Features Of Disease Research Articles

Ocular manifestations of various spondyloarthropathies

Eye inflammation has been described as a crucial prominent feature of several rheumatic diseases. Uveitis, conjunctivitis, and episcleritis have been reported in patients with known spondyloarthropathies or may be significant symptoms for the diagnosis of previously undiagnosed spondyloarthropathy. A hospital-based, cross-sectional, observational study was conducted over twenty-one months, from January 2021 to September 2022. Patients aged more than 18 years with a definitive diagnosis of Spondyloarthropathy, attending the Department of Orthopedics outpatient clinics, SGMH, Rewa, were screened for presence of eye disorders. A total of 100 cases were recruited in the study. The mean age of the study group was 34.58 years (female 33.5 years and male 35.6 years) with a majority of cases (72%) in the study group aged between 20 and 39 years. Ankylosing spondyloarthropathy was the most common diagnosis in the study, with 49% cases being diagnosed with it. Patients with Psoriatic arthropathy were also found to have a significant association with foreign body sensation and diminution of vision while ciliary congestion was significantly associated with ankylosing spondylitis. In addition, uveitis was observed to have a statistically significant association with incidence of ankylosing spondylitis. The various manifestations of seronegative spondyloarthropathies include uveitis, which is a potentially blinding complication was noted in 19% of the patients, that needs to be identified early and treated right away to avoid irreparable vision loss.

A Case Report of Mixed Connective Tissue Disease Predominantly Manifesting as Systemic Sclerosis in a Middle-Aged Nepali Woman

Introduction: Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disorder, first described in 1972, that presents with overlapping features of systemic lupus erythematosus, systemic sclerosis, and polymyositis. The diagnosis of MCTD is complex and often delayed due to its varied clinical manifestations and the requirement of serological confirmation, particularly the presence of anti-U1 RNP antibodies. Despite its global prevalence, data on MCTD are limited, especially in the South Asian population.  Case Report: We present the case of a 42-year-old Nepali woman with a decade-long history of myalgia, muscle weakness, and joint pain, initially misdiagnosed as rheumatoid arthritis. Over time, she developed Raynaud phenomenon, dysphagia, and progressive muscle weakness, which prompted further investigation. Serological testing revealed elevated levels of anti-U1 RNP antibodies and a positive antinuclear antibody (ANA) titer, confirming the diagnosis of MCTD according to the Alarcón-Segovia criteria. The patient was successfully managed with a regimen of corticosteroids, hydroxychloroquine, and nifedipine, resulting in significant symptomatic improvement.  Discussion: This case underscores the diagnostic challenges associated with MCTD, a condition that may present with nonspecific symptoms and mimic other rheumatic diseases. The prolonged diagnostic journey of this patient highlights the need for heightened clinical suspicion and comprehensive serological testing in patients with overlapping connective tissue disease features. Furthermore, the case contributes to the limited body of literature on MCTD in the South Asian population, emphasizing the importance of early recognition and tailored management strategies to improve patient outcomes.  Conclusion: MCTD is a complex and under-recognized autoimmune disorder, particularly in the South Asian context. This case report highlights the importance of considering MCTD in the differential diagnosis of patients with multi-systemic involvement and underscores the role of serological testing in confirming the diagnosis. Early diagnosis and appropriate management are crucial in mitigating disease progression and improving the quality of life for patients with MCTD.

Shotgun Analysis of Gut Microbiota with Body Composition and Lipid Characteristics in Crohn's Disease.

Alterations to intestinal microbiota are assumed to occur in the pathogenesis of inflammatory bowel disease (IBD). This study aims to analyze the association of fecal microbiota composition, body composition, and lipid characteristics in patients with Crohn's disease (CD). In our cross-sectional study, patients with CD were enrolled and blood and fecal samples were collected. Clinical and endoscopic disease activity and body composition were assessed and laboratory tests were made. Fecal bacterial composition was analyzed using the shotgun method. Microbiota alterations based on obesity, lipid parameters, and disease characteristics were analyzed. In this study, 27 patients with CD were analyzed, of which 37.0% were obese based on visceral fat area (VFA). Beta diversities were higher in non-obese patients (p < 0.001), but relative abundances did not differ. C. innocuum had a higher abundance at a high cholesterol level than Bacillota (p = 0.001, p = 0.0034). Adlercreutzia, B. longum, and Blautia alterations were correlated with triglyceride levels. Higher Clostridia (p = 0.009) and B. schinkii (p = 0.032) and lower Lactobacillus (p = 0.035) were connected to high VFA. Disease activity was coupled with dysbiotic elements. Microbiota alterations in obesity highlight the importance of gut microbiota in diseases with a similar inflammatory background and project therapeutic options.

