Search results for: concurrent chemotherapy and radiation therapy
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3611

Search results for: concurrent chemotherapy and radiation therapy

161 Baricitinib Lipid-based Nanosystems as a Topical Alternative for Atopic Dermatitis Treatment

Authors: N. Garrós, P. Bustos, N. Beirampour, R. Mohammadi, M. Mallandrich, A.C. Calpena, H. Colom

Abstract:

Atopic dermatitis (AD) is a persistent skin condition characterized by chronic inflammation caused by an autoimmune response. It is a prevalent clinical issue that requires continual treatment to enhance the patient's quality of life. Systemic therapy often involves the use of glucocorticoids or immunosuppressants to manage symptoms. Our objective was to create and assess topical liposomal formulations containing Baricitinib (BNB), a reversible inhibitor of Janus-associated kinase (JAK), which is involved in various immune responses. These formulations were intended to address flare-ups and improve treatment outcomes for AD. We created three distinct liposomal formulations by combining different amounts of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC), cholesterol (CHOL), and ceramide (CER): (i) pure POPC, (ii) POPC mixed with CHOL (at a ratio of 8:2, mol/mol), and (iii) POPC mixed with CHOL and CER (at a ratio of 3.6:2.4:4.0 mol/mol/mol). We conducted various tests to determine the formulations' skin tolerance, irritancy capacity, and their ability to cause erythema and edema on altered skin. We also assessed the transepidermal water loss (TEWL) and skin hydration of rabbits to evaluate the efficacy of the formulations. Histological analysis, the HET-CAM test, and the modified Draize test were all used in the evaluation process. The histological analysis revealed that liposome POPC and POPC:CHOL avoided any damage to the tissues structures. The HET-CAM test showed no irritation effect caused by any of the three liposomes, and the modified Draize test showed a good Draize score for erythema and edema. Liposome POPC effectively counteracted the impact of xylol on the skin, and no erythema or edema was observed during the study. TEWL values were constant for all the liposomes with similar values to the negative control (within the range 8 - 15 g/h·m2, which means a healthy value for rabbits), whereas the positive control showed a significant increase. The skin hydration values were constant and followed the trend of the negative control, while the positive control showed a steady increase during the tolerance study. In conclusion, the developed formulations containing BNB exhibited no harmful or irritating effects, they did not demonstrate any irritant potential in the HET-CAM test and liposomes POPC and POPC:CHOL did not cause any structural alteration according to the histological analysis. These positive findings suggest that additional research is necessary to evaluate the efficacy of these liposomal formulations in animal models of the disease, including mutant animals. Furthermore, before proceeding to clinical trials, biochemical investigations should be conducted to better understand the mechanisms of action involved in these formulations.

Keywords: baricitinib, HET-CAM test, histological study, JAK inhibitor, liposomes, modified draize test

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160 Targeted Delivery of Docetaxel Drug Using Cetuximab Conjugated Vitamin E TPGS Micelles Increases the Anti-Tumor Efficacy and Inhibit Migration of MDA-MB-231 Triple Negative Breast Cancer

Authors: V. K. Rajaletchumy, S. L. Chia, M. I. Setyawati, M. S. Muthu, S. S. Feng, D. T. Leong

Abstract:

Triple negative breast cancers (TNBC) can be classified as one of the most aggressive with a high rate of local recurrences and systematic metastases. TNBCs are insensitive to existing hormonal therapy or targeted therapies such as the use of monoclonal antibodies, due to the lack of oestrogen receptor (ER) and progesterone receptor (PR) and the absence of overexpression of human epidermal growth factor receptor 2 (HER2) compared with other types of breast cancers. The absence of targeted therapies for selective delivery of therapeutic agents into tumours, led to the search for druggable targets in TNBC. In this study, we developed a targeted micellar system of cetuximab-conjugated micelles of D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) for targeted delivery of docetaxel as a model anticancer drug for the treatment of TNBCs. We examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. The targeting micelles were found preferentially accumulated in tumours immediately after the administration of the micelles compare to normal tissue. The fluorescence signal gradually increased up to 12 h at the tumour site and sustained for up to 24 h, reflecting the increases in targeted micelles (TPFC) micelles in MDA-MB-231/Luc cells. In comparison, for the non-targeting micelles (TPF), the fluorescence signal was evenly distributed all over the body of the mice. Only a slight increase in fluorescence at the chest area was observed after 24 h post-injection, reflecting the moderate uptake of micelles by the tumour. The successful delivery of docetaxel into tumour by the targeted micelles (TPDC) exhibited a greater degree of tumour growth inhibition than Taxotere® after 15 days of treatment. The ex vivo study has demonstrated that tumours treated with targeting micelles exhibit enhanced cell cycle arrest and attenuated proliferation compared with the control and with those treated non-targeting micelles. Furthermore, the ex vivo investigation revealed that both the targeting and non-targeting micellar formulations shows significant inhibition of cell migration with migration indices reduced by 0.098- and 0.28-fold, respectively, relative to the control. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGF-overexpressing MDA-MB-231 tumours.

Keywords: biodegradable polymers, cancer nanotechnology, drug targeting, molecular biomaterials, nanomedicine

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159 Prompt Photons Production in Compton Scattering of Quark-Gluon and Annihilation of Quark-Antiquark Pair Processes

Authors: Mohsun Rasim Alizada, Azar Inshalla Ahmdov

Abstract:

Prompt photons are perhaps the most versatile tools for studying the dynamics of relativistic collisions of heavy ions. The study of photon radiation is of interest that in most hadron interactions, photons fly out as a background to other studied signals. The study of the birth of prompt photons in nucleon-nucleon collisions was previously carried out in experiments on Relativistic Heavy Ion Collider (RHIC) and the Large Hadron Collider (LHC). Due to the large energy of colliding nucleons, in addition to prompt photons, many different elementary particles are born. However, the birth of additional elementary particles makes it difficult to determine the accuracy of the effective section of the birth of prompt photons. From this point of view, the experiments planned on the Nuclotron-based Ion Collider Facility (NICA) complex will have a great advantage, since the energy obtained for colliding heavy ions will reduce the number of additionally born elementary particles. Of particular importance is the study of the processes of birth of prompt photons to determine the gluon leaving hadrons since the photon carries information about a rigid subprocess. At present, paper production of prompt photon in Compton scattering of quark-gluon and annihilation of quark–antiquark processes is investigated. The matrix elements Compton scattering of quark-gluon and annihilation of quark-antiquark pair processes has been written. The Square of matrix elements of processes has been calculated in FeynCalc. The phase volume of subprocesses has been determined. Expression to calculate the differential cross-section of subprocesses has been obtained: Given the resulting expressions for the square of the matrix element in the differential section expression, we see that the differential section depends not only on the energy of colliding protons, but also on the mass of quarks, etc. Differential cross-section of subprocesses is estimated. It is shown that the differential cross-section of subprocesses decreases with the increasing energy of colliding protons. Asymmetry coefficient with polarization of colliding protons is determined. The calculation showed that the squares of the matrix element of the Compton scattering process without and taking into account the polarization of colliding protons are identical. The asymmetry coefficient of this subprocess is zero, which is consistent with the literary data. It is known that in any single polarization processes with a photon, squares of matrix elements without taking into account and taking into account the polarization of the original particle must coincide, that is, the terms in the square of the matrix element with the degree of polarization are equal to zero. The coincidence of the squares of the matrix elements indicates that the parity of the system is preserved. The asymmetry coefficient of annihilation of quark–antiquark pair process linearly decreases from positive unit to negative unit with increasing the production of the polarization degrees of colliding protons. Thus, it was obtained that the differential cross-section of the subprocesses decreases with the increasing energy of colliding protons. The value of the asymmetry coefficient is maximal when the polarization of colliding protons is opposite and minimal when they are directed equally. Taking into account the polarization of only the initial quarks and gluons in Compton scattering does not contribute to the differential section of the subprocess.

Keywords: annihilation of a quark-antiquark pair, coefficient of asymmetry, Compton scattering, effective cross-section

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158 Fast and Non-Invasive Patient-Specific Optimization of Left Ventricle Assist Device Implantation

Authors: Huidan Yu, Anurag Deb, Rou Chen, I-Wen Wang

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The use of left ventricle assist devices (LVADs) in patients with heart failure has been a proven and effective therapy for patients with severe end-stage heart failure. Due to the limited availability of suitable donor hearts, LVADs will probably become the alternative solution for patient with heart failure in the near future. While the LVAD is being continuously improved toward enhanced performance, increased device durability, reduced size, a better understanding of implantation management becomes critical in order to achieve better long-term blood supplies and less post-surgical complications such as thrombi generation. Important issues related to the LVAD implantation include the location of outflow grafting (OG), the angle of the OG, the combination between LVAD and native heart pumping, uniform or pulsatile flow at OG, etc. We have hypothesized that an optimal implantation of LVAD is patient specific. To test this hypothesis, we employ a novel in-house computational modeling technique, named InVascular, to conduct a systematic evaluation of cardiac output at aortic arch together with other pertinent hemodynamic quantities for each patient under various implantation scenarios aiming to get an optimal implantation strategy. InVacular is a powerful computational modeling technique that integrates unified mesoscale modeling for both image segmentation and fluid dynamics with the cutting-edge GPU parallel computing. It first segments the aortic artery from patient’s CT image, then seamlessly feeds extracted morphology, together with the velocity wave from Echo Ultrasound image of the same patient, to the computation model to quantify 4-D (time+space) velocity and pressure fields. Using one NVIDIA Tesla K40 GPU card, InVascular completes a computation from CT image to 4-D hemodynamics within 30 minutes. Thus it has the great potential to conduct massive numerical simulation and analysis. The systematic evaluation for one patient includes three OG anastomosis (ascending aorta, descending thoracic aorta, and subclavian artery), three combinations of LVAD and native heart pumping (1:1, 1:2, and 1:3), three angles of OG anastomosis (inclined upward, perpendicular, and inclined downward), and two LVAD inflow conditions (uniform and pulsatile). The optimal LVAD implantation is suggested through a comprehensive analysis of the cardiac output and related hemodynamics from the simulations over the fifty-four scenarios. To confirm the hypothesis, 5 random patient cases will be evaluated.

