Two-site microendoscopic imaging probe for simultaneous three-dimensional imaging at two anatomic locations in tissues.

Systems that can image in three dimensions at cellular resolution and across different locations within an organism may enable insights into complex biological processes, such as immune responses, for which a single location measurement may be insufficient. In this Letter, we describe an in vivo two-site imaging probe (TIP) that can simultaneously image two anatomic sites with a maximum separation of a few centimeters. The TIP consists of two identical bendable graded index (GRIN) lenses and is demonstrated by a two-photon two-color fluorescence imaging system. Each GRIN lens has a field of view of 162 × 162 × 170 µm3, a nominal numerical aperture of 0.5, a magnification of 0.7, and working distances of 0.2 mm in air for both ends. A blind linear unmixing algorithm is applied to suppress bleedthrough between channels. We use this system to successfully demonstrate two-site two-photon two-color imaging of two biomedically relevant samples, i.e., (1) a mixture of two autofluorescent anti-cancer drugs and (2) a live hybrid tumor consisting of two spectrally distinct fluorescent cell lines.

Novelty preference assessed by eye tracking: A sensitive measure of impaired recognition memory in epilepsy.

OBJECTIVE: Epilepsy patients often report memory deficits despite normal objective testing, suggesting that available measures are insensitive or that non-mnemonic factors are involved. The Visual Paired Comparison Task (VPCT) assesses novelty preference, the tendency to fixate on novel images rather than previously viewed items, requiring recognition memory for the "old" images. As novelty preference is a sensitive measure of hippocampal-dependent memory function, we predicted impaired VPCT performance in epilepsy patients compared to healthy controls. METHODS: We assessed 26 healthy adult controls and 31 epilepsy patients (16 focal-onset, 13 generalized-onset, 2 unknown-onset) with the VPCT using delays of 2 or 30 s between encoding and recognition. Fifteen healthy controls and 17 epilepsy patients (10 focal-onset, 5 generalized-onset, 2 unknown-onset) completed the task at 2-, 5-, and 30-minute delays. Subjects also performed standard memory measures, including the Medical College of Georgia (MCG) Paragraph Test, California Verbal Learning Test-Second Edition (CVLT-II), and Brief Visual Memory Test-Revised (BVMT-R). RESULTS: The epilepsy group was high functioning, with greater estimated IQ (p = 0.041), greater years of education (p = 0.034), and higher BVMT-R scores (p = 0.024) compared to controls. Both the control group and epilepsy cohort, as well as focal- and generalized-onset subgroups, had intact novelty preference at the 2- and 30-second delays (p-values ≤ 0.001) and declined at 30 min (p-values > 0.05). Only the epilepsy patients had early declines at 2- and 5-minute delays (controls with intact novelty preference at p = 0.003 and p ≤ 0.001, respectively; epilepsy groups' p-values > 0.05). CONCLUSIONS: Memory for the "old" items decayed more rapidly in overall, focal-onset, and generalized-onset epilepsy groups. The VPCT detected deficits while standard memory measures were largely intact, suggesting that the VPCT may be a more sensitive measure of temporal lobe memory function than standard neuropsychological batteries.

WNT2 activation through proximal germline deletion predisposes to small intestinal neuroendocrine tumors and intestinal adenocarcinomas.

Many hereditary cancer syndromes are associated with an increased risk of small and large intestinal adenocarcinomas. However, conditions bearing a high risk to both adenocarcinomas and neuroendocrine tumors are yet to be described. We studied a family with 16 individuals in four generations affected by a wide spectrum of intestinal tumors, including hyperplastic polyps, adenomas, small intestinal neuroendocrine tumors, and colorectal and small intestinal adenocarcinomas. To assess the genetic susceptibility and understand the novel phenotype, we utilized multiple molecular methods, including whole genome sequencing, RNA sequencing, single cell sequencing, RNA in situ hybridization and organoid culture. We detected a heterozygous deletion at the cystic fibrosis locus (7q31.2) perfectly segregating with the intestinal tumor predisposition in the family. The deletion removes a topologically associating domain border between CFTR and WNT2, aberrantly activating WNT2 in the intestinal epithelium. These consequences suggest that the deletion predisposes to small intestinal neuroendocrine tumors and small and large intestinal adenocarcinomas, and reveals the broad tumorigenic effects of aberrant WNT activation in the human intestine.