Reduction of RAD23A extends lifespan and mitigates pathology in TDP-43 mice.

Protein misfolding and aggregation are cardinal features of neurodegenerative disease (NDD) and they contribute to pathophysiology by both loss-of-function (LOF) and gain-of-function (GOF) mechanisms. This is well exemplified by TDP-43 which aggregates and mislocalizes in several NDDs. The depletion of nuclear TDP-43 leads to reduction in its normal function in RNA metabolism and the cytoplasmic accumulation of TDP-43 leads to aberrant protein homeostasis. A modifier screen found that loss of rad23 suppressed TDP-43 pathology in invertebrate and tissue culture models. Here we show in a mouse model of TDP-43 pathology that genetic or antisense oligonucleotide (ASO)-mediated reduction in rad23a confers benefits on survival and behavior, histological hallmarks of disease and reduction of mislocalized and aggregated TDP-43. This results in improved function of the ubiquitin-proteasome system (UPS) and correction of transcriptomic alterations evoked by pathologic TDP-43. RAD23A-dependent remodeling of the insoluble proteome appears to be a key event driving pathology in this model. As TDP-43 pathology is prevalent in both familial and sporadic NDD, targeting RAD23A may have therapeutic potential.

Clinical features of gastroesophageal reflux disease and erosive esophagitis: Insights from patients undergoing esophagogastroduodenoscopy in resource-limited Ethiopia.

Gastroesophageal reflux disease (GERD) is a common disease worldwide with varying clinical presentations and risk factors. Prevalence data for Africa is lacking, but an increasing trend is expected due to demographic and epidemiological transitions. Although endoscopic studies for general gastrointestinal disorders have shown some patients with erosive esophagitis (EE), no studies in Ethiopia have investigated the clinical characteristics, risk factors, and severity of GERD using esophagogastroduodenoscopy (EGD). To assess the clinical features of GERD in Ethiopian patients who underwent EGD and determine the severity and risk factors of EE. We conducted a multicenter, retrospective cross-sectional study of 221 patients diagnosed with GERD and endoscopic findings of EE at Trauma Associated Severe Hemorrhage and Amniotic Membrane Stem Cell between January 2019 and August 2022. Data were collected from electronic medical records and phone call interviews. We used descriptive statistics and binary logistic regression analysis with SPSS version 26 to identify the association between variables with a statistical significance set at P value < 0.05. The mean ± SD age of the patients was 44.8 (± 15.9) years, with a male-to-female ratio of 1.6:1. The most commonly reported symptom was epigastric pain (80.5%), followed by heartburn (43%). Los Angeles (LA)-A EE was diagnosed in 71.1% of patients, followed by LA-B (14.9%), LA-C (7.7%), and LA-D (5.9%). Multivariate analysis showed that age 50 or above, presence of bleeding, and endoscopic findings of duodenitis/duodenopathy were significantly associated with severe EE (P < 0.05). Stricture and Barrett's esophagus were observed in 4.5% and 1.36% of patients with EE, respectively. Most of the patients had milder EE with fewer complications. However, severe EE was more prevalent in older patients and those with duodenitis/duodenopathy.

Characterization of fission and fusion mitochondrial dynamics in HD fibroblasts according to patient's severity status

Huntington's Disease (HD) is an inheritable neurodegenerative condition caused by an expanded CAG trinucleotide repeat in the HTT gene with a direct correlation between CAG repeats expansion and disease severity with earlier onset-of- disease. Previously we have shown that primary skin fibroblasts from HD patients exhibit unique phenotype disease features, including distinct nuclear morphology and perturbed actin cap linked with cell motility, that are correlated with the HD patient disease severity. Here we provide further evidence that mitochondrial fission-fusion morphology balance dynamics, classified using a custom image-based high-content analysis (HCA) machine learning tool, that improved correlation with HD severity status. This mitochondrial phenotype is supported by appropriate changes in fission-fusion biomarkers (Drp1, MFN1, MFN2, VAT1) levels in the HD patients' fibroblasts. These findings collectively point towards a dysregulation in mitochondrial dynamics, where both fission and fusion processes may be disrupted in HD cells compared to healthy controls. This study shows for the first time a methodology that enables identification of HD phenotype before patient's disease onset (Premanifest). Therefore, we believe that this tool holds a potential for improving precision in HD patient's diagnostics bearing the potential to evaluate alterations in mitochondrial dynamics throughout the progression of HD, offering valuable insights into the molecular mechanisms and drug therapy evaluation underlying biological differences in any disease stage.

