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1.
bioRxiv ; 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38260539

RESUMO

Recent studies in mice have indicated that the gut microbiome can regulate bone tissue strength. However, prior work involved modifications to the gut microbiome in growing animals and it is unclear if the same changes in the microbiome, applied later in life, would change matrix strength. Here we changed the composition of the gut microbiome before and/or after skeletal maturity (16 weeks of age) using oral antibiotics (ampicillin + neomycin). Male and female mice (n=143 total, n=12-17/group/sex) were allocated into five study groups:1) Unaltered, 2) Continuous (dosing 4-24 weeks of age), 3) Delayed (dosing only 16-24 weeks of age), 4) Initial (dosing 4-16 weeks of age, suspended at 16 weeks), and 5) Reconstituted (dosing from 4-16 weeks following by fecal microbiota transplant from Unaltered donors). Animals were euthanized at 24 weeks of age. In males, bone matrix strength in the femur was 25-35% less than expected from geometry in mice from the Continuous (p= 0.001), Delayed (p= 0.005), and Initial (p=0.040) groups as compared to Unaltered. Reconstitution of the gut microbiota, however, led to a bone matrix strength similar to Unaltered animals (p=0.929). In females, microbiome-induced changes in bone matrix strength followed the same trend as males but were not significantly different, demonstrating sex-related differences in the response of bone matrix to the gut microbiota. Minor differences in chemical composition of bone matrix were observed (Raman spectroscopy). Our findings indicate that microbiome-induced impairment of bone matrix in males can be initiated and/or reversed after skeletal maturity. The portion of the femoral cortical bone formed after skeletal maturity (16 weeks) is small; however, this suggests that microbiome-induced changes in bone matrix occur without osteoblast/osteoclast turnover using an, as of yet unidentified mechanism. These findings add to evidence that the mechanical properties of bone matrix can be altered in the adult skeleton.

2.
Am J Surg ; 214(4): 629-633, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28918848

RESUMO

BACKGROUND: Single-session intraoperative radiation therapy (IORT) minimizes treatment demands associated with traditional whole breast radiation therapy (WBRT) but outcomes on local disease control and morbidity among the elderly is limited. METHODS: A multi-institutional retrospective registry was established from 19 centers utilizing IORT from 2007 to 2013. Patient, tumor, and treatment variables were analyzed for ages <70 and ≥70. RESULTS: We evaluated 686 patients (<70 = 424; ≥70 = 262) who were margin and lymph node negative. Patients <70 were more likely to have longer operative time, oncoplastic closure, higher rates of IORT used as planned boost, and receive chemotherapy and post-operative WBRT. Wound complication rates were low and not significantly different between age groups. Median follow-up was 1.06 (range 0.51-1.9) years for < 70 and 1.01 (range 0.5-1.68) years for ≥ 70. There were 5 (0.73%) breast recurrences (4 in <70 and 1 ≥ 70, p = 0.65) and no axillary recurrences during follow-up. CONCLUSIONS: IORT was associated with a low rate of wound complication and local recurrence on short-term follow-up in this cohort.


Assuntos
Neoplasias da Mama/radioterapia , Cuidados Intraoperatórios , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Terapia Combinada , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , América do Norte , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
5.
Diabet Med ; 33(7): 976-84, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26479152

