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1.
Pain Pract ; 24(5): 739-748, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38379359

RESUMEN

PURPOSE: Exercise prescriptions for chronic low back pain (CLBP) often utilize reductionistic, trunk-focused exercise aimed at addressing proposed pain mechanisms. It is unknown if the use of these trunk-focused exercises imply beliefs to people with CLBP about the rationale for their use (e.g., etiology), even without concurrent biomedical narratives. This study aimed to explore people's perceptions of specific and general exercise without an accompanying narrative when experiencing CLBP. METHODS: An anonymous online survey was distributed. Mixed methods were utilized for analysis. Six-point Likert scales categorized people's beliefs about individual exercises. Open-ended questions were used to gather further beliefs which were then coded into themes. RESULTS: People with CLBP perceived specific exercise as more beneficial than general exercise. Eight themes and five subthemes were defined. A high volume of positive beliefs were centered around strengthening the low back and abdominal musculature, emphasizing the importance of correct technique. Negative beliefs were held against spinal flexion and external load. Both positive and negative beliefs were underpinned by spinal/pelvic stability being important as well as certain exercises being achievable or not. CONCLUSION: This study demonstrated that people with CLBP consider specific exercises to be more beneficial than general exercises for CLBP. Specific exercises irrespective of an accompanying narrative can imply meaning about the intent of an exercise. Understanding this requires practitioners to be mindful when prescribing and communicating exercise.


Asunto(s)
Dolor Crónico , Terapia por Ejercicio , Dolor de la Región Lumbar , Humanos , Dolor de la Región Lumbar/terapia , Dolor de la Región Lumbar/psicología , Masculino , Femenino , Terapia por Ejercicio/métodos , Adulto , Persona de Mediana Edad , Dolor Crónico/psicología , Dolor Crónico/terapia , Encuestas y Cuestionarios , Anciano , Ejercicio Físico/fisiología , Ejercicio Físico/psicología , Adulto Joven
2.
Med Biol Eng Comput ; 59(5): 1065-1079, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33881704

RESUMEN

A finite element (FE)-guided mathematical surrogate modeling methodology is presented for evaluating relative injury trends across varied vehicular impact conditions. The prevalence of crash-induced injuries necessitates the quantification of the human body's response to impacts. FE modeling is often used for crash analyses but requires time and computational cost. However, surrogate modeling can predict injury trends between the FE data, requiring fewer FE simulations to evaluate the complete testing range. To determine the viability of this methodology for injury assessment, crash-induced occupant head injury criterion (HIC15) trends were predicted from Kriging models across varied impact velocities (10-45 mph; 16.1-72.4 km/h), locations (near side, far side, front, and rear), and angles (-45 to 45°) and compared to previously published data. These response trends were analyzed to locate high-risk target regions. Impact velocity and location were the most influential factors, with HIC15 increasing alongside the velocity and proximity to the driver. The impact angle was dependent on the location and was minimally influential, often producing greater HIC15 under oblique angles. These model-based head injury trends were consistent with previously published data, demonstrating great promise for the proposed methodology, which provides effective and efficient quantification of human response across a wide variety of car crash scenarios, simultaneously. This study presents a finite element-guided mathematical surrogate modeling methodology to evaluate occupant injury response trends for a wide range of impact velocities (10-45 mph), locations, and angles (-45 to 45°). Head injury response trends were predicted and compared to previously published data to assess the efficacy of the methodology for assessing occupant response to variations in impact conditions. Velocity and location were the most influential factors on the head injury response, with the risk increasing alongside greater impact velocity and locational proximity to the driver. Additionally, the angle of impact variable was dependent on the location and, thus, had minimal independent influence on the head injury risk.


