Blood cells contain functionally important intracellular structures, such as granules, critical to immunity and thrombosis. Quantitative variation in these structures has not been subjected ...previously to large-scale genetic analysis. We perform genome-wide association studies of 63 flow-cytometry derived cellular phenotypes-including cell-type specific measures of granularity, nucleic acid content and reactivity-in 41,515 participants in the INTERVAL study. We identify 2172 distinct variant-trait associations, including associations near genes coding for proteins in organelles implicated in inflammatory and thrombotic diseases. By integrating with epigenetic data we show that many intracellular structures are likely to be determined in immature precursor cells. By integrating with proteomic data we identify the transcription factor FOG2 as an early regulator of platelet formation and α-granularity. Finally, we show that colocalisation of our associations with disease risk signals can suggest aetiological cell-types-variants in IL2RA and ITGA4 respectively mirror the known effects of daclizumab in multiple sclerosis and vedolizumab in inflammatory bowel disease.
Higher body mass index (BMI) is a risk factor for thrombosis. Platelets are essential for hemostasis but contribute to thrombosis when activated pathologically. We hypothesized that higher BMI leads ...to changes in platelet characteristics, thereby increasing thrombotic risk. The effect of BMI on platelet traits (measured by Sysmex) was explored in 33 388 UK blood donors (INTERVAL study). Linear regression showed that higher BMI was positively associated with greater plateletcrit (PCT), platelet count (PLT), immature platelet count (IPC), and side fluorescence (SFL, a measure of mRNA content used to derive IPC). Mendelian randomization (MR), applied to estimate a causal effect with BMI proxied by a genetic risk score, provided causal estimates for a positive effect of BMI on both SFL and IPC, but there was little evidence for a causal effect of BMI on PCT or PLT. Follow-up analyses explored the functional relevance of platelet characteristics in a pre-operative cardiac cohort (COPTIC). Linear regression provided observational evidence for a positive association between IPC and agonist-induced whole blood platelet aggregation. Results indicate that higher BMI raises the number of immature platelets, which is associated with greater whole blood platelet aggregation in a cardiac cohort. Higher IPC could therefore contribute to obesity-related thrombosis.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Cardio-Oncology in Iran: Cardio-toxicity Registry Alizadehasl, Azin; Akbari Parsa, Niloufar; Noohi, Feridoun ...
Basic and clinical cancer research,
12/2022, Letnik:
13, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Advances in cancer treatment have resulted in a growing number of cancer survivors. However, powerful treatments such as chemotherapy, radiation treatments, and some cancer drugs are not without ...risks, including the potential for serious, long-term damage to the heart. Cardiology and oncology specialists often collaborate to mitigate these risks when treating cancer patients. This joining is known as cardio-oncology. The main goals of cardio-oncology are to screen for and actively manage modifiable cardiovascular risk factors and diseases in cancer patients. Cardio-oncology plays an increasingly active role at every stage of cancer therapy, including baseline risk assessment pretreatment, surveillance and prevention during treatment, response to acute complications, and assessment of survivors’ post-cardiotoxic treatments. Cancer treatment has been optimized through new treatment strategies. The first cardio-oncology clinic in Iran was instituted about 4 years ago (2017) at Shaheed Rajaei Cardiovascular Medical and Research Center in Tehran, which is the first cardio-oncology clinic in the Middle East. It provides care for cancer patients with a history of cardiovascular disease or risk for cardiotoxicity during cancer therapy. Also, all patients are enrolled in the multicenter cardio-oncology Toxicity Registry research database, and 13 other hospitals from different centers in the whole country are involved in the registry. The establishment of the cardio-oncology clinic with a focus on the patient registry is discussed in this article.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Genetic association studies for blood cell traits, which are key indicators of health and immune function, have identified several hundred associations and defined a complex polygenic architecture. ...Polygenic scores (PGSs) for blood cell traits have potential clinical utility in disease risk prediction and prevention, but designing PGS remains challenging and the optimal methods are unclear. To address this, we evaluated the relative performance of 6 methods to develop PGS for 26 blood cell traits, including a standard method of pruning and thresholding (P + T) and 5 learning methods: LDpred2, elastic net (EN), Bayesian ridge (BR), multilayer perceptron (MLP) and convolutional neural network (CNN). We evaluated these optimized PGSs on blood cell trait data from UK Biobank and INTERVAL. We find that PGSs designed using common machine learning methods EN and BR show improved prediction of blood cell traits and consistently outperform other methods. Our analyses suggest EN/BR as the top choices for PGS construction, showing improved performance for 25 blood cell traits in the external validation, with correlations with the directly measured traits increasing by 10%–23%. Ten PGSs showed significant statistical interaction with sex, and sex-specific PGS stratification showed that all of them had substantial variation in the trajectories of blood cell traits with age. Genetic correlations between the PGSs for blood cell traits and common human diseases identified well-known as well as new associations. We develop machine learning-optimized PGS for blood cell traits, demonstrate their relationships with sex, age, and disease, and make these publicly available as a resource.
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•Evaluated the performance of 6 polygenic scoring methods•Developed machine learning-optimized PGSs for blood cell traits•PGSs showed interaction with sex and stratify age-dependent blood cell trait levels•PGSs of blood cell traits were genetically correlated with common diseases
Xu et al. develop and validate polygenic scores (PGSs) for 26 blood cell traits using 6 PGS methods. PGSs developed using machine learning methods show improved polygenic prediction and allow for jointly modeling the effect of correlation, interaction, and low MAF variants. Blood cell trait PGSs were used to stratify the age-based trajectories of blood cell trait levels and showed genetic correlation with common diseases.
