scholarly journals IMMUND: an Early Stage Diagnostic and Therapeutic Frame for Neurodegenerative Diseases and Multiple Sclerosis based on Immunological Markers

2021 ◽  
Author(s):  
Sagnik Sen ◽  
Ashmita Dey ◽  
Dwipanjan Sanyal ◽  
Ujjwal Maulik ◽  
Krishnananda Chattopadhyay
Keyword(s):  
Multiple Sclerosis ◽  
Neurodegenerative Diseases ◽  
Early Stage ◽  
Cellular Systems ◽  
P Value ◽  
Research Areas ◽  
Immunological Markers ◽  
Therapeutic Frame ◽  
Comprehensive Framework ◽  
The Impact

For neurodegenerative diseases, the impact of immunological markers is one of the modern research areas. It has been observed that neuroinflammation increases the cellular precipitation of some of the key proteins associated with neurodegenerative diseases. Therefore, the possibility of functional loss can be enhanced due to neuroinflammation which leads to the initiation of any related diseases. In this regard, autoantibodies, which are known for their autophagy nature, can be considered as key elements for early diagnostic as well as early therapeutics. In this article, we have proposed a comprehensive framework to unveil the diagnostic as well as the therapeutic possibility of the autoantibodies which are largely associated with Mild-Moderate Alzheimer's Disease, Early-Stage Parkinson's Disease, and Multiple Sclerosis. Here, we have introduced a new concept of average p-value where multiple p-values of an autoantibody in a singular disease have been considered as a multi-occurrence of that sample in cellular systems. Also, multiple proteins from a single protein family under a differentially expressed range have been prioritized. As a result, the top ten autoantibodies have been selected for further study and also considered as diagnostic markers. Interestingly, most of the selected autoantibodies are either cytokines or immunoglobulins. Subsequently, we have performed an evolutionary sequence-structure space study to identify the druggable structural facet for the selected autoantibodies. To make the therapeutic perspective more robust, we have introduced the concept of protein moonlighting. Hence, it provides more robustness in therapeutic identification. Finally, two autoantibodies i.e., Q9NYV4 and P01602 are identified as a novel marker.

Stage-differentiated modelling of DNA methylation landscapes uncovers salient biomarkers and prognostic signatures in colorectal cancer progression

2021 ◽  
Author(s):  
Sangeetha Muthamilselvan ◽  
Abirami Raghavendran ◽  
Ashok Palaniappan
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Cpg Island ◽  
Early Stage ◽  
P Value ◽  
Consensus Analysis ◽  
One Stage ◽  
Differentially Methylated Genes ◽  
Methylation Patterns ◽  
The Impact

Abstract Background: Aberrant DNA methylation acts epigenetically to skew the gene transcription rate up or down, with causative roles in the etiology of cancers. However research on the role of DNA methylation in driving the progression of cancers is limited. In this study, we have developed a comprehensive computational framework for the stage-differentiated modelling of DNA methylation landscapes in colorectal cancer (CRC), and unravelled significant stagewise signposts of CRC progression. Methods: The methylation β - matrix was derived from the public-domain TCGA data, converted into M-value matrix, annotated with AJCC stages, and analysed for stage-salient genes using multiple approaches involving stage-differentiated linear modelling of methylation patterns and/or expression patterns. Differentially methylated genes (DMGs) were identified using a contrast against controls (adjusted p-value <0.001 and |log fold-change of M-value| >2). These results were filtered using a series of all possible pairwise stage contrasts (p-value <0.05) to obtain stage-salient DMGs. These were then subjected to a consensus analysis, followed by Kaplan–Meier survival analysis to evaluate the impact of methylation patterns of consensus stage-salient biomarkers on disease prognosis.Results: We found significant genome-wide changes in methylation patterns in cancer cases relative to controls agnostic of stage. Our stage-differentiated analysis yielded the following stage-salient genes: one stage-I gene (FBN1), one stage-II gene (FOXG1), one stage-III gene (HCN1) and four stage-IV genes (NELL1, ZNF135, FAM123A, LAMA1). All the biomarkers were hypermethylated, indicating down-regulation and signifying a CpG island Methylator Phenotype (CIMP) manifestation. A significant prognostic signature consisting of FBN1 and FOXG1 survived all the steps of our analysis pipeline, and represents a novel early-stage biomarker. Conclusions: We have designed a workflow for stage-differentiated consensus analysis, and identified stage-salient diagnostic biomarkers and an early-stage prognostic biomarker panel. Our studies further yield a novel CIMP-like signature of potential clinical import underlying CRC progression.

scholarly journals Should the Number of Metastatic Pelvic Lymph Nodes Be Integrated into the 2018 Figo Staging Classification of Early Stage Cervical Cancer?

