Association between telomere length and complete blood count in US adults

Introduction: Telomere length (TL) is related to age-related health outcomes, but little is known about the relationship between TL and complete blood count (CBC) parameters. We aimed to determine the relationship between TL and CBC in a sample of healthy US adults. Material and methods: Participants in the National Health and Nutrition Examination Survey (NHANES) recruited between 1999 and 2002 who had essential data on total CBC and TL were studied. We computed age- and race-adjusted mean values for total CBC using analysis of covariance (ANCOVA). All statistical analyses accounted for the survey design and sample weights by using SPSS Complex Samples v22.0 (IBM Corp, Armonk, NY). Results: Of the 8892 eligible participants, 47.8% (n = 4123) were men. The mean age was 41.8 years overall, 41.0 years in men and 42.6 in women (p = 0.238). The sex-stratified ANCOVA showed no significant difference in the total CBC across TL quartiles (all p > 0.05) in both sexes. In the adjusted model, there was a significant negative relationship with monocyte count ( = –0.051, 95% CI: –0.422; –0.142), mean cell hemoglobin ( = –0.051, 95% CI: –0.038; –0.011) and red cell distribution width ( = –0.031, 95% CI: –0.054; –0.003), while there was a significant positive relationship with basophil ratio ( = 0.046, 95% CI: 0.049–0.171). Conclusions: These results support the possibility that telomere attrition may be a marker for reduced proliferative reserve in hematopoietic progenitor cells

Genetically determined blood lead is associated with reduced renal function amongst individuals with type 2 diabetes mellitus: insight from Mendelian Randomisation

Some observational studies indicate a link between blood lead and kidney function although results remain controversial. In this study, Mendelian randomisation (MR) analysis was applied to obtain unconfounded estimates of the casual association of genetically determined blood lead with estimated glomerular filtration rate (eGFR) and the risk of chronic kidney disease (CKD). Data from the largest genome-wide association studies (GWAS) on blood lead, eGFR and CKD, from predominantly ethnically European populations, were analysed in total, as well as separately in individuals with or without type 2 diabetes mellitus. Inverse variance weighted (IVW) method, weighted median (WM)-based method, MR-Egger, MR-Pleiotropy RESidual Sum and Outlier (PRESSO) as well as the leave-one-out method were applied. In a general population, lifetime blood lead levels had no significant effect on risk of CKD (IVW: p = 0.652) and eGFR (IVW: p = 0.668). After grouping by type 2 diabetes status (no diabetes vs. diabetes), genetically higher levels of blood lead had a significant negative impact among subjects with type 2 diabetes (IVW = Beta: −0.03416, p = 0.0132) but not in subjects without (IVW: p = 0.823), with low likelihood of heterogeneity for any estimates (IVW p > 0.158). MR-PRESSO did not highlight any outliers. Pleiotropy test, with very negligible intercept and insignificant p-value, indicated a low likelihood of pleiotropy for all estimations. The leave-one-out method demonstrated that links were not driven by a single SNP. Our results show, for the first time, that among subjects with type 2 diabetes, higher blood lead levels are potentially related to less favourable renal function. Further studies are needed to confirm our results

Genetically Determined Serum 25-Hydroxyvitamin D Is Associated with Total, Trunk, and Arm Fat-Free Mass: A Mendelian Randomization Study

Purpose: Low serum vitamin D status has been associated with reduced muscle mass in observational studies although the relationship is controversial and a causal association cannot be determined from such observations. Two-sample Mendelian randomization (MR) was applied to assess the association between serum vitamin D (25(OH)D) and total, trunk, arm and leg fat-free mass (FFM). Methods: MR was implemented using summary-level data from the largest genome-wide association studies (GWAS) on vitamin D (n=73,699) and total, trunk, arm and leg FFM. Inverse variance weighted method (IVW) was used to estimate the causal estimates. Weighted median (WM)-based method, and MR-Egger, leave-one-out were applied as sensitivity analysis. Results: Genetically higher serum 25(OH)D levels had a positive effect on total (IVW = Beta: 0.042, p = 0.038), trunk (IVW = Beta: 0.045, p = 0.023) and arm (right arm IVW = Beta: 0.044, p = 0.002; left arm IVW = Beta: 0.05, p = 0.005) FFM. However, the association with leg FFM was not significant (right leg IVW = Beta: 0.03, p = 0.238; left leg IVW = Beta: 0.039, p = 0.100). The likelihood of heterogeneity and pleiotropy was determined to be low (statistically non-significant), and the observed associations were not driven by single SNPs. Furthermore, MR pleiotropy residual sum and outlier test did not highlight any outliers. Conclusions: Our results illustrate the potentially causal, positive effect of serum 25(OH)D concentration on total, trunk and upper body appendicular fat-free mass

Age-related decline in antibiotic prescribing for uncomplicated respiratory tract infections in primary care in England following the introduction of a national financial incentive (the Quality Premium) for health commissioners to reduce use of antibiotics in the community: an interrupted time series analysis

