Search results for: in vitro and in vivo cancer therapy

Authors: Malkhaz Jokhadze, Vakhtang Mshvildadze, Levan Makaradze, Ekaterine Mosidze, Salome Barbaqadze, Mariam Murtazashvili, Dali Berashvili, Koba sivsivadze, Lasha Bakuridze, Aliosha Bakuridze

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Essential oils are one of the most important groups of biologically active substances present in plants. Due to the chemical diversity of components, essential oils and their preparations have a wide spectrum of pharmacological action. They have bactericidal, antiviral, fungicidal, antiprotozoal, anti-inflammatory, spasmolytic, sedative and other activities. They are expectorant, spasmolytic, sedative, hypotensive, secretion enhancing, antioxidant remedies. Based on preliminary pharmacological studies, we have developed a formulation called “Phytobiotic” containing essential oils, a feed additive for poultry as an alternative to antibiotics. Phytobiotic is a water-soluble powder containing a composition of essential oils of thyme, clary, monarda and auxiliary substances: dry extract of liquorice and inhalation lactose. On this stage of research, the goal was to study the chemical composition of provided phytobiotic, identify the main substances and determine their quantity, investigate the biological activity of phytobiotic through in vitro and in vivo studies. Using gas chromatography-mass spectrometry, 38 components were identified in phytobiotic, representing acyclic-, monocyclic-, bicyclic-, and sesquiterpenes. Together with identification of main active substances, their quantitative content was determined, including acyclic terpene alcohol β-linalool, acyclic terpene ketone linalyl acetate, monocyclic terpenes: D-limonene and γ-terpinene, monocyclic aromatic terpene thymol. Provided phytobiotic has pronounced and at the same time broad spectrum of antibacterial activity. In the cell model, phytobiotic showed weak antioxidant activity, and it was stronger in the ORAC (chemical model) tests. Meanwhile anti-inflammatory activity was also observed. When fowls were supplied feed enriched with phytobiotic, it was observed that gained weight of the chickens in the experimental group exceeded the same data for the control group during the entire period of the experiment. The survival rate of broilers in the experimental group during the growth period was 98% compared to -94% in the control group. As a result of conducted researches probable four different mechanisms which are important for the action of phytobiotics were identified: sensory, metabolic, antioxidant and antibacterial action. General toxic, possible local irritant and allergenic effects of phytobiotic were also investigated. Performed assays proved that formulation is safe.

Keywords: clary, essential oils, monarda, poultry, phytobiotics, thyme

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Authors: Ananya Pal, Neelakshi Sarkar, Debraj Saha, Dipanwita Das, Subhashish Kamal Guha, Bibhuti Saha, Runu Chakravarty

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Presently, tenofovir disoproxil fumurate (TDF) is the most effective anti-viral agent for the treatment of hepatitis B virus (HBV) in individuals co-infected with HIV and HBV as TDF has activity to suppress both wild-type and lamivudine (3TC)-resistant HBV. However, suboptimal response to TDF was reported in HIV-HBV co-infected individuals with prior 3TC therapy from different countries recently. The incidence of 3TC-resistant HBV strains is quite high in HIV-HBV co-infected patients experiencing long-term anti-retroviral therapy (ART) in eastern India. In spite of this risk, most of the patients with long-term 3TC treatment are continued with the same anti-viral agent in this country. Only a few have received TDF in addition to 3TC in the ART regimen since TDF has been available in India for the treatment of HIV-infected patients in 2012. In this preliminary study, we investigated the virologic and biochemical parameters among HIV-HBV co-infected patients who are non-responders to 3TC treatment during the continuation of 3TC or TDF add-on to 3TC in their ART regimen. Fifteen HIV-HBV co-infected patients who experienced long-term 3TC (mean duration months 36.87 ± 24.08 months) were identified with high HBV viremia ( > 20,000 IU/ml) or harbouring 3TC-resistant HBV. These patients receiving ART from School of Tropical Medicine Kolkata, the main ART centre in eastern India were followed-up semi-annually for next three visits. Different virologic parameters including quantification of plasma HBV load by real-time PCR, detection of hepatitis B e antigen (HBeAg) by commercial ELISA and anti-viral resistant mutations by sequencing were studied. During three follow-up among study subjects, 86%, 47%, and 43% had 3TC-mono-therapy (mean treatment-duration 41.54±18.84, 49.67±11.67, 54.17±12.37 months respectively) whereas 14%, 53%, and 57% experienced TDF in addition to 3TC (mean treatment duration 4.5±2.12, 16.56±11.06, and 23±4.07 months respectively). Mean CD4 cell-count in patients receiving 3TC was tended to be lower during third follow-up as compared to the first and the second [520.67±380.30 (1st), 454.8±196.90 (2nd), and 397.5±189.24 (3rd) cells/mm3) and similar trend was seen in patients experiencing TDF in addition to 3TC [334.5±330.218 (1st), 476.5±194.25 (2nd), and 461.17±269.89 (3rd) cells/mm3]. Serum HBV load was increased during successive follow-up of patients with 3TC-mono-therapy. Initiation of TDF lowered serum HBV-load among 3TC-non-responders at the time of second visit ( < 2,000 IU/ml), interestingly during third follow-up, mean HBV viremia increased >1 log IU/ml (mean 3.56±2.84 log IU/ml). Persistence of 3TC-resistant double and triple mutations was also observed in both the treatment regimens. Mean serum alanine aminotransferase remained elevated in these patients during this follow-up study. Persistence of high HBV viraemia and 3TC-resistant mutation in HBV during the continuation of 3TC might lead to major public health threat in India. The inclusion of TDF in the ART regimen of 3TC non-responder HIV-HBV co-infected patients showed adverse treatment response in terms of virologic and biochemical parameters. Therefore, serious attention is necessary for proper management of long-term 3TC experienced HIV-HBV co-infected patients with high HBV viraemia or 3TC-resistant HBV mutants in India.

Keywords: HBV, HIV, TDF, 3TC-resistant

Procedia PDF Downloads 355

Authors: Affiah D. U., Katuri I. P., Emefiene M. E., Amienyo C. A.

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Broccoli (Brassica oleraceae L., var. italica) is one of the most important vegetables that is high in nutrients and bioactive compounds. It easily grown on a wide range of soil types and is adaptable to many different climatic conditions. This study was carried out within Jos North and environs in vitro to evaluate Neem (Azadirachta indica) leaves extract against Albugo candida, the causative agent of white blisters disease of broccoli. Through the survey, prevalence and incidence were accessed and a fluffy white growth symptom on the underside of leaves was also observed on the field. Infected leaves samples were collected from three different farms namely: Farin Gada, Naraguta, and Juth and the organism associated with the disease was isolated. Pathogenicity test carried out revealed the fungal isolate Albugo candida to be responsible for the disease. Antimicrobial susceptibility test was performed using agar well diffusion method to determine the minimum inhibitory concentrations of two extract of Azadirachta indica leaves against the organism. Ethanolic extract had the highest antifungal activities of 3.30±0.21 - 17.61± 0.11 while aqueous extract had the least antifungal activities of 0.00±0.00 - 13.23±0.12. The minimum inhibitory concentration of aqueous was 100 mg/ml while its minimum fungicidal concentration was at 200 mg/ml. For ethanol, the minimum inhibitory concentration was 50 mg/ml while its minimum fungicidal concentration was 100 mg/ml. Plants being less toxic in usage over synthetic or inorganic chemicals makes them easy to handle, easily accessible and renewable. Due to the biosafety of plant extracts and its availability since the plant-based extracts of the two different solvents were found to be effective against the test organism hence, it is recommended for in-depth research to make it readily available for control of other pathogens and pests.

