Effects of blood collection conditions on ovarian cancer serum markers

Background

Evaluating diagnostic and early detection biomarkers requires comparing serum protein concentrations among biosamples ascertained from subjects with and without cancer. Efforts are generally made to standardize blood processing and storage conditions for cases and controls, but blood sample collection conditions cannot be completely controlled. For example, blood samples from cases are often obtained from persons aware of their diagnoses, and collected after fasting or in surgery, whereas blood samples from some controls may be obtained in different conditions, such as a clinic visit. By measuring the effects of differences in collection conditions on three different markers, we investigated the potential of these effects to bias validation studies.

Methodology and Principle Findings

We analyzed serum concentrations of three previously studied putative ovarian cancer serum biomarkers–CA 125, Prolactin and MIF–in healthy women, women with ovarian cancer undergoing gynecologic surgery, women undergoing surgery for benign ovary pathology, and women undergoing surgery with pathologically normal ovaries. For women undergoing surgery, a blood sample was collected either in the clinic 1 to 39 days prior to surgery, or on the day of surgery after anesthesia was administered but prior to the surgical procedure, or both. We found that one marker, prolactin, was dramatically affected by collection conditions, while CA 125 and MIF were unaffected. Prolactin levels were not different between case and control groups after accounting for the conditions of sample collection, suggesting that sample ascertainment could explain some or all of the previously reported results about its potential as a biomarker for ovarian cancer.

Conclusions

Biomarker validation studies should use standardized collection conditions, use multiple control groups, and/or collect samples from cases prior to influence of diagnosis whenever feasible to detect and correct for potential biases associated with sample collection.     

Prevalence and risk factors of overweight and obesity in China

Objective: To examine the prevalence and risk factors of overweight and obesity in China. Research Methods and Procedures: A cross‐sectional survey was conducted in a nationally representative sample of 15,540 Chinese adults in 2000–2001. Body weight, height, and waist circumference were measured by trained observers. Overweight and obesity were defined according to the World Health Organization classification. Central obesity was defined according to guidelines of the International Diabetes Federation. Results: Mean BMI and waist circumference were 23.1 kg/m² and 79.6 cm, respectively, for men and 23.5 kg/m² and 77.2 cm, respectively, for women. The prevalences of overweight and obesity were 24.1% and 2.8% in men and 26.1% and 5.0% in women, respectively. The prevalence of central obesity was 16.1% in men and 37.6% in women. The prevalences of overweight, obesity, and central obesity were higher among residents in northern China compared with their counterparts in southern China and among those in urban areas compared with those in rural areas. Lifestyle factors were the most important risk factors to explain the differences in overweight and central obesity between northern and southern residents. Among women, lifestyle and diet were the most important risk factors to explain the differences between urban and rural residents, whereas socioeconomic status, lifestyle, and diet were all important among men. Discussion: Our study indicates that overweight and obesity have become important public health problems in China. Environmental risk factors may be the main reason for regional differences in the prevalence of overweight and obesity in China.     

Elevated temperature is more effective than elevated [CO2] in exposing genotypic variation in Telopea speciosissima growth plasticity: implications for woody plant populations under climate change

Intraspecific variation in phenotypic plasticity is a critical determinant of plant species capacity to cope with climate change. A long‐standing hypothesis states that greater levels of environmental variability will select for genotypes with greater phenotypic plasticity. However, few studies have examined how genotypes of woody species originating from contrasting environments respond to multiple climate change factors. Here, we investigated the main and interactive effects of elevated [CO₂] (C_E) and elevated temperature (T_E) on growth and physiology of Coastal (warmer, less variable temperature environment) and Upland (cooler, more variable temperature environment) genotypes of an Australian woody species Telopea speciosissima. Both genotypes were positively responsive to C_E (35% and 29% increase in whole‐plant dry mass and leaf area, respectively), but only the Coastal genotype exhibited positive growth responses to T_E. We found that the Coastal genotype exhibited greater growth response to T_E (47% and 85% increase in whole‐plant dry mass and leaf area, respectively) when compared with the Upland genotype (no change in dry mass or leaf area). No intraspecific variation in physiological plasticity was detected under C_E or T_E, and the interactive effects of C_E and T_E on intraspecific variation in phenotypic plasticity were also largely absent. Overall, T_E was a more effective climate factor than C_E in exposing genotypic variation in our woody species. Our results contradict the paradigm that genotypes from more variable climates will exhibit greater phenotypic plasticity in future climate regimes.     

