Models for the bystander effect in gradient radiation fields: Range and signalling type.

Bystander responses to radiation are responsible for a significant fraction of cell death, but are not included in the conventional linear-quadratic (LQ) radiobiological model. Strong dose gradients in radiation fields affect the distribution of bystander signals and can be used to decrease the survival of cancer cells. Predictive models incorporating bystander effects are needed to design the dose gradients in modulated fields to improve cancer treatments. Fundamental questions concern the nature and range of bystander signalling. Some authors propose bystander signals are carried by diffusing molecular factors expressed into the extracellular medium and that strong dose gradients drive their diffusion. Others propose bystander effects occur between neighbouring cells through gap-junctions, leaving no universal agreement. Here we test three assumptions concerning the effective range of bystander signals using both average and local measures of survival. Model 1 assumes short range signalling (e.g. gap-junction mediated) proportional to the local dose gradient, without relying on diffusion across the extracellular medium; Model 2 assumes metabolite diffusion governed by Fick's second law with either negative or both signs of bystander effect; Model 3 assumes that the extent of signal production is dependent on the average of the dose gradient over the field and that the signals have long range distribution. A single bystander parameter for each model was fitted to observed average survival of cancer cells in uniform and modulated fields. All models gave better fits than the classical LQ model. Model 2 fitted best with one sign of bystander effect on survival. Model 3 gave the best overall fit of average survival. The models were then used to predict local survival and survival as a function of dose in modulated fields, using independent datasets, without changing the bystander parameter. Model 3 gave the best overall prediction. This study demonstrates that the bystander effect can be controlled by design of the radiation field modulation.

Grid therapy using high definition multileaf collimators: realizing benefits of the bystander effect.

BACKGROUND: In microbeam radiotherapy (MRT), parallel arrays of high-intensity synchrotron x-ray beams achieve normal tissue sparing without compromising tumor control. Grid-therapy using clinical linacs has spatial modulation on a larger scale and achieves promising results for palliative treatments of bulky tumors. The availability of high definition multileaf collimators (HDMLCs) with 2.5 mm leaves provides an opportunity for grid-therapy to more closely approach MRT. However, challenges to the wider implementation of grid-therapy remain because spatial modulation of the target volume runs counter to current radiotherapy practice and mechanisms for the beneficial effects of MRT are not fully understood. Without more knowledge of cell dose responses, a quantitative basis for planning treatments is difficult. The aim of this study is to determine if therapeutic benefits of MRT can be achieved using a linac with HDMLCs and if so, to develop a predictive model to support treatment planning. MATERIAL AND METHODS: HD120-MLCs of a Varian Novalis TXTM were used to generate grid patterns of 2.5 and 5.0 mm spacing, which were characterized dosimetrically using GafchromicTM EBT3 film. Clonogenic survival of normal (HUVEC) and cancer (NCI-H460, HCC-1954) cell lines following irradiation under the grid and open fields using a 6 MV photon beam were compared in-vitro for the same average dose. RESULTS AND CONCLUSIONS: Relative to an open field, survival of normal cells in a 2.5 mm striped field was the same, while the survival of both cancer cell lines was significantly lower. A mathematical model was developed to incorporate dose gradients of the spatial modulation into the standard linear quadratic model. Our new bystander extended LQ model assumes spatial gradients drive the diffusion of soluble factors that influence survival through bystander effects, successfully predicting the experimental results that show an increased therapeutic ratio. Our results challenge conventional radiotherapy practice and propose that additional gain can be realized by prescribing spatially modulated treatments to harness the bystander effect.

Small field detector correction factors: effects of the flattening filter for Elekta and Varian linear accelerators.

