Stages Of Thedisease Research Articles

Glymphatic inhibition exacerbates tau propagation in an Alzheimer’s disease model

BackgroundThe aggregation and spread of misfolded amyloid structured proteins, such as tau and α-synuclein, are key pathological features associated with neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease. These proteins possess a prion-like property, enabling their transmission from cell to cell leading to propagation throughout the central and peripheral nervous systems. While the mechanisms underlying their intracellular spread are still being elucidated, targeting the extracellular space has emerged as a potential therapeutic approach. The glymphatic system, a brain-wide pathway responsible for clearing extracellular metabolic waste from the central nervous system, has gained attention as a promising target for removing these toxic proteins.MethodsIn this study, we investigated the impact of long-term modulation of glymphatic function on tau aggregation and spread by chronically treating a mouse model of tau propagation with a pharmacological inhibitor of AQP4, TGN-020. Thy1-hTau.P301S mice were intracerebrally inoculated with tau into the hippocampus and overlying cortex, and subsequently treated with TGN-020 (3 doses/week, 50 mg/kg TGN-020, i.p.) for 10-weeks. During this time, animal memory was studied using cognitive behavioural tasks, and structural MR images were acquired of the brain in vivo prior to brain extraction for immunohistochemical characterisation.ResultsOur findings demonstrate increased tau aggregation in the brain and transhemispheric propagation in the hippocampus following the inhibition of glymphatic clearance. Moreover, disruption of the glymphatic system aggravated recognition memory in tau inoculated mice and exacerbated regional changes in brain volume detected in the model. When initiation of drug treatment was delayed for several weeks post-inoculation, the alterations were attenuated.ConclusionsThese results indicate that by modulating AQP4 function and, consequently, glymphatic clearance, it is possible to modify the propagation and pathological impact of tau in the brain, particularly during the initial stages of the disease. These findings highlight the critical role of the glymphatic system in preserving healthy brain homeostasis and offer valuable insights into the therapeutic implications of targeting this system for managing neurodegenerative diseases characterized by protein aggregation and spread.

RISK FACTORS AND CLINICAL CORRELATIONS OF URINARY TGF-Β1 IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS AND EARLY KIDNEY FIBROSIS

