Trends over 5 Decades in U.S. Occupation-Related Physical Activity and Their Associations with Obesity

BACKGROUND: The true causes of the obesity epidemic are not well understood and there are few longitudinal population-based data published examining this issue. The objective of this analysis was to examine trends in occupational physical activity during the past 5 decades and explore how these trends relate to concurrent changes in body weight in the U.S. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of energy expenditure for occupations in U.S. private industry since 1960 using data from the U.S. Bureau of Labor Statistics. Mean body weight was derived from the U.S. National Health and Nutrition Examination Surveys (NHANES). In the early 1960's almost half the jobs in private industry in the U.S. required at least moderate intensity physical activity whereas now less than 20% demand this level of energy expenditure. Since 1960 the estimated mean daily energy expenditure due to work related physical activity has dropped by more than 100 calories in both women and men. Energy balance model predicted weights based on change in occupation-related daily energy expenditure since 1960 for each NHANES examination period closely matched the actual change in weight for 40-50 year old men and women. For example from 1960-62 to 2003-06 we estimated that the occupation-related daily energy expenditure decreased by 142 calories in men. Given a baseline weight of 76.9 kg in 1960-02, we estimated that a 142 calories reduction would result in an increase in mean weight to 89.7 kg, which closely matched the mean NHANES weight of 91.8 kg in 2003-06. The results were similar for women. CONCLUSION: Over the last 50 years in the U.S. we estimate that daily occupation-related energy expenditure has decreased by more than 100 calories, and this reduction in energy expenditure accounts for a significant portion of the increase in mean U.S. body weights for women and men

Individual Recognition in Domestic Cattle (Bos taurus): Evidence from 2D-Images of Heads from Different Breeds

BACKGROUND: In order to maintain cohesion of groups, social animals need to process social information efficiently. Visual individual recognition, which is distinguished from mere visual discrimination, has been studied in only few mammalian species. In addition, most previous studies used either a small number of subjects or a few various views as test stimuli. Dairy cattle, as a domestic species allow the testing of a good sample size and provide a large variety of test stimuli due to the morphological diversity of breeds. Hence cattle are a suitable model for studying individual visual recognition. This study demonstrates that cattle display visual individual recognition and shows the effect of both familiarity and coat diversity in discrimination. [br/]METHODOLOGY/PRINCIPAL FINDINGS: We tested whether 8 Prim'Holstein heifers could recognize 2D-images of heads of one cow (face, profiles, (3/4) views) from those of other cows. Experiments were based on a simultaneous discrimination paradigm through instrumental conditioning using food rewards. In Experiment 1, all images represented familiar cows (belonging to the same social group) from the Prim'Holstein breed. In Experiments 2, 3 and 4, images were from unfamiliar (unknown) individuals either from the same breed or other breeds. All heifers displayed individual recognition of familiar and unfamiliar individuals from their own breed. Subjects reached criterion sooner when recognizing a familiar individual than when recognizing an unfamiliar one (Exp 1: 3.1+/-0.7 vs. Exp 2: 5.2+/-1.2 sessions; Z = 1.99, N = 8, P = 0.046). In addition almost all subjects recognized unknown individuals from different breeds, however with greater difficulty. [br/] CONCLUSIONS/SIGNIFICANCE: Our results demonstrated that cattle have efficient individual recognition based on categorization capacities. Social familiarity improved their performance. The recognition of individuals with very different coat characteristics from the subjects was the most difficult task. These results call for studies exploring the mechanisms involved in face recognition allowing interspecies comparisons, including humans

The prognosis of allocentric and egocentric neglect : evidence from clinical scans

We contrasted the neuroanatomical substrates of sub-acute and chronic visuospatial deficits associated with different aspects of unilateral neglect using computed tomography scans acquired as part of routine clinical diagnosis. Voxel-wise statistical analyses were conducted on a group of 160 stroke patients scanned at a sub-acute stage. Lesion-deficit relationships were assessed across the whole brain, separately for grey and white matter. We assessed lesions that were associated with behavioural performance (i) at a sub-acute stage (within 3 months of the stroke) and (ii) at a chronic stage (after 9 months post stroke). Allocentric and egocentric neglect symptoms at the sub-acute stage were associated with lesions to dissociated regions within the frontal lobe, amongst other regions. However the frontal lesions were not associated with neglect at the chronic stage. On the other hand, lesions in the angular gyrus were associated with persistent allocentric neglect. In contrast, lesions within the superior temporal gyrus extending into the supramarginal gyrus, as well as lesions within the basal ganglia and insula, were associated with persistent egocentric neglect. Damage within the temporo-parietal junction was associated with both types of neglect at the sub-acute stage and 9 months later. Furthermore, white matter disconnections resulting from damage along the superior longitudinal fasciculus were associated with both types of neglect and critically related to both sub-acute and chronic deficits. Finally, there was a significant difference in the lesion volume between patients who recovered from neglect and patients with chronic deficits. The findings presented provide evidence that (i) the lesion location and lesion size can be used to successfully predict the outcome of neglect based on clinical CT scans, (ii) lesion location alone can serve as a critical predictor for persistent neglect symptoms, (iii) wide spread lesions are associated with neglect symptoms at the sub-acute stage but only some of these are critical for predicting whether neglect will become a chronic disorder and (iv) the severity of behavioural symptoms can be a useful predictor of recovery in the absence of neuroimaging findings on clinical scans. We discuss the implications for understanding the symptoms of the neglect syndrome, the recovery of function and the use of clinical scans to predict outcome

