Publications by authors named "Robert Wilson"

999 Publications

Artefacts in Volume Data Generated with High Resolution Episcopic Microscopy (HREM).

Biomedicines 2021 Nov 18;9(11). Epub 2021 Nov 18.

Division of Anatomy, Center for Anatomy and Cell Biology, Medical University of Vienna, 1090 Vienna, Austria.

High resolution episcopic microscopy (HREM) produces digital volume data by physically sectioning histologically processed specimens, while capturing images of the subsequently exposed block faces. Our study aims to systematically define the spectrum of typical artefacts inherent to HREM data and to research their effect on the interpretation of the phenotype of wildtype and mutant mouse embryos. A total of 607 (198 wildtypes, 409 mutants) HREM data sets of mouse embryos harvested at embryonic day (E) 14.5 were systematically and comprehensively examined. The specimens had been processed according to essentially identical protocols. Each data set comprised 2000 to 4000 single digital images. Voxel dimensions were 3 × 3 × 3 µm. Using 3D volume models and virtual resections, we identified a number of characteristic artefacts and grouped them according to their most likely causality. Furthermore, we highlight those that affect the interpretation of embryo data and provide examples for artefacts mimicking tissue defects and structural pathologies. Our results aid in optimizing specimen preparation and data generation, are vital for the correct interpretation of HREM data and allow distinguishing tissue defects and pathologies from harmless artificial alterations. In particular, they enable correct diagnosis of pathologies in mouse embryos serving as models for deciphering the mechanisms of developmental disorders.
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http://dx.doi.org/10.3390/biomedicines9111711DOI Listing
November 2021

Metamemory and financial decision making in older adults without dementia.

Neuropsychology 2021 Oct 28. Epub 2021 Oct 28.

Rush Alzheimer's Disease Center.

Objective: Metamemory refers to self-awareness of one's memory function, and the extent to which metamemory deficit impacts financial decision making is unknown. This study tested the hypothesis that metamemory deficit is associated with poor financial decision making among older adults without dementia.

Method: Data came from 502 community-dwelling older adults participating in the Rush Memory and Aging Project. Metamemory deficit was determined empirically by contrasting subjective memory ratings with performance on objective memory tests. Larger discrepancy of self-rated memory scores from performance-based testing scores indicates greater deficit. Financial decision making was assessed using a performance-based measure. Multivariable regression analyses examined the association of metamemory deficit with financial decision making.

Results: Participants had a mean age of 83 years and a mean education of 15 years. Approximately 75% were female. On average, participants answered two thirds of the financial decision making questions correctly. Female sex, older age, lower education, and lower financial literacy were correlated with poorer financial decision making. In an ordinal logistic regression model controlled for demographics and financial literacy, an 1SD increase in metamemory deficit reduced the odds of having better financial decision making by approximately 15%, OR: 0.844, 95% CI [0.719-0.991]. This association persisted after further controlling for family income, early life socioeconomic status, depressive symptoms and executive function.

Conclusions: Metamemory deficit in older adults is a potential indicator of impaired financial decision making. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/neu0000773DOI Listing
October 2021

Histologic Analysis of Urethral Stricture in 9 Patients Following Dorsal Vaginal Graft Urethroplasty.

Am J Clin Pathol 2021 Nov 1. Epub 2021 Nov 1.

Department of Urology, Wake Forest University, Winston-Salem, NC, USA.

Objective: To present the pathologic analysis of female urethral strictures obtained during reconstructive urethroplasty.

Methods: Nine separate female urethral tissue specimens were obtained during dorsal vaginal graft urethroplasty by a single surgeon (S.P.P.). Samples were serially sectioned and fixed in 10% formalin 6 to 12 hours before routine processing in paraffin blocks. Serial 5-µm sections were subjected to H&E, Masson trichrome, and elastin staining. End point analysis included evaluation for epithelial hyperplasia and cell type, mucosal edema, degree of fibroblast/inflammatory cell infiltrate, and elastin fiber density and distribution.

Results: Nine specimens were examined. Six specimens had epithelial linings of stratified squamous epithelium overlying fibrosis (67%), 1 had mixed squamous and urothelial epithelium, and 2 had only urothelial epithelium. Two specimens (29%) showed acute injury with prominent squamous papillary hyperplasia, focal erosion, and patchy mucosal hemorrhage. Areas of urethral stricture were variably thickened, with increased, densely packed collagen fibers and associated mucosal lymphocytic inflammation ranging from mild and patchy to focally dense with lymphoid aggregates. The highest elastin fiber density appeared to be associated with vessels and overlying muscle bundles in the submucosa.

Conclusions: Further elucidation of histopathologic characteristics may illuminate more appropriate therapeutic pathways for female urethral stricture disease management.
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http://dx.doi.org/10.1093/ajcp/aqab183DOI Listing
November 2021

Neuropsychiatric symptoms in Brazilians with mild cognitive impairment and dementia.

Alzheimers Dement (Amst) 2021 14;13(1):e12219. Epub 2021 Oct 14.

Rush Alzheimer's Disease Center Rush University Medical Center Chicago Illinois USA.

Introduction: Knowledge is limited about behavioral and psychological symptoms of mild cognitive impairment (MCI) and dementia in racial and ethnic minorities.

Methods: As part of the Pathology, Alzheimer's and Related Dementias Study (PARDoS), we interviewed knowledgeable informants of 2319 older Brazilian decedents (67% white, 11% black, 22% mixed) using the informant portion of the Clinical Dementia Rating Scale to classify MCI and dementia and the Neuropsychiatric Inventory to assess behavioral and psychological symptoms.

Results: We identified four clusters of neuropsychiatric symptoms: agitation, affect/apathy, psychosis, and behavioral problems. On the Clinical Dementia Rating Scale, 1407 had no cognitive impairment, 180 had MCI, and 732 had dementia. Both MCI and dementia were associated with symptoms in each behavioral/psychological cluster (all 's < .001). There was little evidence of racial differences in the association of MCI and dementia with these neuropsychiatric symptoms.

Conclusion: MCI and dementia are associated with elevated behavioral and psychological symptoms in older black and white Brazilians.
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http://dx.doi.org/10.1002/dad2.12219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515552PMC
October 2021

A Systems Approach to Interrogate Gene Expression Patterns in African American Men Presenting with Clinically Localized Prostate Cancer.