RESUMO

AIMS: HNF1A gene mutations are the most common cause of maturity-onset diabetes of the young (MODY) in the UK. Persons with HNF1A-MODY display sensitivity to sulphonylurea therapy; however, the long-term efficacy is not established. There is limited literature as to the prevalence of micro- and macrovascular complications in this unique cohort. The aim of this study was to determine the natural progression and clinical management of HNF1A-MODY diabetes in a dedicated MODY clinic. METHODS: Sixty patients with HNF1A-MODY and a cohort of 60 BMI-, age-, ethnicity- and diabetes duration-matched patients with Type 1 diabetes mellitus participated in the study. All patients were phenotyped in detail. Clinical follow-up of the HNF1A-MODY cohort occurred on a bi-annual basis. RESULTS: Following a genetic diagnosis of MODY, the majority of the cohort treated with sulphonylurea therapy remained insulin independent at 84-month follow-up (80%). The HbA1c in the HNF1A-MODY group treated with sulphonylurea therapy alone improved significantly over the study period [from 49 (44-63) mmol/mol, 6.6 (6.2-7.9)% to 41 (31-50) mmol/mol, 5.9 (5-6.7)%; P = 0.003]. The rate of retinopathy was significantly lower than that noted in the Type 1 diabetes mellitus group (13.6 vs. 50%; P = 0.0001).There was also a lower rate of microalbuminuria and cardiovascular disease in the HNF1A-MODY group compared with the Type 1 diabetes mellitus group. CONCLUSIONS: This study demonstrates that the majority of patients with HNF1A-MODY can be maintained successfully on sulphonylurea therapy with good glycaemic control. We note a significantly lower rate of micro- and macrovascular complications than reported previously. The use of appropriate therapy at early stages of the disorder may decrease the incidence of complications.


Assuntos
Complicações do Diabetes/epidemiologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fator 1-alfa Nuclear de Hepatócito/genética , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Adulto , Albuminúria/epidemiologia , Albuminúria/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Doença das Coronárias/epidemiologia , Doença das Coronárias/etiologia , Complicações do Diabetes/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/etiologia , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Progressão da Doença , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Quimioterapia de Manutenção/métodos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Reino Unido , Adulto Jovem
7.
Phys Med Biol ; 58(12): 4071-97, 2013 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-23685866

RESUMO

Image segmentation has become a vital and often rate-limiting step in modern radiotherapy treatment planning. In recent years, the pace and scope of algorithm development, and even introduction into the clinic, have far exceeded evaluative studies. In this work we build upon our previous evaluation of a registration driven segmentation algorithm in the context of 8 expert raters and 20 patients who underwent radiotherapy for large space-occupying tumours in the brain. In this work we tested four hypotheses concerning the impact of manual segmentation editing in a randomized single-blinded study. We tested these hypotheses on the normal structures of the brainstem, optic chiasm, eyes and optic nerves using the Dice similarity coefficient, volume, and signed Euclidean distance error to evaluate the impact of editing on inter-rater variance and accuracy. Accuracy analyses relied on two simulated ground truth estimation methods: simultaneous truth and performance level estimation and a novel implementation of probability maps. The experts were presented with automatic, their own, and their peers' segmentations from our previous study to edit. We found, independent of source, editing reduced inter-rater variance while maintaining or improving accuracy and improving efficiency with at least 60% reduction in contouring time. In areas where raters performed poorly contouring from scratch, editing of the automatic segmentations reduced the prevalence of total anatomical miss from approximately 16% to 8% of the total slices contained within the ground truth estimations. These findings suggest that contour editing could be useful for consensus building such as in developing delineation standards, and that both automated methods and even perhaps less sophisticated atlases could improve efficiency, inter-rater variance, and accuracy.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Encéfalo/citologia , Processamento de Imagem Assistida por Computador/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Algoritmos , Encéfalo/patologia , Encéfalo/efeitos da radiação , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Tomografia Computadorizada por Raios X
8.
Med Phys ; 39(6Part5): 3642, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28517623

