Transient Absorption Microscopy, Instrumentation and Application to Amphotericin B

Transient absorption microscopy (TAM) has emerged as a highly useful tool for studying a wide range of applications ranging from materials to biology. It has the advantage of being able to stimulate signal from non-fluorescent molecules and through microscopy is able to image these molecules without reliance on fluorescent quantum yield. A transient absorption microscope has been fully constructed and an initial instrumentation study is presented with white light compression and imaging of polystyrene beads in a solution of IR 1-44 laser dye. We are utilizing TAM for the study of the small-molecule antifungal, Amphotericin B (AmB) and how it interacts with living cells. There have been multiple studies conducted which present conflicting reports of the mechanism of action in which AmB is killing fungus. By directly imaging the AmB molecules interacting with the cells, we will be able to more clearly determine which, if any, of the previously proposed mechanisms is accurate. We have been able to image what we believe is AmB being internalized into yeast cells which is contradictory to the previously proposed mechanisms. While we have obtained preliminary images of the drug interacting with living cells, further investigations are necessary to obtain a full picture of the interactions with AmB and fungal cells

Home monitoring of foot skin temperatures to prevent ulceration

OBJECTIVE - To evaluate the effectiveness of at-home infrared temperature monitoring as a preventative tool in individuals at high risk for diabetes-related lower-extremity ulceration and amputation. RESEARCH DESIGN AND METHODS - Eighty-five patients who fit diabetic foot risk category 2 or 3 (neuropathy and foot deformity or previous history of ulceration or partial foot amputation) were randomized into a standard therapy group (n = 41) or an enhanced therapy group (n = 44). Standard therapy consisted of therapeutic footwear, diabetic foot education, and regular foot evaluation by a podiatrist. Enhanced therapy included the addition of a handheld infrared skin thermometer to measure temperatures on the sole of the foot in the morning and evening. Elevated temperatures (>4°F compared with the opposite foot) were considered to be "at risk" of ulceration due to inflammation at the site of measurement. When foot temperatures were elevated, subjects were instructed to reduce their activity and contact the study nurse. Study subjects were followed for 6 months. RESULTS - The enhanced therapy group had significantly fewer diabetic foot complications (enhanced therapy group 2% vs. standard therapy group 20%, P = 0.01, odds ratio 10.3, 95% CI 1.2-85.3). There were seven ulcers and two Charcot fractures among standard therapy patients and one ulcer in the enhanced therapy group. CONCLUSIONS - These results suggest that at-home patient self-monitoring with daily foot temperatures may be an effective adjunctive tool to prevent foot complications in individuals at high risk for lower-extremity ulceration and amputation

What do indigenous communities think of the CSR practices of mining companies?

This paper examines how one indigenous community in the Western Province of Papua New Guinea (PNG) views the social responsibility initiatives of OK Tedi Mining Ltd (OTML). This mining operation has been controversial since its inception, and various operators of the mine have sought to engage the community and to undertake a number of CSR-related projects. Insights gained from four focus groups amongst the Ok Tedi River indigenous communities show that while some members of the community are satisfied with the company’s efforts at the macro level, many have reservations about the effectiveness of the programs at the micro level on the village and family unit. The implementation of CSR activities are slow and in many instances do not effectively address stakeholder concerns

Management of oropharyngeal cancer: a cross-sectional review of institutional practice at a large Canadian referral centre