Reengineering the clinical research enterprise to involve more community clinicians

<p>Abstract</p> <p>Background</p> <p>The National Institutes of Health has called for expansion of practice-based research to improve the clinical research enterprise.</p> <p>Methods</p> <p>This paper presents a model for the reorganization of clinical research to foster long-term participation by community clinicians.</p> <p>Based on the literature and interviews with clinicians and other stakeholders, we posited a model, conducted further interviews to test the viability of the model, and further adapted it.</p> <p>Results</p> <p>We propose a three-dimensional system of checks and balances to support community clinicians using research support organizations, community outreach, a web-based registry of clinicians and studies, web-based training services, quality audits, and a feedback mechanism for clinicians engaged in research.</p> <p>Conclusions</p> <p>The proposed model is designed to offer a systemic mechanism to address current barriers that prevent clinicians from participation in research. Transparent mechanisms to guarantee the safety of patients and the integrity of the research enterprise paired with efficiencies and economies of scale are maintained by centralizing some of the functions. Assigning other responsibilities to more local levels assures flexibility with respect to the size of the clinician networks and the changing needs of researchers.</p

Ideal and actual involvement of community pharmacists in health promotion and prevention: a cross-sectional study in Quebec, Canada

<p>Abstract</p> <p>Background</p> <p>An increased interest is observed in broadening community pharmacists' role in public health. To date, little information has been gathered in Canada on community pharmacists' perceptions of their role in health promotion and prevention; however, such data are essential to the development of public-health programs in community pharmacy. A cross-sectional study was therefore conducted to explore the perceptions of community pharmacists in urban and semi-urban areas regarding their ideal and actual levels of involvement in providing health-promotion and prevention services and the barriers to such involvement.</p> <p>Methods</p> <p>Using a five-step modified Dillman's tailored design method, a questionnaire with 28 multiple-choice or open-ended questions (11 pages plus a cover letter) was mailed to a random sample of 1,250 pharmacists out of 1,887 community pharmacists practicing in Montreal (Quebec, Canada) and surrounding areas. It included questions on pharmacists' ideal level of involvement in providing health-promotion and preventive services; which services were actually offered in their pharmacy, the employees involved, the frequency, and duration of the services; the barriers to the provision of these services in community pharmacy; their opinion regarding the most appropriate health professionals to provide them; and the characteristics of pharmacists, pharmacies and their clientele.</p> <p>Results</p> <p>In all, 571 out of 1,234 (46.3%) eligible community pharmacists completed and returned the questionnaire. Most believed they should be very involved in health promotion and prevention, particularly in smoking cessation (84.3%); screening for hypertension (81.8%), diabetes (76.0%) and dyslipidemia (56.9%); and sexual health (61.7% to 89.1%); however, fewer respondents reported actually being very involved in providing such services (5.7% [lifestyle, including smoking cessation], 44.5%, 34.8%, 6.5% and 19.3%, respectively). The main barriers to the provision of these services in current practice were lack of: time (86.1%), coordination with other health care professionals (61.1%), staff or resources (57.2%), financial compensation (50.8%), and clinical tools (45.5%).</p> <p>Conclusions</p> <p>Although community pharmacists think they should play a significant role in health promotion and prevention, they recognize a wide gap between their ideal and actual levels of involvement. The efficient integration of primary-care pharmacists and pharmacies into public health cannot be envisioned without addressing important organizational barriers.</p

Role of 20-Hydroxyeicosatetraenoic Acid in Mediating Hypertension in Response to Chronic Renal Medullary Endothelin Type B Receptor Blockade

