Search results for: therapeutic healing

Authors: Eric Lacoste

Abstract:

Laboratory animals are currently widely used as a model of human pathologies in dermatology such as atopic dermatitis (AD). These models provide a better understanding of the pathophysiology of this complex and multifactorial disease, the discovery of potential new therapeutic targets and the testing of the efficacy of new therapeutics. However, confirmation of the correct development of AD is mainly based on histology from skin biopsies requiring invasive surgery or euthanasia of the animals, plus slicing and staining protocols. However, there are currently accessible imaging technologies such as Optical Coherence Tomography (OCT), which allows non-invasive visualization of the main histological structures of the skin (like stratum corneum, epidermis, and dermis) and assessment of the dynamics of the pathology or efficacy of new treatments. Briefly, female immunocompetent hairless mice (SKH1 strain) were sensitized and challenged topically on back and ears for about 4 weeks. Back skin and ears thickness were measured using calliper at 3 occasions per week in complement to a macroscopic evaluation of atopic dermatitis lesions on back: erythema, scaling and excoriations scoring. In addition, OCT was performed on the back and ears of animals. OCT allows a virtual in-depth section (tomography) of the imaged organ to be made using a laser, a camera and image processing software allowing fast, non-contact and non-denaturing acquisitions of the explored tissues. To perform the imaging sessions, the animals were anesthetized with isoflurane, placed on a support under the OCT for a total examination time of 5 to 10 minutes. The results show a good correlation of the OCT technique with classical HES histology for skin lesions structures such as hyperkeratosis, epidermal hyperplasia, and dermis thickness. This OCT imaging technique can, therefore, be used in live animals at different times for longitudinal evaluation by repeated measurements of lesions in the same animals, in addition to the classical histological evaluation. Furthermore, this original imaging technique speeds up research protocols, reduces the number of animals and refines the use of the laboratory animal.

Keywords: atopic dermatitis, mouse model, oxzolone model, histology, imaging

Procedia PDF Downloads 132

Authors: S. Sreeja, Radhakrishnan R. Nair, Noble Gracious, Sreeja S. Nair, M. Radhakrishna Pillai

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Background: Tacrolimus is a potent immunosuppressant clinically used for the long term treatment of antirejection of transplanted organs in liver and kidney transplant recipients though dose optimization is poorly managed. However, So far no study has been carried out on the South Indian kidney transplant patients. The objective of this study is to evaluate the potential influence of a functional polymorphism in CYP3A5*3 gene on tacrolimus physiological availability/dose ratio in South Indian renal transplant patients. Materials and Methods: Twenty five renal transplant recipients receiving tacrolimus were enrolled in this study. Their body weight, drug dosage, and therapeutic concentration of Tacrolimus were observed. All patients were on standard immunosuppressive regime of Tacrolimus-Mycophenolate mofetil along with steroids on a starting dose of Tac 0.1 mg/kg/day. CYP3A5 genotyping was performed by PCR followed with RFLP. Conformation of RFLP analysis and variation in the nucleotide sequence of CYP3A5*3 gene were determined by direct sequencing using a validated automated generic analyzer. Results: A significant association was found between tacrolimus per dose/kg/d and CYP3A5 gene (A6986G) polymorphism in the study population. The CYP3A5 *1/*1, *1/*3 and *3/*3 genotypes were detected in 5 (20 %), 5 (20 %) and 15 (60 %) of the 25 graft recipients, respectively. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus Concentration/Dose ratio in kidney transplant recipients. Significantly higher L/D was observed among non-expressors 9.483 ng/mL(4.5- 14.1) as compared with the expressors 5.154 ng/mL (4.42-6.5 ) of CYP3A5. Acute rejection episodes were significantly higher for CYP3A5*1 homozygotes compared to patients with CYP3A5*1/*3 and CYP3A5*3/*3 genotypes (40 % versus 20 % and 13 %, respectively ). The dose normalized TAC concentration (ng/ml/mg/kg) was significantly lower in patients having CYP3A5*1/*3 polymorphism. Conclusion: This is the first study to extensively determine the effect of CYP3A5*3 genetic polymorphism on tacrolimus pharmacokinetics in South Indian renal transplant recipients and also shows that majority of our patients carry mutant allele A6986G in CYP3A5*3 gene. Identification of CYP3A5 polymorphism prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus for each patient.

Keywords: kidney transplant patients, CYP3A5 genotype, tacrolimus, RFLP

Procedia PDF Downloads 301

Authors: Misty Attwood, Helgi Schioth

Abstract:

Transmembrane proteins are important components in many essential cell processes such as signal transduction, cell-cell signalling, transport of solutes, structural adhesion activities, and protein trafficking. Due to their involvement in diverse critical activities, transmembrane proteins are implicated in different disease pathways and hence are the focus of intense interest in understanding functional activities, their pathogenesis in disease, and their potential as pharmaceutical targets. Further, as the structure and function of proteins are correlated, investigating a group of proteins with the same tertiary structure, i.e., the same number of transmembrane regions, may give understanding about their functional roles and potential as therapeutic targets. In this in silico bioinformatics analysis, we identify and comprehensively characterize the previously unstudied group of proteins with five transmembrane-spanning regions (5TM). We classify nearly 60 5TM proteins in which 31 are members of ten families that contain two or more family members and all members are predicted to contain the 5TM architecture. Furthermore, nine singlet proteins that contain the 5TM architecture without paralogues detected in humans were also identifying, indicating the evolution of single unique proteins with the 5TM structure. Interestingly, more than half of these proteins function in localization activities through movement or tethering of cell components and more than one-third are involved in transport activities, particularly in the mitochondria. Surprisingly, no receptor activity was identified within this family in sharp contrast with other TM families. Three major 5TM families were identified and include the Tweety family, which are pore-forming subunits of the swelling-dependent volume regulated anion channel in astrocytes; the sidoreflexin family that acts as mitochondrial amino acid transporters; and the Yip1 domain family engaged in vesicle budding and intra-Golgi transport. About 30% of the proteins have enhanced expression in the brain, liver, or testis. Importantly, 60% of these proteins are identified as cancer prognostic markers, where they are associated with clinical outcomes of various tumour types, indicating further investigation into the function and expression of these proteins is important. This study provides the first comprehensive analysis of proteins with 5TM regions and provides details of the unique characteristics and application in pharmaceutical development.

Keywords: 5TM, cancer prognostic marker, drug targets, transmembrane protein

Procedia PDF Downloads 110

Authors: Sweta Agrawal, Sachin Chaugule, Gargi Rane, Shashank More, Madhavi Indap

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Angiogenesis and metastasis are two of the most important hallmarks of cancer. Hence, most of the cancer therapies nowadays are multi-targeted so as to reduce resistance and have better efficacy. As synthetic molecules arise with a burden of their toxicities and side-effects, more and more research is being focussed on exploiting the vast natural resources of drugs, in the form of plants and animals. Although, the idea of using marine organisms as a source of pharmaceuticals is not new, the pace at which marine drugs are being discovered, has definitely up surged! In the present study, we have assessed the anti-angiogenic and in vitro anti-metastatic activity of aqueous fraction from the extract of marine gastropod Euchelus asper. The soft body of Euchelus Asper was extracted with methanol and named EAME. Partition chromatography of EAME gave three fractions EAME I, II and III. Biochemical analysis revealed the presence of proteins in EAME III. Preliminary analysis had revealed the anti-angiogenic activity was exhibited by EAME III out of the three fractions. Hereafter, EAME III (concentration 25µg/ml-400µg/ml) was tested on chick chorioallantoic membrane (CAM) model for the detailed analysis of its potential anti-angiogenic effect. In vitro testing of the fraction (concentration 0.25µg/ml - 1µg/ml), involved cytotoxicity by SRB assay, cell cycle analysis by flow cytometry and anti-proliferative effect by scratch wound healing assay on A549 lung carcinoma cells. Apart from this, a portion of treated CAM as well as conditioned medium from treated A549 were subjected to gelatin zymography for assessment of matrix metalloproteinases MMP-2 and MMP-9 levels. Our results revealed that EAME III exhibited significant anti-angiogenic activity on CAM which was also supported by histological observations. During histological studies of CAM, it was found that EAME III caused reduction in angiogenesis by altering the extracellular matrix of the CAM membrane. In vitro analysis disclosed that EAME III exhibited moderate cytotoxic effect on A549 cells and its effect was not dose-dependent. The results of flow cytometry confirmed that EAME III caused cell cycle arrest in A549 cell line as almost all of the treated cells were found in G1 phase. Further, the migration and proliferation of A549 was significantly reduced by EAME III as observed from the scratch wound assay. Moreover, Gelatin zymography analysis revealed that EAME III caused suppression of MMP-2 in CAM membrane and reduced MMP-9 and MMP-2 expression in A549 cells. This verified that the anti-angiogenic and anti-metastatic effects of EAME III were correlated with the suppression of MMP-2 and -9. To conclude, EAME III shows dual anti-tumour action by reducing angiogenesis and exerting anti-metastatic effect on lung cancer cells, thus it has the potential to be used as an anti-cancer agent against lung carcinoma.

