Search results for: proton therapy

Authors: Azri Yamina Mounia, Zitouni Dalila, Aziza Majda, Tou Insaf, Sadi Meriem

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To confront the fossil fuel crisis and the consequences of global warning, many efforts were devoted to develop alternative electricity generation and attracted numerous researchers, especially in the microbial fuel cell field, because it allows generating electric energy and degrading multiple organics compounds at the same time. However, one of the main constraints on power generation is the slow rate of oxygen reduction at the cathode electrode. This paper describes the potential of algal biomass (Chlorella vulgaris) as photosynthetic cathodes, eliminating the need for a mechanical air supply and the use of often expensive noble metal cathode catalysts, thus improving the sustainability and cost-effectiveness of the MFC system. During polarizations, MFC power density using algal biomass was 0.4mW/m², whereas the MFC with mechanic aeration showed a value of 0.2mW/m². Chlorella vulgaris was chosen due to its fastest growing. C. vulgaris grown in BG11 medium in sterilized Erlenmeyer flask. C. vulgaris was used as a bio‐cathode. Anaerobic activated sludge from the plant of Beni‐Messous WWTP(Algiers) was used in an anodic compartment. A dual‐chamber reactor MFC was used as a reactor. The reactor has been fabricated in the laboratory using plastic jars. The cylindrical and rectangular jars were used as the anode and cathode chambers, respectively. The volume of anode and cathode chambers was 0.8 and 2L, respectively. The two chambers were connected with a proton exchange membrane (PEM). The plain graphite plates (5 x 2cm) were used as electrodes for both anode and cathode. The cyclic voltammetry analysis of oxygen reduction revealed that the cathode potential was proportional to the amount of oxygen available in the cathode surface electrode. In the case of algal aeration, the peak reduction value of -2.18A/m² was two times higher than in mechanical aeration -1.85A/m². The electricity production reached 70 mA/m² and was stimulated immediately by the oxygen produced by algae up to the value of 20 mg/L.

Keywords: Chlorella vulgaris, cyclic voltammetry, microbial fuel cell, oxygen reduction

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Authors: Hosam Abdelhady

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Filming the behaviors of individual DNA molecules in their environment when they interact with individual medicinal nano-polymers in a molecular scale has opened the door to understand the effect of the molecular shape, size, and incubation time with nanocarriers on optimizing the design of robust genetic Nano molecules able to resist the enzymatic degradation, enter the cell, reach to the nucleus and kill individual cancer cells in their environment. To this end, we will show how we applied the 4D AFM as a guide to finetune the design of genetic nanoparticles and to film the effects of these nanoparticles on the nanomechanical and morphological profiles of individual cancer cells.

Keywords: AFM, dendrimers, nanoparticles, DNA, gene therapy, imaging

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Authors: Zuzanna Miodonska, Michal Krecichwost, Pawel Badura

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Sigmatism (lisping) is a speech disorder in which sibilant consonants are mispronounced. The diagnosis of this phenomenon is usually based on the auditory assessment. However, the progress in speech analysis techniques creates a possibility of developing computer-aided sigmatism diagnosis tools. The aim of the study is to statistically verify whether specific acoustic features of sibilant sounds may be related to pronunciation correctness. Such knowledge can be of great importance while implementing classifiers and designing novel tools for automatic sibilants pronunciation evaluation. The study covers analysis of various speech signal measures, including features proposed in the literature for the description of normative sibilants realization. Amplitudes and frequencies of three fricative formants (FF) are extracted based on local spectral maxima of the friction noise. Skewness, kurtosis, four normalized spectral moments (SM) and 13 mel-frequency cepstral coefficients (MFCC) with their 1st and 2nd derivatives (13 Delta and 13 Delta-Delta MFCC) are included in the analysis as well. The resulting feature vector contains 51 measures. The experiments are performed on the speech corpus containing words with selected sibilant sounds (/ʃ, ʒ/) pronounced by 60 preschool children with proper pronunciation or with natural pathologies. In total, 224 /ʃ/ segments and 191 /ʒ/ segments are employed in the study. The Mann-Whitney U test is employed for the analysis of stigmatism and normative pronunciation. Statistically, significant differences are obtained in most of the proposed features in children divided into these two groups at p < 0.05. All spectral moments and fricative formants appear to be distinctive between pathology and proper pronunciation. These metrics describe the friction noise characteristic for sibilants, which makes them particularly promising for the use in sibilants evaluation tools. Correspondences found between phoneme feature values and an expert evaluation of the pronunciation correctness encourage to involve speech analysis tools in diagnosis and therapy of sigmatism. Proposed feature extraction methods could be used in a computer-assisted stigmatism diagnosis or therapy systems.

Keywords: computer-aided pronunciation evaluation, sigmatism diagnosis, speech signal analysis, statistical verification

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Authors: Iman Farasat, Howard M. Salis

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The CRISPR/Cas9 system has revolutionized genome engineering by enabling site-directed and high-throughput genome editing, genome insertion, and gene knockdowns in several species, including bacteria, yeast, flies, worms, and human cell lines. This technology has the potential to enable human gene therapy to treat genetic diseases and cancer at the molecular level; however, the current CRISPR/Cas9 system suffers from seemingly sporadic off-target genome mutagenesis that prevents its use in gene therapy. A comprehensive mechanistic model that explains how the CRISPR/Cas9 functions would enable the rational design of the guide-RNAs responsible for target site selection while minimizing unexpected genome mutagenesis. Here, we present the first quantitative model of the CRISPR/Cas9 genome mutagenesis system that predicts how guide-RNA sequences (crRNAs) control target site selection and cleavage activity. We used statistical thermodynamics and law of mass action to develop a five-step biophysical model of cas9 cleavage, and examined it in vivo and in vitro. To predict a crRNA's binding specificities and cleavage rates, we then compiled a nearest neighbor (NN) energy model that accounts for all possible base pairings and mismatches between the crRNA and the possible genomic DNA sites. These calculations correctly predicted crRNA specificity across 5518 sites. Our analysis reveals that cas9 activity and specificity are anti-correlated, and, the trade-off between them is the determining factor in performing an RNA-mediated cleavage with minimal off-targets. To find an optimal solution, we first created a scheme of safe-design criteria for Cas9 target selection by systematic analysis of available high throughput measurements. We then used our biophysical model to determine the optimal Cas9 expression levels and timing that maximizes on-target cleavage and minimizes off-target activity. We successfully applied this approach in bacterial and mammalian cell lines to reduce off-target activity to near background mutagenesis level while maintaining high on-target cleavage rate.

Keywords: biophysical model, CRISPR, Cas9, genome editing

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Authors: Ji-Chan Jang

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Tuberculosis is still major health problem because there is an increase of multidrug-resistant and extensively drug-resistant forms of the disease. Therefore, the most urgent clinical need is to discover potent agents and develop novel drug combination capable of reducing the duration of MDR and XDR tuberculosis therapy. Three reference strains H37Rv, CDC1551, W-Beijing GC1237 and six clinical isolates of MDRTB were tested to daptomycin in the range of 0.013 to 256 mg/L. Daptomycin is resistant to all tested M. tuberculosis strains not only laboratory strains but also clinical MDR strains that were isolated at different source. Daptomycin will not be an antibiotic of choice for treating infection of Gram positive atypical slowly growing M. tuberculosis.

