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1.
Int J Mol Sci ; 24(4)2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36835642

RESUMO

Dietary lipids induce apolipoprotein A4 (APOA4) production and brown adipose tissue (BAT) thermogenesis. Administration of exogenous APOA4 elevates BAT thermogenesis in chow-fed mice, but not high-fat diet (HFD)-fed mice. Chronic feeding of HFD attenuates plasma APOA4 production and BAT thermogenesis in wildtype (WT) mice. In light of these observations, we sought to determine whether steady production of APOA4 could keep BAT thermogenesis elevated, even in the presence of HFD consumption, with an aim toward eventual reduction of body weight, fat mass and plasma lipid levels. Transgenic mice with overexpression of mouse APOA4 in the small intestine (APOA4-Tg mice) produce greater plasma APOA4 than their WT controls, even when fed an atherogenic diet. Thus, we used these mice to investigate the correlation of levels of APOA4 and BAT thermogenesis during HFD consumption. The hypothesis of this study was that overexpression of mouse APOA4 in the small intestine and increased plasma APOA4 production would increase BAT thermogenesis and consequently reduce fat mass and plasma lipids of HFD-fed obese mice. To test this hypothesis, BAT thermogenic proteins, body weight, fat mass, caloric intake, and plasma lipids in male APOA4-Tg mice and WT mice fed either a chow diet or a HFD were measured. When fed a chow diet, APOA4 levels were elevated, plasma triglyceride (TG) levels were reduced, and BAT levels of UCP1 trended upward, while body weight, fat mass, caloric intake, and plasma lipids were comparable between APOA4-Tg and WT mice. After a four-week feeding of HFD, APOA4-Tg mice maintained elevated plasma APOA4 and reduced plasma TG, but UCP1 levels in BAT were significantly elevated in comparison to WT controls; body weight, fat mass and caloric intake were still comparable. After 10-week consumption of HFD, however, while APOA4-Tg mice still exhibited increased plasma APOA4, UCP1 levels and reduced TG levels, a reduction in body weight, fat mass and levels of plasma lipids and leptin were finally observed in comparison to their WT controls and independent of caloric intake. Additionally, APOA4-Tg mice exhibited increased energy expenditure at several time points when measured during the 10-week HFD feeding. Thus, overexpression of APOA4 in the small intestine and maintenance of elevated levels of plasma APOA4 appear to correlate with elevation of UCP1-dependent BAT thermogenesis and subsequent protection against HFD-induced obesity in mice.


Assuntos
Tecido Adiposo Marrom , Obesidade , Camundongos , Masculino , Animais , Tecido Adiposo Marrom/metabolismo , Camundongos Transgênicos , Obesidade/metabolismo , Gorduras na Dieta/metabolismo , Dieta Hiperlipídica , Metabolismo Energético , Termogênese , Camundongos Endogâmicos C57BL , Proteína Desacopladora 1/metabolismo
2.
Health Promot Pract ; 24(1): 26-30, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-34963374

RESUMO

In this descriptive case series, we detail the theoretical basis, methodology, and impact of a small-scale pilot implementation of graphic medicine workshops as an innovative approach to well-being and resilience in the age of COVID-19 and increasing awareness of racial injustice. The data provided in this article are anecdotal and based on participation in the workshops. Images created during the workshops are also shared as examples of the types of reflection that graphic medicine can enable. The workshops themselves were designed collaboratively and are based on the theoretical principles of graphic medicine, narrative medicine, and racial and social justice. They were conducted as part of a larger wellness initiative and were offered to health care-focused faculty at our academic medical institution. Our findings suggest that this was a beneficial activity which helped participants to reflect and reconsider their experiences with the COVID-19 pandemic and surging awareness of racial injustice. Reflections also showed that drawings were correlated with ProQOL scores and may, in larger numbers, also help to mitigate or bring attention to issues of burnout in frontline providers. Drawings shared show the tremendous impact of COVID-19 and the simultaneous chaos and emptiness of practicing during dual pandemics. Our workshops engaged about 20 frontline health care providers and other health care faculty and highlight the utility of graphic medicine as a tool for building resilience and encouraging self-reflection. Further study is necessary, as is more rigorous analysis of the relationship between the graphics created and the ability to recognize and mitigate burnout.


