bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiometabolic Status in Obese African American Women is Linked to Glycative Stress
Authors: Nance Sierra A. , Duncan A'ja V. , Hairston Kristen G. , Gwathmey TanYa M.
Published: November 2023

It is well established that oxidative stress increases cardiovascular risk by inducing inflammation and damage to target organs. Indeed, a growing number of studies show improvements in markers of oxidative stress following a reduction in body weight, particularly in fat depots. Advanced glycation end‐products (AGE) form non‐enzymatically as proteins and lipids become glycosylated, as a result of exposure to dietary sugars. Accumulation of endogenous or exogenous AGE, and subsequent binding to their receptor (RAGE) can lead to glycative stress, likewise causing inflammation and tissue injury, similar to that of oxidative stress. However, it has not yet been determined whether glycative stress may be altered by reductions in body fat. We evaluated a cohort of pre‐menopausal, non‐diabetic, obese African American women (n=16). Subjects underwent reduced caloric intake by 500–1000 kcal/week for 12 weeks, based on individual basal metabolic rates. Visceral adiposity (VAT) was determined by computed tomography scans and blood samples were collected at baseline and 12‐week follow‐up visits. The mean reduction in VAT over the 12 week period was (−18% ± 4%). We evaluated serum levels of AGE by enzyme‐linked immunosorbent assay (ELISA) and found no correlation between VAT and levels of AGE (p=0.48) in this cohort. However, AGE was positively correlated with levels of the satiety hormone leptin (R2=0.25; p=0.02), and inversely correlated with the appetite‐stimulating hormone, ghrelin (R2=0.24; p=0.03). We further evaluated expression of the soluble receptor for AGE (sRAGE), a decoy‐like receptor that helps to protect against glycative stress by sequestering ligands for RAGE. We found that sRAGE was positively correlated with adiponectin levels (R2=0.37; p=0.007), but inversely correlated with insulin resistance, as represented by HOMA‐IR (R2=0.20; p=0.04). In summary, we report that AGE are strongly linked to determinants of cardiometabolic status in a cohort of non‐diabetic, obese, African American women. As cardiometabolic disease increases epidemically within the U.S., understanding the precise interplay of components that regulate metabolism becomes critical.

Support or Funding Information

Hypertension & Vascular Research Funding (PI: Hairston)
Effect of Substituting Starchy Noodles with Konjac Fiber Noodles on Satiety, Palatability and Subsequent Food Intake in Healthy Individuals: A Dose Response Study
Authors: Jenkins Alexandra , Au‐Yeung Fei , Jovanovski Elena , Zurbau Andreea , Ho Thanh , Vuksan Vladimir
Published: November 2023

Background

Foods that provides satiety with little calories are in high demand. We evaluated the effect of substituting regular noodles with noodles made from Konjac fiber (KF) on signals of appetite and consecutive food intake in healthy individuals.

Methods

Following an overnight fast, sixteen healthy volunteers (12F/4M; Age: 26±12 years; BMI: 23±3kg/m2) were randomly assigned to receive one of three‐isovolumetric pre‐load meals on three separate occasions. Meals differed by increments of ~250 kcal due to partial or full replacement of starchy noodles by KF Shirataki noodles (zero% KF:442kcal; 50% KF:259kcal and 100% KF:77kcal), followed 90min later by an ad libitum wafer cookies post‐load. Measures of satiety using a visual analogue scale were collected over 90 min and ad libitum food intake was assessed.

Results

Hunger was significantly higher after 100%KF compared to zero%KF (control)(p=0.04). Fullness was lower and prospective consumption was higher after100%KF compared to 50% KF (p=0.03). Post‐load energy intake after all preloads were not significantly different (p=0.71), resulting in a net caloric deficit of 201 and 421 kcal in cumulative energy intake compared to control after 50% KF(p<0.001) and 100% KF (p<0.001), respectively. Cumulative energy intake was also significantly lower after the 100%KF meal compared to the 50% KF meal (p<0.05). There were no differences in palatability ratings between the meals.

Conclusion

Replacement of a high carbohydrate preload with a low energy konjac fiber food did not increase subsequent food intake in healthy individuals. The caloric deficit incurred from the volume‐matched preloads may have relevance in weight loss regimes however further studies should evaluate whether the effects of konjac fiber foods extend over the long term and its mechanisms of action.
How Ready Is Mexico to Launch an Effective National Program to Protect, Promote and Support Breastfeeding
Authors: de Cosio Teresita González , Ferre Isabel , Alonso Aranza , Bonvecchio Anabelle , Colmenares Mariana , Cauich Elena , Gris Perla , Hernández Sonia , Mendiola Karla , Piedras Ivonne , Villa Alejandría , Vilar Mireya , Hromi‐Fiedler Amber , Pérez‐Escamilla Rafael
Published: November 2023

In Mexico, the prevalence of exclusive breastfeeding in children under 6 months of age has decreased significantly from 22.3% in 1999 to 14.5% in 2012. The deterioration of breastfeeding practices has affected vulnerable groups of women: a) rural women in the southern region of the country, b) those in the lowest tertile of socioeconomic status, c) those with education lower than primary, d) those without access to health services or without paid employment. Currently, Mexico does not have a National Breastfeeding Program.

