scholarly journals Brain α-tocopherol concentration is inversely associated with neurofibrillary tangle counts in brain regions affected in earlier Braak stages: A cross-sectional finding in the oldest old

2021 ◽  
pp. 1-9
Author(s):  
J. Tanprasertsuk ◽  
T.M. Scott ◽  
M.A. Johnson ◽  
L.W. Poon ◽  
P.T. Nelson ◽  
...  
Keyword(s):  
Vitamin E ◽  
Oldest Old ◽  
Neurofibrillary Tangle ◽  
Brain Structures ◽  
Brain Regions ◽  
Phase Iii ◽  
Neuritic Plaque ◽  
Tocopherol Concentration ◽  
Cross Sectional ◽  
Braak Staging

Objectives: Higher vitamin E status has been associated with lower risk of Alzheimer’s disease (AD). However, evidence of the association of vitamin E concentration in neural tissue with AD pathologies is limited. Design: The cross-sectional relationship between the human brain concentrations of α- and γ-tocopherol and the severity of AD pathologies – neurofibrillary tangle (NFT) and neuritic plaque (NP) – was investigated. Setting & Participants: Brains from 43 centenarians (≥ 98 years at death) enrolled in the Phase III of the Georgia Centenarian Study were collected at autopsy. Measurements: Brain α- and γ-tocopherol concentrations (previously reported) were averaged from frontal, temporal, and occipital cortices. NP and NFT counts (previously reported) were assessed in frontal, temporal, parietal, entorhinal cortices, amygdala, hippocampus, and subiculum. NFT topological progression was assessed using Braak staging. Multiple linear regression was performed to assess the relationship between tocopherol concentrations and NP or NFT counts, with and without adjustment for covariates. Results: Brain α-tocopherol concentrations were inversely associated with NFT but not NP counts in amygdala (β = -2.67, 95% CI [-4.57, -0.79]), entorhinal cortex (β = -2.01, 95% CI [-3.72, -0.30]), hippocampus (β = -2.23, 95% CI [-3.82, -0.64]), and subiculum (β = -2.52, 95% CI [-4.42, -0.62]) where NFT present earlier in its topological progression, but not in neocortices. Subjects with Braak III-IV had lower α-tocopherol (median = 69,622 pmol/g, IQR = 54,389-72,155 pmol/g) than those with Braak I-II (median = 72,108 pmol/g, IQR = 64,056-82,430 pmol/g), but the difference was of borderline significance (p = 0.063). γ-Tocopherol concentrations were not associated with either NFT or NP counts in any brain regions assessed. Conclusions: Higher brain α-tocopherol level is specifically associated with lower NFT counts in brain structures affected in earlier Braak stages. Our findings emphasize the possible importance of α-tocopherol intervention timing in tauopathy progression and warrant future clinical trials.

scholarly journals Utility of FDG-PET in diagnosis of Alzheimer-related TDP-43 proteinopathy

Neurology ◽  
2020 ◽  
Vol 95 (1) ◽  
pp. e23-e34
Author(s):  
Marina Buciuc ◽  
Hugo Botha ◽  
Melissa E. Murray ◽  
Christopher G. Schwarz ◽  
Matthew L. Senjem ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Fdg Pet ◽  
Hippocampal Sclerosis ◽  
Neurofibrillary Tangle ◽  
Statistical Parametric Mapping ◽  
Postmortem Brain ◽  
Neuritic Plaque ◽  
Cross Sectional ◽  
Postmortem Brain Tissue

