bluuebunny/crossref_metadata_2025_split huggingface dataset:
Augmented Adipocyte Browning and Mitochondrial Function in Periadrenal Fat but not Subcutaneous Fat in Pheochromocytoma Patients
Authors: Davies Graeme Robert , Vergnes Laurent , Yeh Michael , Harari Avital , Livhits Masha , Huang Jiaoti , Symonds Michael , Reue Karen , Sacks Harold 
Published: November 2023

Background and aimsThis study aimed to characterize browning in periadrenal (pADR) and subcutaneous adipose tissue (SAT) depots in humans with pheochromocytomaMethodspADR and abdominal SAT samples were collected from patients undergoing adrenalectomy for aldosterone, cortisol‐secreting and non‐functioning neoplasms for the study control group (n=23) and patients with benign unilateral pheochromocytoma (n=15). Plasma catecholamine levels were measured by HPLC. The presence of unilocular or multilocular adipocytes was assessed by H&E staining and brightfield microscopy. UCP1 abundance was measured at the gene expression level by qPCR and protein by immunohistochemistry and western blotting. Mitochondria were isolated from the tissue samples and respiration analysed on an XF24 Seahorse Extracellular Flux Analyzer. Whole transcriptome analysis was carried out in pADR fat by Illumina microarray.Results60% (9/15) of the pheo group showed browning of periadrenal fat recorded by the presence of multilocular adipocytes. Interestingly, those patients with browning in pADR fat had the highest levels of plasma catecholamines. Control pADR fat samples showed no multilocular adipocytes. No patients in either control or pheo groups showed browning of SAT. This was corroborated with UCP1 protein found in multilocular pADR fat in pheos but not in SAT. Pheo patients with multilocular pADR fat had increased mitochondrial respiration in pADR compared to controls or pheos with unilocular adipocytes. Specifically, we detected higher complex 1 to 4 respiration of the electron transport chain, while uncoupled respiration was higher. No difference was observed in respiration from SAT mitochondria. No increase was seen in plasma ANP, BNP or FGF21 in pheo patients compared to controls. Finally, microarray analysis in pADR revealed a distinct gene expression signature in pheo patients with multilocular adipocytes, characterized by enhanced expression of genes required for fatty acid oxidation and mitochondrial respiration.ConclusionsBrowning of pADR occurs in some patients with pheochromocytoma but is not observed in SAT. This browning may be driven by elevated plasma nor‐epinephrine in these subjects. Our data demonstrates for the first time that the multilocular pADR adipose tissue observed in pheo patients has increased mitochondrial respiration, suggesting potentially significant effects on energy metabolism in vivo.Support or Funding InformationFunded by the Leducq Foundation and the Cardiometabolic Research Foundation, Los Angeles
Recommended anthropometric cut‐offs for population screening of diabetes and prediabetes need to be evaluated in resource‐limited settings
Authors: Yu Elaine A , Finkelstein Julia L. , Bonam Wesley , Glesby Marshall J. , Brannon Patsy M. , Mehta Saurabh 
Published: November 2023

