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Imaging Neuroscience (Cambridge, Mass.) Feb 2024Cortical atrophy and aggregates of misfolded tau proteins are key hallmarks of Alzheimer's disease. Computational models that simulate the propagation of pathogens...
Cortical atrophy and aggregates of misfolded tau proteins are key hallmarks of Alzheimer's disease. Computational models that simulate the propagation of pathogens between connected brain regions have been used to elucidate mechanistic information about the spread of these disease biomarkers, such as disease epicentres and spreading rates. However, the connectomes that are used as substrates for these models are known to contain modality-specific false positive and false negative connections, influenced by the biases inherent to the different methods for estimating connections in the brain. In this work, we compare five types of connectomes for modelling both tau and atrophy patterns with the network diffusion model, which are validated against tau PET and structural MRI data from individuals with either mild cognitive impairment or dementia. We then test the hypothesis that a joint connectome, with combined information from different modalities, provides an improved substrate for the model. We find that a combination of multimodal information helps the model to capture observed patterns of tau deposition and atrophy better than any single modality. This is validated with data from independent datasets. Overall, our findings suggest that combining connectivity measures into a single connectome can mitigate some of the biases inherent to each modality and facilitate more accurate models of pathology spread, thus aiding our ability to understand disease mechanisms, and providing insight into the complementary information contained in different measures of brain connectivity.
PubMed: 38947941
DOI: 10.1162/imag_a_00089 -
Cureus May 2024This case report describes the care given to a 58-year-old male patient with severe upper jaw atrophy. The treatment strategy involved utilizing zygomatic implants in...
This case report describes the care given to a 58-year-old male patient with severe upper jaw atrophy. The treatment strategy involved utilizing zygomatic implants in conjunction with endosteal implants to rehabilitate both the maxilla and mandible. Temporary prostheses were used during the healing phase, followed by the fabrication and placement of final prostheses. The utilization of zygomatic implants offers advantages such as immediate stabilization and function without the need for extensive bone grafting. This approach not only reduces treatment time and costs but also enhances patient outcomes. Furthermore, guided surgical techniques are increasingly employed to ensure precise implant placement, optimizing prosthetic support.
PubMed: 38947601
DOI: 10.7759/cureus.61430 -
Journal of Experimental Zoology. Part... Jul 2024Vertebrate animals that run or jump across sparsely vegetated habitats, such as horses and jerboas, have reduced the number of distal limb bones, and many have lost most...
Vertebrate animals that run or jump across sparsely vegetated habitats, such as horses and jerboas, have reduced the number of distal limb bones, and many have lost most or all distal limb muscle. We previously showed that nascent muscles are present in the jerboa hindfoot at birth and that these myofibers are rapidly and completely lost soon after by a process that shares features with pathological skeletal muscle atrophy. Here, we apply an intra- and interspecies differential RNA-Seq approach, comparing jerboa and mouse muscles, to identify gene expression differences associated with the initiation and progression of jerboa hindfoot muscle loss. We show evidence for reduced hepatocyte growth factor and fibroblast growth factor signaling and an imbalance in nitric oxide signaling; all are pathways that are necessary for skeletal muscle development and regeneration. We also find evidence for phagosome formation, which hints at how myofibers may be removed by autophagy or by nonprofessional phagocytes without evidence for cell death or immune cell activation. Last, we show significant overlap between genes associated with jerboa hindfoot muscle loss and genes that are differentially expressed in a variety of human muscle pathologies and rodent models of muscle loss disorders. All together, these data provide molecular insight into the process of evolutionary and developmental muscle loss in jerboa hindfeet.
PubMed: 38946691
DOI: 10.1002/jez.b.23268 -
Physiological Reports Jul 2024Cancer cachexia is a multifactorial syndrome associated with advanced cancer that contributes to mortality. Cachexia is characterized by loss of body weight and muscle...
