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1.
Hum Reprod Open ; 2022(4): hoac051, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36483694

RESUMO

STUDY QUESTION: What is the contemporary prevalence of infertility in world populations and how do they differ by methodological and study characteristics? SUMMARY ANSWER: Pooled estimates of lifetime and period prevalence of 12-month infertility were 17.5% and 12.6%, respectively, but this varied by study population and methodological approach. WHAT IS KNOWN ALREADY: Infertility affects millions of individuals worldwide. Accurate measures of its magnitude are needed to effectively address and manage the condition. There are distinct challenges and variation in how infertility is defined and measured, limiting comparability of estimates across studies. Further research is needed to understand whether and how differences in methodological approaches and study characteristics account for heterogeneity in estimates. STUDY DESIGN SIZE DURATION: We conducted a systematic review and meta-analysis. Six electronic databases, websites of relevant organizations, and conference proceedings were systematically searched. Searches were limited to those published between 1 January 1990 and 11 March 2021, with no language restrictions. PARTICIPANTS/MATERIALS SETTING METHODS: Descriptive and random-effects meta-analysis models were used to examine range of estimates and generate estimates of pooled lifetime and period prevalence of 12-month infertility, respectively, among representative populations. Meta-regression using restricted maximum likelihood was applied to account for definitional and study characteristics and to obtain adjusted estimates. Risk of bias was assessed with a validated tool. MAIN RESULTS AND THE ROLE OF CHANCE: The search yielded 12 241 unique records of which 133 studies met the criteria for the systematic review. There were 65 and 69 studies that provided data for lifetime and period prevalence of 12-month infertility, respectively. Five methodological approaches were identified: prospective time-to-pregnancy (TTP) design, current duration design, retrospective TTP design, self-reported infertility measure and constructed infertility measure. Ranges for lifetime (3.3-39.7%) and period estimates (1.6-34.0%) were similar and wide even after accounting for methodological and study characteristics. Pooled estimates of lifetime and period prevalence were 17.5% (95% CI: 15.0, 20.3, n = 37 studies, I 2 = 99.5%) and 12.6% (95% CI: 10.7, 14.6, n = 43 studies, I 2 = 99.8%), respectively, with some variation in magnitude by region and methodological approach, but with most CIs overlapping. LIMITATIONS REASONS FOR CAUTION: Pooled estimates generated from meta-analysis were derived from 12-month infertility prevalence estimates that were heterogeneous across different domains, even after adjusting for definitional and study characteristics. The number of studies was small for certain strata from which pooled estimates were derived (e.g. there were only two studies for lifetime prevalence in Africa). WIDER IMPLICATIONS OF THE FINDINGS: While findings show a high prevalence of infertility globally and regionally, it also reveals variation in measures to ascertain and compare infertility prevalence. More systematic and comprehensive collection of data using a consistent definition is needed to improve infertility prevalence estimates at global, regional and country-levels. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the World Health Organization. The authors have no conflicts of interest. REGISTRATION NUMBER: PROSPERO CRD42020211704.

2.
Rev Sci Instrum ; 93(2): 023502, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35232152

RESUMO

We report a technique of proton deflectometry that uses a grid and an in situ reference x-ray grid image for precise measurements of magnetic fields in high-energy-density plasmas. A D3He fusion implosion provides a bright point source of both protons and x-rays, which is split into beamlets by a grid. The protons undergo deflections as they propagate through the plasma region of interest, whereas the x-rays travel along straight lines. The x-ray image, therefore, provides a zero-deflection reference image. The line-integrated magnetic fields are inferred from the shifts of beamlets between the deflected (proton) and reference (x-ray) images. We developed a system for analysis of these data, including automatic algorithms to find beamlet locations and to calculate their deflections from the reference image. The technique is verified in an experiment performed at OMEGA to measure a nonuniform magnetic field in vacuum and then applied to observe the interaction of an expanding plasma plume with the magnetic field.