Keywords: antifungal, biocontrol, broccoli, fungi

Procedia PDF Downloads 52

Authors: Pei-Chih Wu, Hsin-Chih Lai, Yung-Lung Lee, Yun-Yao Chi, Ching-Yi Horng, Hsien-Chang Wang

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The impact of climate change to health has always been well documented. Amongst them, water-borne infectious diseases, chronic adverse effects or cancer risks due to chemical contamination in flooding or drought events are especially important in river basin. This study therefore utilizes GIS and different models to integrate demographic, land use, disaster prevention, social-economic factors, and human health assessment in the Erren River basin. Therefore, through the collecting of climatic, demographic, health surveillance, water quality and other water monitoring data, potential risks associated with the Erren River Basin are established and to understand human exposure and vulnerability in response to climate extremes. This study assesses the temporal and spatial patterns of melioidosis (2000-2015) and various cancer incidents in Tainan and Kaohsiung cities. The next step is to analyze the spatial association between diseases incidences, climatic factors, land uses, and other demographic factors by using ArcMap and GeoDa. The study results show that amongst all melioidosis cases in Taiwan, 24% cases (115) residence occurred in the Erren River basin. The relationship between the cases and in Tainan and Kaohsiung cities are associated with population density, aging indicator, and residence in Erren River basin. Risks from flooding due to heavy rainfall and fish farms in spatial lag regression are also related. Through liver cancer, the preliminary analysis in temporal and spatial pattern shows an increases pattern in annual incidence without clusters in Erren River basin. Further analysis of potential cancers connected to heavy metal contamination from water pollution in Erren River is established. The final step is to develop an assessment tool for human exposure from water contamination and vulnerability in response to climate extremes for the second year.

Keywords: climate change, health impact, health adaptation, Erren River Basin

Procedia PDF Downloads 291

Authors: Sasan Khademnematolahi, Kevine Kamga Silihe, Katarína Pružinská, Martina Chrastina, Elisabeth Louise Ndjengue Mindang, František Dráfi, Katarína Bauerová

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Background: In ethnomedicine, plant parts and compounds are traditionally utilized to treat many disorders. Azadirachta indica, known as Neem, has been traditionally used in medicinal practices. Neem has various pharmaceutical activities, such as antioxidant and anti-inflammatory, due to the content of bioactive compounds like nimbolide, azadirachtin, and gedunin.Through its effect on pathological inflammatory processes, supplementation with it could alleviate the symptoms of rheumatoid arthritis (RA). Methods: This research aimed to assess Neem seed oil's impact on rats with adjuvant arthritis. Three doses in monotherapy and two in combination with methotrexate (MTX) have been studied and their effect was compared. Neem p.o. doses of 100, 200, and 300 mg/kg and MTX p.o. doses of 0.3 mg/kg were examined. After clinical parameters assessment, biochemical analysis was performed in plasma. Results: During the acute phase of the experimental arthritis (Day21), levels of MMP-9, MCP-1 and cytokines IL-1beta and IL-17A were measured. The positive results of inflammatory mediators evaluation in plasma encourage additional analysis also in related tissues to prove if Neem seed oil can be used as an adjuvant therapy for RA. Conclusion: In this study, the combination therapy of Neem with MTX was most effective from all therapies investigated.

Keywords: adjuvant, neem, methotrexate, arthritis

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Authors: Oluwasina Folajinmi, Kate Ssamulla, Penninah Lutung, Daniel Reijer

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Background: Despite of well-verified benefits of anti-retroviral therapy (ART) in prolonging life expectancy being lost to follow-up (LTFU) presents a challenge to the success of ART programs in resource limited countries like Nigeria. In several studies of ART programs in developing countries, researchers have reported that there has been a high rate of LTFU among patients receiving care and treatment at ART treatment centers. This study seeks to determine the cause of LTFU among HIV clients. Method: A descriptive cross sectional study focused on a population of 9,280 persons living with HIV/AIDS who were enrolled in nine treatment centers in Nigeria (both pre-ART and ART patients were included). Out of the total population, 1752 (18.9%) were found to be LTFU. Of this group we randomly selected 1200 clients (68.5%) their d patients’ information was generated through a database. Data on demographics and CD4 counts, causes of LTFU were analyzed and summarized. Results: Out of 1200 LTFU clients selected, 462 (38.5%) were on ART; 341 clients (73.8%) had CD4 level < 500cell/µL and 738 (61.5%) on pre-ART had CD4 level >500/µL. In our records we found telephone number for 675 (56.1%) of these clients. 675 (56.1%) were owners of a phone. The majority of the client’s 731 (60.9%) were living at not more than 25km away from the ART center. A majority were females (926 or 77.2%) while 274 (22.8%) were male. 675 (56.1%) clients were reported traced via telephone and home address. 326 (27.2%) of clients phone numbers were not reachable; 173 (14.4%) of telephone numbers were incomplete. 71 (5.9%) had relocated due to communal crises and expert client trackers reported that some patient could not afford transportation to ART centers. Conclusion: This study shows that, low health education levels, poverty, relocations and lack of reliable phone contact were major predictors of LTFU. Periodic updates of home addresses, telephone contacts including at least two next of kin, phone text messages and home visits may improve follow up. Early and consistent tracking of missed appointments is crucial. Creation of more ART decentralized centres are needed to avoid long distances.

Keywords: anti-retroviral therapy, HIV/AIDS, predictors, lost to follow up

Procedia PDF Downloads 288

Authors: Nasrin Hosseinzad

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Troxerutin, a trihydroxyethylated derived of rutin, is a flavonoid existing in tea, coffee, cereal grains, various fruits and vegetables have been conveyed to display radioprotective, antithrombotic, nephron-protective and hepato-protective possessions. Troxerutin, has been well-proved to utilize hepatoprotective assets. Troxerutin could upturn the resistance of hippocampal neurons alongside apoptosis by lessening the action of AChE and oxidative stress. Consequently, troxerutin may have advantageous properties in the administration of Alzheimer's disease and cancer. Troxerutin has been testified to have several welfares and medicinal stuffs. It could shelter the mouse kidney against d-gal-induced damage by refining renal utility, decreasing histopathologic changes, dropping ROS construction, reintroducing the activities of antioxidant enzymes and reducing DNA oxidative destruction. The DNA cleavage study clarifies that troxerutin showed DNA protection against hydroxyl radical persuaded DNA mutilation. Troxerutin uses anti-cancer effect in HuH-7 hepatocarcinoma cells conceivably through synchronized regulation of the molecular signalling pathways, Nrf2 and NF-κB. DNA binding at slight channel by troxerutin may have donated to feature breaks leading to improved radiation brought cell death. Furthermore, the mechanism principal the observed variance in the antioxidant activities of troxerutin and its esters was qualified to equally their free radical scavenging capabilities and dissemination on the cell membrane outward.

