Postnatal growth restriction alters myocardial mitochondrial energetics in mice.

Postnatal growth restriction (PGR) can increase the risk of cardiovascular disease (CVD) potentially due to impairments in oxidative phosphorylation (OxPhos) within cardiomyocyte mitochondria. The purpose of this investigation was to determine if PGR impairs cardiac metabolism, specifically OxPhos. FVB (Friend Virus B-type) mice were fed a normal-protein (NP: 20% protein), or low-protein (LP: 8% protein) isocaloric diet 2 weeks before mating. LP dams produce ∼20% less milk, and pups nursed by LP dams experience reduced growth into adulthood as compared to pups nursed by NP dams. At birth (PN1), pups born to dams fed the NP diet were transferred to LP dams (PGR group) or a different NP dam (control group: CON). At weaning (PN21), all mice were fed the NP diet. At PN22 and PN80, mitochondria were isolated for respirometry (oxygen consumption rate, J O 2 ${J_{{{\mathrm{O}}_{\mathrm{2}}}}}$ ) and fluorimetry (reactive oxygen species emission, J H 2 O 2 ${J_{{{\mathrm{H}}_{\mathrm{2}}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) analysis measured as baseline respiration (LEAK) and with saturating ADP (OxPhos). Western blotting at PN22 and PN80 determined protein abundance of uncoupling protein 3, peroxiredoxin-6, voltage-dependent anion channel and adenine nucleotide translocator 1 to provide further insight into mitochondrial function. ANOVAs with the main effects of diet, sex and age with α-level of 0.05 was set a priori. Overall, PGR (7.8 ± 1.1) had significant (P = 0.01) reductions in respiratory control in complex I when compared to CON (8.9 ± 1.0). In general, our results show that PGR led to higher electron leakage in the form of free radical production and reactive oxygen species emission. No significant diet effects were found in protein abundance. The observed reduced respiratory control and increased ROS emission in PGR mice may increase risk for CVD in mice.

The Effect of Downhill Running on Quadriceps Muscle in Growth-Restricted Mice.

INTRODUCTION: Growth restriction (GR) reduces ribosome abundance and skeletal muscle mass in mice. A reduction in skeletal muscle mass increases the risk of frailty and is associated with high morbidity and mortality rates. As eccentric type exercise increases muscle mass, this investigation aimed to determine if eccentric loading of skeletal muscle via downhill running (DHR) increased muscle mass in GR mice. METHODS: Mice were growth-restricted either gestational undernutrition (GUN, n = 8 litters), postnatal undernutrition (PUN, n = 8 litters), or were not restricted (CON, n = 8 litters) via a validated cross-fostering nutritive model. On postnatal day (PN) 21, all mice were weaned to a healthy diet, isolating the period of GR to early life as seen in humans. At PN45, mice were assigned to either a DHR (CON, n = 4 litters; GUN, n = 4 litters; PUN, n = 4 litters) or sedentary (SED: CON, n = 4 litters; GUN, n = 4 litters; PUN, n = 4 litters) group. Downhill running (16% decline: 18 m·min -1 ) was performed in 30-min bouts, three times per week, for 12 wk on a rodent treadmill. At PN129, the quadriceps femoris was dissected and evaluated for mass, myofiber size and type, and molecular markers of growth. RESULTS: Following training, CON-DHR mice having larger cells than CON-SED, GUN-SED, PUN-SED, and PUN-DHR mice ( P < 0.05). The PUN group (as compared with CON) had reduced body mass ( P < 0.001), upstream binding factor abundance ( P = 0.012), phosphor-mTOR ( P < 0.001), and quadriceps mass ( P = 0.02). The GUN and PUN groups had increased MuRF1 abundance ( P < 0.001) compared with CON ( P < 0.001). CONCLUSIONS: The blunted response to training suggests GR mice may have anabolic resistance when exposed to eccentric type exercise.

Effects of using superheroes in an undergraduate human anatomy curriculum.

