Adjustment For Multiple Comparisons Research Articles

Amplification rationale for hearing aids based on characteristics of the Japanese language

ObjectiveHearing aid amplification rationales have typically been developed by using global averages of the long-term average speech spectrum (LTASS) from Western European languages. However, there are few reports on hearing-aid amplification based on acoustic-phonetic characteristics of the Japanese language. This study’s objective is to investigate the LTASS for Japanese, and to compare a typical amplification rationale originally developed mainly for Western European languages with an amplification rationale specifically adjusted to the LTASS for Japanese. MethodsLTASS for two speech materials provided by four Japanese talkers were analyzed using 1/3 octave bandwidth filters. The speech was recorded with different levels of vocal effort, yielding three LTASS for “soft”, “moderate” and “loud” speech. From these results, a gain offset of the hearing-aid amplification for Japanese was obtained as compared to ANSI S3.5. Speech intelligibility for an amplification rationale for Western European languages and the newly-developed Japanese version was obtained for presentation levels of 50 dB SPL, 65 dB SPL and 80 dB SPL. Nineteen people with mild to moderate hearing loss participated in the speech intelligibility experiment. Scores in% correct were arcsine-transformed and subjected to repeated measures ANOVA with pairwise comparisons of significant main effects using Bonferroni adjustments for multiple comparisons. ResultsThe LTASS for Japanese was slightly different from the values of previous reports. A comparison of LTASS values to ANSI S3.5 with values for Japanese showed that the Japanese amplification rationale for “moderate” speech levels required more gain in the low-frequency area, and less gain in the high-frequency area. There was no significant difference in the speech intelligibility level between the amplification characteristics of Western European languages and Japanese language at each presentation level. ConclusionIt was shown that for hearing-aid amplification for Japanese, adjustments based on LTASS differences for Western European Languages could be made. This preserved speech intelligibility at the same level as the original amplification rationale, suggesting that there was no need to consider differences in phonetics of Japanese to optimize speech understanding.

Genetic Variation and Immunohistochemical Localization of the Glucocorticoid Receptor in Breast Cancer Cases from the Breast Cancer Care in Chicago Cohort.

Simple SummaryBreast cancer, one of the leading causes of death among women, is a complex disease in which several factors, such as psychosocial stress, have been implicated in its initiation and progression. The glucocorticoid receptor (GCR) is one of the molecules that transfers the stress signal into the body. We measured the genetic variation and protein expression of GCR and the genes that regulate GCR function or response and examined whether these variations were associated with breast cancer. We found several genetic variants of functionally important SNPs associated with later disease stage, higher grade, and hormone receptor-negative status. The GCR protein expression was reduced in breast cancer tissue and correlated with the basal cell marker CK5/6.Background: Glucocorticoid, one of the primary mediators of stress, acts via its receptor, the glucocorticoid receptor (GCR/NR3C1), to regulate a myriad of physiological processes. We measured the genetic variation and protein expression of GCR, and the genes that regulate GCR function or response and examined whether these alterations were associated with breast cancer clinicopathological characteristics. Method: We used samples from a multiracial cohort of breast cancer patients to assess the association between breast cancer characteristics and the genetic variants of single nucleotide polymorphisms (SNPs) in GCR/NR3C1, FKBP5, Sgk1, IL-6, ADIPOQ, LEPR, SOD2, CAT, and BCL2. Results: Several SNPs were associated with breast cancer characteristics, but statistical significance was lost after adjustment for multiple comparisons. GCR was detected in all normal breast tissues and was predominantly located in the nuclei of the myoepithelial cell layer, whereas the luminal layer was negative for GCR. GCR expression was significantly decreased in all breast cancer tissue types, compared to nontumor tissue, but was not associated with breast cancer characteristics. We found that high nuclear GCR expression was associated with basal cell marker cytokeratin 5/6 positivity. Conclusion: GCR expression is reduced in breast cancer tissue and correlates with the basal cell marker CK5/6.