The objective of this project was to assess the enabling environment to effectively scale up breastfeeding programs in Mexico using the Becoming Breastfeeding Friendly Index (BBFI), which is comprised of 54 evidence based benchmarks reflecting 8 submetrics: advocacy (4 benchmarks); political will (3 benchmarks); legislation and policy (10 benchmarks), funding and resources (3 benchmarks), training and program delivery (17 benchmarks), promotion (3 benchmarks), research and evaluation (10 benchmarks), and coordination, goals and monitoring (3 benchmarks). An 11‐member expert country committee, composed of representatives of the Mexican federal government, civil society and researchers, has met four times to reach consensus on the BBFI subscores and total score in order to make recommendations to policy makers.

BBFI submetric score(s) were calculated ranged from 0 (not present) to 3 (strong). Submetrics scores were: 1.3 (moderate) for advocacy; 2 (moderate) for political will; 2.1 (strong) for legislation and policy, 0.5 (weak) for funding and resources, 1.2 (moderate) for training and program delivery, 1.7 (moderate) for promotion, 0.9 (weak) for research and evaluation, and 2 (strong) for coordination, goals and monitoring. The overall BBFI score was 1.4 indicating a potential environment for scaling up breastfeeding programs in Mexico that needs substantial improvement.

Findings indicate that it is crucial for civil society to continue engaging in evidence‐based advocacy to foster the political will to secure the funding and resources needed for the establishment of a solid Breastfeeding Protection, Promotion and Support National Strategy in Mexico. This strategy must consider as a priority the training of medical and allied students, health care providers, and breastfeeding paraprofessionals operating at the health facility and community levels. Multi‐level monitoring and evaluation is needed to share information from the local to the national level and to enable proper decision making across the quite fragmented Mexican Health System

Support or Funding Information

Funded by the Family Larsson‐Rosenquist Foundation.
Association of Vitamin D and Smoking in Acute Kidney Injury
Authors: Sukhram Shiryn Devi , El‐Charabaty Elie , Fata Jimmie , El‐Sayegh Suzanne
Published: November 2023

The eighth leading cause of death in the United States, kidney disease affects 20 million adults with the majority unaware of their condition. Acute kidney injury (AKI) is defined as an abrupt or rapid decline in renal filtration function. Examining modifiable risk measures could add important insights to management in patients with AKI. Vitamin D dysfunction may influence common acute complications such as organ failure, leading to worse outcomes. Vitamin D deficiency is associated with inflammatory disease and smoking is a well‐known risk factor for inflammation. The study examined the associations between vitamin D and cigarette smoking in patients with AKI. A single‐center prospective cohort study was conducted among 60 AKI patients, aged 18 years and older, hospitalized at Staten Island University Hospital. Calcifediol [25(OH)D] and calcitriol [1,25(OH)D] serum levels were determined using LC‐MS/MS method. Smoking status was self‐reported. Linear regressions to evaluate the associations yield the following: 25(OH)D has a significant association with smoking (p = 0.008). Results revealed that smokers have approximately 50% less 25(OH)D levels as compared to non‐smokers. Prospective studies to determine cotinine levels to predict smoking status in patients with AKI are recommended to further verify these findings.

Support or Funding Information

This research project is funded by The Professional Staff Congress‐City University of New York (PSC‐CUNY) Research Award # 67543‐00 45.
Are more nutritious products available in the US food supply, and are they consumed more frequently?
Authors: Gressier Mathilde , Vlassopoulos Antonis , Masset Gabriel , Drewnowski Adam
Published: November 2023

Introduction

Reformulation of the food supply has been identified as one of the way to tackle food related chronic diseases (along with others e.g. nutrition education or promotion of physical activity). Several food producers use nutrient profiling systems to guide their reformulation strategy. An example is the Nestlé Nutritional Profiling System (NNPS), a category‐specific system, whose outcome is dichotomous to distinguish more nutritious options within food categories.

The objective of this study was to assess the proportion of products meeting the NNPS standards in the food supply, and their respective frequency of consumption.

Methods

Food intakes of US adults (aged 18y+) were retrieved from the first 24h recall of the National Health and Nutrition Examination Survey 2011–12. All consumed food and beverage products amenable for reformulation were assessed against the NNPS. The proportion of products compliant with the system was evaluated (i) as available in the food supply (i.e. among the food composition dataset, FNDDS 2011–12), and (ii) weighted by frequency of consumptions. The foods were then grouped using the USDA Major Commodity groups. The analysis was further stratified by Income‐to‐Poverty Ratio.

Results

Among the 4110 food items consumed by the study population, 3111 could be assessed against the NNPS. The proportion of products meeting the NNPS standards in the food supply was 39.2%; whereas it was 49.6% when weighted by consumption. Within food groups, the consumption of more nutritious options (i.e. compliant with NNPS) did not appear to be associated with their availability (Figure). In dairy products, grain‐based products, sweets and beverages, and processed fruits, more nutritious options were more likely to be consumed. The opposite was observed in the other food groups. Further, there was a positive association between Income‐to‐Poverty Ratio and the consumption of more nutritious sweets and beverages and eggs products. The opposite was observed for legumes and processed fruits.