The course of juvenile idiopathic arthritis (JIA) is associated with a long-term infl ammatory process and the use of nonsteroidal anti-infl ammatory drugs (NSAIDs), which can cause nephrotoxicity with fi brotic kidney damage in patients with JIA. Regardless of the etiology of joint damage, prolonged infl ammation promotes the progression of fi brosis, and renal fi brosis is the fi nal common stage of chronic kidney disease (CKD). Kidney biopsy, which is invasive, risky and underutilized, is generally considered the only clinical method to detect fi brosis. Over the past decade, some progress has been made in the search for minimally invasive biomarkers of early kidney fi brosis, with transforming growth factor-β1 (TGF-β1) playing a key role in the progression of kidney fi brosis, but the signifi cance of TGF-β1 in children with JIA is unknown.Material and Methods: 80 children with JIA were examined. Urinary TGF-β1 levels were determined using a TGF-β1 ELISA kit(DRG International, Inc., Germany, EIA-1864) according to the manufacturer’s instructions. Methods of variation statistics were used. Informed consent was obtained from all patients. The study has a positive conclusion of the Commission on Biomedical Ethics of Dnipro State Medical University (Minutes of the meeting of the Commission No. 12 dated December 19, 2002), which decided that the scientifi c research can be considered in accordance with generally accepted moral standards, the requirements of respecting the rights, interests and personal dignity of study participants, bioethical standards for work with pediatric patients. There is no risk to the research subjects in the performance of the work. The legal representatives of the children involved in the research are informed about all aspects related to the purpose, objectives, methods and expected benefi ts of the research. Laboratory and instrumental research methods are generally accepted; the drugs to be used are approved for use. No human experiments were performed.Methods of variation statistics were used. Statistical analysis was performed using the STATISTICA 6.1 software package(StatSoft Inc., serial no. AGAR909E415822FA). The work was carried out as part of the research work of the Department of Propaedeutic of Childhood Diseases and Pediatrics 2 of the Dnipro State Medical University «Development of criteria for early diagnosis and prediction of comorbid kidney damage in children with somatic and infectious diseases» (state registration No. 0119U100932, implementation period 01.2019-12.2023).Results. The mean TGF-β1 level in our study was 20.26±16.34 (14.02, 12.5-17.98) pg/ml. Polyarthritis almost quadrupledthe probability of pathological changes in TGF-β1. The overwhelming majority of children with elevated TGF-β1 suff ered from polyarthritis (80.0 %) – one and a half times more often than those with relatively normal TGF-β1 concentration, p<0.04.If the active stage of the disease lasted at least 4 years, the probability of elevated TGF-β1 increased more than sixfold. Thetendency of signifi cant nephrotoxic eff ect of prolonged active JIA was confi rmed by the results of correlation analysis, according to which, in general, the duration of active JIA was directly related to the increase of TGF-β1 (ρ=0.38, p<0.001), and the duration of remission and the total duration of JIA had no signifi cant correlation with it (ρ= –0.19 and ρ=0.18, respectively, p>0.05). The direct dependence of elevated urinary TGF-β1 levels on clinical features such as polyarthritis and the duration of the active phase of JIA has been demonstrated. These clinical features in children with JIA can be considered as risk factors for the development of early renal fi brosis. Against the background of elevated TGF-β1, a reduced GFR according to the Hoek formula (<90 ml/min/1.73 m2) was found in 95 % of cases, i. e. the estimates of the functional state of the kidneys obtained by two diff erent methods were quite clearly the same. In the sample with TGF-β1<17.98 pg/ml, 22.76 % of children received immunobiologic therapy, while in the sample to increase TGF-β1 – only 14.76 %. Immunobiological therapy reduced the risk of increasing this urinary marker by 5.5 times.Conclusions. Elevated levels of the TGF-β1 biomarker were found in 25 % of children with JIA. An association of early renalfi brosis with duration of active phase of JIA ≥ 4 years, increased ESR, polyarthritis, arterial hypertension, and dental carieswas observed. Elevated urinary TGF-β1 levels are associated with reduced eGFR and are observed in almost all children witheGFR<90 ml/min/1.73 m2, confi rming the importance of early renal fi brosis in the development of renal dysfunction.

Assessment of Cobalt Binding Activity of Albumin in COVID-19 Patients and its Correlation with CRP

Background: Covid 19 pandemic has thrown a big challenge in terms of available manpower, space and financial recourses at all levels of healthcare facilities. The disease manifestation ranges from asymptomatic to severe but a pro-inflammatory milieu is the underlying ongoing event. Detection of pro- inflammatory markers in early stages of the disease is instrumental to avert future complications.Method: For the present study 35 RT-PCR positive Covid patients were chosen from indoor admissions along with 35 age and sex matched controls. C Reactive Protein (CRP) and cobalt binding activity of albumin measured in both groups and compared statistically.The values of CRP is elevated in cases (153.92± 87.56) as compared to controls (3.71± 3.07) which is statistically significant (p value= 0.001).Elevation of Cobalt binding activity of albumin is statistically significant (p value=0.0001) in cases (151.04± 37.38) when compared to controls (81.96± 29.49). Moreover elevation of cobalt binding activity of albumin bears moderate positive correlation (r=0.609) with the elevation of CRP levels.Conclusion: As laboratory assay of cobalt binding albumin has manifold advantages, when compared to assay of CRP, the former may emerge as a promising marker if similar result are obtained with a larger study population.

Understanding quality of life's challenges in sarcoma patients: A mixed-methods study

PurposeSarcoma, a highly aggressive form of cancer, profoundly affects patients both physically and psychologically. This study aimed to assess sarcoma patients' health-related quality of life and explore their experiences of living with the disease and their specific care requirements. MethodsThis research employed a convergent parallel mixed-methods design. Fifty-two sarcoma patients completed the European Portuguese version of the EORTC QLQ-C30 questionnaire, and seven of them participated in semi-structured interviews. Descriptive measures, Cronbach alpha for internal consistency, t-teste-Anova and stepwise regression were employed in the quantitative analysis. Qualitative data was analysed thematically. ResultsThe most affected Quality of life (QoL) dimensions were role functioning and global health, areas of functioning that were also described as impacted in patients’ experiences. Symptoms like insomnia, pain, and fatigue were frequently reported. Symptoms such as fatigue, pain, and financial difficulty explain QoL variance. No significant differences in QoL were found according to the different forms of treatment. Analysis of the interviews revealed three overarching themes: (1) disruption of daily life, (2) adaptation to life with sarcoma, and (3) the demand for more personalized care, allowing to gain a deeper understanding of living with sarcoma. ConclusionThe results underscore the significance of delivering care that enhances the quality of life for sarcoma patients, addressing both their physical and psychosocial needs, and providing personalized support throughout all stages of the disease.

