Adjustment For Multiple Comparisons Research Articles

Breast papillomas in the United States: single institution data on underrepresented minorities with a multi-institutional update on incidence

PurposeTo assess the percentage of papillomas from all biopsies performed, comparing differences in patient age and race at a single institution. To assess trends in biopsied papillomas at institutions throughout the United States (US). MethodsThis is a HIPPA-compliant IRB-approved single-institution (Southern1) retrospective review to assess race and age of all-modality-biopsied non-malignant papillomas as a percentage of all biopsies (percentage papillomas calculated as papilloma biopsies/all biopsies) from January 2012 to December 2019. To assess national variation, several academic or large referral centers were contacted to provide data regarding papilloma percentages, biopsy modalities, and trends in case numbers. Trends were estimated using the method of analysis of variance (ANOVA). Comparisons of differences in trends were assessed. ResultsSouthern1 institution demonstrated a significant association between race and percentage of papillomas (p < 0.0001). After adjustment for multiple comparisons with Bonferroni correction at 5% type I family error, the percentage of biopsied papillomas in Black and Asian patients remained significantly higher than in White patients (p < 0.0001 and p = 0.0032, respectively) using a Chi-square test. The regional variation in percentage of papillomas was found to be 3–9%. Southern1 institution showed a 7-year significant trend of increase in percentage of papillomas. Other institutions showed a decreasing trend (p < 0.05). ConclusionBlack and Asian women had significantly higher papilloma percentages compared to white patients in our single institution review. This institution also showed a statistically significant trend of increasing percentage papillomas from 2012 to 2019. Multi-institutional survey found regional variation in percentage papillomas, ranging from 3% to 9%.

Narcissistic Traits and Executive Functions.

Several personality disorders have been associated with cognitive impairment, including executive functions like working memory. Yet, it is unclear whether subclinical expression in non-clinical persons is associated with cognitive functioning. Recent studies indicate that non-clinical subjects might, in fact, perform better with increasing moderate to mild expressions of narcissistic features. We tested working memory performance in a cohort of n=70 psychiatrically and neurologically healthy subjects using Wechsler Adult Intelligence Scale (WAIS/WIE) subtests Arithmetic, Digit Span and Letter-Number Sequencing, and assessed narcissistic features using three different inventories: the widely used Narcissistic Personality Inventory (NPI), as well as two clinically used measures of narcissistic traits and states, respectively, derived from schema-focused therapy, i.e., the Young Schema Questionnaire (YSQ) entitlement/grandiosity subscale and the Schema Mode Inventory (SMI) self-aggrandizer subscale. In accordance with our hypothesis, we found nominally significant positive correlations of WIE Arithmetic performance with NPI total score (Spearman’s rho=0.208; p=0.043) and SMI self-aggrandizer scale (Spearman’s rho=0.231; p=0.027), but findings did not survive false discovery rate (FDR) adjustment for multiple comparisons (pFDR=0.189 and pFDR=0.243, respectively). While our findings add to recent studies on cognitive performance in subclinical narcissism, they fail to demonstrate an association of cognitive performance with narcissistic traits across multiple working memory tests, indicating the need for additional study, including complementary executive functions in larger cohorts and ranges of phenotype expression.

Social status and susceptibility to wildfire smoke among outdoor-housed female rhesus monkeys: A natural experiment

IntroductionWildfire smoke (WFS) exposure is a growing threat to human health, and lower socioeconomic position (SEP) has been shown to increase pollution susceptibility. Studies of SEP-related susceptibility, however, are often compromised due to spatial confounding between lower-SEP and pollution. Here we examine outdoor-housed nonhuman primates, living in natural social hierarchy in a common location, born during years of high vs. low WFS, to examine the separate and combined effects of WFS and social rank, an analog to SEP, on lung and immune function. MethodsTwenty-one females were born during extreme WFS events in summer 2008; 22 were born in summer 2009, during low WFS. Pulmonary function and circulating cytokines were measured three years later, in adolescence. We estimated fine particulate (PM2.5) and ozone exposures during each animal's first 90 days and three years of age using regulatory data. Early-life social status was estimated using maternal rank at birth, as rank in females is relatively stable throughout life, and closely approximates mother's rank. We tested associations among WFS exposure, rank, and endpoints using linear regression and ANOVA. ResultsHigher WFS exposure in infancy was, on average, associated with lower functional residual capacity (FRC), residual volume (RV), tissue compliance (Ct), and IL-8 secretion in adolescence. Higher social rank conferred significantly higher expiratory reserve volume (ERV) and functional residual capacity (FRC) solely among those born in the high-WFS year (2008). Differences in effects of rank between years were not significant after adjustment for multiple comparisons. ConclusionsExposure to WFS in infancy generally conferred lower adolescent respiratory volumes and inflammatory cytokines. Higher rank conferred higher respiratory volumes only among females born during WFS, suggesting the possibility that the health benefits of rank may be more apparent under environmental challenge.