Flattening filter-free (FFF) beams are becoming the preferred beam type for stereotactic radiosurgery (SRS) and stereotactic ablative radiation therapy (SABR), as they enable an increase in dose rate and a decrease in treatment time. This work assesses the effects of the flattening filter on small field output factors for 6 MV beams generated by both Elekta and Varian linear accelerators, and determines differences between detector response in flattened (FF) and FFF beams. Relative output factors were measured with a range of detectors (diodes, ionization cham-bers, radiochromic film, and microDiamond) and referenced to the relative output factors measured with an air core fiber optic dosimeter (FOD), a scintillation dosimeter developed at Chris O'Brien Lifehouse, Sydney. Small field correction factors were generated for both FF and FFF beams. Diode measured detector response was compared with a recently published mathematical relation to predict diode response corrections in small fields. The effect of flattening filter removal on detector response was quantified using a ratio of relative detector responses in FFF and FF fields for the same field size. The removal of the flattening filter was found to have a small but measurable effect on ionization chamber response with maximum deviations of less than ± 0.9% across all field sizes measured. Solid-state detectors showed an increased dependence on the flattening filter of up to ± 1.6%. Measured diode response was within ± 1.1% of the published mathematical relation for all fields up to 30 mm, independent of linac type and presence or absence of a flattening filter. For 6 MV beams, detector correction factors between FFF and FF beams are interchangeable for a linac between FF and FFF modes, providing that an additional uncertainty of up to ± 1.6% is accepted.

Profiling of the secretome of human cancer cells: preparation of supernatant for proteomic analysis.

Secretomic analysis requires removal of serum proteins from cell-culture media. We evaluate the proteins washed from cells prepared in bovine serum-supplemented medium. PBS and serum-free-medium (SFM) were the washing solutions. A Bradford assay was used for total protein concentration and a 1D gel and LC-MS/MS, to assign the protein to human or bovine origin. For both wash solutions, all bovine protein had been removed by the third wash, without compromising the number of living cells. Further washes reduced the number of living cells, especially when using PBS. Proteomic analysis of wash supernatant showed that SFM induced greater lysis of dead cells. Three washes were sufficient to minimize the effects on cell viability, while still removing serum proteins. Washing in SFM resulted in contamination of the wash supernatant with lysed dead cell proteins. Washed cells were incubated in SFM and exposed to ionizing radiation. Analysis of the supernatant showed an increase in human cytoplasmic, plasma membrane, and nuclear protein following irradiation. Secreted proteins were also detected, but in smaller quantities. The significance of these findings extend to in vitro studies of bystander phenomena, since the proteins of lysed dead cells may participate in driving bystander responses.

Protecting Orthopaedic Implants from Infection: Antimicrobial Peptide Mel4 Is Non-Toxic to Bone Cells and Reduces Bacterial Colonisation When Bound to Plasma Ion-Implanted 3D-Printed PAEK Polymers.

Even with the best infection control protocols in place, the risk of a hospital-acquired infection of the surface of an implanted device remains significant. A bacterial biofilm can form and has the potential to escape the host immune system and develop resistance to conventional antibiotics, ultimately causing the implant to fail, seriously impacting patient well-being. Here, we demonstrate a 4 log reduction in the infection rate by the common pathogen S. aureus of 3D-printed polyaryl ether ketone (PAEK) polymeric surfaces by covalently binding the antimicrobial peptide Mel4 to the surface using plasma immersion ion implantation (PIII) treatment. The surfaces with added texture created by 3D-printed processes such as fused deposition-modelled polyether ether ketone (PEEK) and selective laser-sintered polyether ketone (PEK) can be equally well protected as conventionally manufactured materials. Unbound Mel4 in solution at relevant concentrations is non-cytotoxic to osteoblastic cell line Saos-2. Mel4 in combination with PIII aids Saos-2 cells to attach to the surface, increasing the adhesion by 88% compared to untreated materials without Mel4. A reduction in mineralisation on the Mel4-containing surfaces relative to surfaces without peptide was found, attributed to the acellular portion of mineral deposition.

An omics approach to delineating the molecular mechanisms that underlie the biological effects of physical plasma.

