Microglia proliferation plays distinct roles in acquired epilepsy depending on disease stages

Epilepsia ◽  
2021 ◽  
Author(s):  
Martina Di Nunzio ◽  
Rossella Di Sapia ◽  
Diletta Sorrentino ◽  
Valentina Kebede ◽  
Milica Cerovic ◽  
...  
Keyword(s):  
Acquired Epilepsy ◽  
Disease Stages

Invasive therapeutic options in truncal varicosity of the great saphenous vein

VASA ◽  
2006 ◽  
Vol 35 (3) ◽  
pp. 157-166 ◽  
Author(s):  
Hach-Wunderle ◽  
Hach
Keyword(s):  
Minimally Invasive ◽  
Saphenous Vein ◽  
Venous Insufficiency ◽  
Great Saphenous Vein ◽  
Varicose Veins ◽  
Venous Pressure ◽  
Stage Iii ◽  
High Ligation ◽  
Surgical Trauma ◽  
Disease Stages

It is known from current pathophysiology that disease stages I and II of truncal varicosity of the great saphenous vein do not cause changes in venous pressure on dynamic phlebodynamometry. This is possibly also the case for mild cases of the disease in stage III. In pronounced cases of stage III and all cases of stage IV, however, venous hypertension occurs which triggers the symptoms of secondary deep venous insufficiency and all the complications of chronic venous insufficiency. From these facts the therapeutic consequence is inferred that in stages I and II and perhaps also in very mild cases of stage III disease, it is enough "merely" to remove varicose veins without expecting there to be any other serious complications in the patient’s further life caused by the varicosity. Recurrence rates are not included in this analysis. In marked cases of disease stages III and IV of the great saphenous vein, however, secondary deep venous insufficiency is to be expected sooner or later. The classical operation with saphenofemoral high ligation ("crossectomy") and stripping strictly adheres to the recognized pathophysiologic principles. It also takes into account in the greatest detail aspects of minimally invasive surgery and esthetics. In the past few years, developments have been advanced to further minimize surgical trauma and to replace the stripping maneuver using occlusion of the trunk vein which is left in place. Obliteration of the vessel is subsequently performed via transmission of energy through an inserted catheter. This includes the techniques of radiofrequency ablation and endovenous laser treatment. High ligation is not performed as a matter of principle. In a similar way, sclerotherapy using microfoam is minimally invasive in character. All these procedures may be indicated for disease stages I and II, and with reservations also in mild forms of stage III disease. Perhaps high ligation previously constituted overtreatment in some cases. Targeted studies are still needed to prove whether secondary deep venous insufficiency can be avoided in advanced stages of varicose vein disease without high ligation and thus without exclusion of the whole recirculation circuit.

scholarly journals In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kolja Becker ◽  
Holger Klein ◽  
Eric Simon ◽  
Coralie Viollet ◽  
Christian Haslinger ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Rna Sequencing ◽  
Molecular Mechanisms ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Expression Profiles ◽  
Cell Types ◽  
Sequencing Data ◽  
Disease Stages ◽  
Post Transcriptional Regulation

AbstractDiabetic Retinopathy (DR) is among the major global causes for vision loss. With the rise in diabetes prevalence, an increase in DR incidence is expected. Current understanding of both the molecular etiology and pathways involved in the initiation and progression of DR is limited. Via RNA-Sequencing, we analyzed mRNA and miRNA expression profiles of 80 human post-mortem retinal samples from 43 patients diagnosed with various stages of DR. We found differentially expressed transcripts to be predominantly associated with late stage DR and pathways such as hippo and gap junction signaling. A multivariate regression model identified transcripts with progressive changes throughout disease stages, which in turn displayed significant overlap with sphingolipid and cGMP–PKG signaling. Combined analysis of miRNA and mRNA expression further uncovered disease-relevant miRNA/mRNA associations as potential mechanisms of post-transcriptional regulation. Finally, integrating human retinal single cell RNA-Sequencing data revealed a continuous loss of retinal ganglion cells, and Müller cell mediated changes in histidine and β-alanine signaling. While previously considered primarily a vascular disease, attention in DR has shifted to additional mechanisms and cell-types. Our findings offer an unprecedented and unbiased insight into molecular pathways and cell-specific changes in the development of DR, and provide potential avenues for future therapeutic intervention.

scholarly journals The Role of Serum 5-HIAA as a Predictor of Progression and an Alternative to 24-h Urine 5-HIAA in Well-Differentiated Neuroendocrine Neoplasms

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 76
Author(s):  
Maria Wedin ◽  
Sagar Mehta ◽  
Jenny Angerås-Kraftling ◽  
Göran Wallin ◽  
Kosmas Daskalakis
Keyword(s):  
Liver Tumor ◽  
Disease Surveillance ◽  
Tumor Burden ◽  
Neuroendocrine Neoplasms ◽  
Mri Imaging ◽  
Exact Test ◽  
Recist 1.1 ◽  
Tumor Involvement ◽  
Well Differentiated ◽  
Disease Stages

