ABSTRACT
PURPOSE: The purpose of this study was to examine haemodynamic and arterial elasticity responses to aerobic exercise of varying durations. METHODS: Eighteen male subjects (age = 23·4 ± 2·0) performed a maximal aerobic fitness (VO2max ) test. Participants met in the laboratory following an overnight fast for three randomly assigned sessions. Assessments for large and small arterial elasticity (SAE), systemic vascular resistance (SVR), total vascular impedance (TVI), systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), stroke volume (SV), cardiac output (CO), pulse pressure (PP) and cardiac ejection time (CET) were performed using applanation tonometry at the radial artery. Following baseline measurements, participants executed aerobic exercise on a treadmill at 65% of their respective VO2max for 30, 45 or 60 min on three different occasions. Postexercise measurements were performed immediately, 10, 20 and 40 min postexercise cessation. RESULTS: The 60-min exercise bout resulted in significantly increased SAE values (P < 0·04) and decreased SVR values (P < 0·02) when compared with the 30-min exercise bout. The 60-min session also caused significantly higher HR values and significantly lower values for SV and DBP values following exercise (P < 0·04). CONCLUSIONS: The results of this study emphasize that varying the length of moderate-intensity aerobic exercise bouts affects arterial elasticity response and total vascular resistance.
Subject(s)
Arteries/physiology , Exercise Test/methods , Exercise/physiology , Vascular Resistance/physiology , Adult , Blood Pressure/physiology , Cardiac Output/physiology , Heart Rate/physiology , Hemodynamics/physiology , Humans , Male , Time Factors , Young AdultABSTRACT
Over 116 million people worldwide have chronic pain and prescription dependence. In the US, opioids account for the majority of overdose deaths, and in 2014, almost 2 million Americans abused or were dependent on prescription opioids. Genetic factors may play a key role in opioid prescription addiction. Herein, we describe genetic variations between opioid addicted and non-addicted populations and derive a predictive model determining risk of opioid addiction. This case cohort study compares the frequency of 16 single nucleotide polymorphisms involved in the brain reward pathways in patients with and without opioid addiction. Data from 37 patients with prescription opioid or heroin addiction and 30 age and gender matched controls were used to design the predictive score. The predictive score was then tested on an additional 138 samples to determine generalizabilty. Results for Method Derivation of Observed data: ROC statistic=0.92, sensitivity=82% (95% CI: 66-90), specificity=75% (95% CI:56-87). TreeNet "learn" data: ROC statistic=0.92, sensitivity=92%, specificity=90%, precision=92%, and overall correct=91%. Results of Generalizability data: Sensitivity=97% (95% CI: 90 to 100), specificity=87% (95% CI: 86 to 93), positive likelihood ratio=7.3 (95% CI: 4.0 to 13.5), and negative likelihood ratio=0.03 (95% CI: 0.01 to 0.13). This negative likelihood ratio can be used as an evidence based measure to exclude patients with a high risk of opioid addicition or substance use disorder. By identifying patients with a lower risk for opioid addiction, our model may inform therapeutic decisions.
Subject(s)
Genetic Markers , Heroin Dependence/genetics , Opioid-Related Disorders/genetics , Polymorphism, Single Nucleotide , Adult , Case-Control Studies , Cohort Studies , Female , Follow-Up Studies , Genetic Predisposition to Disease , Genotype , Heroin Dependence/diagnosis , Humans , Male , Opioid-Related Disorders/diagnosis , Prognosis , Risk FactorsABSTRACT
BACKGROUND: Frailty is associated with immune activation and inflammation in the elderly general population, but whether this is true in the younger HIV-infected (HIV+) population is not known. METHODS: We analyzed 24 serologic biomarkers of monocyte, T-cell, or B-cell activation in HIV- (n = 207) and HIV+ (n = 714; 75% virologically suppressed) men who have sex with men in the Multicenter AIDS Cohort Study (MACS) and were classified as frail or nonfrail according to expression or nonexpression of the frailty phenotype at 2 consecutive study visits. RESULTS: After correction for multiple comparisons and adjustment for age, race, study site, and education, frailty in HIV+ men was significantly (P < 0.002) associated with higher levels of sCD14, sIL2Rα, sTNF-R2, IL-6, and TNF-α; the association with higher levels of C-reactive protein (CRP) approached significance (P = 0.003). After further adjustment for body mass index (BMI), smoking, and comorbidities, only the association with C-reactive protein was significant at P < 0.002, with levels approximately 50% higher in frail compared with nonfrail men. These conclusions were not altered by restricting the analysis to HIV+ men who were virologically suppressed. Among HIV- men, none of these markers differed significantly by frailty. CONCLUSIONS: These data suggest that frailty in virologically suppressed HIV+ men was associated with immune activation beyond that due to treated HIV infection. The inflammatory markers associated with frailty were primarily products of activated monocytes/macrophages. Much, but not all, activation was accounted for by harmful behaviors and comorbidities. However, C-reactive protein, which is regulated by IL-6, was elevated in HIV+ frail men independent of these factors.
