Medical Student Mentorship for Undergraduate Students Underrepresented in Medicine Improves Confidence and Knowledge About Medical School Application.

Purpose Applying to medical school is accompanied by significant barriers to prospective applicants. Students who are underrepresented in medicine (URiM) may face additional barriers. We created a mentorship program to pair pre-medical URiM students with medical student mentors. The purpose of this study was to determine if providing mentorship and resources to URiM pre-medical students increased their knowledge and confidence regarding the medical school application process. Method A survey was emailed to mentees of the program to assess their knowledge and confidence about the Medical College Admission Test (MCAT) and medical school application before and after receiving mentorship. Wilcoxon-Signed-Rank tests were used for data analysis. Results A total of 28 participants completed the pilot study of which 17 gave qualitative feedback. Students reported feeling significantly more knowledgeable and confident after six months of enrollment on seven (77.8%) of the survey items. Respondents agreed that mentorship was the most valuable aspect of the program, with 13 (76.5%) respondents qualitatively endorsing the positive impact mentorship imparted to them. Conclusion Having a medical student mentor helped URiM pre-medical students feel more knowledgeable and confident about the medical school application process. By providing URiM students with additional resources, the diversity of future classes of physicians may improve and better mirror the populations they will serve.

Mitochondrial antioxidants abate SARS-COV-2 pathology in mice.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection inhibits mitochondrial oxidative phosphorylation (OXPHOS) and elevates mitochondrial reactive oxygen species (ROS, mROS) which activates hypoxia-inducible factor-1alpha (HIF-1α), shifting metabolism toward glycolysis to drive viral biogenesis but also causing the release of mitochondrial DNA (mtDNA) and activation of innate immunity. To determine whether mitochondrially targeted antioxidants could mitigate these viral effects, we challenged mice expressing human angiotensin-converting enzyme 2 (ACE2) with SARS-CoV-2 and intervened using transgenic and pharmacological mitochondrially targeted catalytic antioxidants. Transgenic expression of mitochondrially targeted catalase (mCAT) or systemic treatment with EUK8 decreased weight loss, clinical severity, and circulating levels of mtDNA; as well as reduced lung levels of HIF-1α, viral proteins, and inflammatory cytokines. RNA-sequencing of infected lungs revealed that mCAT and Eukarion 8 (EUK8) up-regulated OXPHOS gene expression and down-regulated HIF-1α and its target genes as well as innate immune gene expression. These data demonstrate that SARS-CoV-2 pathology can be mitigated by catalytically reducing mROS, potentially providing a unique host-directed pharmacological therapy for COVID-19 which is not subject to viral mutational resistance.

Mitochondria-Targeted Catalase Does Not Suppress Development of Cellular Senescence during Aging.

Cellular senescence is a complex stress response marked by stable proliferative arrest and the secretion of biologically active molecules collectively known as the senescence-associated secretory phenotype (SASP). Mitochondria-derived reactive oxygen species (ROS) have been implicated in aging and age-related processes, including senescence. Stressors that increase ROS levels promote both senescence and the SASP, while reducing mitochondrial ROS or mitochondria themselves can prevent senescence or the SASP. Mitochondrially targeted catalase (mCAT), a transgene that reduces mitochondrial levels of ROS, has been shown to extend the lifespan of murine models and protect against the age-related loss of mitochondrial function. However, it remains unclear whether mCAT can prevent senescence or the SASP. In this study, we investigated the impact of mCAT on senescence in cultured cells and aged mice in order to discover if the lifespan-extending activity of mCAT might be due to the reduction in senescent cells or the SASP. Contrary to expectations, we observed that mCAT does not reduce markers of senescence or the SASP in cultured cells. Moreover, mCAT does not prevent the accumulation of senescent cells or the development of the SASP in adipose tissue from aged mice. These results suggest that mitochondrial ROS may not always play a causal role in the development of senescence during natural aging and underscore the need for a nuanced understanding of the intricate relationship between mitochondrial ROS and cellular senescence.

Structure based virtual screening and discovery of novel inhibitors against FabD protein of Mycobacterium tuberculosis.

