Relationship between QT Interval Length and Arterial Stiffness in Systemic Lupus Erythematosus (SLE): A Cross-Sectional Case-Control Study

ResultsClinical basal characteristics were similar in both groups. QTc interval was 415±21.4 milliseconds in all patients, and 407±19.1 milliseconds in the control group (p = 0.007). There was a positive correlation between QTc interval and carotid-femoral pulse-wave velocity (r = 0.235; p = 0.02) in patients with SLE. This association was independent of hypertension and age in a multivariate analysis.ConclusionQTc interval measured by electrocardiogram is prolonged in SLE patients; it is related to subclinical atherosclerosis, measured by carotid-femoral pulse-wave velocity. This measure may help stratify risk in routine clinical practice and select the patients that might benefit from a more aggressive therapy in the prevention of cardiovascular events.     

Sympathovagal Balance,Nighttime Blood Pressure,and QT Intervals in Normotensive Obese Women

Objective : We describe associations among the heart‐rate‐corrected QT (QTc) interval, QTc dispersion (QTc‐d), circadian BP variation, and autonomic function in obese normotensive women and the effect of sustained weight loss. Research Methods and Procedures : In 71 obese (BMI = 37.14 ± 2.6 kg/m²) women, 25 to 44 years of age, circadian BP variations (24‐hour ambulatory BP monitoring), autonomic function (power spectral analysis of RR interval oscillations), and cardiac repolarization times (QTc‐d and QTc interval) were recorded at baseline and after 1 year of a multidisciplinary program of weight reduction. Results : Compared with nonobese age‐matched women (n = 28, BMI = 23 ± 2.0 kg/m²), obese women had higher values of QTc‐d (p < 0.05) and QTc (p < 0.05), an altered sympathovagal balance (ratio of low‐frequency/high‐frequency power, p < 0.01), and a blunted nocturnal drop in BP (p < 0.01). In obese women, QTc‐d and the QTc interval correlated with diastolic nighttime BP (p < 0.01) and sympathovagal balance (p < 0.01). Waist‐to‐hip ratio, free fatty acids, and plasma insulin levels correlated with QT intervals and reduced nocturnal drops in both systolic and diastolic BP and sympathovagal balance (p < 0.01). After 1 year, obese women lost at least 10% of their original weight, which was associated with decrements of QTc‐d (p < 0.02), the QTc interval (p < 0.05), nighttime BP (p < 0.01), and sympathovagal balance (p < 0.02). Discussion : Sustained weight loss is a safe method to ameliorate diastolic nighttime BP drop and sympathetic overactivity, which may reduce the cardiovascular risk in obese women.     

Markers of ventricular repolarization as an additional non-invasive electrocardiography parameters for predicting ventricular tachycardia/fibrillation in patients with Brugada Syndrome – A systematic review and meta-analysis

BackgroundControversies surrounded the management of asymptomatic Brugada syndrome. Prognostication using electrophysiology study (EPS) is disputable. Non-invasive parameters may be a valuable additional tool for risk stratification. We aim to evaluate the use markers of ventricular repolarization including Tpeak-to-Tend (TpTe), Tpe Dispersion, TpTe/QT ratio, and QTc interval as additional non-invasive electrocardiography parameters for predicting ventricular tachycardia/fibrillation in patients with Brugada syndrome.MethodsWe performed a comprehensive search on TpTe, Tpe Dispersion, TpTe/QT ratio, and QTc interval as a predictor for ventricular tachycardia(VT)/fibrillation(VF)/aborted sudden cardiac death/appropriate ICD shock in patients with Brugada syndromes up until October 2018.ResultsWe included ten studies in the qualitative synthesis and eight studies in meta-analysis. There were a total of 2126 subjects from ten studies. We found that TpTe interval (mean difference 11.97 m s [5.02–18.91]; p < 0.001; I² 80% possibly on ≥80–100 m s and maximum QTc interval (mean difference 11.42 m s [5.90–16.93], p < 0.001; I² 28%) were the most potential ECG parameters to predict VT/VF/AT/SCD. Tpe dispersion and TpTe/QT ratio have a high heterogeneity. Upon sensitivity analysis, there is no single study found to markedly affect heterogeneity of Tpe dispersion and TpTe/QT ratio. Removal of a study reduced maximum QTc interval heterogeneity to 0%.ConclusionsMeasurement of TpTe interval, Tp-e dispersion, TpTe/QT ratio, and QTc interval on ECG emerge as a promising prognostication tool which needs further investigations with a more standardized method, outcome, and cut-off points. As for now, only maximum QTc interval has a reliable result with low heterogeneity sufficiently reliable for prognostication.     

