bluuebunny/crossref_metadata_2025 huggingface dataset:
Anatomy of Aging
Authors: Karani Reena , Laitman Jeffrey
Published: June 2021

Adults >65 make up the fastest growing segment of the US population. However, projections indicate that there will never be enough trained geriatricians to care for these citizens. Hence groups have called for geriatrics training for all medical students irrespective of final career choice. Anatomy provides an outstanding venue to educate students about aging. Anatomic gift donations are most common among the elderly and the course offers students their first professional exposure to human patients and the life cycle. Our objectives were to help students identify gross anatomic findings that occur due to aging or the common medical conditions of aging and to discuss these in the context of the current demographic shift. Prior to the session, first year students at the Mt. Sinai SOM documented age related changes in their cadavers. During a 2h lab session, 7 geriatricans spent 20 mins. with each group reviewing their findings, pointing out additional changes and discussing clinical correlates. Cadaver mean age was 81.5y (57–100). Despite no previous training in aging, students identified a mean of 9 findings per cadaver related to aging (2–15). Most common findings included LVH, aortic valve calcification and sarcopenia. Other findings included pressure ulcers, solar lentigines and kyphosis. Our innovation was universally well received and offers a novel way to introduce aging into the Gross Anatomy curriculum.
Stretching the Limits: Dyad Pedagogy and Technology Bolster Anatomy Learning.
Authors: Noronha Alinea Serena , Ahsan Lusana , Sherman Lloyd R , Marquez Samuel
Published: June 2021

Dyad Pedagogy (DP) combined with technology enhances student learning in first‐year Anatomy courses for medical students at SUNY Downstate. Two students working together (dyads) solve and/or explore a problem ‐ maximizing feedback between the two over all other approaches ‐ and thus optimizing learning in the cognitive, affective, and psychomotor domains as defined in Bloom's taxonomies of learning. The dyads create a project that applies the principles of gross anatomy to clinical pathologies in a presentation to be captured on HD video. They define muscles and innervations of a particular region of the body and explain issues associated with injury to these structures. The project integrates all learning modalities: textbook, lectures, gross anatomy labs, and the internet and involves three stages of dyad problem‐solving: 1. they become experts in the anatomy of their region of study; 2. they develop a skit to aid in the communication of the clinical relevance of muscle‐nerve damage; 3. they present the project to the class. The presentation is then video‐taped and posted on the Intranet for their classmates to use during review and study. These dyad‐created anatomy videos augment the learning of gross anatomy principles and are adjudged clear and engaging presentations of muscle action. Their value is evidenced by the impact of this learning method on the entire class as measured in terms of their online use.

Grant Funding Source: SUNY Downstate
Promoting medical student independent learning using radiology PowerPoint self‐study modules in gross anatomy
Authors: Snow Mikel H
Published: June 2021

Providing medical students with opportunities to develop independent learning skills is an objective of the LCME. PowerPoint‐based, self‐study, modules were developed for the KSOM gross anatomy course to teach medical students how to independently interpret radiographic images using their knowledge of anatomy. Radiology was chosen due to a) its reliance on anatomical relationships, b) its dependency on the ability to extrapolate two‐dimensional images into three dimensions, c) its relevance to many fields of medicine, and c) its absence as a required elective at the KSOM. Using PowerPoint's custom animation and hyperlink tools, five radiology modules were developed, one for each of the dissection regions (thorax & back, abdomen, pelvis, head & neck, limbs) of the course. The modules were designed to sequentially highlight structures on a radiograph for the student to identify and self‐test, followed by the correct answer. Hyperlinks were included to provide supplementary information regarding key anatomical relationships. Normal radiographic images were principally used, although a few pathological images were included. Students reported that it takes about 30 to 45 minutes to complete each module. Student feedback confirmed that these self‐study modules were highly effective learning resources that enabled students to learn independently at their own pace.
Utilizing peer, near‐peer, and inter‐professional teaching: A model for integrating embryology into gross anatomy curriculum
Authors: Scoville Elizabeth Ann , Nyauncho Clive P , Kumar Neha , Hassinger James Peyton , Lachman Nirusha , Pawlina Wojciech
Published: June 2021

As embryology becomes increasingly integrated into other basic science courses, questions arise of what teaching method should be used to effectively utilize curriculum time for this subject. At Mayo Medical School, the human structure block integrates gross anatomy, embryology, and radiology. We present a model that utilizes peer and near‐peer teaching, continuous self‐assessment, and inter‐professional collaboration to maximize embryology curriculum time in this integrated course. Students peer teach embryology topics in presentations, and create a patient education pamphlet on a related congenital disorder. Production advice and critique on these pamphlets is provided by an inter‐professional collaboration with the Mayo Clinic patient education department. Third year teaching assistants guide peer teaching with detailed content guides, by reviewing presentations and pamphlets, and being available for near‐peer tutoring. Students are provided with formative feedback in the form of Audience Response System quizzes to assess their learning progress throughout the course. Student satisfaction and utilization of near‐peer and inter‐professional resources will be assessed at the end of the course.

