Search results for: change point analysis

Authors: Magdalena Orth, Gunnar Gotz

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Background: Domestic accountability, budget transparency and public financial management (PFM) are considered vital components of good governance in developing countries. The aid modality budget support (BS) promotes these governance functions in developing countries. BS engages in political decision-making and provides financial and technical support to poverty reduction strategies of the partner countries. Nevertheless, many donors have withdrawn their support from this modality due to cases of corruption, fraud or human rights violations. This exit from BS is leaving a finance and governance vacuum in the countries. The evaluation team analyzed the consequences of terminating the use of this modality and found particularly negative effects for good governance outcomes. Methodology: The evaluation uses a qualitative (theory-based) approach consisting of a comparative case study design, which is complemented by a process-tracing approach. For the case studies, the team conducted over 100 semi-structured interviews in Malawi, Uganda, Rwanda and Zambia and used four country-specific, tailor-made budget analysis. In combination with a previous DEval evaluation synthesis on the effects of BS, the team was able to create a before-and-after comparison that yields causal effects. Main Findings: In all four countries domestic accountability and budget transparency declined if other forms of pressure are not replacing BS´s mutual accountability mechanisms. In Malawi a fraud scandal created pressure from the society and from donors so that accountability was improved. In the other countries, these pressure mechanisms were absent so that domestic accountability declined. BS enables donors to actively participate in political processes of the partner country as donors transfer funds into the treasury of the partner country and conduct a high-level political dialogue. The results confirm that the exit from BS created a governance vacuum that, if not compensated through external/internal pressure, leads to a deterioration of good governance. For example, in the case of highly aid dependent Malawi did the possibility of a relaunch of BS provide sufficient incentives to push for governance reforms. Overall the results show that the three good governance areas are negatively affected by the exit from BS. This stands in contrast to positive effects found before the exit. The team concludes that the relationship is causal, because the before-and-after comparison coherently shows that the presence of BS correlates with positive effects and the absence with negative effects. Conclusion: These findings strongly suggest that BS is an effective modality to promote governance and its abolishment is likely to cause governance disruptions. Donors and partner governments should find ways to re-engage in closely coordinated policy-based aid modalities. In addition, a coordinated and carefully managed exit-strategy should be in place before an exit from similar modalities is considered. Particularly a continued framework of mutual accountability and a high-level political dialogue should be aspired to maintain pressure and oversight that is required to achieve good governance.

Keywords: budget support, domestic accountability, public financial management and budget transparency, Sub-Sahara Africa

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Authors: Tatsiana Ihnatovich, Darya Nizheharodava, Mikalai Halabarodzka, Tatsiana Savitskaya, Marina Zafranskaya

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Liver fibrosis is a complex of histological changes resulting from chronic liver disease accompanied by an excessive production and deposition of extracellular matrix components in the hepatic parenchyma. Liver fibrosis is a serious medical and social problem. Hepatic stellate cells (HSCs) make a significant contribution to the extracellular matrix deposition due to liver injury. Mesenchymal stem cells (MSCs) have a pronounced anti-inflammatory, regenerative and immunomodulatory effect; they are able to differentiate into hepatocytes and induce apoptosis of activated HSCs that opens the prospect of their use for preventing the excessive fibro-formation and the development of liver cirrhosis. The aim of the study is to evaluate the effect of MSCs therapy on the expression of fibrogenesis markers genes in liver tissue and HSCs cultures of rats with experimental liver cirrhosis (ELC). Materials and methods: ELC was induced by the common bile duct ligation (CBDL) in female Wistar rats (n = 19) with an average body weight of 250 (220 ÷ 270) g. Animals from the control group (n = 10) were sham-operated. On the 56th day after the CBDL, the rats of the experimental (n = 12) and the control (n = 5) groups received intraportal MSCs in concentration of 1×106 cells/animal (previously obtained from rat’s bone marrow) or saline, respectively. The animals were taken out of the experiment on the 21st day. HSCs were isolated by sequential liver perfusion in situ with following disaggregation, enzymatic treatment and centrifugation of cell suspension on a two-stage density gradient. The expression of collagen type I (Col1a1) and type III (Col3a1), matrix metalloproteinase type 2 (MMP2) and type 9 (MMP9), tissue inhibitor of matrix metalloproteinases type 1 (TIMP1), transforming growth factor β type 1 (TGFβ1) and type 3 (TGFβ3) was determined by real-time polymerase chain reaction. Statistical analysis was performed using Statistica 10.0. Results: In ELC rats compared to sham-operated animals, a significant increase of all studied markers expression was observed. The administration of MSCs led to a significant decrease of all detectable markers in the experimental group compared to rats without cell therapy. In ELC rats, an increased MMP9/TIMP1 ratio after cell therapy was also detected. The infusion of MSCs in the sham-operated animals did not lead to any changes. In the HSCs from ELC animals, the expression of Col1a1 and Col3a1 exceeded the similar parameters of the control group (p <0.05) and statistically decreased after the MSCs administration. The correlation between Col3a1 (Rs = 0.51, p <0.05), TGFβ1 (Rs = 0.6, p <0.01), and TGFβ3 (Rs = 0.75, p <0.001) expression in HSCs cultures and liver tissue has been found. Conclusion: Intraportal administration of MSCs to rats with ELC leads to a decreased Col1a1 and Col3a1, MMP2 and MMP9, TIMP1, TGFβ1 and TGFβ3 expression. The correlation between the expression of Col3a1, TGFβ1 and TGFβ3 in liver tissue and in HSCs cultures indicates the involvement of activated HSCs in the fibrogenesis that allows considering HSCs to be the main cell therapy target in ELC.

