Search results for: therapeutic jurisprudence
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1463

Search results for: therapeutic jurisprudence

1223 Computational Investigation of V599 Mutations of BRAF Protein and Its Control over the Therapeutic Outcome under the Malignant Condition

Authors: Mayank, Navneet Kaur, Narinder Singh

Abstract:

The V599 mutations in the BRAF protein are extremely oncogenic, responsible for countless of malignant conditions. Along with wild type, V599E, V599D, and V599R are the important mutated variants of the BRAF proteins. The BRAF inhibitory anticancer agents are continuously developing, and sorafenib is a BRAF inhibitor that is under clinical use. The crystal structure of sorafenib bounded to wild type, and V599 is known, showing a similar interaction pattern in both the case. The mutated 599th residue, in both the case, is also found not interacting directly with the co-crystallized sorafenib molecule. However, the IC50 value of sorafenib was found extremely different in both the case, i.e., 22 nmol/L for wild and 38 nmol/L for V599E protein. Molecular docking study and MMGBSA binding energy results also revealed a significant difference in the binding pattern of sorafenib in both the case. Therefore, to explore the role of distinctively situated 599th residue, we have further conducted comprehensive computational studies. The molecular dynamics simulation, residue interaction network (RIN) analysis, and residue correlation study results revealed the importance of the 599th residue on the therapeutic outcome and overall dynamic of the BRAF protein. Therefore, although the position of 599th residue is very much distinctive from the ligand-binding cavity of BRAF, still it has exceptional control over the overall functional outcome of the protein. The insight obtained here may seem extremely important and guide us while designing ideal BRAF inhibitory anticancer molecules.

Keywords: BRAF, oncogenic, sorafenib, computational studies

Procedia PDF Downloads 93
1222 The Bacteriocin Produced by Lactic Acid Bacteria as an Antibacterial of Sub Clinic Mastitis on Dairy Cows

Authors: Nenny Harijani, Dhandy Koesoemo Wardhana

Abstract:

The aim of this study is to know the bacteriocin as antimicrobial activity produced by Lactic Acid Bacteria (LAB) as Antibacterial of Sub Clinic Mastitis on Dairy Cows. The antimicrobial is produced by LAB which isolates from cattle intestine can inhibit the growth Staphylococcus aureus, Steptocococcus agalactiae an Escherichia coli which were caused by dairy cattle subclinical mastitis. The failure of this bacteria growth was indicated by the formation of a clear zone surrounding the colonies on Brain Heart Infusion Agar plate. The bacteriocin was produced by Lactic Acid Bacteria (LAB) as antimicrobial, which could inhibit the growth of indicator bacteria Staphylococcus aureus, S.aglactiae and E.coli. This study was also developed bacteriocin to be used as a therapeutic of subclinical mastitis on dairy cows. The method used in this study was isolation, selection and identification of LAB using Mann Rogosa Sharp Medium, followed by characterization of the bacteriocin produced by LAB. The result of the study showed that bacteriocin isolated from beef cattle’s intestine could inhibit the growth Staphylococcus aureus, S. agalactiae, an Escherichia coli, which was indicated by clear zone surrounding the colonies on Brain Heart Infusion Agar plate. Characteristics of bacteriocin were heat-stable exposed to 80 0C for 30 minutes and 100 ⁰C for 15 minutes and inactivated by proteolytic enzymes such as trypsin. This approach has suggested the development of bacteriocin as a therapeutic agent for subclinical mastitis in dairy cattle.

Keywords: lactic acid bacteria, bacteriocin, staphylococcus aureus, S. agalactiae, E. coli, sub

Procedia PDF Downloads 108
1221 Role of Inflammatory Markers in Arthritic Rats Treated with Ethanolic Bark Extract of Albizia procera

Authors: M. Sangeetha, D. Chamundeeswari, C. Saravanababu, C. Rose, V. Gopal

Abstract:

Rheumatoid arthritis (RA) is a chronic, progressive, systemic inflammatory disorder affecting the synovial joints and typically producing symmetrical arthritis that leads to joint destruction, which is responsible for the deformity and disability. Despite improvements in the treatment of RA over the past decade, there still is a need for new therapeutic agents that are efficacious, less expensive, and free of severe adverse reactions. The present study aimed to investigate role of inflammatory markers in arthritic rats treated with ethanolic bark extract of Albizia procera. The protective effect of ethanolic bark extract of Albizia procera against complete Freund’s adjuvant (CFA) induced arthritis in rats. Arthritis was induced by an intradermal injection of 0.1 ml FCA in the foot pad of left hind limb of rats. ETBE (100 and 200 mg/kg b.wt./p.o) and the reference drug diclofenac (25 mg/kg b.wt./p.o) were administered to arthritic rats. Paw volume was measured for all the animals before inducing arthritis and thereafter once in seven days by using plethysmometer for 42 days. Gene expression of inflammatory markers such as IL-1β and IL-10 were investigated in paw tissues. Up regulation of IL-1β and Down regulation IL-10 were observed in CFA injected rats when compared to normal rats. ETBE attenuated these alterations dose dependently when compared to the vehicle treated rats. These results provide insights into the mechanism of anti-arthritic activity, and unravel potential therapeutic use of Albizia procera in arthritis.

Keywords: CFA-Complete Freund’s adjuvant, ETBE – ethanolic bark extract, IL- interleukins, RA-rheumatoid arthritis

Procedia PDF Downloads 253
1220 Using the Minnesota Multiphasic Personality Inventory-2 and Mini Mental State Examination-2 in Cognitive Behavioral Therapy: Case Studies

Authors: Cornelia-Eugenia Munteanu

Abstract:

From a psychological perspective, psychopathology is the area of clinical psychology that has at its core psychological assessment and psychotherapy. In day-to-day clinical practice, psychodiagnosis and psychotherapy are used independently, according to their intended purpose and their specific methods of application. The paper explores how the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and Mini Mental State Examination-2 (MMSE-2) psychological tools contribute to enhancing the effectiveness of cognitive behavioral psychotherapy (CBT). This combined approach, psychotherapy in conjunction with assessment of personality and cognitive functions, is illustrated by two cases, a severe depressive episode with psychotic symptoms and a mixed anxiety-depressive disorder. The order in which CBT, MMPI-2, and MMSE-2 were used in the diagnostic and therapeutic process was determined by the particularities of each case. In the first case, the sequence started with psychotherapy, followed by the administration of blue form MMSE-2, MMPI-2, and red form MMSE-2. In the second case, the cognitive screening with blue form MMSE-2 led to a personality assessment using MMPI-2, followed by red form MMSE-2; reapplication of the MMPI-2 due to the invalidation of the first profile, and finally, psychotherapy. The MMPI-2 protocols gathered useful information that directed the steps of therapeutic intervention: a detailed symptom picture of potentially self-destructive thoughts and behaviors otherwise undetected during the interview. The memory loss and poor concentration were confirmed by MMSE-2 cognitive screening. This combined approach, psychotherapy with psychological assessment, aligns with the trend of adaptation of the psychological services to the everyday life of contemporary man and paves the way for deepening and developing the field.

