Search results for: therapeutic healing

Authors: S. Z. A. Zaidi, A. Crosky

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Biocomposites is a field that has gained much scientific attention due to the current substantial consumption of non-renewable resources and the environmentally harmful disposal methods required for traditional polymer composites. Research on natural fiber reinforced polyhydroxyalkanoates (PHAs) has gained considerable momentum over the past decade. There is little work on PHAs reinforced with unidirectional (UD) natural fibers and little work on using epoxidized natural rubber (ENR) as a toughening agent for PHA-based biocomposites. In this work, we prepared polyhydroxybutyrate-co-valerate (PHBV) biocomposites reinforced with UD 30 wt.% flax fibers and evaluated the use of ENR with 50% epoxidation (ENR50) as a toughening agent for PHBV biocomposites. Quasi-unidirectional flax/PHBV composites were prepared by hand layup, powder impregnation followed by compression molding.  Toughening agents – polybutylene adiphate-co-terephthalate (PBAT) and ENR50 – were cryogenically ground into powder and mechanically mixed with main matrix PHBV to maintain the powder impregnation process. The tensile, flexural and impact properties of the biocomposites were measured and morphology of the composites examined using optical microscopy (OM) and scanning electron microscopy (SEM). The UD biocomposites showed exceptionally high mechanical properties as compared to the results obtained previously where only short fibers have been used. The improved tensile and flexural properties were attributed to the continuous nature of the fiber reinforcement and the increased proportion of fibers in the loading direction. The improved impact properties were attributed to a larger surface area for fiber-matrix debonding and for subsequent sliding and fiber pull-out mechanisms to act on, allowing more energy to be absorbed. Coating cryogenically ground ENR50 particles with PHBV powder successfully inhibits the self-healing nature of ENR-50, preventing particles from coalescing and overcoming problems in mechanical mixing, compounding and molding. Cryogenic grinding, followed by powder impregnation and subsequent compression molding is an effective route to the production of high-mechanical-property biocomposites based on renewable resources for high-obsolescence applications such as plastic casings for consumer electronics.

Keywords: natural fibers, natural rubber, polyhydroxyalkanoates, unidirectional

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Authors: Sabika Rafiq, Rubaida Mehmood, Sajid Hussain, Atia Iqbal

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Background and objectives: The pathogenesis of liver function abnormalities and cardiac dysfunction in hyperthyroid patients after I131 treatment is still unclear. This study aimed to determine the effects of radioiodine I131 on liver function parameters, lactate dehydrogenase (LDH) and low-density lipoproteins (LDL) before and after I131 therapy hyperthyroidism patients. Material & Methods: A total of 52 patients of hyperthyroidism recommended for I131were involved in this study with ages ranging from 12–65 years (mean age=38.6±14.8 & BMI=11.5±3.7). The significance of the differences between the results of 1st, 2nd and 3rd-time serum analysis was assessed by unpaired student’s t-test. Associations between the parameters were assessed by Spearman correlation analysis. Results: Significant variations were observed for thyroid profile free FT3 (p=0.04), FT4 (p=0.01), TSH (p=0.005) during the follow-up treatment. Before taking I131 (serum analyzed at 1st time), negative correlation of FT3 with AST (r=-0.458, p=0.032) and LDL (r=-0.454, p=0.039) were observed. During 2nd time (after stopping carbimazole), no correlation was assessed. Two months after the administration of I131 drops, a significant negative association of FT3 (r=-0.62, p=0.04) and FT4(r=-0.61, p=0.02) with ALB were observed. FT3(r=-0.82, p=0.00) & FT4 (r=-0.71, p=0.00) also showed negative correlation with LDL after I131 therapy. Whereas TSH showed significant positive association with ALB (r=0.61, p=0.01) and LDL (r=0.70, p=0.00) respectively. Conclusion: Current findings suggested that the association of TFTs with biochemical parameters in patients with goiter recommended for iodine therapy is an important diagnostic and therapeutic tool. The significant changes increased in transaminases and low-density lipoprotein levels after taking I131drops are alarming signs for heart and liver function abnormalities and warrant physicians' attention on an urgent basis.

Keywords: hyperthyroidism, carbimazole, radioiodine I131, liver functions, low-density lipoprotein

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Authors: Ahmed M. Kabel, Maaly A. Abd Elmaaboud

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Scleroderma is one of the connective tissue disorders characterized by skin and systemic fibrosis. Its pathogenesis involves multiple interrelated processes of autoimmunity, vasculopathy, inflammation, and oxidative stress. This study was a trial to explore the possible ameliorative effects of sodium valproate on an experimental model of skin fibrosis induced by bleomycin. Forty male BALB/c mice were divided into four equal groups as follows: control group; bleomycin group; bleomycin + sodium valproate group, and sodium valproate group. Mice were assessed for their body weight every four days throughout the whole study. Skin tissues were used to evaluate the oxidative stress parameters, transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin 15, and mammalian target of rapamycin (mTOR). Skin fibrosis was evaluated by measuring dermal thickness and staining the skin tissues with Masson trichrome stain. Also, the skin tissues were immunostained with alpha smooth muscle actin (α-SMA). Administration of sodium valproate to bleomycin-treated mice resulted in the restoration of the body weight with a significant decrease in the dermal thickness, amelioration of oxidative stress, suppression of TGF-β1 and mTOR expression, and significant reduction of the percentage of α-SMA immunostaining and the proinflammatory cytokine levels compared to mice treated with bleomycin alone. In conclusion, sodium valproate has an antifibrotic effect on skin fibrosis which may represent a beneficial therapeutic modality for the management of scleroderma.

Keywords: scleroderma, bleomycin, sodium valproate, skin fibrosis

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Authors: Morteza Elsa, Amirhossein Moghanian

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The major aim of this study was to evaluate the effect of CaO content on in vitro hydroxyapatite formation, MC3T3 cells cytotoxicity and proliferation as well as antibacterial efficiency of sol-gel derived SiO₂–CaO–P₂O₅ ternary system. For this purpose, first two grades of bioactive glass (BG); BG-58s (mol%: 60%SiO₂–36%CaO–4%P₂O₅) and BG-68s (mol%: 70%SiO₂–26%CaO–4%P₂O₅)) were synthesized by sol-gel method. Second, the effect of CaO content in their composition on in vitro bioactivity was investigated by soaking the BG-58s and BG-68s powders in simulated body fluid (SBF) for time periods up to 14 days and followed by characterization inductively coupled plasma atomic emission spectrometry (ICP-AES), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM) techniques. Additionally, live/dead staining, 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and alkaline phosphatase (ALP) activity assays were conducted respectively, as qualitatively and quantitatively assess for cell viability, proliferation and differentiations of MC3T3 cells in presence of 58s and 68s BGs. Results showed that BG-58s with higher CaO content showed higher in vitro bioactivity with respect to BG-68s. Moreover, the dissolution rate was inversely proportional to oxygen density of the BG. Live/dead assay revealed that both 58s and 68s increased the mean number live cells which were in good accordance with MTT assay. Furthermore, BG-58s showed more potential antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) bacteria. Taken together, BG-58s with enhanced MC3T3 cells proliferation and ALP activity, acceptable bioactivity and significant high antibacterial effect against MRSA bacteria is suggested as a suitable candidate in order to further functionalizing for delivery of therapeutic ions and growth factors in bone tissue engineering.