Cancers (Basel) 2021 Oct 14;13(20). Epub 2021 Oct 14.

Hollings Cancer Center, Medical University of South Carolina (MUSC), Charleston, SC 29425, USA.

An emerging theory about racial differences in cancer risk and outcomes is that psychological and social stressors influence cellular stress responses; however, limited empirical data are available on racial differences in cellular stress responses among men who are at risk for adverse prostate cancer outcomes. In this study, we undertook a systems approach to examine molecular profiles and cellular stress responses in an important segment of African American (AA) and European American (EA) men: men undergoing prostate biopsy. We assessed the prostate transcriptome with a single biopsy core via high throughput RNA sequencing (RNA-Seq). Transcriptomic analyses uncovered impacted biological pathways including PI3K-Akt signaling pathway, Neuroactive ligand-receptor interaction pathway, and ECM-receptor interaction. Additionally, 187 genes mapping to the Gene Ontology (GO) terms RNA binding, structural constituent of ribosome, SRP-dependent co-translational protein targeting to membrane and the biological pathways, translation, L13a-mediated translational silencing of Ceruloplasmin expression were differentially expressed (DE) between EA and AA. This signature allowed separation of AA and EA patients, and AA patients with the most severe clinical characteristics. AA patients with elevated expression levels of this genomic signature presented with higher Gleason scores, a greater number of positive core biopsies, elevated dehydroepiandrosterone sulfate levels and serum vitamin D deficiency. Protein-protein interaction (PPI) network analysis revealed a high degree of connectivity between these 187 proteins.
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http://dx.doi.org/10.3390/cancers13205143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533960PMC
October 2021

Brain β-amyloid links the association of change in BMI with cognitive decline in community-dwelling older adults.

J Gerontol A Biol Sci Med Sci 2021 Oct 22. Epub 2021 Oct 22.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.

Background: We tested the hypothesis that indices of AD and related dementia (ADRD) pathologies may explain associations between change in BMI and cognitive decline in old age.

Methods: We used data from 436 older decedents participating in a prospective longitudinal cohort study who had undergone annual cognitive and BMI assessments and postmortem collection of indices of twelve brain pathologies. We identified ADRD brain pathologies associated with BMI range, a previously published metric of change in BMI. We employed sigmoidal mixed-effect models of cognitive decline to examine the associations of change in BMI and cognitive decline with and without terms for ADRD brain pathologies.

Results: Average age at baseline was 78.6 years, SD=6.5 years with 64% female. On average nine cognitive assessments were obtained with average age at death 88.4 years (SD=6.2 years). Change in BMI as measured by BMI range was associated with cognitive decline (θ2=0.260). β-amyloid, hippocampal sclerosis, and substantia nigra neuronal loss were associated with BMI range. β-amyloid strongly attenuated the association of BMI range with cognitive decline. Hippocampal sclerosis showed only partial attenuation of the association of BMI range and cognitive decline and nigral neuronal loss did not attenuate this association.

Conclusion: Changes in BMI and cognitive decline in older adults may be affected by similar mechanisms underlying the accumulation of brain pathologies like β-amyloid in aging brains. Elucidating the molecular mechanisms underlying these associations may provide novel targets for developing interventions that maintain brain health and metabolic homeostasis in old age.
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http://dx.doi.org/10.1093/gerona/glab320DOI Listing
October 2021

Amino-Heterocycle Tetrahydroisoquinoline CXCR4 Antagonists with Improved ADME Profiles via Late-Stage Buchwald Couplings.

ACS Med Chem Lett 2021 Oct 4;12(10):1605-1612. Epub 2021 Oct 4.

Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, United States.

This work surveys a variety of diamino-heterocycles as an isosteric replacement for the piperazine substructure of our previously disclosed piperarinyl-tetrahydroisoquinoline containing CXCR4 antagonists. A late-stage Buchwald coupling route was developed for rapid access to final compounds from commercial building blocks. Among 13 analogs in this study, compound embodying an aza-piperazine linkage was found to have the best overall profile with potent CXCR4 inhibitory activity and favorable in vitro absorption, distribution, metabolism, and excretion (ADME) properties. An analysis of the calculated physiochemical parameters (ROF, cLogD) and the experimental ADME attributes of the analogs lead to the selection of for pharmacokinetic studies in mice. Compared with the clinical compound AMD11070, compound has no CYP450 3A4 or 2D6 inhibition, higher metabolic stability and PAMPA permeability, greatly improved physiochemical parameters, and superior oral bioavailability (% = 24). A binding rationale for within CXCR4 was elucidated from docking and molecular simulation studies.
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http://dx.doi.org/10.1021/acsmedchemlett.1c00449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521655PMC
October 2021

Raman spectroscopy-based water measurements identify the origin of MRI T2 signal in human articular cartilage zones and predict histopathologic score.

J Biophotonics 2021 Oct 20:e202100212. Epub 2021 Oct 20.

Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, Ohio, USA.

We investigated for the first time zonal-dependent water distribution in articular cartilage by Raman spectroscopy (RS). We further investigated the association of histopathologic score with RS- and magnetic resonance imaging (MRI)-based water measurements. Cadaveric human cartilage plugs (N = 16) with different osteoarthritis (OA) severity were used. Water content distribution in cartilage zones was probed using RS- and MRI-based techniques. Histopathologic scoring was performed by two independent observers blindly. Moderate associations existed between RS- and MRI-based water measurements across all cartilage zones. RS-based analysis of different water compartments helped assign the origin of the T2 signal collected from the various cartilage zones. RS-based water parameters significantly correlated with OA-severity score, whereas MRI-based water measurements did not. RS can probe different water compartments in cartilage zones and predict up to 66% of the variation observed in the histopathologic score. RS-based water measurement could be developed further to assess cartilage quality in the clinic.
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http://dx.doi.org/10.1002/jbio.202100212DOI Listing
October 2021

Relationship of Purpose in Life to Dementia in Older Black and White Brazilians.

J Int Neuropsychol Soc 2021 Oct 19:1-6. Epub 2021 Oct 19.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.

Objectives: To test the hypothesis that higher level of purpose in life is associated with lower likelihood of dementia and mild cognitive impairment (MCI) in older Brazilians.

Methods: As part of the Pathology, Alzheimer's and Related Dementias Study (PARDoS), informants of 1,514 older deceased Brazilians underwent a uniform structured interview. The informant interview included demographic data, the Clinical Dementia Rating scale to diagnose dementia and MCI, the National Institute of Mental Health Diagnostic Interview Schedule for depression, and a 6-item measure of purpose in life, a component of well-being.

