Search results for: rational memory therapy

Authors: Umair Shoukat Ali, Rashna Hoshang Sukhia, Mubassar Fida

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Introduction: The objective of the study was to compare outcomes in terms of Bleeding index (BI), Gingival Index (GI), and Orthodontic Plaque Index (OPI) with video graphics and plaque disclosing tablets (PDT) versus verbal instructions in adult orthodontic patients undergoing fixed appliance treatment (FAT). Materials and Methods: Adult orthodontic patients have recruited from outpatient orthodontic clinics who fulfilled the inclusion criteria and were randomly allocated to three groups i.e., video, PDT, and verbal groups. We included patients undergoing FAT for six months of both genders with all teeth bonded mesial to first molars having no co-morbid conditions such as rheumatic fever and diabetes mellitus. Subjects who had gingivitis as assessed by Bleeding Index (BI), Gingival Index (GI), and Orthodontic Plaque Index (OPI) were recruited. We excluded subjects having > 2 mm of clinical attachment loss, pregnant and lactating females, any history of periodontal therapy within the last six months, and any consumption of antibiotics or anti-inflammatory drugs within the last one month. Pre- and post-interventional measurements were taken at two intervals only for BI, GI, and OPI. The primary outcome of this trial was to evaluate the mean change in the BI, GI, and OPI in the three study groups. A computer-generated randomization list was used to allocate subjects to one of the three study groups using a random permuted block sampling of 6 and 9 to randomize the samples. No blinding of the investigator or the participants was performed. Results: A total of 99 subjects were assessed for eligibility, out of which 96 participants were randomized as three of the participants declined to be part of this trial. This resulted in an equal number of participants (32) that were analyzed in all three groups. The mean change in the oral hygiene indices score was assessed, and we found no statistically significant difference among the three interventional groups. Pre- and post-interventional results showed statistically significant improvement in the oral hygiene indices for the video and PDT groups. No statistically significant difference for age, gender, and education level on oral hygiene indices were found. Simple linear regression showed that the video group produced significantly higher mean OPI change as compared to other groups. No harm was observed during the trial. Conclusions: Visual aids performed better as compared to the verbal group. Gender, age, and education level had no statistically significant impact on the oral hygiene indices. Longer follow-ups will be required to see the long-term effects of these interventions. Trial Registration: NCT04386421 Funding: Aga Khan University and Hospital (URC 183022)

Keywords: oral hygiene, orthodontic treatment, adults, randomized clinical trial

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Authors: Sima E. Rugarabamu, Mecky I. Matee, Elison N. M. Simon

