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Journal of Neurology Oct 2013Focal lesions and brain atrophy are the most extensively studied aspects of multiple sclerosis (MS), but the image acquisition and analysis techniques used can be... (Review)
Review
Focal lesions and brain atrophy are the most extensively studied aspects of multiple sclerosis (MS), but the image acquisition and analysis techniques used can be further improved, especially those for studying within-patient changes of lesion load and atrophy longitudinally. Improved accuracy and sensitivity will reduce the numbers of patients required to detect a given treatment effect in a trial, and ultimately, will allow reliable characterization of individual patients for personalized treatment. Based on open issues in the field of MS research, and the current state of the art in magnetic resonance image analysis methods for assessing brain lesion load and atrophy, this paper makes recommendations to improve these measures for longitudinal studies of MS. Briefly, they are (1) images should be acquired using 3D pulse sequences, with near-isotropic spatial resolution and multiple image contrasts to allow more comprehensive analyses of lesion load and atrophy, across timepoints. Image artifacts need special attention given their effects on image analysis results. (2) Automated image segmentation methods integrating the assessment of lesion load and atrophy are desirable. (3) A standard dataset with benchmark results should be set up to facilitate development, calibration, and objective evaluation of image analysis methods for MS.
Topics: Atrophy; Brain; Humans; Imaging, Three-Dimensional; Longitudinal Studies; Multiple Sclerosis; Neuroimaging
PubMed: 23263472
DOI: 10.1007/s00415-012-6762-5 -
Alimentary Pharmacology & Therapeutics Jul 2002Considerable difficulties persist amongst pathologists in agreeing on the presence and severity of gastric atrophy. An international group of pathologists pursued the... (Review)
Review
BACKGROUND AND AIMS
Considerable difficulties persist amongst pathologists in agreeing on the presence and severity of gastric atrophy. An international group of pathologists pursued the following aims: (i) to generate an acceptable definition and a simple reproducible classification of gastric atrophy; and (ii) to develop guidelines for the recognition of atrophy useful for increasing agreement among observers.
METHODS
After redefining atrophy as the 'loss of appropriate glands' and examining histological samples from different gastric compartments, three categories were identified: (i) negative; (ii) indefinite; (iii) atrophy, with and without intestinalization. Atrophy was graded on a three-level scale. Interobserver reproducibility of the classification was tested by kappa statistics (general and weighted) in a series of 48 cases.
RESULTS
The medians of the general agreement and weighted kappa values were 0.78 and 0.73, respectively. The weighted kappa coefficients, obtained by cross-tabulating the evaluation of each pathologist against all others, were, with only one exception, > 0.4 (moderate to excellent agreement).
CONCLUSIONS
By using the definition of atrophy as the loss of appropriate glands and distinguishing the two main morphological entities of metaplastic and non-metaplastic types, a high level of agreement was achieved by a group of gastrointestinal pathologists trained in different cultural contexts.
Topics: Atrophy; Biopsy; Gastric Mucosa; Gastritis, Atrophic; Humans; Observer Variation; Pyloric Antrum; Reproducibility of Results; Severity of Illness Index
PubMed: 12144574
DOI: 10.1046/j.1365-2036.2002.01301.x -
NeuroImage Nov 2022The thalamus is a central integration structure in the brain, receiving and distributing information among the cerebral cortex, subcortical structures, and the...
