Search results for: therapeutic jurisprudence

Authors: Cameron Wilson, Megan Hanrahan, Katie Brittain, Riona McArdle, Alison Keogh, Lynn Rochester

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Background: The loss of mobility and functional dependence is a significant marker in the progression of neurodegenerative diseases such as Parkinson’s Disease (PD). Pharmacological, surgical, and therapeutic treatments are available that can help in the management and amelioration of PD symptoms; however, these only prolong more severe symptoms. Accordingly, ensuring people with PD can maintain independence and a healthy wellbeing are essential in establishing an effective treatment option for those afflicted. Existing literature reviews have examined experiences in engaging with PD treatment options and the impact of PD on independence and wellbeing. Although, the literature fails to explore the influence of treatment options on independence and wellbeing and therefore misses what people value in their treatment. This review is the first that synthesises the impact of mobility-related treatments on independence and wellbeing in people with PD and their carers, offering recommendations to clinical practice and provides a conceptual framework (in development) for future research and practice. Objectives: To explore the impact of mobility-related treatment (both pharmacological and non-pharmacological) on the independence and wellbeing of people with PD and their carers. To propose a conceptual framework to patients, carers and clinicians which captures the qualities people with PD value as part of their treatment. Methods: We performed a critical interpretive synthesis of qualitative evidence, searching six databases for reports that explored the impact of mobility-related treatments (both drug and non-pharmacological) on independence and wellbeing in Parkinson’s Disease. The types of treatments included medication (Levodopa and Amantadine), dance classes, Deep-Brain Stimulation, aquatic therapies, physical rehabilitation, balance training and foetal transplantation. Data was extracted, and quality was assessed using an adapted version of the NICE Quality Appraisal Tool Appendix H before being synthesised according to the critical interpretive synthesis framework and meta-ethnography process. Results: From 2301 records, 28 were eligible. Experiences and impact of treatment pathway on independence and wellbeing was similar across all types of treatments and are described by five inter-related themes: (i) desire to maintain independence, (ii) treatment as a social experience during and after, (iii) medication to strengthen emotional health, (iv) recognising physical capacity and (v) emphasising the personal journey of Parkinson’s treatments. Conclusion: There is a complex and inter-related experience and effect of PD treatments common across all types of treatment. The proposed conceptual framework (in development) provides patients, carers, and clinicians recommendations to personalise the delivery of PD treatment, thereby potentially improving adherence and effectiveness. This work is vital to disseminate as PD treatment transitions from subjective and clinically captured assessments to a more personalised process supplemented using wearable technology.

Keywords: parkinson's disease, medication, treatment, dance, review, healthcare, delivery, levodopa, social, emotional, psychological, personalised healthcare

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Authors: Katarzyna Drela, Miroslaw Wielgos, Mikolaj Wrobel, Barbara Lukomska

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Mesenchymal stem cells (MSCs) have a great potential in regenerative medicine. Since the initial number of isolated MSCs is limited, in vitro propagation is often required to reach sufficient numbers of cells for therapeutic applications. During long-term culture MSCs may undergo genetic or epigenetic alterations that subsequently increase the probability of spontaneous malignant transformation. Thus, factors that influence genomic stability of MSCs following long-term expansions need to be clarified before cultured MSCs are employed for clinical application. The aim of our study was to investigate the potential for spontaneous transformation of human neonatal cord blood (HUCB-MSCs) and adult bone marrow (BM-MSCs) derived MSCs. Materials and Methods: HUCB-MSCs and BM-MSCs were isolated by standard Ficoll gradient centrifugations method. Isolated cells were initially plated in high density 106 cells per cm2. After 48 h medium were changed and non-adherent cells were removed. The malignant transformation of MSCs in vitro was evaluated by morphological changes, proliferation rate, ability to enter cell senescence, the telomerase expression and chromosomal abnormality. Proliferation of MSCs was analyzed with WST-1 reduction method and population doubling time (PDT) was calculated at different culture stages. Then the expression pattern of genes characteristic for mesenchymal or epithelial cells, as well as transcriptions factors were examined by RT-PCR. Concomitantly, immunocytochemical analysis of gene-related proteins was employed. Results: Our studies showed that MSCs from all bone marrow isolations ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUCB-MSCs from one of the 15 donors displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. In this sample we observed two different cell phenotypes: one mesenchymal-like exhibited spindle shaped morphology and express specific mesenchymal surface markers (CD73, CD90, CD105, CD166) with low proliferation rate, and the second one with round, densely package epithelial-like cells with significantly increased proliferation rate. The PDT of epithelial-like populations was around 1day and 100% of cells were positive for proliferation marker Ki-67. Moreover, HUCB-MSCs showed a positive expression of human telomerase reverse transcriptase (hTERT), cMYC and exhibit increased number of CFU during the long-term culture in vitro. Furthermore, karyotype analysis revealed chromosomal abnormalities including duplications. Conclusions: Our studies demonstrate that HUCB-MSCs are susceptible to spontaneous malignant transformation during long-term culture. Spontaneous malignant transformation process following in vitro culture has enormous effect on the biosafety issues of future cell-based therapies and regenerative medicine regimens.

Keywords: mesenchymal stem cells, spontaneous, transformation, long-term culture

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Authors: Zahra Mohajer, Afsaneh Soltani

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Doping is a major issue in competitive sports and is favored by vast groups of athletes. The feeling of being higher-ranking than others and gaining fame has caused many athletes to misuse drugs. The definition of doping is to use prohibited substances and/or methods that help physical or mental performances or both. Doping counts as the illegal use of chemical substances or drugs, excessive amounts of physiological substances to increase the performance at or out of competition or even the use of inappropriate medications to treat an injury to gain the ability to participate in a competition. The International Olympic Committee (IOC) and World Anti-Doping Agency (WADA) have forbidden these substances to ensure fair and equal competition and also the health of the competitors. As of 2004 WADA has published an international list of illegal substances used for doping, which is updated annually. In the process of the Genome Project scientists have gained the ability to treat numerous diseases by gene therapy, which may result in bodily performance increase and therefore a potential opportunity to misuse by some athletes. Gene doping is defined as the non-therapeutic direct and indirect genetic modifications using genetic materials that can improve the performances in sports events. Biosynthetic drugs are a form of indirect genetic engineering. The method can be performed in three ways such as injecting the DNA directly into the muscle, inserting the genetically engineered cells, or transferring the DNA using a virus as a vector. Erythropoietin is a hormone majorly released by the kidney and in small amounts by the liver. Its function is to stimulate the erythropoiesis and therefore the more production of red blood cells (RBC) which causes an increase in Hemoglobin (Hb). During this process, the oxygen delivery to muscles will increase, which will improve athletic performance and postpone exhaustion. There are ways to increase the oxygen transferred to muscles such as blood transfusion, stimulating the production of red blood cells by using Erythropoietin (EPO), and also using allosteric effectors of Hemoglobin. EPO can either be injected as a protein or can be inserted into the cells as the gene which encodes EPO. Adeno-associated viruses have been employed to deliver the EPO gene to the cells. Employing the genes that naturally exist in the human body such as the EPO gene can reduce the risk of detecting gene doping. The first research about blood doping was conducted in 1947. The study has shown that an increase in hematocrit (HCT) up to 55% following homologous transfusion makes it more unchallenging for the body to perform the exercise at the altitude. Thereafter athletes’ attraction to blood infusion escalated. Also, a study has demonstrated that by reinfusing their own blood 4 weeks after being drawn, three men have shown a rise in Hb level which improved the oxygen uptake, and a delay in exhaustion. The list of performance-enhancing drugs is published by WADA annually and includes the following drugs: anabolic agents, hormones, Beta-2 agonists, Beta-blockers, Diuretics, Stimulants, narcotics, cannabinoids, and corticosteroids.

Keywords: doping, PEDs, sports, WADA

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Authors: Rahaba Marima, Clement Penny

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The Health-related quality of life (HRQoL) for HIV positive patients has improved since the introduction of the highly active antiretroviral treatment (HAART). However, in the present HAART era, HIV co-morbidities such as lung cancer, a non-AIDS (NAIDS) defining cancer have been documented to be on the rise. Under normal physiological conditions, cells grow, repair and proliferate through the cell-cycle as cellular homeostasis is important in the maintenance and proper regulation of tissues and organs. Contrarily, the deregulation of the cell-cycle is a hallmark of cancer, including lung cancer. The association between lung cancer and the use of HAART components such as Efavirenz (EFV) is poorly understood. This study aimed at elucidating the effects of EFV on the cell-cycle genes’ expression in lung cancer. For this purpose, the human cell-cycle gene array composed of 84 genes was evaluated on both normal lung fibroblasts (MRC-5) cells and adenocarcinoma (A549) lung cells, in response to 13µM EFV or 0.01% vehicle. The ±2 up or down fold change was used as a basis of target selection, with p < 0.05. Additionally, RT-qPCR was done to validate the gene array results. Next, In-silico bio-informatics tools, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Ingenuity Pathway Analysis (IPA) were used for gene/gene interaction studies as well as to map the molecular and biological pathways influenced by the identified targets. Interestingly, the DNA damage response (DDR) pathway genes such as p53, Ataxia telangiectasia mutated and Rad3 related (ATR), Growth arrest and DNA damage inducible alpha (GADD45A), HUS1 checkpoint homolog (HUS1) and Role of radiation (RAD) genes were shown to be upregulated following EFV treatment, as revealed by STRING analysis. Additionally, functional enrichment analysis by the KEGG pathway revealed that most of the differentially expressed gene targets function at the cell-cycle checkpoint such as p21, Aurora kinase B (AURKB) and Mitotic Arrest Deficient-Like 2 (MAD2L2). Core analysis by IPA revealed that p53 downstream targets such as survivin, Bcl2, and cyclin/cyclin dependent kinases (CDKs) complexes are down-regulated, following exposure to EFV. Furthermore, Reactome analysis showed a significant increase in cellular response to stress genes, DNA repair genes, and apoptosis genes, as observed in both normal and cancerous cells. These findings implicate the genotoxic effects of EFV on lung cells, provoking the DDR pathway. Notably, the constitutive expression of this pathway (DDR) often leads to uncontrolled cell proliferation and eventually tumourigenesis, which could be the attribute of HAART components’ (such as EFV) effect on human cancers. Targeting the cell-cycle and its regulation holds a promising therapeutic intervention to the potential HAART associated carcinogenesis, particularly lung cancer.