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Background: In Tanzania bacteriological studies of etiological agents of oro-facial infections are very limited, and very few have investigated anaerobes. The aim of this study was to determine the spectrum of bacterial agents involved in oral and maxillofacial infections in patients attending Muhimbili National Hospital, Dar-es-salaam, Tanzania. Method: This was a hospital based descriptive cross-sectional study that was conducted in the Department of Oral and Maxillofacial Surgery of the Muhimbili National Hospital in Dar es Salaam, Tanzania from 1st January 2014 to 31st August 2014. Seventy (70) patients with various forms of oral and maxillofacial infections who were recruited for the study. The study participants were interviewed using a prepared questionnaire after getting their consent. Pus aspirate was cultured on Blood agar, Chocolate Agar, MacConkey agar and incubated aerobically at 37°C. Imported blood agar was used for anaerobic culture whereby they were incubated at 37°Cin anaerobic jars in an atmosphere of generated using commercial gas-generating kits in accordance with manufacturer’s instructions. Plates were incubated at 37°C for 24 hours (For aerobic culture and 48 hours for anaerobic cultures). Gram negative rods were identified using API 20E while all other isolates were identified by conventional biochemical tests. Antibiotic sensitivity testing for isolated aerobic and anaerobic bacteria was detected by the disk diffusion, agar dilution and E-test using routine and commercially available antibiotics used to treat oral facial infections. Results: This study comprised of 41 (58.5%) males and 29 (41.5%) females with a mean age of 32 years SD +/-15.1 and a range of 19 to 70 years. A total of 161 bacteria strains were isolated from specimens obtained from 70 patients which were an average of 2.3 isolates per patient. Of these 103 were aerobic organism and 58 were strict anaerobes. A complex mix of strict anaerobes and facultative anaerobes accounted for 87% of all infections.The most frequent aerobes isolated was streptococcus spp 70 (70%) followed by Staphylococcus spp 18 (18%). Other organisms such as Klebsiella spp 4 (4%), Proteus spp 5 (5%) and Pseudomonas spp 2 (2%) were also seen. The anaerobic group was dominated by Prevotella spp 25 (43%) followed by Peptostreptococcus spp 18 (31%); other isolates were Pseudomonas spp 2 (1%), black pigmented Pophyromonas spp 4 (5%), Fusobacterium spp 3 (3%) and Bacteroides spp 5 (8%). Majority of these organisms were sensitive to Amoxicillin (98%), Gentamycin (89%), and Ciprofloxacin (100%). A 40% resistance to metronidazole was observed in Bacteroides spp otherwise this drug and others displayed good activity against anaerobes. Conclusions: Oral and maxillofacial facial infections at Muhimbili National Hospital are mostly caused by streptococcus spp and Prevotella spp. Strict anaerobes accounted for 36% of all isolates. The profile of isolates should assist in selecting empiric therapy for infections of the oral and maxillofacial region. Inclusion of antimicrobial agents against anaerobic bacteria is highly recommended.

Keywords: bacteria, oral and maxillofacial infections, antibiotic susceptibility, Tanzania

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Authors: Stefan K. Behfar

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The rapid growth of the Ethereum network has brought forth the urgent need for scalable analysis methods to handle the increasing volume of blockchain data. In this research, we propose efficient methodologies for making Ethereum network analysis scalable. Our approach leverages a combination of graph-based data representation, probabilistic sampling, and parallel processing techniques to achieve unprecedented scalability while preserving critical network insights. Data Representation: We develop a graph-based data representation that captures the underlying structure of the Ethereum network. Each block transaction is represented as a node in the graph, while the edges signify temporal relationships. This representation ensures efficient querying and traversal of the blockchain data. Probabilistic Sampling: To cope with the vastness of the Ethereum blockchain, we introduce a probabilistic sampling technique. This method strategically selects a representative subset of transactions and blocks, allowing for concise yet statistically significant analysis. The sampling approach maintains the integrity of the network properties while significantly reducing the computational burden. Graph Convolutional Networks (GCNs): We incorporate GCNs to process the graph-based data representation efficiently. The GCN architecture enables the extraction of complex spatial and temporal patterns from the sampled data. This combination of graph representation and GCNs facilitates parallel processing and scalable analysis. Distributed Computing: To further enhance scalability, we adopt distributed computing frameworks such as Apache Hadoop and Apache Spark. By distributing computation across multiple nodes, we achieve a significant reduction in processing time and enhanced memory utilization. Our methodology harnesses the power of parallelism, making it well-suited for large-scale Ethereum network analysis. Evaluation and Results: We extensively evaluate our methodology on real-world Ethereum datasets covering diverse time periods and transaction volumes. The results demonstrate its superior scalability, outperforming traditional analysis methods. Our approach successfully handles the ever-growing Ethereum data, empowering researchers and developers with actionable insights from the blockchain. Case Studies: We apply our methodology to real-world Ethereum use cases, including detecting transaction patterns, analyzing smart contract interactions, and predicting network congestion. The results showcase the accuracy and efficiency of our approach, emphasizing its practical applicability in real-world scenarios. Security and Robustness: To ensure the reliability of our methodology, we conduct thorough security and robustness evaluations. Our approach demonstrates high resilience against adversarial attacks and perturbations, reaffirming its suitability for security-critical blockchain applications. Conclusion: By integrating graph-based data representation, GCNs, probabilistic sampling, and distributed computing, we achieve network scalability without compromising analytical precision. This approach addresses the pressing challenges posed by the expanding Ethereum network, opening new avenues for research and enabling real-time insights into decentralized ecosystems. Our work contributes to the development of scalable blockchain analytics, laying the foundation for sustainable growth and advancement in the domain of blockchain research and application.

