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Despite the known interplay between blood flow and function, to our knowledge, there is currently no minimally invasive method to monitor diaphragm hemodynamics. We used contrast-enhanced ultrasound to quantify relative diaphragm blood flow (Q ˙ DIA) in humans and assessed the technique's efficacy and reliability during graded inspiratory pressure threshold loading. We hypothesized that: (1) Q ˙ DIA would linearly increase with pressure generation, and (2) that there would be good test-retest reliability and interanalyzer reproducibility. Can we validate what is, to our knowledge, the first minimally invasive method to measure relative diaphragm blood flow in humans? Quantitative contrast-enhanced ultrasound of the costal diaphragm was performed in healthy participants (10 male participants, 6 female participants; mean age 28 ± 5 years; BMI 22.8 ± 2.0 kg/m) during unloaded breathing and three stages of loaded breathing on two separate days. Gastric and esophageal balloon catheters measured transdiaphragmatic pressure. Ultrasonography was performed during a constant-rate IV infusion of lipid-stabilized microbubbles following each stage. Ultrasound images were acquired after a destruction-replenishment sequence and diaphragm specific time-intensity data were used to determine Q ˙ DIA by two individuals. Transdiaphragmatic pressure for unloaded and each loading stage were 15.2 ± 0.8, 26.1 ± 0.8, 34.6 ± 0.8, and 40.0 ± 0.8 percentage of the maximum, respectively. Q ˙ DIA increased with each stage of loading (3.1 ± 3.1, 6.9 ± 3.6, 11.0 ± 4.9, and 13.5 ± 5.4 acoustic units/s; P <.0001). The linear relationship between diaphragmatic flow and pressure was reproducible from day to day. Q ˙ DIA had good to excellent test-retest reliability (0.86 [0.77, 0.92]; P <.0001) and excellent interanalyzer reproducibility (0.93 [0.90, 0.95]; P <.0001) with minimal bias. Relative Q ˙ DIA measurements had valid physiological underpinnings, were reliable day-to-day, and were reproducible analyzer-to-analyzer. This study indicated that contrast-enhanced ultrasound is a viable, minimally invasive method for assessing costal Q ˙ DIA in humans and may provide a tool to monitor diaphragm hemodynamics in clinical settings. [Display omitted] [ABSTRACT FROM AUTHOR]

Prior studies of muscle blood flow and muscle-specific oxygen consumption have required invasive injection of dye and magnetic resonance imaging, respectively. Such measures have limited utility for continuous monitoring of the respiratory muscles. Frequency-domain near-infrared spectroscopy and diffuse correlation spectroscopy (FD-NIRS & DCS) can provide continuous surrogate measures of blood flow index (BFi) and metabolic rate of oxygen consumption (MRO2). This study aimed to validate sternocleidomastoid FD-NIRS & DCS outcomes against electromyography (EMG) and mouth pressure (Pm) during incremental inspiratory threshold loading (ITL). Six female and six male healthy adults (means ± SD; 30 ± 7 yr, maximum inspiratory pressure 118 ± 61 cmH2O) performed incremental ITL starting at low loads (8 ± 2 cmH2O) followed by 50-g increments every 2 min until task failure. FD-NIRS & DCS continuously measured sternocleidomastoid oxygenated and deoxygenated hemoglobin + myoglobin (oxy/deoxy[Hb + Mb]), tissue saturation of oxygen (StO2), BFi, and MRO2. Ventilatory parameters including inspiratory Pm were also evaluated. Pm increased during incremental ITL (P < 0.05), reaching −47[−74 to −34] cmH2O (median [IQR: 25%–75%]) at task failure. Ventilatory parameters were constant throughout ITL (all P > 0.05). Sternocleidomastoid BFi and MRO2 increased from the start of the ITL (both P < 0.05). Deoxy[Hb + Mb] increased close to task failure, concomitantly with a constant increase in MRO2, and decreased StO2. Sternocleidomastoid deoxy[Hb + Mb], BFi, StO2, and MRO2 obtained during ITL via FD-NIRS & DCS correlated with sternocleidomastoid EMG (all P < 0.05). In healthy adults, FD-NIRS & DCS can provide continuous surrogate measures of respiratory BFi and MRO2. Increasing sternocleidomastoid oxygen consumption near task failure was associated with increased oxygen extraction and reduced tissue saturation. NEW & NOTEWORTHY: This study introduces a novel approach, frequency-domain near-infrared spectroscopy and diffuse correlation spectroscopy (FD-NIRS & DCS), for noninvasive continuous monitoring of respiratory muscle blood flow and metabolic rate of oxygen consumption. Unlike prior methods involving invasive dye injection and magnetic resonance imaging, FD-NIRS & DCS offers the advantage of continuous measurement without the need for invasive procedures. It holds promise for advancing muscle physiology understanding and opens avenues for real-time monitoring of respiratory muscles. [ABSTRACT FROM AUTHOR]

The addition of absolute myocardial blood flow (MBF) data improves the diagnostic and prognostic accuracy of relative perfusion imaging with nuclear medicine. Cardiac-specific gamma cameras allow measurement of MBF with SPECT. This paper reviews the evidence supporting the use of SPECT to measure myocardial blood flow (MBF). Studies have evaluated SPECT MBF in large animal models and compared it in humans with invasive angiographic measurements and against the clinical standard of PET MBF. The repeatability of SPECT MBF has been determined in both single-site and multi-center trials. SPECT MBF has excellent correlation with microspheres in an animal model, with the number of stenoses and fractional flow reserve, and with PET-derived MBF. The inter-user coefficient of variability is ∼20% while the COV of test-retest MBF is ∼30%. SPECT MBF improves the sensitivity and specificity of the detection of multi-vessel disease over relative perfusion imaging and provides incremental value in predicting adverse cardiac events. SPECT MBF is a promising technique for providing clinically valuable information in the assessment of coronary artery disease. [ABSTRACT FROM AUTHOR]

This article explores the use of contrast-enhanced ultrasound (CEUS) in evaluating renal microcirculation in the treatment of acute kidney injury (AKI) in intensive care unit (ICU) patients. AKI is a common complication in critically ill patients and can lead to serious health consequences. CEUS allows for the measurement of renal microcirculatory blood flow, which can help guide treatment decisions in critical care-related AKI. The article emphasizes the importance of monitoring renal microcirculation and tailoring treatment to optimize tissue perfusion. It also discusses the factors that can affect CEUS measurements in ICU patients and provides information on the standardized procedures and techniques used for CEUS. The article includes visual aids to illustrate the concepts discussed. [Extracted from the article]

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that causes vascular malformations throughout the body. The most prevalent and accessible of these lesions are found throughout the skin and mucosa, and often rupture causing bleeding and anemia. A recent increase in potential HHT treatments have created a demand for quantitative metrics that can objectively measure the efficacy of new and developing treatments. We employ optical coherence tomography (OCT)-a high resolution, non-invasive imaging modality in a novel pipeline to image and quantitatively characterize dermal HHT lesion behavior over time or throughout the course of treatment. This study is aimed at detecting detailed morphological changes of dermal HHT lesions to understand the underlying dynamic processes of the disease. We present refined metrics tailored for HHT, developed from a pilot study using 3 HHT patients and 6 lesions over the course of multiple imaging dates, totalling to 26 lesion images. Preliminary results from these lesions are presented in this paper alongside representative OCT images. This study provides a new objective method to analyse and understand HHT lesions using a minimally invasive, accessible, cost-effective, and efficient imaging modality with quantitative metrics describing morphology and blood flow.