Grant Funding Source: Department of Anatomy
Teaching of Anatomy in an Integrated, Electronic Curriculum: Implementation and Evaluation
Authors: Klein Robert M , Durham Dianne , Fishback James L , Paolo Anthony , Bonaminio Giulia A , Shaw Pam , Karr Michael , Enders George C
Published: June 2021

In 2006, KUSOM instituted a technology‐ and module‐based, integrated medical curriculum. Tablet PCs are used to integrate technology components and learning concepts, providing 24/7 access to all curricular content. Lectures decreased by 40% replaced by small group, E‐learning, and formative activities. Histology and cell biology begin in the 1st year Foundations of Medicine (FOM) module and continue as integrated histopathology labs using digital videos, virtual microscopy, and electronic quizzes. Human Anatomy starts with thorax dissection in the Cardiopulmonary module and continues in GI/Nutrition (abdomen), Reproduction and Sexuality (pelvis), Musculoskeletal (extremities), and Brain & Behavior [B&B (head and neck)]. Human Anatomy uses team dissection, web‐based radiological anatomy, and lectures for content dissemination. Embryology is taught in FOM and then with each system. For 2010, basic and clinical embryology will be revisited in Medicine Across the Lifespan with transdisciplinary cases. Neurosciences is now integrated with head and neck anatomy and behavioral sciences in B&B. A few early technical problems have been overcome and student satisfaction has been high. USMLE anatomical discipline Step I scores have not changed significantly. There has been a statistically significant increase in NBME Neuroscience subject exam scores in the new compared to the traditional curriculum.
Evolution of primate special senses
Authors: Kirk Edward Christopher
Published: June 2021

The origin and early cladogenesis of primates involved several critical shifts in sensory anatomy and ecology. Comparisons of living and fossil euarchontans suggest that the origin of crown primates was associated with the evolution of (a) increased eye size and (b) greater optic convergence. Functional and comparative evidence indicates that these features are best explained as adaptations for increased visual acuity and improved depth perception in the context of nocturnal visual predation. A second major shift in primate sensory anatomy occurred with the origin of crown Haplorhini. Most living haplorhines share a suite of highly derived adaptations for enhanced visual acuity, including (a) small corneas relative to eye size, (b) a retinal fovea, and (c) a postorbital septum. Haplorhines also demonstrate a derived reduction of the olfactory apparatus, including (a) loss of the rhinarium, (b) loss of an olfactory recess in the nasal cavity, and (c) decreased olfactory bulb size. While the underlying causes of olfactory reduction remain obscure, enhanced visual acuity likely evolved in haplorhines as an adaptation for visually directed predation in a diurnal setting.
Cell‐ and Tissue‐mechanics of Apical Contraction in Embryonic Epithelia
Authors: Davidson Lance A , Joshi Sagar D. , von Dassow Michelangelo
Published: June 2021

Apical contraction is one of the principle cellular mechanisms that sculpt epithelial sheets into structures such as tubes, pits, and furrows. In order to investigate the mechanics of apical contraction and epithelial morphogenesis in vertebrates we have developed three methods (chemical‐, electrical‐, and laser‐activation) to induce contraction in embryonic epithelia of the frog Xenopus laevis. We use these methods together with a biomechanical analytical framework to investigate the molecular signaling pathways regulating contraction and the mechanical coupling of these pathways to tissue movements. Thus far, we find pathways that control exogenously induced contractions are similar to the programs that regulate native epithelial morphogenesis. For instance, laser‐activation induces a Ca++ wave, activates RhoGTPase, and drives F‐actin remodeling. Epithelial stiffness and force‐generation measured during electrically induced contraction suggests these two properties are mechanically independent. In contrast to single‐cell studies we have found no evidence that mechanical‐stimulation can induce apical contraction. In addition to our results on the molecular and mechanical regulation of apical contraction our studies suggest morphogenetic processes can be co‐opted by tissue engineers to build replacement tissues and construct artificial organs.
Sweating the Small Stuff: Stress Effects in Medial Prefrontal Cortex
Authors: Wellman Cara Lynn
Published: June 2021

Stress can precipitate or exacerbate many psychological disorders, and can also disrupt cognitive and emotional behavior. Prefrontal cortex has been implicated in a variety of psychological disorders, is involved in many of the cognitive processes that are influenced by chronic stress, and is a target for the hormones involved in the stress response. Despite this, relatively little work has been done to elucidate the effects of stress on prefrontal cortex, and the mechanisms through which stress produces prefrontal dysfunction. We have shown that stress produces profound changes in the morphology of neurons in medial prefrontal cortex, and that these alterations can happen very quickly and even after a mild stressor. We have further demonstrated stress‐induced deficits in a prefrontally‐mediated behavior, retrieval of extinction of conditioned fear, and these deficits are correlated with stress‐induced alterations in neuronal activity in medial prefrontal cortex. Understanding the mechanisms of these stress‐induced changes in prefrontal structure, function, and behavior will provide valuable insights into the etiology of psychological disorders such as depression, schizophrenia, and posttraumatic stress disorder.
Pro‐survival and pro‐apoptotic factors following axotomy in a murine model of Amyotrophic Lateral Sclerosis.
Authors: Haulcomb Melissa M , Mesnard Nichole A , Politis Christine M , Sanders Virgina M , Jones Kathryn J
Published: June 2021

The facial nerve axotomy is used to study motoneuron (MN) survival and peripheral nerve regeneration. Using this model in wild‐type (WT) mice we have identified two populations of MN; regenerative MN in the ventromedial (VM) subnucleus and degenerative MN in the ventrolateral (VL) subnucleus. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by MN cell death. In the SOD1 mouse model of ALS, a recent study demonstrated the development of two MN populations, one compensatory and one degenerative, following disease progression. To further examine these findings we propose to use facial nerve axotomy as a tool to characterize pre‐symptomatic SOD1 MN or neuropil response compared to WT. We hypothesize that the axotomy‐induced facial motoneuron loss in SOD1 relative to WT, is due to a pro‐inflammatory microenvironment resulting in apoptosis. RT‐PCR was conducted using laser microdissected control vs. axotomized facial nuclei and VM vs. VL subnuclei to determine axotomy‐induced mRNA expression changes in pro‐apoptotic genes (FasR, Caspase‐3, TNFR1) and pro‐survival genes (PAC1‐R, TNFR2, CX3CR1). Localization of TNFR1, TNFR2, and CX3CR1 will also be examined via immunohistoochemistry.