Systematic considerations for a multicomponent pharmacokinetic study of Epimedii wushanensis herba: From method establishment to pharmacokinetic marker selection

BackgroundPrenylflavonoids are major active components of Epimedii wushanensis herba (EWH). The global pharmacokinetics of prenylflavonoids are unclear, as these compounds yield multiple, often unidentified metabolites.PurposeThis study successfully elucidated the pharmacokinetic profiles of EWH extract and five EWH-derived prenylflavonoid monomers in rats.Study designThe study was a comprehensive analysis of metabolic pathways and pharmacokinetic markers.MethodsMajor plasma compounds identified after oral administration of EWH-derived prototypes or extract included: (1) prenylflavonoid prototypes, (2) deglycosylated products, and (3) glucuronide conjugates. To select appropriate EWH-derived pharmacokinetic markers, a high performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method was established to simultaneously monitor 14 major compounds in unhydrolyzed plasma and 10 potential pharmacokinetic markers in hydrolyzed plasma.ResultsThe pharmacokinetic profiles indicated that the glucuronide conjugates of icaritin were the principle circulating metabolites and that total icaritin accounted for ∼99% of prenylflavonoid exposure after administration of EWH-derived materials to rats. To further investigate icaritin as a prospective pharmacokinetic marker, correlation analysis was performed between total icaritin and its glucuronide conjugates, and a strong correlation (r > 0.5) was found, indicating that total icaritin content accurately reflected changes in the exposure levels of the glucuronide conjugates over time. Therefore, icaritin is a sufficient pharmacokinetic marker for evaluating dynamic prenylflavonoid exposure levels. Next, a mathematical model was developed based on the prenylflavonoid content of EWH and the exposure levels in rats, using icaritin as the pharmacokinetic marker. This model accurately predicted exposure levels in vivo, with similar predicted vs. experimental area under the curve (AUC)_0–96 h values for total icaritin (24.1 vs. 32.0 mg/L h).ConclusionIcaritin in hydrolyzed plasma can be used as a pharmacokinetic marker to reflect prenylflavonoid exposure levels, as well as the changes over time of its glucuronide conjugates.     

Carbon storage change and δ13C transitions of peat columns in a partially forestry-drained boreal bog

Background and aims

In forestry-drained peatlands, drying leads to changes in C cycling which could affect peat δ¹³C. Furthermore, the δ¹³C profile of the entire peat column may reveal effects of earlier climatic periods.

Methods

We measured peat δ¹³C and C inventories in adjacent peat profiles, two collected from undrained and two from the drained side of a bog that was partially ditch-drained 37 years earlier. The cores were sliced into 10-cm subsamples for analyses; matching of the profiles based on surface levelling, peat stratigraphic correlation and a horizontal ash layer found in both profiles.

Results

Surface subsidence of 30 cm was observed in the dried site and the uppermost 160 cm in the undrained site contained an excess of 5.9 kg m⁻² of C compared with the corresponding strata of the ditch-drained site. The δ¹³C values increased but markedly only in the thin surface layer of the drained site, indicating low δ¹³C of the missing C (ca. –30‰). In the deeper strata, dating to Mid-Holocene, high dry bulk density, C%, N%, humification index and low C/N ratio were connected to low δ¹³C of peat.

