Search results for: therapeutic jurisprudence

Authors: Krishna Pal Singh, Shailendra Kumar Gupta, Olaf Wolkenhauer

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Background: Our study aimed to identify common genes and potential targets across the four diseases, which include rheumatoid arthritis, melanoma metastasis, ulcerative colitis, and Crohn’s disease. We used a network and systems biology approach to identify the hub gene, which can act as a potential target for all four disease conditions. The regulatory network was extracted from the PPI using the MCODE module present in Cytoscape. Our objective was to investigate the significance of hub genes in these diseases using gene ontology and KEGG pathway enrichment analysis. Methods: Our methodology involved collecting disease gene-related information from DisGeNET databases and performing protein-protein interaction (PPI) network and core genes screening. We then conducted gene ontology and KEGG pathway enrichment analysis. Results: We found that IL6 plays a critical role in all disease conditions and in different pathways that can be associated with the development of all four diseases. Conclusions: The theoretical importance of our research is that we employed various systems and structural biology techniques to identify a crucial protein that could serve as a promising target for treating multiple diseases. Our data collection and analysis procedures involved rigorous scrutiny, ensuring high-quality results. Our conclusion is that IL6 plays a significant role in all four diseases, and it can act as a potential target for treating them. Our findings may have important implications for the development of novel therapeutic interventions for these diseases.

Keywords: melanoma metastasis, rheumatoid arthritis, inflammatory bowel diseases, integrated bioinformatics analysis

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Authors: Surbhi Aggarwal, Jaishree Paul

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Background: Role of GABA has been implicated in autoimmune diseases like multiple sclerosis, type1 diabetes and rheumatoid arthritis where they modulate the immune response but role in gut inflammation has not been defined. Ulcerative colitis (UC) and diarrhoeal predominant irritable bowel syndrome (IBS-D) both involve inflammation of gastrointestinal tract. UC is a chronic, relapsing and idiopathic inflammation of gut. IBS is a common functional gastrointestinal disorder characterised by abdominal pain, discomfort and alternating bowel habits. Mild inflammation is known to occur in IBS-D. Aim: Aim of this study was to investigate the role of GABA in UC as well as in IBS-D. Materials and methods: Blood and biopsy samples from UC, IBS-D and controls were collected. ELISA was used for measuring level of GABA in serum of UC, IBS-D and controls. RT-PCR analysis was done to determine GABAergic signal system in colon biopsy of UC, IBS-D and controls. RT-PCR was done to check the expression of proinflammatory cytokines. CurveExpert 1.4, Graphpad prism-6 software were used for data analysis. Statistical analysis was done by unpaired, two-way student`s t-test. All sets of data were represented as mean± SEM. A probability level of p < 0.05 was considered statistically significant. Results and conclusion: Significantly decreased level of GABA and altered GABAergic signal system was detected in UC and IBS-D as compared to controls. Significantly increased expression of proinflammatory cytokines was also determined in UC and IBS-D as compared to controls. Hence we conclude that insufficient level of GABA in UC and IBS-D leads to overproduction of proinflammatory cytokines which further contributes to inflammation. GABA may be used as a promising therapeutic target for treatment of gut inflammation or other inflammatory diseases.

Keywords: diarrheal predominant irritable bowel syndrome, γ-aminobutyric acid (GABA), inflammation, ulcerative colitis

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Authors: Chengcao Sun, Cuili Yang, Shujun Li, Ruilin Xue, Yongyong Xi, Liang Wang, Dejia Li

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Backgrounds: Inflammation is widely distributed in patients with Duchenne muscular dystrophy (DMD), and ultimately leads to progressive deterioration of muscle function with the co-effects of chronic muscle damage, oxidative stress, and reduced oxidative capacity. NF-E2-related factor 2 (Nrf2) plays a critical role in defending against inflammation in different tissues via activation of phase II enzymes, heme oxygenase-1 (HO-1). However, whether Nrf2/HO-1 pathway can attenuate muscle inflammation on DMD remains unknown. The purpose of this study was to determine the anti-inflammatory effects of Sulforaphane (SFN) on DMD. Methods: 4-week-old male mdx mice were treated with SFN by gavage (2 mg/kg body weight per day) for 4 weeks. Gastrocnemius, tibial anterior and triceps brachii muscles were collected for related analysis. Immune cell infiltration in skeletal muscles was analyzed by H&E staining and immuno-histochemistry. Moreover, the expressions of inflammatory cytokines,pro-inflammatory cytokines and Nrf2/HO-1 pathway were detected by western blot, qRT-PCR, immunohistochemistry and immunofluorescence assays. Results: Our results demonstrated that SFN treatment increased the expression of muscle phase II enzymes HO-1 in Nrf2 dependent manner. Inflammation in mdx skeletal muscles was reduced by SFN treatment as indicated by decreased immune cell infiltration and lower expressions of the inflammatory cytokines CD45, pro-inflammatory cytokines tumour necrosis factor-α and interleukin-6 in the skeletal muscles of mdx mice. Conclusions: Collectively, these results show that SFN can ameliorate muscle inflammation in mdx mice by Nrf2/HO-1 pathway, which indicates Nrf2/HO-1 pathway may represent a new therapeutic target for DMD.

