Search results for: multi-drug therapies

Authors: Adel Dalilottojari, Bahman Delalat, Frances J. Harding, Michaelia P. Cockshell, Claudine S. Bonder, Nicolas H. Voelcker

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Endothelial Progenitor Cell (EPC) based therapies continue to be of interest to treat ischemic events based on their proven role to promote blood vessel formation and thus tissue re-vascularisation. Current strategies for the production of clinical-grade EPCs requires the in vitro isolation of EPCs from peripheral blood followed by cell expansion to provide sufficient quantities EPCs for cell therapy. This study aims to examine the use of different biomolecules to significantly improve the current strategy of EPC capture and expansion on collagen type I (Col I). In this study, four different biomolecules were immobilised on a surface and then investigated for their capacity to support EPC capture and proliferation. First, a cell microarray platform was fabricated by coating a glass surface with epoxy functional allyl glycidyl ether plasma polymer (AGEpp) to mediate biomolecule binding. The four candidate biomolecules tested were Col I, collagen type II (Col II), collagen type IV (Col IV) and vascular endothelial growth factor A (VEGF-A), which were arrayed on the epoxy-functionalised surface using a non-contact printer. The surrounding area between the printed biomolecules was passivated with polyethylene glycol-bisamine (A-PEG) to prevent non-specific cell attachment. EPCs were seeded onto the microarray platform and cell numbers quantified after 1 h (to determine capture) and 72 h (to determine proliferation). All of the extracellular matrix (ECM) biomolecules printed demonstrated an ability to capture EPCs within 1 h of cell seeding with Col II exhibiting the highest level of attachment when compared to the other biomolecules. Interestingly, Col IV exhibited the highest increase in EPC expansion after 72 h when compared to Col I, Col II and VEGF-A. These results provide information for significant improvement in the capture and expansion of human EPC for further application.

Keywords: biomolecules, cell microarray platform, cell therapy, endothelial progenitor cells, high throughput screening

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Authors: Simmi Chopra

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In the last few years, there has been a surge of Autoimmune diseases that have become more like an epidemic all over the world. The reasons vary from stress, insufficient sleep, smoking, genetics, environmental pollution, adulterated foods, and a diet full of “the deadly white,” which is white sugar and white flour. Most of the people diagnosed with these diseases are given steroids, opioids, supplements, or elimination diets to manage their lives, but most of them continue suffering to varying degrees. On the other hand, Ayurveda can help manage autoimmune problems effectively. Ayurveda is a 5000 years old holistic medical system from India that has an individualistic approach where health problems are looked at from the lens of balancing body and mind and by targeting the root cause of the problem. A combination of diet and lifestyle according to Ayurvedic principles, Ayurvedic herbal formulations and Ayurvedic therapies can help in the management of autoimmune and other chronic diseases. Panchkarma, which is an intense six weeks detox method, helps balance our body and mind, and has been very effective in managing autoimmune problems. The paper will introduce the basic concepts of Ayurveda and describe the terminologies- doshas, agni and ama. The paper will discuss the importance of diet and lifestyle according to the individual’s imbalance in the three functional parameters - doshas, which govern every aspect of our body and mind, our cells and tissues. The significance of agni, which can be correlated to digestive strength and ama, which can be correlated to toxins that are formed in our body leading to health problems, will be outlined. The Ayurvedic pathophysiology of autoimmune diseases will be discussed with emphasis on Rheumatoid arthritis, Multiple sclerosis and Psoriasis. Ayurvedic management will be discussed for these autoimmune conditions. As Ayurveda is an individualistic system, one protocol will not work for everyone. Therefore, case studies with Ayurvedic protocols for the above autoimmune disease will be presented. Conclusion: Ayurveda can help in managing as well as arresting the progression of autoimmune problems. Ayurveda is an ancient medical system, is much more needed today than ever. It is a tried and tested holistic system which has been practiced for the past many generations in India.

Keywords: ayurveda, autoimmune, diseases, nutrition

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Authors: Hossam M. Abdallah, Ali M. El-Halawany, Gamal A. Mohamed, Khalid Z. Alshali, Zainy M. Banjar, Hany A. El-Bassossy

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Hypertension and vascular dysfunction are major components and complications of many diseases like metabolic syndrome. In addition, vascular dysfunction is considered the initial step in diabetic atherosclerosis, the main etiology for mortality and a great percent of morbidity in diabetic patients. In spite of the significant developments in antidiabetic therapy, diabetic complications, particularly seen in long-term diabetes, continue to be seriously deleterious. Herbal drugs are prescribed widely in treatment of different aliment because of their effectiveness, fewer side effects and relatively low cost. Nine plants belong to five different families grown in Kingdom of Saudi Arabia were evaluated for their effect on exaggerated vasoconstriction and impaired relaxation in aortae isolated from metabolic syndrome rats. The aerial parts of Onopordum ambiguum Fresen. (OA), Astragalus abyssinicus Steud. (AA), Pulicaria Arabica Cass. (PA), Echinops sheilae Kit Tan (ES), Aizoon canariense L. (AC), Cleome viscosa L. (CV), Chrozophora oblongifolia (Delile) A.Juss. ex Spreng (CO), Centaurea pseudosinaica Mouterde (CP) and Tephrosia nubica Baker (TN) were dried and extracted with methanol. The effect of thirty minute incubation with the total extracts (10-330 µg/ml) or their fractions on the exaggerated vasoconstriction response to phenylephrine (10nM to 10microM) and impaired vasodilation to acetylcholine (10-330 µg /ml) of aortae isolated from metabolic syndrome animals was studied. Incubating aortae isolated from metabolic syndrome animals with total methanol extract of OA, AA, PA, AC, CV, and TN at concentrations (10-330 microgram/ml) in the organ bath led to concentration dependent alleviation of exaggerated vasoconstriction response to phenylephrine without having beneficial effect on impaired vasodilation to acetylcholine. In conclusion, addition of OA, AA, PA, AC, CV and TN to the standard therapies may provide superior means to alleviate the associated vascular complications.