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1552
Author(s):  
Luigi Pedone Anchora ◽  
Vittoria Carbone ◽  
Valerio Gallotta ◽  
Francesco Fanfani ◽  
Francesco Cosentino ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Lymph Nodes ◽  
Early Stage ◽  
Disease Free Survival ◽  
Staging System ◽  
Lymph Node Status ◽  
P Value ◽  
Pelvic Lymph Nodes ◽  
Early Stage Cervical Cancer ◽  
The Impact

Introduction: Lymph node status has become part of the new staging system for cervical cancer (CC). It has been shown that patients staged as IIIC1 had heterogeneous prognoses and, in some cases, experienced better outcomes than patients with lower stages. We evaluated the impact of the number of metastatic pelvic lymph nodes (MPLNs) among patients with stage IIIC1 cervical cancer. Methods: Survival analyses were conducted in order to identify the best cut-off prognostic value relative to the number of MPLNs. Disease free survival (DFS) was considered the main outcome. Results: 541 patients were included in the study. Eighty-nine patients were of stage IIIC1. The best prognostic cut-off value of the number of MPLNs was 2. Patients with >2 MPLNs (n > 2 group) had worse DFS compared with those having <2 (N1-2 group) (5 yr DFS: 54.7% vs. 78.1%, p value = 0.006). Multivariate analyses demonstrated that the extent of MPLNs had little impact on DFS and that replacement of IIIC1 staging with N1-2 and n > 2 grouping provided a better, statistically significant model (p value = 0.006). Discussion: Using a cut-off value of 2, the number of MPLNs could better predict prognostic outcomes within stage IIIC1 cervical cancer and have potential implications for therapeutic decision-making in the treatment of patients with stage IIIC1 CC.

scholarly journals Dementing brain processes in patients with Wilson’s disease and multiple sclerosis (pathogenesis and treatment approaches)

2019 ◽  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Impairment ◽  
Wilson’S Disease ◽  
Early Stage ◽  
Critical Mass ◽  
Wilson's Disease ◽  
Biological Aging ◽  
Cognitive Mechanisms ◽  
The Impact ◽  
The Brain

This article discusses various aspects of dementing processes in patients with Wilson’s disease (WD) and multiple sclerosis (MS), followed by a discussion of current pathogenetic treatment methods for these patients. A comprehensive clinical and laboratory study showed that the pathogenesis and staged development of the dementing process in patients with WD and MS largely coincides with those in patients with Alzheimer's disease and depends on three groups of factors: genetic predisposition, natural (biological) aging, and endo and exogenous pathogenic factors effects on the brain. Therefore, on the basis of the data presented by us, as well as literature data, it allows us to state that dementia is an organic pathophysiological syndrome of destruction of the critical mass of structural-functional blocks and systems of cognitive mechanisms of the brain. Each individual has his own, genetically determined, critical mass of cognitive mechanisms. Like any false system, this one is ultimately subject to both natural (slow) decay and pathological (accelerated) decay due to the death of neurons both in the type of apoptosis and in the type of necrosis. Thus, in patients with WD and MS, the pathogenetic process always involves structures sooner or later that ensure the functioning of the cognitive functions of the brain and lead to the development of their defects, therefore, therapy should be prescribed for the treatment of these patients. Dementia should be treated at its early stage, at the stage of cognitive impairment (CI). The general principles of managing patients with CI are the determination of the etiopathogenetic cause underlying the development of cognitive impairment, the reduction in the degree and prevention of the progression of cognitive deficit and the impact, if possible, on risk factors. Also, at all stages of cognitive deficiency, treatment of concomitant somatic diseases and correction of the emotional state are relevant. Therefore, timely prescribed comprehensive, pathogenetically substantiated personified therapy helps prevent irreversible consequences and improves the quality of life of patients.

