Marker Of Progression Research Articles

Automated Parkinson's Disease Detection: A Review of Techniques, Datasets, Modalities, and Open Challenges

Abstract Parkinson's disease (PsD) is a prevalent neurodegenerative malady, which keeps intensifying with age. It is acquired by the progressive demise of the dopaminergic neurons existing in the substantia nigra pars compacta region of the human brain. In the absence of a single accurate test, and due to the dependency on the doctors, intensive research is being carried out to automate the early disease detection and predict disease severity also. In this study, a detailed review of various artificial intelligence (AI) models applied to different datasets across different modalities has been presented. The emotional intelligence (EI) modality, which can be used for the early detection and can help in maintaining a comfortable lifestyle, has been identified. EI is a predominant, emerging technology that can be used to detect PsD at the initial stages and to enhance the socialization of the PsD patients and their attendants. Challenges and possibilities that can assist in bridging the differences between the fast-growing technologies meant to detect PsD and the actual implementation of the automated PsD detection model are presented in this research. This review highlights the prominence of using the support vector machine (SVM) classifier in achieving an accuracy of about 99% in many modalities such as magnetic resonance imaging (MRI), speech, and electroencephalogram (EEG). A 100% accuracy is achieved in the EEG and handwriting modality using convolutional neural network (CNN) and optimized crow search algorithm (OCSA), respectively. Also, an accuracy of 95% is achieved in PsD progression detection using Bagged Tree, artificial neural network (ANN), and SVM. The maximum accuracy of 99% is attained using K-nearest Neighbors (KNN) and Naïve Bayes classifiers on EEG signals using EI. The most widely used dataset is identified as the Parkinson's Progression Markers Initiative (PPMI) database.

Parkinson’s disease psychosis associated with accelerated multidomain cognitive decline

BackgroundCognitive deficits are associated with poor quality of life and increased risk of development of dementia in patients with Parkinson’s disease (PD) psychosis. The trajectory of cognitive decline in PD...

The association of CSF biomarkers and cognitive decline with choroid plexus volume in early Parkinson's disease

ObjectiveThis study aims to determine the link between choroid plexus (CP) volume and cognitive decline in patients with early-stage Parkinson's disease (PD) and to test whether pathological proteins in the cerebrospinal fluid (CSF) are involved in the modulation of any detrimental effects from CP volume. MethodsData on 95 early-stage PD patients with 5 years of follow-up were collected from the Parkinson's Progression Marker Initiative cohort. The patients were separated into three groups based on tertiles of baseline CP volume. We then used a linear mixed model for longitudinal analysis and conducted path analysis to investigate mediating effects. ResultsAt baseline, the patients in both the upper and middle tertile group were older and had lower concentrations of CSF Aβ1-42 than those in the lowest tertile group. Longitudinal analysis showed that the upper tertile group suffered from a more rapid cognitive decline in the Symbol Digit Modalities test, Hopkins Verbal Learning Test (HVLT)-retention, and HVLT delayed recalled score. Furthermore, path analysis showed that the pathological effects of CP volume on the 5-year decline in memory might be partly mediated by the CSF Aβ1-42/αsyn ratio. ConclusionCP enlargement could be an independent risk factor for decreased cognition in patients with early-stage PD, and this risk may be mediated by CSF pathological proteins.

Correlation between Transforming Growth Factor-Beta Levels and Skin Disorder Levels based on Modified Rodnan’s Skin Scores in Systemic Sclerosis Patients