Keywords: vascular dysfunction, exaggerated vasoconstriction, metabolic syndrome, Saudi plants

Procedia PDF Downloads 279

Authors: Nabiha Bouafia, Asma Ben Cheikh, Asma Ammar, Olfa Ezzi, Mohamed Mahjoub, Khaoula Meddeb, Imed Chouchene, Hamadi Boussarsar, Mansour Njah

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Background: Hospital acquired infections (HAI) cause significant morbidity, mortality, length of stay and hospital costs, especially in the intensive care unit (ICU), because of the debilitated immune systems of their patients and exposure to invasive devices. The aims of this study were to determine the rate and the risk factors of HAI in an ICU of a university hospital in Tunisia. Materials/Methods: A prospective study was conducted in the 8-bed adult medical ICU of a University Hospital (Sousse Tunisia) during 14 months from September 15th, 2015 to November 15th, 2016. Patients admitted for more than 48h were included. Their surveillance was stopped after the discharge from ICU or death. HAIs were defined according to standard Centers for Disease Control and Prevention criteria. Risk factors were analyzed by conditional stepwise logistic regression. The p-value of < 0.05 was considered significant. Results: During the study, 192 patients had admitted for more than 48 hours. Their mean age was 59.3± 18.20 years and 57.1% were male. Acute respiratory failure was the main reason of admission (72%). The mean SAPS II score calculated at admission was 32.5 ± 14 (range: 6 - 78). The exposure to the mechanical ventilation (MV) and the central venous catheter were observed in 169 (88 %) and 144 (75 %) patients, respectively. Seventy-three patients (38.02%) developed 94 HAIs. The incidence density of HAIs was 41.53 per 1000 patient day. Mortality rate in patients with HAIs was 65.8 %( n= 48). Regarding the type of infection, Ventilator Associated Pneumoniae (VAP) and central venous catheter Associated Infections (CVC AI) were the most frequent with Incidence density: 14.88/1000 days of MV for VAP and 20.02/1000 CVC days for CVC AI. There were 5 Peripheral Venous Catheter Associated Infections, 2 urinary tract infections, and 21 other HAIs. Gram-negative bacteria were the most common germs identified in HAIs: Multidrug resistant Acinetobacter Baumanii (45%) and Klebsiella pneumoniae (10.96%) were the most frequently isolated. Univariate analysis showed that transfer from another hospital department (p= 0.001), intubation (p < 10-4), tracheostomy (p < 10-4), age (p=0.028), grade of acute respiratory failure (p=0.01), duration of sedation (p < 10-4), number of CVC (p < 10-4), length of mechanical ventilation (p < 10-4) and length of stay (p < 10-4), were associated to high risk of HAIS in ICU. Multivariate analysis reveals that independent risk factors for HAIs are: transfer from another hospital department: OR=13.44, IC 95% [3.9, 44.2], p < 10-4, duration of sedation: OR= 1.18, IC 95% [1.049, 1.325], p=0.006, high number of CVC: OR=2.78, IC 95% [1.73, 4.487], p < 10-4, and length of stay in ICU: OR= 1.14, IC 95% [1.066,1.22], p < 10-4. Conclusion: Prevention of nosocomial infections in ICUs is a priority of health care systems all around the world. Yet, their control requires an understanding of epidemiological data collected in these units.

Keywords: healthcare associated infections, incidence, intensive care unit, risk factors

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Authors: C. Mayuren, C. K. Paul Wang, K. Purushotham, C. Dinesh Kumar

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Diabetes Mellitus (DM) is one of the most common non-communicable diseases globally. Although significant advances have led to better understanding of the condition and the development of effective therapies and preventive strategies, the pathway to cure remains elusive and DM prevails as a serious medical challenge in the 21st century. Oxidative stress has been suggested to contribute to the progression and pathophysiological conditions of diabetes. Madecassoside (MA) a major pentacyclic triterpenoid, has been demonstrated to possess various biological activities. However, no attempt has been made to study the antioxidant activity in diabetic rats. Therefore, the present study is aimed to evaluate the antioxidant effect of MA on streptozotocin-nicotinamide induced type-2 diabetes in Sprague-Dawley rats. The study protocol was approved by the institutional ethical committee prior to the conduct of research. Adult male Sprague-Dawley rats weighing 250-300 g were used in the study. The animals were rendered diabetic with a single intraperitoneal dose of streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg). The diabetic animals after a stabilisation period of 14 days received various treatments (Madecassoside 50 mg/kg; Glimepiride 2.5 mg/kg) suspended in 0.5% carboxymethyl cellulose orally, for a period of 28 days. The animals fasted overnight after the last treatment were sacrificed and the pancreas, liver and kidneys were isolated. The weighted quantity of the samples of various treatments were homogenised in ice-cold condition and were subjected to lipid peroxidation, catalase and superoxide dismutase assay. The data’s obtained were subjected to statistical analysis. Diabetic rats showed significant increase in lipid peroxidation and decrease in enzymatic antioxidant levels. All the treated groups had significantly higher SOD, CAT and reduced LPO activity in the pancreas, liver and kidney. Results suggest madecassoside to have potential antioxidant effect against the diabetic model. However further investigations are necessary to study the mechanism at the cellular level.

Keywords: antioxidant, diabetes, madecassoside, nicotinamide, streptozotocin

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Authors: Tong Ming Liu

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Human mesenchymal stem cells (MSCs) represent the most used stem cells for clinical application, which have been used in over 1000 clinical trials to treat over 30 diseases due to multilineage differentiation potential, secretome and immunosuppression. Gene therapies of MSCs hold great promise in the treatment of many diseases due to enhanced MSC-based clinical outcomes. To identify genes for gene therapy of MSCs, by comparing gene expression profile before and after MSC differentiation following by functional screening, we have identified ZNF145 that regulated MSC differentiation. Forced expression of ZNF145 resulted in enhanced in vitro chondrogenesis of MSCs as an upstream factor of SOX9 and improved osteochondral repair upon implant into osteochondral defects in rodents. By comparing gene expression profile during differentiation of iPSCs toward MSCs, we also identified gene HOX regulating MSC stemness, which was much downregulated in late-passaged MSCs. Knockdown of this gene greatly compromised MSC stemness including abolished proliferation, decreased CFU-F, promoted senescence and reduced expression of cell surface antigens linked to the MSC phenotype. In addition, multi-linage differentiation was also greatly impaired. Notably, HOX overexpression resulted in improved multi-lineage differentiation. In the mechanism, HOX expression significantly deceased in late passage of MSCs compared with early passage of MSCs, correlating with MSC important genes. ChIP-seq data shown that HOX binds to genes related to MSC self-renewal and differentiation. Most importantly, most HOX binding sites are lost in late passage of MSCs. HOX exerts its effects by directing binding Twist1, one important gene of MSCs. The identification of the genes regulating MSC differentiation and stemness will provide and promising strategies for gene therapy of MSCs in regenerative medicine.

