Unraveling the molecular basis of cannabidiolic acid methyl Ester's anti-depressive effects in a rat model of treatment-resistant depression.

Major depressive disorder (MDD) stands as a significant cause of disability globally. Cannabidiolic Acid-Methyl Ester (CBDA-ME) (EPM-301, HU-580), a derivative of Cannabidiol, demonstrates immediate antidepressant-like effects, yet it has undergone only minimal evaluation in psychopharmacology. Our goal was to investigate the behavioral and potential molecular mechanisms associated with the chronic oral administration of this compound in the Wistar Kyoto (WKY) genetic model of treatment-resistant depression. Male WKY rats were subjected to behavioral assessments before and after receiving chronic (14-day) oral doses of CBDA-ME (0.5 mg/kg), 15 mg/kg of imipramine or vehicle. At the end of the study, plasma corticosterone levels and mRNA expression of various genes in the medial Prefrontal Cortex and Hippocampus were measured. Behavioral outcomes from CBDA-ME treatment indicated an antidepressant-like effect similar to imipramine, as oral ingestion reduced immobility and increased swimming duration in the Forced Swim Test. Neither treatment influenced locomotion in the Open Field Test nor preference in the Saccharin Preference Test. The behavioral impact in WKY rats coincided with reduced corticosterone serum levels, upregulated mRNA expression of Cannabinoid receptor 1, Fatty Acid Amide Hydrolase, and Corticotropin-Releasing Hormone Receptor 1, alongside downregulation of the Serotonin Transporter in the hippocampus. Additionally, there was an upregulation of CB1 mRNA expression and downregulation of Brain-Derived Neurotrophic Factor in the mPFC. These findings contribute to our limited understanding of the antidepressant effects of CBDA-ME and shed light on its potential psychopharmacological mechanisms. This discovery opens up possibilities for utilizing cannabinoids in the treatment of major depressive disorder and related conditions.

Lymphoplasmacytic lymphoma and multiple myeloma coexisting in the same patient: a case series and literature review.

The simultaneous occurrence of Waldenström macroglobulinemia and multiple myeloma in the same patient has been published as case reports. Patients with Waldenström macroglobulinemia often have a small clone of plasma cells. However, the concurrent occurrence of symptomatic myeloma with lytic bone lesions is rare. The diagnosis of this 'hybrid' entity is challenging, and there are no standard therapies. We present six patients from five centers (three in Israel and two in the United States). We describe these patients' unique clinical course and treatment approaches.

Foot drop in patients treated with bortezomib - a case series and review of the literature.

Bortezomib-induced peripheral neuropathy (BIPN) has a profound impact on quality of life, which is an important issue considering the growing number of survivors of multiple myeloma and amyloidosis. BIPN is typically symmetric, distal, "stocking and glove" distribution and predominantly consists of sensory rather than motor symptoms. In this case series, we report an acute neurotoxicity syndrome induced by bortezomib, which is clinically distinct from BIPN by not being peripheral and distal. We describe six patients that developed unilateral or bilateral foot drop attributed to bortezomib. With bortezomib discontinuation symptoms improved gradually over months to years.

The unanticipated resilience of trait self-knowledge in the face of neural damage.

This paper explores the question of what the self is by reviewing research conducted with both normal and neuropsychological participants. Findings converge on the idea that the self may be more complex and differentiated than some previous treatments of the topic have suggested. Although some aspects of self-knowledge such as episodic recollection may be compromised in individuals, other aspects-for instance, semantic trait summaries-appear largely intact. Taken together, these findings support the idea that the self is not a single, unified entity. Rather, it is a set of interrelated, functionally independent systems. In the process of reviewing neuropsychological findings, an unexpected result emerges: trait self-knowledge appears unusually robust with respect to neural and cognitive damage that render other aspects of self-knowledge dysfunctional in varying degrees.

Familiarity and personal experience as mediators of recall when planning for future contingencies.

In this article, we demonstrate that planning tasks enhance recall when the context of planning (a) is self-referential and (b) draws on familiar scenarios represented in episodic memory. Specifically, we show that when planning tasks are sorted according to the degree to which they evoke memories of personally familiar scenarios (e.g., planning a picnic), recall is reliably superior to tasks that fail to do so (e.g., planning an Arctic trek). We discuss the implications of these findings for planning tasks and their relation to episodic memory.