Search results for: gastric cancer surgery

Authors: Su Chul Han, Seungwoo Park

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As the increasing incidence of cancer, the technology and modality of radiotherapy have advanced and the importance of preclinical model is increasing in the cancer research. Furthermore, the small animal dosimetry is an essential part of the evaluation of the relationship between the absorbed dose in preclinical small animal and biological effect in preclinical study. In this study, we carried out realistic modeling of the preclinical small animal phantom possible to verify irradiated dose using commercial software. The small animal phantom was modeling from 4D Digital Mouse whole body phantom. To manipulate Moby phantom in commercial software (Mimics, Materialise, Leuven, Belgium), we converted Moby phantom to DICOM image file of CT by Matlab and two- dimensional of CT images were converted to the three-dimensional image and it is possible to segment and crop CT image in Sagittal, Coronal and axial view). The CT images of small animals were modeling following process. Based on the profile line value, the thresholding was carried out to make a mask that was connection of all the regions of the equal threshold range. Using thresholding method, we segmented into three part (bone, body (tissue). lung), to separate neighboring pixels between lung and body (tissue), we used region growing function of Mimics software. We acquired 3D object by 3D calculation in the segmented images. The generated 3D object was smoothing by remeshing operation and smoothing operation factor was 0.4, iteration value was 5. The edge mode was selected to perform triangle reduction. The parameters were that tolerance (0.1mm), edge angle (15 degrees) and the number of iteration (5). The image processing 3D object file was converted to an STL file to output with 3D printer. We modified 3D small animal file using 3- Matic research (Materialise, Leuven, Belgium) to make space for radiation dosimetry chips. We acquired 3D object of realistic small animal phantom. The width of small animal phantom was 2.631 cm, thickness was 2.361 cm, and length was 10.817. Mimics software supported efficiency about 3D object generation and usability of conversion to STL file for user. The development of small preclinical animal phantom would increase reliability of verification of absorbed dose in small animal for preclinical study.

Keywords: mimics, preclinical small animal, segmentation, 3D printer

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Authors: J. Sagouis, A. Chamel, E. Carre, C. Casasreales, G. Rudnik, M. Cerdan

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Robotics provides answers to amputees. The most expensive solutions surgically connect the prosthesis to nerve endings. There are also several types of non-invasive technologies that recover nerve messages passing through the muscles. After analyzing these messages, myoelectric prostheses perform the desired movement. The main goal is to avoid all surgeries, which can be heavy and offer cheaper alternatives. For an amputee, we use valid muscles to recover the electrical signal involved in a muscle movement. EMG sensors placed on the muscle allows us to measure a potential difference, which our program transforms into control for a robotic arm with two degrees of freedom. We have shown the feasibility of non-invasive prostheses with two degrees of freedom. Signal analysis and an increase in degrees of freedom is still being improved.

Keywords: prosthesis, electromyography (EMG), robotic arm, nerve message

Procedia PDF Downloads 247

Authors: Rubai M. Ochieng

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Cancer, which accounts for 7 percent of deaths per year in Kenya, is the third highest cause of death after infectious and cardiovascular diseases. Awareness Campaigns have tended to focus on leading cancers including breast and cervical for women as well as prostrate and Esophageal for men. Consequently, less common cancers such as Acute Myeloid Leukemia (AML) are rarely properly understood by the general population and a section of the medical fraternity. Diagnoses of AML in patients who may not have heard about it sometimes results in shock, denial and confusion not just to the diagnosed, but also to their family and friends. The diagnosed and caregivers are bound to receive a lot of contradicting information about prognosis, care and treatment of AML. This information, which often comes from diverse sources including doctors, friends, internet and social media platforms, causes further confusion and panic. The situation is handled differently by different people. Religious people sometimes resort to prayer. This paper, written from the perspective of a care giver, is based on data collected from a case of Acute Myeloid Leukemia diagnosed in a 32 year old male who lost his life within six weeks of diagnosis. The sample constitutes of 16 people who participated in prayers. Out of this total, 5 were males including the diagnosed and 11 were females. All the 16 were Christians of protestant orientation including Anglicans, Quakers and Church of God members. Data was collected by the researcher herself through participant of observation. Findings discuss how the 16 participants prayed individually at different times, together in an overnight prayer meeting and every morning through a group social media platform. They shared songs and words of encouragement from the bible. The group prayed for healing, peace and strength to the diagnosed and family, financial breakthrough and doctors’ work and decisions, among other challenges that came with the situation. The paper reveals the immense benefits of prayer to the diagnosed and his close relatives and friends. They include acceptance of the condition and a positive attitude in handling the challenges that arose from the disease and treatment processes. The challenges arising from the prayer approach of handling the situation are also discussed. The paper concludes that prayer as therapy goes a long way in cancer management.

Keywords: acute myeloid leukemia, Kenya, participant observation, prayer

Procedia PDF Downloads 162

Authors: Chen Wang, Jared Evans, Yan Asmann

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With the quick evolvement of next-generation sequencing techniques, whole-exome or exome-panel data have become a cost-effective way for detection of small exonic mutations, but there has been a growing desire to accurately detect copy number variations (CNVs) as well. In order to address this research and clinical needs, we developed a sequencing coverage pattern-based method not only for copy number detections, data integrity checks, CNV calling, and visualization reports. The developed methodologies include complete automation to increase usability, genome content-coverage bias correction, CNV segmentation, data quality reports, and publication quality images. Automatic identification and removal of poor quality outlier samples were made automatically. Multiple experimental batches were routinely detected and further reduced for a clean subset of samples before analysis. Algorithm improvements were also made to improve somatic CNV detection as well as germline CNV detection in trio family. Additionally, a set of utilities was included to facilitate users for producing CNV plots in focused genes of interest. We demonstrate the somatic CNV enhancements by accurately detecting CNVs in whole exome-wide data from the cancer genome atlas cancer samples and a lymphoma case study with paired tumor and normal samples. We also showed our efficient reuses of existing exome sequencing data, for improved germline CNV calling in a family of the trio from the phase-III study of 1000 Genome to detect CNVs with various modes of inheritance. The performance of the developed method is evaluated by comparing CNV calling results with results from other orthogonal copy number platforms. Through our case studies, reuses of exome sequencing data for calling CNVs have several noticeable functionalities, including a better quality control for exome sequencing data, improved joint analysis with single nucleotide variant calls, and novel genomic discovery of under-utilized existing whole exome and custom exome panel data.

Keywords: bioinformatics, computational genetics, copy number variations, data reuse, exome sequencing, next generation sequencing

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Authors: Enoch Kudoahor, Nan Zheng

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We describe the use of readily available self-doped TiO2 and visible light, under a mild condition to synthesize a class of monocyclic, bicyclic, and benzocyclobutene amino compounds containing the endoperoxide bridges; their derivatives and further test their effective clinical activities against malaria, cancer, and their resistances. Considering their stable under photooxidation conditions and recyclability, we use a self-doped TiO2 under a visible condition to synthesize these classes of amino endoperoxides. These amino endoperoxides are stable over a period compared to classes of endoperoxides.

