ABSTRACT
While epigenetic mechanisms such as DNA methylation and histone modification are known to be important for gene suppression, relatively little is still understood about the interplay between these systems. The UHRF1 protein can interact with both DNA methylation and repressive chromatin marks, but its primary function in humans has been unclear. To determine what that was, we first established stable UHRF1 knockdowns (KD) in normal, immortalized human fibroblasts using targeting shRNA, since CRISPR knockouts (KO) were lethal. Although these showed a loss of DNA methylation across the whole genome, transcriptional changes were dominated by the activation of genes involved in innate immune signalling, consistent with the presence of viral RNA from retrotransposable elements (REs). We confirmed using mechanistic approaches that 1) REs were demethylated and transcriptionally activated; 2) this was accompanied by activation of interferons and interferon-stimulated genes and 3) the pathway was conserved across other adult cell types. Restoring UHRF1 in either transient or stable KD systems could abrogate RE reactivation and the interferon response. Notably, UHRF1 itself could also re-impose RE suppression independent of DNA methylation, but not if the protein contained point mutations affecting histone 3 with trimethylated lysine 9 (H3K9me3) binding. Our results therefore show for the first time that UHRF1 can act as a key regulator of retrotransposon silencing independent of DNA methylation.
Subject(s)
DNA Methylation , RNA, Viral , Humans , RNA, Viral/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , CCAAT-Enhancer-Binding Proteins/genetics , CCAAT-Enhancer-Binding Proteins/metabolism , Immunity, Innate/genetics , Interferons/metabolismABSTRACT
PURPOSE: Adolescent idiopathic scoliosis (AIS) patients experience structural spinal deformity, but the impact of AIS on physical activity is not widely studied. Reports of physical activity levels between children with AIS and their peers are mixed. This study sought to characterize the relationship between spinal deformity, spinal range of motion, and self-reported physical activity in AIS patients. METHODS: Patients aged 11-21 completed self-reported measures of physical activity using the HSS Pedi-FABS and PROMIS Physical Activity questionnaires. Radiographic measures were obtained from standing biplanar radiographic imaging. Surface topographic (ST) imaging data was obtained using a whole-body ST scanning system. Hierarchical linear regression models analyzed the relationship between physical activity, ST, and radiographic deformity while controlling for age and BMI. RESULTS: 149 patients with AIS (mean age 14.5 ± 2.0 years, mean Cobb angle 39.7° ± 18.9°) were included. In the hierarchical regression predicting physical activity from Cobb angle, no factors were significant predictors of physical activity. When predicting physical activity from ST ROM measurements, age and BMI served as covariates. No covariates or ST ROM measurements were significant predictors of physical activity levels for either activity measure. CONCLUSIONS: Physical activity levels of patients with AIS were not predicted by levels of radiographic deformity or surface topographic range of motion. Although patients may experience severe structural deformity and range of motion limitations, these factors do not appear to be associated with decreased physical activity level utilizing validated patient activity questionnaires. LEVEL OF EVIDENCE: Level II.
Subject(s)
Kyphosis , Scoliosis , Child , Humans , Adolescent , Scoliosis/diagnostic imaging , Kyphosis/diagnostic imaging , Exercise , Self Report , Standing PositionABSTRACT
Acute myocardial infarction (AMI) patients characterize a large proportion of admissions in coronary care unit and their management and risk stratification is of immense importance. Hypomagnesemia is a long-term risk factor for incident of both myocardial infarction and arrhythmia. We assessed whether serum magnesium levels at admission is associated with arrhythmias and in-hospital mortality in patients with acute myocardial infarction (AMI). The aim of the study was to evaluate the prognostic implications of serum magnesium level in patients with acute myocardial infarction. This cross-sectional observational study was conducted in the department of cardiology in Mymensingh Medical College Hospital from October 2017 to March 2019. Total 259 acute myocardial infarction patients were included considering inclusion and exclusion criteria. The sample population was divided into two groups: Group-I: Patients with acute myocardial infarction with serum magnesium ≥1.82mg/dl. Group-II: Patients with acute myocardial infarction with serum magnesium <1.82mg/dl. Serum magnesium level was measured on admission, and the incidence of in-hospital major cardiac events was assessed. In this study mean serum magnesium level of Group-I, Group-II were 2.21±0.14mg/dl, 1.60±0.15mg/dl respectively. It was statistically significant (p<0.05). In-hospital outcomes of the study group revealed that low risk group patients were uneventful outcome during hospitalization period, they had no any complication. In Group-I patient, 9(4.8%) were developed arrhythmias, 26(13.9%) were developed heart failure, 9(4.8%) were developed cardiogenic shock and 3(1.6%) were died and in Group-II patient, 44(61.10%) developed arrhythmias, 9(12.50%) were developed heart failure, 7(9.7%) were developed cardiogenic shock and 12(16.7%) were died out of them which was statistically significant (p<0.05). Mean duration of hospital stay of the study population according serum magnesium level was in Group-I, 4.27±0.68 days, in Group-II, 5.84±1.05 days which was statistically significant (p<0.05). In conclusion patient with serum magnesium level less than 1.82mg/dl increased the risk of in-hospital arrhythmia and death.
