Stability of Piceatannol in Dulbecco's Modified Eagle's Medium by In Situ UPLC-MS/MS Analysis

Piceatannol is a stilbenoid, which has shown bioactivities in various cell culture models. However, its stability in cell culture medium is not clear. Here, UPLC-MS/MS was applied in situ to analyze the degradation products of piceatannol in Dulbecco's Modified Eagle's Medium (DMEM) and cell culture to investigate the compound's stability in DMEM. During the incubation with cell culture medium (at 4 and 37 °C), several piceatannol derivatives, such as an oxidation product ( m/z 243.06), a reduction product ( m/z 247.09), dimers ( m/z 485.12 and 487.14) and trimers ( m/z 727.18) were detected, which demonstrated the instability of piceatannol in cell culture conditions. To confirm if the new products during the incubation were generated due to the instability of piceatannol, ascorbic acid was added. The presence of ascorbic acid could significantly slow the degradation rate of piceatannol and the generation of piceatannol derivatives, which proved that the new products were generated by the degradation of piceatannol and indicated that the instability of piceatannol might be related to its antioxidant activity

A Unifying Framework for Evaluating the Predictive Power of Genetic Variants Based on the Level of Heritability Explained

An increasing number of genetic variants have been identified for many complex diseases. However, it is controversial whether risk prediction based on genomic profiles will be useful clinically. Appropriate statistical measures to evaluate the performance of genetic risk prediction models are required. Previous studies have mainly focused on the use of the area under the receiver operating characteristic (ROC) curve, or AUC, to judge the predictive value of genetic tests. However, AUC has its limitations and should be complemented by other measures. In this study, we develop a novel unifying statistical framework that connects a large variety of predictive indices together. We showed that, given the overall disease probability and the level of variance in total liability (or heritability) explained by the genetic variants, we can estimate analytically a large variety of prediction metrics, for example the AUC, the mean risk difference between cases and non-cases, the net reclassification improvement (ability to reclassify people into high- and low-risk categories), the proportion of cases explained by a specific percentile of population at the highest risk, the variance of predicted risks, and the risk at any percentile. We also demonstrate how to construct graphs to visualize the performance of risk models, such as the ROC curve, the density of risks, and the predictiveness curve (disease risk plotted against risk percentile). The results from simulations match very well with our theoretical estimates. Finally we apply the methodology to nine complex diseases, evaluating the predictive power of genetic tests based on known susceptibility variants for each trait

Atomic-scale combination of germanium-zinc nanofibers for structural and electrochemical evolution

Alloys are recently receiving considerable attention in the community of rechargeable batteries as possible alternatives to carbonaceous negative electrodes; however, challenges remain for the practical utilization of these materials. Herein, we report the synthesis of germanium-zinc alloy nanofibers through electrospinning and a subsequent calcination step. Evidenced by in situ transmission electron microscopy and electrochemical impedance spectroscopy characterizations, this one-dimensional design possesses unique structures. Both germanium and zinc atoms are homogenously distributed allowing for outstanding electronic conductivity and high available capacity for lithium storage. The as-prepared materials present high rate capability (capacity of similar to 50% at 20 C compared to that at 0.2 C-rate) and cycle retention (73% at 3.0 C-rate) with a retaining capacity of 546 mAh g(-1) even after 1000 cycles. When assembled in a full cell, high energy density can be maintained during 400 cycles, which indicates that the current material has the potential to be used in a large-scale energy storage system

Psychiatric disorders in individuals born very preterm / very low-birth weight: An individual participant data (IPD) meta-analysis

