65). The overall Fleiss kappa was 0·41 (95% CI 0·41-0·41). The Cohen's kappa for differentiating between category 1 and category 2 was 0·76 (95% CI 0·75-0·77). The overall Cohen's kappa was 0·61 (95% CI 0·59-0·62). CONCLUSIONS: The development of the GLOBIAD is a major step towards a better systematic assessment of IAD in clinical practice and research worldwide. However, further validation is needed.


Asunto(s)
Dermatitis Irritante/etiología , Lenguaje , Índice de Severidad de la Enfermedad , Incontinencia Urinaria/complicaciones , Adulto , Dermatitis Irritante/diagnóstico , Femenino , Humanos , Internacionalidad , Masculino , Variaciones Dependientes del Observador , Psicometría , Estándares de Referencia , Sensibilidad y Especificidad , Terminología como Asunto
6.
J Public Health (Oxf) ; 40(4): e552-e559, 2018 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-29897560

RESUMEN

Background: Because of the limited success of population-based prevention methods and due to developments in genomic screening, public health professionals and health policy makers are increasingly interested in more individualized prevention strategies. However, the terminology applied in this field is still ambiguous and thus has the potential to create misunderstandings. Methods: A narrative literature review was conducted to identify how individualized, personalized and precision prevention are used in research papers and documents. Based on the findings a set of definitions were created that distinguish between these activities in a meaningful way. Results: Definitions were found only for precision prevention, not for individualized or personalized prevention. The definitions of individualized, personalized and precision medicine were therefore used to create the definitions for their prevention counterparts. By these definitions, individualized prevention consists of all types of prevention that are individual-based; personalized prevention also consists of at least one form of -omic screening; and precision prevention further includes psychological, behavioral and socioeconomic data for each patient. Conclusions: By defining these three key terms for different types of individual-based prevention both researchers and health policy makers can differentiate and use them in their proper context.


Asunto(s)
Medicina de Precisión , Medicina Preventiva , Práctica de Salud Pública , Terminología como Asunto , Humanos
7.
Heredity (Edinb) ; 119(2): 107-116, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28489073

RESUMEN

Montane environments around the globe are biodiversity 'hotspots' and important reservoirs of genetic diversity. Montane species are also typically more vulnerable to environmental change than their low-elevation counterparts due to restricted ranges and dispersal limitations. Here we focus on two abundant congeneric mayflies (Baetis bicaudatus and B. tricaudatus) from montane streams over an elevation gradient spanning 1400 m. Using single-nucleotide polymorphism genotypes, we measured population diversity and vulnerability in these two species by: (i) describing genetic diversity and population structure across elevation gradients to identify mechanisms underlying diversification; (ii) performing spatially explicit landscape analyses to identify environmental drivers of differentiation; and (iii) identifying outlier loci hypothesized to underlie adaptive divergence. Differences in the extent of population structure in these species were evident depending upon their position along the elevation gradient. Heterozygosity, effective population sizes and gene flow all declined with increasing elevation, resulting in substantial population structure in the higher elevation species (B. bicaudatus). At lower elevations, populations of both species are more genetically similar, indicating ongoing gene flow. Isolation by distance was detected at lower elevations only, whereas landscape barriers better predicted genetic distance at higher elevations. At higher elevations, dispersal was restricted due to landscape effects, resulting in greater population isolation. Our results demonstrate differentiation over small spatial scales along an elevation gradient, and highlight the importance of preserving genetic diversity in more isolated high-elevation populations.


