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1.
Alzheimers Dement ; 20(4): 2397-2407, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38298155

RESUMO

INTRODUCTION: Evidence suggests microglial activation precedes regional tau and neurodegeneration in Alzheimer's disease (AD). We characterized microglia with translocator protein (TSPO) positron emission tomography (PET) within an AD progression model where global amyloid beta (Aß) precedes local tau and neurodegeneration, resulting in cognitive impairment. METHODS: Florbetaben, PBR28, and MK-6240 PET, T1 magnetic resonance imaging, and cognitive measures were performed in 19 cognitively unimpaired older adults and 22 patients with mild cognitive impairment or mild AD to examine associations among microglia activation, Aß, tau, and cognition, adjusting for neurodegeneration. Mediation analyses evaluated the possible role of microglial activation along the AD progression model. RESULTS: Higher PBR28 uptake was associated with higher Aß, higher tau, and lower MMSE score, independent of neurodegeneration. PBR28 mediated associations between tau in early and middle Braak stages, between tau and neurodegeneration, and between neurodegeneration and cognition. DISCUSSION: Microglia are associated with AD pathology and cognition and may mediate relationships between subsequent steps in AD progression.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Microglia/metabolismo , Proteínas tau/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Disfunção Cognitiva/metabolismo , Progressão da Doença , Receptores de GABA/metabolismo
2.
Ann Pharmacother ; 57(2): 148-155, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35656843

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) cause inflammatory immune-related adverse events (irAEs), which are often effectively managed with steroids. Less is known about the best management of irAEs refractory to steroid treatment. OBJECTIVE: We aimed to assess the efficacy of second-line medications used to treat gastrointestinal (GI) irAEs. METHODS: This study was a single-center, retrospective medical record review of patients who received steroids for an ICI GI irAE and at least one dose of infliximab, vedolizumab, or adalimumab for irAE treatment from March 25, 2011 to September 20, 2019, approved by Yale University's Institutional Review Board. Our primary objective was to assess the efficacy of second-line treatment, measured by the change in the Common Terminology Criteria for Adverse Events Version 5.0 grading system. RESULTS: A total of 39 patients met inclusion criteria. Treatment for steroid-refractory GI irAEs demonstrated a high response rate, with irAE resolution seen in 89.7% of patients. Patients who were specifically initiated on infliximab within 14 days of starting steroids had a higher percent resolution seen in 94.4% of patients. The average time to response, defined as the average days from second-line therapy to reported symptom resolution, was 17 days. CONCLUSION AND RELEVANCE: Steroid-refractory GI irAEs can be managed effectively in most patients with immunosuppressive therapy, such as infliximab. Furthermore, initiating second-line immunosuppressive therapy within 14 days of steroid failure resulted in a higher rate of symptom resolution.


Assuntos
Trato Gastrointestinal , Esteroides , Humanos , Estudos Retrospectivos , Infliximab/efeitos adversos , Esteroides/efeitos adversos
3.
Alzheimers Dement ; 18(2): 272-282, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34057284

RESUMO

INTRODUCTION: Positron emission tomography (PET) imaging for neurofibrillary tau allows investigation of the in vivo spatiotemporal progression of Alzheimer's disease (AD) pathology. We evaluated the suitability of 18 F-MK-6240 in a clinical sample and determined the relationships among 18 F-MK-6240 binding, age, cognition, and cerebrospinal fluid (CSF)-based AD biomarkers. METHODS: Participants (n = 101, 72 ± 9 years, 52% women) underwent amyloid PET, tau PET, structural T1-weighted magnetic resonance imaging, and neuropsychological evaluation. Twenty-one participants had lumbar puncture for CSF measurement of amyloid beta (Aß)42 , tau, and phosphorylated tau (p-tau). RESULTS: 18 F-MK-6240 recapitulated Braak staging and correlated with CSF tau and p-tau, normalized to Aß42 . 18 F-MK-6240 negatively correlated with age across Braak regions in amyloid-positive participants, consistent with greater tau pathology in earlier onset AD. Domain-specific, regional patterns of 18 F-MK-6240 binding were associated with reduced memory, executive, and language performance, but only in amyloid-positive participants. DISCUSSION: 18 F-MK-6240 can approximate Braak staging across the AD continuum and provide region-dependent insights into biomarker-based AD models.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Biomarcadores , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Feminino , Humanos , Isoquinolinas/metabolismo , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Proteínas tau/líquido cefalorraquidiano
4.
Subst Use Misuse ; 56(11): 1670-1676, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34279170