Conclusions

Drainage of 37 years increased δ¹³C values in the upper peat profile of the drained bog and led to the selective loss of ¹³C depleted C. Results indicate that C balance studies can be aided by C isotope analyses. Low δ¹³C values in the peat profile indicate the existence of a wet fen stage during the moist and warm period during Mid-Holocene.

     

Biliopancreatic diversion reduces QT interval and dispersion in severely obese patients

Objectives: The objectives were to evaluate QT interval (QTc) and QT‐interval dispersion (QTd) in severely obese individuals and to determine the effects of biliopancreatic diversion (BPD) and weight loss after BPD on ventricular repolarization parameters. Background: People with severe obesity (SO) have a 50% to 100% increased risk of death associated with a 1.6‐fold increased risk of sudden death. BPD surgery induces rapid and considerable weight loss through severe lipid malabsorption, thus achieving long‐term weight control. Research Methods and Procedures: A total of 85 subjects with SO (age, 42 ± 12 years; 66 females; mean body weight, 120 ± 29 kg; BMI, 45 ± 11 kg/m²) of 330 who had a bariatric surgical consultation between January 2001 and July 2002 were enrolled. Inclusion criteria were sinus rhythm, unremarkable 12 leads surface electrocardiogram, no atrioventricular blocks and/or bundle branch blocks, normal serum electrolyte profile, and no medical therapies exerting known effects on QTc. Exclusion criteria were previous diagnosis of coronary artery disease, known cardiovascular disease, atrial fibrillation or any other known cardiac arrhythmias, cancer, or renal dysfunction. Results: A total of 86% of patients had QTc >440 ms and/or QTd >60 ms. Subjects with SO showed a mean maximum QTc of 446 ± 28 ms and a mean QTd of 52 ± 20 ms. A close correlation was found between QTc and QTd (p < 0.0001; R² = 0.33). One month after BPD, mean QTc was 420 ms and remained stable at follow‐up; QTd was 32 ms at 1 and 6 months and became 35 ms at 1 year. Conclusions: Ventricular repolarization abnormalities are significantly increased in subjects with SO. Reduction of QT abnormalities after BPD is independent of weight loss and is caused by the 100% reduction of glucose plasma shortly after surgery. This effect may be related to surgical interruption of the entero‐insular axis.     

Comparison and recalculation of the very different QTc interval durations in young healthy women

The aim was to use some simple way for easier comparison, other expression or recalculation of the QTc duration from one formula to another in order to remove the large QTc differences.Methods and Results: The QT interval duration in 138 young healthy women was taken from our archive. The measured QT interval was corrected for heart rate (QTc) according to nine published regression equations (Bazett, Fridericia, Hodges, Sarma, Lecocq, Rautaharju, Sagie=Framingham, Arrowood, Malik) and compared mathematically by the Pearson correlation coefficient R and graphically by linear correlation.Correlation between two different QTc durations can be of three kinds: small (e.g. Bazett's versus Malik's formulas, R=0.0525, p=0.5405, the QTc values are much dispersed in the graph), larger (Malik's versus Sarma's formulas, R=0.939, p<0.01, the values are less dispersed), and identical (the Rautaharju's versus Arrowood's formulas, R=1.000, p<0.01, all QTc points are situated on one line). The linear correlation QTc1 = a+b·QTc2 enables recalculation from one QTc formula into another, if necessary.In conclusion, the QTc interval durations are differently long according to the QTc formula used. The correlations with the large Pearson R coefficient indicate the QTc pairs inappropriate for recalculation, the small R values indicate the appropriate pairs for recalculation.     

The impact of body condition after calving on metabolism and milk progesterone profiles in two breeds of dairy cows

Background

Optimal body condition in early lactation is generally accepted as a prerequisite for good reproductive performance. Examination of milk progesterone profiles offers an objective method for characterization of postpartum ovarian activity in dairy cows. The present study investigated the relationship between body condition after calving, some metabolic parameters in blood plasma, and fertility, as reflected by milk progesterone profiles in the two dairy breeds Swedish Red (SR) and Swedish Holstein (SH).