Systemic sclerosis is a chronic connective tissue disease characterized by the excessive formation of fibrous tissue. The current determination of systemic sclerosis progression uses the modified Rodnan’s skin score (MRSS), which is checked manually by assessing skin stiffness based on subjective pinching. Transforming growth factor-beta (TGF-β) is a major cytokine in the formation of fibrous tissue as the potential marker of systemic sclerosis progression and the targeting therapy. This study aims to determine the correlation between TGF-β levels and modified Rodnan’s skin score in systemic sclerosis patients.This study was a cross-sectional design and carried out in September 2021 at RSUP Dr. Hasan Sadikin, Bandung. This research examined 33 samples of the biological material of systemic sclerosis patients obtained from a study entitled "Development of a Systemic Sclerosis Registry System Based on Electronic Medical Records" which were stored at -80 ºC. A TGF-β test was performed at the Clinical Laboratory of Hasan Sadikin General Hospital, Bandung.The results of this study showed that the mean TGF-β level was 19.6 + 4.7 ng/mL. We found a significant moderate correlation between TGF-β and modified Rodnan’s skin score with an R-value of 0.513 and a p-value of 0.002.In conclusion, there is a statistically significant moderate positive correlation between TGF-β levels and modified Rodnan’s skin scores in patients with systemic sclerosis. Although TGF-β is the main mediator of fibrous tissue formation, there are many other mediators.

Amyloid PET imaging

Extracellular amyloid deposition in brain tissue is a hallmark of Alzheimer’s disease. Despite being the most common neurodegenerative disorder, it poses a major diagnostic challenge due to the lack of disease-specific biomarkers. Additionally, plaque-forming amyloid deposits are not unique to Alzheimer’s disease, but are also present in a high proportion of the elderly, as well as in patients with other neurodegenerative conditions such as dementia with Lewy bodies. Histopathological examination is the only reliable method for diagnosing the disease, but it is practically impossible to perform in vivo. Since Alzheimer’s disease is a disorder that develops asymptomatically over many years and eventually leads to severe dementia, new insights into the risk factors and markers of disease progression in the preclinical stage of the disease are needed. A better understanding of the underlying pathology is essential for the development of new therapies. In the past, this understanding came mainly from pathological studies. Positron emission tomography (PET) imaging detects the presence and activity of pathophysiological processes in vivo. By targeting different biological pathways, PET elucidates the metabolic activity of the processes that drive disease progression. Ongoing studies aim to clarify whether amyloid PET imaging can also be useful in assessing treatment response. In this review, recent advances in amyloid PET imaging that have significantly improved our understanding of the pathological basis of this disease are discussed.

Proteomic Profiles Associated With Postsurgical Progression in Nonfunctioning Pituitary Adenomas.

There is a lack of reliable biomarkers capable of predicting postoperative tumor progression of nonfunctioning pituitary adenomas (NFPAs). To discover proteomic profiles associated with postoperative tumor progression in patients with NFPAs. This was a case-controlled exploratory study at a tertiary university hospital. Tissue samples were obtained from 46 patients with residual tumor following surgery for NFPAs of gonadotroph lineage. Two patient groups were compared: patients requiring reintervention due to residual tumor progression (cases; reintervention group, n = 29) and patients with a residual tumor showing no progression for a minimum of 5 years (controls; radiologically stable group, n = 17). Differentially expressed proteins (DEPs) between patient groups were measured. Global quantitative proteomic analysis identified 4074 proteins, of which 550 were differentially expressed between the 2 groups (fold change >80%, false discovery rate-adjusted P ≤ .05). Principal component analysis showed good separation between the 2 groups. Functional enrichment analysis of the DEPs indicated processes involving translation, ROBO-receptor signaling, energy metabolism, mRNA metabolism, and RNA splicing. Several upregulated proteins in the reintervention group, including SNRPD1, SRSF10, SWAP-70, and PSMB1, are associated with tumor progression in other cancer types. This is the first exploratory study analyzing proteomic profiles as markers of postoperative tumor progression in NFPAs. The findings clearly showed different profiles between tumors with indolent postoperative behavior and those with postoperative tumor progression. Both enriched pathways involving DEPs and specific upregulated proteins have previously been associated with tumor aggressiveness. These results suggest the value of proteomic profiling for predicting tumor progression in patients with NFPAs.

