Rectified Latent Variable Model-Based EMG Factorization of Inhibitory Muscle Synergy Components Related to Aging, Expertise and Force-Tempo Variations.

Muscle synergy has been widely acknowledged as a possible strategy of neuromotor control, but current research has ignored the potential inhibitory components in muscle synergies. Our study aims to identify and characterize the inhibitory components within motor modules derived from electromyography (EMG), investigate the impact of aging and motor expertise on these components, and better understand the nervous system's adaptions to varying task demands. We utilized a rectified latent variable model (RLVM) to factorize motor modules with inhibitory components from EMG signals recorded from ten expert pianists when they played scales and pieces at different tempo-force combinations. We found that older participants showed a higher proportion of inhibitory components compared with the younger group. Senior experts had a higher proportion of inhibitory components on the left hand, and most inhibitory components became less negative with increased tempo or decreased force. Our results demonstrated that the inhibitory components in muscle synergies could be shaped by aging and expertise, and also took part in motor control for adapting to different conditions in complex tasks.

Fairness and bias correction in machine learning for depression prediction across four study populations.

A significant level of stigma and inequality exists in mental healthcare, especially in under-served populations. Inequalities are reflected in the data collected for scientific purposes. When not properly accounted for, machine learning (ML) models learned from data can reinforce these structural inequalities or biases. Here, we present a systematic study of bias in ML models designed to predict depression in four different case studies covering different countries and populations. We find that standard ML approaches regularly present biased behaviors. We also show that mitigation techniques, both standard and our own post-hoc method, can be effective in reducing the level of unfair bias. There is no one best ML model for depression prediction that provides equality of outcomes. This emphasizes the importance of analyzing fairness during model selection and transparent reporting about the impact of debiasing interventions. Finally, we also identify positive habits and open challenges that practitioners could follow to enhance fairness in their models.

What makes clocks tick? Characterizing developmental dynamics of adult epigenetic clock sites.

DNA methylation (DNAm) at specific sites can be used to calculate 'epigenetic clocks', which in adulthood are used as indicators of age(ing). However, little is known about how these clock sites 'behave' during development and what factors influence their variability in early life. This knowledge could be used to optimize healthy aging well before the onset of age-related conditions. Here, we leveraged results from two longitudinal population-based cohorts (N=5,019 samples from 2,348 individuals) to characterize trajectories of adult clock sites from birth to early adulthood. We find that clock sites (i) diverge widely in their developmental trajectories, often showing non-linear change over time; (ii) are substantially more likely than non-clock sites to vary between individuals already from birth, differences that are predictive of DNAm variation at later ages; and (iii) show enrichment for genetic and prenatal environmental exposures, supporting an early-origins perspective to epigenetic aging.

Ultrasound imaging of the dorsalis pedis artery as an early indicator of the precursory changes for rheumatoid vasculitis: A case series.

Introduction: Clinical verification of rheumatoid vasculitis (RV) persists as a mid-to-late diagnosis with medical imaging or biopsy. Early and subclinical presentations of RV, in particular, can remain underdiagnosed in the absence of adequate diagnostic testing. In this study, the research demonstrated the precursory changes for RV in patients with rheumatoid arthritis (RA) using non-invasive ultrasound imaging of a peripheral vessel. Method: Six participants were recruited: three participants with (RA) and three age- and gender-matched healthy controls. All participants completed a Foot Health Survey Questionnaire (FHSQ), and participants with RA completed a Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5). Bilateral B-mode and Doppler ultrasound of the dorsalis pedis artery (DPA) was performed. The degree of inflammation, lumen and artery diameters, lumen diameter-to-artery diameter ratio and peak systolic velocity in the proximal DPA were compared between the two groups. Results: The mean RADAI-5 score (5.4 ± 0.8 out of 10) indicated moderate disease activity amongst participants with RA. Inflammation was observed in the DPA wall in all participants with RA, compared to no inflammation observed in the control group (Friedmans two-way analysis: χ2 = 15.733, P = 0.003). Differences between groups for inflammation, lumen diameter and lumen diameter-to-artery diameter ratio were found (P < 0.034), without differences for artery diameter and peak systolic velocity (P > 0.605). DPA wall inflammation did not correlate with FHSQ scores (r = -0.770, P = 0.073). Conclusion: Despite moderate RA disease activity, this is the first study to demonstrate the use of ultrasound to observe inflammation in small vessel disease. Our findings suggest ultrasound imaging may be a viable screening tool to demonstrate arterial wall inflammation, indicating the precursory changes of RV.

