DNA methylation of the ELOVL2, FHL2, KLF14, C1orf132/MIR29B2C,and TRIM59 genes for age prediction from blood,saliva, and buccal swab samples

Many studies have reported age-associated DNA methylation changes and age-predictive models in various tissues and body fluids. Although age-associated DNA methylation changes can be tissue-specific, a multi-tissue age predictor that is applicable to various tissues and body fluids with considerable prediction accuracy might be valuable. In this study, DNA methylation at 5 CpG sites from the ELOVL2, FHL2, KLF14, C1orf132/MIR29B2C, and TRIM59 genes were investigated in 448 samples from blood, saliva, and buccal swabs. A multiplex methylation SNaPshot assay was developed to measure DNA methylation simultaneously at the 5 CpG sites. Among the 5 CpG sites, 3 CpG sites in the ELOVL2, KLF14 and TRIM59 genes demonstrated strong correlation between DNA methylation and age in all 3 sample types. Age prediction models built separately for each sample type using the DNA methylation values at the 5 CpG sites showed high prediction accuracy with a Mean Absolute Deviation from the chronological age (MAD) of 3.478 years in blood, 3.552 years in saliva and 4.293 years in buccal swab samples. A tissue-combined model constructed with 300 training samples including 100 samples from each blood, saliva and buccal swab samples demonstrated a very strong correlation between predicted and chronological ages (r = 0.937) and a high prediction accuracy with a MAD of 3.844 years in the 148 independent test set samples of 50 blood, 50 saliva and 48 buccal swab samples. Although more validation might be needed, the tissue-combined model’s prediction accuracies in each sample type were very much similar to those obtained from each tissue-specific model. The multiplex methylation SNaPshot assay and the age prediction models in our study would be useful in forensic analysis, which frequently involves DNA from blood, saliva, and buccal swab samples.     

STRmix™ put to the test: 300 000 non-contributor profiles compared to four-contributor DNA mixtures and the impact of replicates

Probabilistic genotyping approaches are increasingly used for the interpretation of DNA mixtures. To explore the specificity of one of these systems (STRmix^™), we conducted an extensive study using 24 complex mixtures: all were known or apparent 4-person mixtures with at least one contributor representing less than 20% of total DNA, and all mixtures had at least one contributor with suboptimal DNA quantity. Those mixtures were either generated in-house or from casework. All the mixtures were compared to 300,000 virtual non-contributors, resulting in a dataset of 7.2 million comparisons. The great majority of the non-contributor comparisons led to a LR lower than 1 for a specificity of 99.1%. The effect of using replicate amplifications to calculate the LR of non-contributors was also assessed as triplicates were used and led to an increased specificity of 99.8%. The very large extent of the analyzed data shows that STRmix^™ has an excellent ability to discriminate non-contributors from complex DNA mixtures.     

Predictors of postoperative acute kidney injury in patients undergoing hip fracture surgery: A systematic review and meta-analysis

BackgroundThe present study aimed to summarize the predictors of acute kidney injury (AKI) in patients after hip surgery.MethodsA literature search was performed using PubMed, EMBASE, Cochrane Library, and Web of Science for studies assessing the predictors of AKI after hip fracture surgery. Pooled odds ratio (OR) and mean difference (MD) of those who experienced AKI compared to those who did not were calculated for each variable. Evidence was assessed using the Newcastle–Ottawa Scale.ResultsTen studies with 34 potential factors were included in the meta-analysis. In the primary analysis, 12 factors were associated with AKI, comprising males (OR 1.25; 95% confidence interval (CI) 1.14–1.36), advanced age (MD 2.28; 95% CI 0.80–3.75), myocardial infarction (OR 1.39; 95% CI 1.18–1.63), hypertension (OR 1.46; 95% CI 1.13–1.89), diabetes (OR 1.84; 95% CI 1.40–2.42), chronic kidney disease (OR 3.66; 95% CI 2.21–6.07), hip arthroplasty (OR 1.35; 95% CI 1.22–1.50), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers use (OR 2.28; 95% CI 1.68–3.08), more intraoperative blood loss (MD 44.06; 95% CI 2.88–85.24), higher preoperative blood urea nitrogen levels (MD 5.29; 95% CI 3.38–7.20), higher preoperative serum creatinine levels (MD 0.4; 95% CI 0.26–0.53), and lower preoperative estimated glomerular filtration rate (MD −19.59; 95% CI −26.92–−12.26). Another 13 factors related to AKI in individual studies were identified in the systematic review.ConclusionRelated prophylaxis strategies should be implemented in patients involved with the above-mentioned characteristics to prevent AKI after hip surgery.     