RESUMO

BACKGROUND: From the anti-tobacco and anti-marijuana campaigns of the twentieth century to the current controversies surrounding vaporizer use and the opioid epidemic, substances and substance use have been at the forefront of cultural, public health, and legal debates for decades. This work explores treatment outcomes among those with substance use disorders (SUD) by 1) comparing legal, semi-legal, and illegal drug types and their impact on treatment outcomes and 2) evaluating the extent that there exist discrepancies between those who need and those who receive treatment. Methods: Binary logistic regression models were employed with data from the 2018 National Survey on Drug Use and Health (NSDUH) to examine the relationship between type of SUD and treatment outcomes. Results: Results indicate that those with SUD to illegal drugs were generally more likely to report a need and receive treatment than those with SUD to a legal drug (alcohol use disorder). Those with SUD to some types of illegal drugs did not report more need, but in some cases reported more treatment. Additionally, analyses indicated that across treatment outcomes, those with marijuana use disorder (semi-legal drug) were less likely to report needing or receiving treatment than those with alcohol use disorder. Conclusions: This research examined the role of drugs' legal status and type of SUD in need for treatment and treatment received. The discrepancy between needing and receiving treatment suggests those with some types of SUDs may be pushed into treatment at higher rates based on the stigma surrounding the substance they use.


Assuntos
Alcoolismo , Preparações Farmacêuticas , Transtornos Relacionados ao Uso de Substâncias , Inquéritos Epidemiológicos , Humanos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Resultado do Tratamento
5.
Neuroimage ; 209: 116489, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31877375

RESUMO

Spinal cord atrophy measurements obtained from structural magnetic resonance imaging (MRI) are associated with disability in many neurological diseases and serve as in vivo biomarkers of neurodegeneration. Longitudinal spinal cord atrophy rate is commonly determined from the numerical difference between two volumes (based on 3D surface fitting) or two cross-sectional areas (CSA, based on 2D edge detection) obtained at different time-points. Being an indirect measure, atrophy rates are susceptible to variable segmentation errors at the edge of the spinal cord. To overcome those limitations, we developed a new registration-based pipeline that measures atrophy rates directly. We based our approach on the generalised boundary shift integral (GBSI) method, which registers 2 scans and uses a probabilistic XOR mask over the edge of the spinal cord, thereby measuring atrophy more accurately than segmentation-based techniques. Using a large cohort of longitudinal spinal cord images (610 subjects with multiple sclerosis from a multi-centre trial and 52 healthy controls), we demonstrated that GBSI is a sensitive, quantitative and objective measure of longitudinal spinal cord volume change. The GBSI pipeline is repeatable, reproducible, and provides more precise measurements of longitudinal spinal cord atrophy than segmentation-based methods in longitudinal spinal cord atrophy studies.


Assuntos
Progressão da Doença , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico por imagem , Neuroimagem/métodos , Medula Espinal/diagnóstico por imagem , Adulto , Atrofia/patologia , Método Duplo-Cego , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/normas , Estudos Longitudinais , Imageamento por Ressonância Magnética/normas , Masculino , Esclerose Múltipla/patologia , Neuroimagem/normas , Medula Espinal/patologia
6.
J Oral Maxillofac Surg ; 78(10): 1736-1747, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32554066

