Search results for: family treatment drug court

Authors: Jinfeng Zhang, Chun-Sing Lee

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Pure nanodrugs (PNDs) – nanoparticles consisting entirely of drug molecules, have been considered as promising candidates for the next-generation nanodrugs. However, the traditional preparation method via reprecipitation faces critical challenges including low production rates, relatively large particle sizes and batch-to-batch variations. Here, for the first time, we successfully developed a novel, versatile and controllable strategy for preparing PNDs via an anodized aluminium oxide (AAO) template-assisted method. With this approach, we prepared PNDs of an anti-cancer drug (VM-26) with precisely controlled sizes reaching the sub-20 nm range. This template-assisted approach has much higher feasibility for mass production comparing to the conventional reprecipitation method and is beneficial for future clinical translation. The present method is further demonstrated to be easily applicable for a wide range of hydrophobic biomolecules without the need of custom molecular modifications and can be extended for preparing all-in-one nanostructures with different functional agents.

Keywords: drug delivery, pure nanodrugs, size control, template

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Authors: Yuvraj Singh Dangi, Brajesh Kumar Tiwari, Ashok Kumar Jain, Kamta Prasad Namdeo

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The potential use of liposomes as drug carriers by i.v. injection is limited by their low stability in blood stream. Firstly, phospholipid exchange and transfer to lipoproteins, mainly HDL destabilizes and disintegrates liposomes with subsequent loss of content. To avoid the pain associated with injection and to obtain better patient compliance studies concerning various dosage forms, have been developed. Conventional liposomes (unilamellar and multilamellar) have certain drawbacks like low entrapment efficiency, stability and release of drug after single breach in external membrane, have led to the new type of liposomal systems. The challenge has been successfully met in the form of Double Liposomes (DL). DL is a recently developed type of liposome, consisting of smaller liposomes enveloped in lipid bilayers. The outer lipid layer of DL can protect inner liposomes against various enzymes, therefore DL was thought to be more effective than ordinary liposomes. This concept was also supported by in vitro release characteristics i.e. DL formation inhibited the release of drugs encapsulated in inner liposomes. DL consists of several small liposomes encapsulated in large liposomes, i.e., multivesicular vesicles (MVV), therefore, DL should be discriminated from ordinary classification of multilamellar vesicles (MLV), large unilamellar vesicles (LUV), small unilamellar vesicles (SUV). However, for these liposomes, the volume of inner phase is small and loading volume of water-soluble drugs is low. In the present study, the potential of phosphatidylethanolamine (PE) lipid anchored double liposomes (DL) to incorporate two drugs in a single system is exploited as a tool to augment the H. pylori eradication rate. Preparation of DL involves two steps, first formation of primary (inner) liposomes by thin film hydration method containing one drug, then addition of suspension of inner liposomes on thin film of lipid containing the other drug. The success of formation of DL was characterized by optical and transmission electron microscopy. Quantitation of DL-bacterial interaction was evaluated in terms of percent growth inhibition (%GI) on reference strain of H. pylori ATCC 26695. To confirm specific binding efficacy of DL to H. pylori PE surface receptor we performed an agglutination assay. Agglutination in DL treated H. pylori suspension suggested selectivity of DL towards the PE surface receptor of H. pylori. Monotherapy is generally not recommended for treatment of a H. pylori infection due to the danger of development of resistance and unacceptably low eradication rates. Therefore, combination therapy with amoxicillin trihydrate (AMOX) as anti-H. pylori agent and ranitidine bismuth citrate (RBC) as antisecretory agent were selected for the study with an expectation that this dual-drug delivery approach will exert acceptable anti-H. pylori activity.

Keywords: Helicobacter pylorI, amoxicillin trihydrate, Ranitidine Bismuth citrate, phosphatidylethanolamine, multi vesicular systems

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Authors: Evelyn Smith, Susan Simpson

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Background: Eating disorder (ED) treatment is complicated by high rates of chronicity, comorbidity, complex personality traits and client dropout. Given these complexities, Schema Therapy (ST) has been identified as a suitable treatment option. The study primarily aims to evaluate the efficacy of group ST for the treatment of EDs. The study further evaluated the effectiveness of ST in reducing schemas and improving quality of life. Method: Participant suitability was ascertained using the Eating Disorder Examination. Following this, participants attended 90-minute weekly group sessions over 25 weeks. Groups consisted of six to eight participants and were facilitated by two psychologists, at least one of who is trained in ST. Measures were completed at pre, mid and post-treatment. Measures assessed ED symptoms, cognitive schemas, schema mode presentations, quality of life, self-compassion and psychological distress. Results: As predicted, measures of ED symptoms were significantly reduced following treatment. No significant changes were observed in early maladaptive schema severity; however, reductions in schema modes were observed. Participants did not report improvements in general quality of life measures following treatment, though improvement in psychological well-being was observed. Discussion: Overall, the findings from the current study support the use of group ST for the treatment of EDs. It is expected that lengthier treatment is needed for the reduction in schema severity. Given participant dropout was considerably low, this has important treatment implications for the suitability of ST for the treatment of EDs.

Keywords: eating disorders, schema therapy, treatment, quality of life

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Authors: Elham Rezaee, Sayyed Abbas Tabatabai

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Dual inhibition of COX-2 and sEH enzymes represents one of the distinct pharmaceutical approaches for the treatment of inflammation, pain, cancers, and other diseases. The discovery of these inhibitors for treatment is a great deal of attention because of some advantages such as increased efficacy, a promising safety profile, ease of formulation, and better target engagement. In this research, based on the structure-activity relationship of COX-2 and sEH inhibitors, some amide derivatives with oxadiazole and dihydropyrimidinone rings against sEH and COX-2 enzymes were developed. The designed compounds showed high affinity to the active site of both enzymes in docking studies and were synthesized in good yield and characterized by IR, Mass, 1HNMR, and 13CNMR. All of the novel compounds exhibited considerable in-vitro sEH and COX-2 inhibitory activities in comparison with 12-(3-Adamantan-1-yl-ureido)- dodecanoic acid and celecoxib (a potent urea-based sEH inhibitor and selective nonsteroidal anti-inflammatory drug, respectively). Ethyl 6-methyl-4-(4-(4-(methylsulfonyl)benzamido)phenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate was found to be the most selective COX-2 inhibitor (COX-2/COX-1 ratio: 683) with IC50 value of 2.1 nM targeting sEH enzyme.