Prognostic Role of Myocardial Flow Reserve in Heart Failure With Preserved Ejection Fraction.

Aim To study the role of myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients with heart failure with preserved ejection fraction (HFpEF) in stratifying the risk of HFpEF progression during 12 months of follow-up.Material and methods The study included 58 patients with non-obstructive coronary artery disease and HFpEF. Concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured using an enzyme-linked immunosorbent assay. MFR and MBF were determined by dynamic single-photon emission computed tomography of the myocardium.Results At 12 months, the patients were divided into two groups: group 1 (n=11) included patients with an unfavorable course of HFpEF, group 2 (n=47) included patients with a favorable course. A multivariate analysis showed that NT-proBNP concentrations (odds ratio (OR), 3.23; 95% confidence interval (CI), 1.76-6.78; p=0.008) and MFR (OR, 8.09; 95% CI, 5.12-19.98; p<0.001) were independent predictors of adverse outcomes. According to ROC analysis, values of MFR ≤1.62 (area under the curve (AUC)=0.827; p<0.001) and NT-proBNP ≥760.5 pg/ml (AUC=0.708; p=0.040) can be considered as markers for HFpEF progression. Furthermore, the combined measurement of NT-proBNP concentration and MFR had a higher prognostic significance (AUC, 0.954; p<0.001).Conclusion Values of NT-proBNP and MFR can be used as noninvasive markers for an unfavorable course of HFpEF, and their combined measurement increases the prognostic significance.

Occludin is overexpressed in tubo-ovarian high-grade serous carcinoma compared to mesothelioma and is a marker of tumor progression and chemoresistance.

The objective of this study was to analyze the expression and prognostic role of the tight junction protein occludin in high-grade serous carcinoma (HGSC). Occludin protein expression by immunohistochemistry was analyzed in 602 HGSC (417 effusions, 185 surgical specimens). Expression in mesothelioma (n = 87; 45 effusions, 42 surgical specimens) was studied for comparative purposes. Occludin protein expression was found in 587/602 (98%) HGSC vs. 40/87 (46%) mesotheliomas and was predominantly limited to < 5% of cells in the latter (p < 0.001). Occludin was additionally overexpressed in HGSC effusions compared to surgical specimens (p < 0.001) and was overexpressed in post-chemotherapyeffusionscompared tochemo-naive effusions tapped at diagnosis (p = 0.015). Occludin expression in HGSC surgical specimens was associated with poor chemoresponse (p < 0.001) and primary resistance (p = 0.001). Expression in effusions and surgical specimens was unrelated to survival (p > 0.05). In conclusion, occludin expression is higher in HGSC compared to mesothelioma, and this protein is overexpressed in HGSC effusions, possibly reflecting changes in adhesion related to anchorage-independent growth in this microenvironment. Overexpression in post-chemotherapy compared to chemo-naïve effusions suggest a role in disease progression. Occludin expression in surgical specimens may be related to chemoresistance.

Predictivity of Human Telomerase Reverse Transcriptase (h-TERT) in Oral Squamous Cell Carcinoma: Immunohistochemical Study