Keywords: tuberculosis, daptomycin, resistance, Mycobacterium tuberculosis

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Authors: Elsa Reethu, S. Karthik Babu, N. Syed

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Background: Studies in the past focused on the additional benefits of action observation in improving upper and lower limb functions and improving activities of daily living when administered along with conventional therapy. Nevertheless, there is a paucity of literature proving the effects of motor imagery of truncal exercise in improving trunk control in patients with stroke. Aims/purpose: To study the effect of motor imagery of truncal exercises on trunk function and balance in early stroke. Methods: A total of 24 patients were included in the study. 12 were included in the experimental group and 12 were included in control group Trunk function was measured using Trunk Control Test (TCT), Trunk Impairment Scale Verheyden (TIS Verheyden) and Trunk Impairment Scale Fujiwara (TIS Fujiwara). The balance was assessed using Brunel Balance Assessment (BBA) and Tinetti POMA. For the experimental group, each session was for 30 minutes of physical exercises and 15 minutes of motor imagery, once a day, six times a week for 3 weeks and prior to the exercise session, patients viewed a video tape of all the trunk exercises to be performed for 15minutes. The control group practiced the trunk exercises alone for the same duration. Measurements were taken before, after and 4 weeks after intervention. Results: The effect of treatment in motor imagery group showed better improvement when compared with control group when measured after 3 weeks on values of static sitting balance, dynamic balance, total TIS (Verheyden) score, BBA, Tinetti balance and gait with a large effect size of 0.86, 1.99, 1.69, 1.06, 1.63 and 0.97 respectively. The moderate effect size was seen in values of TIS Fujiwara (0.58) and small effect size was seen on TCT (0.12) and TIS coordination component (0.13).at the end of 4 weeks after intervention, the large effect size was identified on values of dynamic balance (2.06), total TIS score (1.59) and Tinetti balance (1.24). The moderate effect size was observed on BBA (0.62) and Tinetti gait (0.72). Conclusion: Trunk motor imagery is effective in improving trunk function and balance in patients with stroke and has a carryover effect in the aspects of mobility. The therapy gain that was observed during the time of discharge was seen to be maintained at the follow-up levels.

Keywords: stroke, trunk rehabilitation, trunk function, balance, motor imagery

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Authors: Serkan Sayin, Songul F. Varol

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High attention on the organic light-emitting diodes has been paid since their efficient properties in the flat panel displays, and solid-state lighting was realized. Because of their high efficient electroluminescence, brightness and providing eminent in the emission range, organic light emitting diodes have been preferred a material compared with the other materials consisting of the liquid crystal. Calixarenes obtained from the reaction of p-tert-butyl phenol and formaldehyde in a suitable base have been potentially used in various research area such as catalysis, enzyme immobilization, and applications, ion carrier, sensors, nanoscience, etc. In addition, their tremendous frameworks, as well as their easily functionalization, make them an effective candidate in the applied chemistry. Herein, a calix[4]arene derivative has been synthesized, and its structure has been fully characterized using Fourier Transform Infrared Spectrophotometer (FTIR), proton nuclear magnetic resonance (¹H-NMR), carbon-13 nuclear magnetic resonance (¹³C-NMR), liquid chromatography-mass spectrometry (LC-MS), and elemental analysis techniques. The calixarene derivative has been employed as an emitting layer in the fabrication of the organic light-emitting diodes. The optical and electrochemical features of calixarane-contained organic light-emitting diodes (Clx-OLED) have been also performed. The results showed that Clx-OLED exhibited blue emission and high external quantum efficacy. As a conclusion obtained results attributed that the synthesized calixarane derivative is a promising chromophore with efficient fluorescent quantum yield that provides it an attractive candidate for fabricating effective materials for fluorescent probes and labeling studies. This study was financially supported by the Scientific and Technological Research Council of Turkey (TUBITAK Grant no. 117Z402).

Keywords: calixarene, OLED, supramolecular chemistry, synthesis

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Authors: David Bakker, Nikki Rickard

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Smartphone apps hold immense potential as mental health and wellbeing tools. Support can be made easily accessible and can be used in real-time while users are experiencing distress. Furthermore, data can be collected to enable machine learning and automated tailoring of support to users. While many apps have been developed for mental health purposes, few have adhered to evidence-based recommendations and even fewer have pursued experimental validation. This paper details the development and experimental evaluation of an app, MoodMission, that aims to provide support for low moods and anxiety, help prevent clinical depression and anxiety disorders, and serve as an adjunct to professional clinical supports. MoodMission was designed to deliver cognitive behavioural therapy for specifically reported problems in real-time, momentary interactions. Users report their low moods or anxious feelings to the app along with a subjective units of distress scale (SUDS) rating. MoodMission then provides a choice of 5-10 short, evidence-based mental health strategies called Missions. Users choose a Mission, complete it, and report their distress again. Automated tailoring, gamification, and in-built data collection for analysis of effectiveness was also included in the app’s design. The development process involved construction of an evidence-based behavioural plan, designing of the app, building and testing procedures, feedback-informed changes, and a public launch. A randomized controlled trial (RCT) was conducted comparing MoodMission to two other apps and a waitlist control condition. Participants completed measures of anxiety, depression, well-being, emotional self-awareness, coping self-efficacy and mental health literacy at the start of their app use and 30 days later. At the time of submission (November 2016) over 300 participants have participated in the RCT. Data analysis will begin in January 2017. At the time of this submission, MoodMission has over 4000 users. A repeated-measures ANOVA of 1390 completed Missions reveals that SUDS (0-10) ratings were significantly reduced between pre-Mission ratings (M=6.20, SD=2.39) and post-Mission ratings (M=4.93, SD=2.25), F(1,1389)=585.86, p < .001, np2=.30. This effect was consistent across both low moods and anxiety. Preliminary analyses of the data from the outcome measures surveys reveal improvements across mental health and wellbeing measures as a result of using the app over 30 days. This includes a significant increase in coping self-efficacy, F(1,22)=5.91, p=.024, np2=.21. Complete results from the RCT in which MoodMission was evaluated will be presented. Results will also be presented from the continuous outcome data being recorded by MoodMission. MoodMission was successfully developed and launched, and preliminary analysis suggest that it is an effective mental health and wellbeing tool. In addition to the clinical applications of MoodMission, the app holds promise as a research tool to conduct component analysis of psychological therapies and overcome restraints of laboratory based studies. The support provided by the app is discrete, tailored, evidence-based, and transcends barriers of stigma, geographic isolation, financial limitations, and low health literacy.