The use of physical plasma to treat cancer is an emerging field, and interest in its applications in oncology is increasing rapidly. Physical plasma can be used directly by aiming the plasma jet onto cells or tissue, or indirectly, where a plasma-treated solution is applied. A key scientific question is the mechanism by which physical plasma achieves selective killing of cancer over normal cells. Many studies have focused on specific pathways and mechanisms, such as apoptosis and oxidative stress, and the role of redox biology. However, over the past two decades, there has been a rise in omics, the systematic analysis of entire collections of molecules in a biological entity, enabling the discovery of the so-called "unknown unknowns." For example, transcriptomics, epigenomics, proteomics, and metabolomics have helped to uncover molecular mechanisms behind the action of physical plasma, revealing critical pathways beyond those traditionally associated with cancer treatments. This review showcases a selection of omics and then summarizes the insights gained from these studies toward understanding the biological pathways and molecular mechanisms implicated in physical plasma treatment. Omics studies have revealed how reactive species generated by plasma treatment preferentially affect several critical cellular pathways in cancer cells, resulting in epigenetic, transcriptional, and post-translational changes that promote cell death. Finally, this review considers the outlook for omics in uncovering both synergies and antagonisms with other common cancer therapies, as well as in overcoming challenges in the clinical translation of physical plasma.

A Comparison of In Vivo Bone Tissue Generation Using Calcium Phosphate Bone Substitutes in a Novel 3D Printed Four-Chamber Periosteal Bioreactor.

Autologous bone replacement remains the preferred treatment for segmental defects of the mandible; however, it cannot replicate complex facial geometry and causes donor site morbidity. Bone tissue engineering has the potential to overcome these limitations. Various commercially available calcium phosphate-based bone substitutes (Novabone®, BioOss®, and Zengro®) are commonly used in dentistry for small bone defects around teeth and implants. However, their role in ectopic bone formation, which can later be applied as vascularized graft in a bone defect, is yet to be explored. Here, we compare the above-mentioned bone substitutes with autologous bone with the aim of selecting one for future studies of segmental mandibular repair. Six female sheep, aged 7-8 years, were implanted with 40 mm long four-chambered polyether ether ketone (PEEK) bioreactors prepared using additive manufacturing followed by plasma immersion ion implantation (PIII) to improve hydrophilicity and bioactivity. Each bioreactor was wrapped with vascularized scapular periosteum and the chambers were filled with autologous bone graft, Novabone®, BioOss®, and Zengro®, respectively. The bioreactors were implanted within a subscapular muscle pocket for either 8 weeks (two sheep), 10 weeks (two sheep), or 12 weeks (two sheep), after which they were removed and assessed by microCT and routine histology. Moderate bone formation was observed in autologous bone grafts, while low bone formation was observed in the BioOss® and Zengro® chambers. No bone formation was observed in the Novabone® chambers. Although the BioOss® and Zengro® chambers contained relatively small amounts of bone, endochondral ossification and retained hydroxyapatite suggest their potential in new bone formation in an ectopic site if a consistent supply of progenitor cells and/or growth factors can be ensured over a longer duration.

Real-time scintillation array dosimetry for radiotherapy: the advantages of photomultiplier detectors.

PURPOSE: In this paper, a photomultiplier tube (PMT) array dosimetry system has been developed and tested for the real-time readout of multiple scintillation signals from fiber optic dosimeters. It provides array dosimetry with the advantages in sensitivity provided by a PMT, but without the need for a separate PMT for each detector element. METHODS: The PMT array system consisted of a multianode PMT, a multichannel data acquisition system, housing and optic fiber connections suitable for clinical use. The reproducibility, channel uniformity, channel crosstalk, acquisition speed, and sensitivity of the PMT array were quantified using a constant light source. Its performance was compared to other readout systems used in scintillation dosimetry. An in vivo HDR brachytherapy treatment was used as an example of a clinical application of the dosimetry system to the measurement of dose at multiple sites in the rectum. The PMT array system was also tested in the pulsed beam of a linear accelerator to test its response speed and its application with two separate methods of Cerenkov background removal. RESULTS: The PMT array dosimetry system was highly reproducible with a measurement uncertainty of 0.13% for a 10 s acquisition period. Optical crosstalk between neighboring channels was accounted for by omitting every second channel. A mathematical procedure was used to account for the crosstalk in next-neighbor channels. The speed and sensitivity of the PMT array system were found be superior to CCD cameras, allowing for measurement of more rapid changes in dose rate. This was further demonstrated by measuring the dose delivered by individual photon pulses of a linear accelerator beam. CONCLUSIONS: The PMT array system has advantages over CCD camera-based systems for the readout of scintillation light. It provided a more sensitive, more accurate, and faster response to meet the demands of future developments in treatment delivery.