Keywords: cell therapy, experimental liver cirrhosis, hepatic stellate cells, mesenchymal stem cells

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Authors: Habiba Nahzat, Karen Crow, Lisa Manuel, Maria Huijbregts

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Background and Rationale: The World Health Organization (WHO) declared COVID-19 a pandemic on March 11, 2020. Shortly after, the Ontario provincial and Toronto municipal governments also released multiple directives that led to the mass closure of businesses both in the public and private sectors. Recent research has identified connections between Intimate Partner Violence (IPV) and COVID-19 related stressors - especially because of lockdown and social isolation measures. Psychological impacts of lengthy seclusion coupled with disconnection from extended family and diminished support services can take a toll on families at risk and may increase mental health issues and the prevalence of IPV. Research Question: Thus, the purpose of the study was to understand the perspective of the Violence Against Women (VAW) program staff on the impact of the COVID-19 pandemic; we especially wanted to understand staff views of restrictions on clients’ counseling experiences and the ability to access services in general. The study also aimed to examine VAW program staff experiences regarding remote work and explore how the pandemic restriction measures affected the ability of their program operations to support their clients and each other. Method: A cross-sectional, descriptive qualitative study was conducted with a purposive sample of 9 VAW program staff – eight VAW counselors and one VAW manager. Prior to data collection, program staff collaborated in the development of the study purpose, interview questions and methodology. Ethics approval was obtained from the sponsoring organization’s Research Ethics Board. In-depth individual interviews were conducted with study participants using a semi-structured interview questionnaire. Brief demographic information was also collected prior to the interview. Descriptive statistics were used to analyze quantitative data and qualitative data was analyzed by thematic content analysis. Results: Findings from this study indicate that the COVID-19 pandemic restrictions had an adverse impact on clients seeking VAW services based on VAW staff perspectives. Program staff reported a perceived increase in abuse among women, especially in emotional and financial abuse and experiences of isolation and trauma. Findings further highlight the challenges women experienced when trying to access services in general as well as counseling and legal services. This was perceived to be more prominent among newcomers and marginalized women. The study also revealed client and staff challenges when participating in virtual counseling, their innovations and clients’ creativity in accessing needed counseling and how staff over time adapted to providing virtual support during the pandemic. Conclusion and Next Steps: This study builds upon existing evidence on the impact of COVID-19 restrictions on VAW and may inform future research to better understand the association between the COVID-19 pandemic restrictions and VAW on a broader scale and to inform and support possible short-term and long-term changes in the client experience and counselling practice.

Keywords: COVID-19, pandemic, virtual, violence against women (VAW)

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Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

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Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

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Authors: Roberta Pecoraro, Elena Maria Scalisi