Keywords: catalysis, endoperoxides, titanium dioxide, visible light

Procedia PDF Downloads 152

Authors: Christos E. Lampropoulos, Maria Konsta, Tamta Sirbilatze, Ifigenia Apostolou, Vicky Dradaki, Konstantina Panouria, Irini Dri, Christina Kordali, Vaggelis Lambas, Georgios Mavras

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Objectives: Full Mini Nutritional Assessment (MNA) questionnaire is one of the most useful tools in diagnosis of malnutrition in hospitalized patients, which is related to increased morbidity and mortality. The purpose of our study was to assess the nutritional status of elderly, hospitalized patients and examine the hypothesis that MNA may predict mortality and extension of hospitalization. Methods: One hundred fifty patients (78 men, 72 women, mean age 80±8.2) were included in this cross-sectional study. The following data were taken into account in analysis: anthropometric and laboratory data, physical activity (International Physical Activity Questionnaires, IPAQ), smoking status, dietary habits, cause and duration of current admission, medical history (co-morbidities, previous admissions). Primary endpoints were mortality (from admission until 6 months afterwards) and duration of admission. The latter was compared to national guidelines for closed consolidated medical expenses. Logistic regression and linear regression analysis were performed in order to identify independent predictors for mortality and extended hospitalization respectively. Results: According to MNA, nutrition was normal in 54/150 (36%) of patients, 46/150 (30.7%) of them were at risk of malnutrition and the rest 50/150 (33.3%) were malnourished. After performing multivariate logistic regression analysis we found that the odds of death decreased 20% per each unit increase of full MNA score (OR=0.8, 95% CI 0.74-0.89, p < 0.0001). Patients who admitted due to cancer were 23 times more likely to die, compared to those with infection (OR=23, 95% CI 3.8-141.6, p=0.001). Similarly, patients who admitted due to stroke were 7 times more likely to die (OR=7, 95% CI 1.4-34.5, p=0.02), while these with all other causes of admission were less likely (OR=0.2, 95% CI 0.06-0.8, p=0.03), compared to patients with infection. According to multivariate linear regression analysis, each increase of unit of full MNA, decreased the admission duration on average 0.3 days (b:-0.3, 95% CI -0.45 - -0.15, p < 0.0001). Patients admitted due to cancer had on average 6.8 days higher extension of hospitalization, compared to those admitted for infection (b:6.8, 95% CI 3.2-10.3, p < 0.0001). Conclusion: Mortality and extension of hospitalization is significantly increased in elderly, malnourished patients. Full MNA score is a useful diagnostic tool of malnutrition.

Keywords: duration of admission, malnutrition, mini nutritional assessment score, prognostic factors for mortality

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Authors: Dins Sumerags, Mara Pilmane, Vita Konopecka, Gunta Sumeraga

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Reinke’s oedema is a specific type of chronic laryngitis evolving only in smokers. Our study aimed to identify the presence and interaction of the immunohistochemical markers for inflammation [IL-1α] and [IL-10], proliferation [Ki-67] and immunoreactive innervation [PGP 9.5] in the laryngeal mucosa using biotin-streptavidin immunochemical staining method. The laryngeal tissue samples were taken from the vocal cord during the surgery of the Reinke’s oedema and compared to the control group from the tissue samples of the cadavers without any visual laryngeal disease. The study results confirm increased cellular proliferation and elevation of the inflammation markers in the laryngeal mucosa in the case of Reinke’s oedema by comparing with the control.

Keywords: reinke`s oedema, immunohistochemical markers, laryngeal mucosa, biotin-streptavidin

Procedia PDF Downloads 132

Authors: E. Locatelli, I. Monaco, R. C. Martin, Y. Li, R. Pini, M. Chiariello, M. Comes Franchini

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Despite the many advantages of application of nanomaterials in the field of nanomedicine, increasing concerns have been expressed on their potential adverse effects on human health. There is urgency for novel green strategies toward novel materials with enhanced biocompatibility using safe reagents. Photothermal ablation therapy, which exploits localized heat increase of a few degrees to kill cancer cells, has appeared recently as a non-invasive and highly efficient therapy against various cancer types; anyway new agents able to generate hyperthermia when irradiated are needed and must have precise biocompatibility in order to avoid damage to healthy tissues and prevent toxicity. Recently, there has been increasing interest in magnesium as a biomaterial: it is the fourth most abundant cation in the human body, and it is essential for human metabolism. However magnesium nanoparticles (Mg NPs) have had limited diffusion due to the high reduction potential of magnesium cations, which makes NPs synthesis challenging. Herein, we report the synthesis of Mg NPs and their surface functionalization for the obtainment of a stable and biocompatible nanomaterial suitable for photothermal ablation therapy against cancer. We synthesized the Mg crystals by reducing MgCl2 with metallic lithium and exploiting naphthalene as an electron carrier: the lithium–naphthalene complex acts as the real reducing agent. Firstly, the nanocrystal particles were coated with the ligand 12-ethoxy ester dodecanehydroxamic acid, and then entrapped into water-dispersible polymeric micelles (PMs) made of the FDA-approved PLGA-b-PEG-COOH copolymer using the oil-in-water emulsion technique. Lately, we developed a more straightforward methodology by introducing chitosan, a highly biocompatible natural product, at the beginning of the process, simultaneously using lithium–naphthalene complex, thus having a one-pot procedure for the formation and surface modification of MgNPs. The obtained MgNPs were purified and fully characterized, showing diameters in the range of 50-300 nm. Notably, when coated with chitosan the particles remained stable as dry powder for more than 10 months. We proved the possibility of generating a temperature rise of a few to several degrees once MgNPs were illuminated using a 810 nm diode laser operating in continuous wave mode: the temperature rise resulted significant (0-15 °C) and concentration dependent. We then investigated potential cytotoxicity of the MgNPs: we used HN13 epithelial cells, derived from a head and neck squamous cell carcinoma and the hepa1-6 cell line, derived from hepatocellular carcinoma and very low toxicity was observed for both nanosystems. Finally, in vivo photothermal therapy was performed on xenograft hepa1-6 tumor bearing mice: the animals were treated with MgNPs coated with chitosan and showed no sign of suffering after the injection. After 12 hours the tumor was exposed to near-infrared laser light. The results clearly showed an extensive damage to tumor tissue after only 2 minutes of laser irradiation at 3Wcm-1, while no damage was reported when the tumor was treated with the laser and saline alone in control group. Despite the lower photothermal efficiency of Mg with respect to Au NPs, we consider MgNPs a promising, safe and green candidate for future clinical translations.

