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1.
Proc Natl Acad Sci U S A ; 121(11): e2309469121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38442181

RESUMO

The early-life environment can profoundly shape the trajectory of an animal's life, even years or decades later. One mechanism proposed to contribute to these early-life effects is DNA methylation. However, the frequency and functional importance of DNA methylation in shaping early-life effects on adult outcomes is poorly understood, especially in natural populations. Here, we integrate prospectively collected data on fitness-associated variation in the early environment with DNA methylation estimates at 477,270 CpG sites in 256 wild baboons. We find highly heterogeneous relationships between the early-life environment and DNA methylation in adulthood: aspects of the environment linked to resource limitation (e.g., low-quality habitat, early-life drought) are associated with many more CpG sites than other types of environmental stressors (e.g., low maternal social status). Sites associated with early resource limitation are enriched in gene bodies and putative enhancers, suggesting they are functionally relevant. Indeed, by deploying a baboon-specific, massively parallel reporter assay, we show that a subset of windows containing these sites are capable of regulatory activity, and that, for 88% of early drought-associated sites in these regulatory windows, enhancer activity is DNA methylation-dependent. Together, our results support the idea that DNA methylation patterns contain a persistent signature of the early-life environment. However, they also indicate that not all environmental exposures leave an equivalent mark and suggest that socioenvironmental variation at the time of sampling is more likely to be functionally important. Thus, multiple mechanisms must converge to explain early-life effects on fitness-related traits.


Assuntos
Experiências Adversas da Infância , Metilação de DNA , Animais , Motivos de Nucleotídeos , Bioensaio , Papio/genética
2.
PLoS Genet ; 20(4): e1011228, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38598567

RESUMO

The laboratory mouse has served as the premier animal model system for both basic and preclinical investigations for over a century. However, laboratory mice capture only a subset of the genetic variation found in wild mouse populations, ultimately limiting the potential of classical inbred strains to uncover phenotype-associated variants and pathways. Wild mouse populations are reservoirs of genetic diversity that could facilitate the discovery of new functional and disease-associated alleles, but the scarcity of commercially available, well-characterized wild mouse strains limits their broader adoption in biomedical research. To overcome this barrier, we have recently developed, sequenced, and phenotyped a set of 11 inbred strains derived from wild-caught Mus musculus domesticus. Each of these "Nachman strains" immortalizes a unique wild haplotype sampled from one of five environmentally distinct locations across North and South America. Whole genome sequence analysis reveals that each strain carries between 4.73-6.54 million single nucleotide differences relative to the GRCm39 mouse reference, with 42.5% of variants in the Nachman strain genomes absent from current classical inbred mouse strain panels. We phenotyped the Nachman strains on a customized pipeline to assess the scope of disease-relevant neurobehavioral, biochemical, physiological, metabolic, and morphological trait variation. The Nachman strains exhibit significant inter-strain variation in >90% of 1119 surveyed traits and expand the range of phenotypic diversity captured in classical inbred strain panels. These novel wild-derived inbred mouse strain resources are set to empower new discoveries in both basic and preclinical research.


Assuntos
Variação Genética , Camundongos Endogâmicos , Fenótipo , Animais , Camundongos , Camundongos Endogâmicos/genética , Genômica/métodos , Animais Selvagens/genética , Genoma/genética , Polimorfismo de Nucleotídeo Único , Haplótipos , Sequenciamento Completo do Genoma
3.
J Surg Res ; 302: 463-468, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39167900

RESUMO

INTRODUCTION: Prophylactic antibiotics (pABX) are commonly used prior to thyroid operations despite clean case classification. The objective of this study was to assess the association of antibiotic prophylaxis with the incidence of surgical site infection (SSI) among patients undergoing thyroidectomy. METHODS: We performed a cohort study of all adults undergoing thyroid operations at a tertiary referral center from 2010 to 2019. The primary outcome was 30-d SSI, based on diagnosis codes and/or antibiotic use and further classified based on whether wound aspiration or operative washout were required. The association between pABX and SSI was determined using propensity score matching based on patient demographics and comorbidities likely to influence SSI risk. RESULTS: We identified 2411 patients who underwent thyroid operations, of whom 1358 (56.3%) received pABX. Patients who received pABX had a higher mean Charlson-Deyo Comorbidity Index score than patients who did not (3.6 versus 2.9). The unadjusted incidence of SSI was higher in patients who received pABX than those who did not (6.1% versus 3.4%, P < 0.001). Few patients with SSI required aspiration or operative washout (0.29% who received pABX versus 0.19% who did not). After propensity score matching, pABX use showed no association with overall 30-d SSI (odds ratio 1.38, 95% confidence interval 0.84-2.26) or SSI requiring procedural intervention (odds ratio 3.01, 95% confidence interval 0.24-158). CONCLUSIONS: In a large cohort of patients with a high prevalence of comorbidity, use of pABX was not associated with a decreased incidence of SSI following thyroid surgery. Efforts should be made to deimplement low-value pABX use in thyroid surgery.