The thalamus is a central integration structure in the brain, receiving and distributing information among the cerebral cortex, subcortical structures, and the peripheral nervous system. Prior studies clearly show that the thalamus atrophies in cognitively unimpaired aging. However, the thalamus is comprised of multiple nuclei involved in a wide range of functions, and the age-related atrophy of individual thalamic nuclei remains unknown. Using a recently developed automated method of identifying thalamic nuclei (3T or 7T MRI with white-matter-nulled MPRAGE contrast and THOMAS segmentation) and a cross-sectional design, we evaluated the age-related atrophy rate for 10 thalamic nuclei (AV, CM, VA, VLA, VLP, VPL, pulvinar, LGN, MGN, MD) and an epithalamic nucleus (habenula). We also used T1-weighted images with the FreeSurfer SAMSEG segmentation method to identify and measure age-related atrophy for 11 extra-thalamic structures (cerebral cortex, cerebral white matter, cerebellar cortex, cerebellar white matter, amygdala, hippocampus, caudate, putamen, nucleus accumbens, pallidum, and lateral ventricle). In 198 cognitively unimpaired participants with ages spanning 20-88 years, we found that the whole thalamus atrophied at a rate of 0.45% per year, and that thalamic nuclei had widely varying age-related atrophy rates, ranging from 0.06% to 1.18% per year. A functional grouping analysis revealed that the thalamic nuclei involved in cognitive (AV, MD; 0.53% atrophy per year), visual (LGN, pulvinar; 0.62% atrophy per year), and auditory/vestibular (MGN; 0.64% atrophy per year) functions atrophied at significantly higher rates than those involved in motor (VA, VLA, VLP, and CM; 0.37% atrophy per year) and somatosensory (VPL; 0.32% atrophy per year) functions. A proximity-to-CSF analysis showed that the group of thalamic nuclei situated immediately adjacent to CSF atrophied at a significantly greater atrophy rate (0.59% atrophy per year) than that of the group of nuclei located farther from CSF (0.36% atrophy per year), supporting a growing hypothesis that CSF-mediated factors contribute to neurodegeneration. We did not find any significant hemispheric differences in these rates of change for thalamic nuclei. Only the CM thalamic nucleus showed a sex-specific difference in atrophy rates, atrophying at a greater rate in male versus female participants. Roughly half of the thalamic nuclei showed greater atrophy than all extra-thalamic structures examined (0% to 0.54% per year). These results show the value of white-matter-nulled MPRAGE imaging and THOMAS segmentation for measuring distinct thalamic nuclei and for characterizing the high and heterogeneous atrophy rates of the thalamus and its nuclei across the adult lifespan. Collectively, these methods and results advance our understanding of the role of thalamic substructures in neurocognitive and disease-related changes that occur with aging.
Topics: Adult; Aged; Aged, 80 and over; Aging; Atrophy; Cross-Sectional Studies; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Thalamic Nuclei; Thalamus; Young Adult
PubMed: 36007822
DOI: 10.1016/j.neuroimage.2022.119584 -
International Journal of Molecular... May 2024Skeletal muscle unloading occurs during a wide range of conditions, from space flight to bed rest. The unloaded muscle undergoes negative functional changes, which... (Review)
Review
Skeletal muscle unloading occurs during a wide range of conditions, from space flight to bed rest. The unloaded muscle undergoes negative functional changes, which include increased fatigue. The mechanisms of unloading-induced fatigue are far from complete understanding and cannot be explained by muscle atrophy only. In this review, we summarize the data concerning unloading-induced fatigue in different muscles and different unloading models and provide several potential mechanisms of unloading-induced fatigue based on recent experimental data. The unloading-induced changes leading to increased fatigue include both neurobiological and intramuscular processes. The development of intramuscular fatigue seems to be mainly contributed by the transformation of soleus muscle fibers from a fatigue-resistant, "oxidative" "slow" phenotype to a "fast" "glycolytic" one. This process includes slow-to-fast fiber-type shift and mitochondrial density decline, as well as the disruption of activating signaling interconnections between slow-type myosin expression and mitochondrial biogenesis. A vast pool of relevant literature suggests that these events are triggered by the inactivation of muscle fibers in the early stages of muscle unloading, leading to the accumulation of high-energy phosphates and calcium ions in the myoplasm, as well as NO decrease. Disturbance of these secondary messengers leads to structural changes in muscles that, in turn, cause increased fatigue.
Topics: Humans; Muscle Fatigue; Animals; Muscle, Skeletal; Muscular Atrophy
PubMed: 38732203
DOI: 10.3390/ijms25094984 -
Antioxidants & Redox Signaling Sep 2020Skeletal muscles play essential roles in key body functions including breathing, locomotion, and glucose homeostasis; therefore, maintaining healthy skeletal muscles is... (Review)
Review
Skeletal muscles play essential roles in key body functions including breathing, locomotion, and glucose homeostasis; therefore, maintaining healthy skeletal muscles is important. Prolonged periods of muscle inactivity (, bed rest, mechanical ventilation, or limb immobilization) result in skeletal muscle atrophy and weakness. Disuse skeletal muscle atrophy occurs due to both accelerated proteolysis and decreased protein synthesis with proteolysis playing a leading role in some types of inactivity-induced atrophy. Although all major proteolytic systems are involved in inactivity-induced proteolysis in skeletal muscles, growing evidence indicates that both calpain and autophagy play an important role. Regulation of proteolysis in skeletal muscle is under complex control, but it is established that activation of both calpain and autophagy is directly linked to oxidative stress. In this review, we highlight the experimental evidence that supports a cause and effect link between reactive oxygen species (ROS) and activation of both calpain and autophagy in skeletal muscle fibers during prolonged inactivity. We also review the sources of oxidant production in muscle fibers during inactivity-induced atrophy, and provide a detailed discussion on how ROS activates both calpain and autophagy during disuse muscle wasting. Future studies are required to delineate the specific mechanisms by which ROS activates both calpain and autophagy in skeletal muscles during prolonged periods of contractile inactivity. This knowledge is essential to develop the most effective strategies to protect against disuse muscle atrophy. . 33, 559-569.