Keywords: chitosan, magnesium nanoparticles, nanomedicine, photothermal therapy

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Authors: Seyedeh Nasim Mirbahari, Taha Azad, Mehdi Totonchi

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Oncolytic viruses, which only replicate in tumor cells, are being extensively studied for their use in cancer therapy. A particular virus known as the vaccinia virus, a member of the poxvirus family, has demonstrated oncolytic abilities glioma. Treating Glioma with traditional methods such as chemotherapy and radiotherapy is quite challenging. Even though oncolytic viruses have shown immense potential in cancer treatment, their effectiveness in glioblastoma treatment is still low. Therefore, there is a need to improve and optimize immunotherapies for better results. In this study, we have designed oncoVV-TT, which can more effectively target tumor cells while minimizing replication in normal cells by replacing the thymidine kinase gene with a luc-p2a-GFP gene expression cassette. Human glioblastoma cell line U251 MG, rat glioblastoma cell line C6, and non-tumor cell line HFF were plated at 105 cells in a 12-well plates in 2 mL of DMEM-F2 medium with 10% FBS added to each well. Then incubated at 37°C. After 16 hours, the cells were treated with oncoVV-TT at an MOI of 0.01, 0.1 and left in the incubator for a further 24, 48, 72 and 96 hours. Viral replication assay, fluorescence imaging and viability tests, including trypan blue and crystal violet, were conducted to evaluate the cytotoxic effect of oncoVV-TT. The finding shows that oncoVV-TT had significantly higher cytotoxic activity and proliferation rates in tumor cells in a dose and time-dependent manner, with the strongest effect observed in U251 MG. To conclude, oncoVV-TT has the potential to be a promising oncolytic virus for cancer treatment, with a more cytotoxic effect in human glioblastoma cells versus rat glioma cells. To assess the effectiveness of vaccinia virus-mediated viral therapy, we have tested U251mg and C6 tumor cell lines taken from human and rat gliomas, respectively. The study evaluated oncoVV-TT's ability to replicate and lyse cells and analyzed the survival rates of the tested cell lines when treated with different doses of oncoVV-TT. Additionally, we compared the sensitivity of human and mouse glioma cell lines to the oncolytic vaccinia virus. All experiments regarding viruses were conducted under biosafety level 2. We engineered a Vaccinia-based oncolytic virus called oncoVV-TT to replicate specifically in tumor cells. To propagate the oncoVV-TT virus, HeLa cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 10 MOI virus was added. After 48 h, cells were harvested by scraping, and viruses were collected by 3 sequential freezing and thawing cycles followed by removal of cell debris by centrifugation (1500 rpm, 5 min). The supernatant was stored at −80 ◦C for the following experiments. To measure the replication of the virus in Hela, cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 5 MOI virus or equal dilution of PBS was added. At the treatment time of 0 h, 24 h, 48 h, 72 h and 96 h, the viral titers were determined under the fluorescence microscope (BZ-X700; Keyence, Osaka, Japan). Fluorescence intensity was quantified using the imagej software according to the manufacturer’s protocol. For the isolation of single-virus clones, HeLa cells seeded in six-well plates (5×105 cells/well). After 24 h (100% confluent), the cells were infected with a 10-fold dilution series of TianTan green fluorescent protein (GFP)virus and incubated for 4 h. To examine the cytotoxic effect of oncoVV-TT virus ofn U251mg and C6 cell, trypan blue and crystal violet assay was used.

Keywords: oncolytic virus, immune therapy, glioma, vaccinia virus

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Authors: P. Uma Devi, S. Sujith, K. Rahul, T. S. Dipu, V. Anil Kumar , Vidya Menon

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Introduction: Candida is an important cause of bloodstream infections (BSIs), causing significant mortality and morbidity. The epidemiology of Candida infection is also changing, mainly in relation to the number of episodes caused by species Candida non-albicans. However, in India, the true burden of candidemia is not clear. Thus, this study was conducted to evaluate the clinical characteristics, species distribution, antifungal susceptibility and outcome of candidemia at our hospital. Methodology: Between January 2012 and April 2014, adult patients with at least one positive blood culture for Candida species were identified through the microbiology laboratory database (for each patient only the first episode of candidemia was recorded). Patient data was collected by retrospective chart review of clinical characteristics including demographic data, risk factors; species distribution, resistance to antifungals and survival. Results: A total of 165 episodes of Candida BSI were identified, with 115 episodes occurring in adult patients. Most of the episodes occurred in males (69.6%). Nearly 82.6% patients were between 41 to 80 years and majority of the patients were in the intensive care unit (65.2%) at the time of diagnosis. On admission, 26.1% and 18.3% patients had pneumonia and urinary tract infection, respectively. Majority of the candidemia episodes were found in the general medicine department (23.5%) followed by gastrointestinal surgery (13.9%) and medical oncology & haematology (13%). Risk factors identified were prior hospitalization within one year (83.5%), antibiotic therapy within the last one month (64.3%), indwelling urinary catheter (63.5%), central venous catheter use (59.1%), diabetes mellitus (53%), severe sepsis (45.2%), mechanical ventilation (43.5%) and surgery (36.5%). C. tropicalis (30.4%) was the leading cause of infection followed by C. parapsilosis (28.7%) and C. albicans (13%). Other non-albicans species isolated included C. haemulonii (7.8%), C. glabrata (7%), C. famata (4.3%) and C. krusei (1.7%). Antifungal susceptibility to fluconazole was 87.9% (C. parapsilosis), 100% (C. tropicalis) and 93.3% (C. albicans). Mortality was noted in 51 patients (44.3%). Early mortality (within 7 days) was noted in 32 patients while late mortality (between 7 and 30 days) was noted in 19 patients. Conclusion: In recent years, candidemia has been flourishing in critically ill patients. Comparison of data from our own hospital from 2005 shows a doubling of the incidence. Rapid changes in the rate of infection, potential risk factors, and emergence of non-albicans Candida demand continued surveillance of this serious BSI. High index of suspicion and sensitive diagnostics are essential to improve outcomes in resource limited settings with emergence of non-albicans Candida.

Keywords: antifungal susceptibility, candida albicans, candidemia, non-albicans candida

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Authors: Y. Teterin, S. Suleymanova, I. Dmitriev, P. Yartcev

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Introduction: One of the most common complications after pancreas transplantation are pancreatic fluid collections (PFCs), which are often complicated not only by infection and subsequent disfunction of the pancreatoduodenal graft (PDG), but also with a rather high mortality rate of recipients. Drainage is not always effective and often requires repeated open surgical interventions, which worsens the outcome of the surgery. Percutaneous drainage of PFCs combined with endoscopic stenting of the main pancreatic duct of the pancreatoduodenal graft (MPDPDG) showed high efficiency in the treatment of PFCs. Aims & Methods: From 01.01.2012 to 31.12.2021 at the Sklifosovsky Research Institute for Emergency Medicine were performed 64 transplantations of PDG. In 11 cases (17.2%), the early postoperative period was complicated by the formation of PFCs. Of these, 7 patients underwent percutaneous drainage of pancreonecrosis with high efficiency and did not required additional methods of treatment. In the remaining 4 patients, drainage was ineffective and was an indication for endoscopic stenting of the MPDPDG. They were the ones who made up the study group. Among them were 3 men and 1 woman. The mean age of the patients was 36,4 years.PFCs in these patients formed on days 1, 12, 18, and 47 after PDG transplantation. We used a gastroscope to stent the MPDPDG, due to anatomical features of the location of the duodenoduodenal anastomosis after PDG transplantation. Through the endoscope channel was performed selective catheterization of the MPDPDG, using a catheter and a guidewire, followed by its contrasting with a water-soluble contrast agent. Due to the extravasation of the contrast, was determined the localization of the defect in the PDG duct system. After that, a plastic pancreatic stent with a diameter of 7 Fr. and a length of 7 cm. was installed along guidewire. The stent was installed in such a way that its proximal edge completely covered the defect zone, and the distal one was determined in the intestinal lumen. Results: In all patients PDG pancreaticography revealed extravasation of a contrast in the area of the isthmus and body of the pancreas, which required stenting of the MPDPDG. In 1 (25%) case, the patient had a dislocation of the stent into the intestinal lumen (III degree according to Clavien-Dindo (2009)). This patient underwent repeated endoscopic stenting of the MPDPDG. On average 23 days after endoscopic stenting of the MPDPDG, the drainage tubes were removed and after approximately 40 days all patients were discharged in a satisfactory condition with follow-up endocrinologist and surgeon consultation. Pancreatic stents were removed after 6 months ± 7 days. Conclusion: Endoscopic stenting of the main pancreatic duct of the donor pancreas is by far the most highly effective and minimally invasive method in the treatment of PFCs after transplantation of the pancreatoduodenal complex.