Self-Rated Executive Functions in Mild Traumatic Brain Injury

Prior research has found that individuals with a pre-injury psychiatric history report greater difficulty with executive functioning after mild traumatic brain injury (mTBI). The present study examined self-rated executive functioning after the acute phase of recovery in individuals with mTBI having no prior psychiatric history. Participants included 59 individuals with mTBI and 27 healthy comparison subjects (HC). They completed the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) and Beck Depression Inventory-II. Participants had no prior history of psychiatric diagnosis based on semi-structured interview. In those with a valid BRIEF-A, the mTBI group (n = 54; days since injury: M = 465.04, SD = 146.92, range = 315–1144) endorsed poorer executive functioning than the HC group (n = 24) on several BRIEF-A scales. Only the Working Memory and Inhibit scales remained significant after adjusting for group differences in education and depression score, but they did not survive adjustment for multiple comparisons. The mean standardized scores for the mTBI group were well within normal limits across scales. Furthermore, there were no group differences on any BRIEF-A scales for percentage of participants with clinically elevated scores. Individuals with mTBI and no prior psychiatric history did not endorse significant executive dysfunction. Our findings support previous literature indicating that self-rated executive dysfunction in those with mTBI after the acute phase of recovery is likely due to factors other than brain injury, such as subclinical symptoms of depression.

136 Sleep and Porphyromonas gingivalis K-Capsular IgG Serotypes: A Study in the Old Order Amish

Abstract Introduction Sleep problems and periodontal disease have a bidirectional relationship and are independently linked with depression, dementia, and metabolic disease. Inadequate sleep can worsen inflammation, a hallmark of periodontal disease, and the activation of the immune system can alter sleep/wake cycles. A key player in periodontal disease is Porphyromonas gingivalis, a bacteria that can translocate to the brain and induce miRNA’s. Antibodies to P. gingivalis capsular virulence factors, K1-7, have been used to estimate P. gingivalis virulence. This study was conducted to explore cross-sectional associations between seropositivity of K serotypes of P. gingivalis and measures of self-reported impairment in sleep. If identified, these links would provide a rationale to initiate causality and mediation studies. We hypothesized that sleep impairment is positively associated with P. gingivalis K IgG serointensity. Methods 880 Old Order Amish aged 44.8 (SD: 17.2 years); 360 men (40.91%), 520 women (59.09%) responded to an adapted Pittsburgh-Sleep-Quality-Index questionnaire. IgG serointensity to 7 K-capsular P. gingivalis serotypes were measured with ELISAs. We tested for the association of log-transformed serotype IgG intensity and positivity (successively defined as within the top 5% and 25% for each serotype) with sleep parameters (as binary and continuous variables) using linear and logistic regressions, adjusting for age and sex. Results We confirmed no hypothesized associations between any of the sleep problems on the PSQI and K serotype serointensity and seropositivity. Exploratory analysis returned a negative association of log-transformed K3 IgG with daytime sleepiness (p=0.01); however, this did not resist adjustment for multiple comparisons and was inconsistent with the direction of the hypothesis. Conclusion Strengths of the study include the reduced smoking prevalence in the Amish and the relatively homogenous lifestyle, reducing confounding. The results imply P. gingivalis serotypes are not associated with sleep disturbance. Limitations are self-reporting of sleep, cross-sectional approach and limited generalizability. Results do not support an association between P. gingivalis K serotypes and sleep-problems. Support (if any) MVM-CoRE

Evaluation of Cardiovascular Functions during the Practice of Different Types of Yogic Breathing Techniques.

Introduction: Yoga is the science of right living practice to promote health. Many studies have documented the cardiovascular effects of various yogic breathing techniques (YBTs), comparing the cardiovascular changes before and after the practice. However, there is a lack of study reporting the cardiovascular changes during the practice of YBT.Materials and Methods: Twenty healthy individuals performed four different YBTs (Bhastrika, Bhramari, Kapalbhati, and Kumbhaka) in four different orders. Cardiovascular variables such as systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), stroke volume (SV), cardiac output (CO), pulse interval (PI), and total peripheral resistant (TPR) were assessed using a continuous noninvasive blood pressure monitoring system, before, during, and immediately after each YBT. Data were analyzed using repeated measures analysis of variance followed by post hoc analysis with Bonferroni adjustment for multiple comparisons using Statistical Package for the Social Sciences, Version 16.0.Results: Results of this study showed a significant increase in DBP, MAP, HR, and CO along with a reduction in PI during Bhastrika; a significant increase in DBP, MAP, HR, and TPR with a reduction in SV, CO, and PI during Bhramari pranayama; a significant increase in SBP, DBP, MAP, HR, and CO with a reduction in PI during Kapalbhati; and a significant increase in SBP, DBP, MAP, and TPR with a reduction in SV and CO during Kumbhaka practice.Conclusion: In healthy individuals, cardiovascular changes during the practice of Bhastrika and Kapalbhati are more or less similar to each other and are different from those of Bhramari and Kumbhaka in most of the variables.

