Project description:Prospective cohort studies often quantify serum immune biomarkers at a single time point to determine risk of cancer and other chronic diseases that develop years later. Estimates of the within-person temporal stability of serum markers partly assess the utility of single biomarker measurements and may have important implications for the design of prospective studies of chronic disease risk.Using archived sera collected from 200 HIV-seronegative men at three visits spaced over approximately 2 years, concentrations of 14 biomarkers (ApoA1, sCD14, sgp130, sIL-6R, sIL-2R?, sTNFR2, BAFF/BLyS, CXCL13, IFN-?, interleukin [IL]-1?, IL-6, IL-8, IL-10, and TNF-?) were measured in a single laboratory. Age- and ethnicity-adjusted intraclass correlation coefficients (ICC) were calculated for each biomarker, and mixed linear regression models were used to examine the influence of age, ethnicity, season, and study site on biomarker concentrations.Across all three study visits, most biomarkers had ICC values indicating fair to excellent within-person stability. ApoA1 (ICC = 0.88) and TNF-? (ICC = 0.87) showed the greatest stability; the ICC for IL-8 (ICC = 0.33) was remarkably less stable. The ICCs were similar when calculated between pairs of consecutive visits. The covariables did not influence biomarker levels or their temporal stability. All biomarkers showed moderate to strong pairwise correlations across visits.Serum concentrations of most evaluated immune biomarkers displayed acceptable to excellent within-person temporal reliability over a 2-year period. Further investigation may be required to clarify the stability of IL-8.These findings lend support to using these serologic immune biomarkers in prospective studies investigating associations with chronic diseases.
Project description:Li-ion battery, separator, multicoreshell structure, thermal stability, long-term stability. A nanofibrous membrane with multiple cores of polyimide (PI) in the shell of polyvinylidene fluoride (PVdF) was prepared using a facile one-pot electrospinning technique with a single nozzle. Unique multicore-shell (MCS) structure of the electrospun composite fibers was obtained, which resulted from electrospinning a phase-separated polymer composite solution. Multiple PI core fibrils with high molecular orientation were well-embedded across the cross-section and contributed remarkable thermal stabilities to the MCS membrane. Thus, no outbreaks were found in its dimension and ionic resistance up to 200 and 250 °C, respectively. Moreover, the MCS membrane (at ~200 °C), as a lithium ion battery (LIB) separator, showed superior thermal and electrochemical stabilities compared with a widely used commercial separator (~120 °C). The average capacity decay rate of LIB for 500 cycles was calculated to be approximately 0.030 mAh/g/cycle. This value demonstrated exceptional long-term stability compared with commercial LIBs and with two other types (single core-shell and co-electrospun separators incorporating with functionalized TiO2) of PI/PVdF composite separators. The proper architecture and synergy effects of multiple PI nanofibrils as a thermally stable polymer in the PVdF shell as electrolyte compatible polymers are responsible for the superior thermal performance and long-term stability of the LIB.
Project description:IntroductionSodium fluoride (NaF) tubes are the recommended tubes for glucose measurements, but these are expensive, have limited number of uses, and are not always available in low resource settings. Alternative sample handling techniques are thus needed. We compared glucose stability in samples collected in various tubes exposed to different pre-analytical conditions in Uganda.MethodsRandom (non-fasted) blood samples were drawn from nine healthy participants into NaF, Ethylenediaminetetraacetic acid (EDTA), and plain serum tubes. The samples were kept un-centrifuged or centrifuged with plasma or serum pipetted into aliquots, placed in cool box with ice or at room temperature and were stored in a permanent freezer after 0, 2, 6, 12 and 24 hours post blood draw before glucose analysis.ResultsRapid decline in glucose concentrations was observed when compared to baseline in serum (declined to 64%) and EDTA-plasma (declined to 77%) after 6 hours when samples were un-centrifuged at room temperature whilst NaF-plasma was stable after 24 hours in the same condition. Un-centrifuged EDTA-plasma kept on ice was stable for up to 6 hours but serum was not stable (degraded to 92%) in the same conditions. Early centrifugation prevented glucose decline even at room temperature regardless of the primary tube used with serum, EDTA-plasma and NaF-plasma after 24 hours.ConclusionIn low resource settings we recommend use of EDTA tubes placed in cool box with ice and analysed within 6 hours as an alternative to NaF tubes. Alternatively, immediate separation of blood with manual hand centrifuges will allow any tube to be used even in remote settings with no electricity.