Keywords: cell-cycle, DNA damage response, Efavirenz, lung cancer

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Authors: Patrícia Pires, Renata Vaz, Bárbara Teles, Marco Pato, Pedro Beckert

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Introduction: The management of lateral third clavicle fractures can be challenging due to difficulty in distinguishing subtle variations in the fracture pattern, which may be suggestive of potential fracture instability. They occur most often in men between 30 and 50 years of age, and in individuals over 70 years of age, its distribution is equal between both men and women. These fractures account for 10%–30% of all clavicle fractures and roughly 30%–45% of all clavicle nonunion fractures. Lateral third clavicle fractures may be treated conservatively or surgically, and there is no gold standard, although the risk of nonunion or pseudoarthrosis impacts the recommendation of surgical treatment when these fractures are unstable. There are many strategies for surgical treatment, including locking plates, hook plates fixation, coracoclavicular fixation using suture anchors, devices or screws, tension band fixation with suture or wire, transacromial Kirschner wire fixation and arthroscopically assisted techniques. Whenever taking the hardware into consideration, we must not disregard that obtaining adequate lateral fixation of small fragments is a difficult task, and plates are more associated to local irritation. The aim of the appropriate treatment is to ensure fracture healing and a rapid return to preinjury activities of daily living but, as explained, definitive treatment strategies have not been established and the variety of techniques avalilable add up to the discussion of this topic. Methods and Results: We present a clinical case of a 43-year-old man with the diagnosis of a lateral third clavicle fracture (Neer IIC) in the sequence of a fall on his right shoulder after a bicycle fall. He was operated three days after the injury, and through K-wire temporary fixation and indirect reduction using a ZipTight, he underwent osteosynthesis with an interfragmentary figure-of-eight tension band with polydioxanone suture (PDS). Two weeks later, there was a good aligment. He kept the sling until 6 weeks pos-op, avoiding efforts. At 7-weeks pos-op, there was still a good aligment, starting the physiotherapy exercises. After 10 months, he had no limitation in mobility or pain and returned to work with complete recovery in strength. Conclusion: Some distal clavicle fractures may be conservatively treated, but it is widely accepted that unstable fractures require surgical treatment to obtain superior clinical outcomes. In the clinical case presented, the authors chose an osteosuture technique due to the fracture pattern, its location. Since there isn´t a consensus on the prefered fixation method, it is important for surgeons to be skilled in various techniques and decide with their patient which approach is most appropriate for them, weighting the risk-benefit of each method. For instance, with the suture technique used, there is no wire migration or breakage, and it doesn´t require a reoperation for hardware removal; there is also less tissue exposure since it requires a smaller approach in comparison to the plate fixation and avoids cuff tears like the hook plate. The good clinical outcome on this case report serves the purpose of expanding the consideration of this method has a therapeutic option.

Keywords: lateral third, clavicle, suture, fixation

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Authors: Bakytzhan Bimbetov, Abay Zhangabilov, Saule Aitbaeva, Galymzhan Meirambekov

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Mare’s milk (saumal) contains in total about 40 biological components necessary for the human body. The most significant among them are amino acids, fats, carbohydrates, enzymes (lysozyme, amylase), more minerals and vitamins which are well balanced with each other. In Kazakhstan, Company "Eurasia Invest Ltd.” produces a freeze-dried saumal in form of powder by the use of modern German innovative technology by means of evaporating at low temperature (-35°C) with an appropriate pasteurization. Research of freeze-dried biomilk for the qualitative content showed that main ingredients of freshly drown milk are being preserved. We are currently studying medical and dietary properties of freeze-dried mare's milk for diseases of the digestive system, including for nonalcoholic steatohepatitis (NASH) and liver cirrhosis (LC) viral etiology. The studied group consisted of 14 patients with NASH, and 7 patients with LC viral etiology of Class A severity degree as per Child-Pugh. Patients took freeze-dried saumal, preliminary dissolved in boiled warm water (24 g. powder per 200 ml water) 3-4 times a day for a month in conjunction with basic therapy. The results were compared to a control group (11 patients with NASH and LC) who received only basic therapy without mare’s milk. Results of preliminary research showed an improvement of subjective and objective conditions of all patients, but more significant improvement of clinical symptoms and syndromes were observed in the treatment group compared to the control one. Patients with NASH significantly over time compared to the beginning of therapy decreased asthenic and dyspeptic syndromes (p<0,01). Hepatomegaly, identified on the basis of ultrasound prior to treatment was observed in 92,8±2,4% of patients, and after combination therapy hepatomegaly the rate decreased by 14,3%, amounting to 78,5±2,8%. Patients with LC also noted the improvement of asthenic (p<0,01) and dyspeptic (p<0,05) syndromes and hemorrhagic syndrome (nosebleeds and bleeding gums when brushing your teeth, p<0,05), and jaundice. Laboratory study also showed improvement in the research group, but more significant changes were observed in the experimental group. Group of patients with NASH showed a significant improvement of index in cytolysis in conjunction with a combination therapy (p<0,05). In the control group, these indicators were also improved, but they were not statistically reliable (p>0,05). Markers of liver failure were additionally studied during the study of laboratory parameters in patients with liver cirrhosis, in particular, bilirubin, albumin and prothrombin index (PTI). Combined therapy with the use of basic treatment and mare's milk showed a significant improvement in cytolysis and bilirubin (p<0,05). In our opinion, a very important and interesting fact is that, in conjunction with basic therapy, the use of mare's milk revealed an improvement of liver function in the form of normalized PTI and albumin in patients with liver cirrhosis viral etiology. Results of this work have shown therapeutic efficiency of the use of mare's milk in complex treatment of patients with liver disease and require further in-depth study.

Keywords: liver cirrhosis, non-alcohol steatohepatitis, saumal, mare’s milk

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Authors: Meenu S. Babu, K. Jayasankara Reddy

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Depression is a serious mental health concern that leads to significant distress and dysfunction in an individual. Due to the high physical, psychological, social, and economic burden it causes, it is important to study various bio-psycho-social factors that influence the onset, course, duration, intensity of depressive symptoms. The study aims to explore relationship between autobiographical memory (AM) functions, perceived control over stressful events and depressive symptoms. AM functions and perceived control were both found to be protective factors for individuals against depression and were both modifiable to predict better behavioral and affective outcomes. An extensive review of literatur, with a systematic search on Google Scholar, JSTOR, Science Direct and Springer Journals database, was conducted for the purpose of this review paper. These were used for all the aforementioned databases. The time frame used for the search was 2010-2021. An additional search was conducted with no time bar to map the development of the theoretical concepts. The relevant studies with quantitative, qualitative, experimental, and quasi- experimental research designs were included for the review. Studies including a sample with a DSM- 5 or ICD-10 diagnosis of depressive disorders were excluded from the study to focus on the behavioral patterns in a non-clinical population. The synthesis of the findings that were obtained from the review indicates there is a significant relationship between cognitive variables of AM functions and perceived control and depressive symptoms. AM functions were found to be have significant effects on once sense of self, interpersonal relationships, decision making, self- continuity and were related to better emotion regulation and lower depressive symptoms. Not all the components of AM function were equally significant in their relationships with various depressive symptoms. While self and directive functions were more related to emotion regulation, anhedonia, motivation and hence mood and affect, the social function was related to perceived social support and social engagement. Perceived control was found to be another protective cognitive factor that provides individuals a sense of agency and control over one’s life outcomes which was found to be low in individuals with depression. This was also associated to the locus of control, competency beliefs, contingency beliefs and subjective well being in individuals and acted as protective factors against depressive symptoms. AM and perceived control over stressful events serve adaptive functions, hence it is imperative to study these variables more extensively. They can be imperative in planning and implementing therapeutic interventions to foster these cognitive protective factors to mitigate or alleviate depressive symptoms. Exploring AM as a determining factor in depressive symptoms along with perceived control over stress creates a bridge between biological and cognitive factors underlying depression and increases the scope of developing a more eclectic and effective treatment plan for individuals. As culture plays a crucial role in AM functions as well as certain aspects of control such as locus of control, it is necessary to study these variables keeping in mind the cultural context to tailor culture/community specific interventions for depression.

Keywords: autobiographical memories, autobiographical memory functions, perceived control, depressive symptoms, depression, young adults

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Authors: Sookbin Im, Myounglyun Heo

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This study aims at analyzing composition and effects of the preliminary intervention to promote resiliency of children whose parents suffer mental illness, and considerations according to the program, and developing the resiliency promotion program for children of psychiatric patients. For participants of preliminary intervention, they were recruited through a community mental health and social welfare center in a city, and there were 10 children (eight girls and two boys) who are from second to five graders in elementary school, and whose parents suffer schizophrenia, depression, or alcoholism, etc. The program was conducted in the seminar room of the community mental illness and social welfare center from October to December 2015 and from July to September 2016. The elements of resiliency were figured out by reviewing the literature. And therapeutic activities to promote resiliency was composed, and total twice, 8 sessions(two hours, once a week) were applied. Each session consisted of playgroup activities, art activities, and role-playing with feedback for achieving goals to promote self-awareness, self-efficacy, positive outlook, ability to solve problems, empathy for others, peer group acceptance, having goals and aspirations, and assertiveness. In addition, auxiliary managers as many as children played a role as mentor and role model, and children's behaviors were collected by participatory observation. As a result of the study, four children quit the program because the schedules of their own school programs were overlapped with it. Therefore, six children completed the program. Children who completed it became active, positive, decreased compulsive actions, and increased self-expressions. The participants reacted the 8-session program is too short and regretted about it. However, recruiting the participants were difficult, and too distracting children caused negative influences in the group activities. Based on the results, the program was developed as follows: The program would consist of total 11 sessions, and the first eight sessions would be made of plays, art activities, role-plays, and presentations for promoting self-understanding, improving positiveness, providing meaning for experiences, emotional control, and interpersonal relations. In order to balance various contents, methods such as structuring environments, storytelling, emotional coaching, and group feedback would be applied, and the ninth to eleventh sessions would be booster sessions consisting of optional activities for children. This program is for children who attend school with active linguistic communications and interactions with peers. Especially, considering that effective development starts at around 10 years old, it would be for children who are third and fourth graders in elementary school. These result showed that this program was useful for improving the key elements of resiliency such as positive thinking or impulse control. It is suggested the necessary of resiliency promoting program model and practical guidance with comprehensive measuring methods(narratives, drawing, self-reported questionnaire, behavioral observation). Also, it is necessary to make a training program for the coaches or leaders to operate this program to spread out for child health.