Keywords: mesenchymal stem cell, novel transcription factor, stemness, gene therapy, cartilage repair, signaling pathway

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Authors: Syed Asif Hassan, Tabrej Khan

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Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

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Authors: Prerna Kalra, Surender Singh

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Cisplatin is the most common chemotherapeutic agent used in different solid tumors, but its main limiting factor is dose-dependent nephrotoxicity by generating reactive oxygen species, by stimulating inflammatory and apoptotic pathways. Additional adjuvant therapies to decrease the toxicity of this chemotherapeutic drug are essential. This study was designed to evaluate the protective role of Emblica officinalis Geartn (Indian gooseberry) against cisplatin induced nephrotoxicity. Emblica officinalis was orally administered to Wistar rats (n=6) for 10 days in 50, 100 and 200mg/kg body weight. On day 7, 8mg/kg of cisplatin was administered intra-peritoneally to rats in all groups. Serum creatinine, blood urea nitrogen and antioxidant levels were measured on day10. The renal damage was evaluated by histopathological and transmission electron microscopy. We found that 200mg/kg dose of Emblica officinalis significantly inhibited the elevation of biochemical parameters i.e. serum creatinine, blood urea nitrogen, oxidant stress marker (malondialdehyde) and increased the reduced levels of antioxidant marker (endogenous glutathione and superoxide dismutase). Cisplatin treated rats have shown acute tubular necrosis and infiltration of inflammatory cells in rat kidney which was reversed after treating the animals with Emblica officinalis in the treatment group. In ultrastructural changes cisplatin treated group showed the damaged mitochondria (M) with dissolved cristae and large number of lysosomes (L) and vacuole (V) formation in tubular epithelial cells. EOE administered group showed visible cristae formation and sign of autophagy vacuoles at a dose of 200mg/kg. Further in-silico studies revealed that ellagic acid is responsible for its nephroprotective effect. The above findings conclude that the Emblica officinalis may be used as an adjuvant therapy in cisplatin induced nephrotoxicity.

Keywords: antioxidant, cisplatin, Emblica officinalis, in silico, nephrotoxicity

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Authors: Tania Vasquez Mata, Luis A. Herrera, Cristian Arriaga Canon

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Background: Locally advanced breast cancer of the luminal B phenotype, poses challenges due to its variable response to neoadjuvant chemotherapy. A predictive biomarker is needed to identify patients who will not respond to treatment, allowing for alternative therapies. This study aims to validate the use of the lncRNA GATA3-AS1, as a predictive biomarker using RNA in situ hybridization. Research aim: The aim of this study is to determine if GATA3-AS1 can serve as a biomarker for resistance to neoadjuvant chemotherapy in patients with locally advanced luminal B breast cancer. Methodology: The study utilizes RNA in situ hybridization with predesigned probes for GATA3-AS1 on Formalin-Fixed Paraffin-Embedded tissue sections. The samples underwent pretreatment and protease treatment to enable probe penetration. Chromogenic detection and signal evaluation were performed using specific criteria. Findings: Patients who did not respond to neoadjuvant chemotherapy showed a 3+ score for GATA3-AS1, while those who had a complete response had a 1+ score. Theoretical importance: This study demonstrates the potential clinical utility of GATA3-AS1 as a biomarker for resistance to neoadjuvant chemotherapy. Identifying non-responders early on can help avoid unnecessary treatment and explore alternative therapy options. Data collection and analysis procedures: Tissue samples from patients with locally advanced luminal B breast cancer were collected and processed using RNA in situ hybridization. Signal evaluation was conducted under a microscope, and scoring was based on specific criteria. Questions addressed: Can GATA3-AS1 serve as a predictive biomarker for neoadjuvant chemotherapy response in locally advanced luminal B breast cancer? Conclusion: The lncRNA GATA3-AS1 can be used as a biomarker for resistance to neoadjuvant chemotherapy in patients with locally advanced luminal B breast cancer. Its identification through RNA in situ hybridization of tissue obtained from the initial biopsy can aid in treatment decision-making.

Keywords: biomarkers, breast neoplasms, genetics, neoadjuvant therapy, tumor

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Authors: Geraldine Landon, Enora Clero, Jean-Rene Jourdain

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In 2005, the Institut de Radioprotection et de Sûreté Nucléaire (IRSN, France) launched a research program named EPICE (acronym for 'Evaluation of Pathologies potentially Induced by CaEsium') to collect scientific information on non-cancer effects possibly induced by chronic exposures to low doses of ionizing radiation with the view of addressing a question raised by several French NGOs related to health consequences of the Chernobyl nuclear accident in children. The implementation of the program was preceded by a pilot phase to ensure that the project would be feasible and determine the conditions for implementing an epidemiological study on a population of several thousand children. The EPICE program focused on childhood cardiac arrhythmias started in May 2009 for 4 years, in partnership with the Russian Bryansk Diagnostic Center. The purpose of this cross-sectional study was to determine the prevalence of cardiac arrhythmias in the Bryansk oblast (depending on the contamination of the territory and the caesium-137 whole-body burden) and to assess whether caesium-137 was or not a factor associated with the onset of cardiac arrhythmias. To address these questions, a study bringing together 18 152 children aged 2 to 18 years was initiated; each child received three medical examinations (ECG, echocardiography, and caesium-137 whole-body activity measurement) and some of them were given with a 24-hour Holter monitoring and blood tests. The findings of the study, currently submitted to an international journal justifying that no results can be given at this step, allow us to answer clearly to the issue of radiation-induced childhood arrhythmia, a subject that has been debated for many years. Our results will be certainly helpful for health professionals responsible for the monitoring of population exposed to the releases from the Fukushima Dai-ichi nuclear power plant and also useful for future comparative study in children exposed to ionizing radiation in other contexts, such as cancer radiation therapies.

