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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.

Jean M Bouquet,1 Rayyan Naji,2 Carlos A Armas,2 Valentina Roldan,2 Shadi Selkhi,2 Camille Z Bentley,1 Isain Zapata,3 Jensen Fisher4 1Department of Family Medicine, Rocky Vista University College of Osteopathic Medicine, Englewood, CO, 80112, USA; 2Department of Biomedical Engineering, College of Engineering and Computing, Florida International University, Miami, FL, 33174, USA; 3Department of Biomedical Sciences, Rocky Vista University College of Osteopathic Medicine, Englewood, CO, 80112, USA; 4Medical Humanities Department, Rocky Vista University College of Osteopathic Medicine, Englewood, CO, 80112, USACorrespondence: Jean M Bouquet, Department of Family Medicine, Rocky Vista University College of Osteopathic Medicine, 8401, S. Chambers, Englewood, CO, 80112, USA, Email jbouquet@rvu.eduIntroduction: The main objective of this study is to evaluate the effectiveness of a newly designed vaginal speculum, the Bouquet Speculum, in-vitro. The setting of this study was at Florida International University and involved four senior students in the Department of Biomedical Engineering.Methods: A phantom vaginal model was used to test three variables of the Bouquet Speculum (Visibility, Pressure and Gynecologic Tools tests). As this was bench-lab testing with simulated models, no human participants were involved in this study.Results: The results of this in-vitro study are as follows: The visibility test demonstrated statistically better visualization of the cervix and the cervical os (sampling area for pap tests) with the Bouquet Speculum over the existing 2-bladed speculum at all intrapelvic pressures; The pressure test demonstrated an equal radial distribution of force, without breakage, across the Bouquet Speculum; The gynecologic tools test demonstrated that the Bouquet Speculum is compatible with the existing speculum and standard gynecologic tools in terms of retrieving samples and accessing the cervical os and entire cervix during gynecologic procedures and screening.Conclusion: The gynecologic screening and procedural value of this innovative change in the design of the vaginal speculum could save hundreds of thousands of lives every year, provide a more comfortable exam for the patient, and result in a more efficient and user-friendly provider experience.Keywords: medical device, vaginal speculum, public health, gynecology

Abstract Background Inequitable access to personalized breast cancer screening and prevention may compound racial and ethnic disparities in outcomes. The Breast Cancer Personalized Risk Assessment, Education and Prevention (B-PREP) program, located within the Brigham and Women’s Hospital (BWH) Comprehensive Breast Health Center (BHC), provides care to patients at high risk for developing breast cancer. We sought to characterize the differences between BWH primary care patients referred specifically to B-PREP for risk evaluation and those referred to the BHC for benign breast conditions. Through interviews with primary care clinicians, we sought to explore contributors to potentially inequitable B-PREP referral patterns. Methods We used electronic health record data and the B-PREP clinical database to identify patients referred by primary care clinicians to the BHC or B-PREP between 2017 and 2020. We examined associations with likelihood of referral to B-PREP for risk assessment. Semi-structured interviews were conducted with nine primary care clinicians from six clinics to explore referral patterns. Results Of 1789 patients, 78.0% were referred for benign breast conditions, and 21.5% for risk assessment. In multivariable analyses, Black individuals were less likely to be referred for risk than for benign conditions (OR 0.38, 95% CI:0.23–0.63) as were those with Medicaid/Medicare (OR 0.72, 95% CI:0.53–0.98; OR 0.52, 95% CI:0.27–0.99) and those whose preferred language was not English (OR 0.26, 95% CI:0.12–0.57). Interviewed clinicians described inconsistent approaches to risk assessment and variable B-PREP awareness. Conclusions In this single-site evaluation, among individuals referred by primary care clinicians for specialized breast care, Black, publicly-insured patients, and those whose preferred language was not English were less likely to be referred for risk assessment. Larger studies are needed to confirm these findings. Interventions to standardize breast cancer risk assessment in primary care may improve equity.