Keywords: troxerutin, DNA, oxidative stress, antioxidant, free radical

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Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia Abdul Majid, Hapipa Mohd Ali, Pouya Hassandarvish, Maryam Zahedi Fard

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Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, andrographolide, colon cancer, aberrant crypt foci (ACF)

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Authors: Snezana Mugosa, Zoran Todorovic, Zoran Bukumiric, Ivan Radosavljevic, Natasa Djordjevic

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Introduction: Various studies have shown that the frequency of clopidogrel resistance ranges from 4-40%. The aim of this study was to provide in depth analysis of genetic and non-genetic factors that influence clopidogrel resistance in cardiology patients. Methods: We have conducted a prospective study in 200 hospitalized patients hospitalized at Cardiology Centre of the Clinical Centre of Montenegro. CYP2C19 genetic testing was conducted, and the PREDICT score was calculated in 102 out of 200 patients treated with clopidogrel in order to determine the influence of genetic and non-genetic factors on outcomes of interest. Adverse cardiovascular events and adverse reactions to clopidogrel were assessed during 12 months follow up period. Results: PREDICT score and CYP2C19 enzymatic activity were found to be statistically significant predictors of expressing lack of therapeutic efficacy of clopidogrel by multivariate logistic regression, without multicollinearity or interaction between the predictors (p = 0.002 and 0.009, respectively). Conclusions: Pharmacogenetics analyses that were done in the Montenegrin population of patients for the first time suggest that these analyses can predict patient response to the certain therapy. Stepwise approach could be used in assessing the clopidogrel resistance in cardiology patients, combining the PREDICT score, platelet aggregation test, and genetic testing for CYP2C19 polymorphism.

Keywords: clopidogrel, pharmacogenetics, pharmacotherapy, PREDICT score

Procedia PDF Downloads 335

Authors: Emil Sakharov, Alex Zotov, Ilkin Osmanov, Oleg Shelest, Aleksander Troitskiy, Robert Khabazov

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Objective: Since 2015, our center has been actively implementing methods of surgical correction of atrial fibrillation, in particular, in patients with coronary heart disease. The study presents a comparative analysis of the late postoperative period in patients with coronary artery bypass grafting and atrial fibrillation. Methods: The study included 150 patients with ischemic heart disease and atrial fibrillation for the period from 2015 to 2021. Patients were divided into 2 groups. The first group is represented by patients with ischemic heart disease and atrial fibrillation who underwent coronary bypass surgery and surgical correction of atrial fibrillation (N=50). The second group is represented by patients with ischemic heart disease and atrial fibrillation who underwent only myocardial revascularization (N=100). Patients were comparable in age, gender, and initial severity of the condition. Among the patients in group 1 there were 82% were men, while in the second group, their number was 75%. Among the patients of the first group, there were 36% with persistent atrial fibrillation, 20% with long-term persistent atrial fibrillation. In the second group, 10% with persistent atrial fibrillation and 17% with long-term persistent atrial fibrillation. Results: Average follow-up for groups 1 and 2 amounted to 47 months. There were no complications in group 1, such as bleeding and stroke. There was only 1 patient in group 1, who had died from cardiovascular disease. Freedom of atrial fibrillation was in 82% without AADs therapy. In group 2 there were 8 patients who had died from cardiovascular diseases and total freedom of atrial fibrillation was in 35% of patients, among which 42.8% had additional AADs therapy. Follow-up data are presented in Table 2. Progression of heart failure was observed in 3% in group 1 and 7% in group 2. Combined endpoints (recurrence of AF, stroke, progression of heart failure, myocardial infarction) were achieved in 16% in group 1 and 34% in group 2, respectively. Freedom from atrial fibrillation without antiarrhythmic therapy was 82% for group 1 and 35% for group 2. In the first group, there is a more pronounced decrease in heart failure rates. Deaths from cardiovascular causes were recorded in 2% for group 1 and 7% for group 2. Conclusion: Surgical treatment of atrial fibrillation helps to reduce adverse complications in the late postoperative period and contributes to the regression of heart failure.

Keywords: atrial fibrillation, coronary artery bypass grafting, ischaemic heart disease, heart failure

Procedia PDF Downloads 106

Authors: Fauziah Mohd Sa’ad, Mohammad Aziz Shah, B. Mohammad Arip, Norazani Ahmad, Mohd Noor Idris, Hapsah M. Yusof

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This study was carried out to assess the application of person-centred therapy and Cognitive Psychology Ad-Din group counseling on self-concept, depression, and resilience of teenage pregnancy. This study involved 55 teenage pregnancy at three women’s refuge centers which are from KEWAJA, Rhaidatus Sakinah, and Taman Seri Puteri Cheras (JKM). Subjects were classed into two treatment groups and one control group. The Multidimensional Self-Concept Scale (MSCS), Beck Depression inventory (BDI) and Adolescent Resiliency Attitude Scale (ARAS) was administered to assess self-concept, depression, and resilience of teenage pregnancy. The control pre and post test design was used for this study. The research data were analyzed using descriptive analysis, ANOVA, MANCOVA and Tuckey Post Hoc with the significant level of .01 and .05. All treatment group received group counseling sessions for 7 consecutive week, once in each week. The Person-centred group and Cognitive Psychology Ad-Din group counseling showed a significant reduction (pre-test to post-test) on depression, enhancing self-concept and resilience of teenage pregnancy.

Keywords: group counseling, person-centred therapy, cognitive psychology Ad-Din, teenage pregnancy

Procedia PDF Downloads 551

Authors: Mary Butler

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Background: Screening programmes for older drivers in Europe (though not the UK), and in many states in the US and in Australia are based on medical assessment of fitness to drive. These programmes require physicians (including general practitioners) to carry out an assessment of fitness to drive in their offices. In 2006, New Zealand changed from doing on-road driving tests with all older drivers from the age of 80, to a screening programme that uses medical assessment of fitness to drive only. Aim: This study set out to understand the experience of New Zealand GPs as they manage the process of medical assessment of fitness to drive assessments for older people. In particular, it aimed to establish how GPs understand the role of specialist driving assessment and rehabilitation carried out by occupational therapists. Design and setting: The study used an interpretive descriptive approach to analyze data from ten interviews with GPs in New Zealand. Results: The results indicated that GPs lack understanding about how occupational therapists can assist their patients, and tend to refer only when there is a disagreement with the patient. Conclusion: There are problems with the medical assessment of fitness to drive carried out by GPs, and there is a need for a more comprehensive community approach to driving cessation. Patients, families and the multidisciplinary team all have a role in deciding when driving cessation should occur. Occupational therapists have a particular responsibility for strategic leadership in this area of practice.