Project description:BackgroundGlucometers are widely used in animal research due to simplicity and ease of utilization, but their accuracy in blood glucose assessment for hyperlipidemic mice is unknown.MethodsHere, we compared blood glucose levels measured by a glucometer with plasma glucose levels measured by a standard enzymatic assay for 325 genetically diverse F2 mice derived from LP and BALB/c (BALB) Apoe-/- mice. Non-fasting glucose levels were measured before initiation of a Western diet and after 11 weeks on the diet.ResultsOn chow diet, lab-measured plasma glucose levels were 279.5 ± 42.6 mg/dl (mean ± SD), while blood glucose values measured by glucometer were 138.7 ± 16.6 mg/dl. The two measures had no correlation (R2 = 0.006, p = 0.167). On the Western diet, plasma glucose levels rose to 351.1 ± 121.6 mg/dl, while glucometer-measured blood glucose fell to 128.7 ± 27.9 mg/dl. The two measures showed a moderate correlation (R2 = 0.111, p = 3.1E-9). Lab-measured plasma glucose showed strong positive correlations with plasma triglyceride and non-high-density lipoprotein cholesterol levels, while glucometer-measured blood glucose showed an inverse correlation with non-high-density lipoprotein levels on the chow diet.ConclusionsOur results indicate that hyperlipidemia affects the accuracy of glucometers in measuring blood glucose levels of mice.
Project description:Sodium-ion batteries (SIBs) are emerging power sources for the replacement of lithium-ion batteries. Recent studies have focused on the development of electrodes and electrolytes, with thick glass fiber separators (~380 μm) generally adopted. In this work, we introduce a new thin (~50 μm) cellulose-polyacrylonitrile-alumina composite as a separator for SIBs. The separator exhibits excellent thermal stability with no shrinkage up to 300°C and electrolyte uptake with a contact angle of 0°. The sodium ion transference number, t Na + , of the separator is measured to be 0.78, which is higher than that of bare cellulose ( t Na + : 0.31). These outstanding physical properties of the separator enable the long-term operation of NaCrO2 cathode/hard carbon anode full cells in a conventional carbonate electrolyte, with capacity retention of 82% for 500 cycles. Time-of-flight secondary-ion mass spectroscopy analysis reveals the additional role of the Al2O3 coating, which is transformed into AlF3 upon long-term cycling owing to HF scavenging. Our findings will open the door to the use of cellulose-based functional separators for high-performance SIBs.
Project description:Hospital samples collected in gel separator tubes are often submitted to forensic toxicology laboratories for analysis in impaired driving and death investigations. Drug adsorption to the gel separator material may lead to underestimation of the drug concentration present at the time of sample collection, potentially affecting the interpretation of analytical results. Using liquid chromatography--tandem mass spectrometry (LC--MS-MS), decreases in plasma concentration of 53 drugs and metabolites relevant to forensic toxicology casework were investigated in samples stored in BD Vacutainer® PSTTM tubes for up to 3 months. After storage for only 1 day, approximately 50% of the drugs and metabolites had significantly lower concentrations in plasma separation tubes (PSTs) compared to non-gel tubes (up to 27% lower). After storage for 3 months, approximately 75% of the drugs and metabolites had significantly lower concentrations in PSTs compared to non-gel tubes (up to 69% lower). Fentanyl, carfentanil, ketamine, diphenhydramine and several antidepressants were among the drugs most susceptible to adsorption. Central nervous system stimulants (e.g., methamphetamine and amphetamine) as well as naturally-occurring and semi-synthetic opioids (e.g., morphine, hydromorphone and oxycodone) were among the drugs least susceptible to adsorption and displayed only minimal relative decreases in concentration (if any) over the 3-month sample storage period. The potential for decreases in drug concentration due to adsorption of drugs to the gel material should be considered for toxicological interpretation based on the analysis of a sample collected in a gel separator tube.
Project description:Fluorosis is caused due to excess of fluoride intake over a long period of time. Aberrant change in RUNX2-mediated signaling cascade is one of the decisive steps during the pathogenesis of fluorosis. Till date, role of fluoride on the epigenetic alterations is not studied. In the present study, global expression profiling ofshort non-coding RNAs, in particular miRNAs and snoRNAs was carried out in NaF treated HOS cells to understand their possible role in the development of fluorosis. RT-PCR and insilico hybridization revealed that miR-124 and miR-155 can be directly involved in the transcriptional regulation of RUNX2 and RANKL genes. Compare to control, C/D box analysis revealed mark elevation in the number of UG dinucleotides and D-box sequences in NaF exposed HOS cells. Herein, we report miR-124 and miR-155 as the new possible players involved in the development of fluorosis. We also state that the alterations in UG dinucleotides and D-box sequences of snoRNAs could be due to NaF exposure.