James Studnicki,1 Tessa Longbons,1 John Fisher,1 David C Reardon,2 Ingrid Skop,1 Christina A Cirucci,1 Donna J Harrison,3 Christopher Craver,1 Maka Tsulukidze,4 Zbigniew Ras5 1Charlotte Lozier Institute, Arlington, VA, USA; 2Elliot Institute, Springfield, IL, USA; 3American Association of Pro-Life Obstetricians and Gynecologists, Eau Claire, MI, USA; 4Department of Health Sciences, Florida Gulf Coast University, Fort Myers, FL, USA; 5Computer Science Department, University of North Carolina at Charlotte, Charlotte, NC, USACorrespondence: Tessa Longbons, Charlotte Lozier Institute, 2776 S. Arlington Mill Drive, PO Box 803, Arlington, VA, 22206, USA, Tel +1 202 223 8073, Email tlongbons@lozierinstitute.orgObjective: To determine whether exposure to a first pregnancy outcome of induced abortion, compared to a live birth, is associated with an increased risk and likelihood of mental health morbidity.Materials and methods: Participants were continuously eligible Medicaid beneficiaries age 16 in 1999, and assigned to either of two cohorts based upon the first pregnancy outcome, abortion (n = 1331) or birth (n = 3517), and followed through to 2015. Outcomes were mental health outpatient visits, inpatient hospital admissions, and hospital days of stay. Exposure periods before and after the first pregnancy outcome, a total of 17 years, were determined for each cohort.Findings: Women with first pregnancy abortions, compared to women with births, had higher risk and likelihood of experiencing all three mental health outcome events in the transition from pre- to post-pregnancy outcome periods: outpatient visits (RR 2.10, CL 2.08– 2.12 and OR 3.36, CL 3.29– 3.42); hospital inpatient admissions (RR 2.75, CL 2.38– 3.18 and OR 5.67, CL 4.39– 7.32); hospital inpatient days of stay (RR 7.38, CL 6.83– 7.97 and OR 19.64, CL 17.70– 21.78). On average, abortion cohort women experienced shorter exposure time before (6.43 versus 7.80 years), and longer exposure time after (10.57 versus 9.20 years) the first pregnancy outcome than birth cohort women. Utilization rates before the first pregnancy outcome, for all three utilization events, were higher for the birth cohort than for the abortion cohort.Conclusion: A first pregnancy abortion, compared to a birth, is associated with significantly higher subsequent mental health services utilization following the first pregnancy outcome. The risk attributable to abortion is notably higher for inpatient than outpatient mental health services. Higher mental health utilization before the first pregnancy outcome for birth cohort women challenges the explanation that pre-existing mental health history explains mental health problems following abortion, rather than the abortion itself.Keywords: abortion, mental health, inpatient mental health utilization, outpatient mental health utilization, repeat abortion

Abstract Background With suppressive antiretroviral therapy, HIV infection is well-managed in most patients. However, eradication and cure are still beyond reach due to latent viral reservoirs in CD4 + T cells, particularly in lymphoid tissue environments including the gut associated lymphatic tissues. In HIV patients, there is extensive depletion of T helper cells, particularly T helper 17 cells from the intestinal mucosal area, and the gut is one of the largest viral reservoir sites. Endothelial cells line lymphatic and blood vessels and were found to promote HIV infection and latency in previous studies. In this study, we examined endothelial cells specific to the gut mucosal area—intestinal endothelial cells—for their impact on HIV infection and latency in T helper cells. Results We found that intestinal endothelial cells dramatically increased productive and latent HIV infection in resting CD4 + T helper cells. In activated CD4 + T cells, endothelial cells enabled the formation of latent infection in addition to the increase of productive infection. Endothelial-cell-mediated HIV infection was more prominent in memory T cells than naïve T cells, and it involved the cytokine IL-6 but did not involve the co-stimulatory molecule CD2. The CCR6 + T helper 17 subpopulation was particularly susceptible to such endothelial-cell-promoted infection. Conclusion Endothelial cells, which are widely present in lymphoid tissues including the intestinal mucosal area and interact regularly with T cells physiologically, significantly increase HIV infection and latent reservoir formation in CD4 + T cells, particularly in CCR6 + T helper 17 cells. Our study highlighted the importance of endothelial cells and the lymphoid tissue environment in HIV pathology and persistence.

