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BACKGROUND: Diabetic gastroenteropathy can cause significant diagnostic challenges. Still, it remains unknown if measures of extraintestinal autonomic function reflect diabetic gastroenteropathy. We aimed to assess the associations between (1) gastrointestinal symptoms and motility measures and (2) gastrointestinal symptoms/motility measures and extraintestinal autonomic markers. METHODS: We included 81 persons with type 1 or type 2 diabetes (65% female, mean age 54) with gastrointestinal symptoms and autonomic neuropathy. The Gastroparesis Cardinal Symptom Index (GCSI) and the Gastrointestinal Symptom Rating Scale (GSRS) assessed gastrointestinal symptoms. The wireless motility capsule (Smartpill™) assessed panenteric transit times and motility indices. Cardiovascular reflex tests (VAGUS™) and cardiac vagal tone (eMotion Faros) estimated cardiovascular autonomic neuropathy, while the SUDOSCAN™ evaluated sudomotor function. KEY RESULTS: Proximal gastrointestinal symptoms were positively associated with the gastric motility index (GCSI: 1.18 (1.04-1.35), p = 0.01; GSRS: 1.15 (1.03-1.29), p = 0.02; median ratio (95% CI)), while only satiety correlated with gastric emptying time (1.24 (1.03-1.49), p = 0.02). Diarrhea was associated with decreased small bowel transit time (0.93 (0.89-0.98), p = 0.005), while constipation were associated with prolonged colonic transit time (1.16 (1.03-1.31), p = 0.02). Gastrointestinal symptoms increased with the degree of abnormal cardiovascular reflex tests (GCSI: 0.67 (0.16-1.19), p = 0.03; GSRS: 0.87 (0.30-1.45), p = 0.01; mean difference (95% CI)) but not with motility measures. Cardiac vagal tone and sudomotor function were not associated with gastrointestinal markers. CONCLUSIONS & INFERENCES: Gastrointestinal and extraintestinal autonomic measures were not associated. However, proximal gastrointestinal symptoms were associated with the gastric motility index and cardiovascular reflex tests. Hence, the latter may contribute to evaluating whether proximal gastrointestinal symptoms are autonomically derived.
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Population-level efforts are needed to increase levels of physical activity and healthy eating to reduce and manage chronic diseases such as obesity, cardiovascular disease, and type 2 diabetes. Interventions to increase public transit use may be one promising strategy, particularly for low-income communities or populations of color who are disproportionately burdened by health disparities and transportation barriers. This study employs a natural experiment design to evaluate the impacts of a citywide zero-fare transit policy in Kansas City, Missouri, on ridership and health indicators. In Aim 1, comparison to 9 similar cities without zero-fare transit is used to examine differential changes in ridership from 3 years before to 4 years after the adoption of zero-fare. In Aim 2, Kansas City residents are being recruited from a large safety net health system to compare health indicators between zero-fare riders and non- riders. Longitudinal data on BMI, cardiometabolic markers, and economic barriers to health are collected from the electronic health record from 2017 to 2024. Cross-sectional data on healthy eating and device-measured physical activity are collected from a subsample of participants as part of the study procedures (N = 360). Numerous baseline characteristics are collected to account for differences between Kansas City and comparison city bus routes (Aim 1) and between zero-fare riders and non-riders within Kansas City (Aim 2). Evidence on how zero-fare transit shapes population health through mechanisms related to improved economic factors, transportation, physical activity, and healthy eating among low-income groups is expected.