Students often find human anatomy courses to be difficult due to the large amount of content covered at a fast pace, which can result in students failing to retain pertinent information. Superheroes are at the forefront of today's popular culture, with many students identifying with specific characters. Utilizing aspects of students' lives, or their agency, that they can resonate with in the classroom, such as their interests in superheroes or personal connections to fictional characters, may help drive students' motivation to learn course content. This study investigated if the use of superheroes in an anatomy curriculum helped undergraduate students learn, apply, and improve their anatomical knowledge. Two courses at The Ohio State University-Columbus Campus, one with a superhero-based curriculum and one with a traditional anatomy curriculum were compared over three semesters using quizzes and survey data. Results from this project found that the use of superheroes/pop culture in anatomy education is an effective way to teach content. The study also showed that most students found the use of superheroes increased their motivation to learn, helped them gain a deeper understanding of the material, and helped them find the content more approachable and enjoyable. In summary, anatomy curricula can still be taught and explained through these creative and "marvel"-ous examples as it can help students connect the material to their own agency and drive motivation to learn.

Essential anatomy for core clerkships: A clinical perspective.

Clerkships are defining experiences for medical students in which students integrate basic science knowledge with clinical information as they gain experience in diagnosing and treating patients in a variety of clinical settings. Among the basic sciences, there is broad agreement that anatomy is foundational for medical practice. Unfortunately, there are longstanding concerns that student knowledge of anatomy is below the expectations of clerkship directors and clinical faculty. Most allopathic medical schools require eight "core" clerkships: internal medicine (IM), pediatrics (PD), general surgery (GS), obstetrics and gynecology (OB), psychiatry (PS), family medicine (FM), neurology (NU), and emergency medicine (EM). A targeted needs assessment was conducted to determine the anatomy considered important for each core clerkship based on the perspective of clinicians teaching in those clerkships. A total of 525 clinical faculty were surveyed at 24 United States allopathic medical schools. Participants rated 97 anatomical structure groups across all body regions on a 1-4 Likert-type scale (1 = not important, 4 = essential). Non-parametric ANOVAs determined if differences existed between clerkships. Combining all responses, 91% of anatomical structure groups were classified as essential or more important. Clinicians in FM, EM, and GS rated anatomical structures in most body regions significantly higher than at least one other clerkship (p = 0.006). This study provides an evidence-base of anatomy content that should be considered important for each core clerkship and may assist in the development and/or revision of preclinical curricula to support the clinical training of medical students.

Serum metabolomic characterization in pigs in relation to birth weight category and neonatal nutrition.

The objective of this study was to characterize developmental differences in low birth weight (LBW) and normal birth weight (NBW) piglets with or without pre-weaning nutrient restriction using serum metabolomic profile analysis. At farrowing, 112 piglets were identified as LBW (1.22 ± 0.28 kg) or NBW (1.70 ± 0.27 kg) and were randomly assigned to receive normal nutrition (NN) or restricted nutrition (RN) (6 h/day no suckling) from days 2 to 28 post farrow (n = 8 pigs/group). On day 28, piglets were weaned onto a common diet. Fasted blood samples were obtained on days 28 and 56 (n = 8 pigs/group) and were analyzed using quantitative metabolomics via a combination of direct injection mass spectrometry with a reverse-phase LC-MS/MS custom assay. Data were normalized using logarithmic transformation and auto-scaling. Partial least squares discriminant analysis (PLS-DA) was carried out to further explore the differential metabolites among the groups (metaboanalyst.ca) with an integrated enrichment and pathway topography analysis. On day 28, LBW piglets had lower levels of essential amino acids as well as reduced metabolites associated with fatty acid oxidation, glycolysis, and the tri-carboxylic acid (TCA) cycle compared to the NBW group. The overall reduction of metabolites associated with energy production and regulation suggests that LBW vs. NBW are in an energy-survival state. On day 56, LBW pigs had increased utilization of fatty acids and resultant ketone production, evident by increased carnitines, acetoacetate, ß-hydroxybutyrate, and glycerol compared to NBW pigs. In addition, compared to the NBW pigs LBW pigs had a consistent decrease in serum glucose and lactate as well as reduced TCA cycle metabolites: pyruvate, succinate, citrate, and α-ketoglutaric acid similar to day 28. Low reliance on glycolysis and the TCA cycle and higher glycerol production in the LBW pigs may indicate impairments in glucose tolerance at 56 d. In summary, LBW piglets appear to have more metabolic alterations in early life, which is not resolved with adequate nutrition or refeeding and may elucidate physiological and metabolic mechanisms of poor growth and life performance compared to NBW pigs later in life.

