scholarly journals Immune defects and cardiovascular risk in X chromosome monosomy mosaicism mediated by loss of chromosome Y. A risk factor for SARS-CoV-2 vulnerability in elderly men?

2020 ◽  
Author(s):  
Luis A. Pérez-Jurado ◽  
Alejandro Cáceres ◽  
Tonu Esko ◽  
Juan R. González
Keyword(s):  
Cardiovascular Risk ◽  
X Chromosome ◽  
Large Scale ◽  
Case Fatality ◽  
Peripheral Blood Cell ◽  
Coagulation Activity ◽  
Chromosome Y ◽  
Immune System Dysfunction ◽  
Cell Counts ◽  
Multiple Biomarkers

AbstractThe ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) has an estimated overall case fatality ratio of 1.38% in China, being 53% higher in males and increasing exponentially with age. Mosaicism for X chromosome monosomy (XCM) shows a similar increase in aging population mostly driven by loss of chromosome Y in males (LOY), and is associated with a raise in all-cause mortality. Using comparative transcriptomic data, we have defined that XCM/LOY is associated with abnormal peripheral blood cell counts with decreased progenitor cells and multiple biomarkers of immune system dysfunction, pro-coagulation activity and increased cardiovascular risk. Several differentially down-regulated genes in XCM/LOY individuals are involved in the initial immune response to SARS-CoV-2 (OR of enrichment=7.23, p=1.5×10−7), mainly interferon-induced genes that code for inhibitors of viral processes. Thus, our data suggest that XCM mosaicism underlies at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential relevance for modulating prognosis and therapeutic response, we propose that evaluation of LOY and XCM by currently established methods should be implemented as biomarkers in infected patients, including currently ongoing clinical trials with different medications and vaccines for COVID-19. Testing for LOY/XCM at large scale among elderly people may also be helpful to identify still unexposed people who may be especially vulnerable to severe Covid-19 disease.

scholarly journals A Positive Association of Overactivated Immunity with Metabolic Syndrome Risk and Mitigation of Its Association by a Plant-Based Diet and Physical Activity in a Large Cohort Study

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2308
Author(s):  
Sunmin Park ◽  
Ting Zhang
Keyword(s):  
Physical Activity ◽  
Metabolic Syndrome ◽  
Cohort Study ◽  
Large Scale ◽  
Smoking Status ◽  
Characteristic Curve ◽  
Daily Intake ◽  
Positive Association ◽  
Cell Counts ◽  
High Hba1c

The association between immunity and metabolic syndrome (MetS) has been studied, but its interaction with lifestyles remains unclear. We studied their association and interactions with lifestyles in 40,768 adults aged over 40 years from a large-scale, hospital-based cohort study collected during 2010–2013. White blood cell counts (WBC) and serum C-reactive protein concentrations (CRP) were used as indexes of immune status. The participants were categorized into four groups by the cutoff points of 6.2 × 109/L WBC(L-WBC) and <0.5 mg/dL CRP(L-CRP): L-WBC+L-CRP(n = 25,604), H-WBC+L-CRP(n = 13,880), L-WBC+H-CRP(n = 464), and H-WBC+H-CRP(n = 820). The participants in the H-WBC+L-CRP were younger and had higher numbers of males than the L-WBC+L-CRP. MetS risk was higher by 1.75- and 1.86-fold in the H-WBC+L-CRP and H-WBC+H-CRP, respectively, than the L-WBC+L-CRP. MetS components, including plasma glucose and triglyceride concentrations, and SBP were elevated in H-WBC+L-CRP and H-WBC+H-CRP compared with L-WBC+L-CR+P. The risk of hyperglycemia and high HbA1c was the highest in the H-WBC+H-CRP among all groups. Areas of WBC counts and serum CRP concentrations were 0.637 and 0.672, respectively, in the receiver operating characteristic curve. Daily intake of energy, carbohydrate, protein, and fat was not significantly different in the groups based on WBC counts and CRP. However, a plant-based diet (PBD), physical activity, and non-smoking were related to lowering WBC counts and CRP, but a Western-style diet was linked to elevating CRP. A high PBD intake and smoking status interacted with immunity to influence MetS risk: a low PBD and current smoking were associated with a higher MetS risk in the H-WBC+H-CRP. In conclusion, overactivated immunity determined by CRP and WBC was associated with MetS risk. Behavior modification with PBD and physical activity might be related to immunity regulation.