Keywords: assessment, driving, older people, occupational therapy

Procedia PDF Downloads 122

Authors: Nouha Bouayed Abdelmoula, Rim Louati, Nawel Abdellaoui, Balkiss Abdelmoula, Oldez Kaabi, Walid Smaoui, Samir Aloulou

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Background and Aims: Cardiofaciocutaneous syndrome (CFC) is an autosomal dominant disorder with the vast majority of cases arising by a new mutation of BRAF, MEK1, MEK2, or rarely, KRAS genes. Here, we report a rare Tunisian case of CFC syndrome for whom we identify SOS1 mutation. Methods: Genomic DNA was obtained from peripheral blood collected in an EDTA tube and extracted from leukocytes using the phenol/chloroform method according to standard protocols. High resolution melting (HRM) analysis for screening of mutations in the entire coding sequence of PTPN11 was conducted first. Then, HRM assays to look for hot spot mutations coding regions of the other genes of the RAS-MAPK pathway (RAt Sarcoma viral oncogene homolog Mitogen-Activated Protein Kinases Pathway): SOS1, SHOC2, KRAS, RAF1, KRAS, NRAS, CBL, BRAF, MEK1, MEK2, HRAS, and RIT1, were applied. Results: Heterozygous SOS1 point mutation clustered in exon 10, which encodes for the PH domain of SOS1, was identified: c.1655 G > A. The patient was a 9-year-old female born from a consanguineous couple. She exhibited pulmonic valvular stenosis as congenital heart disease. She had facial features and other malformations of Noonan syndrome, including macrocephaly, hypertelorism, ptosis, downslanting palpebral fissures, sparse eyebrows, a short and broad nose with upturned tip, low-set ears, high forehead commonly associated with bitemporal narrowing and prominent supraorbital ridges, short and/or webbed neck and short stature. However, the phenotype is also suggestive of CFC syndrome with the presence of more severe ectodermal abnormalities, including curly hair, keloid scars, hyperkeratotic skin, deep plantar creases, and delayed permanent dentition with agenesis of the right maxillary first molar. Moreover, the familial history of the patient revealed recurrent brain malignancies in the paternal family and epileptic disease in the maternal family. Conclusions: This case report of an overlapping RASopathy associated with SOS1 mutation and familial history of brain tumorigenesis is exceptional. The evidence suggests that RASopathies are truly cancer-prone syndromes, but the magnitude of the cancer risk and the types of cancer partially overlap.

Keywords: cardiofaciocutaneous syndrome, CFC, SOS1, brain cancer, germline mutation

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Authors: Kavita Khoiwal, Vatsla Dadhwal, K. Aparna Sharma, Dipika Deka, Plabani Sarkar

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Introduction: About 2.4 million (1.93 - 3.04 million) people are living with HIV/AIDS in India. Of all HIV infections, 39% (9,30,000) are among women. 5.4% of infections are from mother to child transmission (MTCT), 25,000 infected children are born every year. Besides the risk of mother to child transmission of HIV, these women are at risk of the higher adverse pregnancy outcome. The objectives of the study were to compare the obstetric and neonatal outcome in women who are HIV positive with low-risk HIV negative women and effect of antiretroviral drugs on preterm birth and IUGR. Materials and Methods: This is a retrospective case record analysis of 212 HIV-positive women delivering between 2002 to 2015, in a tertiary health care centre which was compared with 238 HIV-negative controls. Women who underwent medical termination of pregnancy and abortion were excluded from the study. Obstetric outcome analyzed were pregnancy induced hypertension, HIV positive intrauterine growth restriction, preterm birth, anemia, gestational diabetes and intrahepatic cholestasis of pregnancy. Neonatal outcome analysed were birth weight, apgar score, NICU admission and perinatal transmission.HIV-positiveOut of 212 women, 204 received antiretroviral therapy (ART) to prevent MTCT, 27 women received single dose nevirapine (sdNVP) or sdNVP tailed with 7 days of zidovudine and lamivudine (ZDV + 3TC), 15 received ZDV, 82 women received duovir and 80 women received triple drug therapy depending upon the time period of presentation. Results: Mean age of 212 HIV positive women was 25.72+3.6 years, 101 women (47.6 %) were primigravida. HIV positive status was diagnosed during pregnancy in 200 women while 12 women were diagnosed prior to conception. Among 212 HIV positive women, 20 (9.4 %) women had preterm delivery (< 37 weeks), 194 women (91.5 %) delivered by cesarean section and 18 women (8.5 %) delivered vaginally. 178 neonates (83.9 %) received exclusive top feeding and 34 neonates (16.03 %) received exclusive breast feeding. When compared to low risk HIV negative women (n=238), HIV positive women were more likely to deliver preterm (OR 1.27), have anemia (OR 1.39) and intrauterine growth restriction (OR 2.07). Incidence of pregnancy induced hypertension, diabetes mellitus and ICP was not increased. Mean birth weight was significantly lower in HIV positive women (2593.60+499 gm) when compared to HIV negative women (2919+459 gm). Complete follow up is available for 148 neonates till date, rest are under evaluation. Out of these 7 neonates found to have HIV positive status. Risk of preterm birth (P value = 0.039) and IUGR (P value = 0.739) was higher in HIV positive women who did not receive any ART during pregnancy than women who received ART. Conclusion: HIV positive pregnant women are at increased risk of adverse pregnancy outcome. Multidisciplinary team approach and use of highly active antiretroviral therapy can optimize the maternal and perinatal outcome.

Keywords: antiretroviral therapy, HIV infection, IUGR, preterm birth

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Authors: Nurul Hamirah Kamsani, Mohd Hamim Rajikin, Nor Ashikin Mohamed Noor Khan, Sharaniza Abdul Rahim

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Cytoskeletal structures, in particular actin and tubulin, provide a fundamental framework in all cells, including embryos. Under influence of nicotine, the cytoskeletal organization may be subjected to oxidative stress (OS) insult and cause alteration. Tocotrienol-rich fraction (TRF) is proven to enhance fertility better than the other sub-group of Vitamin E, tocopherols (TCPs). The objective of this study was to evaluate the effects of TRF on 1) actin and tubulin of 2- and 8-cell murine embryos and 2) the regulation of reactive oxygen species (ROS)-scavenging enzymes; induced by nicotine. Twenty four female Balb/C were subjected to either subcutaneous (sc) injection of 0.9% NaCl; sc injection of 3.0 mg/kg bw/day nicotine; sc injection of 3.0 mg/kg bw/day nicotine + oral gavage (OG) of 60 mg/kg bw/day TRF; or OG of 60 mg/kg bw/day TRF for 7 consecutive days. After superovulation and mating, animals were euthanized. 2-cell developing embryos were retrieved. 50% of the retrieved embryos were visualized under confocal laser staining microscopy (CLSM) for alterations of actin and tubulin. The remaining amount of embryos was cultured in vitro until 8-cell stage followed by CLSM visualization. Blood plasma was subjected to OS assays. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined and analysed accordingly. At both 2- and 8-cell developing stages, actin intensities were significantly reduced in the nicotine group (p<0.001). After the intervention, actin intensity was significantly increased compared to that of the nicotine group (p<0.001). The same trend was seen in tubulin at both cell stages. TRF has minimized the deleterious effects of nicotine in actin and tubulin of both 2- and 8-cell developmental stages during pre-implantation embryonic development in mice in vitro. Levels of endogenous anti-oxidative enzymes were sustained close to control accompanied by decreased levels of OS biomarker.

