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Abstract A major and irreversible complication of diabetes is diabetic peripheral neuropathy (DPN), which can lead to significant disability and decreased quality of life. Prior work demonstrates the peptide hormone Angiotensin II (Ang II) is released locally in neuropathy and drives inflammation and impaired endoneurial blood flow. Therefore, we proposed that by utilizing a local thermoresponsive hydrogel injection, we could deliver inhibitors of angiotensin-converting enzyme (ACE) to suppress Ang II production and reduce nerve dysfunction in DPN through local drug release. The ACE inhibitor captopril was encapsulated into a micelle, which was then embedded into a reversibly thermoresponsive pluronics-based hydrogel matrix. Drug-free and captopril-loaded hydrogels demonstrated excellent product stability and sterility. Rheology testing confirmed sol properties with low viscosity at ambient temperature and increased viscosity and gelation at 37 °C. Captopril-loaded hydrogels significantly inhibited Ang II production in comparison to drug-free hydrogels. DPN mice treated with captopril-loaded hydrogels displayed normalized mechanical sensitivity and reduced inflammation, without side-effects associated with systemic exposure. Our data demonstrate the feasibility of repurposing ACE inhibitors as locally delivered anti-inflammatories for the treatment of sensory deficits in DPN. To the best of our knowledge, this is the first example of a locally delivered ACE inhibitor for the treatment of DPN.

Abstract The automatic analysis of patent publications has potential to accelerate research across various domains, including drug discovery and material science. Within patent documents, crucial information often resides in visual depictions of molecule structures. PatCID (Patent-extracted Chemical-structure Images database for Discovery) allows to access such information at scale. It enables users to search which molecules are displayed in which documents. PatCID contains 81M chemical-structure images and 14M unique chemical structures. Here, we compare PatCID with state-of-the-art chemical patent-databases. On a random set, PatCID retrieves 56.0% of molecules, which is higher than automatically-created databases, Google Patents (41.5%) and SureChEMBL (23.5%), as well as manually-created databases, Reaxys (53.5%) and SciFinder (49.5%). Leveraging state-of-the-art methods of document understanding, PatCID high-quality data outperforms currently available automatically-generated patent-databases. PatCID even competes with proprietary manually-created patent-databases. This enables promising applications for automatic literature review and learning-based molecular generation methods. The dataset is freely accessible for download.

Mitchell L Doucette,1 Dipak Hemraj,1 Douglas Bruce2 ,† Emily Fisher,1 D Luke Macfarlan1 1Health Economics and Outcomes Research, Leafwell, Miami, FL, USA; 2Department of Health Sciences, DePaul University, Chicago, IL, USA†Professor Douglas Bruce passed away on June 11th, 2024Correspondence: Mitchell L Doucette, Health Economics and Outcomes Research, Leafwell Inc., Miami, FL, USA, Tel +1 203 293 9416, Email mdoucette@leafwell.comIntroduction: Existing research on medical cannabis patients has often overlooked those younger than 21. This study aimed to detail the frequency and rate of pediatric medical cannabis patients in the US using a large patient database.Methods: Utilizing Leafwell Patient Database data from 2019 to mid-2023, we described demographics and qualifying conditions, employing descriptive statistics and χ 2 tests to discern differences between minors (0– 17 years) and young adults (18– 20 years). We calculated rates per 100,000 population by state.Results: Analyzing 13,855 patients, 5.7% were minors and 94.3% were young adults. Anxiety emerged as the primary self-reported condition for both groups, yet differences were seen for other conditions. Differences were observed by race/ethnicity, health insurance status, residency in adult-use states, and number of reported conditions. Notably, both groups reported a similar average number of conditions.Conclusion: This study underscores demographic distinctions between minor-aged medical cannabis patients and young adults. There is a need for comprehensive clinical research addressing efficacy, safety, and tailored guidelines specific for pediatric medical cannabis patients. Such insights are pivotal for healthcare providers and policymakers in navigating medical cannabis treatment protocols.Plain Language Summary: This paper describes the demographics and medical conditions of medical cannabis patients under the age of 21 in the United States based on data from the Leafwell Patient Database spanning 2019 to mid-2023. We found that there is a significant number of medical cannabis users aged 20 or younger, with variations in demographics and conditions between minors (under 18) and young adults (18-20). The findings indicate that minor patients are predominantly white, non-Hispanic, residing in non-adult-use states, and report a lower number of conditions per patient compared to young adults. Anxiety, chronic pain, and PTSD are among the most commonly self-reported conditions for both age groups. There is need for additional clinical studies to understand the role of medical cannabis in addressing symptoms and improving the quality of life for conditions such as chronic pain, anxiety, and PTSD in the pediatric population. The study is limited by its reliance on self-reported data but represents the largest cohort of pediatric medical cannabis users in the world. Further investigation by academics and clinical scientists ought to inform the appropriate integration of medical cannabis in young patients.Keywords: medical cannabis, pediatric, patient database, United States

