Patterns and correlates of active commuting in adults with type 2 diabetes: cross-sectional evidence from UK Biobank.

OBJECTIVES: To describe the active commuting (AC) patterns of adults with type 2 diabetes and how these relate to physical activity and sedentary behaviour in UK Biobank. Social and environmental correlates of AC will also be explored. DESIGN: Cross-sectional analysis of a cohort study. SETTINGS: This is a population cohort of over 500 000 people recruited from 22 centres across the UK. Participants aged between 37 and 73 years were recruited between 2006 and 2010. PARTICIPANTS: 6896 participants with a self-reported type 2 diabetes diagnosis who reported commuting to work and had complete covariate data were included in the analysis. EXPOSURE MEASURES: Exposure measures were AC to work, measured as usual mode of transport. OUTCOME MEASURES: Outcome measures were weekly minutes of moderate to vigorous physical activity (MVPA), hours/day of sedentary time and participation in active travel. RESULTS: AC (reporting walking or cycling to work only) was reported by 5.5% of participants, with the great majority using the car to commute (80%). AC was associated with an additional 73 (95% CI 10.8 to 134.9) and 105 (95% CI 41.7 to 167.2) weekly minutes of MVPA for men and women, respectively. AC was associated with reduced sedentary time (β -1.1, 95% CI -1.6 to -0.7 hours/day for men; and β -0.8, 95% CI -1.2 to -0.3 hours/day for women). Deprivation and distance from home to work were identified as correlates of AC behaviour. CONCLUSIONS: Rates of AC are very low in adults with type 2 diabetes. However, AC offers a potentially sustainable solution to increasing physical activity and reducing sedentary behaviour. Therefore, strategies to improve the environment and encourage AC may help to increase population levels of physical activity and reduce the disease burden associated with type 2 diabetes

Neural Circuit Recording from an Intact Cockroach Nervous System

The cockroach ventral nerve cord preparation is a tractable system for neuroethology experiments, neural network modeling, and testing the physiological effects of insecticides. This article describes the scope of cockroach sensory modalities that can be used to assay how an insect nervous system responds to environmental perturbations. Emphasis here is on the escape behavior mediated by cerci to giant fiber transmission in Periplaneta americana. This in situ preparation requires only moderate dissecting skill and electrophysiological expertise to generate reproducible recordings of neuronal activity. Peptides or other chemical reagents can then be applied directly to the nervous system in solution with the physiological saline. Insecticides could also be administered prior to dissection and the escape circuit can serve as a proxy for the excitable state of the central nervous system. In this context the assays described herein would also be useful to researchers interested in limb regeneration and the evolution of nervous system development for which P. americana is an established model organism

Combining simulation modeling and stable isotope analyses to reconstruct the last known movements of one of Nature’s giants

The spatial ecology of rare, migratory oceanic animals is difficult to study directly. Where incremental tissues are available, their chemical composition can provide valuable indirect observations of movement and diet. Interpreting the chemical record in incremental tissues can be highly uncertain, however, as multiple mechanisms interact to produce the observed data. Simulation modeling is one approach for considering alternative hypotheses in ecology and can be used to consider the relative likelihood of obtaining an observed record under different combinations of ecological and environmental processes. Here we show how a simulation modeling approach can help to infer movement behaviour based on stable carbon isotope profiles measured in incremental baleen tissues of a blue whale (Balaenoptera musculus). The life history of this particular specimen, which stranded in 1891 in the UK, was selected as a case study due to its cultural significance as part of a permanent display at the Natural History Museum, London. We specifically tested whether measured variations in stable isotope compositions across the analysed baleen plate were more consistent with residency or latitudinal migrations. The measured isotopic record was most closely reproduced with a period of residency in sub-tropical waters for at least a full year followed by three repeated annual migrations between sub-tropical and high latitude regions. The latitudinal migration cycle was interrupted in the year prior to stranding, potentially implying pregnancy and weaning, but isotopic data alone cannot test this hypothesis. Simulation methods can help reveal movement information coded in the biochemical compositions of incremental tissues such as those archived in historic collections, and provides context and inferences that are useful for retrospective studies of animal movement, especially where other sources of individual movement data are sparse or challenging to validate.© 2019 Trueman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited

Cut-Point Levels of Phosphatidylethanol to Identify Alcohol Misuse in a Mixed Cohort Including Critically Ill Patients

