Search results for: therapeutic embolization

Authors: Noah Emil Glisik

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Multiple sclerosis (MS) is a chronic, immune-mediated disorder characterized by neurodegenerative processes and a highly variable disease course. Recent research highlights a complex interplay between psychological stress and MS progression, with both acute and chronic stressors linked to heightened inflammatory activity, increased relapse risk, and accelerated disability. This review synthesizes findings from systematic analyses, cohort studies, and neuroimaging investigations to examine how stress contributes to disease dynamics in MS. Evidence suggests that psychological stress influences MS progression through neural and physiological pathways, including dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and heightened activity in specific brain regions, such as the insular cortex. Notably, functional MRI studies indicate that stress-induced neural activity may predict future atrophy in gray matter regions implicated in motor and cognitive function, thus supporting a neurobiological link between stress and neurodegeneration in MS. Longitudinal studies further associate chronic stress with reduced quality of life and higher relapse frequency, emphasizing the need for a multifaceted therapeutic approach that addresses both the physical and psychological dimensions of MS. Evidence from intervention studies suggests that stress management strategies, such as cognitive-behavioral therapy and mindfulness-based programs, may reduce relapse rates and mitigate lesion formation in MS patients. These findings underscore the importance of integrating stress-reducing interventions into standard MS care, with potential to improve disease outcomes and patient well-being. Further research is essential to clarify the causal pathways and develop targeted interventions that could modify the stress response in MS, offering an avenue to address disease progression and enhance quality of life.

Keywords: multiple sclerosis, psychological stress, disease progression, neuroimaging, stress management

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Authors: Prathama Guha Chaudhuri, Arunima Datta, Ashis Mukhopadhyay

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Background: Visualization (guided imagery) is a set of techniques which induce relaxation and help people create positive mental images in order to reduce stress.It is relatively inexpensive and can even be practised by bed bound people. Studies have shown visualization to be an effective tool to improve cancer patients’ anxiety, depression and quality of life. The common images used with cancer patients in the developed world are those involving the individual’s body and its strengths. Since breast cancer patients in India are more family oriented and often their main concerns are the stigma of having cancer and subsequent isolation of their families, including their children, we figured that positive images involving acceptance and integration within family and society would be more effective for them. Method: Data was collected from 119 breast cancer patients on chemotherapy willing to undergo psychotherapy, with no history of past psychiatric illness. Their baseline stress, anxiety, depression and quality of life were assessed using validated tools. The participants were then randomly divided into three groups: a) those who received visualization therapy with standard imageries involving the body and its strengths (sVT), b) those who received visualization therapy using indigenous family oriented imageries (mVT) and c) a control group who received supportive therapy. There were six sessions spread over two months for each group. The psychological outcome variables were measured post intervention. Appropriate statistical analyses were done. Results:Both forms of visualization therapy were more effective than supportive therapy alone in reducing patients’ depression, anxiety and quality of life.Modified VT proved to be significantly more effective in improving patients’ anxiety and quality of life. Conclusion: Visualization is a valuable therapeutic option for reduction of psychological distress and improving quality of life of breast cancer patients.In order to be more effective, the images used need to be modified according to the sociocultural background and individual needs of the patients.

Keywords: breast cancer, visualization therapy, quality of life, anxiety, depression

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Authors: Kerry Hull, Mark Wright

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This paper brings light to ethnobotanical medicines used by the Maya of Belize to treat snake bites. The varying ecological zones of Belize boast over fifty species of snakes, nine of which are poisonous and dangerous to humans. Two distinct Maya groups occupy neighboring regions of Belize, the Q’eqchi’ and the Mopan. With Western medical care often far from their villages, what traditional methods are used to treat poisonous snake bites? Based primarily on data gathered with native consultants during the authors’ fieldwork with both groups, this paper details the ethnobotanical resources used by the Q’eqchi’ and Mopan traditional healers. The Q’eqchi’ and Mopan most commonly rely on traditional ‘bush doctors’ (ilmaj in Mopan), both male and female, and specialized ‘snake doctors’ to heal bites from venomous snakes. First, this paper presents each plant employed by healers for bites for the nine poisonous snakes in Belize along with the specific botanical recipes and methods of application for each remedy. Individual chemical and therapeutic qualities of some of those plants are investigated in an effort to explain their possible medicinal value for different toxins or the symptoms caused by those toxins. In addition, this paper explores mythological associations with certain snakes that inform local understanding regarding which plants are considered efficacious in each case, arguing that numerous oral traditions (recorded by the authors) help to link botanical medicines to episodes within their mythic traditions. Finally, the use of plants to counteract snakebites brought about through sorcery is discussed inasmuch as some snakes are seen as ‘helpers’ of sorcerers. Snake bites given under these circumstances can only be cured by those who know both the proper corresponding plant(s) and ritual prayer(s). This paper provides detailed documentation of traditional ethnomedicines and practices from the dying art of traditional Maya healers and argues for multi-faceted diagnostic techniques to determine toxin severity, the presence or absence of sorcery, and the appropriate botanical remedy.

Keywords: ethnobotany, Maya, medicine, snake bites

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Authors: M. Miljkovic, A. Urakpo, M. Simic-Koumoutsaris

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Benefit-risk assessment (BRA) is a valuable tool that takes place in multiple stages during a medicine's lifecycle, and this assessment can be conducted in a variety of ways. The aim was to summarize current BRA methods used during approval decisions and in post-approval settings and to see possible future directions. Relevant reviews, recommendations, and guidelines published in medical literature and through regulatory agencies over the past five years have been examined. BRA implies the review of two dimensions: the dimension of benefits (determined mainly by the therapeutic efficacy) and the dimension of risks (comprises the safety profile of a drug). Regulators, industry, and academia have developed various approaches, ranging from descriptive textual (qualitative) to decision-analytic (quantitative) models, to facilitate the BRA of medicines during the product lifecycle (from Phase I trials, to authorization procedure, post-marketing surveillance and health technology assessment for inclusion in public formularies). These approaches can be classified into the following categories: stepwise structured approaches (frameworks); measures for benefits and risks that are usually endpoint specific (metrics), simulation techniques and meta-analysis (estimation techniques), and utility survey techniques to elicit stakeholders’ preferences (utilities). All these approaches share the following two common goals: to assist this analysis and to improve the communication of decisions, but each is subject to its own specific strengths and limitations. Before using any method, its utility, complexity, the extent to which it is established, and the ease of results interpretation should be considered. Despite widespread and long-time use, BRA is subject to debate, suffers from a number of limitations, and currently is still under development. The use of formal, systematic structured approaches to BRA for regulatory decision-making and quantitative methods to support BRA during the product lifecycle is a standard practice in medicine that is subject to continuous improvement and modernization, not only in methodology but also in cooperation between organizations.