Keywords: Ethereum, scalable network, GCN, probabilistic sampling, distributed computing

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Authors: Jyoti Singh, Ranju Bansal

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Fighting pain and inflammation is a common problem faced by physicians while dealing with a wide variety of diseases. Since ancient time nonsteroidal anti-inflammatory agents (NSAIDs) and opioids have been the cornerstone of treatment therapy, however, the usefulness of both these classes is limited due to severe side effects. NSAIDs, which are mainly used to treat mild to moderate inflammatory pain, induce gastric irritation and nephrotoxicity whereas opioids show an array of adverse reactions such as respiratory depression, sedation, and constipation. Moreover, repeated administration of these drugs induces tolerance to the analgesic effects and physical dependence. Further discovery of selective COX-2 inhibitors (coxibs) suggested safety without any ulcerogenic side effects; however, long-term use of these drugs resulted in kidney and hepatic toxicity along with an increased risk of secondary cardiovascular effects. The basic approaches towards inflammation and pain treatment are constantly changing, and researchers are continuously trying to develop safer and effective anti-inflammatory drug candidates for the treatment of different inflammatory conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, psoriasis and multiple sclerosis. Synthetic 3(2H)-pyridazinones constitute an important scaffold for drug discovery. Structure-activity relationship studies on pyridazinones have shown that attachment of a lactam at N-2 of the pyridazinone ring through a methylene spacer results in significantly increased anti-inflammatory and analgesic properties of the derivatives. Further introduction of the heterocyclic ring at lactam nitrogen results in improvement of biological activities. Keeping in mind these SAR studies, a new series of compounds were synthesized as shown in scheme 1 and investigated for anti-inflammatory, analgesic, anti-platelet activities and docking studies. The structures of newly synthesized compounds have been established by various spectroscopic techniques. All the synthesized pyridazinone derivatives exhibited potent anti-inflammatory and analgesic activity. Homoveratryl substituted derivative was found to possess highest anti-inflammatory and analgesic activity displaying 73.60 % inhibition of edema at 40 mg/kg with no ulcerogenic activity when compared to standard drugs indomethacin. Moreover, 2-substituted-4-benzo[d][1,3]dioxole-6-phenylpyridazin-3(2H)-ones derivatives did not produce significant changes in bleeding time and emerged as safe agents. Molecular docking studies also illustrated good binding interactions at the active site of the cyclooxygenase-2 (hCox-2) enzyme.

Keywords: anti-inflammatory, analgesic, pyridazin-3(2H)-one, selective COX-2 inhibitors

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

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

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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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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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Authors: Agnes Simone

