Giant increase in the metal-enhanced fluorescence of organic molecules in nanoporous alumina templates and large molecule-specific red/blue-shift of the fluorescence peak.

The fluorescence of organic fluorophore molecules is enhanced when they are placed in contact with certain metals (Al, Ag, Cu, Au, etc.) whose surface plasmon waves couple into the radiative modes of the molecules and increase the radiative efficiency. Here, we report a hitherto unknown size dependence of this metal-enhanced fluorescence (MEF) effect in the nanoscale. When the molecules are deposited in nanoporous anodic alumina films with exposed aluminum at the bottom of the pores, they form organic nanowires standing on aluminum nanoparticles whose plasmon waves have much larger amplitudes. This increases the MEF strongly, resulting in several orders of magnitude increase in the fluorescence intensity of the organic fluorophores. The increase in intensity shows an inverse superlinear dependence on nanowire diameter because the nanowires also act as plasmonic "waveguides" that concentrate the plasmons and increase the coupling of the plasmons with the radiative modes of the molecules. Furthermore, if the nanoporous template housing the nanowires has built-in electric fields due to space charges, a strong molecule-specific red- or blue-shift is induced in the fluorescence peak owing to a renormalization of the dipole moment of the molecule. This can be exploited to detect minute amounts of target molecules in a mixture using their optical signature (fluorescence) despite the presence of confounding background signals. It can result in a unique new technology for biosensing and chemical sensing.

Quantifying Recruitment Source and Participant Communication Preferences for Alzheimer's Disease Prevention Research.

BACKGROUND: Evidence on effective engagement of diverse participants in AD prevention research is lacking. OBJECTIVES: To quantify recruitment source in relation to race, ethnicity, and retention. DESIGN: Prospective cohort study. SETTING: University lab. PARTICIPANTS: Participants included older adults (N=1170) who identified as White (86%), Black (8%), and Hispanic/Latino ethnicity (6%). MEASUREMENTS: The Cognitive Aging Lab Marketing Questionnaire assessed recruitment source, social media use, and research opportunity communication preferences. RESULTS: Effective recruitment methods and communication preferences vary by race and ethnicity. The most common referral sources were postcards for racial minorities, friend/family referrals for Hispanic/Latinos, and the newspaper for Whites. Whereas Whites preferred email communications, Hispanic/Latinos preferred texts. CONCLUSIONS: Recruiting diverse samples in AD prevention research is clinically relevant given high AD-risk of minorities and that health disparities are propagated by their under-representation in research. Our questionnaire and these results may be applied to facilitate effective research engagement.

Cognitive speed of processing and functional declines in older cancer survivors: an analysis of data from the ACTIVE trial.

It has been suggested that chemotherapy treatment for cancer may contribute to cognitive decline in older cancer survivors. This issue is particularly important given that subtle cognitive impairment, particularly in cognitive processing speed, can affect functional status and quality of life for older adults. Multivariate regression of data from a longitudinal randomized controlled trial of older adults revealed a trend towards decreased performance after cancer treatment with chemotherapy on several functional measures associated with processing speed (as compared with matched individuals who did not have cancer). Additional analyses revealed that a subset of the chemotherapy-treated adults demonstrated a reliable negative change on several measures of processing speed. While inconclusive, this hypothesis generating work suggests that cognitive dysfunction following cancer treatment may contribute to disability observed in older cancer survivors. Further research is needed to determine the significance of the relationship between cognitive and functional impairment in older cancer survivors.

Motor sequence chunking is impaired by basal ganglia stroke.

Our main aim was to determine whether individuals with stroke that affected the basal ganglia, organized movement sequences into chunks in the same fashion as neurologically intact individuals. To address this question, we compared motor response times during the performance of repeated sequences that were learned, and thus may be planned in advance, with random sequences where there is minimal if any advance preparation or organization of responses. The pattern of responses illustrated that, after basal ganglia stroke, individuals do not chunk elements of the repeated sequence into functional sub-sequences of movement to the same extent as neurologically intact age-matched people. Limited chunking of learned movements after stroke may explain past findings that show overall slower responses even when sequences of action are learned by this population. Further, our data in combination with other work, suggest that chunking may be a function of the basal ganglia.