BackgroundGlobally, waist circumference (WC) and body mass index (BMI) are widely used for population screening to predict disease risk, including for diabetes. We examined the association of anthropometric measurements with diabetes and pre‐diabetes in a cohort where the majority of participants would be classified as low risk based on either BMI or WC.MethodsStudy participants were recruited from an outpatient clinic in rural South India (n=297). Concentrations of glycosylated hemoglobin (HbA1c) were measured by high‐performance liquid chromatography. Diabetes and pre‐diabetes were defined as HbA1c ≥6.5% and ≥5.7% to <6.5%, respectively. Waist circumference was measured by non‐stretch measuring tape to the nearest 0.1 cm by study staff. Whole and segmental body composition were measured by bioelectrical impedance analysis (8 electrode; Tanita BC 418 MA). Binomial regressions were used to assess the associations between diabetes (and pre‐diabetes), and anthropometric indicators (WC, BMI). Restricted cubic splines were used to evaluate non‐linearity.ResultsMean waist circumference was 73.2 cm (SD: 11.3) among males, and 69.7 cm (SD 12.1) among females. Among male study participants, more than 90% had a waist circumference < 90 cm; among females, 80% had a waist circumference <80 cm. Mean BMI was 19.2 kg/m2 (SD 4.1) among men, and 20.4 kg/m2 (SD 5.4) among women. Among males, 50.0% had BMI <18.5 kg/m2, and over 90% had BMI <25.0 kg/m2. Among females, nearly 50% of study participants had BMI <18.5 kg/m2, and more than 80% had BMI <25.0 kg/m2. Study participants with waist circumference in the two lowest tertiles had a lower risk of diabetes (Tertile 1 vs 3: RR 0.40 [95% CI 0.20–0.81]; Tertile 2 vs 3: RR 0.33 [95% CI: 0.15–0.73]), compared to those in the highest tertile (p=0.004). Waist circumference was not associated with pre‐diabetes; BMI was not associated with either diabetes or pre‐diabetes.ConclusionBased on widely used cutoffs of WC and BMI (World Health Organization, International Diabetes Federation for South Asia), nearly 90% of study participants would be considered to be at low or minimal risk for diabetes. However 13% of study participants had diabetes, and 21% had pre‐diabetes. Waist circumference was still associated with increased risk of diabetes among study participants. These findings emphasize the need for the development of population‐specific cutoffs for waist circumference in diabetes screening.Support or Funding InformationCornell University
Vitamin A Supplementation Only Transiently Increases Retinol Concentrations in Extrahepatic Organs of Neonatal Rats Raised under Vitamin A‐Marginal Conditions
Authors: Urbanek J. Kalina , Tan Libo , Green Michael H. , Ross A. Catharine 
Published: November 2023

Vitamin A (VA, retinol) supplementation is recommended for children > 6 mo old in countries with high rates of malnutrition, based on the positive results of clinical trials conducted in the 1990s. However, the results of studies on the benefits of supplementing neonates < 5 mo old are inconsistent. The objective of this study was to determine the distribution of VA in bodies of neonatal rats raised under VA‐marginal conditions (control group) and the effect of VA supplementation on the concentration and mass of retinol in the body, including plasma, liver, and lungs, as well as several understudied extrahepatic organs, such as the brain, brown adipose tissue, and skin.MethodsNeonatal rats (n = 103), nursed by mothers fed a VA‐marginal diet, were randomized and treated on postnatal day 4 (P4) with an oral dose of either VA (6 μg retinyl palmitate/g body weight) or canola oil as control. Subsequently, pups (n = 4/group/time) were euthanized at 13 time points from 30 min to 24 d after dosing and the following organs were collected: plasma, liver, lungs, kidneys, stomach, intestine, brain, white and brown adipose tissue, skin, and the remaining carcass. The total retinol concentration and mass in each organ was measured with ultra‐performance liquid chromatography.ResultsControl pups maintained a marginal plasma VA concentration, while the VA concentration in the liver was deficient. Despite its deficient status, the liver contained most (~77%) of the whole‐body VA mass, similarly as in previous studies of adult rats with an adequate liver VA concentration. White adipose tissue, which was nearly absent prior to P12, contained only ~1% of the whole‐body VA mass, compared to 10–20% reported in adult rats. The remaining extrahepatic, non‐digestive organs together stored < 10% of the whole‐body retinol mass. VA supplementation significantly increased total retinol concentrations in all organs. However, this increase lasted for only 1 d in most extrahepatic organs, with the exception of white adipose tissue, where it lasted for 18 d.ConclusionsOur findings suggest that extrahepatic organs in neonatal rats may not be sufficiently developed to store VA at the adult capacity and that the scarcity of adipose tissue may predispose neonates to a low VA status. Moreover, given the transient effect of VA supplementation on extrahepatic organs, a more frequent supplementation schedule, along with other nutrition interventions, may be necessary to maintain a steady supply of retinol to the rapidly developing extrahepatic organs.Support or Funding InformationSupported by NIH grant HD‐066982
Comparative Cardiac Anatomy and Transmyocardial Laser Revascularization
Authors: Cabral Richard Halti 
Published: November 2023