Assuntos
COVID-19 , Humanos , Pandemias , Pessoal de Saúde
3.
Hum Brain Mapp ; 42(7): 1952-1968, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33544446

RESUMO

Standard magnetic resonance imaging approaches offer high-resolution but indirect measures of neural activity, limiting understanding of the physiological processes associated with imaging findings. Here, we used calibrated functional magnetic resonance imaging during the resting state to recover low-frequency fluctuations of the cerebral metabolic rate of oxygen (CMRO2 ). We tested whether functional connections derived from these fluctuations exhibited organization properties similar to those established by previous standard functional and anatomical connectivity studies. Seventeen participants underwent 20 min of resting imaging during dual-echo, pseudocontinuous arterial spin labeling, and blood-oxygen-level dependent (BOLD) signal acquisition. Participants also underwent a 10 min normocapnic and hypercapnic procedure. Brain-wide, CMRO2 low-frequency fluctuations were subjected to graph-based and voxel-wise functional connectivity analyses. Results demonstrated that connections derived from resting CMRO2 fluctuations exhibited complex, small-world topological properties (i.e., high integration and segregation, cost efficiency) consistent with those observed in previous studies using functional and anatomical connectivity approaches. Voxel-wise CMRO2 connectivity also exhibited spatial patterns consistent with four targeted resting-state subnetworks: two association (i.e., frontoparietal and default mode) and two perceptual (i.e., auditory and occipital-visual). These are the first findings to support the use of calibration-derived CMRO2 low-frequency fluctuations for detecting brain-wide organizational properties typical of healthy participants. We discuss interpretations, advantages, and challenges in using calibration-derived oxygen metabolism signals for examining the intrinsic organization of the human brain.


Assuntos
Encéfalo/metabolismo , Circulação Cerebrovascular/fisiologia , Conectoma , Rede Nervosa/metabolismo , Oxigênio/metabolismo , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Adulto Jovem
4.
Neuroimage ; 215: 116812, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32276075

RESUMO

Behavioral studies investigating fundamental cognitive abilities provide evidence that processing speed accounts for large proportions of performance variability between individuals. Processing speed decline is a hallmark feature of the cognitive disruption observed in healthy aging and in demyelinating diseases such as multiple sclerosis (MS), neuromyelitis optica, and Wilson's disease. Despite the wealth of evidence suggesting a central role for processing speed in cognitive decline, the neural mechanisms of this fundamental ability remain unknown. Intact neurovascular coupling, acute localized blood flow increases following neural activity, is essential for optimal neural function. We hypothesized that efficient coupling forms the neural basis of processing speed. Because MS features neural-glial-vascular system disruption, we used it as a model to test this hypothesis. To assess the integrity of the coupling system, we measured blood-oxygen-level-dependent (BOLD) signal in healthy controls (HCs) and MS patients using a 3T MRI scanner while they viewed radial checkerboards that flickered periodically at 8 â€‹Hz. To assess processing speed and cognitive function, we administered a battery of neuropsychological tests. While MS patients exhibited reduced ΔBOLD with reductions in processing speed, no such relationships were observed in HCs. To further investigate the mechanisms that underlie ΔBOLD-processing speed relationships, we assessed the physiologic components that constitute ΔBOLD signal (i.e., cerebral blood flow, ΔCBF; cerebral metabolic rate of oxygen, ΔCMRO2; neurovascular coupling ratio) in speed-preserved and -impaired MS patients. While ΔCBF and ΔCMRO2 showed no group-differences, the neurovascular coupling ratio was significantly reduced in speed-impaired MS patients compared to speed-preserved MS patients. Together, these results suggest that neurovascular uncoupling might underlie cognitive slowing in MS and might be the central pathogenic mechanism governing processing speed decline.


Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/fisiologia , Esclerose Múltipla/fisiopatologia , Acoplamento Neurovascular/fisiologia , Tempo de Reação/fisiologia , Percepção Visual/fisiologia , Adulto , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Estimulação Luminosa/métodos
5.
Mult Scler ; 26(12): 1486-1496, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31373536

RESUMO

BACKGROUND: Cognitive slowing occurs in ~70% of multiple sclerosis (MS) patients. The pathophysiology of this slowing is unknown. Neurovascular coupling, acute localized blood flow increases following neural activity, is essential for efficient cognition. Loss of vascular compliance along the cerebrovascular tree would result in suboptimal vasodilation, neurovascular uncoupling, and cognitive slowing. OBJECTIVE: To assess vascular compliance along the cerebrovascular tree and its relationship to MS-related cognition. METHODS: We tested vascular compliance along the cerebrovascular tree by dividing cerebral cortex into nested layers. MS patients and healthy controls were scanned using a dual-echo functional magnetic resonance imaging (fMRI) sequence while they periodically inhaled room air and hypercapnic gas mixture. Cerebrovascular reactivity was calculated from both cerebral blood flow (arterial) and blood-oxygen-level-dependent signal (venous) increases per unit increase in end-tidal CO2. RESULTS: Arterial cerebrovascular reactivity changes along the cerebrovascular tree were reduced in cognitively slow MS compared to cognitively normal MS and healthy controls. These changes were fit to exponential functions, the decay constant (arterial compliance index; ACI) of which was associated with individual subjects' reaction time and predicted reaction time after controlling for disease processes. CONCLUSION: Such associations suggest prospects for utility of ACI in predicting future cognitive disturbances, monitoring cognitive deficiencies and therapeutic responses, and implicates neurovascular uncoupling as a mechanism of cognitive slowing in MS.


Assuntos
Circulação Cerebrovascular , Esclerose Múltipla , Encéfalo , Cognição , Humanos , Imageamento por Ressonância Magnética , Esclerose Múltipla/diagnóstico por imagem
6.
Environ Sci Technol ; 54(2): 870-878, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31789027

RESUMO

Compound-specific isotope analysis (CSIA) is a valuable tool in contaminant remediation studies. Chlorofluorocarbons (CFCs) are ozone-depleting substances previously thought to be persistent in groundwater under most geochemical conditions but more recently have been found to (bio)transform in some laboratory experiments. To date, limited applications of CSIA to CFCs have been undertaken. Here, biotransformation-associated carbon isotope enrichment factors, εC,bulk for CFC-113 (εC,bulk = -8.5 ± 0.4‰) and CFC-11 (εC,bulk = -14.5 ± 1.9‰), were determined. δ13C signatures of pure-phase CFCs and hydrochlorofluorocarbons were measured to establish source signatures. These findings were applied to investigate potential in situ CFC transformation in groundwater at a field site, where carbon isotope fractionation of CFC-11 suggests naturally occurring biotransformation by indigenous microorganisms. The maximum extent of CFC-11 transformation is estimated to be up to 86% by an approximate calculation using the Rayleigh concept. CFC-113 δ13C values in contrast were not resolvably different from pure-phase sources measured to date, demonstrating that CSIA can aid in identifying which compounds may, or may not, be undergoing reactive processes at field sites. Science and public attention remains focused on CFCs, as unexplained source inputs to the atmosphere have been recently reported, and the potential for CFC biotransformation in surface and groundwaters remains unclear. This study proposes δ13C CSIA as a novel application to study the fate of CFCs in groundwater.