Results: Purpose scores ranged from 1.5 to 5.0 with higher values indicating higher levels of purpose. On the Clinical Dementia Rating Scale, 940 persons (62.1%) had no cognitive impairment, 121 (8.0%) had MCI, and 453 (29.9%) had dementia. In logistic regression models adjusted for age at death, sex, education, and race, higher purpose was associated with lower likelihood of MCI (odds ratio = .58; 95% confidence interval [CI]: .43, .79) and dementia (odds ratio = .49, 95% CI: .41, .59). Results were comparable after adjusting for depression (identified in 161 [10.6%]). Neither race nor education modified the association of purpose with cognitive diagnoses.

Conclusions: Higher purpose in life is associated with lower likelihood of MCI and dementia in older black and white Brazilians.
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http://dx.doi.org/10.1017/S1355617721001211DOI Listing
October 2021

Criteria and definitions for the radiological and clinical diagnosis of bronchiectasis in adults for use in clinical trials: international consensus recommendations.

Lancet Respir Med 2021 Sep 24. Epub 2021 Sep 24.

Department of Pneumology Dr Josep Trueta Hospital, Biomedical Research Institute of Girona, Universitat de Girona, Girona, Spain.

Bronchiectasis refers to both a clinical disease and a radiological appearance that has multiple causes and can be associated with a range of conditions. Disease heterogeneity and the absence of standardised definitions have hampered clinical trials of treatments for bronchiectasis and are important challenges in clinical practice. In view of the need for new therapies for non-cystic fibrosis bronchiectasis to reduce the disease burden, we established an international taskforce of experts to develop recommendations and definitions for clinically significant bronchiectasis in adults to facilitate the standardisation of terminology for clinical trials. Systematic reviews were used to inform discussions, and Delphi processes were used to achieve expert consensus. We prioritised criteria for the radiological diagnosis of bronchiectasis and suggest recommendations on the use and central reading of chest CT scans to confirm the presence of bronchiectasis for clinical trials. Furthermore, we developed a set of consensus statements concerning the definitions of clinical bronchiectasis and its specific signs and symptoms, as well as definitions for chronic bacterial infection and sustained culture conversion. The diagnosis of clinically significant bronchiectasis requires both clinical and radiological criteria, and these expert recommendations and proposals should help to optimise patient recruitment into clinical trials and allow reliable comparisons of treatment effects among different interventions for bronchiectasis. Our consensus proposals should also provide a framework for future research to further refine definitions and establish definitive guidance on the diagnosis of bronchiectasis.
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http://dx.doi.org/10.1016/S2213-2600(21)00277-0DOI Listing
September 2021

Relation of Literacy and Music Literacy to Dementia in Older Black and White Brazilians.

J Alzheimers Dis 2021 ;84(2):737-744

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.

Background: Literacy is more consistently reported than education as protective against dementia in developing regions.

Objective: To study the association of verbal literacy, numeracy, and music literacy with dementia in older Black and White Brazilians with a broad spectrum of education.

Methods: We studied 1,818 Black, Mixed-race, and White deceased Brazilians 65 years or older at death (mean = 79.64). Data were retrospectively obtained within 36 hours after death in a face-to-face interview with an informant, usually a family member. Dementia was classified using the Clinical Dementia Rating (CDR) scale. Three forms of literacy were ascertained: verbal literacy (10 questions: reading and writing), numeracy (3 questions: multiplication, percentages, and use of a calculator), and music literacy (1 question: reading music). Black (11%) and Mixed-race (23%) older adults were combined in analyses. Models adjusted for age and sex.

Results: Dementia was identified in 531 people. Participants had 0 to 25 years of education (median = 4). More literacy was associated with lower odds of dementia (all p≤0.039). Participants that read music had about half the odds of having dementia. Participants in the highest quartile of numeracy and verbal literacy had respectively 27%and 15%lower odds of having dementia compared to the lowest quartile. Literacy was lower in Blacks (p < 0.001, except music p = 0.894) but the effect of literacy on dementia was similar (interaction p > 0.237). In secondary analyses, playing instruments without reading music was not associated with dementia (p = 0.887).

Conclusion: In a large sample of Brazilians, verbal literacy, numeracy, and music literacy were associated with lower odds of dementia. The effect was similar across races.
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http://dx.doi.org/10.3233/JAD-210601DOI Listing
January 2021

Influence of Preoperative and Postoperative Factors on Prolonged Length of Stay and Readmission after Minimally Invasive Radical Prostatectomy.

J Endourol 2021 Sep 22. Epub 2021 Sep 22.

Wake Forest University School of Medicine, 12279, Medical Center BLVD, Winston-Salem, North Carolina, United States, 27101-4135.

Background: The mean length of stay (LOS) following minimally invasive radical prostatectomy (MI-RP) is less than 2 days. Our main objective was to utilize the National Surgical Quality Improvement Program Database (NSQIP) to evaluate preoperative factors that may contribute to prolonged hospital stay and readmission.

Materials And Methods: Utilizing the NSQIP database, records for surgery with the Current Procedural Terminology (CPT) code 55866 (prostatectomy) between 2007 and 2017 were evaluated. Chi-square and t-tests were used to assess the effects of preoperative factors on prolonged LOS and rates of hospital readmission within 30 days. Odds ratios, p-values, and confidence intervals were determined using multivariable logistic regression.

Results: 40,764 patients underwent MI-RP between 2007 and 2017. Of these, 11.7% reported a LOS of more than 2 days, while 3.9% of patients were readmitted to the hospital within 30 days. Preoperative congestive heart failure within 30 days of surgery was shown to be strongly associated with both prolonged LOS (OR = 6.16) and readmission (OR = 3.28). Bleeding requiring transfusion was demonstrated to be the most significant postoperative factor for prolonged LOS (OR= 23.9), while unplanned intubation was shown to be the most significant postoperative factor for readmission (OR=57.1). BMI over 30 was associated with both prolonged LOS and increase in readmission.

Conclusions: Upon NSQIP database analysis, cardiopulmonary factors and BMI were demonstrated to have negative impacts on postoperative quality indicators. Patients with comorbidities should be counselled preoperatively concerning their individual risk factors. Mitigation of these factors is important in ensuring optimal outcomes.
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http://dx.doi.org/10.1089/end.2021.0571DOI Listing
September 2021

The Orthopaedic Match: Defining the Academic Profile of Successful Candidates.