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Determinantes Sociais da Saúde , Meios de Transporte , Humanos , Missouri , Feminino , Masculino , Adulto , Exercício Físico , Estudos Transversais , Pessoa de Meia-IdadeRESUMO
BACKGROUND: This study analysed treatment strategies with electrochemotherapy (ECT) in melanoma with limb in-transit metastases (ITM). METHODS: We audited AJCC v.8 stage IIIB-IIID patients treated across 22 centres (2006-2020) within the International Network for Sharing Practices of ECT (InspECT). RESULTS: 452 patients were included, 58 % pre-treated (93 % had lower limb ITM, 44 % had ≤10 metastases [median size 1.5 cm]. Treatment strategies included first-line ECT (n = 145, 32 %), ECT with concurrent locoregional/systemic treatment (n = 163, 36 %), and salvage ECT (n = 144, 32 %). The objective response rate was 63 % (complete response [CR], 24 %), increasing to 74 % (CR, 39 %) following retreatment (median two ECT, range 1-8). CR rate in treatment-naïve and pre-treated patients was 50 % vs 32 % (p < 0.001). Bleomycin de-escalation was associated with lower CR (p = 0.004). Small tumour number and size, hexagonal electrode, retreatment, and post-ECT skin ulceration predicted response in multivariable analysis. At a median follow-up of 61 months, local and locoregional recurrence occurred in 55 % and 81 % of patients. Median local progression-free, new lesions-free, and regional recurrence-free survival were 32.9, 6.9, and 7.7 months. Grade-3 toxicity was 15 %. Concurrent treatment and CR correlated with improved regional control and survival. Concomitant checkpoint inhibition did not impact toxicity or survival outcomes. The median overall survival was 5.7 years. CONCLUSIONS: Among patients with low-burden limb-only ITM, standard-dose bleomycin ECT results in durable local response. Treatment naivety, low tumour volume, hexagonal electrode application, retreatment, and post-ECT ulceration predict response. CR and concurrent treatment correlate with improved regional control and survival outcomes. Combination with checkpoint inhibitors is safe but lacks conclusive support.
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The presence of pathogenic bacteria and antibiotic resistance genes (ARGs) in urban air poses a significant threat to public health. While prevailing research predominantly focuses on the airborne transmission of ARGs by bacteria, the potential influence of other vectors, such as bacteriophages, is often overlooked. This study aims to investigate the characteristics of phages and ARGs in aerosols originating from hospitals, public transit centers, wastewater treatment plants, and landfill sites. The average abundance of ARGs carried by phages in the public transit centers was 8.81 ppm, which was 2 to 3 times higher than that at the other three sites. Additionally, the abundance of ARGs across different risk levels at this site was also significantly higher than at the other three sites. The assembled phage communities bearing ARGs in public transit centers are chiefly governed by homogeneous selection processes, likely influenced by human movement. Furthermore, observations at public transit sites revealed that the average abundance ratio of virulent phages to their hosts was 1.01, and the correlation coefficient between their auxiliary metabolic genes and hosts' metabolic genes was 0.59, which were 20 times and 3 times higher, respectively, than those of temperate phages. This suggests that virulent phages may enhance their survival by altering host metabolism, thereby aiding the dispersion of ARGs and bacterial resistance. These revelations furnish fresh insights into phage-mediated ARG transmission, offering scientific substantiation for strategies aimed at preventing and controlling resistance within aerosols.
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Accurate classification of rail transit stations is crucial for successful Transit-Oriented Development (TOD) and sustainable urban growth. This paper introduces a novel classification model integrating traditional methodologies with advanced machine learning algorithms. By employing mathematical models, clustering methods, and neural network techniques, the model enhances the precision of station classification, allowing for a refined evaluation of station attributes. A comprehensive case study on the Chengdu rail transit network validates the model's efficacy, highlighting its value in optimizing TOD strategies and guiding decision-making processes for urban planners and policymakers. The study employs several regression models trained on existing data to generate accurate ridership forecasts, and data clustering using mathematical algorithms reveals distinct categories of stations. Evaluation metrics confirm the rationality and accuracy of the results. Additionally, a neural network achieving high accuracy on labeled data enhances the model's predictive capabilities for unlabeled instances. The research demonstrates high accuracy, with the Mean Squared Error (MSE) for regression models (Multiple Linear Regression (MLR), Deep-Learning Neural Network (DNN), and K-Nearest Neighbor (KNN)) remaining below 0.012, while the neural networks used for station classification achieve 100% accuracy across seven time intervals and 98.15% accuracy for the eighth, ensuring reliable ridership forecasts and classification outcomes. Accuracy in rail transit station classification is critical, as it not only strengthens the model's predictive capabilities but also ensures more reliable data-driven decisions for transit planning and development, allowing for more precise ridership forecasts and evidence-based strategies for optimizing TOD. This classification model provides stakeholders with valuable insights into the dynamics and features of rail transit stations, supporting sustainable urban development planning.