Keywords: COX-2, dual inhibitors, sEH, synthesis

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Authors: Azad Khalid, Sifa Dogan

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Because of its persistence in conventional treatment plants and broad prevalence in water bodies, the pharmaceutical chemical carbamazepine (CBZ) has been suggested as an anthropogenic marker to evaluate water quality. This study provides a thorough examination of the origins and occurrences of CBZ in water bodies, as well as the drug's toxicological effects and laws. Given CBZ's well-documented negative consequences on the human body when used medicinally, cautious monitoring in water is advised. CBZ residues in drinking water may enter embryos and newborns via intrauterine exposure or breast-feeding, causing congenital abnormalities and/or neurodevelopmental issues over time. The insufficiency of solo solutions was shown after an in-depth technical study of traditional and sophisticated treatment technologies. Nanofiltration and reverse osmosis membranes are more successful at removing CBZ than traditional activated sludge and membrane bioreactor techniques. Recent research has shown that severe chemical cleaning, which is essential to prevent membrane fouling, may lower long-term removal efficiency. Furthermore, despite the efficacy of activated carbon adsorption and advanced oxidation processes, a few issues such as chemical cost and activated carbon renewal must be carefully examined. Individual technology constraints lead to the benefits of combined and hybrid systems, namely the heterogeneous advanced oxidation process.

Keywords: carbamazepine, occurrence, toxicity, conventical treatment, advanced oxidation process (AOPs)

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Authors: Karolina Pietras, Joanna Fryt, Aleksandra Gronostaj, Tomasz Smolen

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Young women and men differ from their parents in preferred values. Those differences enable their adaptability to a new socio-cultural context and help with fulfilling developmental tasks specific to young adulthood. At the same time core values, with special importance to family members, are transmitted within families. Intergenerational similarities in values may thus be both an effect of value transmission within a family and a consequence of sharing the same socio-cultural context. These processes are difficult to separate. In our study we assessed similarities and differences in values within four intergenerational family dyads (mothers-daughters, fathers-daughters, mothers-sons, fathers-sons). Sixty Polish young adults (30 women and 30 men aged 19-25) along with their parents (a total of 180 participants) completed the Schwartz’ Portrait Value Questionnaire (PVQ-21). To determine which values may be transmitted within families, we used a correlation analysis and pseudo dyad analysis that allows for the estimation of a baseline likeness between all tested subjects and consequently makes it possible to determine if similarities between actual family members are greater than chance. We also assessed whether different strategies of measuring similarity between family members render different results, and checked whether resemblances in family dyads are influenced by child’s and parent’s gender. Reported similarities were interpreted in light of the evolutionary and the value salience perspective.

Keywords: intergenerational differences in values, gender differences, pseudo dyad analysis, transmission of values

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Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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Authors: Anna Pudlo

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The EU law encompasses many supranational legal systems (EU law, ECHR, international public law and constitutional traditions common to the Member States) which guarantee the protection of fundamental rights, with partly overlapping scopes of applicability, various principles of interpretation of legal norms and a different hierarchy. In EU law, the prohibition of discrimination on grounds of sexual orientation originates from both the primary and secondary EU legislation. At present, the prohibition is considered to be a fundamental right in pursuance of Article 21 of the Charter, but the Court has not yet determined whether it is a right or a principle within the meaning of the Charter. Similarly, the Court has not deemed this criterion to be a general principle of EU law. The personal and materials scope of the prohibition of discrimination on grounds of sexual orientation based on Article 21 of the Charter requires each time to be specified in another legal act of the EU in accordance with Article 51 of the Charter. The effect of the prohibition of discrimination on grounds of sexual orientation understood as above will be two-fold, for the States and for the Union. On the one hand, one may refer to the legal instruments of review of EU law enforcement by a Member State laid down in the Treaties. On the other hand, EU law does not provide for the right to individual petition. Therefore, it is the duty of the domestic courts to protect the right of a person not to be discriminated on grounds of sexual orientation in line with the national procedural rules, within the limits and in accordance with the principles set out in EU law, in particular in Directive 2000/78. The development of the principle of non-discrimination in the Court’s case-law gives rise to certain doubts as to its applicability, namely whether the principle as the general principle of EU law may be granted an autonomous character, with respect to the applicability to matters not included in the personal or material scope of the Directives, although within the EU’s competence. Moreover, both the doctrine and the opinions of the Advocates-General have called for the general competence of CJEU with regard to fundamental rights which, however, might lead to a violation of the principle of separation of competence. The aim of this paper is to answer the question what is the nature of the prohibition of discrimination on grounds of sexual orientation in EU law (a general principle in EU law, or a principle or right under the Charter’s terminology). Therefore, the paper focuses on the nature of Article 21 of the Charter (a right or a principle) and the scope (personal and material) of the prohibition of discrimination based on sexual orientation in EU law as well as its effect (vertical or horizontal). The study has included the provisions of EU law together with the relevant CJEU case-law.

Keywords: EU law, EU principles, non-discrimination in EU law, Charter of the Fundamental Rights

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Authors: Charlene Petersen, Herman Grobler, Karel Botha

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Exposure to family violence has an impact on adolescent development, more specifically the identity process. This article explores the process of change in identity constructs of adolescents’ exposed to family violence in a Cape Town community in South Africa. In order to understand the process of identity formation the article explores and describes how the meaning that these adolescents give to family violence can contribute to change in their identity constructs. A mixed method approached was used in the study. A psycho-education strategy was implemented as the intervention and pretest-post-test scales were used to assess for change after the intervention process. Twelve participants were purposely selected for the study and included both male and female adolescents with ages ranging from 15 to 18 years from three secondary schools. The research data for this article were mainly extracted from the pre-test post-test design and the psycho-education strategy of the overall research study. The research results of the psycho-education strategy were thematically analyzed and a statistical procedure was used to measure for significant change within pre-test-post-test scales. The research merely refers to the outcome of psycho-education strategy and how it correlates with the outcome of the pre-test post-test design. Adolescents’ exposure to a psycho-education strategy, as well the pre-test post-test findings reveal a change within identity construct in terms of how they perceive themselves and interaction with others in the context of family violence.