Humoral profiling of pediatric patients with cancer reveals robust immunity following anti-SARS-CoV-2 vaccination superior to natural infection.

BACKGROUND: Pediatric patients with cancer infected with COVID-19 may be at higher risk of severe disease and may be unable to mount an adequate response to the virus due to compromised immunity secondary to their cancer therapy. PROCEDURE: This study presents immunologic analyses of 20 pediatric patients with cancer, on active chemotherapy or having previously received chemotherapy, and measures their immunoglobulin titers and activation of cellular immunity response to acute SARS-CoV-2 infection and COVID-19 vaccination compared with healthy pediatric controls. RESULTS: Forty-three patients were enrolled, of which 10 were actively receiving chemotherapy, 10 had previously received chemotherapy, and 23 were healthy controls. Pediatric patients with cancer had similar immunoglobulin titers, antibody binding capacity, and effector function assay activity after vaccination against COVID-19 compared with healthy controls, though more variability in response was noted in the cohort actively receiving chemotherapy. Compared with acute infection, vaccination against COVID-19 produced superior immunoglobulin responses, particularly IgA1, IgG1, and IgG3, and elicited superior binding capacity and effector function in children with cancer and healthy controls. CONCLUSIONS: Pediatric patients receiving chemotherapy and those who had previously received chemotherapy had adequate immune activation after both vaccination and acute infection compared to healthy pediatric controls, although there was a demonstrated variability in response for the patients on active chemotherapy. Vaccination against COVID-19 produced superior immune responses compared to acute SARS-CoV-2 infection in pediatric patients with cancer and healthy children, underscoring the importance of vaccination even in previously infected individuals.

Associations Among Physical Activity, Adiposity, and Insulin Resistance in Children Exposed In Utero to Maternal Obesity With and Without Gestational Diabetes.

PURPOSE: Investigate whether obesity risk and current weight status are independently associated with physical activity (PA) and whether PA is associated with adiposity and insulin resistance (homeostatic model assessment of insulin resistance) among children with high versus low obesity risk based on in utero exposure to maternal overweight/obesity with gestational diabetes mellitus (GDM; high risk) or without GDM (overweight/obesity; high risk) or maternal normal weight without GDM (low risk). METHOD: Secondary analysis of data from children born to women with overweight/obesity and GDM, overweight/obesity without GDM, or normal weight without GDM. PA was assessed with accelerometry, percentage of body fat derived from anthropometrics, and homeostatic model assessment of insulin resistance calculated from glucose and insulin. RESULTS: Among 4- to 10-year-old children (N = 163), analyses of covariance showed that children with a current BMI ≥85th percentile had less vigorous PA than those with BMI <85th percentile, but in utero exposure was not an independent predictor of PA. In linear regression modeling, moderate to vigorous PA was inversely associated with percentage of body fat and homeostatic model assessment of insulin resistance independent of age, Tanner stage, and accelerometer wear time, with stronger associations in high-risk groups. CONCLUSIONS: Children's PA is related to current weight status but not underlying risk for obesity but may be especially important to reduce obesity and insulin resistance in high-risk children.

In-scanner head motion and structural covariance networks.

In-scanner head motion systematically reduces estimated regional gray matter volumes obtained from structural brain MRI. Here, we investigate how head motion affects structural covariance networks that are derived from regional gray matter volumetric estimates. We acquired motion-affected and low-motion whole brain T1-weighted MRI in 29 healthy adult subjects and estimated relative regional gray matter volumes using a voxel-based morphometry approach. Structural covariance network analyses were undertaken while systematically increasing the number of included motion-affected scans. We demonstrate that the standard deviation in regional gray matter estimates increases as the number of motion-affected scans increases. This increases pairwise correlations between regions, a key determinant for construction of structural covariance networks. We further demonstrate that head motion systematically alters graph theoretic metrics derived from these networks. Finally, we present evidence that weighting correlations using image quality metrics can mitigate the effects of head motion. Our findings suggest that in-scanner head motion is a source of error that violates the assumption that structural covariance networks reflect neuroanatomical connectivity between brain regions. Results of structural covariance studies should be interpreted with caution, particularly when subject groups are likely to move their heads in the scanner.