Assuntos
Antibioticoprofilaxia , Infecção da Ferida Cirúrgica , Tireoidectomia , Humanos , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Masculino , Tireoidectomia/efeitos adversos , Tireoidectomia/estatística & dados numéricos , Feminino , Pessoa de Meia-Idade , Antibioticoprofilaxia/estatística & dados numéricos , Antibioticoprofilaxia/métodos , Adulto , Idoso , Estudos Retrospectivos , Incidência , Medição de Risco/estatística & dados numéricos , Antibacterianos/uso terapêutico , Pontuação de Propensão
4.
Ann Surg ; 278(2): e302-e308, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36005546

RESUMO

OBJECTIVE: The authors sought to compare the incidence of adverse cardiovascular (CV) events in older adults with primary hyperparathyroidism (PHPT) treated with parathyroidectomy versus nonoperative management. BACKGROUND: PHPT is a common endocrine disorder that is associated with increased CV mortality, but it is not known whether parathyroidectomy reduces the incidence of adverse CV events. METHODS: The authors conducted a population-based, longitudinal cohort study of Medicare beneficiaries diagnosed with PHPT (2006-2017). Multivariable, inverse probability weighted Cox proportional hazards regression was used to determine the associations of parathyroidectomy with major adverse cardiovascular events (MACEs), CV disease-related hospitalization, and CV hospitalization-associated mortality. RESULTS: The authors identified 210,206 beneficiaries diagnosed with PHPT from 2006 to 2017. Among 63,136 (30.0%) treated with parathyroidectomy and 147,070 (70.0%) managed nonoperatively within 1 year of diagnosis, the unadjusted incidence of MACE was 10.0% [mean follow-up 59.1 (SD 35.6) months] and 11.5% [mean follow-up 54.1 (SD 34.0) months], respectively. In multivariable analysis, parathyroidectomy was associated with a lower incidence of MACE [hazard ratio (HR): 0.92; 95% confidence interval (95% CI): 0.90-0.94], CV disease-related hospitalization (HR: 0.89; 95% CI: 0.87-0.91), and CV hospitalization-associated mortality (HR: 0.76; 95% CI: 0.71-0.81) compared to nonoperative management. At 10 years, parathyroidectomy was associated with adjusted absolute risk reduction for MACE of 1.7% (95% CI: 1.3%-2.1%), for CV disease-related hospitalization of 2.5% (95% CI: 2.1%-2.9%), and for CV hospitalization-associated mortality of 1.4% (95% CI: 1.2%-1.6%). CONCLUSIONS: In this large, population-based cohort study, parathyroidectomy was associated with a lower long-term incidence of adverse CV outcomes when compared with nonoperative management for older adults with PHPT, which is relevant to surgical decision making for patients with a long life expectancy.


Assuntos
Doenças Cardiovasculares , Hiperparatireoidismo Primário , Humanos , Idoso , Estados Unidos/epidemiologia , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/cirurgia , Estudos de Coortes , Paratireoidectomia , Estudos Longitudinais , Medicare , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/complicações
5.
Radiology ; 307(2): e220425, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36648347

RESUMO

Background MRI is a powerful diagnostic tool with a long acquisition time. Recently, deep learning (DL) methods have provided accelerated high-quality image reconstructions from undersampled data, but it is unclear if DL image reconstruction can be reliably translated to everyday clinical practice. Purpose To determine the diagnostic equivalence of prospectively accelerated DL-reconstructed knee MRI compared with conventional accelerated MRI for evaluating internal derangement of the knee in a clinical setting. Materials and Methods A DL reconstruction model was trained with images from 298 clinical 3-T knee examinations. In a prospective analysis, patients clinically referred for knee MRI underwent a conventional accelerated knee MRI protocol at 3 T followed by an accelerated DL protocol between January 2020 and February 2021. The equivalence of the DL reconstruction of the images relative to the conventional images for the detection of an abnormality was assessed in terms of interchangeability. Each examination was reviewed by six musculoskeletal radiologists. Analyses pertaining to the detection of meniscal or ligament tears and bone marrow or cartilage abnormalities were based on four-point ordinal scores for the likelihood of an abnormality. Additionally, the protocols were compared with use of four-point ordinal scores for each aspect of image quality: overall image quality, presence of artifacts, sharpness, and signal-to-noise ratio. Results A total of 170 participants (mean age ± SD, 45 years ± 16; 76 men) were evaluated. The DL-reconstructed images were determined to be of diagnostic equivalence with the conventional images for detection of abnormalities. The overall image quality score, averaged over six readers, was significantly better (P < .001) for the DL than for the conventional images. Conclusion In a clinical setting, deep learning reconstruction enabled a nearly twofold reduction in scan time for a knee MRI and was diagnostically equivalent with the conventional protocol. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Roemer in this issue.