Subject(s)
Heart Failure , Myocardial Infarction , Humans , Shock, Cardiogenic/complications , Magnesium , Cross-Sectional Studies , Myocardial Infarction/complications , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/complications , Heart Failure/complications , HospitalsSubject(s)
Endocarditis, Bacterial , Endocarditis , Heart Valve Diseases , Myocardial Infarction , ST Elevation Myocardial Infarction , Humans , Shock, Cardiogenic/diagnosis , Shock, Cardiogenic/etiology , Shock, Cardiogenic/therapy , ST Elevation Myocardial Infarction/complications , ST Elevation Myocardial Infarction/diagnosis , Myocardial Infarction/complications , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/diagnostic imaging , Endocarditis/diagnosis , Endocarditis/diagnostic imaging , Treatment OutcomeABSTRACT
BACKGROUND: The COVID-19 pandemic has significantly impacted family caregivers of adults with intellectual and developmental disabilities (IDD). This study evaluated a virtual course for family caregivers from across Canada, focused on supporting the mental health and well-being of adults with IDD and their families. The evaluation examined the feasibility and acceptability of the course, as well as the impact of the intervention on participants' overall health and well-being. METHODS: The 6-week virtual course, informed by a parallel Extension for Community Healthcare Outcomes (ECHO) course for service providers, combined didactic instruction with applied activities. A total of 126 family caregiver course participants consented to be part of the research evaluation delivered over three cycles between October 2020 and April 2021. Attendance was measured at each weekly session. Satisfaction was assessed weekly and post-program. Learning, self-efficacy, and well-being were assessed pre- and post-course, and again at follow-up (8 weeks post-course). Mixed-effects models assessed changes between and within individuals across time. RESULTS: Participants had consistent attendance, low-dropout rates, and reported high satisfaction, with 93% of participants reporting that their expectations for the course were met. Compared with pre-course, participants reported improved self-efficacy and well-being post-course, which were maintained at follow-up. CONCLUSIONS: An interactive and applied virtual education course delivered to a large group of family caregivers of adults with IDD was both feasible and acceptable. It positively impacted participants' well-being by offering much needed mental health support and creating a peer-led community of practice.