Assuntos
Clorofluorcarbonetos , Água Subterrânea , Biodegradação Ambiental , Biotransformação , Isótopos de Carbono , Compostos Orgânicos
7.
Neuroimage ; 188: 198-207, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30529628

RESUMO

Functional magnetic resonance imaging (fMRI) has been used to infer age-differences in neural activity from the hemodynamic response function (HRF) that characterizes the blood-oxygen-level-dependent (BOLD) signal over time. BOLD literature in healthy aging lacks consensus in age-related HRF changes, the nature of those changes, and their implications for measurement of age differences in brain function. Between-study discrepancies could be due to small sample sizes, analysis techniques, and/or physiologic mechanisms. We hypothesize that, with large sample sizes and minimal analysis assumptions, age-related changes in HRF parameters could reflect alterations in one or more components of the neural-vascular coupling system. To assess HRF changes in healthy aging, we analyzed the large population-derived dataset from the Cambridge Center for Aging and Neuroscience (CamCAN) study (Shafto et al., 2014). During scanning, 74 younger (18-30 years of age) and 173 older participants (54-74 years of age) viewed two checkerboards to the left and right of a central fixation point, simultaneously heard a binaural tone, and responded via right index finger button-press. To assess differences in the shape of the HRF between younger and older groups, HRFs were estimated using FMRIB's Linear Optimal Basis Sets (FLOBS) to minimize a priori shape assumptions. Group mean HRFs were different between younger and older groups in auditory, visual, and motor cortices. Specifically, we observed increased time-to-peak and decreased peak amplitude in older compared to younger adults in auditory, visual, and motor cortices. Changes in the shape and timing of the HRF in healthy aging, in the absence of performance differences, support our hypothesis of age-related changes in the neural-vascular coupling system beyond neural activity alone. More precise interpretations of HRF age-differences can be formulated once these physiologic factors are disentangled and measured separately.


Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/fisiologia , Envelhecimento Saudável/fisiologia , Hemodinâmica/fisiologia , Adulto , Idoso , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Acoplamento Neurovascular/fisiologia , Adulto Jovem
8.
Neuroimage ; 182: 304-313, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28673882

RESUMO

Recent years have seen a growing interest in relating MRI measurements to the structural-biophysical properties of white matter fibers. The fiber g-ratio, defined as the ratio between the inner and outer radii of the axon myelin sheath, is an important structural property of white matter, affecting signal conduction. Recently proposed modeling methods that use a combination of quantitative-MRI signals, enable a measurement of the fiber g-ratio in vivo. Here we use an MRI-based g-ratio estimation to observe the variance of the g-ratio within the corpus callosum, and evaluate sex and age related differences. To estimate the g-ratio we used a model (Stikov et al., 2011; Duval et al., 2017) based on two different WM microstructure parameters: the relative amounts of myelin (myelin volume fraction, MVF) and fibers (fiber volume fraction, FVF) in a voxel. We derived the FVF from the fractional anisotropy (FA), and estimated the MVF by using the lipid and macromolecular tissue volume (MTV), calculated from the proton density (Mezer et al., 2013). In comparison to other methods of estimating the MVF, MTV represents a stable parameter with a straightforward route of acquisition. To establish our model, we first compared histological MVF measurements (West et al., 2016) with the MRI derived MTV. We then implemented our model on a large database of 92 subjects (44 males), aged 7 to 81, in order to evaluate age and sex related changes within the corpus callosum. Our results show that the MTV provides a good estimation of MVF for calculating g-ratio, and produced values from the corpus callosum that correspond to those found in animals ex vivo and are close to the theoretical optimum, as well as to published in vivo data. Our results demonstrate that the MTV derived g-ratio provides a simple and reliable in vivo g-ratio-weighted (GR*) measurement in humans. In agreement with theoretical predictions, and unlike other tissue parameters measured with MRI, the g-ratio estimations were found to be relatively stable with age, and we found no support for a significant sexual dimorphism with age.


Assuntos
Corpo Caloso/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Desenvolvimento Humano , Caracteres Sexuais , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Neuroimage ; 182: 511-521, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28025129

RESUMO

MRI is a valuable tool to assess myelin during development and demyelinating disease processes. While multiexponential T2 and quantitative magnetization transfer measures correlate with myelin content, neither provides the total myelin volume fraction. In many cases correlative measures are adequate; but to assess microstructure of myelin, (e.g. calculate the g-ratio using MRI), an accurate measure of myelin volume fraction is imperative. Using a volumetric model of white matter, we relate MRI measures of myelin to absolute measures of myelin volume fraction and compare them to quantitative histology. We assess our approach in control mice along with two models of hypomyelination and one model of hypermyelination and find strong agreement between MRI and histology amongst models. This work investigates the sensitivities of MRI myelin measures to changes in axon geometry and displays promise for estimating g-ratio from MRI.