Keywords: angiogenesis, anti-cancer, marine drugs, matrix metalloproteinases

Procedia PDF Downloads 231

Authors: Hsin-Hung Lin, Janet Chang, Te-Yi Chang, You-Sheng Huang

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The natural and men-made disasters have become huge challenges for tourism destinations as well as emphasizing the fragility of the industry. Hot springs, among all destinations, are prone to disasters due to their dependence on natural resources and locations. After the COVID-19 outbreak, hot spring destinations have experienced not only the loss of businesses but also the psychological trauma. However, evidence has also shown that the impacts may not necessarily reduce the resilience for people but may be converted into posttraumatic growth. In Taiwan, a large proportion of hot springs are located in rural or indigenous areas. As a result, hot spring resources are associated with community cohesion for local residents. Yet prior research on hot spring destinations has mainly focused on visitors, whereas residents have been overlooked. More specifically, the relationship between hot springs resources and resident resilience in the face of the COVID-19 impacts remains unclear. To fulfill this knowledge gap, this paper aims to explore the COVID-19 impacts on residents’ hot spring experiences as well as individual and community resilience from the perspective of posttraumatic growth. A total of 315 residents of 13 hot spring destinations that are most popular in Taiwan were recruited. Online questionnaires were distributed over travel forums and social networks after the COVID-19. This paper subsequently used Partial Least Squares Structural Equation Modeling for data analysis as the technique offers significant advantages in addressing nonnormal data and small sample sizes. A preliminary test was conducted, and the results showed acceptable internal consistency and no serious common method variance. The path analysis demonstrated that the COVID-19 impacts strengthened residents’ perceptions of hot spring resources and experiences, implying that the pandemic had propelled the residents to visit hot springs for the healing benefits. In addition, the COVID-19 impacts significantly enhanced residents’ individual and community resilience, which indicates that the residents at hot springs are more resilient thanks to their awareness of external risks. Thirdly, residents’ individual resilience was positively associated with hot spring experiences, while community resilience was not affected by hot spring experiences. Such findings may suggest that hot spring experiences are more related to individual-level experiences and, consequently, have insignificant influence on community resilience. Finally, individual resilience was proved to be the most relevant factor that help foster community resilience. To conclude, the authorities may consider exploiting the hot spring resources so as to increase individual resilience for local residents. Such implications can be used as a reference for other post-disaster tourist destinations as well. As for future research, longitudinal studies with qualitative methods are suggested to better understand how the hot spring experiences have changed individuals and communities over the long term. It should be noted that the main subjects of this paper were focused on the hot spring communities in Taiwan. Therefore, the results cannot be generalized for all types of tourism destinations. That is, more diverse tourism destinations may be investigated to provide a broader perspective of post-disaster recovery.

Keywords: community resilience, hot spring destinations, individual resilience, posttraumatic growth

Procedia PDF Downloads 81

Authors: Hsin-Hung Lin, Janet Chang, Te-Yi Chang, You-Sheng Huang

Abstract:

The natural and men-made disasters have become huge challenges for tourism destinations as well as emphasizing the fragility of the industry. Hot springs, among all destinations, are prone to disasters due to their dependence on natural resources and locations. After the COVID-19 outbreak, hot spring destinations have experienced not only the loss of businesses but also the psychological trauma. However, evidence has also shown that the impacts may not necessarily reduce the resilience for people but may be converted into posttraumatic growth. In Taiwan, a large proportion of hot springs are located in rural or indigenous areas. As a result, hot spring resources are associated with community cohesion for local residents. Yet prior research on hot spring destinations has mainly focused on visitors, whereas residents have been overlooked. More specifically, the relationship between hot springs resources and resident resilience in the face of the COVID-19 impacts remains unclear. To fulfill this knowledge gap, this paper aims to explore the COVID-19 impacts on residents’ hot spring experiences as well as individual and community resilience from the perspective of posttraumatic growth. A total of 315 residents of 13 hot spring destinations that are most popular in Taiwan were recruited. Online questionnaires were distributed over travel forums and social networks after the COVID-19. This paper subsequently used Partial Least Squares Structural Equation Modeling for data analysis as the technique offers significant advantages in addressing nonnormal data and small sample sizes. A preliminary test was conducted, and the results showed acceptable internal consistency and no serious common method variance. The path analysis demonstrated that the COVID-19 impacts strengthened residents’ perceptions of hot spring resources and experiences, implying that the pandemic had propelled the residents to visit hot springs for the healing benefits. In addition, the COVID-19 impacts significantly enhanced residents’ individual and community resilience, which indicates that the residents at hot springs are more resilient thanks to their awareness of external risks. Thirdly, residents’ individual resilience was positively associated with hot spring experiences, while community resilience was not affected by hot spring experiences. Such findings may suggest that hot spring experiences are more related to individual-level experiences and, consequently, have insignificant influence on community resilience. Finally, individual resilience was proved to be the most relevant factor that help foster community resilience. To conclude, the authorities may consider exploiting the hot spring resources so as to increase individual resilience for local residents. Such implications can be used as a reference for other post-disaster tourist destinations as well.As for future research, longitudinal studies with qualitative methods are suggested to better understand how the hot spring experiences have changed individuals and communities over the long term. It should be noted that the main subjects of this paper were focused on the hot spring communities in Taiwan. Therefore, the results cannot be generalized for all types of tourism destinations. That is, more diverse tourism destinations may be investigated to provide a broader perspective of post-disaster recovery.

Keywords: community resilience, hot spring destinations, individual resilience, posttraumatic growth (PTG)

Procedia PDF Downloads 74

Authors: Endris Yibru Hanurry, Wei-Hsin Hsu, Hsieh-Chih Tsai

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In recent years, the discovery of small interfering RNAs (siRNAs) has got great attention for the treatment of cancer and other diseases. However, the therapeutic efficacy of siRNAs has been faced with many drawbacks because of short half-life in blood circulation, poor membrane penetration, weak endosomal escape and inadequate release into the cytosol. To overcome these drawbacks, we designed a non-viral vector by conjugating polyamidoamine generation 4.5 dendrimer (PDG4.5) with diethylenetriamine (DETA)- and tetraethylenepentamine (TEPA) followed by binding with siRNA to form polyplexes through electrostatic interaction. The result of 1H nuclear magnetic resonance (NMR), 13C NMR, correlation spectroscopy, heteronuclear single–quantum correlation spectroscopy, and Fourier transform infrared spectroscopy confirmed the successful conjugation of DETA and TEPA with PDG4.5. Then, the size, surface charge, morphology, binding ability, stability, release assay, toxicity and cellular internalization were analyzed to explore the physicochemical and biological properties of PDG4.5-DETA and PDG4.5-TEPA polyplexes at specific N/P ratios. The polyplexes (N/P = 8) exhibited spherical nanosized (125 and 85 nm) particles with optimum surface charge (13 and 26 mV), showed strong siRNA binding ability, protected the siRNA against enzyme digestion and accepted biocompatibility to the HeLa cells. Qualitatively, the fluorescence microscopy image revealed the delocalization (Manders’ coefficient 0.63 and 0.53 for PDG4.5-DETA and PDG4.5-TEPA, respectively) of polyplexes and the translocation of the siRNA throughout the cytosol to show a decent cellular internalization and intracellular biodistribution of polyplexes in HeLa cells. Quantitatively, the flow cytometry result indicated that a significant (P < 0.05) amount of siRNA was internalized by cells treated with PDG4.5-DETA (68.5%) and PDG4.5-TEPA (73%) polyplexes. Generally, PDG4.5-DETA and PDG4.5-TEPA were ideal nanocarriers of siRNA in vitro and might be used as promising candidates for in vivo study and future pharmaceutical applications.

