Drug‐Loaded Multifunctional Nanoparticles Targeted to the Endocardial Layer of the Injured Heart Modulate Hypertrophic Signaling

Ischemic heart disease is the leading cause of death globally. Severe myocardial ischemia results in a massive loss of myocytes and acute myocardial infarction, the endocardium being the most vulnerable region. At present, current therapeutic lines only ameliorate modestly the quality of life of these patients. Here, an engineered nanocarrier is reported for targeted drug delivery into the endocardial layer of the left ventricle for cardiac repair. Biodegradable porous silicon (PSi) nanoparticles are functionalized with atrial natriuretic peptide (ANP), which is known to be expressed predominantly in the endocardium of the failing heart. The ANP–PSi nanoparticles exhibit improved colloidal stability and enhanced cellular interactions with cardiomyocytes and non‐myocytes with minimal toxicity. After confirmation of good retention of the radioisotope 111‐Indium in relevant physiological buffers over 4 h, in vivo single‐photon emission computed tomography (SPECT/CT) imaging and autoradiography demonstrate increased accumulation of ANP–PSi nanoparticles in the ischemic heart, particularly in the endocardial layer of the left ventricle. Moreover, ANP–PSi nanoparticles loaded with a novel cardioprotective small molecule attenuate hypertrophic signaling in the endocardium, demonstrating cardioprotective potential. These results provide unique insights into the development of nanotherapies targeted to the injured region of the myocardium.     

Corrosion of carbon steel underneath a lead/potassium chloride salt mixture

High amounts of lead in waste/recycled wood fuel are known to be a contributing factor to the increased corrosion often related to this type of fuel. In combination with potassium, usually present in the fuel, low‐melting point salt mixtures between lead chloride (PbCl ₂) and potassium chloride (KCl) are expected to form. The purpose of this study is to investigate reactions in the mixed salt of PbCl ₂ and KCl and its interactions with carbon steel P265GH and its oxide. Laboratory exposures were performed in an isothermal tube furnace with a salt mixture of PbCl ₂/KCl (50/50 mol%) put on steel samples. The test duration was 24 hr at either 300°C or 340°C in an atmosphere of 100 ppm HCl and 20 vol% H ₂O in synthetic air. After exposure, the salt mixture consists of distinct areas of KCl and PbCl ₂ but also the compounds K ₂PbCl ₄ and KPb ₂Cl ₅. A general observation is that the oxide thickness increases with temperature and that areas with Pb/K‐mixed salt are frequently found in close connection to more corroded areas. Often the more lead‐rich phase KPb ₂Cl ₅ is located closest to the corrosion product indicating its importance for the corrosion.     

High frequency asynchronous magnetic bead rotation for improved biosensors

Biosensors with increasingly high sensitivity are crucial for probing small scale properties. The asynchronous magnetic bead rotation (AMBR) sensor is an emerging sensor platform, based on magnetically actuated rotation. Here the frequency dependence of the AMBR sensor's sensitivity is investigated. An asynchronous rotation frequency of 145 Hz is achieved. This increased frequency will allow for a calculated detection limit of as little as a 59 nm change in bead diameter, which is a dramatic improvement over previous AMBR sensors and further enables physical and biomedical applications.     

Does condition of Lake Whitefish spawners affect physiological condition of juveniles?

Recent declines in growth and condition of several Great Lakes lake whitefish populations have raised concerns over potential impacts on juvenile physiological condition and ultimately recruitment. To test whether the condition of spawning adults influences juvenile condition via energy allocation dynamics, we partitioned the variation in age 0 juvenile physiological condition (i.e., growth in length and weight, whole-body moisture content, energy density, and protein content) among adult male and female (i.e., body condition, muscle moisture content, energy density, and protein content) and egg (i.e., wet and dry weight, moisture content, energy density, energy content per egg, and protein content) effects using redundancy analysis. Overall, a model that included sampling site, female condition, and egg quality explained 39% of the variation in juvenile physiological condition. After partitioning out the effects of females and eggs, site explained the most variation (23%). When other factors were accounted for, neither females (1.4%) nor eggs (2.7%) explained much variation in juvenile physiological condition. Of the variables studied, female muscle energy density, muscle moisture content, and egg moisture content were most closely associated with juvenile physiological condition. Our results suggest that parental effects, such as size, age, body condition, or body composition, may not be as important as extrinsic site-related effects or density-dependent effects in determining juvenile physiological condition.     