Subject(s)
COVID-19 , Caregivers , Adult , Caregivers/psychology , Child , Developmental Disabilities/psychology , Developmental Disabilities/therapy , Humans , Mental Health , PandemicsABSTRACT
Coronary artery disease (CAD) is the leading cause of death in developed and developing countries. Associated co-morbidities like diabetes, hypertension and obesity are making the situation worse. WHO enlisted obesity as an epidemic which also affects a great number of young population. Some recent studies showed the presence of an apparent paradoxical relationship between obesity and cardiovascular prognosis in certain subsets of patents. As BMI is an established marker of obesity; an attempt has been made to assess relationship between BMI and angiographic severity of coronary artery disease in Acute Coronary Syndrome (ACS) patients of Bangladeshi origin. To assess the association between body mass index and angiographic severity of coronary artery disease in patients with acute coronary syndrome; this cross sectional analytical study was conducted in the Department of Cardiology, Mymensingh Medical College Hospital (MMCH) and Bangabandhu Sheikh Mujib Medical University (BSMMU) from December 2016 to February 2018 among purposively selected 65 patients. Relevant ethical issues were taken into consideration. Coronary angiogram was done in the same index hospitalization period. After coronary angiogram performed patients were grouped into two groups according to their BMI. Patients with BMI <25kg/m² as Group I and those ≥25kg/m² as Group II. Angiographic severity of coronary artery disease was assessed by vessel score and Syntax score. Mean age of Group I was 54.45±10.42 years, while in Group II it was 50.76±8.89 years reflecting the early presentation of higher BMI patients. Male to female ratio was 12:1. Mean BMI of Group I and Group II was 22.56±1.59 and 28.67±2.64 respectively. In Group I, 10(25.0%) had single vessel lesion, 15(37.5%) had double vessel lesion and 14(35.0%) had triple vessel lesion, while in Group II, 6(24.0%) had single vessel lesion, 12(48.0%) had double vessel lesion and 5(20.0%) had triple vessel lesion. Mean Syntax score of Group I and Group II was 13.18±8.45 and 10.42±7.14 respectively. Patients in the increasing BMI class had a higher prevalence of diabetes, hypertension and dyslipidaemia. A negative correlation was observed between BMI and angiographic severity (Vessel score, Syntax score and HRCA e.g. LM disease) of CAD indicating that patients with higher BMI had a lower coronary artery disease (CAD) severity than their normal BMI counterparts. Patients with high BMI have a lower CAD severity than usually expected. After adjustment for co-morbidities, BMI was not found as an independent predictor of severity of coronary artery disease.
Subject(s)
Acute Coronary Syndrome , Coronary Artery Disease , Acute Coronary Syndrome/complications , Acute Coronary Syndrome/diagnostic imaging , Acute Coronary Syndrome/epidemiology , Adult , Body Mass Index , Coronary Angiography , Coronary Artery Disease/complications , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Risk Factors , Severity of Illness IndexABSTRACT
PURPOSE: Molar-incisor hypomineralization (MIH) is a qualitative developmental defect of enamel that affects first permanent molars with or without affecting permanent incisors. We aimed to carry out a quantitative proteomics-based study to compare and evaluate proteins in sound and MIH-affected enamel. MATERIALS AND METHODS: Ten blocks each of the MIH-affected enamel and sound enamel were processed and prepared for LC-MS/MS analysis. Label-free quantitation was carried out to evaluate the differentially expressed proteins in the two groups of samples. RESULTS: A significant increase in the number of proteins in MIH-affected enamel (50.3 ± 29.6) was observed compared to the sound enamel (21.4 ± 3.2). While proteins like collagens, α1-anti-trypsin, kallikrein-4 (KLK4), matrix metalloprotease-20 (MMP-20), alpha-2-macroglobulin, and alpha-2-HS-glycoprotein were upregulated in sound enamel, there was over-expression of albumin, calcium-binding proteins, anti-thrombin III, and dentin sialophosphoprotein (DSPP), along with proteins implicated in stress response and inflammatory processes in MIH. CONCLUSION: We propose that altered biomechanical properties of the enamel in MIH samples arise due to (i) down-regulation of proteins contributing to collagen biosynthesis and fibril formation; (ii) an overall imbalance in required levels of proteases (KLK4 and MMP-20) and anti-proteases (anti-thrombin-III which inhibits KLK-4), essential for optimal mineralization; (iii) very low levels of alpha-2-macroglobulin with important consequences in enamel mineralization and amelogenesis; and (iv) increased albumin in MIH, preventing proper growth of hydroxyapatite crystals. Increased inflammatory component was also seen in MIH; however, whether inflammation is a cause or consequence of the poor mineralization process needs to be assessed.