Keywords: non-viral carrier, oligoalkylamine, poly(amidoamine) dendrimer, polyplexes, siRNA

Procedia PDF Downloads 132

Authors: Kyra Kannen, Sonja D. Roelen, Sebastian Schnieder, Jarek Krajewski, Steffen Holsteg, André Karger, Johanna Askeridis, Celina Slawik, Philip Mildner, Jens Piesk, Ruslan David, Holger Kürten, Benjamin Oster, Robert Malzan, Mike Ludemann

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Virtual Reality (VR) is increasingly recognized for its potential in transforming mental disorder treatment, offering advantages such as cost-effectiveness, time efficiency, accessibility, reduced stigma, and scalability. While the application of VR in the context of anxiety disorders has been extensively evaluated and demonstrated to be effective, the utilization of VR as a therapeutic treatment for depression remains under-investigated. Our goal is to pioneer immersive VR therapy modules for treating major depression, alongside a web-based system for home use. We develop a modular digital therapy platform grounded in psychodynamic therapy interventions which addresses stress reduction, exploration of social situations and relationship support, social skill training, avoidance behavior analysis, and psychoeducation. In addition, an automated depression monitoring system, based on acoustic voice analysis, is implemented in the form of a speech-based diary to track the affective state of the user and depression severity. The use of immersive VR facilitates patient immersion into complex and realistic interpersonal interactions with high emotional engagement, which may contribute to positive treatment acceptance and satisfaction. In a proof-of-concept study, 45 depressed patients were assigned to VR or web-platform modules, evaluating user experience, usability and additional metrics including depression severity, mindfulness, interpersonal problems, and treatment satisfaction. The findings provide valuable insights into the effectiveness and user-friendliness of VR and web modules for depression therapy and contribute to the refinement of more tailored digital interventions to improve mental health.

Keywords: virtual reality therapy, digital health, depression, psychotherapy

Procedia PDF Downloads 63

Authors: Buhari Samaila, Buhari Maidamma

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Background: The use of ionizing radiation in medical diagnostics and treatment is indispensable for accurate imaging and effective cancer therapies. However, radiation exposure carries inherent risks, necessitating strict protection measures to safeguard both patients and healthcare workers. This review critically examines the existing radiation protection measures in diagnostic radiology and radiotherapy, highlighting technological advancements, regulatory frameworks, and challenges. Objective: The objective of this review is to critically evaluate the effectiveness of current radiation protection measures in diagnostic and therapeutic radiology, focusing on minimizing patient and staff exposure to ionizing radiation while ensuring optimal clinical outcomes and propose future directions for improvement. Method: A comprehensive literature review was conducted, covering scientific studies, regulatory guidelines, and international standards on radiation protection in both diagnostic radiology and radiotherapy. Emphasis was placed on ALARA principles, dose optimization techniques, and protective measures for both patients and healthcare workers. Results: Radiation protection measures in diagnostic radiology include the use of shielding devices, minimizing exposure times, and employing advanced imaging technologies to reduce dose. In radiotherapy, accurate treatment planning and image-guided techniques enhance patient safety, while shielding and dose monitoring safeguard healthcare personnel. Challenges such as limited infrastructure in low-income settings and gaps in healthcare worker training persist, impacting the overall efficacy of protection strategies. Conclusion: While significant advancements have been made in radiation protection, challenges remain in optimizing safety, especially in resource-limited settings. Future efforts should focus on enhancing training, investing in advanced technologies, and strengthening regulatory compliance to ensure continuous improvement in radiation safety practices.

Keywords: radiation protection, diagnostic radiology, radiotherapy, ALARA, patient safety, healthcare worker safety

Procedia PDF Downloads 24

Authors: Pinar Erturk, Sevde Altuntas, Fatih Buyukserin

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In order to obtain an effective integration between an implant and a bone, implant surfaces should have similar properties to bone tissue surfaces. Especially mimicry of the chemical, mechanical and topographic properties of the implant to the bone is crucial for fast and effective osseointegration. Titanium-based biomaterials are more preferred in clinical use, and there are studies of coating these implants with oxide layers that have chemical/nanotopographic properties stimulating cell interactions for enhanced osseointegration. There are low success rates of current implantations, especially in craniofacial implant applications, which are large and vital zones, and the oxide layer coating increases bone-implant integration providing long-lasting implants without requiring revision surgery. Our aim in this study is to examine bone-cell behavior on titanium implants with an aluminum oxide layer (AAO) on effective osseointegration potential in the deformation of large zones with difficult spontaneous healing. In our study, aluminum layer coated titanium surfaces were anodized in sulfuric, phosphoric, and oxalic acid, which are the most common used AAO anodization electrolytes. After morphologic, chemical, and mechanical tests on AAO coated Ti substrates, viability, adhesion, and mineralization of adult bone cells on these substrates were analyzed. Besides with atomic layer deposition (ALD) as a sensitive and conformal technique, these surfaces were coated with pure alumina (5 nm); thus, cell studies were performed on ALD-coated nanoporous oxide layers with suppressed ionic content too. Lastly, in order to investigate the effect of the topography on the cell behavior, flat non-porous alumina layers on silicon wafers formed by ALD were compared with the porous ones. Cell viability ratio was similar between anodized surfaces, but pure alumina coated titanium and anodized surfaces showed a higher viability ratio compared to bare titanium and bare anodized ones. Alumina coated titanium surfaces, which anodized in phosphoric acid, showed significantly different mineralization ratios after 21 days over other bare titanium and titanium surfaces which anodized in other electrolytes. Bare titanium was the second surface that had the highest mineralization ratio. Otherwise, titanium, which is anodized in oxalic acid electrolyte, demonstrated the lowest mineralization. No significant difference was shown between bare titanium and anodized surfaces except AAO titanium surface anodized in phosphoric acid. Currently, osteogenic activities of these cells on the genetic level are investigated by quantitative real-time polymerase chain reaction (qRT-PCR) analysis results of RUNX-2, VEGF, OPG, and osteopontin genes. Also, as a result of the activities of the genes mentioned before, Western Blot will be used for protein detection. Acknowledgment: The project is supported by The Scientific and Technological Research Council of Turkey.

Keywords: alumina, craniofacial implant, MG-63 cell line, osseointegration, oxalic acid, phosphoric acid, sulphuric acid, titanium

Procedia PDF Downloads 131

Authors: Shreya Sara Ittycheria, K. C. Sivakumar, Shijulal Nelson Sathi, Priya Srinivas

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hCG, a heterodimer composed of α and β subunits, is a peptide hormone having numerous biological functions. Although hCG is expressed by placenta during pregnancy, ectopic β-hCG secretion is observed in many non-trophoblastic tumors including that of breast. In-vitro and in-vivo studies done in the lab, have proved that BRCA1 defective cancers express β-hCG and when β-hCG is expressed or supplemented, it promotes tumor progression and exhibits resistance to carboplatin and ABT888, in such cancers but not in BRCA1 wild type cancers. In cancer cells, instead of binding to its regular receptor, LH-CGR, β-hCG binds with Transforming Growth Factor Receptor 2 (TGFβRII) and phosphorylates it resulting in faster tumor progression through the Smad signaling pathway. Targeting β-hCG could be a potential therapeutic strategy for managing BRCA1 defective cancers. Here, molecular docking and dynamic simulation studies were done to identify potential small molecule inhibitors against β-hCG as there are currently no such inhibitors reported. The binding sites of TGFβRII on β-hCG were identified from the top 10 predicted complexes from Z Dock. Virtual screening of selected commercially available small molecules from various libraries such as ZINC, NCI and Life Chemicals amounting to a total of 50,025 molecules were done. Four potential small molecule inhibitors were identified, RgcbPs-1, RgcbPs-2, RgcbPs-3 and RgcbPs-4 with binding affinities -60.778 kcal/mol, -45.447 kcal/mol, -65.2268 kcal/mol and -82.040 kcal/mol respectively. Further, 100ns Molecular Dynamics (MD) simulation showed that these molecules form stable complexes with β-hCG. RgcbPs-1 maintains hydrogen bonds with Q54, L52, Q46, C100, G36, C57, C38 residues, RgcbPs-2 maintains hydrogen bonds with A83 residue, RgcbPs-3 maintains hydrogen bonds with C57, Y58, R94, G101 residues and RgcbPs-4 maintains hydrogen bonds with G36, C38, T40, C57, D99, C100, G101 and L104 residues of β-hCG all of which coincide with the TGFβRII binding site on β-hCG. These results show that these two inhibitors could be used either singly or in combination for inhibiting β-hCG from binding to TGFβRII and thereby directly inhibiting the tumorigenesis pathway.