The transcriptomic profile of endometrial receptivity in recurrent miscarriage

ObjectiveTo characterise the endometrial transcriptomic profiles of women who suffered recurrent miscarriage and to set the foundation for the development of an endometrial receptivity test that could predict the fate of subsequent pregnancies. Study designThis was a prospective multicentre cohort study performed at the Tommy's National Centre for Miscarriage Research in Birmingham, Saint Mary’s Hospital in Manchester and Royal Devon & Exeter Hospital, United Kingdom. The study was conducted between December 2017 and December 2019. Endometrial biopsies were obtained during the window of implantation from 24 women aged 18–35 years, who were not pregnant and regularly menstruating, diagnosed with unexplained recurrent miscarriage by standard investigations as per the ESHRE guidelines. Exclusion criteria included risk factors such as smoking, obesity or hyperprolactinemia. The RNA transcripts abundances were quantified using Kallisto. R packages tximport and DESeq2 were used to summarize count estimates at the gene level and to analyse the differential gene expression. ResultsWomen who suffered four or more miscarriages had 19 differently expressed genes after adjustment for multiple comparisons. They were related to biological processes such as immunity (HLA-DMA, CCR8, ALOX5), energy production (ATP12A), hormone secretion (CGA), adhesion (CHAD, ADGRF2, AQP5, TBCD, CTNND1, NKD2) and cell proliferation (NCCRP1). Based on 421 differently expressed genes, women who achieved a subsequent live birth displayed an enrichment of processes related to the regulation of cell structure and proliferation, and a depletion of processes related to immunity, trans-membrane transport and coagulation. ConclusionsWomen in the extreme miscarriage cohort had a distinctive endometrial transcriptomic signature compared to women with low order miscarriages. There was a partial overlap with the transcriptome of asynchronous endometrium suggesting the endometrial factor to be a different entity in the context of recurrent miscarriage. Women who achieved a live birth in their subsequent pregnancy displayed an enrichment of genes related to the regulation of cell structure and proliferation, while women who suffered a subsequent miscarriage displayed an enrichment of genes related to immunity, trans-membrane transport and coagulation.

Metabolic signatures of greater body size and their associations with risk of colorectal and endometrial cancers in the European Prospective Investigation into Cancer and Nutrition

BackgroundThe mechanisms underlying the obesity-cancer relationship are incompletely understood. This study aimed to characterise metabolic signatures of greater body size and to investigate their association with two obesity-related malignancies, endometrial and colorectal cancers, and with weight loss within the context of an intervention study.MethodsTargeted mass spectrometry metabolomics data from 4326 participants enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and 17 individuals from a single-arm pilot weight loss intervention (Intercept) were used in this analysis. Metabolic signatures of body size were first determined in discovery (N = 3029) and replication (N = 1297) sets among EPIC participants by testing the associations between 129 metabolites and body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) using linear regression models followed by partial least squares analyses. Conditional logistic regression models assessed the associations between the metabolic signatures with endometrial (N = 635 cases and 648 controls) and colorectal (N = 423 cases and 423 controls) cancer risk using nested case-control studies in EPIC. Pearson correlation between changes in the metabolic signatures and weight loss was tested among Intercept participants.ResultsAfter adjustment for multiple comparisons, greater BMI, WC, and WHR were associated with higher levels of valine, isoleucine, glutamate, PC aa C38:3, and PC aa C38:4 and with lower levels of asparagine, glutamine, glycine, serine, lysoPC C17:0, lysoPC C18:1, lysoPC C18:2, PC aa C42:0, PC ae C34:3, PC ae C40:5, and PC ae C42:5. The metabolic signature of BMI (OR1-sd 1.50, 95% CI 1.30–1.74), WC (OR1-sd 1.46, 95% CI 1.27–1.69), and WHR (OR1-sd 1.54, 95% CI 1.33–1.79) were each associated with endometrial cancer risk. Risk of colorectal cancer was positively associated with the metabolic signature of WHR (OR1-sd: 1.26, 95% CI 1.07–1.49). In the Intercept study, a positive correlation was observed between weight loss and changes in the metabolic signatures of BMI (r = 0.5, 95% CI 0.06–0.94, p = 0.03), WC (r = 0.5, 95% CI 0.05–0.94, p = 0.03), and WHR (r = 0.6, 95% CI 0.32–0.87, p = 0.01).ConclusionsObesity is associated with a distinct metabolic signature comprising changes in levels of specific amino acids and lipids which is positively associated with both colorectal and endometrial cancer and is potentially reversible following weight loss.