ObjectiveCurrent guidelines for elective surgery of ascending thoracic aortic aneurysms (aTAAs) use aneurysm size as primary determinant for risk stratification of adverse events. Biomechanically, dissection may occur when wall stress exceeds wall strength. Determining patient-specific aTAA wall stresses by finite element analysis can potentially predict patient-specific risk of dissection. This study compared peak wall stresses in patients with ≥5.0 cm versus

BackgroundThe neonatal resuscitation program (NRP) recommends interrupted chest compressions (CCs) with ventilation in the severely bradycardic neonate. The conventional 3:1 compression-to-ventilation (C:V) resuscitation provides 90 CCs/min, significantly lower than the intrinsic newborn heart rate (120-160 beats/min). Continuous CC with asynchronous ventilation (CCCaV) may improve the success of return of spontaneous circulation (ROSC).MethodsTwenty-two near-term fetal lambs were randomized to interrupted 3:1 C:V (90 CCs + 30 breaths/min) or CCCaV (120 CCs + 30 breaths/min). Asphyxiation was induced by cord occlusion. After 5 min of asystole, resuscitation began following NRP guidelines. The first dose of epinephrine was given at 6 min. Invasive arterial blood pressure and left carotid blood flow were continuously measured. Serial arterial blood gases were collected.ResultsBaseline characteristics between groups were similar. Rate of and time to ROSC was similar between groups. CCCaV was associated with a higher PaO2 (partial oxygen tension) (22 ± 5.3 vs. 15 ± 3.5 mmHg, p

Pattern separation, the ability to differentiate new information from previously experienced similar information, is highly sensitive to hippocampal structure and function and declines with age. Functional MRI studies have demonstrated hippocampal hyperactivation in older adults compared to young, with greater task-related activation associated with worse pattern separation performance. The current study was designed to determine whether pattern separation was sensitive to differences in task-free hippocampal cerebral blood flow (CBF) in 130 functionally intact older adults. Given prior evidence that apolipoprotein E e4 (APOE e4) status moderates the relationship between CBF and episodic memory, we predicted a stronger negative relationship between hippocampal CBF and pattern separation in APOE e4 carriers. An interaction between APOE group and right hippocampal CBF was present, such that greater right hippocampal CBF was related to better lure discrimination in noncarriers, whereas the effect reversed directionality in e4 carriers. These findings suggest that neurovascular changes in the medial temporal lobe may underlie memory deficits in cognitively normal older adults who are APOE e4 carriers.

Background: The aim of this research was to determine the functional state of regional blood flow in young people with varying degrees of anatomical and functional disorders of periodontal tissues. Methods and Results: One hundred and thirty-five young patients with varying degrees of anatomical and functional disorders of periodontal tissues (AFDP) and 52 controls with intact periodontium were examined. All patients with AFDP were divided into three groups: Group 1 included 33 patients in the compensation stage (low degree of periodontal risk, intact periodontium, no clinical symptoms, pale pink gums, no bleeding on probing, dentogingival attachment is not disturbed); Group 2 included 38 patients in the sub-compensation stage (average degree of periodontal risk, disorders of the mucogingival complex, without clinical symptoms); and 64 patients in the decompensation stage (high degree of periodontal risk, disorders of the mucogingival complex, the presence of clinical symptoms, individual or combined signs of periodontal pathology, gingival recession (Class I and II according to Miller's classification). We studied the regional blood flow of periodontal tissues, which was assessed by an ultrasound Doppler graph in a non-invasive way. The parameters of linear (PSV, peak systolic velocity) and volumetric (Qs, maximum systolic volume velocity) velocities of blood flow, as well as the parameters of the wall vascularization (PI, pulsation index; RI, resistance index). Results: The PSV increased statistically significantly with a load compared to rest in the control and sub-compensation groups and decreased in the decompensation group with a load, compared to the rest condition. The PSV increased relative to the control in the subcompensation and decompensation groups in rest and under load. The Qs indicator showed a similar trend in the groups. Qs significantly increased under load, compared to the rest condition in the control, compensation, and subcompensation groups, and decreased in the decompensation group. The Qs values, in comparison with the control, increased in the subcompensation and decompensation groups in the rest condition and under load. The PI increased with the load relative to the rest condition in the control, compensation, and decompensation group. At the same time, PI decreased under the load, compared to the rest condition, in the subcompensation group. In comparison with the control, the PI values decreased in the subcompensation and decompensation groups in the rest condition and under load. The RI significantly changed only in the subcompensation group under load, compared to the rest condition. Only RI values decreased significantly in the subcompensation group under load, compared to the control. Conclusion: The use of Doppler ultrasonography in assessing the state of regional blood flow of periodontal tissues is a highly informative and non-invasive method. The velocity characteristics (linear and volumetric velocities) of blood flow are important diagnostic indicators, allowing the most rapid and reliable assessment of the degree of anatomical and functional disorders of periodontal tissues.

BACKGROUND: Single-center studies have shown that single photon emission computed tomography myocardial blood flow (MBF) measurement is accurate compared with MBF measured with microspheres in a porcine model, positron emission tomography, and angiography. Clinical implementation requires consistency across multiple sites. The study goal is to determine the intersite processing repeatability of single photon emission computed tomography MBF and the additional camera time required. METHODS: Five sites (Canada, Italy, Japan, Germany, and Singapore) each acquired 25 to 35 MBF studies at rest and with pharmacological stress using technetium-99m-tetrofosmin on a pinhole-collimated cadmium-zinc-telluride–based cardiac single photon emission computed tomography camera with standardized list-mode imaging and processing protocols. Patients had intermediate to high pretest probability of coronary artery disease. MBF was measured locally and at a core laboratory using commercially available software. The time a room was occupied for an MBF study was compared with that for a standard rest/stress myocardial perfusion study. With motion correction, the overall correlation in MBF between core laboratory and local site was 0.93 (range, 0.87–0.97) at rest, 0.90 (range, 0.84–0.96) at stress, and 0.84 (range, 0.70–0.92) for myocardial flow reserve. The local-to-core difference in global MBF (bias-MBF) was 5.4% (−3.8% to 14.8%; median [interquartile range]) at rest and 5.4% (−6.2% to 19.4%) at stress. Between the 5 sites, bias-MBF ranged from −1.6% to 11.0% at rest and from −1.9% to 16.3% at stress; the interquartile range in bias-MBF was between 9.3% (4.8%–14.0%) and 22.3% (−10.3% to 12.0%) at rest and between 17.0% (−11.3% to 5.6%) and 33.3% (−10.4% to 22.9%) at stress and was not significantly different between most sites. Both bias and interquartile range were like previously reported interobserver variability and less than the SD of the test-retest difference of 30%. The overall difference in myocardial flow reserve was 1.52% (−10.6% to 11.3%). There were no significant differences between with and without motion correction. The average additional acquisition time varied between sites from 44 to 79 minutes. CONCLUSIONS: The average bias-MBF and bias-MFR values were small with standard deviations substantially less than the test-retest variability. This demonstrates that MBF can be measured consistently across multiple sites and further supports that this technique can be reliably implemented. [ABSTRACT FROM AUTHOR]