Keywords: β-hCG, breast cancer, dynamic simulations, molecular docking, small molecule inhibitors, virtual screening.

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Authors: George Shaker, Maike Eylert

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Recurrent urinary tract infections (UTIs) in patients with mesh implants, particularly following pelvic or abdominal surgeries, pose significant clinical challenges. This paper investigates whether flexible cystoscopy is an essential diagnostic and therapeutic tool in managing such patients. With the increasing prevalence of mesh-related complications, it is crucial to explore how diagnostic procedures like cystoscopy can aid in identifying mesh-associated issues that contribute to recurrent UTIs. While flexible cystoscopy is commonly used to evaluate lower urinary tract conditions, its necessity in cases involving patients with mesh implants remains under debate. This study aims to determine the value of flexible cystoscopy in identifying complications such as mesh erosion, fistula formation, and chronic inflammation, which may contribute to recurrent infections. The research compares patients who underwent flexible cystoscopy to those managed without this procedure, examining the diagnostic yield of cystoscopy in detecting mesh-related complications. Furthermore, the study investigates the relationship between recurrent UTIs and the mechanical effects of mesh on the urinary tract, as well as the potential for cystoscopy to guide treatment decisions, such as mesh removal or revision. The results indicate that while flexible cystoscopy can identify mesh-related complications in some cases, its routine use may not be necessary for all patients with recurrent UTIs and mesh. The study emphasizes the importance of patient selection, clinical history, and symptom severity in deciding whether to employ cystoscopy. In cases where there are clear signs of mesh erosion or unexplained recurrent infections despite standard treatments, cystoscopy proves valuable. However, the study also highlights potential risks and discomfort associated with the procedure, suggesting that cystoscopy should be reserved for select cases where non-invasive methods fail to provide clarity. The research concludes that while flexible cystoscopy remains a valuable tool in certain cases, its routine use for all patients with recurrent UTIs and mesh is not justified. The paper provides recommendations for clinical guidelines, emphasizing a more personalized approach to diagnostics that considers the patient’s overall condition, infection history, and mesh type.

Keywords: flexible cystoscopy, recurrent urinary tract infections, mesh implants, mesh erosion, diagnostic procedures, urology

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Authors: Mona Salah El-Din Hassanein

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Faced with a sudden, unexpected, and overwhelming event, the individual's normal cognitive processing may cease to function, trapping the psyche in "speechless terror", while images, feelings and sensations are experienced with emotional intensity. Unable to master such situation, the individual becomes a trauma victim who will be susceptible to traumatic recollections like intrusive thoughts, flashbacks, and repetitive re-living of the primal event in a way that blurs the distinction between past and present, and forecloses the future. Trauma is timeless, repetitious, and contagious; a trauma observer could fall prey to "secondary victimhood". Central to the process of healing the psychic wounds in the aftermath of trauma is verbalizing the traumatic experience (i.e., putting it into words) – an act which provides a chance for assimilation, testimony, and reevaluation. In light of this paradigm, this paper proposes a reading of Oscar Wilde's The Ballad of Reading Gaol, written shortly after his release from prison, as a post-traumatic text which traces the disruptive effects of the traumatic experience of Wilde's imprisonment for homosexual offences and the ensuing reversal of fortune he endured. Post-traumatic writing demonstrates the process of "working through" a trauma which may lead to the possibility of ethical agency in the form of a "survivor mission". This paper draws on fundamental concepts and key insights in literary trauma theory which is characterized by interdisciplinarity, combining the perspectives of different fields like critical theory, psychology, psychiatry, psychoanalysis, history, and social studies. Of particular relevance to this paper are the concepts of "vicarious traumatization" and "survivor mission", as The Ballad of Reading Gaol was written in response to Wilde's own prison trauma and the indirect traumatization he experienced as a result of witnessing the execution of a fellow prisoner whose story forms the narrative base of the poem. The Ballad displays Wilde's sense of mission which leads him to recognize the social as well as ethical implications of personal tragedy. Through a close textual analysis of The Ballad of Reading Gaol within the framework of literary trauma theory, the paper aims to: (a) demonstrate how the poem's thematic concerns, structure and rhetorical figures reflect the structure of trauma; (b) highlight Wilde's attempts to come to terms with the effects of the cataclysmic experience which transformed him into a social outcast; and (c) show how Wilde manages to transcend the victim status and assumes the role of ethical agent to voice a critique of the Victorian penal system and the standards of morality underlying the cruelties practiced against wrong doers and to solicit social action.

Keywords: ballad of reading of reading, post-traumatic writing, trauma theory, Wilde

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Authors: Styliani Soulioti, Helen Fiddler

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The aim of this study was to investigate the approaches used by physiotherapists in the education of patients with chronic low back pain (cLBP) and the rationale that underpins their choice of approach. Therapeutic patient education (TPE) is considered to be an important aspect of modern physiotherapy practice, as it helps patients achieve better self-management and a better understanding of their problem. Previous studies have explored this subject, but the reasoning behind the choices physiotherapists make as educators has not been widely explored, thus making it difficult to understand areas that could be addressed in order to improve the application of TPE.A qualitative study design, guided by a constructivist epistemology was used in this research project. Semi-structured interviews were used to collect data from 7 physiotherapists. Inductive coding and thematic analysis were used, which allowed key themes to emerge. Data analysis revealed two overarching themes: 1) patient-centred versus therapist-centred educational approaches, and 2) behaviourist versus constructivist educational approaches. Physiotherapists appear to use a patient-centred-approach when they explore patients’ beliefs about cLBP and treatment expectations. However, treatment planning and goal-setting were guided by a therapist-centred approach, as physiotherapists appear to take on the role of the instructor/expert, whereas patients were viewed as students. Using a constructivist approach, physiotherapists aimed to provide guidance to patients by combining their professional knowledge with the patients’ individual knowledge, to help the patient better understand their problem, reflect upon it and find a possible solution. However, educating patients about scientific facts concerning cLBP followed a behaviourist approach, as an instructor/student relationship was observed and the learning content was predetermined and transmitted in a one-way manner. The results of this study suggest that a lack of consistency appears to exist in the educational approaches used by physiotherapists. Although patient-centeredness and constructivism appear to be the aims set by physiotherapists in order to optimise the education they provide, a student-teacher relationship appears to dominate when it comes to goal-setting and delivering scientific information.

Keywords: chronic low back pain, educational approaches, health education, patient education

Procedia PDF Downloads 206

Authors: Abdulwahhab Khedr, Tamer Shehata, Hanaa El-Ghamry

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Venlafaxine HCl is a novel antidepressant drug used in the treatment of major depressive disorder, generalized anxiety disorder, social anxiety disorder and panic disorder. Conventional therapeutic regimens with venlafaxine HCl immediate-release dosage forms require frequent dosing due to short elimination half-life of the drug and reduced bioavailability. Hence, this study was carried out to develop sustained-release dosage forms of venlafaxine HCl to reduce its dosing frequency, to improve patient compliance and to reduce side effects of the drug. The polymers used were hydroxypropylmethyl cellulose, xanthan gum, sodium alginate, sodium carboxymethyl cellulose, Carbopol 940 and ethyl cellulose. The physical properties of the prepared tablets including tablet thickness, diameter, weight uniformity, content uniformity, hardness and friability were evaluated. Also, the in-vitro release of venlafaxine HCl from different matrix tablets was studied. Based on physical characters and in-vitro release profiles, certain formulae showing promising sustained-release profiles were subjected to film coating with 15% w/v EC in dichloromethane/ethanol mixture (1:1 ratio) using 1% w/v HPMC as pore former and 30% w/w dibutyl phthalate as plasticizer. The optimized formulations were investigated for drug-excipient compatibility using FTIR and DSC studies. Physical evaluation of the prepared tablets fulfilled the pharmacopoeial requirements for tablet friability test, where the weight loss of the prepared formulae did not exceed 1% of the weight of the tested tablets. Moderate release was obtained from tablets containing HPMC. FTIR and DSC studies for such formulae revealed the absence of any type of chemical interaction between venlafaxine HCl and the used polymers or excipients. Forced swimming test in rats was used to evaluate the antidepressant activity of the selected matrix tablets of venlafaxine HCl. Results showed that formulations significantly decreased the duration of animals’ immobility during the 24 hr-period of the test compared to non-treated group.