Keywords: sulforaphane, Nrf2, HO-1, inflammation

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Authors: John Rothrock

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Background: The role of transthoracic echocardiography (TTE) in the diagnosis and management of patients with acute ischemic stroke remains controversial. While many stroke subspecialist reserve TTE for selected patients, others consider the procedure obligatory for most or all acute stroke patients. This study was undertaken to assess the cost vs. benefit of 'routine' TTE. Methods: We examined a consecutive series of patients who were admitted to a single institution in 2019 for acute ischemic stroke and underwent TTE. We sought to determine the frequency with which the results of TTE led to a new diagnosis of cardioembolism, redirected therapeutic cerebrovascular management, and at least potentially influenced the short or long-term clinical outcome. We recorded the direct cost associated with TTE. Results: There were 1076 patients in the study group, all of whom underwent TTE. TTE identified an unsuspected source of possible/probable cardioembolism in 62 patients (6%), confirmed an initially suspected source (primarily endocarditis) in an additional 13 (1%) and produced findings that stimulated subsequent testing diagnostic of possible/probable cardioembolism in 7 patients ( < 1%). TTE results potentially influenced the clinical outcome in a total of 48 patients (4%). With a total direct cost of $1.51 million, the mean cost per case wherein TTE results potentially influenced the clinical outcome in a positive manner was $31,375. Diagnostically and therapeutically, TTE was most beneficial in 67 patients under the age of 55 who presented with 'cryptogenic' stroke, identifying patent foramen ovale in 21 (31%); closure was performed in 19. Conclusions: The utility of TTE in the setting of acute ischemic stroke is modest, with its yield greatest in younger patients with cryptogenic stroke. Given the greater sensitivity of transesophageal echocardiography in detecting PFO and evaluating the aortic arch, TTE’s role in stroke diagnosis would appear to be limited.

Keywords: cardioembolic, cost-benefit, stroke, TTE

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Authors: Asma Mosbah, Hanane Khither, Kamelia Mosbah, Noreddine Kacem Chaouche, Mustapha Benboubetra

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In the present investigation, total oil (TO) and its neutral lipid fraction (NLF) extracted from the seed of the well know studied medicinal plant Nigella sativa were tested for their therapeutically effect on alcohol-induced liver injury in rat model. Male Albino rats were divided into five groups of eight animals each and fed a Lieber–DeCarli liquid diet containing 5% ethanol for experimental groups and dextran for control group, for a period of six weeks. Afterwards, rats received, orally, treatments with Nigella sativa extracts (TO, NLF) and N- acetylcysteine (NAC) as a positive control for four weeks. Activities of antioxidant enzymes; superoxide dismutase (SOD) and catalase (CAT), as well as malondialdehyde (MDA) and reduced glutathione (GSH). Biochemical parameters for kidney and liver functions, in treated and non treated rats, were evaluated throughout the time course of an experiment. Liver histological changes were taken into account. Enzymatic activities of both SOD and CAT increased significantly in rats treated with NLF and TO. While MDA level decreased in TO and NLF treated rats, GSH level increased significantly in TO and NLF treated rats. We noted equally a decrease in liver enzymes AST, ALT, and ALP. Microscopic observation of slides from the liver of ethanol treated rats showed a severe hepatotoxicity with lesions. Treatment with fractions leads to an improvement in liver lesions and a marked reduction in necrosis and infiltration. As a conclusion, both extracts of Nigella sativa seeds, TO and NLF, possess an important therapeutic protective potential against ethanol-induced hepatotoxicity in rats.