Keywords: pancreas transplantation, endoscopy surgery, diabetes, stenting, main pancreatic duct

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Authors: Liam Martin, Martha Watson

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Patients with learning disabilities (LD) are at increased risk of physical and mental illness due to health inequality. To address this, NICE recommends that people from the age of 14 with a learning disability should have an annual LD health check. This consultation should include a holistic review of the patient’s physical, mental and social health needs with a view of creating an action plan to support the patient’s care. The expected standard set by the Quality and Outcomes Framework (QOF) is that each general practice should review at least 75% of their LD patients annually. During COVID-19, there have been barriers to primary care, including health anxiety, the shift to online general practice and the increase in GP workloads. A surgery in North London wanted to assess whether they were falling short of the expected standard for LD patient annual reviews in order to optimize care post Covid-19. A baseline audit was completed to assess how many LD patients were receiving their annual reviews over the period of 29th September 2020 to 29th September 2021. This information was accessed using EMIS Web Health Care System (EMIS). Patients included were aged 14 and over as per QOF standards. Doctors were not notified of this audit taking place. Following the results of this audit, the creation of learning disability clinics was recommended. These clinics were recommended to be on the ground floor and should be a dedicated time for LD reviews. A re-audit was performed via the same process 6 months later in March 2022. At the time of the baseline audit, there were 71 patients aged 14 and over that were on the LD register. 54% of these LD patients were found to have documentation of an annual LD review within the last 12 months. None of the LD patients between the ages of 14-18 years old had received their annual review. The results were discussed with the practice, and dedicated clinics were set up to review their LD patients. A second pass of the audit was completed 6 months later. This showed an improvement, with 84% of the LD patients registered at the surgery now having a documented annual review within the last 12 months. 78% of the patients between the ages of 14-18 years old had now been reviewed. The baseline audit revealed that the practice was not meeting the expected standard for LD patient’s annual health checks as outlined by QOF, with the most neglected patients being between the ages of 14-18. Identification and awareness of this vulnerable cohort is important to ensure measures can be put into place to support their physical, mental and social wellbeing. Other practices could consider an audit of their annual LD health checks to make sure they are practicing within QOF standards, and if there is a shortfall, they could consider implementing similar actions as used here; dedicated clinics for LD patient reviews.

Keywords: COVID-19, learning disability, learning disability health review, quality and outcomes framework

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Authors: Sandeep Mohindra

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Since 2013, the authors have operated on 568 cases of pituitary tumors through the trans-sphenoidal route, using the binostril approach. The distribution included 486 cases of non-functioning pituitary tumors, 24 cases of Growth hormone(GH) secreting tumors(acromegaly), and 28 cases of adrenocorticotrophic(ACTH) secreting tumors(Cushing's Disease). The authors utilized neuro-navigation for 18 cases, and all belonged to the functional tumor category. Complications included ICA injury in 2 cases, fatal meningitis in 5 cases, while CSF leak required repair in 28 cases. Satisfactory excision was noted in 512 cases, while recurrence/residual required repeat surgery in 32 cases. Authors conclude that trans sphenoidal route remains the best and optimal way of managing sellar tumors, especially pituitary adenomas.

Keywords: pituitary, adenoma, trans-sphenoidal, endonasal, neuronavigation

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Authors: Giuliana Murfet, Heidi Behrens

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Chronic disease is Australia’s biggest health concern and obesity the leading risk factor for many. Obesity and chronic disease have a higher representation in rural Tasmania, where levels of socio-disadvantage are also higher. People living outside major cities have less access to health services and poorer health outcomes. To help primary healthcare professionals manage obesity, the Australian NHMRC evidence-based clinical practice guidelines for management of overweight and obesity in adults were developed. They include recommendations for practice and models for obesity management. To our knowledge there has been no research conducted that investigates translation of these guidelines into practice in rural-regional areas; where implementation can be complicated by limited financial and staffing resources. Also, the systematic review that informed the guidelines revealed a lack of evidence for chronic disease models of obesity care. The aim was to establish and evaluate a multidisciplinary model for obesity management in a group of adult people with type 2 diabetes in a dispersed rural population in Australia. Extensive stakeholder engagement was undertaken to both garner support for an obesity clinic and develop a sustainable model of care. A comprehensive nurse practitioner-led outpatient model for obesity care was designed. Multidisciplinary obesity clinics for adults with type 2 diabetes including a dietitian, psychologist, physiotherapist and nurse practitioner were set up in the north-west of Tasmania at two geographically-rural towns. Implementation was underpinned by the NHMRC guidelines and recommendations focused on: assessment approaches; promotion of health benefits of weight loss; identification of relevant programs for individualising care; medication and bariatric surgery options for obesity management; and, the importance of long-term weight management. A clinical pathway for adult weight management is delivered by the multidisciplinary team with recognition of the impact of and adjustments needed for other comorbidities. The model allowed for intensification of intervention such as bariatric surgery according to recommendations, patient desires and suitability. A randomised controlled trial is ongoing, with the aim to evaluate standard care (diabetes-focused management) compared with an obesity-related approach with additional dietetic, physiotherapy, psychology and lifestyle advice. Key barriers and enablers to guideline implementation were identified that fall under the following themes: 1) health care delivery changes and the project framework development; 2) capacity and team-building; 3) stakeholder engagement; and, 4) the research project and partnerships. Engagement of not only local hospital but also state-wide health executives and surgical services committee were paramount to the success of the project. Staff training and collective development of the framework allowed for shared understanding. Staff capacity was increased with most taking on other activities (e.g., surgery coordination). Barriers were often related to differences of opinions in focus of the project; a desire to remain evidenced based (e.g., exercise prescription) without adjusting the model to allow for consideration of comorbidities. While barriers did exist and challenges overcome; the development of critical partnerships did enable the capacity for a potential model of obesity care for rural regional areas. Importantly, the findings contribute to the evidence base for models of diabetes and obesity care that coordinate limited resources.

Keywords: diabetes, interdisciplinary, model of care, obesity, rural regional

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Authors: Frazer Kirk, Rohen Skiba, Pankaj Saxena

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The natural history of the QAV is poorly understood due to the exceeding rarity of the condition. Incidence rates vary between 0.00028-1%. Classically patients present with Aortic Regurgitation (AR) between 40-60 years of age experiencing palpitations, chest pain, or heart failure. (1, 2) Echocardiography is the mainstay of diagnosis for this condition; however, given the rarity of this condition, it can easily be overlooked, as demonstrated here. The case report that follows serves as a reminder of the condition to reduce the innate cognitive bias to overlook the diagnosis due to the availability heuristic. Intraoperative photography, echocardiographic and magnetic resonance imaging from this case for reference to demonstrate that while the diagnosis of Aortic regurgitation was recognized early, the valve morphology was underappreciated.