Keywords: antibacterial, bioactive glass, hydroxyapatite, proliferation, sol-gel processes

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Authors: Harini Chakkera

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Background: Inpatient hyperglycemia is an established independent risk factor among several patient cohorts with hospital readmission. This has not been studied after kidney transplantation. Nearly one-third of patients who have undergone a kidney transplant reportedly experience 30-day readmission. Methods: Data on first-time solitary kidney transplantations were retrieved between September 2015 to December 2018. Information was linked to the electronic health record to determine a diagnosis of diabetes mellitus and extract glucometeric and insulin therapy data. Univariate logistic regression analysis and the XGBoost algorithm were used to predict 30-day readmission. We report the average performance of the models on the testing set on five bootstrapped partitions of the data to ensure statistical significance. Results: The cohort included 1036 patients who received kidney transplantation, and 224 (22%) experienced 30-day readmission. The machine learning algorithm was able to predict 30-day readmission with an average AUC of 77.3% (95% CI 75.30-79.3%). We observed statistically significant differences in the presence of pretransplant diabetes, inpatient-hyperglycemia, inpatient-hypoglycemia, and minimum and maximum glucose values among those with higher 30-day readmission rates. The XGBoost model identified the index admission length of stay, presence of hyper- and hypoglycemia and recipient and donor BMI values as the most predictive risk factors of 30-day readmission. Additionally, significant variations in the therapeutic management of blood glucose by providers were observed. Conclusions: Suboptimal glucose metrics during hospitalization after kidney transplantation is associated with an increased risk for 30-day hospital readmission. Optimizing the hospital blood glucose management, a modifiable factor, after kidney transplantation may reduce the risk of 30-day readmission.

Keywords: kidney, transplant, diabetes, insulin

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Authors: Jill Garner, Belinda Lange, Sheila Lennon, Maayken van den Berg

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Currently, there are approximately one billion people worldwide affected by a neurological condition. Many of whom are assessed and treated by a physiotherapist in a variety of settings. There is a lack of consensus in the literature related to what is clinically assessed by physiotherapists in people with neurological conditions. This study aimed to explore assessment in people with neurological conditions, including how health care setting, experience, and therapeutic approach, may influence neurological assessment. A national survey targeted Australian physiotherapists who assess adults with neurological conditions as part of their clinical practice. The survey consisted of 39 questions and was distributed to physiotherapists through the Australian Physiotherapy Association, and Chief Allied Health Officers across Australia and advertised on the National Neurological Physiotherapy Facebook page. In total, 395 respondents consented to the survey from all states within Australia. Most respondents were female (85.4%) with a mean (SD) age of 35.7 years. Respondents reported working clinically in acute, community, outpatients, and community settings. Stroke was the most assessed condition (58.0%). There is variability in domains assessed by Australian physiotherapists, with common inclusions of balance, muscle strength, gait, falls and safety, function, goal setting, range of movement, pain, coordination, activity tolerance, postural alignment and symmetry and upper limb. There is little evidence to support what physiotherapists assess in practice, in different settings, and in different states within Australia and not enough information to develop a decision tree regarding what is important for assessment in different settings. Further research is needed to explore this area and develop a consensus around best practices.

Keywords: physiotherapy, neurological, assessment, domains

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Authors: V. I. Kozyavkin, L. F. Shestopalova, T. B. Voloshyn

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Introduction: Rehabilitation of children with Autism is the issue of the day in psychiatry and neurology. It is attributed to constantly increasing quantity of autistic children - Autistic Spectrum Disorders (ASD) Existing rehabilitation approaches in treatment of children with Autism improve their medico- social and social- psychological adjustment. Experience of treatment for different kinds of Autistic disorders in International Clinic of Rehabilitation (ICR) reveals the necessity of complex intensive approach for healing this malady and wider implementation of a Kozyavkin method for treatment of children with ASD. Methods: 19 children aged from 3 to 14 years were examined. They were diagnosed ‘Autism’ (F84.0) with comorbid neurological pathology (from pyramidal insufficiency to para- and tetraplegia). All patients underwent rehabilitation in ICR during two weeks, where INRS approach was used. INRS included methods like biomechanical correction of the spine, massage, physical therapy, joint mobilization, wax-paraffin applications. They were supplemented by art- therapy, ergotherapy, rhythmical group exercises, computer game therapy, team Olympic games and other methods for improvement of motivation and social integration of the child. Estimation of efficacy was conducted using parent’s questioning and done twice- on the onset of INRS rehabilitation course and two weeks afterward. For efficacy assessment of rehabilitation of autistic children in ICR standardized tool was used, namely Autism Treatment Evaluation Checklist (ATEC). This scale was selected because any rehabilitation approaches for the child with Autism can be assessed using it. Results: Before the onset of INRS treatment mean score according to ATEC scale was 64,75±9,23, it reveals occurrence in examined children severe communication, speech, socialization and behavioral impairments. After the end of the rehabilitation course, the mean score was 56,5±6,7, what indicates positive dynamics in comparison to the onset of rehabilitation. Generally, improvement of psychoemotional state occurred in 90% of cases. Most significant changes occurred in the scope of speech (16,5 before and 14,5 after the treatment), socialization (15.1 before and 12,5 after) and behavior (20,1 before and 17.4 after). Conclusion: As a result of INRS rehabilitation course reduction of autistic symptoms was noted. Particularly improvements in speech were observed (children began to spell out new syllables, words), there was some decrease in signs of destructiveness, quality of contact with the surrounding people improved, new skills of self-service appeared. The prospect of the study is further, according to evidence- based medicine standards, deeper examination of INRS and assessment of its usefulness in treatment for Autism and ASD.