Keywords: assessment, cognitive behavioral psychotherapy, MMPI-2, MMSE-2, psychopathology

Procedia PDF Downloads 302
1219 The Effectiveness of a Six-Week Yoga Intervention on Body Awareness, Warnings of Relapse, and Emotion Regulation among Incarcerated Females

Authors: James Beauchemin

Abstract:

Introduction: The incarceration of people with mental illness and substance use disorders is a major public health issue, with social, clinical, and economic implications. Yoga participation has been associated with numerous psychological benefits; however, there is a paucity of research examining impacts of yoga with incarcerated populations. The purpose of this study was to evaluate effectiveness of a six-week yoga intervention on several mental health-related variables, including emotion regulation, body awareness, and warnings of substance relapse among incarcerated females. Methods: This study utilized a pre-post, three-arm design, with participants assigned to intervention, therapeutic community, or general population groups. A between-groups analysis of covariance (ANCOVA) was conducted across groups to assess intervention effectiveness using the Difficulties in Emotion Regulation Scale (DERS), Scale of Body Connection (SBC), and Warnings of Relapse (AWARE) Questionnaire. Results: ANCOVA results for warnings of relapse (AWARE) revealed significant between-group differences F(2, 80) = 7.15, p = .001; np2 = .152), with significant pairwise comparisons between the intervention group and both the therapeutic community (p = .001) and the general population (p = .005) groups. Similarly, significant differences were found for emotional regulation (DERS) F(2, 83) = 10.521, p = .000; np2 = .278). Pairwise comparisons indicated a significant difference between the intervention and general population (p = .01). Finally, significant differences between the intervention and control groups were found for body awareness (SBC) F(2, 84) = 3.69, p = .029; np2 = .081). Between-group differences were clarified via pairwise comparisons, indicating significant differences between the intervention group and both the therapeutic community (p = .028) and general population groups (p = .020). Implications: Study results suggest that yoga may be an effective addition to integrative mental health and substance use treatment for incarcerated women, and contributes to increasing evidence that holistic interventions may be an important component for treatment with this population. Specifically, given the prevalence of mental health and substance use disorders, findings revealed that changes in body awareness and emotion regulation may be particularly beneficial for incarcerated populations with substance use challenges as a result of yoga participation. From a systemic perspective, this proactive approach may have long-term implications for both physical and psychological well-being for the incarcerated population as a whole, thereby decreasing the need for traditional treatment. By integrating a more holistic, salutogenic model that emphasizes prevention, interventions like yoga may work to improve the wellness of this population, while providing an alternative or complementary treatment option for those with current symptoms.

Keywords: yoga, mental health, incarceration, wellness

Procedia PDF Downloads 108
1218 Acceptance and Commitment Therapy for Social Anxiety Disorder in Adolescence: A Manualized Online Approach

Authors: Francisca Alves, Diana Figueiredo, Paula Vagos, Luiza Lima, Maria do Céu Salvador, Daniel Rijo

Abstract:

In recent years, Acceptance and Commitment Therapy (ACT) has been shown to be effective in the treatment of numerous anxiety disorders, including social anxiety disorder (SAD). However, limited evidence exists on its therapeutic gains for adolescents with SAD. The current work presents a weekly 10-session manualized online ACT approach to adolescent SAD, being the first study to do so in a clinical sample of adolescents. The intervention ACT@TeenSAD addresses the six proposed processes of psychological inflexibility (i.e., experiential avoidance, cognitive fusion, lack of values clarity, unworkable action, dominance of the conceptualized past and future, attachment to the conceptualized self) in social situations relevant to adolescents (e.g., doing a presentation). It is organized into four modules. The first module explores the role of psychological (in)flexibility in SAD (session 1 and 2), addressing psychoeducation (i.e., functioning of the mind) according to ACT, the development of an individualized model, and creative hopelessness. The second module focuses on the foundation of psychological flexibility (session 3, 4, and 5), specifically on the development and practice of strategies to promote clarification of values, contact with the present moment, the observing self, defusion, and acceptance. The third module encompasses psychological flexibility in action (sessions 6, 7, 8, and 9), encouraging committed action based on values in social situations relevant to the adolescents. The fourth modules’ focus is the revision of gains and relapse prevention (session 10). This intervention further includes two booster sessions after therapy has ended (3 and 6-month follow-up) that aim to review the continued practice of learned abilities and to plan for their future application to potentially anxious social events. As part of an ongoing clinical trial, the intervention will be assessed on its feasibility with adolescents diagnosed with SAD and on its therapeutic efficacy based on a longitudinal design including pretreatment, posttreatment, 3 and 6-month follow-up. If promising, findings may support the online delivery of ACT interventions for SAD, contributing to increased treatment availability to adolescents. This availability of an effective therapeutic approach will be helpful not only in relation to adolescents who face obstacles (e.g., distance) when attending to face-to-face sessions but also particularly to adolescents with SAD, who are usually more reluctant to look for specialized treatment in public or private health facilities.

Keywords: acceptance and commitment therapy, social anxiety disorder, adolescence, manualized online approach

Procedia PDF Downloads 126
1217 Immunoliposomes for Co-Delivery of Doxorubicin and Ribonucleotide Reductase M2 Sirna Inhibit of Gastric Cancer Growth

Authors: Jie Gao

Abstract:

The combination of chemotherapy with gene therapy is highly effective in cancer therapy. To achieve combined therapeutic effects in human gastric cancer over expressing EGFR, we developed targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab’ for co-delivery of doxorubicin (DOX) and ribonucleotide reductase M2 (RRM2) siRNA (DOX-RRM2-TLPD). The results showed that EGFR was over expressed in several gastric cancer cell lines and gastric cancer tissues. Gene Expression Omnibus (GEO) results showed that RRM2 expression was significantly higher in gastric cancer than in non-gastric cancer tissue, and RRM2 siRNA inhibited the proliferation of several gastric cancer cells, indicating that RRM2 is a candidate target for gastric cancer therapy. Confocal studies and flow cytometry showed that DOX-RRM2-TLPD delivered DOX and RRM2 siRNA to EGFR over expressing gastric cancer cells specifically and efficiently both in vitro and in vivo, resulting in enhanced therapeutic effects (cytotoxicity and apoptosis) compared with single-drug loaded or non-targeted controls, including DOX-NC-TLPD (targeted LPD co-delivering DOX and negative control siRNA), RRM2-TLPD (targeted LPD delivering RRM2 siRNA) and DOX-RRM2-NTLPD (non-targeted LPD co-delivering DOX and RRM2 siRNA). The in vivo antitumor assay showed that the average weight of the gastric cancer in mice treated with DOX-RRM2-TLPD was significantly lighter than that of mice treated with other controls. DOX-RRM2-TLPD represents an effective approach for combined therapy of gastric cancer over expressing EGFR.

