Degree Of Atrophy Research Articles

Compound Probiotics Improve Neuropathic Pain Prognosis in a Murine Model of Chronic Constriction Injury.

Compound probiotics have been reported to ameliorate imbalances in the intestinal flora that may play a critical role in neuropathic pain. This study aimed to investigate the efficacy of compound probiotic treatment on neuropathic pain. Thirty mice were randomly divided into three groups: 1) sham group, 2) mouse with chronic constrictive injury (CCI), and 3) probiotic gavage with CCI (CCI+Prob). The degree of pain and gait recovery was assessed by Mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), and mouse footprints. The degree of atrophy of the gastrocnemius muscle was assessed by muscle weight, hematoxylin and eosin (H&E) staining. Gut microbiota were analyzed by 16S ribosomal RNA sequencing (16SrRNA). Four weeks after surgery, TWL and MWT assessment showed significant increases in the CCI+Prob group compared with the CCI group (P < 0.01). Gait analysis results as well as gastrocnemius muscle weight showed a significant improvement in the CCI+Prob group compared with the CCI group. Measurement of alpha diversity showed a significant increase in the CCI group compared with the sham group, but this increase was attenuated by probiotic intervention in the CCI+Prob group. Although the CCI group had significantly decreased levels of Akkermansia and significantly increased levels of Ruminococcaceae, probiotic treatment reversed these changes. Compound probiotics treatment can improve the pain and muscle atrophy in mice with CCI-induced neuropathic pain. The improvement of symptoms is associated with changes in the composition of gut microbiota.

Formation of urogenital disorders in women at the stage of menopausal transition

At the stage of the menopausal transition which is caused by hormonal and reproductive changes, a spectrum of genitourinary disorders is formed 3-5 years earlier than in the past.The objective: to evaluate the effectiveness of local use of suppositories with anti-inflammatory and regenerating effect, which contain tea tree oil, aloe extract and hyaluronic acid, to eliminate the manifestations of vulvovaginal atrophy in women at the stage of the menopausal transition.Materials and methods. A gynecological, urological, sexological examination of 56 women aged 44 to 46 years at the final stage of the menopausal transition with complaints of burning in the vagina and vagina, lubrication disorders, dyspareunia and discomfort during urination was carried out.Results. Among the examined women, a high degree of vulvovaginal atrophy was found in 4 (7,1 %) patients, manifested degree – in 8 (14,3 %), moderate degree – in 34 (60,7 %), light degree – 10 (17,9 %). In 12 (21,4 %) women with high and manifest degrees of vulvovaginal atrophy, as well as in 24 (42,8 %) with moderate atrophy, dyspareunia was formed on the background of lubrication disorders, which made the sexual intercourse difficult and impossible.Bad mood of patients, dissatisfaction with themselves negatively affected relations with their partners, forming sexual disharmony. Patients with moderate and weak degrees of vulvovaginal atrophy (44 persons – 78,6 %) also noted a decreased sexual desire and arousal, difficulties in reaching orgasm and obtaining pleasure.Conclusions. The conducted studies demonstrated that the leveling of manifestations of vulvovaginal atrophy in 42 (75,0 %) women at the stage of the menopausal transition using suppositories containing tea tree essential oil, aloe vera, hyaluronic acid with delicate regenerative, restorative, anti-inflammatory effects due to the combination of action of tea tree oil, aloe extract, and hyaluronic acid, helps to improve lubrication, eliminate dyspareunia, restore sexual relations – in 48 (85,7%) couples, improve the quality of life and self-assessment of all patients.

Hypometabolic mismatch with atrophy and tau pathology in mixed Alzheimer and Lewy body disease.