Grant Funding Source: NIH grant NS40433
The role of orexin and dopamine in sleep alterations from the progressive, neurotoxin‐induced model of parkinsonism
Authors: McDowell Kimberly Anne , Quiroz Cesar , Ferre Sergi , Yarowsky Paul
Published: June 2021

Parkinson's disease (PD) is classically defined as a motor disorder resulting from decreased dopamine (DA) production in the basal ganglia circuit. To better diagnose PD before the onset of severe motor dysfunction, current attention has focused on the early, non‐motor symptoms. Sleep disorders, such as excessive daytime sleepiness (EDS), are one of the most prominent initial symptoms in PD. Recent studies revealed that orexin (ORX) neurons, a cell type vital to sleep regulation, also degenerate in PD and may contribute to the sleep disorders. We have developed a novel, progressive rat model that can investigate this aspect of PD. Epidemiological studies found a link between the Guamanian variant of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) and the consumption of flour made from the washed seeds of the plant, Cycas micronesica (cycad). Cycad‐fed rats displayed a parkinsonian phenotype. Uniquely, these rats also displayed a hypersomnolent behavior similar to EDS and a significant loss of ORX neurons. We hypothesize that the sleep disturbance is due to orexin dysfunction, which then induces a loss of DA neurons in the SN. To measure this altered neurochemistry, we utilized microdialysis and high performance liquid chromatography to determine levels of DA in the SN and caudate putamen of the cycad‐fed rat.

Support: NIEHS (KM); NIDA (SF); VA (PY)

Grant Funding Source: NIEHS
The regulation of hepatic metabolism by insulin
Authors: Birnbaum Morris J , Leavens Karla
Published: June 2021

Central to the signaling cascade by which insulin regulates metabolism in liver, muscle and adipose tissue is the serine/threonine protein kinase Akt, also known as Protein Kinase B. Each of the three Akt family members has distinct roles in normal physiology. The isoform specificity in hepatic metabolism is evident in liver, in that Akt2 deletion abrogates control of lipogenic gene expression, but insulin is still capable of regulating the genes encoding gluconeogenic proteins. Most impressively, deletion of Akt2 selectively in the liver leads to marked abnormalities in anabolic lipid metabolism, whereas glucose metabolism is relatively normal. Deletion of both Akt2 genes results in significant glucose intolerance. The phenotype of livers deficient in Akt2, which are protected from accumulation of fat in the liver, support the hypothesis insulin resistance under pathological conditions is “selective”, retaining the ability of insulin to regulate anabolic lipid pathways while losing suppression of hepatic glucose output.
Environmental Factors Contributing to the Regulation of Insulin Sensitivity in Type 2 Diabetic Patients
Authors: Zierath Juleen Rae
Published: June 2021

Epigenetic modification through DNA methylation is implicated in metabolic disease and may play a role in the mechanism by which environmental factors influence metabolic responses in diabetes. Using whole genome promoter methylation analysis of skeletal muscle from normal glucose tolerant and Type 2 diabetic subjects, we identified cytosine hypermethylation of Peroxisome Proliferator‐Activated Receptor γ Coactivator‐1 α (PGC‐1α) in diabetic subjects. Methylation levels were negatively correlated with PGC‐1α mRNA and mitochondrial DNA (mtDNA). Bisulfite sequencing revealed that the highest proportion of cytosine methylation within PGC‐1α was found within non‐CpG nucleotides. Non‐CpG methylation was acutely increased in human myotubes by exposure to tumor necrosis factor‐α (TNF‐α) or free fatty acids, but not insulin or glucose. Selective silencing of the DNA methyltransferase 3B (DNMT3B), but not DNMT1 or DNMT3A, prevented palmitate‐induced non‐CpG methylation of PGC‐1α and decreased mtDNA and PGC‐1α mRNA. We provide evidence for PGC‐1α hypermethylation, concomitant with reduced mitochondrial content in Type 2 diabetic patients, and link DNMT3B to the acute fatty‐acid induced non‐CpG methylation of PGC‐1α promoter.

Study supported by the European Research Council and the Swedish Research Council.
Identification of Genome Maintenance Proteins with Functional Genomic Screens
Authors: Cortez David
Published: June 2021

The precise replication of the genome and the continuous surveillance of its integrity are essential for cell survival and the avoidance of various diseases, including cancer. The genome is constantly exposed to environmental and endogenous genotoxic insults. To cope with this challenge, the DNA damage response coordinates DNA repair, replication, and the cell cycle. We have completed several RNAi screens to identify genes that function to maintain genome integrity during DNA replication. SMARCAL1 and CINP are two of the genes identified. SMARCAL1 acts as an annealing helicase to maintain genome integrity at stalled replication forks. Loss of SMARCAL1 activity increases the single‐stranded DNA at stalled replication forks and causes double‐strand breaks to accumulate. SMARCAL1 is regulated by an interaction with replication protein A and phosphorylation by the ATM/ATR family of kinases. CINP also is required to prevent double‐strand break accumulation. It interacts with ATR and regulates ATR checkpoint signaling. Both SMARCAL1‐ and CINP‐deficient cells are hypersensitive to replication stress agents. Thus, our functional genomic screens have identified new genome maintenance proteins inlcuding SMARCAL1 and CINP that maintain genome integrity within DNA damage response pathways. This research is funded by the National Cancer Institute and Susan G. Komen for the Cure.
Drug Resistance in Tuberculosis
Authors: Blanchard John Sears
Published: June 2021

Drug resistance is a common problem in all bacterial infections, but in the particular case of human Tuberculosis (TB), there are few effective drugs that have been developed and approved for use against the disease. Modern chemotherapy against TB consists of treatment for two months with four drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) followed by an additional four months with isoniazid and rifampicin. Significant resistance to isoniazid began to appear in the early 1980's, while the emergence of strains resistant to both isoniazid and rifampicin began to emerge in the 1990's. These are the two compounds that exhibit bactericidal activity against rapidly growing organisms, and strains exhibiting this resistance pattern are termed multi‐drug resistant (MDR). More recently, strains that are extremely‐drug resistant have been reported around the globe. These strains are resistant to both isoniazid and rifampicin, as well as fluoroquinolones and at least one aminoglycoside. These XDR‐TB strains are extremely difficult to treat effectively, and mortality rates are extremely high for persons infected with XDR‐TB.