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On the 20th anniversary of the Alzheimer's Disease Neuroimaging Initiative (ADNI), this paper provides a comprehensive overview of the role of arterial spin labeling (ASL) magnetic resonance imaging (MRI) in understanding perfusion changes in the aging brain and the relationship with Alzheimer's disease (AD) pathophysiology and its comorbid conditions. We summarize previously used acquisition protocols, available data, and the motivation for adopting a multi-post-labeling delay (PLD) acquisition scheme in the latest ADNI MRI protocol (ADNI 4). We also detail the process of setting up this scheme on different scanners, emphasizing the potential of ASL imaging in future AD research. HIGHLIGHTS: The Alzheimer's Disease Neuroimaging Initiative (ADNI) adopted multimodal arterial spin labeling magnetic resonance imaging (ASL MRI) to meet evolving biomarker requirements. The ADNI provides one of the largest multisite, multi-vendor ASL data collections. The ADNI 4 incorporates multi-post-labeling delay ASL techniques to jointly quantify cerebral blood flow and arterial transit time. ADNI 4 ASL MRI protocol is apt for detecting early Alzheimer's disease with cerebrovascular pathology.
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BACKGROUND AND PURPOSE: Transit-Guided Radiation Therapy (TGRT) is a novel technique that uses the transit portal images (TPIs) acquired with Electronic Portal Image Devices (EPID) to quantify patient position errors during the treatment. It has been validated using anthropomorphic phantoms but a validation in a clinical setting was lacking. A pilot clinical study is presented to confirm our previous results. MATERIALS AND METHODS: A prospective study was conducted between June and December 2022 with patients who received whole-brain or breast radiotherapy treatments. The selected treatments were composed of radiation fields using skin-flash, where the body contour projected a sharp edge on the EPID which has been used as a surrogate of the true patient position. Daily imaging procedures were applied as scheduled before running the one- and two-parameter model (1PM and 2PM) of the TGRT formalism on the acquired TPIs to independently estimate the patient position errors. RESULTS: 43 patients and 1015 TPIs have been assessed. The 2PM showed a better correlation with the true position errors (R2 = 0.76 vs. 0.73), a lower detection threshold (0.77 mm vs. 1.24 mm), and a lower overcorrection risk above the detection threshold (7.0 % vs. 11.1 %) than the 1PM. Overall, the 2PM would have significantly reduced the true position errors by a factor of 0.58 (0.49 - 1.27) (p < 0.0001). CONCLUSION: The TGRT technique has confirmed the ability to reduce the position errors in a clinical setting, demonstrating the potential to enhance the patient position monitoring without increasing treatment time or patient dose.
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A 32-year-old Asian male presented to the ED with a one-day history of mild pleuritic chest pain. He was diagnosed with an acute pulmonary embolus on CT Pulmonary Angiography (CT-PA). Transthoracic echocardiography (TTE) performed at the bedside in the ED demonstrated evidence of right heart strain but, most notably, a highly mobile echogenic thrombus in the right atrium, consistent with a clot-in-transit (CIT). This was not visualized on CT due to the influx of contrast in the heart. Based on this, the patient was transferred to the High Dependency Unit for IV heparin and close monitoring. The following day, he underwent clot retrieval using an Inari Flowtriever under direct TTE guidance. He was discharged on oral anticoagulation four days later and experienced no complications on follow-up. CIT is an important feature of pulmonary embolus to identify, as it can escalate the risk stratification of the patient, and management will need to be altered accordingly.
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BACKGROUND: Slow transit constipation (STC) is highly prevalent and has rising incidence. Shouhui Tongbian capsule (SHTB) is a traditional Chinese Medicine formula with extensive and highly efficacious usage in STC treatment, however, its mechanism of action, especially the regulation of microbiome and lipid metabolites, remains unclear. METHODS: After quality control of SHTB using LCâMS to obtain its material basis, we tried to elucidate the cohesive modulatory network of SHTB against STC using hyphenated methods from microbiomics, lipidomics, mass spectrometry imaging (MSI) and molecular methods. RESULTS: SHTB could repair intestinal barrier damage, reduce systemic inflammation and increase intestinal motility in a diphenoxylate-induced STC rat model. Based on 16S rDNA sequencing results, SHTB rehabilitated the abnormal changes in Alloprevotella, Coprococcus, Marvinbryantia, etc., which were associated with STC symptoms. Meanwhile, microbial functional prediction showed that lipid metabolism was improved with SHTB administration. The differential lipids, including fatty acids, lysophosphatidylcholine, phosphatidylcholine, sphingomyelin triglyceride and ceramide, that are closely related to STC disease and SHTB efficacy. Furthermore, SHTB significantly reversed the abnormal expression of these key target enzymes in colon samples, including CTP-phosphocholine cytidylyltransferase, CTP-phosphoethanolamine cytidylyltransferase, phosphatidic acid phosphatase, acid sphingomyelinase etc. CONCLUSIONS: Combined analysis demonstrated that SHTB reducing lipid accumulation and recovery of intestinal microbial homeostasis was the critical mechanism by which SHTB treats STC.