PurposeThe mechanisms of brain metastasis are incompletely understood. Circulating tumor cells travel to the right heart and through the pulmonary circulation, where they may become lung metastases, and can circulate further to the left heart and brain. In patients who develop brain metastases without lung involvement, we hypothesized that cancer cells may travel directly from the right atrium to left atrium via a patent foramen ovale (PFO), akin to paradoxical embolism. If the prevalence of PFO is greater in these individuals compared to the general population (20-30%), PFO may play a role in brain metastasis, and prophylactic closure may provide benefit. Accordingly, we investigated the prevalence of PFO in patients with brain metastases without prior lung involvement.MethodsWe prospectively identified patients with brain metastases from a non-lung primary cancer with no preceding or concurrent lung involvement. Nine eligible participants underwent a transcranial Doppler study with intravenous agitated saline to assess for PFO.ResultsAmong nine participants, primary cancers were breast (n = 6), upper gastrointestinal (n = 2), and thyroid (n = 1). A positive bubble study was identified in 2/9 (22.2%) participants: one female with breast cancer and one male with duodenal adenocarcinoma. No participants developed lung metastases on subsequent chest imaging.ConclusionIn this prospective pilot study, we found a similar prevalence of PFO in patients who developed brain metastases without preceding lung involvement compared to estimates for the general population. Through a larger study is needed, the development of brain metastases in these individuals may primarily reflect tumor-specific biological factors diecting metastasis organotropism.

Hemorrhagic shock (HS) is a severe life-threatening condition characterized by loss of blood volume and a lack of oxygen (O2) delivery to tissues. The objective of this study was to examine the impact of manipulating Starling forces in the microcirculation during HS to increase microvascular perfusion without restoring blood volume or increasing O2 carrying capacity. To decrease interstitial tissue pressure, we developed a non-contact system to locally apply negative pressure and manipulate the pressure balance in capillaries, while allowing for visualization of the microcirculation. Golden Syrian hamsters were instrumented with dorsal window chambers and subjected to a controlled hemorrhaged of 50% of the animal's blood volume without any fluid resuscitation. A negative pressure chamber was attached to the dorsal window chamber and a constant negative pressure was applied. Hemodynamic parameters (including microvascular diameter, blood flow, and functional capillary density [FCD]) were measured before and during the four hours following the hemorrhage, with and without applied negative pressure. Blood flow significantly increased in arterioles during negative pressure. The increase in flow through arterioles also improved microvascular perfusion as reflected by increased FCD. These results indicate that negative pressure increases flow in the microcirculation when fluid resuscitation is not available, thus restoring blood flow, oxygen delivery, and preventing the accumulation of metabolic waste. Applying negative pressure might allow for control of microvascular blood flow and oxygen delivery to specific tissue areas.

PurposeTo develop geometric perfusion deficits (GPD), an optical coherence tomography angiography (OCTA) biomarker based on oxygen diffusion, and to evaluate its utility in a pilot study of healthy subjects and patients with diabetic retinopathy (DR).DesignRetrospective cross-sectional study.MethodsCommercial spectral-domain optical coherence tomography angiography (OCTA) instruments were used to acquire repeated 3 × 3-mm2 and 6 × 6-mm2 motion-corrected macular OCTA volumes. En face OCTA images corresponding to the superficial capillary plexus (SCP), deep capillary plexus (DCP), and full retinal projections were obtained using automatic segmentation. For each projection, the GPD percentage and the vessel density percentage, the control metric, were computed, and their values were compared between the normal and DR eyes. The repeated OCTA acquisitions were used to assess the test-retest repeatability of the GPD and vessel density percentages.ResultsRepeated OCTA scans of 15 normal eyes and 12 DR eyes were obtained. For all en face projections, GPD percentages were significantly higher in DR eyes than in normal eyes; vessel density percentages were significantly lower in all but 1 projection (DCP). Large GPD areas were used to identify focal perfusion deficits. Test-retest analysis showed that the GPD percentage had superior repeatability than the vessel density percentage in most cases. A strong negative correlation between the GPD percentage and the vessel density percentage was also found.ConclusionsGeometric perfusion deficits, an OCTA biomarker based on oxygen diffusion, provides a quantitative metric of macular microvascular remodeling with a strong physiological underpinning. The GPD percentage may serve as a useful biomarker for detecting and monitoring DR.

BackgroundAltered cerebral blood flow (CBF) has been linked to increased risk for Alzheimer's disease (AD). However, whether altered CBF contributes to AD risk by accelerating cognitive decline remains unclear. It also remains unclear whether reductions in CBF accelerate neurodegeneration and development of small vessel cerebrovascular disease.ObjectiveTo examine associations between CBF and trajectories of memory performance, regional brain atrophy, and global white matter hyperintensity (WMH) volume.Method147 Alzheimer's Disease Neuroimaging Initiative participants free of dementia underwent arterial spin labeling (ASL) magnetic resonance imaging (MRI) to measure CBF and serial neuropsychological and structural MRI examinations. Linear mixed effects models examined 5-year rate of change in memory and 4-year rate of change in regional brain atrophy and global WMH volumes as a function of baseline regional CBF. Entorhinal and hippocampal CBF were examined in separate models.ResultsAdjusting for demographic characteristics, pulse pressure, apolipoprotein E ɛ4 positivity, cerebrospinal fluid p-tau/Aβ ratio, and neuronal metabolism (i.e., fluorodeoxyglucose standardized uptake value ratio), lower baseline entorhinal CBF predicted faster rates of decline in memory as well as faster entorhinal thinning and WMH progression. Hippocampal CBF did not predict cognitive or brain structure trajectories.ConclusionFindings highlight the importance of early cerebrovascular dysfunction in AD risk and suggest that entorhinal CBF as measured by noninvasive ASL MRI is a useful biomarker predictive of future cognitive decline and of risk of both.

Advances in intravital microscopy (IVM) have enabled the studies of cellular organization and dynamics in the native microenvironment of intact organisms with minimal perturbation. The abilities to track specific cell populations and monitor their interactions have opened up new horizons for visualizing cell biology in vivo, yet the success of standard fluorescence cell labeling approaches for IVM comes with a "dark side" in that unlabeled cells are invisible, leaving labeled cells or structures to appear isolated in space, devoid of their surroundings and lacking proper biological context. Here we describe a novel method for "filling in the void" by harnessing the ubiquity of extracellular (interstitial) fluid and its ease of fluorescence labelling by commonly used vascular and lymphatic tracers. We show that during routine labeling of the vasculature and lymphatics for IVM, commonly used fluorescent tracers readily perfuse the interstitial spaces of the bone marrow (BM) and the lymph node (LN), outlining the unlabeled cells and forming negative contrast images that complement standard (positive) cell labeling approaches. The method is simple yet powerful, offering a comprehensive view of the cellular landscape such as cell density and spatial distribution, as well as dynamic processes such as cell motility and transmigration across the vascular endothelium. The extracellular localization of the dye and the interstitial flow provide favorable conditions for prolonged Intravital time lapse imaging with minimal toxicity and photobleaching.

Endothelial cell (EC) metabolism is thought to be one of the driving forces for angiogenesis. Here we report the identification of the hexosamine D-mannosamine (ManN) as an EC mitogen and survival factor for bovine and human microvascular EC, with an additivity with VEGF. ManN inhibits glycosylation in ECs and induces significant changes in N-glycan and O-glycan profiles. We further demonstrate that ManN and two N-glycosylation inhibitors stimulate EC proliferation via both JNK activation and the unfolded protein response caused by ER stress. ManN results in enhanced angiogenesis in a mouse skin injury model. ManN also promotes angiogenesis in a mouse hindlimb ischemia model, with accelerated limb blood flow recovery compared to controls. In addition, intraocular injection of ManN induces retinal neovascularization. Therefore, activation of stress pathways following inhibition of protein glycosylation can promote EC proliferation and angiogenesis and may represent a therapeutic strategy for treatment of ischemic disorders.