Keywords: benefit-risk assessment, benefit-risk profile, product lifecycle, quantitative methods, structured approaches

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Authors: Umar Saeed

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Peptidyl-prolyl cis/trans isomerases Par14 and Par17 in humans play crucial roles in diverse cellular processes, including protein folding, chromatin remodeling, DNA binding, ribosome biogenesis, and cell cycle progression. However, the effects of Par14 and Par17 on viral replication have been explored to a limited extent. We first time discovered their influential roles in promoting Hepatitis B Virus replication. In this study, we observed that in the presence of HBx, either Par14 or Par17 could upregulate HBV replication. However, in the absence of HBx, neither Par14 nor Par17 had any effect on replication. Their mechanism of action involves binding to specific motifs within HBc and HBx proteins. Notably, they target the conserved 133Arg-Pro134 (RP) motif of HBc and the 19RP20-28RP29 motifs of HBx. This interaction is fundamental for the stability of HBx, core particles, and HBc. Par14 and Par17 exhibit versatility by binding both outside and inside core particles, thereby facilitating core particle assembly through their participation in HBc dimer-dimer interactions. NAGE and immunoblotting analyses unveiled the binding of Par14/Par17 to core particles. Co-immunoprecipitation experiments further demonstrated the interaction of Par14/Par17 with core particle assembly-defective and dimer-positive HBc-Y132A. It's essential to emphasize that R133 is the key residue in the HBc RP motif that governs their interaction with Par14/Par17. Chromatin immunoprecipitation conducted on HBV-infected cells elucidated the participation of residues S19 and E46/D74 in Par14 and S44 and E71/D99 in Par17 in the recruitment of 133RP134 motif-containing HBc into cccDNA. Depleting PIN4 in liver cell lines results in a significant reduction in cccDNA levels, pgRNA, sgRNAs, HBc, core particle assembly, and HBV DNA synthesis. Notably, parvulin inhibitors like juglone and PiB have proven to be effective in substantially reducing HBV replication. These inhibitors weaken the interaction between HBV core particles and Par14/Par17, underscoring the dynamic nature of this interaction. It's also worth noting that specific Par14/Par17 inhibitors hold promise as potential therapeutic options for chronic hepatitis B.

Keywords: Par14Par17, HBx, HBc, cccDNA, HBV

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Authors: Julia Wong, Hua Beng Lim, Petrina Goh, Johanna Foo, Caleb Ng, Nurul ‘Aqilah Bte Mohd Taufek

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Animal-assisted therapy (AAT) utilizes human-animal interaction to achieve specific therapeutic goals, and its efficacy has been demonstrated across various settings overseas. The use of AAT in Singapore, however, is still limited. Ang Mo Kio-Thye Hua Kwan (AMKH) is one of the first community hospitals in Singapore to use AAT to complement its occupational therapy services with elderly patients. This study explored the perspectives of AMKH’s occupational therapists (OTs) in relation to AAT to understand barriers and enablers in implementing and practising AAT. We also examined how OTs at-large across practice settings perceive AAT. A mixed method design was used. 64 OTs at-large participated in on online survey, and 7 AMKH OTs were interviewed individually via Zoom. Survey results were analysed with descriptive and Mann-Whitney U tests. Interviews were thematically analysed. AMKH OTs perceived various benefits of AAT articulated in overseas studies in domains such as motivation and participation, emotional, social interaction, sensory tactile stimulation, and cognition. Interestingly, this perception was also supported by 67% of OTs who had responded to the survey, even though most of the OTs who had participated in the survey had no experience in AAT. Despite the perceived benefits of AAT, both OTs from AMKH and those at-large articulated concerns on risks pertaining to AAT (e.g., allergies, unexpected animal behaviour, infections, etc). However, AMKH OTs shared several ways to mitigate these risks, demonstrating their ability to develop a safe program. For e.g., volunteers and their dogs must meet specific recruitment criteria, stringent protocols are used to screen and match dogs with patients, and there are strict exclusion criteria for patients participating in AAT. AMKH OTs’ experience suggests that additional skills and knowledge are required to implement AAT, therefore, healthcare institutions should first consider improving their staff training and risk mitigation knowledge before implementing AAT. They can also refer to AMKH’s AAT protocols and those found in overseas studies, but institutions must adapt the protocols to fit their institutional settings and patients’ profiles.

Keywords: animal-assisted therapy, dog-assisted therapy, occupational therapy, complementary therapy

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Authors: Yasmin Begum Mohammed

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Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

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Authors: Ying Chern Yeoh, Mark J. Forshaw

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Although hypnosis has been widely endorsed in Europe since 1950s, it was still viewed as a typically new therapy in Asia. There are very little findings regarding hypnosis in Asian countries, especially in culturally diverse countries such as Malaysia. The knowledge of the beneficial effects of hypnosis was not widespread to the public, however knowledge of the negative effects was frequently being highlighted. Therefore, the acceptance of hypnosis as a new effective health treatment can be a challenge in Malaysia. Recognising Malaysian’s perception, belief and attitude towards hypnosis could increase the public awareness of hypnosis, which in turn will alter their misconception and increase acceptance of hypnosis as an effective therapy. Eight individuals (N = 8) from the general public with different background, ethnicity (Malays, Chinese and Indians) and religion (Islamic, Buddhism, Hinduism, Taoism, Christianity, free-thinker) and two local experienced practitioners with minimum of five years experiences (N = 2) were being interviewed to determine their views, beliefs and level of acceptance towards hypnosis. Semi-structured interviews were conducted, transcribed with pseudonyms and analyzed by using Interpretative Phenomenological Analysis. The three emergent themes were illustrated under the captions of ‘traditional vs mainstream’, ‘myths vs truth’, and ‘dissemination and public awareness’. The finding suggested that individual knowledge and personal experience primarily influenced people’s level of acceptance towards hypnosis as a beneficial health treatment, rather than the diversity of cultural and religious background. Subsequent findings regarding hypnosis and the effort of promoting it will provide the society an opportunity to increase public education and health awareness. Several associations had started to advance its development by organizing conferences and setting up therapeutic centers. However, health promotion on hypnosis is yet to be conducted to raise public awareness of its beneficial effects. By requesting for hypnosis to be included as a subject in medical education and psychology curriculum and formatting it under Ministry of Health’s legislation body might enhance the knowledge of hypnosis for Malaysian as one of the health intervention in the future.

Keywords: awareness, hypnosis, intervention, Malaysian, promotion

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Authors: Naila Safdar, Faria Riasat, Azra Yasmin

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Lychee is an emerging fruit crop in Pakistan. Two famous cultivars of lychee, Gola and Surakhi, were collected from Khanpur Orchard, Pakistan and their whole fruit (including peel, pulp and seed) was investigated for pomological features and therapeutic activities. Both cultivars differ in shape and size with Gola having large size (3.27cm length, 2.36cm width) and more flesh to seed ratio (8.65g). FTIR spectroscopy and phytochemical tests confirmed presence of different bioactive compounds like phenol, flavonoids, quinones, anthraquinones, tannins, glycosides, and alkaloids, in both lychee fruits. Atomic absorption spectroscopy indicated an increased amount of potassium, magnesium, sodium, iron, and calcium in Gola and Surakhi fruits. Small amount of trace metals, zinc and copper, were also detected in lychee fruit, while heavy metals lead, mercury, and nickel were absent. These two lychee cultivars were also screened for antitumor activity by Potato disc assay with maximum antitumor activity shown by aqueous extract of Surakhi seed (77%) followed by aqueous extract of Gola pulp (74%). Antimicrobial activity of fruit parts was checked by agar well diffusion method against six bacterial strains Enterococcus faecium, Enterococcus faecalis, Staphylococcus aureus, Bacillus subtilis, Bacillus sp. MB083, and Bacillus sp. MB141. Highest antimicrobial activity was shown by methanolic extract of Gola pulp (27mm ± 0.70) and seed (19.5mm ± 0.712) against Enterococcus faecalis. DPPH scavenging assay revealed highest antioxidant activity by aqueous extract of Gola peel (98.10%) followed by n-hexane extract of Surakhi peel (97.73%). Results obtained by reducing power assay also corroborated with the results of DPPH scavenging activity.