Keywords: intensive neurophysiological rehabilitation system (INRS), international clinic od rehabilitation, ASD, rehabilitation

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Authors: Omoruyi Gold Idemudia, Alexander P. Sadimenko

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The synthesis of N-heterocycles with novel properties, having broad spectrum biological activities that may become alternative medicinal drugs, have been attracting a lot of research attention due to the emergence of medicinal drug’s limitations such as disease resistance and their toxicity effects among others. Acylpyrazolones have been employed as pharmaceuticals as well as analytical reagent and their application as coordination complexes with transition metal ions have been well established. By way of a condensation reaction with amines acylpyrazolone ketones form a more chelating and superior group of compounds known as azomethines. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one was reacted with phenylhydrazine to get a new phenylhydrazone which was further reacted with aqueous solutions of palladium and platinum salts, in an effort towards the discovery of transition metal based synthetic drugs. The compounds were characterized by means of analytical, spectroscopic, thermogravimetric analysis TGA, as well as x-ray crystallography. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one phenylhydrazone crystallizes in a triclinic crystal system with a P-1 (No. 2) space group based on x-ray crystallography. The bidentate ON ligand formed a square planar geometry on coordinating with metal ions based on FTIR, electronic and NMR spectra as well as magnetic moments. Reported compounds showed antibacterial activities against the nominated bacterial isolates using the disc diffusion technique at 20 mg/ml in triplicates. The metal complexes exhibited a better antibacterial activity with platinum complex having an MIC value of 0.63 mg/ml. Similarly, ligand and complexes also showed antioxidant scavenging properties against 2, 2-diphenyl-1-picrylhydrazyl DPPH radical at 0.5mg/ml relative to ascorbic acid (standard drug).

Keywords: acylpyrazolone, antibacterial studies, metal complexes, phenylhydrazone, spectroscopy

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Authors: Aastha Chaudhry

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This continuous structuring of the ego through the developmental ages, starting with the body, has been understood through various perspectives from the object-relations world. Klein, Ogden, Winnicott to name a few, have been masters at helping mark a trajectory for the self to come to fruition. However, what constitutes those states, those relational structures, the dynamics of transference and the concept of inner objects has been more or less left unexplored in the psychoanalytic developmental theory. In this paper, through the help of a case study, Ogden’s ideas of an autistic contagious position and Kleinian theory of object relations is proposed to visualize a lens that helps to understand the relationship of the autistic self and body and allows us to take a look at object relations through countertransference. With the help of case vignettes, an understanding of experience is seen as dominated in the autistic contagious position with the help of defensive structuring that is not only self-fulfilling and sensorial oriented, but is also a pre symbolic mode of relating to the other. The aim of this clinical, experiential study is to better understand the self-body and the self-other relationships, or the absence thereof, in the autistic world and states. The goal of the study was to find such a relationship between play, body, structuring of experience and an autistic self in these individuals through that. Aim being that psychotherapy is brought to fore in the world of autism. The method was case study with one on one intervention, that was psychodynamically informed and play therapy based. Some of the findings after a year of work with these individuals were that: in the absence of a shared vocabulary, communication in two contrasting individuals happens primarily through the assistance of the body. Somatic countertransference, for instance, is how one can be with someone in a therapeutic relationship – and with autistic adolescents it is a further complicated relationship. With a mind somewhere in infanthood, and body experiencing adulthood, it becomes a challenge for the therapist to meet the client where they are. With pre-verbal states, play becomes such a potential space where two individuals could meet – a safe ground for forces to be contained. Play, then, becomes a mode of communication with such a population.

Keywords: autism, psychoanalytic, play, self

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Authors: Mani Mofidi, Neda Valizadeh, Ali Hashemaghaee, Mona Hashemaghaee, Soudabeh Shafiee Ardestani

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Background: Acute pain and its management remained the most complaint of emergency service admission. Diagnostic and therapeutic procedures add to patients’ pain. Diminishing the pain increases the quality of patient’s feeling and improves the patient-physician relationship. Aim: The aim of this study was to evaluate the outcomes and side effects of opioid administration in emergency patients. Material and Methods: patients admitted to ward II emergency service of Imam Khomeini hospital, who received one of the opioids: morphine, pethidine, methadone or fentanyl as an analgesic were evaluated. Their vital signs and general condition were examined before and after drug injection. Also, patient’s pain experience were recorded as numerical rating score (NRS) before and after analgesic administration. Results: 268 patients were studied. 34 patients were addicted to opioid drugs. Morphine had the highest rate of prescription (86.2%), followed by pethidine (8.5%), methadone (3.3%) and fentanyl (1.68). While initial NRS did not show significant difference between addicted patients and non-addicted ones, NRS decline and its score after drug injection were significantly lower in addicted patients. All patients had slight but statistically significant lower respiratory rate, heart rate, blood pressure and O2 saturation. There was no significant difference between different kind of opioid prescription and its outcomes or side effects. Conclusion: Pain management should be always in physicians’ mind during emergency admissions. It should not be assumed that an addicted patient complaining of pain is malingering to receive drug. Titration of drug and close monitoring must be in the curriculum to prevent any hazardous side effects.

Keywords: numerical rating score, opioid, pain, emergency department

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Authors: Anna Jesionek, Aleksandra Szreniawa-Sztajnert, Zbigniew Jaremicz, Adam Kokotkiewicz, Natalia Filipowicz, Renata Ochocka, Bozena Zabiegala, Maria Luczkiewicz

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Rhododendron tomentosum (formerly Ledum palustre), an evergreen shrub grows in peaty soils in northern Europe, Asia and North America. In Poland, it is classified as an endangered species not only due to the drainage of wetlands, but also to the excessive collection of this repellent plant by human. The other valuable biological properties of R. tomentosum, used for years in folk medicine, include anti-inflammatory, analgesic and anti-microbial activity, conditioned by the essential oil content. Taking into account the importance of biodiversity and the potential therapeutic application, it was decided to establish, for the first time, the micropropagation protocol for R. tomentosum, for ex-situ conservation of this endangered species as well as to obtain the continuous source of in vivo and in-vitro plant material for further studies. This object was achieved by the selection of the explant and the media, which were modified within the scope of mineral composition, sugar content, pH and the growth regulators. As a result, the four-stage micropropagation protocol for R. tomentosum was specified, including shoot multiplication, elongation, rooting and ex-vitro adaptation. The genetic identification of the examined species and the compatibility of progeny plants with maternal ones was tested with molecular biology methods. Moreover, during the research process, the chemical composition of initial and regenerated plant and in vitro shoots was controlled in terms of volatile fraction by phytochemical analysis (GC and TLC methods). The correctness of the micropropagation procedure was confirmed by both types of studies.

