Reservoir-excess pressure parameters are independently associated with NT-proBNP in older adults.

AIMS: Parameters derived from reservoir-excess pressure analysis have been demonstrated to predict cardiovascular events. Thus, altered reservoir-excess pressure parameters could have a detrimental effect on highly-perfused organs like the heart. We aimed to cross-sectionally determine whether reservoir-excess pressure parameters were associated with N-terminal pro-brain-type natriuretic peptide (NT-proBNP) in older adults. METHODS: We studied 868 older adults with diverse cardiovascular risk. Reservoir-excess pressure parameters were obtained through radial artery tonometry including reservoir pressure integral, peak reservoir pressure, excess pressure integral (INTXSP), systolic rate constant (SRC) and diastolic rate constant (DRC). Plasma levels of NT-proBNP, as a biomarker of cardiac overload, were analysed by the Proximity Extension Assay technology. RESULTS: Multivariable linear regression analyses revealed that all reservoir-excess pressure parameters studied were associated with NT-proBNP after adjusting for age and sex. After further adjustments for conventional cardiovascular risk factors, INTXSP [ß = 0.191 (95% confidence interval, CI: 0.099, 0.283), P < 0.001], SRC [ß = -0.080 (95% CI: -0.141, -0.019), P = 0.010] and DRC [ß = 0.138 (95% CI: 0.073, 0.202), P < 0.001] remained associated with NT-proBNP. Sensitivity analysis found that there were occasions where the association between SRC and NT-proBNP was attenuated, but both INTXSP and DRC remained consistently associated with NT-proBNP. CONCLUSIONS: The observed associations between reservoir-excess pressure parameters and NT-proBNP suggest that altered reservoir-excess pressure parameters may reflect an increased load inflicted on the left ventricular cardiomyocytes and could have a potential to be utilized in the clinical setting for cardiovascular risk stratification.

Pulmonary artery wave intensity analysis in pulmonary hypertension associated with heart failure and reduced left ventricular ejection fraction.

Wave intensity analysis (WIA) uses simultaneous changes in pressure and flow velocity to determine wave energy, type, and timing of traveling waves in the circulation. In this study, we characterized wave propagation in the pulmonary artery in patients with pulmonary hypertension associated with left-sided heart disease (PHLHD) and the effects of dobutamine. During right heart catheterization, pressure and velocity data were acquired using a dual-tipped pressure and Doppler flow sensor wire (Combowire; Phillips Volcano), and processed offline using customized Matlab software (MathWorks). Patients with low cardiac output underwent dobutamine challenge. Twenty patients with PHLHD (all heart failure with reduced left ventricular ejection fraction) were studied. Right ventricular systole produced a forward compression wave (FCW), followed by a forward decompression wave (FDW) during diastole. Wave reflection manifesting as backward compression wave (BCW) following the FCW was observed in 14 patients. Compared to patients without BCW, patients with BCW had higher mean pulmonary artery pressure (28.7 ± 6.12 vs. 38.6 ± 6.5 mmHg, p = 0.005), and lower pulmonary arterial capacitance (PAC: 2.88 ± 1.75 vs. 1.73 ± 1.16, p = 0.002). Pulmonary vascular resistance was comparable. Mean pulmonary artery pressure of 34.5 mmHg (area under the curve [AUC]: 0.881) and PAC of 2.29 mL/mmHg (AUC: 0.833) predicted BCW. The magnitude of the FCW increased with dobutamine (n = 11) and correlated with pulmonary artery wedge pressure. Wave reflection in PHLHD is more likely at higher pulmonary artery pressures and lower PAC and the magnitude of reflected waves correlated with pulmonary artery wedge pressure. Dobutamine increased FCW but did not affect wave reflection.

Evaluation of a community-informed multimedia intervention to increase PrEP awareness and intention among African American young adults.