Keywords: antimicrobial evaluation, antitumor assay, gola, phytoconstituents, reactive oxygen species, Surakhi

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Authors: Adeyi Akindele Oluwatosin, Mustapha Kaosarat Keji, Ajisebiola Babafemi Siji, Adeyi Olubisi Esther, Damilohun Samuel Metibemu, Raphael Emuebie Okonji

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Envenoming by Echis ocellatus is potentially life-threatening due to severe hemorrhage, renal failure, and capillary leakage. These effects are attributed to snake venom metalloproteinases (SVMPs). Due to drawbacks in the use of antivenom, natural inhibitors from plants are of interest in studies of new antivenom treatment. Antagonizing effects of bioactive compounds of Moringa oleifera, a known antisnake plant, are yet to be tested against SVMPs of E. ocellatus (SVMP-EO). Ethanol crude extract of M. oleifera was partitioned using n-hexane and ethyl acetate. Each partition was fractionated using column chromatography and tested against SVMP-EO purified through ion-exchange chromatography with EchiTab-PLUS polyvalent anti-venom as control. Phytoconstituents of ethyl acetate fraction were screened against the catalytic site of crystal of BaP1-SVMP, while drug-likeness and ADMET toxicity of compound were equally determined. The molecular weight of isolated SVMP-EO was 43.28 kDa, with a specific activity of 245 U/ml, a percentage yield of 62.83 %, and a purification fold of 0.920. The Vmax and Km values are 2 mg/ml and 38.095 μmol/ml/min, respectively, while the optimal pH and temperature are 6.0 and 40°C, respectively. Polyvalent anti-venom, crude extract, and ethyl acetate fraction of M. oleifera exhibited a complete inhibitory effect against SVMP-EO activity. The inhibitions of the P-1 and P-II metalloprotease’s enzymes by the ethyl acetate fraction are largely due to methanol, 6, 8, 9-trimethyl-4-(2-phenylethyl)-3-oxabicyclo[3.3.1]non-6-en-1-yl)- and paroxypropione, respectively. Both compounds are potential drug candidates with little or no concern of toxicity, as revealed from the in-silico predictions. The inhibitory effects suggest that this compound might be a therapeutic candidate for further exploration for treatment of Ocellatus’ envenoming.

Keywords: Echis ocellatus, Moringa oleifera, anti-venom, metalloproteases, snakebite, molecular docking

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Authors: Sanjay Singh, Karunanithi Priyanka, Ramoji Kosuru, Raju Prasad Sharma

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Herbal drugs are well known for their mixed pharmacological activities with the benefit of no harmful side effects. The use of herbal drugs is limited because of their higher dose requirement, frequent drug administration, poor bioavailability of phytochemicals and delayed onset of action. Ficus religiosa, a potent anti-oxidant plant useful in the treatment of diabetes and cancer was selected for the study. Solid lipid nanoparticles (SLN) of Ficus religiosa extract was developed for the enhancement in oral bioavailability of stigmasterol and β-sitosterol-d-glucoside, principal components present in the extract. Hot homogenization followed by ultrasonication method was used to develop extract loaded SLN. Developed extract loaded SLN were characterized for particle size, PDI, zeta potential, entrapment efficiency, in vitro drug release and kinetics, fourier transform infra-red spectroscopy, differential scanning calorimetry, powder X-ray diffractrometry and stability studies. Entrapment efficiency of optimized extract loaded SLN was found to be 68.46 % (56.13 % of stigmasterol and 12.33 % of β-sitosteryl-d-glucoside, respectively). RP HPLC method development was done for simultaneous estimation of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract in rat plasma. Bioavailability studies were carried out for extract in suspension form and optimized extract loaded SLN. AUC of stigmasterol and β-sitosterol-d-glucoside were increased by 6.7-folds by 9.2-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Also, Cmax of stigmasterol and β-sitosterol-d-glucoside were increased by 4.3-folds by 3.9-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Mean residence times (MRT) for stigmasterol were found to be 12.3 ± 0.67 hours from extract and 7.4 ± 2.1 hours from SLN and for β-sitosterol-d-glucoside, 10.49 ± 2.9 hours from extract and 6.4 ± 0.3 hours from SLN. Hence, it was concluded that SLN enhanced the bioavailability and reduced the MRT of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract which in turn may lead to reduction in dose of Ficus religiosa extract, prolonged duration of action and also enhanced therapeutic efficacy.

Keywords: Ficus religiosa, phytosterolins, bioavailability, solid lipid nanoparticles, stigmasterol and β-sitosteryl-d-glucoside

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Authors: Sachiko Hosoya

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Objectives: The purpose of this paper is to investigate the social policy of preventive genetic medicine in Iran, by following the legalization process of abortion law and the factors affecting the process in wider Iranian contexts. In this paper, ethical discussions of prenatal diagnosis and selective abortion in Iran will be presented, by exploring Iranian social policy to control genetic diseases, especially a genetic hemoglobin disorder called Thalassemia. The ethical dilemmas in application of genetic medicine into social policy will be focused. Method: In order to examine the role of the policy for prevention of genetic diseases and selective abortion in Iran, various resources have been sutudied, not only academic articles, but also discussion in the Parliament and documents related to a court case, as well as ethnographic data on living situation of Thalassemia patients. Results: Firstly, the discussion on prenatal diagnosis and selective abortion is overviewed from the viewpoints of ethics, disability rights activists, and public policy for lower-resources countries. As a result, it should be noted that the point more important in the discussion on prenatal diagnosis and selective abortion in Iran is the allocation of medical resources. Secondly, the process of implementation of national thalassemia screening program and legalization of ‘Therapeutic Abortion Law’ is analyzed, through scrutinizing documents such as the Majlis record, government documents and related laws and regulations. Although some western academics accuse that Iranian policy of selective abortion seems to be akin to eugenic public policy, Iranian government carefully avoid to distortions of the policy as ‘eugenic’. Thirdly, as a comparative example, discussions on an Iranian court case of patient’s ‘right not to be born’ will be introduced. Along with that, restrictive living environments of people with Thalassemia patients and the carriers are depicted, to understand some disabling social factors for people with genetic diseases in the local contexts of Iran.