Keywords: process of change in adolescent identity, family violence, psycho-education strategy, pre and post assessment

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Authors: Mehves Isiklar Ekici, Ceyda Tuna Kirsaclioglu, Zarife Kuloglu, Aydan Kansu

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Malnutrition is an important cause of morbidity and mortality as it accounts for 45% of child deaths under the age of 5 worldwide. Therefore, early recognition and effective treatment of failure to thrive and malnutrition are important. In this study, it was aimed to retrospectively evaluate the nutritional support treatment approaches (nutrition education and diet enrichment / use of enteral nutrition products) applied in children followed up with growth failure without underlying organic causes, and to compare the efficacy of nutritional support treatments. In this study, children aged 1 month to 18 years diagnosed with growth failure who were followed up for at least 12 months between January 2011 and February 2020, were included. Anthropometric measurements at baseline and during follow-up, type of nutritional support therapy and treatment compliance were evaluated based on the retrospective records. 119 children (median age:3.2, 69 girls) were included in the study. Nutrition education and dietary enrichment were provided to 28% of the patients (Group 1). In addition to dietary education and recommendations, enteral nutrition supplements was given in 78% of them (Group 2). Compliance to the treatment rates of the patients in Group 1 and Group 2 were not significantly different at both 6th and 12th month controls. At the end of the follow up children who comply with the treatment in Group 1 had significant increase in weight for age z scores (-1.74 vs 0.05, respectively, p=0.019) and body mass index z scores (-1.47 vs -0.53, respectively, p=0.034) compared with baseline measurements. Similar to Group 1, in Group 2 children with treatment compliance, had a significant increase in weight for age z scores (-2.24 vs. -0.54, respectively, p=0.00) and body mass index z scores (-2.27 vs. -1.06, respectively, p=0.00) compared with baseline measurements. The rate of patients with severe malnutrition decreased from 15% to 12%, for moderate malnutrition decreased from 54% to 33%. Moreover, it was observed that this decrease in the rate of patients with both severe and moderate malnutrition was more prominent in patients under 3 years of age. Although there was a significant increase in anthropometric measurements with treatment in both groups, there was no significant difference in between two groups terms of change in anthropometric measurements (p>0.05), therefore effectiveness. Failure to thrive and malnutrition in infancy and childhood cause health problems that can affect adult life. To conclude, nutritional education - dietary enrichment. recommendations and use of enteral nutrition supplements were both proven beneficial in this study. Researchers are willing to underline that the most important part of the treatment is to include the family to the process to ensure the treatment compliance.

Keywords: enteral nutrition supplements, failure to thrive, malnutrition, nutritional education

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Authors: Tahera Begum, Sabina Yeasmin, Jalal Uddin

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Ten slums of ten wards of Chittagong city corporation of Bangladesh were conveniently selected to know about modern contraceptive use by the slum dwellers. Total 300 family heads or their wives were interviewed with a questionnaire in February 2014. Family size was 4.62. Among 300 families 248 eligible couples were found. 57% eligible couples use different modern contraceptive measures. Remaining 43% eligible couples do not use modern contraceptive measures. Among the users 58% use oral pill, 30% injectables, 8% use condom, 3% were found with ligation and only 1% with vasectomy. Contraceptive prevalence rate has been increased and pattern as changed. A discussion is made with literature review.

Keywords: conraceptive, Bangladesh, family, pill

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Authors: Ikediobi Lottanna Samuel

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Days are gone when perpetrators of core international crimes hide under the cloak of sovereignty to go with impunity. The principle of international criminal responsibility is a reality. This move to end impunity for violation of human rights has led to the creation of international and hybrid tribunals, a permanent international criminal court, and increased prosecution of human rights violations in domestic courts. This article examines the attempts by the international community to bring perpetrators of heinous crimes to book. The work reveals the inadequacy of the current international mechanism for prosecuting core international crimes in order to end the culture of impunity and entrench the culture of accountability. It also identifies that ad hoc international criminal tribunals and the international criminal court face similar challenges ranging from lack of cooperation by nation states, non-existence of hierarchy of crimes, lack of effective enforcement mechanism, limited prosecutorial capacity and agenda, difficulty in apprehending suspects, difficulty in blending different legal tradition, absence of a coherent sentencing guideline, distant location of courts, selective indictment, etc. These challenges adversely affect the functioning of these courts. It is suggested that a more helpful way to end impunity would be to have a more robust and synergistic relationship between national, regional, and international approaches to prosecuting core international crimes.

Keywords: prosecution, criminal, international, tribunal, justice, ad hoc

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Authors: Vladimir Berezin, Aizhan Turmagambetova, Andrey Bogoyavlenskiy, Pavel Alexyuk, Madina Alexyuk, Irina Zaitceva, Nadezhda Sokolova

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Introduction: Influenza viruses could infect approximately 5% to 10% of the global human population annually, resulting in serious social and economic damage. Vaccination and etiotropic antiviral drugs are used for the prevention and treatment of influenza. Vaccination is important; however, antiviral drugs represent the second line of defense against new emerging influenza virus strains for which vaccines may be unsuccessful. However, the significant drawback of commercial synthetic anti-flu drugs is the appearance of drug-resistant influenza virus strains. Therefore, the search and development of new anti-flu drugs efficient against drug-resistant strains is an important medical problem for today. The aim of this work was a study of four phenolic acids of plant origin (Gallic, Syringic, Vanillic, and Protocatechuic acids) as a possible tool for treatment against influenza virus. Methods: Phenolic acids; gallic, syringic, vanillic, and protocatechuic have been prepared by extraction from plant tissues and purified using high-performance liquid chromatography fractionation. Avian influenza virus, strain A/Tern/South Africa/1/1961 (H5N3) and human epidemic influenza virus, strain A/Almaty/8/98 (H3N2) resistant to commercial anti-flu drugs (Rimantadine, Oseltamivir) were used for testing antiviral activity. Viruses were grown in the allantoic cavity of 10 days old chicken embryos. The chemotherapeutic index (CTI), determined as the ratio of an average toxic concentration of the tested compound (TC₅₀) to the average effective virus-inhibition concentration (EC₅₀), has been used as a criteria of specific antiviral action. Results: The results of study have shown that the structure of phenolic acids significantly affected their ability to suppress the reproduction of tested influenza virus strains. The highest antiviral activity among tested phenolic acids was detected for gallic acid, which contains three hydroxyl groups in the molecule at C3, C4, and C5 positions. Antiviral activity of gallic acid against A/H5N3 and A/H3N2 influenza virus strains was higher than antiviral activity of Oseltamivir and Rimantadine. gallic acid inhibited almost 100% of the infection activity of both tested viruses. Protocatechuic acid, which possesses 2 hydroxyl groups (C3 and C4) have shown weaker antiviral activity in comparison with gallic acid and inhibited less than 10% of virus infection activity. Syringic acid, which contains two hydroxyl groups (C3 and C5), was able to suppress up to 12% of infection activity. Substitution of two hydroxyl groups by methoxy groups resulted in the complete loss of antiviral activity. Vanillic acid, which is different from protocatechuic acid by replacing of C3 hydroxyl group to methoxy group, was able to suppress about 30% of infection activity of tested influenza viruses. Conclusion: For pronounced antiviral activity, the molecular of phenolic acid must have at least two hydroxyl groups. Replacement of hydroxyl groups to methoxy group leads to a reduction of antiviral properties. Gallic acid demonstrated high antiviral activity against influenza viruses, including Rimantadine and Oseltamivir resistant strains, and could be used as a potential candidate for the development of antiviral drug against influenza virus.