Assuntos
Aprendizado Profundo , Masculino , Humanos , Imageamento por Ressonância Magnética/métodos , Articulação do Joelho/diagnóstico por imagem , Joelho/diagnóstico por imagem , Razão Sinal-Ruído
6.
J Magn Reson Imaging ; 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37795927

RESUMO

MRI is an expensive and traditionally time-intensive modality in imaging. With the paradigm shift toward value-based healthcare, radiology departments must examine the entire MRI process cycle to identify opportunities to optimize efficiency and enhance value for patients. Digital tools such as "frictionless scheduling" prioritize patient preference and convenience, thereby delivering patient-centered care. Recent advances in conventional and deep learning-based accelerated image reconstruction methods have reduced image acquisition time to such a degree that so-called nongradient time now constitutes a major percentage of total room time. For this reason, architectural design strategies that reconfigure patient preparation processes and decrease the turnaround time between scans can substantially impact overall throughput while also improving patient comfort and privacy. Real-time informatics tools that provide an enterprise-wide overview of MRI workflow and Picture Archiving and Communication System (PACS)-integrated instant messaging can complement these efforts by offering transparent, situational data and facilitating communication between radiology team members. Finally, long-term investment in training, recruiting, and retaining a highly skilled technologist workforce is essential for building a pipeline and team of technologists committed to excellence. Here, we highlight various opportunities for optimizing MRI workflow and enhancing value by offering many of our own on-the-ground experiences and conclude by anticipating some of the future directions for process improvement and innovation in clinical MR imaging. EVIDENCE LEVEL: N/A TECHNICAL EFFICACY: Stage 1.

7.
J Surg Res ; 288: 275-281, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37043874

RESUMO

INTRODUCTION: We sought to investigate the association of concurrent parathyroidectomy (PTX) with risks of total thyroidectomy (TTX) through analysis of Collaborative Endocrine Surgery Quality Improvement Program data. TTXis a common operation with complications including recurrent laryngeal nerve injury, neck hematoma, and hypoparathyroidism. A subset of patients undergoing thyroidectomy undergoes planned concurrent PTX for treatment of primary hyperparathyroidism. There are limited data on the risk profile of TTX with concurrent PTX (TTX + PTX). METHODS: We queried the Collaborative Endocrine Surgery Quality Improvement Program database for patients who underwent TTX or TTX + PTX from January 2014 through April 2020. Multivariable logistic regression was performed to predict hypoparathyroidism, vocal cord dysfunction, neck hematoma, and postoperative emergency department visit. Covariates included patient demographics, patient body mass index, indication for surgery, central neck dissection, anticoagulation use, and surgeon volume. RESULTS: Thirteen thousand six hundred forty seven patients underwent TTX and 654 patients underwent TTX + PTX. Unadjusted rates of hypoparathyroidism were higher in TTX + PTX patients at 30 d (9.6% versus 7.4%, P = 0.04) and 6 mo (7.9% versus 3.1%, P < 0.001). On multivariable regression, TTX + PTX was associated with an increased risk of hypoparathyroidism at 30 d (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.57-2.79) and 6 mo (OR 4.63, 95% CI 3.06-7.00) and an increased risk of postoperative emergency department visit (OR 1.66, 95% CI 1.20-2.31). TTX + PTX was not associated with recurrent laryngeal nerve injury or neck hematoma. CONCLUSIONS: Concurrent PTX in patients undergoing TTX is associated with increased risk of immediate and long-term hypoparathyroidism, which should be considered in informed consent discussions and operative decision-making.