Asunto(s)
Accidentes de Tránsito , Traumatismos Craneocerebrales , Fenómenos Biomecánicos , Traumatismos Craneocerebrales/epidemiología , Análisis de Elementos Finitos , Cabeza , Humanos
3.
J Clin Orthop Trauma ; 10(4): 744-749, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31316248

RESUMEN

INTRODUCTION: The risk of fracture from a non-accidental injury is highest in the infant age group. A spiral fracture of the long bone can occur equally from accidental and non-accidental causes, meaning the clinical judgement of non-accidental injury in an infant is particularly challenging. This study aimed to assist in differentiating accidental, from non-accidental, injury in infants, by establishing whether correlation exists between geometry and torsional strength in the immature long bone. METHODS: Immature porcine third and fourth metacarpals (n = 21) were imaged with a dual energy x-ray absorptiometry (DEXA) scanner to measure their linear bone mineral content (BMCL), bone mineral density (BMD) and section modulus (Z). The specimens were then subjected to a torque of one degree per second until failure. The failure strength and the three DEXA measures were analyzed for a correlation. RESULTS: The mean failure strength of 11 successful tests was 13.71Nm (+/-SD 2.42Nm), with correlation to BMCL, BMD and Z described by r2 = 0.81, 0.283 and 0.75 respectively. CONCLUSION: This study is a novel attempt at estimating torsional strength of long bones in a specific paediatric age group using a size-matched animal bone model. It found a strong correlation between bone and fracture strength parameters over the BMCL range of 0.59-0.77 g/cm.

4.
Phys Rev Lett ; 122(5): 052501, 2019 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-30822018

RESUMEN

One of the most exotic light neutron-rich nuclei currently accessible for experimental study is ^{40}Mg, which lies at the intersection of the nucleon magic number N=28 and the neutron drip line. Low-lying excited states of ^{40}Mg have been studied for the first time following a one-proton removal reaction from ^{41}Al, performed at the Radioactive Isotope Beam Factory of RIKEN Nishina Center with the DALI2 γ-ray array and the ZeroDegree spectrometer. Two γ-ray transitions were observed, suggesting an excitation spectrum that shows unexpected properties as compared to both the systematics along the Z=12, N≥20 Mg isotopes and available state-of-the-art theoretical model predictions. A possible explanation for the observed structure involves weak-binding effects in the low-lying excitation spectrum.

5.
Eur J Pain ; 22(10): 1813-1823, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29956398

RESUMEN

PURPOSE: To investigate the chronic and acute effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on pressure pain thresholds (PPT) in overweight men. METHODS: Twenty-eight participants performed stationary cycling exercise three times per week for 6 weeks. Participants were randomly allocated to HIIT (10 × 1-min intervals at 90% peak heart rate) or MICT (30 min at 65-75% peak heart rate). PPTs were assessed over the rectus femoris, tibialis anterior and upper trapezius before and after the 6-week training programme (chronic effect) as well as before and after the first, middle and final exercise sessions (acute effect). RESULTS: For chronic exercise, PPTs increased more after MICT compared to HIIT over the rectus femoris (p = 0.009, effect size r = 0.54) and tibialis anterior (p = 0.012, r = 0.54), but not the trapezius (p = 0.399, r = 0.29). The effect of acute exercise on PPT was more varied and ranged from moderate hypoalgesia to moderate hyperalgesia. Overall, however, there was no consistent change in PPT after acute exercise for HIIT or MICT (p ≥ 0.231, r ≥ -0.31 and ≤0.31). CONCLUSION: Six weeks of MICT cycling (chronic exercise) increased PPT for the lower body, but not upper body, in overweight men, whereas HIIT did not provide any hypoalgesic effect for chronic exercise. The acute effect of exercise on PPT was highly variable and negligible overall. SIGNIFICANCE: This study shows that aerobic training increases pressure pain threshold in pain-free adults. This effect was observed only for MICT over-exercised muscles, implying intensity- and site-specific effects of exercise training on pain threshold.