Optimisation of exposure conditions for in vitro radiobiology experiments.

Despite the long history of using cell cultures in vitro for radiobiological studies, there is to date no study specifically addressing the dosimetric implications of flask selection and exposure environment in clonogenic assays. The consequent variability in dosimetry between laboratories impedes the comparison of results. In this study we compare the dose to cells adherent to the base of three types of commonly used culture flasks or plates. The cells are exposed to a 6MV clinical photon beam using either an open or a half blocked field. The depth of medium in each flask is varied with the medium surrounding the flask either water or air. The results show that the dose to the cells is more affected by the scattering conditions surrounding the flasks than by the level of filling within the flask. It is recommended that water or a water equivalent phantom material is used to surround the flasks or plates to approximate full scatter conditions at the cell layer. However for modulated fields, surrounding the 24 well plates with water-equivalent material is inadequate because of the large volume of air surrounding individual wells. Our results stress the importance of measuring the dose for new experimental configurations.

Monte Carlo calculations of radiotherapy dose distributions within and around orthopaedic implants.

Background and purpose: Cancer patients often require a titanium orthopaedic implant to support or replace lost bone. In radiation treatment, the dose distribution is perturbed causing regions of high and low dose at material interfaces. Since the survival of integrating bone tissue is critical to implant success, the aim of this study was to determine the dose distribution in and around the scaffold, when constructed from titanium or Poly-ether-ether-ketone (PEEK). Materials and methods: The dose distributions in the pores and along boundaries for three implant scaffold designs were calculated using Monte-Carlo methods in Geant4/GATE, with the material taken as titanium or PEEK. The 3D dose distributions were analysed in MATLAB and segmented using image masks, yielding the dose distributions in key regions of interest. To evaluate the effect of the predicted dose perturbations, the cell survival was calculated using the linear-quadratic model for SAOS-2 cells (bone) using experimentally determined radiation response data. Results: High dose gradients were found along the boundaries of the titanium implants, but not for the corresponding PEEK implants. The dose to the internal cavities of the titanium implants was enhanced by 10-15% near the proximal interface whereas for PEEK, there was no significant dose perturbation. The predicted perturbation caused by the titanium implant was shown to decrease the survival for SAOS-2 cells by 7% which was not found for the PEEK implants. Conclusion: PEEK was shown to be a more favourable orthopaedic implant material over titanium for cancer patients considering radiation therapy.

Radiation responses of cancer and normal cells to split dose fractions with uniform and grid fields: increasing the therapeutic ratio.