A Prospective Diet-Wide Association Study for Risk of Colorectal Cancer in EPIC

Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk. The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci. In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta carotene, fruit, fiber, nonwhite bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in the NLCS, for which a meta-analysis was performed, namely alcohol (summary hazard ratio [HR] per 1-SD increment in intake: 1.07; 95% confidence interval [CI], 1.04-1.09), liquor/spirits (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02-1.06), wine (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02-1.07), beer/cider (HR per 1-SD increment in intake, 1.06; 95% CI, 1.04-1.08), milk (HR per 1-SD increment in intake, 0.95; 95% CI, 0.93-0.98), cheese (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94-0.99), calcium (HR per 1-SD increment in intake, 0.93; 95% CI, 0.90-0.95), phosphorus (HR per 1-SD increment in intake, 0.92; 95% CI, 0.90-0.95), magnesium (HR per 1-SD increment in intake, 0.95; 95% CI, 0.92-0.98), potassium (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94-0.99), riboflavin (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92-0.97), beta carotene (HR per 1-SD increment in intake, 0.96; 95% CI, 0.93-0.98), and total protein (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92-0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons. Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta carotene, and total protein.

Understanding memorably negative provider care delivery experiences: Why patient experiences matter for providers

BackgroundNegative experiences contribute to provider dissatisfaction and burnout. Prior research suggests that negative experiences have greater impact on individuals than positive experiences. MethodsInterviews were conducted with surgical and oncology care providers (107 MDs, 253 non-MDs) working in 10 geographically diverse, academic and community hospitals across the U.S. Using a thematic network approach, we identified core themes describing drivers of memorably negative experiences. We applied logistic regression with adjustments for multiple comparisons to evaluate the relationship between demographic characteristics and types of experiences. ResultsWe identified 13 themes from 360 experiences and from these, developed a framework describing how work culture, environment, individual factors, and patient experiences lead to memorably, negative provider experiences. Providers most frequently described negative work environment experiences (158/360) and poor communication experiences with patients and other care professionals (151/360). Across themes, one third of respondents attributed memorably negative experiences to patient experiences (119/360).Midwest providers described patient centeredness more than other providers (OR = 3.9, p < 0.001). Providers from the Northeast, MDs compared to non-MDs, and providers with 15+ years of work experience identified negative insurance-related experiences more frequently (OR = 0.2, P = 0.007; OR = 2.9, P = 0.002 OR = 4.2, P < 0.001). ConclusionsWe offer a framework for understanding negative experiences among providers. Our study suggests that across a broad set of causes, improving patient experiences could substantially improve the negative, memorable experiences of providers. ImplicationsAddressing negative patient experiences may have the double benefit of improving patient care and reducing provider burnout. Level of evidenceLevel III.

The PRKAR1B p.R115K Variant is Associated with Lipoprotein Profile in African American Youth with Metabolic Challenges.

High childhood obesity rates coincide with increased incidence of nonalcoholic fatty liver disease (NAFLD) and other comorbidities. Understanding the genetics of susceptibility to obesity and its comorbidities could guide intervention. The cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) signaling pathway regulates energy balance, glucose homeostasis, and lipid metabolism. We hypothesized that PKA-related gene variants may be associated with obesity or associated metabolic conditions. We included 457 youths from the Yale Obesity Clinic into the Pathogenesis of Youth-Onset Diabetes cohort (NCT01967849); a variety of clinical tests were performed to characterize NAFLD. Exon sequencing of 54 PKA pathway genes was performed. Variants were confirmed by Sanger sequencing. Clinical data were analyzed, correcting for NAFLD status and body mass index z-score with adjustments for multiple comparisons. Fluorescence resonance energy transfer (FRET) and PKA enzymatic assays were performed in HEK293 cells transfected with the PRKAR1B p.R115K construct. In silico structural analysis for this variant was done. We identified the variant PRKAR1B p.R115K in 4 unrelated, African American patients. Analyses compared this variant group to other African American patients in the cohort. PRKAR1B p.R115K was associated with favorable circulating lipoprotein levels. Analysis of FRET and PKA enzymatic assay showed stronger interaction between the R1β mutant and PKA catalytic subunit Cα and decreased basal PKA activity compared with the wildtype (P < .0001). Structural analysis revealed that p.R115K may hinder conformational changes resulting from cAMP binding at cAMP binding domain A. Data suggest PRKAR1B p.R115K affects cAMP signaling and may favorably modulate lipoprotein profile in African American youth, protecting them from some adverse metabolic outcomes.

