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  • 1
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2019
    In:  Innovation in Aging Vol. 3, No. Supplement_1 ( 2019-11-08), p. S621-S621
    In: Innovation in Aging, Oxford University Press (OUP), Vol. 3, No. Supplement_1 ( 2019-11-08), p. S621-S621
    Abstract: A growing body of evidence has suggested a protective effect on cognition of the ε2 allele of APOE. To determine if APOE ε2 is associated with protection against cognitive decline, we analyzed repeated measures of the Telephone Interview for Cognitive Status (TICS) from 2,933 Long Life Family Study subjects and 679 New England Centenarian Study subjects using a multivariable linear mixed effects model. The median age at first TICS administration was 73 (interquartile range [IQR] 64, 83). Subjects had a median of 3 TICS assessments (IQR 2, 4) and a median follow-up time of 5.0 years (IQR 2.9, 7.0). Carriers of the ε2/ε2 genotype had a significantly slower rate of decline in TICS score compared to the ε3/ε3 reference group (-0.05 points per annum for ε2/ε2 carriers compared with -0.15 points for ε3/ε3 carriers, p-value for difference 0.017). These results support a protective effect of the ε2 allele.
    Type of Medium: Online Resource
    ISSN: 2399-5300
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2905697-4
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  • 2
    In: Innovation in Aging, Oxford University Press (OUP), Vol. 3, No. Supplement_1 ( 2019-11-08), p. S460-S461
    Abstract: We hypothesized large tumors (stage T3 or T4) are less likely to metastasize in centenarians compared to younger patients. We analyzed 2004 to 2015 Surveillance, Epidemiology, and End Results (SEER) data for the most common cancer types (breast, colon, lung, and prostate) among patients with T3 or T4 tumors and compared rates of M1 (presence of metastases) at time of diagnosis according to ages 30-110 years. Among 44,066 breast cancer patients, metastasis rates fell after age 80 for T3 and after age 74 for T4 tumors. The relative risk of metastasis [RR] for T3 patients ages 90-110 years compared to ages 50-89 years was 0.73, 95% CI 0.57;0.94, and the RR for T4 patients was 0.48, 95% CI 0.42;0.55. Among 296,041 colon cancer patients, metastasis rates for T3 and T4 tumors steadily declined after age 60; RR for T3 patients was 0.66, 95% CI 0.62;0.71 and for T4 was 0.73, 95% CI 0.69;0.78 for the older and younger age groups. No difference in metastasis rates at diagnosis was observed for ages 90-110 with small cell and non-small cell lung cancers. Among 52,738 men presenting with stage T3 prostate cancer, the rate of metastasis steadily increased after age 70 (RR = 6.00, 95% CI 4.72;7.63) while there was no substantial difference in metastasis rate according to age for T4 patients. More work is needed to determine whether these findings are related to differences in screening and detection among those at older ages or whether they have a greater resilience to metastasis.
    Type of Medium: Online Resource
    ISSN: 2399-5300
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2905697-4
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  • 3
    In: Gynecologic Oncology, Elsevier BV, Vol. 176 ( 2023-09), p. S117-
    Type of Medium: Online Resource
    ISSN: 0090-8258
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 1467974-7
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  • 4
    In: Alzheimer's & Dementia, Wiley, Vol. 15, No. 7S_Part_30 ( 2019-07)
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2201940-6
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  • 5
    In: Aging Cell, Wiley, Vol. 18, No. 6 ( 2019-12)
    Abstract: The discovery of treatments to prevent or delay dementia and Alzheimer's disease is a priority. The gene APOE is associated with cognitive change and late‐onset Alzheimer's disease, and epidemiological studies have provided strong evidence that the e 2 allele of APOE has a neuroprotective effect, it is associated with increased longevity and an extended healthy lifespan in centenarians. In this study, we correlated APOE genotype data of 222 participants of the New England Centenarian Study, including 75 centenarians, 82 centenarian offspring, and 65 controls, comprising 55 carriers of APOE e 2 , with aptamer‐based serum proteomics (SomaLogic technology) of 4,785 human proteins corresponding to 4,137 genes. We discovered a signature of 16 proteins that associated with different APOE genotypes and replicated the signature in three independent studies. We also show that the protein signature tracks with gene expression profiles in brains of late‐onset Alzheimer's disease versus healthy controls. Finally, we show that seven of these proteins correlate with cognitive function patterns in longitudinally collected data. This analysis in particular suggests that Baculoviral IAP repeat containing two (BIRC2) is a novel biomarker of neuroprotection that associates with the neuroprotective allele of APOE . Therefore, targeting APOE e 2 molecularly may preserve cognitive function.