Keywords: gene therapy, chemotherapy, immunoliposomes, gastric cancer

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1216 E-Pharmacy: An e-Commerce Approach for Buying Medicine Online in Saudi Arabia

Authors: Syed Asif Hassan, Tabrej Khan, Ibrahim Manssor Al Najar, Mohammed Nasser

Abstract:

The incredible accomplishment achieved by e-commerce in consumer durable area encouraged us to implement the online e-commerce model to tap the business benefits of electronic pharmacy in Saudi Arabia. The Kingdom of Saudi Arabia is famous for traditional herbal medicine. The rich heritage of traditional medicine has helped the mushrooming of regional pharmaceutical industries manufacturing drugs and other therapeutic against various diseases. However, the implementation of e-commerce in pharmacy has not been employed in the Kingdom of Saudi Arabia. The electronic pharmacy (E-Pharm) is an important sector that is flourishing across the globe and providing benefits of E-Pharm to the customers and suppliers all around the world. In this context, our web-based application of electronic pharmacy is the one of its kind in the Kingdom of Saudi Arabia. Surveys and personal interviews were used to identify key objectives of the proposed web-based portal. As per the findings of the surveys and personal interviews, following key objectives were identified: (a) The online platform will be used for ordering of prescription based medications for consumers. (b) The e-portal will provide space for pharmaceutical retailers who do not have an electronic platform to upload and sell their therapeutic products in an organized way. (c) The web portal will provide a tracking system to track the customer’s behavior like choice, offer, order, shipment, payment, etc. The web-based e-pharmacy portal will be developed using MySQL and PHP. The development of e-pharmacy web portal and e-prescription practices will not only improve the growth of electronic pharmacy but would also decrease the possibility of prescription alteration thus providing safety and improving the quality of service provided to the patient or consumers.

Keywords: e-commerce, E-Pharm, MySQL, PHP

Procedia PDF Downloads 369
1215 Efficacy of Ethanolic Extract of Aerva javanica Aerial Parts in the Amelioration of CCl4-Induced Hepatotoxicity and Oxidative Damage in Rats

Authors: Mohammad K. Parvez, Ahmed H. Arbab, Mohammed S. Al-Dosari, Adnan J. Al-Rehaily

Abstract:

We investigated ex vivo and in vivo antioxidative and hepatoprotective effect of Aerva javanica. Total ethanol extract of A. javanica aerial parts was prepared, and tested on DCFH-toxicated HepG2 cell in CCl4-injured Wistar rats. MTT-assay was used to determine cell viability, and serum biochemical markers of liver injury as well as histopathology were performed. In vitro DPPH and β-carotene free-radical scavenging assay and phytochemical screening of the extract was done. Furthermore, A. javanica total extract was standardized and validated by HPTLC method. While DCFH-injured cells were recovered to about 56.7% by 100 microg/ml of the extract, a 200 microg/ml dose resulted in hepatocytes recovery by about 90.2%. Oral administration of the extract (100 and 200 mg/kg.bw/day) significantly normalized the serum SGOT, SGPT, GGT, ALP, bilirubin, cholesterol, HDL, LDL, VLDL, TG and MDA levels, including tissue NP-SH and TP in CCl4-injured rats. In addition, the histopathology of dissected liver also revealed that A. javanica cured the tissue lesion compared to reference drug, Silymarin. In vitro assays revealed strong free-radical scavenging ability of the extract and presence of alkaloids, flavonoids, tannins, sterols and saponins where Rutin, a well-known antioxidant flavonoid was identified. Our finding therefore, suggests the therapeutic potential of A. javanica in various liver diseases. However, isolation of the active principles, their mechanism of action and other therapeutic contribution remain to be addressed.

Keywords: Aerva javanica, antioxidant, hepatoprotection, rutin

Procedia PDF Downloads 269
1214 Resolving Conflicts of Constitutional Nature: Inside the Romanian Constitutional Court's Rulings on the Role and Competencies of the Public Authorities

Authors: Marieta Safta

Abstract:

The separation and balance of state powers constitute the basis of the rule of law. Observance of this principle requires framing of public authorities within the limits of competence established by the Constitution and the law, as well as loyal cooperation between them. From this perspective, the attribution of the constitutional courts for settling legal conflicts of a constitutional nature is an important tool for correcting the tendencies of violation of these limits, as well as for identifying solutions for situations that do not find an explicit regulation in the constitutional texts. The present study analyzes the jurisprudence of the Constitutional Court of Romania in the field of legal conflicts of a constitutional nature, revealing, together with the presentation of conflict situations, the vulnerabilities of the constitutional reference texts. It is also highlighted the role of the constitutional courts in the evolution of constitutional law institutions, even in terms of defining and redefining the regime of the forms of government. The conclusion of the study, beyond the subject of legal conflicts of a constitutional nature, bears on the necessity, even more so in this matter, of the certainty of jurisdictional interpretation. This certainty cannot be achieved as long as the interpretation is not authoritative; consequently, the assurance of the effectiveness of constitutional justice constitute a key issue of the rule of law.

Keywords: legal conflicts of constitutional nature, the Constitutional Court of Romania, the separation and balance of powers in the state, the effectiveness of constitutional justice

Procedia PDF Downloads 96
1213 Monitoring Prolong Use of Intravenous Antibiotics: Antimicrobial Stewardship

Authors: Komal Fizza

Abstract:

Irrational and non-judicious use of antibiotics pave the way for an upsurge in antibiotic resistance, diminished effectiveness of different therapeutic regimens and as well as impounding effect on disease management leading to further morbidities. In the backdrop of this the current research is aimed to assess whether antimicrobial prescribing is in accordance with the Infectious Disease Society of America Guidelines in hospitalized patients at Shifa International Hospital, Islamabad, Pakistan. Shifa International Hospital, Islamabad is a 500 bed hospital. With the help of MIS team a form wad developed that gave the information about medical records number, name of the patient, day of start of antibiotic, the day antibiotic is supposed to be stopped and as well as the diagnosis of the patient. A ward pharmacist was employed to generate this report on a daily basis. The therapeutic regiment was reviewed by the pharmacist by monitoring the clinical progress, laboratory report and diagnosis. On the basis of this information, pharmacist made suggestions and forwarded to the hospital doctors responsible for prescribing antibiotics. If desired, changes were made regularly. In the current research our main focus was to implement this action and therefore, started monitoring patients who were on antibiotic regimens for more than 10-15 days. We took this initiative since November, 2013. At the start of the program a maximum 19 patients/day were reported to be on antibiotic regimen for more than 10-15 days. After the implementation of the initiative, the number of patients was decreased to fifteen patients per day in December, further decreased to 7 in the month of January and 9 and 6 in February and March respectively. The average patient census was 350. The current pilot study highlighted the role of pharmacist in initiating antibiotic stewardship programs in hospital settings.

Keywords: stewardship, antibiotics, resistance, clinical process

Procedia PDF Downloads 325
1212 A Learning Package on Medical Cannabis for Nurses

Authors: Kulveer Sandhu

Abstract:

Background: In 1999, the Government of Canada legalized the use of cannabis for the therapeutic purpose (CTP); however, its users remain highly vulnerable to stigma and are judged by care providers and nonusers of cannabis. Findings from a literature review suggest health care providers (HCPs), including nurses in palliative care settings, lack knowledge about medical cannabis. For this reason, it is important to enhance HCPs’awarenessand knowledge of medical cannabis. Significance of the Project: Nurses are the first point of contact and spend more time with patients than other care providers; it is, therefore, important for them to be informed about CTPto provide quality and equitable care for medical cannabis users. Although nurses and other HCPs want information on CTP, the topic is rarely included in their educational curriculum. The purpose of this project is to create an evidence informed Package designed to increase knowledge among palliative care nurses about CTP. The information package will empower palliative nurses to help palliative patients make informed decisions about their treatment plan. Method: The information package will include a basic overview of the endocannabinoid system, common cannabis plants and products, and methods of consumption, as well as information to help nurses better understand consumption and harm reduction. The package will also include a set of cannabis fact sheets for nurses. Each fact sheet will comprise a high-level overview with graphics followed by a description of medical cannabis with links and references. At the end of the learning package, there are five self-reflection questions that allow nurses to examine their personal values, attitudes, and practices regarding medical cannabis. These questions will help each nurse understand their personal approach towards CTP and its users.