A large effort is currently underway to identify new lead compounds with novel targets and mechanisms of action. Several candidates in clinical trails will be discussed. In addition, a reexamination of drugs previously not used to treat TB is underway. The mechanisms of action of, and mechanisms of resistance to, both old and newly developing drugs will be discussed.
Combating Drug Resistance: The balance between inhibition and substrate processing
Authors: Schiffer Celia
Published: June 2021

Resistance is a major problem in the development of robust new therapeutics to quickly evolving diseases. Viral proteases, critical to maturation, are effective targets for antiviral therapy. However, when the virus evolves, resistance quickly emerges. In solving the crystal structures of HIV‐1 protease substrate complexes, we developed the substrate envelope hypothesis and designed potent inhibitors that are less susceptible to drug resistance by staying within the substrate envelope. Yet, we have recently discovered that changes in HIV Gag also confer PI resistance in a PI specific manner. These results reinforce the complexity that resistance occurs as the balance of substrate recognition/processing and inhibitor binding are perturbed. Resistance is also emerging quickly to inhibitors are being developed for another viral protease, Hepatitis C NS3/4A. Once again, crystal structures of product complexes verify that most of resistance mutations are occurring outside of the HCV substrate envelope. Suggesting that the substrate envelope constraint should also be applied to development of HCV inhibitors to make them less susceptible to resistance. Understanding the molecular basis for substrate recognition is critical to develop effective inhibitors that avoid resistance against quickly evolving enzymatic targets.
Neonatal CD44 Null Mice Are Protected From Hypoxia‐Induced Pulmonary Hypertension and Decreased Alveolarization, and Have Defects In TGFβ and ERK Signaling
Authors: Savani Rashmin C. , Wang Lin , Williams Olatunji W.
Published: June 2021

Impaired neonatal vascular and alveolar development, and elevated TGFβ contribute to pulmonary hypertension (PH) and bronchopulmonary dysplasia (BPD). Since the hyaluronan receptor CD44 regulates TGFβ signaling, we examined the effects of hypoxia (12% vs. 21% O2) from birth to postnatal day (PN) 14 in neonatal CD44+/+ (WT) and CD44−/− mice. At PN14, hypoxia‐exposed WT mice had right ventricular hypertrophy and decreased alveolarization. CD44−/− mice exposed to hypoxia were completely protected from these changes. Hypoxia‐exposed WT lungs had increased active TGFβ and phospho‐Smad2 as compared to room air (RA) controls. Surprisingly, lungs from RA CD44−/− mice had elevated active TGFβ and phospho‐Smad2 at baseline and these were not altered by hypoxia. Compared to lungs from hypoxia WT mice, lungs from hypoxia CD44−/− mice had impaired ERK1/2 phosphorylation. After hypoxia, the TGFβ target gene alpha‐smooth muscle actin, was increased in WT, but not CD44−/− mice. We conclude that hypoxia‐induced PH and decreased alveolarization require CD44 and ERK phosphorylation, and that Smad2 phosphorylation is necessary but not sufficient for TGFβ signaling in this context. We speculate that CD44 may be a novel therapeutic target for PH and BPD.
Inhibition of phosphoinositide 3 kinase delta attenuates allergic airway inflammation in mice
Authors: Kang Bit Na , Hosseinkhani Reza M , Bahaie Nooshin S , Ge Xiao Na , Ha Sung Gil , Rao Savita P , Puri Kamal D , Sriramarao P
Published: June 2021

Phosphoinositide 3‐kinase p110δ (PI3Kδ) plays a pivotal role in the recruitment and activation of inflammatory cells. The role of PI3Kδ in a mouse model of cockroach antigen (CRA)‐induced acute allergic airway inflammation was investigated using IC87114, a selective PI3Kδ inhibitor. BALB/c mice exposed to CRA developed airway eosinophilia associated with increased expression of IL‐2, IL‐17, IFNγ, IL‐4 and IL‐5 in lung tissue as well as of pro‐inflammatory chemokines eotaxin‐1 and MCP‐1 in bronchoalveolar lavage fluid (BALF) and lung tissue. Further, these mice developed airway hyperresponsiveness (AHR) to inhaled methacholine. Oral administration of IC87114 significantly attenuated CRA‐induced influx of inflammatory cells in the BALF (eosinophils and macrophages) and lung tissue and suppressed CRA‐induced AHR. Moreover, levels of IL‐2, IL‐17, IFNγ, IL‐4, and IL‐5 in lung tissue and of eotaxin‐1 and MCP‐1 in BALF as well as lung tissue were substantially reduced. Treatment of human eosinophils with IC87114 significantly inhibited eosinophil rolling on human umbilical vein endothelial cells as well as VCAM‐1 in vitro. Overall, these findings implicate that inhibition of the PI3Kδ may have therapeutic potential for the treatment of allergic airway inflammation. Supported by National Institutes of Health grants HL0793041 and AI35796.
Priming and extending: how UbcH5 and Cdc34 act to assemble ubiquitin chains on a SCF substrate
Authors: Pan Zhen‐Qiang , Kovacev Jordan , Wu Kenneth
Published: June 2021