Early-life stress and the gut microbiome: A comprehensive population-based investigation.

Early-life stress (ELS) has been robustly associated with a range of poor mental and physical health outcomes. Recent studies implicate the gut microbiome in stress-related mental, cardio-metabolic and immune health problems, but research on humans is scarce and thus far often based on small, selected samples, often using retrospective reports of ELS. We examined associations between ELS and the human gut microbiome in a large, population-based study of children. ELS was measured prospectively from birth to 10 years of age in 2,004 children from the Generation R Study. We studied overall ELS, as well as unique effects of five different ELS domains, including life events, contextual risk, parental risk, interpersonal risk, and direct victimization. Stool microbiome was assessed using 16S rRNA sequencing at age 10 years and data were analyzed at multiple levels (i.e. α- and ß-diversity indices, individual genera and predicted functional pathways). In addition, we explored potential mediators of ELS-microbiome associations, including diet at age 8 and body mass index at 10 years. While no associations were observed between overall ELS (composite score of five domains) and the microbiome after multiple testing correction, contextual risk - a specific ELS domain related to socio-economic stress, including risk factors such as financial difficulties and low maternal education - was significantly associated with microbiome variability. This ELS domain was associated with lower α-diversity, with ß-diversity, and with predicted functional pathways involved, amongst others, in tryptophan biosynthesis. These associations were in part mediated by overall diet quality, a pro-inflammatory diet, fiber intake, and body mass index (BMI). These results suggest that stress related to socio-economic adversity - but not overall early life stress - is associated with a less diverse microbiome in the general population, and that this association may in part be explained by poorer diet and higher BMI. Future research is needed to test causality and to establish whether modifiable factors such as diet could be used to mitigate the negative effects of socio-economic adversity on the microbiome and related health consequences.

Neural response to threat and reward among young adults at risk for alcohol use disorder.

Alcohol use disorder (AUD) is heritable. Thus, young adults with positive family histories represent an at-risk group relative to those without a family history, and if studied at a time when both groups have similar levels of alcohol use, it provides an opportunity to identify neural processing patterns associated with risk for AUD. Previous studies have shown that diminished response to potential reward is associated with genetic risk for AUD, but it is unclear how threat may modulate this response. We used a modified Monetary Incentive Delay task during fMRI to examine neural correlates of the interaction between threat and reward anticipation in a sample of young adults with (n = 31) and without (n = 44) family histories of harmful alcohol use. We found an interaction (p = 0.048) between cue and group in the right nucleus accumbens where the family history positive group showed less differentiation to the anticipation of gaining $5 and losing $5 relative to gaining $0. The family history-positive group also reported less excitement for trials to gain $5 relative to gaining $0 (p < 0.001). Family history-positive individuals showed less activation in the left insula during both safe and threat blocks compared to family history-negative individuals (p = 0.005), but the groups did not differ as a function of threat (p > 0.70). Young adults with, relative to without, enriched risk for AUD may have diminished reward processing via both neural and behavioural markers to potential rewarding and negative consequences. Neural response to threat may not be a contributing factor to risk at this stage.

HMGB1 mediates microbiome-immune axis dysregulation underlying reduced neutralization capacity in obesity-related post-acute sequelae of SARS-CoV-2.

While obesity is a risk factor for post-acute sequelae of SARS-CoV-2 infection (PASC, "long-COVID"), the mechanism(s) underlying this phenomenon remains poorly understood. To address this gap in knowledge, we performed a 6-week longitudinal study to examine immune activity and gut microbiome dysbiosis in post-acute stage patients recovering from SARS-CoV-2 infection. Self-reported symptom frequencies and blood samples were collected weekly, with plasma assessed by ELISA and Luminex for multiple biomarkers and immune cell profiling. DNA from stool samples were collected at the early stage of recovery for baseline assessments of gut microbial composition and diversity using 16S-based metagenomic sequencing. Multiple regression analyses revealed obesity-related PASC linked to a sustained proinflammatory immune profile and reduced adaptive immunity, corresponding with reduced gut microbial diversity. In particular, enhanced signaling of the high mobility group box 1 (HMGB1) protein was found to associate with this dysregulation, with its upregulated levels in plasma associated with significantly impaired viral neutralization that was exacerbated with obesity. These findings implicate HMGB1 as a candidate biomarker of PASC, with potential applications for risk assessment and targeted therapies.