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A 52-year-old male with unknown psychiatric and medical history was brought to the Psychiatric Emergency Room by ambulance directly from jail. He had been detained for three weeks for possession of a firearm while intoxicated. On initial evaluation, the patient was unable to provide a reliable history. He presented with odd jerking movements of his extremities and catatonic features, including mutism and stupor. His vital signs were stable. Patient was transferred to the medical emergency department for work-up of altered mental status. Due to suspicion for opioid overdose, the patient was given naloxone (Narcan) with no improvement. Laboratory work-up included complete blood count, comprehensive metabolic panel, thyroid stimulating hormone, vitamin B12, folate, magnesium, rapid plasma reagin, HIV, blood alcohol level, aspirin, and Tylenol blood levels, urine drug screen, and urinalysis, which were all negative. CT head and chest X-Ray were also negative. With this negative work-up, the medical team concluded there was no organic etiology and requested inpatient psychiatric admission. Upon re-evaluation by psychiatry, it was evident that the patient continued to have an altered mental status. Of note, the medical team did not include substance withdrawal in the differential diagnosis due to stable vital signs and a negative urine drug screen. The psychiatry team decided to check California's prescription drug monitoring program (CURES) and discovered that the patient was prescribed benzodiazepine alprazolam (Xanax) 2mg BID, a sedative-hypnotic, and hydrocodone/acetaminophen 10mg/325mg (Norco) QID, an opioid. After a thorough chart review, his daughter's contact information was found, and she confirmed his benzodiazepine and opioid use, with recent escalation and misuse. It was determined that the patient was experiencing alprazolam withdrawal, given this collateral information, his current symptoms, negative urine drug screen, and recent abrupt discontinuation of medications while incarcerated. After admission to the medical unit and two doses of alprazolam 2mg, the patient's mental status, alertness, and orientation improved, but he had no memory of the events that led to his hospitalization. He was discharged with a limited supply of alprazolam and a close follow-up to arrange a taper. Accompanying this case report, a qualitative review of presentations with alprazolam withdrawal was completed. This case and the review highlights: (1) Alprazolam withdrawal can occur at low doses and within just one week of use. (2) Alprazolam withdrawal can present without any vital sign instability. (3) Alprazolam withdrawal does not respond to short-acting benzodiazepines but does respond to certain long-acting benzodiazepines due to its unique chemical structure. (4) Alprazolam withdrawal is distinct from and more severe than other benzodiazepine withdrawals. This case highlights (1) the importance of physician utilization of drug-monitoring programs. This case, in particular, relied on California's drug monitoring program. (2) The importance of obtaining collateral information, especially in cases in which the patient is unable to provide a reliable history. (3) The importance of including substance intoxication and withdrawal in the differential diagnosis even when there is a negative urine drug screen. Toxidrome of withdrawal can be delayed. (4) The importance of discussing addiction and withdrawal risks of medications with patients.

Keywords: addiction risk of benzodiazepines, alprazolam withdrawal, altered mental status, benzodiazepines, drug monitoring programs, sedative-hypnotics, substance use disorder

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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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Authors: Moshreka Aditi Huq

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This study shows how a progressive portion of civil intellectuals in Bangladesh contributed as the solidarity activist entities in a movement of tea workers that became the symbol of their unique moral struggle. Their passive yet sharp way of resistance, with the integration of mass tea workers of a tea estate, got demonstrated against certain private companies and government officials who approached to establish a special economic zone inside the tea garden without offering any compensation and rehabilitation for poor tea workers. Due to massive protests and rebellion, the authorized entrepreneurs had to step back and called off the project immediately. The extraordinary features of this movement generated itself from the deep core social need of indigenous tea workers who are still imprisoned in the colonial cage. Following an anthropological and ethnographic perspective, this study adopted the main three techniques of intensive interview, focus group discussion, and laborious observation, to extract empirical data. The intensive interviews were undertaken informally using a mostly conversational approach. Focus group discussions were piloted among various representative groups where observations prevailed as part of the regular documentation process. These were conducted among civil intellectual entities, tea workers, tea estate authorities, civil service authorities, and business officials to obtain a holistic view of the situation. The fieldwork was executed in capital Dhaka city, along with northern areas like Chandpur-Begumkhan Tea Estate of Chunarughat Upazilla and Habiganj city of Habiganj District of Bangladesh. Correspondingly, secondary data were accessed through books, scholarly papers, archives, newspapers, reports, leaflets, posters, writing blog, and electronic pages of social media. The study results find that: (1) civil intellectuals opposed state-sponsored business impositions by producing counter-discourse and struggled against state hegemony through the phases of the movement; (2) instead of having the active physical resistance, civil intellectuals’ strength was preferably in passive form which was portrayed through their intellectual labor; (3) the combined movement of tea workers and civil intellectuals reflected on social security of ethnic worker communities that contrasts state’s pseudo-development motives which ultimately supports offensive and oppressive neoliberal growths of economy; (4) civil intellectuals are revealed as having certain functional limitations in the process of movement organization as well as resource mobilization; (5) in specific contexts, the genuine need of protest by indigenous subaltern can overshadow intellectual elitism and helps to raise the voices of ‘subjugated knowledge’. This study is quite likely to represent two sets of apparent protagonist entities in the discussion of social injustice and oppressive development intervention. On the one, hand it may help us to find the basic functional characteristics of civil intellectuals in Bangladesh when they are in a passive mode of resistance in social movement issues. On the other hand, it represents the community ownership and inherent protest tendencies of indigenous workers when they feel threatened and insecure. The study seems to have the potential to understand the conditions of ‘subjugated knowledge’ of subalterns. Furthermore, being the memory and narratives, these ‘activism mechanisms’ of social entities broadens the path to understand ‘power’ and ‘resistance’ in more fascinating ways.