scholarly journals Peranan Kadar Feritin Serum terhadap Kejadian Preeklampsia

2015 ◽  
Vol 4 (3) ◽  
Author(s):  
Mega Ulfah ◽  
Masrul Masrul ◽  
Arni Amir
Keyword(s):  
Serum Level ◽  
Early Stage ◽  
Serum Levels ◽  
Total Sample ◽  
Normal Pregnancy ◽  
P Value ◽  
Excess Iron ◽  
The Difference ◽  
The Impact ◽  
Biomedical Laboratory

Abstrak Preeklampsia merupakan penyebab utama kematian maternal dan perinatal diseluruh dunia. Peningkatan kadar serum besi dan feritin memiliki potensi untuk digunakan secara diagnostik untuk memperingatkan preeklampsia tahap awal. Tujuan penelitian ini adalah untuk menentukan peranan kadar serum feritin terhadap kejadianpreeklampsia. Penelitian ini merupakan penelitian analitik observasional dengan desain case-control. Penelitian dilakukan dari Agustus 2013 hingga Juli 2014, bertempat di RS dr. M. Djamil, RS dr. Reksodiwiryo dan Laboratorium Biomedik UNAND Padang.  Jumlah sampel yang diteliti adalah 40 responden dimana sampel terdiri dari 2 kelompok,masing-masing terdiri dari 20 sampel. Pemeriksaan serum feritin dilakukan dengan metode ELISA. Perbedaan rerata kadar feritin serum antara kelompok preeklampsia dan kehamilan normal dianalisa dengan mengunakan independen ttest. Hasil penelitian diperoleh rerata kadar serum feritin pada kelompok preeklampsia dan kehamilan normal adalah50,46+4,37 ng/ml dan 17,64+1,6 ng/ml, dengan nilai p=0,004. Kadar feritin pada kedua kelompok masih dalam batas normal dan tidak ditemukan indikasi adanya kelebihan besi sebagai faktor resiko preeklampsia. Kesimpulan penelitian ini yaitu kadar serum feritin tidak memiliki peranan terhadap kejadian preeklampsia. Kata kunci: preeklampsia, hipertensi dalam kehamilan, serum feritin Abstract Preeclampsia is a major cause of worldwide maternal and prenatal mortality. The increase in iron serum and ferritin can be used as a diagnosis to warn of the early stage of preeclampsia. The objective of this study was to determine the impact of ferritin serum levels on preeclampsia. This study was an observational analytic study withcase-control design. It has been done from August 2013 to Juli 2014, in RS dr. M. Djamil, RS dr. Reksodiwiryo and Biomedical Laboratory of Andalas University Padang. Total sample evaluated was 40 samples. The sample consist of two groups, each group consist of 20 respondents. Ferritin serum level was examined by using ELISA method. The difference of ferritin serum level between preeclampsia and normal pregnancy analyzed by using independen t test.The result of this study shows that the avarage of ferritin serum levels in preeclampsia group and normalpregnancy is 50,46+4,37 ng/ml and 17,64+1,6  ng /ml, with a p-value 0,004. The ferritin serum level in both groups is normal  and didn’t find that excess iron as a risk factor for preeclampsia. It can be concluded that ferritin serum level has no role on preeclampsia. Keywords: preeclampsia, hypertension in pregnancy, ferritin serum

scholarly journals Renal Dysfunction in Prediabetes: Confirmed by Glomerular Hyperfiltration and Albuminuria

2021 ◽  
Author(s):  
Alagilawada S. Shilpasree ◽  
Vidya S. Patil ◽  
Manjunath Revanasiddappa ◽  
Vijayetha P. Patil ◽  
Deepti S. Ireshnavar
Keyword(s):  
Odds Ratio ◽  
Renal Damage ◽  
Early Stage ◽  
Glomerular Hyperfiltration ◽  
P Value ◽  
Age And Gender ◽  
Asymptomatic Patients ◽  
And Gender ◽  
The Impact ◽  
Normal Controls