Essential tremor as a prodromal feature of Parkinson's disease

Essential tremor as a prodromal feature of Parkinson's disease

Increased Systemic Immune-Inflammation Index as a Novel Indicator of Alzheimer's Disease Severity.

Inflammatory processes and neurodegeneration are common features of Alzheimer's disease (AD). The systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are easily accessible, cost-effective prognostic indicators of inflammation status. We assessed the diagnostic value of SII and compared the efficacies of NLR, PLR, and SII in predicting AD severity. Between January 2021 and December 2022, this prospective, cross-sectional clinical study included 175 patients with AD and 61 controls. SII, NLR, and PLR were calculated. Age, white blood cell and lymphocyte counts, and NLR and PLR values were significantly different between the patient and control groups (P <.05). Age, hemoglobin, neutrophil, NLR, and SII values were significantly different among dementia severity subgroups (P <.05). Compared with PLR and SII, NLR was more strongly correlated with dementia severity. In the analysis of adjusted data by gender, it was found that hemoglobin level is significantly negatively associated with dementia severity in males, while in females, age and PLR are significantly positively associated with dementia severity, and lymphocyte count and SII are negatively associated. SII, a novel inflammatory marker, was associated with dementia severity in patients with AD. Compared with PLR and SII, NLR was more strongly correlated with dementia severity. In future studies with larger populations, SII and NLR values can be used to determine dementia severity and establish follow-up plans for patients with high dementia risk.

Integration and development of acupuncture and neurology: interviewing Professor SUN Shentian, Master of Traditional Chinese Medicine

The semi-structured interview was adopted to in-depth interview Professor SUN Shentian, a Master of Traditional Chinese Medicine, on the integration and development of acupuncture and neurology. In the interview, we traced the first "ward of acupuncture and neurology" in China, established by Professor SUN Shentian and the origin of his proposal, "transcranial repeated needling stimulation therapy", aiming at advancing the development of acupuncture discipline. Professor SUN Shentian explained that the ward of acupuncture and neurology was established under specific historical conditions, on account of the relationship between acupuncture and nerves and the characteristics of the neurological diseases, as well as the personal practical knowledge and his unique clinical experience. In order to specify the point selection of scalp acupuncture and further expound its mechanism, he innovated "transcranial repeated needling stimulation therapy" that is advantageous at preciser operation, clearer theoretic foundation and better therapeutic effect of scalp acupuncture. Professor SUN Shentian pointed out that the deepening development of acupuncture is firmly based on "inheritance, practice and innovation", and constant exploration practice along with inheriting the experience of predecessors to propel the innovation and development of acupuncture and move towards a new historical stage.

Clinical features of acute coronary syndrome in elderly patients with chronic obstructive pulmonary disease

Aim. To study the clinical features of the course of acute coronary syndrome (ACS) in elderly patients with chronic obstructive pulmonary disease (COPD).Materials and methods. The study included 78 patients with ACS: 43 patients with ACS and COPD (group 1) and 35 patients with ACS without COPD (group 2). All patients underwent comprehensive clinical, instrumental, and laboratory examinations.Results. Among the risk factors for cardiovascular diseases (CVD), the most significant contributors to the development of ACS in patients with COPD were smoking, arterial hypertension, and elevated levels of C-reactive protein (CRP). Patients with ACS and COPD more frequently had non- ST-segment elevation myocardial infarction (NSTEMI). For patients with comorbid pathology, more pronounced changes in the coronary arteries were characteristic due to an increase in the total number of stenoses (p=0.02), hemodynamically significant stenosis (p=0.01), occlusions and critical stenoses (p=0.02), and extensive stenoses (p=0.04). Group 1 patients, compared to group 2, had hemodynamically significant stenosis located in the proximal (p=0.04) and distal (p=0.02) segments of the coronary arteries, as well as in second-order branches (p=0.02). No significant differences were found between the groups in the number of stenoses of the left main coronary artery and the middle segments of the major coronary arteries.Conclusion. In elderly patients with COPD, ACS development was more often preceded by angina symptoms and atypical myocardial infarction presentations, with NSTEMI predominating in the myocardial infarction structure. The main CVD risk factors in COPD patients were smoking, arterial hypertension, and elevated CRP levels. Atherosclerotic coronary artery disease in ACS patients with COPD was characterized by multivessel disease, predominance of middle and distal coronary artery stenosis. A significant feature of coronary artery disease in comorbid elderly patients was the increased total number of stenoses and the number of extensive stenoses.