Keywords: antiviral activity, influenza virus, drug resistance, phenolic acids

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Authors: Aurélie Cassiers

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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

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Authors: Fathonah Siti, Ardiana Irma

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Indonesia is currently on its track to achieve Universal Health Coverage (UHC) by 2019. The program aims to address issues on disintegration in the implementation and coverage of various health insurance schemes and fragmented fund pooling. Family planning service is covered as one of benefit packages under preventive care. However, little has been done to examine how family planning program are appropriately managed across levels of governments and how family planning services are delivered to the end user. The study is performed through focus group discussion to related policy makers and selected programmers at central and district levels. The study is also benefited from relevant studies on family planning in the UHC scheme and other supporting data. The study carefully investigates some programmatic implications when family planning is integrated in the UHC program encompassing the need to recalculate contraceptive logistics for beneficiaries (eligible couple); policy reformulation for contraceptive service provision including supply chain management; establishment of family planning standard of procedure; and a call to update Management Information System. The study confirms that there is a significant increase in the numbers of contraceptive commodities needs to be procured by the government. Holding an assumption that contraceptive prevalence rate and commodities cost will be as expected increasing at 0.5% annually, the government need to allocate almost IDR 5 billion by 2019, excluded fee for service. The government shifts its focus to maintain eligible health facilities under National Population and Family Planning Board networks. By 2019, the government has set strategies to anticipate the provision of family planning services to 45.340 health facilities distributed in 514 districts and 7 thousand sub districts. Clear division of authorities has been established among levels of governments. Three models of contraceptive supply planning have been developed and currently in the process of being institutionalized. Pre service training for family planning services has been piloted in 10 prominent universities. The position of private midwives has been appreciated as part of the system. To ensure the implementation of quality and health expenditure control, family planning standard has been established as a reference to determine set of services required to deliver to the clients properly and types of health facilities to conduct particular family planning services. Recognition to individual status of program participation has been acknowledged in the Family Enumeration since 2015. The data is precisely recorded by name by address for each family and its members. It supplies valuable information to 15.131 Family Planning Field Workers (FPFWs) to provide information and education related to family planning in an attempt to generate demand and maintain the participation of family planning acceptors who are program beneficiaries. Despite overwhelming efforts described above, some obstacles remain. The program experiences poor socialization and yet removes geographical barriers for those living in remote areas. Family planning services provided for this sub population conducted outside the scheme as a complement strategy. However, UHC program has brought remarkable improvement in access and quality of family planning services.

Keywords: beneficiary, family planning services, national population and family planning board, universal health coverage

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Authors: Eileen Y. Wong, Katherine Jin, Anat Talmon

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Background: Help seeking behaviors are highly contingent on socio-cultural factors such as ethnicity. Both Latino and Asian Americans underutilize mental health services compared to their White American counterparts. This difference may be related to the composite of one’s social support system, which includes family cohesion and social networks. Previous studies have found that Latino families are characterized by higher levels of family cohesion and social support, and Asian American families with greater family cohesion exhibit lower levels of help seeking behaviors. While both are broadly considered collectivist communities, within-culture variability is also significant. Therefore, this study aims to investigate the relationship between help seeking behaviors in the two cultures with levels of family cohesion and strength of social network. We also consider such relationships in light of previous traumatic events and diagnoses, particularly post-traumatic stress disorder (PTSD), to understand whether clinically diagnosed individuals differ in their strength of network and help seeking behaviors. Method: An adult sample (N = 2,990) from the National Latino and Asian American Study (NLAAS) provided data on participants’ social network, family cohesion, likelihood of seeking professional help, and DSM-IV diagnoses. T-tests compared Latino American (n = 1,576) and Asian American respondents (n = 1,414) in strength of social network, level of family cohesion, and likelihood of seeking professional help. Linear regression models were used to identify the probability of help-seeking behavior based on ethnicity, PTSD diagnosis, and strength of social network. Results: Help-seeking behavior was significantly associated with family cohesion and strength of social network. It was found that higher frequency of expressing one’s feelings with family significantly predicted lower levels of help-seeking behaviors (β = [-.072], p = .017), while higher frequency of spending free time with family significantly predicted higher levels of help-seeking behaviors (β = [.129], p = .002) in the Asian American sample. Subjective importance of family relations compared to that of one’s peers also significantly predict higher levels of help-seeking behaviors (β = [.095], p = .011) in the Asian American sample. Frequency of sharing one’s problems with relatives significantly predicted higher levels of help-seeking behaviors (β = [.113], p < .01) in the Latino American sample. A PTSD diagnosis did not have any significant moderating effect. Conclusion: Considering the underutilization of mental health services in Latino and Asian American minority groups, it is crucial to understand ways in which help seeking behavior can be encouraged. Our findings suggest that different dimensions within family cohesion and social networks have differential impacts on help-seeking behavior. Given the multifaceted nature of family cohesion and cultural relevance, the implications of our findings for theory and practice will be discussed.