3.
J Mech Behav Biomed Mater ; 122: 104680, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34271404

RESUMO

Motion sensitive MR imaging techniques allow for the non-invasive evaluation of biological tissues by using different excitation schemes, including physiological/intrinsic motions caused by cardiac pulsation or respiration, and vibrations caused by an external actuator. The mechanical biomarkers extracted through these imaging techniques have been shown to hold diagnostic value for various neurological disorders and conditions. Amplified MRI (aMRI), a cardiac gated imaging technique, can help track and quantify low frequency intrinsic motion of the brain. As for high frequency actuation, the mechanical response of brain tissue can be measured by applying external high frequency actuation in combination with a motion sensitive MR imaging sequence called Magnetic Resonance Elastography (MRE). Due to the frequency-dependent behavior of brain mechanics, there is a need to develop brain phantom models that can mimic the broadband mechanical response of the brain in order to validate motion-sensitive MR imaging techniques. Here, we have designed a novel phantom test setup that enables both the low and high frequency responses of a brain-mimicking phantom to be captured, allowing for both aMRI and MRE imaging techniques to be applied on the same phantom model. This setup combines two different vibration sources: a pneumatic actuator, for low frequency/intrinsic motion (1 Hz) for use in aMRI, and a piezoelectric actuator for high frequency actuation (30-60 Hz) for use in MRE. Our results show that in MRE experiments performed from 30 Hz through 60 Hz, propagating shear waves attenuate faster at higher driving frequencies, consistent with results in the literature. Furthermore, actuator coupling has a substantial effect on wave amplitude, with weaker coupling causing lower amplitude wave field images, specifically shown in the top-surface shear loading configuration. For intrinsic actuation, our results indicate that aMRI linearly amplifies motion up to at least an amplification factor of 9 for instances of both visible and sub-voxel motion, validated by varying power levels of pneumatic actuation (40%-80% power) under MR, and through video analysis outside the MRI scanner room. While this investigation used a homogeneous brain-mimicking phantom, our setup can be used to study the mechanics of non-homogeneous phantom configurations with bio-interfaces in the future.


Assuntos
Técnicas de Imagem por Elasticidade , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Humanos , Movimento (Física) , Imagens de Fantasmas
4.
Health Educ Res ; 36(1): 126-139, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33367691

RESUMO

teen Mental Health First Aid (teenMHFA) is a school-based mental health program that trains adolescents to support peers who are experiencing mental health problems or crises. The program has been evaluated for adolescents aged 15-18 years as part of a randomized controlled trial, however qualitative feedback from students on their perceptions of the program is yet to be explored. The current study describes the perspectives of students who took part in the trial. Feedback on the perceived strengths and weaknesses of the program was provided by 979 Year 10 students (M = 15.82 years, female = 43.94%, English as a first language = 72.77%) at four government funded public schools in Melbourne, Australia via online surveys. A content and thematic analysis was performed on the data using a six-step process. Students generally found the program relevant and they connected with the visual material, personal stories and interactive activities. Suggestions for improvements included encouraging active student participation in classroom discussion and providing opportunities to practice skills. School-based mental health education can benefit from input from stakeholder perspectives, particularly when designing mental health content for delivery by external trainers.


Assuntos
Educação em Saúde , Instituições Acadêmicas , Adolescente , Austrália , Feminino , Humanos , Grupo Associado , Avaliação de Programas e Projetos de Saúde , Estudantes
5.
Sci Adv ; 6(41)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33033036

RESUMO

The gravity field of a small body provides insight into its internal mass distribution. We used two approaches to measure the gravity field of the rubble-pile asteroid (101955) Bennu: (i) tracking and modeling the spacecraft in orbit about the asteroid and (ii) tracking and modeling pebble-sized particles naturally ejected from Bennu's surface into sustained orbits. These approaches yield statistically consistent results up to degree and order 3, with the particle-based field being statistically significant up to degree and order 9. Comparisons with a constant-density shape model show that Bennu has a heterogeneous mass distribution. These deviations can be modeled with lower densities at Bennu's equatorial bulge and center. The lower-density equator is consistent with recent migration and redistribution of material. The lower-density center is consistent with a past period of rapid rotation, either from a previous Yarkovsky-O'Keefe-Radzievskii-Paddack cycle or arising during Bennu's accretion following the disruption of its parent body.