ObjectiveTo evaluate FDG-PET as an antemortem diagnostic tool for Alzheimer-related TAR DNA-binding protein of 43 kDa (TDP-43) proteinopathy.MethodsWe conducted a cross-sectional neuroimaging–histologic analysis of patients with antemortem FDG-PET and postmortem brain tissue from the Mayo Clinic Alzheimer's Disease Research Center and Study of Aging with Alzheimer spectrum pathology. TDP-43-positive status was assigned when TDP-43-immunoreactive inclusions were identified in the amygdala. Statistical parametric mapping (SPM) analyses compared TDP-43-positive (TDP-43[+]) with TDP-43-negative cases (TDP-43[−]), correcting for field strength, sex, Braak neurofibrillary tangle, and neuritic plaque stages. Cross-validated logistic regression analyses were used to determine whether regional FDG-PET values predict TDP-43 status. We also assessed the ratio of inferior temporal to medial temporal (IMT) metabolism as this was proposed as a biomarker of hippocampal sclerosis.ResultsOf 73 cases, 27 (37%) were TDP-43(+), of which 6 (8%) had hippocampal sclerosis. SPM analysis showed TDP-43(+) cases having greater hypometabolism of medial temporal, frontal superior medial, and frontal supraorbital (FSO) regions (punc < 0.001). Logistic regression analysis showed only FSO and IMT to be associated with TDP-43(+) status, identifying up to 81% of TDP-43(+) cases (p < 0.001). An IMT/FSO ratio was superior to the IMT in discriminating TDP-43(+) cases: 78% vs 48%, respectively.ConclusionsAlzheimer-related TDP-43 proteinopathy is associated with hypometabolism in the medial temporal and frontal regions. Combining FDG-PET measures from these regions may be useful for antemortem prediction of Alzheimer-related TDP-43 proteinopathy.Classification of evidenceThis study provides Class II evidence that hypometabolism in the medial temporal and frontal regions on FDG-PET is associated with Alzheimer-related TDP-43 proteinopathy.

Mid-sagittal anatomy in late-onset schizophrenia

1999 ◽  
Vol 29 (4) ◽  
pp. 963-970 ◽  
Author(s):  
PERMINDER S. SACHDEV ◽  
HENRY BRODATY
Keyword(s):  
Corpus Callosum ◽  
Late Onset ◽  
Brain Structures ◽  
Brain Regions ◽  
Cross Sectional ◽  
Significant Difference ◽  
Comparison Groups ◽  
Schizophrenic Patients ◽  
Independent Replication ◽  
And Gender

Background. Of the midline brain structures, abnormalities have been demonstrated in the corpus callosum and cerebellum in young schizophrenic patients. Whether similar abnormalities are also present in late-onset schizophrenia (LOS) is not known.Methods. The mid-sagittal cross-sectional areas of brain regions, in particular the corpus callosum and cerebellum, on magnetic resonance imaging were examined in a group of patients with late-onset schizophrenia (N=25) and contrasted with two comparison groups – early-onset schizophrenia (EOS) (N=2524) and healthy volunteers (NC) (N=2530) matched for age and gender.Results. While the mean corpus callosum area in the LOS group was smaller than in the EOS (by 10·2%) and NC (by 6·2%) groups, the three groups did not differ statistically in the corpus callosum area or the corpus callosum to cerebrum ratios. The cross-sectional cerebellar areas or the cerebellum: cerebrum ratios also did not differ across the groups. The brainstem was smaller in the schizophrenic groups because of smaller cross-sectional areas of the pons, a statistically significant difference which could not be accounted for by any gross lesions on visual inspection.Conclusion. We found no abnormality in the mid-sagittal area of the corpus callosum and cerebellum in our early- or late-onset schizophrenia subjects. The significance of the finding of a smaller pontine cross-sectional area is unclear and speculation on it awaits independent replication using a volumetric measure.

scholarly journals The genetic organization of longitudinal subcortical volumetric change is stable throughout the lifespan

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Anders Martin Fjell ◽  
Hakon Grydeland ◽  
Yunpeng Wang ◽  
Inge K Amlien ◽  
David Bartres-Faz ◽  
...  
Keyword(s):  
Genetic Correlations ◽  
Brain Structures ◽  
Brain Regions ◽  
Nucleotide Polymorphisms ◽  
Coordinated Development ◽  
Volumetric Change ◽  
Cross Sectional ◽  
Genetic Organization ◽  
Development And Aging ◽  
Subcortical Regions