Keywords: Caesium-137, cardiac arrhythmia, Chernobyl, children

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Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

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Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

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Authors: Remya Radhakrishnan, Hema Perinbanathan, Anukriti Rath, Reshmi Ramachandran, Rohith Thazhathuvetil Sasindrababu, Maria Karizhenskaia

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Childhood adversities have lasting effects on health and well-being. This abstract explores the connection between adverse childhood experiences (ACEs) and health consequences, including substance abuse and obesity. Understanding the impact of childhood trauma and emphasizing the importance of culturally sensitive treatments and focused interventions help to mitigate these effects. Research consistently shows a strong link between ACEs and poor health outcomes. Our team conducted a comprehensive literature review of depression and anxiety in Canadian children and youth, exploring diverse treatment methods, including medical, psychotherapy, and alternative therapies like art and music therapy. We searched Medline, Google Scholar, and St. Lawrence College Library. Only original research papers, published between 2012 and 2023, peer-reviewed, and reporting on childhood adversities on health and its treatment methods in children and youth in Canada were considered. We focused on their significance in treating depression and anxiety. According to the study's findings, the prevalence of adverse childhood experiences (ACEs) is still a significant concern. In Canada, 40% of people report having had multiple ACEs, and 78% report having had at least one ACE, highlighting the persistence of childhood adversity and indicating that the issue is unlikely to fade off in the near future. Likewise, findings revealed that individuals who experienced abuse, neglect, or violence during childhood are likelier to engage in harmful behaviors like polydrug use, suicidal ideation, and victimization and suffer from mental health problems such as depression and post-traumatic stress disorder (PTSD).

Keywords: adverse childhood experiences (ACEs), obesity, post-traumatic stress disorder (PTSD), resilience, substance abuse, trauma-informed care

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Authors: Yusuf E. Mustapha, Inioluwa A Akindoyeni, Oluwatoyin G. Ezekiel, Ifeoluwa O. Awogbindin, Ebenezer O. Farombi

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Background: Parkinson's disease (PD) is the most prevalent motor disorder. Available therapies are palliative with no effect on disease progression. Kolaviron (KV), a natural anti-inflammatory and antioxidant agent, has been reported to possess neuroprotective effects in Parkinsonian flies and rats. Objective: The present study investigates the neuroprotective effect of KV, focusing on the DJ1/Nrf2 signaling pathway. Methodology: All-trans retinoic acid (ATRA, 10 mg/kg, i.p.) was used to inhibit Nrf2. Murine model of PD was established with four doses of MPTP (20 mg/kg i.p.) at 2 hours interval. MPTP mice were pre-treated with either KV (200 mg/kg/day p.o), ATRA, or both conditions for seven days before PD induction. Motor behaviour was evaluated, and markers of oxidative stress/damage and its regulators were assessed with immunofluorescence and ELISA techniques. Results: MPTP-treated mice covered less distance with reduced numbers of anticlockwise rotations, heightened freezing, and prolonged immobility when compared to control. However, KV significantly attenuated these deficits. Pretreatment of MPTP mice with KV upregulated Nrf2 expression beyond MPTP level with a remarkable reduction in Keap1 expression and marked elevation of DJ-1 level, whereas co-administration with ATRA abrogated these effects. KV treatment restored MPTP-mediated depletion of endogenous antioxidant, striatal oxidative stress, oxidative damage, and inhibition of acetylcholinesterase activity. However, ATRA treatment potentiated acetylcholinesterase inhibition and attenuated the protective effect of KV on the level of nitric oxide and activities of catalase and superoxide dismutase. Conclusion: Kolaviron protects Parkinsonian mice by stabilizing and activating the Nrf2 signaling pathway. Thus, kolaviron can be explored as a pharmacological lead in PD management.

Keywords: Garcinia kola, Kolaviron, Parkinson Disease, Nrf2, behavioral incompetence, neurodegeneration

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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: Duane Booysen, Ashraf Kagee

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There is a high prevalence of violent crime and trauma exposure in South African society. Considering the prevalence of continuous violent crimes and traumatization in South Africa, the public mental health sector is required to combat the burgeoning effect of traumatic stress in South Africa. Trauma counselors, especially, provide important mental health services at primary health care to persons affected by traumatic events. Therefore, the evaluation and implementation of evidence-based trauma therapies is essential at a primary health care level in treating traumatic stress. A single-case design was used to evaluate the treatment effect of a Brief Trauma Treatment Programme treating persons who present with symptoms of posttraumatic stress disorder at a primary care trauma centre in Cape Town, South Africa. The sample consisted of six adult participants who presented with symptoms of posttraumatic stress and were assessed at baseline, during treatment, post-intervention and at 3-month follow. All participants received six sessions of trauma therapy. Assessment measures included the posttraumatic stress disorder symptom scale interviews for Diagnostic and Statistical Manual fifth edition (DSM5), the posttraumatic disorder checklist for DSM5, Beck Depression Inventory and Beck Anxiety Inventory. Results demonstrate that participants had noticeable reduced symptoms for traumatic stress, anxiety and depression despite living in contexts of violent crime and trauma. In conclusion, the article critically reflects on the need to evaluate and implement evidence-based treatments for the South African context, and how evidence-based treatments are used in developing socio-economic and cultural diverse contexts with continuous levels of violence and traumatization.

Keywords: psychological interventions, public mental health, traumatic stress, single-case design

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Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.

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Authors: Z. Kolacinski, L. Szymanski. G. Raniszewski, D. Koza, L. Pietrzak

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Magnetic Bio-Nano-Fluid (BNF) can be composed of a buffer fluid such as plasma and magnetic nanoparticles such as iron, nickel, cobalt and their oxides. However iron is one of the best elements for magnetization by electromagnetic radiation. It can be used as a tool for medical diagnosis and treatment. Radio frequency (RF) radiation is able to heat iron nanoparticles due to magnetic hysteresis. Electromagnetic heating of iron nanoparticles and ferro-fluids BNF can be successfully used for non-invasive thermal ablation of cancer cells. Moreover iron atoms can be carried by carbon nanotubes (CNTs) if iron is used as catalyst for CNTs synthesis. Then CNTs became the iron containers and they screen the iron content against oxidation. We will present a method of CNTs addressing to the required cells. For thermal ablation of cancer cells we use radio frequencies for which the interaction with human body should be limited to minimum. Generally, the application of RF energy fields for medical treatment is justified by deep tissue penetration. The highly iron doped CNTs as the carriers creating magnetic fluid will be presented. An excessive catalyst injection method using electrical furnace and microwave plasma reactor will be presented. This way it is possible to grow the Fe filled CNTs on a moving surface in continuous synthesis process. This also allows producing uniform carpet of the Fe filled CNTs carriers. For the experimental work targeted to cell ablation we used RF generator to measure the increase in temperature for some samples like: solution of Fe2O3 in BNF which can be plasma-like buffer, solutions of pure iron of different concentrations in plasma-like buffer and in buffer used for a cell culture, solutions of carbon nanotubes (MWCNTs) of different concentrations in plasma-like buffer and in buffer used for a cell culture. Then the targeted therapies which can be effective if the carriers are able to distinguish the difference between cancerous and healthy cell’s physiology are considered. We have developed an approach based on ligand-receptor or antibody-antigen interactions for the case of colon cancer.