Serum tyrosine is associated with better cognition in Lewy body dementia

Amino acids’ neuroactivity, and roles in excitotoxity and oxidative stress are linked to dementia. We aimed to investigate whether circulating amino acid concentrations were associated with cognitive decline in patients with mild Alzheimer’s disease (AD) and Lewy body dementia (LBD). Baseline serum amino acid concentrations were measured in 89 patients with AD and 65 with LBD (13 with Parkinson’s disease dementia and 52 with dementia with Lewy bodies). The Mini-Mental State Examination (MMSE) was administered at baseline and annually for five years. Associations between baseline amino acid concentrations and longitudinal MMSE score were assessed using a linear-mixed effects model stratified by diagnosis with adjustment for multiple comparisons. The results of the study indicated that serum tyrosine was positively associated with MMSE performance during the five-year follow-up period in patients with LBD (q-value = 0.012), but not AD. In conclusion, higher baseline serum concentrations of tyrosine, the precursor amino acid in dopamine and norepinephrine synthesis, was associated with better cognitive performance in patients with LBD, but not AD, throughout the 5-year follow-up period.

An international comparison of HIV prevalence and incidence in blood donors and general population: a BEST Collaborative study.

Efficiency in mitigating HIV transmission risk by transfusion may vary internationally. We compared HIV prevalence and incidence in blood donors across different jurisdictions in relation to those rates in the general population and differences in deferral practices. Data from 2007 to 2016 were collected in Australia, Brazil (São Paulo), Canada, England, France, Italy, Ireland, Japan, the Netherlands, New Zealand, Norway, Spain (Basque Country), USA (Vitalant) and Wales. For each country/region, the number of HIV antibody-positive donations and nucleic acid testing (NAT)-only-positive donations was broken down according to first-time or repeat donor status, along with the relevant denominators. There is a modest correlation between HIV prevalence among first-time donors and HIV prevalence in the general population. However, rates of HIV-positive donations in repeat donors, a proxy for incidence, do not correlate with incidence rates in the general population. Rates in donors from Italy and Basque Country, where deferral criteria for men having sex with men are less stringent, are higher compared with most other jurisdictions. Rates of NAT-only-positive donations are extremely low and do not differ significantly after adjustment for multiple comparisons. Donor HIV rates are only weakly associated with those observed in the general population. Countries with less stringent deferral criteria have higher HIV rates in their donor population, but the rates remain very low.

Evaluation of a-amylase and protease on diet nutrient intake and digestibility, and physiological parameters in lambs

The effects of adding exogenous enzymes on the intake and digestibility of dry matter (DM) and on nutrients, and several blood parameters were determined in lambs fed a basal diet of 34% ground corn, 40% tropical grass hay, and 26% soybean meal providing 21% dietary starch. Twelve crossbred lambs (22 kg) were assigned to one of four diets: no additives (1); diets containing α-amylase (2); protease (3); or their combination (4). Diets (DM basis) were offered daily at 4% of animal BW in four 28-day experimental periods each consisting of 21 d of adaptation to the diet followed by 7 d of complete fecal collection. In each period, feed offered, orts and feces were collected, quantified and analyzed for contents of DM, starch, crude protein (CP) and neutral detergent fiber (NDF) to determine intake and digestibility. At the end of each experimental period, blood samples were collected from the individual lambs to determine the concentration of glucose, beta-hidroxy butyrate (BHB), nonesterified fatty acids (NEFA), and insulin. Data were analyzed according to a 4 x 4 Latin Square experimental design. Dietary treatment contrasts were performed using least square means adjustment for multiple comparisons (Tukey-Kramer) as follows: enzymes versus no enzymes, amylase versus no amylase and protease versus no protease. Dry matter intake was similar across treatments (1,106; 1,088; 1,105 and 1,088 g/d for control, and diets containing α-amylase, experimental protease or their combination, respectively). Adding protease to the diet decreased (P&lt;0.05) starch consumption (248 vs. 255 g/d) and increased, but not significantly, NDF digestibility (48.6 vs. 46.8%) as compared to that of lambs fed without the experimental enzyme. Adding enzymes to the diet tended (P&lt;0.10) to decrease blood BHB concentration below the control level (4.26 vs. 4.68 mg/dL). Blood NEFA concentration tended to increase (P&lt;0.10) in lambs fed α-amylase compared to those fed without α-amylase (0.17 vs. 0.14 mEq/L). The insulin level tended (P&lt;0.10) to increase in lambs fed protease versus lambs not receiving the enzyme (80.3 vs. 71.8 pmol/L). Glucose levels were similar for all treatments. Both exogenous enzymes influenced blood metabolites; however, a greater effect was observed in lambs fed the protease.