Keywords: graphic processing unit (GPU) parallel computing, left ventricle assist device (LVAD), lumped-parameter model, patient-specific computational hemodynamics

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157 Chemical and Electrochemical Syntheses of Two Organic Components of Ginger

Authors: Adrienn Kiss, Karoly Zauer, Gyorgy Keglevich, Rita Molnarne Bernath

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Ginger (Zingiber officinale) is a perennial plant from Southeast Asia, widely used as a spice, herb, and medicine for many illnesses since its beneficial health effects were observed thousands of years ago. Among the compounds found in ginger, zingerone [4-hydroxy-3- methoxyphenyl-2-butanone] deserves special attention: it has an anti-inflammatory and antispasmodic effect, it can be used in case of diarrheal disease, helps to prevent the formation of blood clots, has antimicrobial properties, and can also play a role in preventing the Alzheimer's disease. Ferulic acid [(E)-3-(4-hydroxy-3-methoxyphenyl)-prop-2-enoic acid] is another cinnamic acid derivative in ginger, which has promising properties. Like many phenolic compounds, ferulic acid is also an antioxidant. Based on the results of animal experiments, it is assumed to have a direct antitumoral effect in lung and liver cancer. It also deactivates free radicals that can damage the cell membrane and the DNA and helps to protect the skin against UV radiation. The aim of this work was to synthesize these two compounds by new methods. A few of the reactions were based on the hydrogenation of dehydrozingerone [4-(4-Hydroxy-3-methoxyphenyl)-3-buten-2-one] to zingerone. Dehydrozingerone can be synthesized by a relatively simple method from acetone and vanillin with good yield (80%, melting point: 41 °C). Hydrogenation can be carried out chemically, for example by the reaction of zinc and acetic acid, or Grignard magnesium and ethyl alcohol. Another way to complete the reduction is the electrochemical pathway. The electrolysis of dehydrozingerone without diaphragm in aqueous media was attempted to produce ferulic acid in the presence of sodium carbonate and potassium iodide using platinum electrodes. The electrolysis of dehydrozingerone in the presence of potassium carbonate and acetic acid to prepare zingerone was carried out similarly. Ferulic acid was expected to be converted to dihydroferulic acid [3-(4-Hydroxy-3-methoxyphenyl)propanoic acid] in potassium hydroxide solution using iron electrodes, separating the anode and cathode space with a Soxhlet paper sheath impregnated with saturated magnesium chloride solution. For this reaction, ferulic acid was synthesized from vanillin and malonic acid in the presence of pyridine and piperidine (yield: 88.7%, melting point: 173°C). Unfortunately, in many cases, the expected transformations did not happen or took place in low conversions, although gas evolution occurred. Thus, a deeper understanding of these experiments and optimization are needed. Since both compounds are found in different plants, they can also be obtained by alkaline extraction or steam distillation from distinct plant parts (ferulic acid from ground bamboo shoots, zingerone from grated ginger root). The products of these reactions are rich in several other organic compounds as well; therefore, their separation must be solved to get the desired pure material. The products of the reactions described above were characterized by infrared spectral data and melting points. The use of these two simple methods may be informative for the formation of the products. In the future, we would like to study the ferulic acid and zingerone content of other plants and extract them efficiently. The optimization of electrochemical reactions and the use of other test methods are also among our plans.

Keywords: ferulic acid, ginger, synthesis, zingerone

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156 Activating Psychological Resources of DUI (Drivers under the Influence of Alcohol) Using the Traffic Psychology Intervention (IFT Course), Germany

Authors: Parichehr Sharifi, Konrad Reschke, Hans-Liudger Dienel

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Psychological intervention generally targets changes in attitudes and behavior. Working with DUIs is part of traffic psychologists’ work. The primary goal of this field is to reduce the probability of re-conspicuous of the delinquent driver. One of these measurements in Germany is IFT courses for DUI s. The IFT course was designed by the Institute for Therapy Research. Participants are drivers who have fallen several times or once with a blood alcohol concentration of 1.6 per mill and who have completed a medical-psychological assessment (MPU) with the result of the course recommendation. The course covers four sessions of 3.5 hours each (1 hour / 60 m) and in a period of 3 to 4 weeks in the group discussion. This work analyzes interventions for the rehabilitation of DUI (Drunk Drivers offenders) offenders in groups under the aspect of activating psychological resources. From the aspect of sustainability, they should also have long-term consequences for the maintenance of unproblematic driving behavior in terms of the activation of resources. It is also addressing a selected consistency-theory-based intervention effect, activating psychological resources. So far, this has only been considered in the psychotherapeutic field but never in the field of traffic psychology. The methodology of this survey is one qualitative and three quantitative. In four sub-studies, it will be examined which measurements can determine the resources and how traffic psychological interventions can strengthen resources. The results of the studies have the following implications for traffic psychology research and practice: (1) In the field of traffic psychology intervention for the restoration of driving fitness, it can be stated that aspects of resource activation in this work have been investigated for the first time by qualitative and quantitative methods. (2) The resource activation could be confirmed based on the determined results as an effective factor of traffic psychological intervention. (3) Two sub-studies show a range of resources and resource activation options that must be given greater emphasis in traffic psychology interventions: - Social resource activation - improvement of the life skills of participants - Reactivation of existing social support options - Re-experiencing self-esteem, self-assurance, and acceptance of traffic-related behaviors. (4) In revising the IFT-§70 course, as well as other courses on recreating aptitude for DUI, new traffic-specific resource-enabling interventions against alcohol abuse should be developed to further enhance the courses through motivational, cognitive, and behavioral effects of resource activation, Resource-activating interventions can not only be integrated into behavioral group interventions but can also be applied in psychodynamic, psychodynamic (individual psychological) and other contexts of individual traffic psychology. The results are indicative but clearly show that personal resources can be strengthened through traffic psychology interventions. In the research, practice, training, and further education of traffic psychology, the aspect of primary resource activation (Grawe, 1999), therefore, always deserves the greatest attention for the rehabilitation of DUIs and Traffic safety.

Keywords: traffic safety, psychological resources, activating of resources, intervention programs for alcohol offenders, empowerment

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155 Clinical Characteristics of Autistic children Receiving Care in Rehabilitation Centers in Sana'a City, Yemen

Authors: Hamdan Hamood Aldumaini, Amjad Hussein Meqdam, Shamsaldeen kassim Ali, Hamed Mohammed Al-Yousefi, Haron Ahmed Al-Badawi

Abstract:

Background: Autism Spectrum Disorder (ASD) is a complex developmental challenge characterized by significant impairments in social interaction, communication, and behavioral patterns. Diagnosing ASD is challenging due to the lack of definitive medical tests, making early identification crucial. Therefore, increasing people's awareness about autism leads to early diagnosis and better prognosis. Objective: Our study aims to identify the initial symptoms prompting families to seek medical advice, determine the timeline between symptom onset and formal diagnosis, and explore methods for assessing the severity of ASD. Subjects and Methods: The study design employed was a descriptive cross-sectional design, which was suitable for the nature of the research. The data collection took place from March 5, 2022, to April 5, 2022, in Autism Rehabilitation Centers in Sana'a, Yemen. The study population consisted of all children who were diagnosed with autism and visited Autism rehabilitation centers in Sana'a city. The sample size was determined using Epi info version 7, and a total population of 587 autistic children attending the treatment was calculated, but only 250 children were included in this study (176 were male vs. 74 female). Result: In terms of sociability problems, it was found that a significant proportion of Yemeni children with autism experienced difficulties in this area. Specifically, 39.6% were classified as having severe sociability problems, while 28.4% were classified as having moderate issues. Sensory-cognitive awareness problems were also prevalent among the respondents, with 29.6% exhibiting severe difficulties in this domain. Health and physical problems were identified as significant concerns for Yemeni children with autism. The results indicated that 38.4% of the participants experienced severe health and physical issues. Identifying the first symptoms of autism is crucial for early detection and intervention. According to the study, speech delay was the most commonly observed first abnormality, reported by 71.3% of parents. Communication difficulties with others were the second most noticed abnormality, reported by 54.9% of parents. Repetitive movements were the third most commonly observed abnormality, reported by 18% of parents. Regarding the awareness among parents of ASD, our study showed that a significant portion (62%) of parents lack awareness about Autism Spectrum Disorder (ASD) and its causes. Surprisingly, a majority of these parents (over 80%) believe that autism is a curable condition. Additionally, more than half (51.2%) of the parents surveyed reported insufficient knowledge about medication options available to support therapy and rehabilitation for their autistic children.

Keywords: autism characteristics, rehabilitation centres, yemen, children

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154 Efficacy of CAM Methods for Pain Reduction in Acute Non-specific Lower Back Pain

Authors: John Gaber

Abstract:

Objectives: Complementary and alternative medicine (CAM) is a medicine or health practice that is used alongside conventional practice. Nowadays, CAM is commonly used in North America and other countries, and there is a need for more scientific study to understand its efficacy in different clinical cases. This retrospective study explores the effectiveness and recovery time of CAMs such as cupping, acupuncture, and sotai to treat cases of non-specific low back pain (ANLBP). Methods: We assessed the effectiveness of acupuncture, cupping, and sotai methods on pain and for the treatment of ANLBP. We have compared the magnitude of pain relief using a pain scale assessment method to compare the efficacy of each treatment. The Face Pain Scale assessment was conducted before and 24 hours post-treatment. This retrospective study analyzed 40 patients and categorized them according to the treatment they received. The study included the control group, and the three intervention groups, each with ten patients. Each of the three intervention groups received one of the intervention methods. The first group received the cupping treatment, where cups were placed on the lower back of both sides on points: BL23, BL25, BL26, BL54, BL37, BL40, and BL57. After vacuuming, the cups will stay for 10-15 minutes under infrared light (IR) heating. IR heating is applied by an infrared heat lamp. The second group received the acupuncture treatment, placing needles on points: BL23, BL25, BL26, BL52BL54, GB30, BL37, BL40, BL57, BL59, BL60, and KI3. The needles will be simulated with IR light. The final group received the sotai treatment, a Japanese form of structural realignment that relieves pain, balance, and mobility -moving the body naturally and spontaneously towards a comfortable direction by focusing on the inner feeling and synchronizing with the patient’s breathing. The SPSS statistical software was used to analyze the data using repeated-measures ANOVA. The data collected demonstrates the change in the FPS assessment method value over the course of treatment. p<0.05 was considered statistically significant. Results: In the cupping, acupuncture, and sotai therapy groups, the mean of the FPS value reduced from 8.7±1.2, 8.8±1.2, 9.0±0.8 before the intervention to 3.5±1.4, 4.3±1.4, 3.3±1.3, 24 hours after the intervention, respectively. The data collected shows that the CAM methods included in this study all show improvements in pain relief 24 hours after treatment. Conclusion: Complementary and alternative medicine were developed to treat injuries and illnesses with the whole body in mind, designed to be used in addition to standard treatments. The data above shows that the use of these treatments can have a pain-relieving effect, but more research should be done on the matter, as finding CAM methods that are efficacious is crucial in the landscape of health sciences.