Keywords: cancer treatment, carbon nano tubes, drag delivery, hyperthermia, iron

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Authors: Irfan Abdulrahman Sheth, Sohil Pothiawala

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Dermatomyositis is an idiopathic inflammatory myopathy, traditionally characterized by a progressive, symmetrical proximal muscle weakness and pathognomonic or characteristic cutaneous manifestations. We report a case of a 60-year old Chinese female who was referred from polyclinic for allergic rash over the body after applying hair dye 3 weeks ago. It was associated with puffiness of face, shortness of breath and hoarse voice since last 2 weeks with decrease effort tolerance. She also complained of dysphagia/ myalgia with progressive weakness of proximal muscles and palpitations. She denied chest pain, loss of appetite, weight loss, orthopnea or fever. She had stable vital signs and appeared cushingoid. She was noted to have rash over the scalp/ face and ecchymosis over the right arm with puffiness of face and periorbital oedema. There was symmetrical muscle weakness and other neurological examination was normal. Initial impression was of allergic reaction and underlying nephrotic syndrome and Cushing’s syndrome from TCM use. Diagnostic tests showed high Creatinine kinase (CK) of 1463 u/l, CK–MB of 18.7 ug/l and Troponin –T of 0.09 ug/l. The Full blood count and renal panel was normal. EMG showed inflammatory myositis. Patient was managed by rheumatologist and discharged on oral prednisolone with methotrexate/ ergocalciferol capsule and calcium carb, vitamin D tablets and outpatient follow up. In some patients, cutaneous disease exists in the absence of objective evidence of muscle inflammation. Management of dermatomyositis begins with careful investigation for the presence of muscle disease or of additional systemic involvement, particularly of the pulmonary, cardiac or gastrointestinal systems, and for the possibility of an accompanying malignancy. Muscle disease and systemic involvement can be refractory and may require multiple sequential therapeutic interventions or, at times, combinations of therapies. Thus, we want to highlight to the physicians that the cutaneous disease of dermatomyositis should not be confused with allergic reaction. It can be particularly challenging to diagnose. Early recognition aids appropriate management of this group of patients.

Keywords: dermatomyositis, myopathy, allergy, cutaneous disease

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Authors: Buhari Samaila, Buhari Maidamma

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

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

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Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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Authors: Dipanshu Sur, Ratnabali Chakravorty, Rimi Pal, Siddhartha Chatterjee, Joyshree Chaterjee, Amal Mallik

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Background: Women with polycystic ovary disease (PCOD) frequently suffer from metabolic disturbances. PCOD is a common ovulatory disorder in young women, which affects 5-10% of the population and results in infertility due to anovulation. Importantly, aromatase in ovarian granulosa and luteinized granulosa cells plays an important role for women of reproductive age. Generation and metabolism of androgen is directly related to aromatase activity. The E2/T ratio provides important information about aromatase activity because conversion of androgens to estrogens is mediated by CYP19, suggesting that the E2/T ratio may be a direct marker of aromatase activity. The nature of the interaction between ovarian aromatase activity and PCOD in women has been controversial, and the impact of weight gain on aromatase activity as well as E2 levels is unknown. Aim: The objective of this study was to investigate the association and relation between aromatase activity and levels of body mass index (BMI) from a reproductive hormone perspective in a group of women with or without PCOD. Methods: We designed a cohort study which included 200 individuals. It enrolled 100 cases of PCOD based on 2006 Rotterdam criteria and 100 ovulatory normal- non PCOD, healthy, age-matched controls. Plasma sex hormones viz. estradiol (E2), testosterone (T), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were measured by ELISA on the second day of the menstrual cycle, together with BMI and E2/T were calculated. Aromatase activity in PCOD patients with different BMI, T and E2 levels were compared. Results: PCOD patients showed significantly increased levels of BMI, E2 (P=0.004), T and LH, while their E2/T (P= <0.001), FSH and FSH/LH values were decreased compared with the control group. Higher E2 levels correlated with a relatively enhanced E2/T as well as T and LH levels but reduced BMI, FSH and FSH/LH levels in women with PCOD. Hyperandrogenic PCOD patients had increased E2 levels but their aromatase activity was markedly inhibited independent of their BMI values. Conclusions: We found a significant decrease of ovarian aromatase activity in women with PCOD as compared to controls. Our study showed that ovarian aromatase activity in PCOD was decreased which was independent of BMI. Enhancing aromatase activity may become an optimized strategy for developing therapies for PCOD women, especially those with obesity.

Keywords: aromatase activity, polycystic ovary disease, obesity, body mass index

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Authors: Athini Ntloko

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Mycobacterium bovis and other species of Mycobacterium tuberculosis complex (MTBC) can result to a zoonotic infection known as Bovine tuberculosis (bTB). MTBC has members that may contaminate an extensive range of hosts, including wildlife. Diverse wild species are known to cause disease in domestic livestock and are acknowledged as TB reservoirs. It has been a main study worldwide to deliberate on bTB risk factors as a result and some studies focused on particular parts of risk factors such as wildlife and herd management. The significance of the study was to determine the incidence of Mycobacterium tuberculosis complex that is associated with soil, hayfeed and water. Questionnaires were administered to thirty (30) smallholding farm owners in the two villages (kwaMasele and Qungqwala) and three (3) three commercial farms (Fort Hare dairy farm, Middledrift dairy farm and Seven star dairy farm). Detection of M. tuberculosis complex was achieved by Polymerase Chain Reaction using primers for IS6110; whereas a genotypic drug resistance mutation was detected using Genotype MTBDRplus assays. Nine percent (9%) of respondents had more than 40 cows in their herd, while 60% reported between 10 and 20 cows in their herd. Relationship between farm size and vaccination for TB differed from forty one percent (41%) being the highest to the least five percent (5%). The highest number of respondents who knew about relationship between TB cases and cattle location was ninety one percent (91%). Approximately fifty one percent (51%) of respondents had knowledge about wild life access to the farms. Relationship between import of cattle and farm size ranged from nine percent (9%) to thirty five percent (35%). Cattle sickness in relation to farm size differed from forty three (43%) being the highest to the least three percent (3%); while thirty three percent (33%) of respondents had knowledge about health management. Respondents with knowledge about the occurrence of TB infections in farms were forty-eight percent (48%). The frequency of DNA isolation from samples ranged from the highest forty-five percent (45%) from water to the least twenty two percent (22%) from soil. Fort Hare dairy farm had the highest number of positive samples, forty four percent (44%) from water samples; whereas Middledrift dairy farm had the lowest positive from water, seventeen percent (17%). Twelve (22%) out of 55 isolates showed resistance to INH and RIF that is, multi-drug resistance (MDR) and nine percent (9%) were sensitive to either INH or RIF. The mutations at rpoB gene differed from 58% being the highest to the least (23%). Fifty seven percent (57%) of samples showed a S315T1 mutation while only 14% possessed a S531L in the katG gene. The highest inhA mutations were detected in T8A (80 %) and the least was observed in A16G (17%). The results of this study reveal that risk factors for bTB in cattle and dairy farm workers are a serious issue abound in the Eastern Cape of South Africa; with the possibility of widespread dissemination of multidrug resistant determinants in MTBC from the environment.