ABO Blood Group Differentials on Survival in Hepatocellular Carcinoma Patients Treated with Chemoembolization

Background:The association between ABO blood group and the prognosis of hepatocellular carcinoma (HCC) remains unclear. We investigated the impact of ABO blood groups as a prognostic factor in HCC patients treated with transarterial chemoembolization (TACE). Materials and methods:We revisited records of all HCC patients who underwent TACE between January 2007 and December 2019 at a tertiary care hospital. The inclusion criteria were HCC patients, Child-Pugh score A5-B7, and treated with TACE monotherapy. The baseline characteristics of each patient were compared against their blood group and the survival analysis was carried out using Cox’s regression. With Bonferroni adjustment for multiple comparisons, P-values <.0125 were considered statistically significant. Results:Of 211 eligible patients, the frequencies of blood groups O, A, B, and AB were 89, 54, 56, and 12, respectively. Their respective months of median survival were 41, 20, 21, and 42. After adjustments in the six-and-twelve criteria and Child-Pugh scores, and using blood group O as the referent group, the coefficients (SE) of groups A, B, and AB were 0.69 (0.24), 0.47 (0.23), and 0.49 (0.49), respectively. A significant difference in survival was found only between patients with blood group O vs A (hazard ratio, 2.00; confidence interval, 1.25-3.21). Conclusions:ABO blood group is associated with the prognosis of HCC patients treated with TACE monotherapy. In our data, patients with blood group O tended to have the best survival. However, only blood group A patients had a significantly shorter survival rate comparing to blood group O.

Causal considerations can inform the interpretation of surprising associations in medical registries

ABSTRACT: An exploratory analysis of registry data from 2437 patients with advanced gastric cancer revealed a surprising association between astrological birth sign and overall survival (OS) with p = 0.01. After dichotomizing or changing the reference sign, p-values <0.05 were observed for several birth signs following adjustments for multiple comparisons. Bayesian models with moderately skeptical priors still pointed to these associations. A more plausible causal model, justified by contextual knowledge, revealed that these associations arose from the astrological sign association with seasonality. This case study illustrates how causal considerations can guide analyses through what would otherwise be a hopeless maze of statistical possibilities.

Beyond the 21-cm Notch-to-nipple Myth: Golden Proportions in Breast Aesthetics.

Background:The 21-cm notch-to-nipple distance has been accepted without academic scrutiny as a key measure in breast aesthetics. The Fibonacci sequence and phi ratio occur frequently in nature. They have previously been used to assess aesthetics of the face, but not the breast. This study aims to assess if the static 21-cm measure or the proportional phi ratio is associated with ideal breast aesthetics.Method:Subclavicular-breast height and breast width were used to calculate the aesthetic ratio. Subjects were subsequently aesthetically rated. A one-sample t-test was used to determine if the ratio for each breast differed from phi. Breast scores with one, both, or no breasts were compared with an optimal phi ratio. Analysis of variance was performed. Tukey–Kramer adjustment for multiple comparisons was used when pairwise comparisons were conducted.Results:Five subjects (14%) had bilateral optimal phi ratio breasts. Four subjects (11%) had one breast with an optimal phi ratio. Subjects with bilateral optimal phi ratios had significantly higher overall breast scores than those with only one optimal breast (Δ = 0.86, P = 0.025) or no optimal breast (Δ = 0.73, P = 0.008). Distance from optimal Fibonacci nipple position was moderately to strongly correlated with aesthetic score (−0.630, P = 0.016). No correlation was found between 21-cm notch-to-nipple distance and aesthetic score.Conclusion:The bilateral optimal phi ratio is correlated with high overall aesthetic scores, as is the optimal Fibonacci nipple position. No correlation was found between 21-cm notch-to-nipple distance and overall aesthetic score.

