Search results for: therapeutic exercises

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: 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

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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

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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

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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

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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

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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

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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

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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: Abhay Asthana, Shally Toshkhani, Gyati Shilakari

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The objective of the present research work is to develop a topical biodegradable dermal patch based formulation to aid accelerated wound healing. It is always better for patient compliance to be able to reduce the frequency of dressings with improved drug delivery and overall therapeutic efficacy. In present study optimized formulation using biodegradable components was obtained evaluating polymers and excipients (HPMC K4M, Ethylcellulose, Povidone, Polyethylene glycol and Gelatin) to impart significant folding endurance, elasticity, and strength. Molten gelatin was used to get a mixture using ethylene glycol. Chitosan dissolved in acidic medium was mixed with stirring to Gelatin mixture. With continued stirring to the mixture Curcumin was added with the aid of DCM and Methanol in an optimized ratio of 60:40 to get homogenous dispersion. Polymers were dispersed with stirring in the final formulation. The mixture was sonicated casted to get the film form. All steps were carried out under strict aseptic conditions. The final formulation was a thin uniformly smooth textured film with dark brown-yellow color. The film was found to have folding endurance was around 20 to 21 times without a crack in an optimized formulation at RT (23°C). The drug content was in range 96 to 102% and it passed the content uniform test. The final moisture content of the optimized formulation film was NMT 9.0%. The films passed stability study conducted at refrigerated conditions (4±0.2°C) and at room temperature (23 ± 2°C) for 30 days. Further, the drug content and texture remained undisturbed with stability study conducted at RT 23±2°C for 45 and 90 days. Percentage cumulative drug release was found to be 80% in 12h and matched the biodegradation rate as tested in vivo with correlation factor R2>0.9. In in vivo study administration of one dose in equivalent quantity per 2 days was applied topically. The data demonstrated a significant improvement with percentage wound contraction in contrast to control and plain drug respectively in given period. The film based formulation developed shows promising results in terms of stability and in vivo performance.

Keywords: wound healing, biodegradable, polymers, patch

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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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Authors: Yuen Man Yan

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Peer support has been a rising prevalent mental health service in the globe. The community-based mental health services employ persons with lived experience of mental illness to be peer support workers (PSWs) to provide peer support service to those who are in the progress of recovery (PIRs). It represents the transformation of mental health service system to a recovery-oriented and person-centered care. Literatures proved the feasibility and effectiveness of the peer support service. Researchers have attempted to explore the unique good qualities of peer support service that benefit the PIRs. Empirical researches found that the strength of the relationship between those who sought for change and the change agents positively related to the outcomes in one-to-one therapies across theoretical orientations. However, there is lack of literature on investigating the relationship building between the PSWs and PIRs in the one-to-one community-based peer support service. This study aims to identify and characterise the relationship in the community-based one-to-one peer support service from the perspectives of PSWs and PIRs; and to conceptualize the components of relationship building between PSWs and PIRs in the community-based one-to-one peer support service. The study adopted the constructivist grounded theory approach. 10 pairs of the PSWs and PIRs participated in the study. Data were collected through multiple qualitative methods, including observation of the interaction and exchange of the PSWs and PIRs in the 1ₛₜ, 3ᵣ𝒹 and 9th sessions of the community-based one-to-one peer support service; and semi-structural interview with the PSWs and PIRs separately after the 3ᵣ𝒹and 9ₜₕ session of the peer support service. This presentation is going to report the preliminary findings of the study. PSWs and PIRs identified their relationship as “life alliance”. Empathy was found to be one of key components of the relationship between the PSWs and the PIRs. Unlike the empathy, as explained by Carl Roger, in which the service provider was able to put themselves into the shoes of the service recipients as if he was the service recipients, the intensity of the empathy was much greater in the relationship between PSWs and PIRs because PSWs had the lived experience of mental illness and recovery. The dimensions of the empathy in the relationship between PSWs and PIRs was found to be multiple, not only related to the mental illness but also related to various aspects in life, like family relationship, employment, interest of life, self-esteem and etc.