RESUMO

PURPOSE: Fluorescently labeled epidermal growth factor receptor (EGFR) antibodies have successfully identified microscopic tumors in multiple in vivo models of human cancers with limited toxicity. The present study sought to demonstrate the ability of fluorescently labeled anti-EGFR, cetuximab-IRDye800, to localize to ameloblastoma (AB) tumor cells in vitro and in vivo. MATERIAL AND METHODS: EGFR expression in AB cells was confirmed by quantitative real-time polymerase chain reaction and immunohistochemistry. Primary AB cells were labeled in vitro with cetuximab-IRDye800 or nonspecific IgG-IRDye800. An in vivo patient-derived xenograft (PDX) model of AB was developed. The tumor tissue from 3 patients was implanted subcutaneously into immunocompromised mice. The mice received an intravenous injection of cetuximab-IRDye800 or IgG-IRDye800 and underwent imaging to detect infrared fluorescence using a Pearl imaging system (LI-COR Biosciences, Lincoln, NE). After resection of the overlying skin, the tumor/background ratios (TBRs) were calculated and statistically analyzed using a paired t test. RESULTS: EGFR expression was seen in all AB samples. Tumor-specific labeling was achieved, as evidenced by a positive fluorescence signal from cetuximab-IRDye800 binding to AB cells, with little staining seen in the negative controls treated with IgG-IRDye800. In the animal PDX model, imaging revealed that the TBRs produced by cetuximab were significantly greater than those produced by IgG on days 7 to 14 for AB-20 tumors. After skin flap removal to simulate a preresection state, the TBRs increased with cetuximab and were significantly greater than the TBRs with the IgG control for PDX tumors derived from the 3 patients with AB. The excised tissues were embedded in paraffin and examined to confirm the presence of tumor. CONCLUSIONS: Fluorescently labeled anti-EGFR demonstrated specificity for AB cells and PDX tumors. The present study is the first report of tumor-specific, antibody-based imaging of odontogenic tumors, of which AB is one of the most clinically aggressive. We expect this technology will ultimately assist surgeons treating AB by helping to accurately assess the tumor margins during surgery, leading to improved long-term local tumor control and less surgical morbidity.


Assuntos
Ameloblastoma , Animais , Linhagem Celular Tumoral , Cetuximab , Humanos , Indóis , Camundongos , Coloração e Rotulagem
7.
Contemp Clin Trials ; 137: 107427, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38184104

RESUMO

BACKGROUND: Aging is associated with gut dysbiosis, low-grade inflammation, and increased risk of type 2 diabetes (T2D). Prediabetes, which increases T2D and cardiovascular disease risk, is present in 45-50% of mid-life adults. The gut microbiota may link ultra-processed food (UPF) with inflammation and T2D risk. METHODS: Following a 2-week standardized lead-in diet (59% UPF), adults aged 40-65 years will be randomly assigned to a 6-week diet emphasizing either UPF (81% total energy) or non-UPF (0% total energy). Measurements of insulin sensitivity, 24-h and postprandial glycemic control, gut microbiota composition/function, fecal short chain fatty acids, intestinal inflammation, inflammatory cytokines, and vascular function will be made before and following the 6-week intervention period. Prior to recruitment, menus were developed in order to match UPF and non-UPF conditions based upon relevant dietary factors. Menus were evaluated for palatability and costs, and the commercial additive content of study diets was quantified to explore potential links with outcomes. RESULTS: Overall diet palatability ratings were similar (UPF = 7.6 ± 1.0; Non-UPF = 6.8 ± 1.5; Like Moderately = 7, Like Very Much = 8). Cost analysis (food + labor) of the 2000 kcal menu (7-d average) revealed lower costs for UPF compared to non-UPF diets ($20.97/d and $40.23/d, respectively). Additive exposure assessment of the 2000 kcal UPF diet indicated that soy lecithin (16×/week), citric acid (13×/week), sorbic acid (13×/week), and sodium citrate (12×/week) were the most frequently consumed additives. CONCLUSIONS: Whether UPF consumption impairs glucose homeostasis in mid-life adults is unknown. Findings will address this research gap and contribute information on how UPF consumption may influence T2D development.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Adulto , Humanos , Alimento Processado , Inflamação , Homeostase , Glucose , Dieta , Fast Foods
8.
medRxiv ; 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38260648