Keywords: actin, nicotine, pre-implantation embryos, tocotrienol rich fraction, tubulin

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Authors: Itzel Amaro-Estrada, Eduardo Vergara-Rivera, Virginia Juarez-Flores, Mayra Cobaxin-Cardenas, Rosa Estela Quiroz, Jesus F. Preciado, Sergio Rodriguez-Camarillo

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Bovine anaplasmosis is an infectious, tick-borne disease caused mainly by Anaplasma marginale; typical signs include anemia, fever, abortion, weight loss, decreased milk production, jaundice, and potentially death. Sick bovine can recover when antibiotics are administered; however, it usually remains as carrier for life, being a risk of infection for susceptible cattle. Anaplasma marginale is an obligate intracellular Gram-negative bacterium with genetic composition highly diverse among geographical isolates. There are currently no vaccines fully effective against bovine anaplasmosis; therefore, the economic losses due to disease are present. Vaccine formulation became a hard task for several pathogens as Anaplasma marginale, but peptide-based vaccines are an interesting proposal way to induce specific responses. Phage-displayed peptide libraries have been proved one of the most powerful technologies for identifying specific ligands. Screening of these peptides libraries is also a tool for studying interactions between proteins or peptides. Thus, it has allowed the identification of ligands recognized by polyclonal antiserums, and it has been successful for the identification of relevant epitopes in chronic diseases and toxicological conditions. Protective immune response to bovine anaplasmosis includes high levels of immunoglobulins subclass G2 (IgG2) but not subclass IgG1. Therefore, IgG2 from the serum of protected bovine can be useful to identify ligands, which can be part of an immunogen for cattle. In this work, phage display random peptide library Ph.D. ™ -12 was incubating with IgG2 or blood sera of immunized bovines against A. marginale as targets. After three rounds of biopanning, several candidates were selected for additional analysis. Subsequently, their reactivity with sera immunized against A. marginale, as well as with positive and negative sera to A. marginale was evaluated by immunoassays. A collection of recognized peptides tested by ELISA was generated. More than three hundred phage-peptides were separately evaluated against molecules which were used during panning. At least ten different peptides sequences were determined from their nucleotide composition. In this approach, three phage-peptides were selected by their binding and affinity properties. In the case of the development of vaccines or diagnostic reagents, it is important to evaluate the immunogenic and antigenic properties of the peptides. Immunogenic in vitro and in vivo behavior of peptides will be assayed as synthetic and as phage-peptide for to determinate their vaccine potential. Acknowledgment: This work was supported by grant SEP-CONACYT 252577 given to I. Amaro-Estrada.

Keywords: bovine anaplasmosis, peptides, phage display, veterinary vaccines

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Authors: Mohammed Ghazwani, Shyma Ali Alshahrani, Zahra Abdu Yousef, Taif Torki Asiri, Ghofran Abdur Rahman, Asma Ali Alshahrani, Umme Hani

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Background and introduction: Piroxicam is a nonsteroidal anti-inflammatory drug characterized by low solubility-high permeability used to reduce pain, swelling, and joint stiffness from arthritis. Hydrotropes are a class of compounds that normally increase the aqueous solubility of insoluble solutes. Aim: The objective of the present research study was to formulate and optimize Piroxicam hydrotropic starch gel using sodium salicylate, sodium benzoate as hydrotropic salts, and potato starch for topical application. Materials and methods: The prepared Piroxicam hydrotropic starch gel was characterized for various physicochemical parameters like drug content estimation, pH, tube extrudability, and spreadability; all the prepared formulations were subjected to in-vitro diffusion studies for six hours in 100 ml phosphate buffer (pH 7.4) and determined gel strength. Results: All formulations were found to be white opaque in appearance and have good homogeneity. The pH of formulations was found to be between 6.9-7.9. Drug content ranged from 96.8%-99.4.5%. Spreadability plays an important role in patient compliance and helps in the uniform application of gel to the skin as gels should spread easily; F4 showed a spreadability of 2.4cm highest among all other formulations. In in vitro diffusion studies, extrudability and gel strength were good with F4 in comparison with other formulations; hence F4 was selected as the optimized formulation. Conclusion: Isolated potato starch was successfully employed to prepare the gel. Hydrotropic salt sodium salicylate increased the solubility of Piroxicam and resulted in a stable gel, whereas the gel prepared using sodium benzoate changed its color after one week of preparation from white to light yellowish. Hydrotropic potato starch gel proposed a suitable vehicle for the topical delivery of Piroxicam.

Keywords: Piroxicam, potato starch, hydrotropic salts, hydrotropic starch gel

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Authors: Emanuela Zilli, Antonio Madia, Milvia Marchiori, Paola Anello, Chiara Cabbia, Emanuela Velo, Delia Campagnolo, Michele Scomazzon, Emanuela Salvatico, S. Tikvina, Antonio Miotti

Abstract:

Hepatitis C is an inflammation of the liver caused by the hepatitis C virus (HCV). Antiviral medicines can cure more than 95% of cases of hepatitis C infection, but access to diagnosis and treatment remains low. The ULSS 6 Euganea – Health Trust has implemented a campaign to eradicate hepatitis C in the province of Padua (North-East of Italy), which can be subdivided into three areas: North (300.000 inhabitants), Centre (400.000) and South (300.000). In September 2021, the project was launched in the Northern area; a set of brochures was distributed in outpatient services, general practitioners’ clinics and offices, community pharmacy services, social health districts, and through social networks. The Hepatology Service contacted 460 patients selected by the Clinical Laboratory (positivity for HCV antibodies): 83 patients (18.0%) had been already cured of HCV infection, missing or deceased; 377 patients (82.0%) met the criteria to be eligible for HCV eradication therapy and were therefore included in a Day Service specific agenda and followed by a multidisciplinary team of healthcare professionals, with a dedicated telephone line. Haemato-chemical tests, general medical check-ups and ultrasound tests with fibroscan were performed. Patients were tested for Sars-CoV-2 positivity; those not yet vaccinated against Covid-19 were encouraged to complete the vaccination scheme. All 377 patients (100%) received HCV eradication therapy at the community pharmacy service; a detailed explanation of how to take their medication was provided. At the end of the first phase, Covid-19 vaccination rate was 100% (377/377), including patients already vaccinated and new-vaccinated. Check-up appointments were arranged after 2 or 3 months, according to the treatment plan. The awareness campaign and the organization of HCV eradication therapy service by ULSS 6 Euganea are proving to be effective; the project is now going to be applied to Central and Southern areas of the province (1.132 patients).