I will discuss a mechanistic model of polyubiquitination by the SCFβTrCP2 E3 ubiquitin (Ub) ligase using human IκBα as substrate. Biochemical reconstitution experiments revealed that the polyubiquitination of IκBα began with the action of the UbcH5 E2 Ub conjugating enzyme, transferring a single Ub to IκBα K21/K22 rapidly and efficiently. Subsequently, the Cdc34 E2 functioned in the formation of polyubiquitin chains. Our recent work shows that an Ub fused at IκBα K21 acts as a receptor, directing Cdc34 for rapid and efficient K48‐linked Ub chain synthesis that depends on SCFβTrCP2 and the substrate's N terminus. The IκBα‐linked fusion Ub appears to mediate direct contacts with Cdc34 and the SCF's RING sub‐complex. Taken together, these results suggest a role for the multifaceted interactions between the K21/K22‐linked receptor Ub, the SCF's RING complex, and Cdc34~S~Ub in establishing the optimal orientation of the receptor Ub to drive conjugation.
Tips on Grant Writing: What to Put In and Where
Authors: Gentile Lisa N
Published: June 2021

As part of the workshop on tips for grant writing, this presentation will focus on “what to put in and where.” Discussion will be centered on how to organize a grant proposal, what sections can/should be included, and what type of information is essential to each section of the proposal. What do reviewers need to know to be convinced that the science you propose is worth doing, can be done by you and your lab group, and will be supported by your institution? In addition, things that may annoy reviewers, and should be avoided, will be discussed. The presenter is from a primarily undergraduate institution and has experience both as a reviewer as well as a recipient of NSF (CAREER and MRI), ACS‐PRF (B), NIH (AREA), Merck‐AAAS (Summer Undergraduate Science Research Program), and HHMI (Undergraduate Science Education Program) grants.
Native levels and determinants for oxidation of coenzyme Q10 in human plasma
Authors: Franke Adrian A , Morrison Cynthia M , Bakke Jesse L , Custer Laurie J , Li Xingnan , Cooney Robert V
Published: June 2021

Coenzyme Q10 (Q10) is present in the circulation mainly reduced (ubiquinol‐10; UL10), but oxidizes quickly ex vivo to ubiquinone‐10 (UN10). Therefore, native UL10/UN10 ratios, used as markers of redox status and disease risk, are difficult to measure.

We established a RP‐(U)HPLC method with coulometric detection to measure natively circulating UL10 and UN10 concentrations by adding a ubiquinol/ubiquinone mixture as internal standards immediately after plasma preparation. This allowed adjustment for unavoidable artificial UL10 oxidation as well as for total losses (or gains) of analytes during sample storage, processing, and analysis since the internal standards exactly paralleled the chemical behavior of Q10. This technique applied to blood collected from 13 healthy volunteers revealed Q10 levels of 680–3300 nM with a UL10/UN10 ratio of 95:5 (mean) which was inversely associated with total Q10 (r=−0.69; p=0.004).

The oxidation of UL10 to UN10 was equimolar, increased by O2, and decreased by lower temperatures or various degassing methods. Although UL10 was stable in blood or when pure in organic solvents at 22 oC, its oxidation was catalyzed dose dependently by alpha‐tocopherol and butylated hydroxy toluene, particularly when present in combination. Key structural features for the catalytic pro‐oxidant properties of phenolic antioxidants included two aliphatic substituents vicinal to the phenolic hydroxyl group.
Family‐Focused Program Shows Benefit in Treating Excess Weight in Children
Authors: Rost Stephanie Lyn , Miller‐Kovach Karen , Angelopoulos Ted , Rippe James M.
Published: June 2021

OBJECTIVE

To assess a parent‐based, pilot program for treating excess weight in children in a community setting.

METHODS

Parents attended 8‐to‐10 weekly sessions led by a coach trained in childhood and adolescent weight issues and supported by local pediatricians in the Tampa and Orlando areas of Florida. Effective parenting techniques to enact evidence‐based, healthy weight recommendations for the entire family were taught and reinforced in an environment of group support. Discussions and written materials focused on behavior and lifestyle change. To determine impact, independent researchers made home visits to measure height and weight of all children in the household at baseline, 8 weeks and quarterly for one year.

RESULTS

114 children have 59 week results (i.e., at baseline and again 1 year after completion of the 2‐month pilot program). 12 children had a BMI‐for‐Age <85th %‐tile at baseline. Of the 102 children at baseline with a BMI‐for‐Age ≥85th %‐tile, the mean age was 10.3 ± 2.6 years; at baseline, the mean BMI z‐score was 2.01 ± 0.41 and 1.89 ± 0.48 at 59 weeks (p<0.001). 68 children with excess weight reduced their BMI z‐score, 1 stayed the same and 33 increased. The mean BMI z‐score change was +0.14 for those that gained and −0.24 for those that lost.

CONCLUSION

A parent‐focused program appears to have a positive influence on children's weight one year after the intervention.

Weight Watchers International, Inc.
Effects of alcohol and alcohol‐metabolizing SNPs on serum vitamin D levels in postmenopausal women in a controlled feeding study
Authors: Mahabir Somdat , Baer David , Pfeiffer Ruth , Taylor Philip R.
Published: June 2021

Background

Among alcoholics vitamin D metabolism is altered and alcoholics have decreased vitamin D levels. However, no published data is available on the role of low to moderate alcohol consumption on vitamin D levels.

Objective

The objective of this study was to evaluate the effects of 8 weeks of no alcohol, low (1 drink or 15g/d) and moderate (2 drinks or 30g/d) alcohol consumption on serum 25(OH)D concentrations in postmenopausal women in a controlled feeding study and to assess whether alcohol metabolizing SNPs (ADH1B_02, ADH1B_05, ADH1C_01, ADH1C_02, ALDH2_07, CYP2E1_02, CYPE2_06, CYP2E1_07, CYP2E1_12, CYP2E1_13, CYP2E1_21, CYP2E1_22) modified the levels of 25(OH)D.