Assuntos
Doenças Desmielinizantes/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Modelos Teóricos , Bainha de Mielina , Neuroimagem/métodos , Substância Branca/anatomia & histologia , Substância Branca/diagnóstico por imagem , Animais , Doenças Desmielinizantes/patologia , Modelos Animais de Doenças , Imageamento por Ressonância Magnética/normas , Camundongos , Camundongos Knockout , Bainha de Mielina/metabolismo , Neuroimagem/normas , Sensibilidade e Especificidade , Substância Branca/patologia
10.
Neuroimage ; 167: 366-371, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29208572

RESUMO

This study aimed to experimentally evaluate a previously proposed MRI method for mapping axonal g-ratio (ratio of axon diameters, measured to the inner and outer boundary of myelin). MRI and electron microscopy were used to study excised and fixed brains of control mice and three mouse models of abnormal white matter. The results showed that g-ratio measured with MRI correlated with histological measures of myelinated axon g-ratio, but with a bias that is likely due to the presence of non-myelinated axons. The results also pointed to cases where the MRI g-ratio model simplifies to be primarily a function of total myelin content.


Assuntos
Axônios , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Microscopia Eletrônica/métodos , Bainha de Mielina , Substância Branca/diagnóstico por imagem , Animais , Axônios/patologia , Axônios/ultraestrutura , Encéfalo/patologia , Modelos Animais de Doenças , Camundongos , Camundongos Knockout , Bainha de Mielina/patologia , Bainha de Mielina/ultraestrutura , Substância Branca/patologia
11.
Neuroimage ; 125: 1155-1158, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26299793

RESUMO

A key measure of white matter health is the g-ratio, which is defined as the ratio between the inner axon radius and the outer, myelinated, axon radius. Recent methods have been proposed to measure the g-ratio non-invasively using the relationship between two magnetic resonance imaging (MRI) measures. While this relationship is intuitive, it predicates on the simplifying assumption that g-ratio is constant across axons. Here, we extend the model to account for a distribution of g-ratio values within an imaging voxel, and evaluate this model with quantitative histology from normal and hypomyelinated mouse brains.


Assuntos
Corpo Caloso/patologia , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Bainha de Mielina/patologia , Substância Branca/patologia , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Knockout , Fibras Nervosas Mielinizadas/patologia
12.
Neuroimage ; 124(Pt A): 612-626, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26400013

RESUMO

Diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and DKI-derived white matter tract integrity metrics (WMTI) were experimentally evaluated ex vivo through comparisons to histological measurements and established magnetic resonance imaging (MRI) measures of myelin in two knockout mouse models with varying degrees of hypomyelination. DKI metrics of mean and radial kurtosis were found to be better indicators of myelin content than conventional DTI metrics. The biophysical WMTI model based on the DKI framework reported on axon water fraction with good accuracy in cases with near normal axon density, but did not provide additional specificity to myelination. Overall, DKI provided additional information regarding white matter microstructure compared with DTI, making it an attractive method for future assessments of white matter development and pathology.


Assuntos
Encéfalo/ultraestrutura , Imagem de Tensor de Difusão/métodos , Imageamento por Ressonância Magnética/métodos , Bainha de Mielina/ultraestrutura , Esclerose Tuberosa/patologia , Substância Branca/ultraestrutura , Animais , Axônios/ultraestrutura , Proteínas de Transporte/genética , Difusão , Modelos Animais de Doenças , Camundongos , Camundongos Knockout , Proteína Companheira de mTOR Insensível à Rapamicina , Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa , Proteínas Supressoras de Tumor/genética
13.
Environ Sci Technol ; 50(22): 12197-12204, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27771950

