Inhibition of food intake in obese subjects by peptide YY3-36

Background: The gut hormone fragment peptide YY3-36 (PYY) reduces appetite and food intake when infused into subjects of normal weight. In common with the adipocyte hormone leptin, PYY reduces food intake by modulating appetite circuits in the hypothalamus. However, in obesity there is a marked resistance to the action of leptin, which greatly limits its therapeutic effectiveness. We investigated whether obese subjects were also resistant to the anorectic effects of PYY.Methods: We compared the effects of PYY infusion on appetite and food intake in 12 obese and 12 lean subjects in a double-blind, placebo-controlled, crossover study. The plasma levels of PYY, ghrelin, leptin, and insulin were also determined.Results: Caloric intake during a buffet lunch offered two hours after the infusion of PYY was decreased by 30 percent in the obese subjects (P<0.001) and 31 percent in the lean subjects (P<0.001). PYY infusion also caused a significant decrease in the cumulative 24-hour caloric intake in both obese and lean subjects. PYY infusion reduced plasma levels of the appetite-stimulatory hormone ghrelin. Endogenous fasting and postprandial levels of PYY were significantly lower in obese subjects (the mean [+/-SE] fasting PYY levels were 10.2+/-0.7 pmol per liter in the obese group and 16.9+/-0.8 pmol per liter in the lean group, P<0.001). Furthermore, the fasting PYY levels correlated negatively with the body-mass index (r=-0.84, P<0.001).Conclusions: We found that obese subjects were not resistant to the anorectic effects of PYY. Endogenous PYY levels were low in the obese subjects, suggesting that PYY deficiency may contribute to the pathogenesis of obesity

Sampling, Intervention, Prediction, Aggregation: A Generalized Framework for Model-Agnostic Interpretations

Model-agnostic interpretation techniques allow us to explain the behavior of any predictive model. Due to different notations and terminology, it is difficult to see how they are related. A unified view on these methods has been missing. We present the generalized SIPA (sampling, intervention, prediction, aggregation) framework of work stages for model-agnostic interpretations and demonstrate how several prominent methods for feature effects can be embedded into the proposed framework. Furthermore, we extend the framework to feature importance computations by pointing out how variance-based and performance-based importance measures are based on the same work stages. The SIPA framework reduces the diverse set of model-agnostic techniques to a single methodology and establishes a common terminology to discuss them in future work

Stress reducing effects of real and artificial nature in a hospital waiting room

Objectives: This field study investigated the potential stress-reducing effects of exposure to real or artificial nature on patients in a hospital waiting room. Additionally, it was investigated whether perceived attractiveness of the room could explain these effects. Design: In this between-patients experimental design, patients were exposed to one of the following: real plants, posters of plants, or no nature (control). These conditions were alternately applied to two waiting rooms. Location: The location of this study was two waiting rooms at the Radiology Department of a Dutch hospital. Subjects: The subjects comprised 457 patients (60% female and 40% male) who were mostly scheduled for echocardiogram, dual-energy x-ray absorptiometry, magnetic resonance imaging, computed tomography scans, or nuclear research. Results: Patients exposed to real plants, as well as patients exposed to posters of plants, report lower levels of experienced stress compared to the control condition. Further analyses show that these small but significant effects of exposure to nature are partially mediated by the perceived attractiveness of the waiting room. Conclusions: Natural elements in hospital environments have the potential to reduce patients' feelings of stress. By increasing the attractiveness of the waiting room by adding either real plants or posters of plants, hospitals can create a pleasant atmosphere that positively influences patients' well-being

Horizontal force production and multi-segment foot kinematics during the acceleration phase of bend sprinting

This paper investigated horizontal force production, foot kinematics and metatarsophalangeal (MTP) joint push-off axis use during acceleration in bend (anti-clockwise) and straight-line sprinting. It was hypothesised that bend sprinting would cause the left step push-off to occur about the oblique axis, resulting in a decrease in propulsive force. Three-dimensional kinematic and ground reaction force data were collected from nine participants during sprinting on the bend (36.5 m radius) and straight. Anteroposterior force was reduced at 38-44% of stance during bend sprinting compared with the straight. This coincided with an increase in mediolateral force for the majority of the stance phase (3-96%) on the bend compared with the straight. In addition, a lower propulsive impulse was reported on the bend compared with the straight. Analysis of multi-segment foot kinematics provides insight into the possible mechanisms behind these changes in force production. Mean mediolateral centre of pressure position was more lateral in relation to the second metatarsal head in the left step on the bend compared with the straight, indicating the oblique axis was used for push-off at the MTP joint. Greater peak joint angles of the left foot were also reported, in particular, an increase in left step midfoot eversion and internal ankle rotation. It is possible these changes in joint kinematics are associated with the observed decrease in propulsive force. Therefore, practitioners should seek to strengthen muscles such as tibialis posterior in frontal and sagittal planes and ensure specificity of training which may aid in addressing these force reductions

Cost-Effectiveness of Alternative Uses of Polyvalent Meningococcal Vaccines in Niger: An Agent-Based Transmission Modeling Study.