Prenatal ultrasound diagnosis of velamentous cord insertion: a case report and review of the literature.

PURPOSE: The velamentous cord insertion is a rare pathology in which the umbilical blood vessels branch before reaching the placenta; by varying its structure, the cord becomes prone to spontaneous internal ruptures. This pathology is an obstetric emergency, so its early diagnosis is essential. METHODS AND RESULTS: We present a 27-year-old pregnant woman who attends an antenatal check-up for a routine third-trimester examination. Ultrasound reveals grade I polyhydramnios and suggestive findings of a trivascular umbilical cord with velamentous insertion 35 mm from the nearest placental border. The ultrasound diagnosis allowed a term delivery by elective cesarean section, avoiding severe complications of the maternal-fetal binomial. CONCLUSION: Velamentous cord insertion can and should have an early prenatal diagnosis, even from the second trimester, through imaging techniques such as transabdominal ultrasound or color Doppler. Early detection and appropriate peripartum management will highly reduce complications during labor.

Are some children genetically predisposed to poor sleep? A polygenic risk study in the general population.

BACKGROUND: Twin studies show moderate heritability of sleep traits: 40% for insomnia symptoms and 46% for sleep duration. Genome-wide association studies (GWAS) have identified genetic variants involved in insomnia and sleep duration in adults, but it is unknown whether these variants affect sleep during early development. We assessed whether polygenic risk scores for insomnia (PRS-I) and sleep duration (PRS-SD) affect sleep throughout early childhood to adolescence. METHODS: We included 2,458 children of European ancestry (51% girls). Insomnia-related items of the Child Behavior Checklist were reported by mothers at child's age 1.5, 3, and 6 years. At 10-15 years, the Sleep Disturbance Scale for Children and actigraphy were assessed in a subsample (N = 975). Standardized PRS-I and PRS-SD (higher scores indicate genetic susceptibility for insomnia and longer sleep duration, respectively) were computed at multiple p-value thresholds based on largest GWAS to date. RESULTS: Children with higher PRS-I had more insomnia-related sleep problems between 1.5 and 15 years (BPRS-I < 0.001 = .09, 95% CI: 0.05; 0.14). PRS-SD was not associated with mother-reported sleep problems. A higher PRS-SD was in turn associated with longer actigraphically estimated sleep duration (BPRS-SD < 5e08 = .05, 95% CI: 0.001; 0.09) and more wake after sleep onset (BPRS-SD < 0.005 = .25, 95% CI: 0.04; 0.47) at 10-15 years, but these associations did not survive multiple testing correction. CONCLUSIONS: Children who are genetically predisposed to insomnia have more insomnia-like sleep problems, whereas those who are genetically predisposed to longer sleep have longer sleep duration, but are also more awake during the night in adolescence. This indicates that polygenic risk for sleep traits, based on GWAS in adults, affects sleep already in children.

Tracking Bilateral Lower Limb Kinematics of Distance Runners on Treadmill Using a Single Inertial Measurement Unit.

Distance running related injuries are common, and many ailments have been associated with faulty posture. Conventional measurement of running kinematics requires sophisticated motion capture system in laboratory. In this study, we developed a wearable solution to accurately predict lower limb running kinematics using a single inertial measurement unit placed on the left lower leg. The running data collected from participants was used to train a model using long short-term memory (LSTM) neural networks with an inter-subject approach that predicted lower limb kinematics with an average accuracy of 80.2%, 85.8%, and 69.4% for sagittal hip, knee and ankle joint angles respectively for the ipsilateral limb. A comparable accuracy range was observed for the contralateral limb. The average RMSE (root mean squared error) of sagittal hip, knee and ankle were 8.76°, 13.13°, and 9.67° respectively for the ipsilateral limb. Analysis of contralateral limb kinematics was performed. The model established in this study can be used as a monitoring device to track essential running kinematics in natural running environments. Besides, the wearable solution can be an integral part of a real-time gait retraining biofeedback system for injury prevention and rehabilitation.

Comparing the Graphical Features of Simple Artificial Neural Networks and Cortical Development.