Project description:Magnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using approximately 2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 participants of European descent from the international CHARGE Consortium. Study-specific results were combined using fixed-effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide significant (p<5 x 10(-8)) or suggestive associations (p<4 x 10(-7)) were evaluated for replication in an additional 8,463 subjects of European descent. The association of common variants at six genomic regions (in or near MUC1, ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1) with serum magnesium levels was genome-wide significant when meta-analyzed with the replication dataset. All initially significant SNPs from the CHARGE Consortium showed nominal association with clinically defined hypomagnesemia, two showed association with kidney function, two with bone mineral density, and one of these also associated with fasting glucose levels. Common variants in CNNM2, a magnesium transporter studied only in model systems to date, as well as in CNNM3 and CNNM4, were also associated with magnesium concentrations in this study. We observed no associations with serum sodium or potassium levels exceeding p<4 x 10(-7). Follow-up studies of newly implicated genomic loci may provide additional insights into the regulation and homeostasis of human serum magnesium levels.
Project description:AimInhibition of sodium/glucose cotransporter 2 (SGLT2), the key transport protein in renal glucose reabsorption, promotes glucose excretion and represents a new concept in the therapy of type-2 diabetes. In addition, SGLT2 inhibition elevates circulating glucagon concentrations and enhances hepatic glucose production. Since SGLT2 is expressed in human pancreatic α-cells and regulates glucagon release, we tested whether common variants of the SGLT2 gene SLC5A2 associate with altered plasma glucagon concentrations in the fasting state and upon glucose challenge.MethodsA study population of 375 healthy subjects at increased risk for type-2 diabetes, phenotyped by a 5-point oral glucose tolerance test (OGTT) and genotyped for recently described SLC5A2 tagging single nucleotide polymorphisms (SNPs), was selected for plasma glucagon measurements.ResultsAfter adjustment for gender, age, body mass index, and insulin sensitivity, the four tagging SNPs (rs9924771, rs3116150, rs3813008, rs9934336), tested separately or as genetic score, were neither significantly nor nominally associated with plasma glucagon concentrations at any time during the OGTT, with the inverse AUC of glucagon or the glucagon fold-change during the OGTT (p ≥ 0.2, all). Testing for genotype-related differences in the time course of the glucagon response using MANOVA did also not reveal any significant or nominal associations (p ≥ 0.5, all).ConclusionWe could not obtain statistically significant evidence for a role of common SLC5A2 variants in the regulation of glucagon release in the fasting state or upon glucose challenge. Moreover, the reported nominal effects of individual SLC5A2 variants on fasting and post-challenge glucose levels may probably not be mediated by altered glucagon release.
Project description:PurposeAs bone formation is associated with psoriatic arthritis (PsA), positron emission tomography (PET) using a 18F-Fluoride tracer may enable sensitive detection of disease activity. Our primary aim was to determine the feasibility of whole-body 18F-sodium fluoride PET-CT in clinically active PsA patients to depict new bone formation (as a reflection of disease activity) at peripheral joints and entheses. Our secondary aim was to describe 18F-sodium fluoride findings in the axial skeleton.MethodsSixteen patients (female 10/16, age 50.6 ± 8.9 years) with PsA fulfilling CASPAR criteria or with a clinical diagnosis of PsA according to the treating rheumatologist and with ≥ 1 clinically active enthesitis site were included. Of each patient, a whole-body 18F-sodium fluoride PET-CT scan was performed. All scans were scored for PET-positive lesions at peripheral joints, enthesis sites and the spine. Clinical disease activity was assessed by swollen/tender joint count 44, enthesitis according to MASES and SPARCC scores.ResultsOut of 1088 evaluated joints, 109 joints showed PET enhancement, mainly in the interphalangeal and metatarsal joints of the feet (14/109, 12.9%) and the distal interphalangeal joints of the hands (14/109, 12.9%). PET positivity was found at 44/464 enthesis sites, mainly at the patella tendon insertion (11/44, 25%) and quadriceps tendon insertion (10/44, 22.7%). Of the PET-positive joints and enthesis sites, respectively 18.2% and 29.5% were clinically positive; 81.8% and 70.5% of the PET-positive joints and entheses respectively were clinically asymptomatic. In 11 patients, ≥ 1 axial PET-positive lesion was observed, mainly in the cervical spine.ConclusionsNew molecular bone formation was observed on 18F-sodium fluoride PET-CT scans, in all domains in which PsA disease activity can be observed, with a substantial part showing no clinical symptoms.Clinical trial registrationEudraCT: 2017-004,850-40, registered on 13 December 2017.