Blood Flow and Vascular Conductance Responses to Dynamic Handgrip Exercise in Hispanic American and Non-Hispanic White Women

Hispanic Americans (HA) are the fastest growing ethnic minority in the United States, with disproportionately higher incidence of obesity, hyperlipidemia and type 2 diabetes compared to their non-Hispanic white (NHW) counterparts. As such, the risk of cardiovascular complications is significantly higher in this population, while the underlying mechanisms remain largely unexplored. Alterations in vascular function occur early in cardiovascular diseases and have not been comprehensively studied in the HA population. Previous studies have demonstrated higher flow-mediated dilation (FMD, an index of resting vascular function) in young HA compared to NHW women. However, whether these differences in vasodilation also occur in response to dynamic exercise remains unknown. PURPOSE: We tested the hypothesis that during increasing intensities of rhythmic handgrip exercise, young, healthy HA women would demonstrate greater forearm blood flow and vascular conductance responses compared to age- and weight-matched NHW women. METHODS: Six HA women (20 ± 2 yr; BMI = 21.45 ± 2.2 kg/m2) and 9 NHW women (20 ± 2 yr; BMI = 21.49 ± 2.2 kg/m2) performed rhythmic handgrip exercise for 3 minutes at 15%, 30%, and 45% of their maximum voluntary contraction (MVC). Each exercise bout was separated by at least 10 minutes of rest. Mean arterial pressure (MAP; finger photoplethysmography), heart rate (ECG), and forearm blood flow (FBF; duplex Doppler ultrasound) was measured at rest and during the last minute of rhythmic exercise. Forearm vascular conductance was calculated as FBF/MAP. RESULTS: Baseline FBF (HA: 53.3 ± 7.6 and NHW: 52.4 ± 11.3 ml/min, mean ± SD, p = 0.87), FVC (HA: 0.64 ± 0.09 and NHW: 0.62 ± 0.16 ml/min/mmHg, p = 0.85), MAP (HA: 83.3 ± 3.18 and NHW: 84.75 ± 6.85 mmHg, p = 0.64), and MVC (HA: 53 ± 13 and NHW: 49 ± 6 kg, p = 0.36) were similar between groups. In response to exercise, both groups demonstrated an intensity dependent increase in FBF (%DFBF during 45%: HA= 437± 90% and NHW= 459 ± 162%, p = 0.76) but no significant difference was found between groups (repeated-measures 2-way ANOVA; interaction effect: p = 0.66, intensity effect: p = 0.0001, ethnicity effect: p = 0.73). Similar to FBF, there was no significant difference in FVC responses between groups (%DFVC 45%: HA= 385 ± 110 and NHW= 393 ± 135, p = 0.91). CONCLUSION: Forearm blood flow and vascular conductance responses during increasing intensities of rhythmic handgrip exercise were not different between HA and NHW women

Forearm Vascular Responses to Rhythmic Handgrip Exercise in Young Healthy Hispanic Men

Hispanic American (HA) men have higher prevalence of Type 2 Diabetes (T2D) when compared to Caucasian American (CA) men (15.3% vs 10.8%). Impaired vascular function is a hallmark of T2D, increasing the risk of cardiovascular morbidity and mortality in this clinical population. However, vascular function in the Hispanic population has not been investigated thoroughly. To date, only two studies have examined the resting flow mediated dilation (FMD) and found a higher FMD in young, healthy, HA adults. Whether exercise-induced reactive hyperemia is preserved in HA adults remains unknown. PURPOSE: We tested the hypothesis that young, healthy HA men would have a higher response in forearm blood flow (FBF) and forearm vascular conductance (FVC) when compared to age-matched CA men. METHODS: In young, healthy HA (n = 7, BMI = 25±2 cm/kg2) and CA men (n = 6, BMI = 24±3), FBF (Duplex doppler ultrasound), heart rate (3-lead ECG), and mean arterial pressure (MAP; finger plethysmography) were measured at rest and during rhythmic handgrip exercise performed for 3 min at 15%, 30%, and 45% of their maximum voluntary contraction (MVC). FVC was calculated by FBF/MAP. Lean muscle mass was measured via dual-energy X-ray absorptiometry (DEXA). RESULTS: Baseline MAP (HA: 85±7 mmHg, CA: 84±7, Mean ± SD, p = 0.85), and MVC (HA: 74 ± 18 kg, CA: 80 ± 17, p = 0.51) were not significantly different between the groups at baseline. Baseline FBF (HA: 83.9±21.9 mL/min, CA: 135.5±39.7, p\u3c0.05) and FVC (HA: 1.0 ± 0.3 mL/min/mmHg, CA: 1.6 ± 0.5, p \u3c 0.05) were significantly greater in CA when compared to HA. In both groups, an intensity dependent increase in FBF and FVC was observed with a significant ethnicity effect between the groups but no significant interaction effect (repeated-measures 2-way ANOVA; interaction effect: p = 0.63, intensity effect: p \u3c 0.01, ethnicity effect: p = 0.006). For example, increase in FVC from baseline (%DFVC) at 45% MVC in HA men was 442 ± 82%, compared to 311 ± 97% CA men, with similar increases in MAP from baseline (45% MVC DMAP; HA: 15 ± 12, CA: 7 ± 5, p = 0.17) or lean muscle mass (HA: 57 ± 4 kg, CA: 61 ± 9 kg, p = 0.41). CONCLUSION: Our preliminary data indicate a higher forearm blood flow and vascular conductance response in response to rhythmic handgrip in HA men compared to matched CA men