Systemic auto-inflammatory manifestations in patients with spondyloarthritis

Objectives(1) characterizing a group of spondyloarthritis (SpA) patients with systemic auto-inflammatory symptoms (S-SpA); (2) comparing SpA features with and without auto-inflammatory symptoms; (3) comparing the auto-inflammatory features of S-SpA and Still's disease (SD). MethodsRetrospective observational study. Clinical data of adult and pediatric patients with S-SpA, SD or SpA were collected retrospectively and analyzed. ResultsForty-one subjects with S-SpA, 39 with SD and 42 with SpA were enrolled. The median latency between systemic and articular manifestations in S-SpA was 4.4 (IQR: 7.2) years. S-SpA and SpA had similar frequency of peripheral arthritis and enthesitis (N.S.), while tenosynovitis was more frequent (P=0.01) and uveitis less frequent (P<0.01) in S-SpA. MRI showed signs of sacroiliac inflammation and damage in both S-SpA and SpA equally (N.S.). S-SpA patients had less corner inflammatory lesions (P<0.05) and inflammation at the facet joints (P<0.01), more interspinous enthesitis (P=0.01) and inter-apophyseal capsulitis (P<0.01). Compared to SD, S-SpA patients had lower-grade fever (P<0.01), less rash (P<0.01) and weight loss (P<0.05), but more pharyngitis (P<0.01), gastrointestinal symptoms (P<0.01) and chest pain (P<0.05). ESR, CRP, WBC, ANC, LDH tested higher in SD (P<0.01). Resolution of systemic symptoms was less frequent in S-SpA than SD on corticosteroid (P<0.01) and methotrexate (P<0.05) treatment. When considering all SD patients, a complete response to corticosteroids in the systemic phase significantly reduced the likelihood of developing SpA (OR=0.06, coefficient −2.87 [CI: −5.0 to −0.8]). ConclusionsSpA should be actively investigated in patients with auto-inflammatory manifestations, including undifferentiated auto-inflammatory disease and SD.

Therapeutic Prospects of Abemaciclib for Patients with Endometrial Cancer.

Endometrial cancer (EC) is a common gynecologic malignancy with a rising incidence due to obesity, comorbid conditions, and related lifestyle factors. The standard of care for primary disease consists of surgical resection with/without chemotherapy ± radiotherapy for select patients. Recurrence is common in patients with advanced-stage disease and/or high-risk features, who primarily are treated with systemic therapy. The identification of novel targets in malignant EC has led to the development of wide-range inhibitors. Abemaciclib is an orally active unique cyclin-dependent kinase (CDK) inhibitor, selective for the CDK4 and CDK6 cell cycle pathways. This agent has potential anti-neoplastic activity and is indicated in combination with various therapies such as endocrine therapy, aromatase inhibitors, and hormone therapies, primarily in breast cancer (BC). Herein, we sought to summarize the biochemical/pharmacological properties of abemaciclib and its therapeutic potential in EC. While the therapeutic role(s) of abemaciclib was fairly established in a subset of patients with advanced/metastatic BC through the pivotal MONARCH trials, its attributes and clinical utility in EC are limited. Thus, based on some promising pre-clinical/translational insights and a recent phase II study, we highlight abemaciclib's properties and potential clinical usefulness in patients with EC, particularly in recurrent estrogen-receptor-positive cases.

Detection of sex-specific glutamate changes in subregions of hippocampus in an early-stage Alzheimer's disease mouse model using GluCEST MRI.