Keywords: public health, HCV-eradication, Covid-19 emergency, health communication strategies

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Authors: W. J. Zhang, Y. Q. Du, M. L. Wang

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Noninvasive diagnostics of diseases via breath analysis has attracted considerable scientific and clinical interest for many years and become more and more promising with the rapid advancement in nanotechnology and biotechnology. The volatile organic compounds (VOCs) in exhaled breath, which are mainly blood borne, particularly provide highly valuable information about individuals’ physiological and pathophysiological conditions. Additionally, breath analysis is noninvasive, real-time, painless and agreeable to patients. We have developed a wireless sensor array based on single-stranded DNA (ssDNA)-decorated single-walled carbon nanotubes (SWNT) for the detection of a number of physiological indicators in breath. Eight DNA sequences were used to functionalize SWNT sensors to detect trace amount of methanol, benzene, dimethyl sulfide, hydrogen sulfide, acetone and ethanol, which are indicators of heavy smoking, excessive drinking, and diseases such as lung cancer, breast cancer, cirrhosis and diabetes. Our tests indicated that DNA functionalized SWNT sensors exhibit great selectivity, sensitivity, reproducibility, and repeatability. Furthermore, different molecules can be distinguished through pattern recognition enabled by this sensor array. Thus, the DNA-SWNT sensor array has great potential to be applied in chemical or bimolecular detection for the noninvasive diagnostics of diseases and health monitoring.

Keywords: breath analysis, diagnosis, DNA-SWNT sensor array, noninvasive

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Authors: Navah Z. Ratzon, Talia Glick, Iris Manor

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Attention Deficit Hyperactivity Disorder (ADHD) is a chronic disorder that affects the sufferer’s functioning throughout life and in various spheres of activity, including driving. Difficulties in cognitive functioning and executive functions are often part and parcel of the ADHD diagnosis, and thus form a risk factor in driving. Studies examining the effectiveness of intervention programs for improving and rehabilitating driving in typical teenagers have been conducted in relatively small numbers; while studies on similar programs for teenagers with ADHD have been especially scarce. The aim of the present study has been to examine the effectiveness of a metacognitive occupational therapy intervention program for reducing risk factors in driving among teenagers with ADHD. The present study included 37 teenagers aged 17 to 19. They included 23 teenagers with ADHD divided into experimental (11) and control (12) groups; as well as 14 non-ADHD teenagers forming a second control group. All teenagers taking part in the study were examined in the Tel Aviv University driving lab, and underwent cognitive diagnoses and a driving simulator test. Every subject in the intervention group took part in 3 assessment meetings, and two metacognitive treatment meetings. The control groups took part in two assessment meetings with a follow-up meeting 3 months later. In all the study’s groups, the treatment’s effectiveness was tested by comparing monitoring results on the driving simulator at the first and second evaluations. In addition, the driving of 5 subjects from the intervention group was monitored continuously from a month prior to the start of the intervention, a month during the phase of the intervention and another month until the end of the intervention. In the ADHD control group, the driving of 4 subjects was monitored from the end of the first evaluation for a period of 3 months. The study’s findings were affected by the fact that the ADHD control group was different from the two other groups, and exhibited ADHD characteristics manifested by impaired executive functions and lower metacognitive abilities relative to their peers. The study found partial, moderate, non-significant correlations between driving skills and cognitive functions, executive functions, and perceptions and attitudes towards driving. According to the driving simulator test results and the limited sampling results of actual driving, it was found that a metacognitive occupational therapy intervention may be effective in reducing risk factors in driving among teenagers with ADHD relative to their peers with and without ADHD. In summary, the results of the present study indicate a positive direction that speaks to the viability of using a metacognitive occupational therapy intervention program for reducing risk factors in driving. A further study is required that will include a bigger number of subjects, add actual driving monitoring hours, and assign subjects randomly to the various groups.

Keywords: ADHD, driving, driving monitoring, metacognitive intervention, occupational therapy, simulator, teenagers

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Authors: Bambi Ward

Abstract:

Children of Holocaust survivors have been described as inheriting their parents’ trauma as a result of ‘vicarious memory’. The term refers to a process whereby second generation Holocaust survivors subconsciously remember aspects of Holocaust trauma, despite not having directly experienced it. This can occur even when there has been a conspiracy of silence in which survivors chose not to discuss the Holocaust with their children. There are still people born in various parts of the world such as Poland, Hungary, other parts of Europe, USA, Canada and Australia, who have only learnt of their Jewish roots as adults. This discovery may occur during a parent’s deathbed confession, or when an adult child is sorting through the personal belongings of a deceased family member. Some Holocaust survivors chose to deny their Jewish heritage and raise their children as Christians. Reasons for this decision include the trauma experienced during the Holocaust for simply being Jewish, the existence of anti-Semitism, and the desire to protect one’s self and one’s family. Although there has been considerable literature written about the transgenerational impact of trauma on children of Holocaust survivors, there has been little scholarly investigation into the effects of a hidden Jewish identity on these children. This paper presents a case study of an adult child of Hungarian Holocaust survivors who was raised as a Christian. At the age of eight she was told about her family’s Jewish background, but her parents insisted that she keep this a secret, even if asked directly. She honoured their request until she turned forty. By that time she had started the challenging process of reclaiming her Jewish identity. The paper outlines the tension between family loyalty and individual freedom, and discusses the role that art and art therapy played in assisting the subject of the case study to reclaim her Jewish identity and commence writing a memoir about her spiritual journey. The main methodology used in this case study is creative practice-led research. Particular attention is paid to the utilisation of an autoethnographic approach. The autoethnographic tools used include reflective journals of the subject of the case study. These journals reflect on the subject’s collection of autobiographical data relating to her family history, and include memories, drawings, products of art therapy, diaries, letters, photographs, home movies, objects, and oral history interviews with her mother. The case study illustrates how art and art therapy benefitted a second generation Holocaust survivor who was brought up having to suppress her Jewish identity. The process allowed her to express subconscious thoughts and feelings about her identity and free herself from the burden of the long term secret she had been carrying. The process described may also be of assistance to other traumatised people who have been trying to break the silence and who are seeking to express themselves in a positive and healing way.

Keywords: art, hidden identity, holocaust, silence

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Authors: T. Mahesh, M. K. Samanta

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Antibody dug conjugate (ADC’s) concept is a less explored and more trustable for the treatment of Type 1 diabetes (T1D). T1D is thought to arise from selective immunologically mediated destruction of the insulin- producing β-cells in the pancreatic islets of Langerhans with consequent insulin deficiency. It is evident that type 1 diabetes can be conquered, by 1) to stop immune destruction of βcells, 2) to replace or regenerate β-cells, and 3) to preserve β-cell function and mass. Many studies found that the regulatory T cells (Tregs) are crucial for the maintenance of immunological tolerance. Immune tolerance is liable for the activation of the Th1 response. The important role of Th1 response in pathology of T1D entails the depletion of CD4+ T cells, which initiated the use of anti-CD4 monoclonal antibodies (mAbs) against CD4+ T cells to interfere with induction of T1D.Insulin is regulated by Glucagon-Like Peptide-1 hormone (GLP-1) which also stimulates β-cells proliferation as the half-life of GLP-1 harmone is less due to rapid degradation by DPP-IV enzyme an alternative DPP-IV-inhibitors can increase the half-life of GLP-1 through which it conquers the replacement and reserve β-cells mass. Thus in the present study Anti-CD4 mAb was conjugated with Sitagliptin which is a DPP-IV inhibitor Drug loaded in Nanoparticles through Sulfo-MBS cross-linkers. The above study can be an effective approach for treatment to overcome the Passive subcutaneous insulin therapy.