The objective of this study was to characterize developmental differences in low birth weight (LBW) and normal birth weight (NBW) piglets with or without pre-weaning nutrient restriction using serum metabolomic profile analysis. Through the serum metabolite analysis, at weaning, we saw fewer metabolites associated with fatty acid oxidation, and glycolysis in the LBW pigs compared to the NBW, which suggests poor fatty acid and glucose metabolism in these piglets. After weaning, fatty acid metabolism is restored in both LBW and NBW piglets, but glucose and lactate levels remained lower in the LBW piglets, which may be indicative of impairment in glucose tolerance post-weaning. Therefore, in LBW piglets, poor metabolism of glucose at weaning could not be curtailed with nutrition intervention post-weaning.

Longitudinal effects of growth restriction on the murine gut microbiome and metabolome.

Undernutrition-induced growth restriction in the early stages of life increases the risk of chronic disease in adulthood. Although metabolic impairments have been observed, few studies have characterized the gut microbiome and gut-liver metabolome profiles of growth-restricted animals during early-to-mid-life development. To induce growth restriction, mouse offspring were either born to gestational undernutrition (GUN) or suckled from postnatal undernutrition (PUN) dams fed a protein-restricted diet (8% protein) or control diet (CON; 20% protein) until weaning at postnatal age of 21 days (PN21). At PN21, all mice were fed the CON diet until adulthood (PN80). Livers were collected at PN21 and PN80, and fecal samples were collected weekly starting at PN21 (postweaning week 1) until PN80 (postweaning week 5) for gut microbiome and metabolome analyses. PUN mice exhibited the most alterations in gut microbiome and gut and liver metabolome compared with CON mice. These mice had altered fecal microbial ß-diversity (P = 0.001) and exhibited higher proportions of Bifidobacteriales [linear mixed model (LMM) P = 7.1 × 10-6), Clostridiales (P = 1.459 × 10-5), Erysipelotrichales (P = 0.0003), and lower Bacteroidales (P = 4.1 × 10-5)]. PUN liver and fecal metabolome had a reduced total bile acid pool (P < 0.01), as well as lower abundance of riboflavin (P = 0.003), amino acids [i.e., methionine (P = 0.0018), phenylalanine (P = 0.0015), and tyrosine (P = 0.0041)], and higher excreted total peptides (LMM P = 0.0064) compared with CON. Overall, protein restriction during lactation permanently alters the gut microbiome into adulthood. Although the liver bile acids, amino acids, and acyl-carnitines recovered, the fecal peptides and microbiome remained permanently altered into adulthood, indicating that inadequate protein intake in a specific time frame in early life can have an irreversible impact on the microbiome and fecal metabolome.NEW & NOTEWORTHY Undernutrition-induced early-life growth restriction not only leads to increased disease risk but also permanently alters the gut microbiome and gut-liver metabolome during specific windows of early-life development.

Adaptation of an anatomy graduate course in ultrasound imaging from in-person to live, remote instruction during the Covid-19 pandemic.

Health concerns during the Covid-19 pandemic required the adaptation of a lecture-laboratory course in ultrasound imaging for graduate students from an in-person to a live, remote learning format. The adaptation of in-person lectures to live, remote delivery was achieved by using videoconferencing. The adaptation of in-person laboratory sessions to live, remote instruction was achieved in the first half of the course by providing a hand-held ultrasound instrument to each student who performed self-scanning at their remote locations, while the instructor provided live instruction using videoconferencing. In the second half of the course, the students transitioned to using cart-based, hospital-type instruments and self-scanning in the ultrasound laboratory on campus. The aim of this study was to measure the success of this adaptation to the course by comparing assessment scores of students in the live, remote course with assessment scores of students in the in-person course offered in the previous year. There were no statistically significant differences in the assessment scores of students in the two courses. The adaptation of a course in ultrasound imaging from an in-person to a live, remote learning format during the Covid-19 pandemic described here suggests that contrary to the prevailing view, ultrasound imaging can be taught to students without in-person instruction. The adapted course can serve as a model for teaching ultrasound where instructors and learners are physically separated by constraints other than health concerns during a pandemic.