J Am Acad Orthop Surg 2021 Nov;29(21):921-928

From the Division of Plastic Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD (Ngaage, Xue, Benzel, Rawes, Rasko), the Medical College of Georgia, Augusta, GA (Xue), the Department of Orthopaedic Surgery, Howard University, Washington, DC (Andrews, Wilson), the Yorkshire and Humber Foundation School, Leeds, UK (Rawes), and the Department of Orthopaedic Surgery, University of Maryland School of Medicine, Baltimore, MD (Ludwig).

Background: Research productivity forms a vital part of the resident selection process and can markedly affect the chance of a successful match. Current reports regarding the publication record among prospective orthopaedic surgery residents are likely inaccurate. Potential applicants have a poor understanding of the strength of their research credentials in comparison to other candidates.

Methods: We identified matched applicants from the 2013 to 2017 orthopaedic surgery residency application cycles. We performed a bibliometric analysis of these residents using Scopus, PubMed, and Google Scholar to identify published articles and calculate the h-index of each applicant at the time of application. Details were collected on medical school, advanced degrees, publication type, first authorship, and article relatedness to orthopaedic surgery.

Results: We included 3,199 matched orthopaedic surgery applicants. At the time of application, the median h-index was 0, the median number of publications was 1, and 40% of successful candidates did not hold any publications. The h-index (R 0.08, P < 0.0001) and median number of publications of matched orthopaedic surgery residency candidates significantly increased (R 0.09, P < 0.0001) across application cycles. Furthermore, the proportion of matched applicants without publications at the time of application significantly decreased (R -0.90, P = 0.0350). Conversely, the percentage of articles first-authored by applicants decreased (R -0.96, P = 0.0093), but article relatedness to orthopaedic surgery remained constant (R 0.82, P = 0.0905). Strikingly, notable changes were observed in the type of articles published by successful applicants: the proportion of preclinical studies decreased (R -0.07, P = 0.0041), whereas clinical research articles increased (R 0.07, P = 0.0024).

Conclusion: The publication count held by successful orthopaedic surgery applicants is substantially lower than the nationally reported average. Matched orthopaedic surgery candidates demonstrate increasingly impressive research achievements each application cycle. However, increased academic productivity comes at the cost of reduced project responsibility and a shift toward faster-to-publish articles.
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http://dx.doi.org/10.5435/JAAOS-D-20-00727DOI Listing
November 2021

Human inference in changing environments with temporal structure.

Psychol Rev 2021 10 13;128(5):879-912. Epub 2021 Sep 13.

Laboratoire de Physique.

To make informed decisions in natural environments that change over time, humans must update their beliefs as new observations are gathered. Studies exploring human inference as a dynamical process that unfolds in time have focused on situations in which the statistics of observations are history-independent. Yet, temporal structure is everywhere in nature and yields history-dependent observations. Do humans modify their inference processes depending on the latent temporal statistics of their observations? We investigate this question experimentally and theoretically using a change-point inference task. We show that humans adapt their inference process to fine aspects of the temporal structure in the statistics of stimuli. As such, humans behave qualitatively in a Bayesian fashion but, quantitatively, deviate away from optimality. Perhaps more importantly, humans behave suboptimally in that their responses are not deterministic, but variable. We show that this variability itself is modulated by the temporal statistics of stimuli. To elucidate the cognitive algorithm that yields this behavior, we investigate a broad array of existing and new models that characterize different sources of suboptimal deviations away from Bayesian inference. While models with "output noise" that corrupts the response-selection process are natural candidates, human behavior is best described by sampling-based inference models, in which the main ingredient is a compressed approximation of the posterior, represented through a modest set of random samples and updated over time. This result comes to complement a growing literature on sample-based representation and learning in humans. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/rev0000276DOI Listing
October 2021

Detection of SARS-CoV-2 in Wastewater at Residential College, Maine, USA, August-November 2020.

Emerg Infect Dis 2021 1;27(12):3111-3114. Epub 2021 Sep 1.

We used wastewater surveillance to identify 2 coronavirus disease outbreaks at a college in Maine, USA. Cumulative increases of >1 log severe acute respiratory syndrome coronavirus 2 RNA in consecutive 24-hour composite samples preceded the outbreaks. For 76% of cases, RNA was identified in grab samples from residence halls <7 days before case discovery.
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http://dx.doi.org/10.3201/eid2712.211199DOI Listing
November 2021

The venous system of E14.5 mouse embryos-reference data and examples for diagnosing malformations in embryos with gene deletions.

J Anat 2021 Aug 25. Epub 2021 Aug 25.

Division of Anatomy, MIC, BioImaging Austria/CMI, Medical University of Vienna, Vienna, Austria.

Approximately one-third of randomly produced knockout mouse lines produce homozygous offspring, which fail to survive the perinatal period. The majority of these die around or after embryonic day (E)14.5, presumably from cardiovascular insufficiency. For diagnosing structural abnormalities underlying death and diseases and for researching gene function, the phenotype of these individuals has to be analysed. This makes the creation of reference data, which define normal anatomy and normal variations the highest priority. While such data do exist for the heart and arteries, they are still missing for the venous system. Here we provide high-quality descriptive and metric information on the normal anatomy of the venous system of E14.5 embryos. Using high-resolution digital volume data and 3D models from 206 genetically normal embryos, bred on the C57BL/6N background, we present precise descriptive and metric information of the venous system as it presents itself in each of the six developmental stages of E14.5. The resulting data shed new light on the maturation and remodelling of the venous system at transition of embryo to foetal life and provide a reference that can be used for detecting venous abnormalities in mutants. To explore this capacity, we analysed the venous phenotype of embryos from 7 knockout lines (Atp11a, Morc2a, 1700067K01Rik, B9d2, Oaz1, Celf4 and Coro1c). Careful comparisons enabled the diagnosis of not only simple malformations, such as dual inferior vena cava, but also complex and subtle abnormalities, which would have escaped diagnosis in the absence of detailed, stage-specific referenced data.
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http://dx.doi.org/10.1111/joa.13536DOI Listing
August 2021

Simultaneous Temperature Measurements and Aerosol Collection During Vaping for the Analysis of Δ-Tetrahydrocannabinol and Vitamin E Acetate Mixtures in Ceramic Coil Style Cartridges.

