Cytochrome c oxidase-modulatory near-infrared light penetration into the human brain: Implications for the noninvasive treatment of ischemia/reperfusion injury.

Near-infrared light (IRL) has been evaluated as a therapeutic for a variety of pathological conditions, including ischemia/reperfusion injury of the brain, which can be caused by an ischemic stroke or cardiac arrest. Strategies have focused on modulating the activity of mitochondrial electron transport chain (ETC) enzyme cytochrome c oxidase (COX), which has copper centers that broadly absorb IRL between 700 and 1,000 nm. We have recently identified specific COX-inhibitory IRL wavelengths that are profoundly neuroprotective in rodent models of brain ischemia/reperfusion through the following mechanism: COX inhibition by IRL limits mitochondrial membrane potential hyperpolarization during reperfusion, which otherwise causes reactive oxygen species (ROS) production and cell death. Prior to clinical application of IRL on humans, IRL penetration must be tested, which may be wavelength dependent. In the present study, four fresh (unfixed) cadavers and isolated cadaver tissues were used to examine the transmission of infrared light through human biological tissues. We conclude that the transmission of 750 and 940 nm IRL through 4 cm of cadaver head supports the viability of IRL to treat human brain ischemia/reperfusion injury and is similar for skin with different skin pigmentation. We discuss experimental difficulties of working with fresh cadavers and strategies to overcome them as a guide for future studies.

Perception, attitude, practice and barriers towards medical research among undergraduate students.

BACKGROUND: Early exposure to medical research, specifically at the undergraduate level, contributes in building a solid medical education for students. In 2014, the Medical Research Volunteer Program (MRVP) was established at the American University of Beirut (AUB). This program provides undergraduate students with the opportunity to be involved in ongoing medical research projects, on a voluntary basis. Little is known about undergraduates' outlook on medical research and the challenges they face. The aim of this study was to assess, among AUB undergraduate students, the perception, attitude, practice and barriers towards medical research, as well as to identify factors affecting them, such as background characteristics and research involvement. METHODS: A cross sectional study was carried out at AUB, where undergraduate students enrolled in specific chosen classes were surveyed in spring 2019 via paper based questionnaires. Close-ended questions assessed students' attitude, perception, practice and barriers towards medical research using a 5-point likert scale. Moreover, demographic characteristics and research involvement information were collected. RESULTS: Five hundred and twenty three students were surveyed. About half of the students were premedical students (51.5%), and only 43.6% of them were aware of the medical research program at their university. The average attitude, perception, practice and barriers scores were found to be 3.58, 4.35, 3.58 and 2.60, respectively (on a scale from 1 to 5). Students found the lack of mentoring and guidance to be the main barrier in conducting medical research. CONCLUSION: Our findings reveal that students express interest towards medical research and recognize its importance. A medical research program at the undergraduate level is indispensable in guiding students in their future career endeavors. Therefore, research programs should be constantly monitored to assure a research-oriented environment within institutions.

Self-reported preferences and barriers to continued professional development in primary care physicians: a cross-sectional web-based survey in Qatar.

INTRODUCTION: High quality and effective primary healthcare is a national priority in Qatar. Continuing professional development (CPD) for physicians is a cornerstone of this objective, yet little is known about physicians' preferences or barriers to CPD participation. METHOD: A needs assessment was conducted using a cross-sectional web-based survey of primary care physicians registered with the Department of Healthcare Practitioners (DHP) between March and June 2017. RESULTS: Two-hundred-and-eighty-one complete surveys were submitted representing physicians in both public (N = 129) and private sectors (N = 152). Physicians completed medical degrees and postgraduate training across multiple countries, and most had been practicing in Qatar for 5 years or less. 'Activities during working hours', 'cost' and 'work commitments' were the most common barriers. There was little consensus regarding the optimal timing of CPD activities, although public sector physicians were more likely to indicate weekend activities as a barrier to participation (30% vs. 9%). Over 90% of participants preferred traditional lectures, workshops, case-based sessions, small group and online self-paced learning as formats for CPD delivery, however alternative modes of delivery were also deemed acceptable (> 80% agreement). CONCLUSION: Understanding primary care physicians' barriers and preferences is an essential component of a larger necessitated needs assessment of CPD in primary care practitioners in Qatar. Further research is warranted to understand the underlying beliefs driving physicians' choices and the apparent variation between those working in the public and private sectors. CPD developers should consider approaches to mitigate perceived barriers and understand preferences to maximize the quality of participation.

Views of medical residents on a research training program: A qualitative study.

INTRODUCTION: The American University of Beirut Medical Center (AUBMC) developed the Fellowship and Residency Research Program (FRRP) to provide residents and clinical fellows with a supervised and structured research experience. The objective of this study was to explore the views of FRRP participants about the training program and how to enhance it. METHODS: In 2018, we conducted a qualitative study targeting residents where we invited potential participants through email and via snowball sampling. We continued the data collection until we reached data saturation with 21 participants (N = 21) and used thematic analysis to identify emerging themes. RESULTS: Thematic analysis generated four emerging themes: one related to the expectations of residents, while the remaining three themes related to how the program is working to meet those expectations, specifically: coordination, mentorship, and capacity building. For these three latter themes, we discussed the strengths and challenges related to each. In terms of coordination, few residents complained that the deadlines to submit deliverables are not evenly distributed across the years. In terms of mentorship, participants appreciated the flexibility in choosing the mentor. In terms of capacity building activities, participants found the lecture series, both real time and virtual, to be helpful. Finally, participants pointed out that the FRRP program should be mandatory. DISCUSSION: To provide residents and clinical fellows with a supervised and structured research experience, we have built on our findings to introduce several changes to our program such as ensuring the availability and commitment of faculty mentors, and providing capacity building activities to the program participants.

Cytochrome c phosphorylation: Control of mitochondrial electron transport chain flux and apoptosis.

Cytochrome c (Cytc)1is a cellular life and death decision molecule that regulates cellular energy supply and apoptosis through tissue specific post-translational modifications. Cytc is an electron carrier in the mitochondrial electron transport chain (ETC) and thus central for aerobic energy production. Under conditions of cellular stress, Cytc release from the mitochondria is a committing step for apoptosis, leading to apoptosome formation, caspase activation, and cell death. Recently, Cytc was shown to be a target of cellular signaling pathways that regulate the functions of Cytc by tissue-specific phosphorylations. So far five phosphorylation sites of Cytc have been mapped and functionally characterized, Tyr97, Tyr48, Thr28, Ser47, and Thr58. All five phosphorylations partially inhibit respiration, which we propose results in optimal intermediate mitochondrial membrane potentials and low ROS production under normal conditions. Four of the phosphorylations result in inhibition of the apoptotic functions of Cytc, suggesting a cytoprotective role for phosphorylated Cytc. Interestingly, these phosphorylations are lost during stress conditions such as ischemia. This results in maximal ETC flux during reperfusion, mitochondrial membrane potential hyperpolarization, excessive ROS generation, and apoptosis. We here present a new model proposing that the electron transfer from Cytc to cytochrome c oxidase is the rate-limiting step of the ETC, which is regulated via post-translational modifications of Cytc. This regulation may be dysfunctional in disease conditions such as ischemia-reperfusion injury and neurodegenerative disorders through increased ROS, or cancer, where post-translational modifications on Cytc may provide a mechanism to evade apoptosis.