Search results for: hormone suppressive therapy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2137

Search results for: hormone suppressive therapy

1057 The Validation of RadCalc for Clinical Use: An Independent Monitor Unit Verification Software

Authors: Junior Akunzi

Abstract:

In the matter of patient treatment planning quality assurance in 3D conformational therapy (3D-CRT) and volumetric arc therapy (VMAT or RapidArc), the independent monitor unit verification calculation (MUVC) is an indispensable part of the process. Concerning 3D-CRT treatment planning, the MUVC can be performed manually applying the standard ESTRO formalism. However, due to the complex shape and the amount of beams in advanced treatment planning technic such as RapidArc, the manual independent MUVC is inadequate. Therefore, commercially available software such as RadCalc can be used to perform the MUVC in complex treatment planning been. Indeed, RadCalc (version 6.3 LifeLine Inc.) uses a simplified Clarkson algorithm to compute the dose contribution for individual RapidArc fields to the isocenter. The purpose of this project is the validation of RadCalc in 3D-CRT and RapidArc for treatment planning dosimetry quality assurance at Antoine Lacassagne center (Nice, France). Firstly, the interfaces between RadCalc and our treatment planning systems (TPS) Isogray (version 4.2) and Eclipse (version13.6) were checked for data transfer accuracy. Secondly, we created test plans in both Isogray and Eclipse featuring open fields, wedges fields, and irregular MLC fields. These test plans were transferred from TPSs according to the radiotherapy protocol of DICOM RT to RadCalc and the linac via Mosaiq (version 2.5). Measurements were performed in water phantom using a PTW cylindrical semiflex ionisation chamber (0.3 cm³, 31010) and compared with the TPSs and RadCalc calculation. Finally, 30 3D-CRT plans and 40 RapidArc plans created with patients CT scan were recalculated using the CT scan of a solid PMMA water equivalent phantom for 3D-CRT and the Octavius II phantom (PTW) CT scan for RapidArc. Next, we measure the doses delivered into these phantoms for each plan with a 0.3 cm³ PTW 31010 cylindrical semiflex ionisation chamber (3D-CRT) and 0.015 cm³ PTW PinPoint ionisation chamber (Rapidarc). For our test plans, good agreements were found between calculation (RadCalc and TPSs) and measurement (mean: 1.3%; standard deviation: ± 0.8%). Regarding the patient plans, the measured doses were compared to the calculation in RadCalc and in our TPSs. Moreover, RadCalc calculations were compared to Isogray and Eclispse ones. Agreements better than (2.8%; ± 1.2%) were found between RadCalc and TPSs. As for the comparison between calculation and measurement the agreement for all of our plans was better than (2.3%; ± 1.1%). The independent MU verification calculation software RadCal has been validated for clinical use and for both 3D-CRT and RapidArc techniques. The perspective of this project includes the validation of RadCal for the Tomotherapy machine installed at centre Antoine Lacassagne.

Keywords: 3D conformational radiotherapy, intensity modulated radiotherapy, monitor unit calculation, dosimetry quality assurance

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1056 Preparation and Quality Control of a Novel Radiolabeled Complex of 166ho for the Treatment of Somatostatin Receptor Expressing Tumours

Authors: H. Yousefnia, A. Golabi Dezfuli, S. Zolghadri, M. Hosntalab

Abstract:

Peptide receptor radionuclide therapy is nowadays used for the treatment of various abnormalities with somatostatin receptors. In this study, 166Ho-DOTATOC was prepared and the best conditions for its radiolabeling was obtained. For this purpose, a certain of DOTATOC was added to a vial containing 166Ho. various experiments by varying ligand concentration, pH, temperature and time were performed to determine the best conditions. Radiochemical purity of the complex was assessed by instant thin layer chromatography method utilizing 0.9% NaCl as the mobile phase. 166Ho-DOTATOC was prepared with radiochemical purity of higher than 95% at the optimized condition (pH=4, temperature: 95° C, time:30 min). In 0.9% NaCl, free Ho cation was developed at Rf of 0.8 while the complex was remained at the front of the paper.

Keywords: Ho-166, neuroendocrine, octreotide, quality control

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1055 The Current Home Hemodialysis Practices and Patients’ Safety Related Factors: A Case Study from Germany

Authors: Ilyas Khan. Liliane Pintelon, Harry Martin, Michael Shömig

Abstract:

The increasing costs of healthcare on one hand, and the rise in aging population and associated chronic disease, on the other hand, are putting increasing burden on the current health care system in many Western countries. For instance, chronic kidney disease (CKD) is a common disease and in Europe, the cost of renal replacement therapy (RRT) is very significant to the total health care cost. However, the recent advancement in healthcare technology, provide the opportunity to treat patients at home in their own comfort. It is evident that home healthcare offers numerous advantages apparently, low costs and high patients’ quality of life. Despite these advantages, the intake of home hemodialysis (HHD) therapy is still low in particular in Germany. Many factors are accounted for the low number of HHD intake. However, this paper is focusing on patients’ safety-related factors of current HHD practices in Germany. The aim of this paper is to analyze the current HHD practices in Germany and to identify risks related factors if any exist. A case study has been conducted in a dialysis center which consists of four dialysis centers in the south of Germany. In total, these dialysis centers have 350 chronic dialysis patients, of which, four patients are on HHD. The centers have 126 staff which includes six nephrologists and 120 other staff i.e. nurses and administration. The results of the study revealed several risk-related factors. Most importantly, these centers do not offer allied health services at the pre-dialysis stage, the HHD training did not have an established curriculum; however, they have just recently developed the first version. Only a soft copy of the machine manual is offered to patients. Surprisingly, the management was not aware of any standard available for home assessment and installation. The home assessment is done by a third party (i.e. the machines and equipment provider) and they may not consider the hygienic quality of the patient’s home. The type of machine provided to patients at home is similar to the one in the center. The model may not be suitable at home because of its size and complexity. Even though portable hemodialysis machines, which are specially designed for home use, are available in the market such as the NxStage series. Besides the type of machine, no assistance is offered for space management at home in particular for placing the machine. Moreover, the centers do not offer remote assistance to patients and their carer at home. However, telephonic assistance is available. Furthermore, no alternative is offered if a carer is not available. In addition, the centers are lacking medical staff including nephrologists and renal nurses.