6.
Sci Adv ; 6(41)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33033038

RESUMO

We investigate the shape of near-Earth asteroid (101955) Bennu by constructing a high-resolution (20 cm) global digital terrain model from laser altimeter data. By modeling the northern and southern hemispheres separately, we find that longitudinal ridges previously identified in the north extend into the south but are obscured there by surface material. In the south, more numerous large boulders effectively retain surface materials and imply a higher average strength at depth to support them. The north has fewer large boulders and more evidence of boulder dynamics (toppling and downslope movement) and surface flow. These factors result in Bennu's southern hemisphere being rounder and smoother, whereas its northern hemisphere has higher slopes and a less regular shape. We infer an originally asymmetric distribution of large boulders followed by a partial disruption, leading to wedge formation in Bennu's history.

7.
Sci Adv ; 6(18): eaba0513, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32494687

RESUMO

The absence of crustal magnetic fields above the martian basins Hellas, Argyre, and Isidis is often interpreted as proof of an early, before 4.1 billion years (Ga) ago, or late, after 3.9 Ga ago, dynamo. We revisit these interpretations using new MAVEN magnetic field data. Weak fields are present over the 4.5-Ga old Borealis basin, with the transition to strong fields correlated with the basin edge. Magnetic fields, confined to a near-surface layer, are also detected above the 3.7-Ga old Lucus Planum. We conclude that a dynamo was present both before and after the formation of the basins Hellas, Utopia, Argyre, and Isidis. A long-lived, Earth-like dynamo is consistent with the absence of magnetization within large basins if the impacts excavated large portions of strongly magnetic crust and exposed deeper material with lower concentrations of magnetic minerals.

8.
Nat Geosci ; 12(4): 247-252, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31080497

RESUMO

The shapes of asteroids reflect interplay between their interior properties and the processes responsible for their formation and evolution as they journey through the Solar System. Prior to the OSIRIS-REx (Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer) mission, Earth-based radar imaging gave an overview of (101955) Bennu's shape. Here, we construct a high-resolution shape model from OSIRIS-REx images. We find that Bennu's top-like shape, considerable macroporosity, and prominent surface boulders suggest that it is a rubble pile. High-standing, north-south ridges that extend from pole to pole, many long grooves, and surface mass wasting indicate some low levels of internal friction and/or cohesion. Our shape model indicates that, similar to other top-shaped asteroids, Bennu formed by reaccumulation and underwent past periods of fast spin leading to its current shape. Today, Bennu might follow a different evolutionary pathway, with interior stiffness permitting surface cracking and mass wasting.

9.
Nat Astron ; 3(4): 352-361, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32601603

RESUMO

The top-shape morphology of asteroid (101955) Bennu is commonly found among fast-spinning asteroids and binary asteroid primaries, and might have contributed significantly to binary asteroid formation. Yet a detailed geophysical analysis of this morphology for a fast-spinning asteroid has not been possible prior to the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission. Combining the measured Bennu mass and shape obtained during the Preliminary Survey phase of OSIRIS-REx, we find a significant transition in Bennu's surface slopes within its rotational Roche lobe, defined as the region where material is energetically trapped to the surface. As the intersection of the rotational Roche lobe with Bennu's surface has been most recently migrating towards its equator (given Bennu's increasing spin rate), we infer that Bennu's surface slopes have been changing across its surface within the last million years. We also find evidence for substantial density heterogeneity within this body, suggesting that its interior has a distribution of voids and boulders. The presence of such heterogeneity and Bennu's top-shape is consistent with spin-induced failure at some point in its past, although the manner of its failure cannot be determined yet. Future measurements by the OSIRIS-REx spacecraft will give additional insights and may resolve questions regarding the formation and evolution of Bennu's top-shape morphology and its link to the formation of binary asteroids.