Keywords: anxiety, app, CBT, cognitive behavioural therapy, depression, eHealth, mission, mobile, mood, MoodMission

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Authors: Kamila Dus-Szachniewicz, Artur Bednarkiewicz, Katarzyna Gdesz-Birula, Slawomir Drobczynski

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In modern oncology hyperthermia (HT) is defined as a controlled tumor heating. HT treatment temperatures range between 40–48 °C and can selectively damage heat-sensitive cancer cells or limit their further growth, usually with minimal injury to healthy tissues. Despite many advantages, conventional whole-body and regional hyperthermia have clinically relevant side effects, including cardiac and vascular disorders. Additionally, the lack of accessibility of deep-seated tumor sites and impaired targeting micrometastases renders HT less effective. It is believed that above disadvantages can significantly overcome by the application of biofunctionalized microparticles, which can specifically target tumor sites and become activated by an external stimulus to provide a sufficient cellular response. In our research, the unique optical tweezers system have enabled capturing the silica microparticles, primary cells and tumor spheroids in highly controllable and reproducible environment to study the impact of localized heat stimulation on normal and pathological cell and within multicellular tumor spheroid. High throughput spheroid model was introduced to better mimic the response to HT treatment on tumors in vivo. Additionally, application of local heating of tumor spheroids was performed in strictly controlled conditions resembling tumor microenvironment (temperature, pH, hypoxia, etc.), in response to localized and nonhomogeneous hyperthermia in the extracellular matrix, which promotes tumor progression and metastatic spread. The lack of precise control over these well- defined parameters in basic research leads to discrepancies in the response of tumor cells to the new treatment strategy in preclinical animal testing. The developed approach enables also sorting out subclasses of cells, which exhibit partial or total resistance to therapy, in order to understand fundamental aspects of the resistance shown by given tumor cells in response to given therapy mode and conditions. This work was funded by the National Science Centre (NCN, Poland) under grant no. UMO-2017/27/B/ST7/01255.

Keywords: cancer spheroids, hyperthermia, microparticles, optical tweezers

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Authors: Ryotaro Ishikawa

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INTRODUCTION: Post-traumatic stress disorder (PTSD) is a psychiatric label for a collection of psychological symptoms following a traumatic event. PTSD is as a result of a traumatic experience such as rape or sexual assault. A victim may have PTSD if she/he has experienced the following symptoms for at least a month: a) Stressor, b) Intrusion symptoms, c) Avoidance, d) Negative alterations in cognitions and mood, e) Alterations in arousal and reactivity. Studies on the cognitive theory of PTSD emphasized the roles of (a) negative appraisals of trauma memories in maintaining the symptomatology of PTSD, and (b) disorganized trauma memories in the development of PTSD. Mental contamination is primarily caused by experiences involving humans (e.g. violators or perpetrators) as opposed to substances (e.g. dirt or bodily fluids). Feelings of mental contamination may evoke following experiences of ill-treatment, sexual assault, domination, degradation, manipulation, betrayal, or humiliation. Some studies have demonstrated that traumatic thoughts related to sexual assault are particularly strong predictors of mental contamination. Treatment protocols based on cognitive-behavioral therapy appear to be beneficial in reducing the severity of PTSD and mental contamination. Studies on the cognitive theory of PTSD emphasized the roles of (A) negative appraisals of trauma memories in maintaining the symptomatology of PTSD, and (B) disorganized trauma memories in the development of PTSD. We will demonstrate a feasibility study of individual CBT for PTSD and mental contamination in Japanese clinical settings. METHOD: The single-arm trial is a group setting CBT intervention. The primary outcome is the self-rated Posttraumatic Stress Diagnostic Scale, with secondary measurements of depressive severity and mental pollution questionnaire. Assessments are conducted at baseline, after a waiting period before CBT, during CBT, and after CBT. RESULTS: Participants are eligible for the study and complete the outcome measures at all assessment points. In our hypothesis, receiving CBT would lead to improvements in primary and secondary PTSD severity. CONCLUSION: We will demonstrate a feasibility study of individual CBT for PTSD and mental contamination in Japanese clinical settings. Our treatment would achieve favorable treatment outcomes for PTSD with mental contamination in Japanese clinical settings.

Keywords: CBT, cognitive theory, PTSD, mental pollution

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Authors: Christine Eickhoff, Alyssa Adams, Alaine Duncan

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The Washington, DC Veterans Affairs Medical Center (DC VAMC) offers complementary and integrative health (CIH) services such as acupuncture, yoga, meditation, and nutrition education through a coordinated outpatient clinic. The primary population utilizing CIH services are veterans with chronic pain. Acupuncture is one of the most popular of the CIH services available at the DC VAMC. As interest and availability grows, it is important to measure health outcomes associated with CIH service utilization. The purpose of this study was to investigate pain and mental health outcomes for veterans with chronic pain enrolled in individual acupuncture services in the DC VAMC. Veterans at the DC VAMC with self-identified chronic pain and no prior acupuncture experience were recruited for the study (n=70). Veterans were referred for services by a medical provider and completed baseline assessments at the program orientation prior to participating in any CIH services. Veterans received four individual, full-body acupuncture appointments within four weeks of study enrollment. After the first month, participants were scheduled for six appointments that occurred every two weeks and then eight more sessions that were scheduled one month apart. Follow-up assessments were administered at 2, 4, 6, 8, and 12 months. The findings reported will include completed time points at two and four months. Measures include a demographics survey, the Measure Yourself Medical Outcome Profile-2 (MYMOP-2), The Beck Depression Inventory (BDI-II), the Defense Veterans Pain Rating Scale (DVPRS), and the Pain Disability Questionnaire (PDQ). In this sample, 67% identified a pain condition as their primary health concern. Between baseline and two-month follow-up, there were significant improvements in participants’ primary health concern (MYMOP-2 p=0.010), general wellbeing (MYMOP-2 p=0.011), and a significant decrease in the use of medication (MYMOP-2 p<0.000). Between 2 and 4-month follow-up, pain disability (PDQ p=0.035), pain rating (DVPRS p=0.027), and depression (BDI-II p=0.003) significantly improved. Preliminary findings indicate that individual acupuncture therapy can be effective at improving health outcomes, well-being, and decreasing medication use in U.S. military veterans with chronic pain. Findings also suggest that individual acupuncture therapy can improve pain ratings, pain disability, and depression in veterans with chronic pain.

Keywords: acupuncture, chronic pain, depression, integrative health, medication use, military, pain, veterans, wellbeing

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Authors: Shannon Glaspy, Gerald Boon, Jack Lambert