Keywords: children, mental, parents, resilience

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Authors: Vandana Mohan, Ashwani Koul

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Aim: To evaluate the potential of Aqueous Tinospora cordifolia stem extract (Aq.Tc) and Arabinogalactan (AG) on pulmonary carcinogenesis and associated tumor markers. Background: Lung cancer is one of the most frequent malignancy with high mortality rate due to limitation of early detection resulting in low cure rates. Current research effort focuses on identifying some blood-based biomarkers like CEA, ctDNA and LDH which may have potential to detect cancer at an early stage, evaluation of therapeutic response and its recurrence. Medicinal plants and their active components have been widely investigated for their anticancer potentials. Aqueous preparation of T. Cordifolia extract is enriched in the polysaccharide fraction i.e., AG when compared with other types of extract. Moreover, reports are available of polysaccharide fraction of T. Cordifolia in in vitro lung cancer models which showed profound anti-metastatic activity against these cell lines. However, not much has been explored about its effect in in vivo lung cancer models and the underlying mechanism involved. Experimental Design: Mice were randomly segregated into six groups. Group I animals served as control. Group II animals were administered with Aq. Tc extract (200 mg/kg b.w.) p.o.on the alternate days. Group III animals were fed with AG (7.5 mg/kg b.w.) p.o. on the alternate days (thrice a week). Group IV animals were installed with Benzo(a)pyrene (50 mg/kg b.w.), i.p. twice within an interval of two weeks. Group V animals received Aq. Tc extract as in group II along with it B(a)P was installed after two weeks of Aq. Tc administration following the same protocol as for group IV. Group VI animals received AG as in group III along with it B(a)P was installed after two weeks of AG administration. Results: Administration of B(a)P to mice resulted in increased tumor incidence, multiplicity and pulmonary somatic index with concomitant increase in serum/plasma markers like CEA, ctDNA, LDH and TNF-α.Aq.Tc and AG supplementation significantly attenuated these alterations at different stages of tumorigenesis thereby showing potent anti-cancer effect in lung cancer. A pronounced decrease in serum/plasma markers were observed in animals treated with Aq.Tc as compared to those fed with AG. Also, extensive hyperproliferation of alveolar epithelium was prominent in B(a)P induced lung tumors. However, treatment of Aq.Tc and AG to lung tumor bearing mice exhibited reduced alveolar damage evident from decreased number of hyperchromatic irregular nuclei. A direct correlation between the concentration of tumor markers and the intensity of lung cancer was observed in animals bearing cancer co-treated with Aq.Tc and AG. Conclusion: These findings substantiate the chemopreventive potential of Aq.Tc and AG against lung tumorigenesis. Interestingly, Aq.Tc was found to be more effective in modulating the cancer as reflected by various observations which may be attributed to the synergism offered by various components of Aq.Tc. Further studies are in progress to understand the underlined mechanism in inhibiting lung tumorigenesis by Aq.Tc and AG.

Keywords: Arabinogalactan, Benzo(a)pyrene B(a)P, carcinoembryonic antigen (CEA), circulating tumor DNA (ctDNA), lactate dehydrogenase (LDH), Tinospora cordifolia

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Authors: Haftay Abraha Tadesse

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Background: Staphylococcus is a genus of worldwide distributed bacteria correlated to several infectious of different sites in human and animals. They are among the most important causes of infection that are associated with the consumption of contaminated food. Objective: The objective of this study was to determine the isolates, antimicrobial susceptibility patterns and public health significance for Staphylococcus aureus in raw meat from butchery and abattoir houses of Mekelle, Northern Ethiopia. Methodology: A cross-sectional study was conducted from April to October 2019. Sociodemographic data and public health significance were collected using predesigned questionnaire. The raw meat samples were collected aseptically in the butchery and abattoir houses and transported using ice box to Mekelle University, College of Veterinary Sciences for isolating and identification of Staphylococcus aureus. Antimicrobial susceptibility tests were determined by disc diffusion method. Data obtained were cleaned and entered in to STATA 22.0 and logistic regression model with odds ratio were calculated to assess the association of risk factors with bacterial contamination. P-value < 0.05 was considered as statistically significant. Results: In present study, 88 out of 250 (35.2%) were found to be contamination with Staphylococcus aureus. Among the raw meat specimens to be positivity rate of Staphylococcus aureus were 37.6% (n=47) and (32.8% (n=41), butchery and abattoir houses, respectively. Among the associated risk factories not using gloves reduces risk was found to (AOR=0.222; 95% CI: 0.104-0.473), Strict Separation b/n clean & dirty (AOR= 1.37; 95% CI: 0.66-2.86) and poor habit of hand washing (AOR=1.08; 95%CI: 0.35-3.35) were found to be statistically significant and ha ve associated with Staphylococcus aureus contamination. All isolates thirty sevevn of Staphyloco ccus aureus were checked displayed (100%) sensitive to doxycycline, trimethoprim, gentamicin, sulphamethoxazole, amikacin, CN, Co trimoxazole and nitrofurantoi. whereas the showed resistance of cefotaxime (100%), ampicillin (87.5%), Penicillin (75%), B (75%), and nalidixic acid (50%) from butchery houses. On the other hand, all isolates of Staphylococcus aur eu isolate 100% (n= 10) showed sensitive chloramphenicol, gentamicin and nitrofurantoin whereas the showed 100% resistance of Penicillin, B, AMX, ceftriaxone, ampicillin and cefotaxime from abattoirs houses. The overall multi drug resistance pattern for Staphylococcus aureus were 90% and 100% of butchery and abattoirs houses, respectively. Conclusion: 35.3% Staphylococcus aureus isolated were recovered from the raw meat samples collected from the butchery and abattoirs houses. More has to be done in the developed of hand washing behavior, and availability of safe water in the butchery houses to reduce burden of bacterial contamination. The results of the present finding highlight the need to implement protective measures against the levels of food contamination and alternative drug options. The development of antimicrobial resistance is nearly always as a result of repeated therapeutic and/or indiscriminate use of them. Regular antimicrobial sensitivity testing helps to select effective antibiotics and to reduce the problems of drug resistance development towards commonly used antibiotics. Key words: abattoir houses, antimicrobial resistance, butchery houses, Ethiopia,

Keywords: abattoir houses, antimicrobial resistance, butchery houses, Ethiopia, staphylococcus aureuse, MDR

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Authors: D. Dixon, J. Nicol, J. A. Coulter, E. Harrison

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The ease with which they can be functionalized, combined with their excellent biocompatibility, make gold nanoparticles (AuNPs) ideal candidates for various applications in nanomedicine. Indeed several promising treatments are currently undergoing human clinical trials (CYT-6091 and Auroshell). A successful nanoparticle treatment must first evade the immune system, then accumulate within the target tissue, before enter the diseased cells and delivering the payload. In order to create a clinically relevant drug delivery system, contrast agent or radiosensitizer, it is generally necessary to functionalize the AuNP surface with multiple groups; e.g. Polyethylene Glycol (PEG) for enhanced stability, targeting groups such as antibodies, peptides for enhanced internalization, and therapeutic agents. Creating and characterizing the biological response of such complex systems remains a challenge. The two commonly used methods to attach multiple groups to the surface of AuNPs are the creation of a mixed monolayer, or by binding groups to the AuNP surface using a bi-functional PEG linker. While some excellent in-vitro and animal results have been reported for both approaches further work is necessary to directly compare the two methods. In this study AuNPs capped with both PEG and a Receptor Mediated Endocytosis (RME) peptide were prepared using both mixed monolayer and PEG linker approaches. The PEG linker used was SH-PEG-SGA which has a thiol at one end for AuNP attachment, and an NHS ester at the other to bind to the peptide. The work builds upon previous studies carried out at the University of Ulster which have investigated AuNP synthesis, the influence of PEG on stability in a range of media and investigated intracellular payload release. 18-19nm citrate capped AuNPs were prepared using the Turkevich method via the sodium citrate reduction of boiling 0.01wt% Chloroauric acid. To produce PEG capped AuNPs, the required amount of PEG-SH (5000Mw) or SH-PEG-SGA (3000Mw Jenkem Technologies) was added, and the solution stirred overnight at room temperature. The RME (sequence: CKKKKKKSEDEYPYVPN, Biomatik) co-functionalised samples were prepared by adding the required amount of peptide to the PEG capped samples and stirring overnight. The appropriate amounts of PEG-SH and RME peptide were added to the AuNP to produce a mixed monolayer consisting of approximately 50% PEG and 50% RME. The PEG linker samples were first fully capped with bi-functional PEG before being capped with RME peptide. An increase in diameter from 18-19mm for the ‘as synthesized’ AuNPs to 40-42nm after PEG capping was observed via DLS. The presence of PEG and RME peptide on both the mixed monolayer and PEG linker co-functionalized samples was confirmed by both FTIR and TGA. Bi-functional PEG linkers allow the entire AuNP surface to be capped with PEG, enabling in-vitro stability to be achieved using a lower molecular weight PEG. The approach also allows the entire outer surface to be coated with peptide or other biologically active groups, whilst also offering the promise of enhanced biological availability. The effect of mixed monolayer versus PEG linker attachment on both stability and non-specific protein corona interactions was also studied.