10.
Anal Chem ; 90(22): 13475-13482, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30379538

RESUMO

Clostridium difficile is a Gram-positive, spore-forming bacterium that continues to present a worldwide problem in healthcare settings. The bacterium causes disease, the symptoms of which include diarrhea, fever, nausea, abdominal pain and even death. Despite the prevalence of the disease, the diagnosis of C. difficile infection is still challenging, with a variety of methods available, each varying in their effectiveness. In this work we sought to identify a new biomarker for C. difficile, develop affinity reagents and design a diagnostic assay for C. difficile infection which could be used in a typical two-step testing algorithm. Initially a bioinformatics pipeline was developed that identified a surface associated biomarker "AKDGSTKEDQLVDALA" present in all C. difficile strains sequenced to-date and unique to the C. difficile species. Monoclonal antibodies were subsequently raised against peptides corresponding to the biomarker sequence. During characterization studies, monoclonal antibody 521 (mAb521) was shown to bind all known C. difficile surface layer types, but not closely related strains. Surface plasmon resonance measurements were used to calculate an apparent equilibrium dissociation constant of 36.5 nM between the purified protein target containing the biomarker (surface layer protein A) and mAb521. We demonstrate a limit of detection of 12.4 ng/mL against surface layer protein A and 1.7 × 106 cells/mL in minimally processed C. difficile cultures. The utility of this computational approach to antibody design for diagnostic tests is the ability to produce antibodies that can act as universal species identifiers while mitigating the likelihood of false-positive detection by intelligently screening potential biomarkers against RefSeq data for other nontarget bacteria.


Assuntos
Proteínas de Bactérias/análise , Clostridioides difficile/isolamento & purificação , Biologia Computacional/métodos , Fragmentos de Peptídeos/análise , Sequência de Aminoácidos , Anticorpos Monoclonais/imunologia , Proteínas de Bactérias/química , Proteínas de Bactérias/imunologia , Biomarcadores/análise , Clostridioides difficile/química , Clostridioides difficile/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Limite de Detecção , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/imunologia , Ressonância de Plasmônio de Superfície/métodos
12.
Diagn Microbiol Infect Dis ; 90(4): 241-247, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29329757

RESUMO

The accumulation of sequenced Francisella strains has made it increasingly apparent that the 16S rRNA gene alone is not enough to stratify the Francisella genus into precise and clinically useful classifications. Continued whole-genome sequencing of isolates will provide a larger base of knowledge for targeted approaches with broad applicability. Additionally, examination of genomic information on a case-by-case basis will help resolve outstanding questions regarding strain stratification. We report the complete genome sequence of a clinical isolate, designated here as F. novicida-like strain TCH2015, acquired from the lymph node of a 6-year-old male. Two features were atypical for F. novicida: exhibition of functional oxidase activity and additional gene content, including proposed virulence determinants. These differences, which could potentially impact virulence and clinical diagnosis, emphasize the need for more comprehensive methods to profile Francisella isolates. This study highlights the value of whole-genome sequencing, which will lead to a more robust database of environmental and clinical genomes and inform strategies to improve detection and classification of Francisella strains.