Keywords: family cohesion, social networks, Asian American, Latino American, help-seeking behavior

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Authors: Farzana Esmailkassam, Usakorn Kunanuvat, Zahraa Mohammed Ali

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Objective: The key barrier in Clozapine treatment of treatment-resistant schizophrenia (TRS) includes frequent bloods draws to monitor neutropenia, the main drug side effect. WBC and ANC monitoring must occur throughout treatment. Accurate WBC and ANC counts are necessary for clinical decisions to halt, modify or continue clozapine treatment. The CSAN Pronto point-of-care (POC) analyzer generates white blood cells (WBC) and absolute neutrophils (ANC) through image analysis of capillary blood. POC monitoring offers significant advantages over central laboratory testing. This study evaluated the performance of the CSAN Pronto against the Beckman DxH900 Hematology laboratory analyzer. Methods: Forty venous samples (EDTA whole blood) with varying concentrations of WBC and ANC as established on the DxH900 analyzer were tested in duplicates on three CSAN Pronto analyzers. Additionally, both venous and capillary samples were concomitantly collected from 20 volunteers and assessed on the CSAN Pronto and the DxH900 analyzer. The analytical performance including precision using liquid quality controls (QCs) as well as patient samples near the medical decision points, and linearity using a mix of high and low patient samples to create five concentrations was also evaluated. Results: In the precision study for QCs and whole blood, WBC and ANC showed CV inside the limits established according to manufacturer and laboratory acceptability standards. WBC and ANC were found to be linear across the measurement range with a correlation of 0.99. WBC and ANC from all analyzers correlated well in venous samples on the DxH900 across the tested sample ranges with a correlation of > 0.95. Mean bias in ANC obtained on the CSAN pronto versus the DxH900 was 0.07× 109 cells/L (95% L.O.A -0.25 to 0.49) for concentrations <4.0 × 109 cells/L, which includes decision-making cut-offs for continuing clozapine treatment. Mean bias in WBC obtained on the CSAN pronto versus the DxH900 was 0.34× 109 cells/L (95% L.O.A -0.13 to 0.72) for concentrations <5.0 × 109 cells/L. The mean bias was higher (-11% for ANC, 5% for WBC) at higher concentrations. The correlations between capillary and venous samples showed more variability with mean bias of 0.20 × 109 cells/L for the ANC. Conclusions: The CSAN pronto showed acceptable performance in WBC and ANC measurements from venous and capillary samples and was approved for clinical use. This testing will facilitate treatment decisions and improve clozapine uptake and compliance.

Keywords: absolute neutrophil counts, clozapine, point of care, white blood cells

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Authors: Kurt Willems

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This research examines complaints against grading in higher education institutions in four different European regions: England and Wales, Flanders, the Netherlands, and France. The aim of the research is to examine the correlation between the applicable type of complaint handling on the one hand, and selected qualities of the higher education landscape and of public law on the other hand. All selected regions report a rising number of complaints against grading decisions, not only as to internal complaint handling within the institution but also judicially if the dispute persists. Some regions deem their administrative court system appropriate to deal with grading disputes (France) or have even erected a specialty administrative court to facilitate access (Flanders, the Netherlands). However, at the same time, different types of (governmental) dispute resolution bodies have been established outside of the judicial court system (England and Wales, and to lesser extent France and the Netherlands). Those dispute procedures do not seem coincidental. Public law issues such as the underlying legal nature of the education institution and, eventually, the grading decision itself, have an impact on the way the academic complaint procedures are developed. Indeed, in most of the selected regions, contractual disputes enjoy different legal protection than administrative decisions, making the legal qualification of the relationship between student and higher education institution highly relevant. At the same time, the scope of competence of government over different types of higher education institutions; albeit direct or indirect (o.a. through financing and quality control) is relevant as well to comprehend why certain dispute handling procedures have been established for students. To answer the above questions, the doctrinal and comparative legal method is used. The normative framework is distilled from the relevant national legislative rules and their preparatory texts, the legal literature, the (published) case law of academic complaints and the available governmental reports. The research is mainly theoretical in nature, examining different topics of public law (mainly administrative law) and procedural law in the context of grading decisions. The internal appeal procedure within the education institution is largely left out of the scope of the research, as well as different types of non-governmental-imposed cooperation between education institutions, given the public law angle of the research questions. The research results in the categorization of different academic complaint systems, and an analysis of the possibility to introduce each of those systems in different countries, depending on their public law system and higher education system. By doing so, the research also adds to the debate on the public-private divide in higher education systems, and its effect on academic complaints handling.

Keywords: higher education, legal qualification of education institution, legal qualification of grading decisions, legal protection of students, academic litigation

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Authors: Mireya Mateo Gomez

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The purpose of this study was to examine the perceptions first-generation Mexican origin mothers living in San Diego have on postpartum depression (PPD), with a special focus on social influences and cultural beliefs towards those meanings. This study also aimed to examine possible PPD help-seeking behaviors that first-generation Mexican origin mothers can perform. The Health Belief Model (HBM) and Social Ecological Model (SEM) were the guiding theoretical frameworks for this study. Data for this study were collected from three focus groups, four in-depth interviews, and the distribution of an acculturation survey (ARSMA II). There were a total of 15 participants, in which participant’s mean age was 45, and the mean age migrated to the United States being 22. Most participants identified as being married, born in Southern or Western Mexico, and with a strong Mexican identity in relation to the ARSMA survey. Participants identified four salient PPD perceptions corresponding to the interpersonal level of SEM. These four main perceptions were: 1) PPD affecting the identity of motherhood; 2) PPD being a natural part of a mother’s experience but mitigated by networks; 3) PPD being a U.S. phenomenon due to family and community breakdown; and 4) natural remedies as a preferred PPD treatment. In regard to themes relating to help seeking behaviors, participants identified seven being: 1) seeking help from immediate family members; 2) practicing home remedies; 3) seeking help from a medical professional; 4) obtaining help from a clinic or organization; 5) seeking help from God; 6) participating in PPD support groups; and 7) talking to a friend. It was evident in this study that postpartum depression is not a well discussed topic within the Mexican immigrant population. In relation to the role culture and social influences have on PPD perceptions, most participants shared hearing or learning about PPD from their family members or friends. Participants also stated seeking help from family members if diagnosed with PPD and seeking out home remedies. This study as well provides suggestions to increase the awareness of PPD among the Mexican immigrant community.