RESUMO

Monitoring natural recovery of contaminated sediments requires the use of techniques that can provide definitive evidence of in situ contaminant degradation. In this study, a passive diffusion sampler, called "peeper", was combined with Compound Specific Isotope Analysis to determine benzene and monochlorobenzene (MCB) stable carbon isotope values at a fine vertical resolution (3 cm) across the sediment water interface at a contaminated site. Results indicated significant decrease in concentrations of MCB from the bottom to the top layers of the sediment over 25 cm, and a 3.5 ‰ enrichment in δ13C values of MCB over that distance. Benzene was always at lower concentrations than MCB, with consistently more depleted δ13C values than MCB. The redox conditions were dominated by iron reduction along most of the sediment profile. These results provide multiple lines of evidence for in situ reductive dechlorination of MCB to benzene. Stable isotope analysis of contaminants in pore water is a valuable method to demonstrate in situ natural recovery of contaminated sediments. This novel high-resolution approach is critical to deciphering the combined effects of parent contaminant (e.g., MCB) degradation and both production and simultaneous degradation of daughter products, especially benzene.


Assuntos
Benzeno , Isótopos de Carbono , Biodegradação Ambiental , Monitoramento Ambiental , Halogenação , Poluentes Químicos da Água
15.
Mult Scler Relat Disord ; 80: 105074, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37866021

RESUMO

BACKGROUND: Most multiple sclerosis (MS) patients experience fatigue and cognitive decline but the underlying mechanisms remain unknown. Previous work has shown whole brain resting cerebral metabolic rate of oxygen (CMRO2) is associated with the extent of these symptoms. However, it is not known if the association between global CMRO2 and MS-related cognitive speed and fatigue can be localized to specific brain regions. Based upon previous research suggesting prefrontal involvement in MS-related changes in cognitive speed and fatigue, we hypothesized that oxygen metabolic changes within prefrontal cortex (PFC) might form the pathophysiologic basis of cognitive performance and fatigue in MS patients. OBJECTIVE: Investigate whether PFC ΔCMRO2 is associated with cognitive speed and fatigue in MS. METHODS: MS and healthy control (HC) participants were scanned using a dual--echo fMRI sequence and underwent a hypercapnia calibration experiment that permitted estimation of ΔCMRO2 while performing a scanner version of symbol-digit modalities task, a measure of information processing speed and utilized in the clinic as a reliable sentinel biomarker for global cognitive impairment in MS. Participants then completed the Modified Fatigue Impact Scale (MFIS) to measure fatigue. RESULTS: MS patients exhibited significant reductions in cognitive performance relative to HCs (p < 0.04). Prefrontal ΔCMRO2 explained significant variability (ΔR2 = 0.11) in cognitive speed, over and above disease and demographic variables, for the MS group only. Prefrontal ΔCMRO2 was not associated with fatigue across groups. ΔCMRO2 in visual and motor areas were not associated with cognitive performance or fatigue for either group. CONCLUSION: Prefrontal oxygen metabolism may be a sensitive measure of MS-related cognitive decline.


Assuntos
Esclerose Múltipla , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/diagnóstico por imagem , Cognição/fisiologia , Encéfalo/diagnóstico por imagem , Fadiga/psicologia , Oxigênio , Testes Neuropsicológicos
16.
Am J Prev Med ; 64(4): 535-542, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36635197

RESUMO

INTRODUCTION: To mitigate the lack of specialty healthcare, Project ECHO (Extension for Community Health Outcomes) trains community-based primary care clinicians to better prevent the progression of, manage, and treat common health conditions. ECHO-Chicago launched in 2010 as the first urban-centered ECHO program, focusing on safety-net clinicians, and has trained over 5,175 community clinicians across 34 topic areas. This paper examines self-efficacy among ECHO-Chicago participants across 11 clinical series, including a novel use of qualitative themes from self-efficacy questions. METHODS: Five years of baseline and postseries survey data were collected from 2014 to 2019, resulting in 951 participants. Paired t-tests assessed change from baseline survey to postsurvey, and Cohen's d determined effect size. Change was assessed by individual series, adult or pediatric focus, participants' prescription privilege status, and across series by qualitative question theme. Metrics included total change, any improvement, a 10% target, and a clinical competency threshold. Analysis occurred from July 2020 to January 2022. RESULTS: All clinical series achieved statistically significant improvement in self-efficacy, and most had a large effect size. A total of 88% had any improvement, 65% met the 10% target of 0.7 points, and 52% met the competency threshold of 5.0 in the postsurvey. Prescribers had a significantly greater increase in their self-efficacy scores than nonprescribers. With a comparison across series, each theme achieved statistical significance, with most reaching large effect sizes. CONCLUSIONS: ECHO-Chicago successfully increased participants' self-efficacy. This inquiry adds an urban focus, years of data, multiple series, and a novel qualitative theme component to enable comparisons across rather than solely within the ECHO series.


