Plasmonic Nanocomposite Implants for Interstitial Thermotherapy: Experimental and Computational Analysis

The ferromagnetic implant (thermoseeds) technique offers desirable features for interstitial thermotherapy. However, its efficacy has been reported to be limited by issues that are related to the properties of the metal alloys that are used to fabricate them and the high number of thermoseeds needed to achieve therapeutic temperature levels. Here, we present the results of a combination of experimental and computational analysis of plasmonic nanocomposite implants (photoseeds)—a combination of Au nanoparticles (NPs) and poly-dimethylsiloxane (PDMS)—as a model material. We performed structural and optical characterization of the Au NPs and repared Au-PDMS nanocomposites, followed by an elucidation of the heat generation capabilities of the Au-PDMS photoseeds in aqueous solution and in-vitro cancer cell suspension. Based on the experimental results, we developed a three-dimensional (3D) finite element method (FEM) model to predict in-vivo thermal damage profiles in breast tissue. The optical absorbance of the Au-PDMS photoseeds were increasing with the concentration of Au NPs. The photothermal measurements and the in-vivo predictions showed that the photothermal properties of the photoseeds, characteristics of the laser sources, and the duration of heating can be tuned to achieve therapeutic temperature levels under in-vitro and in-vivo conditions. Collectively, the results demonstrate the feasibility of using photoseeds for interstitial thermotherapy.     

Detection of malaria sporozoites by standard ELISA and VecTestTM dipstick assay in field-collected anopheline mosquitoes from a malaria endemic site in Ghana

We compared the VecTestTM dipstick assay for detection of Plasmodium sporozoites in Anopheles vectors of malaria with standard circumsporozoite (CS) microplate ELISA for detection of Plasmodium falciparum circumsporozoite protein (PfCSP) in Anopheles mosquitoes. Mosquitoes were collected from a malaria endemic site (Kassena Nankana district) in northern Ghana. Of 2620 randomly sampled mosquitoes tested, the standard CS-ELISA gave a sporozoite rate of 10.8% compared with 11.2% by VecTestTM, which was not statistically different (P = 0.66). Visual reading of the CS-ELISA results gave a sporozoite rate of 13.4%, which was higher than the other tests (P > 0.05). To allow a more objective evaluation of the sensitivity of the dipstick, an additional 136 known CS-ELISA-positive specimens were analysed. The prevalence of the test (including the additional samples) was 14.6% and 14.7% for CS-ELISA and dipstick, respectively (P > 0.05). The estimated prevalence by visual assessment of the CS-ELISA results was 17.5%. The relative specificity and sensitivity of the VecTestTM dipstick and visually read ELISA were estimated based on the CS-ELISA as a gold standard. The specificities of the dipstick and visual ELISA were high, 98.0% and 96.6%, respectively. However, the sensitivities of the two assays were 88.8% for VecTest and 100% for visual ELISA (P < 0.01). Concordance between VecTest and CS-ELISA was good (kappa = 0.86). Similarly, there was a good concordance between the dipstick and the visually read ELISA (kappa = 0.88). Extrapolating from PfCSP controls (titrated quantities of P. falciparum sporozoites), mean sporozoite loads of CS-ELISA-positive An. gambiae (286 +/- 28.05) and An. funestus (236 +/- 19.32) were determined (P = 0.146). The visual dipstick grades showed high correlation with sporozoite load. The more intense the dipstick colour, the higher the mean sporozoite load (+ = 108, ++ = 207, +++ = 290, r = 0.99, r2 = 1). The VecTest dipstick offers practical advantages for field workers needing rapid and accurate means of detection of sporozoites in mosquitoes.     

Interplay of oxygen-evolution kinetics and photovoltaic power curves on the construction of artificial leaves

An artificial leaf can perform direct solar-to-fuels conversion. The construction of an efficient artificial leaf or other photovoltaic (PV)-photoelectrochemical device requires that the power curve of the PV material and load curve of water splitting, composed of the catalyst Tafel behavior and cell resistances, be well-matched near the thermodynamic potential for water splitting. For such a condition, we show here that the current density-voltage characteristic of the catalyst is a key determinant of the solar-to-fuels efficiency (SFE). Oxidic Co and Ni borate (Co-B_i and Ni-B_i) thin films electrodeposited from solution yield oxygen-evolving catalysts with Tafel slopes of 52 mV/decade and 30 mV/decade, respectively. The consequence of the disparate Tafel behavior on the SFE is modeled using the idealized behavior of a triple-junction Si PV cell. For PV cells exhibiting similar solar power-conversion efficiencies, those displaying low open circuit voltages are better matched to catalysts with low Tafel slopes and high exchange current densities. In contrast, PV cells possessing high open circuit voltages are largely insensitive to the catalyst’s current density-voltage characteristics but sacrifice overall SFE because of less efficient utilization of the solar spectrum. The analysis presented herein highlights the importance of matching the electrochemical load of water-splitting to the onset of maximum current of the PV component, drawing a clear link between the kinetic profile of the water-splitting catalyst and the SFE efficiency of devices such as the artificial leaf.     