The aim of this study was to assess the value of micro flow imaging (MFI) in distinguishing adenomatous polyps from cholesterol polyps. A total of 143 patients who underwent cholecystectomy for gallbladder polyps were retrospectively analyzed. B-mode ultrasound (BUS), color Doppler flow imaging (CDFI), MFI and contrast-enhanced ultrasound (CEUS) were performed before cholecystectomy. The weighted kappa consistency test was used to evaluate the agreement of vascular morphology among CDFI, MFI and CEUS. Ultrasound image characteristics, including BUS, CDFI and MFI images, were compared between adenomatous polyps and cholesterol polyps. The independent risk factors for adenomatous polyps were selected. The diagnostic performance of MFI combined with BUS in determining adenomatous polyps was compared with CDFI combined with BUS. Of the 143 patients, 113 cases were cholesterol polyps, and 30 cases were adenomatous polyps. The vascular morphology of gallbladder polyps was more clearly depicted by MFI than CDFI, and it had better agreement with CEUS. Differences in maximum size, height/width ratio, hyperechoic spot and vascular intensity on CDFI and MFI images were significant between adenomatous polyps and cholesterol polyps (p < 0.05). The maximum size, height/width ratio, and vascular intensity on MFI images were independent risk factors for adenomatous polyps. For MFI combined with BUS, sensitivity, specificity and accuracy were 90.00%, 94.69% and 93.70%, respectively. Area under the receiver operating characteristic curve (AUC) of MFI combined with BUS was significantly higher than that of CDFI combined with BUS (AUC = 0.923 vs. 0.784). Compared with CDFI combined with BUS, MFI combined with BUS had higher diagnostic performance in determining adenomatous polyps. [ABSTRACT FROM AUTHOR]

The global burden of diabetes is rapidly increasing, from 451 million people in 2019 to 693 million by 20451. The insidious onset of type 2 diabetes delays diagnosis and increases morbidity2. Given the multifactorial vascular effects of diabetes, we hypothesized that smartphone-based photoplethysmography could provide a widely accessible digital biomarker for diabetes. Here we developed a deep neural network (DNN) to detect prevalent diabetes using smartphone-based photoplethysmography from an initial cohort of 53,870 individuals (the 'primary cohort'), which we then validated in a separate cohort of 7,806 individuals (the 'contemporary cohort') and a cohort of 181 prospectively enrolled individuals from three clinics (the 'clinic cohort'). The DNN achieved an area under the curve for prevalent diabetes of 0.766 in the primary cohort (95% confidence interval: 0.750-0.782; sensitivity 75%, specificity 65%) and 0.740 in the contemporary cohort (95% confidence interval: 0.723-0.758; sensitivity 81%, specificity 54%). When the output of the DNN, called the DNN score, was included in a regression analysis alongside age, gender, race/ethnicity and body mass index, the area under the curve was 0.830 and the DNN score remained independently predictive of diabetes. The performance of the DNN in the clinic cohort was similar to that in other validation datasets. There was a significant and positive association between the continuous DNN score and hemoglobin A1c (P ≤ 0.001) among those with hemoglobin A1c data. These findings demonstrate that smartphone-based photoplethysmography provides a readily attainable, non-invasive digital biomarker of prevalent diabetes.

RationaleCocoa and its major flavanol component, epicatechin, have therapeutic properties that may improve limb perfusion and increase calf muscle mitochondrial activity in people with lower extremity peripheral artery disease (PAD).ObjectiveIn a phase II randomized clinical trial, to assess whether 6 months of cocoa improved walking performance in people with PAD, compared with placebo.Methods and resultsSix-month double-blind, randomized clinical trial in which participants with PAD were randomized to either cocoa beverage versus placebo beverage. The cocoa beverage contained 15 g of cocoa and 75 mg of epicatechin daily. The identical appearing placebo contained neither cocoa nor epicatechin. The 2 primary outcomes were 6-month change in 6-minute walk distance measured 2.5 hours after a study beverage at 6-month follow-up and 24 hours after a study beverage at 6-month follow-up, respectively. A 1-sided P

Red blood cells (RBCs) transport oxygen to tissues and remove carbon dioxide. Diffuse optical flowmetry (DOF) assesses deep tissue RBC dynamics by measuring coherent fluctuations of multiply scattered near-infrared light intensity. While classical DOF measurements empirically correlate with blood flow, they remain far-removed from light scattering physics and difficult to interpret in layered media. To advance DOF measurements closer to the physics, here we introduce an interferometric technique, surmounting challenges of bulk motion to apply it in awake humans. We reveal two measurement dimensions: optical phase, and time-of-flight (TOF), the latter with 22 picosecond resolution. With this multidimensional data, we directly confirm the unordered, or Brownian, nature of optically probed RBC dynamics typically assumed in classical DOF. We illustrate how incorrect absorption assumptions, anisotropic RBC scattering, and layered tissues may confound classical DOF. By comparison, our direct method enables accurate and comprehensive assessment of blood flow dynamics in humans.

BackgroundMicrovascular blood flow (MBF) impairment in patients with lower extremity arterial disease (LEAD) is associated with more severe major adverse limb events (MALE). The contribution of ticagrelor, a P2Y12 antagonist and an adenosine enhancer, on blood viscosity (BV) and BV-dependent MBF in LEAD is unknown. The aim of the trial is to investigate the effects of ticagrelor on BV, and explore the association of BV-dependent MBF in participants with LEAD and type 2 diabetes (T2DM).MethodsRandomized, double-blind, double-dummy, crossover trial design that compares treatment with aspirin 81 mg/ticagrelor placebo, aspirin 81 mg/ticagrelor 90 mg twice daily and aspirin placebo/ticagrelor 90 mg twice daily on high-shear (300 s-1) and low-shear (5 s-1) BV, and laser Doppler flowmetry (LDF) in the dorsum of the feet of participants with T2DM.ResultsWe randomized 70 (45% female) participants aged (mean ± SD) 72 ± 9 years. The duration of LEAD was 12.3 ± 10.3 years, and 96.9% reported intermittent claudication symptoms. Use of statins was 93% (high-intensity 43%, moderate intensity 49%), renin-angiotensin-aldosterone system inhibitors (75%) and beta-blockers (61%). Treatment with ticagrelor with or without aspirin reduced high-shear BV by 5%, in both cases, while aspirin monotherapy increased high-shear BV by 3.4% (p

The impact of the local inhibition of soluble epoxide hydrolase, which metabolizes vasodilator and anti-inflammatory epoxyeicosanoids, on diabetic skin microvascular dysfunction was assessed. In diabetic db/db mice, basal skin blood flow assessed using laser Doppler imaging was similar to that of control mice, but thermal hyperemia was markedly reduced. At 2 h after the topical administration of an aqueous gel containing the soluble epoxide hydrolase inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB: 400 mg/L), the peak concentration of t-AUCB was detected in the skin of diabetic mice, which quickly decreased thereafter. In parallel, 2 h after application of t-AUCB treatment, thermal hyperemia was increased compared to the control gel. Quantification of t-AUCB in plasma of treated animals showed no or low systemic diffusion. Furthermore, haematoxylin and eosin histological staining of skin biopsies showed that skin integrity was preserved in t-AUCB-treated mice. Finally, for pig ear skin, a surrogate for human skin, using Franz diffusion cells, we observed a continuous diffusion of t-AUCB from 2 h after application to beyond 24 h. A single topical administration of a soluble epoxide hydrolase inhibitor improves microcirculatory function in the skin of db/db mice and might represent a new therapeutic approach for preventing the development of skin complications in diabetic patients.