Regional glucose hypometabolism resulting in glutamate loss has been shown as one of the characteristics of Alzheimer's disease (AD). Because the impact of AD varies between the sexes, we utilized glutamate-weighted chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) for high-resolution spatial mapping of cerebral glutamate and investigated subregional changes in a sex-specific manner. Eight-month-old male and female AD mice harboring mutant amyloid precursor protein (APPNL-F/NL-F: n = 36) and wild-type (WT: n = 39) mice underwent GluCEST MRI, followed by proton magnetic resonance spectroscopy (1H-MRS) in hippocampus and thalamus/hypothalamus using 9.4T preclinical MR scanner. GluCEST measurements revealed significant (p≤0.02) glutamate loss in the entorhinal cortex (% change ± standard error: 8.73±2.12%), hippocampus (11.29±2.41%), and hippocampal fimbriae (19.15±2.95%) of male AD mice. A similar loss of hippocampal glutamate in male AD mice (11.22±2.33%; p = 0.01) was also observed in 1H-MRS. GluCEST MRI detected glutamate reductions in the fimbria and entorhinal cortex of male AD mice, which was not reported previously. Resilience in female AD mice against these changes indicates an intact status of cerebral energy metabolism. Glutamate levels were monitored in different brain regions of early-stage Alzheimer's disease (AD) and wild-type male and female mice using glutamate-weighted chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI). Male AD mice exhibited significant glutamate loss in the hippocampus, entorhinal cortex, and the fimbriae of the hippocampus. Interestingly, female AD mice did not have any glutamate loss in any brain region and should be investigated further to find the probable cause. These findings demonstrate previously unreported sex-specific glutamate changes in hippocampal sub-regions using high-resolution GluCEST MRI.

Energy gap of conformational transition related with temperature for the NACore of α-synuclein.

Pathological aggregation of α-synuclein (α-syn) into amyloid fibrils is a major feature of Parkinson's disease (PD). The self-assembly of α-syn is mainly governed by a non-amyloid-β component core (NACore). However, the effects of concentrations and temperatures on their conformational transition remain unclear. To answer this question, we investigated the aggregation kinetics of NACore oligomers in silico by performing several independent all-atom molecular dynamics simulations. The simulation results show that tetramers are more prone to form β-sheets at 300 K than dimers and octamers. We also found that the NACore oligomers had higher β-sheet and β-barrel contents at 310 K. The inter-chain hydrophobic interactions, the backbone hydrogen bonding, the residue-residue interactions between V70-V77 as well as V77-V77 play important roles in the aggregation tendency of NACore octamers at 310 K. Interestingly, the energy gap analysis revealed that the conformational transition of NACore oligomers from intermediate states (β-barrel conformation) to stable structures (β-sheet layers) was dependent on the temperatures. In short, our study provides insight into the kinetic and thermodynamic mechanisms of the conformational transition of NACore at different concentrations and temperatures, contributing to a better understanding of the aggregation process of α-syn in Parkinson's disease.

Impaired degradation of PLCG1 by chaperone-mediated autophagy promotes cellular senescence and intervertebral disc degeneration

ABSTRACT Defects in chaperone-mediated autophagy (CMA) are associated with cellular senescence, but the mechanism remains poorly understood. Here, we found that CMA inhibition induced cellular senescence in a calcium-dependent manner and identified its role in TNF-induced senescence of nucleus pulposus cells (NPC) and intervertebral disc degeneration. Based on structural and functional proteomic screens, PLCG1 (phospholipase C gamma 1) was predicted as a potential substrate for CMA deficiency to affect calcium homeostasis. We further confirmed that PLCG1 was a key mediator of CMA in the regulation of intracellular calcium flux. Aberrant accumulation of PLCG1 caused by CMA blockage resulted in calcium overload, thereby inducing NPC senescence. Immunoassays on human specimens showed that reduced LAMP2A, the rate-limiting protein of CMA, or increased PLCG1 was associated with disc senescence, and the TNF-induced disc degeneration in rats was inhibited by overexpression of Lamp2a or knockdown of Plcg1. Because CMA dysregulation, calcium overload, and cellular senescence are common features of disc degeneration and other age-related degenerative diseases, the discovery of actionable molecular targets that can link these perturbations may have therapeutic value. Abbreviation: ATRA: all-trans-retinoic acid; BrdU: bromodeoxyuridine; CDKN1A/p21: cyclin dependent kinase inhibitor 1A; CDKN2A/p16-INK4A: cyclin dependent kinase inhibitor 2A; CMA: chaperone-mediated autophagy; DHI: disc height index; ER: endoplasmic reticulum; IP: immunoprecipitation; IP3: inositol 1,4,5-trisphosphate; ITPR/IP3R: inositol 1,4,5-trisphosphate receptor; IVD: intervertebral disc; IVDD: intervertebral disc degeneration; KD: knockdown; KO: knockout; Leu: leupeptin; MRI: magnetic resonance imaging; MS: mass spectrometry; N/L: NH4Cl and leupeptin; NP: nucleus pulposus; NPC: nucleus pulposus cells; PI: protease inhibitors; PLC: phospholipase C; PLCG1: phospholipase C gamma 1; ROS: reactive oxygen species; RT-qPCR: real-time quantitative reverse transcription PCR; SA-GLB1/β-gal: senescence-associated galactosidase beta 1; SASP: senescence-associated secretory phenotype; STV: starvation; TMT: tandem mass tag; TNF: tumor necrosis factor; TP53: tumor protein p53; UPS: ubiquitin-proteasome system.