Keywords: nanomedicine, gold nanoparticles, PEG, biocompatibility

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Authors: Ashish Thakur

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This technical paper was written in view of focusing the biomaterials and its various applications in modern industries. Author tires to elaborate not only the medical, infect plenty of application in other industries. The scope of the research area covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. Biomaterials are invariably in contact with living tissues. Thus, interactions between the surface of a synthetic material and biological environment must be well understood. This paper reviews the benefits and challenges associated with surface modification of the metals in biomedical applications. The paper also elaborates how the surface characteristics of metallic biomaterials, such as surface chemistry, topography, surface charge, and wettability, influence the protein adsorption and subsequent cell behavior in terms of adhesion, proliferation, and differentiation at the biomaterial–tissue interface. The chapter also highlights various techniques required for surface modification and coating of metallic biomaterials, including physicochemical and biochemical surface treatments and calcium phosphate and oxide coatings. In this review, the attention is focused on the biomaterial-associated infections, from which the need for anti-infective biomaterials originates. Biomaterial-associated infections differ markedly for epidemiology, aetiology and severity, depending mainly on the anatomic site, on the time of biomaterial application, and on the depth of the tissues harbouring the prosthesis. Here, the diversity and complexity of the different scenarios where medical devices are currently utilised are explored, providing an overview of the emblematic applicative fields and of the requirements for anti-infective biomaterials. In addition to this, chapter introduces nanomedicine and the use of both natural and synthetic polymeric biomaterials, focuses on specific current polymeric nanomedicine applications and research, and concludes with the challenges of nanomedicine research. Infection is currently regarded as the most severe and devastating complication associated to the use of biomaterials. Osteoporosis is a worldwide disease with a very high prevalence in humans older than 50. The main clinical consequences are bone fractures, which often lead to patient disability or even death. A number of commercial biomaterials are currently used to treat osteoporotic bone fractures, but most of these have not been specifically designed for that purpose. Many drug- or cell-loaded biomaterials have been proposed in research laboratories, but very few have received approval for commercial use. Polymeric nanomaterial-based therapeutics plays a key role in the field of medicine in treatment areas such as drug delivery, tissue engineering, cancer, diabetes, and neurodegenerative diseases. Advantages in the use of polymers over other materials for nanomedicine include increased functionality, design flexibility, improved processability, and, in some cases, biocompatibility.

Keywords: nanomedicine, tissue, infections, biomaterials

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Authors: Noam Markovitz

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People with physical disabilities constitute a very large and simultaneously a diverse group of general population, as the term physical disabilities is extensive and covers a wide range of disabilities. Therefore, individuals with physical disabilities are often faced with a new, threatening and stressful reality leading possibly to a multi-crisis in their lives due to the great changes they experience in somatic, socio-economic, occupational and psychological level. The current study seeks to advance understanding of the complex adaptation to physical disabilities by expanding the dynamic-adaptational model of the pursuit of happiness in a hostile world with a new conception of physical self-integrity. Physical self-integrity incorporates an objective dimension, namely physical self-functioning (PSF), and a subjective dimension, namely physical self-concept (PSC). Both of these dimensions constitute an experience of wholeness in the individual’s identification with her or his physical body. The model guiding this work is dialectical in nature and depicts two systems in the individual’s sense of happiness: subjective well-being (SWB) and meaning in life (MIL). Both systems serve as self-adaptive agents that moderate the complementary system of the hostile-world scenario (HWS), which integrates one’s perceived threats to one’s integrity. Thus, in situations of increased HWS, the moderation may take a form of joint activity in which SWB and MIL are amplified or a form of compensation in which one system produces a stronger effect while the other system produces a weaker effect. The current study investigated PSC in relations to SWB and MIL through pleasantness and meanings that are physically or metaphorically grounded in one’s body. In parallel, PSC also relates to HWS by activating representations of inappropriateness, deformation and vulnerability. In view of possibly dialectical positions of opposing and complementary forces within the current model, the current field study that aims to explore PSC as appearing in an independent, cross-sectional, design addressing the model’s variables in a focal group of people with physical disabilities. This study delineated the participation of the PSC in the adaptational functions of SWB and MIL vis-à-vis HWS-related life adversities. The findings showed that PSC could fully complement the main variables of the pursuit of happiness in a hostile world model. The assumed dialectics in the form of a stronger relationship between SWB and MIL in the face of physical disabilities was not supported. However, it was found that when HWS increased, PSC and MIL were strongly linked, whereas PSC and SWB were weakly linked. This highlights the compensatory role of MIL. From a conceptual viewpoint, the current investigation may clarify the role of PSC as an adaptational agent of the individual’s positive health in complementary senses of bodily wholeness. Methodologically, the advantage of the current investigation is the application of an integrative, model-based approach within a specially focused design with a particular relevance to PSC. Moreover, from an applicative viewpoint, the current investigation may suggest how an innovative model may be translated to therapeutic interventions used by clinicians, counselors and practitioners in improving wellness and psychological well-being, particularly among people with physical disabilities.

Keywords: older adults, physical disabilities, physical self-concept, pursuit of happiness in a hostile-world

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Authors: Ezzi Olfa, Bouafia Nabiha, Ammar Asma, Ben Cheikh Asma, Mahjoub Mohamed, Bannour Wadiaa, Achour Bechir, Khelif Abderrahim, Njah Mansour

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Background: In hematology/oncology, health care improvement has allowed increasingly aggressive management in diagnostic and therapeutic procedures. Nevertheless, these intensified procedures have been associated with higher risk of healthcare associated infections (HAIs). We undertook this study to estimate the burden of HAIs in the cancer patients in an onco -hematology unit in a Tunisian university hospital. Materials/Methods: A prospective, observational study, based on active surveillance for a period of 06 months from Mars through September 2016, was undertaken in the department of onco-hematology in a university hospital in Tunisia. Patients, who stayed in the unit for ≥ 48 h, were followed until hospital discharge. The Centers for Disease Control and Prevention criteria (CDC) for site-specific infections were used as standard definitions for HAIs. Results: One hundred fifty patients were included in the study. The gender distribution was 33.3% for girls and 66.6% boys. They have a mean age of 23.12 years (SD = 18.36 years). The main patient’s diagnosis is: Acute Lymphoblastic Leukemia (ALL): 48.7 %( n=73). The mean length of stay was 21 days +/- 18 days. Almost 8% of patients had an implantable port (n= 12), 34.9 % (n=52) had a lumber puncture and 42.7 % (n= 64) had a medullary puncture. Chemotherapy was instituted in 88% of patients (n=132). Eighty (53.3%) patients had neutropenia at admission. The incidence rate of HAIs was 32.66 % per patient; the incidence density was 15.73 per 1000 patient-days in the unit. Mortality rate was 9.3% (n= 14), and 50% of cases of death were caused by HAIs. The most frequent episodes of infection were: infection of skin and superficial mucosa (5.3%), pulmonary aspergillosis (4.6%), Healthcare associated pneumonia (HAP) (4%), Central venous catheter associated infection (4%), digestive infection (5%), and primary bloodstream infection (2.6%). Finally, fever of unknown origin (FUO) incidence rate was 14%. In case of skin and superficial infection (n= 8), 4 episodes were documented, and organisms implicated were Escherichia.coli, Geotricum capitatum and Proteus mirabilis. For pulmonary aspergillosis, 6 cases were diagnosed clinically and radiologically, and one was proved by positive aspergillus antigen in bronchial aspiration. Only one patient died due this infection. In HAP (6 cases), four episodes were diagnosed clinically and radiologically. No bacterial etiology was established in these cases. Two patients died due to HAP. For primary bloodstream infection (4 cases), implicated germs were Enterobacter cloacae, Geotricum capitatum, klebsiella pneumoniae, and Streptococcus pneumoniae. Conclusion: This type of prospective study is an indispensable tool for internal quality control. It is necessary to evaluate preventive measures and design control guides and strategies aimed to reduce the HAI’s rate and the morbidity and mortality associated with infection in a hematology/oncology unit.

Keywords: cohort prospective studies, healthcare associated infections, hematology oncology department, incidence

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Authors: Ashima Sharma

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Human Serum Albumin (HSA)- one of the most demanded therapeutic proteins with immense biotechnological applications- is a large multidomain protein containing 17 disulfide bonds. The current source of HSA is human blood plasma which is a limited and unsafe source. Thus, there exists an indispensable need to promote non-animal derived recombinant HSA (rHSA) production. Escherichia coli is one of the most convenient hosts which had contributed to the production of more than 30% of the FDA approved recombinant pharmaceuticals. It grows rapidly and reaches high cell density using inexpensive and simple substrates. E. coli derived recombinant products have more economic potential as fermentation processes are cheaper compared to the other expression hosts. The major bottleneck in exploiting E. coli as a host for a disulfide-rich multidomain protein is the formation of aggregates of overexpressed protein. The majority of the expressed HSA forms inclusion bodies (more than 90% of the total expressed rHSA) in the E. coli cytosol. Recovery of functional rHSA from inclusion bodies is not preferred because it is difficult to obtain a large multidomain disulfide bond rich protein like rHSA in its functional native form. Purification is tedious, time-consuming, laborious and expensive. Because of such limitations, the E. coli host system was neglected for rHSA production for the past few decades despite its numerous advantages. In the present work, we have exploited the capabilities of E. coli as a host for the enhanced functional production of rHSA (~60% of the total expressed rHSA in the soluble fraction). Parameters like intracellular environment, temperature, induction type, duration of induction, cell lysis conditions etc. which play an important role in enhancing the level of production of the desired protein in its native form in vivo have been optimized. We have studied the effect of assistance of different types of exogenously employed chaperone systems on the functional expression of rHSA in the E. coli host system. Different aspects of cell growth parameters during the production of rHSA in presence and absence of molecular chaperones in E. coli have also been studied. Upon overcoming the difficulties to produce functional rHSA in E. coli, it has been possible to produce significant levels of functional protein through engineering the biological system of protein folding in the cell, the E. coli-derived rHSA has been purified to homogeneity. Its detailed physicochemical characterization has been performed by monitoring its conformational properties, secondary and tertiary structure elements, surface properties, ligand binding properties, stability issues etc. These parameters of the recombinant protein have been compared with the naturally occurring protein from the human source. The outcome of the comparison reveals that the recombinant protein resembles exactly the same as the natural one. Hence, we propose that the E. coli-derived rHSA is an ideal biosimilar for human blood plasma-derived serum albumin. Therefore, in the present study, we have introduced and promoted the E. coli- derived rHSA as an alternative to the preparation from a human source, pHSA.