PURPOSE: Radiation treatment of cancer is usually delivered in a prescribed sequence of dose fractions within which the dependence of dose on time is determined by the treatment plan. New techniques, such as stereotactic body radiation therapy (SBRT) and image guided radiation therapy (IGRT) have been introduced with the motivation of improving therapeutic outcomes, with the consequence that the time dependence of the dose within a fraction is modified. Here, we test whether an increased toxicity to cancer cells arises when a radiation treatment fraction is delivered in two equal parts, allowing time for the expression of factors, for example, RONS and cytokines, in response to the first dose which may sensitize cells to the second dose. A medium time delay between 15 and 60 minutes is proposed to allow factors to be expressed before repair takes place. A grid field is used to enhance diffusion of the factors. MATERIALS AND METHODS: The cell lines used in the study were two prostate cancers (LNCaP and DU 145), a normal prostate (PNT1A), a non-small cell lung cancer (NCI-H460), and a glioma (Hs 683). Uniform or spatially modulated grid fields, delivering the same mean dose, were used. The results for the clonogenic survival fractions were grouped into a 'short' delay (under 10 minutes) and a 'medium' delay (between 15 and 60 minutes). RESULTS: The medium delay with a grid field yielded a significant increase in toxicity for the four cancer cell lines. The medium delay with a uniform field gave a significant increase in toxicity for the two prostate cancer cell lines. A highly significant increase was found in the therapeutic ratio, defined as the ratio of the survival of prostate normal to prostate cancer cells. CONCLUSIONS: The findings show that the intra-fractional dose schedule with medium time delay offers an opportunity to increase the toxicity of radiation to cancer cells, relative to a single radiation delivery. For all cancer cell lines, a grid field gives a greater toxic effect than a uniform field. The split dose treatment offers an increase in cancer toxicity while preserving normal cells, improving the outcomes of a treatment.

A review of in vitro experimental evidence for the effect of spatial and temporal modulation of radiation dose on response.

BACKGROUND: Intensity modulated radiation therapy introduces strong spatial and temporal modulation of the dose delivery that may have therapeutic benefits, as yet unrealized. MATERIAL AND METHODS: Experimental evidence for spatial and temporal modulation affecting the cell survival following in vitro irradiation has been derived using clonogenic assays. RESULTS AND DISCUSSION: The experimental results show that the survival status of a cell is strongly influenced by the spatial dose modulation. The classical bystander effect of decreased survival has now been supplemented by observations of increased survival, which may result from the same or different signaling mechanisms. Temporal dose modulation experiments show that dose protraction significantly increases cell survival. An appropriate choice of temporal dose modulation pattern enables cell death to be maximized or minimized for a constant dose and delivery time. CONCLUSION: Bystander effects challenge the assumption that outcome is solely dependent on local dose. Intra-fractional temporal modulation via protracted treatments and time varying dose delivery both affect the cell survival. The presence of bystander and temporal effects emphasize the need for a mathematical framework which incorporates their influence on cell survival.

A mathematical framework for separating the direct and bystander components of cellular radiation response.

UNLABELLED: A mathematical model for fractional tumor cell survival was developed incorporating components of cell killing due to direct radiation interactions and bystander signals resulting from non-local dose deposition. MATERIAL AND METHODS: Three possible mechanisms for signal production were tested by fitting predictions to available experimental results for tumor cells (non-small cell lung cancer NCI-H460 and melanoma MM576) exposed to gradient x-ray fields. The parameter fitting allowed estimation of the contribution of bystander signaling to cell death (20-50% for all models). Separation of the two components of cell killing allowed determination of the α and ß parameters of the linear-quadratic model both with and without the presence of bystander signaling. RESULTS AND DISCUSSION: For both cell lines, cell death from bystander signaling and direct radiation interactions were comparable. For NCI-H460 cells, the values for α and ß were 0.18 Gy⁻¹ and 0.10 Gy⁻² respectively when direct and bystander effects were combined, and 0.053 Gy⁻¹ and 0.061 Gy⁻² respectively when the signaling component was removed. For MM576, the corresponding respective values were 0.09 Gy⁻¹ and 0.011 Gy⁻² for the combined response, and 0.014 Gy⁻¹ and 0.002 Gy⁻² for the isolated direct radiation response. The bystander component in cell death was found to be significant and should not be ignored. Further experimental evidence is required to determine how these results translate to the in vivo situation where tumor control probability (TCP) models that currently assume cellular independence may need to be revised.

Cancer treatment with gas plasma and with gas plasma-activated liquid: positives, potentials and problems of clinical translation.