Keywords: hayfeed, isoniazid, multi-drug resistance, mycobacterium tuberculosis complex, polymerase chain reaction, rifampicin, soil, water

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Authors: Yuen Man Yan

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

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

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Authors: Neelam Taneja, Abhishek Mewara, Ajay Kumar

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Multidrug resistant shigellae have emerged as a therapeutic challenge in India. At our 2000 bed tertiary care referral centre in Chandigarh, North India, which caters to a large population of 7 neighboring states, antibiotic resistance in Shigella is being constantly monitored. Shigellae are isolated from 3 to 5% of all stool samples. In 1990 nalidixic acid was the drug of choice as 82%, and 63% of shigellae were resistant to ampicillin and cotrimoxazole respectively. Nalidixic acid resistance emerged in 1992 and rapidly increased from 6% during 1994-98 to 86% by the turn of 21st century. In the 1990s, the WHO recommended ciprofloxacin as the drug of choice for empiric treatment of shigellosis in view of the existing high level resistance to agents like chloramphenicol, ampicillin, cotrimoxazole and nalidixic acid. First resistance to ciprofloxacin in S. flexneri at our centre appeared in 2000 and rapidly rose to 46% in 2007 (MIC>4mg/L). In between we had an outbreak of ciprofloxacin resistant S.dysenteriae serotype 1 in 2003. Therapeutic failures with ciprofloxacin occurred with both ciprofloxacin-resistant S. dysenteriae and ciprofloxacin-resistant S. flexneri. The severity of illness was more with ciprofloxacin-resistant strains. Till 2000, elsewhere in the world ciprofloxacin resistance in S. flexneri was sporadic and uncommon, though resistance to co-trimoxazole and ampicillin was common and in some areas resistance to nalidixic acid had also emerged. Fluoroquinolones due to extensive use and misuse for many other illnesses in our region are thus no longer the preferred group of drugs for managing shigellosis in India. WHO presently recommends ceftriaxone and azithromycin as alternative drugs to fluoroquinolone-resistant shigellae, however, overreliance on this group of drugs also seems to soon become questionable considering the emerging cephalosporin-resistant shigellae. We found 15.1% of S. flexneri isolates collected over a period of 9 years (2000-2009) resistant to at least one of the third-generation cephalosporins (ceftriaxone/cefotaxime). The first isolate showing ceftriaxone resistance was obtained in 2001, and we have observed an increase in number of isolates resistant to third generation cephalosporins in S. flexneri 2005 onwards. This situation has now become a therapeutic challenge in our region. The MIC values for Shigella isolates revealed a worrisome rise for ceftriaxone (MIC90:12 mg/L) and cefepime (MIC90:8 mg/L). MIC values for S. dysenteriae remained below 1 mg/L for ceftriaxone, however for cefepime, the MIC90 has raised to 4 mg/L. These infections caused by ceftriaxone-resistant S. flexneri isolates were successfully treated by azithromycin at our center. Most worrisome development in the present has been the emergence of DSA(Decreased susceptibility to azithromycin) which surfaced in 2001 and has increased from 4.3% till 2011 to 34% thereafter. We suspect plasmid-mediated resistance as we detected qnrS1-positive Shigella for the first time from the Indian subcontinent in 2 strains from 2010, indicating a relatively new appearance of this PMQR determinant among Shigella in India. This calls for a continuous and strong surveillance of antibiotic resistance across the country. The prevention of shigellosis by developing cost-effective vaccines is desirable as it will substantially reduce the morbidity associated with diarrhoea in the country

Keywords: Shigella, antimicrobial, resistance, India

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Authors: Kruttika Bhuse

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Aim: Synergism between periodontists and orthodontists (periodontal accelerated osteogenic orthodontics- PAOO) creates crucial opportunities to enhance clinical outcomes of combined therapies regarding both disciplines and has made adult orthodontics a reality. Thus, understanding the biomechanics of bone remodelling may increase the clinical applications of corticotomy facilitated orthodontics with or without alveolar augmentation. Wilckodontics can be an attractive treatment option and be a “win-win” situation for both the dental surgeon and patient by reducing the orthodontic treatment time in adults. Materials and methods: In this review, data related to the clinical aspects, steps of procedure, biomechanics of bone, indications and contraindications and final outcome of wilckodontic shall be discussed. 50 supporting articles from various international journals and 70 clinical cases were reviewed to get a better understanding to design this wilckodontic - meta analysis. Various journals like the Journal Of Clinical And Diagnostic Research, Journal Of Indian Society Of Periodontology, Journal Of Periodontology, Pubmed, Boston Orthodontic University Journal, Good Practice Orthodontics Volume 2, have been referred to attain valuable information on wilckodontics which was then compiled in this single review study. Result: As a promising adjuvant technique based on the transient nature of demineralization-remineralisation process in healthy tissues, wilckodontics consists of regional acceleratory phenomenon by alveolar corticotomy and bone grafting of labial and palatal/lingual surfaces, followed by orthodontic force. The surgical wounding of alveolar bone potentiates tissue reorganization and healing by a way of transient burst of localized hard and soft tissue remodelling.This phenomenon causes bone healing to occur 10-50 times faster than normal bone turnover. Conclusion: This meta analysis helps understanding that the biomechanics of bone remodelling may increase the clinical applications of corticotomy facilitated orthodontics with or without alveolar augmentation. The main benefits being reduced orthodontic treatment time, increased bone volume and post-orthodontic stability.