Keywords: ex situ conservation, Ledum palustre, micropropagation, Rhododendron tomentosum

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Authors: Driss Cherqaoui, Nouhaila Ait Lahcen, Ismail Hdoufane, Mehdi Oubahmane, Wissal Liman, Christelle Delaite, Mohammed M. Alanazi

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The Ebola virus is a highly contagious and deadly pathogen that causes Ebola virus disease. The Ebola virus glycoprotein (EBOV-GP) is a key factor in viral entry into host cells, making it a critical target for therapeutic intervention. Using a combination of computational approaches, this study focuses on the identification of natural compounds that could serve as potent inhibitors of EBOV-GP. The 3D structure of EBOV-GP was selected, with missing residues modeled, and this structure was minimized and equilibrated. Two large natural compound databases, COCONUT and NPASS, were chosen and filtered based on toxicity risks and Lipinski’s Rule of Five to ensure drug-likeness. Following this, a pharmacophore model, built from 22 reported active inhibitors, was employed to refine the selection of compounds with a focus on structural relevance to known Ebola inhibitors. The filtered compounds were subjected to virtual screening via molecular docking, which identified ten promising candidates (five from each database) with strong binding affinities to EBOV-GP. These compounds were then validated through molecular dynamics simulations to evaluate their binding stability and interactions with the target. The top three compounds from each database were further analyzed using ADMET profiling, confirming their favorable pharmacokinetic properties, stability, and safety. These results suggest that the selected compounds have the potential to inhibit EBOV-GP, offering new avenues for antiviral drug development against the Ebola virus.

Keywords: EBOV-GP, Ebola virus glycoprotein, high-throughput drug screening, molecular docking, molecular dynamics, natural compounds, pharmacophore modeling, virtual screening

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Authors: Anju Joshi, C. N. Tharamani

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Diabetes is one of the leading cause of death at present and remains an important concern as the prevalence of the disease is increasing at an alarming rate. Therefore, it is crucial to diagnose the accurate levels of glucose for developing an efficient therapeutic for diabetes. Due to the availability of convenient and compact self-testing, continuous monitoring of glucose is feasible nowadays. Enzyme based electrochemical sensing of glucose is quite popular because of its high selectivity but suffers from drawbacks like complicated purification and immobilization procedures, denaturation, high cost, and low sensitivity due to indirect electron transfer. Hence, designing a robust enzyme free platform using transition metal oxides remains crucial for the efficient and sensitive determination of glucose. In the present work, manganese doped nickel oxide nanoparticles (Mn-NiO) has been synthesized onto the surface of multiwalled carbon nanotubes using a simple microwave assisted approach for non-enzymatic electrochemical sensing of glucose. The morphology and structure of the synthesized nanostructures were characterized using scanning electron microscopy (SEM) and X-Ray diffraction (XRD). We demonstrate that the synthesized nanostructures show enormous potential for electrocatalytic oxidation of glucose with high sensitivity and selectivity. Cyclic voltammetry and square wave voltammetry studies suggest superior sensitivity and selectivity of Mn-NiO decorated carbon nanotubes towards the non-enzymatic determination of glucose. A linear response between the peak current and the concentration of glucose has been found to be in the concentration range of 0.01 μM- 10000 μM which suggests the potential efficacy of Mn-NiO decorated carbon nanotubes for sensitive determination of glucose.

Keywords: diabetes, glucose, Mn-NiO decorated carbon nanotubes, non-enzymatic

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Authors: Mathumalar Loganathan, Lina Syazana, Bryony Dean Franklin

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Background: The therapeutic benefit of self-administered medication for long-term use is limited by an average 50% non-adherence rate. Patient forgetfulness is a common factor in unintentional non-adherence. With a growing ageing population, strategies to improve self-administration of medication adherence are essential. Our aim was to review systematically the effects of interventions to optimise self-administration of medication. Method: Database searched were MEDLINE, EMBASE, PsynINFO, CINAHL from 1980 to 31 October 2013. Search terms included were ‘self-administration’, ‘self-care’, ‘medication adherence’, and ‘intervention’. Two independent reviewers undertook screening and methodological quality assessment, using the Downs and Black rating scale. Results: The search strategy retrieved 6 studies that met the inclusion and exclusion criteria. Three intervention strategies were identified: self-administration medication programme (SAMP), nursing education and medication packaging (pill calendar). A nursing education programme focused on improving patients’ behavioural self-management of drug prescribing. This was the most studied area and three studies highlighting an improvement in self-administration of medication. Conclusion: Results are mixed and there is no one interventional strategy that has proved to be effective. Nevertheless, self-administration of medication programme seems to show most promise. A multi-faceted approach and clearer policy guideline are likely to be required to improve prescribing for these vulnerable patients. Mixed results were found for SAMP. Medication packaging (pill calendar) was evaluated in one study showing a significant improvement in self-administration of medication. A meta-analysis could not be performed due to heterogeneity in the outcome measures.

Keywords: self-administered medication, intervention, prescribing, older patients

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Authors: Blair Arthur Agero Jr., Lucia Garcia Heras

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The triangular fibrocartilage complex (TFCC) is one of the crucial stabilizing ligaments of the wrist. The TFCC is also subject to excessive stress amongst performance athletes and enthusiasts. The excessive loading of the TFCC may lead to a partial or complete rupture that requires surgery. The recovery from an open TFCC surgical repair may take several months. Immobilization of the repaired wrist for a given period is part of all the current protocols in the post-surgical treatment. The immobilization to prevent the rotation of the forearm can last from six weeks to eight weeks with the wrist held in a neutral position. In all protocols reviewed, the pronosupination is only initiated between the 6th week and 8th week or even later after the cast is removed. The prolonged immobilization can cause stiffness of the wrist and hand. Furthermore, the entire period of post-surgical hand therapy has its economic impact, especially for performing athletes. However, delayed mobilization, specifically rotation of the wrist, is necessary to allow ligament healing. This study aims to report the effects of early mobilization of the wrist in athletes who had an open surgical repair of the TFCC. The surgery was done by the co-author, and the hand therapy was implemented by the main author. The cases documented spans from 2014 to 2019 and were all performed in Dubai, United Arab Emirates. All selected participants in this case study were provided with a follow-up questionnaire to ascertain their current condition since their surgery. The respondents reported high satisfaction in the results of their treatment and have verified zero re-rupture of their TFCC despite mobilizing and rotating the wrist at the third-week post-surgery during their hand therapy. There is also a negligible number of respondents who reported a limitation in their ranges of pronosupination. This case study suggests that early mobilization of the wrist after an open TFCC surgical repair can be more beneficial to the patient as opposed to the traditional treatment of prolonged immobilization. However, it should be considered that the patients selected in this case study are professional performance athletes and advanced fitness enthusiasts. Athletes are known to withstand vigorous physical stress in their training that may correlate to their ability to better cope with the progressive stress that was implemented during their hand therapy. Nevertheless, this approach has its merits, and application of it may be adjusted for patients with a similar injury and surgical procedure.

