AIDS: A public health and psychological emergency.

Reviews the current status and knowledge of acquired immune deficiency syndrome (AIDS), focusing on the demographic characteristics of high-risk groups (e.g., homosexual and bisexual men), assumptions and findings that have guided research to date, and problems that have hampered this research. Because most AIDS research has dealt with gay and bisexual men, misperceptions about this group and their health, lifestyles, and sexual activity, which are common, have fostered flawed research designs. Confidentiality is another sensitive issue in AIDS detection and research. The psychological ramifications of AIDs involve the social stigmas attached to the lifestyles of high-risk groups and the fear of contracting AIDS held by the general public. (46 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mimicking primary processes in photosynthesis Photochemistry of covalently linked porphyrin quinones studied by EPR spectroscopy

Porphyrin quinones (P-Q's), covalently linked via different aliphatic bridges, have been synthesized and studied in their (porphyrin) cationic and (semiquinone) anionic radical states by EPR, ENDOR and TRIPLE resonance techniques. Time-resolved and steady-state photoexcitation experiments showed that intra- and intermolecular electron transfer (ET) processes occur in these systems, both in isotropic and reversed micellar solution. Analysis of the experimental data showed the occurrence of photochemical redox processes which result in the formation of hydroquinoid and chlorin type derivatives. Strong polarisation effects were observed for the doublet species - generated by intermolecular ET - under steady-state illumination. It is demonstrated that the polarisation pattern can be explained by the encounter of a triplet and a doublet species allowing the radical triplet pair mechanism to occur. Using a porphyrin linked to a redox active crown ether quinone, complexation of sodium cations in the crown gave rise to well resolved sodium ENDOR lines with an unusual high spin density at the aikali metal ion. Moreover, interesting photochemically induced conformational changes, such as folding and unfolding of donor and acceptor with respect to one another in the case of a flexible butylene bridge, could be detected.     

Experiments on the edited condensed nearest neighbor rule

Tomek's preprocessing scheme is discussed for editing the training set prior to analyzing it by Hart's condensed nearest neighbor technique. Preprocessing was performed by a κ-nearest-neighbor pdf estimation scheme, although other methods are suggested in this paper. The procedure was studied experimentally and was found to achieve a significant reduction in the storage requirements of the CNN method while maintaining approximately the same error rate, or even improving it.     

Porous Silicon Nanoparticles Embedded in Poly(lactic‐co‐glycolic acid) Nanofiber Scaffolds Deliver Neurotrophic Payloads to Enhance Neuronal Growth

Scaffolds made from biocompatible polymers provide physical cues to direct the extension of neurites and to encourage repair of damaged nerves. The inclusion of neurotrophic payloads in these scaffolds can substantially enhance regrowth and repair processes. However, many promising neurotrophic candidates are excluded from this approach due to incompatibilities with the polymer or with the polymer processing conditions. This work provides one solution to this problem by incorporating porous silicon nanoparticles (pSiNPs) that are preloaded with the therapeutic into a polymer scaffold during fabrication. The nanoparticle‐drug‐polymer hybrids are prepared in the form of oriented poly(lactic‐co‐glycolic acid) nanofiber scaffolds. Three different therapeutic payloads are tested: bpV(HOpic), a small molecule inhibitor of phosphatase and tensin homolog (PTEN); an RNA aptamer specific to tropomyosin‐related kinase receptor type B (TrkB); and the protein nerve growth factor (NGF). Each therapeutic is loaded using a loading chemistry that is optimized to slow the rate of release of these water‐soluble payloads. The drug‐loaded pSiNP‐nanofiber hybrids release approximately half of their TrkB aptamer, bpV(HOpic), or NGF payload in 2, 10, and >40 days, respectively. The nanofiber hybrids increase neurite extension relative to drug‐free control nanofibers in a dorsal root ganglion explant assay.     

Group II innate lymphoid cells and microvascular dysfunction from pulmonary titanium dioxide nanoparticle exposure

Background

The cardiovascular effects of pulmonary exposure to engineered nanomaterials (ENM) are poorly understood, and the reproductive consequences are even less understood. Inflammation remains the most frequently explored mechanism of ENM toxicity. However, the key mediators and steps between lung exposure and uterine health remain to be fully defined. The purpose of this study was to determine the uterine inflammatory and vascular effects of pulmonary exposure to titanium dioxide nanoparticles (nano-TiO₂). We hypothesized that pulmonary nano-TiO₂ exposure initiates a Th2 inflammatory response mediated by Group II innate lymphoid cells (ILC2), which may be associated with an impairment in uterine microvascular reactivity.