Keywords: periodontal osteogenic accelerated orthodontics, alveolar corticotomy, bone augmentation, win-win situation

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Authors: Ching-Yi Yiu, Hui-Chen Hsu

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Objectives: Obstructive sleep apnea syndrome (OSAS) is a popular problem in the modern society. It usually leads to sleep disorder, excessive daytime sleepiness and associated with cardiovascular diseases, cognitive dysfunction and even death. The nonsurgical therapies include continuous positive airway pressure (CPAP), diet and oral appliances. The surgical approaches have nasal surgery, tonsillectomy, adenoidectomy, uvulopalatopharyngoplasty (UPPP) and transoral robotic surgery (TORS).We compare the impact of surgical treatments on these kinds of patients. Methods: Between January 2018 to September 2022, We have enrolled 125 OSAS patients including 82 male and 43 female in Chi Mei Medical Center, Liouying, Taiwan. The age distribution from 6 to 71 years old (y/o) with mean age 36.1 y/o. The averaged body mass index (BMI) is 25 kg/m2 in male and 25.5 kg/m2 in female. In this cohort, we evaluated their upper airway obstruction sites with nasopharyngoscopy and scheduled a planned surgery. Some of cases received polysomnography (PSG) preoperatively, the averaged apnea-hypopnea index (AHI) is 37.7 events/hour. We have 68 patients received tonsillectomy, 9 received UPPP, 42 received UPPP and septomeatoplasty (SMP) and 6 received adenoidectomy and tonsillectomy (A and T). The subjective daytime sleepiness was evaluated with the Epworth sleepiness scale (ESS). Results: In the 68 tonsillectomy group, the averaged BMI is 24.9 kg/m2. In the UPPP group, the averaged BMI is 28.9 kg/m2. In UPPP and SMP group, the averaged BMI is 27.9 kg/m2. In the A and T group, the averaged BMI is 17.2 kg/m2. The reduction of AHI less than 20 is 58% postoperatively. The ESS reduced from 10.9 to 4.9 after surgery. Conclusion: Obstructive sleep apnea syndrome is a common upper airway disturbance in the general population. The prevalence rate is ranging high depending on different regions, age, sex and race. It leads to severe morbidity and mortality including car accident, stroke, nocturnal desaand sudden death and should be considered to be a major public health problem. The CPAP is effective to improve daytime sleepiness but the long-term compliance is low. The surgical treatment with different modalities can produce 50% decrease in AHI and ESS after surgery in the 6 to 12 months short-term period.

Keywords: apnea-hypopnea index, obstructive sleep apnea syndrome, polysomnography, uvulopalatopharyngoplasty

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Authors: Akriti Kafle Baral, Ruixing Zhang, Dzifa K Lalit, Manthar M Alli

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Introduction: Hemodialysis is the most common type of dialysis globally approximately million are reported to receive this type of dialysis. Psychosocial issues in hemodialysis are the psychological and socioeconomic burdens emanating from the initiation and course of treatment and have the potential for gross deterioration in the quality of life and general well-being of patients. Understanding the psychosocial issues and needs of patients undergoing hemodialysis could pave the way for comprehensive support and therapies designed to reduce stress, improve social support, and foster mental resilience. Objectives: The aim of this study was to explore the psychosocial issues and support needs of patients undergoing hemodialysis at a tertiary care center in Nepal. Methods: A qualitative descriptive study was conducted among 20 purposefully selected patients attending hemodialysis treatment at Pokhara Academy of Health Sciences, Nepal. Data was analyzed via thematic analysis. Results: The study resulted in three major themes which included Emotional, psychological, and spiritual struggles, Social and economic impacts, and Support and information needs. Moreover, 16 sub-themes emerged which are Frustration with daily life, Constant fear of death, Thoughts of self-harm, Perceived Burden on Family, Sense of Divine Punishment, Sense of Unfairness, Fear about future uncertainties, Social avoidance, Social stigmatization, Loss of employment, Financial strain, Transportation challenges, Need for early, clear and comprehensive information, Need for support and reassurance from family, Support through peer connections, and Reassurance from healthcare providers. Conclusion: The findings of this study indicate that patients undergoing hemodialysis in Nepal experience numerous hardships and multifaceted struggles that require support from different dimensions. Establishing robust support systems that include family involvement, peer networks, and effective communication from healthcare professionals can significantly mitigate feelings of anxiety and isolation.

Keywords: hemodialysis, psychosocial issues, support needs, chronic kidney disease, end stage renal disease, Nepal

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Authors: Tamrat Girma Biru

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Multidrug-resistant tuberculosis (MDR-TB) is defined as resistant to at least Refampicin and Isoniazed: the most two power full TB drugs. It is a leading cause of high rates of morbidity and mortality, and increasing psychosocial challenges to patients, especially when co-infected with Human Immunodeficiency Virus (HIV). Ethiopia faces the highest rates of MDR-TB infection in the world. Objectives: The main objective of this study was to identify the psychosocial challenges of MDR-TB patients, to investigate the extent of the psychosocial challenges on (self-esteem, depression, and stigma) that MDR-TB patients encounter, to examine whether there is a sex difference in experiencing psychosocial challenges and assess the counseling needs of MDR-TB patients. Methodology: A cross-sectional study was conducted at St. Peter TB Specialized Hospital, Addis Ababa on 40 patients (25 males and 15 females) who are hospitalized for treatment. The patients were identified by using purposive sampling and made fill a questionnaire measuring their level of self-esteem, depression and stigma. Besides, data were collected from 16 participants, 28 care providers and 8 guardians, using semi-structured interview. The obtained data were analyzed using SPSS statistical program, descriptive statistics, independent t-test, and qualitative description. Results and Discussion: The results of the study showed that the majority (80%) of the respondents had suffered psychological challenges and social discriminations. Thus, the significance of MDR-TB and its association with HIV/AIDS problems is considered. Besides the psychosocial challenges, various aggravating factors such as length of treatment, drug burden and insecurity in economy together highly challenges the life of patients. In addition, 60% of participants showed low level of self-esteem. The patients also reported that they experienced high self-stigma and stigma by other members of the society. The majority of the participants (75%) showed moderate and severe level of depression. In terms of sex there is no difference between the mean scores of males and females in the level of depression and stigmatization by others and by themselves. But females showed lower level of self-esteem than males. The analysis of the t-test also shows that there were no statistically significant sex difference on the level of depression and stigma. Based on the qualitative data MDR-TB patients face various challenges in their life sphere such as: Psychological (depression, low self value, lowliness, anxiety), social (stigma, isolation from social relations, self-stigmatization,) and medical (drug side effect, drug toxicity, drug burden, treatment length, hospital stays). Recommendations: Based on the findings of this study possible recommendations were forwarded: develop and extend MDR-TB disease awareness creation through by media (printing and electronic), school net TB clubs, and door to door community education. Strengthen psychological wellbeing and social relationship of MDR-TB patients using proper and consistent psychosocial support and counseling. Responsible bodies like Ministry of Health (MOH) and its stakeholders and Non Governmental Organizations (NGOs) need to assess the challenges of patients and take measures on this pressing issue.