Asunto(s)
Ejercicio Físico/psicología , Entrenamiento de Intervalos de Alta Intensidad , Sobrepeso/psicología , Sobrepeso/terapia , Umbral del Dolor , Adulto , Ejercicio Físico/fisiología , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Sobrepeso/fisiopatología , Consumo de Oxígeno/fisiología , Adulto Joven
6.
J Perinatol ; 37(12): 1335-1340, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28933775

RESUMEN

OBJECTIVE: To assess candidate neonatology EPAs taken from separate but overlapping sets from two organizations. STUDY DESIGN: Using a Delphi process, we asked that neonatology fellowship directors (1) assess importance and scope of 19 candidate EPAs, and (2) propose additional EPAs if necessary. In round 2, we sought clarification of first round responses and evaluated proposed additional EPAs. RESULTS: Twenty program directors participated. In round 1, all EPAs were scored as important, but four were overly broad. In round 2, respondents rejected proposed subdivisions of one overly broad EPA, retaining it as originally proposed. Specification of entrustment criteria improved the scope of the three other broad EPAs. However, after specification, they were re-rated as insufficiently important and therefore rejected. Neither newly proposed EPA from round 1 was rated as sufficiently important. CONCLUSION: The Delphi process yielded 13 EPAs with which to assess capability to practice clinical neonatology.


Asunto(s)
Educación de Postgrado en Medicina/organización & administración , Neonatología/normas , Competencia Clínica , Técnica Delphi , Humanos , Internado y Residencia , Neonatología/educación , Rol del Médico , Encuestas y Cuestionarios
7.
Oncogene ; 35(47): 6077-6086, 2016 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-27157619

RESUMEN

Notch receptors have been implicated as oncogenic drivers in several cancers, the most notable example being NOTCH1 in T-cell acute lymphoblastic leukemia (T-ALL). To characterize the role of activated NOTCH3 in cancer, we generated an antibody that detects the neo-epitope created upon gamma-secretase cleavage of NOTCH3 to release its intracellular domain (ICD3), and sequenced the negative regulatory region (NRR) and PEST (proline, glutamate, serine, threonine) domain coding regions of NOTCH3 in a panel of cell lines. We also characterize NOTCH3 tumor-associated mutations that result in activation of signaling and report new inhibitory antibodies. We determined the structural basis for receptor inhibition by obtaining the first co-crystal structure of a NOTCH3 antibody with the NRR protein and defined two distinct epitopes for NRR antibodies. The antibodies exhibit potent anti-leukemic activity in cell lines and tumor xenografts harboring NOTCH3 activating mutations. Screening of primary T-ALL samples reveals that 2 of 40 tumors examined show active NOTCH3 signaling. We also identified evidence of NOTCH3 activation in 12 of 24 patient-derived orthotopic xenograft models, 2 of which exhibit activation of NOTCH3 without activation of NOTCH1. Our studies provide additional insights into NOTCH3 activation and offer a path forward for identification of cancers that are likely to respond to therapy with NOTCH3 selective inhibitory antibodies.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Antineoplásicos/farmacología , Mutación , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Receptor Notch3/antagonistas & inhibidores , Receptor Notch3/genética , Sustitución de Aminoácidos , Animales , Línea Celular Tumoral , Codón , Modelos Animales de Enfermedad , Epítopos/química , Epítopos/inmunología , Femenino , Humanos , Ratones , Modelos Moleculares , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Conformación Proteica , Receptor Notch3/química , Receptor Notch3/metabolismo , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
8.
Dalton Trans ; 45(12): 5374-87, 2016 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-26907543