Conclusion

Reformulation of the food supply can be an effective way to enhance consumers' intakes only if the resulting products are actually consumed. This study showed that for each major food group, products meeting the NNPS standards existed and were consumed, but with a great heterogeneity between groups. For some groups there was a selection towards products with a better nutrient profile, meaning that the reformulation of these categories may be more easily accepted by consumers. For categories in which consumption of foods with a better profile was low, more efforts should be put on the sensory characteristics of reformulated products.

Support or Funding Information

This study was funded by Nestec SA.
Milk oligosaccharides decrease pathogen associated molecular pattern induced inflammation in intestinal epithelial cells
Authors: Henrick Bethany Michele , Erhlich Amy E , Vang Wendie , Cohen Josh , German J Bruce , Mills David A , Barile Daniela , Raybould Helen E
Published: November 2023

Glycans are a distinguishing constituent of milk; oligosaccharides are the third largest component of milk but are not digestible by the infant and have no direct nutritional benefit. A major benefit of these complex sugars is to establish a healthy commensal microbiome in infants. However, given they are found in urine and blood and absorbed through intestinal epithelial cells (IECs), we hypothesized they function as innate immune modulators in the gut. Using the IEC line, Caco‐2, we investigated the direct effects of human milk oligosaccharides (HMO) on the intestinal epithelium. HMO at physiological concentrations (5–20 mg/mL) induced an immediate and significant decrease in COX‐2 (p=0.0052) expression, but did not alter TLR2 or TLR4 expression. Inulin, a plant based oligosaccharide had no significant effect on COX‐2 expression. Similarly, LPS‐induced production of the proinflammatory cytokine IL‐8 was significantly reduced when cells were incubated with HMO overnight. Exposure of cells to TLR2 or TLR4 ligands (LPS or Pam3CSK4) increased IL‐8 production (p<0.0001; p<0.0001, respectively), and significantly decreased LPS or Pam3CSK4 induced inflammation in a dose‐dependent manner by pretreatment with physiological range HMO (1.25, 5, 20 mg/mL; p=0.0032, p=0.0045, p=0.0007; p=0.0181, p=0.0309, p=0.0335, respectively). The modulating effect of individual oligosaccharides at physiological concentrations was determined. Lactoneotetraose, but not 2′ fucosyllactose (FL) or 3′FL, significantly decreased (p=0.0028) IL‐8 production in response to LPS. Conversely, Lacto‐N‐neotetraose (LNnT) significantly increased (p=0.0074) LPS‐induced IL‐8 production suggesting that IECs exposed to LnNT alone may be more susceptible to PAMP‐induced inflammation. Taken together, these data indicate that HMO may have a signaling ability that reprograms the epithelial cell monolayer in a way that makes it less susceptible to pathogen‐induced inflammation. HMO may serve as innate immune factors that directly provide a protective reprogramming effect to IECs.

Support or Funding Information

National Institute of Health
13C β‐Carotene stability during digestion in healthy humans
Authors: Kopec Rachel E. , Caris‐Veyrat Catherine , Nowicki Marion , Gleize Beatrice , Desmarchelier Charles , Borel Patrick
Published: November 2023

Non‐provitamin A metabolites of β‐carotene may be produced after the consumption of β‐carotene, but to date, no study has investigated their formation during digestion. Nine healthy men were recruited in total, with seven men consuming a liquid test meal containing 20 mg of 13C β‐Carotene, and two men consuming a control meal. Gastric and duodenal samples were taken postprandially over 5 hours using a nasoduodenal tube, while plasma samples, from which the triglyceride‐rich lipoprotein (TRL) fraction containing chylomicrons was isolated, were taken over 7 hours. An LC‐MS/MS method was developed to identify and quantitate 13C β‐apo‐carotenals, 13C β‐apo‐carotenols, and 13C β‐apo‐carotenoic acids in gastric and duodenal digesta, plasma, and TRL samples using mixtures of standards. Gastric and duodenal digesta 13C β‐apo‐carotenal concentrations (including13C retinal) increased over 5 hours relative to 13C β‐carotene, with the exception of 13C β‐apo‐8′‐carotenal which peaked at 2 hours. 13C β‐apo‐carotenols and 13C β‐apo‐carotenoic acids were not observed in the digesta samples. 13C retinyl esters and 13C β‐carotene were observed in the whole plasma and in the TRL fraction, and 13C retinol was observed in whole plasma. However, no non‐vitamin A 13C β‐apo‐carotenals, 13C β‐apo‐carotenols, or 13C β‐apo‐carotenoic acids were observed in the plasma or TRL samples. Taken together, our data suggests that the conditions of digestion favor β‐apo‐carotenal formation. However, it is not clear if these β‐apo‐carotenals are absorbed at levels too low for our limit of detection, or whether they are not absorbed at all. The biological effect(s) of these compounds in the digestive tract remains to be elucidated.