Comparative cardiac anatomy related to the analysis of the initial clinical experience of transmyocardial laser revascularization (tmlr) in patients with severe diffuse coronary artery disease.methods20 patients were submitted to tmlr at the heart institute (incor), university of são paulo medical school, brazil, isolated or in association with conventional coronary artery bypass graft (cabg). all patients had severe diffuse coronary artery disease, with angina functional class iii/iv (canadian cardiovascular society score) unresponsive to medical therapy. fourteen patients were submitted to tmlr as the sole therapy, whereas 6 underwent concomitant cabg. fifty per cent of the patients had either been previously submitted to a cabg or to a percutaneous transluminal coronary angioplasty (ptca). mean age was 60 years, ranging from 45 to 74 years.resultsall patients had three‐vessel disease, with normal or mildly impaired left ventricular global function. follow‐up ranged from 1 to 13 months (mean 6.6 months), with no postoperative short or long term mortality. there was significant symptom improvement after the procedure, with 85% of the patients free of angina, and the remaining 15 % of the patients showing improvement in functional class, as well as in exercise tolerance.
Sodium Overload Induces Remodeling of Aorta and Cardiac Arteries Without Blood Pressure Changes in Mice
Authors: Lacchini Silvia , Silva Juliane Cristina Souza , Lima Cintia Taniguti , da Silva Viegas Katia Aparecida , Oliveira Thais Cristina Souza , Fiorino Patricia , de Moura Azevedo Farah Vera , Cabral Richard Halti 
Published: November 2023

Sodium intake is considered an important mechanism of cardiovascular stress, and can lead to the development of pathologies as hypertension. Hypertension is a well‐known determinant of structural and functional changes of arteries. It is unclear if the effect of salt overload is related to the described hypertension or if there are other mechanisms involved.The objective of this study was to evaluate the effect of sodium overload upon wall structure of elastic and muscular arteries in normotensive male and female mice. For this, 4 weeks age male and female C57Bl/6 mice were divided into 3 groups (n=8 to 10 for each group): control, drinking normal water (cont), treated with 1% NaCl solution for 2 weeks (salt‐2) or 12 weeks (salt‐12). Body weight was measured at weeks 4, 6, 8, 10 and 12, and at the end of the study were also measured pulse blood pressure (BP) and heart rate (HR) by tail plethysmography. Before tissue collection, water ingestion, urine volume and sodium excretion were measured by using metabolic cages. Then, aorta and heart were collected, prepared for histological analysis, and sections (5μm) were stained by Verhoeff‐Van Gieson for analysis of arterial thickening, by picrosirius for analysis of perivascular collagen deposition, and by Weigert for elastic lamellae analysis. The results were compared by ANOVA, using p≤0.05 as significant.At the end of the experiment, we did not observe differences between groups when we compare body weight, BP and HR. Water ingestion (salt‐2M:+95; salt‐12M:+100%), urine volume (salt‐2M:+107; salt‐12M:+114%), and sodium excretion (salt‐2M:+281; salt‐12M:+164%) increased in salt treated mice, particularly in males. Elastic lamellae in aorta increased in females after salt overload (salt‐2F:+20%; salt‐12F:+40%). Interestingly, perivascular collagen deposition in cardiac arteries reduced in salt‐treated males (salt‐2M:−50%; salt‐12M:−55%). On the other hand, aorta collagen deposition increased, both in males (salt‐2M:+26%; salt‐12M:+40%), and females (salt‐2F:+20%; salt‐12F:+80%).The lack of changes in BP and HR suggest that the structural changes observed are not directly related to hemodynamic mechanisms. Morphometric results suggest that sodium overload induces adaptive responses in different fashion in male and female mice, indicating a possible artery thickening in female as consequence of salt chronic ingestion.Support or Funding InformationFAPESP, CAPES and CNPq
Transcriptional Control of Cranial Suture Development
Authors: Maxson Robert , Teng Camilla , Ting Manchun , Crump Gage 
Published: November 2023