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Engineered Nanoparticles (ENPs) and Nanomaterials (ENMs) concern an active research area and a sector in full expansion. They have physical-chemical characteristics and small size that improve their performance compared to common materials. Due to the increase in their production and their subsequent release into the environment, new strategies are emerging to assess risk of nanomaterials. NPs can be released into the environment through aquatic systems by human activities and exert toxicity on living organisms. We evaluated the potential toxic effect of cerium oxide (CeO2) nanoparticles because it’s used in different fields due to its peculiar properties. In order to assess nanoparticles toxicity, Fish Embryo Toxicity (FET) test was performed. Powders of CeO2 NPs supplied by the CNR-IMM of Catania are indicated as CeO2 type 1 (as-prepared) and CeO2 type 2 (modified), while CeO2 type 3 (commercial) is supplied by Sigma-Aldrich. Starting from a stock solution (0.001g/10 ml dilution water) of each type of CeO2 NPs, the other concentration solutions were obtained adding 1 ml of the stock solution to 9 ml of dilution water, leading to three different solutions of concentration (10-4, 10-5, 10-6 g/ml). All the solutions have been sonicated to avoid natural tendency of NPs to aggregate and sediment. FET test was performed according to the OECD guidelines for testing chemicals using our internal protocol procedure. A number of eight selected fertilized eggs were placed in each becher filled with 5 ml of each concentration of the three types of CeO2 NPs; control samples were incubated only with dilution water. Replication was performed for each concentration. During the exposure period, we observed four endpoints (embryo coagulation, lack of formation of somites, failure to lift the yolk bag, no heartbeat) by a stereomicroscope every 24 hours. Immunohistochemical analysis on treated larvae was performed to evaluate the expression of metallothioneins (MTs), Heat Shock Proteins 70 (HSP70) and 7-ethoxyresorufin-O-diethylase (EROD). Our results have not shown evident alterations on embryonic development because all embryos completed the development and the hatching of the eggs, started around the 48th hour after exposure, took place within the last observation at 72 hours. A good reactivity, both in the embryos and in the newly hatched larvae, was found. The presence of heartbeat has also been observed in embryos with reduced mobility confirming their viability. A higher expression of EROD biomarker was observed in the larvae exposed to the three types of CeO2, showing a clear difference with the control. A weak positivity was found for MTs biomarker in treated larvae as well as in the control. HSP70 are expressed homogeneously in all the type of nanoparticles tested but not too much greater than control. Our results are in agreement with other studies in the literature, in which the exposure of Danio rerio larvae to other metal oxide nanoparticles does not show adverse effects on survival and hatching time. Further studies are necessary to clarify the role of these NPs and also to solve conflicting opinions.

Keywords: Danio rerio, endpoints, fish embryo toxicity test, metallic nanoparticles

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Authors: Zofia Wlodarczyk

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I study the experiences of domestic violence survivors who flee their countries of origin in times of political conflict using insight and evidence from forty-five biographical interviews with female Chechen refugees and twelve refugee resettlement professionals in Poland. Both refugees and women are often described as having less agency—that is, they lack the power to decide to migrate – refugees less than economic migrants and women less than men. In this paper, I focus on how female refugees who have been victims of domestic violence make decisions about leaving their countries of origin during times of political conflict. I use several existing migration theories to trace how the migration experience of these women is shaped by dynamics at different levels of society: the macro level, the meso level and the micro level. At the macro level of analysis, I find that political conflict can be both a source of and an escape from domestic violence. Ongoing conflict can strengthen the patriarchal cultural norms, increase violence and constrain women’s choices when it comes to marriage. However, political conflict can also destabilize families and make pathways for women to escape. At the meso level I demonstrate that other political migrants and institutions that emerge due to politically triggered migration can guide those fleeing domestic violence. Finally, at the micro level, I show that family dynamics often force domestic abuse survivors to make their decision to escape alone or with the support of only the most trusted female relatives. Taken together, my analyses show that we cannot look solely at one level of society when describing decision-making processes of women fleeing domestic violence. Conflict-related micro, meso and macro forces interact with and influence each other: on the one hand, strengthening an abusive trap, and on the other hand, opening a door to escape. This study builds upon several theoretical and empirical debates. First, it expands theories of migration by incorporating both refugee and gender perspectives. Few social scientists have used the migration theory framework to discuss the unique circumstances of refugee flows. Those who have mainly focus on “political” migrants, a designation that frequently fails to account for gender, does not incorporate individuals fleeing gender-based violence, including domestic-violence victims. The study also enriches migration scholarship, typically focused on the US and Western-European context, with research from Eastern Europe and Caucasus. Moreover, it contributes to the literature on the changing roles of gender in the context of migration. I argue that understanding how gender roles and hierarchies influence the pre-migration stage of female refugees is crucial, as it may have implications for policy-making efforts in host countries that recognize the asylum claims of those fleeing domestic violence. This study also engages in debates about asylum and refugee law. Domestic violence is normatively and often legally considered an individual-level problem whereas political persecution is recognized as a structural or societal level issue. My study challenges these notions by showing how the migration triggered by domestic violence is closely intertwined with politically motivated refuge.