Polypathology is a major driver of heterogeneity in clinical presentation and extent of neurodegeneration (N) in patients with Alzheimer Disease (AD). Beyond amyloid (A) and tau (T) pathologies, over half of patients with AD have concomitant pathology such as α-synuclein (S) in mixed AD with Lewy Body Disease (LBD). Patients with Mixed Etiology Dementia (MED) such as AD+LBD have faster progression and potentially differential responses to targeted treatments, though the diagnosis of AD+LBD can be challenging given overlapping clinical and imaging features. Development and validation of improved in vivo biomarkers are required to study relationships between N and S and identify imaging patterns reflecting mixed AD+LBD pathologies. We hypothesize that individual proteinopathies, such as T and S, are associated with commensurate levels of N. Thus, we assessed biomarkers of A, T, N and S with positron emission tomography (PET), magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) seeding amplification assay (SAA) data to determine molecular presentations of mixed A+S+ vs. A+S- cognitively impaired patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We found A+S+ patients had parieto-occipital 18F-Fluorodeoxyglucose hypometabolism (a measure of N) disproportionate to the degree of regional atrophy or T burden, highlighting worse hypometabolism associated with S+ SAA. Following up on this hypometabolic mismatch with CSF metabolite and proteome analyses, we found that A+S+ patients exhibited lower CSF levels of dopamine metabolites and synaptic markers like neuronal pentraxin-2 (NPTX2), suggesting that altered neurotransmission and neuron integrity contribute to this dissociation between metabolic PET and MRI. Potential confounders exist when studying relations between N, AD and LBD pathologies, including neuroinflammation and other non-Alzheimer pathologies in MED, though our findings imply posterior hypometabolic mismatch is related more to S than vascular or TDP-43 pathology. A+S+ patients had posterior mismatch with excessive 18F-Fluorodeoxyglucose hypometabolism relative to atrophy or T load, possibly reflecting impaired neuron integrity. Further research must disentangle the impact of multiple proteinopathies and clinicopathologic factors on hypometabolism and atrophy. Cumulatively, patients with mixed AD+LBD etiologies harbor a unique metabolic PET mismatch signature.

Clinical and laboratory-instrumental characteristics of patients with dyspepsia syndrome not associated with &lt;i&gt;Нelicobacter pylori&lt;/i&gt; infection

BACKGROUND: The significant prevalence of dyspepsia in patients without Нelicobacter pylori infection, difficulties in differential diagnosis necessitate the identification of the most common nosological variants, optimization of the diagnosis algorithm. AIM: To study clinical, laboratory and instrumental characteristics of patients with dyspepsia syndrome unrelated to Нelicobacter pylori infection. MATERIALS AND METHODS: A 13C-Urea Breath test was performed to 856 patients with uninvestigated dyspepsia. According to its results, 342 patients with Нelicobacter pylori infection were excluded from the study. The remaining patients (n = 514) with negative Нelicobacter pylori status underwent esophagogastroduodenoscopy and ultrasound examination of the abdominal organs. The patients with an identified organic pathology (n = 129) explaining dyspeptic complaints were excluded from the study. 208 out of the 385 patients without organic pathology agreed to undergo laboratory and instrumental examination in accordance with the study protocol. To assess dyspeptic complaints, 208 patients filled out a “Dyspepsia Questionnaire” developed by the authors. Demographic, anthropometric data, and complaints were recorded in all the study participants; experimental psychological testing was performed (Beck’s questionnaires, generalized anxiety disorder questionnaire-7, Short Form-36) and laboratory and instrumental examination (the level of pepsinogen I, pepsinogen II, immunoglobulin class G to Нelicobacter pylori and gastrin-17 in serum), esophagogastrogastroduodenoscopy with biopsy and pathomorphological assessment according to the Operative Link for Gastritis Assessment (OLGA) system, 24-hour esophageal impedance–pH monitoring, radiography of the esophagus and stomach. RESULTS: The majority of the patients with dyspepsia syndrome were not infected at the time of Нelicobacter pylori complaints — 514 (60.1%) patients. An in-depth examination of 208 people with a negative helicobacter status and the absence of an organic pathology explaining the symptoms revealed the heterogeneity of the final diagnoses. The results of the study demonstrate positive correlations between the level of depression, anxiety and the AET (acid exposure time) index, the number of acid reflux. A decrease in the level of pepsinogen I, gastrin-17, and the ratio of pepsinogen I/II was revealed with an increase in the degree and stage of atrophy according to the results of an Operative Link for Gastritis Assessment biopsy. CONCLUSIONS: The revealed variability of diagnoses and comorbidity in patients with similar complaints deepens the understanding of dyspepsia syndrome and explains the possible ineffectiveness of standard therapy regimens.

Age-Related Association Between Unilateral Single-Channel and Double-Channel Surgery and Postoperative Multifidus Muscle Atrophy and Fat Infiltration.