Keywords: cultural beliefs, health belief model, Mexican origin mothers, perceptions, postpartum depression social ecological model

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Authors: Karissa A. Graham

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Pyoderma gangrenosum (PG) is a prototypic autoinflammatory neutrophilic dermatosis that is a rare disorder. It presents a diagnostic challenge owing to its variable presentation, clinical overlap with other conditions, it is often associated with other systemic conditions, and there is no definitive histological or laboratory characteristic. The Delphai consensus for PG includes the presence of at least one ulcer on the anterior lower limb. Systemic corticosteroids and immunosuppressive therapies are the mainstay treatment for PG. We describe a case report of delayed diagnosis of ulcerative pyoderma gangrenosum in a 44-year-old male on his forearm. The patient presented with an infected ulcer on his right forearm that had been present for over three years. The patient was a Type 2 Diabetic with no personal or family history of inflammatory bowel disease or other autoimmune diseases. The patient was initially investigated for malignancy, but biopsies returned as chronic inflammatory tissue with neutrophilic infiltrate and no malignancy. The patient was commenced on systemic prednisone for the treatment of pyoderma gangrenosum. The diagnosis of ulcerative PG poses a challenge given the vast differential diagnosis for a cutaneous ulcer (i.e., malignant, vascular, autoimmune, trauma, infective, etc.). Diagnostic accuracy is important given that the treatment for PG with steroids does not go without risks and indeed may be contraindicated in other potential causes of the ulcer. Indeed, more common and more sinister causes of ulcers should be investigated first, as death from PG is quite rare.

Keywords: dermatological diagnosis, dermatosis, pyoderma gangrenosum, rare presentation

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Authors: Ida Rosada, Nurliani

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Today, the number of women who seek additional income to help her husband is increasing. They do that in order to be able to express themselves in the midst of the family and society. Nonetheless, housewives are in charge of managing family’s income and prepare food for the family. The objective of this research is 1) to analyze the effect of the dual role of women to household income and 2) to analyze the effect of the dual role to consumption patterns. The study used a qualitative approach, data collection techniques are through observation, interviews, and documentation on farming households. The data was analysed qualitative descriptively. The results found that: 1) The revenue contribution of women who play double role in the informal sector amounted to 34.07% (less than 50%). 2) The main reason that the respondents worked in the informal sector is to be able to send their children to school (34%) and to improve household economy condition (28%). 3) After earning additional income, respondents said that they can contribute to increase the family’s income and to cover the family shortage (82%); 4) Respondents’ opinion to changes in food consumption after performing the dual role is the ability to purchase and provide the desired food (44%) and changing patterns of consumption per day (30%).

Keywords: dual role, the informal sector, consumption patterns, household income

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Authors: Tomohiro Uchida, Noriaki Satake, Toshimichi Nakaho, Akira Inoue, Hidemitsu Saito

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In this study, we assessed the bereavement risk of family caregivers of patients with cancer. In the palliative care unit of Tohoku University Hospital, we conducted a family psychoeducation session to support the family caregivers of patients with cancer. A total of 50 participants (8 males and 42 females; mean age = 62.98 years, SD = 11.10) were assessed after the session for bereavement risk using the Japanese version of the Bereavement Risk Assessment Tool (BRAT-J). According to the BRAT-J scores, eight participants were considered to be having no known risk (Level 1), seventeen had minimal risk (Level 2), twenty had a low risk (Level 3), four had a moderate risk (Level 4), and one had a high risk (Level 5). Of these participants, seven participants had completed the follow-up postal survey that assessed their psychological distress (the Kessler Psychological Distress Scale: K6) to compare the bereavement risk. According to the K6 scores, three-fourth of the individuals, who were considered to be at Level 3 on the BRAT-J, scored higher than the cutoff point (>10) for the detection of depressive disorder. On the other hand, one-third of the individuals, who were considered to be at Level 2 on the BRAT-J, scored higher than the cutoff point. Therefore, it appears that the BRAT-J can predict the likelihood of difficulties or complications in bereaved family caregivers. This research was approved by the Ethics Committee of Tohoku University Graduate School of Medicine and Tohoku University Hospital.

Keywords: palliative care, family caregivers, bereavement risk, BRAT, post-loss psychological distress

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Authors: Amirah Azzeri, Fatiha H. Shabaruddin, Scott A. McDonald, Rosmawati Mohamed, Maznah Dahlui

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Objective: A scaled-up treatment cascade with direct-acting antiviral (DAA) therapy is necessary to achieve global WHO targets for hepatitis C virus (HCV) elimination in Malaysia. Recently, limited access to Sofosbuvir/Daclatasvir (SOF/DAC) is available through compulsory licensing, with future access to Sofosbuvir/Velpatasvir (SOF/VEL) expected through voluntary licensing due to recent agreements. SOF/VEL has superior clinical outcomes, particularly for cirrhotic stages, but has higher drug acquisition costs compared to SOF/DAC. It has been proposed that a stratified treatment cascade might be the most cost-efficient approach for Malaysia whereby all HCV patients are treated with SOF/DAC except for patients with cirrhosis who are treated with SOF/VEL. This study aimed to conduct a five-year budget impact analysis from the provider perspective of the proposed stratified treatment cascade for HCV treatment in Malaysia. Method: A disease progression model that was developed based on model-predicted HCV epidemiology data in Malaysia was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. The model projections estimated the annual numbers of patients in care and the numbers of patients to be initiated on DAA treatment nationally. Healthcare costs associated with DAA therapy and disease stage monitoring was included to estimate the downstream cost implications. For scenario B, the estimated treatment uptake of SOF/VEL for cirrhotic patients were 25%, 50%, 75%, 100% and 100% for 2018, 2019, 2020, 2021 and 2022 respectively. Healthcare costs were estimated based on standard clinical pathways for DAA treatment described in recent guidelines. All costs were reported in US dollars (conversion rate US$1=RM4.09, the price year 2018). Scenario analysis was conducted for 5% and 10% reduction of SOF/VEL acquisition cost anticipated from the competitive market pricing of generic DAA in Malaysia. Results: The stratified treatment cascade with SOF/VEL in Scenario B was found to be cost-saving compared to Scenario A. A substantial portion of the cost reduction was due to the costs associated with DAA therapy which resulted in USD 40 thousand (year 1) to USD 443 thousand (year 5) savings annually, with cumulative savings of USD 1.1 million after 5 years. Cost reductions for disease stage monitoring were seen in year three onwards which resulted in cumulative savings of USD 1.1 thousand. Scenario analysis estimated cumulative savings of USD 1.24 to USD 1.35 million when the acquisition cost of SOF/VEL was reduced. Conclusion: A stratified treatment cascade with SOF/VEL was expected to be cost-saving and can results in a budget impact reduction in overall healthcare expenditure in Malaysia compared to treatment with SOF/DAC. The better clinical efficacy with SOF/VEL is expected to halt patients’ HCV disease progression and may reduce downstream costs of treating advanced disease stages. The findings of this analysis may be useful to inform healthcare policies for HCV treatment in Malaysia.

