Comparing Growth Trajectories of Risk Behaviors From Late Adolescence Through Young Adulthood: An Accelerated Design.

Risk behaviors such as substance use or deviance are often limited to the early stages of the life course. Whereas the onset of risk behavior is well studied, less is currently known about the decline and timing of cessation of risk behaviors of different domains during young adulthood. Prevalence and longitudinal developmental patterning of alcohol use, drinking to the point of drunkenness, smoking, cannabis use, deviance, and HIV-related sexual risk behavior were compared in a Swiss community sample (N = 2,843). Using a longitudinal cohort-sequential approach to link multiple assessments with 3 waves of data for each individual, the studied period spanned the ages of 16 to 29 years. Although smoking had a higher prevalence, both smoking and drinking up to the point of drunkenness followed an inverted U-shaped curve. Alcohol consumption was also best described by a quadratic model, though largely stable at a high level through the late 20s. Sexual risk behavior increased slowly from age 16 to age 22 and then remained largely stable. In contrast, cannabis use and deviance linearly declined from age 16 to age 29. Young men were at higher risk for all behaviors than were young women, but apart from deviance, patterning over time was similar for both sexes. Results about the timing of increase and decline as well as differences between risk behaviors may inform tailored prevention programs during the transition from late adolescence to adulthood

Spectral Asymmetry and Higuchi’s Fractal Dimension Measures of Depression Electroencephalogram

This study was aimed to compare two electroencephalogram (EEG) analysis methods, spectral asymmetry index (SASI) and Higuchi’s fractal dimension (HFD), for detection of depression. Linear SASI method is based on evaluation of the balance of powers in two EEG frequency bands in one channel selected higher and lower than the alpha band spectrum maximum. Nonlinear HFD method calculates fractal dimension directly in the time domain. The resting EEG signals of 17 depressive patients and 17 control subjects were used as a database for calculations. SASI values were positive for depressive and negative for control group (P0.05). The results indicated that the linear EEG analysis method SASI and the nonlinear HFD method both demonstrated a good sensitivity for detection of characteristic features of depression in a single-channel EEG

The Fokker-Planck equation for bistable potential in the optimized expansion

The optimized expansion is used to formulate a systematic approximation scheme to the probability distribution of a stochastic system. The first order approximation for the one-dimensional system driven by noise in an anharmonic potential is shown to agree well with the exact solution of the Fokker-Planck equation. Even for a bistable system the whole period of evolution to equilibrium is correctly described at various noise intensities.Comment: 12 pages, LATEX, 3 Postscript figures compressed an

Absence of Erythrocyte Sequestration and Lack of Multicopy Gene Family Expression in Plasmodium falciparum from a Splenectomized Malaria Patient

BACKGROUND:To avoid spleen-dependent killing mechanisms parasite-infected erythrocytes (IE) of Plasmodium falciparum malaria patients have the capacity to bind to endothelial receptors. This binding also known as sequestration, is mediated by parasite proteins, which are targeted to the erythrocyte surface. Candidate proteins are those encoded by P. falciparum multicopy gene families, such as var, rif, stevor or PfMC-2TM. However, a direct in vivo proof of IE sequestration and expression of multicopy gene families is still lacking. Here, we report on the analysis of IE from a black African immigrant, who received the diagnosis of a malignant lymphoproliferative disorder and subsequently underwent splenectomy. Three weeks after surgery, the patient experienced clinical falciparum malaria with high parasitemia and circulating developmental parasite stages usually sequestered to the vascular endothelium such as late trophozoites, schizonts or immature gametocytes. METHODOLOGY/PRINCIPAL FINDINGS:Initially, when isolated from the patient, the infected erythrocytes were incapable to bind to various endothelial receptors in vitro. Moreover, the parasites failed to express the multicopy gene families var, A-type rif and stevor but expression of B-type rif and PfMC-2TM genes were detected. In the course of in vitro cultivation, the parasites started to express all investigated multicopy gene families and concomitantly developed the ability to adhere to endothelial receptors such as CD36 and ICAM-1, respectively. CONCLUSION/SIGNIFICANCE:This case strongly supports the hypothesis that parasite surface proteins such as PfEMP1, A-type RIFIN or STEVOR are involved in interactions of infected erythrocytes with endothelial receptors mediating sequestration of mature asexual and immature sexual stages of P. falciparum. In contrast, multicopy gene families coding for B-type RIFIN and PfMC-2TM proteins may not be involved in sequestration, as these genes were transcribed in infected but not sequestered erythrocytes

Methylxanthines and Neurodegenerative Diseases: An Update

Methylxanthines (MTX) are purine derived xanthine derivatives. Whereas naturally occurring methylxanthines like caffeine, theophylline or theobromine are widely consumed in food, several synthetic but also non-synthetic methylxanthines are used as pharmaceuticals, in particular in treating airway constrictions. Besides the well-established bronchoprotective effects, methylxanthines are also known to have anti-inflammatory and anti-oxidative properties, mediate changes in lipid homeostasis and have neuroprotective effects. Known molecular mechanisms include adenosine receptor antagonism, phosphodiesterase inhibition, effects on the cholinergic system, wnt signaling, histone deacetylase activation and gene regulation. By affecting several pathways associated with neurodegenerative diseases via different pleiotropic mechanisms and due to its moderate side effects, intake of methylxanthines have been suggested to be an interesting approach in dealing with neurodegeneration. Especially in the past years, the impact of methylxanthines in neurodegenerative diseases has been extensively studied and several new aspects have been elucidated. In this review we summarize the findings of methylxanthines linked to Alzheimer´s disease, Parkinson’s disease and Multiple Sclerosis since 2017, focusing on epidemiological and clinical studies and addressing the underlying molecular mechanisms in cell culture experiments and animal studies in order to assess the neuroprotective potential of methylxanthines in these diseases