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PURPOSE: Our objective was to assess a deconvolution and denoising technique based on Legendre polynomials compared to matrix deconvolution on dynamic 18F-FDG renography of healthy patients. METHOD: The study was carried out and compared to the data of 24 healthy patients from a published study who underwent examinations with 99mTc-MAG3 planar scintigraphy and 18F-FDG PET/MRI. Due to corruption issues in some data used in the published article, post-publication measurements were provided. We have been warned that post-publication data were treated differently. The smoothing method switched from Bezier to Savitzky-Golay and the deconvolution from matrix-based (with Tikhonov Regularization) to Richardson-Lucy. A comparison of the split function and mean transit times of the published and post-publication data against our method based on Legendre polynomials was performed. RESULTS: For split function, we only observed a good agreement between the processing methods for the 99mTc-MAG3 and the post-published data. No correlation was found between the split functions obtained on the 99mTc-MAG3 and the 18F-FDG, contrary to the published study. However, all calculated split function values for 18F-FDG and 99mTc-MAG3 were within the established normal range. For the mean transit time, the correlation was moderate with published data and very good with the post-publication measurements for both 99mTc-MAG3 and 18F-FDG. Bias of the Bland-Altman analysis of the mean transit times for 99mTc-MAG3 versus 18F-FDG was 1.1 min (SD 1.7 min) for the published data, - 0.11 min (SD 1.9 min) for the post-publication results and .05 min (SD 1.9 min) for our method. CONCLUSIONS: The processing methods used in the original publication and in the post-publication work were quite complex and required adaptation of the fitting parameters for each individual and each type of examination. Our method did not require any specific adjustment; the same unmodified and fully automated algorithm was successfully applied to all data.
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OBJECTIVE: Pulse transit time (PTT) is a popular indicator of blood pressure (BP) changes. However, the relationship between PTT and BP is somehow individual dependent, resulting in the inaccuracy of PTT-based BP estimation. Confounding factors, e.g., heart rate (HR), of PTT and BP could be the primary cause. In this study we attempt to explore the impact of HR as a window to look at the influence of confounding factors on the relationship between PTT and BP. APPROACH: We investigated the relationship between PTT and systolic BP (SBP) at different HR levels by introducing the heterogeneous treatment effects (HTE) as a quantitative indicator. Compared to the average HR calculated using traditional indicators (e. g. regression coefficient, correlation coefficient), the HTE calculation method can compute the relationship between PTT and SBP at different HR levels, and reduce the influence of confounding factors. MAIN RESULTS: We analyzed the HTE of PTT and SBP of 47 subjects who are resting healthy young people with varying levels of HR. The results showed that the strength of the HTE of PTT and SBP varied with HR, indicating that the strength of the causal relationship between PTT and SBP is subject to HR levels. Whereas the correlation between SBP and PTT was individual dependent; either the strength or the direction of the correlation can vary with HR. We further investigated the group in which PTT and SBP exhibited a negative correlation, and found that about 50% of the subjects showed enhanced strength of HTE in with an increase in HR and the remaining showed the opposite. SIGNIFICANCE: This study means that HR needs to be considered when PTT is used as an indicator of SBP.