Unilateral biportal endoscopic laminotomy (UBE) and percutaneous endoscopic laminotomy (PEL) are minimally invasive spinal surgery (MISS) techniques used for unilateral and dual-channel endoscopic laminectomy. However, limited research has been conducted on lumbosacral multifidus muscle injuries in elderly individuals undergoing MISS for lumbar spinal canal stenosis. The objective of this study was to investigate the impact of single-channel and double-channel MISS on the multifidus muscle in elderly patients. A total of 107 patients who underwent MISS were stratified into two cohorts: group A (<65 years) and group B (≥65 years). Preoperative imaging data, including magnetic resonance imaging, were gathered to classify the degree of stenosis based on the nerve root compression. The extent of multifidus muscle atrophy and fat infiltration was assessed by calculating the fat-free cross-sectional area (FCSA)/cross-sectional area (CSA) ratio before and after surgery through measurements of CSA and FCSA. Total cross-sectional area/FCSA were calculated using MRI cross-sectional T2WI. The degree of atrophy and fat infiltration did not change between procedures in group A (P>.05), but changed significantly in group B (P<.05). Unilateral single-channel and double-channel surgery had no significant effect on the degree of multifidus muscle atrophy and fat infiltration in patients younger than 65 years. However, in patients 65 years and older, the degree of multifidus muscle atrophy and fat infiltration significantly increased with the increasing incidence of lateral recess stenosis, which was positively correlated with the duration of surgery. [Orthopedics. 202x;4x(x):xx-xx.].

Impact of Spaceflight on Upper Extremity Orthopedic Health

INTRODUCTION: With increased access to commercial spaceflight and space tourism, plus a push for longer duration spaceflights, it is especially important to understand the impact of spaceflight on musculoskeletal health. Upper extremity injuries are the most common musculoskeletal injuries in spaceflight. It is, therefore, vital to determine the changes to the upper extremities during spaceflight. The purpose of this study was to examine the state of knowledge on the impact of spaceflight on upper extremity orthopedic health, and to identify knowledge gaps and future areas of research. METHODS: A literature review was performed and studies and reports that amassed data on shoulder, elbow, wrist, and hand health were included. RESULTS: Spaceflight decreases bone mineral density in the upper extremities and increases risk of fracture, especially upon return to gravitational environments. Spaceflight does not uniformly affect all muscles; in the shoulder, the various muscles crossing the joint appear to be variably affected: the deltoid experiences a greater degree of atrophy than the rotator cuff muscles. Spaceflight additionally affects the peripheral nervous system, with astronauts experiencing hand numbness and loss of manual dexterity but cause of these symptoms is undetermined. Spacesuits have also been implicated in causing upper extremity injury, especially while training for or performing extravehicular activities. DISCUSSION: While upper extremity orthopedic health in spaceflight is incompletely understood, known adaptations increase risk for weakening and injury. Existing research provides valuable information for best practices, but there is still much to be discovered to optimize upper extremity health in spaceflight. Fiedler B, Jami M, Rakauskas T, Ahmed AS. Impact of spaceflight on upper extremity orthopedic health. Aerosp Med Hum Perform. 2024; 95(10):777–783.

Clinicopathologic Features of Early Gastric Cancer after Heli-cobacter pylori Eradication in Japanese Patients: Comparative Study between Early (10 Years) Onset.

Eradication therapy for Helicobacter pylori gastritis was approved for insurance coverage by the Japanese government in 2013. Since then, the incidence of gastric cancer discovered after eradication (GCAE) has increased. However, there are only a few reports of GCAE diagnosed more than 10 years after eradication. We investigated the clinicopathological characteristics of early-stage GCAE, including histological types and the interval from eradication to diagnosis. Overall, 379 patients with a total of 448 GCAE lesions treated with endoscopic resection or surgery at our hospital between January 2015 and December 2021 were assessed, and 315 patients with a known interval from eradication to diagnosis of GCAE with a total of 354 lesions were included. We classified the cases into two groups: differentiated-type GCAE (D-GCAE; 279 patients, 318 lesions) and undifferentiated-type GCAE (UD-GCAE; 36 patients, 36 lesions). Smoking and a mild-to-moderate degree of atrophy were risk factors associated with differentiated-type gastric cancer occurring more than 10 years after H. pylori eradication. Additionally, the rate of a mixture of histological types with relatively high malignant potential was significantly higher in UD-GCAE presenting more than 10 years after eradication group than those presenting within 10 years after eradication.

Anatomo-functional changes in neural substrates of cognitive memory in developmental amnesia: Insights from automated and manual Magnetic Resonance Imaging examinations.

