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1.
Clin Res Hepatol Gastroenterol ; 48(4): 102301, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38355006

RESUMO

BACKGROUND AND AIMS: Colorectal cancer (CRC) is a global health challenge, particularly in Alabama, where the incidence rates exceed national averages. This study investigated the factors influencing adherence to post-endoscopic mucosal resection (EMR) colonoscopies, focusing on travel distance and socioeconomic status. This study aimed to provide evidence-based insights to improve patient care in CRC management. METHODS: This retrospective study in a tertiary care referral center analyzed 465 patients who underwent EMR. The data included demographics, clinical details, and travel-related variables. Descriptive statistics, logistic regression, and spatial analysis were used to assess the factors affecting adherence. RESULTS: Of 465 patients, 36.6 % had adequate follow-up, 21.8 % had inadequate follow-up, and 41.6 % were lost to follow-up. Noteworthy demographic variations were observed, with median ages differing across adherence groups. Traveled distances showcased compelling insights, indicating a median distance of 22.2 miles for adequate follow-up, 15.7 miles for inadequate follow-up, and 31.6 miles for the lost-to-follow-up group (p<0.001). Longer travel distances were associated with better adherence. Longer travel distances from the hospital were associated with significantly lower odds of inadequate follow-up: 10-25 miles OR:0.29, 25-85 miles OR:0.35, and >80 miles OR:0.24 compared to the first quartile (<10 miles). Socioeconomic factors, particularly educational attainment, significantly influenced the follow-up rates. CONCLUSIONS: This study revealed suboptimal post-EMR follow-up rates and underscored the impact of travel distance and socioeconomic factors. Targeted interventions addressing distance-related barriers can enhance treatment adherence and ensure timely CRC surveillance after EMR. Further research is needed in diverse healthcare settings.


Assuntos
Ressecção Endoscópica de Mucosa , Viagem , Humanos , Estudos Retrospectivos , Determinantes Sociais da Saúde , Doença Relacionada a Viagens , Centros de Atenção Terciária
2.
J Clin Endocrinol Metab ; 109(3): e1061-e1071, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-37930769

RESUMO

CONTEXT: In clinical trials, burosumab ameliorates symptoms of pain, fatigue, and stiffness and improves performance on certain muscle function studies in patients with X-linked hypophosphatemia (XLH). OBJECTIVE: This work aimed to determine if burosumab increases adenosine triphosphate (ATP) synthesis in skeletal muscle of treatment-naive adults with XLH, and if so, whether that correlates with improved muscle function. METHODS: Ten untreated, symptomatic adults with XLH had ATP synthesis rates measured in the right calf using the 31P magnetic resonance spectroscopy saturation transfer technique. Baseline muscle function tests and symptoms of pain, fatigue, stiffness, and lower-extremity joint pain were quantified. All participants were treated with burosumab, 1 mg/kg every 4 weeks for 12 weeks. ATP synthesis rates and muscle function tests were repeated 2 weeks ("peak") and 4 weeks ("trough") after the third dose of burosumab. RESULTS: All symptoms improved with treatment. Performance on the 6-Minute Walk Test (6MWT) and Sit to Stand (STS) tests also improved. Muscle strength and ATP synthesis rates did not change over the 3 months of the study. When individuals whose performances on the 6MWT and STS test were at or better than the median outcome for those tests were compared to those whose outcomes were below the median, no difference was observed in the rate of change in ATP synthesis. Intracellular muscle concentrations of phosphate were normal. CONCLUSION: The improvement in the 6MWT and STS test without changes in muscle strength or ATP synthesis rates suggests that reductions in pain, fatigue, and stiffness may partly explain the improved performance. Intracellular phosphate in skeletal muscle is insulated from hypophosphatemia in XLH.