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Slow transit constipation (STC) is a common intestinal disorder. Some studies reported that Shouhui Tongbian Capsule (SHTB) can effectively mitigate STC symptoms. A detailed understanding of the changes in the endogenous metabolite profile of rats is crucial for a more accurate comprehension of the molecular pathological characteristics of SHTB in treating STC. In the present study, a method integrating metabolomics based on Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and Desorption electrospray ionization (DESI)-mass spectrometry imaging (MSI) was proposed to investigate serum, feces and colon tissue metabolic alterations of STC rats induced by diphenoxylate and the effect of SHTB treatment on metabolism. Then, Enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) analysis for verifying the potential mechanism of SHTB in treating STC. As a result, we first indicated that SHTB significantly improved intestinal peristalsis and low fecal water content in STC rats. Furthermore, after treatment with SHTB, the thickness of muscle layers was increased, demonstrated SHTB's effectiveness in reducing intestinal injury in STC rats. Besides, bile acid (BA) metabolomics based on UPLC-MS/MS revealed significant increase in serum levels of Cholic acid (CA), Deoxycholic acid (DCA), Chenodeoxycholic acid (CDCA), Ursodeoxycholic acid (UDCA), and Glycolithocholic acid (GLCA), whereas the contents of CA and DCA in feces were significantly decreased in STC rats. Nonetheless, they returned to the control levels after the SHTB administration. ELISA results showed that SHTB significantly hindered the excessive reabsorption of BAs by inhibiting apical sodium-dependent bile acid transporter (ASBT), organic solute transporter alpha (OSTα) and organic solute transporter beta (OSTß) in the ileum tissue of STC rats. Furthermore, the DESI-MSI analysis revealed that SHTB remarkably enhanced DCA in the colon tissue of STC rats. The WB results indicated that SHTB reinstated Takeda G-protein-coupled receptor 5 (TGR5) expression, a receptor for BAs and a key regulator of colonic motility. Consequently, DCA exerted its effects on TGR5, leading to the promotion of colonic motility. This study provided more comprehensive and detailed information about the BA metabolomics in the serum, feces and colon of STC rats. These findings highlighted the promising potential of metabolomics based on UPLC-MS/MS and DESI-MSI method for application in the study of STC diseases.
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Acceptable swallowability and complete esophageal transit are decisive for the safe and effective administration of solid oral dosage forms. This applies in particular to the main user group of medicines, older adults, who often suffer from swallowing difficulties. It is well known that surface properties play an important role in this respect. In the past, this has led to the development of numerous coating formulations for tablets with improved swallowability. However, in vitro and especially in vivo data investigating a positive effect of different coating materials is limited. Therefore, we investigated coating materials being based on polyvinyl alcohol, hydroxypropyl methylcellulose, and a copolymer of methacrylate in respect to their influence on swallowability and esophageal transit of a tablet formulation. They were compared to uncoated tablets as well as to hard gelatin capsules. Three in vitro assays suitable for routine use in pharmaceutical development were performed: i.) Wettability test in artificial saliva; ii.) Swelling measurement in artificial saliva; iii.) Measurement of the adhesion between surface materials and a simulated mucosa surface. All three assays resulted in a differentiation of the surface materials. The coated tablets showed favorable behavior compared to uncoated tablets and hard gelatin capsules. To test the effect of the different materials in vivo, an intervention study was conducted. 36 adults were included and the likeliness of prolonged esophageal transit of (un-)coated tablets as well as a hard gelatin capsule of the same weight was objectively evaluated by means of magnetic resonance imaging. While hard gelatin capsules showed highest rates for prolonged esophageal transit, the tendency for adhesion was reduced for uncoated tablets, and least for coated tablets, i.e., prolonged esophageal transit in 22.2 %, 11.1 %, and ≤5.6 % of the cases, respectively. Further differentiation of the coating materials was not possible. Subjective evaluations of each participant with respect to subjective swallowability and esophageal transit did not correlate well with the objective measurements by means of magnetic resonance imaging. The use of coatings in general has a positive influence on esophageal transit. However, the selection of coating type seems to be of greater importance in respect to patients' oral perception of the dosage forms compared to their influence on the probability for prolonged esophageal transit.