Keywords: person with lived experience, peer support worker, peer support service, relationship building, therapeutic alliance, community-based mental health setting

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Authors: Luke Sniewski, Pante Farvid, Phil Carter, Rita Csako

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Background and Aims: Self-Perceived Problematic Porn Use (SPPPU) refers to individuals who identify as or perceive themselves to be addicted to porn. These individuals feel they are unable to regulate their porn consumption and experience adverse consequences as a result of their use in everyday life. To the author’s best knowledge, this research represents the first study to intervene with pornography use with mindfulness meditation, and aims to investigate the experiences and challenges of men with SPPPU as they engage in a mindfulness meditation intervention. As meditation is commonly characterized by sitting and observing one’s internal experience with non-reaction and acceptance, the study’s principal hypothesis was that consistent practice of meditation would develop the participant’s capacity to respond to cravings, urges, and unwanted thoughts in less reactive, more productive ways. Method: This 12-mixed method research utilised Single Case Experimental Design (SCED) methodology, with a standard AB design. Each participant was randomly assigned to an initial baseline time period between 2 to 5 weeks before learning the meditation technique and practicing it for the remainder of the 12-week study. The pilot study included 3 participants, while the intervention study included 12. The meditation technique used for the study involved a 15-minute guided breathing exercise in the morning, along with a 15-minute guided concentration meditation in the evening. Results: At the time of submission, only pilot study results were available. Results from the pilot study indicate an improved capacity for self-awareness of the uncomfortable mental and emotional states that drove their participants’ pornography use. Statistically significant reductions were also observed in daily porn use, total weekly time spent viewing porn, as well as lowered Pornography Craving Questionnaire (PCQ) and Problematic Pornography Use Scale (PPUS) scores. Conclusion: Pilot study results suggest that meditation could serve as a complementary tool for health professionals to provide clients in conjunction with therapeutic interventions. Study limitations, directions for future research, and clinical implications to be discussed as well.

Keywords: meditation, behavioural change, pornography, mindfulness

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Authors: Aurora Sheehy, Caitlin Prince

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Within current orthodox medical protocols, trauma and mental health issues are deemed to reside within the realm of cognitive or psychological therapists and are marginalised in these areas, in part due to limited drugs option available, mostly manipulating neurotransmitters or sedating patients to reduce symptoms. By contrast, this research presents examples from the clinical practice of how trauma can be assessed and treated physiologically. Adverse Childhood Experiences (ACEs) are a tally of different types of abuse and neglect. It has been used as a measurable and reliable predictor of the likelihood of the development of autoimmune disease. It is a direct way to demonstrate reliably the health impact of traumatic life experiences. A second assessment tool is Allostatic Load, which refers to the cumulative effects that chronic stress has on mental and physical health. It records the decline of an individual’s physiological capacity to cope with their experience. It uses a specific grouping of serum testing and physical measures. It includes an assessment of neuroendocrine, cardiovascular, immune and metabolic systems. Allostatic load demonstrates the health impact that trauma has throughout the body. It forms part of an initial intake assessment in clinical practice and could also be used in research to evaluate treatment. Examining medicinal plants for their physiological, neurological and somatic effects through the lens of Polyvagal theory offers new opportunities for trauma treatments. In situations where Polyvagal theory recommends activities and exercises to enable parasympathetic activation, many herbs that affect Effector Memory T (TEM) cells also enact these responses. Traditional or Indigenous European herbs show the potential to support the polyvagal tone, through multiple mechanisms. As the ventral vagal nerve reaches almost every major organ, plants that have actions on these tissues can be understood via their polyvagal actions, such as monoterpenes as agents to improve respiratory vagal tone, cyanogenic glycosides to reset polyvagal tone, volatile oils rich in phenyl methyl esters improve both sympathetic and parasympathetic tone, bitters activate gut function and can strongly promote parasympathetic regulation. Auricular Acupuncture uses a system of somatotopic mapping of the auricular surface overlaid with an image of an inverted foetus with each body organ and system featured. Given that the concha of the auricle is the only place on the body where the Vagus Nerve neurons reach the surface of the skin, several investigators have evaluated non-invasive, transcutaneous electrical nerve stimulation (TENS) at auricular points. Drawn from an interdisciplinary evidence base and developed through clinical practice, these assessment and treatment tools are examples of practitioners in the field innovating out of necessity for the best outcomes for patients. This paper draws on case studies to direct future research.