The purpose of this study was to investigate lower limb blood flow responses under varying blood flow restriction (BFR) pressures based on individualized limb occlusion pressures (LOP) using a commonly used occlusion device. Twenty-nine participants (65.5% female, 23.8 ± 4.7 years) volunteered for this study. An 11.5cm tourniquet was placed around participants' right proximal thigh, followed by an automated LOP measurement (207.1 ± 29.4mmHg). Doppler ultrasound was used to assess posterior tibial artery blood flow at rest, followed by 10% increments of LOP (10-90% LOP) in a randomized order. All data were collected during a single 90-minute laboratory visit. Friedman's and one-way repeated-measures ANOVAs were used to examine potential differences in vessel diameter, volumetric blood flow (VolFlow), and reduction in VolFlow relative to rest (%Rel) between relative pressures. No differences in vessel diameter were observed between rest and all relative pressures (all p < .05). Significant reductions from rest in VolFlow and %Rel were first observed at 50% LOP and 40% LOP, respectively. VolFlow at 80% LOP, a commonly used occlusion pressure in the legs, was not significantly different from 60% (p = .88), 70% (p = .20), or 90% (p = 1.00) LOP. Findings indicate a minimal threshold pressure of 50%LOP may be required to elicit a significant decrease in arterial blood flow at rest when utilizing the 11.5cm Delfi PTSII tourniquet system. [ABSTRACT FROM AUTHOR]

BackgroundHookah smoking is marketed to youth as a harmless alternative to cigarettes. Although cigarette smoking acutely impairs endothelial function, the effect of smoking fruit-flavored hookah tobacco is unknown. Because charcoal traditionally is used to heat the hookah tobacco in the waterpipe, hookah smoke delivers tobacco toxicants and nicotine plus charcoal combustion products: not only carbon-rich nanoparticles, oxidants that may destroy nitric oxide and impair endothelial function, but also large amounts of carbon monoxide (CO), a putative vasodilator molecule.MethodsTo test the acute effect of hookah smoking on endothelial function, in young adult hookah smokers (n=30, age 26±1 years, mean±SE), we measured plasma nicotine, exhaled CO, and brachial artery flow-mediated dilation (FMD) before and after charcoal-heated hookah smoking. To remove the effect of charcoal combustion, the same measurements were performed when the same flavored hookah tobacco product was heated electrically (n=20). As a positive internal control, we studied age-matched cigarette smokers (n=15) who smoked 1 cigarette. To isolate the effect of the CO boost on FMD, hookah smokers (n=8) inhaled a 0.1% CO gas mixture to approximate their CO boost achieved with charcoal-heated hookah smoking.ResultsNicotine levels increased similarly with all types of smoking, whereas exhaled CO increased 9- to 10-fold more after charcoal-heated hookah than after either electrically heated hookah or cigarette smoking. FMD did not decrease after smoking charcoal-heated hookah but instead increased by +43±7% ( P

Since of its introduction in 1980s, laser speckle imaging has become a powerful tool in flow imaging. Its high performance and low cost made it one of the preferable imaging methods. Initially, speckle contrast measurements were the main algorithm for analyzing laser speckle images in biological flows. Speckle contrast measurements, also referred as Laser Speckle Contrast Imaging (LSCI), use statistical properties of speckle patterns to create mapped image of the blood vessels. In this communication, a new method named Laser Speckle Optical Flow Imaging (LSOFI) is introduced. This method uses the optical flow algorithms to calculate the apparent motion of laser speckle patterns. The differences in the apparent motion of speckle patterns are used to identify the blood vessels from surrounding tissue. LSOFI has better spatial and temporal resolution compared to LSCI. This higher spatial resolution enables LSOFI to be used for autonomous blood vessels detection. Furthermore, Graphics Processing Unit (GPU) based LSOFI can be used for quasi real time imaging.

Sudden cardiac death (SCD) is the leading global cause of mortality. SCD often arises from cardiac ischemia reperfusion (IR) injury, pathologic sequence variants within ion channel genes, or a combination of the two. Alternative approaches are needed to prevent or ameliorate ventricular arrhythmias linked to SCD. Here, we investigated the efficacy of remote ischemic preconditioning (RIPC) of the limb versus the liver in reducing ventricular arrhythmias in a mouse model of SCD. Mice lacking the Kcne2 gene, which encodes a potassium channel β subunit associated with acquired Long QT syndrome were exposed to IR injury via coronary ligation. This resulted in ventricular arrhythmias in all mice (15/15) and SCD in 5/15 mice during reperfusion. Strikingly, prior RIPC (limb or liver) greatly reduced the incidence and severity of all ventricular arrhythmias and completely prevented SCD. Biochemical and pharmacological analysis demonstrated that RIPC cardioprotection required ERK1/2 and/or AKT phosphorylation. A lack of alteration in GSK-3β phosphorylation suggested against conventional reperfusion injury salvage kinase (RISK) signaling pathway protection. If replicated in human studies, limb RIPC could represent a noninvasive, nonpharmacological approach to limit dangerous ventricular arrhythmias associated with ischemia and/or channelopathy-linked SCD.

BACKGROUND:High ultrafiltration rate (UFR) has been associated with increased mortality in hemodialysis (HD) patients. However, the impact of UFR on decline of residual kidney function (RKF) has not been elucidated among patients receiving conventional HD. METHODS:We performed a retrospective cohort study of 7,753 patients who initiated conventional HD from 2007 to 2011 and survived the first year of dialysis with baseline UFR and renal urea clearance (KRU) data at baseline and 1 year (5th patient-quarter). The primary exposure was average UFR at the 1st patient-quarter from dialysis initiation (

The Fontan procedure provides relief from cyanosis in patients with univentricular hearts. A major clinical unmet need is to understand whether the venous flow patterns of the Fontan circulation lead to the development of congestive hepatopathy and other life-threatening complications. Currently, there is no consensus on whether heart beat or respiration is the main driving force of venous return and which one affects the periodic flow changes for the most (i. e., pulsatility). The present study, for the first time, quantified respiratory and cardiac components of the venous flow in the inferior vena cava (IVC) of 14 Fontan patients and 11 normal controls using a novel approach ("physio-matrix"). We found that in contrast to the normal controls, respiration in Fontan patients had a significant effect on venous flow pulsatility, and the ratio of respiration-dependent to the cardiac-dependent pulsatility was positively associated with the retrograde flow. Nevertheless, the main driving force of net IVC flow was the heart beat and not respiration. The separate analysis of the effects of respiration and heart beat provides new insights into the abnormal venous return patterns that may be responsible for adverse effects on liver and bowel of the patients with Fontan circulation.