Keywords: home hemodialysis, home hemodialysis practices, patients’ related risks in the current home hemodialysis practices, patient safety in home hemodialysis

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1054 Advanced Palliative Aquatics Care Multi-Device AuBento for Symptom and Pain Management by Sensorial Integration and Electromagnetic Fields: A Preliminary Design Study

Authors: J. F. Pollo Gaspary, F. Peron Gaspary, E. M. Simão, R. Concatto Beltrame, G. Orengo de Oliveira, M. S. Ristow Ferreira, J.C. Mairesse Siluk, I. F. Minello, F. dos Santos de Oliveira

Abstract:

Background: Although palliative care policies and services have been developed, research in this area continues to lag. An integrated model of palliative care is suggested, which includes complementary and alternative services aimed at improving the well-being of patients and their families. The palliative aquatics care multi-device (AuBento) uses several electromagnetic techniques to decrease pain and promote well-being through relaxation and interaction among patients, specialists, and family members. Aim: The scope of this paper is to present a preliminary design study of a device capable of exploring the various existing theories on the biomedical application of magnetic fields. This will be achieved by standardizing clinical data collection with sensory integration, and adding new therapeutic options to develop an advanced palliative aquatics care, innovating in symptom and pain management. Methods: The research methodology was based on the Work Package Methodology for the development of projects, separating the activities into seven different Work Packages. The theoretical basis was carried out through an integrative literature review according to the specific objectives of each Work Package and provided a broad analysis, which, together with the multiplicity of proposals and the interdisciplinarity of the research team involved, generated consistent and understandable complex concepts in the biomedical application of magnetic fields for palliative care. Results: Aubento ambience was idealized with restricted electromagnetic exposure (avoiding data collection bias) and sensory integration (allowing relaxation associated with hydrotherapy, music therapy, and chromotherapy or like floating tank). This device has a multipurpose configuration enabling classic or exploratory options on the use of the biomedical application of magnetic fields at the researcher's discretion. Conclusions: Several patients in diverse therapeutic contexts may benefit from the use of magnetic fields or fluids, thus validating the stimuli to clinical research in this area. A device in controlled and multipurpose environments may contribute to standardizing research and exploring new theories. Future research may demonstrate the possible benefits of the aquatics care multi-device AuBento to improve the well-being and symptom control in palliative care patients and their families.

Keywords: advanced palliative aquatics care, magnetic field therapy, medical device, research design

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1053 When Talk Is the Cure for the Morning After: Talking Therapy in Conor Mcpherson’s Dublin Carol and Shining City

Authors: Maha Hamoud Alatawi

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Drawing on the work of John McLeod and Ariel Watson, this paper explains the relationship between narrative and psychotherapy in two plays by the Irish playwright Conor McPherson. Dublin Carol presents John’s chequered past through his reminiscences of alcohol addiction and Shining City tells the story of John who is haunted by the ghost of his wife, recently died in a car accident, and who seeks the help of Ian, a therapist. At first, the significance of storytelling as an integral part of Irish culture is highlighted. Such a tradition features prominently in contemporary Irish drama. The paper concludes that it is the power of narrative and its therapeutic impact and not the act of psychotherapy and treatment which brings signs of change to characters’ lives.

Keywords: Conor McPherson, drama, psychotherapy, storytelling

Procedia PDF Downloads 293
1052 Toxicological Analysis of Some Plant Combinations Used for the Treatment of Hypertension by Lay People in Northern Kwazulu-Natal, South Africa

Authors: Mmbulaheni Ramulondi, Sandy Van Vuuren, Helene De Wet

Abstract:

The use of plant combinations to treat various medical conditions is not a new concept, and it is known that traditional people do not only rely on a single plant extract for efficacy but often combine various plant species for treatment. The knowledge of plant combinations is transferred from one generation to the other in the belief that combination therapy may enhance efficacy, reduce toxicity, decreases adverse effects, increase bioavailability and result in lower dosages. However, combination therapy may also be harmful when the interaction is antagonistic, since it may result in increasing toxicity. Although a fair amount of research has been done on the toxicity of medicinal plants, there is very little done on the toxicity of medicinal plants in combination. The aim of the study was to assess the toxicity potential of 19 plant combinations which have been documented as treatments of hypertension in northern KwaZulu-Natal by lay people. The aqueous extracts were assessed using two assays; the Brine shrimp assay (Artemia franciscana) and the Ames test (Mutagenicity). Only one plant combination (Aloe marlothii with Hypoxis hemerocallidea) in the current study has been previously assessed for toxicity. With the Brine shrimp assay, the plant combinations were tested in two concentrations (2 and 4 mg/ml), while for mutagenicity tests, they were tested at 5 mg/ml. The results showed that in the Brine shrimp assay, six combinations were toxic at 4 mg/ml. The combinations were Albertisia delagoensis with Senecio serratuloides (57%), Aloe marlothii with Catharanthus roseus (98%), Catharanthus roseus with Hypoxis hemerocallidea (66%), Catharanthus roseus with Musa acuminata (89%), Catharanthus roseus with Momordica balsamina (99%) and Aloe marlothii with Trichilia emetica and Hyphaene coriacea (50%). However when the concentration was reduced to 2 mg/ml, only three combinations were toxic which were Aloe marlothii with Catharanthus roseus (76%), Catharanthus roseus with Musa acuminata (66%) and Catharanthus roseus with Momordica balsamina (73%). For the mutagenicity assay, only the combinations between Catharanthus roseus with Hypoxis hemerocallidea and Catharanthus roseus with Momordica balsamina were mutagenic towards the Salmonella typhimurium strains TA98 and TA100. Most of the combinations which were toxic involve C. roseus which was also toxic when tested singularly. It is worth noting that C. roseus was one of the most frequently used plant species both to treat hypertension singularly and in combination and some of the individuals have been using this for the last 20 years. The mortality percentage of the Brine shrimp showed a significant correlation between dosage and toxicity thus toxicity was dosage dependant. A combination which is worth noting is the combination between A. delagoensis and S. serratuloides. Singularly these plants were non-toxic towards Brine shrimp, however their combination resulted in antagonism with the mortality rate of 57% at the total concentration of 4 mg/ml. Low toxicity was mostly observed, giving some validity to combined use, however the few combinations showing increased toxicity demonstrate the importance of analysing plant combinations.

Keywords: dosage, hypertension, plant combinations, toxicity

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1051 The Influence of Nutritional and Immunological Status on the Prognosis of Head and Neck Cancer

Authors: Ching-Yi Yiu, Hui-Chen Hsu

Abstract:

Objectives: Head and neck cancer (HNC) is a big global health problem in the world. Despite the development of diagnosis and treatment, the overall survival of HNC is still low. The well recognition of the interaction of the host immune system and cancer cells has led to realizing the processes of tumor initiation, progression and metastasis. Many systemic inflammatory responses have been shown to play a crucial role in cancer progression. The pre and post-treatment nutritional and immunological status of HNC patients is a reliable prognostic indicator of tumor outcomes and survivors. Methods: Between July 2020 to June 2022, We have enrolled 60 HNC patients, including 59 males and 1 female, in Chi Mei Medical Center, Liouying, Taiwan. The age distribution was from 37 to 81 years old (y/o), with a mean age of 57.6 y/o. We evaluated the pre-and post-treatment nutritional and immunological status of these HNC patients with body weight, body weight loss, body mass index (BMI), whole blood count including hemoglobin (Hb), lymphocyte, neutrophil and platelet counts, biochemistry including prealbumin, albumin, c-reactive protein (CRP), with the time period of before treatment, post-treatment 3 and 6 months. We calculated the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to assess how these biomarkers influence the outcomes of HNC patients. Results: We have carcinoma of the hypopharynx in 21 cases with 35%, carcinoma of the larynx in 9 cases, carcinoma of the tonsil and tongue every 6 cases, carcinoma soft palate and tongue base every 5 cases, carcinoma of buccal mucosa, retromolar trigone and mouth floor every 2 cases, carcinoma of the hard palate and low lip each 1 case. There were stage I 15 cases, stage II 13 cases, stage III 6 cases, stage IVA 10 cases, and stage IVB 16 cases. All patients have received surgery, chemoradiation therapy or combined therapy. We have wound infection in 6 cases, 2 cases of pharyngocutaneous fistula, flap necrosis in 2 cases, and mortality in 6 cases. In the wound infection group, the average BMI is 20.4 kg/m2; the average Hb is 12.9 g/dL, the average albumin is 3.5 g/dL, the average NLR is 6.78, and the average PLR is 243.5. In the PC fistula and flap necrosis group, the average BMI is 21.65 kg/m2; the average Hb is 11.7 g/dL, the average albumin is 3.15 g/dL, average NLR is 13.28, average PLR is 418.84. In the mortality group, the average BMI is 22.3 kg/m2; the average Hb is 13.58 g/dL, the average albumin is 3.77 g/dL, the average NLR is 6.06, and the average PLR is 275.5. Conclusion: HNC is a big challenging public health problem worldwide, especially in the high prevalence of betel nut consumption area Taiwan. Besides the definite risk factors of smoking, drinking and betel nut related, the other biomarkers may play significant prognosticators in the HNC outcomes. We concluded that the average BMI is less than 22 kg/m2, the average Hb is low than 12.0 g/dL, the average albumin is low than 3.3 g/dL, the average NLR is low than 3, and the average PLR is more than 170, the surgical complications and mortality will be increased, and the prognosis is poor in HNC patients.

Keywords: nutritional, immunological, neutrophil-to-lymphocyte ratio, paltelet-to-lymphocyte ratio.

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1050 EMG Based Orthosis for Upper Limb Rehabilitation in Hemiparesis Patients

Authors: Nancy N. Sharmila, Aparna Mishra

Abstract:

Hemiparesis affects almost 80% of stroke patients each year. It is marked by paralysis or weakness on one half of the body. Our model provides both assistance and physical therapy for hemiparesis patients for swift recovery. In order to accomplish our goal a force is provided that pulls the forearm up (as in flexing the arm), and pushes the forearm down (as in extending the arm), which will also assist the user during ADL (Activities of Daily Living). The model consists of a mechanical component which is placed around the patient’s bicep and an EMG control circuit to assist patients in daily activities, which makes it affordable and easy to use. In order to enhance the neuromuscular system’s effectiveness in synchronize the movement, proprioceptive neuromuscular facilitation (PNF) concept is used. The EMG signals are acquired from the unaffected arm as an input to drive the orthosis. This way the patient is invigorated to use the orthosis for regular exercise.

Keywords: EMG, hemiparesis, orthosis, rehabilitation

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1049 Bulbar Conjunctival Kaposi's Sarcoma Unmasked by Immune Reconstitution Syndrome

Authors: S. Mohd Afzal, R. O'Connell

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Kaposi's sarcoma (KS) is the most common HIV-related cancer, and ocular manifestations constitute at least 25% of all KS cases. However, ocular presentations often occur in the context of systemic KS, and isolated lesions are rare. We report a unique case of ocular KS masquerading as subconjunctival haemorrhage, and only developing systemic manifestations after initiation of HIV treatment. Case: A 49-year old man with previous hypertensive stroke and newly diagnosed HIV infection presented with an acutely red left eye following repeated bouts of coughing. Given the convincing history of poorly controlled hypertension and cough, a diagnosis of subconjunctival haemorrhage was made. Over the next week, his ocular lesion began to improve and he subsequently started anti-retroviral therapy. Prior to receiving anti-retroviral therapy, his CD4+ lymphocyte count was 194 cells/mm3 with HIV viral load greater than 1 million/ml. This rapidly improved to a viral load of 150 copies/ml within 2 weeks of starting treatment. However, a few days after starting HIV treatment, his ocular lesion recurred. Ophthalmic examination was otherwise normal. He also developed widespread lymphadenopathy and multiple dark lesions on his torso. Histology and virology confirmed KS, systemically triggered by Immune Reconstitution Syndrome (KS-IRIS). The patient has since undergone chemotherapy successfully. Discussion: Kaposi's sarcoma is an atypical tumour caused by human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV). In immunosuppressed patients, KSHV can also cause lymphoproliferative disorders such as primary effusion lymphoma and Castleman's disease (in our patient’s case, this was excluded through histological analysis of lymph nodes). KSHV is one of the seven currently known human oncoviruses, and its pathogenesis is poorly understood. Up to 13% of patients with HIV-related KS experience worsening of the disease after starting anti-retroviral treatment, due to a sudden increase in CD4 cell counts. Histology remains the diagnostic gold standard. Current British HIV Association (BHIVA) guidelines recommend treatment using anti-retroviral drugs, with either intralesional vinblastine for local disease or systemic chemotherapy for disseminated KS. Conclusion: This case is unique as ocular KS as initial presentation is rare and our patient's diagnosis was only made after systemic lesions were triggered by immune reconstitution. KS should be considered as an important differential diagnosis for red eyes in all patients at risk of acquiring HIV infection.

Keywords: human herpesvirus 8, human immunodeficiency virus, immune reconstitution syndrome, Kaposi’s sarcoma, Kaposi’s sarcoma-associated herpesvirus

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1048 Ecofriendly Approach for the Management of Red Cotton Bug Dysdercus koenigii by Botanicals

