scholarly journals The Relationship between Metabolic Syndrome and Plasma Metals Modified by EGFR and TNF-α Gene Polymorphisms

Toxics ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 225
Author(s):  
Tzu-Hua Chen ◽  
Wei-Shyang Kung ◽  
Hung-Yu Sun ◽  
Joh-Jong Huang ◽  
Jia-Yi Lu ◽  
...  

With the escalating global prevalence of metabolic syndrome (MetS), it is crucial to detect the high-risk population early and to prevent chronic diseases. Exposure to various metals has been indicated to promote MetS, but the findings were controversial, and the effect of genetic modification was not considered. Epidermal growth factor receptor (EGFR) was proposed to be involved in the pathway of metabolic disorders, and tumor necrotic factor-α (TNF-α) was regarded as an early inflammatory biomarker for MetS. This research aimed to analyze the impact of EGFR and TNF-α gene polymorphisms on the prevalence of MetS under environmental or occupational exposure to metals. We gathered data from 376 metal industrial workers and 639 non-metal workers, including physical parameters, biochemical data, and plasma concentrations of six metals. According to the genomic database of Taiwan Biobank, 23 single nucleotide polymorphisms (SNPs) on EGFR gene and 6 SNPs on TNF-α gene were incorporated in our research. We applied multivariable logistic regression to analyze the probability of MetS with various SNPs and metals. Our study revealed some susceptible and protective EGFR and TNF-α genotypes under excessive exposure to cobalt, zinc, selenium, and lead. Thus, we remind the high-risk population of taking measures to prevent MetS.

2021 ◽  
Vol 12 ◽  
Author(s):  
Zuqiang Fu ◽  
Weihua Cai ◽  
Jianguo Shao ◽  
Hong Xue ◽  
Zhijun Ge ◽  
...  

BackgroundThe tumor necrosis factor superfamily (TNFSF) and TNF receptor superfamily (TNFRSF) play important roles in the immune responses to infections. The aim of this study was to determine the impact of single nucleotide polymorphisms (SNPs) of several TNFSF/TNFRSF genes on the risk of hepatitis C virus (HCV) infection in the Chinese high-risk population.MethodsThe TNFSF4-rs1234313, TNFSF4-rs7514229, TNFSF8-rs3181366, TNFSF8-rs2295800, TNFRSF8-rs2298209, and TNFRSF8-rs2230625 SNPs were genotyped in 2309 uninfected controls, 597 subjects with spontaneous HCV clearance and 784 patients with persistent HCV infection using the TaqMan-MGB assay. The putative functions of the positive SNPs were determined using online bioinformatics tools.ResultsAfter adjusting for gender, age, high-risk population, alanine transaminase (ALT), aspartate aminotransferase (AST), IL28B-rs12979860 and rs8099917 genotypes, the non-conditional logistic regression showed that rs7514229-T, rs3181366-T, and rs2295800-C were associated with an increased risk of HCV infection (all PFDR < 0.05). Combined analysis of rs7514229-T and rs3181366-T risk alleles showed that the subjects carrying 2–4 risk alleles were more susceptible to HCV infection compared with those lacking any risk allele (all P < 0.001). Furthermore, the risk of HCV infection increased with the number of risk alleles (Ptrend < 0.001). In silico analysis showed that rs7514229, rs3181366, and rs2295800 polymorphisms may affect the transcription of mRNA by regulating miRNA binding, TF binding, and promoter activation, respectively, which may have biological consequences.ConclusionTNFSF4-rs7514229, TNFSF8-rs3181366, and TNFSF8-rs2295800 are associated with increased risk of HCV infection in the Chinese high-risk population.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Maitri Kalra ◽  
Yan Tong ◽  
David R. Jones ◽  
Tom Walsh ◽  
Michael A. Danso ◽  
...  