A MULTI-SITE ANALYSIS OF THE HUMAN GUT MICROBIOME AND METABOLITES IN ASSOCIATION WITH AMBULATORY BLOOD PRESSURE

Objective: High blood pressure (HBP) is a major risk factor for cardiovascular disease (CVD) and the prevalence of both is higher in regional versus metropolitan areas. The gut microbiome has emerged as important contributor to HBP, however, the relationship between BP and specific gut microbes and their metabolites is unclear. Here we aimed to determine if specific gut microbes and key metabolites such as short-chain fatty acids (SCFAs) were associated with 24 h BP whether geographic differences exist in Australia. Design and method: We recruited 70 subjects from the community in metropolitan (n = 40) and regional (n = 30) locations in Australia. White coat hypertension was present in 6% and masked hypertension in 19% of the cohort, and 34% were hypertensive. We assessed office and ambulatory BP, dietary intake via food frequency questionnaire, gut metabolites by gas-chromatography, and gut microbiome by 16S sequencing. Results: Mean(±SD) 24 h mean arterial pressure was 90.5 ± 10mmHg, systolic BP 122.8 ± 14.9mmHg, and diastolic 74 ± 8.4mmHg. There was a positive correlation between plasma short-chain fatty acid butyrate and 24 h systolic (r = 0.31, P = 0.01) and diastolic BP (r = 0.29, P = 0.02), confirmed by logistic regressions adjusted for age, sex and BMI (P = 0.001). Fifty seven genus were significantly correlated with diastolic BP (r = 0.38–0.41) after adjustment for multiple comparisons (FDR &lt; 0.1). Inverse Simpson index, a marker of alpha diversity, was negatively correlated with 24 h mean arterial pressure (r = -0.24, P = 0.04), being driven particularly by 24 h diastolic BP and day BP. There were no differences in alpha or beta diversity between metropolitan and regional areas. Participants from metropolitan areas, however, had significantly lower levels of total SCFAs, acetate and butyrate (P &lt; 0.05) without having any differences in fibre intake. Conclusions: This is the first study to analyse BP as a continuous variable, suggesting it is associated with a less diverse gut microbiome, higher levels of butyrate, and several genus of gut bacteria. Further studies will need to determine a causal relationship for these associations. We did not find a gut microbial difference between metropolitan and regional participants, but the latter had lower levels of SCFAs, which could help explain their predisposition to hypertension and cardiovascular disease.

Neuroanatomical Substrates and Symptoms Associated With Magnetic Resonance Imaging of Patients With Mild Traumatic Brain Injury

Persistent symptoms after mild traumatic brain injury (mTBI) represent a major public health problem. To identify neuroanatomical substrates of mTBI and the optimal timing for magnetic resonance imaging (MRI). This prospective multicenter cohort study encompassed all eligible patients from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study (December 19, 2014, to December 17, 2017) and a local cohort (November 20, 2012, to December 19, 2013). Patients presented to the hospital within 24 hours of an mTBI (Glasgow Coma Score, 13-15), satisfied local criteria for computed tomographic scanning, and underwent MRI scanning less than 72 hours (MR1) and 2 to 3 weeks (MR2) after injury. In addition, 104 control participants were enrolled across all sites. Data were analyzed from January 1, 2019, to December 31, 2020. Mild TBI. Volumes and diffusion parameters were extracted via automated bespoke pipelines. Symptoms were measured using the Rivermead Post Concussion Symptoms Questionnaire in the short term and the extended Glasgow Outcome Scale at 3 months. Among the 81 patients included in the analysis (73 CENTER-TBI and 8 local), the median age was 45 (interquartile range [IQR], 24-59; range, 14-85) years, and 57 (70.4%) were male. Structural sequences were available for all scans; diffusion data, for 73 MR1 and 79 MR2 scans. After adjustment for multiple comparisons between scans, visible lesions did not differ significantly, but cerebral white matter volume decreased (MR2:MR1 ratio, 0.98; 95% CI, 0.96-0.99) and ventricular volume increased (MR2:MR1 ratio, 1.06; 95% CI, 1.02-1.10). White matter volume was within reference limits on MR1 scans (patient to control ratio, 0.99; 95% CI, 0.97-1.01) and reduced on MR2 scans (patient to control ratio, 0.97; 95% CI, 0.95-0.99). Diffusion parameters changed significantly between scans in 13 tracts, following 1 of 3 trajectories. Symptoms measured by Rivermead Post Concussion Symptoms Questionnaire scores worsened in the progressive injury phenotype (median, +5.00; IQR, +2.00 to +5.00]), improved in the minimal change phenotype (median, -4.50; IQR, -9.25 to +1.75), and were variable in the pseudonormalization phenotype (median, 0.00; IQR, -6.25 to +9.00) (P = .02). Recovery was favorable for 33 of 65 patients (51%) and was more closely associated with MR1 than MR2 (area under the curve, 0.87 [95% CI, 0.78-0.96] vs 0.75 [95% CI, 0.62-0.87]; P = .009). These findings suggest that advanced MRI reveals potential neuroanatomical substrates of mTBI in white matter and is most strongly associated with odds of recovery if performed within 72 hours, although future validation is required.