Gemfibrozil-Induced Intracellular Triglyceride Increase in SH-SY5Y, HEK and Calu-3 Cells

Gemfibrozil is a drug that has been used for over 40 years to lower triglycerides in blood. As a ligand for peroxisome proliferative-activated receptor-alpha (PPARα), which is expressed in many tissues, it induces the transcription of numerous genes for carbohydrate and lipid-metabolism. However, nothing is known about how intracellular lipid-homeostasis and, in particular, triglycerides are affected. As triglycerides are stored in lipid-droplets, which are known to be associated with many diseases, such as Alzheimer’s disease, cancer, fatty liver disease and type-2 diabetes, treatment with gemfibrozil could adversely affect these diseases. To address the question whether gemfibrozil also affects intracellular lipid-levels, SH-SY5Y, HEK and Calu-3 cells, representing three different metabolically active organs (brain, lung and kidney), were incubated with gemfibrozil and subsequently analyzed semi-quantitatively by mass-spectrometry. Importantly, all cells showed a strong increase in intracellular triglycerides (SH-SY5Y: 170.3%; HEK: 272.1%; Calu-3: 448.1%), suggesting that the decreased triglyceride-levels might be due to an enhanced cellular uptake. Besides the common intracellular triglyceride increase, a cell-line specific alteration in acylcarnitines are found, suggesting that especially in neuronal cell lines gemfibrozil increases the transport of fatty acids to mitochondria and therefore increases the turnover of fatty acids for the benefit of additional energy supply, which could be important in diseases, such as Alzheimer’s disease

Unique Role of Caffeine Compared to Other Methylxanthines (Theobromine, Theophylline, Pentoxifylline, Propentofylline) in Regulation of AD Relevant Genes in Neuroblastoma SH-SY5Y Wild Type Cells

Methylxanthines are a group of substances derived from the purine base xanthine with a methyl group at the nitrogen on position 3 and different residues at the nitrogen on position 1 and 7. They are widely consumed in nutrition and used as pharmaceuticals. Here we investigate the transcriptional regulation of 83 genes linked to Alzheimer’s disease in the presence of five methylxanthines, including the most prominent naturally occurring methylxanthines—caffeine, theophylline and theobromine—and the synthetic methylxanthines pentoxifylline and propentofylline. Methylxanthine-regulated genes were found in pathways involved in processes including oxidative stress, lipid homeostasis, signal transduction, transcriptional regulation, as well as pathways involved in neuronal function. Interestingly, multivariate analysis revealed different or inverse effects on gene regulation for caffeine compared to the other methylxanthines, which was further substantiated by multiple comparison analysis, pointing out a distinct role for caffeine in gene regulation. Our results not only underline the beneficial effects of methylxanthines in the regulation of genes in neuroblastoma wild-type cells linked to neurodegenerative diseases in general, but also demonstrate that individual methylxanthines like caffeine mediate unique or inverse expression patterns. This suggests that the replacement of single methylxanthines by others could result in unexpected effects, which could not be anticipated by the comparison to other substances in this substance class

Existence of solutions for stress-rate type strain-limiting viscoelasticity in Gevrey spaces

In this work, we deal with a one-dimensional stress-rate type model for the response of viscoelastic materials, in relation to the strain-limiting theory. The model is based on a constitutive relation of stress-rate type. Unlike classical models in elasticity, the unknown of the model under consideration is uniquely the stress, avoiding the use of the deformation. Here, we treat the case of periodic boundary conditions for a linearized model. We determine an optimal function space that ensures the local existence of solutions to the linearized model around certain steady states. This optimal space is known as the Gevrey-class 3/2, which characterizes the regularity properties of the solutions. The exponent 3/2 in the Gevrey-class reflects the specific dispersion properties of the equation itself. This article is part of the theme issue ‘Foundational issues, analysis and geometry in continuum mechanics’

Standardization of isothermal microcalorimetry in urinary tract infection detection by using artificial urine

Purpose: Isothermal microcalorimetry (IMC) has recently been reported as a new method to rapidly detect urinary tract pathogens (UTP). However, further application of microcalorimetry in the clinical setting requires a standardized procedure. An important step toward such standardization is to use a reproducible growth medium. In this study, we investigated the potential of artificial urine in combination with microcalorimetry for detection of common UTP. Methods: A microcalorimeter equipped with 48 channels was used. Detection was accomplished, and growth was monitored for four bacterial strains in artificial urine at 37°C by measuring metabolic heat flow (μW=μJ/s) as a function of time. The strains were Escherichia coli, Proteus mirabilis, Enterococcus faecalis, and Staphylococcus aureus. Result: Bacterial growth was detected after 3-32h with decreasing inoculums down to 1CFU. The gram-negative strains grew and were detected faster than their gram-positive counterparts. The growth rates the different strains were 0.75±0.11 for E. coli, 0.74±0.10 for E. faecalis, 1.31±0.04 for P. mirabilis, and 0.56±0.20 for S. aureus. The shape of individual heat flow curves was characteristic for each species independent of its initial concentration. Conclusions: IMC allows rapid detection of UTP in artificial urine. Clearly, different heat flow patterns enable accurate pathogen differentiation. UTP detection after only 4h is realistic. The rapid detection of UTP tested in standardized artificial urine proves the diagnostic potential of IMC and warrants further microcalorimetric studies in the clinical setting of urinary tract infection