MBNL splicing factors regulate the microtranscriptome of skeletal muscles.

Muscleblind like splicing regulators (MBNLs) govern various RNA-processing steps, including alternative splicing, polyadenylation, RNA stabilityand mRNA intracellular localization. In myotonic dystrophy type 1 (DM1), the most common muscular dystrophy in adults, MBNLs are sequestered on toxic RNA containing expanded CUG repeats, which leads to disruption of MBNL-regulated processes and disease features of DM1. Herein, we show the significance of MBNLs in regulating microtranscriptome dynamics during the postnatal development of skeletal muscles and in microRNA (miRNA) misregulation observed in mouse models and patients with DM1. We identify multiple miRNAs sensitive to MBNL proteins insufficiency and reveal that many of them were postnatally regulated, which correlates with increases in the activity of these proteins during this process. In adult Mbnl1-knockout mice, miRNA expression exhibited an adult-to-newborn shift. We hypothesize that Mbnl1 deficiency influences miRNA levels through a combination of mechanisms. First, the absence of Mbnl1 protein results in alterations to the levels of pri-miRNAs. Second, MBNLs affect miRNA biogenesis by regulating the alternative splicing of miRNA primary transcripts. We propose that the expression of miR-23b, miR-27b and miR-24-1, produced from the same cluster, depends on the MBNL-sensitive inclusion of alternative exons containing miRNA sequences. Our findings suggest that MBNL sequestration in DM1 is partially responsible for altered miRNA activity. This study provides new insights into the biological roles and functions of MBNL proteins as regulators of miRNA expression in skeletal muscles.

A Lightweight Real-Time Recognition Algorithm for Tomato Leaf Disease Based on Improved YOLOv8

To address the real-time detection challenge of deploying deep learning-based tomato leaf disease detection algorithms on embedded devices, an improved tomato leaf disease detection algorithm based on YOLOv8n is proposed in this paper. It is able to achieve the efficient, real-time detection of tomato leaf diseases while maintaining model’s lightweight requirements. The algorithm incorporated the LMSM (lightweight multi-scale module) and ALSA (Attention Lightweight Subsampling Module) to improve the ability to extract lightweight and multi-scale semantic information for the specific characteristics of tomato leaf disease, which include irregular spot size and lush tomato leaves. The head network was redesigned utilizing partial and group convolution along with a parameter-sharing method. Scalable auxiliary bounding box and loss function optimization strategies were introduced to further enhance performance. After undergoing the pruning technique, computation decreased by 61.7%, the model size decreased by 55.6%, and the FPS increased by 44.8%, all while a high level of accuracy was maintained. A detection speed of 19.70FPS on the Jetson Nano was obtained after undergoing TensorRT quantization, showing a 64.85% improvement compared to the initial detection speed. This method met the high real-time performance and small model size requirements for embedded tomato leaf disease detection systems, indirectly reducing the energy consumption of online detection. It provided an effective solution for the online detection of tomato leaf disease.

Visual hallucinations in Parkinson's disease: spotlight on central cholinergic dysfunction.