Keywords: antibody drug conjugates, anti-CD4 Mab, DPP IV inhibitors, GLP-1

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Authors: Busra Gundede, Ozal Mutlu, Nagihan Gulsoy

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Background: Over the years, material research has led to the development of numerous metals and alloys for using in biomedical applications. One of the major tasks of biomaterial research is the functionalization of the material surface to improve the biocompatibility according to a specific application. 316L and 316L alloys are excellent for various bio-applications. This research was investigated the effect of titanium (Ti), niobium (Nb), and zirconium (Zr) additives on injection molded austenitic grade 316L stainless steels in vitro biocompatibility. For this purpose, cytotoxic tests were performed to evaluate the potential biocompatibility of the specimens. Materials and Methods: 3T3 fibroblast were cultivated in DMEM supplemented with 10% fetal bovine serum and %1 penicillin-streptomycin at 37°C with 5% CO2 and 95%humidity. Trypsin/EDTA solution was used to remove cells from the culture flask. Cells were reseeded at a density of 1×105cell in 25T flasks. The medium change took place every 3 days. The trypan blue assay was used to determine cell viability. Cell viability is calculated as the number of viable cells divided by the total number of cells within the grids on the cell counter machine counted the number of blue staining cells and the number of total cells. Cell viability should be at least 95% for healthy log-phase cultures. MTT assay was assessed for 96-hours. Cells were cultivated in 6-well flask within 5 ml DMEM and incubated as same conditions. 0,5mg/ml MTT was added for 4-hours and then acid-isoprohanol was added for solubilize to formazan crystals. Cell morphology after 96h was investigated by SEM. The medium was removed, samples were washed with 0.15 M PBS buffer and fixed for 12h at 4- 8°C with %2,5 gluteraldehyte. Samples were treated with 1% osmium tetroxide. Samples were then dehydrated and dried, mounted on appropriate stubs with colloidal silver and sputter-coated with gold. Images were collected using a scanning electron microscope. ROS assay is a cell viability test for in vitro studies. Cells were grown for 96h, ROS solution added on cells in 6 well plate flask and incubated for 1h. Fluorescence signal indicates ROS generation by cells. Results: Trypan Blue exclusion assay results were 96%, 92%, 95%, 90%, 91% for negative control group, 316L, 316L-Ti, 316L-Nb and 316L-Zr, respectively. Results were found nearly similar to each other when compared with control group. Cell viability from MTT analysis was found to be 100%, 108%, 103%, 107%, and 105% for the control group, 316L, 316L-Ti, 316L-Nb and 316L-Zr, respectively. Fluorescence microscopy analysis indicated that all test groups were same as the control group in ROS assay. SEM images demonstrated that the attachment of 3T3 cells on biomaterials. Conclusion: We, therefore, concluded that Ti, Nb and Zr additives improved physical properties of 316L stainless. In our in vitro experiments showed that these new additives did not modify the cytocompatibility of stainless steel and these additives on 316L might be useful for biomedical applications.

Keywords: 316L stainles steel, biocompatibility, cell culture, Ti, Nb, Zr

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Authors: Siobhan Hegarty, Michael Bloomfield, Kim Entholt, Dorothy Williams, Helen Kennerley

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Complex Post-Traumatic Stress Disorder (CPTSD) confers greater risk of poor outcomes than does Post-Traumatic Stress Disorder (PTSD). Despite this, the current treatment guidelines for CPTSD aim to reduce only the ‘core’ symptoms of re-experiencing, hyper-vigilance and avoidance, while not addressing the Disturbances of Self Organisation (DSO) symptoms that distinguish this novel diagnosis from PTSD. The Recovering from Child Abuse Programme (RCAP) is a group protocol, based on the principles of cognitive behavioural therapy (CBT). Preliminary evidence suggests the program is effective at reducing DSO symptoms. This pilot study is the first to investigate the potential effectiveness of the RCAP for the specific treatment of CPTSD. This study was conducted as a service evaluation in a secondary care, traumatic stress service. Treatment was delivered once a week, in two-hour sessions, to ten existing female CPTSD patients of the service, who had experienced sexual abuse in childhood. The programme was administered by two therapists and two additional facilitators, following the RCAP protocol manual. Symptom severity was measured before the administration of therapy and was tracked across a range of measures (International Trauma Questionnaire; Patient Health Questionnaire; Community Assessment of Psychic Experience; Work and Social Adjustment Scale) at five time points, over the course of treatment. Qualitative appraisal of the programme was gathered via weekly feedback forms and from audio-taped recordings of verbal feedback given during group sessions. Preliminary results suggest the programme causes a slight reduction in CPTSD and depressive symptom severity and preliminary qualitative analysis suggests that the RCAP is both helpful and acceptable to group members. Final results and conclusions will follow completed thematic analysis of results.

Keywords: Child sexual abuse, Cognitive behavioural therapy, Complex post-traumatic stress disorder, Recovering from child abuse programme

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Authors: Jerzy Slowik, Elzbieta Grochowska-Niedworok

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The analysis of the market needs and trends in both treatment and prophylaxis shows the growing need to implement comprehensive solutions that would enable safe contact of the beneficiaries with the therapeutic and diagnostic support group. Based on the evaluation of the medical and sports industry services market, projects co-financed by the EFRR in the form of comprehensive care systems using IT tools for patients under treatment in the field of obesity and metabolism using the system were implemented under the Regional Operational Program of the Silesian Voivodeship for 2014-2020. SFAO 1.0 (Support for the Fight Against Obesity) number of the WND-RPSL project. 01.02.00-24-06EA / 16) as well as for competitors in qualified sports SK system (qualified sports) project number WND-RPSL. 01.02.00-24-0630 / 17-002. The service provided in accordance with SFAO 1.0 has shown a wide range of therapy possibilities - from monitoring the body's reactions during sports activities of healthy people to remote care for sick patients. As a result of the introduction of an innovative service, it was possible to increase the effectiveness of the therapy, which was manifested in the reduction of the starting doses of drugs by 10%, improvement of the efficiency of the respiratory and blood circulation system, and a 10% increase in bone density. Innovation in the provision of medical services in the field of qualified sports SK was a response to the needs of the athletes and their parents, coaches, physiotherapists, dieticians, and doctors who take care of people actively practicing qualified sports. The creation of the platform made it possible to constantly monitor the trainers necessary for both the proper training process and the control over the health of patients. Monitoring the patient's health by a specialized team in the field of various specialties allows for the proper targeting of the treatment and training process due to the increase in the availability of medical counseling. Specialists taking care of the patient can provide additional advice and modify the medical treatment of the patient on an ongoing basis, which is why we are dealing with a holistic approach.