Development and aging of the cerebral cortex show similar topographic organization and are governed by the same genes. It is unclear whether the same is true for subcortical regions, which follow fundamentally different ontogenetic and phylogenetic principles. We tested the hypothesis that genetically governed neurodevelopmental processes can be traced throughout life by assessing to which degree brain regions that develop together continue to change together through life. Analyzing over 6000 longitudinal MRIs of the brain, we used graph theory to identify five clusters of coordinated development, indexed as patterns of correlated volumetric change in brain structures. The clusters tended to follow placement along the cranial axis in embryonic brain development, suggesting continuity from prenatal stages, and correlated with cognition. Across independent longitudinal datasets, we demonstrated that developmental clusters were conserved through life. Twin-based genetic correlations revealed distinct sets of genes governing change in each cluster. Single nucleotide polymorphisms-based analyses of 38127 cross-sectional MRIs showed a similar pattern of genetic volume-volume correlations. In conclusion, coordination of subcortical change adheres to fundamental principles of lifespan continuity and genetic organization.

scholarly journals Brain γ-Tocopherol Levels Are Associated with Presynaptic Protein Levels in Elderly Human Midfrontal Cortex

2020 ◽  
Vol 77 (2) ◽  
pp. 619-627 ◽  
Author(s):  
Francisca A. de Leeuw ◽  
William G. Honer ◽  
Julie A. Schneider ◽  
Martha Clare Morris
Keyword(s):  
Vitamin E ◽  
Lewy Body Disease ◽  
Brain Regions ◽  
Cross Sectional Study ◽  
Snare Protein ◽  
Linear Regression Models ◽  
Sectional Study ◽  
Cross Sectional ◽  
Protein Levels ◽  
Presynaptic Protein

Background: Higher vitamin E intake has been widely related to lower risks of cognitive decline and dementia. Animal models suggest that this relationship might be (partially) explained by the protection of vitamin E against presynaptic protein oxidation. Objective: In this cross-sectional study, we aimed to examine the associations between brain tocopherols and presynaptic protein levels in elderly humans. Methods: We examined associations of α- and γ-tocopherol brain levels with presynaptic protein levels in 113 deceased participants (age 88.5±6.0 years, 45 (40%) female) from the prospective Memory and Aging project. Three distinct presynaptic proteins, a SNARE protein composite, a synaptotagmin synaptophysin composite and the protein-protein interaction between synaptosomal-associated protein 25 (SNAP-25), and syntaxin were measured in two cortical brain regions. Linear regression models assessed associations of brain tocopherols with presynaptic protein levels. Results: Higher brain γ-tocopherol levels were associated with higher levels of the SNARE protein composite, complexin-I, complexin-II, the synaptotagmin synaptophysin composite, and septin-5 in the midfrontal cortex (B(SE) = 0.272 to 0.412 (0.084 to 0.091), p < 0.001 to 0.003). When additionally adjusted for global Alzheimer’s disease pathology, cerebral infarcts, and Lewy body disease pathology, these associations remained largely similar. No associations were found between α-tocopherol and presynaptic protein levels. Conclusion: In this cross-sectional study, we found higher brain γ-tocopherol levels were associated with presynaptic protein levels in the midfrontal cortex. These results are consistent with a proposed role of vitamin E to maintain presynaptic protein levels.

scholarly journals Predictors of cognitive impairment in primary age-related tauopathy: an autopsy study

2021 ◽  
Author(s):  
Megan A Iida ◽  
Kurt Farrell ◽  
Jamie M Walker ◽  
Timothy E Richardson ◽  
Gabe Marx ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Medial Temporal Lobe ◽  
Neurofibrillary Tangle ◽  
Lewy Bodies ◽  
Brain Regions ◽  
Braak Stage ◽  
Autopsy Study ◽  
Factors Affecting ◽  
Braak Staging ◽  
Age Related