Keywords: alcohol-induced hepatotoxicity, antioxidant enzymes, Nigella sativa seeds, oil fractions

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Authors: Helga Martins, Idália Matias

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Background: Dementia is an important research topic since that life expectancy worldwide is increasing, so people are getting older. The aging of populations has a major impact on the increase in dementia, and nurses play a major role in taking care of these patients. Therefore, the implementation of nursing interventions based on evidence is vital so that we are aware of what we can do in clinical practice in order to provide patient cantered care to patients with dementia. Aim: To identify the nurse´s interventions in patients with dementia during clinical practice. Method: Literature review grounded on an electronic search in the EBSCOhost platform (CINAHL Plus with Full Text, MEDLINE with Full Text, and Nursing & Allied Health Collection), using the search terms of "dementia" AND "nurs*" AND “interventions” in the abstracts. The inclusion criteria were: original papers published up to June 2021. A total of 153 results after de duplicate removal we kept 104. After the application of the inclusion criteria, we included 15 studies This literature review was performed by two independent researchers. Results: A total of 15 results about nurses’ interventions in patients with dementia were included in the study. The major interventions are therapeutic communication strategies, environmental management of stressors involving family/caregivers; strategies to promote patient safety, and assistance in activities of daily living in patients who are clinically deteriorated. Conclusion: Taking care of people with dementia is a complex and demanding task. Nurses are required to have a set of skills and competences in order to provide nursing interventions. We highlight that is necessary an awareness in nursing education regarding providing nursing care to patients with dementia.

Keywords: dementia, interventions, nursing, review

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Authors: Igna Brajevic-Gizdic, Magda Pletikosa Pavić

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Introduction: Research in opiate addiction is increasingly indicating the importance of substitution therapy in opiate addicts. Opiate addiction is a chronic relapsing disease that includes craving as a criterion. Craving has been considered a predictor of a relapse, which is defined as a strong desire with an excessive need to take a substance. The study aimed to measure the intensity of craving using the VAS (visual analog scale) in opioid addicts taking Opioid Substitution Therapy (OST). Method: The total sample compromised of 30 participants in outpatient treatment. Two groups of opiate addicts were considered: Methadone-maintenance and buprenorphine-maintenance addicts. The participants completed the survey questionnaire during the outpatient treatment. Results: The results indicated high levels of cravings in patients during the treatment of OST, which is considered an important destabilization factor in abstinence. Thus, the use of methadone/buprenorphine dose should be considered. Conclusion: These findings provided an objective measurement of methadone /buprenorphine dosage and therapy options. The underdoes of OST can put patients at high risk of relapse, resulting in high levels of craving. Thus, when determining the therapeutic dose of OST, it is crucial to consider patients' cravings. This would achieve stabilization more quickly and avoid relapse in abstinence. Subjective physician assessment and patients' statement are the main criteria to determine OST dosage. Future studies should use larger sample sizes and focus on the importance of intensity craving measurement on OST to objectify methadone /buprenorphine dosage.

Keywords: buprenorphine, craving, heroin addicts, methadone, OST

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Authors: Muhammad Muzamil Khan, Asadullah Madni, Nina Filipczek, Jiayi Pan, Nayab Tahir, Hassan Shah, Vladimir Torchilin

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Lipid-polymer hybrid nanoparticles (LPHNP) are delivery systems for controlled drug delivery at tumor sites. The superior biocompatible properties of lipid and structural advantages of polymer can be obtained via this system for controlled drug delivery. In the present study, cisplatin-loaded lipid-chitosan hybrid nanoparticles were formulated by the single step ionic gelation method based on ionic interaction of positively charged chitosan and negatively charged lipid. Formulations with various chitosan to lipid ratio were investigated to obtain the optimal particle size, encapsulation efficiency, and controlled release pattern. Transmission electron microscope and dynamic light scattering analysis demonstrated a size range of 181-245 nm and a zeta potential range of 20-30 mV. Compatibility among the components and the stability of formulation were demonstrated with FTIR analysis and thermal studies, respectively. The therapeutic efficacy and cellular interaction of cisplatin-loaded LPHNP were investigated using in vitro cell-based assays in A2780/ADR ovarian carcinoma cell line. Additionally, the cisplatin loaded LPHNP exhibited a low toxicity profile in rats. The in-vivo pharmacokinetics study also proved a controlled delivery of cisplatin with enhanced mean residual time and half-life. Our studies suggested that the cisplatin-loaded LPHNP being a promising platform for controlled delivery of cisplatin in cancer therapy.