Keywords: medical cannabis, improve knowledge, cannabis for therapeutic purpose (CTP), patient experience, palliative care

Procedia PDF Downloads 194
1211 The Effectiveness of a Six-Week Yoga Intervention on Body Awareness, Warnings of Relapse, and Emotion Regulation among Incarcerated Females

Authors: James D. Beauchemin

Abstract:

Introduction: The incarceration of people with mental illness and substance use disorders is a major public health issue with social, clinical, and economic implications. Yoga participation has been associated with numerous psychological benefits; however, there is a paucity of research examining impacts of yoga with incarcerated populations. The purpose of this study was to evaluate effectiveness of a six-week yoga intervention on several mental health-related variables, including emotion regulation, body awareness, and warnings of substance relapse among incarcerated females. Methods: This study utilized a pre-post, three-arm design, with participants assigned to intervention, therapeutic community, or general population groups. A between-group analysis of covariance (ANCOVA) was conducted across groups to assess intervention effectiveness using the Difficulties in Emotion Regulation Scale (DERS), Scale of Body Connection (SBC), and Warnings of Relapse (AWARE) Questionnaire. Results: ANCOVA results for warnings of relapse (AWARE) revealed significant between-group differences F(2, 80) = 7.15, p = .001; np2 = .152), with significant pairwise comparisons between the intervention group and both the therapeutic community (p = .001) and the general population (p = .005) groups. Similarly, significant differences were found for emotional regulation (DERS) F(2, 83) = 10.521, p = .000; np2 = .278). Pairwise comparisons indicated a significant difference between the intervention and general population (p = .01). Finally, significant differences between the intervention and control groups were found for body awareness (SBC) F(2, 84) = 3.69, p = .029; np2 = .081). Between-group differences were clarified via pairwise comparisons, indicating significant differences between the intervention group and both the therapeutic community (p = .028) and general population groups (p = .020). Implications: Study results suggest that yoga may be an effective addition to integrative mental health and substance use treatment for incarcerated women and contributes to increasing evidence that holistic interventions may be an important component for treatment with this population. Specifically, given the prevalence of mental health and substance use disorders, findings revealed that changes in body awareness and emotion regulation might be particularly beneficial for incarcerated populations with substance use challenges as a result of yoga participation. From a systemic perspective, this proactive approach may have long-term implications for both physical and psychological well-being for the incarcerated population as a whole, thereby decreasing the need for traditional treatment. By integrating a more holistic, salutogenic model that emphasizes prevention, interventions like yoga may work to improve the wellness of this population while providing an alternative or complementary treatment option for those with current symptoms.

Keywords: wellness, solution-focused coaching, college students, prevention

Procedia PDF Downloads 93
1210 Views on Abortion and Case Law on International and European Levels: Past and Present Jurisprudence

Authors: Aurélie Cassiers

Abstract:

In this presentation, an overview is given of the freedom of states to legislate concerning abortion. Today, access to safe and legal abortion is still a hot topic in many countries in the world. Abortion policies try to strike a balance between women’s rights to self-determination and private life on the one hand, and the protection of the life of unborn children on the other. Each country has different religious, cultural and political views on abortion, and therefore specific legislations. However, citizens may submit a complaint at international courts when they find their national legislation too restrictive. The study is discussed of the development of the ECtHR, UNCHR, and IACHR case law, regarding the question of the ‘right to abort’ and indirectly of the protection of the unborn children. Each relevant case is analyzed to answer the following questions: Is the unborn child protected, and if so, how? Why does the woman want to abort and how is her interest or right protected? How is a fair balance reached between the different interests? Is the state completely free to write policies that restrict abortion? What are the factors to determine the margin of appreciation of the state? In conclusion, does this specific court recognize a right to abort, and if so, under which conditions? To conclude, this presentation shows that each court has its own perspective on and perception of abortion, and its own criteria to determine whether the state is complying with international norms regarding individual liberty and protection of the children.

Keywords: abortion, international courts, unborn children, women rights

Procedia PDF Downloads 107
1209 Therapeutic Effect of Diisopropyldithiocarbamate Sodium Salt Against Diclofenac Induced Testicular Damage in Male Wistar Rats

Authors: Tella Toluwani, Adegbegi Ademuyiwa, Musei Chiedu, Adekunle Odola, Ayangbenro Ayansina, Adaramoye Oluwatosin

Abstract:

Dithiocarbamates are very useful biological agents with antioxidant properties. Diclofenac (DIC) is a non-steroidal analgesic, anti-inflammatory, and antipyretic agent. The use of diclofenac has been linked with reproductive toxicity/damage. The purpose of this study is (i) To investigate the therapeutic potential of diisopropyldithiocarbamate sodium salt (Na(i-Pr₂dtc)) and vitamin E (VIT E) against diclofenac induced toxicity in the testes of male Wistar rats. (ii) To investigate the effect of (Na(i-Pr₂dtc)) and vitamin E on ameliorating damage done to the testes through histological analysis of the testes. Thirty-six (36) male Wistar rats were used for the experiment, they were divided into six (6) groups, the animals in group 1 served as control, animals in groups 2, 3, 4, 5 and 6 received DIC only, DIC and (Na(i-Pr₂dtc)), DIC and VIT E, (Na(i-Pr₂dtc) only and VIT E only respectively. A single dose of 100 mg/kg body weight of DIC was administered to male Wistar rats, while 30 mg/kg body weight of (Na(i-Pr₂dtc)) was used to treat both normal and DIC treated animals, control animals were treated with the vehicle, after 24 hrs of treatment the animals were euthanized and the testes were removed for analysis. The treatment of rats with Na(i-Pr₂dtc) significantly restored catalase (CAT) activity depressed by diclofenac. (Na(i-Pr₂dtc)) also restored glutathione levels reduced by DIC treatment and this was also accompanied by reduced lipid peroxidation (LPO) level. VIT E significantly restored superoxide dismutase (SOD) activity when compared with DIC only treated animals. Photomicrographs of testes from (Na(i-Pr₂dtc)) treated rats showed seminiferous epithelium with no lesions. We conclude that (Na(i-Pr₂dtc)) has an antioxidant effect, which might be related to the dose and duration of administration.

Keywords: diisopropyldithiocarbamate sodium salt, diclofenac, vitamin E, testes

Procedia PDF Downloads 163
1208 Joint Physical Custody after Divorce and Child Well-Being

Authors: Katarzyna Kamińska

Abstract:

Joint physical custody means that both parents after divorce or separation have the right and responsibility to take care of the child on the daily basis. In a joint physical custody arrangement, the child spends substantial, but not necessarily equal, time with both parents. Joint physical custody can be symmetric care arrangement or not. However, it is accepted in the jurisprudence that the best interests of the child is served when the child spends at least 35% of the time during a two-week period with each parent. Joint physical custody, also known as joint, dual, or shared residence, is a challenge in contemporary family law. It has its supporters and opponents. On the one hand, joint physical custody is beneficial because it provides children with frequent and continuous contact with a mother and father after their divorce or separation. On the other hand, it isn’t good for children to be shuttled back and forth between two residences. Children need a home base. The conclusion is therefore that joint physical custody can’t be seen as a panacea for all post-divorce or post-separation parenting cases and the court shouldn’t automatically make such a determination. The possibility to award this arrangement requires the court to carefully weigh the pros and cons of each individual case. It is difficult to say that joint physical custody is better than single physical custody in any case. It depends on the circumstances and needs of each family. It appears that an individual approach is going to be much better as opposed to a one-size-fits-all idea.