MLK Historic District: 493 Auburn Ave. NE

Prepared by the Fall 2010 Conservation of Historic Building Materials class. This Historic Structure Report contains the history of the three double-shotgun houses located at 493 Auburn Avenue built by Alexander Daniel Hamilton and his father, Alexander Hamilton, African-American father-and-son builders. The existing conditions of the interior, exterior, infrastructure, and grounds of the buildings are detailed, as well as a master plan of recommendations for the site. The purpose of this report is to provide a current assessment of the condition of the property, recommendations for needed repairs and options for future consideration.https://scholarworks.gsu.edu/history_heritagepreservation/1052/thumbnail.jp

Strategy Escalation: An emerging paradigm for safe clinical development of T cell gene therapies

Gene therapy techniques are being applied to modify T cells with chimeric antigen receptors (CARs) for therapeutic ends. The versatility of this platform has spawned multiple options for their application with new permutations in strategies continually being invented, a testimony to the creative energies of many investigators. The field is rapidly expanding with immense potential for impact against diverse cancers. But this rapid expansion, like the Big Bang, comes with a somewhat chaotic evolution of its therapeutic universe that can also be dangerous, as seen by recently publicized deaths. Time-honored methods for new drug testing embodied in Dose Escalation that were suitable for traditional inert agents are now inadequate for these novel "living drugs". In the following, I propose an approach to escalating risk for patient exposures with these new immuno-gene therapy agents, termed Strategy Escalation, that accounts for the molecular and biological features of the modified cells and the methods of their administration. This proposal is offered not as a prescriptive but as a discussion framework that investigators may wish to consider in configuring their intended clinical applications

Nicotine exploits a COPI-mediated process for chaperone-mediated up-regulation of its receptors

Chronic exposure to nicotine up-regulates high sensitivity nicotinic acetylcholine receptors (nAChRs) in the brain. This up-regulation partially underlies addiction and may also contribute to protection against Parkinson’s disease. nAChRs containing the α6 subunit (α6* nAChRs) are expressed in neurons in several brain regions, but comparatively little is known about the effect of chronic nicotine on these nAChRs. We report here that nicotine up-regulates α6* nAChRs in several mouse brain regions (substantia nigra pars compacta, ventral tegmental area, medial habenula, and superior colliculus) and in neuroblastoma 2a cells. We present evidence that a coat protein complex I (COPI)-mediated process mediates this up-regulation of α6* or α4* nAChRs but does not participate in basal trafficking. We show that α6β2β3 nAChR up-regulation is prevented by mutating a putative COPI-binding motif in the β3 subunit or by inhibiting COPI. Similarly, a COPI-dependent process is required for up-regulation of α4β2 nAChRs by chronic nicotine but not for basal trafficking. Mutation of the putative COPI-binding motif or inhibition of COPI also results in reduced normalized Förster resonance energy transfer between α6β2β3 nAChRs and εCOP subunits. The discovery that nicotine exploits a COPI-dependent process to chaperone high sensitivity nAChRs is novel and suggests that this may be a common mechanism in the up-regulation of nAChRs in response to chronic nicotine