Keywords: AGENCY, DOMESTIC VIOLENCE, FEMALE REFUGEES, POLITICAL REFUGE, SOCIAL NETWORKS

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Authors: A. Knezović

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21st century has transformed the labor market landscape in a way of posing new and different demands on university graduates as well as university lecturers, which means that the knowledge and academic skills students acquire in the course of their studies should be applicable and transferable from the higher education context to their future professional careers. Given the context of the Languages for Specific Purposes (LSP) classroom, the teachers’ objective is not only to teach the language itself, but also to prepare students to use that language as a medium to develop generic skills and competences. These include media and information literacy, critical and creative thinking, problem-solving and analytical skills, effective written and oral communication, as well as collaborative work and social skills, all of which are necessary to make university graduates more competitive in everyday professional environments. On the other hand, due to limitations of time and large numbers of students in classes, the frequently topic-centered syllabus of LSP courses places considerable focus on acquiring the subject matter and specialist vocabulary instead of sufficient development of skills and competences required by students’ prospective employers. This paper intends to explore some of those issues as viewed both by LSP lecturers and by business professionals in their respective surveys. The surveys were conducted among more than 50 LSP lecturers at higher education institutions in Croatia, more than 40 HR professionals and more than 60 university graduates with degrees in economics and/or business working in management positions in mainly large and medium-sized companies in Croatia. Various elements of LSP course content have been taken into consideration in this research, including reading and listening comprehension of specialist texts, acquisition of specialist vocabulary and grammatical structures, as well as presentation and negotiation skills. The ability to hold meetings, conduct business correspondence, write reports, academic texts, case studies and take part in debates were also taken into consideration, as well as informal business communication, business etiquette and core courses delivered in a foreign language. The results of the surveys conducted among LSP lecturers will be analyzed with reference to what extent those elements are included in their courses and how consistently and thoroughly they are evaluated according to their course requirements. Their opinions will be compared to the results of the surveys conducted among professionals from a range of industries in Croatia so as to examine how useful and important they perceive the same elements of the LSP course content in their working environments. Such comparative analysis will thus show to what extent the syllabi of LSP courses meet the demands of the employment market when it comes to the students’ language skills and competences, as well as transferable skills. Finally, the findings will also be compared to the observations based on practical teaching experience and the relevant sources that have been used in this research. In conclusion, the ideas and observations in this paper are merely open-ended questions that do not have conclusive answers, but might prompt LSP lecturers to re-evaluate the content and objectives of their course syllabi.

Keywords: languages for specific purposes (LSP), language skills, topic-centred syllabus, transferable skills

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Authors: Leigha C. Crout

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This paper will investigate the categorical disregard of the People’s Republic of China (PRC) in establishing and maintaining a baseline standard of civil guarantees for economic migrant women and their dependents. In light of the relative forward strides in terms of policy facilitating the ascension of female workers in China, this oft-invisible subgroup of women remains neglected from the modern-day “iron rice bowl” of the self-identified communist state. This study is being undertaken to rectify the absence of data on this subject and provide a baseline for future studies on the matter, as the human rights of migrants has become an established facet of transnational dialogue and debate. The basic methodology of this research will consist of the evaluation of China’s compliance with its own national guidelines, and the eight international human rights law treaties it has ratified. Data will be extracted and cross-checked from a number of relevant sources to monitor the extent of compliance, including but by no means limited to the United Nations Human Rights Council (UNHRC) Universal Periodic Review (UPR) reports and responses, submissions and responses of international human rights treaty bodies, local and international nongovernmental organizations (NGOs) and their annual reports, and articles and commentaries authored by specialists on the modern state and implementation of Chinese law. Together, these data will illuminate the vast network of compliance that has forced many migrant women to work within situations of extreme economic precarity. The structure will proceed as follows: first, an outline of the current status of migrant workers and the enforcement of stipulated protections will be provided; next, the analysis of the oft-debated regulations directing and the outline of mandatory services guaranteed to external and internal migrants; and finally, a conclusion incorporating various recommendations to improve transparency and gradually decrease the amount of migrant work turned forced labor that typifies the economic migrant experience, especially in the case of women. The internal and international migrant workers in China are bound by different and uncomplimentary systems. The first, which governs Chinese citizens moving to different regions or provinces to find more sustainable employment (internal migrants), is called the hukou (or huji) residency system. This law enforces strict regulation of the movement of peoples, while ensuring that residents of urban areas receive preferential benefits to those received by their so-called “agricultural” resident counterparts. Given the overwhelming presence of the Communist Party of China throughout the vast state, the management of internal migrants and the disregard for foreign domestic workers is, at minimum, a surprising oversight. This paper endeavors to provide a much-needed foundation for future commentary and discussion on the treatment of female migrant workers and their families in the People’s Republic of China.