Aims: Determine the potential role of h-TERT as a prognostic marker for oral squamous cell carcinoma by evaluating its immunohistochemical expression in different OSCC histologic grades in comparison with normal oral mucosa.&#x0D; Study Design: A retrospective study.&#x0D; Place and Duration: Oncology Center, Mansoura University, and Oral Pathology Department, Faculty of Dentistry, Mansoura University. The worked sample selected from the years (2015-2019).&#x0D; Methodology: Our study was accomplished on 30 OSCC cases and a control group of normal oral mucosa. Histopathologic grading of OSCCs was made using the WHO grade and Anneroth`s grading systems. Immunohistochemical expression of h-TERT was assessed in relation to different clinicopathological parameters. The data was analyzed using Pearson`s chi-square test to compare the differences between groups. Spearman's correlation co-efficiency test was used to test the association between different variables. A P value ≤ 0.05 was considered to be statistically significant.&#x0D; Results: A significant increased h-TERT expression was recorded from normal to OSCC groups (P=0.000). Additionally, elevated h-TERT expression was significantly correlated with the higher carcinoma histologic grade (P =0.025). There were high statistically significant differences in h-TERT expression concerning the parameters; Anneroth pattern of invasion (P= 0.049), depth of invasion (DOI, P=0.024), and lymphoplasmacytic infiltration (LPI, P=0.009). There were no statistically significant differences in h-TERT immunoexpression considering the clinical parameters; patient age, gender, anatomical sites, clinical shape of lesion, T, N, M, and TNM stages (Chi-square test, P values were &gt; 0.05).&#x0D; Conclusions: Increased h-TERT immunoexpression from normal to OSCC groups suggests its involvement in malignant transformation. Additionally, the significant differential expression of h-TERT among different OSCC histologic grades signaling its valuable use as a biomarker for assessing the cellular malignant progression of oral carcinomas, but unreliable as a clinical tumor progression marker. Moreover, the significant correlation of h-TERT expression with LPI, DOI and pattern of invasion indicating its possible reliable role in tumor host relation during multistage carcinogenesis.

Different impulse control disorder evolution patterns and white matter microstructural damage in the progression of Parkinson's disease.

The course of impulse control disorders (ICD) varies in the early stage of Parkinson's disease (PD). We aimed to delineate the association between the evolution pattern of ICD and the progression of PD. A total of 321 de novo PD patients from the Parkinson's Progression Markers Initiative database were included. Patients were followed up for a mean of 6.8 years and were classified into different groups according to the evolution patterns of ICD. Disease progression was compared among groups using survival analysis, in which the endpoint was defined as progression to Hoehn and Yahr stage 3 or higher for motor progression and progression to mild cognitive impairment for cognitive decline. In the fourth year of follow-up, four types of ICD evolution patterns were identified: (1) non-ICD-stable (68.2%), a patient who is consistently free of ICD; (2) late-ICD (14.6%), ICD developed during the follow-up of patients; (3) ICD-stable (11.5%), patients showed persistent ICD; and (4) ICD-reversion (5.6%), baseline ICD disappeared during the follow-up of patients with ICD. The ICD-reversion type shows daily life non-motor symptoms [Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) part I], daily life motor symptoms (MDS-UPDRS part II), rapid eye movement sleep behavior disorder, and anxiety symptoms has a greater impact. PD patients with different ICD evolution patterns had different changes in white matter microstructure at the onset of the disease. Those relevant brain regions are involved in ICD and non-motor functions. Four early ICD evolution patterns are identified in de novo PD, with different prognoses and brain white matter microstructural damage patterns, and they may predict motor progression and cognitive decline in PD patients.