Assuntos
Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais , Raquitismo Hipofosfatêmico Familiar , Adulto , Humanos , Anticorpos Monoclonais/uso terapêutico , Raquitismo Hipofosfatêmico Familiar/diagnóstico , Trifosfato de Adenosina , Músculo Esquelético , Polifosfatos/uso terapêutico , Dor/tratamento farmacológico , Perna (Membro) , Fadiga/tratamento farmacológico
3.
EJNMMI Res ; 13(1): 90, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37823919

RESUMO

BACKGROUND: After myocardial infarction, fibrosis and an ongoing dysregulated inflammatory response have been shown to lead to adverse cardiac remodeling. FDG PET is an imaging modality sensitive to inflammation as long as suppression protocols are observed while gadolinium enhanced MRI can be used to determine extracellular volume (ECV), a measure of fibrosis. In patients, glucose suppression is achieved variously through a high fat diet, fasting and injection of heparin. To emulate this process in canines, a heparin injection and lipid infusion are used, leading to similar fatty acids in the blood. The aim of this study was to examine the effect of glucose suppression on the uptake of FDG in the infarcted myocardial tissue and also on the determination of ECV in both the infarcted tissue and in the myocardium remote to the zone of infarction during a long constant infusion of FDG and Gd-DTPA. RESULTS: Extracellular volume was affected neither by suppression nor the length of the constant infusion in remote and infarcted tissue. Metabolic rate of glucose in infarcted tissue decreased during and after suppression of glucose uptake by lipid infusion and heparin injection. An increase in fibrosis and inflammatory cells was found in the center of the infarct as compared to remote tissue. CONCLUSION: The decrease in the metabolic rate of glucose in the infarcted tissue suggests that inflammatory cells may be affected by glucose suppression through heparin injection and lipid infusion.

4.
Aust Health Rev ; 47(4): 487-493, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37455013

RESUMO

Objective Falls in hospital are a significant public health issue and patients with communication disability have unique risk factors that have the potential to contribute to falls. The aim of this study is to determine how the content of hospital falls policies relate to patients with communication disability and to identify gaps in policy that need to be addressed. Methods A scoping review and content analysis of (a) policies and related documents, from a target health service in Victoria, Australia, and all relevant Australian state and territory health departments, and (b) national guidelines was performed. Data were analysed for content relating to inclusion of patients with communication disability. Results Communication disability is not captured as a risk factor for a fall in assessment tools. When included, aspects of communication disability were often conflated with cognitive impairments. There was little guidance for staff on adapting falls prevention education to suit the needs of patients with communication disability and limited identified role for speech pathologists. Conclusion This study suggests that a patient's communication disability is not visible in hospital falls policies and guidelines.


Assuntos
Transtornos da Comunicação , Humanos , Hospitais , Pacientes , Vitória , Políticas
5.
Int J Lang Commun Disord ; 58(6): 2033-2048, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37355936

RESUMO

BACKGROUND: People with communication disability following stroke are at risk of falls during inpatient rehabilitation. However, they are often excluded from hospital falls research, and little is known about the circumstances or outcomes of their falls to inform risk management strategies. AIMS: To examine hospital medical records and incident reports relating to falls of patients with communication disability following stroke for content codes, categories and themes relating to communication. METHODS & PROCEDURES: This medical record chart review examined data on 72 patients and 265 falls. A content thematic analysis was used to identify how patient communication is characterized in relation to falls, and their prevention and management strategies. OUTCOMES & RESULTS: The data reflected that staff viewed patients having difficulty following simple instructions as contributing to falls. Gaining the attention of staff and communicating basic needs were also considered to be contributing factors for falls. Patients were often described as experiencing a fall when taking a risk or attempting to address an unmet basic need. Furthermore, written notes for patients with more severe communication disability reflected that the patient's communication impairments prevented staff from establishing the circumstances of some falls and complicated the assessment for injury following a fall. CONCLUSIONS & IMPLICATIONS: The medical records and incident reports of patients with communication disability following stroke reveal that hospital staff recognize the impact of communication disability as potential risk factors for falls for this group. It was difficult for staff to report the circumstances of the fall for patients with severe communication disability. Despite the recognition of communication as a potential contributing factor, few medical record entries documented strategies related to communication interventions to improve patients' ability to understand instructions, gain attention or communicate basic needs. WHAT THIS PAPER ADDS: What is already known on the subject People with stroke are at a high risk of falls during their hospital admission. However, little is known about the circumstances of their falls and the influence of communication disability on these falls. What this paper adds to existing knowledge Patients with communication disability have unique factors that contribute to their falls in the hospital. Patients were described as experiencing a fall when taking a risk or attempting to address an unmet need, and these falls were often related to a patient's difficulties communicating their basic needs, gaining attention from staff, and following simple instructions. What are the potential or actual clinical implications of this work? Communication disability as a risk factor for a fall, and fall prevention strategies tailored to the communication disability, were typically identified and documented by physiotherapists, occupational therapists and nursing staff. The inclusion of speech pathologists in fall risk assessment, management, and prevention strategies may provide crucial information regarding the patient's communication disability that may enhance their fall prevention plan.