    Type of Medium: Online Resource
    ISSN: 1474-9718 , 1474-9726
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2099130-7
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Society for Neuroscience ; 2023
    In:  The Journal of Neuroscience Vol. 43, No. 38 ( 2023-09-20), p. 6525-6537
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 43, No. 38 ( 2023-09-20), p. 6525-6537
    Abstract: Neuroimaging studies of human memory have consistently found that univariate responses in parietal cortex track episodic experience with stimuli (whether stimuli are 'old' or 'new'). More recently, pattern-based fMRI studies have shown that parietal cortex also carries information about the semantic content of remembered experiences. However, it is not well understood how memory-based and content-based signals are integrated within parietal cortex. Here, in humans (males and females), we used voxel-wise encoding models and a recognition memory task to predict the fMRI activity patterns evoked by complex natural scene images based on (1) the episodic history and (2) the semantic content of each image. Models were generated and compared across distinct subregions of parietal cortex and for occipitotemporal cortex. We show that parietal and occipitotemporal regions each encode memory and content information, but they differ in how they combine this information. Among parietal subregions, angular gyrus was characterized by robust and overlapping effects of memory and content. Moreover, subject-specific semantic tuning functions revealed that successful recognition shifted the amplitude of tuning functions in angular gyrus but did not change the selectivity of tuning. In other words, effects of memory and content were additive in angular gyrus. This pattern of data contrasted with occipitotemporal cortex where memory and content effects were interactive: memory effects were preferentially expressed by voxels tuned to the content of a remembered image. Collectively, these findings provide unique insight into how parietal cortex combines information about episodic memory and semantic content. SIGNIFICANCE STATEMENT Neuroimaging studies of human memory have identified multiple brain regions that not only carry information about “whether” a visual stimulus is successfully recognized but also “what” the content of that stimulus includes. However, a fundamental and open question concerns how the brain integrates these two types of information (memory and content). Here, using a powerful combination of fMRI analysis methods, we show that parietal cortex, particularly the angular gyrus, robustly combines memory- and content-related information, but these two forms of information are represented via additive, independent signals. In contrast, memory effects in high-level visual cortex critically depend on (and interact with) content representations. Together, these findings reveal multiple and distinct ways in which the brain combines memory- and content-related information.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2023
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 7
    In: Journal of Alzheimer's Disease, IOS Press, Vol. 82, No. 1 ( 2021-06-29), p. 17-32
    Abstract: Background: Coupling digital technology with traditional neuropsychological test performance allows collection of high-precision metrics that can clarify and/or define underlying constructs related to brain and cognition. Objective: To identify graphomotor and information processing trajectories using a digitally administered version of the Digit Symbol Substitution Test (DSST). Methods: A subset of Long Life Family Study participants (n = 1,594) completed the DSST. Total time to draw each symbol was divided into ‘writing’ and non-writing or ‘thinking’ time. Bayesian clustering grouped participants by change in median time over intervals of eight consecutively drawn symbols across the 90 s test. Clusters were characterized based on sociodemographic characteristics, health and physical function data, APOE genotype, and neuropsychological test scores. Results: Clustering revealed four ‘thinking’ time trajectories, with two clusters showing significant changes within the test. Participants in these clusters obtained lower episodic memory scores but were similar in other health and functional characteristics. Clustering of ‘writing’ time also revealed four performance trajectories where one cluster of participants showed progressively slower writing time. These participants had weaker grip strength, slower gait speed, and greater perceived physical fatigability, but no differences in cognitive test scores. Conclusion: Digital data identified previously unrecognized patterns of ‘writing’ and ‘thinking’ time that cannot be detected without digital technology. These patterns of performance were differentially associated with measures of cognitive and physical function and may constitute specific neurocognitive biomarkers signaling the presence of subtle to mild dysfunction. Such information could inform the selection and timing of in-depth neuropsychological assessments and help target interventions.