Keywords: antidepressant, sustained-release, matrix tablet, venlafaxine hydrochloride

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Authors: Jerzy Slowik, Elzbieta Grochowska-Niedworok

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The analysis of the market needs and trends in both treatment and prophylaxis shows the growing need to implement comprehensive solutions that would enable safe contact of the beneficiaries with the therapeutic and diagnostic support group. Based on the evaluation of the medical and sports industry services market, projects co-financed by the EFRR in the form of comprehensive care systems using IT tools for patients under treatment in the field of obesity and metabolism using the system were implemented under the Regional Operational Program of the Silesian Voivodeship for 2014-2020. SFAO 1.0 (Support for the Fight Against Obesity) number of the WND-RPSL project. 01.02.00-24-06EA / 16) as well as for competitors in qualified sports SK system (qualified sports) project number WND-RPSL. 01.02.00-24-0630 / 17-002. The service provided in accordance with SFAO 1.0 has shown a wide range of therapy possibilities - from monitoring the body's reactions during sports activities of healthy people to remote care for sick patients. As a result of the introduction of an innovative service, it was possible to increase the effectiveness of the therapy, which was manifested in the reduction of the starting doses of drugs by 10%, improvement of the efficiency of the respiratory and blood circulation system, and a 10% increase in bone density. Innovation in the provision of medical services in the field of qualified sports SK was a response to the needs of the athletes and their parents, coaches, physiotherapists, dieticians, and doctors who take care of people actively practicing qualified sports. The creation of the platform made it possible to constantly monitor the trainers necessary for both the proper training process and the control over the health of patients. Monitoring the patient's health by a specialized team in the field of various specialties allows for the proper targeting of the treatment and training process due to the increase in the availability of medical counseling. Specialists taking care of the patient can provide additional advice and modify the medical treatment of the patient on an ongoing basis, which is why we are dealing with a holistic approach.

Keywords: innovation of medical services, sport, obesity, innovation

Procedia PDF Downloads 127

Authors: Eun Jae Ko, In Young Sung, Eui Soo Joeng

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Cognitive impairment is commonly encountered problem in children with various clinical diseases, including Down syndrome, autism spectrum disorder, brain injury, and others. Cognitive impairment limits participation in education and society, and this further hinders development in cognition. However, young children with cognitive impairment tend not to respond well to traditional cognitive treatments, therefore alternative treatment choices are need. As a cognitive training program, touch screen technology can easily be applied to very young children by involving visual and auditory support. Injini was developed as tablet computer based cognitive rehabilitation program for young children or individuals with severe cognitive impairment, which targeted on cognitive ages of 18 to 36 months. The aim of this study was to evaluate the efficacy of a tablet computer based cognitive rehabilitation program (Injini) for children with cognitive impairment. 38 children between cognitive ages of 18 to 36 months confirmed by cognitive evaluations were recruited and randomly assigned to the intervention group (n=20) and the control group (n=18). The intervention group received tablet computer based cognitive rehabilitation program (Injini) for 30 minutes per session, twice a week, over a period of 12 weeks, in addition to the traditional rehabilitation program. The control group received traditional rehabilitation program only. Mental score of Bayley Scales of Infant Development II (BSID II), Pediatric Evaluation of Disability Inventory (PEDI), Laboratory Temperament Assessment Battery (Lab-TAB), Early Childhood Behavior Questionnaire (ECBQ), and Goal Attainment Scale (GAS) were evaluated before and after 12 weeks of therapeutic intervention. When comparing the baseline characteristics, there was no significant difference between the two groups in the measurements of cognitive function. After 12 weeks of treatment, both group showed improvements in all measurements. However, in comparison of improvements after treatment, the intervention group showed more improvements in the mental score of BSID II, social function domain of PEDI, observation domain of Lab-TAB, and GAS, as compared to the control group. Application of the tablet computer based cognitive rehabilitation program (Injini) would be beneficial for improvement of cognitive function in young children with cognitive impairment.

Keywords: cognitive therapy, computer-assisted therapy, early intervention, tablets

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Authors: Owonikoko Abayomi Dele

Abstract:

Epilepsy is an unresolved disease that needs urgent attention. It is a brain disorder that affects over sixty-five (65) million people around the globe. Despite the availability of commercial anti-epileptic drugs, the war against this unmet condition is yet to be resolved. Most epilepsy patients are resistant to available anti-epileptic medications thus the need for affordable novel therapy against epilepsy is a necessity. Numerous phytochemicals have been reported for their potency, efficacy and safety as therapeutic agents against many diseases. This study investigated 99 isolated phytochemicals from Chasmanthera dependens and Carissa edulis against carbonic anhydrase (ii) drug target. The absorption, distribution, metabolism, excretion and toxicity (ADMET) of the isolated compounds were examined using admet SAR-2 web server while Swiss ADME was used to analyze the oral bioavailability, drug-likeness and lead-likeness properties of the selected leads. PASS web server was used to predict the biological activities of selected leads while other important physicochemical properties and interactions of the selected leads with the active site of the target after successful molecular docking simulation with the pyrx virtual screening tool were also examined. The results of these study identified seven lead compounds; C49- alpha-carissanol (-7.6 kcal/mol), C13- Catechin (-7.4 kcal/mol), C45- Salicin (-7.4 kcal/mol), C6- Bisnorargemonine (-7.3 kcal/mol), C36- Pallidine (-7.1 kcal/mol), S4- Lacosamide (-7.1 kcal/mol), and S7- Acetazolamide (-6.4 kcal/mol) for CA II (3HS4 receptor). These leads compounds are probable inhibitors of this drug target due to the observed good binding affinities and favourable interactions with the active site of the drug target, excellent ADMET profiles, PASS Properties, drug-likeness, lead-likeness and oral bioavailability properties. The identified leads have better binding energies as compared to the binding energies of the two standards. Thus, seven identified lead compounds can be developed further towards the development of new anti-epileptic medications.

Keywords: drug-likeness, phytochemicals, carbonic anhydrases, metalloeazymes, active site, ADMET

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Authors: Valeria Arcucci, Musarat Ishaq, Steven A. Stacker, Greg J. Goodall, Marc G. Achen

Abstract:

Metastasis is the lethal aspect of cancer for most patients. Remodelling of lymphatic vessels associated with a tumour is a key initial step in metastasis because it facilitates the entry of cancer cells into the lymphatic vasculature and their spread to lymph nodes and distant organs. Although it is clear that vascular endothelial growth factors (VEGFs), such as VEGF-C and VEGF-D, are key drivers of lymphatic remodelling, the means by which many signaling pathways in endothelial cells are coordinately regulated to drive growth and remodelling of lymphatics in cancer is not understood. We seek to understand the broader molecular mechanisms that control cancer metastasis, and are focusing on microRNAs, which coordinately regulate signaling pathways involved in complex biological responses in health and disease. Here, using small RNA sequencing, we found that a specific microRNA, miR-132, is upregulated in expression in lymphatic endothelial cells (LECs) in response to the lymphangiogenic growth factors. Interestingly, ectopic expression of miR-132 in LECs in vitro stimulated proliferation and tube formation of these cells. Moreover, miR-132 is expressed in lymphatic vessels of a subset of human breast tumours which were previously found to express high levels of VEGF-D by immunohistochemical analysis on tumour tissue microarrays. In order to dissect the complexity of regulation by miR-132 in lymphatic biology, we performed Argonaute HITS-CLIP, which led us to identify the miR-132-mRNA interactome in LECs. We found that this microRNA in LECs is involved in the control of many different pathways mainly involved in cell proliferation and regulation of the extracellular matrix and cell-cell junctions. We are now exploring the functional significance of miR-132 targets in the biology of LECs using biochemical techniques, functional in vitro cell assays and in vivo lymphangiogenesis assays. This project will ultimately define the molecular regulation of lymphatic remodelling by miR-132, and thereby identify potential therapeutic targets for drugs designed to restrict the growth and remodelling of tumour lymphatics resulting in metastatic spread.