Keywords: cisplatin, lipid-polymer hybrid nanoparticle, chitosan, in vitro cell line study

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Authors: Anusha Sajjad, Sibtain Kazmi, Sadaf Sajjad, Ali Mohsin

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Shia Muslims, a distinct minority within the broader Muslim community, have a unique mourning practice set that remains underexplored in research. These practices hold cultural and religious significance and are essential to Shia spirituality. This study seeks to delve into the emotional and psychological dimensions of Shia Muslims' mourning rituals, specifically investigating how these practices serve as coping strategies during times of grief and adversity. The motivation for this research stems from a gap in understanding the psycho-spiritual aspects of Shia mourning, with a focus on the potential therapeutic value of these practices for individuals experiencing daily life stressors. This qualitative investigation employs an online survey conducted in September 2023 as the primary research method. Data was collected from a sample of 49 Shia Muslims who have actively participated in mourning rituals. Pearson's correlation test was applied to assess the relationship between participants’ reported feelings of mentally feeling ‘Lighter or Heavier' and their 'Coping' responses. Pearson's correlation analysis revealed a positive but relatively weak correlation between 'Mentally Feeling Lighter' and 'Coping' (r = 0.303) with a statistically significant p-value of 0.034. The findings suggest that there is a statistically significant positive correlation between feeling "Mentally Lighter" and coping, as reported by participants in Shia mourning rituals, although the strength of this correlation is relatively weak. This implies that individuals who feel "Mentally Lighter" are more likely to report coping effectively, but other factors likely contribute to the overall coping strategies employed by participants in this context. Further research with a larger sample size would be needed to strengthen this correlation further.

Keywords: shia, mourning, religion, coping

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Authors: N. F. Hamid, A. Kipar, J. Stewart, D. J. Antoine, B. K. Park, D. P. Williams

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Acetaminophen (APAP) is a widely used analgesic that is safe at therapeutic doses. The mouse model of APAP has been extensively used for studies on pathogenesis and intervention of drug induced liver injury based on the CytP450 mediated formation of N-acetyl-p-benzo-quinoneimine and, more recently, as model for mechanism based biomarkers. Delay of the fasted CD1 mice to rebound to the basal level of hepatic GSH compare to fed mice is reported in this study. Histologically, 15 hours fasted mice prior to APAP treatment leading to overall more intense cell loss with no evidence of apoptosis as compared to non-fasted mice, where the apoptotic cells were clearly seen on cleaved caspase-3 immunostaining. After 15 hours post APAP administration, hepatocytes underwent stage of recovery with evidence of mitotic figures in fed mice and return to completely no histological difference to control at 24 hours. On the contrary, the evidence of ongoing cells damage and inflammatory cells infiltration are still present on fasted mice until the end of the study. To further measure the regenerative capacity of the hepatocytes, the inflammatory mediators of cytokines that involved in the progression or regression of the toxicity like TNF-α and IL-6 in liver and spleen using RT-qPCR were also included. Yet, quantification of proliferating cell nuclear antigen (PCNA) has demonstrated the time for hepatic regenerative in fasted is longer than that to fed mice. Together, these data would probably confirm that fasting prior to APAP treatment does not only modulate liver injury, but could have further effects to delay subsequent regeneration of the hepatocytes.

Keywords: acetaminophen, liver, proliferating cell nuclear antigen, regeneration, apoptosis

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Authors: Yi-Hui Lai, Chih-Hsiang Yang, Li-Chung Hsu

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The inflammasome is a protein complex that modulates caspase-1 activity, resulting in proteolytic cleavage of proinflammatory cytokines such as IL-1β and IL-18, into their bioactive forms. It has been shown that the inflammasomes play a crucial role in the clearance of pathogenic infection and tissue repair. However, dysregulated inflammasome activation contributes to a wide range of human diseases such as cancers and auto-inflammatory diseases. Yet, regulation of NLRP3 inflammasome activation remains largely unknown. We discovered a novel DEAD box protein, whose biological function has not been reported, not only negatively regulates NLRP3 inflammasome activation by interfering NLRP3 inflammasome assembly and cellular localization but also mitigate pyroptosis upon pathogen evasion. The DEAD-box protein is the first DEAD-box protein gets involved in modulation of the inflammasome activation. In our study, we found that caspase-1 activation and mature IL-1β production were largely enhanced upon LPS challenge in the DEAD box-containing protein- deleted THP-1 macrophages and bone marrow-derived macrophages (BMDMs). In addition, this DEAD box-containing protein migrates from the nucleus to the cytoplasm upon LPS stimulation, which is required for its inhibitory role in NLRP3 inflammasome activation. The DEAD box-containing protein specifically interacted with the LRR motif of NLRP3 via its DEAD domain. Furthermore, due to the crucial role of the NLRP3 LRR domain in the recruitment of NLRP3 to mitochondria and binding to its adaptor ASC, we found that the interaction of NLRP3 and ASC was downregulated in the presence of the DEAD box-containing protein. In addition to the mechanical study, we also found that this DEAD box protein protects host cells from inflammasome-triggered cell death in response to broad-ranging pathogens such as Candida albicans, Streptococcus pneumoniae, etc., involved in nosocomial infections and severe fever shock. Collectively, our results suggest that this novel DEAD box molecule might be a key therapeutic strategy for various infectious diseases.