Keywords: joint physical custody, shared residence, dual residence, the best interests of the child

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1207 Design of 3D Bioprinted Scaffolds for Cartilage Regeneration

Authors: Gloria Pinilla, Jose Manuel Baena, Patricia Gálvez-Martín, Juan Antonio Marchad

Abstract:

Cartilage is a dense connective tissue with limited self-repair properties. Currently, the therapeutic use of autologous or allogenic chondrocytes makes up an alternative therapy to the pharmacological treatment. The design of a bioprinted 3D cartilage with chondrocytes and biodegradable biomaterials offers a new therapeutic alternative able of bridging the limitations of current therapies in the field. We have developed an enhanced printing processes-Injection Volume Filling (IVF) to increase the viability and survival of the cells when working with high-temperature thermoplastics without the limitation of the scaffold geometry in contact with cells. We have demonstrated the viability of the printing process using chondrocytes for cartilage regeneration. This development will accelerate the clinical uptake of the technology and overcomes the current limitation when using thermoplastics as scaffolds. An alginate-based hydrogel combined with human chondrocytes (isolated from osteoarthritis patients) was formulated as bioink-A and the polylactic acid as bioink-B. The bioprinting process was carried out with the REGEMAT V1 bioprinter (Regemat 3D, Granada-Spain) through a IVF. The printing capacity of the bioprinting plus the viability and cell proliferation of bioprinted chondrociytes was evaluated after five weeks by confocal microscopy and Alamar Blue Assay (Biorad). Results showed that the IVF process does not decrease the cell viability of the chondrocytes during the printing process as the cells do not have contact with the thermoplastic at elevated temperatures. The viability and cellular proliferation of the bioprinted artificial 3D cartilage increased after 5 weeks. In conclusion, this study demonstrates the potential use of Regemat V1 for 3D bioprinting of cartilage and the viability of bioprinted chondrocytes in the scaffolds for application in regenerative medicine.

Keywords: cartilage regeneration, bioprinting, bioink, scaffold, chondrocyte

Procedia PDF Downloads 286
1206 Exploiting the Tumour Microenvironment in Order to Optimise Sonodynamic Therapy for Cancer

Authors: Maryam Mohammad Hadi, Heather Nesbitt, Hamzah Masood, Hashim Ahmed, Mark Emberton, John Callan, Alexander MacRobert, Anthony McHale, Nikolitsa Nomikou

Abstract:

Sonodynamic therapy (SDT) utilises ultrasound in combination with sensitizers, such as porphyrins, for the production of cytotoxic reactive oxygen species (ROS) and the confined ablation of tumours. Ultrasound can be applied locally, and the acoustic waves, at frequencies between 0.5-2 MHz, are transmitted efficiently through tissue. SDT does not require highly toxic agents, and the cytotoxic effect only occurs upon ultrasound exposure at the site of the lesion. Therefore, this approach is not associated with adverse side effects. Further highlighting the benefits of SDT, no cancer cell population has shown resistance to therapy-triggered ROS production or their cytotoxic effects. This is particularly important, given the as yet unresolved issues of radiation and chemo-resistance, to the authors’ best knowledge. Another potential future benefit of this approach – considering its non-thermal mechanism of action – is its possible role as an adjuvant to immunotherapy. Substantial pre-clinical studies have demonstrated the efficacy and targeting capability of this therapeutic approach. However, SDT has yet to be fully characterised and appropriately exploited for the treatment of cancer. In this study, a formulation based on multistimulus-responsive sensitizer-containing nanoparticles that can accumulate in advanced prostate tumours and increase the therapeutic efficacy of SDT has been developed. The formulation is based on a polyglutamate-tyrosine (PGATyr) co-polymer carrying hematoporphyrin. The efficacy of SDT in this study was demonstrated using prostate cancer as the translational exemplar. The formulation was designed to respond to the microenvironment of advanced prostate tumours, such as the overexpression of the proteolytic enzymes, cathepsin-B and prostate-specific membrane antigen (PSMA), that can degrade the nanoparticles, reduce their size, improving both diffusions throughout the tumour mass and cellular uptake. The therapeutic modality was initially tested in vitro using LNCaP and PC3 cells as target cell lines. The SDT efficacy was also examined in vivo, using male SCID mice bearing LNCaP subcutaneous tumours. We have demonstrated that the PGATyr co-polymer is digested by cathepsin B and that digestion of the formulation by cathepsin-B, at tumour-mimicking conditions (acidic pH), leads to decreased nanoparticle size and subsequent increased cellular uptake. Sonodynamic treatment, at both normoxic and hypoxic conditions, demonstrated ultrasound-induced cytotoxic effects only for the nanoparticle-treated prostate cancer cells, while the toxicity of the formulation in the absence of ultrasound was minimal. Our in vivo studies in immunodeficient mice, using the hematoporphyrin-containing PGATyr nanoparticles for SDT, showed a 50% decrease in LNCaP tumour volumes within 24h, following IV administration of a single dose. No adverse effects were recorded, and body weight was stable. The results described in this study clearly demonstrate the promise of SDT to revolutionize cancer treatment. It emphasizes the potential of this therapeutic modality as a fist line treatment or in combination treatment for the elimination or downstaging of difficult to treat cancers, such as prostate, pancreatic, and advanced colorectal cancer.

Keywords: sonodynamic therapy, nanoparticles, tumour ablation, ultrasound

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1205 Investigating Selected Traditional African Medicinal Plants for Anti-fibrotic Potential: Identification and Characterization of Bioactive Compounds Through Fourier-Transform Infrared Spectroscopy and Gas Chromatography-Mass Spectrometry Analysis

Authors: G. V. Manzane, S. J. Modise

Abstract:

Uterine fibroids, also known as leiomyomas or myomas, are non-cancerous growths that develop in the muscular wall of the uterus during the reproductive years. The cause of uterine fibroids includes hormonal, genetic, growth factors, and extracellular matrix factors. Common symptoms of uterine fibroids include heavy and prolonged menstrual bleeding which can lead to a high risk of anemia, lower abdominal pains, pelvic pressure, infertility, and pregnancy loss. The growth of this tumor is a concern because of its negative impact on women’s health and the increase in their economic burden. Traditional medicinal plants have long been used in Africa for their potential therapeutic effects against various ailments. In this study, we aimed to identify and characterize bioactive compounds from selected African medicinal plants with potential anti-fibrotic properties using Fourier-transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GCMS) analysis. Two medicinal plant species known for their traditional use in fibrosis-related conditions were selected for investigation. Aqueous extracts were prepared from the plant materials, and FTIR analysis was conducted to determine the functional groups present in the extracts. GCMS analysis was performed to identify the chemical constituents of the extracts. The FTIR analysis revealed the presence of various functional groups, such as phenols, flavonoids, terpenoids, and alkaloids, known for their potential therapeutic activities. These functional groups are associated with antioxidant, anti-inflammatory, and anti-fibrotic properties. The GCMS analysis identified several bioactive compounds, including flavonoids, alkaloids, terpenoids, and phenolic compounds, which are known for their pharmacological activities. The discovery of bioactive compounds in African medicinal plants that exhibit anti-fibrotic effects, opens up promising avenues for further research and development of potential treatments for fibrosis. This suggests the potential of these plants as a valuable source of novel therapeutic agents for treating fibrosis-related conditions. In conclusion, our study identified and characterized bioactive compounds from selected African medicinal plants using FTIR and GCMS analysis. The presence of compounds with known antifibrotic properties suggests that these plants hold promise as a potential source of natural products for the development of novel anti-fibrotic therapies.