Despite the benefits of pre-exposure prophylaxis (PrEP) in preventing HIV and its potential for reducing racial/ethnic HIV inequities, PrEP remains underutilized among African Americans who may benefit from it. Factors of PrEP uptake include awareness and acceptability of this prevention strategy among this group, yet few community-informed interventions have been developed and evaluated to address these challenges. Thus, this study evaluates the effectiveness of a community-informed, six-month multimedia campaign (print, digital media, internet radio, social media) for African American young adults (age 18-29) in Louisville, Kentucky to increase PrEP awareness and PrEP use intentions. Pretest surveys, posttest surveys, and digital analytic metrics were used to determine campaign effectiveness. Logistic regressions indicate increased PrEP awareness over time (p ≤ 0.0001) and greater PrEP intention among participants reporting greater campaign affinity (p ≤ 0.05). Campaign digital analytic performance was similar to or exceeded that of industry competitors (e.g., healthcare organizations). Findings indicate that a community-informed multimedia campaign increased PrEP use intentions among those exhibiting greater campaign affinity (the extent to which participants report a favorable view of the campaign) and demonstrated similar or greater effectiveness in digital elements as industry competitors at a cost-effective price. Future studies should incorporate community-engaged approaches in developing health communication products for greater PrEP acceptability and efficiency.Trial registration: ClinicalTrials.gov identifier: NCT0355959.

Wheelchair skills training for caregivers of manual wheelchair users: a randomized controlled trial comparing self-study and remote training.

In this single-blind randomized controlled trial, we tested the hypotheses that, in comparison with control participants receiving only self-study materials (SS group), caregivers of manual wheelchair users who additionally receive remote training (RT group) have greater total Wheelchair Skills Test Questionnaire (WST-Q) performance and confidence scores post-training and at follow-up; and that self-study and remote training each individually lead to such gains. We studied 23 dyads of wheelchair users and their caregivers. Caregivers in the SS group received a handbook and videorecording. Those in the RT group also received up to four real-time ("synchronous") sessions remotely. The WST-Q 5.1 was administered pre-training (T1), post-training (T2), and after a 3-month follow-up (T3). The mean total WST-Q scores of both groups rose slightly at each new assessment. For the T2-T1 and T3-T1 gains, there were no statistically significant differences between the groups for either WST-Q performance or WST-Q confidence. For performance, the T2-T1 gain was statistically significant for the RT group and the T3-T2 gain was statistically significant for the SS group. For both groups, the T3-T1 gains in performance were statistically significant with gains of 12.9% and 18.5% relative to baseline for the SS and RT groups. For confidence, only the T3-T1 gain for the SS group was statistically significant with a gain of 4.5% relative to baseline. Although less than the gains previously reported for in-person training, modest but important gains in total WST-Q performance scores can be achieved by self-study, with or without remote training. REGISTRATION NUMBER: NCT03856749.

Self-study can improve the manual wheelchair skills of caregivers.Remote training can improve the manual wheelchair skills of caregivers.Improvements are slightly less than those reported in the literature for in-person training.

Primary versus iatrogenic (post-PCI) coronary microvascular dysfunction: a wire-based multimodal comparison.

BACKGROUND: Although there are studies examining each one separately, there are no data in the literature comparing the magnitudes of the iatrogenic, percutaneous coronary intervention (PCI)-induced, microvascular dysfunction (Type-4 CMD) and coronary microvascular dysfunction (CMD) in the setting of ischaemia in non-obstructed coronary arteries (INOCA) (Type-1 CMD). OBJECTIVES: We aimed to compare the characteristics of Type-1 and Type-4 CMD subtypes using coronary haemodynamic (resistance and flow-related parameters), thermodynamic (wave energy-related parameters) and hyperemic ECG changes. METHODS: Coronary flow reserve (CFR) value of <2.5 was defined as CMD in both groups. Wire-based multimodal perfusion markers were comparatively analysed in 35 patients (21 INOCA/CMD and 14 CCS/PCI) enrolled in NCT05471739 study. RESULTS: Both groups had comparably blunted CFR values per definition (2.03±0.22 vs 2.11±0.37; p: 0.518) and similar hyperemic ST shift in intracoronary ECG (0.16±0.09 vs 0.18±0.07 mV; p: 0.537). While the Type-1 CMD was characterised with impaired hyperemic blood flow acceleration (46.52+12.83 vs 68.20+28.63 cm/s; p: 0.017) and attenuated diastolic microvascular decompression wave magnitudes (p=0.042) with higher hyperemic microvascular resistance (p<0.001), Type-4 CMD had blunted CFR mainly due to higher baseline flow velocity due to post-occlusive reactive hyperemia (33.6±13.7 vs 22.24±5.3 cm/s; p=0.003). CONCLUSIONS: The perturbations in the microvascular milieu seen in CMD in INOCA setting (Type-1 CMD) seem to be more prominent than that of seen following elective PCI (Type-4 CMD), although resulting reversible ischaemia is equally severe in the downstream myocardium.