Design

Postmenopausal women (n = 51) consumed 0, 1 drink, and 2 drinks of alcohol/day for 8 weeks as part of a controlled diet in a randomized crossover design. Fasting blood samples were drawn at baseline, at 4 weeks and at 8 weeks. Serum 25(OH)D concentrations were measured by ELISA. Wilcoxon rank sum and linear mixed models were used to compare differences in serum 25(OH)D concentrations from placebo to 1 and 2 drinks/day in the 8‐week samples.

Results

1 or 2 drinks/day for 8 weeks had no significant impact on serum 25(OH)D concentrations. We did not find any significant interactions between any of the SNPs and alcohol treatment on serum 25(OH)D concentrations.

Conclusion

The data indicate that low to moderate alcohol consumption for 8 weeks had no significant impact on serum 25(OH)D concentrations among postmenopausal women in a tightly controlled feeding study.
Neonatal administration of monosodium glutamate (MSG) to induce Type‐2 diabetes in prepubertal pigs
Authors: Price Kathryn L. , Brown Lindsey A. , Wagner Ashley L. , Utt Matthew D. , Wankhade Umesh D. , Good Deborah J. , Escobar Jeffery
Published: June 2021

Pigs were given 4 mg/g BW of MSG or saline (SAL) i.p. 0, 2, 4, 6, 8, and 10 d after birth. After overnight fasting, 3‐month‐old pigs consumed 2 g/kg BW of D‐glucose. Blood samples were collected 0, 60, and 120 min for plasma glucose (GLC) and insulin (INS) quantification. GLC (mg/dL) was not different (P=0.78 to 0.96) at 0 (SAL, 89.0±11.3; MSG 79.6±11.2) or 60 min (SAL, 179.4±11.3; MSG 194.6±11.2) between treatments. INS (μIU/mL) was not different (P=0.83 to 0.99) between treatments at 0 (SAL, 2.1±2.4; MSG, 1.4±2.8) or 60 min (SAL, 27.6±2.4; MSG 32.5±2.8). At 120 min, GLC was 44% greater (P=0.03) in MSG (121.8±11.2) compared to SAL (84.3±11.3) pigs. INS was 3.2‐fold greater (P=0.0002, ln transformed data) in MSG (7.3±2.8) compared to SAL (2.3±2.4) pigs. GLC‐to‐INS ratio was not different (P=0.99) at 0 or 60 min but was lower at 120 min (P=0.02) in MSG (26.9±4.6) compared to SAL (47.0±4.0) pigs. Collectively, these results indicate that neonatal administration of MSG leads to impaired oral glucose tolerance in prepubertal pigs, which implicates swine as a suitable animal model to study nutritional interventions in children with Type‐2 diabetes. Funding: Virginia Agricultural Experiment Station.

Grant Funding Source: Virginia Agricultural Experiment Station
Cholecystokinin release by STC‐1 cells in response to differentially hydrolyzed soy protein
Authors: Krul Elaine Susan , Li Jia , Napawan Nida , Tulk Barry , Butteiger Dustie N
Published: June 2021

Cholecystokinin (CCK) is a satiety signal released by intestinal I‐cells in response to peptides and other macronutrients. The molecular mechanism of the CCK response is poorly understood. The objective of our research was to identify satiating soy peptide molecules derived from differential enzymatic hydrolyses. Soluble soy protein hydrolysates were generated with at least 9 different food processing enzymes and then added to enteroendocrine cells (STC‐1) at 2 mg/mL protein for 4 hours to screen for their ability to induce CCK release. Phorbol 12‐myristate 13‐acetate (PMA) (100 nM) and 2 mg/mL bovine serum albumin (BSA) were used as positive and basal controls, respectively. Most hydrolyzed soy proteins significantly induced CCK over basal levels while non‐hydrolyzed proteins did not. Select hydrolysates induced CCK by 117 ± 15.0%, 113 ± 19.7% and 99 ± 13.8% (mean ± SEM) versus the PMA control, respectively, indicating that signaling of CCK release was dependent on peptide sequence specificity. CCK release was also modulated by the degree of hydrolysis for each enzyme. In conclusion, specific soy peptides generated by enzyme hydrolysis under defined conditions induce CCK release. Characterizing the specific sequences involved will help us develop peptide hydrolysates with increased satiety‐inducing potential which would have utility as ingredients in food products designed for use in weight management.
Cranberry polyphenols down‐regulate the toll‐like receptor 4 pathway and NF‐κB activation, while still enhancing tumor necrosis factor α secretion
Authors: Muller Catherine E. , Khoo Christina , Percival Susan S.
Published: June 2021

Polyphenols (PP) from plants have been shown to have anti‐inflammatory properties. To study the anti‐inflammatory nature of PP from cranberry, three cranberry fractions (CF) were incubated with HL60 cells, a human promyelocytic leukemia cell line. One CF contained proanthocyanidins (PAC) from cranberry presscake, one was rich in PAC from cranberry juice and the other contained PP, including PAC, from the juice. Differentiated HL60 cells were cultured with each CF and lipopolysaccharide (LPS). Phosphorylated IκBα and IRAK4 protein levels were lower in cells incubated with the CF compared to a LPS control, while total IκBα was increased by the CF compared to the LPS control. TNFα secretion from cells incubated with CF was higher than the LPS control. Cranberry PP seem to protect neutrophils from LPS activation via the Toll‐like receptor 4 signaling pathway that uses IRAK4 as an intermediate signaling protein. IκBα is not phosphorylated and degraded, and, thus, does not release NF‐κB. However, TNFα expression is still upregulated in fraction‐treated cells, so its production and secretion is stimulated by these fractions via an alternate pathway. Funded by Ocean Spray Cranberries, Inc. and FAES.
Nutrient Rich Food Options in Grocery Stores: Buying healthier foods without paying more
Authors: Mammarella Sarah , Colby Sarah E , Gross Kevin , Rivera David , Pawlak Roman
Published: June 2021

Objective

The objective of this research was to assess the price difference between nutrient rich and less nutrient rich paired food items in grocery stores.