Despite bilateral hippocampal damage dating to the perinatal or early childhood period and severely impaired episodic memory, patients with developmental amnesia continue to exhibit well-developed semantic memory across the developmental trajectory. Detailed information on the extent and focality of brain damage in these patients is needed to hypothesize about the neural substrate that supports their remarkable capacity for encoding and retrieval of semantic memory. In particular, we need to assess whether the residual hippocampal tissue is involved in this preservation, or whether the surrounding cortical areas reorganize to rescue aspects of these critical cognitive memory processes after early injury. We used voxel-based morphometry (VBM) analysis, automatic (FreeSurfer) and manual segmentation to characterize structural changes in the brain of an exceptionally large cohort of 23 patients with developmental amnesia in comparison with 32 control subjects. Both the VBM and the FreeSurfer analyses revealed severe structural alterations in the hippocampus and thalamus of patients with developmental amnesia. Milder damage was found in the amygdala, caudate, and parahippocampal gyrus. Manual segmentation demonstrated differences in the degree of atrophy of the hippocampal subregions in patients. The level of atrophy in CA-DG subregions and subicular complex was more than 40%, while the atrophy of the uncus was moderate (-24%). Anatomo-functional correlations were observed between the volumes of residual hippocampal subregions in patients and selective aspects of their cognitive performance, viz, intelligence, working memory, and verbal and visuospatial recall. Our findings suggest that in patients with developmental amnesia, cognitive processing is compromised as a function of the extent of atrophy in hippocampal subregions. More severe hippocampal damage may be more likely to promote structural and/or functional reorganization in areas connected to the hippocampus. In this hypothesis, different levels of hippocampal function may be rescued following this variable reorganization. Our findings document not only the extent, but also the limits of circuit reorganization occurring in the young brain after early bilateral hippocampal damage.

GSDMD KNOCKOUT ALLEVIATES SEPSIS-ASSOCIATED SKELETAL MUSCLE ATROPHY BY INHIBITING IL18/AMPK SIGNALING.

Background: Sepsis commonly leads to skeletal muscle atrophy, characterized by substantial muscle weakness and degeneration, ultimately contributing to an adverse prognosis. Studies have shown that programmed cell death is an important factor in the progression of muscle loss in sepsis. However, the precise role and mechanism of pyroptosis in skeletal muscle atrophy are not yet fully comprehended. Therefore, we aimed to examine the role and mechanism of action of the pyroptosis effector protein GSDMD in recognized cellular and mouse models of sepsis. Methods: The levels of GSDMD and N-GSDMD in skeletal muscle were evaluated 2, 4, and 8 days after cecal ligation and puncture. Sepsis was produced in mice that lacked the Gsdmd gene (Gsdmd knockout) and in mice with the normal Gsdmd gene (wild-type) using a procedure called cecal ligation and puncture. The degree of muscular atrophy in the gastrocnemius and tibialis anterior muscles was assessed 72 h after surgery in the septic mouse model. In addition, the architecture of skeletal muscles, protein expression, and markers associated with pathways leading to muscle atrophy were examined in mice from various groups 72 h after surgery. The in vitro investigations entailed the use of siRNA to suppress Gsdmd expression in C2C12 cells, followed by stimulation of these cells with lipopolysaccharide to evaluate the impact of Gsdmd downregulation on muscle atrophy and the related signaling cascades. Results: This study has demonstrated that the GSDMD protein, known as the "executive" protein of pyroptosis, plays a crucial role in the advancement of skeletal muscle atrophy in septic mice. The expression of N-GSDMD in the skeletal muscle of septic mice was markedly higher compared with the control group. The Gsdmd knockout mice exhibited notable enhancements in survival, muscle strength, and body weight compared with the septic mice. Deletion of the Gsdmd gene reduced muscular wasting in the gastrocnemius and tibialis anterior muscles caused by sepsis. Studies conducted in living organisms ( in vivo ) and in laboratory conditions ( in vitro ) have shown that the absence of the Gsdmd gene decreases indicators of muscle loss associated with sepsis by blocking the IL18/AMPK signaling pathway. Conclusion: The results of this study demonstrate that the lack of Gsdmd has a beneficial effect on septic skeletal muscle atrophy by reducing the activation of IL18/AMPK and inhibiting the ubiquitin-proteasome system and autophagy pathways. Therefore, our research provides vital insights into the role of pyroptosis in sepsis-related skeletal muscle wasting, which could potentially lead to the development of therapeutic and interventional approaches for preventing septic skeletal muscle atrophy.