Keywords: civil intellectuals, resistance, subjugated knowledge, indigenous

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

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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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Authors: John Gaber

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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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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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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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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

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Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.

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Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.

Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial

Procedia PDF Downloads 57

Authors: Tom S. Owens, Tom A. Calverley, Benjamin S. Stacey, Christopher J. Marley, George Rose, Lewis Fall, Gareth L. Jones, Priscilla Williams, John P. R. Williams, Martin Steggall, Damian M. Bailey

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Introduction and aims: Sports-related concussion (SRC) represents a significant and growing public health concern in rugby union, yet remains one of the least understood injuries facing the health community today. Alongside increasing SRC incidence rates, there is concern that prior recurrent concussion may contribute to long-term neurologic sequelae in later-life. This may be due to an accelerated decline in cerebral perfusion, a major risk factor for neurocognitive decline and neurodegeneration, though the underlying mechanisms remain to be established. The present study hypothesised that recurrent concussion in current professional rugby union players would result in elevated systemic oxidative-nitrosative stress, reflected by a free radical-mediated reduction in nitric oxide (NO) bioavailability and impaired cerebrovascular and cognitive function. Methodology: A longitudinal study design was adopted across the 2017-2018 rugby union season. Ethical approval was obtained from the University of South Wales Ethics Committee. Data collection is ongoing, and therefore the current report documents result from the pre-season and first half of the in-season data collection. Participants were initially divided into two subgroups; 23 professional rugby union players (aged 26 ± 5 years) and 22 non-concussed controls (27 ± 8 years). Pre-season measurements were performed for cerebrovascular function (Doppler ultrasound of middle cerebral artery velocity (MCAv) in response to hypocapnia/normocapnia/hypercapnia), cephalic venous concentrations of the ascorbate radical (A•-, electron paramagnetic resonance spectroscopy), NO (ozone-based chemiluminescence) and cognition (neuropsychometric tests). Notational analysis was performed to assess contact in the rugby group throughout each competitive game. Results: 1001 tackles and 62 injuries, including three concussions were observed across the first half of the season. However, no associations were apparent between number of tackles and any injury type (P > 0.05). The rugby group expressed greater oxidative stress as indicated by increased A•- (P < 0.05 vs. control) and a subsequent decrease in NO bioavailability (P < 0.05 vs. control). The rugby group performed worse in the Ray Auditory Verbal Learning Test B (RAVLT-B, learning, and memory) and the Grooved Pegboard test using both the dominant and non-dominant hands (visuomotor coordination, P < 0.05 vs. control). There were no between-group differences in cerebral perfusion at baseline (MCAv: 54 ± 13 vs. 59 ± 12, P > 0.05). Likewise, no between-group differences in CVRCO2Hypo (2.58 ± 1.01 vs. 2.58 ± 0.75, P > 0.05) or CVRCO2Hyper (2.69 ± 1.07 vs. 3.35 ± 1.28, P > 0.05) were observed. Conclusion: The present study identified that the rugby union players are characterized by impaired cognitive function subsequent to elevated systemic-oxidative-nitrosative stress. However, this appears to be independent of any functional impairment in cerebrovascular function. Given the potential long-term trajectory towards accelerated cognitive decline in populations exposed to SRC, prophylaxis to increase NO bioavailability warrants consideration.