Lipid-lowering treatment in hypercholesterolaemic patients: the CEPHEUS Pan-Asian survey

2011 ◽  
Vol 19 (4) ◽  
pp. 781-794 ◽  
Author(s):  
Jeong Euy Park ◽  
Chern-En Chiang ◽  
Muhammad Munawar ◽  
Gia Khai Pham ◽  
Apichard Sukonthasarn ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
High Risk ◽  
Large Scale ◽  
Goal Attainment ◽  
Density Lipoprotein ◽  
Final Analysis ◽  
Relevant Information ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lipid Lowering Drugs

Background: Treatment of hypercholesterolaemia in Asia is rarely evaluated on a large scale, and data on treatment outcome are scarce. The Pan-Asian CEPHEUS study aimed to assess low-density lipoprotein cholesterol (LDL-C) goal attainment among patients on lipid-lowering therapy. Methods: This survey was conducted in eight Asian countries. Hypercholesterolaemic patients aged ≥18 years who had been on lipid-lowering treatment for ≥3 months (stable medication for ≥6 weeks) were recruited, and lipid concentrations were measured. Demographic and other clinically relevant information were collected, and the cardiovascular risk of each patient was determined. Definitions and criteria set by the updated 2004 National Cholesterol Education Program guidelines were applied. Results: In this survey, 501 physicians enrolled 8064 patients, of whom 7281 were included in the final analysis. The mean age was 61.0 years, 44.4% were female, and 85.1% were on statin monotherapy. LDL-C goal attainment was reported in 49.1% of patients overall, including 51.2% of primary and 48.7% of secondary prevention patients, and 36.6% of patients with familial hypercholesterolaemia. The LDL-C goal was attained in 75.4% of moderate risk, 55.4% of high risk, and only 34.9% of very high-risk patients. Goal attainment was directly related to age and inversely related to cardiovascular risk and baseline LDL-C. Conclusion: A large proportion of Asian hypercholesterolaemic patients on lipid-lowering drugs are not at recommended LDL-C levels and remain at risk for cardiovascular disease. Given the proven efficacy of lipid-lowering drugs in the reduction of LDL-C, there is room for further optimization of treatments to maximize benefits and improve outcomes.

Evaluation of Congenital Neutropenic Disorders by in Vitro Bone Marrow Culture

PEDIATRICS ◽  
1977 ◽  
Vol 59 (5) ◽  
pp. 739-748
Author(s):  
Peter M. Falk ◽  
Kenneth Rich ◽  
Stephen Feig ◽  
E. Richard Stiehm ◽  
David W. Golde ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Severe Disease ◽  
Stem Cell Differentiation ◽  
Peripheral Blood Cell ◽  
Clinical Expression ◽  
Essentially Normal ◽  
Cell Counts

The congenital neutropenias are a heterogeneous group of diseases whose etiology and pathogenesis are largely unknown. We studied nine neutropenic patients from seven families. Evaluation included peripheral blood cell and differential cell counts, epinephrine and typhoid vaccine stimulation studies, Rebuck skin windows, and bone marrow aspirations for morphological assessment and for in vitro culture in liquid suspension and in agar plates. Parallel cultures were set up with and without colony-stimulating activity (CSA), and peripheral leukocytes were assayed for cellular production of CSA. Patients were initially classified on the basis of their clinical course: benign, mild, moderately severe, or severe disease. One patient in the moderately severe group had an immunoglobulin disorder. Morphologically normal mature granulocytes were seen in bone marrow aspirates of two patients, and maturational defects of varying degree were seen in the remaining seven. Colony formation in agar was markedly reduced below normal in three of seven, moderately reduced in two of seven, and greater than normal in two patients. Colonies in six of seven patients consisted exclusively of macrophages. Marrow from all but one of the nine patients demonstrated poor neutrophil development in suspension culture, and addition of CSA did not result in augmented granulocytic proliferation or maturation. A scheme of normal neutrophil maturation is proposed, and the nine patients were categorized according to this scheme. Four patterns of congenital neutropenia emerged: type 1 was the most benign form of disease with essentially normal clinical and in vitro parameters, and a defect considered to be due to a small committed stem cell pool, abnormal release, or excessive utilization peripherally; type 2 had mild disease with presumed defective committed stem cell differentiation along the granulocyte line; type 3 included benign to severe clinical expression with an apparent defect at the level of the committed granulocyte precursor more severe than in type 2; type 4 disease had varied clinical expression but evidence for a defect at the level of the pluripotent stem cell.

scholarly journals Integrated Multi-channel PPG and ECG System for Cardiovascular Risk Assessment

Proceedings ◽  
2019 ◽  
Vol 27 (1) ◽  
pp. 8 ◽  
Author(s):  
David Perpetuini ◽  
Antonio Maria Chiarelli ◽  
Vincenzo Vinciguerra ◽  
Piergiusto Vitulli ◽  
Sergio Rinella ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Arterial Stiffness ◽  
Pressure Wave ◽  
Large Scale ◽  
Near Infrared ◽  
Infrared Light ◽  
Invasive Technique ◽  
Cardiovascular Risk Assessment ◽  
Non Invasive ◽  
Cuff Occlusion

Photoplethysmography (PPG) is a non-invasive technique that employs near infrared light to estimate periodic oscillations in blood volume within arteries caused by the pulse pressure wave. Importantly, combined Electrocardiography (ECG) and PPG can be employed to quantify arterial stiffness. The capabilities of a home-made multi-channel PPG-ECG device (7 PPG probes, 4 ECG derivations) to evaluate arterial ageing were assessed. The high numerosity of channels allowed to estimate arterial stiffness at multiple body locations, without supra-systolic cuff occlusion, providing a fast and accurate examination of cardiovascular status and potentially allowing large scale clinical screening of cardiovascular risk.

