The effects of acute oral naltrexone pretreatment on the abuse potential of intranasal methamphetamine, and the relationship between reward/punishment sensitivity and methamphetamine's effects.

One potential medication for treating methamphetamine use disorder is the opioid antagonist naltrexone (NLTX). Despite encouraging preclinical findings, the results of clinical studies have been mixed. The primary aim of the current trial was to examine the effects of acute NLTX pretreatment on the subjective and reinforcing effects of intranasal methamphetamine. Nonmedical psychostimulant users completed outpatient testing sessions in which they received oral placebo (0 mg) or NLTX (50 mg) before intranasal methamphetamine (30 mg/70 kg). Primary outcome measures were peak positive subjective effects (e.g. drug 'Liking') assessed on a visual analog scale (0-100), and methamphetamine self-administration using an operant self-administration task. Participants also completed a probabilistic categorization task to assess reward and punishment learning sensitivity. Complete data were available from 13 male and 1 transgender (male-to-female) participant (age: 33.4 ± 7.6 years). Intranasal methamphetamine significantly increased subjective ratings of drug 'Liking', 'Good Effect' and 'High' from baseline (P's < 0.01), but did not significantly vary as a function of placebo or NLTX pretreatment. Similarly, methamphetamine self-administration did not vary between the placebo and NLTX pretreatment conditions. This sample did not demonstrate a significant 'bias' in learning from positive and negative outcomes (i.e. reward and punishment sensitivity), and reward/punishment sensitivity was not correlated with the effects of methamphetamine or the effects of NLTX on methamphetamine. The current study argues against the use of NLTX as a stand-alone medication for treating methamphetamine use disorder.

Laccase Activity and Azo Dye Decolorization Potential of Podoscypha elegans.

Azo dyes containing effluents from different industries pose threats to the environment. Though there are physico-chemical methods to treat such effluents, bioremediation is considered to be the best eco-compatible technique. In this communication, we discuss the decolorization potentiality of five azo dyes by Podoscypha elegans (G. Mey.) Pat., a macro-fungus, found growing on the leaf-litter layer of Bethuadahari Wildlife Sanctuary in West Bengal, India. The fungus exhibited high laccase and very low manganese peroxidase activities under different culture conditions. Decolorization of five high-molecular weight azo dyes, viz., Orange G, Congo Red, Direct Blue 15, Rose Bengal and Direct Yellow 27 by the fungus was found to be positive in all cases. Maximum and minimum mean decolorization percentages were recorded in Rose Bengal (70.41%) and Direct Blue 15 (24.8%), respectively. This is the first record of lignolytic study and dye decolorization by P. elegans.

High-fidelity tissue engineering of patient-specific auricles for reconstruction of pediatric microtia and other auricular deformities.

INTRODUCTION: Autologous techniques for the reconstruction of pediatric microtia often result in suboptimal aesthetic outcomes and morbidity at the costal cartilage donor site. We therefore sought to combine digital photogrammetry with CAD/CAM techniques to develop collagen type I hydrogel scaffolds and their respective molds that would precisely mimic the normal anatomy of the patient-specific external ear as well as recapitulate the complex biomechanical properties of native auricular elastic cartilage while avoiding the morbidity of traditional autologous reconstructions. METHODS: Three-dimensional structures of normal pediatric ears were digitized and converted to virtual solids for mold design. Image-based synthetic reconstructions of these ears were fabricated from collagen type I hydrogels. Half were seeded with bovine auricular chondrocytes. Cellular and acellular constructs were implanted subcutaneously in the dorsa of nude rats and harvested after 1 and 3 months. RESULTS: Gross inspection revealed that acellular implants had significantly decreased in size by 1 month. Cellular constructs retained their contour/projection from the animals' dorsa, even after 3 months. Post-harvest weight of cellular constructs was significantly greater than that of acellular constructs after 1 and 3 months. Safranin O-staining revealed that cellular constructs demonstrated evidence of a self-assembled perichondrial layer and copious neocartilage deposition. Verhoeff staining of 1 month cellular constructs revealed de novo elastic cartilage deposition, which was even more extensive and robust after 3 months. The equilibrium modulus and hydraulic permeability of cellular constructs were not significantly different from native bovine auricular cartilage after 3 months. CONCLUSIONS: We have developed high-fidelity, biocompatible, patient-specific tissue-engineered constructs for auricular reconstruction which largely mimic the native auricle both biomechanically and histologically, even after an extended period of implantation. This strategy holds immense potential for durable patient-specific tissue-engineered anatomically proper auricular reconstructions in the future.