Primary age-related tauopathy (PART) is a form of Alzheimer-type neurofibrillary degeneration occurring in the absence of amyloid-beta (Aβ) plaques. While PART shares some features with Alzheimer disease (AD), such as progressive accumulation of neurofibrillary tangle pathology in the medial temporal lobe and other brain regions, it does not progress extensively to neocortical regions. Given this restricted pathoanatomical pattern and variable symptomatology, there is a need to reexamine and improve upon how PART is neuropathologically assessed and staged. We performed a retrospective autopsy study in a collection (n=174) of post-mortem PART brains and used logistic regression to determine the extent to which a set of clinical and neuropathological features predict cognitive impairment. We compared Braak staging, which focuses on hierarchical neuroanatomical progression of AD tau and Aβ pathology, with quantitative assessments of neurofibrillary burden using computer-derived positive pixel counts on digitized whole slide images of sections stained immunohistochemically with antibodies targeting abnormal hyperphosphorylated tau (p-tau) in the entorhinal region and hippocampus. We also assessed other factors affecting cognition, including aging-related tau astrogliopathy (ARTAG) and atrophy. We found no association between Braak stage and cognitive impairment when controlling for age (p=0.76). In contrast, p-tau burden was significantly correlated with cognitive impairment even when adjusting for age (p=0.03). The strongest correlate of cognitive impairment was cerebrovascular disease, a well-known risk factor (p<0.0001), but other features including ARTAG (p=0.03) and hippocampal atrophy (p=0.04) were also associated. In contrast, sex, APOE, psychiatric illness, education, argyrophilic grains, and incidental Lewy bodies were not. These findings support the hypothesis that comorbid pathologies contribute to cognitive impairment in subjects with PART. Quantitative approaches beyond Braak staging are critical for advancing our understanding of the extent to which age-related tauopathy changes impact cognitive function.

scholarly journals Volumetric MRI analysis of brain structures in patients with history of first and repeated suicide attempts: a cross sectional study

2020 ◽  
Author(s):  
Milda Sarkinaite ◽  
Rymante Gleizniene ◽  
Virginija Adomaitiene ◽  
Kristina Dambrauskiene ◽  
Nijole Raskauskiene ◽  
...  
Keyword(s):  
Suicide Attempt ◽  
Left Hemisphere ◽  
Cortical Thickness ◽  
Suicide Attempts ◽  
Right Hemisphere ◽  
Brain Structures ◽  
Brain Regions ◽  
Cross Sectional ◽  
Suicide Attempters ◽  
History Of

Abstract Background Structural brain changes are found in suicide attempters, as well as in patients with mental disorders. It remains unclear whether the suicidal behavior is related to atrophy of brain regions and how the morphology of specific brain areas is changing with each suicide attempt. This cross-sectional study examined volumetric differences in brain regions among patients with history of first and repeated suicide attempts in comparison to healthy controls (HC). Methods The sample consisted of 56 adults, non-psychotic patients without cognitive impairment and any organic brain disorders hospitalized after first suicide attempt (first SA) (n=29) and more than one suicide attempt (SA>1) during the lifetime (n=27); and 54 adult volunteers without history of mental disorder and suicide attempts, designated as HC. The MRI data were collected using 1.5 T Siemens Avanto scanner. Brain cortical thickness, grey and white matter volumes were measured using FreeSurfer 6.0 automatic segmentation technique. Results In comparison to HC, patients with first SA had 3.5, 3.58 and 4.19% significantly lower mean cortical thickness of the superior and rostral middle frontal areas of the left hemisphere and superior frontal area of the right hemisphere, respectively; 4.09, 4.02 and 4.49% lower mean cortical thickness of the inferior, middle and superior temporal areas of the left hemisphere, respectively. In comparison to HC, patients after SA>1 had a significantly lower mean cortical thickness (from 4.02 to 8.33%) in ten areas of frontal cortex of the left hemisphere and seven areas of the right hemisphere; from 3.90 to 6.04% difference in six areas of temporal cortex in both hemispheres. The comparison of hippocampus volume showed a significantly lower mean volume (7.86 to 9.89%) of left and right parts in patients with SA>1, but not in patients with first SA. Conclusions Hospitalized suicide attempters had lower frontal and temporal cortical thickness and smaller parts of hippocampus than HC; these differences were significantly higher in repeated suicide attempters than in patients with first SA. Our findings suggest that repeated suicidal behavior is associated with intensifying atrophy of specific brain structures, independently of diagnosis of depressive disorders.

scholarly journals Alpha-tocopherol concentration in serum and colostrum of mothers with gestational diabetes mellitus

2014 ◽  
Vol 32 (2) ◽  
pp. 178-186 ◽  
Author(s):  
Fernanda Barros S. Resende ◽  
Heleni Aires Clemente ◽  
Dalila Fernandes Bezerra ◽  
Evellyn Câmara Grilo ◽  
Larisse Rayanne M. de Melo ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Vitamin E ◽  
Gestational Diabetes ◽  
Nutritional Status ◽  
Gestational Diabetes Mellitus ◽  
High Performance ◽  
Alpha Tocopherol ◽  
Control Group ◽  
Tocopherol Concentration ◽  
Cross Sectional