Topics: Animals; Autophagy; Humans; Muscle, Skeletal; Muscular Atrophy; Oxidation-Reduction; Oxidative Stress; Proteolysis; Reactive Oxygen Species
PubMed: 31941357
DOI: 10.1089/ars.2019.8000 -
Journal of Clinical Immunology Feb 2023About 15% of patients with common variable immunodeficiency (CVID) develop a small intestinal enteropathy, which resembles celiac disease with regard to histopathology...
PURPOSE
About 15% of patients with common variable immunodeficiency (CVID) develop a small intestinal enteropathy, which resembles celiac disease with regard to histopathology but evolves from a distinct, poorly defined pathogenesis that has been linked in some cases to chronic norovirus (NV) infection. Interferon-driven inflammation is a prominent feature of CVID enteropathy, but it remains unknown how NV infection may contribute.
METHODS
Duodenal biopsies of CVID patients, stratified according to the presence of villous atrophy (VA), IgA plasma cells (PCs), and chronic NV infection, were investigated by flow cytometry, multi-epitope-ligand cartography, bulk RNA-sequencing, and RT-qPCR of genes of interest.
RESULTS
VA development was connected to the lack of intestinal (IgA) PC, a T helper 1/T helper 17 cell imbalance, and increased recruitment of granzymeCD8 T cells and pro-inflammatory macrophages to the affected site. A mixed interferon type I/III and II signature occurred already in the absence of histopathological changes and increased with the severity of the disease and in the absence of (IgA) PCs. Chronic NV infection exacerbated this signature when compared to stage-matched NV-negative samples.
CONCLUSIONS
Our study suggests that increased IFN signaling and T-cell cytotoxicity are present already in mild and are aggravated in severe stages (VA) of CVID enteropathy. NV infection preempts local high IFN-driven inflammation, usually only seen in VA, at milder disease stages. Thus, revealing the impact of different drivers of the pathological mixed IFN type I/III and II signature may allow for more targeted treatment strategies in CVID enteropathy and supports the goal of viral elimination.
Topics: Humans; Atrophy; Caliciviridae Infections; CD8-Positive T-Lymphocytes; Common Variable Immunodeficiency; Immunoglobulin A; Inflammation; Interferons; Norovirus
PubMed: 36282455
DOI: 10.1007/s10875-022-01379-2 -
PloS One 2019Sarcopenia due to loss of skeletal muscle mass and strength leads to physical inactivity and decreased quality of life. The number of individuals with sarcopenia is...
Sarcopenia due to loss of skeletal muscle mass and strength leads to physical inactivity and decreased quality of life. The number of individuals with sarcopenia is rapidly increasing as the number of older people increases worldwide, making this condition a medical and social problem. Some patients with sarcopenia exhibit accumulation of peri-muscular adipose tissue (PMAT) as ectopic fat deposition surrounding atrophied muscle. However, an association of PMAT with muscle atrophy has not been demonstrated. Here, we show that PMAT is associated with muscle atrophy in aged mice and that atrophy severity increases in parallel with cumulative doses of PMAT. We observed severe muscle atrophy in two different obese model mice harboring significant PMAT relative to respective control non-obese mice. We also report that denervation-induced muscle atrophy was accelerated in non-obese young mice transplanted around skeletal muscle with obese adipose tissue relative to controls transplanted with non-obese adipose tissue. Notably, transplantation of obese adipose tissue into peri-muscular regions increased nuclear translocation of FoxO transcription factors and upregulated expression FoxO targets associated with proteolysis (Atrogin1 and MuRF1) and cellular senescence (p19 and p21) in muscle. Conversely, in obese mice, PMAT removal attenuated denervation-induced muscle atrophy and suppressed upregulation of genes related to proteolysis and cellular senescence in muscle. We conclude that PMAT accumulation accelerates age- and obesity-induced muscle atrophy by increasing proteolysis and cellular senescence in muscle.
Topics: Adipose Tissue; Aging; Animals; Cellular Senescence; Disease Models, Animal; Forkhead Box Protein O1; Humans; Mice; Mice, Obese; Muscle Proteins; Muscle, Skeletal; Muscular Atrophy; Obesity; Quality of Life; SKP Cullin F-Box Protein Ligases; Sarcopenia; Tripartite Motif Proteins; Ubiquitin-Protein Ligases
PubMed: 31442231
DOI: 10.1371/journal.pone.0221366 -
Journal of Alzheimer's Disease : JAD 2022Apathy is highly frequent in behavioral variant frontotemporal dementia (bvFTD). It is presumed to involve different pathophysiological mechanisms and neuroanatomical...