Keywords: female migrant worker’s rights, the People’s Republic of China, forced labor, Hukou residency system

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Authors: Piyaorn Wajanatinapart, Diane R. Lauver

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The number of persons with dementia (PWD) has increased. Informal caregivers are the major providing care. They can have perceived gains and burdens. Caregivers who reported high in perceived gains may report low in burdens and better health. Gaps of caregiving literature were: no report psychometrics in a few studies and unclear definitions of gains; most studies with no theory-guided and conducting in Western countries; not fully described relationships among caregiving variables: motivations, satisfaction with psychological needs, social support, gains, burdens, and physical and psycho-emotional health. Those gaps were filled by assessing psychometric properties of selected measures, providing clearly definitions of gains, using self-determination theory (SDT) to guide the study, and developing the study in Thailand. The study purposes were to evaluate six measures for internal consistency reliability, content validity, and construct validity. This study also examined relationships of caregiving variables: motivations (controlled and autonomous motivations), satisfaction with psychological needs (autonomy, competency, and relatedness), perceived social support, perceived gains, perceived burdens, and physical and psycho-emotional health. This study was a cross-sectional and correlational descriptive design with two convenience samples. Sample 1 was five Thai experts to assess content validity of measures. Sample 2 was 146 Thai caregivers of PWD to assess construct validity, reliability, and relationships among caregiving variables. Experts rated questionnaires and sent them back via e-mail. Caregivers answered questionnaires at clinics of four Thai hospitals. Data analysis was used descriptive statistics and bivariate and multivariate analyses using the composite indicator structural equation model to control measurement errors. For study results, most caregivers were female (82%), middle age (M =51.1, SD =11.9), and daughters (57%). They provided care for 15 hours/day with 4.6 years. The content validity indices of items and scales were .80 or higher for clarity and relevance. Experts suggested item revisions. Cronbach’s alphas were .63 to .93 of ten subscales of four measures and .26 to .57 of three subscales. The gain scale was acceptable for construct validity. With controlling covariates, controlled motivations, the satisfaction with three subscales of psychological needs, and perceived social support had positive relationships with physical and psycho-emotional health. Both satisfaction with autonomy subscale and perceived social support had negative relationship with perceived burdens. The satisfaction with three subscales of psychological needs had positive relationships among them. Physical and psycho-emotional health subscales had positive relationships with each other. Furthermore, perceived burdens had negative relationships with physical and psycho-emotional health. This study was the first use SDT to describe relationships of caregiving variables in Thailand. Caregivers’ characteristics were consistent with literature. Four measures were valid and reliable except two measures. Breadth knowledge about relationships was provided. Interpretation of study results was cautious because of using same sample to evaluate psychometric properties of measures and relationships of caregiving variables. Researchers could use four measures for further caregiving studies. Using a theory would help describe concepts, propositions, and measures used. Researchers may examine the satisfaction with psychological needs as mediators. Future studies to collect data with caregivers in communities are needed.

Keywords: caregivers, caregiving, dementia, measures

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Authors: Bhupendra Kumar Poudel, Sadhana Amatya, Tirtha Maiya Shrestha, Bharatmani Pokhrel, Mohan Prasad Amatya

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Background: H. salicifolia is a dense, branched, multipurpose, deciduous, nitrogen fixing, thorny willow-like small to moderate tree, restricted to the Himalaya. Among the two species of Nepal (Hippophae salicifolia and H. tibetana), it has been traditionally used as food additive, anticancer (bark), and treating toothache, tooth inflammation (anti-inflammatory) and radiation injury; while people of Western Nepal have largely undermined its veiled treasure by using it for fuel, wood and soil stabilization only. Therefore, the main objective of this study was to explore biological properties (analgesic, antidiabetic, cytotoxic and anti-inflammatory properties of this plant. Methodology: The transverse section of leaves and stems were viewed under microscope. Extracts obtained from soxhlation subjected to tests for phytochemical and biological studies. Rats (used to study antidiabetic and anti-inflammatory properties) and mice (used to study analgesic, CNS depressant, muscle relaxant and locomotor properties) were assumed to be normally distributed; then ANOVA and post hoc tukey test was used to find significance. The data obtained were analyzed by SPSS 17 and Excel 2007. Results and Conclusion: Pharmacognostical analysis revealed the presence of long stellate trichomes, double layered vascular bundle 5-6 in number and double layered compact sclerenchyma. The preliminary phytochemical screening of the extracts was found to exhibit the positive reaction tests for glycoside, steroid, tannin, flavonoid, saponin, coumarin and reducing sugar. The brine shrimp lethality bioassay tested in 1000, 100 and 10 ppm revealed cytotoxic activity inherent in methanol, water, chloroform and ethyl acetate extracts with LC50 (μg/ml) values of 61.42, 99.77, 292.72 and 277.84 respectively. The cytotoxic activity may be due to presence of tannins in the constituents. Antimicrobial screening of the extracts by cup diffusion method using Staphylococcus aereus, Escherichia coli and Pseudomonas aeruginosa against standard antibiotics (oxacillin, gentamycin and amikacin respectively) portrayed no activity against the microorganisms tested. The methanol extract of the stems and leaves showed various pharmacological properties: and antidiabetic, anti-inflammatory, analgesic [chemical writhing method], CNS depressant, muscle relaxant and locomotor activities in a dose-dependent fashion, indicating the possibility of the presence of different constituents in the stems and leaves responsible for these biological activities. All the effects when analyzed by post hoc tukey test were found to be significant at 95% confidence level. The antidiabetic activity was presumed to be due to flavonoids present in extract. Therefore, it can be concluded that this plant’s secondary metabolites possessed strong antidiabetic, anti-inflammatory and cytotoxic activity which could be isolated for further investigation.