Keywords: acupuncture, cupping, alternative medicine, rehabilitation, acute injury

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153 De-Pigmentary Effect of Ayurvedic Treatment on Hyper-Pigmentation of Skin Due to Chloroquine: A Case Report

Authors: Sunil Kumar, Rajesh Sharma

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Toxic epidermal necrolysis, pruritis, rashes, lichen planus like eruption, hyper pigmentation of skin are rare toxic effects of choloroquine used over a long time. Skin and mucus membrane hyper pigmentation is generally of a bluish black or grayish color and irreversible after discontinuation of the drug. According to Ayurveda, Dushivisha is the name given to any poisonous substance which is not fully endowed with the qualities of poison by nature (i.e. it acts as an impoverished or weak poison) and because of its mild potency, it remains in the body for many years causing various symptoms, one among them being discoloration of skin.The objective of this case report is to investigate the effect of Ayurvedic management of chloroquine induced hyper-pigmentation on the line of treatment of Dushivisha. Case Report: A 26-year-old female was suffering from hyper-pigmentation of the skin over the neck, forehead, temporo-mandibular joints, upper back and posterior aspect of both the arms since 8 years had history of taking Chloroquine came to Out Patient Department of National Institute of Ayurveda, Jaipur, India in Jan. 2015. The routine investigations (CBC, ESR, Eosinophil count) were within normal limits. Punch biopsy skin studied for histopathology under hematoxylin and eosin staining showed epidermis with hyper-pigmentation of the basal layer. In the papillary dermis as well as deep dermis there were scattered melanophages along with infiltration by mononuclear cells. There was no deposition of amyloid-like substances. These histopathological findings were suggestive of Chloroquine induced hyper-pigmentation. The case was treated on the line of treatment of Dushivisha and was given Vamana and Virechana (therapeutic emesis and purgation) every six months followed by Snehana karma (oleation therapy) with Panchatikta Ghrit and Swedana (sudation). Arogyavardhini Vati -1 g, Dushivishari Vati 500 mg, Mahamanjisthadi Quath 20 ml were given twelve hourly and Aragwadhadi Quath 25 ml at bed time orally. The patient started showing lightening of the pigments after six months and almost complete remission after 12 months of the treatment. Conclusion: This patient presented with the Dushivisha effect of Chloroquineandwas administered two relevant procedures from Panchakarma viz. Vamana and Virechana. Both Vamana and Virechanakarma here referred to Shodhana karma (purification procedures) eliminates accumulated toxins from the body. In this process, oleation dislodge the toxins from the tissues and sudation helps to bring them to the alimentary tract. The line of treatment did not target direct hypo pigmentary effects; rather aimed to eliminate the Dushivisha. This gave promising results in this condition.

Keywords: Ayurveda, chloroquine, Dushivisha, hyper-pigmentation

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152 The Mitigation of Quercetin on Lead-Induced Neuroinflammation in a Rat Model: Changes in Neuroinflammatory Markers and Memory

Authors: Iliyasu Musa Omoyine, Musa Sunday Abraham, Oladele Sunday Blessing, Iliya Ibrahim Abdullahi, Ibegbu Augustine Oseloka, Nuhu Nana-Hawau, Animoku Abdulrazaq Amoto, Yusuf Abdullateef Onoruoiza, Sambo Sohnap James, Akpulu Steven Peter, Ajayi Abayomi

Abstract:

The neuroprotective role of inflammation from detrimental intrinsic and extrinsic factors has been reported. However, the overactivation of astrocytes and microglia due to lead toxicity produce excessive pro-inflammatory cytokines, mediating neurodegenerative diseases. The present study investigated the mitigatory effects of quercetin on neuroinflammation, correlating with memory function in lead-exposed rats. In this study, Wistar rats were administered orally with Quercetin (Q: 60 mg/kg) and Succimer as a standard drug (S: 10 mg/kg) for 21 days after lead exposure (Pb: 125 mg/kg) of 21 days or in combination with Pb, once daily for 42 days. Working and reference memory was assessed using an Eight-arm radial water maze (8-ARWM). The changes in brain lead level, the neuronal nitric oxide synthase (nNOS) activity, and the level of neuroinflammatory markers such as tumour necrosis factor-alpha (TNF-α) and Interleukin 1 Beta (IL-1β) were determined. Immunohistochemically, astrocyte expression was evaluated. The results showed that the brain level of lead was increased significantly in lead-exposed rats. The expression of astrocytes increased in the CA3 and CA1 regions of the hippocampus, and the levels of brain TNF-α and IL-1β increased in lead-exposed rats. Lead impaired reference and working memory by increasing reference memory errors and working memory incorrect errors in lead-exposed rats. However, quercetin treatment effectively improved memory and inhibited neuroinflammation by reducing astrocytes’ expression and the levels of TNF-α and IL-1β. The expression of astrocytes and the levels of TNF-α and IL-1β correlated with memory function. The possible explanation for quercetin’s anti-neuroinflammatory effect is that it modulates the activity of cellular proteins involved in the inflammatory response; inhibits the transcription factor of nuclear factor-kappa B (NF-κB), which regulates the expression of proinflammatory molecules; inhibits kinases required for the synthesis of Glial fibrillary acidic protein (GFAP) and modifies the phosphorylation of some proteins, which affect the structure and function of intermediate filament proteins; and, lastly, induces Cyclic-AMP Response Element Binding (CREB) activation and neurogenesis as a compensatory mechanism for memory deficits and neuronal cell death. In conclusion, the levels of neuroinflammatory markers negatively correlated with memory function. Thus, quercetin may be a promising therapy in neuroinflammation and memory dysfunction in populations prone to lead exposure.

Keywords: lead, quercetin, neuroinflammation, memory

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151 Genome-Scale Analysis of Streptomyces Caatingaensis CMAA 1322 Metabolism, a New Abiotic Stress-Tolerant Actinomycete

Authors: Suikinai Nobre Santos, Ranko Gacesa, Paul F. Long, Itamar Soares de Melo

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Extremophilic microorganism are adapted to biotopes combining several stress factors (temperature, pressure, radiation, salinity and pH), which indicate the richness valuable resource for the exploitation of novel biotechnological processes and constitute unique models for investigations their biomolecules (1, 2). The above information encourages us investigate bioprospecting synthesized compounds by a noval actinomycete, designated thermotolerant Streptomyces caatingaensis CMAA 1322, isolated from sample soil tropical dry forest (Caatinga) in the Brazilian semiarid region (3-17°S and 35-45°W). This set of constrating physical and climatic factores provide the unique conditions and a diversity of well adapted species, interesting site for biotechnological purposes. Preliminary studies have shown the great potential in the production of cytotoxic, pesticidal and antimicrobial molecules (3). Thus, to extend knowledge of the genes clusters responsible for producing biosynthetic pathways of natural products in strain CMAA1322, whole-genome shotgun (WGS) DNA sequencing was performed using paired-end long sequencing with PacBio RS (Pacific Biosciences). Genomic DNA was extracted from a pure culture grown overnight on LB medium using the PureLink genomic DNA kit (Life Technologies). An approximately 3- to 20-kb-insert PacBio library was constructed and sequenced on an 8 single-molecule real-time (SMRT) cell, yielding 116,269 reads (average length, 7,446 bp), which were allocated into 18 contigs, with 142.11x coverage and N50 value of 20.548 bp (BioProject number PRJNA288757). The assembled data were analyzed by Rapid Annotations using Subsystems Technology (RAST) (4) the genome size was found to be 7.055.077 bp, comprising 6167 open reading frames (ORFs) and 413 subsystems. The G+C content was estimated to be 72 mol%. The closest-neighbors tool, available in RAST through functional comparison of the genome, revealed that strain CMAA1322 is more closely related to Streptomyces hygroscopicus ATCC 53653 (similarity score value, 537), S. violaceusniger Tu 4113 (score value, 483), S. avermitilis MA-4680 (score value, 475), S. albus J1074 (score value, 447). The Streptomyces sp. CMAA1322 genome contains 98 tRNA genes and 135 genes copies related to stress response, mainly osmotic stress (14), heat shock (16), oxidative stress (49). Functional annotation by antiSMASH version 3.0 (5) identified 41 clusters for secondary metabolites (including two clusters for lanthipeptides, ten clusters for nonribosomal peptide synthetases [NRPS], three clusters for siderophores, fourteen for polyketide synthetase [PKS], six clusters encoding a terpene, two clusters encoding a bacteriocin, and one cluster encoding a phenazine). Our work provide in comparative analyse of genome and extract produced (data no published) by lineage CMAA1322, revealing the potential of microorganisms accessed from extreme environments as Caatinga” to produce a wide range of biotechnological relevant compounds.