RESUMEN

Herein we report the synthesis and characterisation of a series of salalen and salan ligands derived from 2-(aminomethyl)piperidine. Depending on the choice of starting salicylaldehyde, a bicyclic salan type ligand (1-3H2) or imino salalen type ligand (4-6H, 7-9H2) were prepared. The ligands were successfully complexed to group 4 metals and aluminium; with hafnium and zirconium octahedral complexes, M(1-3)2, were realised; whilst with aluminium tetrahedral and trigonal bipyramidal complexes, Al(1-9)Mex (x = 1,2), were isolated. The complexes have been characterised in solution via(1)H and (13)C{(1)H} NMR spectroscopy and in the solid state by X-ray crystallography. The group 4 complexes were observed to have a fac-fac arrangement of ligands and there were two isomers present when 3H2 was ligated. The imino aluminium complexes Al(7-9)Me were isolated as a mixture of diastereoisomers. The resultant complexes were trialed in the ring opening polymerisation of rac-lactide with both heterotactic and isotactic PLA being demonstrated. Tacticity was found to be dependent on the nature of the ligand and metal used; the M(1-3)2 complexes were generally found to have a heterotactic preference (Pr = 0.67-0.76) and the aluminium polymerisation outcome was dictated more by the steric influence of the ligand, particularly for Al(4/6)Me2/Al(7/9)Me.

9.
Mol Ecol ; 24(23): 5992-6005, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26507980

RESUMEN

Ectomycorrhizal (EcM) fungal communities may be shaped by both deterministic and stochastic processes, potentially influencing ecosystem development and function. We evaluated community assembly processes for EcM fungi of Pseudotsuga menziesii among 12 sites up to 400 km apart in southwest British Columbia (Canada) by investigating species turnover (ß-diversity) in relation to soil nitrogen (N) availability and physical distance. We then examined functional traits for an N-related niche by quantifying net fluxes of NH4+, NO3- and protons on excised root tips from three contrasting sites using a microelectrode ion flux measurement system. EcM fungal communities were well aligned with soil N availability and pH, with no effect of site proximity (distance-decay curve) on species assemblages. Species turnover was significant (ß(1/2) = 1.48) along soil N gradients, with many more Tomentella species on high N than low N soils, in contrast to Cortinarius species. Ammonium uptake was greatest in the spring on the medium and rich sites and averaged over 190 nmol/m(2)/s for Tomentella species. The lowest uptake rates of NH4+ were by nonmycorrhizal roots of axenically grown seedlings (10 nmol/m(2)/s), followed by Cortinarius species (60 nmol/m(2)/s). EcM roots from all sites displayed only marginal uptake of nitrate (8.3 nmol/m(2)/s). These results suggest NH4+ uptake capacity is an important functional trait influencing the assembly of EcM fungal communities. The diversity of EcM fungal species across the region arguably provides critical belowground adaptations to organic and inorganic N supply that are integral to temperate rainforest ecology.


Asunto(s)
Compuestos de Amonio/metabolismo , Micorrizas/clasificación , Micorrizas/metabolismo , Ciclo del Nitrógeno , Colombia Británica , Datos de Secuencia Molecular , Nitratos/metabolismo , Raíces de Plantas/microbiología , Pseudotsuga/microbiología , Suelo/química
10.
J Vet Intern Med ; 29(5): 1322-6, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26306818

RESUMEN

BACKGROUND: The effect of feeding a limited iodine diet on radioactive iodine uptake in the thyroid glands of hyperthyroid cats is unknown. OBJECTIVES: To determine how feeding limited dietary iodine affects radioactive iodine uptake by the thyroid glands of hyperthyroid cats. ANIMALS: Eight geriatric cats with spontaneous hyperthyroidism. METHODS: Prospective study of eight client owned hyperthyroid cats fed a commercially available iodine limited diet for 6 months. Clinical signs were evaluated and TT4 and fT4 were measured during consumption of the diet. Uptake of (123)I was determined before and 8-16 weeks after exclusive consumption of the diet. RESULTS: Clinical signs of hyperthyroidism resolved in all cats, but there was no significant increase in body weight. TT4 and fT4 decreased into the reference range by 8-16 weeks in all cats. Mean TT4 before consumption of the diet was 9.7 µg/dL (SD 5.2) and after consumption of the diet was 3.1 µg/dL (SD 0.9). Scintigraphy revealed unilateral uptake of isotope in 5 cats and bilateral uptake in 3 cats. Mean percentage uptake of (123)I by the thyroid gland at 8 hours after isotope administration was 16.2 (SD 11.8) before diet consumption and 34.6 (SD 11.7) 8-16 weeks after exclusive consumption of the diet. The percentage increase was variable between cats (38-639%). CONCLUSIONS AND CLINICAL IMPORTANCE: Limited iodine diets increase iodine uptake in the autonomous thyroid glands of hyperthyroid cats. Further studies are necessary to determine if consumption of a limited iodine diet changes sensitivity of the thyroid gland to (131)I treatment.