Hyperalgesia induced by naloxone follows diurnal rhythm in responsivity to painful stimuli.

A diurnal rhythm was observed in the responsiveness of mice to nociceptive stimuli and in the hyperalgesic activity of endogenous opioid peptides and may partly account for previous controversy over the direct action of naloxone in opiate-naive animals.

Dual actions of substance P on nociception: possible role of endogenous opioids.

Substance P produces analgesia when administered to mice in very small doses by the intraventricular route (1.25 to 5 nanograms per mouse). The analgesic effect can be blocked by naloxone. At higher doses (greater than 50 nanograms per mouse), this activity is lost. At these higher doses, however, substance P produced hyperalgesia when combined with naloxone and analgesia when combined with baclofen [beta-(4-chlorophenyl)-gamma-aminobutyric acid]. Substance P may have dual actions in brain, releasing endorphins at very low doses and directly exciting neuronal activity in nociceptive pathways at higher doses.

Ricebase: a breeding and genetics platform for rice, integrating individual molecular markers, pedigrees and whole-genome-based data.

Ricebase (http://ricebase.org) is an integrative genomic database for rice (Oryza sativa) with an emphasis on combining datasets in a way that maintains the key links between past and current genetic studies. Ricebase includes DNA sequence data, gene annotations, nucleotide variation data and molecular marker fragment size data. Rice research has benefited from early adoption and extensive use of simple sequence repeat (SSR) markers; however, the majority of rice SSR markers were developed prior to the latest rice pseudomolecule assembly. Interpretation of new research using SNPs in the context of literature citing SSRs requires a common coordinate system. A new pipeline, using a stepwise relaxation of stringency, was used to map SSR primers onto the latest rice pseudomolecule assembly. The SSR markers and experimentally assayed amplicon sizes are presented in a relational database with a web-based front end, and are available as a track loaded in a genome browser with links connecting the browser and database. The combined capabilities of Ricebase link genetic markers, genome context, allele states across rice germplasm and potentially user curated phenotypic interpretations as a community resource for genetic discovery and breeding in rice.

The World Veterinary Association and animal welfare.

The World Veterinary Association, as the global representative of the veterinary profession, recognises the global influences on animal welfare and the changing role of the veterinarian in response to the changing attitudes of the human population. While urban populations are now dictating animal welfare standards, many practices still have a cultural and even religious basis. Veterinarians recognise these influences, but base their recommendations for animal welfare on scientifically justified practices. Veterinarians work not only for urban clients with their companion animals, but also very importantly with rural clients who provide the source of animal-based foodstuffs and goods sought by an increasingly demanding human population. The controversial areas of intensive animal production and the transportation that is required to move large numbers of animals around the world require veterinary supervision to ensure that animal welfare is preserved. The development of animal welfare standards is an ongoing process, with the major international effort being led by the World Organisation for Animal Health.

Relationship of ECMO duration with outcomes after pediatric cardiac surgery: a multi-institutional analysis.