Keywords: Hippophae salicifolia, constituents, antidiabetic, inflammatory, brine shrimp

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Authors: A. Sottomayor, M. Perez Duque, M. C. Henriques

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Introduction: Migration is not a new phenomenon; nomads often traveled, seeking better living conditions, including food and water. The increase of migrations affects all countries, rising health-related challenges. In Portugal, we have had migrant movements in the last decades, pairing with economic behavior. Irregular immigrants are detained in Santo António detention center from Portuguese Immigration and Borders Service (USHA-SEF) in Porto until court decision for a maximum of 60 days. It is the only long stay officially designated detention center for immigrants in Portugal. Immigrant health is important for public health (PH). It affects and is affected by the community. The XXVII Portuguese Government considered immigrant integration, including access to health, health promotion, protection and reduction of inequities a political priority. Many curative, psychological and legal services are provided for detainees, but until 2015, no structured health promotion or prevention actions were being held at USHA-SEF. That year, Porto Occidental PH Local Unit started to provide vaccination and health literacy on this theme for detainees and SEF workers. Our activities include a vaccine lecture, a medical consultation with vaccine prescription and administration, along with documented proof of vaccination. All vaccines are volunteer and free of charge. This action reduces the risk of importation and transmission of diseases, contributing to world eradication and elimination programs. We aimed to characterize the demography of irregular immigrant detained at UHSA-SEF and describe our activity. Methods: All data was provided by Porto Occidental Public Health Unit. All paper registers of vaccination were uploaded to MicrosoftExcel®. We included all registers and collected demographic variables, nationality, vaccination date, category, and administered vaccines. Descriptive analysis was performed using MicrosoftExcel®. Results: From 2015 to 2018, we delivered care to 256 individuals (179 immigrants; 77 workers). Considering immigrants, 72% were male, and 8 (16%) women were pregnant. 85% were between 20-54 years (ᵡ=30,8y; 2-71y), and 11 didn’t report any age. Migrants came from 48 countries, and India had the highest number (9%). MMR and Tetanus vaccines had > 90% vaccination rate and Poliomyelitis, hepatitis B and flu vaccines had around 85% vaccination rates. We had a consistent number of refusals. Conclusion: Our irregular migrant population comes from many different countries, which increases the risk of disease importation. Pregnant women are present as a particular subset of irregular migrants, and vaccination protects them and the baby. Vaccination of migrant is valuable for them and for the countries in which they pass. It contributes to universal health coverage, for eradication programmes and accomplishment of the Sustainable Development Goals. Peer influence may present as a determinant of refusals so we must consistently educate migrants before vaccination. More studies would be valuable, particularly on the migrant trajectory, duration of stay, destiny after court decision and health impact.

Keywords: migrants, public health, universal health coverage, vaccination

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Authors: Ammal Mokhtar Metwally, Amal Elsaied, Ghada A. Abdel-Latef, Ebtissam M. Salah El-Din, Hanaa R. M. Attia