Background: Data on psychiatric disorders in survivors born very preterm (VP; <32 weeks) or very low birthweight (VLBW; <1500 g) are sparse. We compared rates of psychiatric diagnoses between VP/VLBW and term-born, normal birthweight (term/NBW) control participants. / Methods: This individual participant data (IPD) meta-analysis pooled data from eligible groups in the Adults born Preterm International Collaboration (APIC). Inclusion criteria included: 1) VP/VLBW group (birth weight 2499 g and/or gestational age ≥37 weeks), and 3) structured measure of psychiatric diagnoses using DSM or ICD criteria. Diagnoses of interest were Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Anxiety Disorder, Mood Disorder, Disruptive Behaviour Disorder (DBD), Eating Disorder, and Psychotic Disorder. A systematic search for eligible studies was conducted (PROSPERO Registration Number 47555). / Findings: Data were obtained from 10 studies (1385 VP/VLBW participants, 1780 controls), using a range of instruments and approaches to assigning diagnoses. Those born VP/VLBW had ten times higher odds of meeting criteria for ASD (odds ratio [OR] 10·6, 95% confidence interval [CI] 2·50, 44·7), five times higher odds of meeting criteria for ADHD (OR 5·42, 95% CI 3·10, 9·46), twice the odds of meeting criteria for Anxiety Disorder (OR 1·91, 95% CI 1·36, 2·69), and 1·5 times the odds of meeting criteria for Mood Disorder (OR 1·51, 95% CI 1·08, 2·12) than controls. This pattern of findings was consistent within age (<18 years vs. ≥18 years) and sex subgroups. / Interpretation: Our data suggests that individuals born VP/VLBW might have higher odds of meeting criteria for certain psychiatric disorders through childhood and into adulthood than term/NBW controls. Further research is needed to corroborate our results and identify factors associated with psychiatric disorders in individuals born VP/VLBW. / Funding: Australia's National Health & Medical Research Council; CAPES (Coordenação de Aperfeiçoamento de Pessoal deNível Superior) - International Cooperation General Program; Canadian Institutes of Health Research Team Grant; National Council for Scientific and Technological Development (CNPq); Academy of Finland; Sigrid Juselius Foundation; Signe and Ane Gyllenberg Foundation; European Union's Horizon 2020 research and innovation programme: Project RECAP-Preterm; European Commission Dynamics of Inequality Across the Life-course: structures and processes (DIAL); Neurologic Foundation of New Zealand; MRC programme grant; Health Research Council of New Zealand; National Institutes of Health, USA; The Research Council of Norway; Joint Research Committee between St. Olavs Hospital and Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU); Liaison Committee between Central Norway Regional Health Authority and NTNU

Accounting Problems Under the Excess Profits Tax

DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.Funding Agencies|Research Council of Norway; Odd Fellow</p

Sustained Oscillations of NF-κB Produce Distinct Genome Scanning and Gene Expression Profiles

NF-κB is a prototypic stress-responsive transcription factor that acts within a complex regulatory network. The signaling dynamics of endogenous NF-κB in single cells remain poorly understood. To examine real time dynamics in living cells, we monitored NF-κB activities at multiple timescales using GFP-p65 knock-in mouse embryonic fibroblasts. Oscillations in NF-κB were sustained in most cells, with several cycles of transient nuclear translocation after TNF-α stimulation. Mathematical modeling suggests that NF-κB oscillations are selected over other non-oscillatory dynamics by fine-tuning the relative strengths of feedback loops like IκBα. The ability of NF-κB to scan and interact with the genome in vivo remained remarkably constant from early to late cycles, as observed by fluorescence recovery after photobleaching (FRAP). Perturbation of long-term NF-κB oscillations interfered with its short-term interaction with chromatin and balanced transcriptional output, as predicted by the mathematical model. We propose that negative feedback loops do not simply terminate signaling, but rather promote oscillations of NF-κB in the nucleus, and these oscillations are functionally advantageous

An outbreak of post-acupuncture cutaneous infection due to Mycobacterium abscessus