Background: Although alcohol misuse is associated with deleterious outcomes in critically ill patients, its detection by either self-report or examination of biomarkers is difficult to obtain consistently. Phosphatidylethanol (PEth) is a direct alcohol biomarker that can characterize alcohol consumption patterns; however, its diagnostic accuracy in identifying misuse in critically ill patients is unknown. Methods: PEth values were obtained in a mixed cohort comprising 122 individuals from medical and burn intensive care units (n = 33), alcohol detoxification unit (n = 51), and healthy volunteers (n = 38). Any alcohol misuse and severe misuse were referenced by Alcohol Use Disorders Identification Test (AUDIT) and AUDIT-C scores separately. Mixed-effects logistic regression analysis was performed, and the discrimination of PEth was evaluated using the area under the receiver-operating characteristic (ROC) curve. Results: The area under the ROC curve for PEth was 0.927 (95% CI: 0.877, 0.977) for any misuse and 0.906 (95% CI: 0.850, 0.962) for severe misuse defined by AUDIT. By AUDIT-C, the area under the ROC curves was 0.948 (95% CI: 0.910, 0.956) for any misuse and 0.913 (95% CI: 0.856, 0.971) for severe misuse. The PEth cut-points of ≥250 and ≥400 ng/ml provided optimal discrimination for any misuse and severe misuse, respectively. The positive predictive value for ≥250 ng/ml was 88.7% (95% CI: 77.5, 95.0), and the negative predictive value was 86.7% (95% CI: 74.9, 93.7). PEth ≥ 400 ng/ml achieved similar values, and similar results were shown for AUDIT-C. In a subgroup analysis of critically ill patients only, test characteristics were similar to the mixed cohort. Conclusions: PEth is a strong predictor and has good discrimination for any and severe alcohol misuse in a mixed cohort that includes critically ill patients. Cut-points at 250 ng/ml for any, and 400 ng/ml for severe, are favorable. External validation will be required to establish these cut-points in critically ill patients

Isolation of a Highly Thermal Stable Lama Single Domain Antibody Specific for Staphylococcus aureus Enterotoxin B

<p>Abstract</p> <p>Background</p> <p>Camelids and sharks possess a unique subclass of antibodies comprised of only heavy chains. The antigen binding fragments of these unique antibodies can be cloned and expressed as single domain antibodies (sdAbs). The ability of these small antigen-binding molecules to refold after heating to achieve their original structure, as well as their diminutive size, makes them attractive candidates for diagnostic assays.</p> <p>Results</p> <p>Here we describe the isolation of an sdAb against <it>Staphyloccocus aureus </it>enterotoxin B (SEB). The clone, A3, was found to have high affinity (Kd = 75 pM) and good specificity for SEB, showing no cross reactivity to related molecules such as Staphylococcal enterotoxin A (SEA), Staphylococcal enterotoxin D (SED), and Shiga toxin. Most remarkably, this anti-SEB sdAb had an extremely high Tm of 85°C and an ability to refold after heating to 95°C. The sharp Tm determined by circular dichroism, was found to contrast with the gradual decrease observed in intrinsic fluorescence. We demonstrated the utility of this sdAb as a capture and detector molecule in Luminex based assays providing limits of detection (LODs) of at least 64 pg/mL.</p> <p>Conclusion</p> <p>The anti-SEB sdAb A3 was found to have a high affinity and an extraordinarily high Tm and could still refold to recover activity after heat denaturation. This combination of heat resilience and strong, specific binding make this sdAb a good candidate for use in antibody-based toxin detection technologies.</p

<i>C-elegans</i> model identifies genetic modifiers of alpha-synuclein inclusion formation during aging

Inclusions in the brain containing alpha-synuclein are the pathological hallmark of Parkinson's disease, but how these inclusions are formed and how this links to disease is poorly understood. We have developed a &lt;i&gt;C-elegans&lt;/i&gt; model that makes it possible to monitor, in living animals, the formation of alpha-synuclein inclusions. In worms of old age, inclusions contain aggregated alpha-synuclein, resembling a critical pathological feature. We used genome-wide RNA interference to identify processes involved in inclusion formation, and identified 80 genes that, when knocked down, resulted in a premature increase in the number of inclusions. Quality control and vesicle-trafficking genes expressed in the ER/Golgi complex and vesicular compartments were overrepresented, indicating a specific role for these processes in alpha-synuclein inclusion formation. Suppressors include aging-associated genes, such as sir-2.1/SIRT1 and lagr-1/LASS2. Altogether, our data suggest a link between alpha-synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism. The processes and genes identified here present a framework for further study of the disease mechanism and provide candidate susceptibility genes and drug targets for Parkinson's disease and other alpha-synuclein related disorders