RESUMO

Background: Psychosis in Alzheimer's disease (AD) is associated with worse outcomes, yet no established biomarkers exist for early diagnosis and intervention. We compared tau PET burden across older individuals with and without psychotic symptoms. Methods: [18F]AV1451 tau PET binding was compared between 26 Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects with psychotic symptoms (delusions and/or hallucinations) and 26 ADNI subjects without psychotic symptoms, matched for age, sex, race/ethnicity, and clinical severity. Tau was assessed on a region-of-interest and voxel level, corrected for amyloid PET burden. Results: Tau was greater in individuals with psychotic symptoms in the amygdala in region-of-interest analyses, and in amygdala, thalamus, putamen, right hippocampus, right entorhinal cortex, and right frontal cortex in voxel-based analyses. When considering different onset and type of psychotic symptoms, tau binding was greatest in those with concurrent delusions. Conclusion: Elevated tau in limbic regions may be relevant for psychotic symptoms in aging and AD.

9.
Front Cardiovasc Med ; 10: 1111673, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37025687

RESUMO

Associations between cigarette smoking and increased risk of cardiovascular disease are well established. However, it is unclear whether the association is mediated by exposure to nicotine and/or to other constituents in cigarette smoke. The objective of this systematic review and meta-analysis of randomized control trials (RCTs) was to identify any potential associations between exposure to nicotine and the risk of clinically diagnosed adverse cardiovascular events in adult current users and nonusers of tobacco products. Among 1,996 results, 42 studies, comparing nicotine and non-nicotine groups, were included and were both qualitatively and quantitatively synthesized across the outcomes of arrhythmia, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death. The majority of studies evaluating nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death reported no events that occurred in either the nicotine or non-nicotine control groups. Among the studies that reported events, rates of adverse events were similarly low between both groups. Consistent with findings from previous systematic reviews and meta-analyses, pooled data showed that rates for arrhythmia, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death were not significantly different between nicotine and non-nicotine groups. The overall quality of the body of evidence for each of the four outcomes of interest was graded as "moderate," limited only by the imprecision of results. The findings of this systematic review and meta-analysis indicate that, with moderate certainty, there are no significant associations between the use of nicotine and the risk of clinically diagnosed adverse cardiovascular events-specifically, arrhythmia, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death.

10.
Ann Transl Med ; 11(12): 410, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38213798

RESUMO

Background: The association between cigarette smoking and the increased risk of many cancers is well established. Conversely, epidemiological studies of smokeless tobacco demonstrate decreased risk, or no elevated risk, of certain cancers versus smoking. However, it is unclear what role, if any, nicotine plays in these associations. The objective of this systematic review was to synthesize the available evidence from preclinical studies that examined the potential association between nicotine and the initiation and/or progression of cancer. Methods: MEDLINE, Embase, PsychInfo, and Cochrane Database of Systematic Reviews were searched for articles published from inception until February 13, 2022. Studies were eligible for inclusion if they evaluated animal cancer or tumor models, compared nicotine and non-nicotine groups, and evaluated measures of cancer initiation or progression. Results: Among 1,137 identified articles, 61 were included in qualitative synthesis. Twelve studies reported data on tumor initiation, and 54 studies reported data on tumor progression. The majority of the tumor initiation studies did not identify an association between nicotine exposure and an increased risk of spontaneous tumor initiation. Results of tumor progression studies were inconsistent and varied across the reported measures, cancer type being evaluated, and animal cancer model used. Overall, the quality of reporting was poor, with many studies not demonstrating a high level of internal and/or external validity. Conclusions: In conclusion, although animal models have provided invaluable data for human health risk assessments of chemical exposures, the heterogeneity across the studies included in this systematic review make the interpretation and generalizability of the results difficult.

11.
J Sex Res ; 58(7): 915-942, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-32530721

RESUMO

Contrary to popular media claims that college hookup culture has made romantic relationships obsolete, research indicates many college students see hookups as a pathway to relationships. However, relatively few college hookups actually produce relationships. This study used a sex market framework to explore correlates of college students' interest in future hookups and relationships with hookup partners across other-sex and same-sex hookup markets. Using Online College Social Life Survey data (N = 10,141) we explored variables classified in the following contexts that may shape choices in a sex market: demographic characteristics, the hookup dyad, the hookup event, post-hookup reactions, attitudes toward hookup partners, and hookup opportunity structures. Logistic regression analyses indicated post-hookup reactions (e.g., satisfaction, emotional responses) explained the highest percentage of variance in interest in a subsequent hookup (56% to 61% across markets) and interest in a relationship (35% to 45% across markets). Although past research suggests there are different markets for other- and same-sex hookups, these findings suggest similarity in contexts that may shape interest in relationship formation among other-sex and same-sex hookup markets. Suggestions for fostering positive relationship development on campuses are discussed.