Keywords: caatinga, streptomyces, environmental stresses, biosynthetic pathways

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150 Role of Lipid-Lowering Treatment in the Monocyte Phenotype and Chemokine Receptor Levels after Acute Myocardial Infarction

Authors: Carolina N. França, Jônatas B. do Amaral, Maria C.O. Izar, Ighor L. Teixeira, Francisco A. Fonseca

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Introduction: Atherosclerosis is a progressive disease, characterized by lipid and fibrotic element deposition in large-caliber arteries. Conditions related to the development of atherosclerosis, as dyslipidemia, hypertension, diabetes, and smoking are associated with endothelial dysfunction. There is a frequent recurrence of cardiovascular outcomes after acute myocardial infarction and, at this sense, cycles of mobilization of monocyte subtypes (classical, intermediate and nonclassical) secondary to myocardial infarction may determine the colonization of atherosclerotic plaques in different stages of the development, contributing to early recurrence of ischemic events. The recruitment of different monocyte subsets during inflammatory process requires the expression of chemokine receptors CCR2, CCR5, and CX3CR1, to promote the migration of monocytes to the inflammatory site. The aim of this study was to evaluate the effect of lipid-lowering treatment by six months in the monocyte phenotype and chemokine receptor levels of patients after Acute Myocardial Infarction (AMI). Methods: This is a PROBE (prospective, randomized, open-label trial with blinded endpoints) study (ClinicalTrials.gov Identifier: NCT02428374). Adult patients (n=147) of both genders, ageing 18-75 years, were randomized in a 2x2 factorial design for treatment with rosuvastatin 20 mg/day or simvastatin 40 mg/day plus ezetimibe 10 mg/day as well as ticagrelor 90 mg 2x/day and clopidogrel 75 mg, in addition to conventional AMI therapy. Blood samples were collected at baseline, after one month and six months of treatment. Monocyte subtypes (classical - inflammatory, intermediate - phagocytic and nonclassical – anti-inflammatory) were identified, quantified and characterized by flow cytometry, as well as the expressions of the chemokine receptors (CCR2, CCR5 and CX3CR1) were also evaluated in the mononuclear cells. Results: After six months of treatment, there was an increase in the percentage of classical monocytes and reduction in the nonclassical monocytes (p=0.038 and p < 0.0001 Friedman Test), without differences for intermediate monocytes. Besides, classical monocytes had higher expressions of CCR5 and CX3CR1 after treatment, without differences related to CCR2 (p < 0.0001 for CCR5 and CX3CR1; p=0.175 for CCR2). Intermediate monocytes had higher expressions of CCR5 and CX3CR1 and lower expression of CCR2 (p = 0.003; p < 0.0001 and p = 0.011, respectively). Nonclassical monocytes had lower expressions of CCR2 and CCR5, without differences for CX3CR1 (p < 0.0001; p = 0.009 and p = 0.138, respectively). There were no differences after the comparison between the four treatment arms. Conclusion: The data suggest a time-dependent modulation of classical and nonclassical monocytes and chemokine receptor levels. The higher percentage of classical monocytes (inflammatory cells) suggest a residual inflammatory risk, even under preconized treatments to AMI. Indeed, these changes do not seem to be affected by choice of the lipid-lowering strategy.

Keywords: acute myocardial infarction, chemokine receptors, lipid-lowering treatment, monocyte subtypes

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149 In vitro Regeneration of Neural Cells Using Human Umbilical Cord Derived Mesenchymal Stem Cells

Authors: Urvi Panwar, Kanchan Mishra, Kanjaksha Ghosh, ShankerLal Kothari

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Background: Day-by-day the increasing prevalence of neurodegenerative diseases have become a global issue to manage them by medical sciences. The adult neural stem cells are rare and require an invasive and painful procedure to obtain it from central nervous system. Mesenchymal stem cell (MSCs) therapies have shown remarkable application in treatment of various cell injuries and cell loss. MSCs can be derived from various sources like adult tissues, human bone marrow, umbilical cord blood and cord tissue. MSCs have similar proliferation and differentiation capability, but the human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are proved to be more beneficial with respect to cell procurement, differentiation to other cells, preservation, and transplantation. Material and method: Human umbilical cord is easily obtainable and non-controversial comparative to bone marrow and other adult tissues. The umbilical cord can be collected after delivery of baby, and its tissue can be cultured using explant culture method. Cell culture medium such as DMEMF12+10% FBS and DMEMF12+Neural growth factors (bFGF, human noggin, B27) with antibiotics (Streptomycin/Gentamycin) were used to culture and differentiate mesenchymal stem cells into neural cells, respectively. The characterisations of MSCs were done with Flow Cytometer for surface markers CD90, CD73 and CD105 and colony forming unit assay. The differentiated various neural cells will be characterised by fluorescence markers for neurons, astrocytes, and oligodendrocytes; quantitative PCR for genes Nestin and NeuroD1 and Western blotting technique for gap43 protein. Result and discussion: The high quality and number of MSCs were isolated from human umbilical cord via explant culture method. The obtained MSCs were differentiated into neural cells like neurons, astrocytes and oligodendrocytes. The differentiated neural cells can be used to treat neural injuries and neural cell loss by delivering cells by non-invasive administration via cerebrospinal fluid (CSF) or blood. Moreover, the MSCs can also be directly delivered to different injured sites where they differentiate into neural cells. Therefore, human umbilical cord is demonstrated to be an inexpensive and easily available source for MSCs. Moreover, the hUCMSCs can be a potential source for neural cell therapies and neural cell regeneration for neural cell injuries and neural cell loss. This new way of research will be helpful to treat and manage neural cell damages and neurodegenerative diseases like Alzheimer and Parkinson. Still the study has a long way to go but it is a promising approach for many neural disorders for which at present no satisfactory management is available.

Keywords: bone marrow, cell therapy, explant culture method, flow cytometer, human umbilical cord, mesenchymal stem cells, neurodegenerative diseases, neuroprotective, regeneration

Procedia PDF Downloads 204
148 Assessing the Impact of Physical Inactivity on Dialysis Adequacy and Functional Health in Peritoneal Dialysis Patients

Authors: Mohammad Ali Tabibi, Farzad Nazemi, Nasrin Salimian

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Background: Peritoneal dialysis (PD) is a prevalent renal replacement therapy for patients with end-stage renal disease. Despite its benefits, PD patients often experience reduced physical activity and physical function, which can negatively impact dialysis adequacy and overall health outcomes. Despite the known benefits of maintaining physical activity in chronic disease management, the specific interplay between physical inactivity, physical function, and dialysis adequacy in PD patients remains underexplored. Understanding this relationship is essential for developing targeted interventions to enhance patient care and outcomes in this vulnerable population. This study aims to assess the impact of physical inactivity on dialysis adequacy and functional health in PD patients. Methods: This cross-sectional study included 135 peritoneal dialysis patients from multiple dialysis centers. Physical inactivity was measured using the International Physical Activity Questionnaire (IPAQ), while physical function was assessed using the Short Physical Performance Battery (SPPB). Dialysis adequacy was evaluated using the Kt/V ratio. Additional variables such as demographic data, comorbidities, and laboratory parameters were collected to control for potential confounders. Statistical analyses were performed to determine the relationships between physical inactivity, physical function, and dialysis adequacy. Results: The study cohort comprised 70 males and 65 females with a mean age of 55.4 ± 13.2 years. A significant proportion of the patients (65%) were categorized as physically inactive based on IPAQ scores. Inactive patients demonstrated significantly lower SPPB scores (mean 6.2 ± 2.1) compared to their more active counterparts (mean 8.5 ± 1.8, p < 0.001). Dialysis adequacy, as measured by Kt/V, was found to be suboptimal (Kt/V < 1.7) in 48% of the patients. There was a significant positive correlation between physical function scores and Kt/V values (r = 0.45, p < 0.01), indicating that better physical function is associated with higher dialysis adequacy. Also, there was a significant negative correlation between physical inactivity and physical function (r = -0.55, p < 0.01). Additionally, physically inactive patients had lower Kt/V ratios compared to their active counterparts (1.3 ± 0.3 vs. 1.8 ± 0.4, p < 0.05). Multivariate regression analysis revealed that physical inactivity was an independent predictor of reduced dialysis adequacy (β = -0.32, p < 0.01) and poorer physical function (β = -0.41, p < 0.01) after adjusting for age, sex, comorbidities, and dialysis vintage. Conclusion: This study underscores the critical role of physical activity and physical function in maintaining adequate dialysis in peritoneal dialysis patients. These findings highlight the need for targeted interventions to promote physical activity in this population to improve their overall health outcomes. Future research should focus on developing and evaluating exercise programs tailored for PD patients to enhance their physical function and dialysis adequacy. The findings suggest that interventions aimed at increasing physical activity and improving physical function may enhance dialysis adequacy and overall health outcomes in this population. Further research is warranted to explore the mechanisms underlying these associations and to develop targeted strategies for enhancing patient care.

Keywords: inactivity, physical function, peritoneal dialysis, dialysis adequacy

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147 Diffusion MRI: Clinical Application in Radiotherapy Planning of Intracranial Pathology

Authors: Pomozova Kseniia, Gorlachev Gennadiy, Chernyaev Aleksandr, Golanov Andrey

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In clinical practice, and especially in stereotactic radiosurgery planning, the significance of diffusion-weighted imaging (DWI) is growing. This makes the existence of software capable of quickly processing and reliably visualizing diffusion data, as well as equipped with tools for their analysis in terms of different tasks. We are developing the «MRDiffusionImaging» software on the standard C++ language. The subject part has been moved to separate class libraries and can be used on various platforms. The user interface is Windows WPF (Windows Presentation Foundation), which is a technology for managing Windows applications with access to all components of the .NET 5 or .NET Framework platform ecosystem. One of the important features is the use of a declarative markup language, XAML (eXtensible Application Markup Language), with which you can conveniently create, initialize and set properties of objects with hierarchical relationships. Graphics are generated using the DirectX environment. The MRDiffusionImaging software package has been implemented for processing diffusion magnetic resonance imaging (dMRI), which allows loading and viewing images sorted by series. An algorithm for "masking" dMRI series based on T2-weighted images was developed using a deformable surface model to exclude tissues that are not related to the area of interest from the analysis. An algorithm of distortion correction using deformable image registration based on autocorrelation of local structure has been developed. Maximum voxel dimension was 1,03 ± 0,12 mm. In an elementary brain's volume, the diffusion tensor is geometrically interpreted using an ellipsoid, which is an isosurface of the probability density of a molecule's diffusion. For the first time, non-parametric intensity distributions, neighborhood correlations, and inhomogeneities are combined in one segmentation of white matter (WM), grey matter (GM), and cerebrospinal fluid (CSF) algorithm. A tool for calculating the coefficient of average diffusion and fractional anisotropy has been created, on the basis of which it is possible to build quantitative maps for solving various clinical problems. Functionality has been created that allows clustering and segmenting images to individualize the clinical volume of radiation treatment and further assess the response (Median Dice Score = 0.963 ± 0,137). White matter tracts of the brain were visualized using two algorithms: deterministic (fiber assignment by continuous tracking) and probabilistic using the Hough transform. The proposed algorithms test candidate curves in the voxel, assigning to each one a score computed from the diffusion data, and then selects the curves with the highest scores as the potential anatomical connections. White matter fibers were visualized using a Hough transform tractography algorithm. In the context of functional radiosurgery, it is possible to reduce the irradiation volume of the internal capsule receiving 12 Gy from 0,402 cc to 0,254 cc. The «MRDiffusionImaging» will improve the efficiency and accuracy of diagnostics and stereotactic radiotherapy of intracranial pathology. We develop software with integrated, intuitive support for processing, analysis, and inclusion in the process of radiotherapy planning and evaluating its results.