Influence of water chemistry on the corrosion mechanism of a zirconium-niobium alloy in simulated light water reactor coolant conditions

The oxidation of the zirconium alloy E110 inf simulated nuclear power plant coolant at 310 °C is characterised using in situ Electrochemical Impedance Spectroscopy (EIS) and ex-situ microscopic observations. EIS data have been fitted to a transfer function derived from the Mixed Conduction Model. The kinetic parameters characterising the oxidation process - interfacial rate constant of oxidation, diffusion coefficient of oxygen vacancies, and field strength in the inner layer - have been estimated. The dependence of their values on LiOH/KOH/NaF content are discussed in terms of an enhanced rate of dissolution of the barrier layer at higher level of alkali and fluoride.     

Predicted and observed growth and toxigenesis by Clostridium botulinum type E in vacuum-packaged fishery product challenge tests.

The observed growth and toxigenesis by Clostridium botulinum type E in vacuum-packaged unprocessed, raw pickled and cold-smoked rainbow trout stored at slightly abusive temperatures were compared to predictions generated by two currently available predictive microbiological programs, Food MicroModel and Pathogen Modelling Program. In unprocessed fish there was only a 2 log increase in type E cell count at the time the toxicity first occurred after 2 weeks storage at 8 degrees C. Neither growth or toxin production was observed in raw pickled fish with a NaCl concentration of 6.7% (w/v) during 6 weeks storage at 6 degrees C. In cold-smoked fish with a NaCl level of 3.2% (w/v) toxic samples were detected after 3 and 4 weeks storage at 8 degrees C and 4 degrees C, respectively, without any increase in type E count. Both models were hampered by limitations to controlling environmental factors set by the programs which also had an adverse effect on the reliability of predictions. Most predictions generated by the models were inconsistent with the results observed in the challenge studies. In certain situations, the models seemed to be 'fail-safe', in that, the growth rate predicted from the model was faster or a predicted time to toxicity shorter than that which actually occurred in the food. In other situations, the predictions showed the product to be safe when it was not. The results demonstrate the need for further development and rigorous validation of the models before they are accepted for wider use by inspecting officials and the food industry.     

Reducing Excess Noise in Au/Ti Transition-Edge Sensors

We have studied the noise spectra of Au/Ti bilayer transition-edge sensors with transition temperatures around ∼100 mK. The sensors did not include an absorber element, and were patterned into either a circular Corbino geometry, or a Corbino disk divided into four parallel sections. Both sensor types contained noise in excess of the thermodynamic phonon noise and the equilibrium Johnson noise of the sensor. However, the divided Corbino detector had a significantly lower noise level than the undivided Corbino disk, especially at bias points below the mid-point of the transition.      

The influence of gender, race, and menthol content on tobacco exposure measures.

Research has suggested that race, gender, and menthol cigarette use influence tobacco-smoke exposure measures and smoking-related disease risk. For example, a high proportion of Black smokers prefer menthol cigarettes and, despite smoking fewer cigarettes per day (CPD) than do Whites, tend to have higher cotinine levels. Additionally, Black males are more at risk for smoking-related lung cancer. High cotinine levels and smoking menthol cigarettes may lead to higher toxin intake, which contributes to increased disease risk. We explored the relationship between tobacco exposure variables (i.e., cotinine, CPD, carbon monoxide [CO], nicotine content, and nicotine dependence) with respect to race, gender, and menthol content in a sample of 307 smokers recruited from the greater Boston area to participate in a smoking cessation treatment trial. The pattern of correlations between tobacco exposure measures and cotinine showed a consistently positive correlation between cotinine and CO in all smokers and a correlation between cotinine and CPD in those who smoked nonmenthol cigarettes. Cotinine and CPD correlations varied by gender and race among menthol cigarette smokers. Consistently, we found a significant gender x race x menthol interaction on salivary cotinine level as well as cotinine/CPD ratio. These findings suggest that the relationship between number of cigarettes consumed and salivary cotinine is more complex than previously believed. It is not sufficient to look at race alone; researchers and clinicians need to look at race and gender concurrently, as well as type of cigarette consumed.     

Comparing two burnout interventions: Perceived job control mediates decreases in burnout.

This quasi-experimental study compared the effects of two rehabilitation interventions on burnout and perceived job conditions during a 1-year intervention among female white-collar workers. The participatory intervention (n = 20), involving rehabilitation activities that focused on the individual as well as on individual-organizational levels, assessed exhaustion, cynicism and perceived job control during a 1-year period. Increased job control served as a mechanism through which exhaustion and cynicism decreased in this intervention. The traditional intervention (n = 32), involving rehabilitation activities focusing mainly on the individual level, resulted in a reduction in time pressures during one year. Furthermore, both interventions improved perceived workplace climate. Compared to the traditional approach, the participatory intervention was a more effective strategy for treating burnout. (PsycINFO Database Record (c) 2010 APA, all rights reserved)