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The link between various diet therapies and autism is controversial and limited. Nutritional interventions aim to increase antioxidant levels suggesting a positive effect on the improvement of autism severity. In this study, the effectiveness of a 90-day Dates fruits consumption fruits (a non-pharmacological and risk-free option) on alleviating autism severity symptoms in individuals with ASD was investigated. The study examined also whether the baseline or improvements of some of the clinical and laboratory characteristics of the subjects affected their response to dates fruits intake on the severity of ASD symptoms. Methodology: This study involved a randomized controlled, double-blind 3-month dates fruits intake. 131 Egyptian children aged 3-12 years with confirmed ASD were enrolled in the study. cases were randomized in one of the three groups as follows; 1st regimen: Group I on 3 dates’ fruits/day (47 cases), 2nd regimen: Group II on 5 dates’ fruits/day (42 cases), and 3rd regimen: group III; nondates group (42 cases). ASD severity was assessed using both the Diagnostic and statistical manual of mental disorders, 5th ed. (DSM-V) criteria and the Childhood Autism Rating Scale (CARS) analysis. The following measures were assessed before and after the regimens: blood levels of three oxidative markers; Malondialdehyde (MDA), glutathione peroxidase (GPX1), and superoxide dismutase (SOD), nutritional, dietary assessment & anthropometric measurements Results: A significant reduction in the mean score of autism was detected based on CARS scores for those on dates’ regimens compared to those on non-dates (p < 0.01). Participants on 5 dates’ fruits/day for three months showed the highest improvement for autism severity based on both CARS and DSM5 compared to those in 3 dates’ fruits/day and non-dates groups. Responders to dates fruits intake as reflected on the Improvement of autism severity based on CARS diagnosis was detected among 78.7 % and 62.9 % based on CARS and DSM5 diagnosis, respectively. Responders had significant improvement in BMI z score and in the ratio levels of both MDA/SOD and MDA/GPX. Conclusion: The positive results of this study suggest that palm dates fruits could be recommended for children with ASD as adjuvant therapy on a daily regular basis to achieve consistent improvement of autism symptoms Objective: Investigate the effectiveness of a 90-day Dates fruits consumption fruits on alleviating autism severity symptoms in individuals with ASD and explore the clinical and laboratory characteristics of the subjects affected their response to dates fruits intake. Methodology: The study was a randomized controlled, double-blind for 3-month. 131 autistic Egyptian children aged 3-12 years were enrolled in one of the three groups; 1st: on 3 dates’ fruits/day (47 cases), 2nd: Group II on 5 dates’ fruits/day (42 cases), and 3rd: group III; nondates group (42 cases). Conclusion: The positive results of this study suggest that palm dates fruit (a non-pharmacological and risk-free option) could be recommended for children with ASD as adjuvant therapy on a daily regular basis to achieve consistent improvement of autism symptoms.

Keywords: autism spectrum disorders, palm dates fruits, CARS, DSM5, oxidative markers

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Authors: Truong H. Le, Ngoc M. To, Quang N. Tran, Luu T. Cao, Chi V. Le

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Introduction: In Vietnam, the current monitoring and treatment for ordinary diabetic patient mostly based on glucose monitoring with HbA1c test for every three months (recommended goal is HbA1c < 6.5%~7%). For diabetes in pregnant women or Gestational diabetes mellitus (GDM), glycemic control until the time of delivery is extremly important because it could reduce significantly medical implications for both the mother and the child. Besides, GDM requires continuos glucose monitoring at least every two weeks and therefore an alternative marker of glycemia for short-term control is considering a potential tool for the healthcare providers. There are published studies have indicated that the glycosylated serum protein is a better indicator than glycosylated hemoglobin in GDM monitoring. Based on the actual practice in Vietnam, this study was designed to evaluate the role of serum fructosamine as a monitoring tool in GDM treament and its correlations with fasting blood glucose (G0), 2-hour postprandial glucose (G2) and glycosylated hemoglobin (HbA1c). Methods: A cohort study on pregnant women diagnosed with GDM by the 75-gram oralglucose tolerance test was conducted at Endocrinology Department, Cho Ray hospital, Vietnam from June 2014 to March 2015. Cho Ray hospital is the final destination for GDM patient in the southern of Vietnam, the study population has many sources from other pronvinces and therefore researchers belive that this demographic characteristic can help to provide the study result as a reflection for the whole area. In this study, diabetic patients received a continuos glucose monitoring method which consists of bi-weekly on-site visit every 2 weeks with glycosylated serum protein test, fasting blood glucose test and 2-hour postprandial glucose test; HbA1c test for every 3 months; and nutritious consultance for daily diet program. The subjects still received routine treatment at the hospital, with tight follow-up from their healthcare providers. Researchers recorded bi-weekly health conditions, serum fructosamine level and delivery outcome from the pregnant women, using Stata 13 programme for the analysis. Results: A total of 500 pregnant women was enrolled and follow-up in this study. Serum fructosamine level was found to have a light correlation with G0 ( r=0.3458, p < 0.001) and HbA1c ( r=0.3544, p < 0.001), and moderately correlated with G2 ( r=0.4379, p < 0.001). During study timeline, the delivery outcome of 287 women were recorded with the average age of 38.5 ± 1.5 weeks, 9% of them have macrosomia, 2.8% have premature birth before week 35th and 9.8% have premature birth before week 37th; 64.8% of cesarean section and none of them have perinatal or neonatal mortality. The study provides a reference interval of serum fructosamine for GDM patient was 112.9 ± 20.7 μmol/dL. Conclusion: The present results suggests that serum fructosamine is as effective as HbA1c as a reflection of blood glucose control in GDM patient, with a positive result in delivery outcome (0% perinatal or neonatal mortality). The reference value of serum fructosamine measurement provided a potential monitoring utility in GDM treatment for hospitals in Vietnam. Healthcare providers in Cho Ray hospital is considering to conduct more studies to test this reference as a target value in their GDM treatment and monitoring.