Asunto(s)
Altitud , Ephemeroptera/genética , Flujo Génico , Variación Genética , Genética de Población , Animales , Colorado , Ephemeroptera/clasificación , Genotipo , Polimorfismo de Nucleótido Simple
9.
J Appl Microbiol ; 120(1): 80-9, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26492200

RESUMEN

AIMS: To evaluate the field inactivation of Bacillus anthracis Sterne spores with methyl bromide (MB) using commercial fumigation techniques. METHODS AND RESULTS: Eighty-seven wood and 87 glass coupons each containing ca. 1 × 10(6) B. anthracis Sterne spores, were placed in 22 locations inside a 1444 m(3) conference building. Four additional 12-coupon sets (six wood, six glass) were removed from the building at 16, 24, 32 and 40 h during fumigation. The building was sealed under two tarpaulins and fumigated with MB at ≥225 g m(-3) mean concentration for 48 h at 28°C and 83% RH. All B. anthracis spores fumigated for more than 16 h were inactivated. A single wood coupon from the 16-h set yielded ca. 2 × 10(3)  CFU. No damage to the building or its contents was observed. CONCLUSIONS: MB fumigation is a rapid, economical and effective whole-structure decontamination method for B. anthracis spores. SIGNIFICANCE AND IMPACT OF THE STUDY: MB fumigation offers a method of whole-structure B. anthracis decontamination without removal of materials, damage to sensitive electronics, costly indoor retrofitting.


Asunto(s)
Bacillus anthracis/efectos de los fármacos , Descontaminación/métodos , Hidrocarburos Bromados/farmacología , Esporas Bacterianas/efectos de los fármacos , Bacillus anthracis/crecimiento & desarrollo , Fumigación , Hidrocarburos Bromados/química
10.
Am J Transplant ; 15(12): 3067-80, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26211786

RESUMEN

Renal transplantation is the optimum treatment for end-stage renal failure. B cells have been identified in chronic allograft damage (CAD) and associated with the development of tertiary lymphoid tissue within the human renal allograft. We performed renal transplantation in mice to model CAD and identified B cells forming tertiary lymphoid tissue with germinal centers. Intra-allograft B220(+) B cells comprised of IgM(high) CD23(-) B cells, IgM(lo) CD23(+) B cells, and IgM(lo) CD23(-) B cells with elevated expression of CD86. Depletion of B cells with anti-CD20 was associated with an improvement in CAD but only when administered after transplantation and not before. Isolated intra-allograft B cells were cultured and shown to synthesize multiple cytokines, the most abundant of these were GRO-α (CXCL1), RANTES (CCL5), IL-6 and MCP-1 (CCL2). Tubular loss was observed with T cell accumulation within the allograft and development of interstitial fibrosis, whilst type III collagen deposition was observed in areas of F4/80(+) macrophages and PDGFR-ß(+) and transgelin(+) fibroblasts, all of which were reduced by B cell depletion. We have shown that intra-allograft B cells are key mediators of CAD. B cells possibly contribute to CAD by intra-allograft secretion of cytokines and chemokines.


Asunto(s)
Linfocitos B/patología , Citocinas/toxicidad , Trasplante de Riñón , Túbulos Renales/patología , Nefritis Intersticial/patología , Aloinjertos , Animales , Atrofia , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Citometría de Flujo , Tasa de Filtración Glomerular , Rechazo de Injerto/inducido químicamente , Rechazo de Injerto/inmunología , Rechazo de Injerto/metabolismo , Rechazo de Injerto/patología , Supervivencia de Injerto/efectos de los fármacos , Humanos , Fallo Renal Crónico/cirugía , Pruebas de Función Renal , Túbulos Renales/efectos de los fármacos , Túbulos Renales/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Complicaciones Posoperatorias
11.
Phys Rev Lett ; 115(4): 047601, 2015 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-26252708

RESUMEN

New mechanisms for achieving direct electric field control of ferromagnetism are highly desirable in the development of functional magnetic interfaces. To that end, we have probed the electric field dependence of the emergent ferromagnetic layer at CaRuO_{3}/CaMnO_{3} interfaces in bilayers fabricated on SrTiO_{3}. Using polarized neutron reflectometry, we are able to detect the ferromagnetic signal arising from a single atomic monolayer of CaMnO_{3}, manifested as a spin asymmetry in the reflectivity. We find that the application of an electric field of 600 kV/m across the bilayer induces a significant increase in this spin asymmetry. Modeling of the reflectivity suggests that this increase corresponds to a transition from canted antiferromagnetism to full ferromagnetic alignment of the Mn^{4+} ions at the interface. This increase from 1 µ_{B} to 2.5-3.0 µ_{B} per Mn is indicative of a strong magnetoelectric coupling effect, and such direct electric field control of the magnetization at an interface has significant potential for spintronic applications.

