Are biomarkers of chronic alcohol misuse useful in the assessment of DWI recidivism status?

A first driving while impaired by alcohol (DWI) conviction is a key opportunity to identify offenders who are at high risk for recidivism. Detection of alcohol use disorder (AUD) is a major target of current DWI assessments. However, offenders frequently underreport their alcohol consumption, and use of biomarkers has been proposed as a more objective indicator. Among the best established are aspartate aminotranferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), mean corpuscular red blood cell volume (MCV), carbohydrate-deficient transferrin (CDT), and thiamine. To our knowledge, no research has directly verified whether AUD biomarkers predict DWI recidivism status. Using a cross-sectional design, this study tested three hypotheses related to the utility of biomarkers in DWI assessment.

Hypotheses

(1) DWI recidivists possess biomarkers indicative of greater prevalence of AUD compared to first-time offenders; (2) multiple biomarkers better differentiate first-time offenders from recidivists compared to individual biomarkers; and (3) biomarkers add significantly to the prediction of recidivism over and above psychosocial questionnaires.

Methods

First-time offenders (n = 49) and recidivists (n = 95) participated in the study. In addition to self-reported information on sociodemographic and driving characteristics, data from several AUD questionnaires were gathered: Michigan Alcoholism Screening Test, Alcohol Use Disorders Identification Test, Composite International Diagnostic Interview, and Timeline Follow-Back. Blood samples were collected to measure AST, ALT, GGT, MCV, CDT, and thiamine.

Results

AUD biomarkers, taken individually or in combination, did not indicate that recidivists had more frequent AUD compared to first-time offenders. Also, they failed to significantly differentiate first-time offenders from recidivists or predict recidivism status. Finally, the superiority of biomarkers over psychosocial AUD questionnaires was not supported in the laboratory setting.

Conclusion

The present findings suggest that biomarkers of chronic patterns of heavy drinking may not be adequate to capture the multiple processes that appear to promote recidivism (e.g., binge drinking, other risky behavioural and personality features). Despite their objectivity, caution is warranted in the interpretation of a positive score on these biomarkers in DWI assessment. Longitudinal research is needed to more comprehensively explore the relationship between positive biomarkers in first-time offenders and their risk of becoming recidivists.     

Diet Prevents Social Stress-Induced Maladaptive Neurobehavioural and Gut Microbiota Changes in a Histamine-Dependent Manner

Exposure to repeated social stress may cause maladaptive emotional reactions that can be reduced by healthy nutritional supplementation. Histaminergic neurotransmission has a central role in orchestrating specific behavioural responses depending on the homeostatic state of a subject, but it remains to be established if it participates in the protective effects against the insults of chronic stress afforded by a healthy diet. By using C57BL/6J male mice that do not synthesize histamine (Hdc^−/−) and their wild type (Hdc^+/+) congeners we evaluated if the histaminergic system participates in the protective action of a diet enriched with polyunsaturated fatty acids and vitamin A on the deleterious effect of chronic stress. Behavioural tests across domains relevant to cognition and anxiety were performed. Hippocampal synaptic plasticity, cytokine expression, hippocampal fatty acids, oxylipins and microbiota composition were also assessed. Chronic stress induced social avoidance, poor recognition memory, affected hippocampal long-term potentiation, changed the microbiota profile, brain cytokines, fatty acid and oxylipins composition of both Hdc^−/− and Hdc^+/+ mice. Dietary enrichment counteracted stress-induced deficits only in Hdc^+/+ mice as histamine deficiency prevented almost all the diet-related beneficial effects. Interpretation: Our results reveal a previously unexplored and novel role for brain histamine as a mediator of many favorable effects of the enriched diet. These data present long-reaching perspectives in the field of nutritional neuropsychopharmacology.     

Cardiac- versus diaphragm-based respiratory navigation for proton spectroscopy of the heart

Magnetic Resonance Materials in Physics, Biology and Medicine - To study inter-individual differences of the relation between diaphragm and heart motion, the objective of the present study was to...     

Ramping down a clinical 3 T scanner: a journey into MRI and MRS at 0.75 T

Object

Lower-field MR is reemerging as a viable, potentially cost-effective alternative to high-field MR, thanks to advances in hardware, sequence design, and reconstruction over the past decades. Evaluation of lower field strengths, however, is limited by the availability of lower-field systems on the market and their considerable procurement costs. In this work, we demonstrate a low-cost, temporary alternative to purchasing a dedicated lower-field MR system.

Materials and Methods

By ramping down an existing clinical 3 T MRI system to 0.75 T, proton signals can be acquired using repurposed ¹³C transmit/receive hardware and the multi-nuclei spectrometer interface. We describe the ramp-down procedure and necessary software and hardware changes to the system.