Results

Multiparous dairy cows (n = 73) of SR and SH breeds were selected and divided into three groups based on their body condition score (BCS) after parturition. Selected plasma metabolites were determined, milk progesterone profiles were identified and body condition was scored. Over-conditioned cows and atypical progesterone profiles were more common among SR cows. Insulin sensitivity was lower and IGF 1 higher among SR cows. Insulin was positively related to body condition, but not related to breed.

Conclusions

Atypical progesterone profiles were more common and insulin sensitivity lower in SR than in SH cows, but the SR breed had a higher proportion of over-conditioned SR cows. It is reasonable to assume that breed differences in body condition contributed to these results.

     

Shiftwork and Metabolic Dysfunction

Many of the health problems that are more prevalent among shiftworkers are thought to be linked to their heightened susceptibility to metabolic syndrome, i.e., the association of even moderate degrees of visceral obesity, dyslipidemia, abnormal blood pressure, and serum glucose levels in the same individual. Although previous studies have identified associations between shiftwork and metabolic syndrome, there is relatively little evidence to date of how the risk of developing it varies as a function of exposure to shiftwork. The current study seeks to confirm earlier findings of an association between shiftwork exposure and metabolic dysfunction, and to examine the impact of exposure duration, while adjusting for a number of covariates in the analyses. The analyses were based on data from VISAT, a study involving the measurement of physiological, behavioral, and subjective outcomes from 1757 participants, 989 being current or former shiftworkers. The sample comprised employed and retired wage earners, male and female, who were 32, 42, 52, and 62 yrs old. The first analysis sought to confirm previous findings of an association between exposure to shiftwork and the risk of developing metabolic syndrome. It indicated that participants who were or who had previously been shiftworkers (i.e., working schedules that involved rotating shifts; not being able to go to bed before midnight; having to get up before 05:00?h; or being prevented from sleeping during the night) were more likely to exhibit symptoms of metabolic syndrome, after adjusting for age, sex, socioeconomic status, smoking, alcohol intake, perceived stress, and sleep difficulty (odds ratio [OR] 1.78; 95% confidence interval [CI] 1.03–3.08). The results suggest the association between shiftwork and metabolic syndrome cannot be fully accounted for by either higher levels of strain or increased sleep difficulty among shiftworkers, although it remains a possibility that either one or both of these factors may have played a contributing role. The second analysis addressed the issue of duration of exposure to shiftwork. Participants with >10 yrs' experience of working rotating shifts were more likely to exhibit symptoms of metabolic syndrome than participants without exposure to shiftwork, i.e., dayworkers, even after adjusting for age and sex (OR 1.96; 95% CI 1.03–3.75). Thus, the current study confirms the association between shiftwork exposure and metabolic syndrome. It also provides new information regarding the time course of the development of the illness as function of exposure duration, although this was only examined in relation to rotating shiftwork. It is concluded that those responsible for monitoring workers' health should pay particular attention to indices of metabolic dysfunction in workers who have been exposed to shiftwork for >10 yrs. (Author correspondence: p.t.tucker@swansea.ac.uk)     

Free Fatty Acids,Insulin Resistance,and Corrected QT Intervals in Morbid Obesity: Effect of Weight Loss During 6 Months With Differing Dietary Interventions

ObjectiveTo assess whether shortening of the corrected QT (QTc) interval is most closely associated with changes in weight, insulin resistance, or free fatty acids (FFAs) (or some combination of these factors).MethodsWe randomized 75 severely obese subjects without diabetes to either a low-carbohydrate or a conventional low-fat weight-loss diet for 6 months. We measured QTc, insulin sensitivity, body mass index, and FFAs at baseline and at 6 months. Analysis was performed to determine whether improvement in weight, in insulin resistance, or in FFAs has the greatest effect on reducing the QTc interval.Results“Completers” of both the low-carbohydrate diet (N = 25) and the low-fat diet (N = 22) had a decrease in weight, but the weight loss was greater in the low-carbohydrate group. A statistically significant decrease in QTc from baseline was observed only in the low-carbohydrate group. QTc in the low-carbohydrate group correlated with improvement in insulin resistance, but this finding was not significant after correction for the greater weight loss. FFAs or weight loss was not correlated with QTc in either dietary group.ConclusionLow-carbohydrate dieting is associated with a greater decrease in the QTc interval in comparison with low-fat dieting. Improvements in insulin resistance seem to have a relatively weak mechanistic role, and a decrease in FFAs has no apparent role in the reduction of the QTc interval. (Endocr Pract. 2005;11:234-239)     