12.
Amino Acids ; 47(12): 2593-600, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26255281

RESUMEN

Within the aging population, there exists a subset of individuals termed masters athletes (MA). As masters-level competition increases in popularity, MA must find methods to enhance individual athletic performance. Longitudinal beta-alanine (BA) supplementation is suggested to enhance physical capability during exercise; however, these effects have not been evaluated in MA. To examine the longitudinal effects of BA on time to exhaustion (TTE), total work completed (TWC), and lactate clearance in female MA cyclists. Twenty-two female MA (age = 53.3 ± 1.0) participated in this double-blind design. Subjects were randomly assigned to BA (n = 11; 800 mg BA + 8 g dextrose) or placebo (PLA; n = 11; 8 g dextrose) groups and supplemented 4 doses/day over 28 days. Every 7 days, subjects completed a cycling TTE at 120% VO2max, and TWC was calculated. Blood lactate was measured at baseline, immediate post, and 20-min post each TTE. No significant differences existed between groups for any variable at baseline (p > 0.05). After 28 days supplementation, BA had greater TTE (23 vs 1% change) and TWC (21 vs 2% change) than PLA (p < 0.05). Following the 20-min TTE recovery, lactate was 24% lower in BA compared to PLA (4.35 vs. 5.76 mmol/L, respectively). No differences existed for variables during intermittent weeks. 28 days of BA supplementation increased cycling performance via an enhanced time to exhaustion and total work completed with associated lactate clearance during passive rest in female MA.


Asunto(s)
Atletas , Rendimiento Atlético , Ciclismo , Ácido Láctico/sangre , Resistencia Física/efectos de los fármacos , beta-Alanina/administración & dosificación , Suplementos Dietéticos , Método Doble Ciego , Ejercicio Físico , Prueba de Esfuerzo , Femenino , Glucosa/administración & dosificación , Humanos , Persona de Mediana Edad , Descanso , Factores de Tiempo
13.
Pflugers Arch ; 466(3): 549-62, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23948742

RESUMEN

Excessive alcohol consumption is a major cause of acute pancreatitis, but the mechanism involved is not well understood. Recent investigations suggest that pancreatic ductal epithelial cells (PDECs) help defend the pancreas from noxious agents such as alcohol. Because the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel plays a major role in PDEC physiology and mutated CFTR is often associated with pancreatitis, we tested the hypothesis that ethanol affects CFTR to impair ductal function. Electrophysiological studies on native PDECs showed that ethanol (10 and 100 mM) increased basal, but reversibly blocked, forskolin-stimulated CFTR currents. The inhibitory effect of ethanol was mimicked by its non-oxidative metabolites, palmitoleic acid ethyl ester (POAEE) and palmitoleic acid (POA), but not by the oxidative metabolite, acetaldehyde. Ethanol, POAEE and POA markedly reduced intracellular ATP (ATPi) which was linked to CFTR inhibition since the inhibitory effects were almost completely abolished if ATPi depletion was prevented. We propose that ethanol causes functional damage of CFTR through an ATPi-dependent mechanism, which compromises ductal fluid secretion and likely contributes to the pathogenesis of acute pancreatitis. We suggest that the maintenance of ATPi may represent a therapeutic option in the treatment of the disease.