Multiscale Structure and Function of the Aortic Valve Apparatus.

While studying the aortic valve in isolation has facilitated the development of life-saving procedures and technologies, the dynamic interplay of the aortic valve and its surrounding structures is vital to preserving their function across the wide range of conditions encountered in an active lifestyle. Our view is that these structures should be viewed as an integrated functional unit, herein referred to as the aortic valve apparatus (AVA). The coupling of the aortic valve and root, left ventricular outflow tract, and blood circulation is crucial for AVA's functions: unidirectional flow out of the left ventricle, coronary perfusion, reservoir function, and supporting left ventricular function. In this review, we explore the multiscale biological and physical phenomena that underly the simultaneous fulfilment of these functions. A brief overview of the tools used to investigate the AVA is included, such as: medical imaging modalities, experimental methods, and computational modelling, specifically fluid-structure interaction (FSI) simulations, is included. Some pathologies affecting the AVA are explored, and insights are provided on treatments and interventions that aim to maintain quality of life. The concepts explained in this paper support the idea of AVA being an integrated functional unit and help identify unanswered research questions. Incorporating phenomena through the molecular, micro, meso and whole tissue scales is crucial for understanding the sophisticated normal functions and diseases of the AVA.

Asymmetry of flow in aortic root and its application in hypertrophic obstructive cardiomyopathy.

The aortic root (AR) performs sophisticated functions regulating the blood dynamics during the cardiac cycle. Such complex function depends on the nature of flow in the AR. Here, we investigate the potential of new quantitative parameters of flow asymmetry that could have clinical implications. We developed a MATLAB program to study the AR hemodynamics in each sinus of Valsalva using two-dimensional (2-D) cardiac magnetic resonance imaging during systole and particularly at peak systolic flow in 13 healthy volunteers and compared with 10 patients with hypertrophic obstructive cardiomyopathy (HOCM). We show that the effective area of the aortic jet in healthy volunteers is significantly higher at peak systolic flow and on average during systole. The flow asymmetry index, indicating how the jet is skewed away from the left coronary sinus (LCS), is small in healthy volunteers and much larger in HOCM at peak systole. The average of this index over systole is significantly more different between cohorts. Looking in more detail at the flow in the sinuses during systole, we show that the AR jet in healthy volunteers is more symmetrical, affecting the three sinuses almost equally, unlike the asymmetric AR jet in patients with HOCM that has decreased flow rate in the LCS and increased fractional area of backward flow in the LCS. The percentage of backward flow in the sinuses of Valsalva calculated over systole is a potential indicator of perturbed AR hemodynamics and the distribution of vortical flow and could be used as a measure of flow asymmetry.NEW & NOTEWORTHY The aortic root is a vital organ responsible for performing sophisticated functions to regulate the blood flow dynamics during the cardiac cycle. Such synchronized complex performance affects and is affected by the flow symmetry and type of flow reaching the aorta. Here, we report flow asymmetry in the aortic root which could have clinical implications, and we investigate the potential of various quantitative parameters as measures of flow asymmetry in hypertrophic obstructive cardiomyopathy.

Evaluation of a portable retinal imaging device: towards a comparative quantitative analysis for morphological measurements of retinal blood vessels.