Three‐Dimensional Smart Catalyst Electrode for Oxygen Evolution Reaction

A multifunctional catalyst electrode mimicking external stimuli–responsive property has been prepared by the in situ growth of nitrogen (N)‐doped NiFe double layered hydroxide (N–NiFe LDH) nanolayers on a 3D nickel foam substrate framework. The electrode demonstrates superior performance toward catalyzing oxygen evolution reaction (OER), affording a low overpotential of 0.23 V at the current density of 10 mA cm^?2, high Faradaic efficiency of ≈98%, and stable operation for >60 h. Meanwhile, the electrode can dynamically change its color from gray silver to dark black with the OER happening, and the coloration/bleaching processes persist for at least 5000 cycles, rendering it a useful tool to monitor the catalytic process. Mechanism study reveals that the excellent structural properties of electrode such as 3D conductive framework, ultra thickness of N–NiFe LDH nanolayer (≈0.8 nm), and high N‐doping content (≈17.8%) make significant contribution to achieving enhanced catalytic performance, while N–NiFe LDH nanolayer on electrode is the main contributor to the stimuli‐responsive property with the reversible extraction/insertion of electrons from/into N–NiFe LDH leading to the coloration/bleaching processes. Potential application of this electrode has been further demonstrated by integrating it into a Zn–air battery device to identify the charging process during electrochemical cycling.     

Initial locomotor sensitivity to cocaine varies widely among inbred mouse strains

Initial sensitivity to psychostimulants can predict subsequent use and abuse in humans. Acute locomotor activation in response to psychostimulants is commonly used as an animal model of initial drug sensitivity and has been shown to have a substantial genetic component. Identifying the specific genetic differences that lead to phenotypic differences in initial drug sensitivity can advance our understanding of the processes that lead to addiction. Phenotyping inbred mouse strain panels are frequently used as a first step for studying the genetic architecture of complex traits. We assessed locomotor activation following a single, acute 20 mg/kg dose of cocaine (COC) in males from 45 inbred mouse strains and observed significant phenotypic variation across strains indicating a substantial genetic component. We also measured levels of COC, the active metabolite, norcocaine and the major inactive metabolite, benzoylecgonine, in plasma and brain in the same set of inbred strains. Pharmacokinetic (PK) and behavioral data were significantly correlated, but at a level that indicates that PK alone does not account for the behavioral differences observed across strains. Phenotypic data from this reference population of inbred strains can be utilized in studies aimed at examining the role of psychostimulant‐induced locomotor activation on drug reward and reinforcement and to test theories about addiction processes. Moreover, these data serve as a starting point for identifying genes that alter sensitivity to the locomotor stimulatory effects of COC.     

Proteomic profile of carbonylated proteins in rat liver: Discovering possible mechanisms for tetracycline‐induced steatosis

To investigate biochemical mechanisms for the tetracycline‐induced steatosis in rats, targeted proteins of oxidative modification were profiled. The results showed that tetracycline induced lipid accumulation, oxidative stress, and cell viability decline in HepG2 cells only under the circumstances of palmitic acid overload. Tetracycline administration in rats led to significant decrement in blood lipids, while resulted in more than four times increment in intrahepatic triacylglycerol and typical microvesicular steatosis in the livers. The triacylglycerol levels were positively correlated with oxidative stress. Proteomic profiles of carbonylated proteins revealed 26 targeted proteins susceptible to oxidative modification and most of them located in mitochondria. Among them, the long‐chain specific acyl‐CoA dehydrogenase was one of the key enzymes regulating fatty acid β‐oxidation. Oxidative modification of the enzyme in the tetracycline group depressed its enzymatic activity. In conclusion, the increased influx of lipid into the livers is the first hit of tetracycline‐induced microvesicular steatosis. Oxidative stress is an essential part of the second hit, which may arise from the lipid overload and attack a series of functional proteins, aggravating the development of steatosis. The 26 targeted proteins revealed here provide a potential direct link between oxidative stress and tetracycline‐induced steatosis.     

Trinary Layered Double Hydroxides as High‐Performance Bifunctional Materials for Oxygen Electrocatalysis

Layered double hydroxides (LDHs) are a family of high‐profile layer materials with tunable metal species and interlayer spacing, and herein the LDHs are first investigated as bifunctional electrocatalysts. It is found that trinary LDH containing nickel, cobalt, and iron (NiCoFe‐LDH) shows a reasonable bifunctional performance, while exploiting a preoxidation treatment can significantly enhance both oxygen reduction reaction and oxygen evolution reaction activity. This phenomenon is attributed to the partial conversion of Co²⁺ to Co³⁺ state in the preoxidation step, which stimulates the charge transfer to the catalyst surface. The practical application of the optimized material is demonstrated with a small potential hysteresis (800 mV for a reversible current density of 20 mA cm^?2) as well as a high stability, exceeding the performances of noble metal catalysts (commercial Pt/C and Ir/C). The combination of the electrochemical metrics and the facile and cost‐effective synthesis endows the trinary LDH as a promising bifunctional catalyst for a variety of applications, such as next‐generation regenerative fuel cells or metal–air batteries.