Keywords: Malaysia, direct acting antiviral, compulsory licensing, voluntary licensing

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Authors: Konstancja Syller

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International law and European regulations remain hardly silent about the admissibility of evidence obtained illegally in a criminal trial. However, Article 6 of the European Convention on Human Rights guarantees the right to a fair trial, it does not normalise a proceeding status of specified sources or means of proof outright. Therefore, it is the preserve of national legislation and national law enforcement authorities to decide on this matter. In most countries, especially in Germany and Poland, a rather complex normative approach to the issue of proof obtained in violation of the right to privacy is evident, which pursues in practise to many interpretive doubts. In Germany the jurisprudence has a significant impact within the range of the matter mentioned above. The Constitutional Court and the Supreme Court of Germany protect the right to privacy quite firmly - they ruled on inadmissibility of obtaining a proof in the form of a diary or a journal as a protection measure of constitutional guaranteed right. At the same time, however, the Supreme Court is not very convinced with reference to the issue of whether materials collected as a result of an inspection, call recordings or listening to the premises, which were carried out in breach of law, can be used in a criminal trial. Generally speaking, German courts indicate a crucial importance of the principle of Truth and the principle of proportionality, which both enable a judgement to be made as to the possibility of using an evidence obtained unlawfully. Comparing, in Poland there is almost no jurisprudence of the Constitutional Tribunal relating directly to the issue of illegal evidence. It is somehow surprising, considering the doctrinal analysis of the admissibility of using such proof in a criminal trial is performed in relation to standards resulted from the Constitution. Moreover, a crucial de lega lata legal provision, which enables allowing a proof obtained in infringement of the provisions in respect of criminal proceedings or through a forbidden act, is widely criticised within the legal profession ant therefore many courts give it their own interpretation at odds with legislator’s intentions. The comparison of two civil law legal systems’ standards regarding to the admissibility of an evidence obtained in contravention of the right to privacy in a criminal trial, taking also into account EU legislation and judicature, is the conclusive aim of this article.

Keywords: criminal trial, evidence, Germany, right to privacy, Poland

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Authors: B. J. Mahen, N. E. Lloyd-Gale, S. Johnson, W. P. Rakowicz, M. J. Harris, A. D. Miller

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Background: Migraine is a leading cause of disability in the world. Calcitonin gene-related peptide (CGRP) receptor antagonists offer an approach to migraine prophylaxis by inhibiting the inflammatory and vasodilatory effects of CGRP. In recent years, NICE licensed the use of three CGRP-receptor antagonists: Fremanezumab, Galcanezumab, and Erenumab. Here, we present the outcomes of CGRP-antagonist treatment in a cohort of patients who suffer from episodic or chronic migraine and have failed at least three oral prophylactic therapies. Methods: We offered CGRP antagonists to 86 patients who met the NICE criteria to start therapy. We recorded the number of headache days per month (HDPM) at 0 weeks, 3 months, and 12 months. Of those, 26 patients were switched to an alternative treatment due to poor response or side effects. Of the 112 total cases, 9 cases did not sufficiently maintain their headache diary, and 5 cases were not followed up at 3 months. We have therefore included 98 sets of data in our analysis. Results: Fremanezumab achieved a reduction in HDPM by 51.7% at 3 months (p<0.0001), with 63.7% of patients meeting NICE criteria to continue therapy. Patients trialed on Galcanezumab attained a reduction in HDPM by 47.0% (p=0.0019), with 51.6% of patients meeting NICE criteria to continue therapy. Erenumab, however, only achieved a reduction in HDPM by 17.0% (p=0.29), and this was not statistically significant. Furthermore, 34.4%, 9.7%, and 4.9% of patients taking Fremanezumab, Galcanezumab, and Erenumab, respectively, continued therapy beyond 12 months. Of those who attempted drug holidays following 12 months of treatment, migraine symptoms relapsed in 100% of cases. Conclusion: We observed a significant improvement in HDPM amongst episodic and chronic migraine patients following treatment with Fremanezumab or Galcanezumab.

Keywords: migraine, CGRP, fremanezumab, galcanezumab, erenumab

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Authors: Mohd Sarfaraz

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The objective of this study is to investigate the work-life balance and job satisfaction among women employees in a hospital in India. It is believed that balancing a successful career with a family life or personal life can be challenging. WLB impacts on persons' satisfaction in their work and personal life roles. For this purpose, a questionnaire is developed with 22 items. The data collected from women employees who are working in a hospital in Aligarh, India. The constructs considered in this study include WLB and job satisfaction. The demographic and organisational variables considered in the study are genders, age and tenure of the job. Factors of WLB are flexible working conditions, work-life balance programs, and employee intention to change/leave a job, work pressure/stress and long working hours. This paper examines the relationship between work-family conflict, policies, and job and life satisfaction. Appropriate statistical tool using SPSS will be applied to achieve the objective. The anxiety over work-life balance is progressively becoming a common talk, especially for female employees.Increasing demands from the work and family domains represent a high strain for employees which even lead to the health problems among employees. Although it is believed that work-family role strain is more common among women employees. Therefore, the study will focus on these issues of WLB and job satisfaction among female professionals.