This study investigated the possibility of using low-cost, handheld, retinal imaging devices for the automatic extraction of quantifiable measures of retinal blood vessels. Initially, the available handheld devices were compared using a Zeiss model eye incorporating a USAF resolution test chart to assess their optical properties. The only suitable camera of the five evaluated was the Horus DEC 200. This device was then subjected to a detailed evaluation in which images in human eyes taken from the handheld camera were compared in a quantitative analysis with those of the same eye from a Canon CR-DGi retinal desktop camera. We found that the Horus DEC 200 exhibited shortcomings in capturing images of human eyes by comparison with the Canon. More images were rejected as being unevaluable or suffering failures in automatic segmentation than with the Canon, and even after exclusion of affected images, the Horus yielded lower measurements of vessel density than the Canon. A number of issues affecting handheld cameras in general and some features of the Horus in particular have been identified that might contribute to the observed differences in performance. Some potential mitigations are discussed which might yield improvements in performance, thus potentially facilitating use of handheld retinal imaging devices for quantitative retinal microvascular measurements.

A heavy burden: Metal exposure across the land-ocean continuum in an adaptable carnivore.

Urbanisation and associated anthropogenic activities release large quantities of toxic metals and metalloids into the environment, where they may bioaccumulate and threaten both wildlife and human health. In highly transformed landscapes, terrestrial carnivores may be at increased risk of exposure through biomagnification. We quantified metallic element and metalloid exposure in blood of caracals (Caracal caracal), an adaptable felid inhabiting the rapidly urbanising, coastal metropole of Cape Town, South Africa. Using redundancy analysis and mixed-effect models, we explored the influence of demography, landscape use, and diet on the concentration of 11 metals and metalloids. Although species-specific toxic thresholds are lacking, arsenic (As) and chromium (Cr) were present at potentially sublethal levels in several individuals. Increased use of human-transformed landscapes, particularly urban areas, roads, and vineyards, was significantly associated with increased exposure to aluminium (Al), cobalt (Co) and lead (Pb). Foraging closer to the coast and within aquatic food webs was associated with increased levels of mercury (Hg), selenium (Se) and arsenic, where regular predation on seabirds and waterbirds likely facilitates transfer of metals from aquatic to terrestrial food webs. Further, several elements were linked to lower haemoglobin levels (chromium, mercury, manganese, and zinc) and elevated levels of infection-fighting cells (mercury and selenium). Our results highlight the importance of anthropogenic activities as major environmental sources of metal contamination in terrestrial wildlife, including exposure across the land-ocean continuum. These findings contribute towards the growing evidence suggesting cities are particularly toxic areas for wildlife. Co-exposure to a suite of metal pollutants may threaten the long-term health and persistence of Cape Town's caracal population in unexpected ways, particularly when interacting with additional known pollutant and pathogen exposure. The caracal is a valuable sentinel for assessing metal exposure and can be used in pollution monitoring programmes to mitigate exposure and promote biodiversity conservation in human-dominated landscapes.

Activated CD90/Thy-1 fibroblasts co-express the Δ133p53ß isoform and are associated with highly inflamed rheumatoid arthritis.

BACKGROUND: The p53 isoform Δ133p53ß is known to be associated with cancers driven by inflammation. Many of the features associated with the development of inflammation in rheumatoid arthritis (RA) parallel those evident in cancer progression. However, the role of this isoform in RA has not yet been explored. The aim of this study was to determine whether Δ133p53ß is driving aggressive disease in RA. METHODS: Using RA patient synovia, we carried out RT-qPCR and RNAScope-ISH to determine both protein and mRNA levels of Δ133p53 and p53. We also used IHC to determine the location and type of cells with elevated levels of Δ133p53ß. Plasma cytokines were also measured using a BioPlex cytokine panel and data analysed by the Milliplex Analyst software. RESULTS: Elevated levels of pro-inflammatory plasma cytokines were associated with synovia from RA patients displaying extensive tissue inflammation, increased immune cell infiltration and the highest levels of Δ133TP53 and TP53ß mRNA. Located in perivascular regions of synovial sub-lining and surrounding ectopic lymphoid structures (ELS) were a subset of cells with high levels of CD90, a marker of 'activated fibroblasts' together with elevated levels of Δ133p53ß. CONCLUSIONS: Induction of Δ133p53ß in CD90+ synovial fibroblasts leads to an increase in cytokine and chemokine expression and the recruitment of proinflammatory cells into the synovial joint, creating a persistently inflamed environment. Our results show that dysregulated expression of Δ133p53ß could represent one of the early triggers in the immunopathogenesis of RA and actively perpetuates chronic synovial inflammation. Therefore, Δ133p53ß could be used as a biomarker to identify RA patients more likely to develop aggressive disease who might benefit from targeted therapy to cytokines such as IL-6.