Keywords: psychosocial challenges, counseling, multi-drug resistant tuberculosis (MDR-TB), tuberculosis therapy

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Authors: Sumeet Rai, Anuj Tyagi, B. T. Naveen Kumar, Shubhkaramjeet Kaur, Niraj K. Singh

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Since their discovery, indiscriminate use of antibiotics in human, veterinary and aquaculture systems has resulted in global emergence/spread of multidrug-resistant bacterial pathogens. Thus, the need for alternative approaches to control bacterial infections has become utmost important. High selectivity/specificity of bacteriophages (phages) permits the targeting of specific bacteria without affecting the desirable flora. In this study, a lytic phage (Ahp1) specific to Aeromonas hydrophila subsp. hydrophila was isolated from finfish aquaculture pond. The host range of Ahp1 range was tested against 10 isolates of A. hydrophila, 7 isolates of A. veronii, 25 Vibrio cholerae isolates, 4 V. parahaemolyticus isolates and one isolate each of V. harveyi and Salmonella enterica collected previously. Except the host A. hydrophila subsp. hydrophila strain, no lytic activity against any other bacterial was detected. During the adsorption rate and one-step growth curve analysis, 69.7% of phage particles were able to get adsorbed on host cell followed by the release of 93 ± 6 phage progenies per host cell after a latent period of ~30 min. Phage nucleic acid was extracted by column purification methods. After determining the nature of phage nucleic acid as dsDNA, phage genome was subjected to next-generation sequencing by generating paired-end (PE, 2 x 300bp) reads on Illumina MiSeq system. De novo assembly of sequencing reads generated circular phage genome of 42,439 bp with G+C content of 58.95%. During open read frame (ORF) prediction and annotation, 22 ORFs (out of 49 total predicted ORFs) were functionally annotated and rest encoded for hypothetical proteins. Proteins involved in major functions such as phage structure formation and packaging, DNA replication and repair, DNA transcription and host cell lysis were encoded by the phage genome. The complete genome sequence of Ahp1 along with gene annotation was submitted to NCBI GenBank (accession number MF683623). Stability of Ahp1 preparations at storage temperatures of 4 °C, 30 °C, and 40 °C was studied over a period of 9 months. At 40 °C storage, phage counts declined by 4 log units within one month; with a total loss of viability after 2 months. At 30 °C temperature, phage preparation was stable for < 5 months. On the other hand, phage counts decreased by only 2 log units over a period of 9 during storage at 4 °C. As some of the phages have also been reported as glycerol sensitive, the stability of Ahp1 preparations in (0%, 15%, 30% and 45%) glycerol stocks were also studied during storage at -80 °C over a period of 9 months. The phage counts decreased only by 2 log units during storage, and no significant difference in phage counts was observed at different concentrations of glycerol. The Ahp1 phage discovered in our study had a very narrow host range and it may be useful for phage typing applications. Moreover, the endolysin and holin genes in Ahp1 genome could be ideal candidates for recombinant cloning and expression of antimicrobial proteins.

Keywords: Aeromonas hydrophila, endolysin, phage, narrow host range

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Authors: Seemab Safdar, Shazia Fatima, Ahmad Qureshy, M. Adnan Saeed, M. Faheem

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Background: Thyroid cancer has 586,000 cases per year worldwide, and this translates to 3% of all tumor diagnoses. 90% of the cases fall under differentiated thyroid carcinoma (DTC), which includes follicular thyroid cancer (FTC) and papillary thyroid cancer (PTC). During their illness, 10% of patients develop distant metastases, and two-thirds of them develop resistance to radioactive iodine (RAI) treatment. It has been shown that in some circumstances, like DTC with high TG levels and negative 131I whole-body scintigraphy (TENIS), [18F] FDG-PET-CT is an effective imaging technique. This study determines the role of [18F] FDG-PET-CT in the treatment of TENIS patients. Methods: 16 patients (n = 12 female; 4 males, age 45 ± 15 years) with histologically proven thyroid cancer (Differentiated and poorly differentiated) and high TG with negative iodine scans were included in this prospective study from January 2024 to June 2024. They underwent scanning in state-of-the-art (GE Discovery MI) [18F] FDG-PET-CT for re-staging or diagnostics of recurrent disease using a standardized protocol. All DTC subtypes and PDTC were included. The referring physicians completed standardized questionnaires both before and after PET-CT to prospectively determine the examination's effect on clinical decision-making. Patient outcomes were measured by analysis of medical records. Moreover, after PET-CT, a change in the pre-PET-CT planned therapies was documented in 32% of cases and additional invasive diagnostic procedures could be waived in 37.5 % of cases. TG levels under TSH stimulation were significantly higher in patients showing PET-CT metastases compared to patients without such findings (68.75%). Results: Without PET-CT, physicians referring to the doctors had not established a complete treatment plan for 45% of patients with thyroid carcinoma. 12/16 patients showed FDG avidity in cervical lymph nodes that were not Iodine avid previously, 2 patients had FDG avid disease in the lungs. In the process, PET-CT helped plan patient management and created a clear plan for treatment in 68.75% of patients. Conclusions: This study confirms that [18F] FDG-PET-CT used in a routine clinical setting has a very important impact on the management of patients with thyroid cancer when TG levels are persistently high in the presence of negative Iodine Scans by initiating treatments and replacing additional imaging and invasive tests.

Keywords: PET-CT, TENIS, role, FDG

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