Keywords: abortion, Iran, prenatal diagnosis, public health ethics, Thalassemia prevention program

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Authors: Qi LI, Xu Lin, Nengming Lin

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Objective: The aim of this study was to investigate the role of desmocollin 2 (DSC2) protein in the proliferation, migration and drug resistance of lung cancer cells. Method: CCK-8 assays and colony formation assays were used to evaluate the effect of dsc2 regulation on cancer cell viability and colony formation. Transwell assays and wound healing assays were also performed. Cell flow double staining was used to detect the apoptosis rate of cells with DSC2, which was added cisplatin. Western blot assay was used to detect cell cycle, PI3k/Akt and apoptosis-related proteins. Results: Our data showed that dsc2 is upregulated in clinical lung cancer tissues compared with pericarcinomatous tissues, and it is differentially expressed in lung cancer cell lines. The down-regulation of dsc2 in A549 and H358 lung cancer cells significantly suppressed the cell proliferation, metastasis, and motility. In contrast, the opposite effects were observed in overexpression of dsc2 both in H23 and PC9 cell lines. In addition to lung adenocarcinoma cell lines, we also examined its expression in lung squamous cell lines, such as H226. Western blotting showed that dsc2 could reduce the level of phosphorylated Akt (Ser 473) and p-mTOR. Thus, it is speculated that dsc2 up-regulation promotes proliferation and invasiveness through activation of the PI3K/AKT pathway. Also, knockdown of dsc2 in A549 and H226 could significantly decreased in the levels of cyclinB and wee1 protein. Additionally, flow cytometry showed that dsc2 knockdown combined with cisplatin could significantly enhance cell apoptosis rate. Conclusion: These data suggest that dsc2 promotes the proliferation and migration of lung cancer cells in vitro. Also, the results suggested that dsc2 could affect the cell cycle and apoptosis of lung cells. Furthermore, knockdown of dsc2 could sensitize cisplatin in both lung adenocarcinoma and lung squamous cell lines. Thus we suggested that dsc2 can be used as a therapeutic target for lung cancer.

Keywords: desmocollin 2, cisplatin, lung cancer, PI3K/AKT, lung squamous cell

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Authors: Nishanthi N. S., Srikanth Vedantam

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Intracellular delivery of materials has always proved to be a challenge in research and therapeutic applications. Usually, vector-based methods, such as liposomes and polymeric materials, and physical methods, such as electroporation and sonoporation have been used for introducing nucleic acids or proteins. Reliance on exogenous materials, toxicity, off-target effects was the short-comings of these methods. Microinjection was an alternative process which addressed the above drawbacks. However, its low throughput had hindered its adoption widely. Mechanical deformation of cells by squeezing them through constriction channel can cause the temporary development of pores that would facilitate non-targeted diffusion of materials. Advantages of this method include high efficiency in intracellular delivery, a wide choice of materials, improved viability and high throughput. This cell squeezing process can be studied deeper by employing simple models and efficient computational procedures. In our current work, we present a finite sized dissipative particle dynamics (FDPD) model to simulate the dynamics of the cell flowing through a constricted channel. The cell is modeled as a capsule with FDPD particles connected through a spring network to represent the membrane. The total energy of the capsule is associated with linear and radial springs in addition to constraint of the fixed area. By performing detailed simulations, we studied the strain on the membrane of the capsule for channels with varying constriction heights. The strain on the capsule membrane was found to be similar though the constriction heights vary. When strain on the membrane was correlated to the development of pores, we found higher porosity in capsule flowing in wider channel. This is due to localization of strain to a smaller region in the narrow constriction channel. But the residence time of the capsule increased as the channel constriction narrowed indicating that strain for an increased time will cause less cell viability.

Keywords: capsule, cell squeezing, dissipative particle dynamics, intracellular delivery, microfluidics, numerical simulations

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Authors: Soumaya Mrabet, Taieb Ach, Imen Akkari, Amira Atig, Neirouz Ghannouchi, Koussay Ach, Elhem Ben Jazia

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Introduction: Celiac disease (CD) is an immune-mediated small intestinal disorder that occurs in genetically susceptible people. It is significantly associated with other autoimmune disorders represented mainly by type 1 diabetes and autoimmune dysthyroidism. The aim of our study is to determine the prevalence and the type of the various autoimmune diseases associated with CD in adult patients. Material and methods: This is a retrospective study including patients diagnosed with CD, explored in Internal Medicine, Gastroenterology and Endocrinology and Diabetology Departments of the Farhat Hached University Hospital, between January 2005 and January 2016. The diagnosis of CD was confirmed by serological tests and duodenal biopsy. The screening of autoimmune diseases was based on physical examination, biological and serological tests. Results: Sixty five patients with a female predominance were included, 48women (73.8%) and 17 men (26.2%). The mean age was 31.8 years (17-75). A family history of CD or other autoimmune diseases was present in 5 and 10 patients respectively. Clinical presentation of CD was made by recurrent abdominal pain in 49 cases, diarrhea in 29 cases, bloating in 17 cases, constipation in 25 cases and vomiting in 8 cases. Autoimmune diseases associated with CD were found in 30 cases (46.1%): type 1 diabetes in 15 patients attested by the positivity of anti-GAD antibodies in 11 cases and anti-IA2 in 4 cases, Hashimoto thyroiditis in 8 cases confirmed by the positivity of anti-TPO antibodies, Addison's disease in 2 patients, Anemia of Biermer in 2 patients, autoimmune hepatitis, Systemic erythematosus lupus, Gougerot Sjögren syndrome, rheumatoid arthritis, Vitiligo and antiphospholipid syndrome in one patient each. CD was associated with more than one autoimmune disease defining multiple autoimmune syndrome in 2 female patients. The first patient had Basedow disease, Addison disease and type 1 diabetes. The second patient had systemic erythematosus lupus and Gougerot Sjögren syndrome. Conclusion: In our study autoimmune diseases were associated with CD in 46.1% of cases and were dominated by diabetes and dysthroidism. After establishing the diagnosis of CD the search of associated autoimmune diseases is necessary in order to avoid any therapeutic delay which can alter the prognosis of the patient.

Keywords: association, autoimmune thyroiditis, celiac disease, diabetes

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Authors: Denis Mustafov, Emmanouil Karteris, Maria Braoudaki

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Glioblastoma multiform (GBM) is a heterogenous primary brain tumour that kills most affected patients. To the authors best knowledge, despite all research efforts there is no early diagnostic biomarker for GBM. MicroRNAs (miRNAs) are short non-coding RNA molecules which are deregulated in many cancers. The aim of this research was to determine miRNAs with a diagnostic impact and to potentially identify promising therapeutic targets for glioblastoma multiform. In silico analysis was performed to identify deregulated miRNAs with diagnostic relevance for glioblastoma. The expression profiles of the chosen miRNAs were then validated in vitro in the human glioblastoma cell lines A172 and U-87MG. Briefly, RNA extraction was carried out using the Trizol method, whilst miRNA extraction was performed using the mirVANA miRNA isolation kit. Quantitative Real-Time Polymerase Chain Reaction was performed to verify their expression. The presence of five target proteins within the A172 cell line was evaluated by Western blotting. The expression of the CORO1C protein within 32 GBM cases was examined via immunohistochemistry. The miRNAs identified in silico included miR-21-5p, miR-34a and miR-128a. These miRNAs were shown to target deregulated GBM genes, such as CDK6, E2F3, BMI1, JAG1, and CORO1C. miR-34a and miR-128a showed low expression profiles in comparison to a control miR-RNU-44 in both GBM cell lines suggesting tumour suppressor properties. Opposing, miR-21-5p demonstrated greater expression indicating that it could potentially function as an oncomiR. Western blotting revealed expression of all five proteins within the A172 cell line. In silico analysis also suggested that CORO1C is a target of miR-128a and miR-34a. Immunohistochemistry demonstrated that 75% of the GBM cases showed moderate to high expression of CORO1C protein. Greater understanding of the deregulated expression of miR-128a and the upregulation of CORO1C in GBM could potentially lead to the identification of a promising diagnostic biomarker signature for glioblastomas.