Subject(s)
Aging/immunology , HIV Seronegativity/immunology , HIV Seropositivity/immunology , HIV-1/immunology , Inflammation/immunology , Lymphocyte Activation/physiology , Antiretroviral Therapy, Highly Active/methods , Biomarkers/metabolism , Body Mass Index , C-Reactive Protein/metabolism , HIV-1/drug effects , Humans , Inflammation/drug therapy , Longitudinal Studies , Male , Middle Aged , United StatesABSTRACT
Age-related macular degeneration (AMD) is characterized by complex interactions between genetic and environmental factors. Here we genotyped the selected 25 single-nucleotide polymorphisms (SNPs) in 983 cases with advanced AMD and 271 cases with intermediate AMD and build an AMD life-risk score model for assessment of progression from intermediate to advanced AMD. We analyzed the performance of the prediction model for geographic atrophy progressors or choroidal neovascularization progressors versus non-progressors based on the 25 SNPs plus body mass index and smoking status. Our results suggest that a class prediction algorithm can be used for the risk assessment of progression from intermediate to late AMD stages. The algorithm could also be potentially applied for therapeutic response, and toward personalized care and precision medicine.
ABSTRACT
[This corrects the article DOI: 10.1038/sigtrans.2016.16.].
ABSTRACT
Pattern recognition receptors are preferentially expressed on APCs allowing selective uptake of pathogens for the initiation of antimicrobial immunity. In particular, C-type lectin receptors, including the mannose receptor (MR), facilitate APC-mediated adsorptive endocytosis of microbial glyconjugates. We have investigated the potential of antigenic targeting to the MR as a means to induce Ag-specific humoral and cellular immunity. hMR transgenic (hMR Tg) mice were generated to allow specific targeting with the anti-hMR Ab, B11. We show that hMR targeting induced both humoral and cellular antigenic specific immunity. Immunization of hMR Tg mice with B11 mAbs induced potent humoral responses independent of adjuvant. Injection of hMR Tg mice with mouse anti-hMR Ab clone 19.2 elicited anti-Id-specific humoral immunity while non-Tg mice were unresponsive. B11-OVA fusion proteins (B11-OVA) were efficiently presented to OVA-specific CD4 and CD8 T cells in MR Tg, but not in non-Tg, mice. Effector differentiation of responding T cells in MR Tg mice was significantly enhanced with concomitant immunization with the TLR agonist, CpG. Administration of both CpG and B11-OVA to hMR Tg mice induced OVA-specific tumor immunity while WT mice remained unprotected. These studies support the clinical development of immunotherapeutic approaches in cancer using pattern recognition receptor targeting systems for the selective delivery of tumor Ags to APCs.
Subject(s)
Antigens/immunology , Insulin-Like Growth Factor II/metabolism , Lectins, C-Type/metabolism , Mannose-Binding Lectins/metabolism , Melanoma, Experimental/immunology , Melanoma, Experimental/prevention & control , Receptors, Cell Surface/metabolism , Animals , Antibodies, Monoclonal/metabolism , Antibodies, Neoplasm/biosynthesis , Antigens/metabolism , Cross-Priming/genetics , Cross-Priming/immunology , Humans , Immunoglobulin G/biosynthesis , Lectins, C-Type/biosynthesis , Lectins, C-Type/genetics , Lectins, C-Type/immunology , Mannose Receptor , Mannose-Binding Lectins/biosynthesis , Mannose-Binding Lectins/genetics , Mannose-Binding Lectins/immunology , Melanoma, Experimental/metabolism , Mice , Mice, Inbred C57BL , Mice, Transgenic , Receptors, Cell Surface/biosynthesis , Receptors, Cell Surface/genetics , Receptors, Cell Surface/immunologyABSTRACT
Se evaluaron prospectivamente 50 historias clínicas en el mismo número de pacientes hospitalizados por status asmático. La edad media fue de 46ñ15 años y el tiempo de hospitalizacón 9ñ6 días. El pulso paradojal fue medido en 2 (4 por ciento) casos y el uso de musculatoria accesoria descrito en 4 (8 por ciento), asimismo la presencia de sibilantes en 50 (100 por ciento). No se practicaron pruebas funcionales respiratorias. Tres cuartas partes de la población recibió la modalidad terapéutica recomendada de esteroides sistémicos-ß2 agonistas-aminofilina. Los antibióticos estuvieron injustificadamente indicados en 25 (88 por ciento) casos y 27 (54 por ciento) pacientes tenían anotada la indicación de oxígeno en la hoja terapéutica. Al alta hospitalaria sólo 22 (44 por ciento) casos recibieron esteroides por vía oral y 5 (10 por ciento) ß2 agonistas en forma de inhalador. La muestra evaluada destaca deficiencias notables en el manejo y tratamiento intrahospitalario del status asmático que requieren ser enmendadas. Recomendamos diseñar un protocolo rígido de manejo para esta condición respiratoria