Baseline systemic inflammatory indices and clinicopathological features to predict the outcome of acute tubulointerstitial nephritis : Asingle-center retrospective study.

Acute tubulointerstitial nephritis (AIN) is an immune-mediated disorder that can cause acute kidney injury (AKI). We aimed to investigate the characteristics of patients with AIN and predictive factors for treatment response. In this study, thirty-one patients diagnosed with AIN on kidney biopsy between 2006 and 2021 were included. Baseline clinical, histopathological, and laboratory findings, including complete blood count (CBC), creatinine, erythrocyte sedimentation rate, C‑reactive protein, C3, C4, systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and urinalysis were evaluated. Treatment response, mortality, and creatinine levels at the time of last follow-up were also noted. The median age was 46 years and 80.6% were female. Median baseline creatinine and proteinuria levels were 4.1 mg/dL and 0.84 gram/day. The median follow-up period was 14months and 93.5% received immunosuppressives. End-stage kidney disease (ESKD) developed in five patients (16.1%). Renal recovery (creatinine < 1.4 mg/dL) was observed in 17 patients (54.8%). Higher degrees of interstitial fibrosis, tubular atrophy, granuloma formation, global glomerulosclerosis, and higher baseline hemoglobin levels, in addition to alonger interval between first symptom to initiation of immunosuppressives were associated with renal nonrecovery, statistically. Also, patients who progressed to ESKD had higher baseline hemoglobin (p = 0.033) and lymphocyte (p = 0.044) and lower PLR levels (p = 0.016), as well as higher degrees of global glomerulosclerosis (p = 0.014), interstitial fibrosis (p = 0.042), and tubular atrophy (p = 0.030). Treatment response rates are low for AIN, which may lead to ESKD. Besides chronicity in histopathology specimens, higher baseline hemoglobin levels and lower platelet-to-lymphocyte ratio might be prognostic. Further studies should be conducted on new markers for AIN.

Association of olfactory and cognitive function test scores with hippocampal and amygdalar grey matter volume: a cross-sectional study

Few population-based studies including younger adults have examined the potential of olfactory function tests to capture the degree of atrophy in memory-associated brain regions, which cannot be adequately explained by cognitive function tests screening for cognitive impairment. This population-based study investigated associations between high-resolution olfactory test data with few odours and grey matter volumes (GMVs) of the left and right hippocampi, amygdala, parahippocampi, and olfactory cortex, while accounting for differences in cognitive decline, in 1444 participants (aged 31–91 years). Regression analyses included intracranial volume (ICV)-normalised GMVs of eight memory-related regions as objective variables and age, sex, education duration, smoking history, olfaction test score, and the Montreal Cognitive Assessment-Japanese version (MoCA-J) score as explanatory variables. Significant relationships were found between olfactory test scores and ICV-normalised GMVs of the left and right hippocampi and left amygdala (p = 0.020, 0.024, and 0.028, respectively), adjusting for the MoCA-J score. The olfactory test score was significantly related to the right amygdalar GMV (p = 0.020) in older adults (age ≥ 65 years). These associations remained significant after applying Benjamini–Hochberg multiple testing correction (false discovery rate < 0.1). Therefore, olfactory and cognitive function tests may efficiently capture the degree of atrophy in the hippocampi and amygdala, especially in older adults.

Effectiveness of serological markers of gastric mucosal atrophy in the gastric precancer screening and in cancer prevention.

New markers are needed to improve the effectiveness of serological screening for atrophic gastritis. To develop a cost-effective method for serological screening of atrophic gastritis with a high level of sensitivity. Of the 169 patients with atrophic gastritis, selected by the visual endoscopic Kimura-Takemoto method, 165 showed histological mucosal atrophy using the updated Kimura-Takemoto method. All 169 patients were examined for postprandial levels of gastrin-17 (G17) and pepsinogen-1 (PG1) using GastroPanel® (Biohit Plc, Helsinki, Finland). We used the histological standard of five biopsies of the gastric mucosa, in accordance with the Kimura-Takemoto classification system to assess the sensitivity of G17 in detecting gastric mucosal atrophy. We also compared the morpho-functional relationships between the detected histological degree of gastric mucosal atrophy and the serological levels of G17 and PG1, as the markers of atrophic gastritis. The sensitivity of postprandial G17 was 62.2% for serological levels of G17 (range: 0-4 pmol/L) and 100% for serological G17 (range: 0-10 pmol/L) for the detection of monofocal severe atrophic gastritis. No strong correlation was found between the levels of PG1 and degree of histological atrophy determined by the Kimura-Takemoto classification system to identify the severity of mucosal atrophy of the gastric corpus. In the presented clinical case of a 63-year-old man with multifocal atrophic gastritis, there is a pronounced positive long-term dynamics of the serological marker of atrophy - postprandial G17, after five months of rennet replacement therapy. Serological screening of multifocal atrophic gastritis by assessment of postprandial G17 is a cost-effective method with high sensitivity. Postprandial G17 is an earlier marker of regression of atrophic gastritis than a morphological examination of a gastric biopsy in accordance with the Sydney system. Therefore, postprandial G17 is recommended for dynamic monitoring of atrophic gastritis after treatment.