Results

Apart from presenting system characterization results, we show in vivo examples of cardiac cine imaging, abdominal two- and three-point Dixon-type water/fat separation, water/fat-separated MR Fingerprinting, and point-resolved spectroscopy. In addition, the ramp-down approach allows unique comparisons of, e.g., gradient fidelity of the same MR system operated at different field strengths using the same receive chain, gradient coils, and amplifiers.

Discussion

Ramping down an existing MR system may be seen as a viable alternative for lower-field MR research in groups that already own multi-nuclei hardware and can also serve as a testing platform for custom-made multi-nuclei transmit/receive coils.

     

Carbon nanotube–polyaniline composites

The last decade has seen a growing interest in hybrid electrically conducting nanocomposites. This article aims to provide a detailed overview of the present status of research in carbon nanotube–polyaniline (CNT/PANI) composites, from processing to structural and property evaluations. CNT/PANI are synthesized by electrochemical and chemical processing. When chemical methods are used, the main challenge is to obtain processable CNT/PANI in the emeraldine salt (ES) form composites. Stable dispersions of ES–CNT in organic media are prepared using the post doping method, inverse emulsion polymerization, or ex situ polymerizations. On the contrary, stable water dispersions of CNT/ES are prepared using hydrophilization of a preformed CNT/ES composite, direct synthesis of micelle–CNT hybrid templates, interfacial polymerization, covalent functionalization of CNT with a water soluble polymer, or using electrostatic interactions between two oppositely charged ES and CNT aqueous colloids. Moreover, the strategies for the synthesis of ternary CNT/PANI composites incorporating noble metal nanoparticles, metal oxide, or graphene sheets are also presented and analyzed in depth. Finally, we give a review of potential applications, including chemical sensors, capacitors, fuel cells and electronic devices.     

Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPARγ Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells

The aim of this study was to analyze the expression of peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor α (RxRα), a binding heterodimer playing a pivotal role in the successful trophoblast invasion, in the placental tissue of preeclamptic patients. Furthermore, we aimed to characterize a possible interaction between PPARγ and H3K4me3 (trimethylated lysine 4 of the histone H3), respectively H3K9ac (acetylated lysine 9 of the histone H3), to illuminate the role of histone modifications in a defective trophoblast invasion in preeclampsia (PE). Therefore, the expression of PPARγ and RxRα was analyzed in 26 PE and 25 control placentas by immunohistochemical peroxidase staining, as well as the co-expression with H3K4me3 and H3K9ac by double immunofluorescence staining. Further, the effect of a specific PPARγ-agonist (Ciglitazone) and PPARγ-antagonist (T0070907) on the histone modifications H3K9ac and H3K4me3 was analyzed in vitro. In PE placentas, we found a reduced expression of PPARγ and RxRα and a reduced co-expression with H3K4me3 and H3K9ac in the extravillous trophoblast (EVT). Furthermore, with the PPARγ-antagonist treated human villous trophoblast (HVT) cells and primary isolated EVT cells showed higher levels of the histone modification proteins whereas treatment with the PPARγ-agonist reduced respective histone modifications. Our results show that the stimulation of PPARγ-activity leads to a reduction of H3K4me3 and H3K9ac in trophoblast cells, but paradoxically decreases the nuclear PPARγ expression. As the importance of PPARγ, being involved in a successful trophoblast invasion has already been investigated, our results reveal a pathophysiologic connection between PPARγ and the epigenetic modulation via H3K4me3 and H3K9ac in PE.     

An Expedient Synthesis of Flexible Nucleosides through Enzymatic Glycosylation of Proximal and Distal Fleximer Bases

The structurally unique “fleximer” nucleosides were originally designed to investigate how flexibility in a nucleobase could potentially affect receptor–ligand recognition and function. Recently they have been shown to have low-to-sub-micromolar levels of activity against a number of viruses, including coronaviruses, filoviruses, and flaviviruses. However, the synthesis of distal fleximers in particular has thus far been quite tedious and low yielding. As a potential solution to this issue, a series of proximal fleximer bases (flex-bases) has been successfully coupled to both ribose and 2′-deoxyribose sugars by using the N-deoxyribosyltransferase II of Lactobacillus leichmannii (LlNDT) and Escherichia coli purine nucleoside phosphorylase (PNP). To explore the range of this facile approach, transglycosylation experiments on a thieno-expanded tricyclic heterocyclic base, as well as several distal and proximal flex-bases were performed to determine whether the corresponding fleximer nucleosides could be obtained in this fashion, thus potentially significantly shortening the route to these biologically significant compounds. The results of those studies are reported herein.