Dermascopes are commonly utilized for the qualitative visual inspection of skin lesions. While automated image processing techniques and varied illumination strategies have been used to aid in structural analysis of lesions, robust quantification of functional information is largely unknown. To address this knowledge gap, we have developed a compact, handheld dermascope that enables real-time blood flow measurements of skin during conventional visual inspection. In-vitro characterization demonstrated that the dermascope is capable of quantifying changes in flow across a physiologically relevant range even when used in a handheld manner with clinic lighting and dermascope LEDs on. In a small pilot clinical study, we demonstrated the dermascope's ability to detect flow differences between two distinct lesion types.

ObjectivesAdequate assessment of fluid responsiveness in shock necessitates correct interpretation of hemodynamic changes induced by preload challenge. This study evaluates the accuracy of point-of-care Doppler ultrasound assessment of the change in carotid corrected flow time induced by a passive leg raise maneuver as a predictor of fluid responsiveness. Noninvasive cardiac output monitoring (NICOM, Cheetah Medical, Newton Center, MA) system based on a bioreactance method was used.DesignProspective, noninterventional study.SettingICU at a large academic center.PatientsPatients with new, undifferentiated shock, and vasopressor requirements despite fluid resuscitation were included. Patients with significant cardiac disease and conditions that precluded adequate passive leg raising were excluded.InterventionsCarotid corrected flow time was measured via ultrasound before and after a passive leg raise maneuver. Predicted fluid responsiveness was defined as greater than 10% increase in stroke volume on noninvasive cardiac output monitoring following passive leg raise. Images and measurements were reanalyzed by a second, blinded physician. The accuracy of change in carotid corrected flow time to predict fluid responsiveness was evaluated using receiver operating characteristic analysis.Measurements and main resultsSeventy-seven subjects were enrolled with 54 (70.1%) classified as fluid responders by noninvasive cardiac output monitoring. The average change in carotid corrected flow time after passive leg raise for fluid responders was 14.1 ± 18.7 ms versus -4.0 ± 8 ms for nonresponders (p < 0.001). Receiver operating characteristic analysis demonstrated that change in carotid corrected flow time is an accurate predictor of fluid responsiveness status (area under the curve, 0.88; 95% CI, 0.80-0.96) and a 7 ms increase in carotid corrected flow time post passive leg raise was shown to have a 97% positive predictive value and 82% accuracy in detecting fluid responsiveness using noninvasive cardiac output monitoring as a reference standard. Mechanical ventilation, respiratory rate, and high positive end-expiratory pressure had no significant impact on test performance. Post hoc blinded evaluation of bedside acquired measurements demonstrated agreement between evaluators.ConclusionsChange in carotid corrected flow time can predict fluid responsiveness status after a passive leg raise maneuver. Using point-of-care ultrasound to assess change in carotid corrected flow time is an acceptable and reproducible method for noninvasive identification of fluid responsiveness in critically ill patients with undifferentiated shock.

PROBLEM:Premature birth complicates 10%-12% of deliveries. Infection and inflammation are the most common etiologies and are associated with increased offspring morbidity and mortality. We hypothesize that lipopolysaccharide (LPS)-induced maternal inflammation causes direct placenta injury and subsequent injury to the fetal intestine. METHOD OF STUDY:Pregnant C57Bl6 mice were injected intraperitoneally on day 15.5 with 100 μg/kg LPS or saline. Maternal serum, amniotic fluid, placental samples, and ileal samples of offspring were obtained assessed for inflammation and/or injury. Maternal placental ultrasounds were performed. Placental DNA was isolated for microbiome analysis. RESULTS:Maternal injection with LPS caused elevated IL-1β, IL-10, IL-6, KC-GRO, and TNF. Placental tissue showed increased IL-1β, IL-6, and KC-GRO and decreased IL-10, but no changes were observed in amniotic fluid. Placental histology demonstrated LPS-induced increases in mineralization and necrosis, but no difference in placental blood flow. Most placentas had no detectable microbiome. Exposure to maternal LPS induced significant injury to the ilea of the offspring. CONCLUSION:Lipopolysaccharide causes a maternal inflammatory response that is mirrored in the placenta. Placental histology demonstrates structural changes; however, placental blood flow is preserved. LPS also induces an indirect intestinal injury in the offspring that lasts beyond the neonatal period.

Vasovagal syncope (VVS) is characterized by hypotension and bradycardia followed by lowering of cerebral blood flow. Remote limb ischemic preconditioning (RIPC) is well documented to provide cardio- and neuroprotection as well as to improve cerebral blood flow. We hypothesized that RIPC will provide protection against VVS-induced hypotension, bradycardia, and cerebral hypoperfusion. Second, because endothelial nitric oxide synthase has been reported as a mediator of cerebral blood flow control, we hypothesized that the mechanism by which RIPC primes the vasculature against VVS is via the α1-adrenoceptor-protein kinase Cε-endothelial nitric oxide synthase pathway. We utilized sinusoidal galvanic vestibular stimulation in rats as a model of VVS. RIPC attenuated the lowerings of mean arterial pressure, heart rate, and cerebral blood flow caused by sinusoidal galvanic vestibular stimulation, as well as improving behavior during, and recovery after, stimulation. RIPC induced elevated serum norepinephrine, increased expression of brain α1-adrenoceptors, and reduced brain expression of norepinephrine transporter 1. Antagonizing adrenoceptors and norepinephrine transporter 1 prevented RIPC protection of cerebral perfusion during sinusoidal galvanic vestibular stimulation. Taken together, this study indicates that RIPC may be a potential therapy that can prevent VVS pathophysiology, decrease syncopal episodes, and reduce the injuries associated with syncopal falls. Furthermore, the α1-adrenoceptor-protein kinase Cε-endothelial nitric oxide synthase pathway may be a therapeutic target for regulating changes in cerebral blood flow.

AimsHemodynamic shear stress participates in maintaining vascular redox status. Elucidating flow-mediated endothelial metabolites enables us to discover metabolic biomarkers and therapeutic targets. We posited that flow-responsive vascular endothelial growth factor receptor (VEGFR)-protein kinase C isoform epsilon (PKCɛ)-6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) signaling modulates glycolytic metabolites for vascular repair.ResultsBidirectional oscillatory flow (oscillatory shear stress [OSS]: 0.1 ± 3 dyne·cm-2 at 1 Hz) upregulated VEGFR-dependent PKCɛ expression to a greater degree than did unidirectional pulsatile flow (pulsatile shear stress [PSS]: 23 ± 8 dyne·cm-2 at 1 Hz) in human aortic endothelial cells (p

Abstract Background There is a lack of reports in the literature regarding changes in radial artery blood flow after decannulation. The objective of this study was to investigate changes in radial and ulnar artery blood flow after radial artery decannulation using Doppler ultrasound and to explore the factors that influence radial artery blood flow recovery. Methods In current observational study, we used colour Doppler ultrasound to measure the cross-sectional area of the radial (SR) and ulnar artery (SU) and peak systolic velocity of the radial (PSVR) and ulnar artery (PSVU) for both hands at four time points in patients with radial artery cannulation: pre-cannulation (T0), 30 min after decannulation (T1), 24 h after decannulation (T2), and 7 days after decannulation (T3). Repeated measures analysis of variance and logistic regression analysis were performed to analyse the data. Results Overall, 120 patients were included in the present study. We obtained the following results on the side ipsilateral to the cannulation: compared with T0, the ratio of PSVU/PSVR increased significantly at T1 and T2 (p