SUBJECTIVE COGNITIVE CONCERNS AND 5-YEAR NEUROPSYCHOLOGICAL TRAJECTORIES IN PARKINSON’S DISEASE

Abstract Subjective cognitive concerns (SCC) are often associated with Alzheimer’s disease (AD)-related cognitive declines in cognitively unimpaired (CU) individuals. However, it is unknown whether the same is true for CU individuals with Parkinson’s disease (PD). Therefore, this study examined relationships between SCC and 5-year neuropsychological trajectories in CU individuals with newly-diagnosed PD (mean age=60.45 years; 35.2% female) in the Parkinson’s Progression Markers Initiative (PPMI) cohort. Participants were classified as having SCC (n=52) or no SCC (n=204) based on participant or caregiver report for item 1 on the Unified Parkinson’s Disease Rating Scale, part 1. First, baseline cerebrospinal fluid (CSF) biomarkers were examined by SCC group. Next, linear mixed effects models, adjusting for age, education, sex/gender, APOE genotype, psychiatric factors, and motor symptoms examined 5-year trajectories of individual neuropsychological measures by SCC status. Relative to participants without SCC, those with SCC had worse levels of CSF tau (p=.011), p-tau (p=.016), and p-tau/amyloid ratio (p=.003), but not amyloid or alpha synuclein. SCC was associated with faster rates of decline in learning (β=-.059, p=.018), memory (β=-.050, p=.035), and processing speed (β=-.052, p=.031), but not in semantic fluency, visuoperceptual abilities, working memory, or on a global cognition screening measure. Overall, SCC was associated with learning/memory and processing speed declines, but not other measures that may be more PD-specific (e.g., working memory, visuoperceptual). Given the elevated AD biomarkers, SCC may be particularly related to early changes due to co-occurring AD and PD pathology. Future work should investigate longitudinal AD and PD-related biomarker trajectories by SCC status.

Exploring the joint potential of inflammation, immunity, and receptor-based biomarkers for evaluating ME/CFS progression.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic condition with no identified diagnostic biomarkers to date. Its prevalence is as high as 0.89% according to metastudies, with a quarter of patients bed- or home-bound, which presents a serious public health challenge. Investigations into the inflammation-immunity axis is encouraged by links to outbreaks and disease waves. Recently, the research of our group revealed that antibodies to beta2-adrenergic (anti-β2AdR) and muscarinic acetylcholine (anti-M4) receptors demonstrate sensitivity to the progression of ME/CFS. The purpose of this study is to investigate the joint potential of inflammatome-characterized by interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-21, Il-23, IL-6, IL-17A, Activin-B, immunome (IgG1, IgG2, IgG3, IgG4, IgM, and IgA), and receptor-based biomarkers (anti-M3, anti-M4, and anti-β2AdR)-for evaluating ME/CFS progression, and to identify an optimal selection for future validation in prospective clinical studies. A dataset was used originating from 188 individuals, namely, 54 healthy controls, 30 patients with a "mild" condition, 73 patients with a "moderate" condition, and 31 patients with a "severe" condition, clinically assessed by Fukuda/CDC 1994 and international consensus criteria. Inflammatome, immunome, and receptor-based biomarkers were determined in blood plasma via ELISA and multiplex methods. Statistical analysis was done via correlation analysis, principal component analysis, linear discriminant analysis, and random forest classification; inter-group differences were tested via nonparametric Kruskal-Wallis H test followed by the two-stage linear step-up procedure of Benjamini, Krieger, and Yekutieli, and via Mann-Whitney U test. The association between inflammatome and immunome markers is broader and stronger (coupling) in the severe group. Principal component factoring separates components associated with inflammatome, immunome, and receptor biomarkers. Random forest modeling demonstrates an excellent accuracy of over 90% for splitting healthy/with condition groups, and 45% for splitting healthy/severity groups. Classifiers with the highest potential are anti-β2AdR, anti-M4, IgG4, IL-2, and IL-6. The association between inflammatome and immunome markers is a candidate for controlled clinical study of ME/CFS progression markers that could be used for treatment individualization. Thus, the coupling effects between inflammation and immunity are potentially beneficial for the identification of prognostic factors in the context of ME/CFS progression mechanism studies.

Lysosomal Polygenic Burden Drives Cognitive Decline in Parkinson's Disease with Low Alzheimer Risk.