Keywords: non-coding RNAs, gene expression, brain tumours, immunohistochemistry

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Authors: Albert P. Ekanem, Austin I. Obiekezie, Elizabeth X. Ntia

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Introduction: Some African plants and bile from animals have shown efficacies in the treatment and control of diseases in farmed fish. The background of the study is based on the fact the African rain forest is blessed with the abundance of medicinal plants that should be investigated for their use in the treatment of diseases. The significance of the study is informed by the fact that chemical-based substances accumulate in the tissues of food fish, thereby reducing the food values of such products and moreover, the continuous use of chemotherapeutics in the aquatic environments tends to degrade the affected environment. Methodology: Plants and animal products were extracted, purified and applied under in vitro and in vivo conditions to the affected organisms. Effective plants and bills were analyzed for biologically active substances responsible for the activities by both qualitative and HPLC methods. Results: Extracts of Carica papaya and Mucuna pruriens were effective in the treatment of Ichthyophthiriasis in goldfish (Carassius auratus auratus) with high host tolerance. Similarly, ectoparasitic monogeneans were effectively dislodged from the gills and skin of goldfish by the application of extracts of Piper guineense at therapeutic concentrations. Artemesia annua with known antimalarial activities in human was also effective against fish monogenean parasites of Clarias gariepinus in a concentration-related manner without detriments to the host. Effective antibacterial activities against Aeromonas and Pseudomonas diseases of the African catfish (Heterobranchus longifilis) were demonstrated in some plants such as Phylanthus amarus, Allium sativum, A. annua, and Citrus lemon. Bile from some animals (fish, goat, chicken, cow, and pig) showed great antibacterial activities against some gastrointestinal bacterial pathogens of fish. Conclusions: African plants and some animal bile have shown potential promise in the treatment of diseases in fish and other aquatic animals. The use of chemical-based substances for control of diseases in the aquatic environments should be restricted.

Keywords: control, diseases, fish, treatment

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Authors: Paulina Pergoł, Paulina Pergoł, Tomasz Kryczka

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Aging of societies is a phenomenon that is visible all over the world. The above has social, economic, and medical consequences. Many methods of pro-health stimulation of the elderly, improving cognitive functions and quality of life, are described in the world literature. The most frequently used method of activating the elderly is physical activity, in which, in addition to standard exercise programs, activities such as dance, tai chi, and yoga are often introduced. The introduction of physical activity may be limited due to the disability that often accompanies people aged 65+. Other activating methods mentioned in the literature are therapies with the participation of animals - animal therapy or plant therapy - hortitherapy, as well as music therapy, which is increasingly popular. All of the above-mentioned therapeutic methods require the involvement of a person who would conduct the so-called occupational therapist, which can be a financial barrier for many nursing homes. Researchers all over the world are trying to find solutions that can be applied in any care institution, even in those where financial support for running such centers is small. One of the forms of therapy that is recommended in the group of elderly people and which does not require large financial outlays is the so-called reminiscence therapy based on recalling personal experiences and experiences. Thanks to reminiscence therapy, seniors can return to happy moments in their lives. Research shows that reminiscence therapy increases self-esteem and reduces symptoms of depression. The method of activating older people with the use of correspondence can be an effective and low-cost form of therapy, as shown by the pilot study conducted in 2019 as part of the Queen Silvia Nursing Award competition, consisting in a systematic exchange of correspondence between volunteers and residents of the Nursing Home. This study was conducted with the participation of a small group of participants, therefore, in order to identify and prove the beneficial effect of this form of activation, it should be carried out on a larger group of respondents using standardized scales assessing various psychological parameters.

Keywords: nursing, elderly care, psychiatry, psychology

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Authors: Yogeeta O. Agrawal, Hitendra S. Mahajan, Sanjay J. Surana

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Methotrexate is effective in controlling recalcitrant psoriasis when administered by the oral or parenteral route long-term. However, the systematic use of this drug may provoke any of a number of side effects, notably hepatotoxic effects. To reduce these effects, clinical studies have been done with topical MTx. It is useful in treating a number of cutaneous conditions, including psoriasis. A major problem in topical administration of MTx currently available in market is that the drug is hydrosoluble and is mostly in the dissociated form at physiological pH. Its capacity for passive diffusion is thus limited. Localization of MTx in effected layers of skin is likely to improve the role of topical dosage form of the drug as a supplementary to oral therapy for treatment of psoriasis. One of the possibilities for increasing the penetration of drugs through the skin is the use of Nanostructured lipid Carriers. The objective of the present study was to formulate and characterize Methotrexate loaded Nanostructured Lipid Carriers (MtxNLCs), to understand in vitro drug release and evaluate the role of the developed gel in the topical treatment of psoriasis. MtxNLCs were prepared by solvent diffusion technique using 3(2) full factorial design.The mean diameter and surface morphology of MtxNLC was evaluated. MtxNLCs were lyophilized and crystallinity of NLC was characterized by Differential Scanning Calorimtery (DSC) and powder X-Ray Diffraction (XRD). The NLCs were incorporated in 1% w/w Carbopol 934 P gel base and in vitro skin deposition studies in Human Cadaver Skin were conducted. The optimized MtxNLCs were spherical in shape, with average particle size of 253(±9.92)nm, zeta potential of -30.4 (±0.86) mV and EE of 53.12(±1.54)%. DSC and XRD data confirmed the formation of NLCs. Significantly higher deposition of Methotrexate was found in human cadaver skin from MtxNLC gel (71.52 ±1.23%) as compared to Mtx plain gel (54.28±1.02%). Findings of the studies suggest that there is significant improvement in therapeutic index in treatment of psoriasis by MTx-NLCs incorporated gel base developed in this investigation over plain drug gel currently available in the market.