APOE ε4-associated downregulation of the IL-7/IL-7R pathway in effector memory T cells: Implications for Alzheimer's disease.

The apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive. The present study enrolled 54 patients diagnosed with late-onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non-carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). Plasma tumor necrosis factor α, interferon γ, and interleukin (IL)-33 levels increased in the APOE ε4 carriers but IL-7 expression notably decreased. A negative correlation was observed between plasma IL-7 level and the hippocampal atrophy degree. Additionally, the expression of IL-7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA-seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells. These findings shed light on the role of the downregulated IL-7/IL-7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy. The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)-7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL-7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL-7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL-7/IL-7R signal pathways enriches T cells.

Contrastive Disentanglement for Quantitative Ultrasound Muscle Atrophy Evaluation.

Muscleatrophy reduces the quality of life and increases morbidity and mortality from other diseases. The development of non-invasive muscle atrophy evaluation method is of great practical value. The lack of gold standard for pathological grading usually allows only the duration of weightlessness as a criterion for the degree of atrophy. However, the adaptive reductive remodeling of muscle physiology and structure shows a trend of nonlinear changes in time. Consequently, using weightlessness time as a benchmark for the degree of atrophy is inaccurate. This paper proposes a new ultrasound imaging-based method for quantifying muscle atrophy that utilizes weakly supervised information between multiple data partitions with controlled variance components, overcoming the limitations of using the weightlessness time as a criterion. We introduce a group-supervised contrastive disentanglement network (GCDNet) to disentangle the individual variances, muscle growth and atrophy components of ultrasound images, and quantify the degree of atrophy using the disentangled atrophy component. The feasibility of GCDNet is validated by the separability, independence, and representativeness of the disentangled components. To simplify the application of GCDNet, a muscle atrophy scoring network requiring no reference images is developed by distilling the GCDNet's knowledge of muscle atrophy quantization. The strength of the proposed methodology allows us, for the first time to our knowledge, to study the muscle growth attribute during hind-limb unloading and the spatial distribution of muscle atrophy.

Biomechanical effects of deltoid muscle atrophy on rotator cuff tissue: a finite element study

The deltoid muscle and rotator cuff tissue are structural components that maintain the dynamic stability of the shoulder joint. However, atrophy of the deltoid muscle may affect the stability of the shoulder joint, which in turn alters the mechanical distribution of rotator cuff tissue. Currently, the effect of muscle volume changes in the deltoid muscle on reducing the load on the rotator cuff tissue is still unknown. Therefore, this paper intends to analyze the mechanical changes of rotator cuff tissue by deltoid muscle atrophy through finite elements. Based on previously published finite element shoulder models, the deltoid muscle was modeled by constructing deltoid muscle models with different degrees of atrophy as, 100% deltoid muscle (Group 1), 80% deltoid muscle (Group 2), and 50% deltoid muscle (Group 3), respectively. The three models were given the same external load to simulate glenohumeral joint abduction, and the stress changes in the rotator cuff tissue were analyzed and recorded. In all three models, the stress in the rotator cuff tissue showed different degrees of increase with the increase of abduction angle, especially in the supraspinatus muscle. At 90° of glenohumeral abduction, supraspinatus stress increased by 58% and 118% in Group 2 and Group 3, respectively, compared with Group 1; In the subscapularis, the stress in Group 3 increased by 59% and 25% compared with Group 1 and Group 2, respectively. In addition, the stress of the infraspinatus muscle and teres minor muscle in Group 2 and Group 3 were higher than that in Group 1 during the abduction angle from 30° to 90°. Deltoid atrophy alters the abduction movement pattern of the glenohumeral joint. During glenohumeral abduction activity, deltoid atrophy significantly increases the stress on the rotator cuff tissue, whereas normal deltoid volume helps maintain the mechanical balance of the rotator cuff tissue.