The highly flexible nature of Mycobacterium tuberculosis (Mtb) can be owed to its tough cell wall and multiple gene interaction system which makes it resistant to frontline TB drugs. Mycolic acids are the key components of the unique cell wall that protects the organism from external threats. Proteins of the fatty acid synthesis pathway are evolutionarily conserved that enables cellular survival in harsh conditions and hence have become attractive targets. Malonyl Co-A Acyl carrier protein transacylase (FabD; MCAT, EC2.3.1.39) is an enzyme in the branching point of the unique and vast fatty acid synthase (FAS-I and FAS-II) systems of Mtb. In the present investigation, in-silico structure based drug discovery with the compounds from an open source library (NPASS) is used for target fishing and employed to understand the interaction with the target protein FabD. The potential hit compounds were filtered using exhaustive docking, considering the binding energy, key residue interaction and drug likeness property. Three compounds from the library namely NPC475074 (Hit 1), NPC260631 (Hit 2) and NPC313985 (Hit 3) with binding energies -14.45, -13.29 and -12.37 respectively were taken for molecular dynamic simulation. The results suggested that Hit 3 (NPC313985) has stable interaction with FabD protein. This article further elaborates the interaction of the identified novel compounds Hit 1 and Hit 3 along with the other known compound (Hit 2) against Mtb FabD protein. The hit compounds identified from this study could be further evaluated against mutated FabD protein and considered for in-vitro evaluation.Communicated by Ramaswamy H. Sarma.

Medical Students' Socioeconomic Status and Academic Performance in Medical School.

Background Students from lower socioeconomic groups tend to underestimate their chances of acceptance to medical school and their likelihood of success once admitted. Objective The objective of this study is to determine if socioeconomic disadvantage status is linked to lower medical college admission test (MCAT) scores and academic performance in medical school. Methods Using the Association of American Medical Colleges (AAMC) education/occupation (EO) indicator, we compared economically disadvantaged students to students with no financial disadvantage on the MCAT, Phase 1 National Board of Medical Examiners (NBME), United States Medical Licensing Examination (USMLE) Step 1, Phase 2 NBME, and USMLE Step 2 test scores. Results Medical students in the disadvantaged group scored significantly lower on the MCAT than students with no financial disadvantage. The disadvantaged group showed a non-significant lower trend in performance until USMLE Step 2. Conclusions Applicants from lower socioeconomic backgrounds may perform lower on their MCAT and early medical school benchmark exams, but they appear to catch up with and even surpass their peers on their USMLE Step 2 examination.

MCATs: Case report of adnexal adenocarcinoma of not otherwise specified type.

Malignant cutaneous adnexal tumors are rare dermatosis that can have extradermal twins. Diagnosis of adnexal skin tumors is sometimes difficult. Immunohistochemistry has limited value in the diagnosis. Most adnexal skin tumors are localized on the head and neck. Difficulties in their diagnosis associated with absence of strict clinical criteria.

Recessive pathogenic variants in MCAT cause combined oxidative phosphorylation deficiency.

Malonyl-CoA-acyl carrier protein transacylase (MCAT) is an enzyme involved in mitochondrial fatty acid synthesis (mtFAS) and catalyzes the transfer of the malonyl moiety of malonyl-CoA to the mitochondrial acyl carrier protein (ACP). Previously, we showed that loss-of-function of mtFAS genes, including Mcat, is associated with severe loss of electron transport chain (ETC) complexes in mouse immortalized skeletal myoblasts (Nowinski et al., 2020). Here, we report a proband presenting with hypotonia, failure to thrive, nystagmus, and abnormal brain MRI findings. Using whole exome sequencing, we identified biallelic variants in MCAT. Protein levels for NDUFB8 and COXII, subunits of complex I and IV respectively, were markedly reduced in lymphoblasts and fibroblasts, as well as SDHB for complex II in fibroblasts. ETC enzyme activities were decreased in parallel. Re-expression of wild-type MCAT rescued the phenotype in patient fibroblasts. This is the first report of a patient with MCAT pathogenic variants and combined oxidative phosphorylation deficiency.

Effects of race and test preparation resources on standardized test scores, a pilot study.

BACKGROUND: Little research exists on the relationship between pre-examination resources, race, and standardized test outcomes. This study aimed to determine the effect of test preparation resources and race on test scores. METHODS: We surveyed medical students at an allopathic institution on the use of test preparation materials and their test scores. Students were grouped by self-identified race. Underrepresented in Medicine (URiM) students were defined as Black/African American (AA), Hispanic/Latino (HL), Native American (NA) and multiple races. Univariate analysis and linear regression were used for statistical analysis. RESULTS: 192 students completed the survey (response rate = 33%). URiM students reported more MCAT attempts than other students. No differences between scores existed between races. There was no association between scores and the use of test preparation resources. CONCLUSIONS: We found that URiM students took the MCAT more times than their peers; however, we found no racial/ethnic differences in examination preparation resources or scores.

[Leber hereditary optic neuropathy: update on genetics and pathomechanisms]. / La génétique et physiopathologie de la neuropathie optique de Leber.