BACKGROUND: There are very sparse data on the outcomes of children receiving prolonged extracorporeal membrane oxygenation (ECMO) after cardiac surgery. This study was aimed to evaluate the association of ECMO duration with outcomes in children undergoing surgery for congenital heart disease using the Pediatric Health Information System (PHIS) database. METHODS: Patients aged ≤18 years receiving ECMO after pediatric cardiac surgery (with or without cardiopulmonary bypass) at a PHIS-participating hospital (2004-2013) were included. De-identified data obtained from retrospective, observational dataset included demographic information, baseline characteristics, pre-ECMO risk factors, operation details, patient diagnoses, and center data. Outcomes evaluated included in-hospital mortality, length of mechanical ventilation, length of ICU stay, length of hospital stay, and hospital charges. Cox proportional hazards models were fitted to study the probability of study outcomes as a function of ECMO duration. RESULTS: Nine hundred ninety-eight patients from 37 hospitals qualified for inclusion. The median duration of ECMO run was 4 days (IQR: 1.7). After adjusting for patient and center characteristics, there was 12% increase in the odds of mortality for every 24 hours increase in ECMO duration (OR: 1.12, 95% CI: 1.07-1.18, P<0.001). Patients receiving longer duration of ECMO were associated with longer length of mechanical ventilation, longer length of ICU stay, longer length of hospital stay, and higher hospital charges. CONCLUSION: Data from this large multicenter database suggest that longer duration of ECMO support after pediatric cardiac surgery is associated with worsening outcomes.

Functional and morphological assessment of rat aorta stored in University of Wisconsin and Eurocollins solutions.

University of Wisconsin (UW) and Eurocollins (EC) solutions are widely used for preservation of organs before transplantation. However, effect of storage solutions on vascular interface for transplant success is not known. In this study, we have used rat aorta as a model and assessed the effects of cold storage in UW and EC solutions on smooth muscle and endothelial function and the morphology. Smooth muscle and endothelial functions of the rat aorta were assessed using in vitro isometric tension measurement. Morphologic studies were done with scanning and transmission electron microscopy. No significant difference in contractile response to either norepinephrine (NE) or potassium chloride was observed between control aorta and aorta stored in UW solution for 1 hr or 24 hr. In contrast, sensitivity, but not the reactivity to NE and KCl, was increased in aorta stored in EC solution for 1 hr. If the tissues were stored in EC solution for 24 hr, both sensitivity and reactivity to NE and KCl were significantly reduced. Relaxatory response to acetylcholine, in endothelium-intact vessels were reduced in aortas stored in EC solution, but not in UW solution. The magnitude of relaxations observed in tissues stored in the EC solution for 24 hr was less than in tissues stored for 1 hr. Sodium nitroprusside elicited similar relaxatory response in endothelium-denuded control tissue and in tissues stored in UW and EC solution. Electron microscopy data revealed marked swelling of the cell, loss of mitochondria and other intracellular organelles, and striking calcium deposits after preservation of the vessels in EC for 1 or 24 hr. In aorta stored in UW solution for 24 hr, endothelial and smooth muscle cells were intact, with moderate-size vacuoles in the cytoplasm. These results suggest that the UW solution is more suitable than EC solution for short-term preoperative storage of blood vessels.

Hemodynamic and oxygen transport variables in cardiogenic shock secondary to acute myocardial infarction, and response to treatment.

There are few data on oxygen transport in cardiogenic shock after acute myocardial infarction. This prospective study examined oxygen transport variables in 19 such patients and assessed their responses to treatment. Femoral and pulmonary arterial catheters were inserted before any therapy except correction of hypoxemia by mechanical ventilation in 8 patients, defibrillation (3 patients) or pacing (5 patients). In 3 patients mean arterial pressure was greater than 80 mm Hg and cardiac index greater than 2.1 liters/min/m2 with normal mixed venous oxygen saturation despite simultaneous clinical shock. They recovered with no further treatment. Sixteen patients were treated with varying combinations of intravenous fluids and dobutamine (37 +/- 25 mu/kg/min) and 14 survived long enough for a second set of measurements to be completed. Mean heart rate increased from 83 +/- 22 to 101 +/- 20 beats/min and mean cardiac index from 1.4 +/- 0.5 to 2.5 +/- 0.4 liters/min/m2 (p less than 0.001). Oxygen consumption (VO2) was maintained even when oxygen delivery (DO2) was less than 330 ml/min/m2. After treatment DO2 increased from 230 +/- 69 to 397 +/- 60 ml/min/m2 (p less than 0.001) and VO2 from 103 +/- 31 to 124 +/- 27 ml/min/m2 (p less than 0.05). Mean mixed venous oxygen saturation increased from 54 +/- 16 to 69 +/- 8% (p less than 0.001) and mean oxygen extraction ratio decreased from 48 +/- 16 to 31 +/- 6% (p less than 0.001). There was no correlation between cuff systolic blood pressure and mean arterial pressure before or after resuscitation. Thirteen patients survived to hospital discharge. When cardiogenic shock responds to treatment, large increases in DO2 lead to small increases in VO2 but large increases in mixed venous oxygen saturation, reflecting improved tissue oxygen availability.