Asunto(s)
Enfermedades de los Gatos/dietoterapia , Hipertiroidismo/veterinaria , Yodo/administración & dosificación , Glándula Tiroides/metabolismo , Animales , Enfermedades de los Gatos/diagnóstico por imagen , Gatos , Femenino , Hipertiroidismo/diagnóstico por imagen , Hipertiroidismo/dietoterapia , Yodo/farmacocinética , Radioisótopos de Yodo/administración & dosificación , Radioisótopos de Yodo/farmacocinética , Masculino , Tomografía de Emisión de Positrones/veterinaria , Estudios Prospectivos , Glándula Tiroides/diagnóstico por imagen , Tiroxina/sangre
11.
J Chromatogr B Analyt Technol Biomed Life Sci ; 983-984: 94-100, 2015 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-25635951

RESUMEN

Ultrahigh performance supercritical fluid chromatography (UHPSFC) in combination with sub-2µm particles and either diode array ultraviolet (UV), evaporative light scattering, (ELSD), or mass spectrometric (MS) detection has been shown to be a valuable technique for the determination of acylglycerols in soybean, corn, sesame, and tobacco seed oils. Excellent resolution on an un-endcapped single C18 column (3.0mm×150mm) with a mobile phase gradient of acetonitrile and carbon dioxide in as little as 10min served greatly as an improvement on first generation packed column SFC instrumentation. Unlike high resolution gas chromatography and high performance liquid chromatography with mass spectrometric detection, UHPSFC/MS was determined to be a superior analytical tool for both separation and detection of mono-, di-, and tri-acylglycerols as well as free glycerol itself in biodiesel without derivatization. Baseline separation of residual tri-, di-, and mono-acylglycerols alongside glycerol at 0.05% (w/w) was easily obtained employing packed column SFC. The new analytical methodology was applied to both commercial B100 biodiesel (i.e. fatty acid methyl esters) derived from vegetable oil and to an "in-house" synthetic biodiesel (i.e. fatty acid ethyl esters) derived from tobacco seed oil and ethanol both before and after purification via column chromatography on bare silica.


Asunto(s)
Biocombustibles/análisis , Cromatografía Líquida de Alta Presión/métodos , Cromatografía con Fluido Supercrítico/métodos , Lípidos/química , Estudios de Factibilidad , Glicerol/análisis , Inyecciones , Espectrometría de Masas , Dispersión de Radiación , Triglicéridos/análisis , Rayos Ultravioleta
12.
Chem Sci ; 6(11): 6305-6311, 2015 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-30090248

RESUMEN

Real time and non-invasive detection of pH in live biological systems is crucial for understanding the physiological role of acid-base homeostasis and for detecting pathological conditions associated with pH imbalance. One method to achieve in vivo pH monitoring is NMR. Conventional NMR methods, however, mainly utilize molecular sensors displaying pH-dependent chemical shift changes, which are vulnerable to multiple pH-independent factors. Here, we present a novel ratiometric strategy for sensitive and accurate pH sensing based on a small synthetic molecule, SPE1, which exhibits exceptionally slow proton exchange on the NMR time scale. Each protonation state of the sensor displays distinct NMR signals and the ratio of these signals affords precise pH values. In contrast to standard NMR methods, this ratiometric mechanism is not based on a chemical shift change, and SPE1 binds protons with high selectivity, resulting in accurate measurements. SPE1 was used to measure the pH in a single oocyte as well as in bacterial cultures, demonstrating the versatility of this method and establishing the foundation for broad biological applications.