Keywords: polyvagal, auricular acupuncture, trauma, herbs

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Authors: Cornelia-Eugenia Munteanu

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The goal of this paper is to present the diagnostic contribution that the screening instrument, Mini-Mental State Examination-2: Expanded Version (MMSE-2:EV), brings in detecting the cognitive impairment or in monitoring the progress of degenerative disorders. The diagnostic signification is underlined by the interpretation of the MMSE-2:EV scores, resulted from the test application to patients with mild and major neurocognitive disorders. The original MMSE is one of the most widely used screening tools for detecting the cognitive impairment, in clinical settings, but also in the field of neurocognitive research. Now, the practitioners and researchers are turning their attention to the MMSE-2. To enhance its clinical utility, the new instrument was enriched and reorganized in three versions (MMSE-2:BV, MMSE-2:SV and MMSE-2:EV), each with two forms: blue and red. The MMSE-2 was adapted and used successfully in Romania since 2013. The cases were selected from current practice, in order to cover vast and significant neurocognitive pathology: mild cognitive impairment, Alzheimer’s disease, vascular dementia, mixed dementia, Parkinson’s disease, conversion of the mild cognitive impairment into Alzheimer’s disease. The MMSE-2:EV version was used: it was applied one month after the initial assessment, three months after the first reevaluation and then every six months, alternating the blue and red forms. Correlated with age and educational level, the raw scores were converted in T scores and then, with the mean and the standard deviation, the z scores were calculated. The differences of raw scores between the evaluations were analyzed from the point of view of statistic signification, in order to establish the progression in time of the disease. The results indicated that the psycho-diagnostic approach for the evaluation of the cognitive impairment with MMSE-2:EV is safe and the application interval is optimal. The alternation of the forms prevents the learning phenomenon. The diagnostic accuracy and efficient therapeutic conduct derive from the usage of the national test norms. In clinical settings with a large flux of patients, the application of the MMSE-2:EV is a safe and fast psycho-diagnostic solution. The clinicians can draw objective decisions and for the patients: it doesn’t take too much time and energy, it doesn’t bother them and it doesn’t force them to travel frequently.

Keywords: MMSE-2, dementia, cognitive impairment, neuropsychology

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Authors: R. Dimitri Halley

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The research within Jungian Psychology presented here is on the wave state of Self. What has been discovered via shared dreaming, independently correlating dreams across dreamers, is beyond the Self stage into the deepest layer or the wave state Self: the very quantum ocean, the Self archetype is embedded in. A quantum wave or rhyming of meaning constituting synergy across several dreamers was discovered in dreams and in extensively shared dream work with small groups at a post therapy stage. Within the format of shared dreaming, we find synergy patterns beyond what Jung called the Self archetype. Jung led us up to the phase of Individuation and delivered the baton to Von Franz to work out the next synchronistic stage, here proposed as the finding of the quantum patterns making up the wave state of Self. These enfolded synchronistic patterns have been found in group format of shared dreaming of individuals approximating individuation, and the unfolding of it is carried by belief and faith. The reason for this format and operating system is because beyond therapy and of living reality, we find no science – no thinking or even awareness in the therapeutic sense – but rather a state of mental processing resembling more like that of spiritual attitude. Thinking as such is linear and cannot contain the deepest layer of Self, the quantum core of the human being. It is self reflection which is the container for the process at the wave state of Self. Observation locks us in an outside-in reactive flow from a first-person perspective and hence toward the surface we see to believe, whereas here, the direction of focus shifts to inside out/intrinsic. The operating system or language at the wave level of Self is thus belief and synchronicity. Belief has up to now been almost the sole province of organized religions but was viewed by Jung as an inherent property in the process of Individuation. The shared dreaming stage of the synchronistic patterns forms a larger story constituting a deep connectivity unfolding around individual Selves. Dreams of independent dreamers form larger patterns that come together as puzzles forming a larger story, and in this sense, this group work level builds on Jung as a post individuation collective stage. Shared dream correlations will be presented, illustrating a larger story in terms of trails of shared synchronicity.