Assuntos
Comportamento Sexual , Estudantes , Atitude , Humanos , Satisfação Pessoal , Inquéritos e Questionários , Universidades
12.
Expert Rev Anticancer Ther ; 21(9): 989-1002, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33853476

RESUMO

INTRODUCTION: Intravenous and subcutaneous hypomethylating agents have held a key role in myelodysplastic syndrome, chronic myelomonocytic leukemia and acute myeloid leukemia treatment. Following the approval of the cedazuridine/decitabine combination, ASTX727, as well as development of an oral formulation of azacitidine, CC-486, in the USA in 2020, these agents could gradually replace their injectable counterparts. AREAS COVERED: ASTX727 is approved for the treatment of adult patients with intermediate 1 or high-risk MDS as well as those with chronic myelomonocytic leukemia based on the findings from the ASTX727-01-B and ASCERTAIN trials. Oral azacitidine (CC-486) is approved for maintenance treatment of acute myeloid leukemia after induction chemotherapy for patients unfit for allogeneic hematopoietic cell transplant based on the findings from the QUAZAR AML-001 trial. EXPERT OPINION: Oral hypomethylating agent formulations have the potential to offer a convenient alternative to injectable hypomethylating agent. However, their current FDA-approved indications are narrow and efficacy needs to be shown in clinical trials before considering use beyond the approved indications. Areas of special interest include: identification of predictive biomarkers for clinical benefit, post-transplant maintenance therapy, and potential combination therapies with other oral agents such as venetoclax, IDH and FLT3 inhibitors.


Assuntos
Antimetabólitos Antineoplásicos , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Administração Oral , Antimetabólitos Antineoplásicos/administração & dosagem , Azacitidina/administração & dosagem , Decitabina/administração & dosagem , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico
13.
J Alzheimers Dis ; 80(3): 1051-1065, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33646153

RESUMO

BACKGROUND: Olfactory impairment is evident in Alzheimer's disease (AD); however, its precise relationships with clinical biomarker measures of tau pathology and neuroinflammation are not well understood. OBJECTIVE: To determine if odor identification performance measured with the University of Pennsylvania Smell Identification Test (UPSIT) is related to in vivo measures of tau pathology and neuroinflammation. METHODS: Cognitively normal and cognitively impaired participants were selected from an established research cohort of adults aged 50 and older who underwent neuropsychological testing, brain MRI, and amyloid PET. Fifty-four participants were administered the UPSIT. Forty-one underwent 18F-MK-6240 PET (measuring tau pathology) and fifty-three underwent 11C-PBR28 PET (measuring TSPO, present in activated microglia). Twenty-three participants had lumbar puncture to measure CSF concentrations of total tau (t-tau), phosphorylated tau (p-tau), and amyloid-ß (Aß42). RESULTS: Low UPSIT performance was associated with greater18F-MK-6240 binding in medial temporal cortex, hippocampus, middle/inferior temporal gyri, inferior parietal cortex, and posterior cingulate cortex (p < 0.05). Similar relationships were seen for 11C-PBR28. These relationships were primarily driven by amyloid-positive participants. Lower UPSIT performance was associated with greater CSF concentrations of t-tau and p-tau (p < 0.05). Amyloid status and cognitive status exhibited independent effects on UPSIT performance (p < 0.01). CONCLUSION: Olfactory identification deficits are related to extent of tau pathology and neuroinflammation, particularly in those with amyloid pathophysiology. The independent association of amyloid-positivity and cognitive impairment with odor identification suggests that low UPSIT performance may be a marker for AD pathophysiology in cognitive normal individuals, although impaired odor identification is associated with both AD and non-AD related neurodegeneration.NCT Registration Numbers: NCT03373604; NCT02831283.