Keywords: argonaute HITS-CLIP, cancer, lymphatic remodelling, miR-132, VEGF

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Authors: E. Kilicay, Z. Karahaliloglu, B. Hazer, E. B. Denkbas

Abstract:

In this study, we have prepared concanavaline A (ConA) functionalized curcumin (CUR) loaded PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) nanoparticles as a novel and efficient drug delivery system. CUR is a promising anticancer agent for various cancer types. The aim of this study was to evaluate therapeutic potential of curcumin loaded PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin loaded NPs (ConA-CUR NPs) for ovarian cancer treatment. ConA was covalently connected to the carboxylic group of nanoparticles by EDC/NHS activation method. In the ligand attachment experiment, the binding capacity of ConA on the surface of NPs was found about 90%. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed that the prepared nanoparticles were smooth and spherical in shape. The size and zeta potential of prepared NPs were about 228±5 nm and −21.3 mV respectively. ConA-CUR NPs were characterized by FT-IR spectroscopy which confirmed the existence of CUR and ConA in the nanoparticles. The entrapment and loading efficiencies of different polymer/drug weight ratios, 1/0.125 PHBHHx/CUR= 1.25CUR-NPs; 1/0.25 PHBHHx/CUR= 2.5CUR-NPs; 1/0.5 PHBHHx/CUR= 5CUR-NPs, ConA-1.25CUR NPs, ConA-2.5CUR NPs and ConA-5CUR NPs were found to be ≈ 68%-16.8%; 55%-17.7 %; 45%-33.6%; 70%-15.7%; 60%-17%; 51%-30.2% respectively. In vitro drug release showed that the sustained release of curcumin was observed from CUR-NPs and ConA-CUR NPs over a period of 19 days. After binding of ConA, the release rate was slightly increased due to the migration of curcumin to the surface of the nanoparticles and the matrix integrities was decreased because of the conjugation reaction. This functionalized nanoparticles demonstrated high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. Anticancer activity of ConA-CUR NPs was proved by MTT assay and reconfirmed by apoptosis and necrosis assay. The anticancer activity of ConA-CUR NPs was measured in ovarian cancer cells (SKOV-3) and the results revealed that the ConA-CUR NPs had better tumor cells decline activity than free curcumin. The nacked nanoparticles have no cytotoxicity against human ovarian carcinoma cells. Thus the developed functionalized nanoformulation could be a promising candidate in cancer therapy.

Keywords: curcumin, curcumin-PHBHHx nanoparticles, concanavalin A, concanavalin A-curcumin PHBHHx nanoparticles, PHBHHx nanoparticles, ovarian cancer cell

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Authors: Yutong Wan, John N. Wood

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Introduction: SCN9A encoded Nav1.7 is an ideal therapeutic target with minimal side effects for the pharmaceutical industry because SCN9A variants can cause both human gains of function pain-related mutations and loss of function pain-free mutations. This study reviews the clinical effectiveness of existing Nav1.7 inhibitors, which theoretically should be powerful analgesics. Methods: A systematic review is conducted on the effectiveness of current Nav1.7 blockers undergoing clinical trials. Studies were mainly extracted from PubMed, U.S. National Library of Medicine Clinical Trials, World Health Organization International Clinical Trials Registry, ISRCTN registry platform, and Integrated Research Approval System by NHS. Only studies with full text available and those conducted using double-blinded, placebo controlled, and randomised designs and reporting at least one analgesic measurement were included. Results: Overall, 61 trials were screened, and eight studies covering PF 05089771 (Pfizer), TV 45070 (Teva & Xenon), and BIIB074 (Biogen) met the inclusion criteria. Most studies were excluded because results were not published. All three compounds demonstrated insignificant analgesic effects, and the comparison between PF 05089771 and pregabalin/ibuprofen showed that PF 05089771 was a much weaker analgesic. All three drug candidates only have mild side effects, indicating the potentials for further investigation of Nav1.7 antagonists. Discussion: The failure of current Nav1.7 small molecule inhibitors might attribute to ignorance of the key role of endogenous systems in Nav1.7 null mutants, the lack of selectivity and blocking potency, and central impermeability. The synergistic combination of analgesic drugs, a recent UCL patent, combining a small dose of Nav1.7 blockers and opioids or enkephalinase inhibitors dramatically enhanced the analgesic effects. Conclusion: The current clinical testing Nav1.7 blockers are generally disappointing. However, the newer generation of Nav1.7 targeting analgesics has overcome the major constraints of its predecessors.

Keywords: chronic pain, Nav1.7 blockers, SCN9A, systematic review

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Authors: Yasir Bashawri, Vincent N. Chigor James McDonald, Merfyn Williams, Davey Jones, A. Prysor Williams

Abstract:

Resistance to antibiotics has become a threat to public health. As a result of their misuse and overuse, bacteria have become resistant to many common antibiotics. Βeta lactam (β-lactam) antibiotics are one of the most significant classes of antimicrobials in providing therapeutic benefits for the treatment of bacterial infections in both human and veterinary medicine, for approximately 60% of all antibiotics are used. In particular, some Enterobacteriaceae produce Extend Spectrum Beta Lactamases (ESBLs) that enable them to some break down multi-groups of antibiotics. CTX-M enzymes have rapidly become the most important ESBLs, with increases in mainly CTX-M 15 in many countries during the last decade. Global travel by intercontinental medical ‘tourists’, migrant employees and overseas students could theoretically be a risk factor for spreading antibiotic resistance genes in different parts of the world. Bangor city, North Wales, is subject to sudden demographic changes due to a large proportion (>25%) of the population being students, most of which arrive over a space of days. This makes it a suitable location to study the impacts of large demographic change on the presence of ESBLs. The aim of this study is to monitor the presence of ESBLs in Escherichia coli and faecal coliform bacteria isolated from Bangor wastewater treatment plant, before, during and after the arrival week of students to Bangor University. Over a five-week period, water samples were collected twice a week, from the influent, primary sedimentation tank, aeration tank and the final effluent. Isolation and counts for Escherichia coli and other faecal coliforms were done on selective agar (primary UTI agar). ESBL presence will be confirmed by phenotypic and genotypic methods. Sampling at all points of the tertiary treatment stages will indicate the effectiveness of wastewater treatment in reducing the spread of ESBLs genes. The study will yield valuable information to help tackle a problem which many regard to be the one of the biggest threats to modern-day society.

Keywords: extended spectrum β-lactamase, enterobacteriaceae, international travel, wastewater treatment plant

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Authors: Francesca Lombardi, Francesca Rosaria Augello, Benedetta Cinque, Maria Grazia Cifone, Paola Palumbo

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Glioblastoma multiforme (GBM) is a high-grade primary brain tumor refractory to current forms of treatment. The survival benefits of patients with GBM remain unsatisfactory due to the intrinsic or acquired resistance to temozolomide (TMZ), an alkylating agent, used as the first-line chemotherapeutic drug to treat GBM patients. Its cytotoxic effect is visualized by the induction of O6-methylguanine (O6MeG) within DNA. Cyclooxygenase-2 (COX-2), an inflammation-associated enzyme, has been implicated in tumorigenesis and progression of GBM, its inhibition shows anticancer activities. In the present study, it was verified if the combination of a COX-2 selective inhibitor, NS398, with TMZ could counteract the TMZ resistance. In particular, the effect of NS398 mixed with TMZ was investigated in the GBM TMZ-resistant cell line, T98G. Cells were pretreated with NS398 (100µM, 24 hours) and then exposed to TMZ alone (200µM), NS398 alone, or both for 72 hours, after which cell growth rate and cycle phases, as well as apoptosis level, were evaluated. Coadministration of NS398 and TMZ caused a significant decrease in cell growth and a progressive increase of dead cells detected by trypan blue staining. Moreover, a significant level of apoptotic cell percentage and alteration of cell cycle phases were observed in T98G treated with TMZ-NS398 combination when compared to untreated cells or TMZ-treated cells. TMZ-resistant tumors, as GBM, express elevated levels of DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). The mixture drastically reduced MGMT expression in the TMZ-resistant cell line T98G, known to express high levels of MGMT basically. Moreover, while TMZ alone did not influence the COX-2 protein expression, the combination successfully reduced it. In conclusion, these results demonstrated that NS398 enhanced the efficacy of TMZ through cell number reduction, apoptosis induction, and decreased MGMT levels, suggesting the ability of drug combination to reduce the chemoresistance. This drug combination deserves attention and could be considered as a promising therapeutic strategy for GBM patients.