Support or Funding Information

This work was supported by a grant from the PACA (Provence‐Alpes‐Côte d'Azur) region. Rachel Kopec received support from the European Union, in the framework of the Marie‐Curie FP7 COFUND People Programme, through the award of an AgreenSkills fellowship (under grant agreement n° 267196), as well as the Foundation Olga Triballat.
Cytochrome P450 4A14 and Vascular Restenosis
Authors: Zhang Xiaoyan , Ye Shiqi , Guan Youfei
Published: November 2023

Background

Restenosis after angioplasty remains a major clinical problem. Cytochrome P450 4A (CYP4A) plays an important role in vascular homeostasis. The present study aims to clarify the role and mechanism of CYP4A14 in the pathogenesis and development of restenosis. These would lead to new strategies for effective prevention and treatment for restenosis.

Methods and Results

Wire‐mediated femoral artery injury was used to induce restenosis. Immunohistochemical staining revealed that the levels of CYP4A14 protein were significantly elevated in the tunica media and neointima layer after vascular injury for 28 days. The levels of CYP4A14 mRNA and protein were markedly induced in mouse primary cultured VSMCs after stimulated with fetal bovine serum (FBS) or PDGF‐BB for 24 hours. To further determine the role of CYP4A14 in the restenosis, femoral artery injury was induced in CYP4A14−/− and CYP4A14+/+ mice. Neointimal hyperplasia and proliferation of vascular smooth muscle cells (VSMCs) were markedly attenuated in the injured arteries of the CYP4A14−/− mice compared with CYP4A14+/+ mice (P<0.05). Furthermore, adenovirus‐mediated overexpression of CYP4A14 substantially accelerated the proliferation and migration of cultured VSMCs. Mechanistic study revealed that overexpression of CYP4A14 in VSMCs activated the PI3K‐Akt/p27 Kip1/cyclinD1 and MAPK pathways, which induced cell cycle shifts from the G1 to S phase.

Conclusion

CYP4A14 promotes the proliferation and migration of VSMCs after vascular injury, leading to accelerated neointima formation and eventually restenosis. The underlying mechanism may depend on the activation of the PI3K‐Akt/p27 Kip1/cyclinD1 and/or MAPK signal pathways. CYP4A14 may represent a potential therapeutic target for the treatment of PTCA.

Support or Funding Information

81570636/81390351 from the National Nature Science Foundation; Shenzhen Peacock Program (KQTD20140630100746562); JCY20140418095735626 From the committee of science and technology innovation of shenzhen
Increased Fibrosis and Ductular Reaction in Liver of Offspring Exposed to Maternal High Fat Diet
Authors: Thompson Michael D , Cismowski Mary J , Rogers Lynette K , Brigstock David R
Published: November 2023

Background

The Developmental Origins of Health and Disease hypothesis states that a poor nutritional environment in utero can increase the risk of developing chronic diseases including non‐alcoholic fatty liver disease (NAFLD). Due to the high prevalence of maternal obesity, maternal high fat diet (HFD) is one nutritional exposure of significant concern. Animal models of maternal HFD exposure show that offspring have an increased risk for NAFLD. Whether this impacts disease progression is not clear, but a better understanding could help explain why some patients with NAFLD are prone to develop progressive disease and provide targets for preventative therapy. The goal of the current study was to determine the effect of maternal HFD exposure in utero and during lactation on offspring liver histopathology with a specific focus on fibrosis.

Methods

Female C57Bl6 mice were fed a control diet (CD, 10% kcal from fat) or HFD (60% kcal from fat) for 8 weeks and bred with lean males. Dams were continued on the same diet with offspring maintained on either CD or HFD for 12 weeks. Histology, gene, and protein expression analyses of liver from offspring were performed.

Results

Offspring exposed to perinatal HFD and then placed on HFD (HFD/HFD) at weaning showed more extensive hepatosteatosis than offspring which were placed on HFD after perinatal CD. Offspring exposed to perinatal HFD and then placed on CD (HFD/CD) for 12 weeks develop steatosis and significant pericellular fibrosis in the liver. Increased alpha‐smooth muscle actin positive stellate cells and cytokeratin‐19/beta‐catenin positive ductular reaction are present throughout the liver parenchyma in HFD/CD offspring. HFD/CD offspring liver also exhibit significant hepatocyte proliferation despite overall liver weight being smaller. No difference in F4/80 positive macrophages was observed between each group.

Conclusions

Perinatal HFD exposure induces pathologic changes in liver of offspring that persist into adulthood and impact the response to dietary exposure including worsening steatosis and fibrosis. This indicates that exposure to perinatal HFD promotes more rapid disease progression of NAFLD in the adult offspring with a sustained fibrotic phenotype and ductular reaction even in the absence of post‐natal HFD exposure.

