British College of Osteopathic Medicine

This paper investigates how Nepal’s monetary policy reacts to growing global uncertainty and major structural changes, highlighting the challenges of a small open economy. Annual data from 1977 to 2024 were measured using the Autoregressive Distributed Lag (ARDL) framework which include structural break dummies for the 2015 earthquake and economic blockade, and 2020 COVID-19 pandemic. Unit root and cointegration tests were used; error correction form of ARDL model captures the log-run relationship and speed of adjustment, and Granger causality is applied to measure short-run predictive links between the variables. The Findings highlights that global uncertainty weakens the impact of monetary policy on growth, through foreign-exchange reserves and inflation maintain a positive long-run influence. Structural breaks alter the speed and direction of policy transmission, with rapid but uneven adjustments to equilibrium. Nepal’s monetary system remains highly exposed to external shocks, demanding flexible, credible, and well-coordinated policy actions.

Mounting ambitions and capabilities for public and private, non-government sector crewed space exploration bring with them an increasingly diverse set of space travelers, raising new and nontrivial ethical, legal, and medical policy and practice concerns which are still relatively underexplored. In this piece, we lay out several pressing issues related to ethical considerations for selecting space travelers and conducting human subject research on them, especially in the context of non-governmental and commercial/private space operations.

Abstract Breast cancer is the leading cause of cancer death in women in the US and the second leading cancer after skin cancer in women worldwide. According to the CDC, women from 45-84 years of age are most at risk, with approximately 30% of deaths in this group being from cancer. Increased free radical formation, and oxidative and inflammatory responses have been shown to be major contributing factors for the progression of breast cancer. Several antioxidants and vitamins have been tested for their efficacy in preventing breast cancer. However, the role of vitamin B1 derivatives in the prevention of breast cancer is not known. Therefore, we hypothesize that with potent anti-oxidative and anti-inflammatory actions, lipid-soluble derivatives of vitamin B1 (thiamine), such as benfotiamine and fursultiamine, could prevent breast cancer growth and spread. We have treated human breast cancer cells such as MCF-7 and T-4D1 and mouse breast cancer cells 4T1 with vitamin B1 derivatives and examined the cancer cells growth. Our results indicate that treatment of various breast cancer cells with benfotiamine and fursultiamine prevents the proliferation of cancer cells in a dose-dependent manner. Further, both benfotiamine and fursultiamine by regulating the activation of caspase-3 and cleavage of PARP protein could prevent breast cancer cells growth. Benfotiamine and fursultiamine also regulates generation of reactive oxygen species in breast cancer cells. Further, vitamin B1 derivatives regulate the expression of various anti-apoptotic, pro-apoptotic, survival and inflammatory factors in both human and mouse breast cancer cells. We next planned to examine the effect of vitamin B1 derivatives on breast cancer growth in vivo using athymic nude mouse models. In conclusion, our in vitro results suggest that vitamin B1 derivatives, benfotiamine and fursultiamine, by promoting the apoptotic pathways prevent breast cancer cells growth and could be further developed as chemopreventive drugs. Citation Format: Caroline Ciaciuch O'Neill, Aveline P. Langmead, Kota V. Ramana. Lipid soluble vitamin B1 derivatives, benfotiamine and fursultiamine, prevent breast cancer cells growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7311.

Abstract Melanoma is the second leading invasive cancer with a greater capacity to invade and metastasize. Increased oxidative stress has been shown to be involved in melanoma growth and spread. Several antioxidants, vitamins, and other phytochemicals have been shown to prevent melanoma cancer growth. However, the chemopreventive efficacy of vialinin-A, an edible mushroom-derived p-terphenyl antioxidant, on cancer growth and invasion is unknown. We, therefore, hypothesized that with its potent anti-oxidative and anti-inflammatory actions, vialinin-A could prevent melanoma cell growth and invasion. B16-F10 melanoma cells were treated without or with various concentrations of vialinin-A. The cell viability was determined by MTT assay and apoptosis by annexin-V staining. Our results suggest that vialinin-A prevents melanoma cell growth in a dose-dependent manner. Vialinin-A also prevents the invasion and migration of melanoma cells. Further, vialinin-A prevents the generation of reactive oxygen species and promotes apoptosis of B16-F10 cells. In addition, vialinin-A increases the activation of caspase-3 and cleavage of PARP protein. Vialinin-A also regulated the expression of various anti-apoptotic, pro-apoptotic, and inflammatory markers in melanoma cells. In conclusion, our results suggest that vialinin-A, through regulating oxidative stress-modulated apoptotic pathways, could prevent melanoma cell growth and invasion and has potential chemopreventive properties. Citation Format: Alexandria Vo, Amber Zafar. Edible mushroom derived antioxidant, vialinin A, prevents melanoma growth and invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7309.