RESUMO

PURPOSE: A laboratory-based phase-contrast radiography/tomosynthesis imaging system previously (Med. Phys. Vol. 38, 2353 May 2011) for improved detection of low-contrast soft-tissue masses was used to evaluate the sensitivity for detecting the presence of thin layers of corrosion on aluminum aircraft structures. METHODS: The evaluation utilized a test object of aluminum (2.5 inch × 2.5 inch × 1/8 inch) on which different geometric patterns of 0.0038 inch thick anodized aluminum oxide was deposited. A circular area of radius 1 inch centered on the phantom's midpoint was milled to an approximate thickness of 0.022 inches. The x-ray source used for this investigation was a dual focal spot, tungsten anode x-ray tube. The focal used during the investigation has a nominal size of 0.010 mm. The active area of the imager is 17.1 cm × 23.9 cm (2016 × 2816 pixels) with a pixel pitch of 0.085 mm. X-ray tube voltages ranged from 20-40 kVp and source- to-object and object-to-image distances were varied from 20-100 cm. Performance of the phase-contrast mode was compared to conventional absorption-based radiography using contrast ratio and contrast-to-noise ratios (C/N). Phase-contrast performance was based on edge-enhancement index (EEI) and the edge-enhancement-to-noise (EE/N) ratio. RESULTS: for absorption-based radiography, the best C/N ratio was observed at the lowest kVp value (20 kVp). The optimum sampling angle for tomosynthesis was +/- 8 degrees. CONCLUSIONS: Comparing C/N to EE/N demonstrated the phase-contrast techniques improve the conspicuity of the oxide layer edges. This work provides the optimal parameters that a radiographic imaging system would need to differentiate the two different compounds of aluminum. Subcontractee from Positron Systems Inc. (Boise, Idaho) through United States Air Force grant (AF083-225).

9.
Phys Med Biol ; 56(14): 4557-77, 2011 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-21725140

RESUMO

The purpose of this work was to characterize expert variation in segmentation of intracranial structures pertinent to radiation therapy, and to assess a registration-driven atlas-based segmentation algorithm in that context. Eight experts were recruited to segment the brainstem, optic chiasm, optic nerves, and eyes, of 20 patients who underwent therapy for large space-occupying tumors. Performance variability was assessed through three geometric measures: volume, Dice similarity coefficient, and Euclidean distance. In addition, two simulated ground truth segmentations were calculated via the simultaneous truth and performance level estimation algorithm and a novel application of probability maps. The experts and automatic system were found to generate structures of similar volume, though the experts exhibited higher variation with respect to tubular structures. No difference was found between the mean Dice similarity coefficient (DSC) of the automatic and expert delineations as a group at a 5% significance level over all cases and organs. The larger structures of the brainstem and eyes exhibited mean DSC of approximately 0.8-0.9, whereas the tubular chiasm and nerves were lower, approximately 0.4-0.5. Similarly low DSCs have been reported previously without the context of several experts and patient volumes. This study, however, provides evidence that experts are similarly challenged. The average maximum distances (maximum inside, maximum outside) from a simulated ground truth ranged from (-4.3, +5.4) mm for the automatic system to (-3.9, +7.5) mm for the experts considered as a group. Over all the structures in a rank of true positive rates at a 2 mm threshold from the simulated ground truth, the automatic system ranked second of the nine raters. This work underscores the need for large scale studies utilizing statistically robust numbers of patients and experts in evaluating quality of automatic algorithms.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Encéfalo/patologia , Prova Pericial , Processamento de Imagem Assistida por Computador/métodos , Automação , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Humanos , Imageamento por Ressonância Magnética , Radioterapia de Intensidade Modulada , Fatores de Tempo , Tomografia Computadorizada por Raios X
10.
Pattern Recognit ; 42(6): 1162-1171, 2009 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-20161266

RESUMO

Accumulating evidence suggests that characteristics of pre-treatment FDG-PET could be used as prognostic factors to predict outcomes in different cancer sites. Current risk analyses are limited to visual assessment or direct uptake value measurements. We are investigating intensity-volume histogram metrics and shape and texture features extracted from PET images to predict patient's response to treatment. These approaches were demonstrated using datasets from cervix and head and neck cancers, where AUC of 0.76 and 1.0 were achieved, respectively. The preliminary results suggest that the proposed approaches could potentially provide better tools and discriminant power for utilizing functional imaging in clinical prognosis.

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