Keywords: belief, shared dreaming, synchronistic patterns, wave state of self

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Authors: Zongping Wang, Chengjun Cui, Jiacun Wang

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The concept of intelligence has been widely used to access an individual's cognitive abilities to learn, form concepts, understand, apply logic, and reason. According to the multiple intelligence theory, there are eight distinguished types of intelligence. One of them is the bodily-kinaesthetic intelligence that links to the capacity of an individual controlling his body and working with objects. Motor intelligence, on the other hand, reflects the capacity to understand, perceive and solve functional problems by motor behavior. Both bodily-kinaesthetic intelligence and motor intelligence refer directly or indirectly to bodily capacity. Inspired by these two intelligence concepts, this paper introduces motional intelligence (MI). MI is two-fold. (1) Body strength, which is the capacity of various organ functions manifested by muscle activity under the control of the central nervous system during physical exercises. It can be measured by the magnitude of muscle contraction force, the frequency of repeating a movement, the time to finish a movement of body position, the duration to maintain muscles in a working status, etc. Body strength reflects the objective of MI. (2) Level of psychiatric willingness to physical events. It is a subjective thing and determined by an individual’s self-consciousness to physical events and resistance to fatigue. As such, we call it subjective MI. Subjective MI can be improved through education and proper social events. The improvement of subjective MI can lead to that of objective MI. A quantitative score of an individual’s MI is motional quotient (MQ). MQ is affected by several factors, including genetics, physical training, diet and lifestyle, family and social environment, and personal awareness of the importance of physical exercise. Genes determine one’s body strength potential. Physical training, in general, makes people stronger, faster and swifter. Diet and lifestyle have a direct impact on health. Family and social environment largely affect one’s passion for physical activities, so does personal awareness of the importance of physical exercise. The key to the success of the MQ study is developing an acceptable and efficient system that can be used to assess MQ objectively and quantitatively. We should apply different accessing systems to different groups of people according to their ages and genders. Field test, laboratory test and questionnaire are among essential components of MQ assessment. A scientific interpretation of MQ score is part of an MQ assessment system as it will help an individual to improve his MQ. IQ (intelligence quotient) and EQ (emotional quotient) and their test have been studied intensively. We argue that IQ and EQ study alone is not sufficient for an individual’s all round development. The significance of MQ study is that it offsets IQ and EQ study. MQ reflects an individual’s mental level as well as bodily level of intelligence in physical activities. It is well-known that the American Springfield College seal includes the Luther Gulick triangle with the words “spirit,” “mind,” and “body” written within it. MQ, together with IQ and EQ, echoes this education philosophy. Since its inception in 2012, the MQ research has spread rapidly in China. By now, six prestigious universities in China have established research centers on MQ and its assessment.