Our aim was to investigate the clinical utility of serum 5HIAA for disease surveillance and diagnostic purposes in a cohort of patients with well-differentiated neuroendocrine neoplasms (WD-NENs). Forty-eight patients with WD-NENs and concurrent serum and urinary 5HIAA testing, as well as CT/MRI imaging, were included. Analysis of matching-pairs did not reveal any association between RECIST 1.1 responses and changes in serum 5HIAA levels (p = 0.673). In addition, no correlation was evident between RECIST 1.1 responses and >10%, >25% or >50% changes in serum 5HIAA levels (Fisher’s exact test p = 0.380, p > 0.999, and p > 0.999, respectively). The presence of liver metastases and extensive liver tumor involvement were associated with higher serum 5HIAA levels (p = 0.045 and p = 0.041, respectively). We also confirmed a strong linear correlation between the measurements of serum and urine 5HIAA (n = 24, r = 0.791, p < 0.0001). The concordance rate of serum and urinary 5HIAA positivity at standardized laboratory cut-offs was 75%. In patients with normal renal function tests, the concordance between the two methods was as high as 89%, and a sensitivity and specificity of 80% and 88.9%, respectively, was evident (Cohen’s kappa coefficient = 0.685). In conclusion, serum 5HIAA performs well compared to urinary testing for diagnostic purposes, mainly in advanced disease stages, and corresponds well to liver tumor burden. However, it is not adequate to predict tumor progression.

scholarly journals High-sensitive cardiac troponin for the diagnosis of acute myocardial infarction in different chronic kidney disease stages

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Daijin Ren ◽  
Tianlun Huang ◽  
Xin Liu ◽  
Gaosi Xu
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Cardiac Troponin ◽  
Optimal Cutoff ◽  
Cutoff Values ◽  
Optimal Value ◽  
Disease Stages

Abstract Background Chronic kidney disease (CKD) are associated with acute myocardial infarction (AMI). High-sensitive cardiac troponin (hs-cTn) has been evidenced to enhance the early diagnostic accuracy of AMI, but hs-cTn levels are often chronically elevated in CKD patients, which reduces their diagnostic utility. The aim of this study was to derive optimal cutoff-values of hs-cTn levels in patients with CKD and suspected AMI. Methods In this retrospective paper, a total of 3295 patients with chest pain (2758 in AMI group and 537 in Non-AMI group) were recruited, of whom 23.1% were had an estimated glomerular filtration rate (eGFR) of < 60 mL min−1 (1.73 m2)−1. Hs-cTnI values were measured at presentation. Results AMI was diagnosed in 83.7% of all patients. The optimal value of hs-TnI in diagnosing AMI was 1.15 ng mL−1, which were higher in males than females comparing different cutoff-values of subgroups divided by age, gender and renal function, and which increased monotonically with decreasing of eGFR because in patients with CKD without AMI, the correlation between hs-cTnI and renal function is low but significant (r2 = 0.067, P < 0.001). Conclusions Different optimal cutoff-values of hs-cTnI in the diagnosis of AMI in patients with CKD were helpful to the clinical diagnosis of AMI in various populations and were higher in males than females, but which was needed to be validated by multicenter randomized controlled clinical studies in the future.

scholarly journals Differences in physical symptoms between those with and without kidney disease: a comparative study across disease stages in a UK population

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Thomas J. Wilkinson ◽  
Daniel G. D. Nixon ◽  
Jared Palmer ◽  
Courtney J. Lightfoot ◽  
Alice C. Smith
Keyword(s):  
Kidney Disease ◽  
Early Stage ◽  
Symptom Burden ◽  
Final Analysis ◽  
Physical Symptoms ◽  
Disease Trajectory ◽  
High Prevalence ◽  
Comparative Group ◽  
The Difference ◽  
Disease Stages

Abstract Background Those living with kidney disease (KD) report extensive symptom burden. However, research into how symptoms change across stages is limited. The aims of this study were to 1) describe symptom burden across disease trajectory, and 2) to explore whether symptom burden is unique to KD when compared to a non-KD population. Methods Participants aged > 18 years with a known diagnosis of KD (including haemodialysis (HD) and peritoneal dialysis (PD)) and with a kidney transplant) completed the Leicester Kidney Symptom Questionnaire (KSQ). A non-KD group was recruited as a comparative group. Multinominal logistic regression modelling was used to test the difference in likelihood of those with KD reporting each symptom. Results In total, 2279 participants were included in the final analysis (age 56.0 (17.8) years, 48% male). The main findings can be summarised as: 1) the number of symptoms increases as KD severity progresses; 2) those with early stage KD have a comparable number of symptoms to those without KD; 3) apart from those receiving PD, the most frequently reported symptom across every other group, including the non-KD group, was ‘feeling tired’; and 4) being female independently increased the likelihood of reporting more symptoms. Conclusions Our findings have important implications for patients with KD. We have shown that high symptom burden is prevalent across the spectrum of disease, and present novel data on symptoms experienced in those without KD. Symptoms requiring the most immediate attention given their high prevalence may include pain and fatigue. Trial registration The study was registered prospectively as ISRCTN11596292.