Introduction: Acute ischemic stroke (AIS) is thesecond leading cause of death globally, accounting for approximately 11% of alldeaths, long-term disability, and functional impairments in survivors. TheCOVID-19 pandemic has raised concerns about its impact on AIS patients. Aim: This study aimed to assess the outcomes,including mortality and severity of disability in AIS hospitalizations withCOVID-19. Methods: We performed a retrospective cross-sectionalanalysis of the Nationwide Inpatient Sample (NIS-2020) in adulthospitalizations for AIS to compare the outcomes [death & APRDRGseverity/disability] in COVID-19 patients using ICD-10 codes. We performedweighted analyses using chi-square, unpaired t-test, and multivariate logisticregression models to evaluate COVID-19-associated poor outcomes amongst AISpatients. Results: Out of 504,460 AIS patients, 7,590 had AIStriggered by COVID-19. Amongst AIS hospitalizations, COVID-19 was more frequentin age group >65 year old 63.2%, male 52.6%, White race (51.4%), patientwith Medicare (58.7%), median household income 0-25 percentile (33.6%), Southzone (43.4%), and hypertensives (83.7%). AIS patients with COVID-19 had ahigher mortality (10.93% vs 3.8%) and severe/extreme disability (93.21% vs37.43%) rates in comparison to patients without COVID-19. (p<0.0001) Inregression analysis COVID-19 was associated with 213% higher odds of mortality(aOR: 3.13, 95% CI: 2.90-3.38, p<0.0001, c:0.671) and higher odds of severe/extreme disability(26.85, 24.53-29.39, p<0.0001, c:0.686) compared to AIS patients withoutCOVID-19. Conclusion: These findings emphasize the substantialimpact of COVID-19 on AIS patients by elevating mortality and risk of severedisability compared to their counterparts. Efforts should be directed towards earlyidentification of stroke population that is at higher risk ofCOVID-19-associated poor outcome and prompt management tomitigate the burden of the both diseases.

Skulls of living whales and dolphins (cetaceans) are telescoped-bones of the skull roof are overlapped by expanded facial bones and/or anteriorly extended occipital bones. Evolution of the underlying skull roof (calvarium), which lies between the telescoped regions, is relatively unstudied. We explore the evolution and development of the calvarium of toothed whales (odontocetes) by integrating fetal data with Oligocene odontocete fossils from North America, including eight neonatal and juvenile skulls of Olympicetus†. We identified two potential synapomorphies of crown Cetacea: contact of interparietals with frontals, and a single anterior median interparietal (AMI) element. Within Odontoceti, loss of contact between the parietals diagnoses the clade including Delphinida, Ziphiidae and Platanistidae (=Synrhina). Delphinida is characterized by a greatly enlarged interparietal. New fetal series of delphinoids reveal a consistent developmental pattern with three elements: the AMI and bilateral posterior interparietals (PIs). The PIs most resemble the medial interparietal elements of terrestrial artiodactyls, suggesting that the AMI of cetaceans could be a unique ossification. More broadly, the paucity of conserved anatomical relationships of the interparietals, as well as the fact that the elements often do not coalesce into a single bone, demonstrates that assessing homology of the interparietals across mammals remains challenging. This article is part of the theme issue 'The mammalian skull: development, structure and function'.