Methods

All grocery stores in Greenville, NC (N=13) were assessed using a modified Nutrition Environment Measures Survey (NEMS).

Outcomes Measured

All foods (n=126) with a nutrient rich and a less nutrient rich version were assessed for price difference.

Results

Of 63 food item pairs assessed, less nutrient rich food items never cost more than the more nutrient rich counterpart. The majority (52.4%) of the food item pairs were found to have no difference in price.

Conclusions

In grocery stores, many nutrient rich options can be purchased without increasing food expenditures.

Grant Funding Source: None
Contribution of growth in fetal length to post‐natal length in Bangladesh children
Authors: Frongillo Edward A , Neufeld Lynnette M , Wagatsuma Yukiko , Hoang Lan N , Arifeen Shams E , Alam Dewan S , Persson Lars A
Published: June 2021

Physical growth of children continues during the critical window from conception to 24 mo, punctuated by birth. In Asia especially, prenatal growth deficit is understood to partially explain post‐natal stunting, but this is not well characterized. This study quantified the contribution of pre‐ and post‐natal growth deficits to length at 24 mo using a unique cohort of 1931 children followed from first trimester of gestation to 24 mo from the Maternal Infant Nutritional Interventions Matlab (MINIMat) study in rural Bangladesh. Femur diaphysis length was assessed by trained paramedics at 14, 19, and 30 wk using real‐time ultrasound on a portable machine. Recumbent length was measured at birth then monthly to 12 mo and every 3 mo from 13 to 24 mo using length boards. British reference values (Chitty et al.) for fetal length and from the sex‐specific WHO 2006 growth standards for recumbent length were used to adjust for variation from nominal age. Quintiles formed from length at 24 mo revealed that femur length at 14 wk was unrelated to length at 24 mo. From linear regression with length at 24 mo as outcome, variance explained was 0.0, 1.1, 7.1, 23.2, and 53.2% for models adding sequentially length at 14 wk, 19 wk, 30 wk, birth, and 6 mo. Thus, 23% of variance at 24 mo was explained by fetal growth and 30% by the first 6 mo of post‐natal growth. The critical period of fetal growth for explaining length at 24 mo was the second half of gestation.
Potential impact of zinc‐biofortified rice on zinc intakes of young Bangladeshi children
Authors: Arsenault Joanne E , Yakes Elizabeth A , Lewis Bess , Islam M Muniril , Hossain Bakhtiar , Ahmed Tahmeed , Hotz Christine , Brown Kenneth H
Published: June 2021

Background

Young children in Bangladesh are at risk of zinc deficiency due to a rice‐based diet with few animal‐source foods. Breeding rice for higher zinc content would offer a sustainable approach to increase zinc intakes.

Objectives

To quantify usual rice and zinc intakes in young children and estimate the potential impact of zinc‐biofortified rice on zinc intakes.

Methods

We measured dietary intake in a representative sample of 480 children ages 24–48 mo in rural communities from two districts, Trishal (T) and Pirgaccha (P). Food intakes were estimated by weighed records in homes on 2 non‐consecutive days. Serum zinc concentrations were determined in a sub‐sample of children.

Results

Median (25th, 75th pct) rice intakes of children were 144 (110, 179) g/d in T and 123 (88, 164) g/d in P; and median zinc intakes were 2.4 (2.0, 2.9) mg/d in T and 2.5 (2.1, 3.0) mg/d in P. 27% and 19% of children had inadequate zinc intakes (<2 mg/d) in T and P, respectively. 36% and 11% of children in T and P, respectively, had low serum zinc concentrations (<65 μg/dL) after adjusting for infection status. Rice was the highest source of zinc intakes, providing 59% and 41% of dietary zinc in T and P, respectively. If the rice zinc content were increased by 50% or 100%, the probability of inadequate zinc intakes would decrease to 8% or 3–4%, respectively.

Conclusions

Young children in rural Bangladesh have inadequate intakes of zinc, and zinc‐biofortification of rice has potential to markedly improve the zinc adequacy of the children's diets.

Funding: HarvestPlus, Washington, DC
Thrombolytic activity of Cheonggukjang kinase on the recovery of brain damage in cerebral embolic stroke model
Authors: Song Young‐Sun , Jalin Angela Melinda Anak Anthony , Kang A Reum , Lee Chae Yeon , Park Chung Mu , Radnabazaar Chinzorig , Cha Jae Ho , Kim Jeong Hwan , Kang Sung Goo
Published: June 2021

Stroke has become the secondary leading cause of death and the first cause of major adult disability in the world. Cheonggukjang kinase (CGK), referring to the fibrinolytic enzyme that catalyzes the clot dissolution, was prepared from the culture of pHY3‐5 transformed Bacillus subtilis ISW 1214. Fibrinolytic activity of CGK was confirmed by fibrin clot lysis assay and platelet rich clot lysis assay. 40 hr cultured CGK has the highest plasmin‐like protease activity (44.6±1.50 mU/100 μg CGK) compared with other CGKs (24h, 14.0±2.07; 60h, 12.6±0.85; 80h, 16.3±1.36 mU/100 μg CGK). The effect of doses of CGK (0.1–1 U plasmin) on cerebral embolic stroke, injected intravenously for 10 min, 1 hr after middle cerebral artery occlusion (MCAO) showed that all CGK treated groups significantly reduced the infarct volume in a dose‐dependent manner compared to the control group, However, hemorrhage was identified in the coronal brain sections in rats injected 2 U plasmin‐like activity/kg, rt‐PA at 10 mg/kg and CGK at 1 U plasmin‐like activity/kg on cerebral embolic stroke showed similar efficacy. Furthermore, treatment with CGK also improved functional recovery as measured by neurological deficits, Taken together, these findings suggest that CGK may have a great promise in the treatment of stroke.
A Mediterranean‐style low glycemic diet decreases inflammation and insulin resistance in subjects classified with the metabolic syndrome
Authors: Andersen Catherine Julia , Jones Jennifer , Barona Jacqueline , Calle Mariana , Lerman Robert H , McIntosh Mark , Kalynych Colleen , Vukich Claire , Volek Jeff S , Fernandez Maria Luz
Published: June 2021