Keywords: hand therapy, performance athlete, TFCC repair, wrist ligament

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Authors: Sahraoui Halima, Dahani Ameur, Tigrine Abedelkader

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DigiMesh technology represents a pioneering advancement in wireless networking, offering cost-effective and energy-efficient capabilities. Its inherent simplicity and adaptability facilitate the seamless transfer of data between network nodes, extending the range and ensuring robust connectivity through autonomous self-healing mechanisms. In light of these advantages, this study introduces a medical platform harnessed with DigiMesh wireless network technology characterized by low power consumption, immunity to interference, and user-friendly operation. The primary application of this platform is the real-time, long-distance monitoring of Electrocardiogram (ECG) signals, with the added capacity for simultaneous monitoring of ECG signals from multiple patients. The experimental setup comprises key components such as Raspberry Pi, E-Health Sensor Shield, and Xbee DigiMesh modules. The platform is composed of multiple ECG acquisition devices labeled as Sensor Node 1 and Sensor Node 2, with a Raspberry Pi serving as the central hub (Sink Node). Two communication approaches are proposed: Single-hop and multi-hop. In the Single-hop approach, ECG signals are directly transmitted from a sensor node to the sink node through the XBee3 DigiMesh RF Module, establishing peer-to-peer connections. This approach was tested in the first experiment to assess the feasibility of deploying wireless sensor networks (WSN). In the multi-hop approach, two sensor nodes communicate with the server (Sink Node) in a star configuration. This setup was tested in the second experiment. The primary objective of this research is to evaluate the performance of both Single-hop and multi-hop approaches in diverse scenarios, including open areas and obstructed environments. Experimental results indicate the DigiMesh network's effectiveness in Single-hop mode, with reliable communication over distances of approximately 300 meters in open areas. In the multi-hop configuration, the network demonstrated robust performance across approximately three floors, even in the presence of obstacles, without the need for additional router devices. This study offers valuable insights into the capabilities of DigiMesh wireless technology for real-time ECG monitoring in healthcare applications, demonstrating its potential for use in diverse medical scenarios.

Keywords: DigiMesh protocol, ECG signal, real-time monitoring, medical platform

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Authors: Liang Ning, Chung Hau Yin

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Angiogenesis is the process of new blood vessel development. It has been recognized as a therapeutic target for blocking cancer growth four decades ago. Vascular sprouting is initiated by pro-angiogenic factors. Vascular endothelial cell growth factor (VEGF) plays a central role in angiogenic initiation, many patients with cancer or ocular neovascularization have been benefited from anti-VEGF therapy. Emerging approaches impacting in the later stages of vessel remodeling and maturation are expected to improve clinical efficacy. TIE receptor as well as the corresponding angiopoietin ligands, were identified as another endothelial cell specific receptor tyrosine kinase signaling system. Much efforts were made to reduce the activity of angiopoietin-TIE receptor axis. Two eudesmane-type sesquiterpenes from laggera alata, namely, 15-dihydrocostic acid and ilicic acid were found with strong anti-angiogenic properties in zebrafish model. Meanwhile, the mRNA expression levels of VEGFR2 and TIE2 pathway related genes were down-regulated in the sesquiterpenes treated zebrafish embryos. Besides, in human umbilical vein endothelial cells (HUVECs), the sesquiterpenes have the ability to inhibit VEGF-induced HUVECs proliferation and migration at non-toxic concentration. Moreover, angiopoietin-2 induced TIE2 phosphorylation was inhibited by the sesquiterpenes, the inhibitory effect was detected in angiopoietin-1 induced HUVECs proliferation as well. Thus, we hypothesized the anti-angiogenic activity of the compounds may via the inhibition of VEGF and TIE2 related pathways. How the compounds come into play as the pathways inhibitors need to be evaluated in the future.

Keywords: Laggera alata, eudesmane-type sesquiterpene, anti-angiogenesis, VEGF, angiopoietin, TIE2

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Authors: Bulcha Belay Etana, Benny Malengier, Janarthanan Krishnamoorthy, Timothy Kwa, Lieva Vanlangenhove

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Electromyography measures the electrical activity of muscles using surface electrodes or needle electrodes to monitor various disease conditions. Recent developments in the signal acquisition of electromyograms using textile electrodes facilitate wearable devices, enabling patients to monitor and control their health status outside of healthcare facilities. Here, we have developed and tested wearable textile electrodes to acquire electromyography signals from patients suffering from Parkinson’s disease and incorporated a feedback-control system to relieve muscle cramping through thermal stimulus. In brief, the textile electrodes made of stainless steel was knitted into a textile fabric as a sleeve, and their electrical characteristic, such as signal-to-noise ratio, was compared with traditional electrodes. To relieve muscle cramping, a heating element made of stainless-steel conductive yarn sewn onto a cotton fabric, coupled with a vibration system, was developed. The system integrated a microcontroller and a Myoware muscle sensor to activate the heating element as well as the vibration motor when cramping occurred. At the same time, the element gets deactivated when the muscle cramping subsides. An optimum therapeutic temperature of 35.5°C is regulated and maintained continuously by a heating device. The textile electrode exhibited a signal-to-noise ratio of 6.38dB, comparable to that of the traditional electrode’s value of 7.05 dB. For a given 9 V power supply, the rise time for the developed heating element was about 6 minutes to reach an optimum temperature.

Keywords: smart textile system, wearable electronic textile, electromyography, heating textile, vibration therapy, Parkinson’s disease

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Authors: Mitchell Stanton

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Background: Endovascular management is well established as a mainstay treatment option for cerebral aneurysms. It is also well established that immediate post procedural imaging can be difficult to interpret due to the presence of contrast material. However, through the use of Dual-Energy computed tomography, it has become possible to differentiate contrast extravasation and intracranial haemorrhage. This case illustrates the importance of this technology following endovascular treatment of an unruptured cerebral aneurysm. Case Presentation: A 79-year-old female was found to have an unruptured large intracavernous ICA fusiform aneurysm on CT Brain Angiogram after presenting with acute ophthalmoplegia. This ophthalmoplegia was caused by mass effect from the aneurysm and subsequently the aneurysm was treated with an endovascular flow diverting stent. CT brain was performed post operatively due to a reduced level of consciousness and this showed diffuse subarachnoid hyperdensity of the left hemisphere. The use of Dual-Energy CT allowed accurate differentiation and illustrated diffuse contrast material extravasation, allowing patient to continue on dual-antiplatelets and therapeutic anticoagulation to reduce the risk of ischaemic injury post endovascular stent. Conclusion: Endovascular treatment options for management of intracranial aneurysms are constantly evolving. The use of Dual-Energy CT therefore has an integral role in accurately diagnosing any post-operative complications. Specifically, differentiating between subarachnoid haemorrhage and contrast extravasation is vital in these patients due to the significant consequences to their ongoing management in regards to continuation or cessation of antiplatelets or anticoagulation. With increasing access to this technology, its use should become standard practice in the post-operative investigation of these patients undergoing endovascular treatment.