Front Chem 2021 9;9:734793. Epub 2021 Aug 9.

Forensic Chemistry Center, Office of Regulatory Science, Office of Regulatory Affairs, U.S. Food and Drug Administration, Cincinnati, OH, United States.

Incidence of e-cigarette, or vaping, product use-associated lung injury (EVALI) has been linked to the vaping of tetrahydrocannabinol (THC) products to which vitamin E acetate (VEA) has been added. In this work we vaped THC/VEA mixtures at elevated power levels using a variety of ceramic coil vaping cartridges and a commercially available vaping device, while simultaneously measuring temperature and collecting the vaporized condensate. The collected vapor condensate was analyzed for evidence of VEA decomposition by GC/MS, GC/FT-IR/MS, and LC-APCI-HRMS/MS. Mean temperature maxima for all examined cartridges at the selected power exceeded 430°C, with a range of 375-569°C, well beyond that required for thermal decomposition of VEA. The percent recovery of VEA and Δ-THC from the vaporized mixture in six cartridges ranged from 71.5 to 101% and from 56.4 to 88.0%, respectively. Analysis of the condensed vaporized material identified VEA decomposition products duroquinone (DQ), 1-pristene, and durohydroquinone monoacetate (DHQMA); a compound consistent with 4-acetoxy-2,3,5-trimethyl-6-methylene-2,4-cyclohexadienone (ATMMC) was also detected. The concentration of DQ produced from vaporization of the THC/VEA mixture in one cartridge was found to be 4.16 ± 0.07 μg per mg of vapor condensate.
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http://dx.doi.org/10.3389/fchem.2021.734793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381023PMC
August 2021

The Effect of Stepping Back From the X-Ray Table on Operator Radiation Exposure.

Health Phys 2021 Nov;121(5):522-530

Egg Medical, Inc. Arden Hills, MN.

Abstract: Background: Nearly all radiation safety courses teach that scatter radiation around the x-ray table falls with the inverse of the distance from the imaging site. Humans, however, are complex x-ray reflectors and the application of the inverse square law to clinical imaging is only assumed. Methods: We measured scatter radiation at two positions where staff commonly stand around the x-ray table. Using an anthropomorphic human phantom, human and pig cadavers, and a glass sphere, we measured scatter radiation levels in each position, and then 2- and 3-fold the distance from the imaging site. We compared the measured scatter radiation to that predicted by the common inverse square law and a more detailed geometric inverse square law. Results: In all but the glass sphere, scatter radiation was much higher below the table (68-74% of all scatter radiation, depending on model and position) than above the table (26-32% of scatter radiation, p < 0.01). Scatter radiation fell with increasing distance from the table, but above the table both inverse square laws significantly over-estimated the benefit of stepping back (19-93% overestimation by geometric inverse square law at 2-fold distance, 14-46% at 3-fold). In addition, a pelvis in the phantom appeared to cause significant scatter radiation field anomalies at the angiographer position. Conclusion: Stepping back from the table does not reduce scatter radiation levels as much as the inverse square law predicts. The geometric inverse square law best predicts the reduction in scatter radiation below the table, but above the table it too overestimates the benefit of stepping back. The irregularity of the scatter radiation field should be taken into account by scatter radiation shielding systems.
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http://dx.doi.org/10.1097/HP.0000000000001457DOI Listing
November 2021

Longitudinal Association of Total Tau Concentrations and Physical Activity With Cognitive Decline in a Population Sample.

JAMA Netw Open 2021 Aug 2;4(8):e2120398. Epub 2021 Aug 2.

Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, Illinois.

Importance: Tau is a brain protein located in neurons and develops abnormally in individuals with Alzheimer disease. New technology is convenient for measuring blood total tau concentrations and provides a unique and increased opportunity for early intervention to slow cognitive decline.

Objective: To evaluate the association of physical activity and total tau concentrations with cognitive decline at baseline and over time.

Design, Setting, And Participants: The Chicago Health and Aging Project is a population-based cohort study conducted in 4 Chicago communities. Data collection occurred in 3-year cycles between 1993 and 2012. Participants completed in-home interviews. Clinical evaluations, which included blood samples, were performed with a stratified random sample of 1159 participants. Statistical analyses were conducted from October 30, 2020, to May 25, 2021.

Exposures: Physical activity and total serum tau concentrations. Data on physical activity were obtained through self-report items, and a sum of minutes per week was calculated. Little physical activity was defined as no participation in a minimum of 4 of the items on the physical activity measure. Medium activity was defined as participating in less than 150 minutes of physical activity per week, and high activity was defined as participating in 150 minutes or more of physical activity per week.

Main Outcomes And Measures: The main outcome for this study is global cognitive function, measured through a battery of cognitive tests. The study hypothesis was developed after data were collected.

Results: Of the 1159 participants in the study, 728 were women (63%), and 696 were African American (60%); the mean (SD) age was 77.4 (6.0) years, and the mean (SD) educational level was 12.6 (3.5) years. Participants with high total tau concentrations with medium physical activity had a 58% slower rate of cognitive decline (estimate, -0.028 standard deviation unit [SDU] per year [95% CI, -0.057 to 0.002 SDU per year]; difference, 0.038 SDU per year [95% CI, 0.011-0.065 SDU per year]), and those with high physical activity had a 41% slower rate of cognitive decline (estimate, -0.038 SDU per year [95% CI, -0.068 to -0.009 SDU per year]; difference, 0.027 SDU per year [95% CI, -0.002 to 0.056 SDU per year]), compared with those with little physical activity. Among participants with low total tau concentrations, medium physical activity was associated with a 2% slower rate of cognitive decline (estimate, -0.050 SDU per year [95% CI, -0.069 to -0.031 SDU per year]; difference, 0.001 SDU per year [95% CI, -0.019 to 0.021 SDU per year]), and high physical activity was associated with a 27% slower rate of cognitive decline (estimate, -0.037 SDU per year [95% CI, -0.055 to -0.019 SDU per year]; difference, 0.014 SDU per year [95% CI, -0.007 to 0.034 SDU per year]), compared with little physical activity. Individual tests of cognitive function showed similar results.