Keywords: inflammasome, inflammation, innate immunity, pyroptosis

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Authors: Gyati Shilakari Asthana, Abhay Asthana, Dharm Veer Kohli, Suresh Prasad Vyas

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Purpose: The therapeutic potential of oligonucleotide (ODN) is primarily dependent upon its safe and efficient delivery to specific cells overcoming degradation and maximizing cellular uptake in vivo. The present study is focused to design low molecular weight chitosan nanoconstructs to meet the requirements of safe and effectual delivery of ODNs. LMW-chitosan is a biodegradable, water soluble, biocompatible polymer and is useful as a non-viral vector for gene delivery due to its better stability in water. Methods: LMW chitosan ODN nanoparticles (CHODN NPs) were formulated by self-assembled method using various N/P ratios (moles ratio of amine groups of CH to phosphate moieties of ODNs; 0.5:1, 1:1, 3:1, 5:1, and 7:1) of CH to ODN. The developed CHODN NPs were evaluated with respect to gel retardation assay, particle size, zeta potential and cytotoxicity and transfection efficiency. Results: Complete complexation of CH/ODN was achieved at the charge ratio of 0.5:1 or above and CHODN NPs displayed resistance against DNase I. On increasing the N/P ratio of CH/ODN, the particle size of the NPs decreased whereas zeta potential (ZV) value increased. No significant toxicity was observed at all CH concentrations. The transfection efficiency was increased on increasing N/P ratio from 1:1 to 3:1, whereas it was decreased with further increment in N/P ratio upto 7:1. Maximum transfection of CHODN NPs with both the cell lines (Raw 267.4 cells and Hela cells) was achieved at N/P ratio of 3:1. The results suggest that transfection efficiency of CHODN NPs is dependent on N/P ratio. Conclusion: Thus the present study states that LMW chitosan nanoparticulate carriers would be acceptable choice to improve transfection efficiency in vitro as well as in vivo delivery of oligonucleotide.

Keywords: LMW-chitosan, chitosan nanoparticles, biocompatibility, cytotoxicity study, transfection efficiency, oligonucleotide

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Authors: N. Rajendra Prasad

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Resveratrol (RSV), a grape phytochemical, has drawn greater attention because of its beneficial ef-fects against cancer. However, RSV has some draw-backs such as unstabilization, poor water solubility and short biological half time, which limit the utili-zation of RSV in medicine, food and pharmaceutical industries. In this study, we have encapsulated RSV in gelatin nanoparticles (GNPs) and studied its anti-cancer efficacy in NCI-H460 lung cancer cells. SEM and DLS studies have revealed that the prepared RSV-GNPs possess spherical shape with a mean diameter of 294 nm. The successful encapsulation of RSV in GNPs has been achieved by the cross-linker glutaraldehyde probably through Schiff base reaction and hydrogen bond interaction. Spectrophotometric analysis revealed that the max-imum of 93.6% of RSV has been entrapped in GNPs. In vitro drug release kinetics indicated that there was an initial burst release followed by a slow and sustained release of RSV from GNPs. The prepared RSV-GNPs exhibited very rapid and more efficient cellular uptake than free RSV. Further, RSV-GNPs treatment showed greater antiproliferative efficacy than free RSV treatment in NCI-H460 cells. It has been found that greater ROS generation, DNA damage and apoptotic incidence in RSV-GNPs treated cells than free RSV treatment. Erythrocyte aggregation assay showed that the prepared RSV-GNPs formulation elicit no toxic response. HPLC analysis revealed that RSV-GNPs was more bioavailable and had a longer half-life than free RSV. Hence, GNPs carrier system might be a promising mode for controlled delivery and for improved therapeutic index of poorly water soluble RSV.

Keywords: resveratrol, coacervation, anticancer gelatin nanoparticles, lung cancer, controlled release

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Authors: Sreeparna Majee, G. C. Shit