Effect of travel direction and wheelchair position on the ease of a caregiver getting an occupied wheelchair across a soft surface: a randomized crossover trial.

PURPOSE: To test the hypotheses that, in comparison with pushing an occupied upright manual wheelchair forward, pulling backward on the push-handles improves the objective and subjective ease with which a caregiver can get the wheelchair across a soft surface (e.g., grass, mud, sand, gravel); and the ease with which a caregiver can get the wheelchair across a soft surface improves if the wheelchair is tipped back into the wheelie position. METHODS: We used a randomized crossover trial with within-participant comparisons to study 32 able-bodied pairs of simulated caregivers and wheelchair occupants. The caregiving participants moved an occupied manual wheelchair 5 m across a soft surface (7.5-cm-thick gym mats) under four conditions (upright-forward, upright-backward, wheelie-forward and wheelie-backward) in random order. The main outcome measure was time (to the nearest 0.1 s) and the main secondary measure was the ease of performance (5-point Likert scale). RESULTS: The upright-backward condition was the fastest (p < 0.05) and had the highest ease-of-performance scores. In the forward direction, there was no statistically significant difference in the time required between the upright and wheelie positions, but the wheelie position was considered easier. CONCLUSIONS: Although further study is needed, our findings suggest that caregivers should pull rather than push occupied wheelchairs across soft surfaces. In the forward direction, caregivers may find the wheelie position easier than the upright condition. These techniques have the potential to both improve the effectiveness of and reduce injuries to caregivers. Clinical Trial Registration Number: NCT 04998539Implications for RehabilitationCaregivers should pull rather than push occupied manual wheelchairs across soft surfaces.In the forward direction, caregivers may find the wheelie position easier than and preferable to the upright condition.These techniques have the potential to both improve the effectiveness of and reduce injuries to caregivers.

Residual limb support devices on wheelchairs for people with transtibial amputations: A scoping review and survey of rehabilitation professionals in Nova Scotia.

PURPOSE: To determine what research evidence exists for the use of residual limb supports (RLSs) for people with transtibial amputations and to describe clinicians' use of such supports in Nova Scotia. METHODS: Scoping review of published and gray literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews as a guide and an anonymous online and paper-based clinician survey. RESULTS: We identified 22 publications meeting criteria for review. Seventeen (77%) of the publications were practice guidelines or systematic reviews about care of people with lower-limb amputations, 4 (18%) involved research about the design of stump supports, and 1 (5%) researched the use of supports. Generally, the use of RLSs was recommended (e.g., to prevent contractures, control edema, and to provide comfort), but many authors acknowledged that the evidence was weak, and additional evidence in support of these treatment goals could not be found. We received 44 survey responses from health care professionals involved with the care of people with transtibial amputations in Nova Scotia. Of the 43 health care professionals who responded to the question "… what percent of patients/clients with transtibial amputations do you estimate receive stump supports …," the mean (standard deviation) was 86.1% (21.1). The most common reasons for recommending a stump support were to prevent knee contracture (38 [86.4%]), and to prevent swelling (13 [29.5%]). CONCLUSIONS: Most clinicians who provide services to people with amputations in Nova Scotia believe that RLSs have benefits such as the prevention of contractures, the reduction of edema, and improved patient comfort. However, there is little high-quality research evidence to support their use. There is a need to perform the necessary research or to modify practice guidelines.

Practices and views of wheelchair service providers regarding wheelchair-skills training for clients and their caregivers: a global online survey.