Assuntos
Afasia , Transtornos da Comunicação , Acidente Vascular Cerebral , Masculino , Humanos , Acidentes por Quedas/prevenção & controle , Pacientes Internados , Acidente Vascular Cerebral/complicações , Transtornos da Comunicação/etiologia , Medição de Risco , Registros Médicos , Hospitais
6.
Clin Nurs Res ; 32(3): 478-489, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36541748

RESUMO

Patients with stroke are at high risk of falls during inpatient rehabilitation admission. Communication disability is common following stroke; however, this population is often excluded from falls research. This study aimed to examine the falls of patients with communication disability following stroke, including the circumstances, contributing factors, and outcomes of the fall. This medical record review used the Generic Reference Model of patient safety as the analytical lens and data were analyzed descriptively. The study included 109 patients who experienced 308 falls. The most common type of fall was an "unwitnessed roll from bed." Patient factors contributed to half of all falls, injuries occurred in 15% of falls, and impacts to the hospital system included additional costs and staffing. Understanding the reasons why patients are attempting to get out of bed may identify ways to reduce the risk and incidence of falls in this population.


Assuntos
Transtornos da Comunicação , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Acidentes por Quedas/prevenção & controle , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Transtornos da Comunicação/complicações
7.
Mol Imaging Biol ; 25(2): 271-282, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36418769

RESUMO

INTRODUCTION: The reliance on glycolytic metabolism is a hallmark of tumor metabolism. Excess acid and protons are produced, leading to an acidic tumor environment. Therefore, we explored the relationship between the tumor glycolytic metabolism and tissue pH by comparing 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and hyperpolarized [1-13C]pyruvate MR spectroscopy imaging (MRSI) to chemical exchange saturation transfer (CEST) MRI measurements of tumor pH. METHODS: 106 C6 glioma cells were implanted in the brains of male Wistar rats (N = 11) using stereotactic surgery. A 60-min PET acquisition after a bolus of FDG was performed at 11-13 days post implantation, and standardized uptake value (SUV) was calculated. CEST measurements were acquired the following day before and during constant infusion of glucose solution. Tumor intracellular pH (pHi) was evaluated using amine and amide concentration-independent detection (AACID) CEST MRI. The change of pHi (∆pHi) was calculated as the difference between pHi pre- and during glucose infusion. Rats were imaged immediately with hyperpolarized [1-13C]pyruvate MRSI. Regional maps of the ratio of Lac:Pyr were acquired. The correlations between SUV, Lac:Pyr ratio, and ∆pHi were evaluated using Pearson's correlation. RESULTS: A decrease of 0.14 in pHi was found after glucose infusion in tumor region. Significant correlations between tumor glycolysis measurements of Lac:Pyr and ∆pHi within the tumor (ρ = 0.83, P = 0.01) and peritumoral region (ρ = 0.76, P = 0.028) were observed. No significant correlations were found between tumor SUV and ∆pHi within the tumor (ρ = - 0.45, P = 0.17) and peritumor regions (ρ = - 0.6, P = 0.051). CONCLUSION: AACID detected the changes in pHi induced by glucose infusion. Significant correlations between tumor glycolytic measurement of Lac:Pyr and tumoral and peritumoral pHi and ∆pHi suggest the intrinsic relationship between tumor glycolytic metabolism and the tumor pH environment as well as the peritumor pH environment.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Ratos , Masculino , Animais , Glioblastoma/patologia , Neoplasias Encefálicas/patologia , Fluordesoxiglucose F18 , Glucose , Concentração de Íons de Hidrogênio , Ratos Wistar , Imageamento por Ressonância Magnética/métodos , Glicólise , Piruvatos
8.
Menopause ; 29(10): 1200-1203, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35969885