This systematic literature review aims to enhance our understanding of the Taliban activities in Afghanistan and broaden our knowledge of the associated phenomenon. We employed a Systematic Literature Review protocol and sourced our data from the Scopus index, yielding 164 articles from which 91 were selected following a filtration process. Our analysis reveals that the resurgence of the Taliban and its organizational dynamics over the past four decades have had a significant impact on Afghanistan and its citizens. The majority of the studies in our dataset (52 articles) approached the phenomenon from a political perspective, with health issues being the second most explored topic (17 articles). The data collected in this study indicates that the majority of the literature discussing the Taliban and Afghanistan was qualitative in nature (89 articles). Our results suggest that the Taliban's current influence in Afghanistan is only weakly linked to religious motivations, contrary to the common media portrayal. Only a small number of studies in our dataset (3.29%, n=3) explored the ideological basis of the phenomenon. This paper underscores the need for further research to address the pressing political and health issues faced by the Afghan people and highlights the potential benefits of improved political stability and increased access to healthcare facilities. // // // // //

Samuel A Cohen,1,2 Ann Caroline Fisher,1,2 Suzann Pershing1– 3 1Department of Ophthalmology, Stanford University School of Medicine, Stanford, CA, USA; 2Byers Eye Institute at Stanford, Stanford, CA, USA; 3VA Palo Alto Health Care System, Palo Alto, CA, USACorrespondence: Suzann Pershing, Department of Ophthalmology, Stanford University, 2452 Watson Court, Stanford, CA, USA, 94303, Tel +1 650 723-6995, Email pershing@stanford.eduPurpose: To assess the readability and accountability of online patient education materials related to glaucoma diagnosis and treatment.Methods: We conducted a Google search for 10 search terms related to glaucoma diagnosis and 10 search terms related to glaucoma treatment. For each search term, the first 10 patient education websites populated after Google search were assessed for readability and accountability. Readability was assessed using five validated measures: Flesch Reading Ease (FRE), Gunning Fog Index (GFI), Flesch-Kincaid Grade Level (FKGL), Simple Measure of Gobbledygook (SMOG), and New Dale-Chall (NDC). Accountability was assessed using the Journal of the American Medical Association (JAMA) benchmarks. The source of information for each article analyzed was recorded.Results: Of the 200 total websites analyzed, only 11% were written at or below the recommended 6th grade reading level. The average FRE and grade level for 100 glaucoma diagnosis-related articles were 42.02 ± 1.08 and 10.53 ± 1.30, respectively. The average FRE and grade level for 100 glaucoma treatment-related articles were 43.86 ± 1.01 and 11.29 ± 1.54, respectively. Crowdsourced articles were written at the highest average grade level (12.32 ± 0.78), followed by articles written by private practice/independent users (11.22 ± 1.74), national organizations (10.92 ± 1.24), and educational institutions (10.33 ± 1.35). Websites averaged 1.12 ± 1.15 of 4 JAMA accountability metrics.Conclusion: Despite wide variation in the readability and accountability of online patient education materials related to glaucoma diagnosis and treatment, patient education materials are consistently written at levels above the recommended reading level and often lack accountability. Articles from educational institutions and national organizations were often written at lower reading levels but are less frequently encountered after Google search. There is a need for accurate and understandable online information that glaucoma patients can use to inform decisions about their eye health.Keywords: readability, accountability, glaucoma, diagnosis, treatment