No evidence of EMAST in whole genome sequencing data from 248 colorectal cancers.

Microsatellite instability (MSI) is caused by defective DNA mismatch repair (MMR), and manifests as accumulation of small insertions and deletions (indels) in short tandem repeats of the genome. Another form of repeat instability, elevated microsatellite alterations at selected tetranucleotide repeats (EMAST), has been suggested to occur in 50% to 60% of colorectal cancer (CRC), of which approximately one quarter are accounted for by MSI. Unlike for MSI, the criteria for defining EMAST is not consensual. EMAST CRCs have been suggested to form a distinct subset of CRCs that has been linked to a higher tumor stage, chronic inflammation, and poor prognosis. EMAST CRCs not exhibiting MSI have been proposed to show instability of di- and trinucleotide repeats in addition to tetranucleotide repeats, but lack instability of mononucleotide repeats. However, previous studies on EMAST have been based on targeted analysis of small sets of marker repeats, often in relatively few samples. To gain insight into tetranucleotide instability on a genome-wide level, we utilized whole genome sequencing data from 227 microsatellite stable (MSS) CRCs, 18 MSI CRCs, 3 POLE-mutated CRCs, and their corresponding normal samples. As expected, we observed tetranucleotide instability in all MSI CRCs, accompanied by instability of mono-, di-, and trinucleotide repeats. Among MSS CRCs, some tumors displayed more microsatellite mutations than others as a continuum, and no distinct subset of tumors with the previously proposed molecular characters of EMAST could be observed. Our results suggest that tetranucleotide repeat mutations in non-MSI CRCs represent stochastic mutation events rather than define a distinct CRC subclass.

Methylphenidate for attention problems in epilepsy patients: Safety and efficacy.

Children with attention deficit hyperactivity disorder (ADHD) have an increased risk of seizures, and children with epilepsy have an increased prevalence of ADHD. Adults with epilepsy often have varying degrees of attentional dysfunction due to multiple factors, including anti-seizure medications, frequent seizures, interictal discharges, underlying lesions, and psychiatric comorbidities. Currently, there are no approved medications for the treatment of epilepsy-related attentional dysfunction. Methylphenidate (MPH) is a stimulant, FDA-approved for the treatment of ADHD, and often used for ADHD in the setting of pediatric epilepsy. Large database and registry studies indicate safety of MPH in children with ADHD and epilepsy, with no significant effect on seizure frequency. Small single-dose and open-label studies suggest efficacy of MPH in adults with epilepsy-related attention deficits. Methylphenidate represents a possible treatment for attentional dysfunction due to epilepsy, but large, randomized, placebo-controlled, double-blinded studies are needed.

High conservation combined with high plasticity: genomics and evolution of Borrelia bavariensis.

BACKGROUND: Borrelia bavariensis is one of the agents of Lyme Borreliosis (or Lyme disease) in Eurasia. The genome of the Borrelia burgdorferi sensu lato species complex, that includes B. bavariensis, is known to be very complex and fragmented making the assembly of whole genomes with next-generation sequencing data a challenge. RESULTS: We present a genome reconstruction for 33 B. bavariensis isolates from Eurasia based on long-read (Pacific Bioscience, for three isolates) and short-read (Illumina) data. We show that the combination of both sequencing techniques allows proper genome reconstruction of all plasmids in most cases but use of a very close reference is necessary when only short-read sequencing data is available. B. bavariensis genomes combine a high degree of genetic conservation with high plasticity: all isolates share the main chromosome and five plasmids, but the repertoire of other plasmids is highly variable. In addition to plasmid losses and gains through horizontal transfer, we also observe several fusions between plasmids. Although European isolates of B. bavariensis have little diversity in genome content, there is some geographic structure to this variation. In contrast, each Asian isolate has a unique plasmid repertoire and we observe no geographically based differences between Japanese and Russian isolates. Comparing the genomes of Asian and European populations of B. bavariensis suggests that some genes which are markedly different between the two populations may be good candidates for adaptation to the tick vector, (Ixodes ricinus in Europe and I. persulcatus in Asia). CONCLUSIONS: We present the characterization of genomes of a large sample of B. bavariensis isolates and show that their plasmid content is highly variable. This study opens the way for genomic studies seeking to understand host and vector adaptation as well as human pathogenicity in Eurasian Lyme Borreliosis agents.