Leonurine Ameliorates Diabetic Nephropathy through GPX4-Mediated Ferroptosis of Endothelial Cells.

Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus (DM). Ferroptosis is an atypical form of iron-dependent, modulated cell death that has been shown to occur in human umbilical vein endothelial cells (HUVECs). Leonurine (LEO) is a single active ingredient extracted from Leonurus japonicus Houtt. It has various biological activities, including anti-inflammatory and anti-cancer effects. However, whether LEO affects ferroptosis in DN has yet to be investigated. An animal model of DN was established by subjecting C57/BL6 mice to a high-fat diet (HFD) while being induced with Streptozotocin (STZ). A cellular model of DN was established by exposing HUVECs to a high glucose (HG) concentration of 30 mM. LEO was found to improve DN and to attenuate the degree of glomerulosclerosis and tubular atrophy in the mouse model. Additionally, it markedly decreased the levels of ferroptosis markers. Molecular analyses revealed that LEO inhibited HG-induced oxidative stress in HUVECs, thereby decreasing endothelial cell (EC) dysfunction. Furthermore, LEO was found to reduce ferroptosis and reverse EC dysfunction by increasing the expression of glutathione peroxidase 4 (GPX4) and nuclear factor erythroid 2-related factor 2 (Nrf2). The suppression of Nrf2 in HG-induced HUVECs inhibited LEO-GPX4 axis-mediated ferroptosis and increased EC dysfunction. LEO exerts anti-DN effects both in vivo and in vitro by suppressing GPX4-mediated EC ferroptosis. Mechanistically, LEO appears to induce Nrf2-mediated GPX4 expression to inhibit ferroptosis, thereby reducing EC dysfunction. This study provides a new perspective on the treatment of diseases using natural medicines. It involves a novel form of cell death that could potentially lead to better treatment of DN.

Conventional magnetic resonance imaging key features for distinguishing pathologically confirmed corticobasal degeneration from its mimics: a retrospective analysis of the J-VAC study.

Due to the indistinguishable clinical features of corticobasal syndrome (CBS), the antemortem differentiation between corticobasal degeneration (CBD) and its mimics remains challenging. However, the utility of conventional magnetic resonance imaging (MRI) for the diagnosis of CBD has not been sufficiently evaluated. This study aimed to investigate the diagnostic performance of conventional MRI findings in differentiating pathologically confirmed CBD from its mimics. Semiquantitative visual rating scales were employed to assess the degree and distribution of atrophy and asymmetry on conventional T1-weighted and T2-weighted images. Additionally, subcortical white matter hyperintensity (SWMH) on fluid-attenuated inversion recovery images were visually evaluated. In addition to 19 patients with CBD, 16 with CBD mimics (progressive supranuclear palsy (PSP): 9, Alzheimer's disease (AD): 4, dementia with Lewy bodies (DLB): 1, frontotemporal lobar degeneration with TAR DNA-binding protein of 43kDa(FTLD-TDP): 1, and globular glial tauopathy (GGT): 1) were investigated. Compared with the CBD group, the PSP-CBS subgroup showed severe midbrain atrophy without SWMH. The non-PSP-CBS subgroup, comprising patients with AD, DLB, FTLD-TDP, and GGT, showed severe temporal atrophy with widespread asymmetry, especially in the temporal lobes. In addition to over half of the patients with CBD, two with FTLD-TDP and GGT showed SWMH, respectively. This study elucidates the distinct structural changes between the CBD and its mimics based on visual rating scales. The evaluation of atrophic distribution and SWMH may serve as imaging biomarkers of conventional MRI for detecting background pathologies.