Circulating miR-16-5p, miR-92a-3p and miR-451a are biomarkers of lung cancer in Tunisian patients

Lung cancer is one of the most common type of cancer and, despite significant advances in screening and diagnosis approaches, a large proportion of patients at diagnosis still present advanced stages of the disease with distant metastasis and bad prognosis. Finding and validating biomarkers of lung cancer is therefore essential. Such studies are often conducted on European, American and Asian populations and the relevance of these biomarkers in other populations remains less clear. In that prospect, we investigated the expression level of seven microRNAs, chosen from the medical literature (miR-16-5p, miR-92a-3p, miR-103a-3p, miR-375-3p, miR-451a, miR-520-3p and miR-let-7e-5p), in the blood of Tunisian lung cancer patients, treated or not by chemotherapy, and healthy control individuals. We found that high expression levels of circulating miR-16-5p, miR-92a-3p and miR-451a in the plasma of untreated patients discriminate them from healthy control individuals. In addition, miR-16-5p and miR-451a expression levels are significantly reduced in the plasma of chemotherapy-treated patients compared to untreated patients. Our results confirmed previous work in other populations worldwide and provide further evidence that circulating miR-16-5p, miR-92a-3p and miR-451a potentially regulate key pathways involved in the initiation and progression of cancer.

The change of intimate relationship between people with Alzheimer's disease and their adult child caregivers: An interpretative phenomenological analysis.

This study aims to explore the change of intimate relationship between people with Alzheimer's disease and their adult child caregivers as the disease progresses. Twelve adult child caregivers were recruited through purposive sampling. Explanatory phenomenological analysis was conducted to analyse data collected by semi-structured in-depth interviews. This study found a dynamically changing relationship between adult child caregivers and their parents with Alzheimer's disease during care giving that evolved with the progress of the disease. The relationship was the most intimate in the middle stage of the disease for most caregivers and a new reciprocal relationship developed due to caregiving. Caregivers experienced different degrees of self-growth when providing care, though caregiver burdens were common. The positive experience and perception of caregivers were important for improving the quality of life for adult child caregivers of people with Alzheimer's disease.

Biomarkers of oxidative stress and proteopathies in the diagnosis of neurodegenerative diseases

Introduction. Despite numerous studies in the field of neurodegenerative diseases, the exact mechanisms of these processes have not yet been identified. The purpose of this review is to analyze the methodological approaches necessary to revise the traditional and create new reliable prognostic and diagnostic algorithms that reflect pathogenetic features at different stages of neurodegeneration and atypical course of the disease. Material and methods. The review highlights the results of clinical and experimental studies obtained using a complex of clinical, laboratory and instrumental methods with an emphasis on markers of oxidative stress and proteopathy. In preparing the materials, sources from international and domestic databases were used: Scopus, Web of Science, Pub Medline, RSCI mainly for the last 15 years. Results. An idea has been formed about the molecular mechanisms of neural tissue regression in a number of neurodegenerative diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer’s and Parkinson’s disease. The relationship between the parameters of the oxidative process and the features of metal-energy shifts in organs and organ systems is demonstrated. The role of markers of oxidative stress in the early stages, when the process of inflammation prevails and in the atypical course of the disease, is shown. Valuable biochemical markers are cytokines, glutathione levels, myeloperoxidase activation, and isoprostanes. The review points to the prospect of including in screening indicators of iron and other metals such as Zn, Mg, affecting the clinic accumulation of β-amyloid, in connection with which they can be considered as the basis for the progression of neurodegeneration. New data on the contribution of halogenating stress to the pathogenesis of neuroinflammation are presented. An aspect requiring development in the field of biomarkers for assessing the duration of the disease and prognostic prospects is the data on the correlation of metabolic shifts in the intestinal microbiota with the duration of the disease and the inflammatory process. Essential for the creation of express diagnostic methods is the determination of redox balance as an integral marker in saliva, which has obvious advantages over the use of biological fluids, such as liquor and serum. Conclusion. The prospects of creating new prognostic and diagnostic schemes are associated with complexes, including laboratory and instrumental methods, in blood, liquor and saliva. Evaluation of the sensitivity and specificity of new markers depending on the clinical diagnosis allows the selection of pathogenetically significant markers in the early stages of the disease, with atypical neurodegeneration, to establish subtypes of the disease, to carry out their differential diagnosis.