Measurement of oxygen consumption after uncomplicated acute myocardial infarction.

BACKGROUND: Oxygen consumption (VO2) has been shown to be decreased after acute myocardial infarction (AMI) complicated by cardiogenic shock. STUDY OBJECTIVE: To evaluate early measurement of VO2 by indirect calorimetry after an uncomplicated AMI (UAMI). STUDY DESIGN: Prospective nonrandomized case study. SETTING: Emergency department of a large urban hospital. PARTICIPANTS AND INTERVENTIONS: Twenty-six consecutive patients presenting with confirmed UAMI. VO2 was measured by indirect calorimetry (Deletrac, Datex Ins,) which is noninvasive. All patients received buccal or intravenous nitroglycerin and thrombolytic therapy, and none received opiates before VO2 measurement. RESULTS: Two groups of patients were identified by subsequent development of cardiogenic shock. Group 1 did not develop cardiogenic shock, and group 2 developed shock within 24 h of admission. Group 1 (n = 22) had a significantly higher VO2 compared to group 2 (n = 4), mean 154(SD 25) vs mean 100(SD 13) ml/min.m2, p < 0.002. Group 1 had a significantly higher increase in basal metabolic rate than group 2, mean 30 percent (SD 11) vs mean 10(SD 15) percent, p < 0.007. There was no significant difference in age, heart rate (HR), shock index (SI), or rate-pressure product (RPP) between groups 1 and 2. All patients in group 2 developed cardiogenic shock despite thrombolytic therapy, and two died within 24 h of admission. CONCLUSION: VO2 is increased in UAMI and represents increased metabolic demands of peripheral tissues and not cardiac oxygen uptake. A reduction in VO2 (< 100 ml/min.m2) after AMI may be an early predictor of subsequent development of cardiogenic shock. Measurement of VO2 in UAMI by indirect calorimetry in the emergency department may be of value to identify patients at high risk and could influence their management.

The haemodynamic effects of sublingual nitroglycerin spray in severe left ventricular failure.

The use of sublingual nitroglycerin spray has been studied in twenty patients referred to our Intensive Care Unit for further treatment of severe left ventricular failure. Within five minutes of spray administration significant falls in pulmonary artery occlusion pressure, mean arterial pressure, heart rate, right atrial pressure and systemic vascular resistance occurred. Similarly significant increases in cardiac index, stroke volume index and left ventricular stroke work index were found. These results show a considerable improvement in the haemodynamic parameters of invasively monitored patients and we believe that its administration undoubtedly "buys time" for the critically ill patient. However, we would caution against its routine use at present in view of the potential problem of hypotension, until further information is available.

Short-term preservation of autogenous vein grafts: effectiveness of University of Wisconsin solution.