The skull is a complex, exquisitely patterned structure with key roles in many aspects of vertebrate life, ranging from the acquisition of food to the support of the sense organs for hearing, smell, sight, and taste. During its development it must meet the dual challenges of protecting the brain and accommodating its growth. The flat bones at the top of the skull compose the skull vault, or calvaria. Between the bones are sutures, fibrous joints that allow the skull vault to flex during childbirth and act as a growth center in postnatal growth and homeostasis. A number of congenital disorders affect the development of the skull vault. Prominent among these is Saethre‐Chotzen syndrome is a disorder characterized by premature fusion of the bones of the skull vault (craniosynostosis) and facial irregularities. Heterozygous mutations in the basic helix‐loop‐helix (bHLH) transcription factor TWIST1 account for roughly 71% of Saethre‐Chotzen syndrome diagnoses. Recently, patients with Saethre‐Chotzen syndrome who do not carry TWIST1 mutations were found instead to have mutations in TCF12, another bHLH gene. Suggesting an interaction between these genes, loss of Tcf12 enhances craniosynostosis in Twist1+/− mice. Marker analysis in individual and compound Twist1 and Tcf12 mutants suggests that these two genes cooperatively control a set of downstream processes, including the specification of sutural cells as well as the boundary between osteogenic and non‐osteogenic cells at the coronal suture. To further explore the role of Twist1 and Tcf12 in suture development, we have developed a zebrafish model of suture development that appears to closely mimic mammalian sutures. Using TALEN‐mediated mutagenesis, we have generated null alleles for both zebrafish Twist1 homologs (twist1a and twist1b) and tcf12. Remarkably, a portion of zebrafish doubly null for twist1b and tcf12 are adult viable yet display near complete loss of the coronal suture. Our data provide strong evidence for deep evolutionary homology of the coronal suture between fish and mammals, thus suggesting that the zebrafish will be a useful model for understanding craniosynostosis in humans.Support or Funding InformationThis work was supported by grants from the NIH (NIDCR) to RM, CT, and GC
Prediction, Performance, and Adjustments: Medical Students’ Reflections on the First Gross Anatomy Exam
Authors: Hoffman Leslie A. 
Published: November 2023

BackgroundStudies have found that lower performing medical students tend to exhibit over‐confidence when it comes to predicting exam performance. This overconfidence typically stems from a lack of awareness of their knowledge deficits.PurposeThe purpose of this study was to assess medical students’ accuracy in predicting their grade on the first gross anatomy exam, as well as to examine how they planned to adjust their study habits based on their actual exam performance.MethodsFirst‐year medical students (n=30) were asked to asked to reflect on their study habits and confidence level prior to the first gross anatomy exam. They were also asked to indicate the grade they expected to receive on the exam. Following the exam, students reflected on their exam performance, how their confidence level has changed, and what adjustments they planned to make to their study habits. The students’ grade predictions were also compared to their actual exam performance.ResultsFollowing the exam, students were divided into three groups based on their performance: High performers, average performers, and low performers. The low performers (n=9) all received a failing grade on the exam (< 70%). There were no significant differences in the grade predictions between the three groups, although all of the low performing students overestimated their grade. Qualitative analysis of students’ proposed adjustments to their study habits revealed that high performing students intended to adjust their study habits in focused and content‐specific ways, such as spending more time on radiology or clinical correlations, while their overall strategies remained largely unchanged. Low performing students frequently indicated that they intended to change their overall study strategy as a result of their exam performance, for example, by incorporating more quizzing, studying with peers, or spending more time preparing for lecture and lab so that time spent in class yielded higher level learning.DiscussionThis study reinforces observations that low performing students are often unaware of their knowledge deficits. These findings also suggest that many low performing students had not developed basic study habits prior to entering medical school and often engage in trial and error to discover which study strategies work best for them. These low performing students would likely benefit from an introductory study skills course early on in their medical training.
Remediation in an Integrated Medical School Curriculum ‐ Lessons Learned
Authors: Ward Peter 
Published: November 2023