Conclusions And Relevance: This study suggests that, among participants with both high and low total tau concentrations, physical activity was associated with slower cognitive decline. Results support the potential utility of blood biomarkers in measuring the benefits associated with health behaviors and may contribute to specifying target populations or informing interventions for trials that focus on improving physical activity behavior. Future work should examine the association of total tau concentrations with other health behaviors and physical activity types.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.20398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358733PMC
August 2021

Microclimate and resource quality determine resource use in a range-expanding herbivore.

Biol Lett 2021 08 4;17(8):20210175. Epub 2021 Aug 4.

College of Life and Environmental Sciences, University of Exeter, Exeter, UK.

The consequences of climate change for biogeographic range dynamics depend on the spatial scales at which climate influences focal species directly and indirectly via biotic interactions. An overlooked question concerns the extent to which microclimates modify specialist biotic interactions, with emergent properties for communities and range dynamics. Here, we use an in-field experiment to assess egg-laying behaviour of a range-expanding herbivore across a range of natural microclimatic conditions. We show that variation in microclimate, resource condition and individual fecundity can generate differences in egg-laying rates of almost two orders of magnitude in an exemplar species, the brown argus butterfly (). This within-site variation in fecundity dwarfs variation resulting from differences in average ambient temperatures among populations. Although higher temperatures did not reduce female selection for host plants in good condition, the thermal sensitivities of egg-laying behaviours have the potential to accelerate climate-driven range expansion by increasing egg-laying encounters with novel hosts in increasingly suitable microclimates. Understanding the sensitivity of specialist biotic interactions to microclimatic variation is, therefore, critical to predict the outcomes of climate change across species' geographical ranges, and the resilience of ecological communities.
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http://dx.doi.org/10.1098/rsbl.2021.0175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8331228PMC
August 2021

HumGut: a comprehensive human gut prokaryotic genomes collection filtered by metagenome data.

Microbiome 2021 07 31;9(1):165. Epub 2021 Jul 31.

Department of Chemistry, Biotechnology and Food Sciences, Norwegian University of Life Sciences, P.O. Box 5003, 1432, Ås, Norway.

Background: A major bottleneck in the use of metagenome sequencing for human gut microbiome studies has been the lack of a comprehensive genome collection to be used as a reference database. Several recent efforts have been made to re-construct genomes from human gut metagenome data, resulting in a huge increase in the number of relevant genomes. In this work, we aimed to create a collection of the most prevalent healthy human gut prokaryotic genomes, to be used as a reference database, including both MAGs from the human gut and ordinary RefSeq genomes.

Results: We screened > 5,700 healthy human gut metagenomes for the containment of > 490,000 publicly available prokaryotic genomes sourced from RefSeq and the recently announced UHGG collection. This resulted in a pool of > 381,000 genomes that were subsequently scored and ranked based on their prevalence in the healthy human metagenomes. The genomes were then clustered at a 97.5% sequence identity resolution, and cluster representatives (30,691 in total) were retained to comprise the HumGut collection. Using the Kraken2 software for classification, we find superior performance in the assignment of metagenomic reads, classifying on average 94.5% of the reads in a metagenome, as opposed to 86% with UHGG and 44% when using standard Kraken2 database. A coarser HumGut collection, consisting of genomes dereplicated at 95% sequence identity-similar to UHGG, classified 88.25% of the reads. HumGut, half the size of standard Kraken2 database and directly comparable to the UHGG size, outperforms them both.

Conclusions: The HumGut collection contains > 30,000 genomes clustered at a 97.5% sequence identity resolution and ranked by human gut prevalence. We demonstrate how metagenomes from IBD-patients map equally well to this collection, indicating this reference is relevant also for studies well outside the metagenome reference set used to obtain HumGut. All data and metadata, as well as helpful code, are available at http://arken.nmbu.no/~larssn/humgut/ . Video Abstract.
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http://dx.doi.org/10.1186/s40168-021-01114-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325300PMC
July 2021

Cognitive Activity and Onset Age of Incident Alzheimer Disease Dementia.

Neurology 2021 08 14;97(9):e922-e929. Epub 2021 Jul 14.

From the Rush Alzheimer's Disease Center (R.S.W., T.W., L.Y., F.G., D.A.B., P.A.B.), Department of Neurological Sciences (R.S.W., T.W., L.Y., F.G., D.A.B.), and Department of Psychiatry and Behavioral Sciences (R.S.W., P.A.B.), Rush University Medical Center, Chicago, IL.

Objective: To test the hypothesis that higher level of cognitive activity predicts older age at dementia onset in Alzheimer disease (AD) dementia.

Methods: As part of a longitudinal cohort study, 1,903 older persons without dementia at enrollment reported their frequency of participation in cognitively stimulating activities. They had annual clinical evaluations to diagnose dementia and AD, and the deceased underwent neuropathologic examination. In analyses, we assessed the relation of baseline cognitive activity to age at diagnosis of incident AD dementia and to postmortem markers of AD and other dementias.

Results: During a mean of 6.8 years of follow-up, 457 individuals were diagnosed with incident AD at a mean age of 88.6 (SD 6.4, range 64.1-106.5) years. In an extended accelerated failure time model, higher level of baseline cognitive activity (mean 3.2, SD 0.7) was associated with older age at AD dementia onset (estimate 0.026; 95% confidence interval 0.013-0.039). Low cognitive activity (score 2.1, 10th percentile) was associated with a mean onset age of 88.6 years compared to a mean onset age of 93.6 years associated with high cognitive activity (score 4.0, 90th percentile). Results were comparable in subsequent analyses that adjusted for potentially confounding factors. In 695 participants who died and underwent a neuropathologic examination, cognitive activity was unrelated to postmortem markers of AD and other dementias.

Conclusion: A cognitively active lifestyle in old age may delay the onset of dementia in AD by as much as 5 years.
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http://dx.doi.org/10.1212/WNL.0000000000012388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408511PMC
August 2021

Invaplex functions as an intranasal adjuvant for subunit and DNA vaccines co-delivered in the nasal cavity of nonhuman primates.

Vaccine X 2021 Aug 24;8:100105. Epub 2021 Jun 24.

Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.