RESUMO

OBJECTIVE: The aim of this study was to examine the effect of either conjugated equine estrogen or transdermal estradiol on vitamin D metabolism in postmenopausal women. METHODS: Twenty-five women from the Kronos Early Estrogen Prevention Study who were randomized to conjugated equine estrogen 0.45 mg/d and 20 women who were treated with transdermal estradiol 50 mg/d (patch replaced weekly) were analyzed in the present study. All participants received micronized progesterone for 12 days per month. RESULTS: There was no significant treatment effect on serum total 25-hydroxyvitamin D over 48 months in either study group, and there were no significant differences between treatment arms. In contrast, at 12 months, directly measured free 25-hydroxyvitamin D was significantly higher in the transdermal estradiol group than in the conjugated equine estrogen group. Directly measured free 25-hydroxyvitamin D subsequently increased significantly from 12 to 48 months in both treatment arms. Calculated free 25-hydroxyvitamin D was also significantly higher in the transdermal estradiol group at 36 months. Vitamin D-binding protein decreased significantly in both treatment groups from 12 to 48 months, but at 48 months, least square mean values were no different based on treatment assignment. CONCLUSIONS: Directly measured free 25-hydroxyvitamin D levels, but not serum total 25-hydroxyvitamin D levels, are different within the first 12 months of estrogen replacement depending on the preparation. However, this difference is transient, in that there were no differences at 36 or 48 months. These findings suggest that there may be a short-term benefit to prescribing transdermal estradiol for women who are either vitamin D deficient or vitamin D insufficient.


Assuntos
Estradiol , Estrogênios Conjugados (USP) , Administração Cutânea , Administração Oral , Estradiol/farmacologia , Terapia de Reposição de Estrogênios , Estrogênios/farmacologia , Estrogênios Conjugados (USP)/farmacologia , Feminino , Humanos , Estudos Longitudinais , Pós-Menopausa , Progesterona , Vitamina D/farmacologia , Proteína de Ligação a Vitamina D/farmacologia
9.
PLoS One ; 17(7): e0269592, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35802680

RESUMO

BACKGROUND: Atrial fibrillation (AF) is associated with extracellular matrix (ECM) remodelling and often coexists with myocardial fibrosis (MF); however, the causality of these conditions is not well established. OBJECTIVE: We aim to corroborate AF to MF causality by quantifying left atrial (LA) fibrosis in cardiac magnetic resonance (CMR) images after persistent rapid ventricular pacing and subsequent AF using a canine model and histopathological validation. METHODS: Twelve canines (9 experimental, 3 control) underwent baseline 3D LGE-CMR imaging at 3T followed by insertion of a pacing device and 5 weeks of rapid ventricular pacing to induce AF (experimental) or no pacing (control). Following the 5 weeks, pacing devices were removed to permit CMR imaging followed by excision of the hearts and histopathological imaging. LA myocardial segmentation was performed manually at baseline and post-pacing to permit volumetric %MF quantification using the image intensity ratio (IIR) technique, wherein fibrosis was defined as pixels > mean LA myocardium intensity + 2SD. RESULTS: Volumetric %MF increased by an average of 2.11 ± 0.88% post-pacing in 7 of 9 experimental dogs. While there was a significant difference between paired %MF measurements from baseline to post-pacing in experimental dogs (P = 0.019), there was no significant change in control dogs (P = 0.019 and P = 0.5, Wilcoxon signed rank tests). The median %MF for paced animals was significantly greater than that of non-paced dogs at the 5-week post-insertion time point (P = 0.009, Mann Whitney U test). Histopathological imaging yielded an average %MF of 19.42 ± 4.80% (mean ± SD) for paced dogs compared to 1.85% in one control dog. CONCLUSION: Persistent rapid ventricular pacing and subsequent AF leads to an increase in LA fibrosis volumes measured by the IIR technique; however, quantification is limited by inherent image acquisition parameters and observer variability.


Assuntos
Fibrilação Atrial , Cardiomiopatias , Animais , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/patologia , Fibrilação Atrial/terapia , Cardiomiopatias/patologia , Meios de Contraste , Cães , Fibrose , Gadolínio , Átrios do Coração , Imageamento por Ressonância Magnética/métodos
10.
Ther Adv Gastrointest Endosc ; 14: 26317745211049967, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34708203

RESUMO

Endoscopic eradication therapy for Barrett's esophagus has been established as an effective management strategy for patients with Barrett's esophagus with dysplasia and early esophageal cancer. Among the endoscopic therapies, ablation techniques such as radiofrequency ablation and cryoablation are effective primary treatment interventions with acceptable low complication rates forming the spectrum of a multimodal approach. Appropriate selection of patients, high-definition endoscopic evaluation, and dedicated histological assessment are important cornerstones to help navigate to the best effective treatment method. Carefully structured surveillance programs and preventive measures will be needed to provide long-term durability for maintaining complete remission.