Cancer cachexia is a multifactorial syndrome associated with advanced cancer that contributes to mortality. Cachexia is characterized by loss of body weight and muscle atrophy. Increased skeletal muscle mitochondrial reactive oxygen species (ROS) is a contributing factor to loss of muscle mass in cachectic patients. Mice inoculated with Lewis lung carcinoma (LLC) cells lose weight, muscle mass, and have lower muscle sirtuin-1 (sirt1) expression. Nicotinic acid (NA) is a precursor to nicotinamide dinucleotide (NAD+) which is exhausted in cachectic muscle and is a direct activator of sirt1. Mice lost body and muscle weight and exhibited reduced skeletal muscle sirt1 expression after inoculation with LLC cells. C2C12 myotubes treated with LLC-conditioned media (LCM) had lower myotube diameter. We treated C2C12 myotubes with LCM for 24 h with or without NA for 24 h. C2C12 myotubes treated with NA maintained myotube diameter, sirt1 expression, and had lower mitochondrial superoxide. We then used a sirt1-specific small molecule activator SRT1720 to increase sirt1 activity. C2C12 myotubes treated with SRT1720 maintained myotube diameter, prevented loss of sirt1 expression, and attenuated mitochondrial superoxide production. Our data provides evidence that NA may be beneficial in combating cancer cachexia by maintaining sirt1 expression and decreasing mitochondrial superoxide production.
Topics: Animals; Cachexia; Sirtuin 1; Muscle Fibers, Skeletal; Mice; Oxidative Stress; Mice, Inbred C57BL; Carcinoma, Lewis Lung; Male; Heterocyclic Compounds, 4 or More Rings; Mitochondria, Muscle; Cell Line; Niacin; Mitochondria; Reactive Oxygen Species
PubMed: 38946587
DOI: 10.14814/phy2.16103 -
European Review For Medical and... Jun 2024Sarcopenia is a condition characterized by muscle mass loss. Skeletal muscle is capable of producing and secreting different molecules called myokines, and apelin is one...
OBJECTIVE
Sarcopenia is a condition characterized by muscle mass loss. Skeletal muscle is capable of producing and secreting different molecules called myokines, and apelin is one of them. The literature contains contradictory data on the relationship between apelin and sarcopenia. We decided to investigate the role of apelin in sarcopenia in subjects with disease-related malnutrition (DRM), a group of patients with a high rate of sarcopenia.
PATIENTS AND METHODS
83 elderly patients with DRM assessed according to the Global Leadership Initiative on Malnutrition (GLIM) criteria were included in the study, with a mean age of 69.9±3.8 years. Anthropometric data, muscle mass by ultrasound at the rectus femoris quadriceps (RFQ) level, bioimpedance [skeletal muscle mass (SMM), appendicular SMM (aSMM) and aSMM index (aSMMI)], dynamometry, biochemical parameters, dietary intake, circulating apelin levels were determined in all patients.
RESULTS
a total of 33 patients (37.9%) were diagnosed with sarcopenia, while 54 patients did not present sarcopenia (60.1%). Body weight (-5.5±2.0 kg, p=0.01), calf circumference (-1.9±0.2 cm, p=0.02), phase angle (-0.6±0.2º, p=0.01), reactance (-6.8±2.3 Ohms, p=0.03), resistance (-38.8±12.3 Ohms, p=0.04), SMM (-2.2±0.3 kg, p=0.04), aSMM (-2.2±0.2 kg, p=0.03) and aSMMI (-0.6±0.2 kg, p=0.02), dominant muscle area (-0.6±0.2 cm2, p=0.04), dominant Y axis (-0.4±0.1 cm, p=0.03), dominant X/Y axis (1.1±0.3 cm, p=0.04), strength (-5.1±1.3 kg, p=0.01), albumin (-0.9±0.1 g/dl, p=0.02) and prealbumin (-4.6±0.7 mg/dl, p=0.02) were worse in patients with sarcopenia than non-sarcopenic patients. Circulating apelin levels were similar in both groups. No significant correlation of apelin levels was detected, either with bioimpedance data or with muscle ultrasonography data. The multivariant analysis did not detect a significant association of apelin with the presence of sarcopenia.
CONCLUSIONS
Our study shows a lack of association between apelin and sarcopenia in elderly malnourished patients.
