In search of logotherapy

In his authoritative and extraordinarily influential book Man’s Search for Meaning, psychiatrist Viktor Frankl proposed that any individual’s life task is to find meaning, that meaning cannot be obtained without suffering, and that suffering allows meaning to be identified. He also articulated his therapeutic model—logotherapy, the so-called third Viennese school of psychotherapy. This article contemplates why logotherapy currently has seemingly little salience and suggests that the most likely reasons reflect some components being taken over by other therapies and by tenets of positive psychology articulated in recent decades.

Improved In Vivo Delivery of Small RNA Based on the Calcium Phosphate Method

In the past few years, we have demonstrated the efficacy of a nanoparticle system, super carbonate apatite (sCA), for the in vivo delivery of siRNA/miRNA. Intravenous injection of sCA loaded with small RNAs results in safe, high tumor delivery in mouse models. To further improve the efficiency of tumor delivery and avoid liver toxicity, we successfully developed an inorganic nanoparticle device (iNaD) via high-frequency ultrasonic pulverization combined with PEG blending during the production of sCA. Compared to sCA loaded with 24 μg of miRNA, systemic administration of iNaD loaded with 0.75 μg of miRNA demonstrated similar delivery efficiency to mouse tumors with little accumulation in the liver. In the mouse therapeutic model, iNaD loaded with 3 μg of the tumor suppressor small RNA MIRTX resulted in an improved anti-tumor effect compared to sCA loaded with 24 μg. Our findings on the bio-distribution and therapeutic effect of iNaD provide new perspectives for future nanomedicine engineering.

Ganoderma formosanum Exopolysaccharides Inhibit Tumor Growth via Immunomodulation

Ganoderma formosanum (GF) is a medicinal mushroom endemic to Taiwan. Previous research established the optimal culture conditions to produce exopolysaccharide rich in β-glucan (GF-EPS) from submerged fermentation of GF. The present study investigated the antitumor effects of GF-EPS in a Lewis lung carcinoma cell (LLC1) tumor-bearing mice model. In the preventive model, GF-EPS was orally administered to mice before LLC1 injection. In the therapeutic model, GF-EPS oral administration was initiated five days after tumor cell injection. The tumor size and body weight of the mice were recorded. After sacrifice, the lymphocyte subpopulation was analyzed using flow cytometry. Spleen tissues were used to analyze cytokine mRNA expression. The results showed that GF-EPS (80 mg/kg) effectively suppressed LLC1 tumor growth in both the preventive and therapeutic models. GF-EPS administration increased the proportion of natural killer cells in the spleen and activated gene expression of several cytokines. Our results provide evidence that GF-EPS promotes tumor inhibition through immunomodulation in tumor-bearing mice.

The Curious Case of Earthworms and COVID-19

Earthworms have been used for centuries in traditional medicine and are used globally as an ecotoxicological standard test species. Studies of the earthworm Eisenia fetida have shown that exposure to nanomaterials activates a primary corona-response, which is covering the nanomaterial with native proteins, the same response as to biological invaders such as a virus. We outline that the earthworm Eisenia fetida is possibly immune to COVID-19 (Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2), and we describe the likely mechanisms of highly receptor-specific pore-forming proteins (PFPs). A non-toxic version of this protein is available, and we hypothesize that it is possible to use the earthworm’s PFPs based anti-viral mechanism as a therapeutic model for human SARS-CoV-2 and other corona viruses. The proteins can be used as a drug, for example, delivered with a nanoparticle in a similar way to the current COVID-19 vaccines. Obviously, careful consideration should be given to the potential risk of toxicity elicited by lysenin for in vivo usage. We aim to share this view to activate its exploration by the wider scientific community while promoting a potential therapeutic development.

The Birth of Naloxone: An Intellectual History of an Ambivalent Opioid

Naloxone, which reverses the effects of opioids, was synthesized in 1960, though the hunt for opioid antagonists began a half-century earlier. The history of this quest reveals how cultural and medical attitudes toward opioids have been marked by a polarization of discourse that belies a keen ambivalence. From 1915 to 1960, researchers were stymied in seeking a “pure” antidote to opioids, discovering instead numerous opioid molecules of mixed or paradoxical properties. At the same time, the quest for a dominant explanatory and therapeutic model for addiction was likewise unsettled. After naloxone’s discovery, new dichotomizing language arose in the “War on Drugs,” in increasingly divergent views between addiction medicine and palliative care, and in public debates about layperson naloxone access. Naloxone, one of the emblematic drugs of our time, highlights the ambivalence latent in public and biomedical discussions of opioids as agents of risk and relief.