    Type of Medium: Online Resource
    ISSN: 1387-2877 , 1875-8908
    Language: Unknown
    Publisher: IOS Press
    Publication Date: 2021
    detail.hit.zdb_id: 2070772-1
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  • 8
    In: The Journal of Heart and Lung Transplantation, Elsevier BV, Vol. 43, No. 7 ( 2024-07), p. 1135-1141
    Type of Medium: Online Resource
    ISSN: 1053-2498
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
    detail.hit.zdb_id: 1500494-6
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  • 9
    In: Journal of Clinical Gastroenterology, Ovid Technologies (Wolters Kluwer Health)
    Abstract: Hyperbaric oxygen therapy (HBOT) delivers 100% oxygen in a pressurized chamber, increasing tissue oxygen levels and regulating inflammatory pathways. Mounting evidence suggests that HBOT may be effective for inflammatory bowel disease. Our systematic review and meta-analysis aimed to quantify the efficacy and safety of HBOT in fistulizing Crohn’s disease (CD). Methods: A systematic review was conducted using the EMBASE, Web of Science, Pubmed, and Cochrane Library databases according to the “Preferred Reporting Items for Systematic Reviews and Meta-analyses” criteria. Study bias was assessed using the Cochrane Handbook guidelines. Results: Sixteen studies with 164 patients were included in the analysis. For all fistula subtypes, the pooled overall clinical response was 87% (95% CI: 0.70-0.95, I 2 = 0) and the pooled clinical remission was 59% (95% CI: 0.35-0.80, I 2 = 0). The overall clinical response was 89%, 84%, and 29% for perianal, enterocutaneous, and rectovaginal fistulas, respectively. On meta-regression, hours in the chamber and the number of HBOT sessions were not found to correlate with clinical response. The pooled number of adverse events was low at 51.7 per 10,000 HBOT sessions for all fistula types (95% CI: 16.8-159.3, I 2 = 0). The risk of bias was observed across all studies. Conclusion: HBOT is a safe and potentially effective treatment option for fistulizing CD. Randomized control trials are needed to substantiate the benefit of HBOT in fistulizing CD.
    Type of Medium: Online Resource
    ISSN: 1539-2031
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2041558-8
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  • 10
    In: Inflammatory Bowel Diseases, Oxford University Press (OUP), Vol. 29, No. Supplement_1 ( 2023-01-26), p. S63-S63
    Abstract: Hyperbaric oxygen therapy (HBOT) delivers 100% oxygen in a pressurized chamber, increasing tissue oxygen levels and regulating inflammatory pathways. Despite significant expansion of the inflammatory bowel disease (IBD) therapeutics, there remains a significant gap in achieving fistula healing. Mounting evidence suggests that HBOT may be effective for IBD. Our systematic review and meta-analysis aimed to quantify the efficacy and safety of HBOT in fistulizing Crohn’s disease (CD). METHODS A systematic review was conducted using the EMBASE, Web of Science, Pubmed, and Cochrane Library databases according to PRISMA criteria. Study bias was assessed using the Cochrane handbook guidelines. Published articles and abstracts were included for analysis if they met study design criteria, evaluated HBOT efficacy in patients with fistulizing CD, and reported sufficient outcome data. Outcome data were considered sufficient when measured clinically, radiographically, and/or endoscopically. Randomized controlled trials, case-controlled studies, and case-series were included in the analysis. Our primary outcome of interest was overall clinical response with HBOT. Overall clinical response was defined as either clinical remission or partial response. Clinical remission was defined as closure of fistula and complete cessation of drainage. Partial response was defined as improvement in fistula drainage. RESULTS Sixteen studies with 164 patients who underwent 5,125 HBOT sessions were included in the analysis. For all fistula subtypes, the pooled overall clinical response was 87% (95% CI 0.70-0.95, I2=0) (Figure) and the pooled clinical remission was 59% (95% CI 0.35-0.80, I2=0). The overall clinical response was 89%, 84%, and 29% for perianal, enterocutaneous, and rectovaginal fistulas, respectively. (Table) On meta-regression, hours in the chamber and number of HBOT sessions were not found to correlate with a clinical response. The pooled number of adverse events was low at 51.7 per 10,000 HBOT sessions for all fistula types (95% CI 16.8-159.3, I2=0). DISCUSSION With a pooled overall clinical response rate of 87% and low adverse event rate, our review emphasizes the potential clinical benefit and safety of adjunctive HBOT in refractory cases of fistulizing CD. Rectovaginal fistulas were the fistula subtype least responsive to HBOT. Data limitations include study design heterogeneity and lack of control group presence. Randomized control trials are needed to substantiate the benefit of HBOT in fistulizing CD.
    Type of Medium: Online Resource
    ISSN: 1078-0998 , 1536-4844
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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