Authors: S: Kayesth, K. K. Gupta

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The indiscriminate use of insecticides causes environmental contamination, adversely affects non-target organisms and develops resistance among insects and pests. There has always been felt a need for methods of control which can overcome these environmental and other ecological issues. The present study was designed to evaluate the effect of different plants volatiles on survival, longevity, growth, development and reproduction of Dysdercus koenigii. The hexane extract of three different plants (Catharanthus roseus, Ocimum sanctum and Lantana camara) was used. The fifth instars were exposed to hexane extract with concentrations of 10%, 5%, 2.5%, 1.25%, 0.1%, 0.5%, 0.25%, 0.13% and 0.06% while adults were treated with 10%, 5%, 2.5% and 1.25%. 1-ml of each of these concentrations was used to make a thin film in sterilized glass jars of 500 ml capacity. Fifteen newly emerged fifth instar nymphs and ten pairs of adult bugs were treated separately with the extracts for 24 hour exposure to the plant volatiles. The effect of these plant extract was observed and readings were recorded for 23 days. Survival and longevity of both fifth instars and adults were in correlation with the concentrations of the plant extracts. The extracts did not influence growth of fifth instars significantly but impaired their development significantly at higher concentrations. The treated nymphs at higher concentrations either could not moult or died and those which could moult moulted into supranumery instars, adultoids or adults with wing deformities. The supranumery insects retained the nymphal characters except increased body size and wing pads. The adultoids had wing deformities and non-functional reproductive organs. Adultoids exhibited courtship and mounting attempts but were not able to mate. At lower concentrations from 0.1 to 0.06% the fifth instars developed into adults with fewer deformities. At these concentrations, the fecundity and fertility of these adults were drastically reduced. On the contrary, the treated adults also had reduced fecundity and fertility compared to control. Among three plant extracts Ocimcum was most toxic for both fifth instars and adults in terms of survival and longevity. Catharanthus, Ocimum and Lantana appeared to have potential molecules which possessed insect juvenile hormone like activity. Potential application of these plant extracts in IPM was discussed.

Keywords: Catharanthus, Ocimum, Lantana, Dysdercus koenigii

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1047 A Prospective Study of a Clinically Significant Anatomical Change in Head and Neck Intensity-Modulated Radiation Therapy Using Transit Electronic Portal Imaging Device Images

Authors: Wilai Masanga, Chirapha Tannanonta, Sangutid Thongsawad, Sasikarn Chamchod, Todsaporn Fuangrod

Abstract:

The major factors of radiotherapy for head and neck (HN) cancers include patient’s anatomical changes and tumour shrinkage. These changes can significantly affect the planned dose distribution that causes the treatment plan deterioration. A measured transit EPID images compared to a predicted EPID images using gamma analysis has been clinically implemented to verify the dose accuracy as part of adaptive radiotherapy protocol. However, a global gamma analysis dose not sensitive to some critical organ changes as the entire treatment field is compared. The objective of this feasibility study is to evaluate the dosimetric response to patient anatomical changes during the treatment course in HN IMRT (Head and Neck Intensity-Modulated Radiation Therapy) using a novel comparison method; organ-of-interest gamma analysis. This method provides more sensitive to specific organ change detection. Random replanned 5 HN IMRT patients with causes of tumour shrinkage and patient weight loss that critically affect to the parotid size changes were selected and evaluated its transit dosimetry. A comprehensive physics-based model was used to generate a series of predicted transit EPID images for each gantry angle from original computed tomography (CT) and replan CT datasets. The patient structures; including left and right parotid, spinal cord, and planning target volume (PTV56) were projected to EPID level. The agreement between the transit images generated from original CT and replanned CT was quantified using gamma analysis with 3%, 3mm criteria. Moreover, only gamma pass-rate is calculated within each projected structure. The gamma pass-rate in right parotid and PTV56 between predicted transit of original CT and replan CT were 42.8%( ± 17.2%) and 54.7%( ± 21.5%). The gamma pass-rate for other projected organs were greater than 80%. Additionally, the results of organ-of-interest gamma analysis were compared with 3-dimensional cone-beam computed tomography (3D-CBCT) and the rational of replan by radiation oncologists. It showed that using only registration of 3D-CBCT to original CT does not provide the dosimetric impact of anatomical changes. Using transit EPID images with organ-of-interest gamma analysis can provide additional information for treatment plan suitability assessment.

Keywords: re-plan, anatomical change, transit electronic portal imaging device, EPID, head, and neck

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1046 A Case of Postpartum Pulmonary Edema Induced by Oxytocin

Authors: May Zaw, Amber Latif, William Lim

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Postpartum dyspnea can be due to many causes, such as pulmonary embolism, amniotic fluid embolism, and peripartum cardiomyopathy, but less frequently due to acute pulmonary edema. The incidence of acute pulmonary edema during pregnancy and in the postpartum period has been estimated to be around 0.08%. About half of the cases are attributed to tocolytic therapy. Herein, we present a case of a young woman presenting with acute hypoxia after induction of labor with oxytocin and found to have acute pulmonary edema. This case aims to illustrate and add to a growing body of literature regarding oxytocin-induced acute pulmonary edema and highlights the importance of recognizing the rare complication of oxytocin and necessary interventions to avoid complications. Oxytocin-induced pulmonary edema is a relatively uncommon condition, but physicians should have a high index of suspicion to initiate timely intervention and avoid fetal complications.

Keywords: pulmonary, pregnancy, oxytocin, postpartum

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1045 Video-Based System for Support of Robot-Enhanced Gait Rehabilitation of Stroke Patients

Authors: Matjaž Divjak, Simon Zelič, Aleš Holobar

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We present a dedicated video-based monitoring system for quantification of patient’s attention to visual feedback during robot assisted gait rehabilitation. Two different approaches for eye gaze and head pose tracking are tested and compared. Several metrics for assessment of patient’s attention are also presented. Experimental results with healthy volunteers demonstrate that unobtrusive video-based gaze tracking during the robot-assisted gait rehabilitation is possible and is sufficiently robust for quantification of patient’s attention and assessment of compliance with the rehabilitation therapy.

Keywords: video-based attention monitoring, gaze estimation, stroke rehabilitation, user compliance

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1044 The Physiological Effect of Cold Atmospheric Pressure Plasma on Cancer Cells, Cancer Stem Cells, and Adult Stem Cells

Authors: Jeongyeon Park, Yeo Jun Yoon, Jiyoung Seo, In Seok Moon, Hae Jun Lee, Kiwon Song

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Cold Atmospheric Pressure Plasma (CAPP) is defined as a partially ionized gas with electrically charged particles at room temperature and atmospheric pressure. CAPP generates reactive oxygen species (ROS) and reactive nitrogen species (RNS), and has potential as a new apoptosis-promoting cancer therapy. With an annular type dielectric barrier discharge (DBD) CAPP-generating device combined with a helium (He) gas feeding system, we showed that CAPP selectively induced apoptosis in various cancer cells while it promoted proliferation of the adipose tissue-derived stem cell (ASC). The apoptotic effect of CAPP was highly selective toward p53-mutated cancer cells. The intracellular ROS was mainly responsible for apoptotic cell death in CAPP-treated cancer cells. CAPP induced apoptosis even in doxorubicin-resistant cancer cell lines, demonstrating the feasibility of CAPP as a potent cancer therapy. With the same device and exposure conditions to cancer cells, CAPP stimulated proliferation of the ASC, a kind of mesenchymal stem cell that is capable of self-renewing and differentiating into adipocytes, chondrocytes, osteoblasts and neurons. CAPP-treated ASCs expressed the stem cell markers and differentiated into adipocytes as untreated ASCs. The increase of proliferation by CAPP in ASCs was offset by a NO scavenger but was not affected by ROS scavengers, suggesting that NO generated by CAPP is responsible for the activated proliferation in ASCs. Usually, cancer stem cells are reported to be resistant to known cancer therapies. When we applied CAPP of the same device and exposure conditions to cancer cells to liver cancer stem cells (CSCs) that express CD133 and epithelial cell adhesion molecule (EpCAM) cancer stem cell markers, apoptotic cell death was not examined. Apoptotic cell death of liver CSCs was induced by the CAPP generated from a device with an air-based flatten type DBD. An exposure of liver CSCs to CAPP decreased the viability of liver CSCs to a great extent, suggesting plasma be used as a promising anti-cancer treatment. To validate whether CAPP can be a promising anti-cancer treatment or an adjuvant modality to eliminate remnant tumor in cancer surgery of vestibular schwannoma, we applied CAPP to mouse schwannoma cell line SC4 Nf2 ‑/‑ and human schwannoma cell line HEI-193. A CAPP treatment leads to anti-proliferative effect in both cell lines. We are currently studying the molecular mechanisms of differential physiological effect of CAPP; the proliferation of ASCs and apoptosis of various cancer cells and CSCs.