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Studies on AE of highly active antiretroviral therapy (HAART) in children and adolescents are rare. The aim of this study is to observe the frequency of treatment limiting adverse drug reactions against years on ARVs and specific ARV regimen. Methods: A retrospective cohort study was conducted in East London, South Africa. All patient files in the pediatric (0 – 18 years) ARV cohort were examined, selecting only those patients started on HAART. ARV regimen changes explicitly due to AE, age on ARV treatment onset, age of AE onset, and gender were extrapolated. Eligible subjects were obtained from patient folders, anonymized and cross-referenced with data obtained from electronic records. A total of 1120 patients [592 male (52.9%) and 528 female (47.1%)] were charted by incidence and year. Additional information was extrapolated in cases where the patient experienced lipodystrophy and lipoatrophy to include the number of years on ARVs prior to the onset of the AE. Results: Of the 1120 HIV infected children of the hospital cohort, a total of 105 (9.37%) AE (53.3% male) observed were deemed eligible for the study due to completeness of medical history and agreement between electronic records and paper files. The AE cited were as follows: lipoatrophy 62 (5.53% of all subjects), lipodystrophy 27 (2.41%), neuropathy 9 (0.8%), anemia 2 (0.17%), Steven Johnsons Syndrome 1 (0.08%), elevated LFTs 1 (0.8%), breast hypertrophy (0.08%), gastritis 1 (0.08%) and rash 1 (0.08%). The most prevalence ARV regimens associated with the onset of the AE are: D4T/3TC/EFV 72 cases (64.86% of all AE), D4T/3TC/LOPr 24 cases (21.62%). Lipoatrophy and lipodystrophy combined represent 84.76% (89 cases) of all adverse events documented in this cohort. Within the 60 cases of lipoatrophy, the average number of years on ARVs associated with an AE is 3.54, with 14 cases experiencing an AE between 0-2 years of HAART. Within the 29 cases of lipodystrophy, the average number of years on ARVs associated with an AE is 3.89, with 4 cases experiencing an AE between 0-2 years on HAART. The regimen D4T/3TC/EFV is associated with 43 cases (71.66%) of lipoatrophy and 21 cases (72.41%) of lipodystrophy. D4T/3TC/LOPr is associated with 15 cases (25%) of lipoatrophy and 7 cases (24.14%) of lipodystrophy. The frequency of AE associated with ARV regimens could be misrepresented due to prevalence of different 1st line regimens which were not captured in this study, particularly with the systematic change of 1st line drugs from D4T to ABC in 2010. Conclusion: In this descriptive study we found a 9.37% prevalence of AE were significant enough to be treatment limiting among our cohort. Lipoatrophy accounted for 59.04% of all documented AE. Overall, D4T/3TC/EFV was associated with 64.86% of all AE, 71.66% of lipoatrophy cases and 72.41% of lipodystrophy cases.

Keywords: ARV, adverse events, HAART, pediatric

Procedia PDF Downloads 173

Authors: Shouta Sora, Shizuki Kuriu, Radhika Mishra, Ariunbuyan Sukhbaatar, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

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Lymph node (LN) metastasis accounts for 20 - 30 % of all deaths in patients with head and neck cancer. Therefore, the control of metastatic lymph nodes (MLNs) is necessary to improve the life prognosis of patients with cancer. In a classical metastatic theory, tumor cells are thought to metastasize hematogenously through a bead-like network of lymph nodes. Recently, a lymph node-mediated hematogenous metastasis theory has been proposed, in which sentinel LNs are regarded as a source of distant metastasis. Therefore, the treatment of MLNs at the early stage is essential to prevent distant metastasis. Radiation therapy is one of the primary therapeutic modalities in cancer treatment. In addition, total body irradiation (TBI) has been reported to act as activation of natural killer cells and increase of infiltration of CD4+ T-cells to tumor tissues. However, the treatment effect of TBI for MLNs remains unclear. This study evaluated the possibilities of low-dose total body irradiation (L-TBI) and middle-dose total body irradiation (M-TBI) for the treatment of MLNs. Mouse breast cancer FM3A-Luc cells were injected into subiliac lymph node (SiLN) of MXH10/Mo/LPR mice to induce the metastasis to the proper axillary lymph node (PALN) and lung. Mice were irradiated for the whole body on 4 days after tumor injection. The L-TBI and M-TBI were defined as irradiations to the whole body at 0.2 Gy and 1.0 Gy, respectively. Tumor growth was evaluated by in vivo bioluminescence imaging system. In the non-irradiated group, tumor activities on SiLN and PALN significantly increased over time, and the metastasis to the lung from LNs was confirmed 28 days after tumor injection. The L-TBI led to a tumor growth delay in PALN but did not control tumor growth in SiLN and metastasis to the lung. In contrast, it was found that the M-TBI significantly delayed the tumor growth of both SiLN and PALN and controlled the distant metastasis to the lung compared with non-irradiated and L-TBI groups. These results suggest that the M-TBI is an effective treatment method for MLNs in the early stage and distant metastasis from lymph nodes via blood vessels connected with LNs.

Keywords: metastatic lymph node, lung metastasis, radiation therapy, total body irradiation, lymphatic system

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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: Philip Friedlander, John Rutledge, Jason Suh

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Inhibition of programmed death-1 (PD-1) or its ligand PD-L1 confers therapeutic efficacy in a wide range of solid tumor malignancies. Primary or acquired resistance can develop through activation of immunosuppressive immune cells such as tumor-associated macrophages. The renin angiotensin system (RAS) systemically regulates fluid and sodium hemodynamics, but components are expressed on and regulate the activity of immune cells, particularly of myeloid lineage. We hypothesized that inhibition of RAS would improve the efficacy of PD-1/PD-L-1 treatment. A retrospective analysis was performed through a chart review of patients with solid metastatic malignancies treated with a PD-1/PD-L1 inhibitor between 1/2013 and 6/2019 at Valley Hospital, a community hospital in New Jersey, USA. Efficacy was determined by medical oncologist documentation of clinical benefit in visit notes and by the duration of time on immunotherapy treatment. The primary endpoint was the determination of efficacy differences in patients treated with an inhibitor of RAS ( ace inhibitor, ACEi, or angiotensin blocker, ARB) compared to patients not treated with these inhibitors. To control for broader antihypertensive effects, efficacy as a function of treatment with beta blockers was assessed. 173 patients treated with PD-1/PD-L-1 inhibitors were identified of whom 52 were also treated with an ACEi or ARB. Chi-square testing revealed a statistically significant relationship between being on an ACEi or ARB and efficacy to PD-1/PD-L-1 therapy (p=0.001). No statistically significant relationship was seen between patients taking or not taking beta blocker antihypertensives (p= 0.33). Kaplan-Meier analysis showed statistically significant improvement in the duration of therapy favoring patients concomitantly treated with ACEi or ARB compared to patients not exposed to antihypertensives and to those treated with beta blockers. Logistic regression analysis revealed that age, gender, and cancer type did not have significant effects on the odds of experiencing clinical benefit (p=0.74, p=0.75, and p=0.81, respectively). We conclude that retrospective analysis of the treatment of patients with solid metastatic tumors with anti-PD-1/PD-L1 in a community setting demonstrates greater clinical benefit in the context of concomitant ACEi or ARB inhibition, irrespective of gender or age. This data supports the development of prospective assessment through randomized clinical trials.