Objectives: To assess the impact of the 2015/16 NHS England Quality Premium (which provided a financial incentive for Clinical Commissioning Groups to reduce antibiotic prescribing in primary care) on antibiotic prescribing by General Practitioners (GPs) for respiratory tract infections (RTIs). Method: Interrupted time series analysis using monthly patient-level consultation and prescribing data obtained from the Clinical Practice Research Datalink (CPRD), between April 2011 and March 2017. The study population comprised patients consulting a GP who were diagnosed with an RTI. We assessed the rate of antibiotic prescribing in patients (both aggregate and stratified by age) with a recorded diagnosis of uncomplicated RTI, before and after the implementation of the Quality Premium. Results: Prescribing rates decreased over the six year study period, with evident seasonality. Notably, there was a 3% drop in the rate of antibiotic prescribing (equating to 14.65 prescriptions per 1,000 RTI consultations) (p<0.05) in April 2015, coinciding with the introduction of the Quality Premium. This reduction was sustained, such that after two years there was a 3% decrease in prescribing relative to that expected had the pre-intervention trend continued. There was also a concurrent 2% relative reduction in the rate of broad-spectrum antibiotic prescribing. Antibiotic prescribing for RTIs diagnosed in children showed the greatest decline with a 6% relative change two years after the intervention. Of the RTI indications studied, the greatest reductions in antibiotic prescribing were seen for patients with sore throats. Conclusions: Community prescribing of antibiotics for RTIs significantly decreased following the introduction of the Quality Premium, with the greatest reduction seen in younger patients

Association of Dietary Intakes and Genetically Determined Serum Concentrations of Mono and Poly Unsaturated Fatty Acids on Chronic Kidney Disease: Insights from Dietary Analysis and Mendelian Randomization.

Polyunsaturated fatty acid (PUFA) intake is generally associated with better renal function, while the association of monounsaturated fatty acids (MUFAs) remains unconfirmed. Mendelian randomization (MR) analysis was used to obtain unconfounded estimates of the causal association of dietary intake and genetically determined serum PUFA and MUFA levels with measures of renal function. Data from participants of the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2010 were used. Data from the largest genome-wide association studies (GWAS) on MUFAs, PUFAs, eGFR, and chronic kidney disease (CKD) were analysed for the entire sample. A total of 16,025 participants were included. eGFR improved across increasing quartiles of total PUFA intake from 86.3 ± 0.5 (Q1) to 96.2 ± 0.5 mL/min/1.73 m² (Q4), (p &lt; 0.001). Conversely, there was no association between MUFA intake and measures of renal function (all p &gt; 0.21). In multivariable models, the top quartile of PUFA intake had a 21% lower risk for CKD, but there was no significant association between CKD risk and MUFA intake. Genetically determined serum MUFA (heptadecenoate (17:1), myristoleic acid (14:1), and palmitoleic acid (16:1)) and PUFA (α-linolenic acid and eicosapentaenoic acid) concentrations had no significant association with eGFR and CKD risk. Additionally, no association was found in the analyses stratified by diabetes status. Higher dietary PUFA intake is associated with lower risk of CKD, while there was no association with serum levels of MUFAs or PUFAs. Additional studies including clinical trials are warranted

Preclinical studies of166Ho-chitosan for treatment of hepatocellular carcinoma

Introduction: Recently, due to the special characteristics of166Ho and chitosan,166Ho-chitosan complex was developed for treatment of tumors such as hepatocellular carcinoma. This complex has been lately prepared with high radiochemical purity in our lab. The preclinical studies of the complex however should be performed to evaluate the tracer concentration in target and normal tissues before human use. Methods: In this study,166Ho-chitosan was prepared and its preclinical studies for treatment of hepatocellular carcinoma was carried out by injection of the radiopharmaceutical into the rabbit's liver via two different methods, surgery and venography. Leakage of the injected activity from the injection site in the rabbit organs was investigated using SPECT and SPECT-CT imaging up to 24 hours. Results: Both SPECT and SPECT-CT imaging of the rabbits showed that there was no significant leakage of the injected activity. Almost all the activity would remain in the injection site at least 24 h post injection. Conclusion: Considering all of the excellent features of the complex, this radiopharmaceutical is suggestive for treatment of hepatocellular carcinoma by radioembolization method

Fuzzy uncertainty analysis in the flutter boundary of an aircraft wing subjected to a thrust force

In this study, flutter uncertainty analysis of an aircraft wing subjected to a thrust force is investigated using fuzzy method. The linear wing model contains bending and torsional flexibility and the engine is considered as a rigid external mass with thrust force. Peters’ unsteady thin airfoil theory is used to model the aerodynamic loading. The aeroelastic governing equations are derived based on Hamilton’s principle and converted to a set of ordinary differential equations using Galerkin method. In the flutter analysis, it is assumed that the wing static deflections do not have influence on the results. The wing bending and torsional rigidity, aerodynamic lift curve slope and air density are considered as uncertain parameters and modelled as triangle and trapezium membership functions. The eigenvalue problem with fuzzy input parameters is solved using fuzzy Taylor expansion method and a sensitivity analysis is performed. Also, the upper and lower bounds of flutter region at different α-cuts are extracted. Results show that this method is a low-cost method with reasonable accuracy to estimate the flutter speed and frequency in the presence of uncertainties