Enalapril decreases rat plasma concentration of TMAO,a gut bacteria-derived cardiovascular marker

Introduction: Increased plasma level of trimethylamine N-oxide (TMAO), a bacterial metabolite of choline, is associated with an increased cardiovascular risk. Indoxyl sulfate, a bacterial metabolite of tryptophan, is thought to be associated with higher mortality in cardiorenal syndrome. We hypothesized that enalapril, a well-established drug reducing cardiovascular mortality, may affect the plasma level of gut bacteria-derived metabolites and gut bacteria composition.

Materials and methods: 14–16-week-old Wistar rats were maintained either on water (controls) or water solution of enalapril for two weeks (5.3 or 12.6?mg/kg b.w.). Blood plasma and urine were analyzed for the concentration of TMAO and indoxyl sulfate using liquid chromatography coupled with triple-quadrupole mass spectrometry. Gut bacteria composition was analyzed with 16S rRNA gene sequence analysis.

Results: Rats treated with enalapril showed a significantly lower plasma TMAO level and a trend towards higher 24?h urine excretion of TMA and TMAO. Plasma indoxyl level was similar between the groups. There was no significant difference between the groups in gut bacteria composition.

Conclusions: Enalapril decreases rat plasma TMAO, but does not affect the plasma level of indoxyl sulfate and gut bacteria composition. The enalapril-induced decrease in plasma TMAO level may be of therapeutic and diagnostic importance.     

Plasma levels of nesfatin-1 as a new biomarker in depression in Asians: evidence from meta-analysis

Abstract

Objective: This study aims to review the alteration of plasma nesfatin-1 levels in patients with depression.

Methods: Under the guidance of the latest PRISMA checklist, a systematic review and meta-analysis were conducted by searching English database (PubMed, Web of Science, EMDASE) and Chinese database for relevant studies up to August, 2019. Pooled standardised mean difference (SMD) with 95% confidence intervals (CI) was calculated with the random effects model.

Results: Nine studies that reported the association between plasma levels of nesfatin-1 and the risk of depression with 567 patients and 447 control participants were included in the meta-analysis. Compared with the healthy controls, depressive patients had a higher plasma level of nesfatin-1 [SMD (95% CI):1.58(0.75, 2.41), Z?=?3.74, p for Z?<?0.001; I² = 96.8%, p for I² < 0.001]. The subgroup analyses and meta-regression failed to find the source of the heterogeneity. No evidence of publication bias was found either in Begg’s test (p?=?0.348) or the Egger’s test (p?=?0.523).

Conclusion: The present meta-analysis indicated that a higher plasma level of nesfatin-1 was associated with an increased risk of depression.     

Quantitative relationship between plasma potassium levels and QT interval in beagle dogs

The aim of the current study was to establish the quantitative relationship between plasma potassium concentrations and the QT interval of the electrocardiogram in dogs. Furosemide, a potent diuretic, was given at increasing doses (5-60 mg/kg) to five male and five female beagle dogs. Electrocardiogram (ECG) was recorded three times each day, simultaneous to blood sampling for measurement of plasma potassium. Furosemide treatment produced a clear hypokalaemia, which was associated with an increase in QT and corrected QT intervals (QTc) duration. On average, the slopes of the negative linear correlation between potassium plasma levels and QT or QTc were steeper in females than in males. These results show that a decrease in potassium plasma level may explain a concomitant increase in QT duration in a toxicity study in dogs, in particular if potassium values are decreased below 3.3 mmol/L. Correction of QT interval for K+ plasma level has, therefore, been established separately for males and females. A global formula correcting QT for K+ and heart rate simultaneously was established. Hypokalaemia was also associated with changes in the morphology of the T wave recorded in CV5RL, in particular, with a flattening and/or a notching of the wave (appearance of a second peak), biphasic aspect or inversion of polarity. These changes are probably related to an increased heterogeneity of repolarization between different populations of cardiomyocytes. In conclusion, hypokalaemia is quantitatively associated with an increase in QT and QTc duration in dogs. The relationship is apparently stronger for females than for males. A formula may be used to correct QT for potassium plasma level.     