13.
Metallomics ; 7(4): 662-73, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25521693

RESUMEN

Nickel is an essential transition metal for the survival of Helicobacter pylori in the acidic human stomach. The nickel-responsive transcriptional regulator HpNikR is important for maintaining healthy cytosolic nickel concentrations through the regulation of multiple genes, but its complete regulon and role in nickel homeostasis are not well understood. To investigate potential gene targets of HpNikR, ChIP sequencing was performed using H. pylori grown at neutral pH in nickel-supplemented media and this experiment identified HPG27_866 (frpB2) and HPG27_1499 (ceuE). These two genes are annotated to encode a putative iron transporter and a nickel-binding, periplasmic component of an ABC transporter, respectively. In vitro DNA-binding assays revealed that HpNikR binds both gene promoter sequences in a nickel-responsive manner with affinities on the order of ∼10(-7) M. The recognition sites of HpNikR were identified and loosely correlate with the HpNikR pseudo-consensus sequence (TATTATT-N11-AATAATA). Quantitative PCR experiments revealed that HPG27_866 and HPG27_1499 are transcriptionally repressed following growth of H. pylori G27 in nickel-supplemented media, and that this response is dependent on HpNikR. In contrast, iron supplementation results in activation of HPG27_1499, but no impact on the expression of HPG27_866 was observed. Metal analysis of the Δ866 strain revealed that HPG27_866 has an impact on nickel accumulation. These studies demonstrate that HPG27_866 and HPG27_1499 are both direct targets of HpNikR and that HPG27_866 influences nickel uptake in H. pylori.


Asunto(s)
Proteínas Bacterianas/química , Helicobacter pylori/metabolismo , Níquel/química , Proteínas Represoras/química , Secuencia de Bases , Sitios de Unión , Inmunoprecipitación de Cromatina , Citosol/metabolismo , ADN/química , ADN Bacteriano , Desoxirribonucleasa I/química , Regulación Bacteriana de la Expresión Génica , Concentración de Iones de Hidrógeno , Metales/química , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas , ARN/química , Homología de Secuencia de Ácido Nucleico
14.
Rev Sci Instrum ; 85(11): 113103, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25430094

RESUMEN

We present a dual-species oven and Zeeman slower setup capable of producing slow, high-flux atomic beams for loading magneto-optical traps. Our compact and versatile system is based on electronic switching between different magnetic field profiles and is applicable to a wide range of multi-species experiments. We give details of the vacuum setup, coils, and simple electronic circuitry. In addition, we demonstrate the performance of our system by optimized, sequential loading of magneto-optical traps of lithium-6 and cesium-133.

16.
Mol Syndromol ; 4(4): 184-96, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23801935

RESUMEN

Hereditary haemorrhagic telangiectasia (HHT) is a disease characterised by abnormal vascular structures, and most commonly caused by mutations in ENG, ACVRL1 or SMAD4 encoding endothelial cell-expressed proteins involved in TGF-ß superfamily signalling. The majority of mutations reported on the HHT mutation database are predicted to lead to stop codons, either due to frameshifts or direct nonsense substitutions. The proportion is higher for ENG (67%) and SMAD4 (65%) than for ACVRL1 (42%), p < 0.0001. Here, by focussing on ENG, we report why conventional views of these mutations may need to be revised. Of the 111 stop codon-generating ENG mutations, on ExPASy translation, all except one were premature termination codons (PTCs), sited at least 50-55 bp upstream of the final exon-exon boundary of the main endoglin isoform, L-endoglin. This strongly suggests that the mutated RNA species will undergo nonsense-mediated decay. We provide new in vitro expression data to support dominant negative activity of stable truncated endoglin proteins but suggest these will not generate HHT: the single natural stop codon mutation in L-endoglin (sited within 50-55 nucleotides of the final exon-exon boundary) is unlikely to generate functional protein since it replaces the entire transmembrane domain, as would 8 further natural stop codon mutations, if the minor S-endoglin isoform were implicated in HHT pathogenesis. Finally, next-generation RNA sequencing data of 7 different RNA libraries from primary human endothelial cells demonstrate that multiple intronic regions of ENG are transcribed. The potential consequences of heterozygous deletions or duplications of such regions are discussed. These data support the haploinsufficiency model for HHT pathogenesis, explain why final exon mutations have not been detected to date in HHT, emphasise the potential need for functional examination of non-PTC-generating mutations, and lead to proposals for an alternate stratification system of mutational types for HHT genotype-phenotype correlations.