Anatomists Assemble! Integrating superheroes into the anatomy and physiology classroom.

Anatomy and physiology courses are sometimes seen as difficult, which can lead to a lack of motivation in students to learn and engage in the course material. Students may also see the material as "dry," have issues forming personal connections, or struggle to connect the content to the real world. These issues may lead to students not performing well in the course or feeling that the health field is not ideal for them. Popular culture, especially mainstream superheroes, can serve as an option for mending these gaps by being a gateway to connecting to many students' lives. Superheroes can be integrated into the classroom through relevant, creative, and unique examples that include clinical correlates, modern scientific innovations, and some real-life "supers" living among us. Real anatomy and physiology can still be taught and explained through discussing these "incredible" examples and also present an opportunity for students to be creative in generating their own anatomical and physiological explanations for various superpowers. Superheroes also help open the classroom up to being a place of acceptance, primarily through their secret identities, which cover a broad range of idols that students can look up to, whether it is their career or based on a character's race or sexual orientation. Professors can become the superhero in their classroom and help students become more engaged and interested in the material.

Ultrasound's Impact on Preclinical Medical Student Neurology Unit Grades: Findings After 2 Years.

OBJECTIVES: Ultrasound is a valuable tool for anatomy education, but limited evidence exists for using ultrasound to teach neuroanatomy and neurophysiology. Previous work demonstrated a potential increase in medical knowledge in preclinical medical students participating in a neurology ultrasound workshop, however, without comparison to a control group. After 2 years, we assessed how a neurology ultrasound workshop affected the medical knowledge of participating preclinical medical students compared to a traditional curriculum control group. METHODS: This quasiexperimental study compared academic performance of ultrasound workshop participants to nonparticipant classmates. The primary outcome was the overall neurologic disorders unit total score. An analysis of covariance was conducted to test for statistically significant differences while controlling for the average quiz score. RESULTS: A total of 360 medical students were included in the study. The intervention group (n = 57) showed no significant difference in the total unit score (F = 3.206; P = .074), with averages for the control and experimental groups being 87.3% ± 5.0% and 88.4% ± 4.8%, respectively. Additionally, anatomy practical scores and written final examination scores were not significantly different between groups (F = 1.035; P = .310; F = 2.035; P = .155). CONCLUSIONS: Participation in a neurologic disorders ultrasound workshop did not appear to be correlated with improved curricular performance in our cohort. Further research should continue to assess ultrasound workshops in other organ systems to elucidate the relationship between learning ultrasound and the impact on medical school academic performance.

Global chemical effects of the microbiome include new bile-acid conjugations.

A mosaic of cross-phylum chemical interactions occurs between all metazoans and their microbiomes. A number of molecular families that are known to be produced by the microbiome have a marked effect on the balance between health and disease1-9. Considering the diversity of the human microbiome (which numbers over 40,000 operational taxonomic units10), the effect of the microbiome on the chemistry of an entire animal remains underexplored. Here we use mass spectrometry informatics and data visualization approaches11-13 to provide an assessment of the effects of the microbiome on the chemistry of an entire mammal by comparing metabolomics data from germ-free and specific-pathogen-free mice. We found that the microbiota affects the chemistry of all organs. This included the amino acid conjugations of host bile acids that were used to produce phenylalanocholic acid, tyrosocholic acid and leucocholic acid, which have not previously been characterized despite extensive research on bile-acid chemistry14. These bile-acid conjugates were also found in humans, and were enriched in patients with inflammatory bowel disease or cystic fibrosis. These compounds agonized the farnesoid X receptor in vitro, and mice gavaged with the compounds showed reduced expression of bile-acid synthesis genes in vivo. Further studies are required to confirm whether these compounds have a physiological role in the host, and whether they contribute to gut diseases that are associated with microbiome dysbiosis.

A Novel Approach to Gross Dissection of the Human Pelvis and Perineum.