Assuntos
Francisella/classificação , Francisella/isolamento & purificação , Genótipo , Linfonodos/microbiologia , Tularemia/diagnóstico , Criança , DNA Bacteriano/química , DNA Bacteriano/genética , Francisella/genética , Genes Bacterianos , Variação Genética , Genoma Bacteriano , Humanos , Masculino , Oxirredutases/genética , Análise de Sequência de DNA , Fatores de Virulência/genética , Sequenciamento Completo do Genoma
13.
J Hosp Infect ; 99(2): 139-144, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29111352

RESUMO

BACKGROUND: Adult long-term care (LTC) facilities have high rates of antibiotic use, raising concerns about antimicrobial resistance. Few studies have examined antibiotic use in paediatric LTC facilities. AIM: To describe antibiotic use in three paediatric LTC facilities and to describe the factors associated with use. METHODS: A retrospective cohort study was conducted from September 2012 to December 2015 in three paediatric LTC facilities. Medical records were reviewed for demographics, healthcare-associated infections (HAIs), antimicrobial use and diagnostic testing. Logistic regression was used to identify predictors for antibiotic use. The association between susceptibility testing results and appropriate antibiotic coverage was determined using Chi-squared test. FINDINGS: Fifty-eight percent (413/717) of residents had at least one HAI, and 79% (325/413) of these residents were treated with at least one antibiotic course, totalling 2.75 antibiotic courses per 1000 resident-days. Length of enrolment greater than one year, having a neurological disorder, having a tracheostomy, and being hospitalized at least once during the study period were significantly associated with receiving antibiotics when controlling for facility (all P < 0.001). Diagnostic testing was performed for 40% of antibiotic-treated HAIs. Eighty-six percent of antibiotic courses for identified bacterial pathogens (201/233) provided appropriate coverage. Access to susceptibility testing was not associated with appropriate antibiotic choice (P = 0.26). CONCLUSION: Use of antibiotics in paediatric LTC facilities is widespread. There is further need to assess antibiotic use in paediatric LTC facilities. Evaluation of the adverse outcomes associated with inappropriate antibiotic use, including the prevalence of resistant organisms in paediatric LTC facilities, is critical.


Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Uso de Medicamentos , Hospitais Pediátricos , Assistência de Longa Duração , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Estudos Retrospectivos , Adulto Jovem
14.
Br J Surg ; 103(2): e106-14, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26662377

RESUMO

BACKGROUND: Treatment guidelines for stage II and III rectal cancer include neoadjuvant chemoradiotherapy, surgery and postoperative adjuvant chemotherapy. Although data support this recommendation in younger patients, it is unclear whether this benefit can be extrapolated to elderly patients (aged 75 years or older). METHODS: This was a retrospective review of patients aged at least 75 years with stage II or III rectal cancer who underwent surgery with curative intent from 1996 to 2013 at the Mayo Clinic. Kaplan-Meier analysis and log rank test were used to compare overall survival between therapy groups. Cox proportional hazards model was used to estimate the independent effect of treatment group on survival. RESULTS: A total of 160 elderly patients (median age 80 years) with stage II (66) and stage III (94) rectal cancer underwent surgical resection. Only 30·0 and 33·8 per cent received neoadjuvant or adjuvant therapy respectively. Among patients with stage II disease, there was no significant difference in 60-month survival between patients who received any additional therapy and those who had surgery alone (55 versus 38 per cent respectively; P = 0·184), whereas additional therapy improved survival in patients with stage III tumours (58 versus 30 per cent respectively; P = 0·007). Multivariable analysis found a survival benefit for additional therapy in elderly patients with stage III disease (hazard ratio 0·58, 95 per cent c.i. 0·34 to 0·98). CONCLUSION: A multimodal approach in elderly patients with stage III rectal cancer improved oncological outcomes.