Keywords: motional Intelligence, motional quotient, multiple intelligence, motor intelligence, all round development

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Authors: David Pinzauti, Simon De Jaegher, Maria D'Aguano, Manuele Biazzo

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The COVID-19 pandemic has left an indelible mark on global health, leading to a pressing need for understanding the intricate interactions between the virus and the human microbiome. This study focuses on characterizing the nasal microbiota of patients affected by COVID-19, with a specific emphasis on the comparison with unaffected individuals, to shed light on the crucial role of the microbiome in the development of this viral disease. To achieve this objective, Nanopore technology was employed to analyze the bacterial 16s rRNA full-length gene present in nasal swabs collected in Malta between January 2021 and August 2022. A comprehensive dataset consisting of 268 samples (126 SARS-negative samples and 142 SARS-positive samples) was subjected to a comparative analysis using an in-house, custom pipeline. The findings from this study revealed that individuals affected by COVID-19 possess a nasal microbiota that is significantly less diverse, as evidenced by lower α diversity, and is characterized by distinct microbial communities compared to unaffected individuals. The beta diversity analyses were carried out at different taxonomic resolutions. At the phylum level, Bacteroidota was found to be more prevalent in SARS-negative samples, suggesting a potential decrease during the course of viral infection. At the species level, the identification of several specific biomarkers further underscores the critical role of the nasal microbiota in COVID-19 pathogenesis. Notably, species such as Finegoldia magna, Moraxella catarrhalis, and others exhibited relative abundance in SARS-positive samples, potentially serving as significant indicators of the disease. This study presents valuable insights into the relationship between COVID-19 and the nasal microbiota. The identification of distinct microbial communities and potential biomarkers associated with the disease offers promising avenues for further research and therapeutic interventions aimed at enhancing public health outcomes in the context of COVID-19.

Keywords: COVID-19, nasal microbiota, nanopore technology, 16s rRNA gene, biomarkers

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Authors: A. Ibovi Mouondayi, S. Zaher, R. Assadi, K. Erraoui, S. Sboul, J. Daoudim, S. Bousselham, K. Nassar, S. Janani

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INTRODUCTION: Neuropathic pain (NP) caused by damage to the somatosensory nervous system has a significant impact on quality of life and is associated with a high economic burden on the individual and society. The treatment of neuropathic pain consists of the use of a wide range of therapeutic agents, including gabapentin, which is used in the treatment of neuropathic pain. OBJECTIF: The objective of this study was to evaluate the efficacy and tolerance of gabapentin in the treatment of neuropathic pain. MATERIAL AND METHOD: This is a monocentric, cross-sectional, descriptive, retrospective study conducted in our department over a period of 19 months from October 2020 to April 2022. The missing parameters were collected during phone calls of the patients concerned. The diagnostic tool adopted was the DN4 questionnaire in the dialectal Arabic version. The impact of NP was assessed by the visual analog scale (VAS) on pain, sleep, and function. The impact of PN on mood was assessed by the "Hospital anxiety, and depression scale HAD" score in the validated Arabic version. The exclusion criteria were patients followed up for depression and other psychiatric pathologies. RESULTS: A total of 67 patients' data were collected. The average age was 64 years (+/- 15 years), with extremes ranging from 26 years to 94 years. 58 women and 9 men with an M/F sex ratio of 0.15. Cervical radiculopathy was found in 21% of this population, and lumbosacral radiculopathy in 61%. Gabapentin was introduced in doses ranging from 300 to 1800 mg per day with an average dose of 864 mg (+/- 346) per day for an average duration of 12.6 months. Before treatment, 93% of patients had a non-restorative sleep quality (VAS>3). 54% of patients had a pain VAS greater than 5. The function was normal in only 9% of patients. The mean anxiety score was 3.25 (standard deviation: 2.70), and the mean HAD depression score was 3.79 (standard deviation: 1.79). After treatment, all patients had improved the quality of their sleep (p<0.0001). A significant difference was noted in pain VAS, function, as well as anxiety and depression, and HAD score. Gabapentin was stopped for side effects (dizziness and drowsiness) and/or unsatisfactory response. CONCLUSION: Our data demonstrate a favorable effect of gabapentin on the management of neuropathic pain with a significant difference before and after treatment on the quality of life of patients associated with an acceptable tolerance profile.