Leber Hereditary Optic Neuropathy is still a dramatic disease of optic nerve. Origins and mechanisms are extensively studied in the last decades, in link with emergent therapeutic approaches. This article is an update on genetics and pathophysiology of LHON and leber-like inherited optic neuropathies.

Mitochondria-Targeted Human Catalase in the Mouse Longevity MCAT Model Mitigates Head-Tilt Bedrest-Induced Neuro-Inflammation in the Hippocampus.

Microgravity (modeled by head-tilt bedrest and hind-limb unloading), experienced during prolonged spaceflight, results in neurological consequences, central nervous system (CNS) dysfunction, and potentially impairment during the performance of critical tasks. Similar pathologies are observed in bedrest, sedentary lifestyle, and muscle disuse on Earth. In our previous study, we saw that head-tilt bedrest together with social isolation upregulated the milieu of pro-inflammatory cytokines in the hippocampus and plasma. These changes were mitigated in a MCAT mouse model overexpressing human catalase in the mitochondria, pointing out the importance of ROS signaling in this stress response. Here, we used a head-tilt model in socially housed mice to tease out the effects of head-tilt bedrest without isolation. In order to find the underlying molecular mechanisms that provoked the cytokine response, we measured CD68, an indicator of microglial activation in the hippocampus, as well as changes in normal in-cage behavior. We hypothesized that hindlimb unloading (HU) will elicit microglial hippocampal activations, which will be mitigated in the MCAT ROS-quenching mice model. Indeed, we saw an elevation of the activated microglia CD68 marker following HU in the hippocampus, and this pathology was mitigated in MCAT mice. Additionally, we identified cytokines in the hippocampus, which had significant positive correlations with CD68 and negative correlations with exploratory behaviors, indicating a link between neuroinflammation and behavioral consequences. Unveiling a correlation between molecular and behavioral changes could reveal a biomarker indicative of these responses and could also result in a potential target for the treatment and prevention of cognitive changes following long space missions and/or muscle disuse on Earth.

Examining the First Peer-to-Peer Mentorship Program (F1Doctors) for International Medical Students.

In this study, we report international medical students in the United States and conduct an analysis of the first, peer-to-peer, national mentorship program for international medical students and international pre-med applicants in the US (F1Doctors). We used analyzed survey data collected through F1Doctors and the Association of American Medical Colleges yearly matriculation reports. Results indicated that the average college grade point average (GPA) and Medical College Admission Test score (MCAT) of international applicants was higher than that of all applicants. Additionally, non-US applicants reported facing numerous unique challenges such as limited access to extracurricular opportunities and difficulty finding mentors who are familiar with the application process. International applicants have the potential to increase the diversity of healthcare professionals, and F1Doctors is the first platform to support international healthcare applicants in the US.

Promoting cultural competency and osteopathic medicine awareness among premedical students through a summer premedical rural enrichment program.

CONTEXT: Premedical preparatory programs at osteopathic medical schools that recruit students from medically underserved areas (MUAs) may promote interest in practicing osteopathic medicine in underserved or rural areas. In these programs, emphasis on cultural competency may increase diversity among medical school applicants and decrease healthcare disparities in the future. OBJECTIVES: The goal of this study is to determine whether a summer premedical rural enrichment program (PREP) held at an osteopathic medical school located in a MUA will foster greater prioritization of cultural competency in medicine, enhance interest in practicing in rural or underserved areas, and increase familiarity with osteopathic medicine. METHODS: An eight-week summer PREP was hosted at the California Health Sciences University College of Osteopathic Medicine (CHSU-COM) in Clovis, California. Seventy-eight diverse participants were recruited from the Central Valley, an underserved region of California. Attendees were required to finish the formal application process and were recommended to have completed medical school prerequisite courses. The curriculum included Medical College Admission Test (MCAT) preparation through team-based learning sessions, introduction to the osteopathic medical school curriculum, osteopathic philosophy, and osteopathic manipulative medicine, as well as integrated anatomy and physiology sessions, medical school application workshops, mock interviews, simulation workshops, and sociology and cultural competency sessions. Data were collected via a voluntary and anonymous survey administered before and after the program with questions about familiarity with osteopathy, interest in practicing in underserved areas, medical school preparedness, and a post-course survey about cultural competency. The surveys had students rate statements on a Likert scale. RESULTS: Seventy-four of the 78 premedical students (95%) completed the pre-and postsurvey. There was a significant increase in agreement to statements evaluating medical school preparedness, osteopathic familiarity, and desire to practice medicine locally in the postprogram survey, compared to the preprogram survey. In the cultural competency postsurvey, 75.0% of the responses to questions that evaluated the positive effect of the course were "Agree" or "Strongly Agree." Of the reported postcourse outcomes, the average MCAT score was 504 ± 6.2 (38 students reported, 50.7%). Of the 27 participants who reported matriculation, 16 (59.2%) were admitted to osteopathic medical schools, 9 (33.3%) to allopathic medical schools, and 2 to other health programs. CONCLUSIONS: After completing the PREP program, premedical participants reported that they have better understanding of cultural competency and improvement in preparation for medical school, including familiarity with osteopathic medicine, and interest in serving MUAs. These findings indicate that similar programs may have a positive impact on MUAs. These programs may help create diverse and culturally competent osteopathic physicians.