Ophthalmic Findings in the KIF1A-Associated Neurologic Disorder (KAND)

PurposeTo define the ophthalmic manifestations in KIF1A-associated neurological disorder (KAND), a rare, progressive neurodegenerative disorder caused by pathogenic variants in the KIFA1 gene. DesignCross-sectional study. MethodsClinical ophthalmic examination and multimodal imaging were performed for 24 participants enrolled in the KIF1AOutcome measures, Assessments, Longitudinal And endpoints (KOALA) Study. Visual evoked potentials (VEP) were performed on select participants. ResultsThe average central visual acuity in pediatric participants was 20/43 (logMAR 0.329, range 0.0-1.0), and 20/119 (logMAR 0.773, range 0.471-1.351) in adults. Ninety-five percent of participants examined had some degree of optic nerve atrophy detected by clinical examination and/or optical coherence tomography (OCT). Almost forty percent had strabismus. Color vision, visual fields and stereopsis were impaired in most participants who were able to participate in testing. VEP showed varying degrees of signal slowing and diffuseness. ConclusionsOptic nerve atrophy is the primary ocular finding in individuals with KAND and is present at higher prevalence than previously reported. The degree of the atrophy is likely dependent on the severity of the pathogenic variant and possibly the age of the patient. Adults had worse vision on average than children, suggesting possible decline in vision with age. Strabismus in this cohort was common. Visual evoked potentials showed findings consistent with optic neuropathy and visual dysfunction even in the absence of obvious structural changes on OCT. Families should be counseled regarding visual impairment in KAND patients, so as to obtain appropriate support and assistance to maximize safety, functionality, and learning.

The relationship between the duration and the retraction and atrophy grades in traumatic isolated full-thickness supraspinatus tears in young patients

BackgroundThe study aimed to determine the grade of retraction and atrophy according to the time elapsed in traumatic isolated full-thickness supraspinatus (SS) tears in young patients.MethodsOne thousand twenty-six patients, who underwent arthroscopic shoulder surgery, were retrospectively reviewed. Pre-operative magnetic resonance imaging (MRI) of 69 patients aged 18 to 40 years with isolated traumatic full-thickness SS lesions remaining after exclusion criteria were evaluated for tendon retraction and atrophy grades. SS retraction was determined from a T2-weighted oblique coronal MRI slice, and the atrophy grade was determined from the T1-weighted oblique sagittal MRI slice. The patients were divided into four groups 0–1 month, 1–3 months, 3–6 months, and 6–12 months according to the time between trauma and MRI. The relationship of tendon retraction and muscle atrophy with elapsed time was evaluated, in addition, comparisons between groups were made.ResultsThirty-one (45%) of the patients were female and their mean age was 30 ± 7.3 (18–40) years. The mean age of men was 30.5 ± 6.9 (18–39) years (p = 0.880). The time between rupture and MRI was moderately correlated with retraction and strongly correlated with atrophy grades (r = 0.599, 0.751, respectively). It was observed that there was a statistically significant difference between the 1st (0–1 month) and 2nd (1–3 months) groups (p = 0.003, 0.001, respectively), and between the 2nd and 3rd (3–6 months) groups (p = 0.032, 0.002, respectively), but there was no significant difference between the 3rd and 4th (6–12 months) groups (p = 0.118, 0.057, respectively). In addition, there was a moderate correlation between tendon retraction and atrophy grades (r = 0.668). Power (1- b) in post hoc analysis was calculated as 0.826.ConclusionsThe current study, supported by arthroscopy, showed that there is a moderate and strong positive correlation between the time elapsed after trauma and the level of retraction and degree of atrophy in traumatic full-thickness SS tears, and demonstrated the importance of early surgical intervention in young patients.

Factors Influencing the Degree of Gastric Atrophy in Helicobacter pylori Eradication Patients with Drinking Habits.

Chronic gastritis caused by Helicobacter pylori (H. pylori) infection can lead to gastric atrophy. This study aimed to identify the factors associated with gastric atrophy in H. pylori eradication patients with drinking habits. Of the 250 patients who visited Hamamatsu University Hospital for H. pylori eradication and underwent eradication treatment between April 2017 and December 2020, 127 patients with drinking habits were included in this study. The degree of gastric atrophy of the patients was classified based on endoscopy. The relationship between patient attributes (sex, age, alcohol consumption, frequency of drinking, smoking status, and medication use) and a highly atrophic stomach was statistically analyzed. The results showed that gastric atrophy was significantly higher in males and in those aged 60 years or older and that gastric atrophy tended to be higher in those who drank 20 g or more per day and 5 days or more a week. There was also a trend toward higher atrophy in sake drinkers and lower atrophy in wine drinkers. This study provides useful knowledge for patient management and guidance after H. pylori eradication treatment and indicates the importance of comprehensive measures, including alcohol consumption control and lifestyle modification, especially for men and older people.