Dynamics of Immune Reconstitution and Activation Markers in HIV+ Treatment-Naïve Patients Treated with Raltegravir, Tenofovir Disoproxil Fumarate and Emtricitabine

Background: The dynamics of CD4+ T cell reconstitution and changes in immune activation and inflammation in HIV-1 disease following initiation of antiretroviral therapy (ART) are incompletely defined and their underlying mechanisms poorly understood. Methods: Thirty-nine treatment-naïve patients were treated with raltegravir, tenofovir DF and emtricitabine. Immunologic and inflammatory indices were examined in persons with sustained virologic control during 48 weeks of therapy. Results: Initiation of ART increased CD4+ T cell numbers and decreased activation and cell cycle entry among CD4+ and CD8+ T cell subsets, and attenuated markers of coagulation (D-dimer levels) and inflammation (IL-6 and TNFr1). These indices decayed at different rates and almost all remained elevated above levels measured in HIV-seronegatives through 48 weeks of viral control. Greater first and second phase CD4+ T cell restoration was related to lower T cell activation and cell cycling at baseline, to their decay with treatment, and to baseline levels of selected inflammatory indices, but less so to their changes on therapy. Conclusions: ART initiation results in dynamic changes in viral replication, T cell restoration, and indices of immune activation, inflammation, and coagulation. These findings suggest that determinants of T cell activation/cycling and inflammation/coagulation may have distinguishable impact on immune homeostasis. Trial Registration Clinicaltrials.gov NCT0066097

Delays in seeking an abortion until the second trimester: a qualitative study in South Africa

<p>Abstract</p> <p>Background</p> <p>Despite changes to the South African abortion legislation in 1996, barriers to women accessing abortions still exist. Second trimester abortions, an inherently more risky procedure, continue to be 20% of all abortions. Understanding the reasons why women delay seeking an abortion until the second trimester is important for informing interventions to reduce the proportion of second trimester abortions in South Africa.</p> <p>Methods</p> <p>Qualitative research methods were used to collect data. Twenty-seven in-depth interviews were conducted in 2006 with women seeking a second trimester abortion at one public sector tertiary hospital and two NGO health care facilities in the greater Cape Town area, South Africa. Data were analysed using a grounded theory approach.</p> <p>Results</p> <p>Almost all women described multiple and interrelated factors that influenced the timing of seeking an abortion. Reasons why women delayed seeking an abortion were complex and were linked to changes in personal circumstances often leading to indecision, delays in detecting a pregnancy and health service related barriers that hindered access to abortion services.</p> <p>Conclusion</p> <p>Understanding the complex reasons why women delay seeking an abortion until the second trimester can inform health care interventions aimed at reducing the proportion of second trimester abortions in South Africa.</p

Enteric Neurospheres Are Not Specific to Neural Crest Cultures: Implications for Neural Stem Cell Therapies

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited

Genetic and physiologic analysis of the role of uncoupling protein 3 in human energy homeostasis

By virtue of its potential effects on rates of energy expenditure, uncoupling protein 3 (UCP3) is an obesity candidate gene. We identified nine sequence variants in UCP3, including Va19Met, Val102Ile, Arg282Cys, and a splice site mutation in the intron between exons 6 and 7. The splice mutation results in an inability to synthesize mRNA for the long isoform (UCP3L) of UCP3. Linkage (sib pair), association, and transmission disequilibrium testing studies on 942 African-Americans did not suggest a significant effect of UCP3 on body composition in this group. In vastus lateralis skeletal muscle of individuals homozygous for the splice mutation, no UCP3L mRNA was detectable; the short isoform (UCP3S) was present in an increased amount. In this muscle, we detected no alterations of in vitro mitochondrial coupling activity, mitochondrial respiratory enzyme activity, or systemic oxygen consumption or respiratory quotient at rest or during exercise. These genetic and physiologic data suggest the following possibilities: UCP3S has uncoupling capabilities equivalent to UCP3L; other UCPs may compensate for a deficiency of bioactive UCP3L; UCP3L does not function primarily as a mitochondrial uncoupling protein