Keywords: methotrexate, psoriasis, NLCs, hepatotoxic effects

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Authors: Lynn Louis, Bor Shin Chee, Marion McAfee, Michael Nugent

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This article aims to develop a sustained release formulation of microspheres containing the mTOR inhibitor Everolimus (EVR) using Polyvinyl alcohol (PVA) to enhance the bioavailability of the drug and to overcome poor solubility characteristics of Everolimus. This paper builds on recent work in the manufacture of microspheres using the sessile droplet technique by freezing the polymer-drug solution by suspending the droplets into pre-cooled ethanol vials immersed in liquid nitrogen. The spheres were subjected to 6 freezing cycles and 3 freezing cycles with thawing to obtain proper geometry, prevent aggregation, and achieve physical cross-linking. The prepared microspheres were characterised for surface morphology by SEM, where a 3-D porous structure was observed. The in vitro release studies showed a 62.17% release over 12.5 days, indicating a sustained release due to good encapsulation. This result is comparatively much more than the 49.06% release achieved within 4 hours from the solvent cast Everolimus film as a control with no freeze-thaw cycles performed. The solvent cast films were made in this work for comparison. A prolonged release of Everolimus using a polymer-based drug delivery system is essential to reach optimal therapeutic concentrations in treating SEGA tumours without systemic exposure. These results suggest that the combination of PVA and Everolimus via a rheological synergism enhanced the bioavailability of the hydrophobic drug Everolimus. Physical-chemical characterisation using DSC and FTIR analysis showed compatibility of the drug with the polymer, and the stability of the drug was maintained owing to the high molecular weight of the PVA. The obtained results indicate that the developed PVA/EVR microsphere is highly suitable as a potential drug delivery system with improved bioavailability in treating Subependymal Giant cell astrocytoma (SEGA).

Keywords: drug delivery system, everolimus, freeze-thaw cycles, polyvinyl alcohol

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Authors: Eimar Yadir Quintero Tapias

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Background: Science is not generally self-correcting; many clinical studies end with the same conclusion "more research is needed." This study hypothesizes that first, we need a better appraisal of the available (and unavailable) evidence instead of creating more of the same false inquiries. Methods: Systematic review of ClinicalTrials.gov study records using the following Boolean operators: (food OR nut OR milk OR egg OR shellfish OR wheat OR peanuts) AND (allergy OR allergies OR hypersensitivity OR hypersensitivities). Variables included the status of the study (e g., active and completed), availability of results, sponsor type, sample size, among others. To determine the rates of non-publication in journals indexed by PubMed, an advanced search query using the specific Number of Clinical Trials (e.g., NCT000001 OR NCT000002 OR...) was performed. As a prophylactic measure to prevent P-hacking, data analyses only included descriptive statistics and not inferential approaches. Results: A total of 2092 study records matched the search query described above (date: September 13, 2019). Most studies were interventional (n = 1770; 84.6%) and the remainder observational (n = 322; 15.4%). Universities, hospitals, and research centers sponsored over half of these investigations (n = 1208; 57.7%), 308 studies (14.7%) were industry-funded, and 147 received NIH grants; the remaining studies got mixed sponsorship. Regarding completed studies (n = 1156; 55.2%), 248 (21.5%) have results available at the registry site, and 417 (36.1%) matched NCT numbers of journal papers indexed by PubMed. Conclusions: The internal and external validity of human research is critical for the appraisal of medical evidence. It is imperative to analyze the entire dataset of clinical studies, preferably at a patient-level anonymized raw data, before rushing to conclusions with insufficient and inadequate information. Publication bias and non-registration of clinical trials limit the evaluation of the evidence concerning therapeutic interventions for food allergy, such as oral and sublingual immunotherapy, as well as any other medical condition. Over half of the food allergy human research remains unpublished.

Keywords: allergy, clinical trials, immunology, systematic reviews

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Authors: Hala Raslan, Noha Eltaweel, Hanaa Rasmi, Solaf Kamel, May Magdy, Sherif Ismail, Khalda Amr

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Introduction: Rheumatoid arthritis (RA) is an inflammatory, autoimmune disorder with progressive joint damage. Osteoarthritis (OA) is a degenerative disease of the articular cartilage that shows multiple clinical manifestations or symptoms resembling those of RA. Genetic predisposition is believed to be a principal etiological factor for RA and OA. In this study, we aimed to measure the expression of the top deregulated miRNAs that might be the cause of pathogenesis in both diseases, according to our latest NGS analysis. Six of the deregulated miRNAs were selected as they had multiple target genes in the RA pathway, so they are more likely to affect the RA pathogenesis.Methods: Eighty cases were recruited in this study; 45 rheumatoid arthiritis (RA), 30 osteoarthiritis (OA) patients, as well as 20 healthy controls. The selection of the miRNAs from our latest NGS study was done using miRwalk according to the number of their target genes that are members in the KEGG RA pathway. Total RNA was isolated from plasma of all recruited cases. The cDNA was generated by the miRcury RT Kit then used as a template for real-time PCR with miRcury Primer Assays and the miRcury SYBR Green PCR Kit. Fold changes were calculated from CT values using the ΔΔCT method of relative quantification. Results were compared RA vs Controls and OA vs Controls. Target gene prediction and functional annotation of the deregulated miRNAs was done using Mienturnet. Results: Six miRNAs were selected. They were miR-15b-3p, -128-3p, -194-3p, -328-3p, -542-3p and -3180-5p. In RA samples, three of the measured miRNAs were upregulated (miR-194, -542, and -3180; mean Rq= 2.6, 3.8 and 8.05; P-value= 0.07, 0.05 and 0.01; respectively) while the remaining 3 were downregulated (miR-15b, -128 and -328; mean Rq= 0.21, 0.39 and 0.6; P-value= <0.0001, <0.0001 and 0.02; respectively) all with high statistical significance except miR-194. While in OA samples, two of the measured miRNAs were upregulated (miR-194 and -3180; mean Rq= 2.6 and 7.7; P-value= 0.1 and 0.03; respectively) while the remaining 4 were downregulated (miR-15b, -128, -328 and -542; mean Rq= 0.5, 0.03, 0.08 and 0.5; P-value= 0.0008, 0.003, 0.006 and 0.4; respectively) with statistical significance compared to controls except miR-194 and miR-542. The functional enrichment of the selected top deregulated miRNAs revealed the highly enriched KEGG pathways and GO terms. Conclusion: Five of the studied miRNAs were greatly deregulated in RA and OA, they might be highly involved in the disease pathogenesis and so might be future therapeutic targets. Further functional studies are crucial to assess their roles and actual target genes.

Keywords: MiRNAs, expression, rheumatoid arthritis, osteoarthritis

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Authors: KuiDong Kang, Hye Bin Yim, Su Ah Kim

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Purpose: Tectorigenin is an isoflavone derived from the rhizome of Belamacanda chinensis. In this study, oxygen-induced retinopathy was used to characterize the anti-angiogenic properties of tectorigenin in mice. Methods: ICR neonatal mice were exposed to 75% oxygen from postnatal day P7 until P12 and returned to room air (21% oxygen) for five days (P12 to P17). Mice were subjected to daily intraperitoneal injection of tectorigenin (1 mg/kg, 10 mg/kg) and vehicle from P12 to P17. Retro-orbital injection of FITC-dextran was performed and retinal flat mounts were viewed by fluorescence microscopy. The Central avascular area was quantified from the digital images in a masked fashion using image analysis software (NIH ImageJ). Neovascular tufts were quantified by using SWIFT_NV and neovascular lumens were quantified from a histologic section in a masked fashion. Immunohistochemistry and Western blot analysis were also performed to demonstrate the anti-angiogenic activity of this compound in vivo. Results: In the retina of tectorigenin injected mouse (10mg/kg), the central non-perfusion area was significantly decreased compared to the vehicle injected group (1.76±0.5 mm2 vs 2.85±0.6 mm2, P<0.05). In vehicle-injected group, 33.45 ± 5.51% of the total retinal area was avascular, whereas the retinas of pups treated with high-dose (10 mg/kg) tectorigenin showed avascular retinal areas of 21.25 ±4.34% (P<0.05). High dose of tectorigenin also significantly reduced the number of vascular lumens in the histologic section. Tectorigenin (10 mg/kg) significantly reduced the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), MMP-9, and angiotensin II compared to the vehicle injected group. Tectorigenin did not affect CD31 abundance at any tested dose. Conclusions: Our results show that tectorigenin possesses powerful anti-angiogenic properties and can attenuate new vessel formation in the retina after systemic administration. These results imply that this compound can be considered as a candidate substance for therapeutic inhibition of retinal angiogenesis.