Keywords: uterine fibroids, african medicinal plants, bioactive compounds, identify and characterized

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1204 Expanding the Therapeutic Utility of Curcumin

Authors: Azza H. El-Medany, Hanan H. Hagar, Omnia A. Nayel, Jamila H. El-Medany

Abstract:

In search for drugs that can target cancer cell micro-environment in as much as being able to halt malignant cellular transformation, the natural dietary phytochemical curcumin was currently assessed in DMH-induced colorectal cancer rat model. The study enrolled 50 animals divided into a control group (n=10) and DMH-induced colorectal cancer control group (n=20) (20mg/kg-body weight for 28 weeks) versus curcumin-treated group (n=20) (160 mg/kg suspension daily oral for further 8 weeks). Treatment by curcumin succeeded to significantly decrease the percent of ACF and tended to normalize back the histological changes retrieved in adenomatous and stromal cells induced by DMH. The drug also significantly elevated GSH and significantly reduced most of the accompanying biochemical elevations (namely MDA, TNF-α, TGF-β and COX2) observed in colonic carcinomatous tissue, induced by DMH, thus succeeding to revert that of MDA, COX2 and TGF-β back to near normal as justified by being non-significantly altered as compared to normal controls. The only exception was PAF that was insignificantly altered by the drug. When taken together, it could be concluded that curcumin possess the potentiality to halt some of the orchestrated cross-talk between cancerous transformation and its micro-environmental niche that contributes to cancer initiation, progression and metastasis in this experimental cancer colon model. Envisioning these merits to a drug with already known safety preferentiality, awaits final results of current ongoing clinical trials, before curcumin can be added to the new therapeutic armamentarium of anticancer therapy.

Keywords: curcumin, dimethyl hydralazine, aberrant crypt foci, malondialdehyde, reduced glutathione, cyclooxygenase-2, tumour necrosis factor-alpha, transforming growth factor-beta, platelet activating factor

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1203 Sirhindi Family's Islamic Movements in Sindh, Pakistan

Authors: Nasurullah Qureshi

Abstract:

Shaikh Ahmad Sirhindi Mujadid Alif Thani (1564-1624) and his philosophy had influenced sub-continent as the whole; its rulers and nation. In his reign, he convinced the rulers toward Islamic way of life and succeed in his goal. After his death in 1624, his family consecutively produced prominent scholars to present. Some of them moved to Afghanistan and Pakistan's cities i.e., Jalalabad, Qandhar, Peshawar, Queta, Shikarpur, Hyderabad, and Sehwan. They played a vital role in their areas and transmitted spiritual and legal Islamic teachings to people. This research is aimed to elaborate efforts of the family's Sindh settled branch from 1898-present in fields of politics and Islamic education. Their link with Shaikh Ahmad Sirhindi will be provided in the introduction. After that, the work will explain their scholarly published work briefly in different fields of Islamic studies such as Quran exegeses and its translation in Sindhi language, Hadith and its sciences, Islamic Jurisprudence, Sufism and etc. In addition, their political role will be briefly discussed in the research throughout the period, especially their noticeable role in the separate homeland for Muslims in the subcontinent. Furthermore, the impact of their scholarly work, political influence and spirituality will be enlightened. Lastly, the research will present the critical viewpoint on their struggle.

Keywords: Shaikh Ahmad Sirhindi, Sirhindi scholars, Sindh, Sufism

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1202 Control of Asthma in Children with Asthma during the Containment Period following the Covid-19 Pandemic

Authors: Meryam Labyad, Karima Fakiri, Widad Lahmini, Ghizlane Draiss, Mohamed Bouskraoui, Nadia Ouzennou

Abstract:

Background: Asthma is the most common chronic disease in children, affecting nearly 235 million people worldwide (OMS). In Morocco, asthma is much more common in children than in adults; the prevalence rate in children between 13 and 14 years of age is 20%.1 This pathology is marked by high morbidity, a significant impact on the quality of life and development of children 2 This requires a rigorous management strategy in order to achieve clinical control and reduce any risk to the patient 3 A search for aggravating factors is mandatory if a child has difficulty maintaining good asthma control. The objective of the present study is to describe asthma control during this confinement period in children aged 4 to 11 years followed by a pneumo-paediatric consultation. For children whose asthma is not controlled, a search for associations with promoting factors and adherence to treatment is also among the objectives of the study. Knowing the level of asthma control and influencing factors is a therapeutic priority in order to reduce hospitalizations and emergency care use. Objective: To assess asthma control and determine the factors influencing asthma levels in children with asthma during confinement following the COVID 19 pandemic. Method: Prospective cross-sectional study by questionnaire and structured interview among 66 asthmatic children followed in pediatric pneumology consultation at the CHU MED VI of Marrakech from 13/06/2020 to 13/07/2020, asthma control was assessed by the Childhood Asthma Control Test (C-ACT). Results: 66 children and their parents were included (mean age is 7.5 years), asthma was associated with allergic rhinitis (13.5% of cases), conjunctivitis (9% of cases), eczema (12% of cases), occurrence of infection (10.5% of cases). The period of confinement was marked by a decrease in the number of asthma attacks translated by a decrease in the number of emergency room visits (7.5%) of these asthmatic children, control was well controlled in 71% of the children, this control was significantly associated with good adherence to treatment (p<0.001), no infection (p<0.001) and no conjunctivitis (p=002) or rhinitis (p<0.001). This improvement in asthma control during confinement can be explained by the measures taken in the Kingdom to prevent the spread of COVID 19 (school closures, reduction in industrial activity, fewer means of transport, etc.), leading to a decrease in children's exposure to triggers, which justifies the decrease in the number of children having had an infection, allergic rhinitis or conjunctivitis during this period. In addition, the close monitoring of parents resulted in better therapeutic adherence (42.4% were fully observant). Confinement was positively perceived by 68% of the parents; this perception is significantly associated with the level of asthma control (p<0.001). Conclusion: Maintaining good control can be achieved through improved therapeutic adherence and avoidance of triggers, both of which were achieved during the containment period following the VIDOC pandemic 19.