Assuntos
Hipoparatireoidismo , Traumatismos do Nervo Laríngeo Recorrente , Humanos , Paratireoidectomia/efeitos adversos , Tireoidectomia/efeitos adversos , Traumatismos do Nervo Laríngeo Recorrente/etiologia , Hipoparatireoidismo/epidemiologia , Hipoparatireoidismo/etiologia , Hematoma/epidemiologia , Hematoma/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
8.
J Arthroplasty ; 37(5): 925-929, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35114320

RESUMO

BACKGROUND: Periprosthetic joint infection (PJI) after total hip arthroplasty (THA) is challenging to diagnose. We aimed to evaluate the impact of dry taps requiring saline lavage during preoperative intra-articular hip aspiration on the accuracy of diagnosing PJI before revision surgery. METHODS: A retrospective review was conducted for THA patients with suspected PJI who received an image-guided hip aspiration from May 2016 to February 2020. Musculoskeletal Infection Society (MSIS) diagnostic criteria for PJI were compared between patients who had dry tap (DT) vs successful tap (ST). Sensitivity and specificity of synovial markers were compared between the DT and ST groups. Concordance between preoperative and intraoperative cultures was determined for the 2 groups. RESULTS: In total, 335 THA patients met inclusion criteria. A greater proportion of patients in the ST group met MSIS criteria preoperatively (30.2% vs 8.3%, P < .001). Patients in the ST group had higher rates of revision for PJI (28.4% vs 17.5%, P = .026) and for any indication (48.4% vs 36.7%, P = .039). MSIS synovial white blood cell count thresholds were more sensitive in the ST group (90.0% vs 66.7%). There was no difference in culture concordance (67.9% vs 65.9%, P = .709), though the DT group had a higher rate of negative preoperative cultures followed by positive intraoperative cultures (85.7% vs 41.1%, P = .047). CONCLUSION: Our results indicate that approximately one third of patients have dry hip aspiration, and in these patients cultures are less predictive of intraoperative findings. This suggests that surgeons considering potential PJI after THA should apply extra scrutiny when interpreting negative results in patients who require saline lavage for hip joint aspiration.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Prótese de Quadril , Infecções Relacionadas à Prótese , Artrite Infecciosa/cirurgia , Artroplastia de Quadril/efeitos adversos , Prótese de Quadril/efeitos adversos , Humanos , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/cirurgia , Reoperação , Estudos Retrospectivos , Sensibilidade e Especificidade , Líquido Sinovial
9.
J Magn Reson Imaging ; 53(4): 1015-1028, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32048372

RESUMO

Artificial intelligence (AI) shows tremendous promise in the field of medical imaging, with recent breakthroughs applying deep-learning models for data acquisition, classification problems, segmentation, image synthesis, and image reconstruction. With an eye towards clinical applications, we summarize the active field of deep-learning-based MR image reconstruction. We review the basic concepts of how deep-learning algorithms aid in the transformation of raw k-space data to image data, and specifically examine accelerated imaging and artifact suppression. Recent efforts in these areas show that deep-learning-based algorithms can match and, in some cases, eclipse conventional reconstruction methods in terms of image quality and computational efficiency across a host of clinical imaging applications, including musculoskeletal, abdominal, cardiac, and brain imaging. This article is an introductory overview aimed at clinical radiologists with no experience in deep-learning-based MR image reconstruction and should enable them to understand the basic concepts and current clinical applications of this rapidly growing area of research across multiple organ systems.


Assuntos
Inteligência Artificial , Processamento de Imagem Assistida por Computador , Algoritmos , Artefatos , Humanos , Radiografia
10.
J Surg Res ; 264: 534-543, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33862581

RESUMO

BACKGROUND: Healthcare systems and surgical residency training programs have been significantly affected by the novel coronavirus disease 2019 (COVID-19) pandemic. A shelter-in-place and social distancing mandate went into effect in our county on March 16, 2020, considerably altering clinical and educational operations. Along with the suspension of elective procedures, resident academic curricula transitioned to an entirely virtual platform. We aimed to evaluate the impact of these modifications on surgical training and resident concerns about COVID-19. MATERIALS AND METHODS: We surveyed residents and fellows from all eight surgical specialties at our institution regarding their COVID-19 experiences from March to May 2020. Residents completed the survey via a secure Qualtrics link. A total of 38 questions addressed demographic information and perspectives regarding the impact of the COVID-19 pandemic on surgical training, education, and general coping during the pandemic. RESULTS: Of 256 eligible participants across surgical specialties, 146 completed the survey (57.0%). Junior residents comprised 43.6% (n = 61), compared to seniors 37.1% (n = 52) and fellows 19.3% (n = 27). Most participants, 97.9% (n = 138), anticipated being able to complete their academic year on time, and 75.2% (n = 100) perceived virtual learning to be the same as or better than in-person didactic sessions. Participants were most concerned about their ability to have sufficient knowledge and skills to care for patients with COVID-19, and the possibility of exposure to COVID-19. CONCLUSIONS: Although COVID-19 impacted residents' overall teaching and clinical volume, residency programs may identify novel virtual opportunities to meet their educational and research milestones during these challenging times.