Keywords: angiotensin, cancer, immunotherapy, PD-1, efficacy

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Authors: Trenton Hubbard, Kenneth Soyemi, Emily Siffermann

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Introduction: According to the American Academy of Pediatrics (AAP) there are different weight-based recommendations for the treatment of Chlamydia trachomatis (CT) in patients who are being evaluated for sexual assault. Current AAP Red Book guidelines recommend that uncomplicated C. trachomatis anogenital infection in prepubertal patients weighing less than =<45 kg be treated with oral erythromycin 50 mg/kg/day QID for 14 days with no alternative therapies, and for patients whose weight => 45 kg are Azithromycin 1 gm PO once. Our study objective was to determine the efficacy of single-dose Azithromycin therapy for the treatment of Chlamydia trachomatis in patients weighing less than 50 kg who were evaluated for child sexual abuse in an urban setting. Methods: We conducted a retrospective chart review of historical medical records (paper and electronic) patients weighing less than 50 kg who were evaluated for child sexual abuse and subsequently treated for C. trachomatis infection with Azithromycin (20 mg/kg PO once up to a maximum 1 gm) and received a Test of Cure (TOC) from 2006-2016. Qualitative variables were expressed as percentages. Quantitative variables were expressed as mean values (+/- standard deviation [SD]) if they followed a normal distribution or as median values (interquartile range[IQR]) if they did not. Wilcoxson two-sample test was used to compare means of Azithromycin Dose, mg/kg, and TOC timing between treatment responders and non-responders. Results: We reviewed records of 34 patients, average age (SD) was 5.4 (2.0) years, 33 (97%) were treated for CT and 1(3%) for both GC and CT. 25 (74%) were females. Urine PCR was the most commonly used test at evaluation and as TOC with 13 (38%) patients completing both tests. The average (SD) dose of Azithromycin at treatment was 470 (136) mg and average (SD) mg/kg dose of 20 (1.9) mg/kg for all patients. Median (IQR) timing for TOC testing was 19 (14-26) days. Of the 33 with complete data 25 (74%) had a negative TOC. When compared with treatment non-responders (TOC failures), treatment responders received higher doses (average dose (SD) received 495 (139) vs 401(110), P 0.06)); similar average (SD) weight base dosing received (20.8(2.0) vs 19.7 (1.5), P 0.15)), and earlier average (SD)TOC test timing (18.8 (5.6) vs 32 (28.6) P 0.02)). Conclusion: Azithromycin dosing appears to be efficacious in the treatment of CT post sexual assault as majority of patients responded. Although treatment responders and non-responders received similar weight based doses, there is need for additional studies to understand variances and predictors of response.

Keywords: child sexual abuse, chlmaydia trachmotis infection, single-dose azithromycin, weight less than or equal to 45 kilograms

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Authors: Jenee Gooden, Kevin Vasquez-monterroso, Lady Paula Dejesus, Sandra Wainwright, Daniel Kim, Mackenzie Walker

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Introduction: Pyoderma gangrenosum (PG) is a rare, rapidly progressive, neutrophilic ulcerative colitis condition with an incidence of 3 to 10 cases per year ¹ ². Due to the similar appearance, PG is often misdiagnosed as a diabetic ulcer in diabetic patients. Though they may clinically appear similar in appearance, the treatment protocol and diagnostic criteria differ. Also, end-stage renal disease (ESRD) is often a condition seen in diabetic patients, which can have a significant impact on wound healing due to the wide range of uremic toxins³. This case study demonstrates a multidisciplinary team and multimodal treatment approach by podiatric surgery, general surgery, rheumatology, infectious disease, interventional cardiology, wound care and hyperbaric medicine for an uncontrolled diabetic with pyoderma gangrenosum of a significant circumferential wound, covering almost the entire right lower extremity. Methods:56 y.o male presents with multiple PG ulcerations, including the chest, right posterior lower extremity and sacrum. All ulcerations were previously managed by the same wound care specialist. His chief complaint was worsening PG ulcerations accompanied by a fever of 103 °F . This case study focuses on the wound to his RLE. Past medical history significant for diabetes mellitus type 2 with hemoglobin A1c of 10% and end stage renal disease (ESRD) on hemodialysis. A multidisciplinary team approach by podiatric surgery, general surgery, rheumatology, infectious disease, interventional cardiology, wound care and hyperbaric medicine was successfully used to perform right lower extremity limb salvage. The patient was managed by rheumatology for the continuation of prior medication, as well as the mutual agreement with wound care for the addition of dapsone. A coronary CT angiogram was performed by interventional cardiology, but no significant disease was noted, and no further vascular workup was necessary. Multiple surgical sharp wide excisional debridements with application of allografts and split thickness skin grafts for the circumferential ulceration that encompassed almost the entire right lower extremity were performed by both podiatric surgery and general surgery. Wound cultures and soft tissue biopsies were performed, and infectious disease managed antibiotic therapy. Hyperbaric oxygen therapy and wound vac therapy by wound care were also completed as adjunct management. Results: Prevention of leg amputation by limb salvage of the RLE was accomplished by a multidisciplinary team approach, with the wound size decreasing over a total of 29 weeks from 600 cm² to 12.0 x 3.5 x 0.2 cm. Our multidisciplinary team included podiatric surgery, general surgery, rheumatology, infectious disease, interventional cardiology, wound care and hyperbaric medicine. Discussion: Wound healing, in general, can have its challenges, and those challenges are only magnified when accompanied by multiple systemic illnesses. Though the negative impact of diabetes on wound healing is well known, the compound impact of being a diabetic with ESRD and having pyoderma gangrenosum is not. This case demonstrates the necessity for a multidisciplinary team approach with a wide array of treatment modalities to optimize wound healing and perform limb salvage with prevention of lower extremity amputation.

Keywords: diabetes, podiatry, pyoderma gangrenosum, end stage renal disease

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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

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Authors: Magdalena Korytowska, Gunnar Lengstrand, Cecilia Larsson Wexell

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Background: Breast cancer (BC) is the most common cancer among women worldwide, and cases are continuing to increase in Sweden. Bone is the most common metastatic site in breast cancer patients, where > 65-75% of women with advanced breast cancer develop bone metastases during their disease. To prevent the skeletal-related events of metastases (e.g., pathological fractures, bone loss, cancer-induced bone pain, and hypercalcemia bone), two different classes of antiresorptive medications (AR), bisphosphonate and denosumab are typically administered every 3 to 4 weeks. Since 2015, adjuvant bisphosphonate treatment has been used every six months for three to five years in postmenopausal women for the prevention of skeletal metastases and improved survival. Methods: A case-control study was conducted to test the hypotheses that patients treated with high-dose AR are at higher risk of developing MRONJ than breast cancer patients with adjuvant bisphosphonate treatment at a lower dose. Medical and odontological data was collected between 2015-2020. Assessment of oral health and dental care before and during oncological treatment took place at the specialist clinic for Orofacial medicine linked to the specific hospital. Results: In total, 220 patients were included, 101 patients in the high-dose group and 119 patients in the adjuvant BP-treatment group. MRONJ was diagnosed in 13 patients (14%) in the high-dose group. The mandible was affected in most of the cases (84.6%), with a mean duration of high-dose treatment of 19.7 months. In 46.2% of cases, no dental cause of MRONJ could be identified. Overall, estrogen receptor-positive (ER+) BC was the most representative type in 172 patients (78.2%). However, this was 83.9% in the high-dose cases group. The most used drug was denosumab. Twenty-five patients (26.9%) switched their medication from ZOL to denosumab during their oncological treatment. Patients with ER+ breast cancer were reported in 88 patients (87.8%) in the adjuvant group that was treated with ZOL. Conclusions: MRONJ was diagnosed only in the high-dose AR group. Dental assessment and care of patients in the adjuvant group should be considered, with a recommendation to potentially prolong ZOL treatment from 3 to 5 years, with concomitant use of hormonal therapy in patients diagnosed with ER+ breast cancer to prevent bone loss induced by oncological treatment. A new referral for dental assessment is very important in the case of bone metastases when treatment with high dose AR will be required since it is associated with a higher risk of MRONJ.