OBJECTIVE: To evaluate and compare the levels of α-tocopherol in colostrum and in the serum of healthy and diabetic mothers.METHODS: This cross-sectional study enrolled 51 volunteer mothers, 20 with the diagnosis of gestational diabetes mellitus and 31 without associated diseases. Serum and colostrum samples were collected in fasting in the immediate postpartum period and α-tocopherol was analyzed by high performance liquid chromatography (HPLC). In order to define the nutritional status of vitamin E, the cutoff point for the serum (697.7µg/dL) was adopted. Student's t-test for independent variables compared the average concentrations of α-tocopherol in the serum and in the colostrum between control and gestational diabetes mellitus groups. Pearson's correlation was used to assess the relationship between the concentration of α-tocopherol in serum and colostrum for both groups. Differences were considered significant when p<0.05.RESULTS: The α-tocopherol concentration in colostrum was 1,483.1±533.8µg/dL for Control Group and 1,368.8±681.8µg/dL for diabetic women, without differences between groups (p=0.50). However, α-tocopherol concentration in the serum was 1,059.5±372.7µg/dL in the Control Group and 1,391.4±531.5µg/dL in the diabetic one (p<0.01). No correlation was found between the concentration of α-tocopherol in the serum and in the colostrum for control and diabetic groups.CONCLUSIONS: The groups had adequate nutritional status of vitamin E. Gestational diabetes was not associated with changes in α-tocopherol concentration in colostrum.

Psychotic Symptoms in Alzheimer's Disease Are Not Associated With More Severe Neuropathologic Features

2000 ◽  
Vol 12 (4) ◽  
pp. 547-558 ◽  
Author(s):  
Robert A. Sweet ◽  
Ronald L. Hamilton ◽  
Oscar L. Lopez ◽  
William E. Klunk ◽  
Stephen R. Wisniewski ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Functional Decline ◽  
Neurofibrillary Tangle ◽  
Temporal Cortex ◽  
Lewy Bodies ◽  
Occipital Cortex ◽  
Brain Regions ◽  
Neuritic Plaque ◽  
Psychotic Symptoms

Psychotic symptoms in Alzheimer's disease (AD) have been associated with increased rates of cognitive impairment and functional decline. Prior studies have been conflicting with regard to whether AD patients with psychosis (AD+P) have evidence of more severe neuropathologic findings at postmortem exam. We examined the severity of neuritic plaques and neurofibrillary tangles in six brain regions—middle frontal cortex, hippocampus, inferior parietal cortex, superior temporal cortex, occipital cortex, and transentorhinal cortex—in 24 AD+P subjects and 25 matched AD subjects without psychosis (AD-P). All analyses controlled for the presence of cortical Lewy bodies, and corrected for multiple comparisons. We found no significant associations between neuritic plaque and neurofibrillary tangle severity and AD+P, and no significant associations with any individual psychotic symptom. The association of AD+P with a more rapidly progressive course of AD appears to be mediated by a neuropathologic process other than increased severity of plaque and tangle formation.

scholarly journals Volumetric MRI Analysis of Brain Structures in Patients With History of First and Repeated Suicide Attempts: A Cross Sectional Study

2020 ◽  
Author(s):  
Milda Sarkinaite ◽  
Rymante Gleizniene ◽  
Virginija Adomaitiene ◽  
Kristina Dambrauskiene ◽  
Nijole Raskauskiene ◽  
...  
Keyword(s):  
Suicide Attempt ◽  
Left Hemisphere ◽  
Cortical Thickness ◽  
Suicide Attempts ◽  
Right Hemisphere ◽  
Brain Structures ◽  
Brain Regions ◽  
Cross Sectional ◽  
Suicide Attempters ◽  
History Of