Educational Studies Examining Knowledge of Substance Use Disorders and Career Aspirations Among Medical Trainees in an Inner-City Hospital.

Gaps in addiction medicine training are a reason for poor substance use care in North America. Hospital addiction medicine consult services (AMCS) provide critical medical services, including screening and treatment of substance use disorders. Although these programs often feature an educational component for medical learners, the impact of AMCS teaching on objective knowledge and career aspirations in addiction medicine has not been well described. The authors report findings from two sequential studies conducted at a large academic hospital in Vancouver, Canada. The first study assessed the impact of an AMCS clinical rotation on medical trainee addiction medicine objective knowledge using an online survey of 6 true/false questions before and after the rotation. The second study examined the impact of an AMCS rotation on career aspirations using 4 seven-point Likert-type questions. One-sample t tests on mean differences (MD) with Benjamini-Hochberg adjustment for multiple comparisons were employed for statistical analyses. Between May 2017 and June 2018, knowledge scores were significantly higher postrotation (MD = 4.78, standard deviation [SD] = 19.5, P = 0.034) among 115 medical trainees. Between July 2018 and July 2019, aspirations to practice addiction medicine were significantly more favorable postrotation (MD = 3.48, SD = 3.15, P < 0.001) among 101 medical trainees. AMCS rotations appear to improve addiction medicine knowledge and aspirations to practice addiction medicine among medical trainees. Larger-scale evaluations and outcomes research on integrating substance use disorders teaching in these settings will help move the discipline forward.

Metabolomics shows the Australian dingo has a unique plasma profile

Dingoes occupy a wide range of the Australian mainland and play a crucial role as an apex predator with a generalist omnivorous feeding behaviour. Dingoes are ecologically, phenotypically and behaviourally distinct from modern breed dogs and have not undergone artificial selection since their arrival in Australia. In contrast, humans have selected breed dogs for novel and desirable traits. First, we examine whether the distinct evolutionary histories of dingoes and domestic dogs has lead to differences in plasma metabolomes. We study metabolite composition differences between dingoes (n = 15) and two domestic dog breeds (Basenji n = 9 and German Shepherd Dog (GSD) n = 10). Liquid chromatography mass spectrometry, type II and type III ANOVA with post-hoc tests and adjustments for multiple comparisons were used for data evaluation. After accounting for within group variation, 62 significant metabolite differences were detected between dingoes and domestic dogs, with the majority of differences in protein (n = 14) and lipid metabolites (n = 12), mostly lower in dingoes. Most differences were observed between dingoes and domestic dogs and fewest between the domestic dog breeds. Next, we collect a second set of data to investigate variation between pure dingoes (n = 10) and dingo-dog hybrids (n = 10) as hybridisation is common in regional Australia. We detected no significant metabolite differences between dingoes and dingo-dog hybrids after Bonferroni correction. However, power analysis showed that increasing the sample size to 15 could result in differences in uridine 5′-diphosphogalactose (UDPgal) levels related to galactose metabolism. We suggest this may be linked to an increase in Amylase 2B copy number in hybrids. Our study illustrates that the dingo metabolome is significantly different from domestic dog breeds and hybridisation is likely to influence carbohydrate metabolism.