Clinical photodynamic therapy: The evolution of photodynamic therapy treatment of head and neck cancer

The modern era of photodynamic therapy (PDT) treatment of human cancer began in earnest in 1978, with the publication by Dougherty et al. of the first large series of humans with refractory or recurrent skin cancers successfully treated with PDT using HpD (Photofrin). The first human series of head and neck cancer patients successfully treated with PDT (Photofrin) was published in 1985, by Keller et al. Since that time, numerous clinical investigators around the world have treated thousands of head and neck cancer patients with PDT in clinical trials. These head and neck cancer PDT clinical trials enrolled patients with various stages of disease, and locations of the tumor and were treated using a variety of photosensitizers. Head and neck cancer PDT treatments were performed as the primary treatment with the intent to cure, as a late-stage treatment for palliation of the tumor, or as an adjuvant or neoadjuvant treatment in combination with surgery, radiation, chemotherapy and most recently immunotherapy. Over the past five decades, head and neck cancer PDT has evolved as newer and more targeted photosensitizers became available for clinical use, as well as advances in laser and fiberoptic technologies allowing for the activating light to be successfully and more easily delivered deep into large invasive tumors. In addition, PDT can be accurately delivered using endoscopic, robotic, CT, ultrasound and MRI guidance thereby specifically targeting the tumor and reducing treatment morbidity. Significant progress has been achieved in the ease of use and treatment efficacy of head and neck cancer PDT in various stages of the disease.

Infiltration by monocytes of the central nervous system and its role in multiple sclerosis: reflections on therapeutic strategies

Abstract Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood-brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.

Global trends in chronic kidney disease-related mortality: a systematic review protocol

IntroductionIn recent decades, all-cause mortality has increased among individuals with chronic kidney disease (CKD), influenced by factors such as aetiology, standards of care and access to kidney replacement therapies (dialysis...

Analysis of the treatment and prognosis of 266 cases of extranodal natural killer/T-cell lymphoma, nasal type in a single medical center.

To assess the impact of different treatment strategies and risk factors on the prognosis of patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL) in a single medical center. The clinical features of 266 patients with ENKTL were retrospectively analyzed, among whom those in stages I and II received sandwich therapy, while those in stages III and IV underwent chemotherapy plus autologous hematopoietic stem cell transplantation. The Kaplan-Meier curves, univariate and multivariate Cox regression analyses were employed for survival and prognosis analysis. Statistical significance was set at P<0.05. Following treatment, the post-intervention outcomes demonstrated a complete remission (CR) rate of 71.05% and a partial remission (PR) rate of 3.76%. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 70.4% and 70.9%, respectively. In addition, the PFS for patients in stage I/II was 79.8%, with an OS of 81.1%, whereas for those in stage III/IV, the PFS was 41.7% and the OS was 40.9%. Notably, the achievement of CR immediately after treatment was an independent prognostic factor (P<0.001). Patients in stage I/II depicted a favorable 5-year OS rate, while those in stage III/IV manifested a less favorable prognosis. Stages of the disease and whether CR was achieved following treatment are important factors determining the survival and prognosis of patients with ENKTL. Further researches focusing on disease onset and mechanisms of drug resistance will contribute to better management of ENKTL.