Gas plasmas, created in atmospheric pressure conditions, both thermal (hot) and non-thermal (cold) are emerging as useful tools in medicine. During surgery, hot gas plasmas are useful to reduce thermal damage and seal blood vessels. Gas plasma pens use cold gas plasma to produce reactive chemical species with selective action against cancers, which can be readily exposed in surgery or treated from outside of the body. Solutions activated by cold gas plasma have potential as a novel treatment modality for treatment of less readily accessible tumours, or those with high metastatic potential. This review summarises the preclinical and clinical trial evidence currently available, as well as the challenges for translation of direct gas plasma and gas plasma-activated solution treatment into regular practice.

Imaging prior to radiotherapy impacts in-vitro survival.

BACKGROUND AND PURPOSE: Cone Beam Computed Tomography (CBCT) is routinely used in radiotherapy to identify the position of the target volume. The aim of this study was to determine whether the CBCT dose, when followed by the treatment, influences the therapeutic outcomes as determined by in-vitro clonogenic cell survival in a radiobiological experiment. MATERIALS AND METHODS: Human cell lines, four cancer and one normal, were exposed to a 6 MV photon beam, produced by a linear accelerator. For half of each sample, a prior imaging dose was delivered using the on-board CBCT. A sample size of n = 103 was used to achieve statistical power. RESULTS: The experimental group of cell lines exposed to CBCT imaging prior to treatment exhibited a reduction in mean cancer cell survival of ~17 times (p = 0.02) greater than predicted from the average dose response and equivalent to more than 5% of the therapeutic dose, compared to 11 times greater than predicted for normal cells (n.s.). CONCLUSION: The greater than predicted reduction in survival resulting from the additional CBCT dose is consistent with radiation-induced bystander effects.

Transcriptional regulation of G2/M regulatory proteins and perturbation of G2/M Cell cycle transition by a traditional Chinese medicine recipe.

ETHNOPHARMACOLOGICAL RELEVANCE: Hedyotis diffusa Willd. (H) and Scutellaria barbata D.Don (S) are ancient anti-cancer Chinese herb medicines. When combined, known as HS, it is one of the most commonly prescribed Chinese Medicines for cancer patients today in China. AIM OF THE STUDY: The prevention of disease progression is a dominant concern for the growing number of men with prostate cancer. The purpose of this work is to evaluate the action and mode of action of Chinese Medicine recipe HS in inhibiting prostate cancer progression in preclinical models. METHODS: Effects of HS were analyzed in prostate cancer cell lines by evaluating proliferation, cell cycle profile, DNA damage and key regulators responsible for G2 to M phase transition. The transcriptional activities of these regulators were determined by RT-PCR and ChIP. The efficacy of HS in vitro was validated in an animal model. RESULTS: HS treatment was observed to reduce DNA content and accumulated prostate cancer cells at the G2/M phase. Immunolabeling for phospho-Histone H3 in association with nocodazole to capture mitotic cells confirmed that HS impeded G2 to M transition. After excluding DNA damage-induced G2 arrest, it was revealed that HS reduced expression of Cyclin B1, CDK1, PLK1 and Aurora A at both protein and mRNA levels, with concomitant reduction of H3K4 tri-methylation at their promoter-regions. Animals that received oral administration of HS with a dosage relevant to clinical application showed reduced tumor volume and weight with a reduction of Cyclin B1, CDK1, PLK1 and Aurora A protein levels. CONCLUSIONS: HS acts by impeding the G2 to M transition of prostate cancer cells. It is likely that the mode of action is transcriptionally suppressing proteins governing mitotic entry, without eliciting significant DNA damage.

Irradiation enhances the efficiency of testicular germ cell transplantation in sheep.