Keywords: diffusion-weighted imaging, medical imaging, stereotactic radiosurgery, tractography

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146 Destruction of Colon Cells by Nanocontainers of Ferromagnetic

Authors: Lukasz Szymanski, Zbigniew Kolacinski, Grzegorz Raniszewski, Slawomir Wiak, Lukasz Pietrzak, Dariusz Koza, Karolina Przybylowska-Sygut, Ireneusz Majsterek, Zbigniew Kaminski, Justyna Fraczyk, Malgorzata Walczak, Beata Kolasinska, Adam Bednarek, Joanna Konka

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The aim of this work is to investigate the influence of electromagnetic field from the range of radio frequencies on the desired nanoparticles for cancer therapy. In the article, the development and demonstration of the method and the model device for hyperthermic selective destruction of cancer cells are presented. This method was based on the synthesis and functionalization of carbon nanotubes serving as ferromagnetic material nanocontainers. The methodology of the production carbon - ferromagnetic nanocontainers (FNCs) includes: The synthesis of carbon nanotubes, chemical, and physical characterization, increasing the content of a ferromagnetic material and biochemical functionalization involving the attachment of the key addresses. The ferromagnetic nanocontainers were synthesised in CVD and microwave plasma system. Biochemical functionalization of ferromagnetic nanocontainers is necessary in order to increase the binding selectively with receptors presented on the surface of tumour cells. Multi-step modification procedure was finally used to attach folic acid on the surface of ferromagnetic nanocontainers. Pristine ferromagnetic carbon nanotubes are not suitable for application in medicine and biotechnology. Appropriate functionalization of ferromagnetic carbon nanotubes allows to receiving materials useful in medicine. Finally, a product contains folic acids on the surface of FNCs. The folic acid is a ligand of folate receptors – α which is overexpressed on the surface of epithelial tumours cells. It is expected that folic acids will be recognized and selectively bound by receptors presented on the surface of tumour cells. In our research, FNCs were covalently functionalized in a multi-step procedure. Ferromagnetic carbon nanotubes were oxidated using different oxidative agents. For this purpose, strong acids such as HNO3, or mixture HNO3 and H2SO4 were used. Reactive carbonyl and carboxyl groups were formed on the open sides and at the defects on the sidewalls of FNCs. These groups allow further modification of FNCs as a reaction of amidation, reaction of introduction appropriate linkers which separate solid surface of FNCs and ligand (folic acid). In our studies, amino acid and peptide have been applied as ligands. The last step of chemical modification was reaction-condensation with folic acid. In all reaction as coupling reagents were used derivatives of 1,3,5-triazine. The first trials in the device for hyperthermal RF generator have been done. The frequency of RF generator was in the ranges from 10 to 14Mhz and from 265 to 621kHz. Obtained functionalized nanoparticles enabled to reach the temperature of denaturation tumor cells in given frequencies.

Keywords: cancer colon cells, carbon nanotubes, hyperthermia, ligands

Procedia PDF Downloads 317
145 Facial Recognition and Landmark Detection in Fitness Assessment and Performance Improvement

Authors: Brittany Richardson, Ying Wang

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For physical therapy, exercise prescription, athlete training, and regular fitness training, it is crucial to perform health assessments or fitness assessments periodically. An accurate assessment is propitious for tracking recovery progress, preventing potential injury and making long-range training plans. Assessments include necessary measurements, height, weight, blood pressure, heart rate, body fat, etc. and advanced evaluation, muscle group strength, stability-mobility, and movement evaluation, etc. In the current standard assessment procedures, the accuracy of assessments, especially advanced evaluations, largely depends on the experience of physicians, coaches, and personal trainers. And it is challenging to track clients’ progress in the current assessment. Unlike the tradition assessment, in this paper, we present a deep learning based face recognition algorithm for accurate, comprehensive and trackable assessment. Based on the result from our assessment, physicians, coaches, and personal trainers are able to adjust the training targets and methods. The system categorizes the difficulty levels of the current activity for the client or user, furthermore make more comprehensive assessments based on tracking muscle group over time using a designed landmark detection method. The system also includes the function of grading and correcting the form of the clients during exercise. Experienced coaches and personal trainer can tell the clients' limit based on their facial expression and muscle group movements, even during the first several sessions. Similar to this, using a convolution neural network, the system is trained with people’s facial expression to differentiate challenge levels for clients. It uses landmark detection for subtle changes in muscle groups movements. It measures the proximal mobility of the hips and thoracic spine, the proximal stability of the scapulothoracic region and distal mobility of the glenohumeral joint, as well as distal mobility, and its effect on the kinetic chain. This system integrates data from other fitness assistant devices, including but not limited to Apple Watch, Fitbit, etc. for a improved training and testing performance. The system itself doesn’t require history data for an individual client, but the history data of a client can be used to create a more effective exercise plan. In order to validate the performance of the proposed work, an experimental design is presented. The results show that the proposed work contributes towards improving the quality of exercise plan, execution, progress tracking, and performance.

Keywords: exercise prescription, facial recognition, landmark detection, fitness assessments

Procedia PDF Downloads 136
144 Mapping of Urban Micro-Climate in Lyon (France) by Integrating Complementary Predictors at Different Scales into Multiple Linear Regression Models

Authors: Lucille Alonso, Florent Renard

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The characterizations of urban heat island (UHI) and their interactions with climate change and urban climates are the main research and public health issue, due to the increasing urbanization of the population. These solutions require a better knowledge of the UHI and micro-climate in urban areas, by combining measurements and modelling. This study is part of this topic by evaluating microclimatic conditions in dense urban areas in the Lyon Metropolitan Area (France) using a combination of data traditionally used such as topography, but also from LiDAR (Light Detection And Ranging) data, Landsat 8 satellite observation and Sentinel and ground measurements by bike. These bicycle-dependent weather data collections are used to build the database of the variable to be modelled, the air temperature, over Lyon’s hyper-center. This study aims to model the air temperature, measured during 6 mobile campaigns in Lyon in clear weather, using multiple linear regressions based on 33 explanatory variables. They are of various categories such as meteorological parameters from remote sensing, topographic variables, vegetation indices, the presence of water, humidity, bare soil, buildings, radiation, urban morphology or proximity and density to various land uses (water surfaces, vegetation, bare soil, etc.). The acquisition sources are multiple and come from the Landsat 8 and Sentinel satellites, LiDAR points, and cartographic products downloaded from an open data platform in Greater Lyon. Regarding the presence of low, medium, and high vegetation, the presence of buildings and ground, several buffers close to these factors were tested (5, 10, 20, 25, 50, 100, 200 and 500m). The buffers with the best linear correlations with air temperature for ground are 5m around the measurement points, for low and medium vegetation, and for building 50m and for high vegetation is 100m. The explanatory model of the dependent variable is obtained by multiple linear regression of the remaining explanatory variables (Pearson correlation matrix with a |r| < 0.7 and VIF with < 5) by integrating a stepwise sorting algorithm. Moreover, holdout cross-validation is performed, due to its ability to detect over-fitting of multiple regression, although multiple regression provides internal validation and randomization (80% training, 20% testing). Multiple linear regression explained, on average, 72% of the variance for the study days, with an average RMSE of only 0.20°C. The impact on the model of surface temperature in the estimation of air temperature is the most important variable. Other variables are recurrent such as distance to subway stations, distance to water areas, NDVI, digital elevation model, sky view factor, average vegetation density, or building density. Changing urban morphology influences the city's thermal patterns. The thermal atmosphere in dense urban areas can only be analysed on a microscale to be able to consider the local impact of trees, streets, and buildings. There is currently no network of fixed weather stations sufficiently deployed in central Lyon and most major urban areas. Therefore, it is necessary to use mobile measurements, followed by modelling to characterize the city's multiple thermal environments.

Keywords: air temperature, LIDAR, multiple linear regression, surface temperature, urban heat island

Procedia PDF Downloads 142
143 Synthesis and Characterization of pH-Sensitive Graphene Quantum Dot-Loaded Metal-Organic Frameworks for Targeted Drug Delivery and Fluorescent Imaging

Authors: Sayed Maeen Badshah, Kuen-Song Lin, Abrar Hussain, Jamshid Hussain

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Liver cancer is a significant global health issue, ranking fifth in incidence and second in mortality. Effective therapeutic strategies are urgently needed to combat this disease, particularly in regions with high prevalence. This study focuses on developing and characterizing fluorescent organometallic frameworks as distinct drug delivery carriers with potential applications in both the treatment and biological imaging of liver cancer. This work introduces two distinct organometallic frameworks: the cake-shaped GQD@NH₂-MIL-125 and the cross-shaped M8U6/FM8U6. The GQD@NH₂-MIL-125 framework is particularly noteworthy for its high fluorescence, making it an effective tool for biological imaging. X-ray diffraction (XRD) analysis revealed specific diffraction peaks at 6.81ᵒ (011), 9.76ᵒ (002), and 11.69ᵒ (121), with an additional significant peak at 26ᵒ (2θ), corresponding to the carbon material. Morphological analysis using Field Emission Scanning Electron Microscopy (FE-SEM), and Transmission Electron Microscopy (TEM) demonstrated that the framework has a front particle size of 680 nm and a side particle size of 55±5 nm. High-resolution TEM (HR-TEM) images confirmed the successful attachment of graphene quantum dots (GQDs) onto the NH2-MIL-125 framework. Fourier-Transform Infrared (FT-IR) spectroscopy identified crucial functional groups within the GQD@NH₂-MIL-125 structure, including O-Ti-O metal bonds within the 500 to 700 cm⁻¹ range, and N-H and C-N bonds at 1,646 cm⁻¹ and 1,164 cm⁻¹, respectively. BET isotherm analysis further revealed a specific surface area of 338.1 m²/g and an average pore size of 46.86 nm. This framework also demonstrated UV-active properties, as identified by UV-visible light spectra, and its photoluminescence (PL) spectra showed an emission peak around 430 nm when excited at 350 nm, indicating its potential as a fluorescent drug delivery carrier. In parallel, the cross-shaped M8U6/FM8U6 frameworks were synthesized and characterized using X-ray diffraction, which identified distinct peaks at 2θ = 7.4 (111), 8.5 (200), 9.2 (002), 10.8 (002), 12.1 (220), 16.7 (103), and 17.1 (400). FE-SEM, HR-TEM, and TEM analyses revealed particle sizes of 350±50 nm for M8U6 and 200±50 nm for FM8U6. These frameworks, synthesized from terephthalic acid (H₂BDC), displayed notable vibrational bonds, such as C=O at 1,650 cm⁻¹, Fe-O in MIL-88 at 520 cm⁻¹, and Zr-O in UIO-66 at 482 cm⁻¹. BET analysis showed specific surface areas of 740.1 m²/g with a pore size of 22.92 nm for M8U6 and 493.9 m²/g with a pore size of 35.44 nm for FM8U6. Extended X-ray Absorption Fine Structure (EXAFS) spectra confirmed the stability of Ti-O bonds in the frameworks, with bond lengths of 2.026 Å for MIL-125, 1.962 Å for NH₂-MIL-125, and 1.817 Å for GQD@NH₂-MIL-125. These findings highlight the potential of these organometallic frameworks for enhanced liver cancer therapy through precise drug delivery and imaging, representing a significant advancement in nanomaterial applications in biomedical science.