Support or Funding Information

Nationwide Children's Hospital Research Institute
Prolonged Sensory Loss Results in Altered Cortico‐cortical Connectivity Patterns
Authors: Voss Patrice
Published: November 2023

Congenital sensory deprivation results in significant functional and anatomical brain changes. I will discuss how both auditory and visual deprivation specifically lead to significant changes in corticocortical connectivity patterns between the deafferented primary sensory area and the rest of the brain. Using covariance analyses of cortical morphology in human individuals, I will show that early auditory deprivation significantly alters connectivity patterns between auditory and multisensory areas. In contrast, a somewhat different pattern emerges in the blind, where early visual deprivation results in a significant reduction of connectivity between primary visual cortex and areas of the dorsal visual stream responsible for oculomotor control. Furthermore, the strength of the connectivity between visual and multimodal parietal areas in the blind is predictive of auditory perceptual abilities. These findings constitute the first evidence linking altered anatomical covariance to early sensory deprivation.
A 50 Year Review and Meta‐analysis of Anatomy Laboratory Pedagogies
Authors: Wilson Adam , Miller Corinne , Klein Barbie , Taylor Melissa , Goodwin Michael , Boyle Eve , Brown Kirsten , Hoppe Chantal , Lazarus Michelle
Published: November 2023

The debate regarding effective anatomy teaching methods is ongoing and highly controversial. Previously, Winkelmann(2007) attempted to address this discussion through a literature review that compared the efficacy of new anatomy laboratory pedagogies to traditional dissection approaches. This review, however, had considerable methodological weaknesses that undermined the significance and generalizability of its findings and raised further questions about the influence of educational interventions on student performance. One question left unanswered was “What impact, if any, does dissection have on learning anatomy within formal, informal, and hidden curricula?” To address this question, a meta‐analysis was undertaken to objectively, and more conclusively, summarize the effectiveness of instructional laboratory approaches used in anatomy education.

Studies published between January 1965 and December 2015 were searched through five databases. Titles and abstracts of the retrieved records were screened using eligibility criteria to determine their appropriateness for study inclusion. Both numerical and qualitative data were extracted for analysis. A summary effect size was estimated to determine the effects of laboratory pedagogies on learner performance and a thematic review was performed to understand the perceptions of key stakeholders.

Of the 3,045 records screened, 327 underwent full‐text review. Twenty‐six studies, comprising a total of 7,689 participants, were viable to include in the effect size calculations. The meta‐analysis detected no effect (standardized mean difference = −0.02; 95% CI=−0.15–0.11; p=0.43) on learner performance. Across studies, student performance on knowledge examinations was found to be equivalent regardless of being exposed to either dissection or another laboratory instructional strategy. This was true of every comparison investigated (i.e., dissection vs prosection, dissection vs digital media, dissection vs models/modeling, and dissection vs hybrid). The total heterogeneity was moderate (p<0.001; I2=82%) indicating sizable variation among the included studies.

In the context of assessing only knowledge gains, this meta‐analysis revealed that the instructional approach of dissection is no better, and no worse, than alternative instructional modalities used in laboratory settings. As identified throughout the systematic review, many authors argued that donor dissection teaches essential ancillary skills such as professional identity, clinical communication and leadership, and introduces students to concepts of death and dying. Few studies, however, have evaluated whether similar themes emerge as a consequence of anatomy teaching in general or whether some of these skills are best imparted through active dissection.
The Long‐Term Effects of an Interprofessional Education Dissection Course on Healthcare Professional Students
Authors: Zheng Eric , Palombella Andrew , Salfi Jenn , Bayer Ilana , Wainman Bruce
Published: November 2023

An intensive interprofessional gross anatomy dissection course was created in 2009 to facilitate interprofessional education (IPE) at McMaster University. First year students from Medicine, Nursing, Midwifery, Physician Assistant, Occupational Therapy, and Physiotherapy programs were randomly assigned into four interprofessional teams for this 10‐week course. Previously, data was collected from 2011 to 2016 using a before/after design to measure differences in attitudes and perceptions towards IPE and collaboration using the revised Readiness for Interprofessional Learning Scale (RIPLS) and Interdisciplinary Education Perception Scale (IEPS), while focus group data elaborated on the student experience with the course. Pre‐ and post‐matched data revealed significant improvements in positive professional identity, competency and autonomy, role clarity, and attitudes toward other health professions. Qualitative analysis of intraprofessional focus group interviews revealed meaningful improvements in a number of areas including learning anatomy, role clarity, and attitudes towards other health professions.

The purpose of this study is to assess the long‐term effects of our IPE gross anatomy dissection course on past participants by quantitatively and qualitatively evaluating how their attitudes and perceptions have changed now that they have started working with other health care professionals outside of the IPE course setting. Past students were contacted via email and asked to fill out a follow‐up questionnaire consisting of a modified RIPLS and open‐ended questions to measure both quantitative and qualitative change, respectively. Thirty‐four past participants who have clinical experience working in an interprofessional setting or who are working in the healthcare field responded to the survey. Post‐course and follow‐up subscale score mean differences were analyzed using the Wilcoxon Signed‐Rank Test. Quantitative analysis revealed a significant decrease in teamwork and collaboration, and positive professional identity, but a significant improvement in their understanding of roles and responsibilities compared to their time in the course. Qualitative analysis of open‐ended questions revealed a number of themes including development of interprofessional competencies, anatomy learning through dissection, relationship building, and appreciation of the gross anatomy dissection course. Our results indicate that the IPE experience in anatomy was highly valued by the students and that past participants maintain a clear understanding of their scope of practice, but the reality of clinical practice may have eroded gains made in the program.
Formative Assessments in Anatomy: Promoting Self‐Directed Learning with Self‐Assessment
Authors: Lee Vaughan , Higgins Katie , Schneider Brandt
Published: November 2023