Assuntos
Adaptação Psicológica , COVID-19/prevenção & controle , Internato e Residência/métodos , Especialidades Cirúrgicas/educação , Cirurgiões/psicologia , Adulto , COVID-19/epidemiologia , COVID-19/psicologia , Competência Clínica , Educação a Distância/organização & administração , Educação a Distância/normas , Procedimentos Cirúrgicos Eletivos/educação , Procedimentos Cirúrgicos Eletivos/normas , Feminino , Humanos , Internato e Residência/organização & administração , Internato e Residência/normas , Internato e Residência/estatística & dados numéricos , Masculino , Pandemias/prevenção & controle , Distanciamento Físico , Cirurgiões/educação , Cirurgiões/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos , Estados Unidos/epidemiologia
11.
AJR Am J Roentgenol ; 216(5): 1300-1307, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32783552

RESUMO

BACKGROUND. Literature on glenohumeral dislocations has focused on younger patient populations because of high recurrence rates. However, the spectrum of injuries sustained in younger versus older patient populations is reported to be quite different. OBJECTIVE. The purpose of this article is to describe MRI findings and management of anterior shoulder instability in the aging (≥ 60 years) population. METHODS. Shoulder MRI examinations of anterior glenohumeral dislocations in patients 40 years old and older were subdivided into groups younger than 60 years old or 60 years old and older and reviewed by two musculoskeletal radiologists for a Hill-Sachs lesion, other fracture, glenoid injury, capsulolabral injury, rotator cuff tear, muscle atrophy, and axillary nerve injury. Fischer exact test and logistic regression was evaluated for significant differences between cohorts, and interreader agreement was assessed. Surgical management was recorded, if available. RESULTS. A total of 104 shoulder MRI examinations (age range, 40-79 years; mean age, 58.3 years; 52 women, 52 men) were reviewed (54 examinations < 60 years; 50 examinations ≥ 60 years). Acute high-grade or full-thickness supraspinatus (64.0% vs 37.0%; p = .001), infraspinatus (28.0% vs 14.8%; p = .03), and subscapularis (22.0% vs 3.7%; p = .003) tears were more common in the group 60 years old and older. Hill-Sachs lesions were more common in the younger group (81.5% vs 62.0%; p = .046). Greater tuberosity fractures were seen in 15.4% of the overall cohort, coracoid fractures in 4.8%, and acute axillary nerve injuries in 9.6%. Interreader concordance was 88.5-89.4% for rotator cuff tears and 89.4-97.1% for osseous injury. In the group younger than 60 years old, 11 of 37 subjects (29.7%) had rotator cuff repair and 11 of 37 (29.7%) had labral repair, whereas 17 of 36 (47.2%) of the older group underwent rotator cuff repair, six of 36 (16.7%) underwent reverse shoulder arthroplasty, and six of 36 (16.7%) underwent labral repair. CONCLUSION. Radiologists should have a high index of suspicion for acute rotator cuff tears in anterior shoulder instability, especially in aging populations. Greater tuberosity or coracoid fractures and axillary nerve injury occur across all ages, whereas Hill-Sachs injuries are more common in younger patients. CLINICAL IMPACT. Acute high-grade or full-thickness rotator cuff tears are seen with higher frequency in older populations after anterior glenohumeral dislocation. Osseous and nerve injuries are important causes of patient morbidity that if not carefully sought out may be overlooked by the interpreting radiologist on routine imaging.


Assuntos
Envelhecimento , Avaliação Geriátrica/métodos , Instabilidade Articular/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Lesões do Ombro , Articulação do Ombro/diagnóstico por imagem , Adulto , Fatores Etários , Idoso , Feminino , Avaliação Geriátrica/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
PLoS Genet ; 14(9): e1007672, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30248095

RESUMO

House mice (Mus musculus) arrived in the Americas only recently in association with European colonization (~400-600 generations), but have spread rapidly and show evidence of local adaptation. Here, we take advantage of this genetic model system to investigate the genomic basis of environmental adaptation in house mice. First, we documented clinal patterns of phenotypic variation in 50 wild-caught mice from a latitudinal transect in Eastern North America. Next, we found that progeny of mice from different latitudes, raised in a common laboratory environment, displayed differences in a number of complex traits related to fitness. Consistent with Bergmann's rule, mice from higher latitudes were larger and fatter than mice from lower latitudes. They also built bigger nests and differed in aspects of blood chemistry related to metabolism. Then, combining exomic, genomic, and transcriptomic data, we identified specific candidate genes underlying adaptive variation. In particular, we defined a short list of genes with cis-eQTL that were identified as candidates in exomic and genomic analyses, all of which have known ties to phenotypes that vary among the studied populations. Thus, wild mice and the newly developed strains represent a valuable resource for future study of the links between genetic variation, phenotypic variation, and climate.