Spatial quantification of clinical biomarker pharmacokinetics through deep learning-based segmentation and signal-oriented analysis of MSOT data.

Although multispectral optoacoustic tomography (MSOT) significantly evolved over the last several years, there is a lack of quantitative methods for analysing this type of image data. Current analytical methods characterise the MSOT signal in manually defined regions of interest outlining selected tissue areas. These methods demand expert knowledge of the sample anatomy, are time consuming, highly subjective and prone to user bias. Here we present our fully automated open-source MSOT cluster analysis toolkit Mcat that was designed to overcome these shortcomings. It employs a deep learning-based approach for initial image segmentation followed by unsupervised machine learning to identify regions of similar signal kinetics. It provides an objective and automated approach to quantify the pharmacokinetics and extract the biodistribution of biomarkers from MSOT data. We exemplify our generally applicable analysis method by quantifying liver function in a preclinical sepsis model whilst highlighting the advantages of our new approach compared to the severe limitations of existing analysis procedures.

Long-term immunogenicity and safety of a non-typeable Haemophilus influenzae-Moraxella catarrhalis vaccine: 4-year follow-up of a phase 1 multicentre trial.

A multicomponent vaccine has been developed to reduce the frequency of acute exacerbations of COPD associated with non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) infections, containing NTHi (PD and PE-PilA) and Mcat (UspA2) surface proteins. In a randomised, observer-blind, placebo-controlled study with two steps (NCT02547974), the investigational vaccine had good immunogenicity and no safety concerns were identified. In step 2, 90 adults aged 50-71 years with smoking history received two doses 60 days apart of one of two AS01E-adjuvanted formulations containing 10 µg of each antigen (10-10-AS01) or 10 µg NTHi antigens and 3.3 µg UspA2 (10-3-AS01), or placebo. Long-term persistence of antigen-specific humoral antibodies was assessed in 81 participants during 3 years of follow-up after the initial 14-month study (NCT03201211). Antigen-specific antibody concentrations were measured in blood samples taken every 6 months. Safety monitoring evaluated serious adverse events (SAEs) and potential immune-mediated disease (pIMD). Immune responses against NTHi antigens persisted up to 4 years post-vaccination. For PD, PE and PilA, at each follow-up time point, adjusted antibody geometric mean concentrations (GMCs) were higher (non-overlapping 95% confidence intervals [CIs]) in the vaccine groups versus placebo and versus pre-vaccination. Antibody GMC point estimates were higher with 10-3-AS01 than with 10-10-AS01. For UspA2, 95% CIs included 1 for GMC ratios of 10-10-AS01 or 10-3-AS01 to placebo at each time point. During follow-up, SAEs were reported in nine (11.1%) participants, one of which was fatal (lung cancer, 607 days after second 10-10-AS01 dose). One non-serious pIMD, trigeminal neuralgia, was reported 771 days after second 10-3-AS01 dose. The SAEs and pIMD were considered not related to vaccination. Immune responses against NTHi antigens persisted for 4 years after two-dose vaccination with the investigational NTHi-Mcat vaccine. There was no persistent response against the Mcat antigen. No safety concerns were identified during the long-term follow-up.

Medical Student Selection.

Medical school admissions committees are tasked with fulfilling the values of their institutions through careful recruitment. Making accurate predictions regarding the enrollment behavior of admitted students is critical to intentionally formulating class composition and impacts long-term physician representation.

Improving the Delivery of Function-Directed Care During Acute Hospitalizations: Methods to Develop and Validate the Functional Assessment in Acute Care Multidimensional Computerized Adaptive Test (FAMCAT).