Keywords: liver cancer cells, metal organic frameworks, Doxorubicin (DOX), drug release.

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142 Human Immuno-Deficiency Virus Co-Infection with Hepatitis B Virus and Baseline Cd4+ T Cell Count among Patients Attending a Tertiary Care Hospital, Nepal

Authors: Soma Kanta Baral

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Background: Since 1981, when the first AIDS case was reported, worldwide, more than 34 million people have been infected with HIV. Almost 95 percent of the people infected with HIV live in developing countries. As HBV & HIV share similar routes of transmission by sexual intercourse or drug use by parenteral injection, co-infection is common. Because of the limited access to healthcare & HIV treatment in developing countries, HIV-infected individuals are present late for care. Enumeration of CD4+ T cell count at the time of diagnosis has been useful to initiate the therapy in HIV infected individuals. The baseline CD4+ T cell count shows high immunological variability among patients. Methods: This prospective study was done in the serology section of the Department of Microbiology over a period of one year from august 2012 to July 2013. A total of 13037 individuals subjected for HIV test were included in the study comprising of 4982 males & 8055 females. Blood sample was collected by vein puncture aseptically with standard operational procedure in clean & dry test-tube. All blood samples were screened for HIV as described by WHO algorithm by Immuno-chromatography rapid kits. Further confirmation was done by biokit ELISA method as per the manufacturer’s guidelines. After informed consent, HIV positive individuals were screened for HBsAg by Immuno-chromatography rapid kits (Hepacard). Further confirmation was done by biokit ELISA method as per the manufacturer’s guidelines. EDTA blood samples were collected from the HIV sero-positive individuals for baseline CD4+ T count. Then, CD4+ T cells count was determined by using FACS Calibur Flow Cytometer (BD). Results: Among 13037 individuals screened for HIV, 104 (0.8%) were found to be infected comprising of 69(66.34%) males & 35 (33.65%) females. The study showed that the high infection was noted in housewives (28.7%), active age group (30.76%), rural area (56.7%) & in heterosexual route (80.9%) of transmission. Out of total HIV infected individuals, distribution of HBV co-infection was found to be 6(5.7%). All co- infected individuals were married, male, above the age of 25 years & heterosexual route of transmission. Baseline CD4+ T cell count of HIV infected patient was found higher (mean CD4+ T cell count; 283cells/cu.mm) than HBV co-infected patients (mean CD4+ T cell count; 91 cells/cu.mm). Majority (77.2%) of HIV infected & all co-infected individuals were presented in our center late (CD4+ T cell count;< 350/cu. mm) for diagnosis and care. Majority of co- infected 4 (80%) were late presented with advanced AIDS stage (CD4+ count; <200/cu.mm). Conclusions: The study showed a high percentage of HIV sero-positive & co- infected individuals. Baseline CD4+ T cell count of majority of HIV infected individuals was found to be low. Hence, more sustained and vigorous awareness campaigns & counseling still need to be done in order to promote early diagnosis and management.

Keywords: HIV/AIDS, HBsAg, co-infection, CD4+

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141 Advancing Equitable Healthcare for Trans and Gender-Diverse Students: A Community-Based Participatory Action Project

Authors: Al Huuskonen, Clio Lake, K. M. Naude, Polina Petlitsyna, Sorsha Henning, Julia Wimmers-Klick

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This project presents the outcomes of a community-based participatory action initiative aimed at advocating for equitable healthcare and human rights for trans, two-spirit, and gender-diverse individuals, building upon the University of British Columbia (UBC) Trans Coalition's ongoing efforts. Participatory Action Research (PAR) was chosen as the research method with the goal of improving trans rights on the UBC campus, particularly regarding equitable access to healthcare. PAR involves active community contribution throughout the research process, which in this case was done by way of liaising with student resource groups and advocacy leaders. The goals of this project were as follows: a) identify gaps in gender-affirming healthcare for UBC students by consulting the community and collaborating with UBC services, b) develop an information package outlining provincial and university-based health insurance for gender-affirming care (including hormone therapy and surgeries), FAQs, and resources for UBC's trans students, c) make this package available to UBC students and other national transgender advocacy organizations. The initiative successfully expanded the UBC AMS Student Health and Dental Plan to include gender-affirming procedural coverage, developed a care access guide for students, and advocated for improved health records inclusivity, mechanisms for trans students to report negative care experiences, and increased access to gender-affirming primary care through the on-campus health clinic. Collaboration with other universities' pride organizations and Trans Care BC yielded positive outcomes through broader coalition building and resource sharing. Ongoing efforts are underway to update provincial policies, particularly through expanding coverage under fair pharma care and addressing the compounding effects of the primary care crisis for trans individuals. The project's tangible results include improved trans rights on campus, especially in terms of healthcare access. Expanding healthcare coverage through student care benefits thousands of students, making the ability to undergo important affirming procedures more affordable. Providing students with information on extended coverage options and communication with their doctors further removes barriers to care and positively impacts student wellbeing. This initiative demonstrates the effectiveness of community-based participatory action in advancing equitable healthcare for trans and gender-diverse individuals and serves as a model for other institutions and organizations striving to promote inclusivity and advocate for marginalized populations' rights.

Keywords: equitable healthcare, trans and gender-diverse individuals, inclusivity, participatory action research project

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140 Study of Silent Myocardial Ischemia in Type 2 Diabeic Males: Egyptian Experience

Authors: Ali Kassem, Yhea Kishik, Ali Hassan, Mohamed Abdelwahab

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Introduction: Accelerated coronary and peripheral vascular atherosclerosis is one of the most common and chronic complications of diabetes mellitus. A recent aspect of coronary artery disease in this condition is its silent nature. The aim of the work: Detection of the prevalence of silent myocardial ischemia (SMI) in Upper Egypt type 2 diabetic males and to select male diabetic population who should be screened for SMI. Patients and methods: 100 type 2 diabetic male patients with a negative history of angina or anginal equivalent symptoms and 30 healthy control were included. Full medical history and thorough clinical examination were done for all participants. Fasting and post prandial blood glucose level, lipid profile, (HbA1c), microalbuminuria, and C-reactive protein were done for all participants Resting ECG, trans-thoracic echocardiography, treadmill exercise ECG, myocardial perfusion imaging were done for all participants and patients positive for one or more NITs were subjected for coronary angiography. Results Twenty nine patients (29%) were positive for one or more NITs in the patients group compared to only one case (3.3%) in the controls. After coronary angiography, 20 patients were positive for significant coronary artery stenosis in the patients group, while it was refused to be done by the patient in the controls. There were statistical significant difference between the two groups regarding, hypertension, dyslipidemia and obesity, family history of DM and IHD with higher levels of microalbuminuria, C-reactive protein, total lipids in patient group versus controls According to coronary angiography, patients were subdivided into two subgroups, 20 positive for SMI (positive for coronary angiography) and 80 negative for SMI (negative for coronary angiography). No statistical difference regarding family history of DM and type of diabetic therapy was found between the two subgroups. Yet, smoking, hypertension, obesity, dyslipidemia and family history of IHD were significantly higher in diabetics positive versus those negative for SMI. 90% of patients in subgroup positive for SMI had two or more cardiac risk factors while only two patients had one cardiac risk factor (10%). Uncontrolled DM was detected more in patients positive for SMI. Diabetic complications were more prevalent in patients positive for SMI versus those negative for SMI. Most of the patients positive for SMI have DM more than 5 years duration. Resting ECG and resting Echo detected only 6 and 11 cases, respectively, of the 20 positive cases in group positive for SMI compared to treadmill exercise ECG and myocardial perfusion imaging that detected 16 and 18 cases respectively, Conclusion: Type 2 diabetic male patients should be screened for detection of SMI when aged above 50 years old, diabetes duration is more than 5 years, presence of two or more cardiac risk factors and/or patients suffering from one or more of the chronic diabetic complications. CRP, is an important parameter for selection of type 2 diabetic male patients who should be screened for SMI. Non invasive cardiac tests are reliable for screening of SMI in these patients in our locality.