Keywords: aneurysm, computed tomography, contrast extravasation, dual-energy CT, endovascular, subarachnoid haemorrhage

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Authors: Ahmed Gaber Abdel Raheem, Nashwa Ahmed Mohamed

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Introduction: Sensorineural hearing loss (SNHL) is largely caused by the degeneration of the cochlea. Therapeutic options for SNHL are limited to hearing aids and cochlear implants. The cell transplantation approach to the regeneration of hair cells has gained considerable attention because stem cells are believed to accumulate in the damaged sites and have the potential for the repair of damaged tissues. The aim of the work: was to assess the use of bone marrow transplantation in repair of damaged inner ear hair cells in rats after the damage had been inflicted by Amikacin injection. Material and Methods: Thirty albino rats were used in this study. They were divided into three groups. Each group ten rats. Group I: used as control. Group II: Were given Amikacin- intratympanic injection till complete loss of hearing function. This could be assessed by Distortion product Otoacoustic Emission (DPOAEs) and / or auditory brain stem evoked potential (ABR). GroupIII: were given intra-peritoneal injection of bone marrow stem cell after complete loss of hearing caused by Amikacin. Clinical assessment was done using DPOAEs and / or auditory brain stem evoked potential (ABR), before and after bone marrow injection. Histological assessment of the inner ear was done by light and electron microscope. Also, Detection of stem cells in the inner ear by immunohistochemistry. Results: Histological examination of the specimens showed promising improvement in the structure of cochlea that may be responsible for the improvement of hearing function in rats detected by DPOAEs and / or ABR. Conclusion: Bone marrow stem cells transplantation might be useful for the treatment of SNHL.

Keywords: amikacin, hair cells, sensorineural hearing loss, stem cells

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Authors: Austin Jiang, Richard M. Salmon, Nicholas W. Morrell, Wei Li

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BMP10 is highly expressed in the developing heart and plays essential roles in cardiogenesis. BMP10 deletion in mice results in embryonic lethality due to impaired cardiac development. In adults, BMP10 expression is restricted to the right atrium, though ventricular hypertrophy is accompanied by increased BMP10 expression in a rat hypertension model. However, reports of BMP10 activity in the circulation are inconclusive. In particular it is not known whether in vivo secreted BMP10 is active or whether additional factors are required to achieve its bioactivity. It has been shown that high-affinity binding of the BMP10 prodomain to the mature ligand inhibits BMP10 signaling activity in C2C12 cells, and it was proposed that prodomain-bound BMP10 (pBMP10) complex is latent. In this study, we demonstrated that the BMP10 prodomain did not inhibit BMP10 signaling activity in multiple endothelial cells, and that recombinant human pBMP10 complex, expressed in mammalian cells and purified under native conditions, was fully active. In addition, both BMP10 in human plasma and BMP10 secreted from the mouse right atrium were fully active. Finally, we confirmed that active BMP10 secreted from mouse right atrium was in the prodomain-bound form. Our data suggest that circulating BMP10 in adults is fully active and that the reported vascular quiescence function of BMP10 in vivo is due to the direct activity of pBMP10 and does not require an additional activation step. Moreover, being an active ligand, recombinant pBMP10 may have therapeutic potential as an endothelial-selective BMP ligand, in conditions characterized by loss of BMP9/10 signaling.

Keywords: bone morphogenetic protein 10 (BMP10), endothelial cell, signal transduction, transforming growth factor beta (TGF-B)

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Authors: Chanya Inprasit, Yi-Wen Lin

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Inflammation causes changes of peripheral and central nervous system properties, affecting both neuronal and non-neuronal cells, resulting in inflammatory pain. Acupoint injection (AI) was developed in the 1950s and has been widely used for relieving pain. It is an acupoint-stimulating technique that utilizes anatomically based meridians derived from Chinese medicine theory. AI has been accepted as an effective treatment and is thought to display superior results when compared to traditional acupuncture methods. However, the mechanism of AI needs to be ratified by more scientific evidence in order to support the theory and its therapeutic development. In this study, we explored the effect of AI on the comorbidity of chronic pain and depression. Mice hindpaw was injected by complete Freund’s adjuvant (CFA) to induce the condition of chronic pain. Measurements of mechanical and thermal hyperalgesia and depression-like behavior were analyzed. The results indicated a positive tendency to AI treatment. The comorbidity of chronic pain and depression was investigated with relation to transient receptor potential V1 (TRPV1) mechanism through the use of TRPV1 gene deletion. The expression of nociceptors such as voltage-gated sodium channels (Navs) or TRPV1, was significantly down-regulated by AI. The expression of inflammation-activated molecules: astrocytic marker glial fibrillary acidic protein (GFAP), the microglial marker Iba-1, S100B, and related kinases, were reversed by AI in both the peripheral and central nervous system. Taken together, these data provided a detailed molecular mechanism of AI-induced analgesia and anti-inflammatory properties. This finding may be utilized for clinical practice to treat chronic pain and depression comorbidity.

Keywords: inflammatory pain, acupoint injection, TRPV1, GFAP, S100B

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Authors: A. H. Taghdisi, M. Mirmohammadi, S. Kamali

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Evening primrose (Oenothera biennis L.) is a biennial and herbaceous and one of the most important species of medicinal plants in the world. due to the production of unsaturated fatty acids such as linoleic acid, alpha-linolenic acid, etc. in its seeds and roots, and compounds such as kaempferol in its leaves, Evening primrose has important medicinal efficiency such as reducing premenstrual problems, acceleration of wound healing, inhibiting platelet aggregation, sedation of cardiovascular diseases, and treatment of viral infections. The sap of the plant is used to treat warts, and the plant itself is used as a charm against mental and spiritual diseases and poisonous animals. Its leaves have significant antibacterial activity against yellow staphylococci. It is also used in the treatment of poisoning, especially the toxication caused by the consumption of alcoholic beverages, in the treatment of arteriosclerosis and diseases caused by liver cell insufficiency. Low germination and production speed are the problems of evening primrose growth and propagation. In the present study, extracts were obtained from four components (flowers, stems, seeds, leaves) of the evening primrose plant using the Soxhlet apparatus. To measure the antibacterial properties against MDR bacteria, microbial methods, including dilution, cultivation on a plate containing nutrient agar culture medium, and disc diffusion in agar, were performed using Staphylococcus aureus and Escherichia coli bacteria on all four extracts. The maximum antibacterial activity related to the dilution method was obtained in all extracts. In the plate culture method, antibacterial activity was obtained for all extracts in the nutrient agar medium. The maximum diameter of the non-growth halo was obtained in the disc diffusion method in agar in the leaf extract. The statistical analysis of the microbial part was done by one-way ANOVA test (SPSS). By comparing the amount of omega-3 in extracts of Iranian and foreign oils available in the market and the extracts extracted from evening primrose plant samples with gas chromatography, it is shown that the stem extract had the most omega-3 (oleic acid) and compared to the extract of the mentioned oils, it had the highest amount of omega-3 overall. Also, the amount of omega-3 in the extract of Iranian oils was much higher than in the extract of foreign oils. It should be noted that the extract of foreign oils had a more complete composition of omega-3 than the extract of Iranian oils.