Assuntos
Neoplasias Retais/terapia , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada/métodos , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Estadiamento de Neoplasias/estatística & dados numéricos , Neoplasias Retais/mortalidade , Estudos Retrospectivos , Resultado do Tratamento
15.
Environ Manage ; 56(3): 587-602, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25968139

RESUMO

This study examined whether a measured increase in average body size of adult sea scallops inside three fishery closed areas on Georges Bank (GB), United States (US), was sufficient to increase larval supply to closed areas and open fishing areas in both US and Canadian areas of the Bank. The effects of adult scallop density-at-size and fecundity-at-size on egg production were compared among open and closed fishery areas, countries, and time periods before and after the closed areas were established. Estimated egg production was then used to define spawning conditions in a coupled biological-physical larval tracking model that simulated larval development, mortality, and dispersal. Results showed that order of magnitude increases in larval settlement after closure were facilitated by increases in size-dependant egg production inside and dispersal from Closed Areas I and II, but not Nantucket Lightship Closed Area. The distributions of both egg production and larval settlement became more uniform across the Bank, causing the relative contribution of Canadian larvae to US scallop aggregations to decrease after establishment of Closed Areas I and II. Decreases in small and medium-sized scallop density in Canada and decreases in large scallops over the US-Southern Flank after closure caused local declines in egg production but were not sufficient to negatively affect larval settlement at the regional scale. Our model suggests that the establishment of fishery closed areas on GB considerably strengthened larval supply and settlement within and among several adult scallop aggregations.


Assuntos
Pesqueiros/métodos , Modelos Biológicos , Pectinidae/crescimento & desenvolvimento , Animais , Canadá , Ecossistema , Larva/crescimento & desenvolvimento , Estados Unidos
16.
Med Phys ; 42(2): 947-57, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25652507

RESUMO

PURPOSE: Descriptions of the structure of brain tissue as a porous cellular matrix support application of a poroelastic (PE) mechanical model which includes both solid and fluid phases. However, the majority of brain magnetic resonance elastography (MRE) studies use a single phase viscoelastic (VE) model to describe brain tissue behavior, in part due to availability of relatively simple direct inversion strategies for mechanical property estimation. A notable exception is low frequency intrinsic actuation MRE, where PE mechanical properties are imaged with a nonlinear inversion algorithm. METHODS: This paper investigates the effect of model choice at each end of the spectrum of in vivo human brain actuation frequencies. Repeat MRE examinations of the brains of healthy volunteers were used to compare image quality and repeatability for each inversion model for both 50 Hz externally produced motion and ≈1 Hz intrinsic motions. Additionally, realistic simulated MRE data were generated with both VE and PE finite element solvers to investigate the effect of inappropriate model choice for ideal VE and PE materials. RESULTS: In vivo, MRE data revealed that VE inversions appear more representative of anatomical structure and quantitatively repeatable for 50 Hz induced motions, whereas PE inversion produces better results at 1 Hz. Reasonable VE approximations of PE materials can be derived by equating the equivalent wave velocities for the two models, provided that the timescale of fluid equilibration is not similar to the period of actuation. An approximation of the equilibration time for human brain reveals that this condition is violated at 1 Hz but not at 50 Hz. Additionally, simulation experiments when using the "wrong" model for the inversion demonstrated reasonable shear modulus reconstructions at 50 Hz, whereas cross-model inversions at 1 Hz were poor quality. Attenuation parameters were sensitive to changes in the forward model at both frequencies, however, no spatial information was recovered because the mechanisms of VE and PE attenuation are different. CONCLUSIONS: VE inversions are simpler with fewer unknown properties and may be sufficient to capture the mechanical behavior of PE brain tissue at higher actuation frequencies. However, accurate modeling of the fluid phase is required to produce useful mechanical property images at the lower frequencies of intrinsic brain motions.


Assuntos
Técnicas de Imagem por Elasticidade , Elasticidade , Modelos Biológicos , Algoritmos , Encéfalo/citologia , Estudos de Viabilidade , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Dinâmica não Linear , Porosidade , Adulto Jovem
17.
Toxicol Pathol ; 43(4): 464-73, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25476797