Keywords: work-life balance, job satisfaction, work- family conflict, health

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Authors: Adam Reilly

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The major claim of this paper is that both the English and Canadian branches of the common law have been ill-served by the 'institutional'/'remedial' taxonomy of constructive trusts; what shall be termed the 'orthodox taxonomy'.  The orthodox taxonomy is found both within the case law and the attendant academic commentary.  In truth, the orthodox taxonomy is especially dangerous because it contains a kernel of truth together with a misconception; the interplay of both has caused more harm than the misconception alone would have managed.  The kernel of truth is that some trusts arise automatically when the necessary facts occur ('institutional') and other trusts arise only by way of court order ('remedial').  The misconception is that these two labels represent an exhaustive nomenclature of two distinct 'kinds' of constructive trust such that any particular constructive trust must necessarily be 'institutional' if it is not 'remedial' and vice versa.  The central difficulty is that our understanding of 'remedial' trusts is relatively poor, with the result that anyone using the orthodox taxonomy shall be led astray in one of three ways: (i) by rejecting it wholesale; (ii) by adopting one ‘type’ of trust to the exclusion of the other (as in English law); or (iii) by applying it as an analytical device with sub-optimal results which are difficult to defend.  This paper shall seek to resolve these difficulties by clarifying the criteria for identifying and distinguishing true 'remedial' constructive trusts.  It shall then provide some working examples of how English and Canadian private law at present misunderstand constructive trusts and how that misunderstanding might be resolved once we distinguish the orthodox taxonomy's kernel of truth from the misconception outlined above.

Keywords: comparative law, constructive trusts, equitable remedies, remedial constructive trusts

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Authors: Chigbo Ikechukwu Emmanuel

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Microalgae can be used for tertiary treatment of wastewater due to their capacity to assimilate nutrients. The pH increase which is mediated by the growing algae also induces phosphorus precipitation and ammonia stripping to the air, and may in addition act disinfecting on the wastewater. Domestic wastewater is ideal for algal growth since it contains high concentrations of all necessary nutrients. The growth limiting factor is rather light, especially at higher latitudes. The most important operational factors for successful wastewater treatment with microalgae are depth, turbulence and hydraulic retention time.

Keywords: microalgae, wastewater treatment, phosphorus, nitrogen, light, operation, ponds, growth

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Authors: X. King, E. Nazarzadeh, J. Reboud, J. Cooper

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Pulmonary diseases, such as asthma, are generally treated by the inhalation of aerosols that has the advantage of reducing the off-target (e.g., toxicity) effects associated with systemic delivery in blood. Effective respiratory drug delivery requires a droplet size distribution between 1 and 5 µm. Inhalation of aerosols with wide droplet size distribution, out of this range, results in deposition of drug in not-targeted area of the respiratory tract, introducing undesired side effects on the patient. In order to solely deliver the drug in the lower branches of the lungs and release it in a targeted manner, a control mechanism to produce the aerosolized droplets is required. To regulate the drug release and to facilitate the uptake from cells, drugs are often encapsulated into protective liposomes. However, a multistep process is required for their formation, often performed at the formulation step, therefore limiting the range of available drugs or their shelf life. Using surface acoustic waves (SAWs), a pulmonary drug delivery platform was produced, which enabled the formation of defined size aerosols and the formation of liposomes in situ. SAWs are mechanical waves, propagating along the surface of a piezoelectric substrate. They were generated using an interdigital transducer on lithium niobate with an excitation frequency of 9.6 MHz at a power of 1W. Disposable silicon superstrates were etched using photolithography and dry etch processes to create an array of cylindrical through-holes with different diameters and pitches. Superstrates were coupled with the SAW substrate through water-based gel. As the SAW propagates on the superstrate, it enables nebulisation of a lipid solution deposited onto it. The cylindrical cavities restricted the formation of large drops in the aerosol, while at the same time unilamellar liposomes were created. SAW formed liposomes showed a higher monodispersity compared to the control sample, as well as displayed, a faster production rate. To test the aerosol’s size, dynamic light scattering and laser diffraction methods were used, both showing the size control of the aerosolised particles. The use of silicon superstate with cavity size of 100-200 µm, produced an aerosol with a mean droplet size within the optimum range for pulmonary drug delivery, containing the liposomes in which the medicine could be loaded. Additionally, analysis of liposomes with Cryo-TEM showed formation of vesicles with narrow size distribution between 80-100 nm and optimal morphology in order to be used for drug delivery. Encapsulation of nucleic acids in liposomes through the developed SAW platform was also investigated. In vitro delivery of siRNA and DNA Luciferase were achieved using A549 cell line, lung carcinoma from human. In conclusion, SAW pulmonary drug delivery platform was engineered, in order to combine multiple time consuming steps (formation of liposomes, drug loading, nebulisation) into a unique platform with the aim of specifically delivering the medicament in a targeted area, reducing the drug’s side effects.

Keywords: acoustics, drug delivery, liposomes, surface acoustic waves

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Authors: Wenjie Wu, Peng Cheng, Zehua Zhang, Fei Luo, Feng Wu, Min Zhong, Jianzhong Xu

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Background: There has been limited research into the therapeutic efficacy of rapid diagnosis of spinal tuberculosis complicated with pulmonary tuberculosis. We attempted to discover whether the utilization of a DNA microarray assay to detect multidrug-resistant spinal tuberculosis complicated with pulmonary tuberculosis can improve clinical outcomes. Methods: A prospective study was conducted from February 2006 to September 2015. One hundred and forty-three consecutive culture–confirmed, clinically and imaging diagnosed MDR-TB patients with spinal tuberculosis complicated by pulmonary tuberculosis were enrolled into the study. The initial time to treatment for MDR-TB, the method of infection control, radiological indicators of spinal tubercular infectious foci, culture conversion, and adverse drug reactions were compared with the standard culture methods. Results: Of the total of 143 MDR-TB patients, 68 (47.6%) were diagnosed by conventional culture methods and 75 (52.4%) following the implementation of detection using the DNA microarray. Patients in the microarray group began rational use of the second-line drugs schedule more speedily than sufferers in the culture group (17.3 vs. 74.1 days). Among patients were admitted to a general tuberculosis ward, those from the microarray group spent less time in the ward than those from the culture group (7.8 vs. 49.2 days). In those patients with six months follow-up (n=134), patients in the microarray group had a higher rate of sputum negativity conversion at six months (89% vs. 73%). In the microarray group, the rate of drug adverse reactions was significantly lower (22.2% vs. 67.7%). At the same time, they had a more obvious reduction of the area with spinal tuberculous lesions in radiological examinations (77% vs. 108%). Conclusions: The application of the CapitalBio™ DNA Microarray assay caused noteworthy clinical advances including an earlier time to begin MDR-TB treatment, increased sputum culture conversion, improved infection control measures and better radiographical results

Keywords: tuberculosis, multidrug-resistant, tuberculous spondylitis, DNA microarray, clinical outcomes

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