AbstractPatients with triple-negative breast cancer (TNBC) who have residual disease after neoadjuvant therapy have a high risk of recurrence. We tested the impact of DNA-damaging chemotherapy alone or with PARP inhibition in this high-risk population. Patients with TNBC or deleterious BRCA mutation (TNBC/BRCAmut) who had >2 cm of invasive disease in the breast or persistent lymph node (LN) involvement after neoadjuvant therapy were assigned 1:1 to cisplatin alone or with rucaparib. Germline mutations were identified with BROCA analysis. The primary endpoint was 2-year disease-free survival (DFS) with 80% power to detect an HR 0.5. From Feb 2010 to May 2013, 128 patients were enrolled. Median tumor size at surgery was 1.9 cm (0–11.5 cm) with 1 (0–38) involved LN; median Residual Cancer Burden (RCB) score was 2.6. Six patients had known deleterious BRCA1 or BRCA2 mutations at study entry, but BROCA identified deleterious mutations in 22% of patients with available samples. Toxicity was similar in both arms. Despite frequent dose reductions (21% of patients) and delays (43.8% of patients), 73% of patients completed planned cisplatin. Rucaparib exposure was limited with median concentration 275 (82–4694) ng/mL post-infusion on day 3. The addition of rucaparib to cisplatin did not increase 2-year DFS (54.2% cisplatin vs. 64.1% cisplatin + rucaparib; P = 0.29). In the high-risk post preoperative TNBC/BRCAmut setting, the addition of low-dose rucaparib did not improve 2-year DFS or increase the toxicity of cisplatin. Genetic testing was underutilized in this high-risk population.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ausenda Machado ◽  
Irina Kislaya ◽  
Amparo Larrauri ◽  
Carlos Matias Dias ◽  
Baltazar Nunes

Abstract Background All aged individuals with a chronic condition and those with 65 and more years are at increased risk of severe influenza post-infection complications. There is limited research on cases averted by the yearly vaccination programs in high-risk individuals. The objective was to estimate the impact of trivalent seasonal influenza vaccination on averted hospitalizations and death among the high-risk population in Portugal. Methods The impact of trivalent seasonal influenza vaccination was estimated using vaccine coverage, vaccine effectiveness and the number of influenza-related hospitalizations and deaths. The number of averted events (NAE), prevented fraction (PF) and number needed to vaccinate (NVN) were estimated for seasons 2014/15 to 2016/17. Results The vaccination strategy averted on average approximately 1833 hospitalizations and 383 deaths per season. Highest NAE was observed in the ≥65 years population (85% of hospitalizations and 95% deaths) and in the 2016/17 season (1957 hospitalizations and 439 deaths). On average, seasonal vaccination prevented 21% of hospitalizations in the population aged 65 and more, and 18.5% in the population with chronic conditions. The vaccination also prevented 29% and 19.5% of deaths in each group of the high-risk population. It would be needed to vaccinate 3360 high-risk individuals, to prevent one hospitalization and 60,471 high-risk individuals to prevent one death. Conclusion The yearly influenza vaccination campaigns had a sustained positive benefit for the high-risk population, reducing hospitalizations and deaths. These results can support public health plans toward increased vaccine coverage in high-risk groups.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Maheer Gandhavadi ◽  
Kendrick A Shunk ◽  
Edward J McNulty

Background Data regarding the impact of drug eluting stent (DES) use on long-term outcomes outside trial populations are limited. Methods 1,547 consecutive patients underwent stent implantation from January 2000 until December 2006 at the San Francisco Veterans Affairs Medical Center. To assess the impact of DES availability on mortality, that population was partitioned into a pre-DES cohort (N=591) and a post-DES availability cohort (N=956). Kaplan-Meier survival curves for the two cohorts were compared. Results The entire population was relatively high risk: 37% had diabetes, 38% a reduced ejection fraction, and 53% a prior MI or elevated troponin prior to the procedure. Median follow up was 4.7 years for the pre-DES cohort and 1.8 years for the post-DES cohort. DES were used in 83% of procedures in the post-DES cohort. Survival improved significantly in the post-DES cohort (P = .04, Log Rank)(see Figure ). Baseline characteristics, procedural variables and discharge medications were analyzed in a Cox proportional hazards model (see Table ). DES use was an independent predictor of improved survival (Hazard Ratio for death 0.52, 95% CI .28–.95). Conclusions In an unselected, high risk population, long-term survival improved following the availability of drug eluting stents. After adjusting for potential confounding factors, DES use was an independent predictor of improved survival. Independent Predictors of Death in all 1,547 Patients


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Shozab S Ali ◽  
Ebenezer Oni ◽  
Ehimen C Aneni ◽  
Lara Roberson ◽  
Janisse Post ◽  
...  