Adherence to Mediterranean diet and its associations with circulating cytokines, musculoskeletal health and incident falls in community-dwelling older men: The Concord Health and Ageing in Men Project

Mediterranean dietary patterns may exert favourable effects on various health conditions. This study aimed to determine associations of adherence to Mediterranean diet as well as its components, with circulating cytokine levels, musculoskeletal health and incident falls in community-dwelling older men. Seven hundred ninety-four (794) community-dwelling men with mean age 81.1±4.5 years, who participated in the five-year follow-up of the Concord Health and Ageing in Men Project (CHAMP) were included in the cross-sectional analysis, and 616 attended follow-up three years later. Adherence to Mediterranean diet was assessed using MEDI-LITE (literature-derived Mediterranean diet) score which was obtained using a validated diet history questionnaire. Twenty-four evaluable circulating cytokines were analyzed using Bio-Plex Pro Human Cytokine 27-plex Assay kit. Appendicular lean mass (ALM) and bone mineral density (BMD) were measured using dual-energy x-ray absorptiometry (DXA). Three-year changes in gait speed and hand grip strength were assessed by walking a 6-m course and using a dynamometer respectively and analyzed using linear mixed-effects models. Incident falls over three years were determined through telephone interviews every four months. Multivariable linear regression was utilized to determine the cross-sectional associations between MEDI-LITE scores and circulating cytokines, bone mineral density, ALM, and ALMBMI. Linear mixed-effects models were performed to estimate associations between MEDI-LITE scores and three-year change in hand grip strength and gait speed while negative binomial regression was applied to estimate associations between MEDI-LITE scores and three-year incident falls as well as associations between each MEDI-LITE component and three-year incident falls. Adjustments for multiple comparisons were performed using Benjamini-Hochberg adjustment for multiple testing. A higher MEDI-LITE score, indicating greater adherence to Mediterranean diet, was associated with higher appendicular lean mass adjusted for body mass index (ALMBMI) (β: 0.004kg; 95% CI: 0.000, 0.008), and lower incident falls rates (IRR: 0.94; 95% CI: 0.89, 0.99). Higher consumption of monounsaturated fatty acids (IRR: 0.76; 95% CI: 0.59, 0.98) and monounsaturated fatty acids to saturated fatty acids ratio (IRR: 0.72; 95% CI: 0.57, 0.90) were associated with 24%, and 28% lower falls risk in older men respectively. MEDI-LITE scores were not associated with BMD or physical function parameters. Adherence to a Mediterranean diet is associated with higher ALMBMI, and fewer falls in community-dwelling older men. Monounsaturated and saturated fatty acids were the most important contributors to the association between Mediterranean diet and falls risk.

Parental Life Span and Polygenic Risk Score of Longevity Are Associated With White Matter Hyperintensities.

Human longevity is moderately heritable and is hence influenced by both genetic and environmental factors. However, there remains considerable uncertainty regarding its relationship with brain aging. Here, we used a discovery sample (N = 19 136, aged 45-81 years) from the UK Biobank and a replication sample (N = 809, aged 66-93 years) from the Sydney Memory and Ageing Study and the Older Australian Twins Study to investigate the associations between both parental life span (parental age at death) and polygenic risk score (PRS) for longevity (longevity-PRS) and structural magnetic resonance imaging brain metrics, which are considered to reflect the brain aging process, namely white matter hyperintensities (WMHs), total gray matter, and cortical volumes. We found lower volumes of WMHs to be significantly associated with longer parental life span in the discovery (whole WMH, β = -0.0323, padj = .0002) and replication samples (whole WMH, β = -0.0871, padj = .0208) and higher longevity-PRS in the discovery sample (whole WMH, β = -0.0331, padj = .0015) and a similar trend in the replication sample (significant before multiple comparison adjustment). The association of longevity-PRS with WMH remained significant after removing the influence of the apolipoprotein E locus (whole WMH, β = -0.0297, padj = .0048). While total gray matter and cortical volumes were related to parental life span in the discovery sample, they were not significantly associated with longevity-PRS. Additionally, the effects of longevity-PRS on the association were more prominent in males. Our findings suggest that enrichment of longevity-related alleles may provide some protection against WMH burden and highlight the important aspect of genetic relationship between longevity and WMH.

Snacking on Almonds Lowers Glycaemia and Energy Intake Compared to a Popular High-Carbohydrate Snack Food: An Acute Randomised Crossover Study.