Abstract Objectives Prediabetes is defined as an intermediate state of hyperglycemia with glucose levels above normal but below the diagnostic cutoff of diabetes mellitus. Prediabetes is considered as an important risk factor for the development of diabetes and complications associated with diabetes. Since glomerular hyperfiltration (elevated GFR) and albuminuria represent early and reversible stages of kidney damage seen in patients with type 2 diabetes, we aim to assess the impact of hyperglycemia in prediabetic range on renal functions measured by estimated GFR and urine albumin excretion (UAE). Materials and Methods The study included 1,031 patients aged 30 to 70 years, attending regular health checkup. Patients were grouped as normal, prediabetes, and diabetes according to the American Diabetic Association (ADA) criteria based on fasting blood sugar and hemoglobin A1c (HbA1c). Further, the patients were grouped into multiple subgroups based on age and gender. UAE was measured by using immunoturbidimetric method, and GFR was estimated by chronic kidney disease epidemiology collaboration (CKD EPI) equation. Statistical Analysis Prevalence of hyperfiltration (estimated glomerular filtration rate above the age and gender specific 95th percentile), and albuminuria in prediabetes and diabetes was compared with normal controls. Odds ratio and 95% confidence interval were calculated by using logistic regression analysis to predict the occurrence of hyperfiltration in prediabetes and diabetes. Analysis of variance followed by post hoc comparison was done to assess the significance of difference, and p-value < 0.05 was considered statistically significant. Results Prevalence of hyperfiltration was more in prediabetes and diabetes compared with normal controls, and it increased with surging HbA1c level that was shown as higher odds ratio for hyperfiltration in both the groups. UAE was more in the prediabetes and diabetes group when compared with normal controls, but the difference was significant only in diabetes. Conclusion Since glomerular hyperfiltration represents an early and reversible stage of renal damage manifesting before the appearance of albuminuria, elevated GFR can be used to identify asymptomatic patients with intermediate hyperglycemia having high risk of developing nephropathy in the future. Prediabetes represents a window of opportunity to initiate preventive strategies at an early stage before the occurrence of significant renal damage.

scholarly journals Enteral immunonutrition versus enteral nutrition for patients undergoing oesophagectomy: a systematic review and meta-analysis

2020 ◽  
Vol 30 (6) ◽  
pp. 854-862 ◽  
Author(s):  
Xiao-Kun Li ◽  
Hai Zhou ◽  
Yang Xu ◽  
Zhuang-Zhuang Cong ◽  
Wen-Jie Wu ◽  
...  
Keyword(s):  
Enteral Nutrition ◽  
Clinical Outcomes ◽  
English Language ◽  
Early Stage ◽  
Meta Analysis ◽  
Mean Difference ◽  
Cochrane Library ◽  
P Value ◽  
Standard Mean Difference ◽  
The Impact

Abstract OBJECTIVES According to retrospective studies, oesophageal carcinoma is the second deadliest gastrointestinal cancer after gastric cancer. Enteral immunonutrition (EIN) has been increasingly used to enhance host immunity and relieve the inflammatory response of patients undergoing oesophagectomy; however, conclusions across studies remain unclear. We aimed to evaluate the effect of EIN on the clinical and immunological outcomes of patients undergoing oesophagectomy. METHODS Four electronic databases (MEDLINE, Embase, Web of Science and Cochrane Library) were used to search articles in peer-reviewed, English-language journals. The mean difference, relative risk or standard mean difference with 95% confidence interval were calculated. Heterogeneity was assessed by the Cochran’s Q test and I2 statistic combined with the corresponding P-value. The analysis was carried out with RevMan 5.3. RESULTS Six articles were finally included, with a total of 320 patients with oesophageal cancer. The meta-analysis results showed that EIN did not improve clinical outcomes (such as infectious complications, pneumonia, surgical site infection, anastomotic leak and postoperative hospital stay) or immune indices [referring to C-reactive protein, interleukin (IL)-6, IL-8, tumour necrosis factor-α]. Descriptive analysis suggested that EIN also increased the serum concentrations of IgG and the percentage of the B-cell fraction. Thus, its impact on IL-8 and IL-6 remains inconsistent. CONCLUSIONS The early-stage impact of EIN on immunological status in patients undergoing oesophagectomy is still unclear. According to the results of this meta-analysis, whether EIN could improve the clinical outcomes or biological status after oesophagectomy compared to standard enteral nutrition is uncertain. Since the impact of EIN is unclear, current guidelines that strongly advise the use of EIN should be changed, as the utility of EIN is very uncertain. More appropriately powered clinical studies are warranted to confirm its effectiveness.