Keywords: COX-2, COX-2 inhibitor, glioblastoma, NS398, T98G, temozolomide

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Authors: Nitin Rajan, Kashif Shakeel, Shashank Tiwari, Shachan Sagar

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Background: - Aegle Marmelos (Bael) leaf extract is taken twice daily to treat ophthalmia, ulcers, and intestinal worms, among other ailments. Poultice made from bael leaf is used in the treatment of eye conditions. The leaf juice has a variety of therapeutic applications, with the most notable being the treatment of diabetes. Fenugreek is used to cure red spots around the eyes, as well as to soften the throat and chest and to give relief from coughing. The use of this plant in the form of infusion, powder, pomade, and decoction has been extremely popular in Iranian traditional medicine. The plant may be used to wash one's vaginal linings. This plant is used as an emollient in the lack of appetite, treatment of pellagra, and gastrointestinal problems, as well as a general tonic. Calendula officinalis leaves are used to treat varicose veins on the outside of the body by infusing them. In Europe, the leaves are diaphoretic and resolvent in nature, while the blooms are employed as an emmenagogue and antispasmodic stimulant in Canada and the United States. The flowers were decocted and served as a posset drink when smallpox and measles were common in England, and the fresh juice was used to treat jaundice. Objective: - This study is done to compare the physicochemical parameter of the alcoholic extract of the leaves of Aegle Marmelos, Calendula Officinalis, and Fenugreek. Materials and Methods: Extraction and Isolation of Aegle Marmelos, Calendula Officinalis, Fenugreek, were done. Preliminary phytochemical study for alkaloids, cardiac glycosides, flavonoids, glycosides, phenols, resins, saponins, steroids, tannins, terpenoids of the extract was done individual by using the standard procedure. Result: - The phytochemical screening of Aegle Marmelos, Calendula Officinalis, and Fenugreek shows the presence of alkaloids, carbohydrates, total phenolics, total flavonoids, tannins, saponins gum. Conclusion: - In this study, we have found that crude aqueous and organic solvent extracts of Aegle Marmelos, Calendula Officinalis, and Fenugreek leaves contain some important bioactive compounds and it justifies their use in the traditional medicines for the treatment of different diseases.

Keywords: Aegle Marmelos, Calendula Officinalis, Fenugreek, physiochemical parameter

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Authors: Solene Masloh, Anne Chevrel, Maxime Culot, Leonardo Scapozza, Magali Zeisser-Labouebe

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The limited stability of clinically proven therapeutic antibodies limits their administration by the parenteral route. However, oral administration remains the best alternative as it is the most convenient and less invasive one. Obtaining a targeted treatment based on biologics, which can be orally administered, would, therefore, be an ideal situation to improve patient adherence and compliance. Nevertheless, the delivery of macromolecules through the intestine remains challenging because of their sensitivity to the harsh conditions of the gastrointestinal tract and their low permeability across the intestinal mucosa. To address this challenge, this project aims to demonstrate that targeting receptor-mediated endocytosis followed by transcytosis could maximize the intestinal uptake and transport of large molecules, such as Nanofitins. These affinity proteins of 7 kDa with binding properties similar to antibodies have already demonstrated retained stability in the digestive tract and local efficiency. However, their size does not allow passive diffusion through the intestinal barrier. Nanofitins having a controlled affinity for membrane receptors involved in the transcytosis mechanism used naturally for the transport of large molecules in humans were generated. Proteins were expressed using ribosome display and selected based on affinity to the targeted receptor and other characteristics. Their uptake and transport ex vivo across viable porcine intestines were investigated using an Ussing chambers system. In this paper, we will report the results achieved while addressing the different challenges linked to this study. To validate the ex vivo model, first, we proved the presence of the receptors targeted in humans on the porcine intestine. Then, after the identification of an optimal way of detection of Nanofitins, transport experiments were performed on porcine intestines with viability followed during the time of the experiment. The results, showing that the physiological process of transcytosis is capable of being triggered by the binding of Nanofitins on their target, will be reported here. In conclusion, the results show that Nanofitins can be transported across the intestinal barrier by triggering the receptor-mediated transcytosis and that the ex vivo model is an interesting technique to assess biologics absorption through the intestine.

Keywords: ex-vivo, Nanofitins, oral administration, transcytosis

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Authors: L. L. Tundisi, A. Pessoa Jr., E. B. Tambourgi, E. Silveira, P. G. Mazzola

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L-asparaginase (L-ASNase) is the gold standard treatment for acute lymphoblastic leukemia that mainly affects pediatric patients; treatment increases survival from 20% to 90%. The characterization of other L-Asparaginases, apart from the most used from Escherichia coli and Erwinia chrysanthemi, has been reported, but the choice of the most appropriate is still under debate. This choice should be based on its pharmacokinetics, immune hypersensitivity, doses, prices, pharmacodynamics. The main factors influencing the antileukemic activity of ASNase are enzymatic activity, Km, glutaminase activity, clearance of the enzyme and development of resistance. However, most of the commercialized enzyme present an intrinsic glutaminase activity, which is responsible for some side effects. In this study, glutaminase free asparaginase produced from Aspergillus oryzae was precipitated in different percentages of ethanol (0–80%), until optimum ethanol concentration of 60% (w/w) was found. Following, precipitation of crude L-ASNase was performed in a single step, using 60% (w/w) ethanol, under constant agitation and temperature. It presented activity of 135.45 U/mg and after gel filtration chromatography with Sephadex G-the enzymatic activity was 322.02 U/mg. The apparent molecular mass of the purified L-ASNase fraction was estimated by 10% SDS-PAGE. Proteins were stained with Coomassie Brilliant Blue R-250. The molar mass range was from 10 kDa to 250 kDa. L-ASNase from Aspergillus oryzae was characterized aiming possible therapeutic use. Four different buffers (phosphate-citrate buffer pH 2.6 to 5.8; phosphate buffer pH 5.8 to 7.4; Tris - HCl pH 7.4 to 9.0; and carbonate buffer pH 9.8 to 10.6) were used to measure the optimum pH for L-ASNase activity. The optimum temperature for enzyme activity was measured at optimal pH conditions (Tris-HCl and phosphate buffer, pH 7.4) at different temperatures ranging from 5 to 55°C. All activities were calculated by quantifying the free ammonia, using the Nessler reagent. The kinetic parameters calculation, e.g. Michaelis-Menten constant (Km), maximum velocity (Vmax) and Hills coefficient (n), were performed by incubating the enzyme in different concentrations of the substrate at optimum conditions of pH and fitted on Hill’s equation. This glutaminase free asparaginase showed a low Km (3.39 mM and 3.81 mM) and enzymatic activity of 135.45 U/mg after precipitation with ethanol. After gel filtration chromatography it rose to 322.02 U/mg. Optimum activity was found between pH 5.8 - 9.0, best activity results with phosphate buffer pH 7.4 and Tris-HCl pH 7.4 and showed activity from 5°C to 55°C. These results indicate that L-ASNase from A. oryzae has the potential for human use.