Keywords: cognition, concussion, mild traumatic brain injury, rugby

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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

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Authors: C. Bel, J. Nevado, F. Ciceri, M. Ropacki, T. Hoffmann, P. Lapunzina, C. Buesa

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Background: The Phelan-McDermid syndrome (PMS) is a genetic disorder caused by the deletion of the terminal region of chromosome 22 or mutation of the SHANK3 gene. Shank3 disruption in mice leads to dysfunction of synaptic transmission, which can be restored by epigenetic regulation with both Lysine Specific Demethylase 1 (LSD1) inhibitors. PMS subjects result in a variable degree of intellectual disability, delay or absence of speech, autistic spectrum disorders symptoms, low muscle tone, motor delays and epilepsy. Vafidemstat is an LSD1 inhibitor in Phase II clinical development with a well-established and favorable safety profile, and data supporting the restoration of memory and cognition defects as well as reduction of agitation and aggression in several animal models and clinical studies. Therefore, vafidemstat has the potential to become a first-in-class precision medicine approach to treat PMS patients. Aims: The goal of this research is to perform an observational trial to psychometrically characterize individuals carrying deletions in SHANK3 and build a foundation for subsequent precision psychiatry clinical trials with vafidemstat. Methodology: This study is characterizing the clinical profile of 20 to 40 subjects, > 16-year-old, with genotypically confirmed PMS diagnosis. Subjects will complete a battery of neuropsychological scales, including the Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, Escala de Observación para el Diagnostico del Autismo (Autism Diagnostic Observational Scale) (ADOS)-2, the Battelle Developmental Inventory and the Behavior Problems Inventory (BPI). Results: By March 2021, 19 patients have been enrolled. Unsupervised hierarchical clustering of the results obtained so far identifies 3 groups of patients, characterized by different profiles of cognitive and behavioral scores. The first cluster is characterized by low Battelle age, high ADOS and low Vineland, RBQ and BPI scores. Low Vineland, RBQ and BPI scores are also detected in the second cluster, which in contrast has high Battelle age and low ADOS scores. The third cluster is somewhat in the middle for the Battelle, Vineland and ADOS scores while displaying the highest levels of aggression (high BPI) and repeated behaviors (high RBQ). In line with the observation that female patients are generally affected by milder forms of autistic symptoms, no male patients are present in the second cluster. Dividing the results by gender highlights that male patients in the third cluster are characterized by a higher frequency of aggression, whereas female patients from the same cluster display a tendency toward higher repetitive behavior. Finally, statistically significant differences in deletion sizes are detected comparing the three clusters (also after correcting for gender), and deletion size appears to be positively correlated with ADOS and negatively correlated with Vineland A and C scores. No correlation is detected between deletion size and the BPI and RBQ scores. Conclusions: Precision medicine may open a new way to understand and treat Central Nervous System disorders. Epigenetic dysregulation has been proposed to be an important mechanism in the pathogenesis of schizophrenia and autism. Vafidemstat holds exciting therapeutic potential in PMS, and this study will provide data regarding the optimal endpoints for a future clinical study to explore vafidemstat ability to treat shank3-associated psychiatric disorders.