Efficiency of cognitive control recruitment in the very early stage of multiple sclerosis: a one-year fMRI follow-up study

2008 ◽  
Vol 14 (6) ◽  
pp. 786-792 ◽  
Author(s):  
B Audoin ◽  
F Reuter ◽  
MVA Duong ◽  
I Malikova ◽  
S Confort-Gouny ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Early Stage ◽  
Random Effect ◽  
Analysis Of Covariance ◽  
Standard Pattern ◽  
Group A ◽  
One Year ◽  
Group B ◽  
The Right ◽  
The Impact

Functional magnetic resonance imaging (FMRI) studies have established that patients with multiple sclerosis show stronger activation in the lateral prefrontal cortices (LPFC) than healthy control subjects during effortful cognitive tasks. The aim of the present study was to assess the impact of these activation changes on cognitive performances. In addition to 19 controls, who were tested at a single time-point to define a standard pattern of fMRI activation during the performance of the Paced Auditory Serial Addition Task (PASAT), 13 patients with clinically isolated syndrome underwent a longitudinal fMRI examination while performing the PASAT at the beginning of the study (M0) and one year later (M12). Relative to the M0 scores, PASAT performances improved in eight patients (group A) and either decreased ( n = 4) or remained unchanged ( n = 1) (group B) in five patients at M12. Random effect analyses (SPM2; Wellcome Institute, London, England) were performed to compare intra-group time-related effects on brain activation (paired t-test between M0 and M12), and inter-group differences were also compared between the two groups of patients (analysis of covariance with PASAT performances as the covariate). Relative to group B, group A showed larger increase in activation between M0 and M12 in the right LPFC. In the whole group of patients, interaction analyses showed that the differences in the PASAT scores between M0 and M12 were correlated with the differences in activation observed in the right LPFC. This longitudinal study shows that in patients with early multiple sclerosis, the increased levels of activation in the right LPFC was associated with improved individual working memory and processing speed performances.

Brief Overview and Experience of Visual Evoked Potential of First 67 cases at Referral Neuroscience Hospital in Bangladesh

2020 ◽  
Vol 6 (2) ◽  
pp. 74-77
Author(s):  
Mohammad Enayet Hussain ◽  
Bithi Debnath ◽  
AFM Al Masum Khan ◽  
Md Ferdous Mian ◽  
Md Nahidul Islam ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Optic Neuritis ◽  
Clinical Diagnosis ◽  
Optic Neuropathy ◽  
Cross Sectional Study ◽  
P Value ◽  
Pattern Reversal ◽  
Cross Sectional ◽  
The Mean ◽  
Visual Evoked

Background: The visual evoked potentials (VEP) is a valuable tool to document occult lesions of the central visual channels especially within the optic nerve. Objectives: The purpose of the present study was to observe the findings of first few cases of VEP done in the neurophysiology department of the National Institute of Neurosciences (NINS), Dhaka, Bangladesh. Methodology: This cross-sectional study was conducted in the Department of Neurophysiology at the National Institute of Neurosciences and Hospital, Dhaka, Bangladesh from September 2017 to March 2020. All patients referred to the Neurophysiology Department of NINS for VEP were included. Pattern reversal VEPs were done using standard protocol set by International Federation of Clinical Neurophysiology (IFCN). Results: The mean age of the study population was 30.70 (±12.11) years (6-68 years) with 31 (46.3%) male and 36 (53.7%) female patients. The mean duration of illness was 8.71 (±1.78) months (3 days- 120 months). Most common presenting symptom was blurring of vision (37.3%) and dimness of vision (32.8%). Patterned VEP revealed mixed type (both demyelinating and axonal) of abnormality in most cases [29(43.35)]. The most common clinical diagnosis was multiple sclerosis (29.85%) and optic neuropathy (26.87%). In the clinically suspected cases of multiple sclerosis, optic neuropathy and optic neuritis most of the cases of VEP were abnormal and the p value is 0.04 in optic neuropathy and optic neuritis. Conclusion: The commonest presentation of the patients in this series were blurring of vision and dimness of vision. The most common clinical diagnosis for which VEP was asked for, was optic neuritis and multiple sclerosis. Most abnormalities were of mixed pattern (demyelinating and axonal). Journal of National Institute of Neurosciences Bangladesh, 2020;6(2): 74-77

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