Keywords: tectorigenin, anti-angiogenic, retinopathy, Belamacanda chinensis

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Authors: Sadeq Al Yaari, Nassr Almaflehi, Ayman Al Yaari, Adham Al Yaari, Montaha Al Yaari, Aayah Al Yaari, Sajedah Al Yaari

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Background: Assessment of language-related functional activities (ALFA) is of vital importance in assessing aphasics’ performance of both sexes. However, the validity and reliability of this language therapeutic test has never been validated in the Arabic medical literature. Purpose: The aim of this study was to validate the test by assessing the language-related functional activities of 100 gender aphasics based in a medical faculty. Design: ALFA Pre-and-posttest was administered twice in three weeks to test the language-related functional activities of 100 gender aphasics. Settings: Al Khars hospital in Al Ahsa’a, Kingdom of Saudi Arabia (KSA). Participants: Sixteen to eight-year-old participants (N = 100 men and women) were enrolled in this experiment. Again, the purpose was to assess their language-related functional activities using ALFA. Procedures: The first step was to translate the English version of ALFA test into the mother tongue of the patients (Arabic). Secondly, the translated text is reviewed and edited by three specialists of Arabic language. Having the test standardized, the third step was to assess language-related functional activities of the participants in natural environment. Assessment took place in three weeks. In the first week, a pre-test was administered to the participants at hand and after two weeks, a post-test was administered to identify whether or not significant differences between the two tests (pre-and-posttest) could be observed. Interventions: Outcomes of the results obtained from the analyses were broadly discussed. Linguistic and statistical comparisons were held to illustrate the findings of this study. Main outcomes and Results: The analysis of the obtained results indicated that the performance of the aphasic participants in the post-test did not differ from that of the pre-test (, respectively). Conclusions & Implications: ALFA was proved to be a valid and reliable test. Moreover, outlined results pointed out the importance of assessing not only gender aphasics’ language, but also their language-related functional activities. Further research is needed to explore how gender aphasics’ verbal and non-verbal performances interact.

Keywords: ALFA, language test, Arab aphasics, validity, reliability, psychoneurolinguistics.

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Authors: Afrah Aladwani, Alexander Mullen, Mohammad AlRashidi, Omamah Alfarisi, Faisal Alterkit, Abdulwahab Aladwani, Asit Kumar, Emad Eldosouky

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Introduction: Trastuzumab is a HER-2 targeted humanized monoclonal antibody that significantly improves the therapeutic outcomes of metastatic and non-metastatic breast cancer. However, it is associated with increased risk of cardiotoxicity that ranges from mild decline in the cardiac ejection fraction to permanent cardiomyopathy. Concerns have been raised in treating eligible older patients. This study compares trastuzumab outcomes between two age cohorts in the Kuwait Cancer Control Centre (KCCC). Methods: In a prospective comparative observational study, 93 HER-2 positive breast cancer patients undergoing different chemotherapy protocols + trastuzumab were included and divided into two cohorts based on their age (˂60 and ≥60 years old). The baseline left ventricular ejection fraction (LVEF) was assessed and monitored every three months during trastuzumab treatment. Event of cardiotoxicity was defined as ≥10% decline in the LVEF from the baseline. The lower accepted normal limit of the LVEF was 50%. Results: The median baseline LVEF was 65% in both age cohorts (IQR 8% and 9% for older and younger patients respectively). Whereas, the median LVEF post-trastuzumab treatment was 51% and 55% in older and younger patients respectively (IQR 8%; p-value = 0.22), despite the fact that older patients had significantly lower exposure to anthracyclines compared to younger patients (60% and 84.1% respectively; p-value ˂0.001). 86.7% and 55.6% of older and younger patients, respectively, developed ≥10% decline in their LVEF from the baseline. Among those, only 29% of older and 27% of younger patients reached a LVEF value below 50% (p-value = 0.88). Statistically, age was the only factor that significantly correlated with trastuzumab induced cardiotoxicity (OR 4; p-value ˂0.012), but it did not increase the requirement for permanent discontinuation of treatment. A baseline LVEF value below 60% contributed to developing a post-treatment value below normal ranges (50%). Conclusion: Breast cancer patients aged 60 years and above in Kuwait were at 4-fold higher risk of developing ≥10% decline in their LVEF from the baseline than younger patients during trastuzumab treatment. Surprisingly, previous exposure to anthracyclines and multiple comorbidities were not associated with significant increased risk of cardiotoxicity.

Keywords: breast cancer, elderly, Trastuzumab, cardiotoxicity

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Authors: Mehrnaz Mostafavi

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Lung cancer is one of the most harmful forms of cancer. The long-term survival rate of lung cancer patients treated by conventional modalities such as surgical resection, radiation, and chemotherapy remains far from satisfactory. Systemic drug delivery is rarely successful because only a limited amount of the chemotherapeutic drug targets lung tumor sites, even when administered at a high dose. Targeted delivery of drug molecules to organs or special sites is one of the most challenging research areas in pharmaceutical sciences. By developing colloidal delivery systems such as liposomes, micelles and nanoparticles a new frontier was opened for improving drug delivery. Nanoparticles with their special characteristics such as small particle size, large surface area and the capability of changing their surface properties have numerous advantages compared with other delivery systems. Targeted nanoparticle delivery to the lungs is an emerging area of interest.Multimodal or combination therapy represents a promising new method to fight disease. Therefore, a combination of different therapeutic strategies may be the best alternative to improve treatment outcomes for lung cancer. Photothermal therapy was proposed as a novel approach to treatment. In this work, photothermal therapy with gold nanoparticles and near infrared laser (NIR) irradiation was investigated.Four types of small (<100nm), NIR absorbing gold nanoparticles (nanospheres, nanorods) were synthesized using wet chemical methods and characterized by transmission electron microscopy, dynamic light scattering and UV-vis spectroscopy. Their synthesis and properties were evaluated, to determine their feasibility as a photothermal agent for clinical applications. In vitro cellular uptake studies of the nanoparticles into lung cancer cell lines was measured using light scattering microscopy.Small gold nanorods had good photothermal properties and the greatest cellular uptake, and were used in photothermal studies. Under 4W laser irradiation, an increase in temperature of 10°C and decrease in cell viability of up to 80% were obtained.