Topics: Humans; Sarcopenia; Apelin; Aged; Malnutrition; Male; Female; Muscle, Skeletal
PubMed: 38946382
DOI: 10.26355/eurrev_202406_36461 -
Muscle-Protective Effect of Carnosine against Dexamethasone-Induced Muscle Atrophy in C2C12 Myotube.Journal of Nutritional Science and... 2024This study investigated the protective effect of carnosine and its components (L-histidine and β-alanine [HA]) against dexamethasone (Dex)-induced muscle atrophy in...
This study investigated the protective effect of carnosine and its components (L-histidine and β-alanine [HA]) against dexamethasone (Dex)-induced muscle atrophy in C2C12 myotubes. Myotubes were treated with Dex (10 μM) to induce muscle atrophy manifested by decreased myotube diameter, low myosin heavy chain content, and increased expression of muscle atrophy-associated ubiquitin ligases (Atrogin-1, MuRF-1, and Cbl-b). Carnosine (20 mM) treatment significantly improved the myotube diameter and MyHC protein expression level in Dex-treated C2C12 myotubes. It also downregulated the expression of Atrogin-1, MuRF-1, and Cbl-b and suppressed the expression of forkhead box O3 (FoxO3a) mediated by Dex. Furthermore, reactive oxygen species production was increased by Dex but was ameliorated by carnosine treatment. However, HA (20 mM), the component of carnosine, treatment was found ineffective in preventing Dex-induced protein damage. Therefore, based on above results it can be suggested that carnosine could be a potential therapeutic agent to prevent Dex-induced muscle atrophy compared to its components HA.
Topics: Carnosine; Dexamethasone; Muscular Atrophy; Muscle Fibers, Skeletal; Animals; Mice; Muscle Proteins; Cell Line; Reactive Oxygen Species; SKP Cullin F-Box Protein Ligases; Ubiquitin-Protein Ligases; Forkhead Box Protein O3; Tripartite Motif Proteins; Myosin Heavy Chains
PubMed: 38945887
DOI: 10.3177/jnsv.70.219 -
Journal of Nutritional Science and... 2024L-Theanine is contained in green tea at 1-3% per dry matter as an amino acid with an umami taste, and the antidepressant effect and protective effect against...
L-Theanine is contained in green tea at 1-3% per dry matter as an amino acid with an umami taste, and the antidepressant effect and protective effect against stress-induced brain atrophy in mice, as well as the related mechanism have been reported. However, effects of theanine on the hippocampus from the proteome analysis and the action mechanism have not been examined. In this study, we mainly investigated the possibility of theanine's cognitive impairment-preventing function and the action mechanism by proteomics in the hippocampus of SAMP8 administered with theanine. In addition to improvement in the aging score with theanine administration, in proteomics, significant suppressions in the expressions of synapsin 2, α-synuclein, β-synuclein, and protein tau were observed by theanine administration, and the expression of CAM kinase II beta and alpha exhibited a significant increase and increasing tendency with theanine administration, respectively. The expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein tended to increase by theanine administration. On the other hand, serotonin/tryptophan, GABA/glutamic acid and glutamine/glutamic acid ratios in the hippocampus showed an increasing tendency, a significant increase, and an increasing tendency with theanine administration, respectively. These results suggested that theanine might have been involved in the improvement of neurodegeneration or cognitive impairment by suppressing the productions of synapsin, synuclein and protein tau which are considered to be produced along with aging and oxidation, and by enhancing the production of serotonin by increasing the expression of CAM kinase II, and further by affecting the metabolism of glutamate.
Topics: Animals; Glutamates; Hippocampus; Mice; Male; Aging; Synapsins; Glutamic Acid; alpha-Synuclein; tau Proteins; Proteomics; Dietary Supplements; Serotonin; Diet; gamma-Aminobutyric Acid; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cognitive Dysfunction
PubMed: 38945886
DOI: 10.3177/jnsv.70.210 -
Clinical Radiology Jun 2024Spinal muscular atrophy (SMA) is an autosomal recessive genetic disease caused by the degeneration of the α-motor neurons in the anterior horn of the spinal cord. SMA... (Review)
Review
Spinal muscular atrophy (SMA) is an autosomal recessive genetic disease caused by the degeneration of the α-motor neurons in the anterior horn of the spinal cord. SMA is clinically characterized by progressive and symmetrical muscle weakness and muscle atrophy and ends up with systemic multisystem abnormalities. Quantitative MRI (qMRI) has the advantages of non-invasiveness, objective sensitivity, and high reproducibility, and has important clinical value in evaluating the severity of neuromuscular diseases and monitoring the efficacy of treatment. This article summarizes the clinical use of muscular MRI and magnetic resonance neurography in assessing the progress of SMA.