Keywords: antibacterial activity, MDR bacteria, evening primrose, omega-3

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Authors: Sarah K. Amer, Walaa Alaa

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Epilepsy is an important cause of mortality and morbidity, according to WHO statistics. It is characterized by the presence of frequent seizures occurring more than 24 hours apart. Carbamazepine (CBZ) is considered first-line treatment for epilepsy. However, reports have shown that CBZ oral formulations failed to achieve optimum systemic delivery, minimize side effects, and enhance patient compliance. Besides, the literature has signified the lack of therapeutically efficient CBZ transdermal formulation and the urge for its existence owing to its ease and convenient method of application and highlighted capability to attain higher bioavailability and more extended-release profiles compared to conventional oral CBZ tablets. This work aims to prepare CBZ microspheres (MS) that are embedded in a transdermal gel containing Vitamin B to be co-delivered. MS were prepared by emulsion-solvent diffusion method using Eudragit S as core forming polymer and hydroxypropyl methylcellulose (HPMC) polymer. The MS appeared to be spherical and porous in nature, offering a large surface area and high entrapment efficiency of CBZ. The transdermal gel was prepared by solvent-evaporation technique using HPMC that, offered high entrapment efficiency and Eudragit S that provided an extended-release profile. Polyethylene glycol, Span 80 and Pyridoxine were also added. Data indicated that combinations of CBZ with pyridoxine can reduce epileptic seizures without affecting motor coordination. Extended-release profiles were evident for this system. The patches were furthermore tested for thickness, moisture content, folding endurance, spreadability and viscosity measurements. This novel pharmaceutical formulation would be of great influence on seizure control, offering better therapeutic effects.

Keywords: epilepsy, carbamazepine, pyridoxine, transdermal

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Authors: F. Bosca, F. Foglietta, F. Turci, E. Calcio Gaudino, S. Mana, F. Dosio, R. Canaparo, L. Serpe, A. Barge

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In recent years, medical science has improved chemotherapy, radiation therapy and adjuvant therapy and has developed newer targeted therapies as well as refining surgical techniques for removing cancer. However, the chances of surviving the disease depend greatly on the type and location of the cancer and the extent of the disease at the start of treatment. Moreover, mainstream forms of cancer treatment have side effects which range from the unpleasant to the fatal. Therefore, the continuation of progress in anti-cancer therapy may depend on placing emphasis on other existing but less thoroughly investigated therapeutic approaches such as Sonodynamic Therapy (SDT). SDT is based on the local activation of a so called 'sonosensitizer', a molecule able to be excited by ultrasound, the radical production as a consequence of its relaxation processes and cell death due to different mechanisms induced by radical production. The present work deals with synthesis, characterization and preliminary in vitro test of Single Walled Carbon Nanotubes (SWCNT) decorated with porphyrins and biological vectors. The SWCNT’s surface was modified exploiting 1, 3-dipolar cycloaddition or Dies Alder reactions. For this purpose, different porphyrins scaffolds were ad-hoc synthesized using also non-conventional techniques. To increase cellular specificity of porphyrin-conjugated SWCNTs and to improve their ability to be suspended in aqueous solution, the modified nano-tubes were grafted with suitable glutamine or hyaluronic acid derivatives. These nano-sized sonosensitizers were characterized by several methodologies and tested in vitro on different cancer cell lines.

Keywords: sonodynamic therapy, porphyrins synthesis and modification, SWNCT grafting, hyaluronic acid, anti-cancer treatment

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Authors: Nunila Ferreira de Oliveira, Silvana Martins Mishima

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Diabetes mellitus type 2 (DM2) prevalence, is increasing on the world, in Brazil is considered a public health problem. Treatment focuses on glycemic control depending primarily of lifestyle changes - not drug treatment (NDT), may involve drug therapy (DT) and requires continuous health monitoring. In Brazil this monitoring is performed by the Unified Health System (SUS) through Primary Health Care (PHC), which stimulate people with DM2 empowerment for care management. SUS was approved in 1988 and the PHC operationalization was strengthened with the creation of the Family Health Strategy (FHS) in 1994. Our aim was to analyze the people with DM2 participation in front of the care management health monitoring in the FHS. Qualitative research was carried out through non-participant observation of attendance of 25 people with DM2 in the FHS and interviewed at home. Ethical guidelines were followed. It was found that people with DM2 only follow professionals’ recommendations that make sense according to their own conceptions of health/disease; most of them emphasize the importance of (DT) with little emphasis on the NDT, was found great difficulty in the NDT and lack of knowledge about the disease and care. As regards monitoring the FHS, were observed therapeutic practices based on the bio medical model, although the APS search for another care perspective; NDT is not systematically accompanied by the health team and takes place a few educational activities on the DM2 in the FHS, with low user adoption. The work of the FHS is done by multidisciplinary teams, but we see the need for greater participation of nurses in clinical-care follow-up of this population and may also act in adapting to the NDT. Finally we emphasize the need for professional practices that consider the difficulties to care management by people with DM2, especially because of the NDT. It is noticed that the measures recommended by the FHS professionals are not always developed by people with DM2. We must seek the empowerment of people with DM2 to manage the form of care associated with the FHS team, seeking to reduce the incidence of complications and higher quality of life.