Assuntos
Adaptação Fisiológica/genética , Variação Genética , Camundongos Endogâmicos/genética , Camundongos/fisiologia , Locos de Características Quantitativas/genética , Animais , Clima , Feminino , Masculino , Modelos Genéticos , Fenótipo
13.
Mol Ecol ; 29(10): 1873-1889, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32282951

RESUMO

Gut microbial diversity is thought to reflect the co-evolution of microbes and their hosts as well as current host-specific attributes such as genetic background and environmental setting. To explore interactions among these parameters, we characterized variation in gut microbiome composition of California voles (Microtus californicus) across a contact zone between two recently diverged lineages of this species. Because this contact zone contains individuals with mismatched mitochondrial-nuclear genomes (cybrids), it provides an important opportunity to explore how different components of the genotype contribute to gut microbial diversity. Analyses of bacterial 16S rRNA sequences and joint species distribution modelling revealed that host genotypes and genetic differentiation among host populations together explained more than 50% of microbial community variation across our sampling transect. The ranked importance (most to least) of factors contributing to gut microbial diversity in our study populations were: genome-wide population differentiation, local environmental conditions, and host genotypes. However, differences in microbial communities among vole populations (ß-diversity) did not follow patterns of lineage divergence (i.e., phylosymbiosis). Instead, among-population variation was best explained by the spatial distribution of hosts, as expected if the environment is a primary source of gut microbial diversity (i.e., dispersal limitation hypothesis). Across the contact zone, several bacterial taxa differed in relative abundance between the two parental lineages as well as among individuals with mismatched mitochondrial and nuclear genomes. Thus, genetic divergence among host lineages and mitonuclear genomic mismatches may also contribute to microbial diversity by altering interactions between host genomes and gut microbiota (i.e., hologenome speciation hypothesis).


Assuntos
Arvicolinae/microbiologia , Microbioma Gastrointestinal , Animais , California , Microbioma Gastrointestinal/genética , Mamíferos , RNA Ribossômico 16S/genética
14.
AJR Am J Roentgenol ; 215(6): 1421-1429, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32755163

RESUMO

OBJECTIVE. Deep learning (DL) image reconstruction has the potential to disrupt the current state of MRI by significantly decreasing the time required for MRI examinations. Our goal was to use DL to accelerate MRI to allow a 5-minute comprehensive examination of the knee without compromising image quality or diagnostic accuracy. MATERIALS AND METHODS. A DL model for image reconstruction using a variational network was optimized. The model was trained using dedicated multisequence training, in which a single reconstruction model was trained with data from multiple sequences with different contrast and orientations. After training, data from 108 patients were retrospectively undersampled in a manner that would correspond with a net 3.49-fold acceleration of fully sampled data acquisition and a 1.88-fold acceleration compared with our standard twofold accelerated parallel acquisition. An interchangeability study was performed, in which the ability of six readers to detect internal derangement of the knee was compared for clinical and DL-accelerated images. RESULTS. We found a high degree of interchangeability between standard and DL-accelerated images. In particular, results showed that interchanging the sequences would produce discordant clinical opinions no more than 4% of the time for any feature evaluated. Moreover, the accelerated sequence was judged by all six readers to have better quality than the clinical sequence. CONCLUSION. An optimized DL model allowed acceleration of knee images that performed interchangeably with standard images for detection of internal derangement of the knee. Importantly, readers preferred the quality of accelerated images to that of standard clinical images.


Assuntos
Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Traumatismos do Joelho/diagnóstico por imagem , Articulação do Joelho/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão Sinal-Ruído
15.
Semin Musculoskelet Radiol ; 24(1): 38-49, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31991451

RESUMO

Artificial intelligence (AI) has the potential to affect every step of the radiology workflow, but the AI application that has received the most press in recent years is image interpretation, with numerous articles describing how AI can help detect and characterize abnormalities as well as monitor disease response. Many AI-based image interpretation tasks for musculoskeletal (MSK) pathologies have been studied, including the diagnosis of bone tumors, detection of osseous metastases, assessment of bone age, identification of fractures, and detection and grading of osteoarthritis. This article explores the applications of AI for image interpretation of MSK pathologies.