原发性肾小球肾炎患者血浆高同型半胱氨酸水平的变化及与钙磷乘积和血尿酸的相关性分析

目的:分析原发性肾小球肾炎患者血浆高同型半胱氨酸(Hcy)水平的变化及其与钙磷乘积、血尿酸(UA)的相关性。方法:选择2016年3月至2018年3月在我院就诊的80例原发性肾小球肾炎患者作为观察组,另选取同期于我院接受体检的50例健康者作为对照组。采用循环酶法测定受检者血浆Hcy水平,通过比色法测定血清UA,采用离子选择电极法测定血清钙离子(Ca^2+)、磷离子(P3+),对比两组各项血液指标水平及阳性检出率,并通过Pearson分析法分析血浆Hcy与钙磷乘积、UA的相关性。结果:观察组血浆Hcy、P^3+、钙磷乘积及UA水平高于对照组,Ca^2+低于对照组,差异有统计学意义(P<0.05)。观察组Hcy、Ca^2+、P^3+、UA阳性检出率高于对照组,差异有统计学意义(P<0.05)。血浆Hcy水平与Ca^2+呈负相关(r=-2.208,P<0.05),与P3+、钙磷乘积、UA呈正相关(r=0.102、0.592、0.703,P均<0.05)。结论:原发性肾小球肾炎患者血浆Hcy水平较高,且其水平与钙磷乘积、UA水平呈正相关,故监测三项指标变化可为临床防治该病提供科学依据。     

Early dinner or “dinner like a pauper”: Evidence,the habitual time of the largest meal of the day – dinner – is predisposing to severe COVID-19 outcome – death

ABSTRACT

COVID-19 and metabolic syndrome are devastating pandemics. Effective control of metabolic parameters and their dysfunction may help prevent or minimize the acute and devastating effects of SARS-CoV-2 by reducing the local inflammatory response and blocking the entry of the virus into cells. With such consideration in mind, we gathered data from dietary surveys conducted in nine European countries to explore the relationship between actual clock hour of the large dinner meal and also interval in minutes between it and sunset in the respective countries and death rate above the median rate of per one million people as an index of mortality due to COVID-19 infection. Clock time of the dinner meal varied between 16:00 and 21:00 h across the European counties sampled, and the correlation between dinner mealtime and death rate was strongly correlated, R = 0.7991 (two-tailed p = 0.0098), with R ² explaining 63% of the variation within the data. This strong linear positive correlation indicates that the later the clock time of the dinner meal, the higher is the death rate (and vice versa). The relationship between meal timing in reference to sunset, utilized as a gross surrogate marker of the activity/rest synchronizer of circadian rhythms, and death rate was negative and even slightly stronger, R = ?0.8025 (two-tailed p = 0.0092), with R ² explaining 64% of the variation within the data. This strong linear negative correlation indicates that the shorter the interval between the dinner meal and sunset, i.e., the closer the time of the largest meal of the day to bedtime, the greater is the death rate (and vice versa). Our preliminary approach to nighttime eating, in terms of the day’s largest caloric intake, as a risk factor for the predisposing conditions of obesity, metabolic syndrome, type 2 diabetes, and other commonly associated comorbidities of being overweight, and death from COVID-19 infection reveals strong correlation with the time of the dinner meal, both in terms of its actual clock and circadian time.     