Consuming nuts may have advantages over other snack foods for health and body-weight regulation. Suggested mechanisms include increased satiety and lower glycaemia. We used an acute randomised crossover trial to assess glycaemic and appetite responses to consuming two isocaloric snacks (providing 10% of participants’ total energy requirements or 1030 kJ (equivalent to 42.5 g almonds), whichever provided greater energy): raw almonds and sweet biscuits among 100 participants with available data (25 males and 75 females) following 106 being randomised. Two hours after consuming a standardised breakfast, participants consumed the snack food. Finger-prick blood samples measuring blood glucose and subjective appetite ratings using visual analogue scales were taken at baseline and at 15 or 30 min intervals after consumption. Two hours after snack consumption, an ad libitum lunch was offered to participants and consumption was recorded. Participants also recorded food intake for the remainder of the day. The mean area under the blood glucose response curve was statistically and practically significantly lower for almonds than biscuits (mean (95% CI) difference: 53 mmol/L.min (45, 61), p < 0.001). Only the composite appetite score at 90 min was higher in the almond treatment compared to the biscuit treatment (45.7 mm vs. 42.4 mm, p = 0.035 without adjustment for multiple comparisons). There was no evidence of differences between the snacks for all other appetite ratings or for energy intake at the ad libitum lunch. However, mean energy intakes following snack consumption were significantly lower, both statistically and in practical terms, for the almond treatment compared to the biscuit (mean (95% CI) diff: 638 kJ (44, 1233), p = 0.035). Replacing popular snacks with almonds may have advantages in terms of glycaemia and energy balance.

Increased Impact of Air Pollution on Lung Function in Preterm versus Term Infants: The BILD Study.

Rationale: Infants born prematurely have impaired capacity to deal with oxidative stress shortly after birth. Objectives: We hypothesize that the relative impact of exposure to air pollution on lung function is higher in preterm than in term infants. Methods: In the prospective BILD (Basel-Bern Infant Lung Development) birth cohort of 254 preterm and 517 term infants, we investigated associations of particulate matter ⩽10 μm in aerodynamic diameter (PM10) and nitrogen dioxide with lung function at 44 weeks' postconceptional age and exhaled markers of inflammation and oxidative stress response (fractional exhaled nitric oxide [FeNO]) in an explorative hypothesis-driven study design. Multilevel mixed-effects models were used and adjusted for known confounders. Measurements and Main Results: Significant associations of PM10 during the second trimester of pregnancy with lung function and FeNO were found in term and preterm infants. Importantly, we observed stronger positive associations in preterm infants (born 32-36 wk), with an increase of 184.9 (95% confidence interval [CI], 79.1-290.7) ml/min [Formula: see text]e per 10-μg/m3 increase in PM10, than in term infants (75.3; 95% CI, 19.7-130.8 ml/min) (pprematurity × PM10 interaction = 0.04, after multiple comparison adjustment padj = 0.09). Associations of PM10 and FeNO differed between moderate to late preterm (3.4; 95% CI, -0.1 to 6.8 ppb) and term (-0.3; 95% CI, -1.5 to 0.9 ppb) infants, and the interaction with prematurity was significant (pprematurity × PM10 interaction = 0.006, padj = 0.036). Conclusions: Preterm infants showed significantly higher susceptibility even to low to moderate prenatal air pollution exposure than term infants, leading to increased impairment of postnatal lung function. FeNO results further elucidate differences in inflammatory/oxidative stress response when comparing preterm infants with term infants.

Assessing the association of common genetic variants in EPHB4 and RASA1 with phenotype severity in familial cerebral cavernous malformation.

BackgroundTo investigate whether common variants in EPHB4 and RASA1 are associated with cerebral cavernous malformation (CCM) disease severity phenotypes, including intracranial hemorrhage (ICH), total and large lesion counts.MethodsFamilial CCM cases enrolled in the Brain Vascular Malformation Consortium were included (n = 338). Total lesions and large lesions (≥5 mm) were counted on MRI; clinical history of ICH at enrollment was assessed by medical records. Samples were genotyped on the Affymetrix Axiom Genome‐Wide LAT1 Human Array. We tested the association of seven common variants (three in EPHB4 and four in RASA1) using multivariable logistic regression for ICH (odds ratio, OR) and multivariable linear regression for total and large lesion counts (proportional increase, PI), adjusting for age, sex, and three principal components. Significance was based on Bonferroni adjustment for multiple comparisons (0.05/7 variants = 0.007).Results EPHB4 variants were not significantly associated with CCM severity phenotypes. One RASA1 intronic variant (rs72783711 A>C) was significantly associated with ICH (OR = 1.82, 95% CI = 1.21–2.37, p = 0.004) and nominally associated with large lesion count (PI = 1.17, 95% CI = 1.03–1.32, p = 0.02).ConclusionA common RASA1 variant may be associated with ICH and large lesion count in familial CCM. EPHB4 variants were not associated with any of the three CCM severity phenotypes.