BACKGROUND: Over the years, the treatment of oropharyngeal cancer has changed; in the past, first-line treatment consisted of surgery followed by adjuvant radiotherapy, today however, primary treatment typically involves concomitant chemoradiation, and reserves surgery for salvage. While chemoradiation is the modality of choice for primary management of oropharyngeal cancer, disease characteristics, institutional bias, and patient preferences influence treatment choice. This has lead to variation in the treatment of OPC, and has generated some uncertainly regarding the ideal therapeutic approach. The objective of this study was to describe the treatment of OPC a large Canadian referral center, highlighting trends in treatment choice and outcome. METHODS: This is a cross-sectional retrospective review of clinical practice at Sunnybrook Health Science Centre (Toronto, ON). This investigation documents type of first-line treatment, rates of treatment failure, rates of surgical salvage, and 5-year disease-free survival. This study also asses the therapeutic impact of free-flap reconstruction on the use of a postoperative tracheostomy and/or percutaneous endoscopic gastrostomy tube. RESULTS: The majority of oropharyngeal cancer patients presented with regionally metastatic disease (stage III-IV) and underwent concomitant chemoradiation as first-line treatment. Just over half of patients who failed chemoradiation were eligible for salvage surgery. Forty-six percent of salvage patients recurred at approximately 6 months, and died approximately 12 months following the first sign of disease recurrence. Five-year survival for salvage patients stage II, III, IVA, and IVB was 100%, 54.5%, 53.8%, and 50%, respectively. The incidence of percutaneous endoscopic gastrostomy tubes and tracheostomies was comparable between patients who underwent free-flap reconstruction and patients who did not. CONCLUSION: The modality of choice for first-line treatment of oropharyngeal cancer is concomitant chemoradiation. The moderate failure rate following chemoradiation and the modest survival rate following salvage surgery could indicate that selected patients may benefit from undergoing surgery as first-line treatment. While this study did not show that functional outcomes were better for free-flap patients, it is highly likely that those who received a free-flap did better then they would have had they not undergone reconstructive surgery. More research regarding the therapeutic effects of free-flaps in OPC survivors is needed

Colour Doppler and Volume Changes—Anterolateral Thigh Flap: The Sunnybrook Experience

This paper summarizes two recent ALT studies from our institution focusing on the utility of colour flow Doppler's ultrasonography and volumetric changes with radiation. Lastly, we will discuss recommended changes to practice due to the aforementioned studies. Our findings suggest that special care should be made to identify patients at high risk for peripheral arterial disease, and, if the reconstructive surgeon has any concerns, preoperative colour flow Doppler's ultrasonography should be undertaken to better characterize the perforator anatomy and avoid inappropriate flap elevation in patients with silent claudication. Particular detail should be paid to flap thickness especially in patients with increased body habitus. Radiation therapy has on average 20% flap volume-reducing effect, and an overestimation of volume in patients who will be undergoing radiotherapy should lead to the best contour and cosmetic outcomes

Clinicopathological characteristics of histiocytic sarcoma affecting the central nervous system in dogs.

BackgroundHistiocytic sarcoma affecting the central nervous system (CNS HS) in dogs may present as primary or disseminated disease, often characterized by inflammation. Prognosis is poor, and imaging differentiation from other CNS tumors can be problematic.ObjectiveTo characterize the clinicopathological inflammatory features, breed predisposition, and survival in dogs with CNS HS.AnimalsOne hundred two dogs with HS, 62 dogs with meningioma.MethodsRetrospective case series. Records were reviewed for results of cerebrospinal fluid (CSF) analysis, CBC, treatment, and outcome data.ResultsPredisposition for CNS HS was seen in Bernese Mountain Dogs, Golden Retrievers, Rottweilers, Corgis, and Shetland Sheepdogs (P ≤ .001). Corgis and Shetland Sheepdogs had predominantly primary tumors; Rottweilers had exclusively disseminated tumors. Marked CSF inflammation was characteristic of primary rather than disseminated HS, and neoplastic cells were detected in CSF of 52% of affected dogs. Increased neutrophil to lymphocyte ratios were seen in all groups relative to controls (P <.008) but not among tumor subtypes. Definitive versus palliative treatment resulted in improved survival times (P < .001), but overall prognosis was poor.Conclusions and clinical importanceClinicopathological differences between primary and disseminated HS suggest that tumor biological behavior and origin may be different. Corgis and Shetland Sheepdogs are predisposed to primary CNS HS, characterized by inflammatory CSF. High total nucleated cell count and the presence of neoplastic cells support the use of CSF analysis as a valuable diagnostic test. Prognosis for CNS HS is poor, but further evaluation of inflammatory mechanisms may provide novel therapeutic opportunities