Detecting neuronal dysfunction of hand motor cortex in ALS: A MRSI study

Background: Although hand motor cortex (HMC) has been constantly used for identification of primary motor cortex in magnetic resonance spectroscopy (MRS) studies of amyotrophic lateral sclerosis (ALS), neurochemical profiles of HMC have never been assessed independently. As HMC has a constant location and the clinic–anatomic correlation between hand motor function and HMC has been established, we hypothesize that HMC may serve as a promising region of interest in diagnosing ALS.

Patients and methods: Fourteen ALS patients and 14 age- and gender-matched healthy controls (HC) were recruited in this study. An optimized magnetic resonance spectroscopic imaging (MRSI) method was developed and for each subject bilateral HMC areas were scanned separately (two-dimensional multi-voxel MRSI, voxel size 0.56?cm³). N-acetyl aspartate (NAA)–creatine (Cr) ratio was measured from HMC and the adjacent postcentral gyrus.

Results: Compared with HC, NAA/Cr ratios from HMC and the postcentral gyrus were significantly reduced in ALS. However, in each group the difference of NAA/Cr ratios between HMC and the postcentral gyrus was not significant. Limb predominance of HMC was not found in either ALS or HC. In ALS, there was a significant difference in NAA/Cr ratio between the most affected HMC and the less affected HMC. A positive relationship between NAA/Cr ratio of HMC and the severity of hand strength (assessed by finger tapping speed) was demonstrated.

Conclusion: Neuronal dysfunction of HMC can differentiate ALS patients from HC when represented as reduced NAA/Cr ratio. Postcentral gyrus could not serve as normal internal reference tissue in diagnosing ALS. Asymmetrical NAA/Cr ratios from bilateral HMC may serve as a promising diagnostic biomarker of ALS at the individual level.     

No genetic footprints of the fat mass and obesity associated (FTO) gene in human plasma 1H CPMG NMR metabolic profiles

In this paper it was investigated if any genotypic footprints from the fat mass and obesity associated (FTO) SNP could be found in 600 MHz ¹H CPMG NMR profiles of around 1,000 human plasma samples from healthy Danish twins. The problem was addressed with a combination of univariate and multivariate methods. The NMR data was substantially compressed using principal component analysis or multivariate curve resolution-alternating least squares with focus on chemically meaningful feature selection reflecting the nature of chemical signals in an NMR spectrum. The possible existence of an FTO signature in the plasma samples was investigated at the subject level using supervised multivariate classification in the form of extended canonical variate analysis, classification tree modeling and Lasso (L1) regularized linear logistic regression model (GLMNET). Univariate hypothesis testing of peak intensities was used to explore the genotypic effect on the plasma at the population level. The multivariate classification approaches indicated poor discriminative power of the metabolic profiles whereas univariate hypothesis testing provided seven spectral regions with p < 0.05. Applying false discovery rate control, no reliable markers could be identified, which was confirmed by test set validation. We conclude that it is very unlikely that an FTO-correlated signal can be identified in these ¹H CPMG NMR plasma metabolic profiles and speculate that high-throughput un-targeted genotype-metabolic correlations will in many cases be a difficult path to follow.     

Dose-response relationship of elements with blood lipids and the potential interaction: A cross-sectional study from four areas with different pollution levels in China

BackgroundA growing number of researches indicated the association between plasma trace elements and blood lipids. However, the potential interaction and dose-response relationship were less frequently reported.MethodsIn this study, a total of 3548 participants were recruited from four counties in Hunan Province, South China. Demographic characteristics were collected by face-to-face interviews and inductively coupled plasma mass spectrometry (ICPMS) was used to determine the levels of 23 trace elements in plasma. We applied a fully adjusted generalized linear regression model (GLM) and a multivariate restricted cubic spline (RCS) to estimate the correlation, dose-response relationship and possible interaction between 23 trace elements and four blood lipid markers.ResultsThe results indicated positive dose-response relationships of plasma ⁶⁶zinc with triglycerides (TG) and low density lipoprotein cholesterol (LDL-C), plasma ⁷⁸selenium with LDL-C and total cholesterol (TCH), and plasma ⁵⁹cobalt with high-density lipoprotein cholesterol (HDL-C). There was a negative dose-response relationship between ⁵⁹cobalt and LDL-C. Further analysis found that ⁶⁶zinc and ⁵⁹cobalt had an antagonistic effect on the risk of increased LDL-C level.ConclusionsThis study added new evidence for the potential adverse effects of ⁶⁶Zn and ⁷⁸Se on blood lipids, and provided new insight into the threshold value setting for metals as well as the intervention strategy for dyslipidemia.     