Determinants and Biomarkers of Progression Independent of Relapses in Multiple Sclerosis.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) suggests that a smoldering inflammatory activity is present from the earliest stages of the disease and underlies the progression of disability, which proceeds relentlessly and independently of clinical and radiological relapses (PIRA). The complex system of pathological events driving "chronic" worsening is likely linked with the early accumulation of compartmentalized inflammation within the central nervous system as well as insufficient repair phenomena and mitochondrial failure. These mechanisms are partially lesion-independent and differ from those causing clinical relapses and the formation of new focal demyelinating lesions; they lead to neuroaxonal dysfunction and death, myelin loss, glia alterations, and finally, a neuronal network dysfunction outweighing central nervous system (CNS) compensatory mechanisms. This review aims to provide an overview of the state of the art of neuropathological, immunological, and imaging knowledge about the mechanisms underlying the smoldering disease activity, focusing on possible early biomarkers and their translation into clinical practice. ANN NEUROL 2024.

Alzheimer Disease Using Machine Learning

The successful development of amyloid-based biomarkers and tests for Alzheimer’s disease (AD) represents an important milestone in AD diagnosis. However, two major limitations remain. Amyloid-based diagnostic biomarkers and tests provide limited information about the disease process and they are unable to identify individuals with the disease before significant amyloid-beta accumulation in the brain develops. The objective in this study is to develop a method to identify potential blood-based non-amyloid biomarkers for early AD detection. The use of blood is attractive because it is accessible and relatively inexpensive. Our method is mainly based on machine learning (ML) techniques (support vector machines in particular) because of their ability to create multivariable models by learning patterns from complex data. Using novel feature selection and evaluation modalities we identified 5 novel panels of non-amyloid proteins with the potential to serve as biomarkers of early AD. In particular, we found that the combination of A2M, ApoE, BNP, Eot3, RAGE and SGOT may be a key biomarker profile of early disease. Disease detection models based on the identified panels achieved sensitivity (SN) &gt; 80%, specificity (SP) &gt; 70%, and area under receiver operating curve (AUC) of at least 0.80 at prodromal stage (with higher performance at later stages) of the disease. Existing ML models performed poorly in comparison at this stage of the disease suggesting that the underlying protein panels may not be suitable for early disease detection. Our results demonstrate the feasibility of early detection of AD using non-amyloid based biomarkers.

Molecular-oriented therapy of lung tumors in animals with BRAF mutations – possibilities and limitations of the method

Lung cancer (LC) is malignant epithelial tumors that differ in origin, histological structure, clinical course, and treatment results. Lung cancer ranks first in terms of male morbidity in Russia, and in terms of mortality in the world. In animals, LC is diagnosed much less frequently, but with an increase in the number of animals kept in cities, the incidence of LC increases, since companion animals are exposed to the same risk factors as humans. We conducted a retrospective analysis of the medical records of 43 animals (28 cats and 15 dogs) admitted to the VEGA veterinary clinics for treatment in the period from 2020 to 2023. The criterion for the inclusion of animals in the study was a tumor process in the thoracic cavity and lungs, diagnosed by instrumental and laboratory methods. High-dose intravenous chemotherapy, which is used in humans, is ineffective in the treatment of LC in animals, therefore, it is necessary to search, develop and introduce into clinical practice targeted drugs that will be effective in animals. Since the most widely used group of targeted drugs in human medicine are low-molecular kinase inhibitors that act on the corresponding molecular target in the tumor, the development of molecular genetic methods available for practical use by veterinary oncologists for the study of tumor cells in animals is relevant in veterinary medicine. The choice of treatment methods and prognosis depend on the stage of the disease, therefore, the issue of introducing biomarkers of various types and stages of oncological processes into veterinary practice deserves research. Also, to improve the effectiveness of treatment, it is recommended to conduct research and develop a lung cancer staging scale for cats.