Keywords: innovation of medical services, sport, obesity, innovation

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Authors: Ling-Ling E, Lin Feng, Hong-Chen Liu, Dong-Sheng Wang, Zhanping Shi, Juncheng Wang, Wei Luo, Yan Lv

Abstract:

The objective of this study was to compare the effects of the two calcium phosphate composite scaffolds on the attachment, proliferation and osteogenic differentiation of rabbit dental pulp stem cells (DPSCs). One nano-hydroxyapatite/collagen/poly (L-lactide) (nHAC/PLA), imitating the composition and the micro-structure characteristics of the natural bone, was made by Beijing Allgens Medical Science & Technology Co., Ltd. (China). The other beta-tricalcium phosphate (β-TCP), being fully interoperability globular pore structure, was provided by Shanghai Bio-lu Biomaterials Co, Ltd. (China). We compared the absorption water rate and the protein adsorption rate of two scaffolds and the characterization of DPSCs cultured on the culture plate and both scaffolds under osteogenic differentiation media (ODM) treatment. The constructs were then implanted subcutaneously into the back of severe combined immunodeficient (SCID) mice for 8 and 12 weeks to compare their bone formation capacity. The results showed that the ODM-treated DPSCs expressed osteocalcin (OCN), bone sialoprotein (BSP), type I collagen (COLI) and osteopontin (OPN) by immunofluorescence staining. Positive alkaline phosphatase (ALP) staining, calcium deposition and calcium nodules were also observed on the ODM-treated DPSCs. The nHAC/PLA had significantly higher absorption water rate and protein adsorption rate than ß-TCP. The initial attachment of DPSCs seeded onto nHAC/PLA was significantly higher than that onto ß-TCP; and the proliferation rate of the cells was significantly higher than that of ß-TCP on 1, 3 and 7 days of cell culture. DPSCs+ß-TCP had significantly higher ALP activity, calcium/phosphorus content and mineral formation than DPSCs+nHAC/PLA. When implanted into the back of SCID mice, nHAC/PLA alone had no new bone formation, newly formed mature bone and osteoid were only observed in β-TCP alone, DPSCs+nHAC/PLA and DPSCs+β-TCP, and this three groups displayed increased bone formation over the 12-week period. The percentage of total bone formation area had no difference between DPSCs+β-TCP and DPSCs+nHAC/PLA at each time point，but the percentage of mature bone formation area of DPSCs+β-TCP was significantly higher than that of DPSCs+nHAC/PLA. Our results demonstrated that the DPSCs on nHAC/PLA had a better proliferation and that the DPSCs on β-TCP had a more mineralization in vitro, much more newly formed mature bones in vivo were presented in DPSCs+β-TCP group. These findings have provided a further knowledge that scaffold architecture has a different influence on the attachment, proliferation and differentiation of cells. This study may provide insight into the clinical periodontal bone tissue repair with DPSCs+β-TCP construct.

Keywords: dental pulp stem cells, nano-hydroxyapatite/collagen/poly(L-lactide), beta-tricalcium phosphate, periodontal tissue engineering, bone regeneration

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Authors: Ovidiu Vlaicu, Leontina Banica, Dan Otelea, Andrei-Jose Petrescu, Costin-Ioan Popescu

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Hepatitis C Virus (HCV) infects 170 million peoples worldwide. Major advances have been made recently in HCV standard of care with interferon-free therapy being already approved. Despite major progress in HCV therapy, the genotype associated treatment efficacy and toxicity still represent issues to address. To identify endogenous factors involved in different stages of HCV life cycle, we have developed a trans-packaging system for HCV subgenomic replicons lacking core protein gene. Huh7 cells were used to generate a packaging cell line expressing the core protein in an inducible manner. The core packaging cell line was able to trans-complemented various subgenomic replicons to secret infectious trans-complemented HCV particles (HCV-TCP). Further, we constructed subgenomic replicons with foreign epitopes suitable for immunoaffinity purification or fluorescence microscopy studies. We have shown that the insertion has not effects on the efficacy of trans-complementation yielding similar titers to the control subgenomic replicon. This system will be a valuable tool in studying pre- and post-assembly events in HCV life cycle and for the fast identification of HCV assembly inhibitors.

Keywords: assembly inhibitors, core protein, HCV, trans-complementation

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Authors: Sanaa Mekdad, Leenah Alsayed

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Pharmacists play an important role in the CDTM in the care of patients with heart failure (HF). CDTM allows specialized, dedicated clinical pharmacists in a formal agreement in collaborative practice with physicians. Thus, the aim of this study is to investigate the role of cardiology clinical pharmacists in CDTM in decreasing hospitalization and cost. We studied patients with left ventricular systolic dysfunction in a cluster-randomized selection in a tertiary care center. We allocated 296 patients to pharmacist intervention from 1480 patients. Results: With an acceptance rate of 86%, we documented 696 interventions carried out by clinical pharmacists in cardiology. The average intervention was 2.4 patients, and the admission after interventions decreased from 0.79 to. 0.24 (p value = 0.001). Conclusions: In HF CDTM, clinical pharmacists play a crucial role in enhancing medication management, patient education, and lifestyle modification of patients with chronic heart failure. These efforts improve patients' outcomes and lower costs by reducing hospitalization and other associated expenses.

Keywords: cardiology, medication management, heart failure, outpatient therapy, pharmacist-based services, chronic heart failure, heart failure recommendations, CDTM, Middle East, pharmacist-based services, quality of life, pharmacist

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Authors: P. Narrima, C. Y. Looi, M. A. Mohd, H. M. Ali

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Persea declinata (Bl.) Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill), which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl.) Kosterm bark methanolic crude extract (PDM). PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH) release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development.

Keywords: antiproliferative, apoptosis, MCF-7 human breast cancer, Persea declinata

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Authors: David C. Boettiger, Tracy Kuo Lin, Maram Almansour, Mariam M. Hamza, Reem Alsukait, Christopher H. Herbst, Nada Altheyab, Ayman Afghani, Faisal Kattan

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Background The number of people aged greater than 65 years per 100 people aged 20–64 years is expected to almost double in The Kingdom of Saudi Arabia (KSA) between 2020 and 2030. We therefore aimed to quantify the growing non-communicable disease (NCD) burden in KSA between 2020 and 2030, and the impact this will have on the national health budget. Methods Ten priority NCDs were selected: ischemic heart disease, stroke, type 2 diabetes, chronic obstructive pulmonary disease, chronic kidney disease, dementia, depression, osteoarthritis, colorectal cancer, and breast cancer. Age- and sex-specific prevalence was projected for each priority NCD between 2020 and 2030. Treatment coverage rates were applied to the projected prevalence estimates to calculate the number of patients incurring treatment costs for each condition. For each priority NCD, the average cost-of-illness was estimated based on published literature. The impact of changes to our base-case model in terms of assumed disease prevalence, treatment coverage, and costs of care, coming into effect from 2023 onwards, were explored. Results The prevalence estimates for colorectal cancer and stroke were estimated to almost double between 2020 and 2030 (97% and 88% increase, respectively). The only priority NCD prevalence projected to increase by less than 60% between 2020 and 2030 was for depression (22% increase). It is estimated that the total cost of managing priority NCDs in KSA will increase from USD 19.8 billion in 2020 to USD 32.4 billion in 2030 (an increase of USD 12.6 billion or 63%). The largest USD value increases were projected for osteoarthritis (USD 4.3 billion), diabetes (USD 2.4 billion), and dementia (USD 1.9 billion). In scenario analyses, our 2030 projection for the total cost of managing priority NCDs varied between USD 29.2 billion - USD 35.7 billion. Conclusions Managing the growing NCD burden in KSA’s aging population will require substantial healthcare spending increases over the coming years.

Keywords: aging, non communicable disease, costs, Saudi Arabia

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