Introduction: Metabolic syndrome, the clustering of multiple cardiovascular risk factors, is established as a risk factor for CVD. Shorter or longer sleep duration has been reported to be associated with increased risk of metabolic syndrome (MS) and diabetes mellitus (DM) through increased insulin resistance (IR). However, it is not known if impaired sleep alters IR in a high-risk population with known MS/DM. Methods: The Baptist Employee Healthy Heart Study is an ongoing lifestyle intervention study examining the effects of web-based interventions on reducing CVD risk in individuals with MS/DM. Sleep duration was self reported by the participants. Daily sleep duration was categorized into sleep <7 hours (short), 7 to 8 hours (normal) and >8 hours (long). Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated from fasting insulin and fasting glucose level. Results: The population consisted of 182 participants (74% women, 49% Hispanic, mean age 52 ± 9 years). In this study the mean sleep duration was 7±5 hours and mean HOMA-IR was 5.2 ± 5.6 units. Systolic and diastolic blood pressure, BMI, waist circumference, total cholesterol level and LDL cholesterol level did not apparently differ across the groups. Both short and long sleepers tended to have lower HDL cholesterol level and higher triglyceride level (p<0.05). The mean HOMA-IR was significantly higher in short and long sleepers {7-8hrs (4.09±4.8); <7hrs (5.36±4.7); >8hrs (9.52±10.7), p<0.001}, and were more likely to have HOMA-IR in the highest quartile as compared to normal sleepers. In ordinal logistic regression, after adjustment for traditional risk factors, short and long sleepers were at 2-3 fold higher risk of increasing levels of HOMA-IR. Conclusions: In this study of high metabolic risk individuals, sleep duration was associated with increased insulin resistance and highlights the importance of improving sleep hygiene in the clinical management of high risk individuals with MS and DM.


2021 ◽  
Vol 22 (6) ◽  
pp. 1253-1256
Author(s):  
Amy Albright ◽  
Karen Gross ◽  
Michael Hunter ◽  
Laurel O'Connor

Introduction: Emergency medical services (EMS) dispatchers have made efforts to determine whether patients are high risk for coronavirus disease 2019 (COVID-19) so that appropriate personal protective equipment (PPE) can be donned. A screening tool is valuable as the healthcare community balances protection of medical personnel and conservation of PPE. There is little existing literature on the efficacy of prehospital COVID-19 screening tools. The objective of this study was to determine the positive and negative predictive value of an emergency infectious disease surveillance tool for detecting COVID-19 patients and the impact of positive screening on PPE usage. Methods: This study was a retrospective chart review of prehospital care reports and hospital electronic health records. We abstracted records for all 911 calls to an urban EMS from March 1–July 31, 2020 that had a documented positive screen for COVID-19 and/or had a positive COVID-19 test. The dispatch screen solicited information regarding travel, sick contacts, and high-risk symptoms. We reviewed charts to determine dispatch-screening results, the outcome of patients’ COVID-19 testing, and documentation of crew fidelity to PPE guidelines. Results: The sample size was 263. The rate of positive COVID-19 tests for all-comers in the state of Massachusetts was 2.0%. The dispatch screen had a sensitivity of 74.9% (confidence interval [CI], 69.21-80.03) and a specificity of 67.7% (CI, 66.91-68.50). The positive predictive value was 4.5% (CI, 4.17-4.80), and the negative predictive value was 99.3% (CI, 99.09-99.40). The most common symptom that triggered a positive screen was shortness of breath (51.5% of calls). The most common high-risk population identified was skilled nursing facility patients (19.5%), but most positive tests did not belong to a high-risk population (58.1%). The EMS personnel were documented as wearing full PPE for the patient in 55.7% of encounters, not wearing PPE in 8.0% of encounters, and not documented in 27.9% of encounters. Conclusion: This dispatch-screening questionnaire has a high negative predictive value but moderate sensitivity and therefore should be used with some caution to guide EMS crews in their PPE usage. Clinical judgment is still essential and may supersede screening status.


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