Keywords: quadricuspid aortic valve, cardiac surgery, echocardiography, congenital

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Authors: Otana A. Jakpor

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Air pollution is without a doubt one of the gravest environmental threats the world is facing today in terms of its sheer toll on human lives. Each year an estimated 70,000 Americans lose their lives to air pollution -- a number equal to deaths from both breast and prostate cancer combined. Since Americans spend nearly 90% of their time indoors, more research is needed on indoor air pollution and common exposures such as candles. Paraffin wax is a by-product of petroleum, and similarities have been observed between fine particulate emissions from paraffin candles and diesel exhaust. The purpose of this study is to determine whether or not paraffin candles are a major potential source of indoor air pollution. Furthermore, this study aims to determine whether or not soy candles are a safer, cleaner alternative to paraffin candles.

Keywords: soy candle, soy, paraffin candle, paraffin

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Authors: Yael Wolff Sagy, Yiska Loewenberg Weisband, Vered Kaufman Shriqui, Michal Krieger, Arie Ben Yehuda, Ronit Calderon Margalit

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Background: Obesity is both a risk factor and common comorbidity of diabetes. Obesity impedes the achievement of glycemic control, and enhances damage caused by hyperglycemia to blood vessels; thus it increases diabetes-related complications. This study assessed the prevalence of obesity and morbid obesity among Israeli adults with diabetes, and estimated disparities associated with sex and socioeconomic position (SEP). Methods: A cross-sectional study was conducted in the setting of the Israeli National Program for Quality Indicators in Community Healthcare. Data on all the Israeli population is retrieved from electronic medical records of the four health maintenance organizations (HMOs). The study population included all Israeli patients with diabetes aged 20-64 with documented body mass index (BMI) in 2016 (N=180,451). Diabetes was defined as the existence of one or more of the following criteria: (a) Plasma glucose level >200 mg% in at least two tests conducted at least one month apart in the previous year; (b) HbA1c>6.5% at least once in the previous year (c) at least three prescriptions of diabetes medications were dispensed during the previous year. Two measures were included: the prevalence of obesity (defined as last BMI≥ 30 kg/m2 and <35 kg/m2) and the prevalence of morbid obesity (defined as last BMI≥ 35 kg/m2) in individuals aged 20-64 with diabetes. The cut-off value for morbid obesity was set in accordance with the eligibility criteria for bariatric surgery in diabetics. Data were collected by the HMOs and aggregated by age, sex and SEP. SEP was based on statistical areas ranking by the Israeli Central Bureau of Statistics and divided into 4 categories, ranking from 1 (lowest) to 4 (highest). Results: BMI documentation among adults with diabetes was 84.9% in 2016. The prevalence of obesity in the study population was 30.5%. Although the overall rate was similar in both sexes (30.8% in females, 30.3% in males), SEP disparities were stronger in females (32.7% in SEP level 1 vs. 27.7% in SEP level 4; 18.1% relative difference) compared to males (30.6% in SEP level 1 vs. 29.3% in SEP level 4; 4.4% relative difference). The overall prevalence of morbid obesity in this population was 20.8% in 2016. The rate among females was almost double compared to the rate in males (28.1% and 14.6%, respectively). In both sexes, the prevalence of morbid obesity was strongly associated with lower SEP. However, in females, disparities between SEP levels were much stronger (34.3% in SEP level 1 vs. 18.7% in SEP level 4; 83.4% relative difference) compared to SEP-disparities in males (15.7% in SEP level 1 vs. 12.3% in SEP level 4; 27.6% relative difference). Conclusions: The overall prevalence of BMI≥ 30 kg/m2 among adults with diabetes in Israel exceeds 50%; and the prevalence of morbid obesity suggests that 20% meet the BMI-criteria for bariatric surgery. Prevalence rates show major SEP- and sex-disparities; especially strong SEP disparities in morbid obesity among females. These findings highlight the need for greater consideration of different population groups when implementing interventions.

Keywords: diabetes, health disparities, health policy, obesity, socio-economic position

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Authors: Zhen Cao, Yu Zhu, Junxue Fu

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Immunoassay, i.e., antigen-antibody reaction, is crucial for disease diagnostics. To achieve the adequate signal of the antigen protein detection, a large amount of sample and long incubation time is needed. However, the amount of protein is usually small at the early stage, which makes it difficult to detect. Unlike cells and DNAs, no valid chemical method exists for protein amplification. Thus, an alternative way to improve the signal is through particle manipulation techniques to concentrate proteins, among which dielectrophoresis (DEP) is an effective one. DEP is a technique that concentrates particles to the designated region through a force created by the gradient in a non-uniform electric field. Since DEP force is proportional to the cube of particle size and square of electric field gradient, it is relatively easy to capture larger particles such as cells. For smaller ones like proteins, a super high gradient is then required. In this work, three-dimensional Ag/SiO2 nanorods arrays, fabricated by an easy physical vapor deposition technique called as oblique angle deposition, have been integrated with a DEP device and created the field gradient as high as of 2.6×10²⁴ V²/m³. The nanorods based DEP device is able to enrich bovine serum albumin (BSA) protein by 1800-fold and the rate has reached 180-fold/s when only applying 5 V electric potential. Based on the above nanorods integrated DEP platform, an immunoassay of mouse immunoglobulin G (IgG) proteins has been performed. Briefly, specific antibodies are immobilized onto nanorods, then IgG proteins are concentrated and captured, and finally, the signal from fluorescence-labelled antibodies are detected. The limit of detection (LoD) is measured as 275.3 fg/mL (~1.8 fM), which is a 20,000-fold enhancement compared with identical assays performed on blank glass plates. Further, prostate-specific antigen (PSA), which is a cancer biomarker for diagnosis of prostate cancer after radical prostatectomy, is also quantified with a LoD as low as 2.6 pg/mL. The time to signal saturation has been significantly reduced to one minute. In summary, together with an easy nanorod fabrication and integration method, this nanorods based DEP platform has demonstrated highly sensitive immunoassay performance and thus poses great potentials in applications for early point-of-care diagnostics.

Keywords: dielectrophoresis, immunoassay, oblique angle deposition, protein concentration

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Authors: Muhammad Faisal Khilji, Rana Shoaib Hamid

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Subdural hematoma (SDH) is an extremely rare complication of immune thrombocytopenic purpura (ITP). We present a case of a 34 years old female who presented to the Emergency department of a tertiary care hospital with complaints of headache, on and off gums bleeding and upper respiratory tract symptoms for the last two weeks. Examination was unremarkable except some purpura over limbs. Investigations revealed zero platelets and peripheral film suggestive of ITP. Computerized tomography (CT) brain revealed bilateral SDH in the frontal areas extending into Falx cerebri. Impression of ITP with SDH was made. Patient was treated with intravenous immunoglobulin (IVIg), methyl prednisolone and initial Platelets transfusion. Patient recovered uneventfully with platelets reaching normal levels within a few days and resolution of SDH without surgery.