Asunto(s)
Adenosina Trifosfato/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Células Epiteliales/metabolismo , Etanol/farmacología , Acetaldehído/farmacología , Potenciales de Acción/efectos de los fármacos , Animales , Línea Celular Tumoral , Células Cultivadas , Células Epiteliales/efectos de los fármacos , Células Epiteliales/fisiología , Ácidos Grasos Monoinsaturados/farmacología , Cobayas , Humanos , Conductos Pancreáticos/citología
14.
J Econ Entomol ; 107(3): 1069-75, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25026666

RESUMEN

Among the insects reported in biofuel crops, the yellow sugarcane aphid, Sipha flava (Forbes), is a potential pest of giant miscanthus, Miscanthus x giganteus Greef et Deu ex Hodkinson et Renvoize (M x g) and energy cane 'L79-1002', Saccharum spp. L. We studied the biology of S. flava on M x g and energy cane and estimated the development period, fecundity, longevity, intrinsic rate of increase, doubling time, reproductive value, and survivorship curves. To demonstrate the host suitability in a susceptible species, we studied the aphid life table on sorghum 'PL 18200,' Sorghum bicolor (L.) Moench. Life-table information was recorded under greenhouse conditions on the host plants. Our results suggested that both M x g and energy cane are suitable hosts for S. flava. We observed similar aphid development period on both hosts. Life-table estimates including longevity and fecundity suggested that M x g is a more suitable host for the aphid than energy cane. The intrinsic rate of increase for S. flava was lower on energy cane (0.231) than on M x g (0.258).


Asunto(s)
Áfidos/fisiología , Cadena Alimentaria , Poaceae/crecimiento & desarrollo , Animales , Biocombustibles , Fertilidad , Control de Insectos , Tablas de Vida , Longevidad , Dinámica Poblacional , Reproducción , Saccharum/crecimiento & desarrollo
15.
J Perinatol ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39198556

RESUMEN

OBJECTIVE: To assess the impact of NRP virtual simulations (eSim™), video or no refresher training, on simulation performance, six months after a provider course; and to evaluate eSim™ acceptability. STUDY DESIGN: In this multi-site randomized controlled trial, NRP providers from four U.S. institutions were randomized to receive refreshers every two months with NRP eSim™, NRP resuscitation video, or no refresher (control). Simulation performance was assessed immediately after an NRP course and six months later. RESULT: 248 participants completed the baseline simulation and 148 completed the six-month follow-up simulation. The majority (71%) of subjects had a decline in resuscitation skills at 6 months. There were no differences in performance between the study groups, but participants who reported using either the video or eSim™ had less decline in performance at the 6-month follow-up (p < 0.05). CONCLUSION: NRP refreshers with either eSim™ or NRP video may mitigate the decline in resuscitation skills after training.

16.
Front Cardiovasc Med ; 11: 1359500, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38500753

RESUMEN

Atherosclerotic coronary artery disease (CAD) is the causal pathological process driving most major adverse cardiovascular events (MACE) worldwide. The complex development of atherosclerosis manifests as intimal plaque which occurs in the presence or absence of traditional risk factors. There are numerous effective medications for modifying CAD but new pharmacologic therapies require increasingly large and expensive cardiovascular outcome trials to assess their potential impact on MACE and to obtain regulatory approval. For many disease areas, nearly a half of drugs are approved by the U.S. Food & Drug Administration based on beneficial effects on surrogate endpoints. For cardiovascular disease, only low-density lipoprotein cholesterol and blood pressure are approved as surrogates for cardiovascular disease. Valid surrogates of CAD are urgently needed to facilitate robust evaluation of novel, beneficial treatments and inspire investment. Fortunately, advances in non-invasive imaging offer new opportunity for accelerating CAD drug development. Coronary computed tomography angiography (CCTA) is the most advanced candidate, with the ability to measure accurately and reproducibly characterize the underlying causal disease itself. Indeed, favourable changes in plaque burden have been shown to be associated with improved outcomes, and CCTA may have a unique role as an effective surrogate endpoint for therapies that are designed to improve CAD outcomes. CCTA also has the potential to de-risk clinical endpoint-based trials both financially and by enrichment of participants at higher likelihood of MACE. Furthermore, total non-calcified, and high-risk plaque volume, and their change over time, provide a causally linked measure of coronary artery disease which is inextricably linked to MACE, and represents a robust surrogate imaging biomarker with potential to be endorsed by regulatory authorities. Global consensus on specific imaging endpoints and protocols for optimal clinical trial design is essential as we work towards a rigorous, sustainable and staged pathway for new CAD therapies.