Background: Access to quality healthcare education across the world is disproportionate. This study explores the potential for Cardiovascular Perfusion education to be delivered online to reach international students. Methods: Exploratory mixed methods were used to identify the barriers, facilitators, and early outcomes of online international health professions education. Results: Qualitative analysis yielded four primary and nine subthemes. Multiple interventions were implemented in the planning of a novel online international Extracorporeal Science (ECS) program based on these themes. Quantitative data from the first semester of the new ECS program was collected along with data from the traditional entry-level program and historic data from previous entry-level cohorts. No significant correlations or differences were found between students. Student satisfaction surveys were determined to be equivalent for each group. Mixed data analysis revealed exceptional student satisfaction in areas where qualitative feedback was incorporated into the program design. Conclusions: Online international education may be a viable option in the health professions. Barriers and facilitators to this mode of education were identified and utilized in designing one such program. Early outcomes from the novel ECS program reveal that student performance and satisfaction are equivalent to those of a traditional in-person training program.

Early cardiac surgery in neonates and infants with congenital heart disease has been performed since the middle to late years of the twentieth century. To date, there are very few reports of successful congenital heart surgery using cardiopulmonary bypass (CPB) in premature babies less than 1000 g with serious congenital heart disease. Limited information is available in the literature describing perfusion techniques for this extremely fragile patient population. Miniaturization of the CPB circuit contributes to multiple factors that affect this population significantly. These factors include the reduction of patient-to-circuit ratios, volume of distribution of pharmacological agents, management of pressure gradients within the CPB system, and increased tactile control by the attending perfusionist. Careful management of the physiological environment of the patient is of utmost importance and can mitigate risks during CPB, including volume shifts into the interstitial space, electrolyte, and acid-base imbalance, and intracranial hemorrhage. We report perfusion techniques successfully utilized during the surgical repair of transposition of the great arteries for an 800 g, 28-week-old neonate. CPB techniques for the smallest and youngest patients may be executed safely when proper physical, chemical, and perfusion process adjustments are made and managed meticulously.

Leptospermum tairawhitiense G.J. Atkins, de Lange & M.A.M. Renner sp. nov. (Myrtaceae) is segregated from L. scoparium J.R. Forst. & G. Forst. (sensu lato). The new species is endemic to Tairāwhiti / East Cape, Te Ika a Māui / North Island of Aotearoa / New Zealand. The new species is genetically distinct from L. scoparium sensu lato, L. hoipolloi L.M.H. Schmid & de Lange, and L. repo de Lange & L.M.H. Schmid, and chemically it is distinguished by having unusually high levels of triketones. Morphologically, Leptospermum tairawhitiense differs from these species in vegetative characters by the shortly and densely branching growth habit; the often suckering growth habit; the patent leaves, arising at 70–90° from the stem; the lamina is narrow-lanceolate, elliptic lanceolate, or rarely narrowly ovate and (3.0–4.8–6.2(–9.0) mm long by (1.0–1.3(–2.1) mm wide and coloured dull green to dark green, red-tinged, ± glaucescent (new growth yellow-green, red-tinged, glaucescent); and in reproductive characters, the flowers are cupped and small in comparison to other species, being 8–14 mm in diameter, with 5(–8) white petals, 5.0–7.0 × 4.6–6.4 mm and 20–32 stamens with white or pink filaments. The capsules of Leptospermum tairawhitiense are up to 6.8 mm wide and 5.5 mm tall when unopened, with exserted valves that comprise half the capsule height in profile, and when opened the valves exceed the capsule rim. A conservation assessment using the New Zealand Threat Classification System is proposed and a revised key to Leptospermum of Aotearoa / New Zealand provided.