BACKGROUND
Apathy is highly frequent in behavioral variant frontotemporal dementia (bvFTD). It is presumed to involve different pathophysiological mechanisms and neuroanatomical regions.
OBJECTIVE
We explored the hypothesis that subgroups showing distinct profiles of apathy and distinct patterns of atrophy within frontal lobes could be disentangled in bvFTD.
METHODS
Using data-driven clustering applied to 20 bvFTD patients, we isolated subgroups according to their profiles on the three subscales of the Dimensional Apathy Scale (DAS). We explored their apathy profiles and atrophy patterns. Apathy profiles were characterized through both subjective measures of apathy by questionnaires and measures including objective behavioral metrics. Atrophy patterns were obtained by voxel-based morphometry, contrasting each bvFTD subgroup with healthy controls (N = 16).
RESULTS
By clustering based on DAS dimensions, we disentangled three subgroups of bvFTD patients, with distinct apathy profiles and atrophy patterns. One subgroup, which presented the smallest pattern of atrophy (including orbitofrontal cortex) with a right asymmetry, was characterized by high self-reported emotional and initiation apathy and by a self-initiation deficit reversible by external guidance. In other subgroups showing more diffuse bilateral atrophies extending to lateral prefrontal cortex, apathy was not reversible by external guidance and more difficulty to focus on goal-management was observed, especially in the subgroup with the largest atrophy and highest levels of executive apathy.
CONCLUSION
Distinct clinical profiles of apathy, corresponding to distinct anatomical subtypes of bvFTD, were identified. These findings have implications for clinicians in a perspective of precision medicine as they could contribute to personalize treatments of apathy.
Topics: Humans; Atrophy; Cognition; Frontal Lobe; Frontotemporal Dementia; Magnetic Resonance Imaging; Neuropsychological Tests
PubMed: 36155506
DOI: 10.3233/JAD-220370 -
Biochimica Et Biophysica Acta Sep 2013With the extension of life span over the past several decades, the age-related loss of muscle mass and strength that characterizes sarcopenia is becoming more evident... (Review)
Review
With the extension of life span over the past several decades, the age-related loss of muscle mass and strength that characterizes sarcopenia is becoming more evident and thus, has a more significant impact on society. To determine ways to intervene and delay, or even arrest the physical frailty and dependence that accompany sarcopenia, it is necessary to identify those biochemical pathways that define this process. Animal models that mimic one or more of the physiological pathways involved with this phenomenon are very beneficial in providing an understanding of the cellular processes at work in sarcopenia. The ability to influence pathways through genetic manipulation gives insight into cellular responses and their impact on the physical expression of sarcopenia. This review evaluates several murine models that have the potential to elucidate biochemical processes integral to sarcopenia. Identifying animal models that reflect sarcopenia or its component pathways will enable researchers to better understand those pathways that contribute to age-related skeletal muscle mass loss, and in turn, develop interventions that will prevent, retard, arrest, or reverse this phenomenon. This article is part of a Special Issue entitled: Animal Models of Disease.
Topics: Animals; Cachexia; Disease Models, Animal; Humans; Muscle, Skeletal; Muscular Atrophy; Sarcopenia
PubMed: 23523469
DOI: 10.1016/j.bbadis.2013.03.011 -
Maturitas Nov 2012The brain atrophies in late life. However, there are many factors that either magnify or mitigate the rate of atrophy. Loss of estrogens during menopause and... (Review)
Review
The brain atrophies in late life. However, there are many factors that either magnify or mitigate the rate of atrophy. Loss of estrogens during menopause and administration of hormone therapy have both been hypothesized as sources of individual variation in the prevalence of cortical and subcortical atrophy and loss of cognitive function in late adulthood. In this review we critically summarize and assess the extant rodent and human neuroimaging studies that examine the link between estrogens and hippocampal morphology and function and focus predominantly on human studies of the hippocampus in postmenopausal women. Several cross-sectional studies report that the size of the hippocampus is larger in women receiving hormone therapy while several other cross-sectional studies report either negligible effects or smaller volumes in women receiving hormone therapy. We suggest that these differences might be caused by the variation between studies in the age of the samples studied, the duration of therapy, and the age at which hormone therapy is initiated. Unfortunately, all of the human studies reviewed here are cross-sectional in nature. With the lack of well-controlled randomized trials with neuroimaging measures on postmenopausal women both before and after some exposure interval, the effect of hormone therapy on hippocampal atrophy will remain equivocal and poorly understood.
Topics: Animals; Atrophy; Cognition Disorders; Estrogen Replacement Therapy; Estrogens; Female; Hippocampus; Humans; Postmenopause
PubMed: 22858056
DOI: 10.1016/j.maturitas.2012.07.001