Subject(s)
Dental Enamel Hypoplasia , Proteomics , Chromatography, Liquid , Humans , Incisor , Prevalence , Tandem Mass SpectrometrySubject(s)
Cataract , Eye Foreign Bodies , Eye Injuries, Penetrating , Cataract/etiology , Eye Foreign Bodies/complications , Eye Foreign Bodies/diagnostic imaging , Eye Foreign Bodies/surgery , Eye Injuries, Penetrating/complications , Eye Injuries, Penetrating/diagnostic imaging , Eye Injuries, Penetrating/surgery , HumansABSTRACT
Background Myocardial revascularization surgery has shown better long term survival expectancy compared to medical therapy in patient with impaired left ventricular function. Objective To evaluate the change in ejection fraction after 90 days in patients who underwent coronary artery bypass surgery and had preoperative left ventricular ejection fraction of less than and equal to 45% in a single cardiac center of Nepal over the period of 2 years. Method Out of 82 eligible patients during 2 years, 3 patients expired in immediate postoperatively and 24 patients had loss of 90 days' follow up. So, they were excluded from the study. Total 55 patients were taken for the study for whom statistical analysis was done to compare preoperative ejection fraction with post-operative 90 days' ejection fraction. Result Single vessel disease was present in 2(3.6%) patients, double vessel disease in 7(12.7%) patients and triple vessel disease in 46(83.6%) of the patients. In 2(3.6%) patients 2 grafts, in 18(32.7%) patients 3 grafts, in 33(60%) patients 4 grafts and in 2(3.6%) patients 5 grafts were placed for revascularization. The mean left ventricular EF in preoperative patients was 37.12±5.69% which improved to 45.80±10.00% in postoperative follow up at 90 days which was statistically significant (p=0.000). Conclusion Surgical revascularization of myocardium in preoperatively impaired left ventricular function patients helps improve left ventricular ejection fraction postoperatively. So we suggest surgical revascularization in patient with low ejection fraction for improvement of myocardial function. Hence improve survival rate in these patients.
Subject(s)
Ventricular Dysfunction, Left , Ventricular Function, Left , Coronary Artery Bypass , Humans , Stroke Volume , Survival Rate , Treatment Outcome , Ventricular Dysfunction, Left/surgeryABSTRACT
It has been widely reported that vitamin D deficiency is associated with Coronary heart disease (CHD), especially acute Myocardial infarction (MI). Many factors are responsible for reduced Left ventricular ejection fraction (LVEF) and acute Left ventricular fraction (LVF) after acute MI. This cross sectional descriptive type of study was conducted in the Cardiology department of Mymensingh Medical College Hospital from October 2017 to March 2019 to investigate the relationship of plasma vitamin D with LVEF in patients with first attack of acute MI. Total 185 patients of first attack of acute MI were included considering inclusion and exclusion criteria. Fasting blood samples were analyzed for plasma vitamin D level. Sample population were grouped at first into two, normal and low vitamin D level, taking 30ng/ml as cut-off value, low vitamin D level is further subdivided into insufficiency (21-29ng/ml), deficiency (10-20ng/ml) and severe deficiency (<10ng/ml). LVEF among the patients was observed. LVEF was found 49.88±8.58% patients having normal vitamin D level (>30ng/ml), 47.60±8.24% of patients having vitamin D insufficiency (21-29ng/ml), 44.38±8.12% of patients having vitamin D deficiency (10-20ng/ml) and 40.61±8.64% patients having severe vitamin D deficiency (<10ng/ml), which was statistically significant (p<0.05). So, low plasma vitamin D level is associated with reduced LVEF in patients hospitalized with first attack of acute MI.