Keywords: antiresorptive therapy, breast cancer, dental care, MRONJ

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Authors: Bidisha Chatterjee, Sonal Grover, Rekha Gurung

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Postpartum dissection of the internal carotid artery is a relatively rare condition and is considered as an underlying aetiology in 5% to 25% of strokes under the age of 30 to 45 years. However, 86% of these cases recover completely and 14% have mild focal neurological symptoms. Prognosis is generally good with early intervention. The risk quoted for a repeat carotid artery dissection in subsequent pregnancies is less than 2%. 36-year Caucasian primipara presented on postnatal day one of forceps delivery with tachycardia. In the intrapartum period she had a history of prolonged rupture of membranes and developed intrapartum sepsis and was treated with antibiotics. Postpartum ECG showed septal inferior T wave inversion and a troponin level of 19. Subsequently Echocardiogram ruled out post-partum cardiomyopathy. Repeat ECG showed improvement of the previous changes and in the absence of symptoms no intervention was warranted. On day 4 post-delivery, she had developed symptoms of droopy right eyelid, pain around the right eye and itching in the right ear. On examination, she had developed right sided ptosis, unequal pupils (Rt miotic pupil). Cranial nerve examination, reflexes, sensory examination and muscle power was normal. Apart from migraine, there was no medical or family history of note. In view of Horner’s on the right, she had a CT Angiogram and subsequently MR/MRA and was diagnosed with dissection of the cervical portion of the right internal carotid artery. She was discharged on a course of Aspirin 75mg. By 6 week post-natal follow up patient had recovered significantly with occasional episodes of unequal pupils and tingling of right toes which resolved spontaneously. Cervical artery dissection, including VAD and carotid artery dissection, are rare complications of pregnancy with an estimated annual incidence of 2.6–3 per 100,000 pregnancy hospitalizations. Aetiology remains unclear though trauma during straining at labour, underlying arterial disease and preeclampsia have been implicated. Hypercoagulable state during pregnancy and puerperium could also be an important factor. 60-90% cases present with severe headache and neck pain and generally precede neurological symptoms like ipsilateral Horner’s syndrome, retroorbital pain, tinnitus and cranial nerve palsy. Although rare, the consequences of delayed diagnosis and management can lead to severe and permanent neurological deficits. Patients with a strong index of suspicion should undergo an MRI or MRA of head and neck. Antithrombotic and antiplatelet therapy forms the mainstay of therapy with selected cases needing endovascular stenting. Long term prognosis is favourable with either complete resolution or minimal deficit if treatment is prompt. Patients should be counselled about the recurrence risk and possibility of stroke in future pregnancy. Coronary artery dissection is rare and treatable but needs early diagnosis and treatment. Post-partum headache and neck pain with neurological symptoms should prompt urgent imaging followed by antithrombotic and /or antiplatelet therapy. Most cases resolve completely or with minimal sequelae.

Keywords: postpartum, dissection of internal carotid artery, magnetic resonance angiogram, magnetic resonance imaging, antiplatelet, antithrombotic

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Authors: Getahun Nigusie Demise

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Background; antiretroviral treatment reduce HIV-related morbidity, and prolonged survival of patients however, there is lack of up-to-date information concerning the treatment long term effect on the survival of HIV positive children especially in the study area. Objective: The aim of this study is to assess the incidence and predictors of mortality among HIV positive children on antiretroviral therapy (ART) in public hospitals of Harer town who were enrolled from 2011 to 2021. Methodology: Institution based retrospective cohort study was conducted among 429 HIV positive children enrolled in ART clinic from January 1st 2011 to December30th 2021. Data were collected from medical cards by using a data extraction form, Descriptive analyses were used to Summarized the results, and life table was used to estimate survival probability at specific point of time after introduction of ART. Kaplan Meier survival curve together with log rank test was used to compare survival between different categories of covariates, and Multivariate Cox-proportional hazard regression model was used to estimate adjusted Hazard rate. Variables with p-values ≤0.25 in bivariable analysis were candidates to the multivariable analysis. Finally, variables with p-values < 0.05 were considered as significant variables. Results: The study participants had followed for a total of 2549.6 child-years (30596 child months) with an overall mortality rate of 1.5 (95% CI: 1.1, 2.04) per 100 child-years. Their median survival time was 112 months (95% CI: 101–117). There were 38 children with unknown outcome, 39 deaths, and 55 children transfer out to different facility. The overall survival at 6, 12, 24, 48 months were 98%, 96%, 95%, 94% respectively. being in WHO clinical Stage four (AHR=4.55, 95% CI:1.36, 15.24), having anemia(AHR=2.56, 95% CI:1.11, 5.93), baseline low absolute CD4 count (AHR=2.95, 95% CI: 1.22, 7.12), stunting (AHR=4.1, 95% CI: 1.11, 15.42), wasting (AHR=4.93, 95% CI: 1.31, 18.76), poor adherence to treatment (AHR=3.37, 95% CI: 1.25, 9.11), having TB infection at enrollment (AHR=3.26, 95% CI: 1.25, 8.49),and no history of change their regimen(AHR=7.1, 95% CI: 2.74, 18.24), were independent predictors of death. Conclusion: more than half of death occurs within 2 years. Prevalent tuberculosis, anemia, wasting, and stunting nutritional status, socioeconomic factors, and baseline opportunistic infection were independent predictors of death. Increasing early screening and managing those predictors are required.

Keywords: human immunodeficiency virus-positive children, anti-retroviral therapy, survival, treatment, Ethiopia

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Authors: Tharwat Ibrahim Rushdy, Warda Youssef Mohammed Morsy, Hanaa Ali Ahmed Elfeky

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Background: Intra-aortic balloon pump (IABP) is the first and the most commonly used mechanical circulatory support for patients with acute coronary syndromes and cardiogenic shock. Therefore, critical care nurses not only have to know how to monitor and operate the IABP, but also to provide interventions for preventing possible complications. Aim of the study: To assess nurses' knowledge and practices regarding care of patients connected to IABP at the ICUs of Cairo University Hospitals. Research design: A descriptive exploratory design was utilized. Sample: Convenience samples of 40 nurses were included in the current study. Setting: This study was carried out at the Intensive Care Units of Cairo University Hospitals. Tools of data collection: Three tools were developed, tested for clarity, and feasibility: a- Nurses' personal background sheet, b- IABP nurses' knowledge self-administered questionnaire, and c- IABP Nurses' practice observational checklist. Results: The majority of the studied sample had unsatisfactory knowledge and practice level (88% & 95%) respectively with a mean of 9.45+2.94 and 30.5+8.7, respectively. Unsatisfactory knowledge was found regarding description and physiological effects, nursing care, indications, contraindications, complications, weaning, and removal of IABP in percentage of 95%, 90%, 72.5%, and 57.5%, respectively, with a mean total knowledge score of 9.45 +2.94. In addition, unsatisfactory practice was found regarding about preparation and initiation of IABP therapy, nursing practice during therapy, weaning, and removal of IABP in percentages of (97.5%, 97.5%, and 90%), respectively. Finally, knowledge level was found to differ significantly in relation to gender (t = 2.46 at P ≤ 0.018). However, gender didn't play a role in relation to practice (t = 0.086 at P≤ 0.932). Conclusion: In spite of having vital role in assessment and management of critically ill patients, critical care nurses in the current study had in general unsatisfactory knowledge and practice regarding care of patients connected to IABP. Recommendation: updating knowledge and practice of ICU nurses through carrying out continuing educational programs about IABP; strict observation of nurses' practice when caring for patients connected to IABP and provision of guidance to correct of poor practices and replication of this study on larger probability sample selected from different geographical locations.