Maternal smoking with obligatory nicotine inhalation is associated with preterm delivery, low birth weight, fetal growth retardation and developmental defects. We tested the hypothesis that cigarette smoking-relevant nicotine inhalation during pregnancy impairs cardiovascular function and uterine hemodynamics with consequential fetal ischemia. Pregnant rats exposed to episodic inhaled nicotine via a novel lung alveolar region-targeted aerosol method produced nicotine pharmacokinetics resembling cigarette smoking in humans. This clinically relevant nicotine aerosol inhalation (NAI) induced transient reduction and irregular fluctuations in uterine artery blood flow associated with cardiac arrhythmia and high magnitude irregular fluctuations of systemic blood pressure. The arrhythmia included sinoatrial (SA) block, sinus arrest, 2° and 3° atrioventricular (A-V) block and supraventricular escape rhythm. These effects were blocked by the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine. Resection of the ovarian nerve, which innervates uterine blood vessels, counteracted the NAI-induced reduction in uterine blood flow. We suggest that the rapid rise pattern of arterial blood nicotine concentration stimulates and then desensitizes autonomic nAChRs leading to disruptions of cardiac function as well as systemic and uterine hemodynamics that reduces uteroplacental blood flow, a mechanism underlying maternal smoking-associated pregnancy complications and developmental disorders. These findings challenge the safety of pure nicotine inhalation, i.e., E-cigarettes.

A large portion of the central nervous system is dedicated to vision and therefore strokes have a high likelihood of involving vision in some way. Vision loss can be the most disabling residual effect after a cerebral infarction. Transient vision problems can likewise be a harbinger of stroke and prompt evaluation after recognition of visual symptoms can prevent future vascular injury. In this review, we discuss the visual aspects of stroke. First, anatomy and the vascular supply of the visual system are considered. Then, the different stroke syndromes which involve vision are discussed. Finally, topics involving the assessment, prognosis, treatment and therapeutic intervention of vision-specific stroke topics are reviewed.

Little is known about the prognostic significance of specific characteristics of magnetic resonance imaging (MRI) measured plaque in the superficial femoral artery (SFA). Associations of MRI-measured plaque quantity, lumen area, and plaque composition in the SFA with subsequent mobility loss were studied in people with lower extremity peripheral artery disease (PAD). Participants with an ankle-brachial index (ABI) < 1.00 were identified from Chicago medical centers and underwent direct visualization of atherosclerotic plaque in the SFA using MRI. Participants were followed annually for up to 4 years. Mobility loss was defined as becoming unable to walk up and down a flight of stairs or walk one-quarter of a mile without assistance among participants without mobility impairment at baseline. Analyses adjusted for age, sex, race, comorbidities, ABI, physical activity, and other confounders. Of 308 PAD participants without baseline mobility impairment, 100 (32.5%) developed mobility loss during follow-up. Compared to the lowest mean plaque area tertile at baseline, participants in the highest (worst) plaque area tertile had a higher rate of mobility loss (hazard ratio (HR) = 2.08, 95% confidence interval (CI) = 1.14-3.79, p = 0.018). Compared to the highest mean lumen area tertile, the smallest (worst) mean lumen area tertile was associated with greater mobility loss (HR = 2.18, 95% CI = 1.20-3.96, p = 0.011). Neither lipid rich necrotic core nor calcium in the SFA were associated with mobility loss. In conclusion, greater plaque quantity and smaller lumen area in the proximal SFA, but not lipid rich necrotic core or calcium, were associated with higher mobility loss in people with PAD.

BackgroundMildly elevated lactate levels (i.e., 1-2 mmol/L) are increasingly recognized as a prognostic finding in critically ill patients. One of several possible underlying mechanisms, microcirculatory dysfunction, can be assessed at the bedside using sublingual direct in vivo microscopy. We aimed to evaluate the association between relative hyperlactatemia, microcirculatory flow, and outcome.MethodsThis study was a predefined subanalysis of a multicenter international point prevalence study on microcirculatory flow abnormalities, the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Microcirculatory flow abnormalities were assessed with sidestream dark-field imaging. Abnormal microcirculatory flow was defined as a microvascular flow index (MFI)  1.5 mmol/L was independently associated with a MFI

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Older adults demonstrate gait impairments that increase their risk for falls. These age-related mobility impairments are in part due to declines in muscle mass and strength. High-intensity exercise can improve muscle strength and mobility but may not be tolerable for older adults due to musculoskeletal injury and pain. Blood flow restriction (BFR) with lower-intensity exercise offers a strategy that may be more tolerable for older adults, but whether BFR improves gait and mobility in older adults is unclear. The purpose of this systematic review and meta-analysis was to determine the effect of BFR on gait and mobility in healthy older adults. PubMed, Embase, Cochrane Library, and CINAHL were systematically searched for articles utilizing BFR in older adults. Articles were included if adults were over 60 years, did not have chronic health conditions, had undergone randomized controlled trials, and presented objectively measured gait outcomes. The search identified 1501 studies, of which 9 were included in the systematic review and 8 studies in the meta-analysis. Outcome measures included the Timed Up and Go (TUG), 6-Minute Walk Test (6MWT), 400 m walk test, Short Physical Performance Battery (SPPB), and 10 m walk test. Meta-analyses found improvements in the TUG (mean difference (MD) = -0.71; 95% CI = -1.05, -0.37; p < 0.001) and SPPB (MD = -0.94; 95% CI = -1.48, -0.39; p < 0.001) in BFR compared to no BFR. There were no differences in gait speed (MD = 0.59; 95% CI = -0.22, 1.41; p = 0.16). BFR may be effective for gait and mobility tasks over shorter distances. Clinicians may consider incorporating BFR to improve mobility and gait function in older adults.