Perioperative,short-, and long-term outcomes of gastric cancer surgery: Propensity score-matched analysis of patients with or without prior solid organ transplantation

BackgroundDetails of perioperative outcomes and survival after gastric cancer surgery in prior transplant recipients have received minimal research attention.MethodsWe performed an observational cohort study using the database of 20,147 gastric cancer patients who underwent gastrectomy at a single gastric cancer center in Korea. Forty-one solid organ recipients [kidney (n = 35), liver (n = 5), or heart (n = 1)] were matched with 205 controls using propensity score matching.ResultsOperation time, blood loss, and postoperative pain were similar between groups. Short-term complication rates were similar between transplantation and control groups (22.0% vs. 20.1%, P = 0.777). Transplantation group patients with stage 1 gastric cancer experienced no recurrence, while those with stage 2/3 cancer had significantly higher recurrence risk compared to the controls (P = 0.049). For patients with stage 1 cancer, the transplantation group had a significantly higher rate of non-gastric cancer-related deaths compared to the controls (19.2% vs. 1.4%, P = 0.001). For those with stage 2/3 cancer, significantly lower proportion of the transplantation group received adjuvant chemotherapy compared to the control group (26.7% vs. 80.3%, P < 0.001). The transplantation group had a higher (albeit not statistically significant) rate of gastric cancer-related deaths compared to the controls (40.0% vs. 18.0%, P = 0.087).ConclusionTransplant recipients and non-transplant recipients exhibited similar perioperative and short-term outcomes after gastric cancer surgery. From long-term outcome analyses, we suggest active surveillance for non-gastric cancer-related deaths in patients with early gastric cancer, as well as strict oncologic care in patients with advanced cancer, as effective strategies for transplant recipients.     

Acute consumption of pecans decreases angiopoietin-like protein-3 in healthy males: a secondary analysis of randomized controlled trials

Angiopoietin-like proteins (ANGPTL)-3 and -4 regulate lipid metabolism, but the effect of tree nuts of varying fatty acid composition on post-meal responses is unknown. The purpose of the study was to conduct a secondary analysis of two studies on ANGPTL3 and -4 responses to meals containing different tree nuts. We hypothesized that the pecan-containing meal would mitigate postprandial rises in ANGPTL3 compared to the traditional meal without nuts in males, but not females. In addition, we hypothesized that there would be no other differences between any other treatments in ANGPTL3 or -4 responses. The two studies were double-blind, randomized crossover trials. Twenty-two adults (10=male, 12=female) completed study 1, which compared meals containing pecans vs. no nuts (control), and thirty adults (14=male, 16=female) completed study 2, which compared meals containing black walnuts, English walnuts (EW), or no nuts (control). Blood was collected at fasting, 30, 60, 120, and 180min postprandially. In study 1, ANGPTL3 was suppressed more in pecan vs. control in males (iAUC: -579.4±219.4 vs. -128.4±87.1pg/mL/3h, P<.05). In study 2, there was no difference in ANGPTL3 between black walnuts vs. EW, but ANGPTL3 was suppressed more in control vs. black walnuts in females only (iAUC: -196.4±138.4 vs. 102.1±90.1pg/mL/3h, P<.05). There were no differences in ANGPTL4 between treatments. In conclusion, adding pecans to a meal decreased ANGPTL3 in males, but not females. These data highlight the importance of investigating the impact of nutrients and sex on postprandial ANGPTL3 ad -4 responses to better understand their ability to reduce cardiovascular disease risk.     

Studies on the contact system of coagulation during therapy with high doses of recombinant IL-2: implications for septic shock

Patients treated with high doses of interleukin-2 (IL-2) because of cancer, develop hemodynamic and vasopermeability changes, that resemble those observed in sepsis. These patients thus provide a unique opportunity to study the early events in the development of septic shock. We analysed the changes that occurred in the contact system of coagulation in plasma from 4 patients, who together received seven 12-day cycles of high doses of IL-2. Levels of factor XII and prekallikrein during the cycles progressively fell to 50 and 30% of their initial levels, respectively, whereas significant increases in plasma factor XIIa- and kallikrein-C1-inhibitor complexes were not observed (in 3 out of 211 samples slightly increased levels of both complexes were found). The reductions in factor XII and prekallikrein were only in part due to protein leakage, since levels were still significantly lower, i.e., 80 and 50%, respectively, when corrected for albumin decreases. Levels of high molecular weight kininogen (HMWK) also decreased during IL-2 therapy, however, this decrease paralleled that of albumin. SDS-PAGE analysis of plasma HMWK did not reveal increased cleavage of this protein. The reduction of factor XII and prekallikrein, corrected for protein leakage, significantly correlated with albumin levels and inversely with daily cumulative weight gain in the patients. Thus, we demonstrate that factor XII and prekallikrein decrease during IL-2 therapy. As these decreases, already observed after 1 day treatment, were disproportional to that of albumin, a negative acute phase reactant, and correlated with signs of the vascular leak syndrome, we favor the explanation that they reflected activation rather than a decreased synthesis of the contact system proteins.(ABSTRACT TRUNCATED AT 250 WORDS)     

Twist在胃癌中的表达及其与临床病理学指标关系研究

目的：检测Twist蛋白在胃癌组织中的表达及与临床病理学指标的关系，探讨Twist蛋白在胃癌诊治中的临床应用价值。方法：应用鼠抗人Twist单克隆抗体免疫组织化学方法检测98例不同类型胃癌组织及32例正常胃组织中Twist的表达。结果：在98例胃癌组织中，Twist阳性表达60例（61.2％）；在正常胃组织中其阳性表达5例（15.2％），两者比较，P=0.000（X^2=20.06）；结合临床病理资料统计分析发现，Twist在胃癌组织中表达与肿瘤的分化程度、胃壁浸润、淋巴结转移及远处转移有关（X^2分别为6.577、9.557、9.87、4.88，P值分别为0.01、0.002、0.002、0.027）；而其表达与病人年龄、性别无关（X^2分别为0.226、0.331，P值分别为0.634、0.565）。结论：Twist在胃癌诊断中作用明确，并且在判断肿瘤分化程度、浸润、淋巴结转移等方面均具有较好的辅助诊断价值。