Genetics influence cognitive progression in Parkinson's disease, possibly through mechanisms related to Lewy and Alzheimer's disease pathology. Lysosomal polygenic burden has recently been linked to more severe Lewy pathology post mortem. To assess the influence of lysosomal polygenic burden on cognitive progression in Parkinson's disease patients with low Alzheimer's disease risk. Using Cox regression we assessed association between lysosomal polygenic scores and time to Montreal Cognitive Assessment score ≤ 21 in the Parkinson's Progression Markers Initiative cohort (n = 374), with replication in data from the Parkinson's Disease Biomarker Program (n = 777). Patients were stratified by Alzheimer's disease polygenic risk. The lysosomal polygenic score was associated with faster progression of cognitive decline in patients with low Alzheimer's disease risk in both datasets (P = 0.0032 and P = 0.0054, respectively). Our study supports complex interplay between genetics and neuropathology in Parkinson's disease-related cognitive impairment, emphasizing the role of lysosomal polygenic burden. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Prediction of dyskinesia in Parkinson’s disease patients using machine learning algorithms

Dyskinesias are non preventable abnormal involuntary movements that represent the main challenge of the long term treatment of Parkinson’s disease (PD) with the gold standard dopamine precursor levodopa. Applying machine learning techniques on the data extracted from the Parkinson’s Progression Marker Initiative (PPMI, Michael J. Fox Foundation), this study was aimed to identify PD patients who are at high risk of developing dyskinesias. Data regarding clinical, behavioral and neurological features from 697 PD patients were included in our study. Our results show that the Random Forest was the classifier with the best and most consistent performance, reaching an area under the receiver operating characteristic (ROC) curve of up to 91.8% with only seven features. Information regarding the severity of the symptoms, the semantic verbal fluency, and the levodopa treatment were the most important for the prediction, and were further used to create a Decision Tree, whose rules may guide the pharmacological management of PD symptoms. Our results contribute to the identification of PD patients who are prone to develop dyskinesia, and may be considered in future clinical trials aiming at developing new therapeutic approaches for PD.

Markers of end-stage renal disease progression: beyond the GFR

Chronic kidney disease may progress to end-stage renal disease (ESRD) with a high risk of morbidity and mortality. ESRD requires immediate initiation of therapy or a decision on dialysis or kidney transplantation. Therefore, timely diagnosis of pathology progression is critical for many patients. ESRD is associated with pathological changes, including inflammation, fibrosis, endocrine disorders and following epigenetic changes in various cells, all these alterations could serve as markers for ESRD identification. This review summarizes conventional and promising biomarkers of ESRD, which can be evaluated in kidney tissue, blood, or urine. Some of them are narrowly specific to a particular pathology, while others are more versatile. We suggested several universal inflammatory, fibrotic, hormonal, and epigenetic markers indicative of severe deterioration of renal function and progression of ESRD for improvement of ESRD diagnostics.

Anemia as a Prognostic Marker for Disease Progression in HIV Infection

Anemia, a prevalent hematologic manifestation in individuals living with Human Immunodeficiency Virus (HIV) infection, has garnered considerable attention as a prognostic indicator for disease progression and adverse clinical outcomes. This abstract presents a comprehensive review elucidating the intricate relationship between anemia and the progression of HIV infection, incorporating epidemiological trends, underlying pathophysiological mechanisms, clinical implications, and prognostic significance. Despite advances in antiretroviral therapy (ART), anemia remains a frequent complication in HIVinfected individuals, posing substantial challenges to patient management. This paper aims to provide a nuanced understanding of anemia's role as a prognostic marker, surpassing its conventional characterization as a hematologic abnormality in the context of HIV infection. Anemia's role as a predictive marker for adverse clinical outcomes in HIV patients is explored, encompassing increased mortality rates, heightened risk of opportunistic infections, accelerated disease progression, and compromised quality of life. The review delves into its prognostic significance, shaping therapeutic decisions and prognostic assessments. This paper encapsulates the criticality of anemia as a prognostic marker for disease progression in HIV infection. Understanding its epidemiology, pathophysiological mechanisms, clinical implications, and prognostic significance is pivotal for informed clinical decision-making, prognostic assessments, and optimizing care paradigms in HIV management. Keywords: Anemia, Prognostic Marker, Disease Progression and HIV

Understanding the Impact of HIV-Associated Bone Marrow Alterations on Erythropoiesis