Association of gestational diabetes with child feeding practices: A secondary analysis using data from mother-child dyads in the deep south.

BACKGROUND: The purpose of this study was to examine whether mothers with prior gestational diabetes (GDM) used different feeding practices for their children compared to those without prior GDM. We hypothesized that mothers with prior GDM would express a greater concern for their child's weight, and greater monitoring and restrictive feeding practices compared to non-diabetic mothers. METHODS: Data for this secondary analysis came from studies examining body composition and metabolism in children (aged 4-10 years) born to women with (N = 41) and without (N = 71) GDM. A Child Feeding Questionnaire (CFQ) was used to assess maternal perception of the child's weight and her feeding practices. Analysis of covariance was used to assess group differences in feeding practices, after adjusting for parent study code, maternal education, child BMI-z, and maternal age. RESULTS: In fully adjusted models, mothers with prior GDM did not express greater concern about their children's body weight as compared to those without prior GDM (P = 0.50). Restriction and pressure to eat also did not differ by group, and women with prior GDM reported less monitoring of their children's intake as compared to those without prior GDM (P < 0.05). CONCLUSION: There is no evidence from this study that women with prior GDM are more concerned about their children's body weight or endorse more restrictive feeding practices than do those without prior GDM. Future research should investigate whether women with prior GDM are aware that their children have greater risk for obesity and comorbid health problems, and develop interventions to support parents in efforts to mitigate this risk.

The Dynamic and Transient Immune Microenvironment in Locally Advanced Esophageal Adenocarcinoma Post Chemoradiation.

OBJECTIVE: The aim of this study was to assess the impact of chemoradiation on the immune microenvironment to influence and optimally design future neoadjuvant clinical trials. SUMMARY BACKGROUND DATA: Programmed death (PD)-1 inhibitors in metastatic gastroesophageal cancer have demonstrated response rates of approximately 25% in programmed death ligand-1 (PD-L1+) tumors. Unfortunately, the majority of patients do not respond. Therefore, a rationale strategy of combining immunotherapeutic agents with chemoradiation in earlier stage esophageal cancer may prevent metastatic disease in patients. METHODS: To determine the effects of chemoradiation on resected esophageal adenocarcinomas, we examined the immune microenvironment pre- and post-chemoradiation using immunohistochemistry, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and functional analysis of tumor-infiltrating lymphocytes. Additionally, to assess the duration and dependency of radiation-induced PD-L1 upregulation, a surgical rat reflux model of esophageal adenocarcinoma is used. First, tumor-bearing animals were dosed with single-fraction 13Gy or 16Gy radiation to determine safety, dose correlation, and PD-L1 upregulation using qRT-PCR post-radiation. Next, longitudinal PD-L1 expression levels within individual animals were determined using serial endoscopic biopsies at baseline, 1, 5, and 9 weeks post 16Gy radiation. RESULTS: The majority of cancers displayed enhanced interferon γ and activated CD8+ T lymphocytes at the tumor stroma interface. These tumors also demonstrated enhanced upregulation of PD-L1 and multiple other immune checkpoints including TIM3, GITR, IDO1, LAG3, OX40, and KIR. The animal model results indicated PD-L1 upregulation is dose-dependent and transiently elevated post radiation exposure. CONCLUSIONS: Collectively, these findings provide insights into the evolving immune landscape after chemoradiation and have significant implications for neoadjuvant trial designs that will combine radiotherapy with immune checkpoint inhibitors.

