Metabolically Healthy Obesity

Accumulating evidence suggests that not all obese subjects are at increased cardiometabolic risk and that the “metabolically healthy obese” phenotype may exist in the absence of metabolic abnormalities. Limited data regards the determinants of metabolically healthy obesity exist, particularly in relation to genetics, dietary and lifestyle behaviours. In light of the current obesity epidemic, it is clear that current “one size fits all” approaches to tackle obesity are largely unsuccessful. Whether dietary, lifestyle and/or therapeutic interventions, based on stratification of obese individuals according to their metabolic health phenotype, are more effective remains to be seen, with limited and conflicting data available. This book includes original research articles and reviews of the scientific literature that contribute to our understanding of the role of clinical, biological, genetic, and environmental factors in metabolically healthy and unhealthy obesity

Giardia Cyst Wall Protein 1 Is a Lectin That Binds to Curled Fibrils of the GalNAc Homopolymer

The infectious and diagnostic stage of Giardia lamblia (also known as G. intestinalis or G. duodenalis) is the cyst. The Giardia cyst wall contains fibrils of a unique β-1,3-linked N-acetylgalactosamine (GalNAc) homopolymer and at least three cyst wall proteins (CWPs) composed of Leu-rich repeats (CWPLRR) and a C-terminal conserved Cys-rich region (CWPCRR). Our goals were to dissect the structure of the cyst wall and determine how it is disrupted during excystation. The intact Giardia cyst wall is thin (~400 nm), easily fractured by sonication, and impermeable to small molecules. Curled fibrils of the GalNAc homopolymer are restricted to a narrow plane and are coated with linear arrays of oval-shaped protein complex. In contrast, cyst walls of Giardia treated with hot alkali to deproteinate fibrils of the GalNAc homopolymer are thick (~1.2 µm), resistant to sonication, and permeable. The deproteinated GalNAc homopolymer, which forms a loose lattice of curled fibrils, is bound by native CWP1 and CWP2, as well as by maltose-binding protein (MBP)-fusions containing the full-length CWP1 or CWP1LRR. In contrast, neither MBP alone nor MBP fused to CWP1CRR bind to the GalNAc homopolymer. Recombinant CWP1 binds to the GalNAc homopolymer within secretory vesicles of Giardia encysting in vitro. Fibrils of the GalNAc homopolymer are exposed during excystation or by treatment of heat-killed cysts with chymotrypsin, while deproteinated fibrils of the GalNAc homopolymer are degraded by extracts of Giardia cysts but not trophozoites. These results show the Leu-rich repeat domain of CWP1 is a lectin that binds to curled fibrils of the GalNAc homopolymer. During excystation, host and Giardia proteases appear to degrade bound CWPs, exposing fibrils of the GalNAc homopolymer that are digested by a stage-specific glycohydrolase. Author SummaryWhile the walls of plants and fungi contain numerous sugar homopolymers (cellulose, chitin, and β-1,3-glucans) and dozens of proteins, the cyst wall of Giardia is relatively simple. The Giardia wall contains a unique homopolymer of β-1,3-linked N-acetylgalactosamine (GalNAc) and at least three cyst wall proteins (CWPs), each of which is composed of Leu-rich repeats and a C-terminal Cys-rich region. The three major discoveries here are: 1) Fibrils of the GalNAc homopolymer are curled and form a lattice that is compressed into a narrow plane by bound protein in intact cyst walls. 2) Leu-rich repeats of CWP1 form a novel lectin domain that is specific for fibrils of the GalNAc homopolymer, which can be isolated by methods used to deproteinate fungal walls. 3) A cyst-specific glycohydrolase is able to degrade deproteinated fibrils of the GalNAc homopolymer. We incorporate these findings into a new curled fiber and lectin model of the intact Giardia cyst wall and a protease and glycohydrolase model of excystation.National Institutes of Health (AI048082, AI44070, GM31318, RR1088

Metabolically healthy obesity across the life course: epidemiology, determinants and implications

