TRASER - Total Reflection Amplification of Spontaneous Emission of Radiation

Background and Objective: Light and lasers in medical therapy have made dramatic strides since their invention five decades ago. However, the manufacture of lasers can be complex and expensive which often makes treatments limited and costly. Further, no single laser will provide the correct parameters to treat all things. Hence, laser specialists often need multiple devices to practice their specialty. A new concept is described herein that has the potential to replace many lasers and light sources with a single ‘tunable ’ device. Study Design/Material and Methods: This device amplifies spontaneous emission of radiation by capturing and retaining photons through total internal reflection, hence the acronym Total Reflection Amplification of Spontaneous Emission of Radiation, or TRASER. Results: Specific peaks of light can be produced in a reproducible manner with high peak powers of variable pulse durations, a large spot size, and high repetition rate. Conclusion: Considering the characteristics and parameters of Traser technology, it is possible that this one device woul

Clinical and morphological characteristics of head-facial haemangiomas

BACKGROUND: Haemangiomas of the head or face are a frequent vascular pathology, consisting in an embryonic dysplasia that involves the cranial-facial vascular network. Haemangiomas show clinical, morphological, developmental and structural changes during their course. METHODS: The clinical characteristics of head-facial haemagiomas were studied in 28 individuals (9 males and 19 females) admitted in our Hospital. Sixteen of these patients(n = 16) underwent surgery for the removal of the haemangiomas. All the removed tissues were transferred in experimental laboratories for the staining of microanatomical details, somatic and visceral nerve fibres, adrenergic and catecholaminergic nerve fibres. Beta-adrenergic receptors were died with a fluorescent method. All results were submitted to the quantitative analysis of images and statistical evaluation of the data. RESULTS: The morphological results revealed numerous micro-anatomical characteristics of the haemangiomatous vessels. The somatic and visceral nerve fibres were poor and located exclusively in the adventitial layer. There was a marked decrease of adrenergic nerve fibres in the haemangiomatous vessels. The fluorescence of catecholaminergic nerve fibres and the overall area of fluorescent structures were also decreased in haemangiomatous vessels. Beta adrenergic receptors are strongly decreased in haemangiomatous vessels. The morphometrical analysis of images and statistical evaluation of the data confirmed all our experimental results. CONCLUSION: The catecholaminergic innervation of the human haemangiomatous vessels comprises nerve fibres containing the main catecholaminergic neurotransmitters that are sympathetic in nature. These neurotransmitters are closely related to beta-adrenergic receptors. The sympathetic nervous system plays a key role in the control of the vascular bed flow and vascular motility in both normal and haemangiomatous vessels

The pathology of familial breast cancer: Immunohistochemistry and molecular analysis

Extensive studies of BRCA1- and BRCA2-associated breast tumours have been carried out in the few years since the identification of these familial breast cancer predisposing genes. The morphological studies suggest that BRCA1 tumours differ from BRCA2 tumours and from sporadic breast cancers. Recent progress in immunohistochemistry and molecular biology techniques has enabled in-depth investigation of molecular pathology of these tumours. Studies to date have investigated issues such as steroid hormone receptor expression, mutation status of tumour suppressor genes TP53 and c-erbB2, and expression profiles of cell cycle proteins p21, p27 and cyclin D(1). Despite relative paucity of data, strong evidence of unique biological characteristics of BRCA1-associated breast cancer is accumulating. BRCA1-associated tumours appear to show an increased frequency of TP53 mutations, frequent p53 protein stabilization and absence of imunoreactivity for steroid hormone receptors. Further studies of larger number of samples of both BRCA1- and BRCA2-associated tumours are necessary to clarify and confirm these observations

Electrochemical activation and inhibition of neuromuscular systems through modulation of ion concentrations with ion-selective membranes

Conventional functional electrical stimulation aims to restore functional motor activity of patients with disabilities resulting from spinal cord injury or neurological disorders. However, intervention with functional electrical stimulation in neurological diseases lacks an effective implantable method that suppresses unwanted nerve signals. We have developed an electrochemical method to activate and inhibit a nerve by electrically modulating ion concentrations in situ along the nerve. Using ion-selective membranes to achieve different excitability states of the nerve, we observe either a reduction of the electrical threshold for stimulation by up to approximately 40%, or voluntary, reversible inhibition of nerve signal propagation. This low-threshold electrochemical stimulation method is applicable in current implantable neuroprosthetic devices, whereas the on-demand nerve-blocking mechanism could offer effective clinical intervention in disease states caused by uncontrolled nerve activation, such as epilepsy and chronic pain syndromes.Massachusetts Institute of Technology. Faculty Discretionary Research FundNational Institutes of Health (U.S.) (Award UL1 RR 025758)Harvard Catalyst (Grant

An Overview of Three Promising Mechanical, Optical, and Biochemical Engineering Approaches to Improve Selective Photothermolysis of Refractory Port Wine Stains