RESUMO

Tetrabromobisphenol A (TBBPA), a widely used flame retardant, caused uterine tumors in rats. In this study, TBBPA was administered to male and female Wistar Han rats and B6C3F1/N mice by oral gavage in corn oil for 2 years at doses up to 1,000 mg/kg. TBBPA induced uterine epithelial tumors including adenomas, adenocarcinomas, and malignant mixed Müllerian tumors (MMMTs). In addition, endometrial epithelial atypical hyperplasia occurred in TBBPA-treated rats. Also found to be related to TBBPA treatment, but at lower incidence and at a lower statistical significance, were testicular tumors in rats, and hepatic tumors, hemangiosarcomas (all organs), and intestinal tumors in male mice. It is hypothesized that the TBBPA uterine tumor carcinogenic mechanisms involve altered estrogen levels and/or oxidative damage. TBBPA treatment may affect hydroxysteroid-dehydrogenase-17ß (HSD17ß) and/or sulfotransferases, enzymes involved in estrogen homeostasis. Metabolism of TBBPA may also result in the formation of free radicals. The finding of TBBPA-mediated uterine cancer in rats is of concern because TBBPA exposure is widespread and endometrial tumors are a common malignancy in women. Further work is needed to understand TBBPA cancer mechanisms.


Assuntos
Carcinógenos/toxicidade , Poluentes Ambientais/toxicidade , Bifenil Polibromatos/toxicidade , Neoplasias Uterinas/induzido quimicamente , Animais , Peso Corporal/efeitos dos fármacos , Testes de Carcinogenicidade , Feminino , Neoplasias Uterinas/patologia , Útero/efeitos dos fármacos , Útero/patologia
18.
Hepatol Int ; 8(2): 179-84, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26202500

RESUMO

Immunomodulatory cell therapy as a complement to standard pharmacotherapy represents a novel approach to solid organ allograft acceptance. This methodology may allow for a reduced dose of immunosuppressive drug to be administered and thus attenuate the severe side effects associated with long-term immunosuppression such as drug-related impairment of renal function, increased risk from opportunistic infections and malignancies. Mesenchymal stem cells (MSCs) have been shown to possess both immune modulatory and regenerative properties in vitro and in preclinical models. Encouraging results have been reported from studies examining the safety and efficacy of MSCs as a treatment for acute graft-versus-host disease. MSCs represent a promising candidate cell therapy to supplement immunosuppression in recipients of solid organs, and initial reports on the clinical use of MSCs in kidney transplantation have been recently published (Tan et al. in J Am Med Assoc 307:1169-1177, 2012; Reinders et al. in Stem Cells Transl Med 2:107-111, 2013; Perico et al. in Transpl Int 26:867-878, 2013; Perico et al. in Clin J Am Soc Nephrol 6:412-422, 2011). An area of even greater interest might be the application of MSCs in clinical liver transplantation as graft survival is closely associated with overall patient survival. Here, we present preclinical findings and discuss their possible impact on clinical liver transplantation. Then we discuss clinical studies designed to investigate how MSCs may be distributed and act in solid organ transplantation.