Development of intranasal vaccines for HIV-1 and other mucosal pathogens has been hampered by the lack of adjuvants that can be given safely to humans. We have found that an intranasal Shigella vaccine (Invaplex) which is well tolerated in humans can also function as an adjuvant for intranasal protein and DNA vaccines in mice. To determine whether Invaplex could potentially adjuvant similar vaccines in humans, we simultaneously administered a simian immunodeficiency virus (SIV) envelope (Env) protein and DNA encoding simian-human immunodeficiency virus (SHIV) with or without Invaplex in the nasal cavity of female rhesus macaques. Animals were intranasally boosted with adenoviral vectors expressing SIV or to evaluate memory responses. Anti-SIV antibodies in sera and nasal, genital tract and rectal secretions were quantitated by ELISA. Intracellular cytokine staining was used to measure Th1-type T cells in blood. Macaques given DNA/protein immunizations with 0.5 mg Invaplex developed greater serum IgG, nasal IgA and cervicovaginal IgA responses to SIV Env and SHIV Gag,Pol proteins when compared to non-adjuvanted controls. Rectal IgA responses to Env were only briefly elevated and not observed to Gag,Pol. Invaplex increased frequencies of IFNγ-producing CD4 and CD8 T cells to the Env protein, but not T cell responses induced by the DNA. Ad-SIV boosting increased Env-specific polyfunctional T cells and Env- and Gag,Pol-specific antibodies in serum and all secretions. The data suggest that Invaplex could be highly effective as an adjuvant for intranasal protein vaccines in humans, especially those intended to prevent infections in the genital or respiratory tract.
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http://dx.doi.org/10.1016/j.jvacx.2021.100105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255935PMC
August 2021

A Case of Tumor-Induced Osteomalacia: Finding the Culprit Acetabular Tumor and Successful Resection with a Novel Hip Joint-Preserving Surgery.

J Orthop Case Rep 2021 Mar;11(3):37-41

Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, The University of Pennsylvania, Philadelphia, PA, United States.

Introduction: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic disorder caused by tumors that produce fibroblast growth factor 23 (FGF23) resulting in phosphate wasting and inadequate bone mineralization. Complete resection of the tumor can be curative. However, these tumors are typically difficult to find anatomically due to small size and location.

Case Report: We present the case of a patient who presented for evaluation of recurrent fractures and hypophosphatemia in the setting of elevated FGF23 suggestive of TIO. 68Gallium-DOTATATE revealed multiple somatostatin avid lesions in several ribs, left acetabulum, sacrum, right tibia, and feet, some of which appeared with fracture on computed tomography scan, initially concerning for metastatic disease. However, the lesion in acetabulum was considered the culprit tumor given its remarkably higher maximum standard uptake values. Complete surgical removal of the FGF23-secreting tumor led to cure of this disease.

Conclusion: This case report highlights the challenges with functional imaging differentiating fractures from the culprit lesion and reports on a novel surgical technique that allowed for surgical cure while preserving the hip joint.
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http://dx.doi.org/10.13107/jocr.2021.v11.i03.2078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241250PMC
March 2021

Oral Vaccination Approaches for Anti-SHIV Immunity.

Front Immunol 2021 21;12:702705. Epub 2021 Jun 21.

Department of Medicine, Boston Children's Hospital, Boston, MA, United States.

We modified a Sabin Oral Poliovirus Vaccine (OPV) vector to permit secretion of the antigens of interest with the goal of improving anti-HIV Env humoral responses in a SHIV mucosal immunization composed of DNA and recombinant OPVs. We evaluated stimulation of systemic and mucosal cell-mediated and humoral immunity in Rhesus macaques by two regimens, both involving a prime with a SHIVDNA construct producing non-infectious particles formulated in lipid nanoparticles, administered in the oral cavity, and two different viral vector boostings, administered in the oral cavity and intestinally.Group 1 was boosted with rMVA-SHIVBG505, expressing SIV Gag/Pol and HIV Env. Group 2 was boosted with a SHIV-OPV vaccine including a non-secreting SIVCA-p6-OPV, expressing Gag CA, NC and p6 proteins, and a HIVC1-V2-OPV, secreting the C1-V2 fragment of HIV Env, recognized by the broadly neutralizing antibody PG16. A time course analysis of anti-SHIV Gag and Env CD4+ and CD8+ T-cell responses in PBMC and in lymph node, rectal, and vaginal MNC was carried out. Both regimens stimulated significant cell-mediated responses in all compartments, with SHIV-OPV immunization stimulating more significant levels of responses than rMVA- SHIV. Boolean analysis of these responses revealed predominantly monofunctional responses with multifunctional responses also present in all tissues. Stimulation of antibody responses was disappointing in both groups with negative anti-SHIV IgG in plasma, and IgA in salivary, rectal and vaginal secretions being restricted to a few animals. After repeated rectal challenge with SHIV, two Group 1 animals remained uninfected at challenge termination. No significant differences were observed in post-infection viral loads between groups. After the acute phase decline, CD4+ T cell percentages returned to normal levels in vaccinated as well as control animals. However, when compared to controls, vaccinate groups had more significant preservation of PBMC and rectal MNC Th17/Treg ratios, considered the strongest surrogate marker of progression to AIDS. We conclude that the vaccine platforms used in this study are insufficient to stimulate significant humoral immunity at the tested doses and schedule but sufficient to stimulate significant mucosal and systemic cell-mediated immunity, impacting the preservation of key Th17 CD4+ T cells in blood and rectal mucosa.
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http://dx.doi.org/10.3389/fimmu.2021.702705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256843PMC
June 2021

Accumulation Dynamics of Transcripts and Proteins of Cold-Responsive Genes in Genotypes of Differing Cold Tolerance.

Int J Mol Sci 2021 Jun 7;22(11). Epub 2021 Jun 7.

Biology Department 723 W Michigan Street IUPUI, Indianapolis, IN 46202, USA.

Identifying and characterizing cold responsive genes in associated with or responsible for low temperature tolerance is a vital part of strawberry cultivar development. In this study we have investigated the transcript levels of eight genes, two dehydrin genes, three putative ABA-regulated genes, two cold-inducible CBF genes and the alcohol dehydrogenase gene, extracted from leaf and crown tissues of three genotypes that vary in cold tolerance. Transcript levels of the CBF/DREB1 transcription factor exhibited stronger cold up-regulation in comparison to in all genotypes. Transcripts of were highly up-regulated in both crown and leaf tissues from all three genotypes. In the 'ALTA' genotype, transcripts were significantly higher in leaf than crown tissues and more than 10 to 20-fold greater than in the less cold-tolerant 'NCGR1363' and 'FDP817' genotypes. , containing the conserved ABRE promoter element, transcript was found to be cold-regulated in crowns. Direct comparison of the kinetics of transcript and protein accumulation of dehydrins was scrutinized. In all genotypes and organs, the changes of transcript levels generally preceded protein changes, while levels of COR47 protein accumulation preceded the increases in RNA in 'ALTA' crowns.
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http://dx.doi.org/10.3390/ijms22116124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201005PMC
June 2021

Purpose in Life May Delay Adverse Health Outcomes in Old Age.