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Esôfago , Voluntários Saudáveis , Derivados da Hipromelose , Imageamento por Ressonância Magnética , Propriedades de Superfície , Comprimidos , Humanos , Masculino , Adulto , Administração Oral , Feminino , Esôfago/fisiologia , Esôfago/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Derivados da Hipromelose/química , Deglutição/fisiologia , Álcool de Polivinil/química , Trânsito Gastrointestinal , Gelatina/química , Pessoa de Meia-Idade , Cápsulas , Adulto JovemRESUMO
Compared with the general urban rail transit, some of the current rapid urban rail transit can reach a maximum speed of 140 km/h when the train is running, which exceeds the speed level of the general urban rail transit. To consider the influence of different speeds and loads on the vibration of viaducts and the surrounding soil environment, this paper establishes a three-dimensional finite element model of rail-viaduct soil. The results show that: the frequency domain acceleration of each measurement point increases with the increase of train speed; except for the measurement point which is 20 m away from the centerline of the track, the frequency domain speed of each measurement point increases with the increase of train speed; the frequency domain speed under the low-frequency component of the viaduct measurement point increases with the increase of train loading, and the growth rate is obviously larger than that of the middle and high frequency bands, and the frequency domain speed of the measurement points in the site also increases with the increase of train loading, and the growth rate of the low-frequency band is obviously larger than that of the middle and high frequency bands. The frequency domain velocity at each measurement point of the site also increases with the increase of train load, and the growth rate of the low-frequency band is obviously larger than that of the middle and high-frequency bands.
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Cerebral blood flow (CBF) and arterial transit time (ATT), markers of brain vascular health, worsen with age. The primary aim of this cross-sectional study was to identify modifiable determinants of CBF and ATT in healthy older adults (n = 78, aged 60-81 years). Associations between cardiorespiratory fitness and CBF or ATT were of particular interest because the impact of cardiorespiratory fitness is not clear within existing literature. Secondly, this study assessed whether CBF or ATT relate to cognitive function in older adults. Multiple post-labelling delay pseudo-continuous arterial spin labelling estimated resting CBF and ATT in grey matter. Results from multiple linear regressions found higher BMI was associated with lower global CBF (ß = -0.35, P = 0.008) and a longer global ATT (ß = 0.30, P = 0.017), global ATT lengthened with increasing age (ß = 0.43, P = 0.004), and higher cardiorespiratory fitness was associated with longer ATT in parietal (ß = 0.44, P = 0.004) and occipital (ß = 0.45, P = 0.003) regions. Global or regional CBF or ATT were not associated with processing speed, working memory, or attention. In conclusion, preventing excessive weight gain may help attenuate age-related declines in brain vascular health. ATT may be more sensitive to age-related decline than CBF, and therefore useful for early detection and management of cerebrovascular impairment. Finally, cardiorespiratory fitness appears to have little effect on CBF but may induce longer ATT in specific regions.
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Aptidão Cardiorrespiratória , Circulação Cerebrovascular , Humanos , Idoso , Circulação Cerebrovascular/fisiologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Idoso de 80 Anos ou mais , Aptidão Cardiorrespiratória/fisiologia , Cognição/fisiologia , Imageamento por Ressonância Magnética , Envelhecimento/fisiologia , Substância Cinzenta/irrigação sanguínea , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/fisiologia , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Índice de Massa CorporalRESUMO
Pulse arrival time (PAT), Pulse transit time (PTT), and Pulse Wave Velocity (PWV) have all been used as metrics for assessing a number of cardiovascular applications, including arterial stiffness and cuffless blood pressure monitoring. These have been measured using various sensing methods, including electrocardiogram (ECG) with photoplethysmogram (PPG), two PPG sensors, or two Bioimpedance (BioZ) sensors. Our study addresses the mathematical inaccuracies of previous bioimpedance approaches and incorporates PTT weights for the peak-peak (PTTpp), middle-middle (PTTmm), and foot-foot (PTTff) segments of the sensing signal into a single neuron model to determine a more accurate and stable PWV. In addition, we developed a tetherless bioimpedance device and compared our PTT estimation approaches, which yielded PWV across six subjects and two different arteries. Specifically, using our model, we found that the most reliable combination of weights corresponding to PTTpp, PTTmm, and PTTff was (0.260, 0.704, 0.036) for the brachial artery and (0.104, 0.858, 0.038) for radial artery. This model consistently yielded stable values across repetitions, with PWV values of 5.2 m/s, 5.3 m/s, and 5.9 m/s for the brachial artery and values of 5.8 m/s, 6.6 m/s, and 6.5 m/s for the radial artery. This system and model offer the possibility of obtaining higher reliability PTT and PWV values yielding better monitoring of cardiovascular health measures such as blood pressure and arterial stiffness.