In recent years, different subphenotypes of obesity have been described, including metabolically healthy obesity (MHO), in which a proportion of obese individuals, despite excess body fat, remain free of metabolic abnormalities and increased cardiometabolic risk. In the absence of a universally accepted set of criteria to classify MHO, the reported prevalence estimates vary widely. Our understanding of the determinants and stability of MHO over time and the associated cardiometabolic and mortality risks is improving, but many questions remain. For example, whether MHO is truly benign is debatable, and whether risk stratification of obese individuals on the basis of their metabolic health status may offer new opportunities for more personalized approaches in diagnosis, intervention, and treatment of diabetes remains speculative. Furthermore, as most of the research to date has focused on MHO in adults, little is known about childhood MHO. In this review, we focus on the epidemiology, determinants, stability, and health implications of MHO across the life course

Reduction in apathy following epilepsy surgery

Introduction: Surgical treatment for patients with epilepsy who do not respond to antiepileptic medication can lead to changes in behavior, including new onset of neuropsychiatric symptoms such as depression and anxiety. In other cases, neuropsychiatric symptoms present before surgery may be alleviated. Because application of diagnostic criteria for primary psychiatric disorders may not be valid in assessing behavior in epilepsy populations, we sought to determine the feasibility of measuring behaviors associated with frontal-subcortical dysfunction using the Frontal Systems Behavior Scale (FrSBe) in patients who had received surgical intervention for medically refractory epilepsy. Materials and Methods: Twenty-three patients who had previously undergone epilepsy surgery and their family member informants completed the FrSBe. The FrSBe includes separate forms for patients and informants to rate symptoms associated with three frontal lobe syndromes - executive dysfunction, disinhibition, and apathy - prior to and following a neurological condition. Patients and informants were asked to rate frontal lobe behaviors before and after epilepsy surgery using the FrSBe. Results: Informants rated patients as showing a significantly greater reduction in apathy on the FrSBe compared to either disinhibition or executive dysfunction subscales. A trend in reduction of apathy following right hemisphere resection was found. Conclusions: Patients who have undergone epilepsy surgery show a reduction in apathy but it is unclear whether this behavioral change is directly related to the surgical intervention. We suggest that these preliminary findings support the utility of implementing dimensional scales such as the FrSBe to study behavioral changes following epilepsy surgery

Aberrant migration and surgical removal of a heartworm (Dirofilaria immitis) from the femoral artery of a cat.

A cat was evaluated for an acute-onset of right pelvic limb paresis. Thoracic radiographs revealed normal cardiac size and tortuous pulmonary arteries. Abdominal ultrasound identified a heartworm (HW) extending from the caudal abdominal aorta into the right external iliac artery and right femoral artery. The cat was HW-antigen positive. Echocardiography revealed a HW within the right branch of the main pulmonary artery and evidence of pulmonary hypertension. An agitated-saline contrast echocardiogram revealed a small right to left intracardiac shunt at the level of the atria. Surgical removal of the HW was performed with no substantial postoperative complications. There was return of blood flow and improved motor function to the limb. The cat remains mildly paretic on the affected limb with no other clinical signs

Effects of Housing System on Dairy Heifer Replacement Cost from Birth to Calving: Evaluating Costs of Confinement, Dry-Lot, and Pasture-Based Systems and Their Impact on Total Rearing Investment

Replacement heifer rearing is critical for the future of dairy operations, to improve genetic merit and maintain herd size. A myriad of options exist on how to manage, feed, and ultimately raise replacement heifers. Pasture is perceived to offer optimal welfare and an economical housing system for replacement animals, but confinement systems are gaining popularity. This study investigates the costs associated with replacement heifer management decisions from birth to calving, considering the factors of housing systems, labor, feed, and health. The objective of this study was to develop an economic model to determine the cost of raising a replacement heifer managed in confinement, dry-lot, and pasture-based scenarios post-weaning. We accounted for variation in feed, labor, and health inputs and quantified the impact of these individual management decisions. An economic simulation with 10,000 iterations were completed for each situation using @Risk and PrecisionTree add-ons (Palisade Corporation, Ithaca, NY) where health incidence, commodity prices, and management variables were made stochastic. Published literature or sample farm data created parameters used in Pert distributions. Costs and biological responses were reflective of published surveys, literature, and market conditions. Management decision inputs had 3 main factors: housing type, ration composition, and labor utilization. Housing systems were calculated separately for confinement, dry-lot, and pasture scenarios. The mean total cost (min, max) to raise a replacement heifer from birth to calving, assuming the same pre-weaning strategy of group housing with an automatic calf feeder, was found to be $1,919.02 ($1,777.25, $2,100.57),$1,593.57 ($1,490.30,$1,737.26), and $1,335.84 ($1,266.69, $1,423.94) for confinement, dry-lot, and pasture, respectively. Total housing cost per replacement heifer was$423.05, $117.96, and$207.96 for confinement, dry-lot, and pasture management systems, respectively. When compared to total cost, housing contributed 21% for confinement, 7% for dry-lot, and 15% for pasture. Upon analysis of all scenarios, utilizing pasture to raise heifers resulted in a lower overall cost when compared to confinement housing options. Percentage breakdowns of feed, labor, housing, and fixed and variable costs provided more information on efficiency rather than total cost, which makes each situation different in relation to on-farm cost. This cost analysis is critical to assisting farms in making decisions in the utilization of their resources for replacement dairy heifers