The Role of Age on Beta-Amyloid1–42 Plasma Levels in Healthy Subjects

Beta-amyloid (Aβ) plaques have been observed in the brain of healthy elderlies with frequencies strongly influenced by age. The aim of the study is to evaluate the role of age and other biochemical and hematological parameters on Aβ1–42 plasma levels in cognitively and neurologically normal individuals. Two-hundred and seventy-five normal subjects stratified by age groups (<35 years, 35–65 years, and >65 years) were included in the study. Aβ1–42 plasma levels significantly correlated with age (rs = 0.27; p < 0.0001) in the whole sample, inversely correlated with age in the first age group (rs = −0.25, p = 0.01), positively correlated in the second group (rs = 0.22, p = 0.03), while there was no significant correlation in the older group (rs = 0.02, p = 0.86). Both age (β-estimate = 0.08; p < 0.001) and cholesterol (β-estimate = 0.03; p = 0.009) were significantly associated with Aβ1–42 plasma level in multivariable analysis. However, only the association with age survived post hoc adjustment for multiple comparisons. The different effects of age on the Aβ level across age groups should be explored in further studies to better understand the age-dependent variability. This could better define the value of plasma Aβ as a biomarker of the Alzheimer neuropathology.

Microbial Cell-Free DNA Identifies Etiology of Bloodstream Infections, Persists Longer Than Conventional Blood Cultures, and Its Duration of Detection Is Associated With Metastatic Infection in Patients With Staphylococcus aureus and Gram-Negative Bacteremia

Microbial cell-free DNA (mcfDNA) sequencing of plasma can identify the presence of a pathogen in a host. In this study, we evaluated the duration of pathogen detection by mcfDNA sequencing vs conventional blood culture in patients with bacteremia. Blood samples from patients with culture-confirmed bloodstream infection were collected within 24 hours of the index positive blood culture and 48 to 72 hours thereafter. mcfDNA was extracted from plasma, and next-generation sequencing was applied. Reads were aligned against a curated pathogen database. Statistical significance was defined with Bonferroni adjustment for multiple comparisons (P < .0033). A total of 175 patients with Staphylococcus aureus bacteremia (n = 66), gram-negative bacteremia (n = 74), or noninfected controls (n = 35) were enrolled. The overall sensitivity of mcfDNA sequencing compared with index blood culture was 89.3% (125 of 140), and the specificity was 74.3%. Among patients with bacteremia, pathogen-specific mcfDNA remained detectable for significantly longer than conventional blood cultures (median 15 days vs 2 days; P < .0001). Each additional day of mcfDNA detection significantly increased the odds of metastatic infection (odds ratio, 2.89; 95% confidence interval, 1.53-5.46; P = .0011). Pathogen mcfDNA identified the bacterial etiology of bloodstream infection for a significantly longer interval than conventional cultures, and its duration of detection was associated with increased risk for metastatic infection. mcfDNA could play a role in the diagnosis of partially treated endovascular infections.

Adverse Events Following One Dose of mRNA COVID-19 Vaccination Among US Nursing Home Residents With and Without a Previous SARS-CoV-2 Infection