Keywords: knowledge, practice, intra-aortic balloon pump (IABP), ICU nurses, intensive care unit (ICU), introduction

Procedia PDF Downloads 475

Authors: Maria Stepankova, Lucie Vistejnova, Pavel Klein, Tereza Blassova, Marketa Slajerova, Radek Sedlacek, Martin Bartos, Jaroslav Chlupac

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Background: Clinical outcome benefits of the segment rib fracture surgical therapy are well known and follow from better stabilization of the chest wall. Despite this, some authors still incline to conservative therapy and point out to possible rib fracture healing failure in connection with the bone vascular supply disturbance caused by metal plate implantation. This suggestion met neither experimental nor clinical verification and remains the object of discussion. In our pilot study we investigated the titanium plate fixation effect on the rib fracture healing in porcine model and its histological, biomechanical and radiological aspects. Materials and Method: Two porcine models (experimental group) underwent the operative chest wall stabilization with a titanium plate implantation after osteotomy. Two other porcine models (control group) were treated conservatively after osteotomy. Three weeks after surgery, all animals were sacrificed, treated ribs were explanted and the histological analysis, µCT imaging and biomechanical testing of the calluses tissue were performed. Results: In µCT imaging, experimental group showed a higher cortical bone volume compared to the control group. Histological analysis using the non-decalcified bone tissue blocks demonstrated more maturated callus with higher newly-formed osseous tissue ratio in experimental group in comparison to controls. In contrast, no significant differences in bone blood vessels supply in both groups were observed. This finding suggests that the bone blood supply in experimental group was not impaired. Biomechanical analysis using 3-point bending test demonstrated significantly higher bending stiffness and the maximum force in experimental group. Conclusion: Based on our observation, it could be concluded, that the titanium plate fixation of the rib fractures leads to faster bone callus maturation whereas does not cause the vascular supply impairment after 3 weeks and thus has a beneficial effect on the rib fracture healing.

Keywords: bone vascular supply, chest wall stabilization, fracture healing, histological analysis, titanium plate implantation

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Authors: Q. Ni, J. A. Serna, D. Holland, X. Wang

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The objective of this study is to develop Nuclear Magnetic Resonance (NMR) techniques to enhance bone related research applied on normal and disuse (Biglycan knockout) mice bone in vitro by using both low-field and high-field NMR simultaneously. It is known that the total amplitude of T₂ relaxation envelopes, measured by the Carr-Purcell-Meiboom-Gill NMR spin echo train (CPMG), is a representation of the liquid phase inside the pores. Therefore, the NMR CPMG magnetization amplitude can be transferred to the volume of water after calibration with the NMR signal amplitude of the known volume of the selected water. In this study, the distribution of mobile water, porosity that can be determined by using low-field (20 MHz) CPMG relaxation technique, and the pore size distributions can be determined by a computational inversion relaxation method. It is also known that the total proton intensity of magnetization from the NMR free induction decay (FID) signal is due to the water present inside the pores (mobile water), the water that has undergone hydration with the bone (bound water), and the protons in the collagen and mineral matter (solid-like protons). Therefore, the components of total mobile and bound water within bone that can be determined by low-field NMR free induction decay technique. Furthermore, the bound water in solid phase (mineral and organic constituents), especially, the dominated component of calcium hydroxyapatite (Ca₁₀(OH)₂(PO₄)₆) can be determined by using high-field (400 MHz) magic angle spinning (MAS) NMR. With MAS technique reducing NMR spectral linewidth inhomogeneous broadening and susceptibility broadening of liquid-solid mix, in particular, we can conduct further research into the ¹H and ³¹P elements and environments of bone materials to identify the locations of bound water such as OH- group within minerals and bone architecture. We hypothesize that with low-field and high-field magic angle spinning NMR can provide a more complete interpretation of water distribution, particularly, in bound water, and these data are important to access bone quality and predict the mechanical behavior of bone.

Keywords: bone, mice bone, NMR, water in bone

Procedia PDF Downloads 157

Authors: Yvonne Howard

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This project currently under development is centered around current learning processes, including a thorough literature review and ongoing practical experiences gained as a deputy head in a school. These daily experiences with students engaging in animal-assisted interventions and the school therapy dog form a strong base for this research. The primary objective of this research is to comprehensively explore the impact of dog-assisted well-being interventions on student motivation and affective engagement within primary and secondary school settings. The educational domain currently encounters a significant challenge due to the lack of substantial research in this area. Despite the perceived positive outcomes of such interventions being acknowledged and shared in various settings, the evidence supporting their effectiveness in an educational context remains limited. This study aims to bridge the gap in the research and shed light on the potential benefits of dog-assisted well-being interventions in promoting student motivation and affective engagement. The significance of this topic recognizes that education is not solely confined to academic achievement but encompasses the overall well-being and emotional development of students. Over recent years, there has been a growing interest in animal-assisted interventions, particularly in healthcare settings. This interest has extended to the educational context. While the effectiveness of these interventions in these areas has been explored in other fields, the educational sector lacks comprehensive research in this regard. Through a systematic and thorough research methodology, this study seeks to contribute valuable empirical data to the field, providing evidence to support informed decision-making regarding the implementation of dog-assisted well-being interventions in schools. This research will utilize a mixed-methods design, combining qualitative and quantitative measures to assess the research objectives. The quantitative phase will include surveys and standardized scales to measure student motivation and affective engagement, while the qualitative phase will involve interviews and observations to gain in-depth insights from students, teachers, and other stakeholders. The findings will contribute evidence-based insights, best practices, and practical guidelines for schools seeking to incorporate dog-assisted interventions, ultimately enhancing student well-being and improving educational outcomes.