Keywords: recombinant human serum albumin, Escherichia coli, biosimilar, chaperone assisted protein folding

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Authors: Jessie Rapoza, Petr Moroshkin, Jimmy Xu

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Chirality is omnipresent, in nature, in life, and in the field of physics. One intriguing example is the homochirality that has remained a great secret of life. Another is the pairs of mirror-image molecules – enantiomers. They are identical in atomic composition and therefore indistinguishable in the scalar physical properties. Yet, they can be either therapeutic or toxic, depending on their chirality. Recent studies suggest a potential link between abnormal levels of certain D-amino acids and some serious health impairments, including schizophrenia, amyotrophic lateral sclerosis, and potentially cancer. Although indistinguishable in their scalar properties, the chirality of a molecule reveals itself in interaction with the surrounding of a certain chirality, or more generally, a broken mirror-symmetry. In this work, we report on a system for chiral molecule detection, in which the mirror-symmetry is doubly broken, first by asymmetric structuring a nanopatterned plasmonic surface than by the incidence of circularly polarized light (CPL). In this system, the incident circularly-polarized light induces a surface plasmon polariton (SPP) wave, propagating along the asymmetric plasmonic surface. This SPP field itself is chiral, evanescently bound to a near-field zone on the surface (~10nm thick), but with an amplitude greatly intensified (by up to 104) over that of the incident light. It hence probes just the molecules on the surface instead of those in the volume. In coupling to molecules along its path on the surface, the chiral SPP wave favors one chirality over the other, allowing for chirality detection via the change in an optical rectification current measured at the edges of the sample. The asymmetrically structured surface converts the high-frequency electron plasmonic-oscillations in the SPP wave into a net DC drift current that can be measured at the edge of the sample via the mechanism of optical rectification. The measured results validate these design concepts and principles. The observed optical rectification current exhibits a clear differentiation between a pair of enantiomers. Experiments were performed by focusing a 1064nm CW laser light at the sample - a gold grating microchip submerged in an approximately 1.82M solution of either L-arabinose or D-arabinose and water. A measurement of the current output was then recorded under both rights and left circularly polarized lights. Measurements were recorded at various angles of incidence to optimize the coupling between the spin-momentums of the incident light and that of the SPP, that is, spin-momentum locking. In order to suppress the background, the values of the photocurrent for the right CPL are subtracted from those for the left CPL. Comparison between the two arabinose enantiomers reveals a preferential signal response of one enantiomer to left CPL and the other enantiomer to right CPL. In sum, this work reports on the first experimental evidence of the feasibility of chiral molecule detection via optical rectification in a metal meta-grating. This nanoscale interfaced electrical detection technology is advantageous over other detection methods due to its size, cost, ease of use, and integration ability with read-out electronic circuits for data processing and interpretation.

Keywords: Chirality, detection, molecule, spin

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Authors: Fernanda Bravo Cornejo, Camilo Cerda Sarabia, Belén Díaz Díaz, Diego Santibañez Oyarce, Esteban Gómez Terán, Hugo Osses Prado, Raúl Caulier-Cisterna, Jorge Vergara-Quezada, Ana Moya-Beltrán

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Streptococcus pyogenes is a gram-positive bacteria involved in a wide range of diseases and is a major-human-specific bacterial pathogen. In Chile, this year the 'Ministerio de Salud' declared an alert due to the increase in strains throughout the year. This increase can be attributed to the multitude of factors including antimicrobial resistance (AMR) and Virulence Factors (VF). Understanding these VF and AMR is crucial for developing effective strategies and improving public health responses. Moreover, experimental identification and characterization of these pathogenic mechanisms are labor-intensive and time-consuming. Therefore, new computational methods are required to provide robust techniques for accelerating this identification. Advances in Machine Learning (ML) algorithms represent the opportunity to refine and accelerate the discovery of VF associated with Streptococcus pyogenes. In this work, we evaluate the accuracy of various machine learning models in predicting the virulence factors and antimicrobial resistance of Streptococcus pyogenes, with the objective of providing new methods for identifying the pathogenic mechanisms of this organism.Our comprehensive approach involved the download of 32,798 genbank files of S. pyogenes from NCBI dataset, coupled with the incorporation of data from Virulence Factor Database (VFDB) and Antibiotic Resistance Database (CARD) which contains sequences of AMR gene sequence and resistance profiles. These datasets provided labeled examples of both virulent and non-virulent genes, enabling a robust foundation for feature extraction and model training. We employed preprocessing, characterization and feature extraction techniques on primary nucleotide/amino acid sequences and selected the optimal more for model training. The feature set was constructed using sequence-based descriptors (e.g., k-mers and One-hot encoding), and functional annotations based on database prediction. The ML models compared are logistic regression, decision trees, support vector machines, neural networks among others. The results of this work show some differences in accuracy between the algorithms, these differences allow us to identify different aspects that represent unique opportunities for a more precise and efficient characterization and identification of VF and AMR. This comparative analysis underscores the value of integrating machine learning techniques in predicting S. pyogenes virulence and AMR, offering potential pathways for more effective diagnostic and therapeutic strategies. Future work will focus on incorporating additional omics data, such as transcriptomics, and exploring advanced deep learning models to further enhance predictive capabilities.

Keywords: antibiotic resistance, streptococcus pyogenes, virulence factors., machine learning

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Authors: George Zhou, Yunchan Chen, Candace Chien

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Kidney replacement therapy is the current standard of care for end-stage renal diseases. In-center or home hemodialysis remains an integral component of the therapeutic regimen. Arteriovenous fistulas (AVF) make up the vascular circuit through which blood is filtered and returned. Naturally, AVF patency determines whether adequate clearance and filtration can be achieved and directly influences clinical outcomes. Our aim was to build a deep learning model for automated AVF stenosis screening based on the sound of blood flow through the AVF. A total of 311 patients with AVF were enrolled in this study. Blood flow sounds were collected using a digital stethoscope. For each patient, blood flow sounds were collected at 6 different locations along the patient’s AVF. The 6 locations are artery, anastomosis, distal vein, middle vein, proximal vein, and venous arch. A total of 1866 sounds were collected. The blood flow sounds are labeled as “patent” (normal) or “stenotic” (abnormal). The labels are validated from concurrent ultrasound. Our dataset included 1527 “patent” and 339 “stenotic” sounds. We show that blood flow sounds vary significantly along the AVF. For example, the blood flow sound is loudest at the anastomosis site and softest at the cephalic arch. Contextualizing the sound with location metadata significantly improves classification performance. How to encode and incorporate categorical metadata is an active area of research1. Herein, we study ordinal (i.e., integer) encoding schemes. The numerical representation is concatenated to the flattened feature vector. We train a vision transformer (ViT) on spectrogram image representations of the sound and demonstrate that using scalar multiples of our integer encodings improves classification performance. Models are evaluated using a 10-fold cross-validation procedure. The baseline performance of our ViT without any location metadata achieves an AuROC and AuPRC of 0.68 ± 0.05 and 0.28 ± 0.09, respectively. Using the following encodings of Artery:0; Arch: 1; Proximal: 2; Middle: 3; Distal 4: Anastomosis: 5, the ViT achieves an AuROC and AuPRC of 0.69 ± 0.06 and 0.30 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 10; Proximal: 20; Middle: 30; Distal 40: Anastomosis: 50, the ViT achieves an AuROC and AuPRC of 0.74 ± 0.06 and 0.38 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 100; Proximal: 200; Middle: 300; Distal 400: Anastomosis: 500, the ViT achieves an AuROC and AuPRC of 0.78 ± 0.06 and 0.43 ± 0.11. respectively. Interestingly, we see that using increasing scalar multiples of our integer encoding scheme (i.e., encoding “venous arch” as 1,10,100) results in progressively improved performance. In theory, the integer values do not matter since we are optimizing the same loss function; the model can learn to increase or decrease the weights associated with location encodings and converge on the same solution. However, in the setting of limited data and computation resources, increasing the importance at initialization either leads to faster convergence or helps the model escape a local minimum.

Keywords: arteriovenous fistula, blood flow sounds, metadata encoding, deep learning

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Authors: Leo Nnamdi Ozurumba-Dwight

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Messenger ribooxynucleic acid (mRNA) molecules are compositional, protein-based. These proteins, encoding mRNA molecules (which collectively connote the transcriptome), when analyzed by RNA sequencing (RNAseq), unveils the nature of gene expression in the RNA. The obtained gene expression provides clues of cellular traits and their dynamics in presentations. These can be studied in relation to function and responses. RNAseq is a practical concept in Genomics as it enables detection and quantitative analysis of mRNA molecules. Single cell and spatial transcriptomics both present varying avenues for expositions in genomic characteristics of single cells and pooled cells in disease conditions such as cancer, auto-immune diseases, hematopoietic based diseases, among others, from investigated biological tissue samples. Single cell transcriptomics helps conduct a direct assessment of each building unit of tissues (the cell) during diagnosis and molecular gene expressional studies. A typical technique to achieve this is through the use of a single-cell RNA sequencer (scRNAseq), which helps in conducting high throughput genomic expressional studies. However, this technique generates expressional gene data for several cells which lack presentations on the cells’ positional coordinates within the tissue. As science is developmental, the use of complimentary pre-established tissue reference maps using molecular and bioinformatics techniques has innovatively sprung-forth and is now used to resolve this set back to produce both levels of data in one shot of scRNAseq analysis. This is an emerging conceptual approach in methodology for integrative and progressively dependable transcriptomics analysis. This can support in-situ fashioned analysis for better understanding of tissue functional organization, unveil new biomarkers for early-stage detection of diseases, biomarkers for therapeutic targets in drug development, and exposit nature of cell-to-cell interactions. Also, these are vital genomic signatures and characterizations of clinical applications. Over the past decades, RNAseq has generated a wide array of information that is igniting bespoke breakthroughs and innovations in Biomedicine. On the other side, spatial transcriptomics is tissue level based and utilized to study biological specimens having heterogeneous features. It exposits the gross identity of investigated mammalian tissues, which can then be used to study cell differentiation, track cell line trajectory patterns and behavior, and regulatory homeostasis in disease states. Also, it requires referenced positional analysis to make up of genomic signatures that will be sassed from the single cells in the tissue sample. Given these two presented approaches to RNA transcriptomics study in varying quantities of cell lines, with avenues for appropriate resolutions, both approaches have made the study of gene expression from mRNA molecules interesting, progressive, developmental, and helping to tackle health challenges head-on.

Keywords: transcriptomics, RNA sequencing, single cell, spatial, gene expression.