BACKGROUND: Despite the increasing popularity of acupuncture, the importance of infection control is not adequately emphasized in Oriental medicine. In December 2001, an Oriental medical doctor in Seoul, South Korea, encountered several patients with persistent, culture-negative skin lesions on the trunk and extremities at the sites of prior acupuncture treatment. We identified and investigated an outbreak of Mycobacterium abscessus cutaneous infection among the patients who attended this Oriental medicine clinic. METHODS: Patients were defined as clinic patients with persistent cutaneous infections at the acupuncture sites. Medical records for the previous 7 months were reviewed. Clinical specimens were obtained from the patients and an environmental investigation was performed. M. abscessus isolates, cultured from patients, were compared by pulsed-field gel electrophoresis (PFGE). RESULTS: Forty patients who attended the Oriental medicine clinic and experienced persistent cutaneous wound infections were identified. Cultures from five of these patients proved positive, and all other diagnoses were based on clinical and histopathologic examinations. All environmental objects tested were negative for M. abscessus, however, most were contaminated by various nosocomial pathogens. Molecular analysis using PFGE found all wound isolates to be identical. CONCLUSION: We have identified a large outbreak of rapidly growing mycobacterial infection among patients who received acupuncture at a single Oriental medicine clinic. Physicians should suspect mycobacterial infections in patients with persistent cutaneous infections following acupuncture, and infection control education including hygienic practice, should be emphasized for Oriental medical doctors practicing acupuncture

Evaluation of a fiberoptic-based system for measurement of optical properties in highly attenuating turbid media

BACKGROUND: Accurate measurements of the optical properties of biological tissue in the ultraviolet A and short visible wavelengths are needed to achieve a quantitative understanding of novel optical diagnostic devices. Currently, there is minimal information on optical property measurement approaches that are appropriate for in vivo measurements in highly absorbing and scattering tissues. We describe a novel fiberoptic-based reflectance system for measurement of optical properties in highly attenuating turbid media and provide an extensive in vitro evaluation of its accuracy. The influence of collecting reflectance at the illumination fiber on estimation accuracy is also investigated. METHODS: A neural network algorithm and reflectance distributions from Monte Carlo simulations were used to generate predictive models based on the two geometries. Absolute measurements of diffuse reflectance were enabled through calibration of the reflectance system. Spatially-resolved reflectance distributions were measured in tissue phantoms at 405 nm for absorption coefficients (μ(a)) from 1 to 25 cm(-1 )and reduced scattering coefficients ([Formula: see text]) from 5 to 25 cm(-1). These data and predictive models were used to estimate the optical properties of tissue-simulating phantoms. RESULTS: By comparing predicted and known optical properties, the average errors for μ(a )and [Formula: see text] were found to be 3.0% and 4.6%, respectively, for a linear probe approach. When bifurcated probe data was included and samples with μ(a )values less than 5 cm(-1 )were excluded, predictive errors for μ(a )and [Formula: see text] were further reduced to 1.8% and 3.5%. CONCLUSION: Improvements in system design have led to significant reductions in optical property estimation error. While the incorporation of a bifurcated illumination fiber shows promise for improving the accuracy of [Formula: see text] estimates, further study of this approach is needed to elucidate the source of discrepancies between measurements and simulation results at low μ(a )values

The prognostic value of multivoxel magnetic resonance spectroscopy determined metabolite levels in white and grey matter brain tissue for adverse outcome in term newborns following perinatal asphyxia

Magnetic resonance spectroscopy can identify brain metabolic changes in perinatal asphyxia by providing ratios of metabolites, such as choline (Cho), creatine (Cr), N-acetyl aspartate (NAA) and lactate (Lact) [Cho/Cr, Lact/NAA, etc.]. The purpose of this study was to quantify the separate white and grey matter metabolites in a slab cranial to the ventricles and relate these to the outcome. A standard 2D-chemical shift imaging protocol was used for measuring a transverse volume of interest located cranial to the ventricles allowing for direct comparison of the metabolites in white and grey matter brain tissue in 24 term asphyxiated newborns aged 3 to 16 days. Cho, NAA and Lact showed significant differences between four subgroups of asphyxiated infants with more and less favourable outcomes. High levels of Cho and Lact in the grey matter differentiated non-survivors from survivors (P = 0.003 and P = 0.017, respectively). In perinatal asphyxia the levels of Cho, NAA and Lact in both white and grey matter brain tissue are affected. The levels of Cho and Lact measured in the grey matter are the most indicative of survival. It is therefore advised to include grey matter brain tissue in the region of interest examined by multivoxel MR spectroscopy. aEuro cent Magnetic resonance spectroscopy can identify brain metabolic changes in perinatal asphyxia. aEuro cent Choline and lactate levels in grey matter seem the best indicators of survival. aEuro cent Both grey and white matter should be examined during spectroscopy for perinatal asphyxia