A Written Instrument for Assessing Students’ Units Coordination Structures

Units coordination refers to students’ abilities to create units and maintain their relationships with other units that they contain or constitute. In recent research, units coordination has arisen as a key construct that mediates opportunities for student learning across several domains of mathematics, including fractions knowledge and algebraic reasoning. To date, assessments of students’ stages of units coordinating ability have relied upon clinical interviews or teaching experiments whose time-intensive nature precludes opportunities for conducting large-scale studies. We introduce a written instrument that teachers and researchers can use with large populations of students. We report on the reliability and validity of assessments based on the instrument

Nectar Yeasts in the Tall Larkspur Delphinium barbeyi (Ranunculaceae) and Effects on Components of Pollinator Foraging Behavior

Microorganisms frequently colonize the nectar of angiosperm species. Though capable of altering a suite of traits important for pollinator attraction, few studies exist that test the degree to which they mediate pollinator foraging behavior. The objective of our study was to fill this gap by assessing the abundance and diversity of yeasts associated with the perennial larkspur Delphinium barbeyi (Ranunculaceae) and testing whether their presence affected components of pollinator foraging behavior. Yeasts frequently colonized D. barbeyi nectar, populating 54–77% of flowers examined depending on site. Though common, the yeast community was species-poor, represented by a single species, Metschnikowia reukaufii. Female-phase flowers of D. barbeyi were more likely to have higher densities of yeasts in comparison to male-phase flowers. Pollinators were likely vectors of yeasts, as virgin (unvisited) flowers rarely contained yeasts compared to flowers open to pollinator visitation, which were frequently colonized. Finally, pollinators responded positively to the presence of yeasts. Bombus foragers both visited and probed more flowers inoculated with yeasts in comparison to uninoculated controls. Taken together, our results suggest that variation in the occurrence and density of nectar-inhabiting yeasts have the potential to alter components of pollinator foraging behavior linked to pollen transfer and plant fitness

Comparison of diabetes risk score estimates and cardiometabolic risk profiles in a middle-aged Irish population

Background: To compare diabetes risk assessment tools in estimating risk of developing type 2 diabetes (T2DM) and to evaluate cardiometabolic risk profiles in a middle-aged Irish population. Methods: Future risk of developing T2DM was estimated using 7 risk scores, including clinical measures with or without anthropometric, biological and lifestyle data, in the cross-sectional Mitchelstown cohort of 2,047 middle-aged men and women. Cardiometabolic phenotypes including markers of glucose metabolism, inflammatory and lipid profiles were determined. Results: Estimates of subjects at risk for developing T2DM varied considerably according to the risk assessment tool used (0.3% to 20%), with higher proportions of males at risk (0-29.2% vs. 0.1-13.4%, for men and women, respectively). Extrapolated to the Irish population of similar age, the overall number of adults at high risk of developing T2DM ranges from 3,378 to 236,632. Numbers of non-optimal metabolic features were generally greater among those at high risk of developing T2DM. However, cardiometabolic profile characterisation revealed that only those classified at high risk by the Griffin (UK Cambridge) score displayed a more pro-inflammatory, obese, hypertensive, dysglycaemic and insulin resistant metabolic phenotype. Conclusions: Most diabetes risk scores examined offer limited ability to identify subjects with metabolic abnormalities and at risk of developing T2DM. Our results highlight the need to validate diabetes risk scoring tools for each population studied and the potential for developing an Irish diabetes risk score, which may help to promote self awareness and identify high risk individuals and diabetes hot spots for targeted public health interventions