► Adolescent marijuana users have reduced cortical thickness in the prefrontal cortex. ► Adolescent marijuana users have reduced cortical thickness in the insula. ► Age of onset of regular marijuana ...use may impact cortical gray matter development. ► Reduced insula cortical thickness may be a risk marker for substance use disorders.
There are limited data regarding the impact of marijuana (MJ) on cortical development during adolescence. Adolescence is a period of substantial brain maturation and cortical thickness abnormalities may be indicative of disruptions of normal cortical development. This investigation applied cortical-surface based techniques to compare cortical thickness measures in MJ using adolescents compared to non-using controls.
Eighteen adolescents with heavy MJ use and 18 non-using controls similar in age received MRI scans using a 3T Siemens scanner. Cortical reconstruction and volumetric segmentation was performed with FreeSurfer. Group differences in cortical thickness were assessed using statistical difference maps covarying for age and gender.
Compared to non-users, MJ users had decreased cortical thickness in right caudal middle frontal, bilateral insula and bilateral superior frontal cortices. Marijuana users had increased cortical thickness in the bilateral lingual, right superior temporal, right inferior parietal and left paracentral regions. In the MJ users, negative correlations were found between frontal and lingual regions for urinary cannabinoid levels and between age of onset of use and the right superior frontal gyrus.
This is one of the first studies to evaluate cortical thickness in a group of adolescents with heavy MJ use compared to non-users. Our findings are consistent with prior studies that documented abnormalities in prefrontal and insular regions. Our results suggest that age of regular use may be associated with altered prefrontal cortical gray matter development in adolescents. Furthermore, reduced insular cortical thickness may be a biological marker for increased risk of substance dependence.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•Hepatocyte growth factor (HGF) is an important cytokine in the inflammatory milieu of cardiovascular disease.•Elevated serum HGF levels are associated with incident heart failure (HF).•On HF subtype ...assessment, HGF was significantly associated with HF with preserved ejection fraction and not HF with reduced ejection fraction.•Future studies may examine mechanisms underlying these associations and evaluate whether HGF has usefulness as a biomarker to improve HF risk prediction or to direct therapy.
Hepatocyte growth factor (HGF) is a cytokine and marker of cardiovascular disease (CVD) risk. Less is known about HGF and incident heart failure (HF). We examined the association of HGF with incident HF and its subtypes in a multiethnic cohort.
We included 6597 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, free of clinical CVD and HF at baseline, with HGF measured at baseline. Incident hospitalized HF was assessed and adjudicated for HF with preserved ejection fracture (HFpEF) vs HF with reduced ejection fraction (HFrEF). Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for HF risk by HGF levels, adjusted for socio-demographics, CVD risk factors and N-terminal pro-B-type natriuretic peptide. The mean age was 62 ± 10 years. The median HGF level was 950 pg/mL (interquartile range, 758–1086 pg/mL); 53% were women. Over 14 years (IQR, 11.5–14.7 years), there were 324 cases of HF (133 HFpEF and 157 HFrEF). For the highest HGF tertile compared with lowest, adjusted HRs were 1.59 (95% CI, 1.10–2.31), 1.90 (95% CI, 1.03–3.51), and 1.09 (95% CI, 0.65–1.82) for overall HF, HFpEF, and HFrEF, respectively. For continuous analysis per 1-standard deviation log-transformed HGF, adjusted HRs were 1.22 (95% CI, 1.06–1.41), 1.35 (95% CI, 1.09–1.69), and 1.00 (95% CI, 0.81–1.24) for HF, HFpEF, and HFrEF, respectively.
HGF was independently associated with incident HF. HGF remained significantly associated with HFpEF but not HFrEF upon subtype assessment. Future studies should examine the mechanisms underlying these associations and evaluate whether HGF can be used to improve HF risk prediction or direct therapy.
Included are the hazard ratios (HRs) for incident heart failure (HF) and its subtypes of HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) for the highest hepatocyte growth factor tertile compared to lowest. Display omitted
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The impact of azacytidine (Aza C) on the quality of life of 191 patients with myelodysplastic syndrome was assessed in a phase III Cancer and Leukemia Group B trial (9221).
One hundred ninety-one ...patients (mean age, 67.5 years; 69% male) were randomized to receive either Aza C (75 mg/m(2) subcutaneous for 7 days every 4 weeks) or supportive care, with supportive care patients crossing over to Aza C upon disease progression. Quality of life was assessed by centrally conducted telephone interviews at baseline and days 50, 106, and 182. Overall quality of life, psychological state, and social functioning were assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and the Mental Health Inventory (MHI).