Human Immunodeficiency Virus (HIV) infection presents a multifaceted challenge, extending beyond its primary impact on the immune system to affect various organ systems. Among these, the bone marrow, the primary site for hematopoiesis, undergoes substantial alterations during HIV infection, profoundly influencing erythropoiesis—the process of red blood cell production. Anemia, a prevalent hematologic complication in HIV-infected individuals, often serves as a marker of disease progression and impacts overall health outcomes. This paper aims to delve into the intricate relationship between HIV-associated bone marrow alterations and their consequential effects on erythropoiesis. The mechanisms underlying bone marrow changes in HIV infection, including direct viral effects, dysregulation of cytokine networks, and inflammatory processes, significantly disrupt the delicate balance necessary for efficient erythropoiesis. The impact of these alterations on erythropoiesis manifests through ineffective red blood cell production, decreased erythropoietin responsiveness, and shortened red blood cell lifespan. Chronic inflammation further complicates erythropoietic processes, contributing to the development and perpetuation of anemia in HIV-infected individuals. Therapeutic interventions encompass a multifaceted approach, including antiretroviral therapy (ART) to control viral replication, erythropoiesis-stimulating agents, and adjunctive nutritional support to manage anemia. However, emerging research targeting bone marrow microenvironmental factors and novel agents stimulating erythropoiesis offer promising avenues for future therapeutic development. Keywords: HIV, bone marrow, erythropoiesis, erythropoietin, antiretroviral therapy

One-month assessment of Th-cell axis related inflammatory cytokines, IL-17 and IL-22 and their role in alcohol-associated liver disease.

Changes in the expression of cyto- and chemokines due to alcohol-associated liver disease (ALD) have been reported to be both protective and pathogenic. This study examined plasma levels of two key cytokines, Il-17 and Il-22, which construct the proinflammatory vs. anti-inflammatory axes across the spectrum of alcohol use disorder (AUD) and ALD including alcohol-associated hepatitis (AH) to determine the underlying status of the inflammation. Forty-two males and females aged 25-63 yrs. were grouped as healthy controls (HV[n=8]), AUD with no liver injury (AUDNLI [n=8]), AUD with liver injury (AUDLI [n=8]), non-severe alcohol-associated hepatitis (NSAH [n=9]), and severe alcohol-associated hepatitis (SAH [n=9]). Demographic, drinking, and clinical data were collected. Blood samples were collected at baseline (BL, all subjects) and during week 4 (W4, only patients) for IL-17 and IL-22; and statistically analyzed. IL-17 was highly elevated in the SAH group both at BL and post-SOC. LTDH and BL IL-22 in non-severe AH patients were associated significantly. LTDH significantly predicted W4 IL-22 levels, positively (increasing) in NSAH and inversely (lowering) in SAH patients. BL and W4 IL-22 levels were significantly higher (4-fold, p≤0.001) in all AH patients compared to all AUD patients (AUROC=0.988, p≤0.001). IL-22 showed significant affinity with AST, AST: ALT ratio, total bilirubin, INR, and PT both at BL and W4. IL-22 was inversely associated with IL-1β; and positively with TNF-α and IL-8 both at BL, and W4. BL IL-17 showed a positive correlation with MELD (p=0.017) in all AH patients. In SAH, > 2-fold W4 IL-17 level compared to BL showed significant within subjects' effects, p=0.006. In AUD patients without AH, the drop in IL-17 at W4 vs. BL showed a significant within subjects' effect, p=0.031. Drinking chronicity predicted opposite effects in IL-22 levels in NSAH (antiinflammatory) and SAH (pro-inflammatory) patients at post-SOC. BL IL-22 levels differentiated AH patients robustly from the AUD patients (with or without liver injury); and showed corresponding increases stepwise with the stages of ALD. IL-22 was closely associated with progression and injury markers of the liver; and response to the cytokines of pro-inflammatory nature. Pro-inflammatory indicator of IL-17 cell axis, IL-17 showed a strong positive association with MELD, a severity indicator of AH.