During the last three decades, several laser systems, ancillary technologies, and treatment modalities have been developed for the treatment of port wine stains (PWSs). However, approximately half of the PWS patient population responds suboptimally to laser treatment. Consequently, novel treatment modalities and therapeutic techniques/strategies are required to improve PWS treatment efficacy. This overview therefore focuses on three distinct experimental approaches for the optimization of PWS laser treatment. The approaches are addressed from the perspective of mechanical engineering (the use of local hypobaric pressure to induce vasodilation in the laser-irradiated dermal microcirculation), optical engineering (laser-speckle imaging of post-treatment flow in laser-treated PWS skin), and biochemical engineering (light- and heat-activatable liposomal drug delivery systems to enhance the extent of post-irradiation vascular occlusion)

Targeted apoptosis in ovarian cancer cells through mitochondrial dysfunction in response to Sambucus nigra agglutinin

Ovarian carcinoma (OC) patients encounter the severe challenge of clinical management owing to lack of screening measures, chemoresistance and finally dearth of non-toxic therapeutics. Cancer cells deploy various defense strategies to sustain the tumor microenvironment, among which deregulated apoptosis remains a versatile promoter of cancer progression. Although recent research has focused on identifying agents capable of inducing apoptosis in cancer cells, yet molecules efficiently breaching their survival advantage are yet to be classified. Here we identify lectin, Sambucus nigra agglutinin (SNA) to exhibit selectivity towards identifying OC by virtue of its specific recognition of α-2, 6-linked sialic acids. Superficial binding of SNA to the OC cells confirm the hyper-sialylated status of the disease. Further, SNA activates the signaling pathways of AKT and ERK1/2, which eventually promotes de-phosphorylation of dynamin-related protein-1 (Drp-1). Upon its translocation to the mitochondrial fission loci Drp-1 mediates the central role of switch in the mitochondrial phenotype to attain fragmented morphology. We confirmed mitochondrial outer membrane permeabilization resulting in ROS generation and cytochrome-c release into the cytosol. SNA response resulted in an allied shift of the bioenergetics profile from Warburg phenotype to elevated mitochondrial oxidative phosphorylation, altogether highlighting the involvement of mitochondrial dysfunction in restraining cancer progression. Inability to replenish the SNA-induced energy crunch of the proliferating cancer cells on the event of perturbed respiratory outcome resulted in cell cycle arrest before G2/M phase. Our findings position SNA at a crucial juncture where it proves to be a promising candidate for impeding progression of OC. Altogether we unveil the novel aspect of identifying natural molecules harboring the inherent capability of targeting mitochondrial structural dynamics, to hold the future for developing non-toxic therapeutics for treating OC

A New Single-Step PCR Assay for the Detection of the Zoonotic Malaria Parasite Plasmodium knowlesi

Recent studies in Southeast Asia have demonstrated substantial zoonotic transmission of Plasmodium knowlesi to humans. Microscopically, P. knowlesi exhibits several stage-dependent morphological similarities to P. malariae and P. falciparum. These similarities often lead to misdiagnosis of P. knowlesi as either P. malariae or P. falciparum and PCR-based molecular diagnostic tests are required to accurately detect P. knowlesi in humans. The most commonly used PCR test has been found to give false positive results, especially with a proportion of P. vivax isolates. To address the need for more sensitive and specific diagnostic tests for the accurate diagnosis of P. knowlesi, we report development of a new single-step PCR assay that uses novel genomic targets to accurately detect this infection.We have developed a bioinformatics approach to search the available malaria parasite genome database for the identification of suitable DNA sequences relevant for molecular diagnostic tests. Using this approach, we have identified multi-copy DNA sequences distributed in the P. knowlesi genome. We designed and tested several novel primers specific to new target sequences in a single-tube, non-nested PCR assay and identified one set of primers that accurately detects P. knowlesi. We show that this primer set has 100% specificity for the detection of P. knowlesi using three different strains (Nuri, H, and Hackeri), and one human case of malaria caused by P. knowlesi. This test did not show cross reactivity with any of the four human malaria parasite species including 11 different strains of P. vivax as well as 5 additional species of simian malaria parasites.The new PCR assay based on novel P. knowlesi genomic sequence targets was able to accurately detect P. knowlesi. Additional laboratory and field-based testing of this assay will be necessary to further validate its utility for clinical diagnosis of P. knowlesi

Mapping the Complex Morphology of Cell Interactions with Nanowire Substrates Using FIB-SEM

Using high resolution focused ion beam scanning electron microscopy (FIB-SEM) we study the details of cell-nanostructure interactions using serial block face imaging. 3T3 Fibroblast cellular monolayers are cultured on flat glass as a control surface and on two types of nanostructured scaffold substrates made from silicon black (Nanograss) with low- and high nanowire density. After culturing for 72 hours the cells were fixed, heavy metal stained, embedded in resin, and processed with FIB-SEM block face imaging without removing the substrate. The sample preparation procedure, image acquisition and image post-processing were specifically optimised for cellular monolayers cultured on nanostructured substrates. Cells display a wide range of interactions with the nanostructures depending on the surface morphology, but also greatly varying from one cell to another on the same substrate, illustrating a wide phenotypic variability. Depending on the substrate and cell, we observe that cells could for instance: break the nanowires and engulf them, flatten the nanowires or simply reside on top of them. Given the complexity of interactions, we have categorised our observations and created an overview map. The results demonstrate that detailed nanoscale resolution images are required to begin understanding the wide variety of individual cells' interactions with a structured substrate. The map will provide a framework for light microscopy studies of such interactions indicating what modes of interactions must be considered