Keywords: therapy dog, wellbeing, engagement, motivation, AAI, intervention, school

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Authors: Amrit Vasdev, Edwin Rho, Gurinder Vasdev

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Robotic surgery has enabled a new spectrum of minimally invasive breast reconstruction by improving visualization, surgeon posturing, and improved patient outcomes.1 The DaVinci robot system can be utilized in nipple sparing mastectomies and reconstructions. The process involves the insufflation of the subglandular space and a dissection of the mammary gland with a combination of cautery and blunt dissection. This case outlines a 35-year-old woman who has a long-standing family history of breast cancer and a diagnosis of a deleterious BRCA2 genetic mutation. She has decided to proceed with bilateral nipple sparing mastectomies with implants. Her perioperative mammogram and MRI were negative for masses, however, her left internal mammary lymph node was enlarged. She has taken oral contraceptive pills for 3-5 years and denies DES exposure, radiation therapy, human replacement therapy, or prior breast surgery. She does not smoke and rarely consumes alcohol. During the procedure, the patient received a standardized anesthetic for out-patient surgery of propofol infusion, succinylcholine, sevoflurane, and fentanyl. Aprepitant was given as an antiemetic and preoperative Tylenol and gabapentin for pain management. Concerns for the patient during the procedure included CO2 insufflation into the subcutaneous space. With CO2 insufflation, there is a potential for rapid uptake leading to severe acidosis, embolism, and subcutaneous emphysema.2To mitigate this, it is important to hyperventilate the patient and reduce both the insufflation pressure and the CO2 flow rate to the minimal acceptable by the surgeon. For intraoperative monitoring during this 6-9 hour long procedure, it has been suggested to utilize an Arterial-Line for end-tidal CO2 monitoring. However, in this case, it was not necessary as the patient had excellent cardiovascular reserve, and end-tidal CO2 was within normal limits for the duration of the procedure. A BIS monitor was also utilized to reduce anesthesia burden and to facilitate a prompt discharge from the PACU. Minimal Invasive Robotic Surgery will continue to evolve, and anesthesiologists need to be prepared for the new challenges ahead. Based on our limit number of patients, robotic mastectomy appears to be a safe alternative to open surgery with the promise of clearer tissue demarcation and better cosmetic results.

Keywords: anesthesia, mastectomies, robotic, hypercarbia

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Authors: Michele L. Tilstra, Tiffany J. Peets

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Interprofessional collaboration in behavioral healthcare education is increasingly recognized for its value in training students to address diverse client needs. While interprofessional education (IPE) is well-documented in occupational therapy education to address physical health, limited research exists on collaboration with counselors to address mental health concerns and the psychosocial needs of individuals receiving care. Counseling education literature primarily examines the collaboration of counseling students with psychiatrists, psychologists, social workers, and marriage and family therapists. This pretest/posttest survey research study explored changes in attitudes toward interprofessional teams among 56 Master of Occupational Therapy (MOT) (n = 42) and Counseling and Human Development (CHD) (n = 14) students participating in the Counselors and Occupational Therapists Professionally Engaged in the Community (COPE) program. The COPE program was designed to strengthen the behavioral health workforce in high-need and high-demand areas. Students accepted into the COPE program were divided into small MOT/CHD groups to complete multiple interprofessional multicultural learning modules using videos, case studies, and online discussion board posts. The online modules encouraged reflection on various behavioral healthcare roles, benefits of team-based care, cultural humility, current mental health challenges, personal biases, power imbalances, and advocacy for underserved populations. Using the Student Perceptions of Interprofessional Clinical Education- Revision 2 (SPICE-R2) scale, students completed pretest and posttest surveys using a 5-point Likert scale (Strongly Agree = 5 to Strongly Disagree = 1) to evaluate their attitudes toward interprofessional teamwork and collaboration. The SPICE-R2 measured three different factors: interprofessional teamwork and team-based practice (Team), roles/responsibilities for collaborative practice (Roles), and patient outcomes from collaborative practice (Outcomes). The mean total scores for all students improved from 4.25 (pretest) to 4.43 (posttest), Team from 4.66 to 4.58, Roles from 3.88 to 4.30, and Outcomes from 4.08 to 4.36. A paired t-test analysis for the total mean scores resulted in a t-statistic of 2.54, which exceeded both one-tail and two-tail critical values, indicating statistical significance (p = .001). When the factors of the SPICE-R2 were analyzed separately, only the Roles (t Stat=4.08, p =.0001) and Outcomes (t Stat=3.13, p = .002) were statistically significant. The item ‘I understand the roles of other health professionals’ showed the most improvement from a mean score for all students of 3.76 (pretest) to 4.46 (posttest). The significant improvement in students' attitudes toward interprofessional teams suggests that the unique integration of OT and CHD students in the COPE program effectively develops a better understanding of the collaborative roles necessary for holistic client care. These results support the importance of IPE through structured, engaging interprofessional experiences. These experiences are essential for enhancing students' readiness for collaborative practice and align with accreditation standards requiring interprofessional education in OT and CHD programs to prepare practitioners for team-based care. The findings contribute to the growing body of evidence supporting the integration of IPE in behavioral healthcare curricula to improve holistic client care and encourage students to engage in collaborative practice across healthcare settings.

Keywords: behavioral healthcare, counseling education, interprofessional education, mental health education, occupational therapy education

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Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar

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The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.

Keywords: UFLC, LC-MS-TOF, NMR, Zileuton, impurities, toxicity, bio-activity

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Authors: Seyedeh Nasim Mirbahari, Taha Azad, Mehdi Totonchi

Abstract:

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

Procedia PDF Downloads 59

Authors: Maria Hopkins, Sarah Koch, Fred Biasini

Abstract:

Autism is lifelong disorder that affects one out of every 110 Americans. The deficits that accompany Autism Spectrum Disorders (ASD), such as abnormal behaviors and social incompetence, often make it extremely difficult for these individuals to gain functional independence from caregivers. These long-term implications necessitate an immediate effort to improve social skills among children with an ASD. Any technology that could teach individuals with ASD necessary social skills would not only be invaluable for the individuals affected, but could also effect a massive saving to society in treatment programs. The overall purpose of the first study was to develop, implement, and evaluate an avatar tutor for social skills training in children with ASD. “Face Say” was developed as a colorful computer program that contains several different activities designed to teach children specific social skills, such as eye gaze, joint attention, and facial recognition. The children with ASD were asked to attend to FaceSay or a control painting computer game for six weeks. Children with ASD who received the training had an increase in emotion recognition, F(1, 48) = 23.04, p < 0.001 (adjusted Ms 8.70 and 6.79, respectively) compared to the control group. In addition, children who received the FaceSay training had higher post-test scored in facial recognition, F(1, 48) = 5.09, p < 0.05 (adjusted Ms: 38.11 and 33.37, respectively) compared to controls. The findings provide information about the benefits of computer-based training for children with ASD. Recent research suggests the value of also using socially assistive robots with children who have an ASD. Researchers investigating robots as tools for therapy in ASD have reported increased engagement, increased levels of attention, and novel social behaviors when robots are part of the social interaction. The overall goal of the second study was to develop a social robot designed to teach children specific social skills such as emotion recognition. The robot is approachable, with both an animal-like appearance and features of a human face (i.e., eyes, eyebrows, mouth). The feasibility of the robot is being investigated in children ages 7-12 to explore whether the social robot is capable of forming different facial expressions to accurately display emotions similar to those observed in the human face. The findings of this study will be used to create a potentially effective and cost efficient therapy for improving the cognitive-emotional skills of children with autism. Implications and study findings using the robot as an intervention tool will be discussed.

Keywords: autism, intervention, technology, emotions

Procedia PDF Downloads 363