11.
CJC Open ; 3(2): 182-194, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33644732

RESUMO

BACKGROUND: The hormone ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR) are expressed in myocardium. GHSR binding activates signalling pathways coupled to cardiomyocyte survival and contractility. These properties have made the ghrelin-GHSR axis a candidate for a biomarker of cardiac function. The dynamics of ghrelin-GHSR are altered significantly in late stages of heart failure (HF) and cardiomyopathy, when left ventricular (LV) function is failing. We examined the relationship of GHSR with ghrelin in cardiac tissue from patients with valvular disease with no detectable changes in LV function. METHODS: Biopsy samples from the left ventricle and left atrium were obtained from 25 patients with valvular disease (of whom 13 also had coronary artery disease) and preserved LV ejection fraction, and compared to control samples obtained via autopsy. Using quantitative confocal fluorescence microscopy, levels of GHSR were determined using [Dpr3(n-octanoyl),Lys19(sulfo-Cy5)]ghrelin(1-19), and immunofluorescence determined ghrelin, the heart failure marker natriuretic peptide type-B (BNP), and contractility marker sarcoplasmic reticulum ATPase pump (SERCA2a). RESULTS: A positive correlation between GHSR and ghrelin was apparent in only diseased tissue. Ghrelin and BNP significantly correlated in the left ventricle and strongly colocalized to the same intracellular compartment in diseased and control tissue. GHSR, ghrelin, and BNP all strongly and significantly correlated with SERCA2a in the left ventricle of diseased tissue only. CONCLUSIONS: Our results suggest that the dynamics of the myocardial ghrelin-GHSR axis is altered in cardiovascular disease in the absence of measurable changes in heart function, and might accompany a regional shift in endocrine programming.


CONTEXTE: L'hormone ghréline et son récepteur, le récepteur sécrétagogue de l'hormone de croissance (GHSR, de l'anglais growth hormone secretagogue receptor), sont exprimés dans le myocarde. La liaison au récepteur GHSR active les voies de signalisation associées à la survie et à la contractilité des cardiomyocytes. Ces propriétés font de l'axe ghréline-récepteur GHSR un bon candidat biomarqueur de la fonction cardiaque. En effet, la dynamique de cet axe est considérablement altérée aux stades avancés de l'insuffisance cardiaque et de la cardiomyopathie, lorsque la fonction ventriculaire gauche décline. Nous avons donc étudié la relation entre le récepteur GHSR et la ghréline dans le tissu cardiaque de patients présentant une valvulopathie sans changements détectables dans la fonction ventriculaire gauche. MÉTHODOLOGIE: Des échantillons de tissus du ventricule et de l'oreillette gauches ont été prélevés par biopsie chez 25 patients présentant une valvulopathie (dont 13 avaient aussi une coronaropathie) et une fraction d'éjection ventriculaire gauche préservée, puis comparés avec des échantillons témoins prélevés à l'autopsie. Les taux du récepteur GHSR ont été mesurés par microscopie en fluorescence confocale quantitative à l'aide de [Dpr3(n-octanoyl),Lys19(sulfo-Cy5)] ghréline(1-19); les taux de ghréline, de peptide natriurétique de type B (BNP, un marqueur de l'insuffisance cardiaque), et de pompe ATPase du réticulum sarcoplasmique (SERCA2a; un marqueur de la contractilité) ont quant à eux été mesurés par immunofluorescence. RÉSULTATS: Nous avons noté une corrélation positive entre le récepteur GHSR et la ghréline uniquement dans les tissus lésés. Il existe une corrélation significative entre les taux de ghréline et de BNP dans le ventricule gauche, les deux substances étant fortement localisées dans le même compartiment intracellulaire, tant dans les tissus malades que dans les tissus témoins. Le récepteur GHSR, la ghréline et le BNP sont tous fortement et significativement corrélés avec la SERCA2a SERCA2a dans le tissu ventriculaire gauche malade seulement. CONCLUSIONS: Nos résultats semblent indiquer que la dynamique de l'axe ghréline-récepteur GHSR dans le myocarde est altérée en cas de maladie cardiovasculaire même en l'absence de changements mesurables de la fonction cardiaque, et que cette altération pourrait être attribuable à une modification régionale de la programmation endocrinienne.