Keywords: cold atmospheric pressure plasma, apoptosis, proliferation, cancer cells, adult stem cells

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1043 A Systematic Review on the Whole-Body Cryotherapy versus Control Interventions for Recovery of Muscle Function and Perceptions of Muscle Soreness Following Exercise-Induced Muscle Damage in Runners

Authors: Michael Nolte, Iwona Kasior, Kala Flagg, Spiro Karavatas

Abstract:

Background: Cryotherapy has been used as a post-exercise recovery modality for decades. Whole-body cryotherapy (WBC) is an intervention which involves brief exposures to extremely cold air in order to induce therapeutic effects. It is currently being investigated for its effectiveness in treating certain exercise-induced impairments. Purpose: The purpose of this systematic review was to determine whether WBC as a recovery intervention is more, less, or equally as effective as other interventions at reducing perceived levels of muscle soreness and promoting recovery of muscle function after exercise-induced muscle damage (EIMD) from running. Methods: A systematic review of the current literature was performed utilizing the following MeSH terms: cryotherapy, whole-body cryotherapy, exercise-induced muscle damage, muscle soreness, muscle recovery, and running. The databases utilized were PubMed, CINAHL, EBSCO Host, and Google Scholar. Articles were included if they were published within the last ten years, had a CEBM level of evidence of IIb or higher, had a PEDro scale score of 5 or higher, studied runners as primary subjects, and utilized both perceived levels of muscle soreness and recovery of muscle function as dependent variables. Articles were excluded if subjects did not include runners, if the interventions included PBC instead of WBC, and if both muscle performance and perceived muscle soreness were not assessed within the study. Results: Two of the four articles revealed that WBC was significantly more effective than treatment interventions such as far-infrared radiation and passive recovery at reducing perceived levels of muscle soreness and restoring muscle power and endurance following simulated trail runs and high-intensity interval running, respectively. One of the four articles revealed no significant difference between WBC and passive recovery in terms of reducing perceived muscle soreness and restoring muscle power following sprint intervals. One of the four articles revealed that WBC had a harmful effect compared to CWI and passive recovery on both perceived muscle soreness and recovery of muscle strength and power following a marathon. Discussion/Conclusion: Though there was no consensus in terms of WBC’s effectiveness at treating exercise-induced muscle damage following running compared to other interventions, it seems as though WBC may at least have a time-dependent positive effect on muscle soreness and recovery following high-intensity interval runs and endurance running, marathons excluded. More research needs to be conducted in order to determine the most effective way to implement WBC as a recovery method for exercise-induced muscle damage, including the optimal temperature, timing, duration, and frequency of treatment.

Keywords: cryotherapy, physical therapy intervention, physical therapy, whole body cryotherapy

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1042 Evaluation of Cooperative Hand Movement Capacity in Stroke Patients Using the Cooperative Activity Stroke Assessment

Authors: F. A. Thomas, M. Schrafl-Altermatt, R. Treier, S. Kaufmann

Abstract:

Stroke is the main cause of adult disability. Especially upper limb function is affected in most patients. Recently, cooperative hand movements have been shown to be a promising type of upper limb training in stroke rehabilitation. In these movements, which are frequently found in activities of daily living (e.g. opening a bottle, winding up a blind), the force of one upper limb has to be equally counteracted by the other limb to successfully accomplish a task. The use of standardized and reliable clinical assessments is essential to evaluate the efficacy of therapy and the functional outcome of a patient. Many assessments for upper limb function or impairment are available. However, the evaluation of cooperative hand movement tasks are rarely included in those. Thus, the aim of this study was (i) to develop a novel clinical assessment (CASA - Cooperative Activity Stroke Assessment) for the evaluation of patients’ capacity to perform cooperative hand movements and (ii) to test its inter- and interrater reliability. Furthermore, CASA scores were compared to current gold standard assessments for upper extremity in stroke patients (i.e. Fugl-Meyer Assessment, Box & Blocks Test). The CASA consists of five cooperative activities of daily living including (1) opening a jar, (2) opening a bottle, (3) open and closing of a zip, (4) unscrew a nut and (5) opening a clipbox. Here, the goal is to accomplish the tasks as fast as possible. In addition to the quantitative rating (i.e. time) which is converted to a 7-point scale, also the quality of the movement is rated in a 4-point scale. To test the reliability of CASA, fifteen stroke subjects were tested within a week twice by the same two raters. Intra-and interrater reliability was calculated using the intraclass correlation coefficient (ICC) for total CASA score and single items. Furthermore, Pearson-correlation was used to compare the CASA scores to the scores of Fugl-Meyer upper limb assessment and the box and blocks test, which were assessed in every patient additionally to the CASA. ICC scores of the total CASA score indicated an excellent- and single items established a good to excellent inter- and interrater reliability. Furthermore, the CASA score was significantly correlated to the Fugl-Meyer and Box & Blocks score. The CASA provides a reliable assessment for cooperative hand movements which are crucial for many activities of daily living. Due to its non-costly setup, easy and fast implementation, we suggest it to be well suitable for clinical application. In conclusion, the CASA is a useful tool in assessing the functional status and therapy related recovery in cooperative hand movement capacity in stroke patients.