Patients on the Aza C arm experienced significantly greater improvement in fatigue (EORTC, P =.001), dyspnea (EORTC, P =.0014), physical functioning (EORTC, P =.0002), positive affect (MHI, P =.0077), and psychological distress (MHI, P =.015) over the course of the study period than those in the supportive care arm. Particularly striking were improvements in fatigue and psychological state (MHI) in patients treated with Aza C compared with those receiving supportive care for patients who remained on study through at least day 106, corresponding to four cycles of Aza C. Significant differences between the two groups in quality of life were maintained even after controlling for the number of RBC transfusions.
Improved quality of life for patients treated with Aza C coupled with significantly greater treatment response and delayed time to transformation to acute myeloid leukemia or death compared with patients on supportive care (P <.001) establishes Aza C as an important treatment option for myelodysplastic syndrome.
Through a comprehensive review of the Mayo Clinic experience with patients who had Meckel diverticulum, we sought to determine which diverticula should be removed when discovered incidentally during ...abdominal surgery.
Meckel diverticula occur so infrequently that most articles have reported either small series or isolated cases. From these limited series, various conclusions have been reported without clearly indicating which incidental diverticula should be removed.
Medical records were reviewed of 1476 patients found to have a Meckel diverticulum during surgery from 1950 to 2002. Preoperative diagnosis; age; sex; date of surgery; and intraoperative, macroscopic, and microscopic findings from operative and pathology reports were recorded. Logistic regression analysis was used to determine which clinical or histologic features were associated with symptomatic Meckel diverticulum. The features analyzed were age; sex; length, base width, and ratio of length to base width of the diverticulum; and the presence of ectopic tissue or abnormal tissue (inflammation or enteroliths).
Among the 1476 patients, 16% of the Meckel diverticula were symptomatic. The most common clinical presentation in adults was bleeding; in children, obstruction. Among patients with a symptomatic Meckel diverticulum, the male-female ratio was approximately 3:1. Clinical or histologic features most commonly associated with symptomatic Meckel diverticula were patient age younger than 50 years (odds ratio OR, 3.5; 95% confidence interval CI, 2.6-4.8; P < 0.001), male sex (OR, 1.8; 95% CI, 1.3-2.4; P < 0.001); diverticulum length greater than 2 cm (OR, 2.2; 95% CI, 1.1-4.4; P = 0.02), and the presence of histologically abnormal tissue (OR, 13.9; 95% CI, 9.9-19.6; P < 0.001).
After analyzing our data, we neither support nor reject the recommendation that all Meckel diverticula found incidentally should be removed, although the procedure today has little risk. If a selective approach is taken, we recommend removing all incidental Meckel diverticula that have any of the 4 features most commonly associated with symptomatic Meckel diverticulum.
Side-swiped Frelich, Lee E; Blossey, Bernd; Cameron, Erin K ...
Frontiers in ecology and the environment,
11/2019, Volume:
17, Issue:
9
Journal Article
Peer reviewed
Open access
Non-native, invasive earthworms are altering soils throughout the world. Ecological cascades emanating from these invasions stem from rapid consumption of leaf litter by earthworms. This occurs at a ...midpoint in the trophic pyramid, unlike the more familiar bottom-up or top-down cascades. These cascades cause fundamental changes (“microcascade effects”) in soil morphology, bulk density, and nutrient leaching, and a shift to warmer, drier soil surfaces with a loss of leaf litter. In North American temperate and boreal forests, microcascade effects can affect carbon sequestration, disturbance regimes, soil and water quality, forest productivity, plant communities, and wildlife habitat, and can facilitate other invasive species. These broader-scale changes (“macrocascade effects”) are of greater concern to society. Interactions among these fundamental changes and broader-scale effects create “cascade complexes” that interact with climate change and other environmental processes. The diversity of cascade effects, combined with the vast area invaded by earthworms, leads to regionally important changes in ecological functioning.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
The delivery of safe and effective radiation therapy relies on accurate target delineation, particularly in the era of highly conformal treatment techniques. Current contouring resources are ...fragmented and can be cumbersome to use. The present study reports on the efficacy and usability of a web-based contouring atlas compared with those of existing contouring resources in a randomized trial.
We enrolled radiation oncology residents into a 2-phase contouring study. All residents contoured a T1N1 nasopharyngeal cancer case using the currently available resources. The participants were then randomized to recontour the case with access to existing resources or an interactive web-based contouring atlas (eContour.org). Contour analysis was performed using conformation number and simultaneous truth and performance level estimation. At completion of the second contouring session, the residents completed a multiple choice question knowledge test and a 10-item System Usability Scale.
