Intellectual Property of Psychedelics for Addiction Treatment: Enabling Access and Protecting Innovation Opportunities Through Preserving the Public Domain.

OBJECTIVE: Recent research has shown potential for psychedelic therapeutics as addiction treatments; however, some academic institutions, commercial entities and individuals are attempting to monopolize psychedelic compounds through exploiting the patent process. METHODS: This Perspective article describes efforts that have been devised to mitigate exclusionary patent practices pertinent to psychedelic therapeutics for addiction. RESULTS: The non-profit Porta Sophia has identified 170 patent documents focused on treating addiction through psychedelics, and many of these patents could threaten to privatize public domain knowledge and severely limit or increase the cost of research if granted. Patent examiners who determine if a patent application should be granted must negate false claims to innovation. Yet, given the unique history of psychedelics, prior knowledge can be difficult to find. As a result, overreaching patents may be granted, causing dramatic shifts in access to addiction-focused psychedelic research, treatments, and funding. CONCLUSIONS: As the field of psychedelics approaches this critical inflection point of FDA decisions, it is imperative for all stakeholders - including university investigators, academic and commercial patent seekers, and policy makers - to utilize available tools for determining prior knowledge. Maintaining an informed awareness of legal patent eligibility and limitations is crucial for establishing an ethical patent landscape and ensuring subsequent access to these potential life-altering psychedelic therapeutics for addiction.

Harnessing EGLN1 Gene Editing to Amplify HIF-1α and Enhance Human Angiogenic Response.

Therapeutic angiogenesis has been the focus of hundreds of clinical trials but approval for human treatment remains elusive. Current strategies often rely on the upregulation of a single proangiogenic factor, which fails to recapitulate the complex response needed in hypoxic tissues. Hypoxic oxygen tensions dramatically decrease the activity of hypoxia inducible factor prolyl hydroxylase 2 (PHD2), the primary oxygen sensing portion of the hypoxia inducible factor 1 alpha (HIF-1α) proangiogenic master regulatory pathway. Repressing PHD2 activity increases intracellular levels of HIF-1α and impacts the expression of hundreds of downstream genes directly associated with angiogenesis, cell survival, and tissue homeostasis. This study explores activating the HIF-1α pathway through Sp Cas9 knockout of the PHD2 encoding gene EGLN1 as an innovative in situ therapeutic angiogenesis strategy for chronic vascular diseases. Our findings demonstrate that even low editing rates of EGLN1 lead to a strong proangiogenic response regarding proangiogenic gene transcription, protein production, and protein secretion. In addition, we show that secreted factors of EGLN1 edited cell cultures may enhance human endothelial cell neovascularization activity in the context of proliferation and motility. Altogether, this study reveals that EGLN1 gene editing shows promise as a potential therapeutic angiogenesis strategy.

Unraveling Muscle Impairment Associated With COVID-19 and the Role of 3D Culture in Its Investigation.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been considered a public health emergency, extensively investigated by researchers. Accordingly, the respiratory tract has been the main research focus, with some other studies outlining the effects on the neurological, cardiovascular, and renal systems. However, concerning SARS-CoV-2 outcomes on skeletal muscle, scientific evidence is still not sufficiently strong to trace, treat and prevent possible muscle impairment due to the COVID-19. Simultaneously, there has been a considerable amount of studies reporting skeletal muscle damage in the context of COVID-19. Among the detrimental musculoskeletal conditions associated with the viral infection, the most commonly described are sarcopenia, cachexia, myalgia, myositis, rhabdomyolysis, atrophy, peripheral neuropathy, and Guillain-Barré Syndrome. Of note, the risk of developing sarcopenia during or after COVID-19 is relatively high, which poses special importance to the condition amid the SARS-CoV-2 infection. The yet uncovered mechanisms by which musculoskeletal injury takes place in COVID-19 and the lack of published methods tailored to study the correlation between COVID-19 and skeletal muscle hinder the ability of healthcare professionals to provide SARS-CoV-2 infected patients with an adequate treatment plan. The present review aims to minimize this burden by both thoroughly exploring the interaction between COVID-19 and the musculoskeletal system and examining the cutting-edge 3D cell culture techniques capable of revolutionizing the study of muscle dynamics.