12.
Int J Lang Commun Disord ; 55(6): 837-851, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32970385

RESUMO

BACKGROUND: Falls are a common safety incident in people with stroke. Studies report that between 14% and 65% of people with stroke fall at least once during their hospital admission. Risk factors for falls in people with stroke have been reported to include neglect, balance and dependence for activities of daily living. Communication disability has been identified as a risk factor for patient safety incidents in hospital that has not been closely examined as a potential risk factor for falls in people with stroke. AIM: To determine the association between communication disability secondary to stroke and falls in people with stroke in hospital. METHODS & PROCEDURES: Systematic searches of five electronic databases were conducted in June 2019 using the key concepts of 'falls' and 'stroke' (PROSPERO CRD 42019137199). Included studies provided comparative data of falls in patients with stroke with and without communication disability. The methodological quality of the studies was examined using the Quality Assessment Tool for Studies with Diverse Designs (QATSDD). Both a narrative synthesis and a meta-analysis were completed. MAIN CONTRIBUTION: A total of 15 studies met the criteria for inclusion and 11 were included in a meta-analysis. Three studies found people with communication disability had an increased rate of falls in hospital. However, a meta-analysis showed no significant association between a non-specific classification of communication disability and an increased risk of falls. There was some indication from individual studies that higher risk of falls may be associated with severe communication disability, but there were insufficient data reported on the severity of the communication disability to draw robust conclusions. CONCLUSION & IMPLICATIONS: The results of this systematic review suggest that a generic classification of communication disability following stroke is not a risk factor for falls. However, further research that is inclusive of this population and considers severity of communication disability more specifically is required. What this paper adds What is already known on the subject The association between communication disability following stroke and falls in hospital is unclear. The literature reports mixed results regarding the impact of a communication disability following stroke on falls risk or rates of falls during hospital admission. What this paper adds to existing knowledge This review is the first to bring together this diverse literature to examine the association between communication disability following stroke and falls in hospital. The results suggest that a generic classification of communication disability following stroke is not a risk factor for falls. What are the potential or actual clinical implications of this work? There is a possibility that moderate to severe communication disability may be related to falls in patients in hospital. Further research is indicated to be more inclusive of people with communication disability, including those with severe communication disability.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Transtornos da Comunicação/reabilitação , Pacientes Internados/estatística & dados numéricos , Reabilitação do Acidente Vascular Cerebral/estatística & dados numéricos , Acidente Vascular Cerebral/complicações , Idoso , Transtornos da Comunicação/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
AANA J ; 87(2): 16, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31587732
15.
Nat Commun ; 10(1): 3698, 2019 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420548

RESUMO

Phosphonates are rare and unusually bioactive natural products. However, most bacterial phosphonate biosynthetic capacity is dedicated to tailoring cell surfaces with molecules like 2-aminoethylphosphonate (AEP). Although phosphoenolpyruvate mutase (Ppm)-catalyzed installation of C-P bonds is known, subsequent phosphonyl tailoring (Pnt) pathway steps remain enigmatic. Here we identify nucleotidyltransferases in over two-thirds of phosphonate biosynthetic gene clusters, including direct fusions to ~60% of Ppm enzymes. We characterize two putative phosphonyl tailoring cytidylyltransferases (PntCs) that prefer AEP over phosphocholine (P-Cho) - a similar substrate used by the related enzyme LicC, which is a virulence factor in Streptococcus pneumoniae. PntC structural analyses reveal steric discrimination against phosphocholine. These findings highlight nucleotidyl activation as a predominant chemical logic in phosphonate biosynthesis and set the stage for probing diverse phosphonyl tailoring pathways.


Assuntos
Ácido Aminoetilfosfônico/metabolismo , Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Vias Biossintéticas/fisiologia , N-Acilneuraminato Citidililtransferase/metabolismo , Organofosfonatos/metabolismo , Actinobacteria , Bactérias/genética , Proteínas de Bactérias/genética , Parede Celular/metabolismo , Cristalização , Cristalografia por Raios X , Escherichia coli , N-Acilneuraminato Citidililtransferase/genética , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Fosfolipídeos/metabolismo , Fosforilcolina/metabolismo , Fosfotransferases (Fosfomutases) , Polissacarídeos/metabolismo , Especificidade por Substrato
16.
J Endocr Soc ; 3(4): 748-762, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30937420