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A study on targeted drug delivery is carried out in an unsteady flow of blood infused with magnetic NPs (nanoparticles) with an aim to understand the flow pattern and nanoparticle aggregation in a diseased arterial segment having stenosis. The magnetic NPs are supervised by the magnetic field which is significant for therapeutic treatment of arterial diseases, tumor and cancer cells and removing blood clots. Coupled thermal energy have also been analyzed by considering dissipation of energy because of the application of the magnetic field and the viscosity of blood. Simulation technique used to solve the mathematical model is vorticity-stream function formulations in the diseased artery. An elevation in SLP (Specific loss power) is noted in the aortic bloodstream when the agglomeration of nanoparticles is higher. This phenomenon has potential application in the treatment of hyperthermia. The study focuses on the lowering of WSS (Wall Shear Stress) with increasing particle concentration at the downstream of the stenosis which depicts the vigorous flow circulation zone. These low shear stress regions prolong the residing time of the nanoparticles carrying drugs which soaks up the LDL (Low Density Lipoprotein) deposition. Moreover, an increase in NP concentration enhances the Nusselt number which marks the increase of heat transfer from the arterial wall to the surrounding tissues to destroy tumor and cancer cells without affecting the healthy cells. The results have a significant influence in the study of medicine, to treat arterial diseases such as atherosclerosis without the need for surgery which can minimize the expenditures on cardiovascular treatments.

Keywords: magnetic nanoparticles, blood flow, atherosclerosis, hyperthermia

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Authors: Ana Lucia Molina

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Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique for the investigation and modulation of cortical excitability in humans. The modulation of the processing of different cortical areas can result in several areas for rehabilitation, showing great potential in the treatment of motor disorders. In the human brain, the supplementary motor area (SMA) is involved in the control of the pelvic floor muscles (MAP), where dysfunctions of these muscles can lead to urinary incontinence. Peripheral magnetic stimulation, specifically sacral magnetic stimulation, has been used as a safe and effective treatment option for patients with lower urinary tract dysfunction. A systematic literature review was carried out (Pubmed, Medline and Google academic database) without a time limit using the keywords: "transcranial magnetic stimulation", "sacral neuromodulation", and "urinary incontinence", where 11 articles attended to the inclusion criteria. Results: Thirteen articles were selected. Magnetic stimulation is a non-invasive neuromodulation technique widely used in the evaluation of cortical areas and their respective peripheral areas, as well as in the treatment of lesions of brain origin. With regard to pelvic-perineal disorders, repetitive transcranial stimulation showed significant effects in controlling urinary incontinence, as well as sacral peripheral magnetic stimulation, in addition to exerting the potential to restore bladder sphincter function. Conclusion: Data from the literature suggest that both transcranial stimulation and peripheral stimulation are non-invasive references that can be promising and effective means of treatment in pelvic and perineal disorders. More prospective and randomized studies on a larger scale are needed, adapting the most appropriate and resolving parameters.

Keywords: urinary incontinence, non-invasive neuromodulation, sacral neuromodulation, transcranial magnetic stimulation.

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Authors: Agung A. Ginanjar, Lilitasari, Indra Prasetya, Rizal R. Hanif, Yusrina Rismandini, Atina Hussaana, Nurita P. Sari

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Hyperlipidemia is an increase of lipids and cholesterol in the blood that causes the formation of atherosklerosis. The recent pharmacological therapy nowadays is statin. Many Indonesian people use of medicinal plants. There are several medical plants that people always use to cure hyperlipidemia such as bulbs onion sabrang, areca nuts, and seed of fenugreek. Most people often use a combination therapy of conventional medicine and herbs to achieve the desired therapeutic effect of combination therapy. The use of combination therapy might cause the interaction of pharmacodynamic from those medicines so that it influences the pharmacological effect of one of medicine. The aim of this study is to know the interaction of simvastatin and a cholesterol-lowering herb seen in rats pharmacodynamic simvastatin phase. This research used post-test only controlled group design. Analysis of statistical data normality and homogenity were tested by Kolmogorov Smirnov. The ANOVA test is used when the data is obtained homogeneous but if it is found that the data are not homogeneous then kruskal-wallis test is used. Normal (63.196 mg/dl), negative (70.604 mg/dl), positive (62.512 mg/dl), areca nuts (56.564 mg/dl), fenugreek seed (47.538 ,g/dl), onion sabrang (62.312 mg/dl). The results prove that the combination of herbs and simvastatin did not have a significant difference (P>0,05). The conclusion of this study is that the combination of simvastatin and a cholesterol-lowering herb can cause some pharmacodynamic interactions such as a synergistic effect, antagonist, and a powerful additive, so that combination therapy is not more effective than single simvastatin therapy. The use of the combination therapy is not given in the same time. It would be better if there are some period of time when the combination therapy is applied.