17.
Neurobiol Dis ; 51: 82-92, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23069680

RESUMEN

We investigated two measures of neural integrity, T1-weighted volumetric measures and diffusion tensor imaging (DTI), and explored their combined potential to differentiate pre-diagnosis Huntington's disease (pre-HD) individuals from healthy controls. We applied quadratic discriminant analysis (QDA) to discriminate pre-HD individuals from controls and we utilised feature selection and dimension reduction to increase the robustness of the discrimination method. Thirty six symptomatic HD (symp-HD), 35 pre-HD, and 36 control individuals participated as part of the IMAGE-HD study and underwent T1-weighted MRI, and DTI using a Siemens 3 Tesla scanner. Volume and DTI measures [mean diffusivity (MD) and fractional anisotropy (FA)] were calculated for each group within five regions of interest (ROI; caudate, putamen, pallidum, accumbens and thalamus). QDA was then performed in a stepwise manner to differentiate pre-HD individuals from controls, based initially on unimodal analysis of motor or neurocognitive measures, or on volume, MD or FA measures from within the caudate, pallidum and putamen. We then tested for potential improvements to this model, by examining multi-modal MRI classifications (volume, FA and MD), and also included motor and neurocognitive measures, and additional brain regions (i.e., accumbens and thalamus). Volume, MD and FA differed across the three groups, with pre-HD characterised by significant volumetric reductions and increased FA within caudate, putamen and pallidum, relative to controls. The QDA results demonstrated that the differentiation of pre-HD from controls was highly accurate when both volumetric and diffusion data sets from basal ganglia (BG) regions were used. The highest discriminative accuracy however was achieved in a multi-modality approach and when including all available measures: motor and neurocognitive scores and multi-modal MRI measures from the BG, accumbens and thalamus. Our QDA findings provide evidence that combined multi-modal imaging measures can accurately classify individuals up to 15 years prior to onset when therapeutic intervention is likely to have maximal effects in slowing the trajectory of disease development.


Asunto(s)
Ganglios Basales/patología , Enfermedad de Huntington/patología , Interpretación de Imagen Asistida por Computador/métodos , Anisotropía , Imagen de Difusión por Resonancia Magnética , Análisis Discriminante , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad
18.
Pharmacogenomics J ; 13(1): 70-9, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22333911

RESUMEN

Brain imaging studies contribute to the neurobiological understanding of Autism Spectrum Conditions (ASC). Herein, we tested the prediction that distributed neurodevelopmental abnormalities in brain development impact on the homogeneity of brain tissue measured using texture analysis (TA; a morphological method for surface pattern characterization). TA was applied to structural magnetic resonance brain scans of 54 adult participants (24 with Asperger syndrome (AS) and 30 controls). Measures of mean gray-level intensity, entropy and uniformity were extracted from gray matter images at fine, medium and coarse textures. Comparisons between AS and controls identified higher entropy and lower uniformity across textures in the AS group. Data reduction of texture parameters revealed three orthogonal principal components. These were used as regressors-of-interest in a voxel-based morphometry analysis that explored the relationship between surface texture variations and regional gray matter volume. Across the AS but not control group, measures of entropy and uniformity were related to the volume of the caudate nuclei, whereas mean gray-level was related to the size of the cerebellar vermis. Similar to neuropathological studies, our study provides evidence for distributed abnormalities in the structural integrity of gray matter in adults with ASC, in particular within corticostriatal and corticocerebellar networks. Additionally, this in-vivo technique may be more sensitive to fine microstructural organization than other more traditional magnetic resonance approaches and serves as a future testable biomarker in AS and other neurodevelopmental disorders.