Keywords: headache, immune thrombocytopenia, purpura, subdural hematoma

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Authors: Mohammad Ali Al Qatawneh, Bespalchuk Pavel Ivanovich

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Computer navigation has been introduced in total knee arthroplasty to improve the accuracy of the procedure. Computer navigation improves the accuracy of bone resection in the coronal and sagittal planes. It was also noted that it normalizes the rotational alignment of the femoral component and fully assesses and balances the deformation of soft tissues in the coronal plane. The work is devoted to the advantages of using computer navigation technology in total knee arthroplasty in 62 patients (11 men and 51 women) suffering from gonarthrosis, aged 51 to 83 years, operated using a computer navigation system, followed up to 3 years from the moment of surgery. During the examination, the deformity variant was determined, and radiometric parameters of the knee joints were measured using the Knee Society Score (KSS), Functional Knee Society Score (FKSS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scales. Also, functional stress tests were performed to assess the stability of the knee joint in the frontal plane and functional indicators of the range of motion. After surgery, improvement was observed in all scales; firstly, the WOMAC values decreased by 5.90 times, and the median value to 11 points (p < 0.001), secondly KSS increased by 3.91 times and reached 86 points (p < 0.001), and the third one is that FKSS data increased by 2.08 times and reached 94 points (p < 0.001). After TKA, the axis deviation of the lower limbs of more than 3 degrees was observed in 4 patients at 6.5% and frontal instability of the knee joint just in 2 cases at 3.2%., The lower incidence of sagittal instability of the knee joint after the operation was 9.6%. The range of motion increased by 1.25 times; the volume of movement averaged 125 degrees (p < 0.001). Computer navigation increases the accuracy of the spatial orientation of the endoprosthesis components in all planes, reduces the variability of the axis of the lower limbs within ± 3 °, allows you to achieve the best results of surgical interventions, and can be used to solve most basic tasks, allowing you to achieve excellent and good outcomes of operations in 100% of cases according to the WOMAC scale. With diaphyseal deformities of the femur and/or tibia, as well as with obstruction of their medullary canal, the use of computer navigation is the method of choice. The use of computer navigation prevents the occurrence of flexion contracture and hyperextension of the knee joint during the distal sawing of the femur. Using the navigation system achieves high-precision implantation for the endoprosthesis; in addition, it achieves an adequate balance of the ligaments, which contributes to the stability of the joint, reduces pain, and allows for the achievement of a good functional result of the treatment.

Keywords: knee joint, arthroplasty, computer navigation, advantages

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Authors: D. Muyama, M. Luyiga, P. Buyungo, D. Chemonges, M. Namukwaya, L. Ssekabembe, B. Lukwago, D. Kyamagwa

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Context: The study focuses on the sustainability of health interventions in Uganda, particularly in the private sector, beyond donor-funded project periods. The Population Services International (PSI) implemented the Women Health Project (WHP) to ensure continued access to quality family planning, cervical cancer screening, and post-abortion care services through private clinics. Research Aim: The aim of the study is to assess the continued access to quality family planning, cervical cancer screening, and post-abortion care services through the private sector after the closure or reduction in funding of the WHP. Methodology: PSI trained and mentored 83 clinics to establish functional systems in self-regulatory quality improvement, supply chain, referral, and demand creation. The clinics were also connected to the national reporting system and utilized Ministry of Health reporting tools. An assessment tool with six criteria was designed and used to evaluate the progress of the clinics. Clinics scoring 75% and above were considered independent and graduated from the program. Findings: Out of the 83 private clinics, 56 successfully met the graduation criteria and graduated from the program, while 25 lost interest and were gradually dropped. Two clinics failed to achieve the criteria due to leadership challenges. The 59 graduating clinics continued to provide high-quality family planning services, including IUD, implant, Depo-Provera, oral contraceptives, and post-abortion care. All graduating clinics were reassessed and found to still be capable of offering services, attributing their success to government stock availability and acquired skills through mentorships. The clinics expressed appreciation to PSI for the sustainable plan that allowed them to operate beyond the project period. Theoretical Importance: This study contributes to the understanding of sustainability planning and the importance of clinic owners' attitudes and buy-in for continued service provision. It emphasizes the implementation of sustainability plans through existing structures to leverage available resources and ensure continuity of care. Data Collection and Analysis Procedures: The study collected data through the assessment tool that evaluated the progress of clinics based on the established criteria. The tool was scored out of 100%, and clinics scoring above 75% were deemed independent. The findings were analyzed quantitatively to determine the success rate of clinics in meeting the graduation criteria. Questions Addressed: The study addresses the question of whether private clinics in Uganda can sustain the provision of family planning, cervical cancer screening, and post-abortion care services after the closure or reduction in funding of the WHP. Conclusion: The study concludes that the attitude and buy-in of clinic owners are essential for sustainability planning. Implementing sustainability plans through existing structures and leveraging available resources are crucial for the continuity of care after the end of a project or reduced funding. The findings highlight the importance of establishing sustainable plans to ensure continued access to essential health services beyond the project period. Contributions: This study contributes to the existing knowledge for programmers implementing or intending to implement donor-funded projects. It provides insights into designing sustainable plans that enable the independent operation of clinics even after the end of a project.

Keywords: graduation, family planning, systems strengthening, sustainability

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Authors: Hamsa T. Tayeb, Mohammad A. Arafah, Dana M. Bakheet, Duaa M. Khalaf, Agnieszka Tarnoska, Nduna Dzimiri

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Background: CYP2D6 is a member of the cytochrome P450 mixed-function oxidase system. The enzyme is responsible for the metabolism and elimination of approximately 25% of clinically used drugs, especially in breast cancer and psychiatric therapy. Different phenotypes have been described displaying alleles that lead to a complete loss of enzyme activity, reduced function (poor metabolizers – PM), hyperfunctionality (ultrarapid metabolizers–UM) and therefore drug intoxication or loss of drug effect. The prevalence of these variants may vary among different ethnic groups. Furthermore, the xTAG system has been developed to categorized all patients into different groups based on their CYP2D6 substrate metabolization. Aim of the study: To determine the prevalence of the different CYP2D6 variants in our population, and to evaluate their clinical relevance in personalized medicine. Methodology: We used the Luminex xMAP genotyping system to sequence 305 Saudi individuals visiting the Blood Bank of our Institution and determine which polymorphisms of CYP2D6 gene are prevalent in our region. Results: xTAG genotyping showed that 36.72% (112 out of 305 individuals) carried the CYP2D6_*2. Out of the 112 individuals with the *2 SNP, 6.23% had multiple copies of *2 SNP (19 individuals out of 305 individuals), resulting in an UM phenotype. About 33.44% carried the CYP2D6_*41, which leads to decreased activity of the CYP2D6 enzyme. 19.67% had the wild-type alleles and thus had normal enzyme function. Furthermore, 15.74% carried the CYP2D6_*4, which is the most common nonfunctional form of the CYP2D6 enzyme worldwide. 6.56% carried the CYP2D6_*17, resulting in decreased enzyme activity. Approximately 5.73% carried the CYP2D6_*10, consequently decreasing the enzyme activity, resulting in a PM phenotype. 2.30% carried the CYP2D6_*29, leading to decreased metabolic activity of the enzyme, and 2.30% carried the CYP2D6_*35, resulting in an UM phenotype, 1.64% had a whole-gene deletion CYP2D6_*5, thus resulting in the loss of CYP2D6 enzyme production, 0.66% carried the CYP2D6_*6 variant. One individual carried the CYP2D6_*3(B), producing an inactive form of the enzyme, which leads to decrease of enzyme activity, resulting in a PM phenotype. Finally, one individual carried the CYP2D6_*9, which decreases the enzyme activity. Conclusions: Our study demonstrates that different CYP2D6 variants are highly prevalent in ethnic Saudi Arabs. This finding sets a basis for informed genotyping for these variants in personalized medicine. The study also suggests that xTAG is an appropriate procedure for genotyping the CYP2D6 variants in personalized medicine.