Abstract Anthracyclines such as daunorubicin and doxorubicin (DOX) are currently used as chemotherapeutic agents in the prevention of various cancers including breast cancer, lung cancer, leukemia, and lymphoma. Although, anthracyclines are successful in controlling various cancers growth, the major drawback is the unwanted cardiotoxicity. Specifically, high doses of DOX used for the therapy of advanced cancers could cause life threating conditions. Therefore, specific interventions are required to decrease the cardiac toxicity associated with the DOX. Benfotiamine, a lipid soluble vitamin B1 derivative has shown be a potent anti-oxidant and anti-inflammatory agent. However, the efficacy of benfotiamine in the prevention of cardiotoxicity associated with the anthracyclines is not known. In this study, we examined the effect of benfotiamine in the prevention of DOX-induced cytotoxicity in the human umbilical vascular endothelial cells (HUVECs). Treatment of HUVECs with DOX caused significant endothelial cells death and benfotiamine in a concentration-dependent manner prevented the dox-induced endothelial cell death. Further, benfotiamine prevents the DOX-induced apoptosis in endothelial cells by preventing the activation of caspase-3. Benfotiamine also prevents DOX-induced reactive oxygen species generation. Our results also indicate that benfotiamine regulates DOX-induced expression of pro-apoptotic mediators such as BAD, phosphor-P53, and pro-caspase-3, and anti-apoptotic mediators such as BCL-2, BCL-x, IAPs, and HSP and others such as FADD, DR5, and SMAC/diablo. We plan to further explore how benfotiamine prevents DOX-induced cardiotoxicity using human cardiac myocytes and mouse models. Thus, based on our cell culture studies, benfotiamine through its potent anti-oxidative property could prevent endothelial cytotoxicity and suggests that it could be further developed as adjuvant therapy in controlling cardiotoxicity associated with the anthracycline chemotherapy. Citation Format: Justin R. Taylor, Kyra Harames. Prevention of doxorubicin-induced cardiotoxicity by benfotiamine. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4771.

Most students pursuing careers in anatomy or related disciplines have a limited understanding of how, over the centuries, the intricate structure of the human body came to be known. To provide students with the relevant historical perspective, we developed a team‐taught survey course in the history of anatomical sciences—including gross anatomy, histology, neuroanatomy, and embryology—from antiquity to the present. Taught entirely via Zoom during the Spring semester of 2021, History of Anatomy (2 semester hours credit) met once per week for approximately 2 hours. Enrollment consisted of 5 undergraduate students majoring in Biology (2), Human Biology (2), or Anthropology (1), as well as 3 graduate students pursuing either a master’s degree in Clinical Anatomy (1) or a Ph.D. in Anatomy Education (2). Three of the students had no prior coursework in anatomy. Through assigned readings, lectures, and discussions, the class explored the work of the great anatomists and their discoveries. A particular emphasis was placed on the evolution of anatomy as a discipline and the cultural influences, scientific controversies, and ethical dilemmas facing its practitioners. Syllabus topics included critical appraisals of the role of gender, race, and ethnicity in anatomical discovery. A key feature of the course was the opportunity for students to engage in robust discussions about such controversial issues as: Eurocentric biases in our understanding of human anatomy and the untold story of Muslim contributions to anatomical knowledge well before Vesalius; Competing claims of priority for who “discovered” the pulmonary circulation; The underappreciated role of women in the history of anatomy and medicine; The ethical quandary of teaching anatomy from archival fetal specimens obtained before the era of informed consent; Accusations that famed anatomist William Hunter used the bodies of murdered pregnant women to create his anatomical atlas of the gravid uterus; Complicity of Eduard Pernkopf and other Nazi‐era anatomists in the unethical use of executed victims to obtain images for a renowned anatomical atlas. All students were assessed through weekly homework (written responses to study questions), a mid‐term writing assignment, and a term paper about an historical topic of the student’s choosing. Graduate students had the additional requirement of a class presentation about their term paper topic. The end‐of‐course evaluation suggested that the course was well‐received by the students (mean Likert score = 4.63 on a 5‐point scale; n = 6). Based on this positive reception, we plan to offer History of Anatomy again on a recurring basis. We believe that by knowing our history, both the good and the bad, future practitioners of anatomy and related disciplines will be less likely to perpetuate the biases and ethical transgressions of earlier eras.