Keywords: biopharmaceuticals, bioprocessing, bioproducts, biotechnology, enzyme activity, ethanol precipitation

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Authors: B. A. Alwahaby

Abstract:

Background: The number of Total Knee Replacement (TKR) and Anterior Cruciate Ligament Reconstruction (ACLR) performed every year is increasing. The main aim of physiotherapy early recovery rehabilitation after these surgeries is to control pain and edema and regain Range of Motion (ROM) and physical activity. All of these outcomes need to be managed by safe and effective modalities. Kinesiotaping (KT) is an elastic non-invasive therapeutic tape that has become recognised in different physiotherapy situation as injury prevention, rehabilitation, and performance enhancement and been used with different conditions. However, there is still clinical doubt regarding the effectiveness of KT due to inconclusive supporting evidence. The aim of this systematic review is to collate all the available evidence on the effectiveness of KT in the early rehabilitation of ACLR and TKR patients and analyse whether the use of KT combined with standard rehabilitation would facilitate recovery of postoperative outcome than standard rehabilitation alone. Methodology: A systematic review was conducted. Medline, EMBASE, Scopus, AMED PEDro, CINAHL, and Web of Science databases were searched. Each study was assessed for inclusion and methodological quality appraisal was undertaken by two reviewers using the JBI critical appraisal tools. The studies were then synthesised qualitatively due to heterogeneity between studies. Results: Five moderate to low quality RCTs were located. All five studies demonstrated statistically significant improvements in pain, swelling, ROM, and functional outcomes (p < 0.05). Between group comparison, KT combined with standardised rehabilitation were shown to be significantly more effective than standardised rehabilitation alone for pain and swelling (p < 0.05). However, there were inconstant findings for ROM, and no statistically significant differences reported between groups for functional outcomes (p > 0.05). Conclusion: Research in the area is generally low quality; however, there is consistent evidence to support the use of KT combined with standardised post-operative rehabilitation for reducing pain and swelling. There is also some evidence that KT may be effective in combination with standardised rehabilitation to regain knee extension ROM faster than standardised rehabilitation alone, but further primary research is required to confirm this.

Keywords: anterior cruciate ligament reconstruction, ACLR, kinesio taping, KT, postoperative, total knee replacement, TKR

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Authors: Sanjay Dhiraaj, Puneet Goyal, Aditya Kapoor, Gaurav Misra

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In electrocardiography, an ECG artefact is used to indicate something that is not heart-made. Although technological advancements have produced monitors with the potential of providing accurate information and reliable heart rate alarms, despite this, interference of the displayed electrocardiogram still occurs. These interferences can be from the various electrical gadgets present in the operating room or electrical signals from other parts of the body. Artefacts may also occur due to poor electrode contact with the body or due to machine malfunction. Knowing these artefacts is of utmost importance so as to avoid unnecessary and unwarranted diagnostic as well as interventional procedures. We report a case of ECG artefacts occurring due to patient warming blanket and its consequences. A 20-year-old male with a preoperative diagnosis of exstrophy epispadias complex was posted for surgery under epidural and general anaesthesia. Just after endotracheal intubation, we observed nonspecific ECG changes on the monitor. At a first glance, the monitor strip revealed broad QRs complexes suggesting a ventricular bigeminal rhythm. Closer analysis revealed these to be artefacts because although the complexes were looking broad on the first glance there was clear presence of normal sinus complexes which were immediately followed by 'broad complexes' or artefacts produced by some device or connection. These broad complexes were labeled as artefacts as they were originating in the absolute refractory period of the previous normal sinus beat. It would be physiologically impossible for the myocardium to depolarize so rapidly as to produce a second QRS complex. A search for the possible reason for the artefacts was made and after deepening the plane of anaesthesia, ruling out any possible electrolyte abnormalities, checking of ECG leads and its connections, changing monitors, checking all other monitoring connections, checking for proper grounding of anaesthesia machine and OT table, we found that after switching off the patient’s warming apparatus the rhythm returned to a normal sinus one and the 'broad complexes' or artefacts disappeared. As misdiagnosis of ECG artefacts may subject patients to unnecessary diagnostic and therapeutic interventions so a thorough knowledge of the patient and monitors allow for a quick interpretation and resolution of the problem.

Keywords: ECG artefacts, patient warming blanket, peri-operative arrhythmias, mobile messaging services

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Authors: Rihab Gamaoun, Cynthia El Hage, Laura Ruiz, Erin Prosk, Antonio Vigano

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Introduction: Santé Cannabis (SC), a Canadian medical cannabis-specialized group of clinics based in Montreal and in the province of Québec, has served more than 5000 patients seeking cannabis-based treatment prescription for medical indications over the past five years. Within a research frame, data on the use of medical cannabis products from all the above patients were prospectively collected, leading to a large real-world database on the use of medical cannabis. The aim of this study was to gather information on the profiles of both patients and prescribed medical cannabis products at SC clinics and to assess the safety of medical cannabis among Canadian patients. Methods: Using a retrospective analysis of the database, records of 2585 patients who were prescribed medical cannabis products for therapeutic purposes between 01-November 2017 and 04-September 2019 were included. Patients’ demographics, primary diagnosis, route of administration, and chemovars recorded at the initial visits were investigated. Results: At baseline: 9% of SC patients were female, with a mean age of 57 (SD= 15.8, range= [18-96]); Cannabis products were prescribed mainly for patients with a diagnosis of chronic pain (65.9% of patients), cancer (9.4%), neurological disorders (6.5%), mood disorders (5.8 %) and inflammatory diseases (4.1%). Route of administration and chemovars of prescribed cannabis products were the following: 96% of patients received cannabis oil (51% CBD rich, 42.5% CBD:THC); 32.1% dried cannabis (21.3% CBD:THC, 7.4% THC rich, 3.4 CBD rich), and 2.1% oral spray cannabis (1.1% CBD:THC, 0.8% CBD rich, 0.2% THC rich). Most patients were prescribed simultaneously, a combination of products with different administration routes and chemovars. Safety analysis is undergoing. Conclusion: Our results provided initial information on the profile of medical cannabis products prescribed in a Canadian population and the experienced adverse events over the past three years. The Santé Cannabis database represents a unique opportunity for comparing clinical practices in prescribing and titrating cannabis-based medications across different centers. Ultimately real-world data, including information about safety and effectiveness, will help to create standardized and validated guidelines for choosing dose, route of administration, and chemovars types for the cannabis-based medication in different diseases and indications.

Keywords: medical cannabis, real-world data, safety, pharmacovigilance

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Authors: Zsuzsanna Schnell, Francesca Ervas

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Background: Our study aims to clarify how language fosters further cognitive development and how we eventually arrive at the complex human specific skill of pragmatic competence and reveal what levels of mentalization and theory of mind are in place before language. Method: Our experimental pragmatic investigation maps the interaction of mentalization and pragmatic competence. We map the different levels of mentalization that empower different levels of pragmatic meaning construction and evaluate the results with statistical analysis (MannWhitney and ANOVA). Analyzing the comprehension of literal and non-compositional (figurative) utterances, we apply linguistic trials, among them metaphor-, irony-, irony with surface cue-, humor- and the recognition of maxim infringements trial in neurotypical (NT) preschoolers with a coherent and comparative methodology. Results: The findings reveal the relationship and direction of interaction between Language and theory of mind. On the one hand social-cognitive skills enhance, facilitate and provide a basis for language acquisition, and in return linguistic structures (DeVilliers 2000, 2007) provide a framework for further development of mentalizing skills. Conclusions: Findings confirm that this scaffolding becomes a mutually supportive system where language and social cognition develops in interaction. Certain stages in ToM development serve as a precursor of understanding grammatically complex sentences, like embedded phrases which mirror embedded mental states; which, in turn, facilitates the development of pragmatic competence, thus, the social use of language, integrating social, cognitive, linguistic and psychological factors in discourse. Future implications: Our investigation functions as a differential-diagnostic measure, with typically developing results thus serve as a baseline in further empirical research for atypical cases. This enables the study of populations where language and ToM development is disturbed, reveals how language and ToM are acquired and interact, and gives an insight into what this has to do with clinical symptoms. This in turn can reveal the causal link to the syndrome at hand, which can set directions for therapeutic development and training.

Keywords: theory of mind, language development, mentalization, language philosophy, experimental pragmatics

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