PURPOSE: To determine the extent to which wheelchair service providers conduct wheelchair-skills training, the nature of training, and the providers' perceptions on training. MATERIALS AND METHODS: Anonymous global online survey consisting of 29 questions administered via the REDCap electronic data-capture tool to English-speaking wheelchair service providers. RESULTS: We received 309 responses from wheelchair service providers in 35 countries. Of the respondents who responded to the question "…do you typically provide wheelchair-skills training…?" 227 (81.6%) reported "yes, always" or "yes, usually" for clients and 213 (81.9%) for caregivers. The median duration of training sessions for clients and caregivers was 45 and 30 min; the median number of sessions was 2 for both. Regarding the importance of training, 251 (94.4%) answered "very important" for clients and 201 (78.5%) for caregivers. For clients and caregivers, 182 (68.4%) and 191 (74.3%) of respondents considered themselves adequately prepared for the trainer role. A variety of barriers and facilitators to training were identified. CONCLUSIONS: Most wheelchair service providers report that they provide wheelchair-skills training for clients and their caregivers, most consider such training to be important and most consider themselves adequately prepared for the training role. However, the amount of training is generally minimal. Further efforts are needed to address the identified barriers to training.IMPLICATIONS FOR REHABILITATIONMost wheelchair-service providers report that they provide wheelchair-skills training.Most consider such training to be important.Most consider themselves adequately prepared.However, the extent of training is generally minimal.These findings have implications for clinicians, educators, and policymakers.

Corrigendum: Carotid reservoir pressure decrease after prolonged head down tilt bed rest in young healthy subjects is associated with reduction in left ventricular ejection time and diastolic length.

[This corrects the article DOI: 10.3389/fphys.2022.866045.].

Reservoir Pressure Integral Is Independently Associated With the Reduction in Renal Function in Older Adults.

BACKGROUND: Arterial hemodynamic parameters derived from reservoir-excess pressure analysis exhibit prognostic utility. Reservoir-excess pressure analysis may provide useful information about an influence of altered hemodynamics on target organ such as the kidneys. We determined whether the parameters derived from the reservoir-excess pressure analysis were associated with the reduction in estimated glomerular filtration rate in 542 older adults (69.4±7.9 years, 194 females) at baseline and after 3 years. METHODS: Reservoir-excess pressure parameters, including reservoir pressure integral, excess pressure integral, systolic, and diastolic rate constants, were obtained by radial artery tonometry. RESULTS: After 3 years, and in a group of 94 individuals (72.4±7.6 years, 26 females), there was an estimated glomerular filtration rate reduction of >5% per year (median reduction of 20.5% over 3 years). A multivariable logistic regression analysis revealed that higher baseline reservoir pressure integral was independently associated with a smaller reduction in estimated glomerular filtration rate after accounting for conventional cardiovascular risk factors and study centers (odds ratio: 0.660 [95% CIs, 0.494-0.883]; P=0.005). The association remained unchanged after further adjustments for potential confounders and baseline renal function (odds ratio: 0.528 [95% CIs, 0.351-0.794]; P=0.002). No other reservoir-excess pressure parameters exhibited associations with the reduction in renal function. CONCLUSIONS: This study demonstrates that baseline reservoir pressure integral was associated with the decline in renal function in older adults at 3-year follow-up, independently of conventional cardiovascular risk factors. This suggests that reservoir pressure integral may play a role in the functional decline of the kidneys.

Carotid Reservoir Pressure Decrease After Prolonged Head Down Tilt Bed Rest in Young Healthy Subjects Is Associated With Reduction in Left Ventricular Ejection Time and Diastolic Length.

Background: The arterial pressure waveform reflects the interaction between the heart and the arterial system and carries potentially relevant information about circulatory status. According to the commonly accepted 'wave transmission model', the net BP waveform results from the super-position of discrete forward and backward pressure waves, with the forward wave in systole determined mainly by the left ventricular (LV) ejection function and the backward by the wave reflection from the periphery, the timing and amplitude of which depend on arterial stiffness, the wave propagation speed and the extent of downstream admittance mismatching. However, this approach obscures the 'Windkessel function' of the elastic arteries. Recently, a 'reservoir-excess pressure' model has been proposed, which interprets the arterial BP waveform as a composite of a volume-related 'reservoir' pressure and a wave-related 'excess' pressure. Methods: In this study we applied the reservoir-excess pressure approach to the analysis of carotid arterial pressure waveforms (applanation tonometry) in 10 young healthy volunteers before and after a 5-week head down tilt bed rest which induced a significant reduction in stroke volume (SV), end-diastolic LV volume and LV longitudinal function without significant changes in central blood pressure, cardiac output, total peripheral resistance and aortic stiffness. Forward and backward pressure components were also determined by wave separation analysis. Results: Compared to the baseline state, bed rest induced a significant reduction in LV ejection time (LVET), diastolic time (DT), backward pressure amplitude (bP) and pressure reservoir integral (INTPR). INTPR correlated directly with LVET, DT, time to the peak of backward wave (bT) and stroke volume, while excess pressure integral (INTXSP) correlated directly with central pressure. Furthermore, Δ.INTPR correlated directly with Δ.LVET, and Δ.DT, and in multivariate analysis INTPR was independently related to LVET and DT and INTXSP to central systolic BP. Conclusion: This is an hypothesis generating paper which adds support to the idea that the reservoir-wave hypothesis applied to non-invasively obtained carotid pressure waveforms is of potential clinical usefulness.