In the past decade, reduced curricular time, decreasing numbers of anatomy faculty, and the demand for self‐directed learning activities have been major drivers in anatomical curriculum redesign. At TTUHSC we have developed a battery of formative assessments to improve the efficiency of anatomical education and promote metacognition (thinking about how we learn). Specifically, in the 2016–2017 Clinically Oriented Anatomy course at TTUHSC/SOM we instituted daily student audience response questions in lectures, weekly quizzes, unit practice written exams, unit practice practical exams, and group and individual practical quizzes following peer‐taught laboratory sessions. Preliminary evaluation of this initiative reveals: 1) Formative assessments were used by a majority of the class, (written, 85–93%; practical 70–74%); 2) Summative exam scores were 8–10 points higher than their formative counterparts suggesting that students successfully used these educational tools and self‐directed learning to improve their anatomical comprehension; and 3) Tracking formative performance may identify academically at risk students in time for successful interventions. Student evaluation of the formative written and practical assessments was very favorable, 4.26 and 3.7 (5pt Likert), respectively. Detailed analyses of preliminary data, outcomes, limitations and future plans will be presented.

Support or Funding Information

This project was funded by the TTUHSC/SOM.
Visualizing the Anatomy and Position of the Larynx in Balaenopterid Whales
Authors: Smith Christopher M. , Tang Cheuk Ying , Ng Johnny , Reidenberg Joy S.
Published: November 2023

The anatomy of large cetaceans, such as Balaenopterid whales, is extremely difficult to understand. This is due to physical constraints, limited time for field dissection, and rarity of specimens. In particular, the laryngeal structure and position is extremely hard to understand three dimensionally, as they exhibit a complexly integrated morphology involving bone, muscle, cartilage, and soft tissue air sacs. In previous studies, the muscular anatomy and associated position and movements of the larynx have only been schematically diagrammed. Our study reconstructs the surrounding spaces, positions, and ranges of laryngeal movement by applying muscle volumes and vectors of trajectories between points on a reconstructed 3‐D model of skull, hyoid, and laryngeal cartilages. This gives us a better understanding of how these whales may position and use the laryngeal apparatus in a variety of functions (vocalization, bubble making, etc.). Laryngeal structure and position were reconstructed using a variety of approaches, including dissections of one infant minke whale (Balaenoptera acutorostrata) head, and two adult larynges of a fin whale (Balaenoptera physalus) and a humpback whale (Balaenoptera physalus). CT and MR imaging were obtained on all three specimens. Additional osteological data was obtained from an infant minke whale skull and one publicly available humpback whale skeleton. Photogrammetry and CT reconstruction software were used to create 3‐D digital reconstructions of the skulls. Photogrammetry was also used to document shape, articulations, and positions of cartilage structures during dissection. These data culminate in the construction of an animated 3‐D model that elucidates the hard and soft tissue anatomy, relative positions of structures and spaces, and movements of the laryngeal apparatus of a generic Balaenopterid whale. Using this model, we can elucidate both intrinsic and extrinsic movements of the larynx. Our results indicate that intrinsic cartilage movement is restricted primarily to the cricoarytenoid synovial joint, although the thyroepiglottic fibrous joint also shows limited movement. Our model enhances understanding of the laryngeal movements supporting upper respiratory function in Balaenopterid whales.
Investigating the roles of Fascin in collective cell migration using Drosophila border cell migration
Authors: Lamb Maureen , Tootle Tina
Published: November 2023

Fascin is an actin bundling protein that regulates dynamics of cytoskeletal structures, such as filopodia and invadopodia, during cell migration. Importantly, Fascin is known to mediate retinal formation and axonal growth during development by promoting cell migration. In addition, recent research has demonstrated Fascin plays a significant role in cancer invasion and metastasis. However, additional roles of Fascin, including regulation of microtubules, interaction with mechanotransduction machinery, and nuclear localization, have been uncovered that may contribute to its roles in cellular migration. To study the role of Fascin in invasive, collective cellular migration in vivo we use Drosophila border cells as a model. Border cell migration occurs during Stage 9 of oogenesis in which a specified group of follicular epithelial cells cluster together and migrate posteriorly in between the nurse cells to the nurse cell ‐ oocyte border. This process is crucial for oocyte development since aberrant or delayed border cell migration leads to female sterility. While fascin mutants have been highly studied during Drosophila oogenesis, they have not been reported to have border cell migration defects. However, Fascin is highly expressed in the border cells and fascin‐null flies are sterile. These and other findings led us to hypothesize that Fascin plays a critical role in promoting border cell migration during oogenesis. Contrary to prior reports, we find that follicles from young fascin‐null flies display a significant delay in border cell migration. Cell‐specific knockdown studies suggest that Fascin is required within the somatic cells or specifically the border cells to mediate migration. Together these findings implicate a role for Fascin in collective cell migration in vivo during Drosophila oogenesis. Furthermore, these findings provide a system to investigate the actin bundling‐independent functions of Fascin in invasive cellular migration. Overall, this research will lead to a more complete understanding of the function of Fascin in developmental cell migrations and cancer metastasis.