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Water exchange rate (Kw) across the blood-brain barrier (BBB) is an important physiological parameter that may provide new insight into ageing and neurodegenerative disease. Recently, two non-invasive arterial spin labelling (ASL) MRI methods have been developed to measure Kw, but results from the different methods have not been directly compared. Furthermore, the association of Kw with age for each method has not been investigated in a single cohort. Thirty participants (70% female, 63.8 ± 10.4 years) were scanned at 3 T with Diffusion-Prepared ASL (DP-ASL) and Multi-Echo ASL (ME-ASL) using previously implemented acquisition and analysis protocols. Grey matter Kw, cerebral blood flow (CBF) and arterial transit time (ATT) were extracted. CBF values were consistent; approximately 50 ml/min/100 g for both methods, and a strong positive correlation in CBF from both methods across participants (r = 0.82, p < 0.001). ATT was significantly different between methods (on average 147.7 ms lower when measured with DP-ASL compared to ME-ASL) but was positively correlated across participants (r = 0.39, p < 0.05). Significantly different Kw values of 106.6 ± 19.7 min-1 and 306.8 ± 71.7 min-1 were measured using DP-ASL and ME-ASL, respectively, and DP-ASL Kw and ME-ASL Kw were negatively correlated across participants (r = -0.46, p < 0.01). Kw measured using ME-ASL had a significant linear relationship with age (p < 0.05). In conclusion, DP-ASL and ME-ASL provided estimates of Kw with significantly different quantitative values and inconsistent dependence with age. We propose future standardisation of modelling and fitting methods for DP-ASL and ME-ASL, to evaluate the effect on Kw quantification. Also, sensitivity and bias analyses should be performed for both approaches, to assess the effect of varying acquisition and fitting parameters. Lastly, comparison with independent measures of BBB water transport, and with physiological and clinical biomarkers known to be associated with changes in BBB permeability, are essential to validate the ASL methods, and to demonstrate their clinical utility.
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Methadone is an opioid receptor agonist medication used in the treatment of opioid use disorder (OUD). Geographic distance to opioid treatment programs (OTPs) is a major barrier to treatment, given requirements for direct observation of dosing and periodic drug screens, and 'methadone treatment deserts' are defined as a public transit threshold of 30 minutes. The purpose of this study was to examine public transit access to methadone treatment for participants of a syringe services program (SSP) in Miami-Dade County, Florida. Public transit times were calculated using the R library r5r, which facilitates multi-modal transportation network routing. General Transit Feed Specification data was combined with street network data from OpenStreetMap for Miami-Dade County. Transit times were estimated from the population-weighted centroid of each zip code (n=79) with participants of Miami's only SSP (n=1597) to the nearest OTP (n=4) using 10 departure windows aligned with OTP service hours. The mean one-way transit time from zip codes with SSP participants in Miami-Dade County to the nearest OTP was 80 minutes. 75 of the 79 (95%) zip codes with SSP participants in Miami-Dade County have a mean transit time to the closest OTP greater than 30 minutes. Transit times differ substantially between zip codes with different numbers of SSP participants, but not between departure windows. Nearly all zip codes with SSP participants in Miami-Dade County can be classified as 'methadone treatment deserts'. Geographic isolation of methadone treatment from public transit routes represents a significant barrier to equitable OUD treatment.
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Myocardial revascularization has been known to not affect the prognosis in some patients. Coronary artery bypass graft (CABG) failure may develop one year after CABG surgery. This is accompanied by a high risk of developing myocardial infarction after complete myocardial revascularization in obstructive coronary artery disease (CAD) due to microvascular dysfunction. The study of microvascular dysfunction using intraoperative stress tests with adenosine triphosphate (ATP) allows for the assessment of the coronary bypass flow reserve (CBFR) and the risk of graft failure one year after surgery. The study included 79 CAD patients (238 grafts) who underwent dynamic single-photon emission computed tomography (SPECT) before CABG and dynamic transit time flow measurement (TTFM) during CABG at rest and at stress. The CBFR was calculated by the ratio of the mean graft flow (MGF) at stress to the MGF at rest. A multivariate regression model showed that the MGF at rest (p = 0.043), the MGF at stress (p = 0.026) and the CBFR (p = 0.0001) were significant independent predictors of graft failure. As a result of ROC analysis, the threshold CBFR < 1.67 units correlated with graft failure more closely (sensitivity 82%, specificity 90%) The CBFR is a significant independent predictor of graft failure for up to 16 months.