Testis germ cell transplantation in livestock has the potential for production of transgenic genotypes and for use as an alternative to artificial insemination in animal breeding systems. In a pilot experiment, we investigated a workable protocol for testis germ cell transplantation in sheep, including donor cell isolation, rete testis injection, and microsatellite detection of donor spermatozoa in recipient semen. In a second experiment, the effect of depletion of endogenous stem cells with a single irradiation dose of 9 Gy (n = 5) or 15 Gy (n = 5) on the outcome of germ cell transplantation was investigated. Irradiation of recipient testes with a single dose of 15 Gy, followed by transplantation 6 wk after depletion, may be most advantageous because it resulted in all recipients (five of five) producing donor-derived spermatozoa, while the 9-Gy and control groups had limited success rates (two of five and one of three, respectively). Using microsatellite markers to detect the presence of donor DNA, 10 rams were identified that produced spermatozoa of donor origin. The proportion of donor DNA was between 1% and 30% of total ejaculate DNA. When three of these positive rams were used in breeding experiments, four donor-derived offspring (four of 50 [8% of progeny])resulted from a recipient in Merino to Merino transplantation. Six lambs (six of 41 [15% of progeny]) were sired by donor-derived Border Leicester sperm produced in a Merino recipient ram; however, no donor-derived offspring were detected among 34 progeny from a second Border Leicester to Merino combination. These results confirm that preparation of recipient animals with a correct dose of irradiation not only enhances the success rate of the transplantation procedure but also increases the proportion of donor spermatozoa in recipient semen. This study represents the first report of the production of live progeny following testis germ cell transplantation using irradiated recipients in a livestock species.

Radiation recall dermatitis after pre-sensitization with pegylated liposomal doxorubicin.

Radiation recall dermatitis (RRD) is a rare cutaneous reaction occurring within a previously irradiated field, precipitated by certain drugs. We report a case of RRD occurring after pre-sensitization with pegylated liposomal doxorubicin (PLD) in a woman with Stage IV breast cancer. The RRD occurred in one of the patient's four previous radiotherapy fields. We discuss the time/dose factors of radiation exposure and measure the corresponding skin dose. In our case the radiation dose was low and below previously reported thresholds, and illustrates that there is a more complex interaction between the radiotherapy and the trigger agent than has previously been considered.

Cerenkov light spectrum in an optical fiber exposed to a photon or electron radiation therapy beam.

A Cerenkov signal is generated when energetic charged particles enter the core of an optical fiber. The Cerenkov intensity can be large enough to interfere with signals transmitted through the fiber. We determine the spectrum of the Cerenkov background signal generated in a poly(methyl methacrylate) optical fiber exposed to photon and electron therapeutic beams from a linear accelerator. This spectral measurement is relevant to discrimination of the signal from the background, as in scintillation dosimetry using optical fiber readouts. We find that the spectrum is approximated by the theoretical curve after correction for the wavelength dependent attenuation of the fiber. The spectrum does not depend significantly on the angle between the radiation beam and the axis of the fiber optic but is dependent on the depth in water at which the fiber is exposed to the beam.

Single Step Plasma Process for Covalent Binding of Antimicrobial Peptides on Catheters To Suppress Bacterial Adhesion.

Catheter-associated biofilms are responsible for a large fraction of hospital acquired infections. Antimicrobial surface coating on catheters providing prevention at source is extensively studied to reduce bacterial adhesion. Antimicrobial peptides such as melimine and Mel4, covalently linked to surfaces, have shown excellent potential in animal and human studies to suppress infection without toxicity. Covalent binding of the peptides on catheter surfaces improves efficacy but so far has been implemented using multistep wet chemical coupling that will impede widespread adoption. Here we demonstrate plasma immersion ion implantation (PIII) as a single step treatment that covalently couples antimicrobial peptides to polyvinyl chloride (PVC). Strong antimicrobial activity was demonstrated by higher than 3 log kill of S. aureus. A variant of the process was demonstrated as an antimicrobial treatment for chemically inert glass surfaces. Covalent coupling was rigorously tested by stringent SDS washing. We further demonstrated that the plasma treatment can effectively functionalize both internal and external surfaces of catheter tubing, reducing 99% of bacterial adhesion. The process is feasible as a patient-safe treatment for treating various types of catheters and is suitable for commercial mass production. In a logical extension of the work, the process could be adapted to bone replacement scaffolds of all types including metallic, polymeric, and ceramic.