Abstract Background: Structural brain changes are found in suicide attempters, as well as in patients with mental disorders. It remains unclear whether the suicidal behavior is related to atrophy of brain regions and how the morphology of specific brain areas is changing with each suicide attempt. This cross-sectional study examined volumetric differences in brain regions among patients with history of first and repeated suicide attempts in comparison to healthy controls (HC).Methods: The sample consisted of 56 adults, non-psychotic patients without cognitive impairment and any organic brain disorders hospitalized after first suicide attempt (first SA) (n=29) and more than one suicide attempt (SA>1) during the lifetime (n=27); and 54 adult volunteers without history of mental disorder and suicide attempts, designated as HC. The MRI data were collected using 1.5 T Siemens Avanto scanner. Brain cortical thickness, grey and white matter volumes were measured using FreeSurfer 6.0 automatic segmentation technique.Results: In comparison to HC, patients with first SA had 3.5, 3.58 and 4.19% significantly lower mean cortical thickness of the superior and rostral middle frontal areas of the left hemisphere and superior frontal area of the right hemisphere, respectively; 4.09, 4.02 and 4.49 % lower mean cortical thickness of the inferior, middle and superior temporal areas of the left hemisphere, respectively. In comparison to HC, patients after SA>1 had a significantly lower mean cortical thickness (from 4.02 to 8.33%) in ten areas of frontal cortex of the left hemisphere and seven areas of the right hemisphere; from 3.90 to 6.04% difference in six areas of temporal cortex in both hemispheres. The comparison of hippocampus volume showed a significantly lower mean volume (7.86 to 9.89%) of left and right parts in patients with SA>1, but not in patients with first SA. Conclusions: Hospitalized suicide attempters had lower frontal and temporal cortical thickness and smaller parts of hippocampus than HC; these differences were significantly higher in repeated suicide attempters than in patients with first SA. Our findings suggest that repeated suicidal behavior is associated with intensifying atrophy of specific brain structures, independently of diagnosis of depressive disorders.

scholarly journals Predictors of cognitive impairment in primary age-related tauopathy: an autopsy study

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Megan A. Iida ◽  
Kurt Farrell ◽  
Jamie M. Walker ◽  
Timothy E. Richardson ◽  
Gabriel A. Marx ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Medial Temporal Lobe ◽  
Neurofibrillary Tangle ◽  
Lewy Bodies ◽  
Brain Regions ◽  
Braak Stage ◽  
Autopsy Study ◽  
Factors Affecting ◽  
Braak Staging ◽  
Age Related

AbstractPrimary age-related tauopathy (PART) is a form of Alzheimer-type neurofibrillary degeneration occurring in the absence of amyloid-beta (Aβ) plaques. While PART shares some features with Alzheimer disease (AD), such as progressive accumulation of neurofibrillary tangle pathology in the medial temporal lobe and other brain regions, it does not progress extensively to neocortical regions. Given this restricted pathoanatomical pattern and variable symptomatology, there is a need to reexamine and improve upon how PART is neuropathologically assessed and staged. We performed a retrospective autopsy study in a collection (n = 174) of post-mortem PART brains and used logistic regression to determine the extent to which a set of clinical and neuropathological features predict cognitive impairment. We compared Braak staging, which focuses on hierarchical neuroanatomical progression of AD tau and Aβ pathology, with quantitative assessments of neurofibrillary burden using computer-derived positive pixel counts on digitized whole slide images of sections stained immunohistochemically with antibodies targeting abnormal hyperphosphorylated tau (p-tau) in the entorhinal region and hippocampus. We also assessed other factors affecting cognition, including aging-related tau astrogliopathy (ARTAG) and atrophy. We found no association between Braak stage and cognitive impairment when controlling for age (p = 0.76). In contrast, p-tau burden was significantly correlated with cognitive impairment even when adjusting for age (p = 0.03). The strongest correlate of cognitive impairment was cerebrovascular disease, a well-known risk factor (p < 0.0001), but other features including ARTAG (p = 0.03) and hippocampal atrophy (p = 0.04) were also associated. In contrast, sex, APOE, psychiatric illness, education, argyrophilic grains, and incidental Lewy bodies were not. These findings support the hypothesis that comorbid pathologies contribute to cognitive impairment in subjects with PART. Quantitative approaches beyond Braak staging are critical for advancing our understanding of the extent to which age-related tauopathy changes impact cognitive function.

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