Serial Endoscopic Evaluation of Esophageal Disease in a Cancer Model: A Paradigm Shift for Esophageal Adenocarcinoma (EAC) Drug Discovery and Development.

A rat model of surgically induced reflux recapitulates the development and progression of human esophageal adenocarcinoma (EAC). In this study, reflux was induced in rats followed by postoperative endoscopy with biopsy, to diagnose and monitor disease progression. Overall, percentage agreement between visual endoscopy and gold standard histology was 95%, with disease-specific classification accuracies of 100% and 75% for Barrett's with dysplasia and EAC, respectively. Additionally, the percentage agreement for biopsy in tumors >4 mm was 75%. Thereby, establishing endoscopic evaluation as a reliable tool to assess disease progression and provide biopsies for downstream correlates in a de novo EAC model.

Pilot investigation: randomized-controlled analog trial for alcohol and tobacco smoking co-addiction using contingency management.

Contingency management (CM) is associated with decreases in off-target drug and alcohol use during primary target treatment. The primary hypothesis for this trial was that targeting alcohol use or tobacco smoking would yield increased abstinence in the opposite, nontargeted drug. We used a 2 [CM vs. noncontingent control (NC) for alcohol]×2 (CM vs. NC for smoking tobacco) factorial design, with alcohol intake (through urinary ethyl glucuronide) and tobacco smoking (through urinary cotinine) as the primary outcomes. Thirty-four heavy-drinking smokers were randomized into one of four groups, wherein they received CM, or equivalent NC reinforcement, for alcohol abstinence, smoking abstinence, both drugs, or neither drug. The CM for alcohol and tobacco group had only two participants and therefore was not included in analysis. Compared with the NC for alcohol and tobacco smoking group, both the CM for the tobacco smoking group [odds ratio (OR)=12.03; 95% confidence interval (CI): 1.50-96.31] and the CM for the alcohol group (OR=37.55; 95% CI: 4.86-290.17) submitted significantly more tobacco-abstinent urinalyses. Similarly, compared with the NC for the alcohol and tobacco group, both the CM for smoking (OR=2.57; 95% CI: 1.00-6.60) and the CM for alcohol groups (OR=3.96; 95% CI: 1.47-10.62) submitted significantly more alcohol-abstinent urinalyses. These data indicate cross-over effects of CM on indirect treatment targets. Although this is a pilot investigation, it could help to inform the design of novel treatments for alcohol and tobacco co-addiction.

Sep70/Pepsin expression in hypopharynx combined with hypopharyngeal multichannel intraluminal impedance increases diagnostic sensitivity of laryngopharyngeal reflux.

BACKGROUND: Improved methods of diagnosis of laryngopharyngeal reflux (LPR) would enable surgeons to better identify patients who may benefit from antireflux surgery (ARS). The objective of the present study was to assess if hypopharyngeal Pepsin and Sep70 expression combined with hypopharyngeal multichannel intraluminal impedance (HMII) has the potential to increase diagnostic sensitivity of LPR. METHODS: This study was performed on patients who underwent unsedated transnasal endoscopy with hypopharyngeal biopsy and 24-h HMII to determine abnormal proximal exposure (APE) and DeMeester score (DMS) from 2013 to 2016. Pepsin and Sep70 protein expression was assessed by Western blots of biopsy specimens. The outcomes of ARS were assessed using reflux symptom index (RSI). HMII APE classification, Sep 70, and Pepsin protein levels were compared in normative and symptomatic LPR patients and further analyzed alongside quality of life changes following ARS. RESULTS: Of 30 subjects enrolled, 23 were excluded for abnormal HMII results or endoscopic evidence of esophagitis. Seven subjects and 105 patients were included in the normative and symptomatic groups, respectively. Compared to the normative group, only Pepsin expression was significantly higher in the symptomatic group [APE+/LPR+ (p = 0.000), APE+/LPR- (p = 0.001), and APE- (p = 0.047)]. Further, the ratio of Sep70/Pepsin was significantly lower in the symptomatic group [APE+/LPR+ (p = 0.008), APE+/LPR- (p = 0.000), and APE- (p = 0.050)], and a cutoff ratio for a diagnosis of LPR was established as < 158. Of 105 symptomatic patients, 48 patients underwent ARS. Of these, 17 patients had complete pre- and post-RSI questionnaires. LPR symptoms improved in 15 (88%), of whom 2 were APE- but met criteria for a diagnosis of LPR based on the Sep70/Pepsin cutoff. CONCLUSIONS: The identified Sep70/Pepsin ratio may serve as a reliable biomarker for the diagnosis of LPR. As a result, this may help identify additional patients who have a false-negative HMII result due to the 24-h testing window.