Keywords: diabetes mellitus, primary health care, nursing, management of care

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Authors: Sophie Mills, Leila L. Touil, Richard Sisson

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Introduction: The TNM classification is the global standard for the staging of head and neck cancers. Accurate clinical-radiological staging of tumours (cTNM) is essential to predict prognosis, facilitate surgical planning and determine the need for other therapeutic modalities. This study aims to determine the accuracy of pre-operative cTNM staging using pathological TNM (pTNM) and consider possible causes of TNM stage migration, noting any variation throughout the COVID-19 pandemic. Materials and Methods: A retrospective cohort study examined records of patients with surgical management of head and neck cancer at a tertiary head and neck centre from November 2019 to November 2020. Data was extracted from Somerset Cancer Registry and histopathology reports. cTNM and pTNM were compared before and during the first wave of COVID-19, as well as with other potential prognostic factors such as tumour site and tumour stage. Results: 119 cases were identified, of which 52.1% (n=62) were male, and 47.9% (n=57) were female with a mean age of 67 years. Clinical and pathological staging differed in 54.6% (n=65) of cases. Of the patients with stage migration, 40.4% (n=23) were up-staged and 59.6% (n=34) were down-staged compared with pTNM. There was no significant difference in the accuracy of cTNM staging compared with age, sex, or tumour site. There was a statistically highly significant (p < 0.001) correlation between cTNM accuracy and tumour stage, with the accuracy of cTNM staging decreasing with the advancement of pTNM staging. No statistically significant variation was noted between patients staged prior to and during COVID-19. Conclusions: Discrepancies in staging can impact management and outcomes for patients. This study found that the higher the pTNM, the more likely stage migration will occur. These findings are concordant with the oncology literature, which highlights the need to improve the accuracy of cTNM staging for more advanced tumours.

Keywords: COVID-19, head and neck cancer, stage migration, TNM staging

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Authors: Umme Hani, H. G. Shivakumar, M. D. Younus Pasha

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The purpose of this work was to design and optimize a novel vaginal drug delivery system for more effective treatment against vaginal candidiasis. To achieve a better therapeutic efficacy and patient compliance in the treatment for vaginal candidiasis, herbal antifungal agent Curcumin which is 2.5 fold more potent than fluconazole at inhibiting the adhesion of candida albicans has been formulated in a bio-adhesive vaginal film. Curcumin was formulated in bio-adhesive film formulations that could be retained in the vagina for prolonged intervals. The polymeric films were prepared by solvent evaporation and optimized for various physicodynamic and aesthetic properties. Curcumin HPβCD (Hydroxypropyl β Cyclodextrin) was first developed to increase the solubility of curcumin. The formation of the Curcumin HPβCD complex was characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and FT-IR and evaluated for its solubility. Curcumin HPβCD complex was formulated in a bio-adhesive film using hydroxypropyl methyl cellulose (HPMC) and Carbopol 934P and characterized. DSC and FT-IR data of Curcumin HPβCD indicate there was complex formation between the drug and HPβCD. The little moisture content (8.02±0.34% w/w) was present in the film, which helps them to remain stable and kept them from being completely dry and brittle. The mechanical properties, tensile strength, and percentage elongation at break reveal that the formulations were found to be soft and tough. The films showed good peelability, relatively good swelling index, and moderate tensile strength and retained vaginal mucosa up to 8 h. The developed Curcumin vaginal film could be a promising safe herbal medication and can ensure longer residence at the vagina and provide an efficient therapy for vaginal candidiasis.

Keywords: curcumin, curcumin-HPβCD complex, bio-adhesive vaginal film, vaginal candidiasis, 23 factorial design

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Authors: Peng Hou

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Natural products produced from marine bacteria serve as an immense reservoir for anti-infective drugs and therapeutic agents. Nowadays, heterologous expression of gene clusters of interests has been widely adopted as an effective strategy for natural product discovery. Briefly, the heterologous expression flowchart would be: biosynthetic gene cluster identification, pathway construction and expression, and product detection. However, gene cluster capture using traditional Transformation-associated recombination (TAR) protocol is low-efficient (0.5% positive colony rate). To make things worse, most of these putative new natural products are only predicted by bioinformatics analysis such as antiSMASH, and their corresponding natural products biosynthetic pathways are either not expressed or expressed at very low levels under laboratory conditions. Those setbacks have inspired us to focus on seeking new technologies to efficiently edit and refractor of biosynthetic gene clusters. Recently, two cutting-edge techniques have attracted our attention - the CRISPR-Cas9 and Gibson Assembly. By now, we have tried to pretreat Brevibacillus laterosporus strain genomic DNA with CRISPR-Cas9 nucleases that specifically generated breaks near the gene cluster of interest. This trial resulted in an increase in the efficiency of gene cluster capture (9%). Moreover, using Gibson Assembly by adding/deleting certain operon and tailoring enzymes regardless of end compatibility, the silent construct (~80kb) has been successfully refactored into an active one, yielded a series of analogs expected. With the appearances of the novel molecular tools, we are confident to believe that development of a high throughput mature pipeline for DNA assembly, transformation, product isolation and identification would no longer be a daydream for marine natural product discovery.

Keywords: biosynthesis, CRISPR-Cas9, DNA assembly, refactor, TAR cloning

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Authors: Williams A. Adu, Cynthia A. Danquah, Paul P. S. Ossei, Selase Ativui, Michael Ofori, James Asenso, George Owusu

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Background Silicosis is an occupational disease of the lung that is caused by chronic exposure to silica dust. There is a higher frequency of co-existence of silicosis with tuberculosis (TB), ultimately resulting in lung fibrosis and respiratory failure. Chronic intake of synthetic drugs has resulted in undesirable side effects. Diosgenin is a steroidal saponin that has been shown to exert a therapeutic effect on lung injury. Therefore, we investigated the ability of diosgenin to reduce the susceptibility of silica-induced TB in rats. Method Silicosis was induced by intratracheal instillation of 50 mg/kg crystalline silica in Sprague Dawley rats. Different doses of diosgenin (1, 10, and 100 mg/kg), Mycobacterium smegmatis and saline were administered for 30 days. Afterwards, 5 of the rats from each group were sacrificed, and the 5 remaining rats in each group, except the control, received Mycobacterium smegmatis. Treatment of diosgenin continued until the 50th day, and the rats were sacrificed at the end of the experiment. The result was analysed using a one-way analysis of variance (ANOVA) with a Graph-pad prism Result At a half-maximal inhibition concentration of 48.27 µM, diosgenin inhibited the growth of Mycobacterium smegmatis. There was a marked decline in the levels of immune cell infiltration and cytokines production. Lactate dehydrogenase and total protein levels were significantly reduced compared to control. There was an increase in the survival rate of the treatment group compared to the control. Conclusion Diosgenin ameliorated silica-induced pulmonary tuberculosis by declining the levels of inflammatory and pro-inflammatory cytokines and, in effect, significantly reduced the susceptibility of rats to pulmonary TB.

Keywords: silicosis, tuberculosis, diosgenin, fibrosis, crystalline silica

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