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Authors: Akanksha Agrawal, Richa Rathor, Geetha Suryakumar

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Muscle represents about ¾ of the body mass, and a healthy muscular system is required for human performance. A healthy muscular system is dynamically balanced via the catabolic and anabolic process. High altitude associated hypoxia altered this redox balance via producing reactive oxygen and nitrogen species that ultimately modulates protein structure and function, hence, disrupts proteostasis or protein homeostasis. The mechanism by which proteostasis is clinched includes regulated protein translation, protein folding, and protein degradation machinery. Perturbation in any of these mechanisms could increase proteome imbalance in the cellular processes. Altered proteostasis in skeletal muscle is likely to be responsible for contributing muscular atrophy in response to hypoxia. Therefore, we planned to elucidate the mechanism involving altered proteostasis leading to skeletal muscle atrophy under chronic hypobaric hypoxia. Material and Methods-Male Sprague Dawley rats weighing about 200-220 were divided into five groups - Control (Normoxic animals), 1d, 3d, 7d and 14d hypobaric hypoxia exposed animals. The animals were exposed to simulated hypoxia equivalent to 282 torr pressure (equivalent to an altitude of 7620m, 8% oxygen) at 25°C. On completion of chronic hypobaric hypoxia (CHH) exposure, rats were sacrificed, muscle was excised and biochemical, histopathological and protein synthesis signaling were studied. Results-A number of changes were observed with the CHH exposure time period. ROS was increased significantly on 07 and 14 days which were attributed to protein oxidation via damaging muscle protein structure by oxidation of amino acids moiety. The oxidative damage to the protein further enhanced the various protein degradation pathways. Calcium activated cysteine proteases and other intracellular proteases participate in protein turnover in muscles. Therefore, we analysed calpain and 20S proteosome activity which were noticeably increased at CHH exposure as compared to control group representing enhanced muscle protein catabolism. Since inflammatory markers (myokines) affect protein synthesis and triggers degradation machinery. So, we determined inflammatory pathway regulated under hypoxic environment. Other striking finding of the study was upregulation of Akt/PKB translational machinery that was increased on CHH exposure. Akt, p-Akt, p70 S6kinase, and GSK- 3β expression were upregulated till 7d of CHH exposure. Apoptosis related markers, caspase-3, caspase-9 and annexin V was also increased on CHH exposure. Conclusion: The present study provides evidence of disrupted proteostasis under chronic hypobaric hypoxia. A profound loss of muscle mass is accompanied by the muscle damage leading to apoptosis and cell death under CHH. These cellular stress response pathways may play a pivotal role in hypobaric hypoxia induced skeletal muscle atrophy. Further research in these signaling pathways will lead to development of therapeutic interventions for amelioration of hypoxia induced muscle atrophy.

Keywords: Akt/PKB translational machinery, chronic hypobaric hypoxia, muscle atrophy, protein degradation

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Authors: Jessica Neri, Elena Faccio

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In Europe, except for Denmark and Malta, the legal gender change and the stages of the possible process of gender transition are bound to the diagnosis of a gender identity disorder. The requirement of the evaluation of a mental disorder might have many implications on trans people’s self-representations, interpersonal relations in different social contexts and the therapeutic relations with clinicians during the transition. Psychopathological language may contribute to define the individual’s reality from normative presuppositions with value implications related to the dominant cultural principles. In an effort to mark the boundaries between sanity and pathology, it concurs to the definition of the management procedures of the constructed diversities and deviances, legitimizing the operational practices of particular professional figures. The aim of this research concerns the analysis of the diagnostic category of gender dysphoria contained in the last edition of the Diagnostic and Statistical Manual of Mental Disorders. In particular, this study focuses on the relationship between the implicit and explicit assumptions related to the expressions of gender non-conformity, that sustain the language and the criteria characterizing the Manual, and the possible implications on people’s narratives of transition. In order to achieve this objective two main research methods were used: historical reconstruction of the diagnostic category in the different versions of the Manual and content analysis of that category in the present version. From the historical analysis, in the medical and psychiatric field gender non-conformity has been predominantly explicated by naturalistic perspectives, naming it ‘transsexualism’ and collocating it in the category of gender identity disorder. Currently, pathological judged experiences are represented by gender dysphoria, described in the DSM-5 as the distress that may accompany the incongruence between one's experienced or expressed gender and one's assigned gender, specifying that there must be ‘evidence’ of this. Implicit theories about gender binary, parallelism between gender identity, sex and sexuality and the understanding of the mental health and the subject’s agency as subordinated to the expert knowledge, can be found in the process of designation of the category. A lack of awareness of the historical, social and political aspects connected to the cultural and normative dimensions at the basis of these implicit theories, can be noticed and data given by culture and data given by supposed -biological or psychological- nature, are often confused. This reductionist interpretation of gender and its presumed diversities legitimize the clinician to assume the role of searching and orienting, in a correctional perspective, the biographical elements that correspond to him specific expectations, with no space for other possibilities and identity configurations for people in transition. This research may contribute to the current critical debate about the epistemological foundation of the psychodiagnosis, emphasizing the pragmatic effects on the individuals and on the psychological practice in its wider social context. This work also permits to underline the risks due to the lack of awareness of the processes of social construction of the diagnostic system and its essential role of defence of the values that hold up the symbolic universe of reference.

Keywords: diagnosis, gender dysphoria, narratives, social constructionism

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Authors: K. Yu Vlasova, M. A. Abakumov, H. Wishwarsao, M. Sokolsky, N. V. Nukolova, A. G. Majouga, Y. I. Golovin, N. L. Klyachko, A. V. Kabanov

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Introduction:Nowadays pharmaceutical medicine is aimed to create systems for combined therapy, diagnostic, drug delivery and controlled release of active molecules to target cells. Magnetic nanoparticles (MNPs) are used to achieve this aim. MNPs can be applied in molecular diagnostics, magnetic resonance imaging (T1/T2 contrast agents), drug delivery, hyperthermia and could improve therapeutic effect of drugs. The most common drug containers, containing MNPs, are liposomes, micelles and polymeric molecules bonded to the MNPs surface. Usually superparamagnetic nanoparticles are used (the general diameter is about 5-6 nm) and all effects of high frequency magnetic field (MF) application are based on Neel relaxation resulting in heating of surrounded media. In this work we try to develop a new method to improve drug release from MNPs under super low frequency MF. We suppose that under low frequency MF exposures the Brown’s relaxation dominates and MNPs rotation could occur leading to conformation changes and release of bioactive molecules immobilized on MNPs surface.The aim of this work was to synthesize different systems with active drug (biopolymers coated MNPs nanoclusters with immobilized enzymes and doxorubicin (Dox) loaded magnetic liposomes/micelles) and investigate the effect of super low frequency MF on these drug containers. Methods: We have synthesized MNPs of magnetite with magnetic core diameter 7-12 nm . The MNPs were coated with block-copolymer of polylysine and polyethylene glycol. Superoxide dismutase 1 (SOD1) was electrostatically adsorbed on the surface of the clusters. Liposomes were prepared as follow: MNPs, phosphatidylcholine and cholesterol were dispersed in chloroform, dried to get film and then dispersed in distillated water, sonicated. Dox was added to the solution, pH was adjusted to 7.4 and excess of drug was removed by centrifugation through 3 kDa filters. Results: Polylysine coated MNPs formed nanosized clusters (as observed by TEM) with intensity average diameter of 112±5 nm and zeta potential 12±3 mV. After low frequency AC MF exposure we observed change of immobilized enzyme activity and hydrodynamic size of clusters. We suppose that the biomolecules (enzymes) are released from the MNPs surface followed with additional aggregation of complexes at the MF in medium. Centrifugation of the nanosuspension after AC MF exposures resulted in increase of positive charge of clusters and change in enzyme concentration in comparison with control sample without MF, thus confirming desorption of negatively charged enzyme from the positively charged surface of MNPs. Dox loaded magnetic liposomes had average diameter of 160±8 nm and polydispersity index (PDI) 0.25±0.07. Liposomes were stable in DW and PBS at pH=7.4 at 370C during a week. After MF application (10 min of exposure, 50 Hz, 230 mT) diameter of liposomes raised to 190±10 nm and PDI was 0.38±0.05. We explain this by destroying and/or reorganization of lipid bilayer, that leads to changes in release of drug in comparison with control without MF exposure. Conclusion: A new application of low frequency AC MF for drug delivery and controlled drug release was shown. Investigation was supported by RSF-14-13-00731 grant, K1-2014-022 grant.

Keywords: magnetic nanoparticles, low frequency magnetic field, drug delivery, controlled drug release

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Authors: Lucile Rapin, Cynthia El Hage, Rihab Gamaoun, Maria-Fernanda Arboleda, Erin Prosk

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Introduction: Sante Cannabis (SC), a Canadian group of clinics dedicated to medical cannabis, based in Montreal and in the province of Quebec, has served more than 8000 patients seeking cannabis-based treatment over the past five years. As randomized clinical trials with natural medical cannabis are scarce, real-world evidence offers the opportunity to fill research gaps between scientific evidence and clinical practice. Data on the use of medical cannabis products from SC patients were prospectively collected, leading to a large real-world database on the use of medical cannabis. The aim of this study was to report information on the profiles of both patients and prescribed medical cannabis products at SC clinics, and to assess the safety of medical cannabis among Canadian patients. Methods: This is an observational retrospective study of 1342 adult patients who were authorized with medical cannabis products between October 2017 and September 2019. Information regarding demographic characteristics, therapeutic indications for medical cannabis use, patterns in dosing and dosage form of medical cannabis and adverse effects over one-year follow-up (initial and 4 follow-up (FUP) visits) were collected. Results: 59% of SC patients were female, with a mean age of 56.7 (SD= 15.6, range= (19-97)). Cannabis products were authorized mainly for patients with a diagnosis of chronic pain (68.8% of patients), cancer (6.7%), neurological disorders (5.6%), and mood disorders (5.4 %). At initial visit, a large majority (70%) of patients were authorized exclusively medical cannabis products, 27% were authorized a combination of pharmaceutical cannabinoids and medical cannabis and 3% were prescribed only pharmaceutical cannabinoids. This pattern was recurrent over the one-year follow-up. Overall, oil was the preferred formulation (average over visits 72.5%) followed by a combination of oil and dry (average 19%), other routes of administration accounted for less than 4%. Patients were predominantly prescribed products with a balanced THC:CBD ratio (59%-75% across visits). 28% of patients reported at least one adverse effect (AE) at the 3-month follow-up visit and 12% at the six-month FUP visit. 84.8% of total AEs were mild and transient. No serious AE was reported. Overall, the most common side effects reported were dizziness (11.95% of total AEs), drowsiness (11.4%), dry mouth (5.5%), nausea (4.8%), headaches (4.6%), cough (4.4%), anxiety (4.1%) and euphoria (3.5%). Other adverse effects accounted for less than 3% of total AE. Conclusion: Our results confirm that the primary area of clinical use for medical cannabis is in pain management. Patients in this cohort are largely utilizing plant-based cannabis oil products with a balanced ratio of THC:CBD. Reported adverse effects were mild and included dizziness and drowsiness. This real-world data confirms the tolerable safety profile of medical cannabis and suggests medical indications not yet validated in controlled clinical trials. Such data offers an important opportunity for the investigation of the long-term effects of cannabinoid exposure in real-life conditions. Real-world evidence can be used to direct clinical trial research efforts on specific indications and dosing patterns for product development.