Study on different pathogenic factors in different disease stages of patients with Wilson disease

2021 ◽  
Author(s):  
Xiang-xue Zhou ◽  
Xia Xiao ◽  
Haoling Qin ◽  
Dingbang Chen ◽  
Chao Wu
Keyword(s):  
Wilson Disease ◽  
Pathogenic Factors ◽  
Disease Stages

scholarly journals Clock/Sleep-Dependent Learning and Memory in Male 3xTg-AD Mice at Advanced Disease Stages and Extrinsic Effects of Huprine X and the Novel Multitarget Agent AVCRI104P3

2021 ◽  
Vol 11 (4) ◽  
pp. 426
Author(s):  
Lydia Giménez-Llort ◽  
Mikel Santana-Santana ◽  
Míriam Ratia ◽  
Belén Pérez ◽  
Pelayo Camps ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Advanced Disease ◽  
Active Phase ◽  
Task Demands ◽  
The Novel ◽  
Training Time ◽  
Drug Effectiveness ◽  
Dependent Learning ◽  
Disease Stages

A new hypothesis highlights sleep-dependent learning/memory consolidation and regards the sleep-wake cycle as a modulator of β-amyloid and tau Alzheimer’s disease (AD) pathologies. Sundowning behavior is a common neuropsychiatric symptom (NPS) associated with dementia. Sleep fragmentation resulting from disturbances in sleep and circadian rhythms in AD may have important consequences on memory processes and exacerbate the other AD-NPS. The present work studied the effect of training time schedules on 12-month-old male 3xTg-AD mice modeling advanced disease stages. Their performance in two paradigms of the Morris water maze for spatial-reference and visual-perceptual learning and memory were found impaired at midday, after 4 h of non-active phase. In contrast, early-morning trained littermates, slowing down from their active phase, exhibited better performance and used goal-directed strategies and non-search navigation described for normal aging. The novel multitarget anticholinesterasic compound AVCRI104P3 (0.6 µmol·kg−1, 21 days i.p.) exerted stronger cognitive benefits than its in vitro equipotent dose of AChEI huprine X (0.12 μmol·kg−1, 21 days i.p.). Both compounds showed streamlined drug effectiveness, independently of the schedule. Their effects on anxiety-like behaviors were moderate. The results open a question of how time schedules modulate the capacity to respond to task demands and to assess/elucidate new drug effectiveness.

scholarly journals Gynecologic Malignancies in Children and Adolescents: How Common is the Uncommon?

2021 ◽  
Vol 10 (4) ◽  
pp. 722
Author(s):  
Christoph Wohlmuth ◽  
Iris Wohlmuth-Wieser
Keyword(s):  
Pediatric Population ◽  
Age Groups ◽  
Germ Cell Tumors ◽  
Population Based ◽  
Prognostic Indicators ◽  
Gynecologic Malignancies ◽  
Kaplan Meier ◽  
Disease Stages ◽  
Malignant Germ Cell Tumors ◽  
Vaginal Neoplasms

The aim of this study is to assess the projected incidence and prognostic indicators of gynecologic malignancies in the pediatric population. In this population-based retrospective cohort study, girls ≤18 years with ovarian, uterine, cervical, vaginal and vulvar malignancies diagnosed between 2000 and 2016 were identified from the Surveillance, Epidemiology and End Results (SEER)-18 registry. The Kaplan–Meier method was used to analyze overall survival (OS). The age-adjusted annual incidence of gynecologic malignancies was 6.7 per 1,000,000 females, with neoplasms of the ovary accounting for 87.5%, vagina 4.5%, cervix 3.9%, uterus 2.5% and vulva 1.6% of all gynecologic malignancies. Malignant germ-cell tumors represented the most common ovarian neoplasm, with an increased incidence in children from 5–18 years. Although certain subtypes were associated with advanced disease stages, the 10-year OS rate was 96.0%. Sarcomas accounted for the majority of vaginal, cervical, uterine and vulvar malignancies. The majority of vaginal neoplasms were observed in girls between 0–4 years, and the 10-year OS rate was 86.1%. Overall, gynecologic malignancies accounted for 4.2% of all malignancies in girls aged 0–18 years and the histologic subtypes and prognosis differed significantly from patients in older age groups.

Detecting Sensitive Mobility Features for Parkinson's Disease Stages Via Machine Learning

2021 ◽  
Author(s):  
Anat Mirelman ◽  
Mor Ben Or Frank ◽  
Michal Melamed ◽  
Lena Granovsky ◽  
Alice Nieuwboer ◽  
...  
Keyword(s):  
Machine Learning ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Stages
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