Leveraging the Treg-intrinsic CTLA4–PKCη signaling pathway for cancer immunotherapy

BackgroundOur previous studies revealed a critical role of a novel CTLA4-protein kinase C-eta (PKCη) signaling axis in mediating the suppressive activity of regulatory T cells (Tregs) in antitumor immunity. These studies have employed adoptive transfer of germline PKCη-deficient (Prkch−/−) Tregs into Prkch+/+ mice prior to tumor implantation. Here, we extended these findings into a biologically and clinically more relevant context.MethodsWe have analyzed the role of PKCη in antitumor immunity and the tumor microenvironment (TME) in intact tumor-bearing mice with Treg-specific or CD8+ T cell-specific Prkch deletion, including in a therapeutic model of combinatorial treatment. In addition to measuring tumor growth, we analyzed the phenotype and functional attributes of tumor-infiltrating immune cells, particularly Tregs and dendritic cells (DCs).ResultsUsing two models of mouse transplantable cancer and a genetically engineered autochthonous hepatocellular carcinoma (HCC) model, we found, first, that mice with Treg-specific Prkch deletion displayed a significantly reduced growth of B16–F10 melanoma and TRAMP-C1 adenocarcinoma tumors. Tumor growth reduction was associated with a less immunosuppressive TME, indicated by increased numbers and function of tumor-infiltrating CD8+ effector T cells and elevated expression of the costimulatory ligand CD86 on intratumoral DCs. In contrast, CD8+ T cell-specific Prkch deletion had no effect on tumor growth or the abundance and functionality of CD8+ effector T cells, consistent with findings that Prkch−/− CD8+ T cells proliferated normally in response to in vitro polyclonal or specific antigen stimulation. Similar beneficial antitumor effects were found in mice with germline or Treg-specific Prkch deletion that were induced to develop an autochthonous HCC. Lastly, using a therapeutic model, we found that monotherapies consisting of Treg-specific Prkch deletion or vaccination with irradiated Fms-like tyrosine kinase 3 ligand (Flt3L)-expressing B16–F10 tumor cells post-tumor implantation significantly delayed tumor growth. This effect was more pronounced in mice receiving a combination of the two immunotherapies.ConclusionThese findings demonstrate the potential utility of PKCη inhibition as a viable clinical approach to treat patients with cancer, especially when combined with adjuvant therapies.

Using Functional Electrical Stimulation With Tetraplegia to Improve Activities of Daily Living: An Evidence-Based Capstone Project

Date Presented 04/22/21 This evidence-based OT project was conducted to determine whether a 6-week intervention using functional electrical stimulation combined with occupation-based tasks would improve the performance of activities of daily living in individuals with tetraplegia. The concept of the project provides OT practitioners with a therapeutic model that encourages the engagement of clients to perform occupation-based tasks while using an effective therapeutic modality. Primary Author and Speaker: Ashley McKnight Additional Authors and Speakers: Penelope Moyers Cleveland

Co-creating secure attachment imagery to enhance relational healing

All treatments for adult attachment insecurity include in some form a set of principles and methods that can be termed therapist-as-good-attachment-figure. This relational context is widely and appropriately accepted as a foundation for any attachment-focused therapy. After highlighting some of the principles of this approach, this article describes a therapeutic model that includes using patient-and-therapist co-created imagery of positive attachment experience. This imagery method is intrapersonal, in that it focuses on the patient's inner experience of mental representations of attachment relationships; it is interpersonal, in that the process calls upon the therapist to be highly attuned and responsive — as a good attachment figure — to the patient experiencing the imagery; and it is metainterpersonal, in that the patient experiences the imagined interaction with the positive attachment relationships in the context of the therapist supporting and participating in the process. The use of imagery in this way can be a valuable contribution towards relational healing and adult earned secure attachment.