Women classified with metabolic syndrome (MS) adhered to a low glycemic diet alone (n = 40) or accompanied by intake of a medical food containing plant sterols, soy protein (PSS), rho iso‐alpha acids, and proanthocyanidins from acacia (n = 44). All women decrreased energy intake (p < 0.00001) after 12 wk. The intake of fat was reduced by 42 % (P < 0.0001), carbohydrate by 38.5% (P < 0.0001), while protein was increased by 13.6%, with the PSS group consuming higher levels of vegetable protein (P < 0.05). Glycemic load was also decreased from 128.5 to 48.2. The adipokines, leptin (P < 0.0001) and tumor necrosis factor alpha (TNF‐α) (P< 0.0005) significantly decreased over time. Waist circumference (WC) decreased for all women (P < 0.0001) and these reductions were strongly correlated with decreases in leptin (r = 0.316, P < 0.05). Interestingly, protein intake was negatively correlated with plasma concentrations of TNF‐α (r= −0.319, P < 0.05). Decreases in interleukin‐6 were correlated with decreased energy intake (r = 0.305, P < 0.05) while the reductions in fat (r = 0.380, P < 0.01) and glycemic load (r = 0.386, P < 0.01) were correlated with decreases in insulin. In contrast, changes in adiponectin were negatively correlated with energy (P < 0.001) and carbohydrate intake (P < 0.05). These data suggests that energy reduction and high vegetable protein, in combination with weight loss improves the chronic inflammatory state in subjects with MetS. [Supported by MetaProteomics, LLC, Gig Harbor, WA]
The Cortisol Response to a Buffet Meal Changes with Energy Restriction in Overweight Women
Authors: Witbracht Megan Gage , Thomas Anthony P. , Souza Elaine , Horn William F. , Adams Sean H. , Laugero Kevin , Van Loan Marta D. , Keim Nancy L.
Published: June 2021

Research has suggested that stress affects eating behavior. We examined the relationship between cortisol and food choice at a buffet meal before and in response to a 12‐wk intervention (I) with an energy‐restricted diet. Overweight females (ages 20–45; n=49) maintained body weight (BW) during a 3‐wk baseline (B) period and lost weight during energy‐restriction (500 kcal/d deficit). The eating behavior protocol was conducted at B wk 0 and I wk 11 and included the provision of a standardized breakfast & lunch followed by ad lib buffet dinner. Salivary cortisol was measured at 10 specific times on both test days. Percent BW and fat loss averaged 5.9% and 3.0%, respectively. Energy (kcal), carbohydrate (CHO), fat and protein (PRO) intake at the buffet averaged 1345kcal, 134g, 63g, 64g, and ranged from 420 to 2667kcal, 43 to 297g, 11 to 126g, and 21 to 126g, respectively. Energy and grams of CHO, fat or PRO intake did not differ between test days. Analysis of the cortisol data revealed a correlation between kcal and cortisol taken 30 min after the completion of the buffet meal (r= 0.470; p=0.001) but only at wk 11. Similarly, cortisol was correlated with intakes of CHO (r=0.512; p=0.001), fat (r=0.375; p=0.008) and PRO (r=0.325; p=0.023). These data suggest factors related to energy restriction may increase the sensitivity of the hypothalamic‐pituitary‐adrenal axis to food intake.

Funding: NDC/ARS Project 5306‐51530‐016‐00D
Dietary Restriction or Dietary Restriction and Exercise, but Not Exercise Intervention Alone, Reduces Weight and Fat Mass in Overweight and Obese Women Postpartum
Authors: Bertz Fredrik , Brekke Hilde , Ellegård Lars , Wennergren Margareta , Rasmussen Kathleen M. , Winkvist Anna
Published: June 2021

The prevalence of obesity is increasing in young women and lifestyle changes are difficult to make. However, postpartum (pp) women may be motivated to do this. In a 2×2 factorial design, we studied if 12‐wk dietary restriction (D), physical exercise (E) or a combination (DE) led to a reduction in weight and fat mass (FM), compared to controls (C) at 12 wk and 1 y post intervention. At 10 wk pp, 68 breastfeeding women with pre‐pregnancy BMI 25–35 kg/m2 were randomized to treatment. The treatments were: E, A 45‐min walk 4 times/wk at 60–70% of maximum heart rate, with a heart rate monitor for self‐monitoring, and D, Dietary change following WHO nutrient composition to reduce weight by 0.5 kg/wk, with a scale for self‐monitoring. Women received 2.5 h of individual counselling. Follow‐up text messages were sent every second wk. Body composition was measured with DEXA. Preliminary results at 12 wk (n=48): Δ weight D: −7.4 (3.3) kg, DE: −6.4 (2.9) kg, E: −2.2 (3.7) kg and C: −1.3 (3.4) kg; ΔFM: D: −6.0 (2.6) kg, DE: −5.7 (3.3) kg, E: −1.7 (3.4) kg and C: −0.8 (3.6) kg. The main effects of D on weight and FM were significant (p=0.000, p=0.000), but the main effects of E were not. No significant effects on fat free mass were found. Conclusion: Obese and overweight women pp may reduce weight and FM through a programme of dietary restrictions with or without exercise, but not with exercise alone. (Funded in part by the Swedish Research Council.)