Diagnosis and Management of Orbital Cellulitis in a Reference Center in Senegal

The severity of orbital cellulitis is the risk of blindness and cerebro-meningeal complications that can be life-threatening. The objective of our study was to report the clinical, paraclinical, therapeutic and progressive aspects of orbital cellulitis. This was a retrospective, descriptive study over 5-year, from 1st January 2017 to December 31st 2021, in the ophthalmology department of Aristide le Dantec University Hospital. We glued 102 patients. The incidence was 32.8 cases per year. The average age was 23 years, the age group from 0 to 15 years was the most representative (49%). The most frequent reason for consultation was eyelid swelling (87%). There was a predominance of preseptal cellulitis (64%). An ORL etiology was found in 21.5% of cases. Orbital-cerebral CT was performed in 57 patients. It made this possible to classify cellulite and identify sinusitis in 21.6% of cases. All patients received antibiotics and corticosteroid therapy were combined 48 hours after the start of treatment in 41 patients. The evolution was favorable in 73.5% of cases. Ten patients (9.8%) presented a complication. We aim for 3 cases of blindness. Death occurred in a patient who presented a bilateral orbital cellulitis complicated by cavernous sinus thrombophlebitis. The prognosis depends on the delay in treatment, the stage of the disease and the existence of comorbidity factors.

An early and trustable indicator suggestive of non-tuberculosis mycobacteria isolation in a high tuberculosis burden setting

Distinguishing between nontuberculous mycobacterial (NTM) lung infections and pulmonary tuberculosis becomes challenging due to their similar clinical manifestations and radiological images. Consequently, instances of delayed diagnosis or misdiagnosis are highly frequent. A feasible and reliable indicator of the existence of NTM in the early stages of the disease would help to solve this dilemma. In this study, we evaluated the potential of smear-positive and Xpert assay (Cepheid, USA) negative outcomes as an early indicator of possible NTM infection in a high TB-burden setting retrospectively and prospectively. During the study period, 12·77% (138/1081) of the smear-positive cases yielded negative outcomes with the simultaneous Xpert assay. From the 110 patients who yielded smear-positive/Xpert-negative outcomes and cultivated strain as well, 105 (95·45%) were proved to have NTM isolated. By incorporating an additional criterion of a negative result from the Interferon-gamma release assay, the accuracy of the screening method reached 100%. Regarding the NTM presence prediction value, smear-positive/Xpert-negative has a sensitivity of 24·86% (45/181) in all NTM isolated cases but 93·75-96·55% accuracy in retrospective study or 93·75% accuracy in prospective study in smear-positive NTM isolated cases. In addition, the specificity was ∼99·47% (943/948) in smear-positive tuberculosis cases. The clue of the presence of NTM could be obtained on the first day of the hospital visit due to the point of care (POC) feature of smear testing and Xpert assay. About one-fourth of the NTM-isolated patients would benefit from this rapid, convenient, and reliable screening strategy in the given circumstance. Smear-positive/Xpert-negative outcome is an early, trustable indicator that is indicative of NTM isolation.

Neuron-level explainable AI for Alzheimer’s Disease assessment from fundus images

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease and the leading cause of dementia. Early diagnosis is critical for patients to benefit from potential intervention and treatment. The retina has emerged as a plausible diagnostic site for AD detection owing to its anatomical connection with the brain. However, existing AI models for this purpose have yet to provide a rational explanation behind their decisions and have not been able to infer the stage of the disease’s progression. Along this direction, we propose a novel model-agnostic explainable-AI framework, called Granula̲\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\underline{la}$$\\end{document}r Neuron-lev̲\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\underline{v}$$\\end{document}el Expla̲\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\underline{a}$$\\end{document}iner (LAVA), an interpretation prototype that probes into intermediate layers of the Convolutional Neural Network (CNN) models to directly assess the continuum of AD from the retinal imaging without the need for longitudinal or clinical evaluations. This innovative approach aims to validate retinal vasculature as a biomarker and diagnostic modality for evaluating Alzheimer’s Disease. Leveraged UK Biobank cognitive tests and vascular morphological features demonstrate significant promise and effectiveness of LAVA in identifying AD stages across the progression continuum.

MRl and MRS hints for the differentiation of cerebellar multiple system atrophy from spinocerebellar ataxia type II