Keywords: medical cannabis, safety, real-world data, Canada

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Authors: Bernice Jeanne Lottering, Yi-Wen Lin

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Introduction: Chronic pain has a definitive lack of objective parameters in the measurement and treatment efficacy of diseases such as Fibromyalgia (FM). Persistent widespread pain and generalized tenderness are the characteristic symptoms affecting a large majority of the global population, particularly females. This disease has indicated a refractory tendency to conventional treatment ventures, largely resultant from a lack of etiological and pathogenic understanding of the disease development. Emerging evidence indicates that the central nervous system (CNS) plays a critical role in the amplification of pain signals and the neurotransmitters associated therewith. Various stimuli have been found to activate the channels existent on nociceptor terminals, thereby actuating nociceptive impulses along the pain pathways. The transient receptor potential vanalloid 1 (TRPV1) channel functions as a molecular integrator for numerous sensory inputs, such as nociception, and was explored in the current study. Current intervention approaches face a multitude challenges, ranging from effective therapeutic interventions to the limitation of pathognomonic criteria resultant from incomplete understanding and partial evidence on the mechanisms of action of FM. It remains unclear whether electroacupuncture (EA) plays an integral role in the functioning of the TRPV1 pathway, and whether or not it can reduce the chronic pain induced by FM. Aims: The aim of this study was to explore the mechanisms underlying the activation and modulation of the TRPV1 channel pathway in a cold stress model of FM applied to a murine model. Furthermore, the effect of EA in the treatment of mechanical and thermal pain, as expressed in FM was also to be investigated. Methods: 18 C57BL/6 wild type and 6 TRPV1 knockout (KO) mice, aged 8-12 weeks, were exposed to an intermittent cold stress-induced fibromyalgia-like pain model, with or without EA treatment at ZusanLi ST36 (2Hz/20min) on day 3 to 5. Von Frey and Hargreaves behaviour tests were implemented in order to analyze the mechanical and thermal pain thresholds on day 0, 3 and 5 in control group (C), FM group (FM), FM mice with EA treated group (FM + EA) and FM in KO group. Results: An increase in mechanical and thermal hyperalgesia was observed in the FM, EA and KO groups when compared to the control group. This initial increase was reduced in the EA group, which directs focus at the treatment efficacy of EA in nociceptive sensitization, and the analgesic effect EA has attenuating FM associated pain. Discussion: An increase in the nociceptive sensitization was observed through higher withdrawal thresholds in the von Frey mechanical test and the Hargreaves thermal test. TRPV1 function in mice has been scientifically associated with these nociceptive conduits, and the increased behaviour test results suggest that TRPV1 upregulation is central to the FM induced hyperalgesia. This data was supported by the decrease in sensitivity observed in results of the TRPV1 KO group. Moreover, the treatment of EA showed a decrease in this FM induced nociceptive sensitization, suggesting TRPV1 upregulation and overexpression can be attenuated by EA at bilateral ST36. This evidence compellingly implies that the analgesic effect of EA is associated with TRPV1 downregulation.

Keywords: fibromyalgia, electroacupuncture, TRPV1, nociception

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Authors: Gabriela Prins, Quinette Louw, Dawn Ernstzen

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Background: Access to rehabilitation services is a major challenge globally, especially in low-and-middle income countries (LMICs) where resources and infrastructure are extremely limited. Telerehabilitation (TR) has emerged in recent decades as a highly promising method to dramatically expand accessibility to rehabilitation services globally. TR provides rehabilitation care remotely using communication technologies such as video conferencing, smartphones, and internet-connected devices. This boosts accessibility to underprivileged regions and allows for greater flexibility for patients. Despite this, TR is hindered by several factors, including limited technological resources, high costs, lack of digital access, and the unavailability of healthcare systems, which are major barriers to widespread adoption among LMIC patients. These barriers have collectively hindered the potential implementation and adoption of TR services in LMICs healthcare settings. Adoption of TR will also require the buy-in of end users and limited information is known on the perspectives of the SA population. Aim: The study aimed to understand patients' perspectives regarding the use of digital technology as part of their OA rehabilitation at a public community healthcare centre in the Cape Metropole Area. Methods: A qualitative descriptive study design was used on 10 OA patients from a public community rehabilitation centre in South Africa. Data collection included semi-structured interviews and patient-reported outcome measures (PSFS, ASES-8, and EuroQol EQ-5D-5L) on functioning and quality of life. Transcribed interview data were coded in Atlas.ti. 22.2 and analyzed using thematic analysis. The results were narratively documented. Results: Four themes arose from the interviews. The themes were Telerehabilitation awareness (Use of Digital Technology Information Sources and Prior Experience with Technology /TR), Telerehabilitation Benefits (Access to healthcare providers, Access to educational information, Convenience, Time and Resource Efficiency and Facilitating Family Involvement), Telerehabilitation Implementation Considerations (Openness towards TR Implementation, Learning about TR and Technology, Therapeutic relationship, and Privacy) and Future use of Telerehabilitation (Personal Preference and TR for the next generation). The ten participants demonstrated limited awareness and exposure to TR, as well as minimal digital literacy and skills. Skepticism was shown when comparing the effectiveness of TR to in-person rehabilitation and valued physical interactions with health professionals. However, some recognized potential benefits of TR for accessibility, convenience, family involvement and improving community health in the long term. Willingness existed to try TR with sufficient training. Conclusion: With targeted efforts addressing identified barriers around awareness, technological literacy, clinician readiness and resource availability, perspectives on TR may shift positively from uncertainty towards endorsement of this expanding approach for simpler rehabilitation access in LMICs.

Keywords: digital technology, osteoarthritis, primary health care, telerehabilitation

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Authors: Aleksander Ejsmont, Aleksandra Galarda, Joanna Goscianska

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Smart porous carriers with defined structure and physicochemical properties are required for releasing the therapeutic drug with precise control of delivery time and location in the body. Due to their non-toxicity, ordered structure, chemical, and thermal stability, mesoporous carbons can be considered as modern carriers for active pharmaceutical ingredients (APIs) whose effectiveness needs frequent dosing algorithms. Such an API-carrier system, if programmed precisely, may stabilize the pharmaceutical and increase its dissolution leading to enhanced bioavailability. The substance conjugated with the material, through its prior adsorption, can later be successfully applied internally to the organism, as well as externally if the API release is feasible under these conditions. In the present study, ordered mesoporous carbons of different morphologies and structures, prepared by hard template method, were applied as carriers in the adsorption and controlled release of active pharmaceutical ingredients. In the first stage, the carbon materials were synthesized and functionalized with carboxylic groups by chemical oxidation using ammonium persulfate solution and then with amine groups. Materials obtained were thoroughly characterized with respect to morphology (scanning electron microscopy), structure (X-ray diffraction, transmission electron microscopy), characteristic functional groups (FT-IR spectroscopy), acid-base nature of surface groups (Boehm titration), parameters of the porous structure (low-temperature nitrogen adsorption) and thermal stability (TG analysis). This was followed by a series of tests of adsorption and release of paracetamol, benzocaine, and losartan potassium. Drug release experiments were performed in the simulated gastric fluid of pH 1.2 and phosphate buffer of pH 7.2 or 6.8 at 37.0 °C. The XRD patterns in the small-angle range and TEM images revealed that functionalization of mesoporous carbons with carboxylic or amine groups leads to the decreased ordering of their structure. Moreover, the modification caused a considerable reduction of the carbon-specific surface area and pore volume, but it simultaneously resulted in changing their acid-base properties. Mesoporous carbon materials exhibit different morphologies, which affect the host-guest interactions during the adsorption process of active pharmaceutical ingredients. All mesoporous carbons show high adsorption capacity towards drugs. The sorption capacity of materials is mainly affected by BET surface area and the structure/size matching between adsorbent and adsorbate. Selected APIs are linked to the surface of carbon materials mainly by hydrogen bonds, van der Waals forces, and electrostatic interactions. The release behavior of API is highly dependent on the physicochemical properties of mesoporous carbons. The release rate of APIs could be regulated by the introduction of functional groups and by changing the pH of the receptor medium. Acknowledgments—This research was supported by the National Science Centre, Poland (project SONATA-12 no: 2016/23/D/NZ7/01347).