Neuroprotective activity of new Δ3-N-acylethanolamines in a focal ischemia stroke model.

N-acylethanolamines (NAE, also called ethanolamides) are significant lipid signaling molecules with anti-inflammatory, pain-relieving, cell-protective, and anticancer properties. Here, we present the use of a hitherto unreported group of Δ3-NAE and also some Δ4- and Δ5-NAE, in in vitro and in vivo assays to gain a better understanding of their structure-bioactivity relationships. We have developed an efficient synthetic method to rapidly produce novel unlabeled and 13 C-labeled Δ3-NAE (NAE-18:5n-3, NAE-18:4n-6) and Δ4-NAE (NAE-22:5n-6). The new NAE with shorter carbon backbone structures confers greater neuroprotection than their longer carbon backbone counterparts, including anandamide (Δ5-NAE-20:4n-6) in a focal ischemia mouse model of stroke. This study highlights structure-dependent protective effects of new NAE following focal ischemia, in which some of the new NAE, administered intranasally, lead to significantly reduced infarct volume and improved recovery of limb use. The relative affinity of the new NAE toward cannabinoid receptors was assessed against anandamide, NAE-22:6n-3 and NAE-20:5n-3, which are known cannabinoid receptor ligands with high-binding constants. Among the newly synthesized NAE, Δ4-NAE-22:5n-6 shows the greatest relative affinity to cannabinoid receptors hCB1 and hCB2 , and inhibition of cyclic adenosine monophosphate activity through hCB2 compared to anandamide.

The Use of Maximum Entropy to Enhance Wave Intensity Analysis: An Application to Coronary Arteries in Hypertrophic Obstructive Cardiomyopathy.

Background: Wave intensity analysis is useful for analyzing coronary hemodynamics. Much of its clinical application involves the identification of waves indicated by peaks in the wave intensity and relating their presence or absence to different cardiovascular events. However, the analysis of wave intensity peaks can be problematic because of the associated noise in the measurements. This study shows how wave intensity analysis can be enhanced by using a Maximum Entropy Method (MEM). Methods: We introduce a MEM to differentiate between "peaks" and "background" in wave intensity waveforms. We apply the method to the wave intensity waveforms measured in the left anterior descending coronary artery from 10 Hypertrophic Obstructive Cardiomyopathy (HOCM) and 11 Controls with normal cardiac function. We propose a naming convention for the significant waves and compare them across the cohorts. Results: Using a MEM enhances wave intensity analysis by identifying twice as many significant waves as previous studies. The results are robust when MEM is applied to the log transformed wave intensity data and when all of the measured data are used. Comparing waves across cohorts, we suggest that the absence of a forward expansion wave in HOCM can be taken as an indication of HOCM. Our results also indicate that the backward compression waves in HOCM are significantly larger than in Controls; unlike the forward compression waves where the wave energy in Controls is significantly higher than in HOCM. Comparing the smaller secondary waves revealed by MEM, we find some waves that are present in the majority of Controls and absent in almost all HOCM, and other waves that are present in some HOCM patients but entirely absent in Controls. This suggests some diagnostic utility in the clinical measurement of these waves, which can be a positive sign of HOCM or a subgroup with a particular pathology. Conclusion: The MEM enhances wave intensity analysis by identifying many more significant waves. The method is novel and can be applied to wave intensity analysis in all arteries. As an example, we show how it can be useful in the clinical study of hemodynamics in the coronary arteries in HOCM.