Background and objectivesThe differentiation of spinocerebellar ataxia type II (SCA 2) from idiopathic multiple systemic atrophy of the cerebellar type (MSA-C) is often difficult in patients with cerebellar ataxia when molecular testing is not available. Besides genetic testing, magnetic resonance imagining (MRI) and magnetic resonance spectroscopy (MRS) prove to be beneficial. Nevertheless, the characteristics observed through radiology change as the disease advances. Different radiological criteria may be needed across different stages of the disease. This study aimed to assess the radiological characteristics of MSA-C or SCA 2 patients across various stages of the disease and to identify potential distinguishing factors. MethodsBetween January 2000 and January 2020, a total of 390 patients, diagnosed with probable MSA-C according to the second consensus on MSA (317 cases) or with molecularly confirmed SCA 2 (73 cases), who had undergone at least one brain MRI and MRS targeting the cerebellar hemispheres, were enrolled in the study. The clinical parameters and neuroimaging features between these two diseases were compared and analyzed. ResultsA greater occurrence of a pontine hot cross bun sign (HCBS), higher scores on the scale for the assessment and rating of ataxia, and reduced levels of cerebellar N-acetyl aspartate (NAA)/creatine (Cr), and cerebellar choline (Cho)/Cr were found in MSA-C patients as compared with SCA 2 patients at similar disease durations. For the patients with an HCBS, a cerebellar Cho/Cr level of <0.53 was indicative of the potential presence of MSA-C, with significant level of specificity (85.96%). DiscussionDiscerning SCA2 from MSA-C using MRI and MRS appears to be plausible at various disease stages.

Expression and clinical significance of pattern recognition receptor-associated genes in hand, foot and mouth disease

Objective: To explore which pattern recognition receptors (PRRs) play a key role in the development of hand, foot, and mouth disease (HFMD) by analyzing PRR-associated genes. Methods: We conducted a comparative analysis of PRR-associated gene expression in human peripheral blood mononuclear cells (PBMCs) infected with enterovirus 71 (EV-A71) which were derived from patients with HFMD of different severities and at different stages. A total of 30 PRR-associated genes were identified as significantly upregulated both over time and across different EV-A71 isolates. Subsequently, ELISA was employed to quantify the expression of the six most prominent genes among these 30 identified genes, specifically, BST2, IRF7, 1FI16, TRIM21, MX1, and DDX58. Results: Compared with those at the recovery stage, the expression levels of BST2 (P=0.027), IFI16 (P=0.016), MX1 (P=0.046) and DDX58 (P=0.008) in the acute stage of infection were significantly upregulated, while no significant difference in the expression levels of IRF7 (P=0.495) and TRIM21 (P=0.071) was found between different stages of the disease. The expression levels of BST2, IRF7, IFI16 and MX1 were significantly higher in children infected with single pathogen than those infected with mixed pathogens, and BST2, IRF7, IFI16 and MX1 expression levels were significantly lower in coxsackie B virus (COXB) positive patients than the negative patients. Expression levels of one or more of BST2, IRF7, IFI16, TRIM21, MX1 and DDX58 genes were correlated with PCT levels, various white blood cell counts, and serum antibody levels that reflect disease course of HFMD. Aspartate aminotransferase was correlated with BST2, MX1 and DDX58 expression levels. Conclusions: PRR-associated genes likely initiate the immune response in patients at the acute stage of HFMD.

EARLY-ONSET OF FAMILIAL EXUDATIVE VITREORETINOPATHY: Clinical Characteristics, Management, and Outcomes.

To describe the clinical characteristics, management, and outcomes of toddlers (under the age of 3) diagnosed with familial exudative vitreoretinopathy. In this retrospective study, patients diagnosed with familial exudative vitreoretinopathy before the age of 3 were included. Presenting characteristics, genetic testing, management, and outcomes were collected. A total of 54 patients (108 eyes) with a mean age at diagnosis of 10.9 ± 2.6 months were included. Poor visual behavior (33%) and strabismus (26%) were the most common presenting symptoms, whereas screening only represented 11%. About half of included patients had a severe disease (stages 4 and 5). Genetic testing was positive in 40.7% of patients with 24% having a family history of familial exudative vitreoretinopathy. LRP5 was the most prevalent mutation (54.5%).Surgery was performed in 44.4% of eyes and was successful in 69.8% of cases. Failure exclusively occurred in eyes with severe stages. Among eyes evaluated for visual acuity (72 eyes), most (76.4%) had a vision of hand motion or better. Familial exudative vitreoretinopathy tended to be worse with earlier age at diagnosis, subsequently affecting the prognosis. Surgical intervention was common and primarily included lens-sparing vitrectomy and combined lensectomy and vitrectomy. Surgical success hinged on the stage of the disease.