Seasonal variation of circulating plasma carotenoids in Mediterranean Great Tit males Parus major

Capsule Mediterranean Great Tits showed a marked increase in levels of circulating carotenoids during moult and autumn.

Aims To study seasonal variation in plasma carotenoid content during a whole annual cycle for Great Tits Parus major inhabiting a Mediterranean woodland.

Methods We used a sample of 71 adult male Great Tits captured in NE Spain during a whole year. Data were organized into four seasons (winter, breeding, moult and autumn). We sampled blood to extract plasma. Carotenoid plasma concentrations were analysed by High-performance liquid chromatography (HPLC).

Results Lutein and zeaxanthin content varied seasonally, with a marked increase in levels during moult and autumn. Within the moulting period, levels increased gradually as the season progressed. This pattern differed significantly from that previously described in northern European populations, where high values appear mainly in the breeding season. Carotenoid concentrations (lutein: 1.2?±?0.25, zeaxanthin: 0.07?±?0.03?µg mL^?1) were also lower than in northern Europe.

Conclusion Mediterranean Great Tits show a very different pattern of circulating carotenoids and lower levels than northern European populations. The increasing pattern of carotenoid availability found within the moulting period raises the need to control for the effect of sampling date when analysing data on carotenoid concentrations at different times of year.     

Hydroxychloroquine and QTc prolongation in patients with COVID-19: A systematic review and meta-analysis

BackgroundAmong many drugs that hold potential in COVID-19 pandemic, chloroquine (CQ), and its derivative hydroxychloroquine (HCQ) have generated unusual interest. With increasing usage, there has been growing concern about the prolongation of QTc interval and Torsades de Pointes (TdP) with HCQ, especially in combination with azithromycin.AimsThis meta-analysis is planned to study the risk of QTc prolongation and Torsades de pointes (TdP) by a well-defined criterion for HCQ, CQ alone, and in combination with Azithromycin in patients with COVID-19.MethodsA comprehensive literature search was made in two databases (PubMed, Embase). Three outcomes explored in the included studies were frequency of QTc > 500 ms (ms) or ΔQTc > 60 ms (Outcome 1), frequency of QTc > 500 ms (Outcome 2) and frequency of TdP (Outcome 3). Random effects method with inverse variance approach was used for computation of pooled summary and risk ratio.ResultsA total of 13 studies comprising of 2138 patients were included in the final analysis. The pooled prevalence of outcome 1, outcome 2 and outcome 3 for HCQ, CQ with or without Azithromycin were 10.18% (5.59–17.82%, I² – 92%), 10.22% (6.01–16.85%, I² – 79%), and 0.72% (0.34–1.51, I² – 0%) respectively. The prevalence of outcome 2 in subgroup analysis for HCQ and HCQ + Azithromycin was 7.25% (3.22–15.52, I² – 59%) and 8.61% (4.52–15.79, I² – 76%), respectively. The risk ratio (RR) for outcome 1 and outcome 2 between HCQ + Azithromycin and HCQ was 1.22 (0.77–1.93, I² – 0%) & 1.51 (0.79–2.87, I² – 13%), respectively and was not significant. Heterogeneity was noted statistically as well clinically (regimen types, patient numbers, study design, and outcome definition).ConclusionThe use of HCQ/CQ is associated with a high prevalence of QTc prolongation. However, it is not associated with a high risk of TdP.