ObjectivesTo compare rates of adverse events following Coronavirus Disease 2019 (COVID-19) vaccination among nursing home residents with and without previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DesignProspective cohort. Setting and ParticipantsA total of 20,918 nursing home residents who received the first dose of messenger RNA COVID-19 vaccine from December 18, 2020, through February 14, 2021, in 284 facilities within Genesis Healthcare, a large nursing home provider spanning 24 US states. MethodsWe screened the electronic health record for adverse events, classified by the Brighton Collaboration, occurring within 15 days of a resident’s first COVID-19 vaccine dose. All events were confirmed by physician chart review. To obtain risk ratios, multilevel logistic regression model that accounted for clustering (variability) across nursing homes was implemented. To balance the probability of prior SARS-CoV-2 infection (previous positive test or diagnosis by the International Classification of Diseases, 10th Revision, Clinical Modification) more than 20 days before vaccination, we used inverse probability weighting. To adjust for multiplicity of adverse events tested, we used a false discovery rate procedure. ResultsStatistically significant differences existed between those without (n = 13,163) and with previous SARS-CoV-2 infection [symptomatic (n = 5617) and asymptomatic (n = 2138)] for all baseline characteristics assessed. Only 1 adverse event was reported among those with previous SARS-CoV-2 infection (asymptomatic), venous thromboembolism [46.8 per 100,000 residents 95% confidence interval (CI) 8.3–264.5], which was not significantly different from the rate reported for those without previous infection (30.4 per 100,000 95% CI 11.8–78.1). Several other adverse events were observed for those with no previous infection, but were not statistically significantly higher than those reported with previous infection after adjustments for multiple comparisons. Conclusions and ImplicationsAlthough reactogenicity increases with preexisting immunity, we did not find that vaccination among those with previous SARS-CoV-2 infection resulted in higher rates of adverse events than those without previous infection. This study stresses the importance of monitoring novel vaccines for adverse events in this vulnerable population.

The impact of COVID-19 on complementary and alternative medicine providers: A cross-sectional survey in Norway

BackgroundThe Norwegian authorities decided in March 2020 to implement a nationwide lockdown to prevent spread of the COVID-19 virus. The lockdown had vast socioeconomic consequences for the society. The aim of this study was to investigate how COVID-19 affected Complementary and Alternative Medicine (CAM) providers’ practice, financial situation, recommendations to patients, and how they perceived their future practice as CAM providers. MethodData were collected in this cross-sectional survey using a self-administrated electronic questionnaire. A total of 581 CAM providers completed the questionnaire, which was designed to describe consequences for CAM providers and their clinical practice caused by the nationwide lockdown. Descriptive statistics were carried out using frequency analyses to describe the demographics and consequences of the lockdown. Between group differences (gender and age) were analyzed using Pearson chi-square tests and Fisher’s exact tests for categorical variables, and ANOVA tests and t-tests for continuous variables. Significance level was defined as p < 0.05 without adjustment for multiple comparisons. ResultDuring the nationwide lockdown of Norway, 38.4% of the respondents were able to provide CAM treatment to their patients. Of those, the majority (96.4%) had reorganized their clinical practice in accordance with COVID-19 hygiene regulations, offered video consultations (57.4%) or telephone consultations (46.6%). To manage financially during the lockdown, half of the providers spent their savings (48.7%). More than one third (35.1%) was supported by their partner, and 26.7% received compensation from the Norwegian state. A total of 26.3% of the CAM providers had other paid work that provided them with income. Nearly a fifth (18.6%) borrowed money from friends and family, changed their loan terms, or took out new bank loans. More than half (62.7%) expressed uncertainty about the future of their practice. CAM providers who had reorganized their practice to online consultations were more optimistic. ConclusionThe impact of COVID-19 on CAM providers was considerable. It adversely affected their clinical practice, financial situation, and view on their future practice. To ensure that the health needs of the Norwegian population regarding CAM use are met during pandemic times like COVID-19, it is recommended to support and train CAM providers in the development of online CAM services, as well as efficient implementation of infection prevention and control measures.

Effects of Exercise and Weight Loss on Proximal Aortic Stiffness in Older Adults With Obesity.