A reference library for Canadian invertebrates with 1.5 million barcodes, voucher specimens, and DNA samples

The synthesis of this dataset was enabled by funding from the Canada Foundation for Innovation, from Genome Canada through Ontario Genomics, from NSERC, and from the Ontario Ministry of Research, Innovation and Science in support of the International Barcode of Life project. It was also enabled by philanthropic support from the Gordon and Betty Moore Foundation and from Ann McCain Evans and Chris Evans. The release of the data on GGBN was supported by a GGBN – Global Genome Initiative Award and we thank G. Droege, L. Loo, K. Barker, and J. Coddington for their support. Our work depended heavily on the analytical capabilities of the Barcode of Life Data Systems (BOLD, www.boldsystems.org). We also thank colleagues at the CBG for their support, including S. Adamowicz, S. Bateson, E. Berzitis, V. Breton, V. Campbell, A. Castillo, C. Christopoulos, J. Cossey, C. Gallant, J. Gleason, R. Gwiazdowski, M. Hajibabaei, R. Hanner, K. Hough, P. Janetta, A. Pawlowski, S. Pedersen, J. Robertson, D. Roes, K. Seidle, M. A. Smith, B. St. Jacques, A. Stoneham, J. Stahlhut, R. Tabone, J.Topan, S. Walker, and C. Wei. For bioblitz-related assistance, we are grateful to D. Ireland, D. Metsger, A. Guidotti, J. Quinn and other members of Bioblitz Canada and Ontario Bioblitz. For our work in Canada’s national parks, we thank S. Woodley and J. Waithaka for their lead role in organizing permits and for the many Parks Canada staff who facilitated specimen collections, including M. Allen, D. Amirault-Langlais, J. Bastick, C. Belanger, C. Bergman, J.-F. Bisaillon, S. Boyle, J. Bridgland, S. Butland, L. Cabrera, R. Chapman, J. Chisholm, B. Chruszcz, D. Crossland, H. Dempsey, N. Denommee, T. Dobbie, C. Drake, J. Feltham, A. Forshner, K. Forster, S. Frey, L. Gardiner, P. Giroux, T. Golumbia, D. Guedo, N. Guujaaw, S. Hairsine, E. Hansen, C. Harpur, S. Hayes, J. Hofman, S. Irwin, B. Johnston, V. Kafa, N. Kang, P. Langan, P. Lawn, M. Mahy, D. Masse, D. Mazerolle, C. McCarthy, I. McDonald, J. McIntosh, C. McKillop, V. Minelga, C. Ouimet, S. Parker, N. Perry, J. Piccin, A. Promaine, P. Roy, M. Savoie, D. Sigouin, P. Sinkins, R. Sissons, C. Smith, R. Smith, H. Stewart, G. Sundbo, D. Tate, R. Tompson, E. Tremblay, Y. Troutet, K. Tulk, J. Van Wieren, C. Vance, G. Walker, D. Whitaker, C. White, R. Wissink, C. Wong, and Y. Zharikov. For our work near Canada’s ports in Vancouver, Toronto, Montreal, and Halifax, we thank R. Worcester, A. Chreston, M. Larrivee, and T. Zemlak, respectively. Many other organizations improved coverage in the reference library by providing access to specimens – they included the Canadian National Collection of Insects, Arachnids and Nematodes, Smithsonian Institution’s National Museum of Natural History, the Canadian Museum of Nature, the University of Guelph Insect Collection, the Royal British Columbia Museum, the Royal Ontario Museum, the Pacifc Forestry Centre, the Northern Forestry Centre, the Lyman Entomological Museum, the Churchill Northern Studies Centre, and rare Charitable Research Reserve. We also thank the many taxonomic specialists who identifed specimens, including A. Borkent, B. Brown, M. Buck, C. Carr, T. Ekrem, J. Fernandez Triana, C. Guppy, K. Heller, J. Huber, L. Jacobus, J. Kjaerandsen, J. Klimaszewski, D. Lafontaine, J-F. Landry, G. Martin, A. Nicolai, D. Porco, H. Proctor, D. Quicke, J. Savage, B. C. Schmidt, M. Sharkey, A. Smith, E. Stur, A. Tomas, J. Webb, N. Woodley, and X. Zhou. We also thank K. Kerr and T. Mason for facilitating collections at Toronto Zoo and D. Iles for servicing the trap at Wapusk National Park. This paper contributes to the University of Guelph’s Food from Thought research program supported by the Canada First Research Excellence Fund. The Barcode of Life Data System (BOLD; www.boldsystems.org)8 was used as the primary workbench for creating, storing, analyzing, and validating the specimen and sequence records and the associated data resources48. The BOLD platform has a private, password-protected workbench for the steps from specimen data entry to data validation (see details in Data Records), and a public data portal for the release of data in various formats. The latter is accessible through an API (http://www.boldsystems.org/index.php/resources/api?type=webservices) that can also be controlled through R75 with the package ‘bold’76.Peer reviewedPublisher PD