Keywords: CYP2D6, hormonal breast cancer, pharmacogenetics, polymorphism, psychiatric treatment, Saudi population

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Authors: Amirul Adlan, Robert A McCulloch, Neil Jenkins, MIchael Parry, Jonathan Stevenson, Lee Jeys

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Background and Objectives: The current antibiotic prophylaxis for oncological patients is based upon evidence from primary arthroplasty despite significant differences in both patient group and procedure. The aim of this study was to compare the microbiology organisms responsible for PJI in patients who underwent two-stage revision for infected primary knee replacement with those of infected oncological endoprostheses of the lower limb in a single institution. This will subsequently guide decision making regarding antibiotic prophylaxis at primary implantation for oncological procedures and empirical antibiotics for infected revision procedures (where the infecting organism(s) are unknown). Patient and Methods: 118 patients were treated with two-stage revision surgery for infected knee arthroplasty and lower limb endoprostheses between 1999 and 2019. 74 patients had two-stage revision for PJI of knee arthroplasty, and 44 had two-stage revision of lower limb endoprostheses. There were 68 males and 50 females. The mean age for the knee arthroplasty cohort and lower limb endoprostheses cohort were 70.2 years (50-89) and 36.1 years (12-78), respectively (p<0.01). Patient host and extremity criteria were categorised according to the MSIS Host and Extremity Staging System. Patient microbiological culture, the incidence of polymicrobial infection and multi-drug resistance (MDR) were analysed and recorded. Results: Polymicrobial infection was reported in 16% (12 patients) from knee arthroplasty PJI and 14.5% (8 patients) in endoprostheses PJI (p=0.783). There was a significantly higher incidence of MDR in endoprostheses PJI, isolated in 36.4% of cultures, compared to knee arthroplasty PJI (17.2%) (p=0.01). Gram-positive organisms were isolated in more than 80% of cultures from both cohorts. Coagulase-negative Staphylococcus (CoNS) was the commonest gram-positive organism, and Escherichia coli was the commonest Gram-negative organism in both groups. According to the MSIS staging system, the host and extremity grade of knee arthroplasty PJI cohort were significantly better than endoprostheses PJI(p<0.05). Conclusion: Empirical antibiotic management of PJI in orthopaedic oncology is based upon PJI in arthroplasty despite differences in both host and microbiology. Our results show a significant increase in MDR pathogens within the oncological group despite CoNS being the most common infective organism in both groups. Endoprosthetic patients presented with poorer host and extremity criteria. These factors should be considered when managing this complex patient group, emphasising the importance of broad-spectrum antibiotic prophylaxis and preoperative sampling to ensure appropriate perioperative antibiotic cover.

Keywords: microbiology, periprosthetic Joint infection, knee arthroplasty, endoprostheses

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Authors: Mamdouh Abu-Zaied, K. Mohamed, Galal A. Nawwar

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Microwave-assisted synthesis of a new class of pyridine or purine thioglycoside analogs from readily available starting materials has been described. The key step of this protocol is the formation of sodium pyridine 4-thiolate 4 and pyrazolo[1,5-a]pyrimidine-7-thiolate 5 derivatives via condensation of 1 with cyanoacetanilide derivative 2 or 5-aminopyrazole derivative 3 respectively under microwave irradiation, followed by coupling with halo sugars to give the corresponding pyridine and purine thioglycoside analogs. The obtained compounds were evaluated in vitro against lung (A549), colon (HCT116), liver (HEPG2), and MCF-7(breast) cancer cell lines. Some of them recorded promising activities.

Keywords: antitumor, cyclic sugars, pyrazoles, pyridines, pyrimidines, purines, thioglycosides

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Authors: Prodromos E. Atlamazoglou

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The method of moments combined with the method of symmetrical components is used for the analysis of interstitial hyperthermia applicators. The basis and testing functions are both piecewise sinusoids, qualifying our technique as a Galerkin one. The dielectric coatings are modeled by equivalent volume polarization currents, which are simply related to the conduction current distribution, avoiding in that way the introduction of additional unknowns or numerical integrations. The results of our method for a four dipole circular array, are in agreement with those already published in literature for a same hyperthermia configuration. Apart from being accurate, our approach is more general, more computationally efficient and takes into account the coupling between the antennas.

Keywords: hyperthermia, integral equations, insulated antennas, method of symmetrical components

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Authors: Farah Al Zaabi, Sarah Amrani

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Complex regional pain syndrome (CRPS) is a chronic pain condition that develops in an extremity following a fracture, soft tissue injury, or surgery. It is a neuropathic pain disorder that is accompanied by the characteristic skin manifestations that are needed for the diagnosis. We report the case of a 30 year old male, who has findings consistent with CRPS and has been followed for over two years by multiple specialties within the healthcare system without obtaining a diagnosis. The symptoms he presented with were treated based on the specialty he was seeing, rather than unified and recognized as a single disease process. Our case highlights the complexity of chronic pain, which can sometimes present with skin manifestations, and the importance of involving a pain specialist early for both the medical and physical recovery of CRPS patients.

Keywords: complex regional pain syndrome, chronic pain, skin changes of CRPS, dermatological manifestions of CRPS

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Authors: Georges F. Hatoum, Thomas H. Temple, Silvio Garcia, Xiaodong Wu

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Soft Tissue Sarcomas (STS) represent a diverse group of malignancies with heterogeneous clinical and pathological features. The treatment of extremity STS aims to achieve optimal local tumor control, improved survival, and preservation of limb function. The National Comprehensive Cancer Network guidelines, based on the cumulated clinical data, recommend radiation therapy (RT) in conjunction with limb-sparing surgery for large, high-grade STS measuring greater than 5 cm in size. Such treatment strategy can offer a cure for patients. However, when recurrence occurs (in nearly half of patients), the prognosis is poor, with a median survival of 12 to 15 months and with only palliative treatment options available. The spatially-fractionated-radiotherapy (SFRT), with a long history of treating bulky tumors as a non-mainstream technique, has gained new attention in recent years due to its unconventional therapeutic effects, such as bystander/abscopal effects. Combining single fraction of GRID, the original form of SFRT, with conventional RT was shown to have marginally increased the rate of pathological necrosis, which has been recognized to have a positive correlation to overall survival. In an effort to consistently increase the pathological necrosis rate over 90%, multiple fractions of Lattice RT (LRT), a newer form of 3D SFRT, interdigitated with the standard RT as neoadjuvant therapy was conducted in a preliminary clinical setting. With favorable results of over 95% of necrosis rate in a small cohort of patients, a Phase I/II clinical study was proposed to exam the safety and feasibility of this new strategy. Herein the design of the clinical study is presented. In this single-arm, two-stage phase I/II clinical trial, the primary objectives are >80% of the patients achieving >90% tumor necrosis and to evaluation the toxicity; the secondary objectives are to evaluate the local control, disease free survival and overall survival (OS), as well as the correlation between clinical response and the relevant biomarkers. The study plans to accrue patients over a span of two years. All patient will be treated with the new neoadjuvant RT regimen, in which one of every five fractions of conventional RT is replaced by a LRT fraction with vertices receiving dose ≥10Gy while keeping the tumor periphery at or close to 2 Gy per fraction. Surgical removal of the tumor is planned to occur 6 to 8 weeks following the completion of radiation therapy. The study will employ a Pocock-style early stopping boundary to ensure patient safety. The patients will be followed and monitored for a period of five years. Despite much effort, the rarity of the disease has resulted in limited novel therapeutic breakthroughs. Although a higher rate of treatment-induced tumor necrosis has been associated with improved OS, with the current techniques, only 20% of patients with large, high-grade tumors achieve a tumor necrosis rate exceeding 50%. If this new neoadjuvant strategy is proven effective, an appreciable improvement in clinical outcome without added toxicity can be anticipated. Due to the rarity of the disease, it is hoped that such study could be orchestrated in a multi-institutional setting.