Keywords: neuropathic pain, chronic pain, treatment, gabapentin

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Authors: N. Chougui, R. Larbat

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The first economic importance of Opuntia ficus-indica relies on the production of edible fruits. This food transformation generates a large amount of by-products (seeds and peels) in addition to cladodes produced by the plant. Several studies showed the richness of these products with bioactive substances like phenolics that have potential applications. Indeed, phenolics have been associated with protection against oxidation and several biological activities responsible of different pathologies. Consequently, there has been a growing interest in identifying natural antioxidants from plants. This study falls within the framework of the industrial exploitation of by-products of the plant. The study aims to investigate the metabolic profile of three by-products (cladodes, peel seeds) regarding total phenolic content by liquid chromatography coupled to mass spectrometry approach (LC-MSn). The byproducts were first washed, crushed and stored at negative temperature. The total phenolic compounds were then extracted by aqueous-ethanolic solvent in order to be quantified and characterized by LC-MS. According to the results obtained, the peel extract was the richest in phenolic compounds (1512.58 mg GAE/100 g DM) followed by the cladode extract (629.23 GAE/100 g DM) and finally by the seed extract (88.82 GAE/100 g DM) which is mainly used for its oil. The LC-MS analysis revealed diversity in phenolics in the three extracts and allowed the identification of hydroxybenzoic acids, hydroxycinnamic acids and flavonoids. The highest complexity was observed in the seed phenolic composition; more than twenty compounds were detected that belong to acids esters among which three feruloyl sucrose isomers. Sixteen compounds belonging to hydroxybenzoic acids, hydroxycinnamic acids and flavonoids were identified in the peel extract, whereas, only nine compounds were found in the cladode extract. It is interesting to highlight that the phenolic composition of the cladode extract was closer to that of the peel exact. However, from a quantitative viewpoint, the peel extract presented the highest amounts. Piscidic and eucomic acids were the two most concentrated molecules, corresponding to 271.3 and 121.6 mg GAE/ 100g DM respectively. The identified compounds were known to have high antioxidant and antiradical potential with the ability to inhibit lipid peroxidation and to exhibit a wide range of biological and therapeutic properties. The findings highlight the importance of using the Opuntia ficus-indica by-products.

Keywords: characterization, LC-MSn analysis, Opuntia ficus-indica, phenolics

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Authors: Vincenzo Piemonte

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The liver is a complex, large-scale biochemical reactor which plays a unique role in the human physiology. When liver ceases to perform its physiological activity, a functional replacement is required. Actually, liver transplantation is the only clinically effective method of treating severe liver disease. Anyway, the aforementioned therapeutic approach is hampered by the disparity between organ availability and the number of patients on the waiting list. In order to overcome this critical issue, research activities focused on liver support device systems (LSDs) designed to bridging patients to transplantation or to keep them alive until the recovery of native liver function. In recirculating albumin dialysis devices, such as MARS (Molecular Adsorbed Recirculating System), adsorption is one of the fundamental steps in albumin-dialysate regeneration. Among the albumin-bound toxins that must be removed from blood during liver-failure therapy, bilirubin and tryptophan can be considered as representative of two different toxin classes. The first one, not water soluble at physiological blood pH and strongly bounded to albumin, the second one, loosely albumin bound and partially water soluble at pH 7.4. Fixed bed units are normally used for this task, and the design of such units requires information both on toxin adsorption equilibrium and kinetics. The most common adsorptive media used in LSDs are activated carbon, non-ionic polymeric resins and anionic resins. In this paper, bilirubin adsorption isotherms on different adsorptive media, such as polymeric resin, albumin-coated resin, anionic resin, activated carbon and alginate beads with entrapped albumin are presented. By comparing all the results, it can be stated that the adsorption capacity for bilirubin of the five different media increases in the following order: Alginate beads < Polymeric resin < Albumin-coated resin < Activated carbon < Anionic resin. The main focus of this paper is to provide useful guidelines for the optimization of liver support devices which implement adsorption columns to remove albumin-bound toxins from albumin dialysate solutions.

Keywords: adsorptive media, adsorption equilibrium, artificial liver devices, bilirubin, mathematical modelling

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