Keywords: autism, epigenetics, LSD1, personalized medicine

Procedia PDF Downloads 141

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

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Authors: Haji Mohammad Zulfan Farhi Bin Haji Sulaini, Mohammad Azeezudde’en Bin Mohd Ismaon

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The demands placed on military athletes extend beyond physical prowess to encompass cognitive resilience in high-stress environments. This study investigates the effects of resilience training on the cognitive performance of military athletes, shedding light on the potential benefits and implications for optimizing their overall readiness. In a rapidly evolving global landscape, armed forces worldwide are recognizing the importance of cognitive resilience alongside physical fitness. The study employs a mixed-methods approach, incorporating quantitative cognitive assessments and qualitative data from military athletes undergoing resilience training programs. Cognitive performance is evaluated through a battery of tests, including measures of memory, attention, decision-making, and reaction time. The participants, drawn from various branches of the military, are divided into experimental and control groups. The experimental group undergoes a comprehensive resilience training program, while the control group receives traditional physical training without a specific focus on resilience. The initial findings indicate a substantial improvement in cognitive performance among military athletes who have undergone resilience training. These improvements are particularly evident in domains such as attention and decision-making. The experimental group demonstrated enhanced situational awareness, quicker problem-solving abilities, and increased adaptability in high-stress scenarios. These results suggest that resilience training not only bolsters mental toughness but also positively impacts cognitive skills critical to military operations. In addition to quantitative assessments, qualitative data is collected through interviews and surveys to gain insights into the subjective experiences of military athletes. Preliminary analysis of these narratives reveals that participants in the resilience training program report higher levels of self-confidence, emotional regulation, and an improved ability to manage stress. These psychological attributes contribute to their enhanced cognitive performance and overall readiness. Moreover, this study explores the potential long-term benefits of resilience training. By tracking participants over an extended period, we aim to assess the durability of cognitive improvements and their effects on overall mission success. Early results suggest that resilience training may serve as a protective factor against the detrimental effects of prolonged exposure to stressors, potentially reducing the risk of burnout and psychological trauma among military athletes. This research has significant implications for military organizations seeking to optimize the performance and well-being of their personnel. The findings suggest that integrating resilience training into the training regimen of military athletes can lead to a more resilient and cognitively capable force. This, in turn, may enhance mission success, reduce the risk of injuries, and improve the overall effectiveness of military operations. In conclusion, this study provides compelling evidence that resilience training positively impacts the cognitive performance of military athletes. The preliminary results indicate improvements in attention, decision-making, and adaptability, as well as increased psychological resilience. As the study progresses and incorporates long-term follow-ups, it is expected to provide valuable insights into the enduring effects of resilience training on the cognitive readiness of military athletes, contributing to the ongoing efforts to optimize military personnel's physical and mental capabilities in the face of ever-evolving challenges.

Keywords: military athletes, cognitive performance, resilience training, cognitive enhancement program

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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+

Procedia PDF Downloads 192

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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Authors: B. Petrović, L. Rutonjski, M. Baucal, M. Teodorović, O. Čudić, B. Basarić

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Purpose/Objective: Radiotherapy treatment planning requires use of CT simulator, in order to acquire CT images. The overall performance of CT simulator determines the quality of radiotherapy treatment plan, and at the end, the outcome of treatment for every single patient. Therefore, it is strongly advised by international recommendations, to set up a quality control procedures for every machine involved in radiotherapy treatment planning process, including the CT scanner/ simulator. The overall process requires number of tests, which are used on daily, weekly, monthly or yearly basis, depending on the feature tested. Materials/Methods: Two phantoms were used: a dedicated phantom CIRS 062QA, and a QA phantom obtained with the CT simulator. The examined CT simulator was Siemens Somatom Definition as Open, dedicated for radiation therapy treatment planning. The CT simulator has a built in software, which enables fast and simple evaluation of CT QA parameters, using the phantom provided with the CT simulator. On the other hand, recommendations contain additional test, which were done with the CIRS phantom. Also, legislation on ionizing radiation protection requires CT testing in defined periods of time. Taking into account the requirements of law, built in tests of a CT simulator, and international recommendations, the intitutional QC programme for CT imulator is defined, and implemented. Results: The CT simulator parameters evaluated through the study were following: CT number accuracy, field uniformity, complete CT to ED conversion curve, spatial and contrast resolution, image noise, slice thickness, and patient table stability.The following limits are established and implemented: CT number accuracy limits are +/- 5 HU of the value at the comissioning. Field uniformity: +/- 10 HU in selected ROIs. Complete CT to ED curve for each tube voltage must comply with the curve obtained at comissioning, with deviations of not more than 5%. Spatial and contrast resultion tests must comply with the tests obtained at comissioning, otherwise machine requires service. Result of image noise test must fall within the limit of 20% difference of the base value. Slice thickness must meet manufacturer specifications, and patient stability with longitudinal transfer of loaded table must not differ of more than 2mm vertical deviation. Conclusion: The implemented QA tests gave overall basic understanding of CT simulator functionality and its clinical effectiveness in radiation treatment planning. The legal requirement to the clinic is to set up it’s own QA programme, with minimum testing, but it remains user’s decision whether additional testing, as recommended by international organizations, will be implemented, so to improve the overall quality of radiation treatment planning procedure, as the CT image quality used for radiation treatment planning, influences the delineation of a tumor and calculation accuracy of treatment planning system, and finally delivery of radiation treatment to a patient.