Posttraumatic Stress, Coping Flexibility, and Risky Drinking Among Trauma-Exposed Male and Female College Students: The Mediating Effect of Delay of Gratification.

BACKGROUND: The co-occurence of posttraumatic stress (PTS) and risky drinking has been demonstrated in diverse populations, including college students. However, the mechanisms underlying this co-occurrence, as well as the protective factors that may reduce risky drinking among trauma-exposed college students have yet to be fully understood in the literature. OBJECTIVES: The present study builds upon self-regulation theories and previous empirical work to determine whether the effects of PTS and coping flexibility on risky drinking were mediated by delay of gratification among trauma-exposed college students. In addition, the potential moderating effect of gender on these relationships was examined. METHODS: Participants included 624 trauma-exposed college students (68.4% female) attending a public university in the southeast region of the United States. Data were collected through an online survey. The hypothesized model was examined using a multigroup structural equation modeling approach. RESULTS: As hypothesized, PTS had a significant, positive indirect effect on risky drinking through delay of gratification; however, the effect of PTS on delay of gratification was stronger for males than for females. Results also indicated that the indirect effect of coping flexibility on risky drinking through delay of gratification was significant and negative for males and females. Conclusions/Importance: The findings of this study suggest that delay of gratification might be an important mechanism underlying the co-occurrence of PTS and risky drinking. In addition, our results highlight the potential benefits of coping flexibility for college students coping with PTS.

Epigenetic-based combinatorial resveratrol and pterostilbene alters DNA damage response by affecting SIRT1 and DNMT enzyme expression, including SIRT1-dependent γ-H2AX and telomerase regulation in triple-negative breast cancer.

BACKGROUND: Nutrition is believed to be a primary contributor in regulating gene expression by affecting epigenetic pathways such as DNA methylation and histone modification. Resveratrol and pterostilbene are phytoalexins produced by plants as part of their defense system. These two bioactive compounds when used alone have been shown to alter genetic and epigenetic profiles of tumor cells, but the concentrations employed in various studies often far exceed physiologically achievable doses. Triple-negative breast cancer (TNBC) is an often fatal condition that may be prevented or treated through novel dietary-based approaches. METHODS: HCC1806 and MDA-MB-157 breast cancer cells were used as TNBC cell lines in this study. MCF10A cells were used as control breast epithelial cells to determine the safety of this dietary regimen. CompuSyn software was used to determine the combination index (CI) for drug combinations. RESULTS: Combinatorial resveratrol and pterostilbene administered at close to physiologically relevant doses resulted in synergistic (CI <1) growth inhibition of TNBCs. SIRT1, a type III histone deacetylase (HDAC), was down-regulated in response to this combinatorial treatment. We further explored the effects of this novel combinatorial approach on DNA damage response by monitoring γ-H2AX and telomerase expression. With combination of these two compounds there was a significant decrease in these two proteins which might further resulted in significant growth inhibition, apoptosis and cell cycle arrest in HCC1806 and MDA-MB-157 breast cancer cells, while there was no significant effect on cellular viability, colony forming potential, morphology or apoptosis in control MCF10A breast epithelial cells. SIRT1 knockdown reproduced the effects of combinatorial resveratrol and pterostilbene-induced SIRT1 down-regulation through inhibition of both telomerase activity and γ-H2AX expression in HCC1806 breast cancer cells. As a part of the repair mechanisms and role of SIRT1 in recruiting DNMTs, the effects of this combination treatment was also explored on DNA methyltransferases (DNMTs) expression. Interestingly, the compounds resulted in a significant down-regulation of DNMT enzymes with no significant effects on DNMT enzyme expression in MCF10A control cells. CONCLUSION: Collectively, these results provide new insights into the epigenetic mechanisms of a novel combinatorial nutrient control strategy that exhibits synergy and may contribute to future recalcitrant TNBC prevention and/or therapy.