Subject(s)
Myocardial Infarction , Ventricular Dysfunction, Left , Cross-Sectional Studies , Humans , Stroke Volume , Ventricular Function, Left , Vitamin D , VitaminsABSTRACT
Acute occlusive thrombosis of the coronary artery is the principal cause of myocardial infarction where platelets play an important role. Large size platelets, easily measured by mean platelets volume (MPV) are thrombogenic and commonly seen after ST-segment elevation myocardial infarction (STEMI). ST segment resolution has been shown as a simple non-invasive marker that reflects both epicardial and myocardial reperfusion following thrombolysis. The present study intended to investigate whether MPV on admission correlated with ST segment resolution following thrombolysis in STEMI patient. This cross-sectional analytical study was conducted in the department of cardiology, Mymensingh Medical College and Hospital (MMCH), Mymensingh, Bangladesh from December, 2016 to June, 2018. Total 284 patients with first attack of STEMI were included after considering inclusion and exclusion criteria. Sample population was divided into two groups, Group I - Patients with successful ST segment resolution (≥50%). Group II - Patients with impaired ST segment resolution (<50%). MPV on admission was estimated during estimation of Complete Blood Count (CBC) by Automated Haematology Analyzer & compared between two groups. Successful ST segment resolution (≥50%) was seen in 67% of patients after thrombolysis. Admission MPV was higher in patients with impaired ST segment resolution (<50%) group than patients with ≥50% ST-segment resolution group (12.42±0.89fl vs.10.35±0.77fl respectively, p=0.001). Statistically significant strong negative correlation between MPV and ST segment resolution percentage (r = -0.742, p=0.001) suggesting that the higher the level of MPV, the lower the ST segment resolution percentage in first attack of STEMI patients. Multivariate regression analysis found MPV level on admission as an independent predictor of ST segment resolution. The study concluded that high MPV on admission correlate with impaired ST segment resolution following thrombolysis in STEMI patients.
Subject(s)
Mean Platelet Volume , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Bangladesh , Cross-Sectional Studies , Humans , Thrombolytic Therapy , Treatment OutcomeABSTRACT
Malignant glioma is a fatal brain tumor whose pathological progression is closely associated with glycolytic reprogramming, leading to the high expression of monocarboxylate transporter 1 (MCT1) and its ancillary protein, cluster of differentiation 147 (CD147) for enhancing lactate efflux. In particular, malignant glioma cells (GMs) release tremendous number of exosomes, nanovesicles of 30 to 200 nm in size, promoting tumor progression by the transport of pro-oncogenic molecules to neighboring cells. In the present study, we found that hypoxia-induced malignant GMs strongly enhanced MCT1 and CD147 expression, playing a crucial role in promoting calcium-dependent exosome release. Furthermore, it was first identified that hypoxic GMs-derived exosomes contained significantly high levels of MCT1 and CD147, which could be quantitatively detected by noninvasive localized surface plasmon resonance and atomic force microscopy biosensors, demonstrating that they could be precise surrogate biomarkers for tracking parent GMs' metabolic reprogramming and malignant progression as liquid biopsies.
Subject(s)
Brain Neoplasms , Glioma , Symporters , Basigin/metabolism , Brain Neoplasms/pathology , Glioma/pathology , Humans , Monocarboxylic Acid Transporters/metabolism , Symporters/metabolismABSTRACT
BACKGROUND & OBJECTIVES: Dengue and chikungunya are two mosquito-borne viral diseases transmitted by Aedes mosquito species and are a great public health concern in India. The present study was aimed to check the influence of antagonistic crustaceans, especially Mesocyclops aspericornis and Daphnia magna on Ae. aegypti L. mosquito population. METHOD: Variable ratios of these crustaceans (Aedes: Mesocyclops: Daphnia) against Ae. aegypti larvae were tested by putting them in plastic beakers having dechlorinated water along with yeast stock solution provided as food, and kept in BOD incubator at a temperature of 26 ±1°C. RESULTS: Out of all tested concentrations, 1:1:3 where the number of D. magna was thrice the number of Mesocyclops and Aedes; larvae showed a significant delay of 5-6 days in the developmental period. Maximum reduction in the emergence of females was recorded in the ratio 1:1:3, i.e. only 6.5 ± 0.47 females emerged when Daphnia used thrice the number of Aedes larvae. Body size of both males and females emerged from treated sets was found to be significantly reduced. The longevity of adults was also reduced from 8-17 days to 5-8 days in the case of males and from 14-26 days to 5-9 days in females. INTERPRETATION & CONCLUSION: Among variable ratios tested under laboratory conditions, 1:1:2 and 1:1:3 ratios were found to be the effective ratios that greatly reduced the development duration, survivorship of larvae, and the number of larvae emerging into adulthood. Thus, antagonistic crustaceans specifically Mesocyclops and Daphnia can be used as biocontrol agents for the sustainable control of container breeding mosquitoes.