BACKGROUND: Suboptimal preservation of autologous veins in storage solutions causes endothelial cell damage that can contribute to graft failure. The purpose of this study was to compare the effects of short-term storage of veins in autologous whole blood (AWB), 0.9% normal saline solution (NS), and University of Wisconsin solution (UWs) on vein structure and function after grafting. METHODS: Autogenous jugular and femoral veins were atraumatically harvested from mongrel dogs. One vein segment was immediately implanted to serve as a control, and the other segments were stored for 45 minutes in AWB, NS, or UWs. The veins were implanted as reversed interposition graft in the carotid or femoral arteries. After 6 weeks light and scanning electron microscopy and isometric tension studies were performed on explanted vein grafts. RESULTS: Morphologic studies revealed an intact endothelium that stained positively for factor VIII. Intimal thickness was similar between controls (48 +/- 12 microns) and veins stored in UWs (53 +/- 8 microns) (p = not significant), but it was significantly increased in veins stored in AWB (151 +/- 29 microns) and NS (149 +/- 18 microns) (p < 0.05). Sensitivity and maximum contraction to norepinephrine were not altered in veins preserved in UWs (6.0 +/- 0.1 mumol/L and 0.19 +/- 0.02 gm/mm2) but were significantly reduced (p < 0.05) in those stored in AWB (7.2 +/- 0.1 mumol/L and 0.08 +/- 0.02 gm/mm2) and NS (7.0 +/- 0.3 mumol/L and 0.09 +/- 0.02 gm/mm2) compared with controls (5.9 +/- 0.2 mumol/L and 0.20 +/- 0.02 gm/mm2). The sensitivity and maximum relaxation to acetylcholine and sodium nitroprusside of veins preserved in AWB, NS, and UWs were similar to controls (p = not significant). CONCLUSIONS: Vein storage in UWs preserves smooth muscle cell function compared with veins stored in NS or AWB. Therefore UWs is a more suitable medium for short-term preservation of veins in cardiovascular operation.

Technique for assessment of leukocyte adherence to human umbilical vein endothelial cell monolayers.

The interaction between endothelial cells and immune/inflammatory cells plays an important role in the pathogenesis of vascular diseases. Inflammatory cells also activate endothelial cells and release both proliferative and cytotoxic mediators. In order to examine the interaction between leukocytes and endothelial cells and the effect of various drugs, we established the methodology for isolating and culturing the endothelial cells from human umbilical vein. Endothelial cells were harvested by using 0.1% collagenase within 48 hr of collecting the cord. Cells were grown to confluency in 96-well plates in Medium 199 containing 20% fetal calf serum, endothelial cell growth supplement, heparin, and antibiotics. Using this method, we obtained a confluent layer of the cells in all the 96 wells within 48 hr. We then examined the effect of peptides, endothelin-1, substance P, and neurokinin-A on the adherence of human blood neutrophils (purity and viability > 98%) to endothelial monolayers. All the peptides enhanced (p < 0.05) the adherence of neutrophils to endothelial cells in a time-dependent manner. This method of endothelial cell culturing is reliable, reproducible, and effective in evaluating the role of various mediators and drugs on the adherence of various white blood cells to endothelium.

Effect of endothelin-1 on arterial response to Bay K 8644. A comparison of ischemic and nonischemic arteries.

Endothelin-1 (ET-1) has been proposed as one of the possible mediators of the vasoconstriction seen following ischemia and reperfusion. We investigated the effect of ischemia and reperfusion on the contractile response of canine renal and iliac arteries to the dihydropyridine-type calcium channel agonist (+/-)Bay K 8644, following subthreshold doses of ET-1. No significant difference in the maximum tension was observed between the ischemic and nonischemic arteries in response to Bay K 8644 in the absence of ET-1. The addition of subthreshold dose of ET-1 (10(-10) M) resulted in a significant increase in sensitivity to Bay K 8644 in both the ischemic-reperfused and non-ischemic-reperfused arteries, with a 38 fold increase in iliac arteries and about 8 fold increase in the renal arteries. However, the ET-1 potentiated response was enhanced in the ischemic-reperfused in comparison to the non-ischemic-reperfused vessels in the iliac artery. These data suggest that the potentiating mechanism of ET-1 is not only intact, but enhanced in ischemic-reperfused vessels. Since the enhanced release of ET-1 in vivo is preceded by ischemia and reperfusion, the vasospastic phenomenon observed following these events could well be mediated by ET-1.

Shock index: a re-evaluation in acute circulatory failure.