Keywords: activitites of daily living, clinical assessment, cooperative hand movements, reliability, stroke

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1041 Management Problems in a Patient With Long-term Undiagnosed Permanent Hypoparathyroidism

Authors: Babarina Maria, Andropova Margarita

Abstract:

Introduction: Hypoparathyroidism (HypoPT) is a rare endocrine disorder with an estimated prevalence of 0.25 per 1000 individuals. The most common cause of HypoPT is the loss of active parathyroid tissue following thyroid or parathyroid surgery. Sometimes permanent postoperative HypoPT occures, manifested by hypocalcemia in combination with low levels of PTH during 6 months or more after surgery. Cognitive impairments in patients with hypocalcemia due to chronic HypoPT are observed, and this can lead to problems and challenges in everyday living: memory loss and impaired concentration, that may be the cause of poor compliance. Clinical case: Patient K., 66 years old, underwent thyroidectomy in 2013 (at the age of 55) because of papillary thyroid cancer T1NxMx, histopathology findings confirmed the diagnosis. 5 years after the surgery, she was followed up on an outpatient basis, TSH levelsonly were monitored, and the dose of levothyroxine was adjusted. In 2018 due to, increasing complaints include tingling and cramps in the arms and legs, memory loss, sleep disorder, fatigue, anxiety, hair loss, muscle pain, tachycardia, positive Chvostek, and Trousseau signs were diagnosed during examination, also in blood analyses: total Ca 1.86 mmol/l (2.15-2.55), Ca++ 0.96 mmol/l (1.12-1.3), P 1.55 mmol/l (0.74-1.52), Mg 0.79 mmol/l (0.66-1.07) - chronic postoperative HypoPT was diagnosed. Therapy was initiated: alfacalcidol 0.5 mcg per day, calcium carbonate 2000 mg per day, cholecalciferol 1000 IU per day, magnesium orotate 3000 mg per day. During the case follow-up, hypocalcemia, hyperphosphatemia persisted, hypercalciuria15.7 mmol/day (2.5-6.5) was diagnosed. Dietary recommendations were given because of the high content of phosphorus rich foods, and therapy was adjusted: the dose of alfacalcidol was increased to 2.5 mcg per day, and the dose of calcium carbonate was reduced to 1500 mg per day. As part of the screening for complications of hypoPT, data for cataracts, Fahr syndrome, nephrocalcinosis, and kidney stone disease were not obtained. However, HypoPT compensation was not achieved, and therefore hydrochlorothiazide 25 mg was initiated, the dose of alfacalcidol was increased to 3 mcg per day, calcium carbonate to 3000 mg per day, magnesium orotate and cholecalciferol were continued at the same doses. Therapeutic goals were achieved: calcium phosphate product <4.4 mmol2/l2, there were no episodes of hypercalcemia, twenty-four-hour urinary calcium excretion was significantly reduced. Conclusion: Timely prescription, careful explanation of drugs usage rules, and monitoring and maintaining blood and urine parameters within the target contribute to the prevention of HypoPT complications development and life-threatening events.

Keywords: hypoparathyroidism, hypocalcemia, hyperphosphatemia, hypercalciuria

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1040 Development a Home-Hotel-Hospital-School Community-Based Palliative Care Model for Patients with Cancer in Suratthani, Thailand

Authors: Patcharaporn Sakulpong, Wiriya Phokhwang

Abstract:

Background: Banpunrug (Love Sharing House) established in 2013 provides a community-based palliative care for patients with cancer from 7 provinces in southern Thailand. These patients come to receive outpatient chemotherapy and radiotherapy at Suratthani Cancer Hospital. They are poor and uneducated; they need an accommodation during their 30-45 day course of therapy. Methods: A community-participatory action research (PAR) was employed to establish a model of palliative care for patients with cancer. The participants included health care providers, community, and patients and families. The PAR process includes problem identification and need assessment, community and team establishment, field survey, organization founding, model of care planning, action and inquiry (PDCA), outcome evaluation, and model distribution. Results: The model of care at Banpunrug involves the concepts of HHHS model, in that Banpunrug is a Home for patients; patients live in a house comfortable like in a Hotel resource; the patients are given care and living facilities similarly to those in a Hospital; the house is a School for patients to learn how to take care themselves, how to live well with cancer, and most importantly how to prepare themselves for a good death. The house is also a humanized care school for health care providers. Banpunrug’s philosophy of care is based on friendship therapy, social and spiritual support, community partnership, patient-family centeredness, Live & Love sharing house, and holistic and humanized care. With this philosophy, the house is managed as a home of the patients and everyone involved; everything is costless for all eligible patients and their family members; all facilities and living expense are donated from benevolent people, friends, and community. Everyone, including patients and family, has a sense of belonging to the house and there is no authority between health care providers and the patients in the house. The house is situated in a temple and a community and supported by many local nonprofit organizations and healthcare facilities such as a health promotion hospital at sub-disctrict level and Suratthani Cancer Hospital. Village health volunteers and multi-professional health care volunteers have contributed not only appropriate care, but also knowledge and experience to develop a distinguishing HHHS community-based palliative care model for patients with cancer. Since its opening the house has been a home for more than 400 patients and 300 family members. It is also a model for many national and international healthcare organizations and providers, who come to visit and learn about palliative care in and by community. Conclusions: The success of this palliative care model comes from community involvement, multi-professional volunteers and distributions, and concepts of HHHS model. Banpunrug promotes a consistent care across the cancer trajectory independent of prognosis in order to strengthen a full integration of palliative

Keywords: community-based palliative care, model, participatory action research, patients with cancer

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1039 Novel EGFR Ectodomain Mutations and Resistance to Anti-EGFR and Radiation Therapy in H&N Cancer

Authors: Markus Bredel, Sindhu Nair, Hoa Q. Trummell, Rajani Rajbhandari, Christopher D. Willey, Lewis Z. Shi, Zhuo Zhang, William J. Placzek, James A. Bonner

Abstract:

Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligand-independent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.

Keywords: head and neck cancer, EGFR mutation, resistance, cetuximab

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1038 Modeling and Control of a 4DoF Robotic Assistive Device for Hand Rehabilitation

Authors: Christopher Spiewak, M. R. Islam, Mohammad Arifur Rahaman, Mohammad H. Rahman, Roger Smith, Maarouf Saad

Abstract:

For those who have lost the ability to move their hand, going through repetitious motions with the assistance of a therapist is the main method of recovery. We have been developed a robotic assistive device to rehabilitate the hand motions in place of the traditional therapy. The developed assistive device (RAD-HR) is comprised of four degrees of freedom enabling basic movements, hand function, and assists in supporting the hand during rehabilitation. We used a nonlinear computed torque control technique to control the RAD-HR. The accuracy of the controller was evaluated in simulations (MATLAB/Simulink environment). To see the robustness of the controller external disturbance as modelling uncertainty (±10% of joint torques) were added in each joints.

Keywords: biorobotics, rehabilitation, robotic assistive device, exoskeleton, nonlinear control

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1037 Erythema Multiforme Exudativum Major Caused by Isoniazid Hypersensitivity in a Child

Authors: Azwin Lubis, Rika Hapsari, Zahrah Hikmah, Anang Endaryanto, Ariyanto Harsono

Abstract:

Erythema Multiforme Exudativum Major (EMEM) is one of the drug allergy diseases. Drug allergies caused by isoniazid rarely causes EMEM. Cutaneous reactions caused by isoniazid were obtained in 0.98% of patients, but the precise occurrence of Steven Johnson’s Syndrome (SJS) and Toxic Epidermolisis Necrolisis (TEN) due to isoniazid is not known for certain. We present this case to show hypersensitivity of isoniazid in a child. Based on the history of drug intake, physical diagnostic tests, drug elimination and provocation; we established the diagnosis of isoniazid hypersensitivity. The child showed improvement on skin manifestation after stopped isoniazid therapy.