DNA repair gene polymorphisms and chromosomal aberrations in healthy, nonsmoking population

Nonspecific structural chromosomal aberrations (CAs) can be found at around 1% of circulating lymphocytes from healthy individuals but the frequency may be higher after exposure to carcinogenic chemicals or radiation. The frequency of CAs has been measured in occupational monitoring and an increased frequency of CAs has also been associated with cancer risk. Alterations in DNA damage repair and telomere maintenance are thought to contribute to the formation of CAs, which include chromosome type of aberrations and chromatid type of aberrations. In the present study, we used the result of our published genome-wide association studies to extract data on 153 DNA repair genes from 866 nonsmoking persons who had no known occupational exposure to genotoxic substances. Considering an arbitrary cut-off level of P< 5 × 10−3, single nucleotide polymorphisms (SNPs) tagging 22 DNA repair genes were significantly associated with CAs and they remained significant at P < 0.05 when adjustment for multiple comparisons was done by the Binomial Sequential Goodness of Fit test. Nucleotide excision repair pathway genes showed most associations with 6 genes. Among the associated genes were several in which mutations manifest CA phenotype, including Fanconi anemia, WRN, BLM and genes that are important in maintaining genome stability, as well as PARP2 and mismatch repair genes. RPA2 and RPA3 may participate in telomere maintenance through the synthesis of the C strand of telomeres. Errors in NHEJ1 function may lead to translocations. The present results show associations with some genes with known CA phenotype and suggest other pathways with mechanistic rationale for the formation of CAs in healthy nonsmoking population.

Utility of CT texture analysis to differentiate olfactory neuroblastoma from sinonasal squamous cell carcinoma

The purpose of this study was to examine differences in texture features between olfactory neuroblastoma (ONB) and sinonasal squamous cell carcinoma (SCC) on contrast-enhanced CT (CECT) images, and to evaluate the predictive accuracy of texture analysis compared to radiologists’ interpretations. Forty-three patients with pathologically-diagnosed primary nasal and paranasal tumor (17 ONB and 26 SCC) were included. We extracted 42 texture features from tumor regions on CECT images obtained before treatment. In univariate analysis, each texture features were compared, with adjustment for multiple comparisons. In multivariate analysis, the elastic net was used to select useful texture features and to construct a texture-based prediction model with leave-one-out cross-validation. The prediction accuracy was compared with two radiologists’ visual interpretations. In univariate analysis, significant differences were observed for 28 of 42 texture features between ONB and SCC, with areas under the receiver operating characteristic curve between 0.68 and 0.91 (median: 0.80). In multivariate analysis, the elastic net model selected 18 texture features that contributed to differentiation. It tended to show slightly higher predictive accuracy than radiologists’ interpretations (86% and 74%, respectively; P = 0.096). In conclusion, several texture features contributed to differentiation of ONB from SCC, and the texture-based prediction model was considered useful.

White Matter Connectivity in Incident Mild Cognitive Impairment: A Diffusion Spectrum Imaging Study of World Trade Center Responders at Midlife.

Background:Individuals who participated in response efforts at the World Trade Center (WTC) following 9/11/2001 are experiencing elevated incidence of mild cognitive impairment (MCI) at midlife.Objective:We hypothesized that white matter connectivity measured using diffusion spectrum imaging (DSI) would be restructured in WTC responders with MCI versus cognitively unimpaired responders.Methods:Twenty responders (mean age 56; 10 MCI/10 unimpaired) recruited from an epidemiological study were characterized using NIA-AA criteria alongside controls matched on demographics (age/sex/occupation/race/education). Axial DSI was acquired on a 3T Siemen’s Biograph mMR scanner (12-channel head coil) using a multi-band diffusion sequence. Connectometry examined whole-brain tract-level differences in white matter integrity. Fractional anisotropy (FA), mean diffusivity (MD), and quantified anisotropy were extracted for region of interest (ROI) analyses using the Desikan-Killiany atlas.Results:Connectometry identified both increased and decreased connectivity within regions of the brains of responders with MCI identified in the corticothalamic pathway and cortico-striatal pathway that survived adjustment for multiple comparisons. MCI was also associated with higher FA values in five ROIs including in the rostral anterior cingulate; lower MD values in four ROIs including the left rostral anterior cingulate; and higher MD values in the right inferior circular insula. Analyses by cognitive domain revealed nominal associations in domains of response speed, verbal learning, verbal retention, and visuospatial learning.Conclusions:WTC responders with MCI at midlife showed early signs of neurodegeneration characterized by both increased and decreased white matter diffusivity in regions commonly affected by early-onset Alzheimer’s disease.