STUDY OBJECTIVE: To evaluate the relationship between the shock index SI (ratio of heart rate to systolic arterial pressure) and cardiac function and oxygen transport in an experimental model of hemorrhage and clinical septic shock. METHODS AND RESULTS: This study was conducted in a hypovolemic circulatory failure model; 40% hemorrhage in the anesthetized pig and normovolemic hyperdynamic septic patients in the intensive care unit (ICU). Hemodynamic and oxygen transport variables were measured and their relationships to SI was examined. SI was inversely related to blood loss, cardiac index (CI), stroke volume (SV), mean arterial pressure (MAP) and left ventricular stroke work (LVSW) (r = -0.73, -0.75, -0.89 and -0.75, respectively P less than 0.01) following hemorrhage in the anesthetized pig. Oxygen transport variables, i.e. oxygen delivery (DO2) and mixed venous oxygen saturation (SvO2P) (r = -0.68 and -0.74, respectively, P less than 0.01) were also inversely related to the SI. Oxygen consumption (VO2) increased initially with increasing SI and fell when SI was greater than 3.0. In clinical septic shock and following blood volume expansion, the SI was not correlated to CI, SVI, MAP or systemic vascular resistance (SVR) (r = -0.01, -0.47, -0.34 and -0.14, respectively, P-value NS) but was inversely related to LVSWI (r = -0.68, P less than 0.01). There were no relationships between the SI and oxygen transport variables (DO2, SvO2) (r = -0.02 and -0.17, P-value NS) in septic shock. CONCLUSION: SI provides a non-invasive means to monitor deterioration or recovery of LVSW during acute hypovolemic and normovolemic circulatory failure and its therapy. SI may be of limited value in the assessment of systemic oxygen transport and response to therapy in clinical shock.

Effects of diazepam and ethanol alone and in combination on conditioned suppression of key-pecking in the pigeon.

Pigeons were intermittently given grain reinforcement for key pecks. Occasional 30-sec keylight changes (warning stimulus) were followed by a brief electric shock, which suppressed responding during the warning stimuli. This suppression was reduced by diazepam and ethanol, yet combinations of the two drugs did not reduce suppression (antagonistic effect). Each drug reduced responding in the absence of the warning stimulus, and combinations of the drug produced still greater reductions in this safe-period responding (synergistic effect).

Schedule-dependent effect of d-amphetamine on pausing by pigeons.

Two pigeons were exposed to a multiple schedule of grain reinforcement where key-pecks were reinforced according to a fixed ratio schedule in the presence of one stimulus and a fixed interval schedule in another stimulus. The fixed interval was adjusted to match average interreinforcer time for the fixed ratio schedule. d-Amphetamine decreased overall rate of responding in the fixed ratio schedule -- primarily by increasing pausing, especially just after a change from the fixed interval component. Rate of responding in the fixed interval schedule was increased for one bird and little affected for the other bird by d-Amphetamine. Again, changes in pausing primarily determined rate change. Since pausing was differently affected, a schedule-dependent rather than rate-dependent effect was indicated.

Effects of scopolamine, pentobarbital, and amphetamine on radial arm maze performance in the rat.

Rats were trained to obtain food pellets from the end of each arm of an eight-arm radial maze. Baseline performance was characterized by very few entries into arms from which the food pellet had already been obtained. In Experiment 1, neither d-amphetamine (0.1-3.0 mg/kg) nor pentobarbital (1.0-10.0 mg/kg) affected choice accuracy, although the rate of arm-entry increased after d-amphetamine and decreased after pentobarbital. Scopolamine (0.1-1.0 mg/kg), on the other hand, reduced both accuracy and the rate of arm entry. In a second experiment, the effects of scopoalmine were replicated using a between-subjects design. Methylscopolamine (0.17, 1.0 mg/kg) was found to have little effect on performance. Multiple response criteria were also compared in the second experiment. Scopolamine was found to affect runs farther out the arm differently than it affected abbreviated arm entrances. A post-trial feeding test was also included to evaluate changes in reinforcer effectiveness, and showed that food continued to be a reinforcer after both scopolamine and methylscopolamine.