The Therapeutic Landscape of Rheumatoid Arthritis: Current State and Future Directions.

Rheumatoid arthritis (RA) is a debilitating autoimmune disease with grave physical, emotional and socioeconomic consequences. Despite advances in targeted biologic and pharmacologic interventions that have recently come to market, many patients with RA continue to have inadequate response to therapies, or intolerable side effects, with resultant progression of their disease. In this review, we detail multiple biomolecular pathways involved in RA disease pathogenesis to elucidate and highlight pathways that have been therapeutic targets in managing this systemic autoimmune disease. Here we present an up-to-date accounting of both emerging and approved pharmacological treatments for RA, detailing their discovery, mechanisms of action, efficacy, and limitations. Finally, we turn to the emerging fields of bioengineering and cell therapy to illuminate possible future targeted therapeutic options that combine material and biological sciences for localized therapeutic action with the potential to greatly reduce side effects seen in systemically applied treatment modalities.

SARS-CoV-2 and the possible connection to ERs, ACE2, and RAGE: Focus on susceptibility factors.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has provoked major stresses on the health-care systems of several countries, and caused the death of more than a quarter of a million people globally, mainly in the elderly population with preexisting pathologies. Previous studies with coronavirus (SARS-CoV) point to gender differences in infection and disease progression with increased susceptibility in male patients, indicating that estrogens may be associated with physiological protection against the coronavirus. Therefore, the objectives of this work are threefold. First, we aim to summarize the SARS-CoV-2 infection pathway and the roles both the virus and patient play in COVID-19 (Coronavirus disease 2019) progression, clinical symptomatology, and mortality. Second, we detail the effect estrogen has on viral infection and host infection response, including its role in both the regulation of key viral receptor expression and the mediation of inflammatory activity. Finally, we describe how ERs (estrogen receptors) and RAGE (receptor for advanced glycation end-products) play a critical role in metabolic pathways, which we envisage could maintain a close interplay with SARS-CoV and COVID-19 mortality rates, despite a current lack of research directly determining how. Taken together, we present the current state of the field regarding SARS-CoV-2 research and illuminate where research is needed to better define the role both estrogen and metabolic comorbidities have in the COVID-19 disease state, which can be key in screening potential therapeutic options as the search for effective treatments continue.

Effect of Preoperative Anesthesia Consultation on Decreasing Anxiety in Patients Undergoing Oral and Maxillofacial Surgery.

STATEMENT OF THE PROBLEM: Preoperative anxiety is the subject of major concern for many patients. PURPOSE: The current study aimed at determining the effect of anesthesia consultation on decreasing anxiety in patients undergoing oral and maxillofacial surgery. MATERIALS AND METHOD: This randomized clinical trial was conducted on 250 patients undergoing different maxillofacial surgeries. The data collection instruments included a questionnaire containing the Spielberger state-trait anxiety inventory (STAI) and a researcher-made questionnaire with queries on the demographic characteristics and surgery-related information. Analysis of the data was performed in SPSS, using descriptive and inferential statistics. RESULTS: The findings showed that the majority of patients (38.4%) had moderate anxiety; there was no significant difference between the consultation and control groups in terms of age and gender. Also, the scores of state and trait anxiety were significantly lower in the consultation group, compared with the control group. CONCLUSION: The present results showed that preoperative anesthetic consultation reduced preoperative anxiety, compared with the control group. Our findings suggest that anesthetic counseling services should be provided for individuals experiencing high levels of stress.

Positron emission tomography imaging of novel AAV capsids maps rapid brain accumulation.