Decreasing the hospital length of stay (LOS) in ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI) is an issue which is related to reducing ...hospital costs. This study was aimed to determine the average number of hospital LOS among patients with STEMI treated by PPCI and predictors of longer LOS.
This cross-sectional study was performed on 561 patients with STEMI who referred to Heshmat Hospital, Rasht, north of Iran, within 2015-2018. As soon as STEMI was detected, patients were transferred to the catheterization laboratory (cath lab) in the shortest possible time and underwent PPCI. A questionnaire including characteristics of patients, procedures, and in-hospital adverse events was completed. Data were analyzed with SPSS software.
The mean age of patients was 59.36 ± 11.90 years. 74.2% (n = 416) of subjects were men and 25.8% (n = 145) were women. The hospital LOS of 3 to 6 days had the highest prevalence up to 47%. The results of the multiple logistic regression showed that risk of hospital LOS > 6 days in unsuccessful percutaneous coronary intervention (PCI) was 33.2 versus 66.8 in successful PCI (P = 0.001). Moreover, the risk of hospital LOS > 6 days in subjects who had post-procedure complication, problems at admission, and primary comorbidities was 9.13 (7.22-11.53)-fold, 4.09 (2.86-5.85)-fold, and 1.75 (1.35-2.27)-fold more than those who had not, respectively.
By identifying controllable predictive factors associated with prolonged hospitalization after PPCI, the length of hospitalization can be decreased; also, the patient remission can be enhanced and hospital costs reduced.
A 23-year-old woman with history of tetralogy of Fallot presented with new hypertension and constitutional symptoms first diagnosed as coartation of aorta based on primary imaging but that turned out ...to be Takayasu arteritis after more evaluation by laboratory data and complementary imaging modalities .
<Learning objective: Inflammatory vasculitis involving large vessels such as Takayasu arteritis might mimic congenital structural heart diseases like aortic coarctation in rare cases due to post inflammatory strictures in thoracic aorta and aortic arch main branches. This report demonstrates the importance of history taking, physical examination, and using different imaging modalities for the most accurate diagnosis.>
Background: Eosinophils are immune cells which are critical to the pathophysiology of autoimmune disorders and skin cancer. We performed an integrated causal inference analysis with Mendelian ...randomization to demonstrate that although individuals with reduced eosinophil cell count are protected against autoimmune disorders such as asthma, they are at increased risk of skin cancer.
Methods: Epidemiology and public health has historically relied on observational studies to identify risk factors for disease; however, these methods are limited by reverse causation and confounding effects. In this study, we utilize genetic epidemiology and Mendelian randomization, a methodology that removes the risk for reverse causation, reduces pathways for confounding variables, and is an effective tool in identifying causal effects between risk factors and outcomes. Our analysis combines results from 12 genetic analyses from 5 different studies to explore the differential effect of eosinophil cell count on autoimmune and skin cancer disease risk.
Results: Raised eosinophil count resulted in increased risk of multiple autoimmune disorders including psoriasis (OR 0.0029 (95% CI: 0.0013-0.0046), P-value = 5.0x10-4), ankylosing spondylitis (OR 1.397x10-3 (95% CI: 0.0006-0.002), P-value = 4.0x10-4), and rheumatoid arthritis (OR 0.0011 (95% CI: 0.0004-0.0019), P-value = 2.1x10-3). In contrast, increased eosinophil cell count was protective against malignant melanoma (OR -0.001 (95% CI: -0.0017-(-0.0003)), P-value = 0.0074) and basal cell carcinoma (OR -0.0012 (95% CI: -0.0024-(-0.00007)), P-value = 3.7x10-2).
Conclusions: Results indicated that the causal effect of increased eosinophil count differentially increases the risk of immune related disorders and decreases the risk of oncology related skin diseases.
Purpose
Erectile dysfunction (ED) is a common male sexual dysfunction and affects the individual’s physical and psychological well-being. It has been classified as organic and psychogenic. Men with ...low testosterone levels have an increased risk of ED. On the other hand, direct detrimental effect of metabolic syndrome on the endothelium, smooth muscle and nerves of the vascular system of the penis is what causes ED to develop in men with metabolic syndrome. Therefore, it is supposed that a large number of men with erectile dysfunction are patients who have ED, metabolic syndrome and testosterone deficiency as a triad. The aim of this study is determining relative frequencies of metabolic syndrome and testosterone deficiency in a group of men with ED.
Methods
Men suffering from ED who were referred to a certain private urology clinic between 22.11.2009 and 22.9.2010 were evaluated for metabolic syndrome criteria; their morning free testosterone levels were measured, and then the related questionnaires were filled out.
Results
Of 241 men with ED, the relative frequency of metabolic syndrome was 41.5%, of testosterone deficiency was 36.5% and of metabolic syndrome in combination with testosterone deficiency was 19.5%.
Conclusion
The relative frequencies of metabolic syndrome and testosterone deficiency in men with ED seem to be significant, and it is the time that we should evaluate ED not as a disease but as a presentation of multiple underlying pathologies which needs medical attention to general health.
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