Background. Despite the introduction of an effective serogroup A conjugate vaccine (MenAfriVac™), sporadic epidemics of other Neisseria meningitidis serogroups remain a concern in Africa. Polyvalent meningococcal conjugate (PMC) vaccines may offer alternatives to current strategies that rely on routine infant vaccination with MenAfriVac plus, in the event of an epidemic, district-specific reactive campaigns using polyvalent meningococcal polysaccharide (PMP) vaccines. Methods. We developed an agent-based transmission model of N. meningitidis in Niger to compare the health effects and costs of current vaccination practice and 3 alternatives. Each alternative replaces MenAfriVac in the infant vaccination series with PMC and either replaces PMP with PMC for reactive campaigns or implements a one-time catch up campaign with PMC for children and young adults. Results. Over a 28-year period, replacement of MenAfriVac with PMC in the infant immunization series and of PMP in reactive campaigns would avert 63% of expected cases (95% prediction interval 49%-75%) if elimination of serogroup A is not followed by serogroup replacement. At a PMC price of $4/dose, this would cost$1412 ($81-$3510) per disability-adjusted life-year (DALY) averted. If serogroup replacement occurs, the cost-effectiveness of this strategy improves to $662 (cost-saving,$2473) per DALY averted. Sensitivity analyses accounting for incomplete laboratory confirmation suggest that a catch-up PMC campaign would also meet standard cost-effectiveness thresholds. Limitations. The assumption that polyvalent vaccines offer similar protection against all serogroups is simplifying. Conclusions. The use of PMC vaccines to replace MenAfriVac in routine infant immunization and in district-specific reactive campaigns would have important health benefits and is likely to be cost-effective in Niger. An additional PMC catch-up campaign would also be cost-effective if we account for incomplete laboratory reporting.PAT

Nonuniform sampling of urodynamic signals: a comparison of different methods

Several different techniques for urodynamic signal compression have been proposed in the last few years. Using these techniques it is possible to reduce the requirements for digital storage or transmission. There are a number of applications where it is essential to use such techniques in diagnostic and ambulatory urodynamics. The purpose of this study is to compare different techniques of urodynamic data compression. The so-called FAN, voltage triggered, two point projection and second difference methods. The comparison between the methods is based on 65 pressure, 46 uroflow and 18 surface electromyogram signals. The reduction ratio achieved for different allowable errors between the original and compressed signals is calculated and compared for the different techniques. Results show that it is possible to store urodynamic signals accurately at a low sampling rate, where FAN and voltage triggered methods seem to be superior to the rest

Aidnogenesis via Leptogenesis and Dark Sphalerons

We discuss aidnogenesis, the generation of a dark matter asymmetry via new sphaleron processes associated to an extra non-abelian gauge symmetry common to both the visible and the dark sectors. Such a theory can naturally produce an abundance of asymmetric dark matter which is of the same size as the lepton and baryon asymmetries, as suggested by the similar sizes of the observed baryonic and dark matter energy content, and provide a definite prediction for the mass of the dark matter particle. We discuss in detail a minimal realization in which the Standard Model is only extended by dark matter fermions which form "dark baryons" through an SU(3) interaction, and a (broken) horizontal symmetry that induces the new sphalerons. The dark matter mass is predicted to be approximately 6 GeV, close to the region favored by DAMA and CoGeNT. Furthermore, a remnant of the horizontal symmetry should be broken at a lower scale and can also explain the Tevatron dimuon anomaly.Comment: Minor changes, discussion of present constraints expanded. 16 pages, 2 eps figures, REVTeX

Biomedical prevention: state of the science.

Preexposure prophylaxis (PrEP) and treatment as prevention (TasP) involve the use of antiretroviral (ARV) drugs by human immunodeficiency virus (HIV)-negative and -positive individuals to reduce HIV acquisition and transmission, respectively. Clinical science has delivered a consistently high effect size for TasP and a range from 0%-73% reduction in incidence across placebo-controlled PrEP trials. However, the quality of evidence for PrEP compares favorably with evidence for postexposure prophylaxis (PEP). It is clear from treatment programs and PrEP trials that daily adherence presents challenges to a large proportion of the population. Although there are factors associated with inconsistent use (ie, younger age), they do not assist clinicians at the point of care. There are additional provider concerns about PrEP (covering cost of drug and delivery, undermining condom promotion, and facilitating resistant strains) that have delayed widespread acceptance. These issues need to be addressed in order to realize the full public health potential of antiretrovirals

Impact of Structural and Metabolic Variations on the Toxicity and Carcinogenicity of Hydroxy- and Alkoxy-Substituted Allyl- and Propenylbenzenes

The metabolic fate of a compound is determined by numerous factors including its chemical structure. Although the metabolic options for a variety of functional groups are well understood and can often provide a rationale for the comparison of toxicity based on structural analogy, at times quite minor structural variations may have major consequences for metabolic outcomes and toxicity. In this perspective, the effects of structural variations on metabolic outcomes is detailed for a group of related hydroxy- and alkoxy-substituted allyl- and propenylbenzenes. These classes of compounds are naturally occurring constituents of a variety of botanical-based food items. The classes vary from one another by the presence or absence of alkylation of their para-hydroxyl substituents and/or the position of the double bond in the alkyl side chain. We provide an overview of how these subtle structural variations alter the metabolism of these important food-borne compounds, ultimately influencing their toxicity, particularly their DNA reactivity and carcinogenic potential. The data reveal that detailed knowledge of the consequences of subtle structural variations for metabolism is essential for adequate comparison of structurally related chemicals. Taken together, it is concluded that predictions in toxicological risk assessment should not be performed on the basis of structural analogy only but should include an analogy of metabolic pathways across compounds and species