Assuntos
Doença de Alzheimer/patologia , Encéfalo/patologia , Transtornos do Olfato/etiologia , Proteínas tau/líquido cefalorraquidiano , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Biomarcadores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/metabolismo , Transtornos do Olfato/patologia , Tomografia por Emissão de Pósitrons
14.
Neurobiol Aging ; 103: 109-116, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33894641

RESUMO

It is unclear whether women have higher brain tau pathology. The objective of this study was to examine whether women have higher tau burden than men, and whether tau differences are independent of amyloid ß (Aß) burden. We conducted a cross-sectional analysis of a multiethnic sample of 252 nondemented late middle-aged (mean age: 64.1 years) adults with tau and amyloid Positron Emission Tomography (PET) data. Tau burden was measured as global standardized uptake value ratio (SUVR) in the middle/inferior temporal gyri and medial temporal cortex with 18F-MK-6240 PET. Aß was measured as global SUVR with 18F-Florbetaben PET. Women had higher middle/inferior temporal gyri tau SUVR compared to men. However, no sex differences in the medial temporal cortex were observed. Women had higher brain Aß SUVR compared to men. Continuous Aß SUVR was positively correlated with medial temporal cortex and middle/inferior temporal gyri tau SUVR. However, there was no evidence of effect modification by Aß SUVR on sex and tau. Compared with men, women in late middle age show higher tau burden, independent of Aß.


Assuntos
Caracteres Sexuais , Tauopatias/diagnóstico , Lobo Temporal/metabolismo , Proteínas tau/metabolismo , Idoso , Peptídeos beta-Amiloides/metabolismo , Biomarcadores/metabolismo , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem , Tomografia por Emissão de Pósitrons , Fatores Sexuais , Tauopatias/epidemiologia , Lobo Temporal/diagnóstico por imagem
15.
Alzheimers Dement (Amst) ; 13(1): e12264, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35005197

RESUMO

INTRODUCTION: Positron emission tomography (PET) imaging targeting neurofibrillary tau tangles is increasingly used in the study of Alzheimer's disease (AD), but its utility may be limited by conventional quantitative or qualitative evaluation techniques in earlier disease states. Convolutional neural networks (CNNs) are effective in learning spatial patterns for image classification. METHODS: 18F-MK6240 (n = 320) and AV-1451 (n = 446) PET images were pooled from multiple studies. We performed iterations with differing permutations of radioligands, heuristics, and architectures. Performance was compared to a standard region of interest (ROI)-based approach on prediction of memory impairment. We visualized attention of the network to illustrate decision making. RESULTS: Overall, models had high accuracy (> 80%) with good average sensitivity and specificity (75% and 82%, respectively), and had comparable or higher accuracy to the ROI standard. Visualizations of model attention highlight known characteristics of tau radioligand binding. DISCUSSION: CNNs could improve tau PET's role in early disease and extend the utility of tau PET across generations of radioligands.

16.
Neurobiol Aging ; 85: 11-21, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31698286

RESUMO

We sought to determine if upstream amyloid accumulation and downstream cognitive impairment have independent relationships with microglial activation and tau pathology. Fifty-eight older adults were stratified by amyloid and cognitive status based on 18F-florbetaben PET, history, and neuropsychological testing. Of these, 57 had 11C-PBR28 PET to measure microglial activation and 43 had 18F-MK-6240 PET to measure tau pathology. Amyloid and cognitive status were associated with increased overall binding for both 11C-PBR28 and 18F-MK-6240 (p's < 0.01). While there was no interaction between amyloid and cognitive status in their association with 11C-PBR28 binding (p = 0.6722), there was an interaction in their association with 18F-MK-6240 binding (p = 0.0115). Binding of both radioligands was greater in amyloid-positive controls than in amyloid-negative controls; however, this difference was seen in neocortical regions for 11C-PBR28 and only in medial temporal cortex for 18F-MK-6240. We conclude that, in the absence of cognitive symptoms, amyloid deposition has a greater association with microglial activation than with tau pathology.