Progressive curricular changes in medical education over the past two decades have resulted in the diaspora of gross anatomy content into integrated curricula while significantly reducing total contact hours. Despite the development of a wide range of alternative teaching modalities, gross dissection remains a critical component of medical education. The challenge posed to modern anatomists is how to maximize and integrate the time spent dissecting under the current curricular changes. In this study, an alternative approach to the dissection of the pelvis and perineum is presented in an effort to improve content delivery and student satisfaction. The approach involves removal of the perineum en bloc from the cadaver followed by excision of the pubic symphysis, removal and examination of the bladder and associated structures, examination and bisection of the midline pelvic organs in situ, and midsagittal hemisection of the pelvis for identification of the neurovasculature. Results indicate that this novel dissecting approach increases the number of structures identified by 46% ± 14% over current dissecting methods. Survey results indicate that students were better able to integrate lecture and laboratory concepts, understand the concepts, and successfully identify more structures using the new approach (P < 0.05). The concept of anatomic efficiency is introduced and proposed as a standard quantitative measure of gross dissection proficiency across programs and institutions. These findings provide evidence that innovative solutions to anatomy education can be found that help to maintain critical content and student satisfaction in a modern medical curriculum.

Pentamidine for Prophylaxis against Pneumocystis jirovecii Pneumonia in Pediatric Oncology Patients Receiving Immunosuppressive Chemotherapy.

Pneumocystis jirovecii pneumonia is a life-threatening opportunistic infection in children receiving immunosuppressive chemotherapy. Without prophylaxis, up to 25% of pediatric oncology patients receiving chemotherapy will develop Pneumocystis jirovecii pneumonia. Trimethoprim-sulfamethoxazole is the preferred agent for prophylaxis against Pneumocystis jirovecii pneumonia. Pentamidine may be an acceptable alternative for pediatric patients unable to tolerate trimethoprim-sulfamethoxazole. A retrospective review was conducted of pediatric oncology patients who received ≥1 dose of pentamidine for Pneumocystis jirovecii pneumonia prophylaxis between January 2007 and August 2014. Electronic medical records were reviewed to determine the incidence of breakthrough Pneumocystis jirovecii pneumonia or discontinuation of pentamidine associated with adverse events. A total of 754 patients received pentamidine prophylaxis during the period. There were no cases of probable or proven Pneumocystis pneumonia, and 4 cases (0.5%) of possible Pneumocystis pneumonia. The incidence of possible breakthrough Pneumocystis pneumonia was not significantly different between subgroups based on age (<12 months [1.7%] versus ≥12 months [0.4%], P = 0.3), route of administration (aerosolized [0%] versus intravenous [1.0%], P = 0.2), or hematopoietic stem cell transplant status (transplant [0.4%] versus no transplant [0.8%], P = 0.6). Pentamidine was discontinued due to an adverse drug event in 23 children (3.1%), more frequently for aerosolized than for intravenous administration (7.6% versus 2.2%, respectively, P = 0.004). Intravenous or inhaled pentamidine may be a safe and effective second-line alternative for prophylaxis against Pneumocystis jirovecii pneumonia in children with cancer receiving immunosuppressive chemotherapy or hematopoietic stem cell transplantation.

What type of learner are your students? Preferred learning styles of undergraduate gross anatomy students according to the index of learning styles questionnaire.

Students learn and process information in many different ways. Learning styles are useful as they allow instructors to learn more about students, as well as aid in the development and application of useful teaching approaches and techniques. At the undergraduate level there is a noticeable lack of research on learning style preferences of students enrolled in gross anatomy courses. The Index of Learning Styles (ILS) questionnaire was administered to students enrolled in a large enrollment undergraduate gross anatomy course with laboratory to determine their preferred learning styles. The predominant preferred learning styles of the students (n = 505) enrolled in the gross anatomy course were active (54.9%), sensing (85.1%), visual (81.2%), and sequential (74.4%). Preferred learning styles profiles of particular majors enrolled in the course were also constructed; analyses showed minor variation in the active/reflective dimension. An understanding of students' preferred learning styles can guide course design but it should not be implemented in isolation. It can be strengthened (or weakened) by concurrent use of other tools (e.g., flipped classroom course design). Based on the preferred learning styles of the majority of undergraduate students in this particular gross anatomy course, course activities can be hands on (i.e., active), grounded in concrete information (i.e., sensing), utilize visual representation such as images, figures, models, etc. (i.e., visual), and move in small incremental steps that build on each topic (i.e., sequential). Anat Sci Educ 11: 358-365. © 2017 American Association of Anatomists.