RESUMO

Currently, the early preclinical detection of left ventricular dysfunction is difficult because biomarkers are not specific for the cardiomyopathic process. The underlying molecular mechanisms leading to heart failure remain elusive, highlighting the need for identification of cardiac-specific markers. The growth hormone secretagogue receptor (GHSR) and its ligand ghrelin are present in cardiac tissue and are known to contribute to myocardial energetics. Here, we examined tissue ghrelin-GHSR levels as specific markers of cardiac dysfunction in patients who underwent cardiac transplantation. Samples of cardiac tissue were obtained from 10 patients undergoing cardiac transplant at the time of organ harvesting and during serial posttransplant biopsies. Quantitative fluorescence microscopy using a fluorescent ghrelin analog was used to measure levels of GHSR, and immunofluorescence was used to measure levels of ghrelin, B-type natriuretic peptide (BNP), and tissue markers of cardiomyocyte contractility and growth. GHSR and ghrelin expression levels were highly variable in the explanted heart, less in the grafted heart biopsies. GHSR and ghrelin were strongly positively correlated, and both markers were negatively correlated with left ventricular ejection fraction. Ghrelin had stronger positive correlations than BNP with the signaling markers for contractility and growth. These data suggest that GHSR-ghrelin have potential use as an integrated marker of cardiac dysfunction. Interestingly, tissue ghrelin appeared to be a more sensitive indicator than BNP to the biochemical processes that are characteristic of heart failure. This work allows for further use of ghrelin-GHSR to interrogate cardiac-specific biochemical mechanisms in preclinical stages of heart failure (HF).

17.
Top Stroke Rehabil ; 26(4): 288-293, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30890038

RESUMO

BACKGROUND: Falls in hospital are common and serious complications of stroke. Associations have been found between communication disorders and increased rates of falls, but have received relatively little consideration as a risk factor for falls among stroke survivors. OBJECTIVES: To investigate whether there is an association between severe communication impairment and falls among patients receiving inpatient rehabilitation after stroke. METHODS: A retrospective audit of 149 records of consecutive patients admitted to an inpatient rehabilitation facility after stroke over a two-year period was conducted. The relationship between falls and severe communication impairment was explored using (1) direct comparison of falls in patients with and without functional communication for the inpatient ward environment and (2) multivariate logistic regression to examine factors that may predict falls, including presence or absence of functional communication. In each analysis, falls were examined both as a binary outcome (fall or no fall), and the rate of falls per day. RESULTS: The 32 patients in the sample (21.7%) who were unable to communicate their basic needs were almost twice as likely to fall in hospital as those with functional communication (RR 1.94, 95% CI 1.15 to 3.24). Several commonly assessed factors were not significant predictors of falls (including falls history, polypharmacy, and cognitive impairment) in this population. Lack of functional communication was the strongest independent predictor of falls rate. CONCLUSIONS: Findings suggest that severe communication disorders may be under recognized as a falls risk factor after stroke.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Transtornos da Comunicação/complicações , Hospitalização , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
18.
Am J Physiol Heart Circ Physiol ; 316(3): H586-H595, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30575441

RESUMO

Radiotherapy for the treatment of left-sided breast cancer increases the long-term risk of cardiovascular disease. The purpose of the present study was to noninvasively image the progression of radiation-induced cardiac inflammation in a large animal model using a hybrid PET and MRI system. Five canines were imaged using [18F]fluorodeoxyglucose PET to assess changes in myocardial inflammation. All animals were imaged at baseline, 1 wk, and 1, 3, 6, and 12 mo after focused cardiac external beam irradiation with image guidance. Radiation was delivered in a single fraction. The linear quadratic model was used to convert a typical multifractionated heart dose to a corrected single-fraction biologically equivalent dose. Immunohistochemistry was performed on excised left ventricular tissue samples from all five irradiated canines and one nonirradiated control canine to confirm the presence of inflammation. The mean doses delivered to the entire heart, left ventricle, left anterior descending artery, and left circumflex artery were 1.7 ± 0.2, 2.7 ± 0.2, 5.5 ± 0.9, and 1.1 ± 0.4 Gy, respectively. FDG standard uptake values remained persistently elevated compared with baseline (1.1 ± 0.03 vs. 2.6 ± 0.19, P < 0.05). The presence of myocardial inflammation was confirmed histologically and correlated with myocardial dose. This study suggests a global inflammatory response that is persistent up to 12 mo postirradiation. Inflammation PET imaging should be considered in future clinical studies to monitor the early changes in cardiac function that may play a role in the ultimate development of radiation-induced cardiac toxicity. NEW & NOTEWORTHY Using advanced cardiac PET imaging, we have shown the spatial and quantitative relationship between radiation dose deposition and temporal changes in inflammation. We have shown that the progression of radiation-induced cardiac inflammation is immediate and does not subside for up to 1 yr after radiation. Results are presented in a large animal model that closely resembles the size and vessel architecture of humans. The proposed imaging protocol can be easily replicated for clinical use.