Correlation of slow-wave sleep with motor and nonmotor progression in Parkinson's disease.

This study aimed to explore the association between slow-wave sleep and the progression of motor and nonmotor symptoms in patients with PD. Data were collected from the Parkinson's Progression Markers Initiative study. Slow-wave sleep, also known as deep non-rapid eye movement (DNREM) sleep, was objectively assessed using the Verily Study Watch. Motor function was assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III score, Hoehn and Yahr stage, freezing of gait, motor fluctuations, and dyskinesia severity. Comprehensive assessments were conducted on nonmotor symptoms, including depression, anxiety, global cognitive function, and autonomic dysfunction. Statistical analyses involved repeated-measures analysis of variance and linear regression. A total of 102 patients with PD were included in the study, with a median follow-up duration of 3.4 years. In the long DNREM sleep duration group (n = 55), better motor function (DNREM × time interaction: F(1,100) = 4.866, p = 0.030), less severe sexual dysfunction (p = 0.026), and improved activities of daily living (p = 0.033) were observed at the last follow-up visit compared with the short DNREM sleep duration group (n = 47). Reduced DNREM sleep duration is a risk factor for motor progression (β = -0.251, p = 0.021; 95% confidence interval = -0.465 to -0.038). The findings suggest an association between longer DNREM sleep duration and slower motor and nonmotor progression in patients with PD.

KL-6 in adult polymyositis and dermatomyositis patients and its correlation with interstitial lung disease

BackgroundPulmonary involvement is still regarded as a common cause of morbidity in Polymyositis/Dermatomyositis. Interstitial lung disease can result in potentially fatal consequences such as ventilatory failure, secondary pulmonary arterial hypertension, or cor pulmonale. Early diagnosis of interstitial lung disease is hence a top priority in Polymyositis/Dermatomyositis patients. Krebs von den Lungen-6 is a transmembrane mucoprotein that has recently been identified as a promising marker for interstitial lung disease diagnosis and progression. As a result, it is regarded as a powerful predictor of interstitial lung disease severity. Thirty polymyositis/dermatomyocitis patients were enrolled in this study. Thirty age and sex matched healthy individuals were selected as control group. Cutaneous Dermatomyositis Disease Area Severity index(CDASI) was used for evaluation of skin severity, KL6 was measured using Elisa kit, High-resolution computed tomography, pulmonary function tests were made.ResultsSixteen female and 14 male patients had a mean age of 41.64–8.02 and amedian of the disease duration of 4 years. Fifteen patients (50%) had normal readings on High-resolution computed tomography of the chest HRCT chest, while the other half had significant HRCT chest findings. KL-6 concentrations were seen to be higher in Polymyositis/Dermatomyositis patients mainly those with ILD (mean ± SD 38.66 ± 22.98), compared to the control group (Mean ± S 589.04 ± 409) and in patients without ILD (Mean ± SD 86.70 ± 8.99), (p < 0.001). KL-6 serum concentrations were shown to have a significant connection with the HRCT score (r = 0.803, P < 0.001). Forced vital capacity (FVC%) (r = − 0.910, P < 0.001), forced expiratory volume in 1 s (FEV1%) (r = − 0.767, P < 0.001), and FEV1/FVC% (r = − 0.228, P = 0.112) were all inversely related to KL-6 concentrations.ConclusionIndividuals with PM and DM with concomitant ILD have increased KL-6 serum concentrations in comparison to myositis individuals without ILD, denoting its potential role in diagnosis and follow up of PM/DM with ILD. Further studies are needed to discuss the role of KL6 in large sample of the patient's population, and its correlation with other organ affection rather than ILD. Also to clarify the potentiality of adding the KL6 biomarker to the guidelines of treat to target for Rheumatic diseases with lung affection and to see the effect of treatment on KL6 serum level.