19.
J Anim Sci ; 91(9): 4158-67, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23825331

RESUMO

The objective was to examine the relationship between ovulatory follicle size and embryo and fetal survival by using circulating concentrations of bovine pregnancy associated glycoproteins (bPAG) to detect the presence of an embryo or fetus and monitor placental function. Before examining the relationship between bPAG, ovulatory follicle size, and embryo and fetal survival, the half-life of bPAG was determined in Exp. 1. The half-life of bPAG after PGF2α-induced abortion on d 32 to 36 postinsemination was 35.8 ± 21.9 h (mean ± SD; range 7.1 to 78.5 h). In Exp. 2, suckled beef cows (n = 91) were treated with the CO-Synch protocol (GnRH on d -9, PGF2α on d -2, and GnRH and AI 48 h later [d 0]) and classified into 1 of 2 ovulatory follicle size groups: 1) small follicle (<12.5 mm; n = 25) or 2) large follicle (≥ 12.5 mm; n = 66). The first increase (P < 0.0001) in serum bPAG occurred in pregnant cows on d 24 after insemination and circulating bPAG decreased before a decrease in progesterone in 3 of 4 cows that lost an embryo or fetus. Pattern of secretion of bPAG in serum from d 24 to 60 after insemination (d 0) was affected by day (P < 0.0001), but not ovulatory follicle size. In Exp. 3, suckled beef cows (n = 1164) were administered the CO-Synch protocol either with (donor cows; n = 810) or without (recipient cows; n = 354) AI on d 0. Single embryos (n = 394) or oocytes (n = 45) were recovered from the donor cows [d 7; embryo transfer (ET)] and all live embryos were transferred into recipients the same day. Cows were classified on d 0 as having a small (<12.5 mm) or large (≥ 12.5 mm) ovulatory follicle, and randomly chosen as donors or recipients to remove confounding effects of ovulatory follicle size on fertility. Serum concentration of bPAG at d 28 was not affected by ovulatory follicle size (P = 0.85), embryo stage at ET (P = 0.75), embryo quality at ET (P = 0.64), estradiol at GnRH2 (P = 0.62) or serum progesterone at ET (d7; P = 0.14). Compared with cows that maintained pregnancy (n = 176), cows that exhibited late embryonic or fetal mortality (n = 19) after d 28 had decreased (P < 0.05) concentrations of bPAG on d 28. In summary, there was no relationship between serum bPAG and ovulatory follicle size or embryo stage or quality at ET; however, cows that lost an embryo after d 28 had reduced concentrations of bPAG on d 28 compared with cows that maintained pregnancy.


Assuntos
Bovinos/fisiologia , Folículo Ovariano/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Glicoproteínas beta 1 Específicas da Gravidez/metabolismo , Aborto Animal/epidemiologia , Aborto Animal/etiologia , Animais , Dinoprosta/farmacologia , Transferência Embrionária/veterinária , Estradiol/análogos & derivados , Estradiol/sangue , Feminino , Fertilidade , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Liberador de Gonadotropina/fisiologia , Meia-Vida , Folículo Ovariano/fisiologia , Gravidez , Progesterona/sangue , Distribuição Aleatória
20.
Med Phys ; 39(10): 6388-96, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23039674

RESUMO

PURPOSE: Nonlinear inversion (NLI) in MR elastography requires discretization of the displacement field for a finite element (FE) solution of the "forward problem", and discretization of the unknown mechanical property field for the iterative solution of the "inverse problem". The resolution requirements for these two discretizations are different: the forward problem requires sufficient resolution of the displacement FE mesh to ensure convergence, whereas lowering the mechanical property resolution in the inverse problem stabilizes the mechanical property estimates in the presence of measurement noise. Previous NLI implementations use the same FE mesh to support the displacement and property fields, requiring a trade-off between the competing resolution requirements. METHODS: This work implements and evaluates multiresolution FE meshes for NLI elastography, allowing independent discretizations of the displacements and each mechanical property parameter to be estimated. The displacement resolution can then be selected to ensure mesh convergence, and the resolution of the property meshes can be independently manipulated to control the stability of the inversion. RESULTS: Phantom experiments indicate that eight nodes per wavelength (NPW) are sufficient for accurate mechanical property recovery, whereas mechanical property estimation from 50 Hz in vivo brain data stabilizes once the displacement resolution reaches 1.7 mm (approximately 19 NPW). Viscoelastic mechanical property estimates of in vivo brain tissue show that subsampling the loss modulus while holding the storage modulus resolution constant does not substantially alter the storage modulus images. Controlling the ratio of the number of measurements to unknown mechanical properties by subsampling the mechanical property distributions (relative to the data resolution) improves the repeatability of the property estimates, at a cost of modestly decreased spatial resolution. CONCLUSIONS: Multiresolution NLI elastography provides a more flexible framework for mechanical property estimation compared to previous single mesh implementations.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Dinâmica não Linear , Análise de Elementos Finitos , Processamento de Imagem Assistida por Computador , Fenômenos Mecânicos , Fatores de Tempo
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