Assuntos
Doença de Alzheimer/etiologia , Amiloide/metabolismo , Transtornos da Memória/etiologia , Microglia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Feminino , Humanos , Masculino , Transtornos da Memória/diagnóstico por imagem , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Proteínas tau/metabolismo
17.
J Alzheimers Dis ; 74(4): 1243-1252, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32250303

RESUMO

BACKGROUND: Females may have a higher risk of dementia than males. It is not clear if sex differences in Alzheimer's disease (AD) neuropathology explain the higher risk of dementia in females. Sex differences in AD neuropathology might begin in middle age, decades before the sex differences in dementia are apparent. OBJECTIVE: To examine sex differences in in vivo AD neuropathology in late middle age. METHODS: We conducted a cross-sectional comparison of AD biomarkers among 266 Hispanic males and females (mean age: 64.0; 71.8% females) without dementia. Amyloid burden was measured as global standardized uptake value ratio (SUVR) with18F-Florbetaben positron emission tomography (PET). Neurodegeneration was ascertained as cortical thickness in AD signature areas using brain magnetic resonance imaging. Tau burden was measured as tau SUVR in the middle/inferior temporal gyri and medial temporal cortex with 18F-MK-6240 in 75 of the 266 participants. RESULTS: Females had higher amyloid SUVR and tau SUVR in the middle/inferior temporal gyri than males. However, females had higher cortical thickness than males and performed better in a test of verbal memory despite having higher AD neuropathology burden. CONCLUSION: Higher amyloid and tau in females compared to males in late middle-age may explain the reported higher dementia risk in elderly females compared to males. Longitudinal follow-up is necessary to examine whether higher amyloid and tau burden in late middle age is followed by increased neurodegeneration and cognitive decline in females as compared with males.


Assuntos
Doença de Alzheimer/patologia , Hispânico ou Latino/estatística & dados numéricos , Proteínas Amiloidogênicas/metabolismo , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/patologia , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Tomografia por Emissão de Pósitrons , Fatores Sexuais , Proteínas tau/metabolismo
18.
J Pediatr Surg ; 44(5): 918-23, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19433170

RESUMO

OBJECTIVE: The objective of the study was to determine factors predicting outcome in newborns with gastroschisis. METHODS: A retrospective analysis of 155 consecutive cases admitted from 1 January 1990 to 31 December 2007 was performed. Prenatal ultrasound findings were available for 89 of 155 (57%) patients and were compared with final outcome. Both univariate and multiple regression analyses were used. RESULTS: All patients survived to discharge home. The primary outcome measure was length of stay. Multiple regression identified 4 factors associated with length of stay: (1) gestational age (P = .004), (2) nonelective silo (P < .001), (3) gastrointestinal (GI) complication (intestinal atresia, perforation, or resection) (P < .001), and (4) non-GI anomaly (P = .029). Non-GI anomalies occurred in 17 of 155 (11%) patients and tended to increase the risk of a nonelective silo or GI complication (59% vs 39%, P = .190). Dilated bowel (>10 mm) on prenatal ultrasound was associated with GI complications (22% vs 3%, P = .010). However, 78% of patients with dilated bowel on prenatal ultrasound did not have a GI complication. The absence of dilated bowel on prenatal ultrasound accurately predicted the absence of GI complications in 97% of cases. CONCLUSION: Prematurity, nonelective silo, GI complications, and non-GI anomalies predict the short-term outcome of newborns with gastroschisis. Prenatal ultrasound serves primarily to predict the absence of GI complications.


Assuntos
Gastrosquise/cirurgia , Ultrassonografia Pré-Natal , Anormalidades Múltiplas/epidemiologia , Adulto , Anormalidades do Sistema Digestório/epidemiologia , Dilatação Patológica/diagnóstico por imagem , Dilatação Patológica/embriologia , Feminino , Gastrosquise/diagnóstico por imagem , Gastrosquise/embriologia , Gastrosquise/epidemiologia , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/diagnóstico por imagem , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/cirurgia , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Tempo de Internação , Masculino , Idade Materna , Minnesota/epidemiologia , Gravidez , Prognóstico , Estudos Retrospectivos , Fatores de Risco
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