OBJECTIVE: To (1) develop a patient-reported, multidomain functional assessment tool focused on medically ill patients in acute care settings; (2) characterize the measure's psychometric performance; and (3) establish clinically actionable score strata that link to easily implemented mobility preservation plans. DESIGN: This article describes the approach that our team pursued to develop and characterize this tool, the Functional Assessment in Acute Care Multidimensional Computer Adaptive Test (FAMCAT). Development involved a multistep process that included (1) expanding and refining existing item banks to optimize their salience for hospitalized patients; (2) administering candidate items to a calibration cohort; (3) estimating multidimensional item response theory models; (4) calibrating the item banks; (5) evaluating potential multidimensional computerized adaptive testing (MCAT) enhancements; (6) parameterizing the MCAT; (7) administering it to patients in a validation cohort; and (8) estimating its predictive and psychometric characteristics. SETTING: A large (2000-bed) Midwestern Medical Center. PARTICIPANTS: The overall sample included 4495 adults (2341 in a calibration cohort, 2154 in a validation cohort) who were admitted either to medical services with at least 1 chronic condition or to surgical/medical services if they required readmission after a hospitalization for surgery (N=4495). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Not applicable. RESULTS: The FAMCAT is an instrument designed to permit the efficient, precise, low-burden, multidomain functional assessment of hospitalized patients. We tried to optimize the FAMCAT's efficiency and precision, as well as its ability to perform multiple assessments during a hospital stay, by applying cutting edge methods such as the adaptive measure of change (AMC), differential item functioning computerized adaptive testing, and integration of collateral test-taking information, particularly item response times. Evaluation of these candidate methods suggested that all may enhance MCAT performance, but none were integrated into initial MCAT parameterization. CONCLUSIONS: The FAMCAT has the potential to address a longstanding need for structured, frequent, and accurate functional assessment among patients hospitalized with medical diagnoses and complications of surgery.

Medical Anthropology Courses and Concepts Tested on the MCAT: A Content Analysis of 40 U.S. Course Syllabi.

The Association of American Medical Colleges recommends students seeking to enter medical school complete courses in the social sciences. Despite calls to teach social science-including anthropology-in pre-medical curriculum, little is known about what is taught in undergraduate medical anthropology courses and if concepts taught in those courses addresses topics tested in the MCAT exam. Given the growing number of anthropology students in baccalaureate allied health fields, there is a growing need to examine if anthropological coursework addresses relevant MCAT topics. Using a mixed methods content analysis, this study examined syllabi from forty U.S.-based medical anthropology courses to assess if MCAT concepts are taught in Medical Anthropology courses. Survey data was examined using descriptive statistics; syllabi were analyzed with NVivo using a binary coding scheme and modified grounded theory. Overall, only 8.69% of 155 possible concepts and terms from the Psychological, Social, and Biological Foundations of Behavior section of the MCAT were present in the syllabi. We close with considerations for future course design of medical anthropology courses.

Admissions to Medical School during the COVID-19 Era without the MCAT.

As medical schools cope with the consequences of the COVID-19 pandemic, a new cohort of students will be admitted in the fall. Administrators are again challenged to make unprecedented enrollment decisions without standardized exams. This challenge provides unique opportunities to re-evaluate admission processes that has been employed since 1928 and support holistic admissions. This article highlights key factors that are being considered during current medical school admission cycles, including limited opportunities to take standardized exams, heightened student anxiety, and potential exam alternatives. These factors are framed and discussed within the context of the medical college admission test (MCAT) exam.

Perceptions of Barriers and Facilitators to Becoming a Medical Professional Among Underrepresented Undergraduate and Postbaccalaureate Learners.

OBJECTIVE: To assess underrepresented undergraduate and postbaccalaureate learners' perceptions of (1) the medical field, (2) barriers that might prevent individuals from pursuing professional medical careers, and (3) resources that assist in overcoming these barriers. PARTICIPANTS AND METHODS: A qualitative study with focus groups was designed to achieve the objective. Participants were recruited from a community initiative to provide early exploration of the medical field to disadvantaged and minority individuals. Thirty-five individuals voluntarily participated in semistructured interviews. Audio from the interviews was analyzed using a qualitative descriptive approach and thematic analysis. This study was conducted from October 20, 2018, to April 6, 2019. RESULTS: Participants identified multiple characteristics related to the health care work environment and desirable attributes of health care personnel. The following barriers were identified: financial burden, lacking knowledge of the path to becoming a medical professional, inadequate social support, and lacking the metrics of a competitive candidate. Resources identified by participants to overcome barriers included professional networks and programmatic considerations. CONCLUSION: The study participants discussed negative and positive aspects of the health care environment, such as implicit and explicit biases and attributes that promote or sustain success. Participants expounded on financial, academic, social, and personal factors as barriers to success. In regard to resources that were believed to be helpful to mitigate barriers and promote success, participants commented on activities that simulate a professional medical environment, include networking with medical personnel, support well-being, and provide exposure to structured information on the process of obtaining professional medical training.