Pre-diagnostic circulating insulin-like growth factor-I and bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition

Previous in vitro and case–control studies have found an association between the insulin‐like growth factor (IGF)‐axis and bladder cancer risk. Circulating concentrations of IGF‐I have also been found to be associated with an increased risk of several cancer types; however, the relationship between pre‐diagnostic circulating IGF‐I concentrations and bladder cancer has never been studied prospectively. We investigated the association of pre‐diagnostic plasma concentrations of IGF‐I with risk of overall bladder cancer and urothelial cell carcinoma (UCC) in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 843 men and women diagnosed with bladder cancer between 1992 and 2005 were matched with 843 controls by recruitment centre, sex, age at recruitment, date of blood collection, duration of follow‐up, time of day and fasting status at blood collection using an incidence density sampling protocol. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression with adjustment for smoking status. No association was found between pre‐diagnostic circulating IGF‐I concentration and overall bladder cancer risk (adjusted OR for highest versus lowest fourth: 0.91, 95% CI: 0.66–1.24, ptrend = 0.40) or UCC (n of cases = 776; 0.91, 0.65–1.26, ptrend = 0.40). There was no significant evidence of heterogeneity in the association of IGF‐I with bladder cancer risk by tumour aggressiveness, sex, smoking status, or by time between blood collection and diagnosis (pheterogeneity > 0.05 for all). This first prospective study indicates no evidence of an association between plasma IGF‐I concentrations and bladder cancer risk

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a non-neoplastic pulmonary disease that is characterized by the formation of scar tissue within the lungs in the absence of any known provocation. IPF is a rare disease which affects approximately 5 million persons worldwide. The prevalence is estimated to be slightly greater in men (20.2/100,000) than in women (13.2/100,000). The mean age at presentation is 66 years. IPF initially manifests with symptoms of exercise-induced breathless and dry coughing. Auscultation of the lungs reveals early inspiratory crackles, predominantly located in the lower posterior lung zones upon physical exam. Clubbing is found in approximately 50% of IPF patients. Cor pulmonale develops in association with end-stage disease. In that case, classic signs of right heart failure may be present. Etiology remains incompletely understood. Some environmental factors may be associated with IPF (cigarette smoking, exposure to silica and livestock). IPF is recognized on high-resolution computed tomography by peripheral, subpleural lower lobe reticular opacities in association with subpleural honeycomb changes. IPF is associated with a pathological lesion known as usual interstitial pneumonia (UIP). The UIP pattern consists of normal lung alternating with patches of dense fibrosis, taking the form of collagen sheets. The diagnosis of IPF requires correlation of the clinical setting with radiographic images and a lung biopsy. In the absence of lung biopsy, the diagnosis of IPF can be made by defined clinical criteria that were published in guidelines endorsed by several professional societies. Differential diagnosis includes other idiopathic interstitial pneumonia, connective tissue diseases (systemic sclerosis, polymyositis, rheumatoid arthritis), forme fruste of autoimmune disorders, chronic hypersensitivity pneumonitis and other environmental (sometimes occupational) exposures. IPF is typically progressive and leads to significant disability. The median survival is 2 to 5 years from the time of diagnosis. Medical therapy is ineffective in the treatment of IPF. New molecular therapeutic targets have been identified and several clinical trials are investigating the efficacy of novel medication. Meanwhile, pulmonary transplantation remains a viable option for patients with IPF. It is expected that, during the next decade, considerable progress will be made toward the understanding and treatment of this devastating illness