Brain development is characterized by changes in connections and information processing complexity. These changes inspire the training process of artificial neural network (ANN), which requires adjusting the neuron weights and biases to enhance efficiency in performing a specific task. In this work, we found affinities in the ratio of positive and negative weights in simple ANNs during training with that of excitatory and inhibitory synapses in the cortex. Additionally, we present a graphical representation of simple ANNs formed by pruning unimportant weights and aligning neurons and connections of different layers. Our findings suggest a strong relationship between the accuracy of simple neural network and graphical representation features, with graphical features at the inflection point resembling the graphical representation of the cortex.

Cord Blood Metabolite Profiles and Their Association with Autistic Traits in Childhood.

Autism Spectrum Disorder (ASD) is a diverse neurodevelopmental condition. Gene-environmental interactions in early stages of life might alter metabolic pathways, possibly contributing to ASD pathophysiology. Metabolomics may serve as a tool to identify underlying metabolic mechanisms contributing to ASD phenotype and could help to unravel its complex etiology. In a population-based, prospective cohort study among 783 mother-child pairs, cord blood serum concentrations of amino acids, non-esterified fatty acids, phospholipids, and carnitines were obtained using liquid chromatography coupled with tandem mass spectrometry. Autistic traits were measured at the children's ages of 6 (n = 716) and 13 (n = 648) years using the parent-reported Social Responsiveness Scale. Lower cord blood concentrations of SM.C.39.2 and NEFA16:1/16:0 were associated with higher autistic traits among 6-year-old children, adjusted for sex and age at outcome. After more stringent adjustment for confounders, no significant associations of cord blood metabolites and autistic traits at ages 6 and 13 were detected. Differences in lipid metabolism (SM and NEFA) might be involved in ASD-related pathways and are worth further investigation.

An epigenome-wide association study of child appetitive traits and DNA methylation.

The etiology of childhood appetitive traits is poorly understood. Early-life epigenetic processes may be involved in the developmental programming of appetite regulation in childhood. One such process is DNA methylation (DNAm), whereby a methyl group is added to a specific part of DNA, where a cytosine base is next to a guanine base, a CpG site. We meta-analyzed epigenome-wide association studies (EWASs) of cord blood DNAm and early-childhood appetitive traits. Data were from two independent cohorts: the Generation R Study (n = 1,086, Rotterdam, the Netherlands) and the Healthy Start study (n = 236, Colorado, USA). DNAm at autosomal methylation sites in cord blood was measured using the Illumina Infinium HumanMethylation450 BeadChip. Parents reported on their child's food responsiveness, emotional undereating, satiety responsiveness and food fussiness using the Children's Eating Behaviour Questionnaire at age 4-5 years. Multiple regression models were used to examine the association of DNAm (predictor) at the individual site- and regional-level (using DMRff) with each appetitive trait (outcome), adjusting for covariates. Bonferroni-correction was applied to adjust for multiple testing. There were no associations of DNAm and any appetitive trait when examining individual CpG-sites. However, when examining multiple CpGs jointly in so-called differentially methylated regions, we identified 45 associations of DNAm with food responsiveness, 7 associations of DNAm with emotional undereating, 13 associations of DNAm with satiety responsiveness, and 9 associations of DNAm with food fussiness. This study shows that DNAm in the newborn may partially explain variation in appetitive traits expressed in early childhood and provides preliminary support for early programming of child appetitive traits through DNAm. Investigating differential DNAm associated with appetitive traits could be an important first step in identifying biological pathways underlying the development of these behaviors.

Tetrahydrocannabinol in Pediatrics: Room for Improvement?

Introduction: The use of medical cannabis in pediatrics is not common in clinical practice, and there is a lack of prospective studies, especially in pediatric subpopulations. This study aimed to provide data on the off-label administration of tetrahydrocannabinol (∆9-THC) in a pediatric tertiary center in Austria. Methods: A retrospective data analysis was performed to assess the use of ∆9-THC at the Department of Pediatrics and Adolescent Medicine at the Comprehensive Center of Pediatrics (Medical University Vienna) from 2016 to 2018. The use of ∆9-THC in the Pediatric Department at the Medical University Vienna between 2016 and 2018 was analyzed using a retrospective design. Results: The most common diagnoses of patients receiving ∆9-THC were brain cancer and genetic diseases, including inborn metabolic disorders. The 32 patients who had received ∆9-THC had an arithmetic mean of 9.42 diagnoses and were treated with an arithmetic mean of 13.52 other drugs. Eleven of the 32 patients died by the end of the study period, indicating palliative use. Conclusion: The data shows that only severely ill patients were treated with ∆9-THC. A lack of information on the drug's indications, duration, and dosage was noticed in the files, which could represent problems for patient safety.