Keywords: onion bulb sabrang, areca nuts, seed of fenugreek, interaction medicine, hyperlipidemia

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Authors: José Nogueira

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This research aims to analyze the impact of autism spectrum disorders (ASD) in families with children and youth (0-25 years) with ASD in Portugal. The impact will be evaluated on a multidimensional perspective, following the work on the concept of quality life from WHOQOL Group (UN). The study includes quantitative and qualitative methodology. It correlates statistical sources and other information with the data obtained through a survey of a sample of about 100 families with children/youth with ASD (October and November 2013). The results indicate a strong impact of autism on the quality of life for families in all study dimensions. The research shows a negative impact on quality of life for families in material and financial conditions, physical and emotional well-being, career progression, feelings of injustice, social participation and self-perception of happiness. The quality of life remained in the relationship with the family and the spouse, interpersonal relationships and beliefs about himself. The ASD improved the quality of life aspects such as interest, knowledge and exercise of rights on disability, autonomy to make decisions and be able to deal with stress. Other dimensions are contemplated: a detailed characterization of the child/young with ASD and all family members (household composition, relationship status, academic qualifications, occupation, income, and leisure) the impact of diagnosis in the family wellbeing, medical and therapeutic processes, school inclusion, public support, social participation, and the adequacy and implementation of legislation. The study evaluates also the strengths and weaknesses of the Portuguese public rehabilitation system and demonstrates how a good law-in-theory may not solve the problems of families in practice due to the allocation of insufficient public resources, both financial and human resources.

Keywords: autism, families, quality of life, autism spectrum disorder

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Authors: Choumous Mannoubi, Dahlia Kairy, Brigitte Vachon

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The use of technology allows clinicians to provide an individualized approach in a cost-effective manner and to reach a broader client base more easily. Such interventions can be effective in ensuring self-management and follow-up of people with diabetes, reducing the risk of complications by improving accessibility to care services, and better adherence to health recommendations. Consideration of users' opinions and fears to inform the design and implementation stages of these telehealth services seems to be essential to improve their acceptance and usability. The objective of this study is to describe the telepractice of nutritionists supporting the therapeutic management of diabetic patients and document the functional requirements of nutritionists for the design of a tele-nutrition platform. To best identify the requirements and constraints of nutritionists, we conducted individual semi-structured interviews with 10 nutritionists who offered tele-nutrition services. Using a qualitative design with a descriptive approach based on the Nutrition Care Process Model (mNCP) framework, we explored in depth the state of nutritionists' telepractice in public and private health care settings, as well as their requirements for teleconsultation. Qualitative analyses revealed that nutritionists primarily used telephone calls during the COVID 19 pandemic to provide teleconsultations. Nutritionists identified the following important features for the design of a tele-nutrition platform: it should support interprofessional collaboration, allow for the development and monitoring of a care plan, integrate with the existing IT environment, be easy to use, accommodate different levels of patient literacy, and allow for easy sharing of educational materials to support nutrition education.

Keywords: telehealth, nutrition, diabetes, telenutrition, teleconsultation, telemonitoring

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Authors: Swanand Pathak, Kiran R. Giri, Reena R. Giri, Kamlesh Palandurkar, Sangita Totade, Rajesh Jha, S. S. Patel

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Background: Population burden, illiteracy, availability of few doctors for larger group of population leads to many unanswered questions left in a patient’s mind. Incomplete information results into noncompliance, therapeutic failure, and adverse drug reactions (ADR). It is very important to establish a system which will provide noncommercial, independent, unbiased source of medicine information. Medicines Info OPD is a concept and step towards safe and appropriate use of medicines. Objective: (1) to assess the present status of knowledge about the medicines in the patients and its correlation with education; (2) to assess the medicine information dispensing modalities, their use and sufficiency from the patients view point; (3) to assess the overall need for Medicines Information OPD in present scenario. Materials and Methods: A pre-validated questionnaire based study was conducted amongst 500 patients of tertiary health care hospital. The questionnaire consisted of specific questions regarding understanding of prescription, knowledge about adverse drug reaction, view about self-medication and opinion regarding the need of Medicines Info OPD. Results: Significantly large proportion of patients opined that doctors do not have sufficient time in current Indian healthcare to explain the prescription and they are not aware of adverse drug reactions, expiry date or use the package inserts etc. Conclusion: Clinically relevant, up to date, user specific, independent, objective and unbiased Medicines Info OPD is essential for appropriate drug use and can help in a big way to common public to address many problems faced by them.