Obesity may accelerate age-related increases in aortic stiffness. Although aerobic exercise training generally has favorable effects on aortic structure and function, exercise alone may not be sufficient to improve aortic stiffness in older adults with obesity. We determined the effects of aerobic exercise training with and without moderate- to high-caloric restriction (CR) on the structure and function of the proximal aorta in 160 older (65-79 years) men and women with obesity (body mass index=30-45 kg/m2). Participants were randomly assigned to 1 of 3 groups: aerobic exercise training only (treadmill 4 days/week for 30 minutes at 65% to 70% of heart rate reserve; n=56), aerobic exercise training plus moderate CR (n=55), or aerobic exercise training plus more intensive CR (n=49) for 20 weeks. Aortic pulse wave velocity, aortic distensibility, and other measures of aortic structure and function were assessed by cardiovascular magnetic resonance imaging. Pearson correlation coefficients were examined to assess associations between changes in proximal aortic stiffness and changes in fitness, fatness, and other potential confounders. Weight loss in the aerobic exercise training plus moderate CR (-8.0 kg [95% CI, -9.17 to -6.87]) and aerobic exercise training plus more intensive CR (-8.98 kg [95% CI, -10.23 to -7.73) groups was significantly greater compared with the aerobic exercise training-only group (-1.66 kg [95% CI, -2.94 to -0.38]; P<0.017 for both). There were significant treatment effects for descending aorta distensibility (P=0.008) and strain (P=0.004) and aortic arch pulse wave velocity (P=0.01) with the aerobic exercise training plus moderate CR group having a 21% increase in distensibility (P=0.016) and an 8% decrease in pulse wave velocity (P=0.058). None of the aortic stiffness measures changed significantly in the aerobic exercise training-only or aerobic exercise training plus more intensive CR groups, and there were no significant changes in any other measure of aortic structure or function in these groups. Overall, increases in aortic distensibility were correlated with improvements in body weight and body fat distribution, but these associations were not statistically significant after adjustment for multiple comparisons. In older adults with obesity, combining aerobic exercise with moderate CR leads to greater improvements in proximal aortic stiffness than exercise alone. Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT01048736.

The bacterial microbiota of Hunner lesion interstitial cystitis/bladder pain syndrome.

To undertake the first comprehensive evaluation of the urinary microbiota associated with Hunner lesion (HL) interstitial cystitis/bladder pain syndrome (IC/BPS). Despite no previous identification of a distinct IC/BPS microbial urotype, HL IC/BPS, an inflammatory subtype of IC/BPS, was hypothesized most likely to be associated with a specific bacterial species or microbial pattern. The bacterial microbiota of midstream urine specimens from HL IC/BPS and age- and gender-matched IC/BPS patients without HL (non-HL IC/BPS) were examined using the pan-bacterial domain clinical-level molecular diagnostic Pacific Biosciences full-length 16S gene sequencing protocol, informatics pipeline and database. We characterized the differential presence, abundances, and diversity of species, as well as gender-specific differences between and among HL and non-HL IC/BPS patients. A total of 59 patients with IC/BPS were enrolled (29 HL, 30 non-HL; 43 women, 16 men) from a single centre and the microbiota in midstream urine specimens was available for comparison. The species abundance differentiation between the HL and non-HL groups (12 species) was not significantly different after Bonferroni adjustments for multiple comparisons. Similarly, the nine differentiating species noted between female HL and non-HL patients were not significantly different after similar statistical correction. However, four species abundances (out of the 10 species differences identified prior to correction) remained significantly different between male HL and non-HL subjects: Negativicoccus succinivorans, Porphyromonas somerae, Mobiluncus curtisii and Corynebacterium renale. Shannon diversity metrics showed significantly higher diversity among HL male patients than HL female patients (P = 0.045), but no significant diversity differences between HL and non-HL patients overall. We were not able to identify a unique pathogenic urinary microbiota that differentiates all HL from all non-HL IC/BPS. It is likely that the male-specific differences resulted from colonization/contamination remote from the bladder. We were not able to show that bacteria play an important role in patients with HL IC/BPS.

Effect of Aerobic Exercise on White Matter Tract Microstructure in Young and Middle-Aged Healthy Adults

Recent evidence suggests that being physically active can mitigate age-related white matter (WM) changes. In a randomized clinical trial, the effect of 6-month aerobic exercise (AE) or stretching/toning interventions on measures of WM microstructure (WMM) was assessed in a sample of 74 adults aged 20–67 years. Major WM pathways were reconstructed. No significant group-level change in WM tract microstructure following an AE training was observed. Without adjustment for multiple comparisons, an increase in fractional anisotropy (FA) and a decrease in mean diffusivity (MD) of the uncinate fasciculus were observed post-intervention in the AE group in comparison with the stretching group. In the AE group, a significant increase in cardiorespiratory fitness was measured but did not correlate with FA and MD change. The present results of this study are in accordance with similar studies in healthy adults that did not show significant benefit on WMM after participating in an AE program.Clinical Trial Registration: Clinicaltrials.gov identifier, NCT01179958.