Keywords: erythema multiforme exudativum major, hypersensitivity, elimination test, provocation test

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1036 Low Density Lipoprotein: The Culprit in the Development of Obesity

Authors: Ojiegbe Ikenna Nathan

Abstract:

Obesity is a medical condition in which excess body fat has accumulated to the extent that it leads to reduced life expectancy and or increased health problems. Obesity as a worldwide problem is seen clustered in the families and it moves from generation to generation. It causes some disabilities, mortality and morbidity if left unattended to. The predisposing factors to obesity are either genetic or environment in origin. Nevertheless, the main predisposing factor to obesity is the excessive consumption of food rich in low-density lipoprotein (LDL) such as organ meats, saturated fats etc. This low-density lipoprotein causes an increase in adipose tissue and complicates to obesity. There are varieties of obesity which one needs to take appropriate measures to avoid; such as android, gynoid and morbid obesity. Nonetheless, studies have shown that there is hope for the obese individuals, despite the cause, type and degree of their obesity. This is through the use of the different available treatment measures which increase in physical activities, caloric restrictions, drug therapy and surgical intervention.

Keywords: low-density, lipoprotein, culprit, obesity

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1035 An Elbow Biomechanical Model and Its Coefficients Adjustment

Authors: Jie Bai, Yongsheng Gao, Shengxin Wang, Jie Zhao

Abstract:

Through the establishment of the elbow biomechanical model, it can provide theoretical guide for rehabilitation therapy on the upper limb of the human body. A biomechanical model of the elbow joint can be built by the connection of muscle force model and elbow dynamics. But there are many undetermined coefficients in the model like the optimal joint angle and optimal muscle force which are usually specified as the experimental parameters of other workers. Because of the individual differences, there is a certain deviation of the final result. To this end, the RMS value of the deviation between the actual angle and calculated angle is considered. A set of coefficients which lead to the minimum RMS value will be chosen to be the optimal parameters. The direct search method and the conjugacy search method are used to get the optimal parameters, thus the model can be more accurate and mode adaptability.

Keywords: elbow biomechanical model, RMS, direct search, conjugacy search

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1034 A Measurement Instrument to Determine Curricula Competency of Licensure Track Graduate Psychotherapy Programs in the United States

Authors: Laith F. Gulli, Nicole M. Mallory

Abstract:

We developed a novel measurement instrument to assess Knowledge of Educational Programs in Professional Psychotherapy Programs (KEP-PPP or KEP-Triple P) within the United States. The instrument was designed by a Panel of Experts (PoE) that consisted of Licensed Psychotherapists and Medical Care Providers. Licensure track psychotherapy programs are listed in the databases of the Commission on Accreditation for Marriage and Family Therapy Education (COAMFTE); American Psychological Association (APA); Council on Social Work Education (CSWE); and the Council for Accreditation of Counseling & Related Educational Programs (CACREP). A complete list of psychotherapy programs can be obtained from these professional databases, selecting search fields of (All Programs) in (All States). Each program has a Web link that electronically and directly connects to the institutional program, which can be researched using the KEP-Triple P. The 29-item KEP Triple P was designed to consist of six categorical fields; Institutional Type: Degree: Educational Delivery: Accreditation: Coursework Competency: and Special Program Considerations. The KEP-Triple P was designed to determine whether a specific course(s) is offered in licensure track psychotherapy programs. The KEP-Triple P is designed to be modified to assess any part or the entire curriculum of licensure graduate programs. We utilized the KEP-Triple P instrument to study whether a graduate course in Addictions was offered in Marriage and Family Therapy (MFT) programs. Marriage and Family Therapists are likely to commonly encounter patients with Addiction(s) due to the broad treatment scope providing psychotherapy services to individuals, couples and families of all age groups. Our study of 124 MFT programs which concluded at the end of 2016 found that we were able to assess 61 % of programs (N = 76) since 27 % (N = 34) of programs were inaccessible due to broken Web links. From the total of all MFT programs 11 % (N = 14) did not have a published curriculum on their Institutional Web site. From the sample study, we found that 66 % (N = 50) of curricula did not offer a course in Addiction Treatment and that 34 % (N =26) of curricula did require a mandatory course in Addiction Treatment. From our study sample, we determined that 15 % (N = 11) of MFT doctorate programs did not require an Addictions Treatment course and that 1 % (N = 1) did require such a course. We found that 99 % of our study sample offered a Campus based program and 1 % offered a hybrid program with both online and residential components. From the total sample studied, we determined that 84 % of programs would be able to obtain reaccreditation within a five-year period. We recommend that MFT programs initiate procedures to revise curricula to include a required course in Addiction Treatment prior to their next accreditation cycle, to improve the escalating addiction crisis in the United States. This disparity in MFT curricula raises serious ethical and legal consideration for national and Federal stakeholders as well as for patients seeking a competently trained psychotherapist.

Keywords: addiction, competency, curriculum, psychotherapy

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1033 The Role of Genetic Markers in Prostate Cancer Diagnosis and Treatment

Authors: Farman Ali, Asif Mahmood

Abstract:

The utilization of genetic markers in prostate cancer management represents a significant advance in personalized medicine, offering the potential for more precise diagnosis and tailored treatment strategies. This paper explores the pivotal role of genetic markers in the diagnosis and treatment of prostate cancer, emphasizing their contribution to the identification of individual risk profiles, tumor aggressiveness, and response to therapy. By integrating current research findings, we discuss the application of genetic markers in developing targeted therapies and the implications for patient outcomes. Despite the promising advancements, challenges such as accessibility, cost, and the need for further validation in diverse populations remain. The paper concludes with an outlook on future directions, underscoring the importance of genetic markers in revolutionizing prostate cancer care.

Keywords: prostate cancer, genetic markers, personalized medicine, BRCA1 and BRCA2

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1032 The Writing Eight Exercise and Its Impact on Kindergartners

Authors: Karima Merchant

Abstract:

The aim of this study was to analyze the impact of the Writing Eight Exercise, an exercise from the Brain Integration Therapy, with Kindergartners who are struggling with writing tasks in school. With the help of this exercise, children were able to cross the midline, an invisible line running from our brain to our feet, which separates the body’s right from left. Crossing the midline integrates the brain hemispheres, thus encouraging bilateral movement. The study was spread over 15 weeks where the children were required to do the Writing Eight Exercise 4 times a week. The data collection methods included observations, student work samples and feedback from teachers and parents. Based on the results of this study, it can be concluded that the Writing Eight Exercise had a positive impact on students’ approach towards writing tasks, letter formation, and fine motor skills.