17.
World J Surg ; 37(10): 2443-53, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23716026

RESUMEN

BACKGROUND: The purpose of the present study was to describe the impact of treatment of pancreatic and peri-ampullary malignancy on patient reported outcomes (PRO). However, limited data are available describing the impact of curative or palliative therapy on pancreatic/peri-ampullary malignancy and quality of life. METHODS: Patients selected for pancreaticoduodenectomy (PD) completed the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire pre-surgery and 6 weeks, 3, 6, 12, 18, and 24 months postoperatively. Patients selected for palliative treatments completed the same questionnaire before treatment and monthly thereafter. Mean scores and 95 % confidence intervals (CI) were calculated for functional scales. Symptom scales and single items were categorized as either minimal or severe, and they were reported as proportions of patients experiencing severe symptoms with 95 % CI. RESULTS: A total of 100 patients (53 planned PD, 47 palliative) were enrolled. Of the 53 patients planned for surgery, 12 had tumors that were unresectable and 41 underwent pancreatoduodenectomy (PD). Seven patients were excluded because of benign histology or concurrent malignancy. Baseline questionnaire compliance was 70 %. For those undergoing PD, there were 53 complications, 7 deaths at 1 year, and 14 deaths at 2 years. Post-surgery most functions and symptoms deteriorated. Recovery in global health and most symptoms occurred by 3 months, and functional scales recovered by 6 months. Recovery of PRO was maintained in the survivors at 2 years. Palliative patients had poorer function and more symptoms at baseline; however, poor follow-up questionnaire compliance prevented further analysis of this group. CONCLUSIONS: Pancreaticoduodenectomy has a short-term negative impact on PRO that recovers within 6 months and is maintained at 2 years in survivors. Further work evaluating palliative and curative treatment in larger patient groups with disease-specific questionnaires is necessary.


Asunto(s)
Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco/terapia , Cuidados Paliativos , Neoplasias Pancreáticas/terapia , Pancreaticoduodenectomía , Satisfacción del Paciente/estadística & datos numéricos , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recuperación de la Función , Autoinforme , Encuestas y Cuestionarios , Resultado del Tratamiento
18.
Ann Oncol ; 23(7): 1713-22, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22241899

RESUMEN

BACKGROUND: Current staging methods for pancreatic cancer (PC) are inadequate, and biomarkers to aid clinical decision making are lacking. Despite the availability of the serum marker carbohydrate antigen 19.9 (CA19.9) for over two decades, its precise role in the management of PC is yet to be defined, and as a consequence, it is not widely used. METHODS: We assessed the relationship between perioperative serum CA19.9 levels, survival and adjuvant chemotherapeutic responsiveness in a cohort of 260 patients who underwent operative resection for PC. RESULTS: By specifically assessing the subgroup of patients with detectable CA19.9, we identified potential utility at key clinical decision points. Low postoperative CA19.9 at 3 months (median survival 25.6 vs 14.8 months, P=0.0052) and before adjuvant chemotherapy were independent prognostic factors. Patients with postoperative CA 19.9 levels>90 U/ml did not benefit from adjuvant chemotherapy (P=0.7194) compared with those with a CA19.9 of ≤90 U/ml (median 26.0 vs 16.7 months, P=0.0108). Normalization of CA19.9 within 6 months of resection was also an independent favorable prognostic factor (median 29.9 vs 14.8 months, P=0.0004) and normal perioperative CA19.9 levels identified a good prognostic group, which was associated with a 5-year survival of 42%. CONCLUSIONS: Perioperative serum CA19.9 measurements are informative in patients with detectable CA19.9 (defined by serum levels of >5 U/ml) and have potential clinical utility in predicting outcome and response to adjuvant chemotherapy. Future clinical trials should prioritize incorporation of CA19.9 measurement at key decision points to prospectively validate these findings and facilitate implementation.