Methods

Female, virgin, Sprague-Dawley rats (8–12 weeks) were exposed to 100 μg of nano-TiO₂ via intratracheal instillation 24 h prior to microvascular assessments. Serial blood samples were obtained at 0, 1, 2 and 4 h post-exposure for multiplex cytokine analysis. ILC2 numbers in the lungs were determined. ILC2s were isolated and phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) levels were measured. Pressure myography was used to assess vascular reactivity of isolated radial arterioles.

Results

Pulmonary nano-TiO₂ exposure was associated with an increase in IL-1ß, 4, 5 and 13 and TNF- α 4 h post-exposure, indicative of an innate Th2 inflammatory response. ILC2 numbers were significantly increased in lungs from exposed animals (1.66?±?0.19%) compared to controls (0.19?±?0.22%). Phosphorylation of the transactivation domain (Ser-468) of NF-κB in isolated ILC2 and IL-33 in lung epithelial cells were significantly increased (126.8?±?4.3% and 137?±?11% of controls respectively) by nano-TiO₂ exposure. Lastly, radial endothelium-dependent arteriolar reactivity was significantly impaired (27?±?12%), while endothelium-independent dilation (7?±?14%) and α-adrenergic sensitivity (8?±?2%) were not altered compared to control levels. Treatment with an anti- IL-33 antibody (1 mg/kg) 30 min prior to nano-TiO₂ exposure resulted in a significant improvement in endothelium-dependent dilation and a decreased level of IL-33 in both plasma and bronchoalveolar lavage fluid.

Conclusions

These results provide evidence that the uterine microvascular dysfunction that follows pulmonary ENM exposure may be initiated via activation of lung-resident ILC2 and subsequent systemic Th2-dependent inflammation.

     

Nanomechanical detection of antibiotic-mucopeptide binding in a model for superbug drug resistance

The alarming growth of the antibiotic-resistant superbugs methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) is driving the development of new technologies to investigate antibiotics and their modes of action. We report the label-free detection of vancomycin binding to bacterial cell wall precursor analogues (mucopeptides) on cantilever arrays, with 10 nM sensitivity and at clinically relevant concentrations in blood serum. Differential measurements have quantified binding constants for vancomycin-sensitive and vancomycin-resistant mucopeptide analogues. Moreover, by systematically modifying the mucopeptide density we gain new insights into the origin of surface stress. We propose that stress is a product of a local chemical binding factor and a geometrical factor describing the mechanical connectivity of regions activated by local binding in terms of a percolation process. Our findings place BioMEMS devices in a new class of percolative systems. The percolation concept will underpin the design of devices and coatings to significantly lower the drug detection limit and may also have an impact on our understanding of antibiotic drug action in bacteria.     

Distribution and fibre field similarity mapping of the human anterior commissure fibres by diffusion tensor imaging

Object

The anterior commissure is a critical interhemispheric pathway in animals, yet its connections in humans are not clearly understood. Its distribution has shown to vary greatly between species, and it is thought that in humans it may convey axons from a larger territory than previously thought. The aim was to use an anatomical mapping tool to look at the anterior commissure fibres and to compare the distribution findings with published anatomical understanding.

Materials and methods

Two different diffusion-weighted imaging data sets were acquired from eight healthy subjects using a 3 Tesla MR scanner with 32 gradient directions. Diffusion tensor imaging tractography was performed, and the anterior commissure fibres were selected using three-dimensional regions of interest. Distribution of the fibres was observed by means of registration with T2-weighted images. The fibre field similarity maps were produced for five of the eight subjects by comparing each subject’s fibres to the combined map of the five data sets.

Results

Fibres were shown to lead into the temporal lobe and towards the orbitofrontal cortex in the majority of subjects. Fibres were also distributed to the parietal or occipital lobes in all five subjects in whom the anterior commissure was large enough for interhemispheric fibres to be tracked through. The fibre field similarity maps highlighted areas where the local distances of fibre tracts were displayed for each subject compared to the combined bundle map.

Conclusion

The anterior commissure may play a more important role in interhemispheric communication than currently presumed by conveying axons from a wider territory, and the fibre field similarity maps give a novel approach to quantifying and visualising characteristics of fibre tracts.