Keywords: C-reactive protein, Silent myocardial ischemia, Stress tests, type 2 DM

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139 Differential Survival Rates of Pseudomonas aeruginosa Strains on the Wings of Pantala flavescens

Authors: Banu Pradheepa Kamarajan, Muthusamy Ananthasubramanian

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Biofilm forming Pseudomonads occupy the top third position in causing hospital acquired infections. P. aeruginosa is notoriously known for its tendency to develop drug resistance. Major classes of drug such as β-lactams, aminoglycosides, quinolones, and polymyxins are found ineffective against multi-drug resistance Pseudomonas. To combat the infections, rather than administration of a single antibiotic, use of combinations (tobramycin and essential oils from plants and/or silver nanoparticles, chitosan, nitric oxide, cis-2-decenoic acid) in single formulation are suggested to control P. aeruginosa biofilms. Conventional techniques to prevent hospital-acquired implant infections such as coatings with antibiotics, controlled release of antibiotics from the implant material, contact-killing surfaces, coating the implants with functional DNase I and, coating with glycoside hydrolase are being followed. Coatings with bioactive components besides having limited shelf-life, require cold-chain and, are likely to fail when bacteria develop resistance. Recently identified nano-scale physical architectures on the insect wings are expected to have potential bactericidal property. Nanopillars are bactericidal to Staphylococcus aureus, Bacillus subtilis, K. pnuemoniae and few species of Pseudomonas. Our study aims to investigate the survival rate of biofilm forming Pseudomonas aeruginosa strain over non-biofilm forming strain on the nanopillar architecture of dragonfly (Pantala flavescens) wing. Dragonflies were collected near house-hold areas and, insect identification was carried out by the Department of Entomology, Tamilnadu Agricultural University, Coimbatore, India. Two strains of P. aeruginosa such as PAO1 (potent biofilm former) and MTCC 1688 (non-weak biofilm former) were tested against the glass coverslip (control) and wings of dragonfly (test) for 48 h. The wings/glass coverslips were incubated with bacterial suspension in 48-well plate. The plates were incubated at 37 °C under static condition. Bacterial attachment on the nanopillar architecture of the wing surface was visualized using FESEM. The survival rate of P. aeruginosa was tested using colony counting technique and flow cytometry at 0.5 h, 1 h, 2 h, 7 h, 24 h, and 48 h post-incubation. Cell death was analyzed using propidium iodide staining and DNA quantification. The results indicated that the survival rate of non-biofilm forming P. aeruginosa is 0.2 %, whilst that of biofilm former is 45 % on the dragonfly wings at the end of 48 h. The reduction in the survival rate of biofilm and non-biofilm forming P. aeruginosa was 20% and 40% respectively on the wings compared to the glass coverslip. In addition, Fourier Transformed Infrared Radiation was used to study the modification in the surface chemical composition of the wing during bacterial attachment and, post-sonication. This result indicated that the chemical moieties are not involved in the bactericidal property of nanopillars by the conserved characteristic peaks of chitin pre and post-sonication. The nanopillar architecture of the dragonfly wing efficiently deters the survival of non-biofilm forming P. aeruginosa, but not the biofilm forming strain. The study highlights the ability of biofilm formers to survive on wing architecture. Understanding this survival strategy will help in designing the architecture that combats the colonization of biofilm forming pathogens.

Keywords: biofilm, nanopillars, Pseudomonas aeruginosa, survival rate

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138 Anxiety Treatment: Comparing Outcomes by Different Types of Providers

Authors: Melissa K. Hord, Stephen P. Whiteside

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With lifetime prevalence rates ranging from 6% to 15%, anxiety disorders are among the most common childhood mental health diagnoses. Anxiety disorders diagnosed in childhood generally show an unremitting course, lead to additional psychopathology and interfere with social, emotional, and academic development. Effective evidence-based treatments include cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRI’s). However, if anxious children receive any treatment, it is usually through primary care, typically consists of medication, and very rarely includes evidence-based psychotherapy. Despite the high prevalence of anxiety disorders, there have only been two independent research labs that have investigated long-term results for CBT treatment for all childhood anxiety disorders and two for specific anxiety disorders. Generally, the studies indicate that the majority of youth maintain gains up to 7.4 years after treatment. These studies have not been replicated. In addition, little is known about the additional mental health care received by these patients in the intervening years after anxiety treatment, which seems likely to influence maintenance of gains for anxiety symptoms as well as the development of additional psychopathology during the subsequent years. The original sample consisted of 335 children ages 7 to 17 years (mean 13.09, 53% female) diagnosed with an anxiety disorder in 2010. Medical record review included provider billing records for mental health appointments during the five years after anxiety treatment. The subsample for this study was classified into three groups: 64 children who received CBT in an anxiety disorders clinic, 56 who received treatment from a psychiatrist, and 10 who were seen in a primary care setting. Chi-square analyses resulted in significant differences in mental health care utilization across the five years after treatment. Youth receiving treatment in primary care averaged less than one appointment each year and the appointments continued at the same rate across time. Children treated by a psychiatrist averaged approximately 3 appointments in the first two years and 2 in the subsequent three years. Importantly, youth treated in the anxiety clinic demonstrated a gradual decrease in mental health appointments across time. The nuanced differences will be presented in greater detail. The results of the current study have important implications for developing dissemination materials to help guide parents when they are selecting treatment for their children. By including all mental health appointments, this study recognizes that anxiety is often comorbid with additional diagnoses and that receiving evidence-based treatment may have long-term benefits that are associated with improvements in broader mental health. One important caveat might be that the acuity of mental health influenced the level of care sought by patients included in this study; however, taking this possibility into account, it seems those seeking care in a primary care setting continued to require similar care at the end of the study, indicating little improvement in symptoms was experienced.

Keywords: anxiety, children, mental health, outcomes

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137 Reducing System Delay to Definitive Care For STEMI Patients, a Simulation of Two Different Strategies in the Brugge Area, Belgium

Authors: E. Steen, B. Dewulf, N. Müller, C. Vandycke, Y. Vandekerckhove

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Introduction: The care for a ST-elevation myocardial infarction (STEMI) patient is time-critical. Reperfusion therapy within 90 minutes of initial medical contact is mandatory in the improvement of the outcome. Primary percutaneous coronary intervention (PCI) without previous fibrinolytic treatment, is the preferred reperfusion strategy in patients with STEMI, provided it can be performed within guideline-mandated times. Aim of the study: During a one year period (January 2013 to December 2013) the files of all consecutive STEMI patients with urgent referral from non-PCI facilities for primary PCI were reviewed. Special attention was given to a subgroup of patients with prior out-of-hospital medical contact generated by the 112-system. In an effort to reduce out-of-hospital system delay to definitive care a change in pre-hospital 112 dispatch strategies is proposed for these time-critical patients. Actual time recordings were compared with travel time simulations for two suggested scenarios. A first scenario (SC1) involves the decision by the on scene ground EMS (GEMS) team to transport the out-of-hospital diagnosed STEMI patient straight forward to a PCI centre bypassing the nearest non-PCI hospital. Another strategy (SC2) explored the potential role of helicopter EMS (HEMS) where the on scene GEMS team requests a PCI-centre based HEMS team for immediate medical transfer to the PCI centre. Methods and Results: 49 (29,1% of all) STEMI patients were referred to our hospital for emergency PCI by a non-PCI facility. 1 file was excluded because of insufficient data collection. Within this analysed group of 48 secondary referrals 21 patients had an out-of-hospital medical contact generated by the 112-system. The other 27 patients presented at the referring emergency department without prior contact with the 112-system. The table below shows the actual time data from first medical contact to definitive care as well as the simulated possible gain of time for both suggested strategies. The PCI-team was always alarmed upon departure from the referring centre excluding further in-hospital delay. Time simulation tools were similar to those used by the 112-dispatch centre. Conclusion: Our data analysis confirms prolonged reperfusion times in case of secondary emergency referrals for STEMI patients even with the use of HEMS. In our setting there was no statistical difference in gain of time between the two suggested strategies, both reducing the secondary referral generated delay with about one hour and by this offering all patients PCI within the guidelines mandated time. However, immediate HEMS activation by the on scene ground EMS team for transport purposes is preferred. This ensures a faster availability of the local GEMS-team for its community. In case these options are not available and the guideline-mandated times for primary PCI are expected to be exceeded, primary fibrinolysis should be considered in a non-PCI centre.

Keywords: STEMI, system delay, HEMS, emergency medicine

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136 Using the Clinical Decision Support Platform, Dem DX, to Assess the ‘Urgent Community Care Team’s Notes Regarding Clinical Assessment, Management, and Healthcare Outcomes

Authors: R. Tariq, R. Lee

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Background: Heywood, Middleton & Rochdale Urgent Community Care Team (UCCT)1 is a great example of using a multidisciplinary team to cope with demand. The service reduces unnecessary admissions to hospitals and ensures that patients can leave the hospital quicker by making care more readily available within the community and patient’s homes. The team comprises nurses, community practitioners, and allied health professions, including physiotherapy, occupational therapy, pharmacy, and GPs. The main challenge for a team with a range of experiences and skill sets is to maintain consistency of care, which technology can help address. Allied healthcare professionals (HCPs) are often used in expanded roles with duties mainly involving patient consultations and decision making to ease pressure on doctors. The Clinical Reasoning Platform (CRP) Dem Dx is used to support new as well as experienced professionals in the decision making process. By guiding HCPs through diagnosing patients from an expansive directory of differential diagnoses, patients can receive quality care in the community. Actions on the platform are determined using NICE guidelines along with local guidance influencing the assessment and management of a patient. Objective: To compare the clinical assessment, decisions, and actions taken by the UCCT multidisciplinary team in the community and Dem Dx, using retrospective clinical cases. Methodology: Dem Dx was used to analyse 192 anonymised cases provided by the HMR UCCT. The team’s performance was compared with Dem Dx regarding the quality of the documentation of the clinical assessment and the next steps on the patient’s journey, including the initial management, actions, and any onward referrals made. The cases were audited by two medical doctors. Results: The study found that the actions outlined by the Dem Dx platform were appropriate in almost 87% of cases. When in a direct comparison between DemDX and the actions taken by the clinical team, it was found that the platform was suitable 83% (p<0.001) of the time and could lead to a potential improvement of 66% in the assessment and management of cases. Dem Dx also served to highlight the importance of comprehensive and high quality clinical documentation. The quality of documentation of cases by UCCT can be improved to provide a detailed account of the assessment and management process. By providing step-by-step guidance and documentation at every stage, Dem Dx may ensure that legal accountability has been fulfilled. Conclusion: With the ever expanding workforce in the NHS, technology has become a key component in driving healthcare outcomes. To improve healthcare provision and clinical reasoning, a decision support platform can be integrated into HCPs’ clinical practice. Potential assistance with clinical assessments, the most appropriate next step and actions in a patient’s care, and improvements in the documentation was highlighted by this retrospective study. A further study has been planned to ascertain the effectiveness of improving outcomes using the clinical reasoning platform within the clinical setting by clinicians.