INFLUENCE OF SEASON, ENVIRONMENT, AND SEX ON SELECTED BLOOD PARAMETERS OF GEOFFROY'S SIDE-NECKED TURTLES, PHRYNOPS GEOFFROANUS (SCHWEIGGER, 1812).

Laboratory tests help to determine a diagnosis, to plan treatment, and to indicate prognosis of diseases. However, the interpretation of test results in reptiles is challenging, because they are influenced by environmental and individual factors. Therefore, the objective of this study was to establish hematologic parameters of Geoffroy's side-necked turtle (Phrynops geoffroanus), including variables such as season, environment, sex, and straight carapace length (SCL). Blood samples were analyzed from 38 P. geoffroanus (23 males and 15 females) collected during the rainy and dry seasons. Some of the animals were from captivity and others from an urban stream. To verify the influence of the variables on blood parameters, the general linear model was performed. The Pearson correlation coefficient was also used to verify the association between SCL and hematologic parameters. Among these parameters, hemoglobin (P = 0.008) and mean corpuscular hemoglobin concentration (P = 0.001) were statistically higher during the rainy season. On the other hand, WBC (P = 0.011), heterophils (P = 0.045), eosinophils (P < 0.001), lymphocytes (P = 0.014), and monocytes (P = 0.039) were higher in the dry season. The RBC count (P = 0.035), PCV (P = 0.029), basophils (P = 0.013), and monocytes (P = 0,013) were significantly higher in individuals from captivity, but lymphocytes (P = 0.033) were higher in the urban turtles. Only eosinophils (P = 0.025) were higher in females than in males. There was no influence of the variables season, environment, and sex on the mean corpuscular volume (P = 0.071; P = 0.458; P = 0.052), total solids (P = 0.773; P = 0.121; P = 0.131), and heterophil:lymphocyte ratio (P = 0.992; P = 0.58; P = 0.119). No influence of the size on hematologic parameters was observed. Season, environment, and sex may influence the blood parameters of P. geoffroanus, and these factors should be routinely considered in the interpretation of laboratory results.

DLATA: Deep Learning-Assisted transformation alignment of 2D brain slice histology.

Accurate alignment of brain slices is crucial for the classification of neuron populations by brain region, and for quantitative analysis in in vitro brain studies. Current semi-automated alignment workflows require labor intensive labeling of feature points on each slice image, which is time-consuming. To speed up the process in large-scale studies, we propose a method called Deep Learning-Assisted Transformation Alignment (DLATA), which uses deep learning to automatically identify feature points in images after training on a few labeled samples. DLATA only requires approximately 10% of the sample size of other semi-automated alignment workflows. Following feature point recognition, local weighted mean method is used as a geometrical transformation to align slice images for registration, achieving better results with about 4 fewer pixels of error than other semi-automated alignment workflows. DLATA can be retrained and successfully applied to the alignment of other biological tissue slices with different stains, including the typically challenging fluorescent stains. Reference codes and trained models for Nissl-stained coronal brain slices of mice can be found at https://github.com/ALIGNMENT2023/DLATA.

Sequencing the SARS-CoV-2 Genome from Stool Samples of Post-acute Cases Implicates a Novel Mutation Associated with Reduced Antibody Neutralization.