Adeno-associated viruses (AAVs) are typically single-stranded deoxyribonucleic acid (ssDNA) encapsulated within 25-nm protein capsids. Recently, tissue-specific AAV capsids (e.g. PHP.eB) have been shown to enhance brain delivery in rodents via the LY6A receptor on brain endothelial cells. Here, we create a non-invasive positron emission tomography (PET) methodology to track viruses. To provide the sensitivity required to track AAVs injected at picomolar levels, a unique multichelator construct labeled with a positron emitter (Cu-64, t1/2 = 12.7 h) is coupled to the viral capsid. We find that brain accumulation of the PHP.eB capsid 1) exceeds that reported in any previous PET study of brain uptake of targeted therapies and 2) is correlated with optical reporter gene transduction of the brain. The PHP.eB capsid brain endothelial receptor affinity is nearly 20-fold greater than that of AAV9. The results suggest that novel PET imaging techniques can be applied to inform and optimize capsid design.

PRP and BMAC for Musculoskeletal Conditions via Biomaterial Carriers.

Platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) are orthobiologic therapies considered as an alternative to the current therapies for muscle, bone and cartilage. Different formulations of biomaterials have been used as carriers for PRP and BMAC in order to increase regenerative processes. The most common biomaterials utilized in conjunction with PRP and BMAC clinical trials are organic scaffolds and natural or synthetic polymers. This review will cover the combinatorial strategies of biomaterial carriers with PRP and BMAC for musculoskeletal conditions (MsCs) repair and regeneration in clinical trials. The main objective is to review the therapeutic use of PRP and BMAC as a treatment option for muscle, bone and cartilage injuries.

Characterizing the encapsulation and release of lentivectors and adeno-associated vectors from degradable alginate hydrogels.

Gene therapy using viral vectors has been licensed for clinical use both in the European Union and the United States. Lentivectors (LV) and adeno-associated vectors (AAV) are two promising and FDA approved gene-therapy viral vectors. Many future applications of these vectors will benefit from targeting specific regions of interest within the body. Therefore, building on the early success of these vectors may depend on finding effective delivery systems to localize therapeutic administration. Degradable alginate hydrogels have been tested as appealing delivery vehicles for the controlled delivery of vector payloads. In this study, we compare the ability of two different degradable alginate hydrogel formulations to efficiently deliver LV and AAV. We propose that release rates of viral vectors are dependent on the physical properties of both the hydrogels and vectors. Here, we demonstrate that the initial strength and degradation rate of alginate hydrogels provides levers of control for tuning LV release but do not provide control in the release of AAV. While both alginate formulations used showed sustained release of both LV and AAV, LV release was shown to be dependent on alginate hydrogel degradation, while AAV release was largely governed by diffusive mechanisms. Altogether, this study demonstrates alginate's use as a possible delivery platform for LV and, for the first time, AAV - highlighting the potential of injectable degradable alginate hydrogels to be used as a versatile delivery tool in gene therapy applications.

Comprehensive Treatment of Upper Lip Arteriovenous Malformation.

Arteriovenous malformations are uncommon congenital disorders in vascular development. They frequently involve craniofacial structures and result in a morphogenic abnormality with ominous arteriovenous shunting. We present a huge AVM of the upper lip in an 18-year-old patient who was successfully treated by the combination method of presurgical endovascular embolization and complete resection of the lesion. Subsequent surgical defect in upper lip, which involved more than two-third of the lip length, was reconstructed via Webster's modification of cheek advancement flap.

Facial gel complication after dental injection: a case report.

Injectable gel is becoming increasingly popular for cosmetic reasons. The polyacrylamide gel (PAAG) is a permanent filler material used worldwide. In spite of the fact that the filler materials used today are considered quite safe, various complications have been reported in the literature. Hence PAAG use in the United States is not popular. As the area is very close to the dental field, a large complication potential is relatively considered following buccal dental injections. The aim of this article is to highlight a rare complication observed following a local anesthetic administration of a simple molar restoration in a healthy 33-year-old woman who had history of a filler augmentation in her cheek approximately 6 years ago.