Keywords: allied health professional, assessment, clinical reasoning, clinical records, clinical decision-making, ocumentation

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135 Bioresorbable Medicament-Eluting Grommet Tube for Otitis Media with Effusion

Authors: Chee Wee Gan, Anthony Herr Cheun Ng, Yee Shan Wong, Subbu Venkatraman, Lynne Hsueh Yee Lim

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Otitis media with effusion (OME) is the leading cause of hearing loss in children worldwide. Surgery to insert grommet tube into the eardrum is usually indicated for OME unresponsive to antimicrobial therapy. It is the most common surgery for children. However, current commercially available grommet tubes are non-bioresorbable, not drug-treated, with unpredictable duration of retention on the eardrum to ventilate middle ear. Their functionality is impaired when clogged or chronically infected, requiring additional surgery to remove/reinsert grommet tubes. We envisaged that a novel fully bioresorbable grommet tube with sustained antibiotic release technology could address these drawbacks. In this study, drug-loaded bioresorbable poly(L-lactide-co-ε-caprolactone)(PLC) copolymer grommet tubes were fabricated by microinjection moulding technique. In vitro drug release and degradation model of PLC tubes were studied. Antibacterial property was evaluated by incubating PLC tubes with P. aeruginosa broth. Surface morphology was analyzed using scanning electron microscopy. A preliminary animal study was conducted using guinea pigs as an in vivo model to evaluate PLC tubes with and without drug, with commercial Mini Shah grommet tube as comparison. Our in vitro data showed sustained drug release over 3 months. All PLC tubes revealed exponential degradation profiles over time. Modeling predicted loss of tube functionality in water to be approximately 14 weeks and 17 weeks for PLC with and without drug, respectively. Generally, PLC tubes had less bacteria adherence, which were attributed to the much smoother tube surfaces compared to Mini Shah. Antibiotic from PLC tube further made bacteria adherence on surface negligible. They showed neither inflammation nor otorrhea after 18 weeks post-insertion in the eardrums of guinea pigs, but had demonstrated severe degree of bioresorption. Histology confirmed the new PLC tubes were biocompatible. Analyses on the PLC tubes in the eardrums showed bioresorption profiles close to our in vitro degradation models. The bioresorbable antibiotic-loaded grommet tubes showed good predictability in functionality. The smooth surface and sustained release technology reduced the risk of tube infection. Tube functional duration of 18 weeks allowed sufficient ventilation period to treat OME. Our ongoing studies include modifying the surface properties with protein coating, optimizing the drug dosage in the tubes to enhance their performances, evaluating their functional outcome on hearing after full resoption of grommet tube and healing of eardrums, and developing animal model with OME to further validate our in vitro models.

Keywords: bioresorbable polymer, drug release, grommet tube, guinea pigs, otitis media with effusion

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134 A Case of Myelofibrosis-Related Arthropathy: A Rare and Underrecognized Entity

Authors: Geum Yeon Sim, Jasal Patel, Anand Kumthekar, Stanley Wainapel

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A 65-year-old right-hand dominant African-American man, formerly employed as a security guard, was referred to Rehabilitation Medicine with bilateral hand stiffness and weakness. His past medical history was only significant for myelofibrosis, diagnosed 4 years earlier, for which he was receiving scheduled blood transfusions. Approximately 2 years ago, he began to notice stiffness and swelling in his non-dominant hand that progressed to pain and decreased strength, limiting his hand function. Similar but milder symptoms developed in his right hand several months later. There was no history of prior injury or exposure to cold. Physical examination showed enlargement of metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints with finger flexion contractures, Swan-neck and Boutonniere deformities, and associated joint tenderness. Changes were more prominent in the left hand. X-rays showed mild osteoarthritis of several bilateral PIP joints. Anti-nuclear antibodies, rheumatoid factor, and cyclic citrullinated peptide antibodies were negative. MRI of the hand showed no erosions or synovitis. A rheumatology consultation was obtained, and the cause of his symptoms was attributed to myelofibrosis-related arthropathy with secondary osteoarthritis. The patient was tried on diclofenac cream and received a few courses of Occupational Therapy with limited functional improvement. Primary myelofibrosis (PMF) is a rare myeloproliferative neoplasm characterized by clonal proliferation of myeloid cells with variable morphologic maturity and hematopoietic efficiency. Rheumatic manifestations of malignancies include direct invasion, paraneoplastic presentations, secondary gout, or hypertrophic osteoarthropathy. PMF causes gradual bone marrow fibrosis with extramedullary metaplastic hematopoiesis in the liver, spleen, or lymph nodes. Musculoskeletal symptoms are not common and are not well described in the literature. The first reported case of myelofibrosis related arthritis was seronegative arthritis due to synovial invasion of myeloproliferative elements. Myelofibrosis has been associated with autoimmune diseases such as systemic lupus erythematosus, progressive systemic sclerosis, and rheumatoid arthritis. Gout has been reported in patients with myelofibrosis, and the underlying mechanism is thought to be related to the high turnover of nucleic acids that is greatly augmented in this disease. X-ray findings in these patients usually include erosive arthritis with synovitis. Treatment of underlying PMF is the treatment of choice, along with anti-inflammatory medications. Physicians should be cognizant of recognizing this rare entity in patients with PMF while maintaining clinical suspicion for more common causes of joint deformities, such as rheumatic diseases.

Keywords: myelofibrosis, arthritis, arthralgia, malignancy

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133 Physiological Effects during Aerobatic Flights on Science Astronaut Candidates

Authors: Pedro Llanos, Diego García

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Spaceflight is considered the last frontier in terms of science, technology, and engineering. But it is also the next frontier in terms of human physiology and performance. After more than 200,000 years humans have evolved under earth’s gravity and atmospheric conditions, spaceflight poses environmental stresses for which human physiology is not adapted. Hypoxia, accelerations, and radiation are among such stressors, our research involves suborbital flights aiming to develop effective countermeasures in order to assure sustainable human space presence. The physiologic baseline of spaceflight participants is subject to great variability driven by age, gender, fitness, and metabolic reserve. The objective of the present study is to characterize different physiologic variables in a population of STEM practitioners during an aerobatic flight. Cardiovascular and pulmonary responses were determined in Science Astronaut Candidates (SACs) during unusual attitude aerobatic flight indoctrination. Physiologic data recordings from 20 subjects participating in high-G flight training were analyzed. These recordings were registered by wearable sensor-vest that monitored electrocardiographic tracings (ECGs), signs of dysrhythmias or other electric disturbances during all the flight. The same cardiovascular parameters were also collected approximately 10 min pre-flight, during each high-G/unusual attitude maneuver and 10 min after the flights. The ratio (pre-flight/in-flight/post-flight) of the cardiovascular responses was calculated for comparison of inter-individual differences. The resulting tracings depicting the cardiovascular responses of the subjects were compared against the G-loads (Gs) during the aerobatic flights to analyze cardiovascular variability aspects and fluid/pressure shifts due to the high Gs. In-flight ECG revealed cardiac variability patterns associated with rapid Gs onset in terms of reduced heart rate (HR) and some scattered dysrhythmic patterns (15% premature ventricular contractions-type) that were considered as triggered physiological responses to high-G/unusual attitude training and some were considered as instrument artifact. Variation events were observed in subjects during the +Gz and –Gz maneuvers and these may be due to preload and afterload, sudden shift. Our data reveal that aerobatic flight influenced the breathing rate of the subject, due in part by the various levels of energy expenditure due to the increased use of muscle work during these aerobatic maneuvers. Noteworthy was the high heterogeneity in the different physiological responses among a relatively small group of SACs exposed to similar aerobatic flights with similar Gs exposures. The cardiovascular responses clearly demonstrated that SACs were subjected to significant flight stress. Routine ECG monitoring during high-G/unusual attitude flight training is recommended to capture pathology underlying dangerous dysrhythmias in suborbital flight safety. More research is currently being conducted to further facilitate the development of robust medical screening, medical risk assessment approaches, and suborbital flight training in the context of the evolving commercial human suborbital spaceflight industry. A more mature and integrative medical assessment method is required to understand the physiology state and response variability among highly diverse populations of prospective suborbital flight participants.

Keywords: g force, aerobatic maneuvers, suborbital flight, hypoxia, commercial astronauts

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132 Assessing the Structure of Non-Verbal Semantic Knowledge: The Evaluation and First Results of the Hungarian Semantic Association Test

Authors: Alinka Molnár-Tóth, Tímea Tánczos, Regina Barna, Katalin Jakab, Péter Klivényi

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Supported by neuroscientific findings, the so-called Hub-and-Spoke model of the human semantic system is based on two subcomponents of semantic cognition, namely the semantic control process and semantic representation. Our semantic knowledge is multimodal in nature, as the knowledge system stored in relation to a conception is extensive and broad, while different aspects of the conception may be relevant depending on the purpose. The motivation of our research is to develop a new diagnostic measurement procedure based on the preservation of semantic representation, which is appropriate to the specificities of the Hungarian language and which can be used to compare the non-verbal semantic knowledge of healthy and aphasic persons. The development of the test will broaden the Hungarian clinical diagnostic toolkit, which will allow for more specific therapy planning. The sample of healthy persons (n=480) was determined by the last census data for the representativeness of the sample. Based on the concept of the Pyramids and Palm Tree Test, and according to the characteristics of the Hungarian language, we have elaborated a test based on different types of semantic information, in which the subjects are presented with three pictures: they have to choose the one that best fits the target word above from the two lower options, based on the semantic relation defined. We have measured 5 types of semantic knowledge representations: associative relations, taxonomy, motional representations, concrete as well as abstract verbs. As the first step in our data analysis, we examined the normal distribution of our results, and since it was not normally distributed (p < 0.05), we used nonparametric statistics further into the analysis. Using descriptive statistics, we could determine the frequency of the correct and incorrect responses, and with this knowledge, we could later adjust and remove the items of questionable reliability. The reliability was tested using Cronbach’s α, and it can be safely said that all the results were in an acceptable range of reliability (α = 0.6-0.8). We then tested for the potential gender differences using the Mann Whitney-U test, however, we found no difference between the two (p < 0.05). Likewise, we didn’t see that the age had any effect on the results using one-way ANOVA (p < 0.05), however, the level of education did influence the results (p > 0.05). The relationships between the subtests were observed by the nonparametric Spearman’s rho correlation matrix, showing statistically significant correlation between the subtests (p > 0.05), signifying a linear relationship between the measured semantic functions. A margin of error of 5% was used in all cases. The research will contribute to the expansion of the clinical diagnostic toolkit and will be relevant for the individualised therapeutic design of treatment procedures. The use of a non-verbal test procedure will allow an early assessment of the most severe language conditions, which is a priority in the differential diagnosis. The measurement of reaction time is expected to advance prodrome research, as the tests can be easily conducted in the subclinical phase.

Keywords: communication disorders, diagnostic toolkit, neurorehabilitation, semantic knowlegde

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