Keywords: Asthma, control , COVID-19 , children

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1201 Site-Specific Delivery of Hybrid Upconversion Nanoparticles for Photo-Activated Multimodal Therapies of Glioblastoma

Authors: Yuan-Chung Tsai, Masao Kamimura, Kohei Soga, Hsin-Cheng Chiu

Abstract:

In order to enhance the photodynamic/photothermal therapeutic efficacy on glioblastoma, the functionized upconversion nanoparticles with the capability of converting the deep tissue penetrating near-infrared light into visible wavelength for activating photochemical reaction were developed. The drug-loaded nanoparticles (NPs) were obtained from the self-assembly of oleic acid-coated upconversion nanoparticles along with maleimide-conjugated poly(ethylene glycol)-cholesterol (Mal-PEG-Chol), as the NP stabilizer, and hydrophobic photosensitizers, IR-780 (for photothermal therapy, PTT) and mTHPC (for photodynamic therapy, PDT), in aqueous phase. Both the IR-780 and mTHPC were loaded into the hydrophobic domains within NPs via hydrophobic association. The peptide targeting ligand, angiopep-2, was further conjugated with the maleimide groups at the end of PEG adducts on the NP surfaces, enabling the affinity coupling with the low-density lipoprotein receptor-related protein-1 of tumor endothelial cells and malignant astrocytes. The drug-loaded NPs with the size of ca 80 nm in diameter exhibit a good colloidal stability in physiological conditions. The in vitro data demonstrate the successful targeting delivery of drug-loaded NPs toward the ALTS1C1 cells (murine astrocytoma cells) and the pronounced cytotoxicity elicited by combinational effect of PDT and PTT. The in vivo results show the promising brain orthotopic tumor targeting of drug-loaded NPs and sound efficacy for brain tumor dual-modality treatment. This work shows great potential for improving photodynamic/photothermal therapeutic efficacy of brain cancer.

Keywords: drug delivery, orthotopic brain tumor, photodynamic/photothermal therapies, upconversion nanoparticles

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1200 Biosynthesis of a Nanoparticle-Antibody Phthalocyanine Photosensitizer for Use in Targeted Photodynamic Therapy of Cervical Cancer

Authors: Elvin P. Chizenga, Heidi Abrahamse

Abstract:

Cancer cell resistance to therapy is the main cause of treatment failures and the poor prognosis of cancer convalescence. The progression of cervical cancer to other parts of the genitourinary system and the reported recurrence rates are overwhelming. Current treatments, including surgery, chemo and radiation have been inefficient in eradicating the tumor cells. These treatments are also associated with poor prognosis and reduced quality of life, including fertility loss. This has inspired the need for the development of new treatment modalities to eradicate cervical cancer successfully. Photodynamic Therapy (PDT) is a modern treatment modality that induces cell death by photochemical interactions of light and a photosensitizer, which in the presence of molecular oxygen, yields a set of chemical reactions that generate Reactive Oxygen Species (ROS) and other free radical species causing cell damage. Enhancing PDT using modified drug delivery can increase the concentration of the photosensitizer in the tumor cells, and this has the potential to maximize its therapeutic efficacy. In cervical cancer, all infected cells constitutively express genes of the E6 and E7 HPV viral oncoproteins, resulting in high concentrations of E6 and E7 in the cytoplasm. This provides an opportunity for active targeting of cervical cancer cells using immune-mediated drug delivery to maximize therapeutic efficacy. The use of nanoparticles in PDT has also proven effective in enhancing therapeutic efficacy. Gold nanoparticles (AuNps) in particular, are explored for their use in biomedicine due to their biocompatibility, low toxicity, and enhancement of drug uptake by tumor cells. In this present study, a biomolecule comprising of AuNPs, anti-E6 monoclonal antibodies, and Aluminium Phthalocyanine photosensitizer was synthesized for use in targeted PDT of cervical cancer. The AuNp-Anti-E6-Sulfonated Aluminium Phthalocyanine mix (AlPcSmix) photosensitizing biomolecule was synthesized by coupling AuNps and anti-E6 monoclonal antibodies to the AlPcSmix via Polyethylene Glycol (PEG) chemical links. The final product was characterized using Transmission Electron Microscope (TEM), Zeta Potential, Uv-Vis Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD), to confirm its chemical structure and functionality. To observe its therapeutic role in treating cervical cancer, cervical cancer cells, HeLa cells were seeded in 3.4 cm² diameter culture dishes at a concentration of 5x10⁵ cells/ml, in vitro. The cells were treated with varying concentrations of the photosensitizing biomolecule and irradiated using a 673.2 nm wavelength of laser light. Post irradiation cellular responses were performed to observe changes in morphology, viability, proliferation, cytotoxicity, and cell death pathways induced. Dose-Dependent response of the cells to treatment was demonstrated as significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation This study presented a synthetic biomolecule for targeted PDT of cervical cancer. The study suggested that PDT using this AuNp- Anti-E6- AlPcSmix photosensitizing biomolecule is a very effective treatment method for the eradication of cervical cancer cells, in vitro. Further studies in vivo need to be conducted to support the use of this biomolecule in treating cervical cancer in clinical settings.

Keywords: anti-E6 monoclonal antibody, cervical cancer, gold nanoparticles, photodynamic therapy

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1199 In-Depth Analysis on Sequence Evolution and Molecular Interaction of Influenza Receptors (Hemagglutinin and Neuraminidase)

Authors: Dong Tran, Thanh Dac Van, Ly Le

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Hemagglutinin (HA) and Neuraminidase (NA) play an important role in host immune evasion across influenza virus evolution process. The correlation between HA and NA evolution in respect to epitopic evolution and drug interaction has yet to be investigated. In this study, combining of sequence to structure evolution and statistical analysis on epitopic/binding site specificity, we identified potential therapeutic features of HA and NA that show specific antibody binding site of HA and specific binding distribution within NA active site of current inhibitors. Our approach introduces the use of sequence variation and molecular interaction to provide an effective strategy in establishing experimental based distributed representations of protein-protein/ligand complexes. The most important advantage of our method is that it does not require complete dataset of complexes but rather directly inferring feature interaction from sequence variation and molecular interaction. Using correlated sequence analysis, we additionally identified co-evolved mutations associated with maintaining HA/NA structural and functional variability toward immunity and therapeutic treatment. Our investigation on the HA binding specificity revealed unique conserved stalk domain interacts with unique loop domain of universal antibodies (CR9114, CT149, CR8043, CR8020, F16v3, CR6261, F10). On the other hand, NA inhibitors (Oseltamivir, Zaninamivir, Laninamivir) showed specific conserved residue contribution and similar to that of NA substrate (sialic acid) which can be exploited for drug design. Our study provides an important insight into rational design and identification of novel therapeutics targeting universally recognized feature of influenza HA/NA.

Keywords: influenza virus, hemagglutinin (HA), neuraminidase (NA), sequence evolution

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1198 Combined Treatment of Estrogen-Receptor Positive Breast Microtumors with 4-Hydroxytamoxifen and Novel Non-Steroidal Diethyl Stilbestrol-Like Analog Produces Enhanced Preclinical Treatment Response and Decreased Drug Resistance

Authors: Sarah Crawford, Gerry Lesley

Abstract:

This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

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1197 Biophysical Study of the Interaction of Harmalol with Nucleic Acids of Different Motifs: Spectroscopic and Calorimetric Approaches

Authors: Kakali Bhadra

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Binding of small molecules to DNA and recently to RNA, continues to attract considerable attention for developing effective therapeutic agents for control of gene expression. This work focuses towards understanding interaction of harmalol, a dihydro beta-carboline alkaloid, with different nucleic acid motifs viz. double stranded CT DNA, single stranded A-form poly(A), double-stranded A-form of poly(C)·poly(G) and clover leaf tRNAphe by different spectroscopic, calorimetric and molecular modeling techniques. Results of this study converge to suggest that (i) binding constant varied in the order of CT DNA > poly(C)·poly(G) > tRNAphe > poly(A), (ii) non-cooperative binding of harmalol to poly(C)·poly(G) and poly(A) and cooperative binding with CT DNA and tRNAphe, (iii) significant structural changes of CT DNA, poly(C)·poly(G) and tRNAphe with concomitant induction of optical activity in the bound achiral alkaloid molecules, while with poly(A) no intrinsic CD perturbation was observed, (iv) the binding was predominantly exothermic, enthalpy driven, entropy favoured with CT DNA and poly(C)·poly(G) while it was entropy driven with tRNAphe and poly(A), (v) a hydrophobic contribution and comparatively large role of non-polyelectrolytic forces to Gibbs energy changes with CT DNA, poly(C)·poly(G) and tRNAphe, and (vi) intercalated state of harmalol with CT DNA and poly(C)·poly(G) structure as revealed from molecular docking and supported by the viscometric data. Furthermore, with competition dialysis assay it was shown that harmalol prefers hetero GC sequences. All these findings unequivocally pointed out that harmalol prefers binding with ds CT DNA followed by ds poly(C)·poly(G), clover leaf tRNAphe and least with ss poly(A). The results highlight the importance of structural elements in these natural beta-carboline alkaloids in stabilizing different DNA and RNA of various motifs for developing nucleic acid based better therapeutic agents.