It is not clear if fat oxidation is attenuated at higher exercise intensities, when exercising with a small muscle mass, and therefore, we studied leg fat oxidation during graded one-leg exercise. Ten males (age: 27 ± 2 years, body mass: 82 ± 3 kg, BMI: 24 ± 1 kg m -2 , V̇O 2max : 49 ± 2 mL min -1  kg -1 ) performed one-leg exercise at 25% of maximal workload (W max ) for 30 min, followed by 120-min exercise at 55% W max with the contralateral leg, and finally 30-min exercise at 85% W max with the first leg. Blood was sampled from an artery and both femoral veins, and blood flow was determined using Doppler ultrasound. Muscle biopsies were obtained before and after 30 min at each workload. One-way RM ANOVA was applied to determine the impact of exercise intensity. Data are expressed as mean ± SEM. From rest through exercise average blood flow (0.4 ± 0.1, 2.1 ± 0.1, 2.6 ± 0.2, 3.7 ± 0.2 L min -1 ) and oxygen uptake across the leg (0.03 ± 0.01, 0.23 ± 0.02, 0.35 ± 0.03, 0.53 ± 0.04 L min -1 ) increased with exercise intensity (p < 0.001). Leg RQ (0.76 ± 0.04, 0.86 ± 0.02,0.87 ± 0.01, 0.92 ± 0.01, p < 0.001), leg plasma FA uptake (2 ± 2, 46 ± 8,83 ± 9, 114 ± 16 μmol min -1 ; p < 0.001) and rate of leg fat oxidation (0.016 ± 0.005, 0.062 ± 0.012, 0.075 ± 0.011, 0.084 ± 0.018 g min -1 , p < 0.007) increased with exercise intensity. Muscle-free carnitine content was unchanged from rest at 25% W max and decreased after 30 min exercise at 55% and 85% W max (17.4 ± 1.6, 16.6 ± 0.7, 14.5 ± 1.2, 10.5 ± 1.0 mmol/kg dry muscle, respectively; p < 0.006). During incremental one-leg exercise, the rate of leg fat oxidation was not attenuated with increasing exercise intensity, probably due to an insufficient muscle metabolic stress response., (© 2024 The Author(s). Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Background: To date, PCSK9 inhibitors are well known for eliminating cardiac and cerebral artery ischemia events by lowering the serum lipid level. However, the pathophysiological value of in-plaque PCSK9 expression is still unclear., Methods: Advanced plaques removed by carotid endarterectomy were sectioned and stained to identify the PCSK9 expression pattern and its co-expression with rupture-relevant markers. To investigate the correlation of PCSK9 expression with regional blood shear flow, hemodynamic characteristics were analyzed using computational fluid dynamics, and representative parameters were compared between PCSK9 positive and negative staining plaques. To explore this phenomenon in vitro, human aortic vascular smooth muscle cells were used to overexpress and knock down PCSK9. The impacts of PCSK9 modulations on mechanical sensor activity were testified by western blot and immunofluorescence. Real-time polymerase chain reaction was used to evaluate the transcription levels of downstream rupture-prone effectors., Results: PCSK9 distribution in plaque preferred cap and shoulder regions, residing predominantly in smooth muscle actin-positive cells. Cap PCSK9 expression correlated with fibrous cap thickness negatively and co-expressed with MMP-9, both pointing to the direction of plaque rupture. A hemodynamic profile indicated a rupture-prone feature of cap PCSK9 expression. In vitro, overexpression and knockdown of PCSK9 in human aortic vascular smooth muscle cells has positive modulation on mechanical sensor Yes-associated protein 1 (YAP) activity and transcription levels of its downstream rupture-prone effectors. Serial section staining verified in situ colocalization among PCSK9, YAP, and downstream effectors., Conclusions: Cap PCSK9 possesses a biomarker for rupture risk, and its modulation may lead to a novel biomechanical angle for plaque interventions., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Strain-gauge venous occlusion plethysmography (SGVOP) is a means of acquiring hemodynamic data non-invasively, unlike other methods used routinely for the diagnosis and follow-up of venous diseases. The present study compares the plethysmographic data with early- and mid-term routine data of patients with acute deep-vein thrombosis (DVT) who underwent pharmacomechanical thrombolysis., Patients and Method: Included in this retrospective study were 118 patients with acute DVT, who underwent pharmacomechanical thrombolysis between February 2018 and July 2019. Pre- and post-procedure follow-up data including CIVIQ-20 (quality of life), VCSS (Venous Clinical Severity Score), D-Dimer, Doppler USG results, venous capacity (VC), and venous outflow (VO) obtained by SGVOP were recorded and compared., Results: In all 118 (100%) patients who underwent the procedure, early- and mid-term patency was seen to have been provided on Doppler USG follow-up, and various degrees of venous insufficiency were identified. A statistically significant improvement was observed in VCSS, CIVIQ-20, D-Dimer, VO, and VC measurements, although when the discrepancies between CIVIQ-20 and plethysmographic measurements were examined individually during the 6-month follow-up, nine (13.1%) patients were identified with comorbidities., Conclusions: Pharmacomechanical thrombolysis is an effective treatment approach for patients with acute DVT. Providing non-invasive objective data supporting the diagnosis and follow-up of venous diseases, the SGVOP approach offers significant benefits and should be considered more frequently as a viable therapy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Chronic venous disease (CVD) is a prevalent pathology, and endothelial dysfunction is recognized as a core of its physiopathology. Flow-mediated dilation (FMD) is one of the most widely used tests for evaluating endothelial function. The aim of this study is to evaluate the influence of varicose vein (VV) surgery on FMD., Methods: A prospective study with patients with superficial CVD and saphenous incompetence on Doppler ultrasonography that were proposed for VV surgery. The FMD test was performed before and 6 months after the procedure. The operator performing the post-operative evaluation was blinded to the pre-operative result., Results: A total of 42 patients were included in the analysis. The median pre-operative percent change of FMD was 4.20% (±1.30) and the post-operative was 4.56% (±1.25) ( p = 0.819)., Conclusions: Our findings do not corroborate the presence of an overall endothelial dysfunction prone to modulation by surgery. Nevertheless, further studies are needed to confirm our findings., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To identify the effects of patient risk factors and pelvic venous reflux (PVR) patterns on treatment outcomes of Pelvic Vein Embolisation (PVE) for Pelvic Venous Disorder (PeVD)., Methods: We performed a retrospective cohort review assessing population, intervention, comparison, and outcomes (PICO) for women undergoing PVE for PVR January 2017-January 2021. We identified 190 patients who had completed both questionnaires and who had given consent for their information to be used for research (Median age 46, IQR 40-52). The distribution of pathological pelvic venous reflux found on transvaginal duplex ultrasound (TVDUS) was analysed for all patients. Pre- and post-procedure symptom burden scores were studied using a standardised questionnaire protocol. We used inferential univariate non-parametric statistics to describe our data., Results: 190 cases were reviewed; 62.6% (119/190) premenopausal, 11.1% (21/190) perimenopausal, 25.3% (48/190) postmenopausal and menopausal status not documented 1% (2/190). 10.1% (19/188) were nulliparous (average age 34 years; range 20-55 years). There was a statistically significant improvement in all symptoms and in the appearance of varicosities on TVDUS post-PVE ( P < 0.05) of the ovarian vein plexus, uterus plexus, arcuate veins, vaginal wall, peri-urethral, peri-anal, haemorrhoids, labial and proximal thigh. The locations of veins requiring embolisation having demonstrated reflux were analysed; 82.8% (154/186) underwent embolisation of at least one internal iliac vein tributary and ovarian vein embolisation. Age, parity, menopausal status and previous laparoscopy did not affect symptom improvement ( P > 0.05). No significant complications such as coil migration were observed., Conclusions: PVE is an effective treatment for pelvic pain due to PeVD and its diagnosis should not be limited to multiparous women of childbearing age, as a significant proportion of patients who benefited from PVE were either nulliparous and/or postmenopausal., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Contemporary quality control methods are often insufficient in predicting clinical outcomes after revascularization in lower extremity arterial disease (LEAD) patients. This study evaluates the potential of near-infrared fluorescence imaging with indocyanine green to predict the clinical outcome following revascularization. Near-infrared fluorescence imaging was performed before and within 5 days following the revascularization procedure. Clinical improvement was defined as substantial improvement of pain free walking distance, reduction of rest- and/or nocturnal pain, or tendency toward wound healing. Time-intensity curves and 8 perfusion parameters were extracted from the dorsum of the treated foot. The quantified postinterventional perfusion improvement was compared within the clinical outcome groups. Successful near-infrared fluorescence imaging was performed in 72 patients (76 limbs, 52.6% claudication, 47.4% chronic limb-threatening ischemia) including 40 endovascular- and 36 surgical/hybrid revascularizations. Clinical improvement was observed in 61 patients. All perfusion parameters showed a significant postinterventional difference in the clinical improvement group ( P -values <.001), while no significant differences were seen in the group without clinical improvement ( P -values .168-.929). Four parameters demonstrated significant differences in percentage improvement comparing the outcome groups ( P -values within .002-.006). Near-infrared fluorescence imaging has promising additional value besides clinical parameters for predicting the clinical outcome of revascularized LEAD patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.