Leptin causes body weight loss in the absence of in vivo activities typical of cytokines of the IL-6 family

1998 ◽  
Vol 275 (3) ◽  
pp. R913-R919 ◽  
Author(s):  
Davide Agnello ◽  
Cristina Meazza ◽  
Christopher G. Rowan ◽  
Pia Villa ◽  
Pietro Ghezzi ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Body Weight Loss ◽  
Peripheral Blood Cell ◽  
Serum Corticosterone ◽  
Amyloid A ◽  
Cell Counts ◽  
Control Body ◽  
The One

To investigate if leptin shares in vivo activities with interleukin (IL)-6 family cytokines, it was tested in normal mice for the ability, after a single injection, to induce the acute-phase protein serum amyloid A, to potentiate the induction by IL-1 of serum corticosterone and IL-6, and to inhibit the induction by lipopolysaccharide of serum tumor necrosis factor and, after seven daily injections, to cause body weight loss and to change peripheral blood cell counts. At a 0.5 mg/kg dose, leptin caused body weight loss but did not show any of the other activities above. At a dose of 5 mg/kg, which also caused body weight loss, leptin potentiated the induction by IL-1 of serum corticosterone and IL-6 but did not show any other activity. In addition to causing body weight loss, leptin shows only some of the in vivo activities typical of IL-6 family cytokines and only if used at a dose that exceeds the one sufficient to affect body weight. In vivo, leptin seems to chiefly control body weight and not inflammatory or hematopoietic processes.

scholarly journals Status quo report on wastewater treatment plant, receiving water's biocoenosis and quality as basis for evaluation of large-scale ozonation process

2017 ◽  
Vol 77 (2) ◽  
pp. 337-345 ◽  
Author(s):  
I. Brückner ◽  
K. Kirchner ◽  
Y. Müller ◽  
S. Schiwy ◽  
K. Klaer ◽  
...  
Keyword(s):  
Wastewater Treatment ◽  
Wastewater Treatment Plant ◽  
Large Scale ◽  
Treatment Plant ◽  
Treated Wastewater ◽  
Antibiotic Resistant ◽  
Cell Counts ◽  
Endocrine Disrupting ◽  
Ozonation Process ◽  
Receiving Water

Abstract The project DemO3AC (demonstration of large-scale wastewater ozonation at the Aachen-Soers wastewater treatment plant, Germany) of the Eifel-Rur Waterboard contains the construction of a large-scale ozonation plant for advanced treatment of the entire 25 million m³/yr of wastewater passing through its largest wastewater treatment plant (WWTP). In dry periods, up to 70% of the receiving water consists of treated wastewater. Thus, it is expected that effects of ozonation on downstream water biocoenosis will become observable. Extensive monitoring of receiving water and the WWTP shows a severe pollution with micropollutants (already prior to WWTP inlet). (Eco-)Toxicological investigations showed increased toxicity at the inlet of the WWTP for all assays. However, endocrine-disrupting potential was also present at other sampling points at the WWTP and in the river and could not be eliminated sufficiently by the WWTP. Total cell counts at the WWTP are slightly below average. Investigations of antibiotic resistances show no increase after the WWTP outlet in the river. However, cells carrying antibiotic-resistant genes seem to be more stress resistant in general. Comparing investigations after implementation of ozonation should lead to an approximation of the correlation between micropollutants and water quality/biocoenosis and the effects that ozonation has on this matter.

scholarly journals Subclinical Hypothyroidism and Cardiovascular Risk – An Overview of Current Understanding

2010 ◽  
Vol 7 (1) ◽  
pp. 53 ◽  
Author(s):  
Ulla Feldt Rasmussen ◽  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Subclinical Hypothyroidism ◽  
Large Scale ◽  
Thyroid Stimulating Hormone ◽  
Individual Variability ◽  
Overt Hypothyroidism ◽  
Therapeutic Trial ◽  
Treatment Benefit

Subclinical or mild hypothyroidism is often associated with adverse cardiovascular risk factors, such as high cholesterol, together with hypertension, endothelial dysfunction and other atherosclerotic cardiovascular risk factors. The ischaemic abnormalities are probably related to long-term consequences of a slowly progressing development of hypothyroidism. In recent years, it has become evident that a consensus on the exact limits for cut-off between normal and subclinically hypothyroid individuals is not currently possible. The main reasons for this are differences for measurement of serum thyroid-stimulating hormone (TSH), that reference populations are very different and that a person’s intra-individual variability is much narrower than any population-based interval. Finally, the prevalence of subclinical hypothyroidism varies from 4 to 17% in different normal populations. Available evidence indicates that patients with subclinical hypothyroidism have developed or are at risk of developing an adverse cardiovascular profile and subclinical hypothyroidism is most likely a mild variant of overt hypothyroidism. There is currently no evidence for a treatment benefit, but studies to demonstrate the expected minor improvements have not been performed on a sufficiently large scale. Patients should be informed about the disease and based on a combined clinical and laboratory judgement, should be offered a therapeutic trial in case of even vague symptoms.

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