Keywords: information, prescription, unbiased, clinically relevant

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Authors: Dileep G., Akash Singh, Dalchand Ahirwar, Arkadeep Ghosh, Ashutosh Purohit, Gaurav Guleria, Kshatriya Om Prashant, Pushkar Patel, Saksham Kumar, Vanshaj Nathani, Vikas Dangi, Shubhajit Roy Chowdhury, Varun Dutt

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Transcranial direct current stimulation (tDCS) has shown promise as a novel approach to enhance cognitive performance and provide therapeutic benefits for various brain disorders. However, the exact underlying brain mechanisms are not fully understood. We conducted a study to examine the brain's functional changes when subjected to simultaneous tDCS and music (Indian classical raga). During the study, participants in the experimental group underwent a 20-minute session of tDCS at two mA while listening to music (raga) for a duration of seven days. In contrast, the control group received a sham stimulation for two minutes at two mA over the same seven-day period. The objective was to examine whether repetitive tDCS could lead to the formation of additional functional connections between the medial prefrontal cortex (the stimulated area) and the auditory cortex in comparison to a sham stimulation group. In this study, 26 participants (5 female) underwent pre- and post-intervention scans, where changes were compared after one week of either tDCS or sham stimulation in conjunction with music. The study revealed significant effects of tDCS on functional connectivity between the stimulated area and the auditory cortex. The combination of tDCS applied over the mPFC and music resulted in newly formed connections. Based on our findings, it can be inferred that applying anodal tDCS over the mPFC enhances functional connectivity between the stimulated area and the auditory cortex when compared to the effects observed with sham stimulation.

Keywords: fNIRS, tDCS, neuroplasticity, music

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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: Dan Yan, Yunuo Zhang, Yuhan Huang, Weijie Ouyang

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The cornea serves as a vital protective barrier for the eye; however, it is prone to injury and damage that can disrupt corneal epithelium and nerves, triggering inflammation. Therefore, understanding the biological effects and molecular mechanisms involved in corneal wound healing and identifying drugs targeting these pathways is crucial for researchers in this field. This study aimed to investigate the therapeutic potential of progranulin (PGRN) in treating corneal injuries. Our findings demonstrated that PGRN significantly enhanced corneal wound repair by accelerating corneal re-epithelialization and re-innervation. In vitro experiments with cultured epithelial cells and trigeminal ganglion cells further revealed that PGRN stimulated corneal epithelial cell proliferation and promoted axon growth in trigeminal ganglion cells. Through RNA-sequencing (RNA-seq) analysis and other experimental techniques, we discovered that PGRN exerted its healing effects by modulating the Wnt signaling pathway, which played a critical role in repairing epithelial cells and promoting axon regeneration in trigeminal neurons. Importantly, our study highlighted the anti-inflammatory properties of PGRN by inhibiting the NF-κB signaling pathway, leading to decreased infiltration of macrophages. In conclusion, our findings underscored the potential of PGRN in facilitating corneal wound healing by promoting corneal epithelial cell proliferation, trigeminal ganglion cell axon regeneration, and suppressing ocular inflammation. These results suggest that PGRN could potentially expedite the healing process and improve visual outcomes in patients with corneal injuries.

Keywords: cornea, wound healing, progranulin, corneal epithelial cells, trigeminal ganglion cells

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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: 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: Min Bae

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Hygiene had traditionally meant ways of healthy and right living. However, the nineteenth century was the time when a gradual shift in medical and hygienic paradigms took place from holism to reductionism. Against this medical and social background, E. W. Lane (MD, Edinburgh, 1853) formulated his own medical philosophies in his book Hydropathy: Or Hygienic Medicine (1859). Until the 1880s when he published his last book on the hygienic medicine, he consistently intended to raise the importance of hygienic holism in medicine, while adopting hydropathy as his main therapeutic measure. Lane’s case reflects the mid-nineteenth century trend in which since the 1840s, the rational and holistic facets in medicine had significantly transferred to hydropathy, which was the most naturalistic healing system in the medical market. Hygiene for Lane was no longer the ancient form of ‘six non-naturals’. He emphasised physiology as the rational grounds for his project of the medicalisation of hygiene. His medical philosophy was profoundly naturalistic and holistic against the opposite trend of the contemporary hygiene and medicine. Conflicting aspects may often be best embodied in persons who stood on the boundaries between inside and outside. Lane’s theories on hygienic medicine did not develop into a new medical system which he believed would reconciliate orthodox medicine and hydropathy of his time had also adopted increasingly reductionist approaches since 1860s. Nevertheless, the naturalistic philosophies and approaches in Lane’s hygienic medicine demonstrates a continuous effort for a theoretical reformulation of hydropathy during its stagnant and declining period to constantly fit into the holistic paradigm of medicine and hygiene. Considering the fact that the nature cure concept in hydropathy and its individualistic approach were succeeded by naturopathy at the end of the century, analysis of Lane’s medical thoughts reveals part of a ‘thin red line’ of naturalism in the battleground between reductionism and holism during the nineteenth century in the history of medicine and hygiene.

Keywords: E. W. Lane, hygienic medicine, hydropathy, naturopath

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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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