Assuntos
Neoplasias da Mama/radioterapia , Doenças Cardiovasculares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Lesões por Radiação/diagnóstico por imagem , Radioterapia/efeitos adversos , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/patologia , Cães , Feminino , Fluordesoxiglucose F18 , Imageamento por Ressonância Magnética , Imagem Multimodal , Doses de Radiação , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Compostos Radiofarmacêuticos
19.
J Palliat Med ; 22(5): 480-488, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30461347

RESUMO

Background: Little is known about research priorities in adult palliative care. Identifying research priorities for adult palliative care will help in increasing research quality and translation. Objective: The aim was to identify the views of health professionals' research priorities in adult palliative care that lead to development of a palliative care research agenda in Australia. Design: A modified three-round Delphi survey. Setting/Subjects: Palliative care researchers and clinicians in Australia were invited to participate. Results: A total of 25 panelists completed round 1, 14 completed round 2, and 13 completed round 3. Round 1 resulted in 90 research priorities in 13 categories. Round 2 showed consensus agreement on 19/90 research priorities. Round 3 resulted in the top 10 research priorities of the 19 achieving consensus in round 2. Panelists agreed that research is needed on the transition to palliative care; improving communication about prognosis; increasing access to palliative care for indigenous communities, people who wish to remain at home, and people in aged care; addressing family caregivers' needs; promoting patients' and families' decision making; improving cross-cultural aspects of palliative care; determining the effects of assisted dying legislation; and improving bereavement care in rural, remote, and Aboriginal populations. Conclusions: The expert panelists identified the top 10 research priorities for adult palliative care. These identified research priorities are the most urgent topics requiring attention to increase the quality of life of patients requiring palliative care and their family members.


Assuntos
Pesquisa Biomédica/estatística & dados numéricos , Pessoal de Saúde/psicologia , Enfermagem de Cuidados Paliativos na Terminalidade da Vida/métodos , Cuidados Paliativos/métodos , Pesquisa/estatística & dados numéricos , Adulto , Atitude do Pessoal de Saúde , Austrália , Técnica Delfos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa , Inquéritos e Questionários
20.
J Endocr Soc ; 2(2): 178-189, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29450407

RESUMO

Ghrelin and its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), are present in cardiac tissue. Activation of GHSR1a by ghrelin promotes cardiomyocyte contractility and survival, and changes in myocardial GHSR1a and circulating ghrelin track with end-stage heart failure, leading to the hypothesis that GHSR1a is a biomarker for heart failure. We hypothesized that GHSR1a could also be a biomarker for diabetic cardiomyopathy (DCM). We used two models of streptozotocin (STZ)-induced DCM: group 1, adult mice treated with 35 mg/kg STZ for 3 days; and group 2, neonatal mice treated with 70 mg/kg STZ at days 2 and 5 after birth. In group 1, mild fasting hyperglycemia (11 mM) was first detected 8 weeks after the last injection, and in group 2, severe fasting hyperglycemia (20 mM) was first detected 1 to 3 weeks after the last injection. In group 1, left ventricular function was slightly impaired as measured by echocardiography, and Western blot analysis showed a significant decrease in myocardial GHSR1a. In group 2, GHSR1a levels were also decreased as assessed by Cy5-ghrelin(1-19) fluorescence microscopy, and there was a significant negative correlation between GHSR1a levels and glucose tolerance. There were significant positive correlations between GHSR1a and ghrelin and between GHSR1a and sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a), a marker for contractility, but not between GHSR1a and B-type natriuretic peptide, a marker for heart failure. We conclude that the subclinical stage of DCM is accompanied by alterations in the myocardial ghrelin-GHSR1a system, suggesting the possibility of a biomarker for DCM.

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