Exercise has increasingly been recognized as an adjunctive therapy for alcohol-use disorder (AUD), yet our understanding of its underlying neurological mechanisms remains limited. This knowledge gap impedes the development of evidence-based exercise guidelines for AUD treatment. Chronic ethanol (EtOH) exposure has been shown to upregulate and sensitize kappa opioid receptors (KORs) in the nucleus accumbens (NAc), which is innervated by dopamine (DA) neurons in the midbrain ventral tegmental area (VTA), which may contribute to AUD-related behaviors. In this study, we investigated the impact of voluntary exercise in EtOH-dependent mice on EtOH consumption, KOR and delta opioid receptor (DOR) expression in the NAc and VTA, and functional effects on EtOH-induced alterations in DA release in the NAc. Our findings reveal that voluntary exercise reduces EtOH consumption, reduces KOR and enhances DOR expression in the NAc, and modifies EtOH-induced adaptations in DA release, suggesting a competitive interaction between exercise-induced and EtOH-induced alterations in KOR expression. We also found changes to DOR expression in the NAc and VTA with voluntary exercise but no significant changes to DA release. These findings elucidate the complex interplay of AUD-related neurobiological processes, highlighting the potential for exercise as a therapeutic intervention for AUD.

Introduction: The successful outcome of maintaining natural extreme monovision in a patient through the implantation of extended depth-of-focus (EDOF) intraocular lenses (IOLs) in both eyes is reported. Patient and Clinical Findings: A 75-year-old woman with a history of extreme monovision (−3.50 diopters [D] spheroequivalent left eye) presented to the clinic for cataract evaluation. At presentation, bilateral blurry vision (both distance and near) was observed with or without spectacles. The patient noted that previous attempts at restoring binocularity with spectacles correction had been unsuccessful, and she maintained a strong desire to maintain her natural extreme monovision. Diagnosis, Intervention, and Outcomes: The patient underwent EDOF IOL implantation (both eyes) with full monovision refractive targets of plano (right eye) and −1.50 D (left eye). Postoperatively, the patient expressed dissatisfaction about her limited near vision (left eye). 7 months later, she underwent an EDOF IOL exchange (left eye) with a new refractive target of −3.25 D. The patient perceived her extreme monovision correction to be a success. Conclusions: This case highlights that although EDOF IOLs are not specifically designed for monovision correction, they may still provide satisfactory results for certain patients.

Lichen Planopilaris (LPP) is a lymphocyte-mediated scarring alopecia characterized by progressive follicular destruction and fibrosis. In this clinical trial, patients with biopsy proven LPP were treated with deucravacitinib (an oral inhibitor of tyrosine kinase 2 (TYK2)) 6 mg BID for 24 weeks (NCT-06091956). Bulk and single-cell RNA sequencing was performed on paired pre- and post-treatment scalp biopsies from baseline and week 4. Patients (N=10) demonstrated improvements in PGA (88.9%, p=0.008), LPPAI (−2.3 points, SD 1.1, p=0.002) and Skindex-16 (−21.0 points, SD 22.1, p=0.014) scores at week 24. Bulk transcriptomic analysis of untreated LPP revealed upregulation of type I Interferon (IFN)-stimulated genes and pathways related to inflammation, immune activation, keratinization, and extracellular matrix remodelling, with downregulation of immune and inflammatory pathways following treatment. Single-cell RNA-seq of LPP was characterized by enrichment of CD8+GZMK+ T cells which showed downregulation of T-cell receptor signaling as well as antiviral pathways with treatment. Basal keratinocytes exhibited reduced cytokine and interferon signaling and decreased communication with NK cells following treatment. CCL19+ fibroblasts were prominent in untreated disease was attenuated after treatment, with downregulation of type I IFN signaling. Selective TYK2 inhibition with deucravacitinib effectively suppresses these inflammatory circuits in LPP and represents a promising therapeutic strategy.