Whole-genome SARS-CoV-2 sequencing tools are crucial for tracking the COVID-19 pandemic. However, current techniques require sampling of actively infectious patients following COVID-19 testing to recover enough SARS-CoV-2 RNA from the nasopharyngeal passage, which rapidly clears during the first few weeks of infection. A prospective assessment of the viral genome sourced from recovered non-infectious patients would greatly facilitate epidemiological tracking. Thus, we developed a protocol to isolate and sequence the genome of SARS-CoV-2 from stool samples of post-acute SARS-CoV-2 patients, at timepoints ranging from 10-120 days after onset of symptoms. Stool samples were collected from patients at varying timepoints post-convalescence, and viral DNA was isolated and sequenced using the QIAamp Viral RNA Mini Kit (Qiagen Inc.) and Ion Ampliseq™ Library Kit Plus (Life Technologies Corporation). Capacity of neutralizing antibodies in patient plasma was tested using a Luminex panel (Coronavirus Ig Total Human 11-Plex ProcartaPlex™ Panel, ThermoFisher). Of 64 samples obtained from post-acute patients, 21 (32.8%) yielded sufficient material for whole-genome sequencing. This allowed us to identify widely divergent phylogenetic relativity of the SARS-CoV-2 genome from post-acute patients living in the same households and infected around the same time. Additionally, we observed that individuals who recovered from infection expressed varying degrees of antibodies against SARS-CoV-2 structural proteins that corresponded to distinct variants. Interestingly, we identified a novel point mutation in the viral genome where infected patients expressed antibodies with a significantly reduced capacity to neutralize the virus in vitro relative to that of those infected with the wild-type strain. Altogether, we demonstrate a protocol to successfully sequence the SARS-CoV-2 genome from stool samples from patients up to 4 months post-infection, which can be applied to studies that assess the relationship between variants and immune response post-hoc and safe monitoring of the SARS-CoV-2 genome during the pandemic.

NEURAL RESPONSE TO THREAT AND REWARD AMONG YOUNG ADULTS AT RISK FOR ALCOHOL USE DISORDER.

Alcohol use disorder is 50% heritable; those with positive family histories represent an at-risk group within which we can test anticipation of threat and reward prior to development of harmful alcohol use. We examined neural correlates of the interaction between family history, threat anticipation (unpredictable threat), and monetary reward anticipation, in a sample of healthy young adults with (n=31) and without (n=44) family histories of harmful alcohol use. We used a modified Monetary Incentive Delay task with sustained threat of hearing a scream during fMRI. We examined the interaction between family history group, anticipation of threat, and anticipation of reward in the insula, nucleus accumbens, and medial prefrontal cortex. Family history positive individuals showed less activation in the left insula during both safe and threat blocks compared to family history negative individuals (p=0.005), but the groups did not differ as a function of unpredictable threat (p>0.70). We found an interaction (p=0.048) between cue and group in the right nucleus accumbens where the family history positive group showed less differentiation to the anticipation of gaining $5 and losing $5 relative to gaining $0. The family history positive group also reported less excitement for trials to gain $5 relative to gaining $0 (p<0.001). Prior to chronic heavy alcohol use, individuals with, relative to without, enriched risk may have diminished reward processing via both neural and behavioral markers to potential rewarding and negative consequences. Neural response to unpredictable threat may not be a contributing factor to risk at this stage.

Reliability of Ultrasound Imaging in Examining Integrity and Inflammation in the Dorsalis Pedis Artery.

OBJECTIVE: Assessment of small vessel inflammatory diseases such as rheumatoid vasculitis is challenging. Small arteries such as the dorsalis pedis artery (DPA) are difficult to assess for changes in the arterial wall with medical imaging. Ultrasound imaging is a viable tool for examining the integrity and inflammatory changes in the arterial wall; however, no empirical data on its reliability have been described. METHODS: We measured the intra- and inter-rater reliability of ultrasound measurements across five parameters evaluating arterial integrity of the proximal DPA in participants with and without small vessel disease. We recruited 10 participants with rheumatoid arthritis and 10 healthy controls. Two sonographers using ultrasound independently measured DPA lumen diameter, artery diameter, lumen-to-arterial diameter ratio, arterial Doppler velocity and inflammatory changes in the proximal wall of the DPA. The intraclass correlation coefficient (ICC) was used to evaluate 95% confidence intervals within and between raters. Bland-Altman analyses were used to assess limits of agreement and were compared with minimal clinically important differences (MCID). RESULTS: Four of five selected parameters were found to have excellent intra- and inter-rater reliability within and between raters (ICC = 0.903-0.996). Acceptable reliability was found for measurement of arterial blood flow velocity within raters (ICC = 0.815-0.909), but not between raters (ICC = 0.634). Standard mean errors in all parameters were within minimal clinically important differences. CONCLUSION: Ultrasound imaging has been found to be a reliable method of assessment of arterial integrity and inflammation of the proximal DPA in people with small vessel disease. Evaluation of arterial blood flow velocity requires cautious interpretation.