Asunto(s)
Síndrome de Asperger/patología , Cerebelo/anomalías , Cerebelo/patología , Adulto , Síndrome de Asperger/diagnóstico , Biomarcadores , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Neuroimagen/métodos
19.
J Acoust Soc Am ; 133(3): 1503-14, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23464021

RESUMEN

Pulse compression is normally applied only to time-invariant systems, as the variation of a system's properties during its interrogation violates assumptions of the compression process. However, there is an exact solution to the pulse-compression problem when the time variance satisfies two criteria, which are the same as those required for the operation of an ultrasonic vibrometer in the context of a tissue elastography system. One is that the variations be very small in comparison with the wavelength of the interrogating ultrasound. The other is that the bandwidth of the variations be within one Nyquist band as sampled by the periodic interrogation signal. The solution to this problem involves a step-wise interpolation of the static pulse-compression transfer function in the frequency domain. This technique, in conjunction with the selection of an appropriate interrogation signal, offers significant advantages in measurement time or measurement resolution for an ultrasonic vibrometer limited by additive noise at the receiver. The characteristics of optimal interrogation signals for this technique are the signal's crest factor, spectral energy distribution, and phasing. These relate to the intended compression pulse, the noise, and the static response of the system. The technique has been demonstrated analytically, experimentally, and with numerical models.


Asunto(s)
Diagnóstico por Imagen de Elasticidad/métodos , Sonido , Ultrasonido/métodos , Simulación por Computador , Diagnóstico por Imagen de Elasticidad/instrumentación , Diseño de Equipo , Modelos Teóricos , Movimiento (Física) , Análisis Numérico Asistido por Computador , Presión , Procesamiento de Señales Asistido por Computador , Relación Señal-Ruido , Factores de Tiempo , Transductores de Presión , Ultrasonido/instrumentación , Vibración
20.
J Sports Med Phys Fitness ; 53(4): 428-36, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23828291

RESUMEN

AIM: The purpose of this 48-week exercise intervention was designed to examine the effects of power and resistance training on bone mineral density (BMD). METHODS: Premenopausal women were recruited and randomly assigned to either a power (N.=8) or resistance (N.=11) training group. The power exercises included jumping rope, skipping, hopping, and other power-type exercises. The resistance training group performed 8-10 whole-body strengthening exercises at 70% one-repetition maximum (1RM). Before and after the exercise intervention, BMD was measured via dual energy x-ray absorptiometry (DXA) for the total-body, lumbar spine, left femoral neck, and left greater trochanter. Muscular strength was measured by hand grip dynamometer and 1RM of chest press and leg press. Muscular power was assessed by the Margaria-Kalamen stair climb test. Data were analyzed using repeated measures ANOVA. RESULTS: There were no statistical differences between the two training groups for any of the BMD measurements. Chest press strength was different between the two groups, increasing 6.41 and 1.1kg for the resistance and power groups, respectively over the course of the training period (F[1.15]=9.44, P<0.01). There was a significant time effect for leg press 1RM (F[1.15]=6.04, P=0.03). The participants increased by 12.37kg after the 48-week intervention. Hand grip strength also increased after the study intervention (F[1.16]=46.32, P<0.01). CONCLUSION: The results of this study suggest that power and resistance training are comparable techniques for maintaining bone density.


Asunto(s)
Densidad Ósea/fisiología , Terapia por Ejercicio/métodos , Fuerza de la Mano/fisiología , Músculo Esquelético/fisiología , Premenopausia , Entrenamiento de Fuerza/métodos , Absorciometría de Fotón , Adulto , Composición Corporal , Femenino , Humanos , Vértebras Lumbares/diagnóstico por imagen , Persona de Mediana Edad , Osteoporosis/diagnóstico por imagen , Osteoporosis/fisiopatología , Osteoporosis/prevención & control
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