Visual hallucinations are a common non-motor feature of Parkinson's disease and have been associated with accelerated cognitive decline, increased mortality and early institutionalisation. Despite their prevalence and negative impact on patient outcomes, the repertoire of treatments aimed at addressing this troubling symptom is limited. Over the last two decades, significant contributions have been made in uncovering the pathological and functional mechanisms of visual hallucinations, bringing us closer to the development of a comprehensive neurobiological framework. Convergent evidence now suggests that degeneration within the central cholinergic system may play a significant role in the genesis and progression of visual hallucinations. Here, we outline how cholinergic dysfunction may serve as a potential unifying neurobiological substrate underlying the multifactorial and dynamic nature of visual hallucinations. Drawing upon previous theoretical models, we explore the impact that alterations in cholinergic neurotransmission has on the core cognitive processes pertinent to abnormal perceptual experiences. We conclude by highlighting that a deeper understanding of cholinergic neurobiology and individual pathophysiology may help to improve established and emerging treatment strategies for the management of visual hallucinations and psychotic symptoms in Parkinson's disease.

Characteristics of Alzheimer’s Disease and Mild Cognitive Impairment Influenced by the Time of Onset

Introduction: Although the prevalence of Alzheimer’s disease (AD) is higher in older people compared to younger people, dementia has also been documented in younger adults. Although early-onset dementia and late-onset dementia had been considered a single disease in pathological investigations, many studies revealed differences in cognitive and neuroimaging changes between them. We evaluated differences in cognitive and neuroimaging changes among the following groups: individuals with early-onset AD (EOAD), late-onset AD (LOAD), early-onset mild cognitive impairment (EOMCI), or late-onset MCI (LOMCI), and healthy controls (HCs). Methods: Patients underwent both a 1.5 Tesla magnetic resonance imaging scan and the Mini-Mental State Examination (MMSE). Differences in regional gray matter volumes and MMSE subscales were investigated among the five diagnostic groups. Results: Compared to the EOAD group, the LOAD group had significantly higher scores on orientation in place. Compared to the LOMCI patients, the EOMCI patients achieved significantly higher recall scores. The LOAD and LOMC groups showed significant volume reductions in bilateral medial temporal regions compared to the HCs. The EOAD and EOMCI groups did not show significant atrophy of the medial temporal region compared to the HC group. Conclusions: The hippocampal volume and memory were preserved in the patients with EOMCI or EOAD compared to those with LOMCI or LOAD. These findings may indicate that the distinct and differing patterns of neuropsychological changes between EOAD and LOAD are also common in MCI, which is intermediate between normal cognition and AD.

Combined effects of vitamin D3 and dioxopiperidinamide derivative on lipid homeostasis, inflammatory pathways, and redox imbalance in non-alcoholic fatty liver disease in vivo zebrafish model.

Liver damage and metabolic dysfunctions, the defining features of non-alcoholic fatty liver disease (NAFLD), are marked by inflammation, oxidative stress, and excessive hepatic fat accumulation. The current therapeutic approaches for NAFLD are limited, necessitating exploring novel treatment strategies. Dioxopiperidinamide derivatives, particularly DOPA-33, have shown effective anti-inflammatory and antioxidant properties, potentially offering therapeutic benefits against NAFLD. This study investigated the combined potential of vitamin D3 (Vit D3) and DOPA-33 in treating NAFLD. The network pharmacology analysis identified key NAFLD targets modulated by Vit D3 and DOPA-33, emphasizing their potential mechanisms of action. In NAFLD-induced zebrafish models, Vit D3 and DOPA-33 significantly reduced hepatic lipid accumulation, oxidative stress, and apoptosis, demonstrating superior efficacy over individual treatments. The treatment also lowered reactive oxygen species (ROS) levels, decreased liver damage, and enhanced antioxidant defense mechanisms. Moreover, behavioral analyses showed improved locomotion and reduced weight gain in treated zebrafish. Biochemical analyses revealed lower triglycerides (TG) and glucose levels with improved oxidative markers. Furthermore, histological analyses indicated reduced hepatic steatosis and inflammation, with decreased expression of lipogenesis-related genes and inflammatory mediators. Finally, high-performance liquid chromatography (HPLC) confirmed a significant reduction in hepatic cholesterol levels, indicating the effectiveness of the combination therapy in addressing key NAFLD-related dyslipidemias. These findings suggest that Vit D3 + DOPA-33 targets pathways involved in lipid metabolism, inflammation, and oxidative stress by offering a promising therapeutic approach for NAFLD.