Keywords: photothermal, therapy, cancer, gold nanorods

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Authors: Muhammad Adeel Arshad, Shaukat Ali Bhatti, Faiz-ul Hassan

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Manipulating microbial ecosystem in the rumen is considered as an important strategy to optimize production efficiency in ruminants. In the past, antibiotics and synthetic chemical compounds have been used for the manipulation of rumen fermentation. However, since the non-therapeutic use of antibiotics has been banned, efforts are being focused to search out safe alternative products. In tropics, crop residues and forage grazing are major dietary sources for ruminants. Poor digestibility and utilization of these feedstuffs by animals is a limiting factor to exploit the full potential of ruminants in this area. Hence, there is a need to enhance the utilization of these available feeding resources. One of the potential strategies in this regard is the use of direct-fed microbes. Bacteria and fungi are mostly used as direct-fed microbes to improve animal health and productivity. Commonly used bacterial species include lactic acid-producing and utilizing bacteria (Lactobacillus, Streptococcus, Enterococcus, Bifidobacterium, and Bacillus) and fungal species of yeast are Saccharomyces and Aspergillus. Direct-fed microbes modulate microbial balance in the gastrointestinal tract through the competitive exclusion of pathogenic species and favoring beneficial microbes. Improvement in weight gain and feed efficiency has been observed as a result of feeding direct-fed bacteria. The use of fungi as a direct-fed microbe may prevent excessive production of lactate and harmful oxygen in the rumen leading to better feed digestibility. However, the mechanistic mode of action for bacterial or fungal direct-fed microbes has not been established yet. Various reports have confirmed an increase in dry matter intake, milk yield, and milk contents in response to the administration of direct-fed microbes. However, the application of a direct-fed microbe has shown variable responses mainly attributed to dosages and strains of microbes. Nonetheless, it is concluded that the inclusion of direct-fed microbes may mediate the rumen ecosystem to manage lactic acid production and utilization in both clinical and sub-acute rumen acidosis.

Keywords: microbes, roughages, rumen, feed efficiency, production, fermentation

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Authors: Genziana Lay

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A wide majority of older children and adolescents who enter the juvenile court system present with an array of problematic symptoms and behaviors including anxiety, depression, aggressive acting out, detachment, and substance abuse. Attachment theory offers a framework for understanding normative and pathological functioning, which during development is influenced by emotional, social and cognitive elements. There is clear evidence that children and adolescents with the highest risk of developing adaptation problems present an insecure attachment profile. Most offending minors have experienced dysfunctional family relationships as well as social and/or economic deprivation. Their maladaptive attachment develops not only through their relationship with caregivers but with the environment at large. Activation of their faulty attachment system leads them to feel emotionally overwhelmed and engage in destructive behaviors and decision-making. A psycho-social intervention with this population conceptualized as attachment therapy is a multi-faceted, practical approach that has shown excellent results in terms of increased psychological well-being and drastically reduced rates of re-offense/ destructive behavior. Through several; components including psychotherapy, monitoring, volunteering, meditation and socialization, the program focuses on seven dimensions: self-efficacy, responsibility, empathy/reparation, autonomy/security, containment/structure, insight building, and relational health. This paper presents the program and illustrates how the framework of attachment theory practically applied to psycho-social intervention has great therapeutic and social reparation potential. Preliminary evidence drawn from the Sassari Juvenile Court is very promising; this paper will illustrate these results and propose an even more comprehensive, applicable approach to psycho-social reparative intervention that leads to greater psychological health and reduced recidivism in the child and adolescent population.

Keywords: attachment, child, adolescent, crime, juvenile, psychosocial

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Authors: Hercules Argyropoulos, Thomas F. Johnson, Nigel B Jackson, Kalliopi Zourna, Daniel G. Bracewell

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Lipid encapsulation has become essential in drug delivery, notably for mRNA vaccines during the COVID-19 pandemic. However, their sterile filtration poses challenges due to the risk of deformation, filter fouling and product loss from adsorption onto the membrane. Choosing the right filtration membrane is crucial to maintain sterility and integrity while minimizing product loss. The objective of this study is to develop a rigorous analytical framework utilizing confocal microscopy and filtration blocking models to elucidate the fouling mechanisms of liposomes as a model system for this class of delivery vehicle during sterile filtration, particularly in response to variations in transmembrane pressure (TMP) during the filtration process. Experiments were conducted using fluorescent Lipoid S100 PC liposomes formulated by micro fluidization and characterized by Multi-Angle Dynamic Light Scattering. Dual-layer PES/PES and PES/PVDF membranes with 0.2 μm pores were used for filtration under constant pressure, cycling from 30 psi to 5 psi and back to 30 psi, with 5, 6, and 5-minute intervals. Cross-sectional membrane samples were prepared by microtome slicing and analyzed with confocal microscopy. Liposome characterization revealed a particle size range of 100-140 nm and an average concentration of 2.93x10¹¹ particles/mL. Goodness-of-fit analysis of flux decline data at varying TMPs identified the intermediate blocking model as most accurate at 30 psi and the cake filtration model at 5 psi. Membrane resistance analysis showed atypical behavior compared to therapeutic proteins, with resistance remaining below 1.38×10¹¹ m⁻¹ at 30 psi, increasing over fourfold at 5 psi, and then decreasing to 1-1.3-fold when pressure was returned to 30 psi. This suggests that increased flow/shear deforms liposomes enabling them to more effectively navigate membrane pores. Confocal microscopy indicated that liposome fouling mainly occurred in the upper parts of the dual-layer membrane.

Keywords: sterile filtration, membrane resistance, microfluidization, confocal microscopy, liposomes, filtration blocking models

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Authors: Albert P. Ekanem, Austin I. Obiekezie, Elizabeth X. Ntia

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Introduction: Some African plants and bile from animals have shown efficacies in the treatment and control of diseases in farmed fish. The background of the study is based on the fact the African rain forest is blessed with abundance of medicinal plants that should be investigated for their use in the treatment of diseases. The significance of the study is informed by the fact that chemical-based substances accumulates in the tissues of food fish, thereby reducing the food values of such products and moreover, the continuous use of chemotherapeutants in the aquatic environments tends to degrades the affected environment. Methodology: Plants and animal products were extracted, purified and applied under in vitro and in vivo conditions to the affected organisms. Effective plants and biles were analyzed for active biological substances responsible for the activities by both qualitative and HPLC methods. Results: Extracts of Carica papaya and Mucuna pruriens were effective in the treatment of Ichthyophthiriasis in goldfish (Carassius auratus auratus) with high host tolerance. Similarly, ectoparasitic monogeneans were effectively dislodged from the gills and skin of goldfish by the application of extracts of Piper guineense at therapeutic concentrations. Artemesia annua with known antimalarial activities in human was also effective against fish monogenean parasites of Clarias gariepinus in a concentration related manner without detriments to the host. Effective antibacterial activities against Aeromonas and Pseudomonas diseases of the African catfish (Heterobranchus longifilis) were demonstrated in some plants such as Phylanthus amarus, Allium sativum, A. annua, and Citrus lemon. Bile from some animals (fish, goat, chicken, cow, and pig) showed great antibacterial activities against some gastrointestinal bacterial pathogens of fish. Conclusions: African plants and some animal bile have shown potential promise in the treatment of diseases in fish and other aquatic animals. The use of chemical-based substances for control of diseases in the aquatic environments should be restricted.

Keywords: control, diseases, fish, natural products, treatment

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