Medical schools are finding that curricular reform and adoption of integrated curricular designs are expected by their accrediting bodies. From a faculty perspective, curricular reform can be a relatively traumatic event that is often mandated but rarely embraced. Faculty members’ immediate concern is typically the conservation or pruning of content as it moves from well‐defined disciplines (e.g. anatomy, pharmacology, pathology) to a novel place in more obscure categories such as back pain, nausea, fever, etc. In addition to re‐ordering the content, a task that is akin to assembling a new picture from an existing jigsaw puzzle, there are often expectations that more topics will be delivered outside of lecture. Inclusion of team‐based sessions, application exercises, or via flipped‐classroom sessions bring additional challenges to teaching faculty. In the process of implementing a new curricular scheme, some important aspects are only considered after the content has been put into place. One of these concerns is how to remediate students after a course failure. This session will focus on how remediation can be conducted in a longitudinal curriculum by showcasing the challenges that were identified and addressed at the West Virginia School of Osteopathic Medicine.WVSOM adopted a longitudinal, patient‐presentation curriculum starting in the 2012–13 academic year. We found that the previous remediation process and resources were inadequate to meet the needs of remediating students in the new curricular arrangement. We also discovered that sensible and seemingly‐minor changes made during the academic year sometimes had unintended consequences for remediation. This session will show how deficiencies in the remediation process were identified, how they were remedied, and will finish by presenting our revised remediation process. Remediation is intended to strengthen the curriculum by maintaining high standards of our students and they work through content that challenged them on the first attempt. The revised remediation process at WVSOM accomplishes these goals by limiting the number of courses that can be remediated, provides resources to the students that are commensurate with the way content had been delivered during their regular courses, gives them opportunities to diagnose weaknesses in their learning, and then address those weaknesses through Q&A sessions with the teaching faculty.Support or Funding InformationNo extramural or other grant funding was used during preparation of this session. The presenter has no conflicts of interest to report.
Dissecting the Development of Clinical Reasoning in the Gross Anatomy Laboratory
Authors: Rae Guenevere , Karpinski Aryn C. , McGoey Robin 
Published: November 2023

This project examined the relationship between the act of identifying pathologic lesions in the gross anatomy laboratory and the development of clinical diagnostic reasoning. During the first year gross anatomy course at Louisiana State University Health Science Center (LSUHSC), Pathology faculty and residents visited the laboratory four times (9.5 hours total) throughout the course and interacted with the first year medical students. During these interactive sessions, the Pathologists discussed grossly observable signs of pathology in the cadavers and discussed their potential role in the cadaver's cause of death. In situations where gross identification of the pathology was questionable, the pathology faculty and residents took tissue samples from the cadavers and histo‐pathologically confirmed the diagnoses. An assessment was designed for the measurement of the student's ability to assimilate the data in making an accurate diagnosis of the cadaver's cause of death. The assessment merged elements from two commonly used clinical reasoning assessments: a Script Concordance Test and a Triple Jump Test. Students were given the assignment to record data on the cadaver they were dissecting as if they were performing an autopsy. After the conclusion of the dissection procedures, the students (n=202) were asked to rate the degree to which they felt that each finding contributed to their “first patient's” cause of death. The ratings were compared to ratings given by a panel of clinical experts who reviewed the student's autopsy reports. The assessment is designed to detect clinical reasoning skills gained by first year medical students while dissecting within the gross anatomy laboratory environment.Support or Funding InformationAmerican Association of Anatomists Educational Scholarship
New Approaches and Insights into Cortical Microcircuits
Authors: Adesnik Hillel , Mardinly Alan , Pegard Nicolas , Oldenburg Ian , Waller Laura 
Published: November 2023

The brain encodes and processes information through precise spatiotemporal patterns of neural activity. Despite recent technological advances, no approach offers sufficient resolution to decipher the neural code in order to reveal its logic and possible syntax. Doing so could offer unparalleled access to understanding brain function and disease. To address this technical gap, we developed and optimized a new approach to bi‐directionally edit neural populations codes in the neocortex during behavior using spatiotemporally precise multiphoton optogenetics. We overcame major barriers in temporal fidelity and spatial precision in order to add or remove action potentials from naturally active populations with single cell resolution and millisecond precision. By using ultrafast opsins, amplified infrared lasers, and optimized holographic stimulation, we present a method to arbitrarily write in or silence precise trains of action potentials in large populations of neurons and in three dimensions in the neocortex of behaving animals.Support or Funding InformationArnold and Mabel Beckman Foundation, New York Stem Cell Foundation Robertson Investigator, NIH New Innovator, McKnight Endowment for Neuroscience