Keywords: calorimetry, docking, DNA/RNA-alkaloid interaction, harmalol, spectroscopy

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1196 Contesting Blind Obedience in Islam within the Malay-Language Media: Case Study of 'I Want to Touch a Dog' Event

Authors: Aisya Zaharin

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The reporting of Islam in the Malaysian government-controlled press is complicated and occurs almost daily. This is due to the Islamisation process that has been heavily politicized in recent years. This article analyses media representations of Islam in the Malaysian media through the social responsibility theory. A provocative case study of media reporting on the “I want to touch a dog” event was analysed since dog’s saliva is ritually considered unhygienic by Muslims. This paper will not question the Islamic ruling on the dog’s issue. Instead, it calls for discussions in relation to openness and maturity in religious discourse with respect to the dog’s saliva dialogue in 1937. It applies Hage’s “minor and major reality” to explain the increasing percentage of Muslim who define their own understandings of Islam vs the government’s dogmatic versions. This paper employs Alatas’s method of “sociological investigation in Southeast Asia” by using ethnographic examination on selected mass media. Through Asiacentricity approach, this paper revisited the local framework of Alatas’s New Man encouraging Muslims to engage in knowledge and to appreciate diversities in Islamic jurisprudences. Despite government’s control, findings showed that non-Malay languages and online media are more comprehensive in reporting the news about Islam. Clearly, there has to be a re-conceptualization of Islamic discourses in the Malay-language media.

Keywords: dog, Fiqh, Islamic jurisprudence, Malaysian media, New Man, social responsibility

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1195 PCR Detection, Histopathological Characterization, and Autogenous Immunization of Bovine Papillomatosis (Wart) in Cattle, in Mekelle, Northern Ethiopia

Authors: Kidane Workelul, Yohans Tekle, Guesh Negash, Haftay Abraha, Nigus Abebe Shumuye, Yisehak Tsegaye Redda

Abstract:

Bovine papillomatosis (wart) is one of the economically important bovine skin diseases worldwide, caused by a group of viruses named papillomaviruses (PVs). However, it has often been misdiagnosed as other skin diseases and remained untreated. In order to determine the status of the diseases, twenty-two farms were visited, and fourteen infected cattle with cutaneous papillomatosis were identified from a total of 235. Papilloma biopsies were taken for molecular and histopathological characterization, the therapeutic trial of an autogenous vaccine was evaluated on infected animals. The overall status of bovine papillomatosis in this study was calculated as 5.96% (14/235). The disease was found to be statistically significant in the age groups less than two years (X² = 26.69, P = 0.0001). The more prominent histologically characterized lesions in the sampled tissue were identified as squamous papilloma and fibro-papilloma. The Polymerase Chain Reaction (PCR) based identification revealed that all the clinically and histo-pathologically characterized papillomatosis cases were found to be infected with Bovine Papilloma Virus1(BPV1), indicating that BPV1 was the most common and sole causative agent of the diseases in the study area. In immunizing active bovine papillomatosis, an autogenous vaccine therapeutic trial demonstrated excellent results, with practically full recovery and no recurrence of the infection. Hence, it is concluded that bovine papillomatosis is an economically important disease of young age group cattle as well as a treatable disease. So, the production of marketable autogenous vaccines against bovine papillomatosis should be started and given at an early stage.

Keywords: autogenous vaccine, bovine papillomatosis, bovine papilloma virus1 clinical-pathology, polymerase chine reaction, wart

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1194 A Therapeutic Approach for Bromhidrosis with Glycopyrrolate 2% Cream: Clinical Study of 20 Patients

Authors: Vasiliki Markantoni, Eftychia Platsidaki, Georgios Chaidemenos, Georgios Kontochristopoulos

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Introduction: Bromhidrosis, also known as osmidrosis, is a common distressing condition with a significant negative effect on patient’s quality of life. Its etiology is multifactorial. It usually affects axilla, genital skin, breasts and soles, areas where apocrine glands are mostly distributed. Therapeutic treatments include topical antibacterial agents, antiperspirants and neuromuscular blocker agents-toxins. In this study, we aimed to evaluate the efficacy and possible complications of topical glycopyrrolate, an anticholinergic agent, for treatment of bromhidrosis. Glycopyrrolate, applied topically as a cream, solution or spray at concentrations between 0,5% and 4%, has been successfully used to treat different forms of focal hyperhidrosis. Materials and Methods: Twenty patients, six males and fourteen females, meeting the criteria for bromhidrosis were treated with topical glycopyrrolate for two months. The average age was 36. Eleven patients had bromhidrosis located to the axillae, four to the soles, four to both axillae and soles and one to the genital folds. Glycopyrrolate was applied topically as a cream at concentration 2%, formulated in Fitalite. During the first month, patients were using the cream every night and thereafter twice daily. The degree of malodor was assessed subjectively by patients and scaled averagely as ‘none’, ‘mild’, ‘moderate’, and ‘severe’ with corresponding scores of 0, 1, 2, and 3, respectively. The modified Dermatology Life Quality Index (DLQI) was used to assess the quality of life. The clinical efficacy was graded by the patient scale of excellent, good, fair and poor. In the end, patients were given the power to evaluate whether they were totally satisfied with, partially satisfied or unsatisfied and possible side effects during the treatment were recorded. Results: All patients were satisfied at the end of the treatment. No patient defined the response as no improvement. The subjectively assessed score level of bromhidrosis was remarkably improved after the first month of treatment and improved slightly more after the second month. DLQI score was also improved to all patients. Adverse effects were reported in 2 patients. In the first case, topical irritation was reported. This was classed as mild (erythema and desquamation), appeared during the second month of treatment and was treated with low-potency topical corticosteroids. In the second case, mydriasis was reported, that recovered without specific treatment, as soon as we insisted to the importance of careful hygiene after cream application so as not to contaminate the periocular skin or ocular surface. Conclusions: Dermatologists often encounter patients with bromhidrosis, therefore should be aware of treatment options. To the best of our knowledge, this is the first study to evaluate the use of topical glycopyrrolate as a therapeutic approach for bromhidrosis. Our findings suggest that topical glycopyrrolate has an excellent safety profile and demonstrate encouraging results for the management of this distressful condition.

Keywords: Bromhidrosis, glycopyrrolate, topical treatment, osmidrosis

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