Assuntos
Inteligência Artificial , Neoplasias Ósseas/diagnóstico por imagem , Diagnóstico por Imagem/métodos , Fraturas Ósseas/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Osteoartrite/diagnóstico por imagem , Humanos
16.
Proc Natl Acad Sci U S A ; 114(52): 13768-13773, 2017 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-29229828

RESUMO

The gut bacterial communities of mammals have profound effects on host fitness, but the processes that generate and maintain gut bacterial diversity remain poorly understood. We mapped compositional variation (i.e., ß-diversity) in the gut microbiotas of 136 pairs of wild mammalian species living throughout the Americas to assess how the distribution of mammals across geographic space influences the diversification of their gut bacteria. Comparing the gut microbiotas of sympatric and allopatric mammalian populations provided insights into the flow of gut bacteria within and between mammalian communities, revealing that spatial limits on bacterial dispersal promote ß-diversity between the gut microbiotas of mammalian species. Each geographic locale displayed a unique gut-microbiota composition that could not be fully explained by the diets and phylogenetic histories of the resident mammalian hosts, indicating that some gut bacteria are geographically restricted. Across the western hemisphere, the compositional overlap between the gut microbiotas of allopatric mammalian populations decayed exponentially with the geographic distance separating the hosts. The relationship between geographic distances among hosts and compositional differences among their gut microbiotas was independent of dietary and phylogenetic divergence among hosts. Within mammalian communities, we observed widespread sharing of gut bacteria between predator-prey host-species pairs, indicating horizontal transfer of gut bacteria through mammalian food chains. Collectively, these results indicate that compositional differences between the gut microbiotas of mammalian taxa are generated and maintained by limits to bacterial dispersal imposed by physical distance between hosts.


Assuntos
Biodiversidade , Cadeia Alimentar , Microbioma Gastrointestinal/fisiologia , Mamíferos/microbiologia , Filogenia , Animais
17.
Skeletal Radiol ; 49(5): 731-738, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31811348

RESUMO

OBJECTIVE: The purpose of this study was to determine whether SWE can detect biomechanical changes in the supraspinatus muscle that occur with increasing supraspinatus tendon abnormality prior to morphologic gray-scale changes. MATERIALS AND METHODS: An IRB approved, HIPAA compliant retrospective study of shoulder ultrasounds from 2013-2018 was performed. The cohort consisted of 88 patients (mean age 55 ± 15 years old) with 110 ultrasounds. Images were acquired in longitudinal orientation to the supraspinatus muscle with shear wave velocity (SWV) point quantification. The tendon and muscle were graded in order of increasing tendinosis/tear (1-4 scale) and increasing fatty infiltration (0-3 scale). Mixed model analysis of variance, analysis of covariance, and Spearman rank correlation were used for statistical analysis. RESULTS: There was no statistically significant age or sex dependence for supraspinatus muscle SWV (p = 0.314, 0.118, respectively). There was no significant correlation between muscle SWV and muscle or tendon grade (p = 0.317, 0.691, respectively). In patients with morphologically normal muscle on gray-scale ultrasound, there were significant differences in muscle SWV when comparing tendon grade 3 with grades 1, 2, and 4 (p = 0.018, 0.025, 0.014, respectively), even when adjusting for gender and age (p = 0.044, 0.028, 0.018, respectively). Pairwise comparison of tendon grades other than those mentioned did not achieve statistical significance (p > 0.05). CONCLUSION: SWE can detect biomechanical differences within the supraspinatus muscle that are not morphologically evident on gray-scale ultrasound. Specifically, supraspinatus tendon partial tears with moderate to severe tendinosis may correspond to biomechanically distinct muscle properties compared to both lower grades of tendon abnormality and full-thickness tears.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/fisiopatologia , Tendinopatia/diagnóstico por imagem , Tendinopatia/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/fisiopatologia , Lesões do Manguito Rotador/complicações , Tendinopatia/complicações , Tendões/diagnóstico por imagem , Tendões/fisiopatologia , Adulto Jovem
18.
Mol Ecol ; 28(13): 3197-3207, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31141224