Support or Funding Information

National Institutes of Health: R01GM116885
FoxO6 Regulates Hippo Signaling to Control Face Morphology
Authors: Cao Huojun , Sun Zhao , de Fontoura Clarissa , Holton Nathan , Bidlack Felicitas , Martin James , Moreno‐Uribe Lina , Amendt Brad
Published: November 2023

Hippo signaling controls tissue growth and organ size but, its role in development of the craniofacial structures is unknown. We demonstrate that tissue specific Hippo signaling regulates growth of the face and is a crucial component in determining human facial characteristics. We have identified the transcriptional factor FoxO6 as an activator of Hippo signaling with specific expression in craniofacial tissues. FoxO6 loss‐of‐function mice undergo expansion of the face and skull, enlargement of the mandible and maxilla and lengthening of the incisors associated with increases in cell proliferation. FoxO6 activates Lats1/2 expression, thereby increasing Yap phosphorylation to control Hippo signaling. A phenotype‐genotype correlation test identified significant associations (p<0.001) with three FOXO6 human single nucleotide polymorphisms in Caucasian adults with dento‐skeletal bite problems ranging from retrognathism to prognathism of both jaws. One mutation creates a new cFOS binding element in the FOXO6 5′flanking region that increases FOXO6 expression. This mutation is associated with bimaxillary retrusion and correlates with the role of FOXO6 and Hippo signaling. FoxO6−/− mice also exhibited decreases in the expression of Shh and Runx2, suggesting that these factors are linked to Hippo signaling. Together, these results identify a FoxO6‐Hippo regulatory pathway that controls skull growth, odontogenesis and face morphology. These data suggest that human FOXO6 mutations explain differences in the human face form.
Modular 3D dense surface analysis and GWAS reveal localized genetic effects on human facial morphology involving multiple novel loci
Authors: Weinberg Seth M , Lee Myoung Keun , Leslie Elizabeth J , Orlova Ekaterina , Carlson Jenna C , Roosenboom Jasmien , Mattern Brooke C , Liebowitz Corey R , White Julie D , Zaidi Arslan , Hernandez Diego , Gonzalez Tomas , Pearson Laurel N , Sero Dzemila , Li Jiarui , Feingold Eleanor , Marazita Mary L , Shaffer John R , Wysocka Joanna , Shriver Mark D , Claes Peter
Published: November 2023

Many aspects of human facial morphology are under strong genetic control. Several GWASs of normal facial variation have been completed, with each identifying a handful of significant findings. However, a large number of genes are expected to influence facial morphology, suggesting that a different approach is needed. We performed a GWAS on 2329 individuals of European descent with available 3D facial scans. To derive phenotypes, we established a dense correspondence among the 3D facial surfaces (~10,000 pseudolandmarks) and applied a novel hierarchical modular facial decomposition approach. Facial modules were identified based on pair‐wise 3D correlations of spatially‐dense landmark configurations in a hierarchical spectral clustering approach. This resulted in a decomposition of the 3D facial surface morphology into 63 distinct modules. Shape variation in each of the modules was captured separately using principal component (PC) analysis. SNPs were tested for association with modular shape PCs via multivariate canonical correlation analysis, controlling for sex, age, height, weight, and population stratification. In total, we identified 41 genome‐wide significant (5×10E‐8) loci associated with at least one facial module. Most of the associated loci were novel, but contained one or more plausible craniofacial candidate genes based on evidence from mouse models and/or syndromes (TBX15, SOX9, PAX1). While many of the signals were associated with a single highly localized facial module (e.g. tip of the nose), others involved multiple hierarchically related modules (e.g. all parts of the nose). Bioinformatics analysis of the variants around our GWAS peaks revealed evidence of enrichment for active cranial neural crest cell enhancers (p<0.006), suggesting an important role during craniofacial development. To date, we have replicated 15 of our discovery GWAS signals in an independent cohort of 1978 individuals. Finally, we tested 27 previously reported SNPs from the GWAS literature, with 26 replicating at p≤0.05. In multiple instances we were able to confirm the same previously reported phenotype‐genotype relationships, providing additional validation of the methodology. In conclusion, using highly innovative and comprehensive facial phenotyping methods, we have identified a large number of novel and replicated loci associated with a range of facial features, involving both highly localized effects and larger more global effects.

Support or Funding Information

U01‐DE020078; U01‐DE020057; R01‐DE016148
From the top of your head: phenotypic integration in the head and neck
Authors: Villamil Catalina Isabel
Published: November 2023

Phenotypic integration is a powerful way of understanding morphological evolution. However, it remains unclear how integration itself evolves. I discuss here a variety of factors shaping phenotypic integration of the head and neck in a wide range of mammalian taxa.

