A taxonomy of regulatory and policy matters relevant to psychedelic-assisted therapy in Australia.

OBJECTIVES: The Australian government recently rescheduled psilocybin and 3,4-methylenedioxymethamphetamine for limited clinical uses. This change has raised various regulatory concerns and challenges for the field of psychedelic-assisted therapy. To provide clarity, we aimed to comprehensively catalogue the matters relating to psychedelic-assisted therapy that are or could be regulated. METHODS: We conducted a desktop review of the literature and current regulatory sources, semi-structured interviews with professionals who had expertise in fields relating to psychedelic-assisted therapy and a framework analysis to generate a taxonomy of relevant regulatory matters. In relation to each matter, we further identified what type of regulation (if any) currently applies to that matter, any uncertainty as to how the matter should be addressed in clinical practice in the context of current regulation and whether there are conflicting views as to how the matter could or should be further regulated. RESULTS: The taxonomy is structured into six main regulatory domains, three of which have a substantial proportion of matters with uncertainty or conflicting views: Service Establishment, Practitioner, and Treatment Delivery. Key examples of such matters include the location of services and facilities required, which professionals are eligible to become psychedelic therapists, and with what qualifications and experience. Matters in the remaining three domains, Patient Evaluation, Drug Supply and Service Oversight, appear by comparison relatively settled, with regulation either well-established or thought unnecessary. CONCLUSIONS: The taxonomy provides a roadmap for health services establishing and implementing a psychedelic-assisted therapy program, or for government and other policymakers when determining areas that may require further regulation.

Acute Loss of miR-221 and miR-222 in the Atherosclerotic Plaque Shoulder Accompanies Plaque Rupture.

BACKGROUND AND PURPOSE: Atherosclerotic plaque vulnerability is accompanied by changes in the molecular and cellular function in the plaque shoulder, including a decrease in vascular smooth muscle cell proliferation. We aimed to determine whether the expression of 3 miRNAs that regulate vascular smooth muscle cell proliferation (miR-145, miR-221, and miR-222) is altered with plaque rupture, suggesting a role in regulating plaque stability. METHODS: miRNAs were measured in the plaque shoulder of carotid plaques obtained from patients undergoing carotid endarterectomy (CEA) for 3 distinct clinical scenarios: (1) patients without previous neurological events but high-grade carotid stenosis (asymptomatic), (2) patients with an acute neurological event within 5 days of the CEA (urgent), and (3) patients undergoing CEA>5 days after a neurological event (symptomatic). RESULTS: Mean time from plaque rupture event to CEA was 2.4 days in the urgent group. The urgent group exhibited a significant decrease in miR-221 and miR-222 expression in the plaque shoulder, whereas no significant differences were seen in miR-145 across the 3 groups. Regression analysis demonstrated a significant correlation between time from the neurological event to CEA and increasing miR-221 and miR-222, but not miR-145. mRNA encoding p27Kip1, a target of miR-221 and miR-222 that inhibits vascular smooth muscle cell proliferation, was increased in the urgent group. CONCLUSIONS: Atherosclerotic plaque rupture is accompanied by a loss of miR-221 and miR-222 and an increase in p27Kip1 mRNA expression in the plaque shoulder, suggesting an association between these miRNAs and atherosclerotic plaque stability.

Implementation and Cost Analysis of a Novel Silicosis Case-Finding Program For Mine Workers in Rural Rwanda.

Little is known about the burden of silicosis in Africa, despite extensive mining and construction operations in the region putting numerous people at risk. The implementation experience and costs of case-finding for occupational lung disease in resource-limited settings are also currently unknown. We describe the first-ever silicosis case-finding project in rural Rwanda using chest X-ray, symptom questionnaires, and spirometry. This was coupled with routine noncommunicable disease case-finding for diabetes and hypertension. We performed an ingredient-based analysis of the costs of all case-finding activities. In 2022, over 25 days, 1,032 mine workers were included in the program, of which 1,014 (98.3%) completed silicosis case-finding activities. The total cost of the program was estimated to be US$38,656, representing a cost of US$37.49 per person. We conclude that conducting large-scale occupational lung disease case-finding is clinically and economically feasible in resource-limited settings and can be effectively integrated with routine noncommunicable disease case-finding.

Modulation of inflammation in wounds of diabetic patients treated with porcine urinary bladder matrix.

Aim: To determine if porcine urinary bladder matrix (UBM) treatment is associated with modulation of wound inflammation in diabetic patients. Patients & methods: mRNA associated with M1 and M2 macrophages were measured in wounds of diabetic and nondiabetic patients pre- and post-treatment with UBM and an M1:M2 score was calculated. Results: Wound tissue from diabetic subjects exhibited elevated M1:M2 scores compared with nondiabetic patients, suggesting a greater pro-inflammatory state prior to treatment. Post-treatment, there was significantly greater reduction in the magnitude of the individual M1:M2 scores in the diabetic patients resulting in similar levels in both groups of patients. Conclusions: UBM may assist in diabetic wound healing by restoring an inflammatory state similar to that of nondiabetic patients.

Carotid Plaque Rupture Is Accompanied by an Increase in the Ratio of Serum circR-284 to miR-221 Levels.

BACKGROUND: Atherosclerotic plaque rupture is accompanied by an acute decrease in the carotid plaque expression of micro-RNAs (miRs)-221 and miR-222. Circular RNA (circR)-284 is a potential inhibitor of miR-221/miR-222 activity. We aimed to determine whether changes in the serum levels of these noncoding RNAs are observed in patients with asymptomatic high-grade carotid disease versus patients with acutely symptomatic carotid disease and recent ischemic stroke. Additionally, we tested the use of functionally related noncoding RNA pairs to enhance the discriminatory power of noncoding RNAs as circulating biomarkers. METHODS AND RESULTS: Serum levels of miR-221, miR-222, miR-145, and circR-284 were measured in 24 asymptomatic (asymptomatic) and 17 acutely symptomatic patients ([urgent] ischemic cerebrovascular event within the previous 5 days) undergoing carotid endarterectomy. miR-221 was significantly lower, whereas circR-284 was elevated in the serum of the urgent compared with the asymptomatic group. The ratio of serum circR-284:miR-221 was significantly elevated in the urgent group (P=0.0002) and exhibited favorable characteristics as a biomarker indicative of carotid plaque rupture and stroke. A validation study in 112 patients (47 asymptomatic, 41 urgent, and 24 patients with a cerebrovascular event between 5 and 180 days of the carotid endarterectomy [symptomatic]) confirmed elevation of serum circR-284:miR-221 uniquely in the urgent group (P<0.001) and favorable sensitivity and specificity for detecting plaque rupture and stroke. CONCLUSIONS: Serum circR-284:miR-221 has potential as a diagnostic biomarker of carotid plaque rupture and stroke. Moreover, we demonstrate the use of functionally related pairs of circulating noncoding RNAs as biomarkers in cardiovascular disease.