BACKGROUND: The renal medullary endothelin (ET-1) system plays an important role in the control of sodium excretion and arterial pressure (AP) through the activation of renal medullary ET-B receptors. We have previously shown that blockade of endothelin type B receptors (ET-B) leads to salt-sensitive hypertension through mechanisms that are not fully understood. One possible mechanism is through a reduction in renal medullary production of 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE, a metabolite of arachidonic acid, has natriuretic properties similar to ET-B activation. While these findings suggest a possible interaction between ET-B receptor activation and 20-HETE production, it is unknown whether blockade of medullary ET-B receptors in rats maintained on a high sodium intake leads to reductions in 20-HETE production. METHODOLOGY/PRINCIPAL FINDINGS: The effect of increasing sodium intake from low (NS = .8%) to high (HS = 8%) on renal medullary production of 20-HETE in the presence and absence of renal medullary ET-B receptor antagonism was examined. Renal medullary blockade of ET-B receptors resulted in salt sensitive hypertension. In control rats, blood pressure rose from 112.8±2.4 mmHg (NS) to 120.7±9.3 mmHg (HS). In contrast, when treated with an ET-B receptor blocker, blood pressure was significantly elevated from 123.7±3.2 (NS) to 164.2±7.1 (HS). Furthermore, increasing sodium intake was associated with elevated medullary 20-HETE (5.6±.8 in NS vs. 14.3±3.7 pg/mg in HS), an effect that was completely abolished by renal medullary ET-B receptor blockade (4.9±.8 for NS and 4.5±.6 pg/mg for HS). Finally, the hypertensive response to intramedullary ET-B receptor blockade was blunted in rats pretreated with a specific 20-HETE synthesis inhibitor. CONCLUSION: These data suggest that increases in renal medullary production of 20-HETE associated with elevating salt intake may be, in part, due to ET-B receptor activation within the renal medulla

Renal ischemia–reperfusion injury causes intercalated cell-specific disruption of occludin in the collecting duct

Renal ischemic events open tight junctions and disrupt epithelial polarity. The purpose of this study was to examine the effects of ischemia–reperfusion (IR) injury on expression and distribution of the tight junction proteins, occludin and ZO-1, in the rat kidney. IR injury was induced by clamping both renal pedicles for 30 min and animals were killed at 6 h after the reperfusion. IR injury decreased blood bicarbonate level, but did not persistently alter pH, Na+, K+, or Cl−. In control kidneys, occludin immunoreactivity was intense in the tight junctions in the thick ascending limb, distal convoluted tubule, and collecting duct, moderate in the thin limbs of the loop of Henle, and was not detected in the proximal tubule, glomerulus, and blood vessels. ZO-1 was expressed in the same sites in which occludin was expressed, and additionally was also expressed in the proximal tubule, glomerulus, and vascular endothelial cells. IR kidneys exhibited damaged renal tubular epithelial cells in both proximal tubule and collecting duct segments in the outer medulla. In the collecting duct, the response of intercalated cells and principal cells differed. Following IR injury, intercalated cells, but not principal cells, lost their normal epithelial polarity and were frequently extruded into the tubule lumen. Occludin, instead of being localized to tight junctions, was localized diffusely in the cytoplasm in intercalated cells of IR kidneys. Principal cells, in contrast, were not detectably affected and neither occludin nor ZO-1 expression were altered in response to IR injury. The normal localization of ZO-1 expression to tight junction sites in both the proximal tubule and collecting duct was altered in response to IR, and, instead, ZO-1 expression was present diffusely in the cytoplasm. IR injury did not alter detectably either occludin or ZO-1 localization to the tight junction of the thick ascending limb cells. The abundance of total occludin protein by immunoblot analysis was not changed with IR injury. These results demonstrate that renal IR injury causes tight junction disruptions in both the proximal tubule and the collecting duct, and that altered distribution of the tight junction protein, occludin, may play a critical role in the collecting duct dysfunction which IR induces

Restoration of Podocyte Structure and Improvement of Chronic Renal Disease in Transgenic Mice Overexpressing Renin