Keywords: crossing the midline, fine motor skills, letter formation, writing

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1031 Molecular Insights into the 5α-Reductase Inhibitors: Quantitative Structure Activity Relationship, Pre-Absorption, Distribution, Metabolism, and Excretion and Docking Studies

Authors: Richa Dhingra, Monika, Manav Malhotra, Tilak Raj Bhardwaj, Neelima Dhingra

Abstract:

5-Alpha-reductases (5AR), a membrane bound, NADPH dependent enzyme and convert male hormone testosterone (T) into more potent androgen dihydrotestosterone (DHT). DHT is the required for the development and function of male sex organs, but its overproduction has been found to be associated with physiological conditions like Benign Prostatic Hyperplasia (BPH). Thus the inhibition of 5ARs could be a key target for the treatment of BPH. In present study, 2D and 3D Quantitative Structure Activity Relationship (QSAR) pharmacophore models have been generated for 5AR based on known inhibitory concentration (IC₅₀) values with extensive validations. The four featured 2D pharmacophore based PLS model correlated the topological interactions (–OH group connected with one single bond) (SsOHE-index); semi-empirical (Quadrupole2) and physicochemical descriptors (Mol. wt, Bromines Count, Chlorines Count) with 5AR inhibitory activity, and has the highest correlation coefficient (r² = 0.98, q² =0.84; F = 57.87, pred r² = 0.88). Internal and external validation was carried out using test and proposed set of compounds. The contribution plot of electrostatic field effects and steric interactions generated by 3D-QSAR showed interesting results in terms of internal and external predictability. The well validated 2D Partial Least Squares (PLS) and 3D k-nearest neighbour (kNN) models were used to search novel 5AR inhibitors with different chemical scaffold. To gain more insights into the molecular mechanism of action of these steroidal derivatives, molecular docking and in silico absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Studies have revealed the hydrophobic and hydrogen bonding of the ligand with residues Alanine (ALA) 63A, Threonine (THR) 60A, and Arginine (ARG) 456A of 4AT0 protein at the hinge region. The results of QSAR, molecular docking, in silico ADME studies provide guideline and mechanistic scope for the identification of more potent 5-Alpha-reductase inhibitors (5ARI).

Keywords: 5α-reductase inhibitor, benign prostatic hyperplasia, ligands, molecular docking, QSAR

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1030 Prediction of Outcome after Endovascular Thrombectomy for Anterior and Posterior Ischemic Stroke: ASPECTS on CT

Authors: Angela T. H. Kwan, Wenjun Liang, Jack Wellington, Mohammad Mofatteh, Thanh N. Nguyen, Pingzhong Fu, Juanmei Chen, Zile Yan, Weijuan Wu, Yongting Zhou, Shuiquan Yang, Sijie Zhou, Yimin Chen

Abstract:

Background: Endovascular Therapy (EVT)—in the form of mechanical thrombectomy—following intravenous thrombolysis is the standard gold treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). It is well established that an ASPECTS ≥ 7 is associated with an increased likelihood of positive post-EVT outcomes, as compared to an ASPECTS < 7. There is also prognostic utility in coupling posterior circulation ASPECTS (pc-ASPECTS) with magnetic resonance imaging for evaluating the post-EVT functional outcome. However, the value of pc-ASPECTS applied to CT must be explored further to determine its usefulness in predicting functional outcomes following EVT. Objective: In this study, we aimed to determine whether pc-ASPECTS on CT can predict post-EVT functional outcomes among patients with AIS due to LVO. Methods: A total of 247 consecutive patients aged 18 and over receiving EVT for LVO-related AIS were recruited into a prospective database. The data were retrospectively analyzed between March 2019 to February 2022 from two comprehensive tertiary care stroke centers: Foshan Sanshui District People’s Hospital and First People's Hospital of Foshan in China. Patient parameters included EVT within 24hrs of symptom onset, premorbid modified Rankin Scale (mRS) ≤ 2, presence of distal and terminal cerebral blood vessel occlusion, and subsequent 24–72-hour post-stroke onset CT scan. Univariate comparisons were performed using the Fisher exact test or χ2 test for categorical variables and the Mann–Whitney U test for continuous variables. A p-value of ≤ 0.05 was statistically significant. Results: A total of 247 patients met the inclusion criteria; however, 3 were excluded due to the absence of post-CTs and 8 for pre-EVT ASPECTS < 7. Overall, 236 individuals were examined: 196 anterior circulation ischemic strokes and 40 posterior strokes of basilar artery occlusion. We found that both baseline post- and pc-ASPECTS ≥ 7 serve as strong positive markers of favorable outcomes at 90 days post-EVT. Moreover, lower rates of inpatient mortality/hospice discharge, 90-day mortality, and 90-day poor outcome were observed. Moreover, patients in the post-ASPECTS ≥ 7 anterior circulation group had shorter door-to-recanalization time (DRT), puncture-to-recanalization time (PRT), and last known normal-to-puncture-time (LKNPT). Conclusion: Patients of anterior and posterior circulation ischemic strokes with baseline post- and pc-ASPECTS ≥ 7 may benefit from EVT.

Keywords: endovascular therapy, thrombectomy, large vessel occlusion, cerebral ischemic stroke, ASPECTS

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1029 How Geant4 Hadronic Models Handle Tracking of Pion Particles Resulting from Antiproton Annihilation

Authors: M. B. Tavakoli, R. Reiazi, M. M. Mohammadi, K. Jabbari

Abstract:

From 2003, AD4/ACE experiment in CERN tried to investigate different aspects of antiproton as a new modality in particle therapy. Because of lack of reliable absolute dose measurements attempts to find out the radiobiological characteristics of antiproton have not reached to a reasonable result yet. From the other side, application of Geant4 in medical approaches is increased followed by Geant4-DNA project which focuses on using this code to predict radiation effects in the cellular scale. This way we can exploit Geant4-DNA results for antiproton. Unfortunately, previous studies showed there are serious problem in simulating an antiproton beam using Geant4. Since most of the problem was in the Bragg peak region which antiproton annihilates there, in this work we tried to understand if the problem came from the way in which Geant4 handles annihilation products especially pion particles. This way, we can predict the source of the dose discrepancies between Geant4 simulations and dose measurements done in CERN.

Keywords: Geant4, antiproton, annihilation, pion plus, pion minus

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1028 Combined Treatment of Estrogen-Receptor Positive Breast Microtumors with 4-Hydroxytamoxifen and Novel Non-Steroidal Diethyl Stilbestrol-Like Analog Produces Enhanced Preclinical Treatment Response and Decreased Drug Resistance

Authors: Sarah Crawford, Gerry Lesley

Abstract:

This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

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