Keywords: lattice RT, necrosis, SFRT, soft tissue sarcoma

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Authors: Mariia V. Efremova, Iana O. Tcareva, Anastasia D. Blokhina, Ivan S. Grebennikov, Anastasia S. Garanina, Maxim A. Abakumov, Yury I. Golovin, Alexander G. Savchenko, Alexander G. Majouga, Natalya L. Klyachko

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During last decades magnetite nanoparticles (NPs) attract a deep interest of scientists due to their potential application in therapy and diagnostics. However, magnetite nanoparticles are toxic and non-stable in physiological conditions. To solve these problems, we decided to create two types of hybrid systems based on magnetite and gold which is inert and biocompatible: gold as a shell material (first type) and gold as separate NPs interfacially bond to magnetite NPs (second type). The synthesis of the first type hybrid nanoparticles was carried out as follows: Magnetite nanoparticles with an average diameter of 9±2 nm were obtained by co-precipitation of iron (II, III) chlorides then they were covered with gold shell by iterative reduction of hydrogen tetrachloroaurate with hydroxylamine hydrochloride. According to the TEM, ICP MS and EDX data, final nanoparticles had an average diameter of 31±4 nm and contained iron even after hydrochloric acid treatment. However, iron signals (K-line, 7,1 keV) were not localized so we can’t speak about one single magnetic core. Described nanoparticles covered with mercapto-PEG acid were non-toxic for human prostate cancer PC-3/ LNCaP cell lines (more than 90% survived cells as compared to control) and had high R2-relaxivity rates (>190 mМ-1s-1) that exceed the transverse relaxation rate of commercial MRI-contrasting agents. These nanoparticles were also used for chymotrypsin enzyme immobilization. The effect of alternating magnetic field on catalytic properties of chymotrypsin immobilized on magnetite nanoparticles, notably the slowdown of catalyzed reaction at the level of 35-40 % was found. The synthesis of the second type hybrid nanoparticles also involved two steps. Firstly, spherical gold nanoparticles with an average diameter of 9±2 nm were synthesized by the reduction of hydrogen tetrachloroaurate with oleylamine; secondly, they were used as seeds during magnetite synthesis by thermal decomposition of iron pentacarbonyl in octadecene. As a result, so-called dumbbell-like structures were obtained where magnetite (cubes with 25±6 nm diagonal) and gold nanoparticles were connected together pairwise. By HRTEM method (first time for this type of structure) an epitaxial growth of magnetite nanoparticles on gold surface with co-orientation of (111) planes was discovered. These nanoparticles were transferred into water by means of block-copolymer Pluronic F127 then loaded with anti-cancer drug doxorubicin and also PSMA-vector specific for LNCaP cell line. Obtained nanoparticles were found to have moderate toxicity for human prostate cancer cells and got into the intracellular space after 45 minutes of incubation (according to fluorescence microscopy data). These materials are also perspective from MRI point of view (R2-relaxivity rates >70 mМ-1s-1). Thereby, in this work magnetite-gold hybrid nanoparticles, which have a strong potential for biomedical application, particularly in targeted drug delivery and magnetic resonance imaging, were synthesized and characterized. That paves the way to the development of special medicine types – theranostics. The authors knowledge financial support from Ministry of Education and Science of the Russian Federation (14.607.21.0132, RFMEFI60715X0132). This work was also supported by Grant of Ministry of Education and Science of the Russian Federation К1-2014-022, Grant of Russian Scientific Foundation 14-13-00731 and MSU development program 5.13.

Keywords: drug delivery, magnetite-gold, MRI contrast agents, nanoparticles, toxicity

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Authors: Y. Landkocz, P. Gosset, A. Héliot, C. Corbière, C. Vendeville, V. Keravec, S. Billet, A. Verdin, C. Monteil, D. Préterre, J-P. Morin, F. Sichel, T. Douki, P. J. Martin

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Air Pollution produced by automobile traffic is one of the main sources of pollutants in urban atmosphere and is largely due to exhausts of the diesel engine powered vehicles. The International Agency for Research on Cancer, which is part of the World Health Organization, classified in 2012 diesel engine exhaust as carcinogenic to humans (Group 1), based on sufficient evidence that exposure is associated with an increased risk for lung cancer. Amongst the strategies aimed at limiting exhausts in order to take into consideration the health impact of automobile pollution, filtration of the emissions and use of biofuels are developed, but their toxicological impact is largely unknown. Diesel exhausts are indeed complex mixtures of toxic substances difficult to study from a toxicological point of view, due to both the necessary characterization of the pollutants, sampling difficulties, potential synergy between the compounds and the wide variety of biological effects. Here, we studied the potential indirect genotoxicity of emission of Diesel engines through on-line exposure of rats in inhalation chambers to a subchronic high but realistic dose. Following exposure to standard gasoil +/- rapeseed methyl ester either upstream or downstream of a particle filter or control treatment, rats have been sacrificed and their lungs collected. The following indirect genotoxic parameters have been measured: (i) telomerase activity and telomeres length associated with rTERT and rTERC gene expression by RT-qPCR on frozen lungs, (ii) γH2AX quantification, representing double-strand DNA breaks, by immunohistochemistry on formalin fixed-paraffin embedded (FFPE) lung samples. These preliminary results will be then associated with global cellular response analyzed by pan-genomic microarrays, monitoring of oxidative stress and the quantification of primary DNA lesions in order to identify biological markers associated with a potential pro-carcinogenic response of diesel or biodiesel, with or without filters, in a relevant system of in vivo exposition.

Keywords: diesel exhaust exposed rats, γH2AX, indirect genotoxicity, lung carcinogenicity, telomerase activity, telomeres length

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Authors: Carlos Escobar-del Pozo, César Ahumada-Monroy, Azael García-Rebolledo, Alberto Brambila-Solórzano, Gregorio Martínez-Sánchez, Luis Ortiz-Rincón

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Numerical simulations of flow in complex biological structures have gained considerable attention in the last years. However, the major issue is the validation of the results. The present work shows a Particle Image Velocimetry PIV flow visualization technique in complex biological structures, particularly in intracranial aneurysms. A methodology to reconstruct and generate a transparent model has been developed, as well as visualization and particle tracking techniques. The generated transparent models allow visualizing the flow patterns with a regular camera using the visualization techniques. The final goal is to use visualization as a tool to provide more information on the treatment and surgery decisions in aneurysms.

Keywords: aneurysms, PIV, flow visualization, particle tracking

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