Abstract LB079: Circulating plasma phospholipid fatty acid levels &amp; breast cancer risk in the CPS-II Nutrition Cohort

Abstract Circulating plasma phospholipid fatty acid levels and breast cancer risk in the CPS-II Nutrition Cohort Background The association between dietary fat intake and breast cancer risk has been a source of controversy with conflicting results reported in past decades. Additional prospective studies that objectively measure circulating levels of fatty acids are now needed to better understand the associations between dietary fat and breast cancer development. MethodsWe assessed the relation between breast cancer risk and plasma levels of 60 phospholipid fatty acids in a nested case-control study of 2,718 postmenopausal women (905 breast cancer cases and 1,813 matched controls) enrolled in the Cancer Prevention Study II (CPS-II) Nutrition Cohort. Blood samples were collected at baseline (1997-1998). Multivariable-adjusted conditional logistic regression models that included established breast cancer risk factors (alcohol use, postmenopausal hormone use, smoking status, waist circumference, body mass index, and weight change from age 18 years to blood draw) were used to compute odds ratios (OR) and 95% confidence intervals (CI). The false discovery rate (FDR; q-value) was computed to control for multiple comparisons. ResultsAfter adjustment for multiple comparisons and in continuous log-transformed multivariable models, plasma levels of myristic acid (a saturated fatty acid) were positively associated with breast cancer risk (OR per log-value, 1.17, 95% CI: 1.07-1.28; q-value = 0.03), with similar magnitude associations found for estrogen receptor (ER) positive and ER negative breast cancer (p-interaction = 0.39). Positive associations were also found for plasma levels of monounsaturated fatty acid (OR per log-value, 1.09, 95% CI: 1.00-1.18; q-value = 0.24), palmitoleic acid (OR per log-value, 1.14, 95% CI: 1.04-1.24; q-value = 0.09), palmitic acid (OR per log-value, 1.12, 95% CI: 1.01-1.24; q-value = 0.17), dihomo-γ-linolenic acid (OR per log-value, 1.14, 95% CI: 1.04-1.25; q-value = 0.09), and adrenic acid (OR per log-value, 1.13, 95% CI: 1.03-1.24; q-value = 0.11) with breast cancer risk; however, after adjustment for multiple comparisons these associations did not reach the threshold of statistical significance. Similarly, inverse associations between plasma levels of trans α-linolenic acid (OR per log-value, 0.85, 95% CI: 0.76-0.96; q-value = 0.09), heptadecanoic acid (OR per log-value, 0.90, 95% CI: 0.82-0.99; q-value = 0.17), and vaccenic acid (OR per log-value, 0.88, 95% CI: 0.80-0.97; q-value = 0.11) with breast cancer risk were not statistically significant after adjustment for multiple comparisons. ConclusionThese findings suggest that higher circulating levels of myristic acid, that can be sourced from dietary intake of dairy foods or via de novo synthesis, may increase breast cancer risk. Additional studies are needed to replicate this finding and provide mechanistic insights. Citation Format: Michele Matta, Emily Deubler, Veronique Chajès, Marc Gunter, Neil Murphy, Mia M. Gaudet. Circulating plasma phospholipid fatty acid levels &amp; breast cancer risk in the CPS-II Nutrition Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB079.

Mortality Before and After Border Wall Construction Along the US-Mexico Border, 1990-2017.

Objectives. To evaluate changes in mortality in US counties along the US-Mexico border in which there was substantial new border wall construction after the Secure Fence Act of 2006 relative to border counties in which there was no such border wall construction. Methods. Using complete 1990 to 2017 mortality microdata and a quasi-experimental difference-in-differences design, we evaluated changes in overall (all-cause) mortality, mortality from drug overdose, and mortality from homicide in the 10 counties with substantial new border wall construction and 11 counties with no such construction. We fit a linear model, adjusting for population characteristics and county and year fixed effects, with Bonferroni adjustments for multiple comparisons. Sensitivity analyses included the addition of adjacent inland counties and modifications to the statistical model. Results. Relative to counties without substantial new border wall construction, counties in which a substantial amount of new border wall was constructed exhibited a nonsignificant 0.02-percentage-point increase (95% confidence interval [CI] = -0.06, 0.10; P > .99) in overall mortality after construction. Border wall construction was not associated with changes in either deaths from overdose or deaths from homicide. Conclusions. Wall construction along the US-Mexico border after the Secure Fence Act of 2006 was not associated with discernible changes in mortality.