Associations Between Estimates of Arterial Stiffness and Cognitive Functioning in Adults With HIV.

BACKGROUND: Vascular aging, a precursor of arterial stiffness, is associated with neurocognitive impairment (NCI) and cardiovascular disease. Although HIV is associated with rapid vascular aging, it is unknown whether arterial stiffness mediates changes in cognitive function. We explored whether estimated markers of vascular aging were associated with NCI indices in HIV-positive individuals. METHODS: This study was a secondary analysis of an observational study. Neurocognitive functioning was assessed using a battery of 7 domains (verbal fluency, executive functioning, speed of information processing, attention/working memory, memory [learning and delayed recall], and motor skills). Vascular aging was assessed using estimated markers of arterial stiffness (ie, estimated pulse wave velocity, pulse pressure, and vascular overload index). A multivariable regression adjusted for demographics, cardiovascular disease risk factors, and HIV clinical variables was used to examine the association between vascular aging and NCI outcomes. RESULTS: Among 165 people with HIV, the mean age was 51.5 ± 6.9 years (62% men and 83% African American/Black or Other). In fully adjusted models, an increase in estimated pulse wave velocity and pulse pressure was associated with lower T scores in learning (-2.95 [-5.13, -0.77]) and working memory (-2.37 [-4.36, -0.37]), respectively. An increase in vascular overload index was associated with lower T scores in working memory (-2.33 [-4.37, -0.29]) and learning (-1.85 [-3.49, -0.21]). CONCLUSIONS: Estimated markers of arterial stiffness were weakly associated with neurocognitive functioning, suggesting that vascular aging may have a role in cognitive decline among people with HIV.

Tracking activity-based therapy for people living with spinal cord injury or disease: insights gained through focus group interviews with key stakeholders.

PURPOSE: The development of a tool to track participation in activity-based therapy (ABT) for people with spinal cord injury or disease (SCI/D) was identified as a priority of the Canadian ABT Community of Practice. The objective of this study was to understand multi-stakeholder perspectives on tracking ABT participation across the continuum of care. MATERIALS AND METHODS: Forty-eight individuals from six stakeholder groups (persons living with SCI/D; hospital therapists; community trainers; administrators; researchers; and funders, advocates and policy experts) were recruited to participate in focus group interviews. Participants were asked open-ended questions concerning the importance of and parameters around tracking ABT. Transcripts were analyzed using conventional content analysis. RESULTS: Themes reflected the Who, What, Where, When, Why and How of tracking ABT. Participants described the importance of involving hospital therapists, community trainers and individuals with SCI/D in tracking ABT to capture both subjective and objective parameters across the continuum of care and injury trajectory. Digital tracking tools were favoured, although paper-based versions were regarded as a necessity in some circumstances. CONCLUSIONS: Findings highlighted the importance of tracking ABT participation for individuals with SCI/D. The information may guide the development of ABT practice guidelines and support the implementation of ABT in Canada.

Tracking the details of activity-based therapy (ABT) sessions and programs across the continuum of care and injury trajectory may provide important information to support the development of ABT practice guidelines and implementation strategies.Tracking objective and subjective parameters are needed to provide a comprehensive description of an ABT session and program.Clinicians and individuals with spinal cord injury or disease (SCI/D) should both be able to track ABT to accommodate all settings and types of data.Digital tracking tools, such as an app, may provide an accessible, versatile and efficient way of tracking ABT.