Keywords: ordered mesoporous carbons, sorption capacity, drug delivery, carbon nanocarriers

Procedia PDF Downloads 176

Authors: Wanvipa Thongborisute, Punyaphat Sirithanabadeekul, Pichit Suvanprakorn, Anan Jiraviroon

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Background: Acne vulgaris is one of the most common dermatologic problems, and can have a significant psychological and physical effect on patients. Propionibacterium acnes' roles in acne vulgaris involve the activation of toll-like receptor 4 (TLR4), and toll-like receptor 2 (TLR2) pathways. By activating these pathways, inflammatory events of acne lesions, comedogenesis and sebaceous lipogenesis can occur. Currently, there are several topical agents commonly use in treating acne vulgaris that are known to have an effect on TLRs, such as retinoic acid and adapalene, but these drugs still have some irritating effects. At present, there is an alarming increase in rate of bacterial resistance due to irrational used of antibiotics both orally and topically. For this reason, acne treatments should contain bioactive molecules targeting at the site of action for the most effective therapeutic effect with the least side effects. Sparganium stoloniferumis a Chinese aquatic herb containing a compound called Sparstolonin B (SsnB), which has been reported to selectively blocks Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4)-mediated inflammatory signals. Therefore, this topical TLR2 and TLR4 antagonist, in a form of Sparganium stoloniferum-derived compound containing SsnB, should give a benefit in reducing inflammation of acne vulgaris lesions and providing an alternative treatments for patients with this condition. Materials and Methods: The objectives of this randomized double blinded split faced placebo controlled trial is to study the safety and efficacy of the Sparganium stoloniferum-derived compound. 32 volunteered patients with mild to moderate degree of acne vulgaris according to global acne grading system were included in the study. After being informed and consented the subjects were given 2 topical treatments for acne vulgaris, one being topical 2.40% Sparganium stoloniferum extraction (containing Sparstolonin B) and the other, placebo. The subjects were asked to apply each treatment to either half of the face daily morning and night by randomization for 8 weeks, and come in for a weekly follow up. For each visit, the patients went through a procedure of lesion counting, including comedones, papules, nodules, pustules, and cystic lesions. Results: During 8 weeks of experimentation, the result shows a reduction in total lesions number between the placebo and the treatment side show statistical significance starting at week 4, where the 95% confidence interval begin to no longer overlap, and shows a trend of continuing to be further apart. The decrease in the amount of total lesions between week 0 and week 8 of the placebo side shows no statistical significant at P value >0.05. While the decrease in the amount of total lesions of acne vulgaris of the treatment side comparing between week 0 and week 8 shows statistical significant at P value <0.001. Conclusion: The data demonstrates that 2.40% Sparganium stoloniferum extraction (containing Sparstolonin B) is more effective in treating acne vulgaris comparing to topical placebo in treating acne vulgaris, by showing significant reduction in the total numbers of acne lesions. Therefore, this topical Sparganium stoloniferum extraction could become a potential alternative treatment for acne vulgaris.

Keywords: acne vulgaris, sparganium stoloniferum, sparstolonin B, toll-like receptor 2, toll-like receptor 4

Procedia PDF Downloads 187

Authors: Mariyah Poonawala, Selvan Ravindran, Anuradha Vaidya

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Despite much progress in understanding the regulatory factors and cytokines that support the maturation of the various cell lineages of the hematopoietic system, factors that govern the self-renewal and proliferation of hematopoietic stem cells (HSCs) is still a grey area of research. Hematopoietic stem cell transplantation (HSCT) has evolved over the years and gained tremendous importance in the treatment of both malignant and non-malignant diseases. However, factors such as graft rejection and multiple organ failure have challenged HSCT from time to time, underscoring the urgent need for development of milder processes for successful hematopoietic transplantation. An emerging concept in the field of stem cell biology states that the interactions between the bone-marrow micro-environment and the hematopoietic stem and progenitor cells is essential for regulation, maintenance, commitment and proliferation of stem cells. Understanding the role of mesenchymal stromal cells in modulating the functionality of HSCs is, therefore, an important area of research. Trans-resveratrol has been extensively studied for its various properties to combat and prevent cancer, diabetes and cardiovascular diseases etc. The aim of the present study was to understand the effect of trans-resveratrol on HSCs using single and co-culture systems. We have used KG1a cells since it is a well accepted hematopoietic stem cell model system. Our preliminary experiments showed that low concentrations of trans-resveratrol stimulated the HSCs to undergo proliferation whereas high concentrations of trans-resveratrol did not stimulate the cells to proliferate. We used a murine fibroblast cell line, M210B4, as a stromal feeder layer. On culturing the KG1a cells with M210B4 cells, we observed that the stimulatory as well as inhibitory effects of trans-resveratrol at low and high concentrations respectively, were enhanced. Our further experiments showed that low concentration of trans-resveratrol reduced the generation of reactive oxygen species (ROS) and nitric oxide (NO) whereas high concentrations increased the oxidative stress in KG1a cells. We speculated that perhaps the oxidative stress was imposing inhibitory effects at high concentration and the same was confirmed by performing an apoptotic assay. Furthermore, cell cycle analysis and growth kinetic experiments provided evidence that low concentration of trans-resveratrol reduced the doubling time of the cells. Our hypothesis is that perhaps at low concentration of trans-resveratrol the cells get pushed into the G0/G1 phase and re-enter the cell cycle resulting in their proliferation, whereas at high concentration the cells are perhaps arrested at G2/M phase or at cytokinesis and therefore undergo apoptosis. Liquid Chromatography-Quantitative-Time of Flight–Mass Spectroscopy (LC-Q-TOF MS) analyses indicated the presence of trans-resveratrol and its metabolite(s) in the supernatant of the co-cultured cells incubated with high concentration of trans-resveratrol. We conjecture that perhaps the metabolites of trans-resveratrol are responsible for the apoptosis observed at the high concentration. Our findings may shed light on the unsolved problems in the in vitro expansion of stem cells and may have implications in the ex vivo manipulation of HSCs for therapeutic purposes.

Keywords: co-culture system, hematopoietic micro-environment, KG1a cell line, M210B4 cell line, trans-resveratrol

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Authors: J. Desbrieres, M. Popa, C. Peptu, S. Bacaita

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Because of their favorable properties (non-toxicity, biodegradability, mucoadhesivity etc.), polysaccharides were studied as biomaterials and as pharmaceutical excipients in drug formulations. These formulations may be produced in a wide variety of forms including hydrogels, hydrogel based particles (or capsules), films etc. In these formulations, the polysaccharide based materials are able to provide local delivery of loaded therapeutic agents but their delivery can be rapid and not easily time-controllable due to, particularly, the burst effect. This leads to a loss in drug efficiency and lifetime. To overcome the consequences of burst effect, systems involving liposomes incorporated into polysaccharide hydrogels may appear as a promising material in tissue engineering, regenerative medicine and drug loading systems. Liposomes are spherical self-closed structures, composed of curved lipid bilayers, which enclose part of the surrounding solvent into their structure. The simplicity of production, their biocompatibility, the size and similar composition of cells, the possibility of size adjustment for specific applications, the ability of hydrophilic or/and hydrophobic drug loading make them a revolutionary tool in nanomedicine and biomedical domain. Drug delivery systems were developed as hydrogels containing chitosan or carboxymethylcellulose (CMC) as polysaccharides and gelatin (GEL) as polypeptide, and phosphatidylcholine or phosphatidylcholine/cholesterol liposomes able to accurately control this delivery, without any burst effect. Hydrogels based on CMC were covalently crosslinked using glutaraldehyde, whereas chitosan based hydrogels were double crosslinked (ionically using sodium tripolyphosphate or sodium sulphate and covalently using glutaraldehyde). It has been proven that the liposome integrity is highly protected during the crosslinking procedure for the formation of the film network. Calcein was used as model active matter for delivery experiments. Multi-Lamellar vesicles (MLV) and Small Uni-Lamellar Vesicles (SUV) were prepared and compared. The liposomes are well distributed throughout the whole area of the film, and the vesicle distribution is equivalent (for both types of liposomes evaluated) on the film surface as well as deeper (100 microns) in the film matrix. An obvious decrease of the burst effect was observed in presence of liposomes as well as a uniform increase of calcein release that continues even at large time scales. Liposomes act as an extra barrier for calcein release. Systems containing MLVs release higher amounts of calcein compared to systems containing SUVs, although these liposomes are more stable in the matrix and diffuse with difficulty. This difference comes from the higher quantity of calcein present within the MLV in relation with their size. Modeling of release kinetics curves was performed and the release of hydrophilic drugs may be described by a multi-scale mechanism characterized by four distinct phases, each of them being characterized by a different kinetics model (Higuchi equation, Korsmeyer-Peppas model etc.). Knowledge of such models will be a very interesting tool for designing new formulations for tissue engineering, regenerative medicine and drug delivery systems.

Keywords: controlled and delayed release, hydrogels, liposomes, polysaccharides

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Authors: Anna Mucha, Ewa Wojtyna, Anita Pollak

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The environment in which an individual resides and observes may play a meaningful role in well-being and related constructs. Contact with nature may have a positive influence of natural environments on individuals, impacting mood and psychophysical sensations, such as pain relief. Conversely, urban settings, dominated by concrete elements, might lead to mood decline and heightened stress levels. Similarly, the situation may appear in the case of the perception of virtual environments. However, this is a topic that requires further exploration, especially in the context of relationships with pain. The aforementioned matters served as the basis for formulating and executing the outlined experimental research within the realm of environmental psychology, leveraging new technologies, notably virtual reality (VR), which is progressively gaining prominence in the domain of mental health. The primary objective was to investigate the impact of a simulated virtual environment, mirroring a natural setting abundant in greenery, on the perception of acute pain induced by thermal stimuli (high temperature) – encompassing intensity, unpleasantness, and pain tolerance. Comparative analyses were conducted between the virtual natural environment (intentionally constructed in the likeness of a therapeutic garden), virtual urban environment, and a control group devoid of virtual projections. Secondary objectives aimed to determine the mutual relationships among variables such as positive and negative emotions, preferences regarding virtual environments, sense of presence, and restorative experience in the context of the perception of presented virtual environments and induced thermal pain. The study encompassed 126 physically healthy Polish adults, distributing 42 individuals across each of the three comparative groups. Oculus Rift VR technology and the TSA-II neurosensory analyzer facilitated the experiment. Alongside demographic data, participants' subjective feelings concerning virtual reality and pain were evaluated using the Visual Analogue Scale (VAS), the original Restorative Experience in the Virtual World questionnaire (Doświadczenie Regeneracji w Wirtualnym Świecie), and an adapted Slater-Usoh-Steed (SUS) questionnaire. Results of statistical and psychometric analyses, such as Kruskal-Wallis tests, Wilcoxon tests, and contrast analyses, underscored the positive impact of the virtual natural environment on individual pain perception and mood. The virtual natural environment outperformed the virtual urban environment and the control group without virtual projection, particularly in subjective pain components like intensity and unpleasantness. Variables such as restorative experience, sense of presence and virtual environment preference also proved pivotal in pain perception and pain tolerance threshold alterations, contingent on specific conditions. This implies considerable application potential for virtual natural environments across diverse realms of psychology and related fields, among others as a supportive analgesic approach and a form of relaxation following psychotherapeutic sessions.

Keywords: environmental psychology, nature, acute pain, emotions, vitrual reality, virtual environments

Procedia PDF Downloads 63