Asunto(s)
Biomarcadores de Tumor/sangre , Antígeno CA-19-9/sangre , Carcinoma Ductal Pancreático/sangre , Recurrencia Local de Neoplasia , Neoplasias Pancreáticas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/terapia , Quimioterapia Adyuvante , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pancreatectomía , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/terapia , Periodo Perioperatorio , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos
19.
Med Sci Law ; 51(4): 203-7, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22021589

RESUMEN

When considering cases of infant head injury as a result of a short fall, investigators often have to base their opinions on the potential severity of a head injury on a scene description and/or photographic evidence of the potential impact surfaces. While variation in the attenuation properties of typical domestic surfaces and underlying support structures have been reported in the literature, this study investigates whether there is a need to consider the nature and composition of specific potential impact floor surfaces/sites, within a scene, prior to providing an opinion about the likely head impact injury outcome. An instrumented headform was impacted within a suspected crime scene to determine whether different potential impact sites posed different risks of producing head injury. The impact acceleration-time waveform, for the headform, was shown to vary considerably across the floor. By applying recognized head impact injury risk measures (peak g and head injury criterion), it was illustrated that the risk of an infant sustaining a significant head injury could vary considerably, depending upon the exact point of impact with the floor. This study highlights the potential for variation in impact force across a scene and illustrates the need to consider surface composition at specific sites across the entire potential impact area, since the risk of head injury can vary significantly. Caution should therefore be exercised when expressing opinions based solely on verbal, written or photographic evidence of head impact surfaces, without due consideration of the specific area onto which a head might have impacted.


Asunto(s)
Accidentes por Caídas , Pisos y Cubiertas de Piso , Traumatismos Cerrados de la Cabeza/patología , Modelos Biológicos , Aceleración , Fenómenos Biofísicos , Patologia Forense , Humanos , Lactante , Recién Nacido , Puntaje de Gravedad del Traumatismo
20.
Proc Inst Mech Eng H ; 225(2): 141-8, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21428148

RESUMEN

The use of synthetic connective tissue grafts became popular in the mid-1980s, particularly for anterior cruciate ligament reconstruction; however, this trend was soon changed given the high failure rate due to abrasive wear. More than 20 years later, a vast range of grafts are available to the orthopaedic surgeon for augmenting connective tissue following rupture or tissue loss. While the biomechanical properties of these synthetic grafts become ever closer to the natural tissue, there have been no reports of their bio-tribological (i.e. bio-friction) characteristics. In this study, the bio-tribological performance of three clinically available synthetic tissue grafts, and natural tendon, was investigated. It was established that the natural tissue exhibits fluid-film lubrication characteristics and hence is highly efficient when sliding against opposing tissues. Conversely, all the synthetic tissues demonstrated boundary or mixed lubrication regimes, resulting in surface-surface contact, which will subsequently cause third body wear. The tribological performance of the synthetic tissue, however, appeared to be dependent on the macroscopic structure. This study indicates that there is a need for synthetic tissue designs to have improved frictional characteristics or to use a scaffold structure that encourages tissue in-growth. Such a development would optimize the bio-tribological properties of the synthetic tissue and thereby maximize longevity.


Asunto(s)
Materiales Biocompatibles/química , Fibrocartílago/química , Trasplantes , Animales , Fenómenos Biomecánicos , Bovinos , Fibrocartílago/fisiología , Vidrio , Ensayo de Materiales , Rodilla de Cuadrúpedos , Tendones/química , Tendones/fisiología
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