The head serves as a site for many important functions and is integrated in complex ways. Across mammals (marsupials=231, carnivores=100, primates=473) the facial skeleton is integrated with the basicranium, regardless of the factors influencing the morphology of the skull. Magnitudes of integration (MI) within the basicranium (carnivores=348, primates=1159) are strongly linked to relative brain size and to the height and breadth of the cranial vault, such that taxa with large brain sizes and relatively broad and tall cranial vaults have lower MI. When the brain can grow upwards and outwards, it may not require such tightly matched basicranial anatomy to support it. Facial size also influences MI, such that taxa with large faces tend to have higher MI. The mechanical requirements of supporting a relatively large face may serve to functionally constrain the basicranium. However, the interplay of facial and brain morphology also plays a role in these relationships. The age divergence or appearance of specific taxa may play a small role in MI as well. Although smaller taxa are better able to respond to selection generally, body size does not specifically affect MI.

The head is also tightly integrated with the neck. Patterns and magnitudes of integration in the head and neck in hominoids (Homo=120, Pan=112, Hylobates=92) largely follow those hypothesized based on Hox expression patterns in mice. Transitional vertebrae C2 and C7 differ markedly in MI from all others. Locomotor and postural behavior appears to have no influence on these relationships. Instead, aspects of facial anatomy are likely ultimately driving cervical vertebral morphology.

My results support the contention that phenotypic integration patterns match underlying genetic developmental relationships. Strong natural selection favoring particular anatomical features, such as relatively large brains, may alter patterns of phenotypic integration by breaking down existing developmental patterns, especially those that are not tightly constrained. However, cervical vertebrae may be strongly buffered from environmental pressures. The extent to which external environmental influences act during ontogeny on other features, such as the face, has yet to be examined. Knowledge of such interactions will serve as an important complement to studies of phenotypic integration.

Support or Funding Information

This work was funded by the Wenner‐Gren Foundation and New York University.
Integration and coevolution of the mammalian skeleton in “real time”: the case of the Longshanks mouse
Authors: Rolian Campbell
Published: November 2023

Since the publication of Olson and Miller's seminal book “Morphological Integration” in 1958, there have been over 200 studies on integration, modularity and evolvability of the mammalian skeletal and dental systems. These studies have yielded fundamental insights into the role of genetic, developmental and functional constraints on the evolutionary history, and evolutionary potential, of complex skeletal traits in diverse mammalian lineages. Yet integration and evolvability studies in skeletal systems suffer from two important limitations. First, they are by nature post‐hoc, i.e., they rely on observed patterns of covariation among traits to reconstruct the (often deep) history of (co)evolution in skeletal traits, and/or to identify the genetic, developmental and functional sources of covariation that have influenced this history. Second, and related, evolvability studies are theoretical, relying on the multivariate breeder's equation to predict the potential response of more or less integrated skeletal phenotypes to selection. Since 2010, my lab has been selectively breeding mice for increases in tibia length relative to body mass. This long‐term selection experiment provides an opportunity to validate empirically how the magnitude and pattern of covariation among skeletal traits (i.e., integration) impacts “real time” evolutionary change in the target of selection, as well as in genetically and developmentally correlated traits. Here, I use an evolutionary quantitative genetics framework and a large multi‐generational dataset of full body micro‐CT scans of the selectively bred mice (Longshanks) and random‐bred mice to: (1) quantify correlated evolution of skeletal traits in the Longshanks postcranium and cranium, and (2) determine how the magnitude and pattern of integration across the skeleton has evolved in response to strong selection on a single trait. Results show that while tibia length has changed the most, other skeletal traits (e.g. tibia cross‐sectional shape, other fore‐ and hind limb bone lengths) have also responded to selection, though to a lesser extent (i.e., allometrically). Interestingly, skull shape in Longshanks has changed significantly. The types of changes observed over ontogeny suggest the involvement of both local and systemic factors underlying mechanisms of endochondral ossification in the limbs and cranial base. Finally, the magnitude of covariation among postcranial skeletal traits increased over generations, which suggests that unidirectional selection on a single skeletal trait in Longshanks has actually reduced the evolvability of its skeleton overall. This study in “real time” vertebrate evolution thus validates and complements the insights gleaned from classical, yet largely theoretical, integration, modularity and evolvability in the mammalian skeleton.

Support or Funding Information

This work was supported by NSERC Discovery Grant 4181932, and by the Faculty of Veterinary Medicine at the University of Calgary.
Getting to the Heart of Anatomical Sciences Education
Authors: Pawlina Wojciech
Published: November 2023

In modern medical curricula, anatomists share responsibility for training the next generation of health care providers. As expectations for medical professionals continue to evolve, anatomy teachers are strategically positioned to support students' acquisition of the core anatomy knowledge together with skills and attitudes necessary to produce caring and effective health care providers. Anatomists must ensure that learners not only possess the necessary breath of knowledge in anatomical sciences but also skills such as leadership, teamwork, communication and professionalism among others. To attain this, anatomy curricula need to follow a path of authentic learning in which students are expected to exercise higher levels of thinking and clinical reasoning through discovery and inquiry. Learning‐by‐doing is the most effective learning strategy not only in the laboratory and interactive classroom, but also in the real‐life environment of imaging technologies. To ensure the success of this strategy, students must receive frequent performance feedback to advance their learning and capability for improvement. When anatomists embrace the maxim “the needs of the patient come first,” the learning becomes as much social as cognitive, as much solid as intangible, and becomes entwined with judgment and exploration just as it is in the real clinical world.