Assuntos
Atenção à Saúde , Autoeficácia , Adulto , Humanos , Criança , Inquéritos e Questionários , Chicago
17.
Methods Mol Biol ; 2588: 131-156, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36418686

RESUMO

Colonization of surfaces in the human body by microorganisms is an early, essential, step in the initiation of infectious disease. We have developed in vitro assays to investigate interactions between yeast or bacterial cells and human tissues, fluids, or prostheses. Such assays can be used to identify the adhesins, ligands, and receptors involved in these interactions, for example, by determining which components of the microbe or human tissue/fluid interfere with adherence in the assay. The assays can also be applied to find ways of preventing adhesion, and subsequent disease, by investigating the effects of different conditions and added compounds on adherence in the in vitro assays. Here we describe assays for measuring adhesion of the oral yeast Candida albicans, a common commensal and opportunistic pathogen, or the bacterium Staphylococcus epidermidis, which is not normally pathogenic but is known to form biofilms on medical prostheses. The assays described belong to two approaches to investigating adhesion and biofilm formation: (i) retention at a fixed time point following liquid washes, and (ii) retention against a continuous flow of medium.


Assuntos
Candida albicans , Leveduras , Humanos , Biofilmes , Staphylococcus epidermidis , Adesinas Bacterianas
18.
Nutrients ; 15(11)2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37299447

RESUMO

Long-chain fatty acids induce apolipoprotein A4 (APOA4) production in the small intestine and activate brown adipose tissue (BAT) thermogenesis. The increase in BAT thermogenesis enhances triglyceride clearance and insulin sensitivity. Acute administration of recombinant APOA4 protein elevates BAT thermogenesis in chow-fed mice. However, the physiological role of continuous infusion of recombinant APOA4 protein in regulating sympathetic activity, thermogenesis, and lipid and glucose metabolism in low-fat-diet (LFD)-fed mice remained elusive. The hypothesis of this study was that continuous infusion of mouse APOA4 protein would increase sympathetic activity and thermogenesis in BAT and subcutaneous inguinal white adipose tissue (IWAT), attenuate plasma lipid levels, and improve glucose tolerance. To test this hypothesis, sympathetic activity, BAT temperature, energy expenditure, body weight, fat mass, caloric intake, glucose tolerance, and levels of BAT and IWAT thermogenic and lipolytic proteins, plasma lipids, and markers of fatty acid oxidation in the liver in mice with APOA4 or saline treatment were measured. Plasma APOA4 levels were elevated, BAT temperature and thermogenesis were upregulated, and plasma triglyceride (TG) levels were reduced, while body weight, fat mass, caloric intake, energy expenditure, and plasma cholesterol and leptin levels were comparable between APOA4- and saline-treated mice. Additionally, APOA4 infusion stimulated sympathetic activity in BAT and liver but not in IWAT. APOA4-treated mice had greater fatty acid oxidation but less TG content in the liver than saline-treated mice had. Plasma insulin in APOA4-treated mice was lower than that in saline-treated mice after a glucose challenge. In conclusion, continuous infusion of mouse APOA4 protein stimulated sympathetic activity in BAT and the liver, elevated BAT thermogenesis and hepatic fatty acid oxidation, and consequently attenuated levels of plasma and hepatic TG and plasma insulin without altering caloric intake, body weight gain and fat mass.