Am J Geriatr Psychiatry 2021 May 21. Epub 2021 May 21.

Rush University Medical Center, Rush Alzheimer's Disease Center, Chicago, IL; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL.

Objective: Test the hypothesis that a higher level of purpose in life is associated with an older age of Alzheimer's dementia onset and later mortality.

Design: Prospective cohort studies of aging and Alzheimer's dementia.

Setting: Community-based.

Participants: Two thousand five hundred fifty-eight older adults initially free of dementia underwent assessments of purpose in life and detailed annual clinical evaluations to document incident Alzheimer's dementia and mortality. General accelerated failure time models examined the relation of baseline purpose in life with age at Alzheimer's dementia diagnosis and mortality.

Exposures: Purpose in life was assessed at baseline.

Main Outcomes: Alzheimer's dementia diagnosis was documented annually based on detailed clinical evaluations and mortality was documented via regular contacts and annual evaluations.

Results: During a mean of 6.89 years of follow-up, 520 individuals were diagnosed with incident Alzheimer's dementia at a mean age of 88 (SD = 6.7; range: 64.1-106.5). They had a mean baseline level of purpose in life of 3.7 (SD = 0.47; range: 1-5). A higher level of purpose in life was associated with a considerably later age of dementia onset (estimate = 0.044; 95% CI: 0.023, 0.065); specifically, individuals with high purpose (90th percentile) developed Alzheimer's dementia at a mean age of about 95 compared to a mean age of about 89 for individuals with low purpose (10th percentile). Further, the estimated mean age of death was about 89 for individuals with high purpose compared to 85 for those with low purpose. Results persisted after controlling for sex and education.

Conclusion And Relevance: Purpose in life delays dementia onset and mortality by several years. Interventions to increase purpose in life among older persons may increase healthspan and offer considerable public health benefit.
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http://dx.doi.org/10.1016/j.jagp.2021.05.007DOI Listing
May 2021

Adaptive learning is structure learning in time.

Neurosci Biobehav Rev 2021 09 16;128:270-281. Epub 2021 Jun 16.

Carney Institute for Brain Sciences, Brown University, 164 Angell Street, Providence, RI, 02912, USA.

People use information flexibly. They often combine multiple sources of relevant information over time in order to inform decisions with little or no interference from intervening irrelevant sources. They adjust the degree to which they use new information over time rationally in accordance with environmental statistics and their own uncertainty. They can even use information gained in one situation to solve a problem in a very different one. Learning flexibly rests on the ability to infer the context at a given time, and therefore knowing which pieces of information to combine and which to separate. We review the psychological and neural mechanisms behind adaptive learning and structure learning to outline how people pool together relevant information, demarcate contexts, prevent interference between information collected in different contexts, and transfer information from one context to another. By examining all of these processes through the lens of optimal inference we bridge concepts from multiple fields to provide a unified multi-system view of how the brain exploits structure in time to optimize learning.
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http://dx.doi.org/10.1016/j.neubiorev.2021.06.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422504PMC
September 2021

The link between social and emotional isolation and dementia in older black and white Brazilians.

Int Psychogeriatr 2021 Jun 15:1-7. Epub 2021 Jun 15.

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.

Objective: To examine the link between social and emotional isolation and likelihood of dementia among older black and white Brazilians.

Design: Cross-sectional clinical-pathological cohort study.

Setting: Medical center in Sao Paulo, Brazil.

Participants: As part of the Pathology, Alzheimer's and Related Dementias Study, we conducted uniform structured interviews with knowledgeable informants (72% children) of 1,493 older (age > 65) Brazilian decedents.

Measurements: The interview included measures of social isolation (number of family and friends in at least monthly contact with decedent), emotional isolation (short form of UCLA Loneliness Scale), and major depression plus the informant portion of the Clinical Dementia Rating Scale to diagnose dementia and its precursor, mild cognitive impairment (MCI).

Results: Decedents had a median social network size of 8.0 (interquartile range = 9.0) and a median loneliness score of 0.0 (interquartile range = 1.0). On the Clinical Dementia Rating Scale, 947 persons had no cognitive impairment, 122 had MCI, and 424 had dementia. In a logistic regression model adjusted for age, education, sex, and race, both smaller network size (odds ratio [OR] = 0.975; 95% confidence interval [CI]: 0.962, 0.989) and higher loneliness (OR = 1.145; 95% CI: 1.060, 1.237) were associated with higher likelihood of dementia. These associations persisted after controlling for depression (present in 10.4%) and did not vary by race. After controlling for depression, neither network size nor loneliness was related to MCI.

Conclusion: Social and emotional isolation are associated with higher likelihood of dementia in older black and white Brazilians.
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http://dx.doi.org/10.1017/S1041610221000673DOI Listing
June 2021

Bilateral Pulmonary Emboli and Deep Venous Thrombi in Association With Chronic Inflammatory Demyelinating Polyneuropathy.

Cureus 2021 May 2;13(5):e14802. Epub 2021 May 2.

Department of Neurology, Cleveland Clinic, Cleveland, USA.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune neurological disorder primarily affecting the peripheral nervous system. It is important to recognize because treatment with immunomodulators can improve symptoms. We present the case of a 61-year-old man who developed a saddle pulmonary embolus as well as right-sided deep venous thrombi following left knee arthroplasty. Two months later, he had persistent pre-syncopal symptoms with exertion and had developed paraesthesias in both feet. Invasive cardiopulmonary exercise testing revealed preload failure with no evidence of pulmonary hypertension. He was then referred to neurology where clinical history, physical examination, autonomic battery, and nerve biopsy were consistent with a diagnosis of CIDP with autonomic dysfunction. Extensive venous thromboembolism may be a unique presentation of CIDP. The mechanisms, which may lead to hypercoagulability in CIDP, include the presence of systemic inflammation and denervation of peripheral vasculature leading to stasis.
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http://dx.doi.org/10.7759/cureus.14802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191853PMC
May 2021
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