RESUMO

Identifying a common set of genes that mediate host-microbial interactions across populations and species of mammals has broad relevance for human health and animal biology. However, the genetic basis of the gut microbial composition in natural populations remains largely unknown outside of humans. Here, we used wild house mouse populations as a model system to ask three major questions: (a) Does host genetic relatedness explain interindividual variation in gut microbial composition? (b) Do population differences in the microbiota persist in a common environment? (c) What are the host genes associated with microbial richness and the relative abundance of bacterial genera? We found that host genetic distance is a strong predictor of the gut microbial composition as characterized by 16S amplicon sequencing. Using a common garden approach, we then identified differences in microbial composition between populations that persisted in a shared laboratory environment. Finally, we used exome sequencing to associate host genetic variants with microbial diversity and relative abundance of microbial taxa in wild mice. We identified 20 genes that were associated with microbial diversity or abundance including a macrophage-derived cytokine (IL12a) that contained three nonsynonymous mutations. Surprisingly, we found a significant overrepresentation of candidate genes that were previously associated with microbial measurements in humans. The homologous genes that overlapped between wild mice and humans included genes that have been associated with traits related to host immunity and obesity in humans. Gene-bacteria associations identified in both humans and wild mice suggest some commonality to the host genetic determinants of gut microbial composition across mammals.


Assuntos
Bactérias/classificação , Microbioma Gastrointestinal , Interações entre Hospedeiro e Microrganismos/genética , Camundongos/microbiologia , Animais , Animais Selvagens/microbiologia , Biodiversidade , Exoma , Genética Populacional , Estudo de Associação Genômica Ampla , Humanos , Modelos Lineares , Modelos Genéticos , Análise Multivariada , América do Norte , Polimorfismo de Nucleotídeo Único , RNA Ribossômico 16S/genética
19.
AJR Am J Roentgenol ; 212(4): 867-873, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30699009

RESUMO

OBJECTIVE: The purpose of this study was to determine whether ulnar collateral ligament (UCL) insertion below the articular margin (so-called T sign) exists in the pediatric population and whether MRI features can be used to identify insertional UCL injuries in overhead athletes that are symptomatic or require surgery. MATERIALS AND METHODS: Retrospective review of elbow MR images of patients younger than 21 years from 2011 to 2017 yielded 26 control subjects who were not overhead athletes and 97 overhead athletes. According to the clinical diagnosis, 50 of the overhead athletes had symptoms. Two radiologists evaluated the UCL for thickness, abnormal insertional signal intensity, insertion distance, and adjacent marrow or soft-tissue edema. Insertion distance was defined as the coronal length of any T sign measured from the articular margin. RESULTS: Mean insertion distance was greater in overhead athletes than in control subjects (1.42 vs 0.23 mm, p = 0.001) but not significantly different in athletes with symptoms compared with those without symptoms or in those who underwent operative treatment compared with those who did not. Mean UCL thickness was greater in overhead athletes than in control subjects (2.64 vs 1.74 mm, p < 0.0001), athletes with than those without symptoms (2.84 vs 2.41 mm, p = 0.005), and athletes who did versus those who did not undergo operative treatment (3.40 vs 2.73 mm, p = 0.011). Marrow (p = 0.002) and soft-tissue (p = 0.016) edema were found more frequently in athletes with symptoms. ROC analysis of UCL thickness and insertion distance as predictors of symptoms showed AUCs of 0.69 and 0.49, respectively. CONCLUSION: The T sign is likely not an anatomic variation but is a poor predictor of symptoms and need for surgery. Soft-tissue and marrow edema are more frequently seen in overhead athletes with symptomatic injuries and can aid in the diagnosis of clinically relevant injury.


Assuntos
Traumatismos em Atletas/diagnóstico por imagem , Beisebol/lesões , Ligamento Colateral Ulnar/lesões , Imageamento por Ressonância Magnética/métodos , Adolescente , Traumatismos em Atletas/cirurgia , Ligamento Colateral Ulnar/cirurgia , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto Jovem
20.
AJR Am J Roentgenol ; 213(3): 506-513, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31166761

RESUMO

OBJECTIVE. The objective of this article is to show how artificial intelligence (AI) has impacted different components of the imaging value chain thus far as well as to describe its potential future uses. CONCLUSION. The use of AI has the potential to greatly enhance every component of the imaging value chain. From assessing the appropriateness of imaging orders to helping predict patients at risk for fracture, AI can increase the value that musculoskeletal imagers provide to their patients and to referring clinicians by improving image quality, patient centricity, imaging efficiency, and diagnostic accuracy.


Assuntos
Inteligência Artificial , Doenças Musculoesqueléticas/diagnóstico por imagem , Previsões , Humanos
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