Assuntos
Dieta Hiperlipídica , Insulinas , Masculino , Animais , Camundongos , Peso Corporal , Tecido Adiposo Marrom/metabolismo , Apolipoproteínas A , Triglicerídeos/metabolismo , Metabolismo Energético , Ácidos Graxos/metabolismo , Glucose/metabolismo , Termogênese , Insulinas/metabolismo , Camundongos Endogâmicos C57BL
19.
BJU Int ; 109 Suppl 3: 15-21, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22458487

RESUMO

UNLABELLED: What's known on the subject? and What does the study add? Priapism is a rare event. However, various medications and medical conditions may increase the risk. Priapism can be ischaemic, non-ischaemic or stuttering. It is paramount to distinguish the type of priapism, as misdiagnosis may lead to significant morbidity. Ischaemic priapism represents a compartment syndrome of the penis and is therefore a medical emergency. A delay in management may significantly affect future erectile function. Stuttering priapism represents recurrent subacute episodes of ischaemic priapism, which may lead to erectile dysfunction. Thus episodes must be minimised. Non-ischaemic priapism is not a medical emergency. However, misdiagnosis and injection with sympathomimetic agents can result in system absorption and toxicity. This review article provides a summary of the evaluation and management of priapism. Furthermore, a step by step flow chart is provided to guide the clinician through the assessment and management of this complex issue. OBJECTIVES: To review the literature regarding ischaemic, non-ischaemic and stuttering priapism. To provide management recommendations. PATIENTS AND METHODS: A Medline search was carried out to identify all relevant papers with management guidelines for priapism. RESULTS: Ischaemic priapism represents a compartment syndrome of the penis and urgent intervention is required to decrease the risk of erectile dysfunction. Non-ischaemic priapism is not a medical emergency; however, it can result in erectile dysfunction. The treatment objective for stuttering priapism is to reduce future episodes with systemic treatments, whilst treating each ischaemic episode as an emergency. CONCLUSIONS: Priapism is a complex condition that requires expert care to prevent complications and irreversible erectile dysfunction.


Assuntos
Gerenciamento Clínico , Modalidades de Fisioterapia , Priapismo/terapia , Simpatomiméticos/administração & dosagem , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Humanos , Injeções , Masculino , Priapismo/diagnóstico , Resultado do Tratamento
20.
BJU Int ; 109 Suppl 3: 57-63, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22458496

RESUMO

OBJECTIVE: To evaluate the accuracy of calculated prostate volume variables in a radical prostatectomy (RP) cohort, as many recent studies use these measures of prostate size instead of prostate weight. To determine whether this accuracy could be improved by modifying the mathematical model used in the volume estimation. PATIENTS AND METHODS: Patients who underwent RP for prostate cancer at our associated institutions had calculated specimen volumes and weights from RP specimens determined at one pathology institution and transrectal ultrasonography (TRUS) volumes were recorded preoperatively (n= 236). Correlation analysis was performed and errors were determined for calculated volume variables when compared with prostate weight. Bland-Altman plots were drawn and concordance coefficients calculated. Analysis was repeated with smaller prostates mathematically modelled as bullet-shaped rather than ellipsoid (n= 165). RESULTS: Although correlation was good for both TRUS and specimen volumes, they equally underestimated prostate weight with a large range of errors and poor concordance coefficients. Only 22% of TRUS volumes and 11% of calculated specimen volumes were within 10% of weight measurements. Application of a bullet-shaped mathematical model for prostates <55 g did not correct the large individual variation seen within these values. CONCLUSION: Calculated prostate volume variables are prone to a large range of individual error regardless of the mathematical model used and should be avoided in statistical studies involving RP cohorts, and the more accurate prostate weight variable should instead be used as a size variable or correction factor.


Assuntos
Modelos Teóricos , Próstata/patologia , Prostatectomia/métodos , Neoplasias da Próstata/diagnóstico , Endossonografia , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Reprodutibilidade dos Testes , Estudos Retrospectivos
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