Proteinuria is a major marker of the decline of renal function and an important risk factor of coronary heart disease. Elevated proteinuria is associated to the disruption of slit-diaphragm and loss of podocyte foot processes, structural alterations that are considered irreversible. The objective of the present study was to investigate whether proteinuria can be reversed and to identify the structural modifications and the gene/protein regulation associated to this reversal.We used a novel transgenic strain of mouse (RenTg) that overexpresses renin at a constant high level. At the age of 12-month, RenTg mice showed established lesions typical of chronic renal disease such as peri-vascular and periglomerular inflammation, glomerular ischemia, glomerulosclerosis, mesangial expansion and tubular dilation. Ultrastructural analysis indicated abnormal heterogeneity of basement membrane thickness and disappearance of podocyte foot processes. These structural alterations were accompanied by decreased expressions of proteins specific of podocyte (nephrin, podocin), or tubular epithelial cell (E-cadherin and megalin) integrity. In addition, since TGFbeta is considered the major pro-fibrotic agent in renal disease and since exogenous administration of BMP7 is reported to antagonize the TGFbeta-induced phenotype changes in kidney, we have screened the expressions of several genes belonging in the TGFbeta/BMP superfamily. We found that the endogenous inhibitors of BMPs such as noggin and Usag-1 were several-fold activated inhibiting the action of BMPs and thus reinforcing the deleterious action of TGFbeta.Treatment with an AT1 receptor antagonist, at dose that did not decrease arterial pressure, gradually reduced albuminuria. This decrease was accompanied by re-expression of podocin, nephrin, E-cadherin and megalin, and reappearance of podocyte foot processes. In addition, expressions of noggin and Usag-1 were markedly decreased, permitting thus activation of the beneficial action of BMPs.These findings show that proteinuria and alterations in the expression of proteins involved in the integrity and function of glomerular and renal epithelial phenotype are reversible events when the local action of angiotensin II is blocked, and provide hope that chronic renal disease can be efficiently treated

In vitro characterization and inhibition of the CXCR4/CXCL12 chemokine axis in human uveal melanoma cell lines

<p>Abstract</p> <p>Purpose</p> <p>The CXCR4/CXCL12 chemokine axis may play a critical role in guiding CXCR4+ circulating malignant cells to organ specific locations that actively secrete its ligand CXCL12 (SDF-1) such as bone, brain, liver, and lungs. We sought to characterize the presence of the CXCR4/CXCL12 axis in five uveal melanoma (UM) cell lines in vitro. The ability of TN14003, a synthetic peptide inhibitor that targets the CXCR4 receptor complex, to inhibit this axis was also assessed.</p> <p>Methods</p> <p>Immunocytochemistry was performed against CXCR4 to confirm expression of this chemokine receptor in all five UM cell lines. Flow cytometry was preformed to evaluate CXCR4 cell surface expression on all five UM cell lines. A proliferation assay was also used to test effects TN14003 would have on cellular proliferation. Inhibition of cellular migration by specifically inhibiting the CXCR4/CXCL12 axis with TN14003 was also investigated. The binding efficacy of TN14003 to the CXCR4 receptor was assessed through flow cytometric methods.</p> <p>Results</p> <p>The CXCR4 receptor was present on all five UM cell lines. All five cell lines expressed different relative levels of surface CXCR4. TN14003 did not affect the proliferation of the five cell lines (p > 0.05). All cell lines migrated towards the chemokine CXCL12 at a level greater than the negative control (p < 0.05). All 5 cell lines pre-incubated with TN14003 prevented cellular migration towards chemokine CXCL12 (p < 0.01). TN14003 preferentially binds CXCR4 to native ligand CXCL12.</p> <p>Conclusion</p> <p>Interfering with the CXCR4/CXCL12 axis, using TN14003 was shown to effectively down regulate UM cell migration in vitro. Knowing that UM expresses the CXCR4 receptor, these CXCR4+ cells may be less likely to colonize distant organs that secrete the CXCL12 ligand, if treated with an inhibitor that binds CXCR4. Further studies should be pursued in order to test TN14003 efficacy in vivo.</p

Structure of Herpes Simplex Virus Glycoprotein D Bound to the Human Receptor Nectin-1

Binding of herpes simplex virus (HSV) glycoprotein D (gD) to a cell surface receptor is required to trigger membrane fusion during entry into host cells. Nectin-1 is a cell adhesion molecule and the main HSV receptor in neurons and epithelial cells. We report the structure of gD bound to nectin-1 determined by x-ray crystallography to 4.0 Å resolution. The structure reveals that the nectin-1 binding site on gD differs from the binding site of the HVEM receptor. A surface on the first Ig-domain of nectin-1, which mediates homophilic interactions of Ig-like cell adhesion molecules, buries an area composed by residues from both the gD N- and C-terminal extensions. Phenylalanine 129, at the tip of the loop connecting β-strands F and G of nectin-1, protrudes into a groove on gD, which is otherwise occupied by C-terminal residues in the unliganded gD and by N-terminal residues in the gD/HVEM complex. Notably, mutation of Phe129 to alanine prevents nectin-1 binding to gD and HSV entry. Together these data are consistent with previous studies showing that gD disrupts the normal nectin-1 homophilic interactions. Furthermore, the structure of the complex supports a model in which gD-receptor binding triggers HSV entry through receptor-mediated displacement of the gD C-terminal region