Keywords: CT simulator, radiotherapy, quality control, QA programme

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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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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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Authors: Mumtaz Mooncey, Alexander Jolly, Megan Fisher, Kerry Robinson, Robert Lloyd, Dave Fielding

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Introduction: The integration of the WingFactors in-situ simulation programme has transformed the education landscape at the Whittington Health NHS Trust. To date, there have been a total of 90 simulations - 19 aimed at Paediatric trainees, including 2 Child and Adolescent Mental Health (CAMHS) scenarios. The opportunity for joint debriefs provided by clinical faculty and airline pilots, has created a new exciting avenue to explore human factors within psychiatry. Through the use of real clinical environments and primed actors; the benefits of high fidelity simulation, interdisciplinary and interprofessional learning has been highlighted. The use of in-situ simulation within Psychiatry is a newly emerging concept and its success here has been recognised by unanimously positive feedback from participants and acknowledgement through nomination for the Health Service Journal (HSJ) Award (Best Education Programme 2021). Methodology: The first CAMHS simulation featured a collapsed patient in the toilet with a ligature tied around her neck, accompanied by a distressed parent. This required participants to consider:; emergency physical management of the case, alongside helping to contain the mother and maintaining situational awareness when transferring the patient to an appropriate clinical area. The second simulation was based on a 17- year- old girl attempting to leave the ward after presenting with an overdose, posing potential risk to herself. The safe learning environment enabled participants to explore techniques to engage the young person and understand their concerns, and consider the involvement of other members of the multidisciplinary team. The scenarios were followed by an immediate ‘hot’ debrief, combining technical feedback with Human Factors feedback from uniformed airline pilots and clinicians. The importance of psychological safety was paramount, encouraging open and honest contributions from all participants. Key learning points were summarized into written documents and circulated. Findings: The in-situ simulations demonstrated the need for practical changes both in the Emergency Department and on the Paediatric ward. The presence of airline pilots provided a novel way to debrief on Human Factors. The following key themes were identified: -Team-briefing (‘Golden 5 minutes’) - Taking a few moments to establish experience, initial roles and strategies amongst the team can reduce the need for conversations in front of a distressed patient or anxious relative. -Use of checklists / guidelines - Principles associated with checklist usage (control of pace, rigor, team situational awareness), instead of reliance on accurate memory recall when under pressure. -Read-back - Immediate repetition of safety critical instructions (e.g. drug / dosage) to mitigate the risks associated with miscommunication. -Distraction management - Balancing the risk of losing a team member to manage a distressed relative, versus it impacting on the care of the young person. -Task allocation - The value of the implementation of ‘The 5A’s’ (Availability, Address, Allocate, Ask, Advise), for effective task allocation. Conclusion: 100% of participants have requested more simulation training. Involvement of airline pilots has led to a shift in hospital culture, bringing to the forefront the value of Human Factors focused training and multidisciplinary simulation. This has been of significant value in not only physical health, but also mental health simulation.

Keywords: human factors, in-situ simulation, inter-professional, multidisciplinary

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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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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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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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