Endothelium-derived fibronectin regulates neonatal vascular morphogenesis in an autocrine fashion

Fibronectin containing alternatively spliced EIIIA and EIIIB domains is largely absent from mature quiescent vessels in adults, but is highly expressed around blood vessels during developmental and pathological angiogenesis. The precise functions of fibronectin and its splice variants during developmental angiogenesis however remain unclear due to the presence of cardiac, somitic, mesodermal and neural defects in existing global fibronectin KO mouse models. Using a rare family of surviving EIIIA EIIIB double KO mice, as well as inducible endothelial-specific fibronectin-deficient mutant mice, we show that vascular development in the neonatal retina is regulated in an autocrine manner by endothelium-derived fibronectin, and requires both EIIIA and EIIIB domains and the RGD-binding α5 and αv integrins for its function. Exogenous sources of fibronectin do not fully substitute for the autocrine function of endothelial fibronectin, demonstrating that fibronectins from different sources contribute differentially to specific aspects of angiogenesis.     

Quantitative evaluation of integrated schistosomiasis control: the example of passive case finding in Ghana

Passive case finding based on adequate diagnosis and treatment of symptomatic individuals with praziquantel by the health care facilities is a minimum requirement for integrated schistosomiasis control. Two field studies were conducted in Ghana to obtain quantifications about the steps in this process: (1) a study of health-seeking behaviour through interview of individuals with reported schistosomiasis-related symptoms; (2) a study of the performance of the Ghanaian health system with regard to schistosomiasis case management by presenting clinical scenarios to health workers and collecting information about availability of praziquantel. It appeared that cases of blood in urine (the most typical symptom of Schistosoma haematobium) and blood in stool (the most typical symptom of S. mansoni) have a very small probability of receiving praziquantel (4.4% and 1.4%, respectively) from health facilities. Programmes aimed at making the drug available at all levels of the health care delivery system and encouraging health-seeking behaviour through health education are not likely to increase these probabilities beyond 30%. This is because many cases with blood in urine do not consider it serious enough to seek health care, and blood in stool usually requires (imperfect) diagnostic testing and referral. We therefore conclude that additional control activities, especially for high-risk groups, will remain necessary.     

Native matrix metalloproteinase characteristics may influence early stenosis of venous versus arterial coronary artery bypass grafting conduits

PURPOSE: Stenosis and occlusion rates of internal mammary artery (IMA) and saphenous vein (SV) coronary artery bypass grafts (CABGs) are markedly different, which result from respective disparities in vascular remodeling. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate vascular structure and may have important influence on graft patency. However, the MMP milieu and expression profile of the IMA and SV have not been contrasted. Therefore, the aim of this study was to assess and compare the native MMP systems in IMA vs SV conduits. METHODS: IMA (n = 10) and SV (n = 10) specimens were obtained from patients undergoing CABG surgery. Protein levels of MMP-1, MMP-2, and MMP-9, TIMP-1, a membrane-bound MMP activator (MT1-MMP), and an extracellular MMP inducer protein (EMMPRIN) were determined by immunoblotting and quantified by densitometric analysis. MMP-2 and MMP-9 activity was determined by gelatin zymography. RESULTS: MMP-2 levels were significantly higher in SV (2,218 +/- 351 pixels) vs IMA (1,012 +/- 213 pixels) specimens (mean +/- SEM]). There were no significant differences in MMP-1, MMP-9, or TIMP-1 content; however, MT1-MMP and EMMPRIN levels were significantly lower in SV (847 +/- 190 pixels, 1,742 +/- 461 pixels) vs IMA conduits (2,590 + 403 pixels, 5,606 + 678 pixels), respectively (p < 0.05). MMP-9 activity was similar while MMP-2 activity was significantly increased in SV vs IMA specimens. CONCLUSIONS: SV and IMA conduits harbor the same MMP molecular constituents. However, MMP-2 levels and activity are significantly more abundant in the SV compared to the IMA. These differences may contribute to the early pathologic remodeling of the SV vs IMA conduit following CABG surgery.     

Functional circuitry for peripheral suppression in Mammalian Y-type retinal ganglion cells

A retinal ganglion cell receptive field is made up of an excitatory center and an inhibitory surround. The surround has two components: one driven by horizontal cells at the first synaptic layer and one driven by amacrine cells at the second synaptic layer. Here we characterized how amacrine cells inhibit the center response of on- and off-center Y-type ganglion cells in the in vitro guinea pig retina. A high spatial frequency grating (4-5 cyc/mm), beyond the spatial resolution of horizontal cells, drifted in the ganglion cell receptive field periphery to stimulate amacrine cells. The peripheral grating suppressed the ganglion cell spiking response to a central spot. Suppression of spiking was strongest and observed most consistently in off cells. In intracellular recordings, the grating suppressed the subthreshold membrane potential in two ways: a reduced slope (gain) of the stimulus-response curve by approximately 20-30% and, in off cells, a tonic approximately 1-mV hyperpolarization. In voltage clamp, the grating increased an inhibitory conductance in all cells and simultaneously decreased an excitatory conductance in off cells. To determine whether center response inhibition was presynaptic or postsynaptic (shunting), we measured center response gain under voltage-clamp and current-clamp conditions. Under both conditions, the peripheral grating reduced center response gain similarly. This result suggests that reduced gain in the ganglion cell subthreshold center response reflects inhibition of presynaptic bipolar terminals. Thus amacrine cells suppressed ganglion cell center response gain primarily by inhibiting bipolar cell glutamate release.