Twenty-four residents from 5 institutions completed the study. Compared with the residents using currently available resources, the residents using eContour had improved contour agreement with both the consensus (0.63 vs 0.52; P=.02) and the expert (0.58 vs 0.50; P=.01) contours for the high-risk clinical target volume and greater agreement with the expert contour for the contralateral parotid gland (0.44 ± 0.12 vs 0.56 ± 0.08; P=.003). The residents using eContour demonstrated greater knowledge of contour delineation and radiographic anatomy on a multiple-choice knowledge-based test (89% vs 77%; P=.03). Usability (89 vs 66; P<.0001) and satisfaction (4.1 vs 3.0; P=.002) were greater for eContour than for the existing resources.
This study demonstrates the capacity of an interactive 3-dimensional contouring atlas to improve quality of resident target delineation in radiation oncology. Further research is needed to define the utility of easily accessible interactive educational reference tool to improve adherence to contouring-based guidelines and quality of care in routine clinical practice.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer’s disease neuropathologic change (ADNC) are each associated with substantial cognitive impairment ...in aging populations. However, the prevalence of LATE-NC across the full range of ADNC remains uncertain. To address this knowledge gap, neuropathologic, genetic, and clinical data were compiled from 13 high-quality community- and population-based longitudinal studies. Participants were recruited from United States (8 cohorts, including one focusing on Japanese–American men), United Kingdom (2 cohorts), Brazil, Austria, and Finland. The total number of participants included was 6196, and the average age of death was 88.1 years. Not all data were available on each individual and there were differences between the cohorts in study designs and the amount of missing data. Among those with known cognitive status before death (
n
= 5665), 43.0% were cognitively normal, 14.9% had MCI, and 42.4% had dementia—broadly consistent with epidemiologic data in this age group. Approximately 99% of participants (
n
= 6125) had available CERAD neuritic amyloid plaque score data. In this subsample, 39.4% had autopsy-confirmed LATE-NC of any stage. Among brains with “frequent” neuritic amyloid plaques, 54.9% had comorbid LATE-NC, whereas in brains with no detected neuritic amyloid plaques, 27.0% had LATE-NC. Data on LATE-NC stages were available for 3803 participants, of which 25% had LATE-NC stage > 1 (associated with cognitive impairment). In the subset of individuals with Thal Aβ phase = 0 (lacking detectable Aβ plaques), the brains with LATE-NC had relatively more severe primary age-related tauopathy (PART). A total of 3267 participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of definite FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In the 10 cohorts with detailed neurocognitive assessments proximal to death, cognition tended to be worse with LATE-NC across the full spectrum of ADNC severity. This study provided a credible estimate of the current prevalence of LATE-NC in advanced age. LATE-NC was seen in almost 40% of participants and often, but not always, coexisted with Alzheimer’s disease neuropathology.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Transcriptome-wide association analysis is a powerful approach to studying the genetic architecture of complex traits. A key component of this approach is to build a model to impute gene expression ...levels from genotypes by using samples with matched genotypes and gene expression data in a given tissue. However, it is challenging to develop robust and accurate imputation models with a limited sample size for any single tissue. Here, we first introduce a multi-task learning method to jointly impute gene expression in 44 human tissues. Compared with single-tissue methods, our approach achieved an average of 39% improvement in imputation accuracy and generated effective imputation models for an average of 120% more genes. We describe a summary-statistic-based testing framework that combines multiple single-tissue associations into a powerful metric to quantify the overall gene-trait association. We applied our method, called UTMOST (unified test for molecular signatures), to multiple genome-wide-association results and demonstrate its advantages over single-tissue strategies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Hepatocyte growth factor (HGF) is a cytokine released in response to endothelial injury and a potential biomarker of cardiovascular disease (CVD) risk. We examined the association between ...cardiovascular health (CVH) and HGF in a multi-ethnic cohort of adults free from CVD at baseline.
This cross-sectional study conducted between 2020 and 2021 used MESA baseline examination data (2000-2002) from 6,490 US adults aged 45-84 years. The independent variable was CVH measured by the CVH score and number of ideal metrics. The score was derived from seven metrics: smoking, body mass index, physical activity, diet, total cholesterol, blood pressure and blood glucose. Each metric was scored 0 points (poor), 1 point (intermediate) and 2 points (ideal). The total CVH score ranged from 0 to 14. An inadequate score was 0-8, average, 9-10 and optimal, 11-14. The dependent variable was logarithmically transformed HGF. We used regression analyses to estimate associations between CVH and HGF adjusting for sociodemographic factors.
Participants' mean (SD) age was 62 (10) years. Fifty-three percent were female. A one-unit increment in the CVH score was significantly associated with 3% lower HGF levels. Average and optimal CVH scores were significantly associated with 8% and 12% lower HGF levels, respectively, compared to inadequate scores. Additionally, a greater number of ideal metrics was associated with lower HGF levels.
Favorable CVH was significantly associated with lower HGF levels in this ethnically diverse cohort. Interventions aimed at promoting and preserving favorable CVH may reduce the risk of endothelial injury as indicated by lower serum HGF levels.
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