PubMed: 38945793
DOI: 10.1016/j.crad.2024.06.004 -
American Journal of Ophthalmology Jun 2024To investigate the clinical, functional, and imaging characteristics in patients affected by inherited retinal diseases associated with RDH5 and RLBP1 gene variants, and...
PURPOSE
To investigate the clinical, functional, and imaging characteristics in patients affected by inherited retinal diseases associated with RDH5 and RLBP1 gene variants, and to report novel genotype-phenotype correlations.
DESIGN
Retrospective single-center cohort study.
METHODS
Twenty-two patients with molecularly confirmed RLBP1-associated retinopathy and 5 with RDH5-associated retinopathy. Medical records were reviewed to obtain data on family history and ophthalmologic examinations, including retinal imaging and full-field electroretinography (ffERG). Genotype was determined by targeted next-generation sequencing followed by confirmation and familial segregation by Sanger sequencing.
RESULTS
The median (IQR) age at baseline for the RDH5 and RLBP1 cohort was 44.6 (38.2-67.9) years and 36.9 (23.1-45.2) years, respectively. Macular atrophy was found in approximately 80% of eyes from both cohorts. The RLBP1 genotype was associated with a lower macular volume by 0.28 mm (95% CI, -0.46 to -0.11; P = .005) compared to the RDH5 genotype. In both genotypic cohorts, we found a significant annual rate of macular volume loss, estimated at -0.007 mm/y (95% CI, -0.012 to -0.001; P = .02), without any significant difference the two genotypes. Three unrelated patients homozygous for the c.361C>T p.(Arg121Trp) RLBP1 variant showed minimal impairment of both the rod and cone systems function on ffERG and absence of macular atrophy.
CONCLUSIONS
Progressive macular atrophy in addition to congenital night blindness can be identified in adult patients with RDH5-associated retinopathy. Vice versa, hypomorphic RLBP1 variants may cause milder retinal phenotypes rather than the typical severe rod-cone dystrophy with macular atrophy. These findings could prove beneficial to improve the prognostication of patients and help in designing future interventional trials.
PubMed: 38945349
DOI: 10.1016/j.ajo.2024.06.016 -
Advances in Gerontology = Uspekhi... 2024The foundation of healthy aging is the prevention of disability. In modern medical usage, a syndrome refers to a collection of symptoms and signs with a single... (Review)
Review
The foundation of healthy aging is the prevention of disability. In modern medical usage, a syndrome refers to a collection of symptoms and signs with a single underlying cause that may not yet be known. Geriatric syndromes, on the other hand, refer to multifactorial health conditions and occur when the accumulated effects of impairments in multiple systems make an older person vulnerable to situational changes. The use of the term "syndrome" in geriatrics emphasizes the multiple causes of a single manifestation involving an abundance of factors involving multiple organs and systems and is characterized by unique features of common health problems in older adults. It is the geriatric syndromes that can have a significant impact on quality of life and disability. Therefore, early detection of these medical conditions using targeted geriatric assessment is essential in geriatrics. Understanding the essence and feminology of geriatric syndromes, their correct positioning and interpretation is an extremely urgent problem. The main purpose of the presented review is precisely to try to answer these questions. In addition, it has not yet been determined whether geriatric syndromes should be included in the diagnosis (the only exception is sarcopenia syndrome, which was officially included in the 10th International Classification of Diseases in 2016).
Topics: Humans; Aged; Terminology as Topic; Geriatric Assessment; Syndrome; Quality of Life; Geriatrics; Sarcopenia; Aging
PubMed: 38944774
DOI: No ID Found