Keywords: gestational diabetes mellitus, monitoring tool, serum fructosamine, Vietnam

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Authors: Lacramioara Ochiuz, Manuela Hortolomei, Aurelia Vasile, Iulian Stoleriu, Marcel Popa, Cristian Peptu

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Local antibiotherapy is one of the most effective acne therapies. Erythromycin (ER) is a macrolide antibiotic topically administered for over 30 years in the form of gel, ointment or hydroalcoholic solution for the acne therapy. The use of ER as a base for topical dosage forms raises some technological challenges due to the physicochemical properties of this substance. The main disadvantage of ER is the poor water solubility (2 mg/mL) that limits both formulation using hydrophilic bases and skin permeability. Cyclodextrins (CDs) are biocompatible cyclic oligomers of glucose, with hydrophobic core and hydrophilic exterior. CDs are used to improve the bioavailability of drugs by increasing their solubility and/or their rate of dissolution after including the poorly water soluble substances (such as ER) in the hydrophobic cavity of CDs. Adding CDs leads to the increase of solubility and improved stability of the drug substance, increased permeability of substances of low water solubility, decreased toxicity and even to active dose reduction as a result of increased bioavailability. CDs increase skin tolerability by reducing the irritant effect of certain substances. We have included ER to lactide modified β-cyclodextrin, in order to improve the therapeutic effect of topically administered ER. The aims of the present study were to synthesise and describe a new complex with prolonged release of ER with lactide modified β-cyclodextrin (CD-LA_E), to investigate the CD-LA_E complex by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), to analyse the effect of semisolid base on the in vitro and ex vivo release characteristics of ER in the CD-LA_E complex by assessing the permeability coefficient and the release kinetics by fitting on mathematical models. SEM showed that, by complexation, ER changes its crystal structure and enters the amorphous phase. FTIR analysis has shown that certain specific bands of some groups in the ER structure move during the incapsulation process. The structure of the CD-LA_E complex has a molar ratio of 2.12 to 1 between lactide modified β-cyclodextrin and ER. The three semisolid bases (2% Carbopol, 13% Lutrol 127 and organogel based on Lutrol and isopropyl myristate) show a good capacity for incorporating the CD-LA_E complex, having a content of active ingredient ranging from 98.3% to 101.5% as compared to the declared value of 2% ER. The results of the in vitro dissolution test showed that the ER solubility was significantly increased by CDs incapsulation. The amount of ER released from the CD-LA_E gels was in the range of 76.23% to 89.01%, whereas gels based on ER released a maximum percentage of 26.01% ER. The ex vivo dissolution test confirms the increased ER solubility achieved by complexation, and supports the assumption that the use of this process might increase ER permeability. The highest permeability coefficient was obtained in ER released from gel based on 2% Carbopol: in vitro 33.33 μg/cm2/h, and ex vivo 26.82 μg/cm2/h, respectively. The release kinetics of complexed ER is performed by Fickian diffusion, according to the results obtained by fitting the data in the Korsmeyer-Peppas model.

Keywords: erythromycin, acne, lactide, cyclodextrin

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Authors: Eliana Bergamin

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This philosophical inquiry, influenced by the seminal works of Annemarie Mol and Jeannette Pols, critically examines the transformative impact of artificial intelligence (AI) on emotional caregiving practices within virtual healthcare. Rooted in the traditions of philosophy of care, philosophy of emotions, and applied philosophy, this study seeks to unravel nuanced shifts in the moral and emotional fabric of healthcare mediated by AI-powered technologies. Departing from traditional empirical studies, the approach embraces the foundational principles of care ethics and phenomenology, offering a focused exploration of the ethical and existential dimensions of AI-mediated emotional caregiving. At its core, this research addresses the introduction of AI-powered technologies mediating emotional and care practices in the healthcare sector. By drawing on Mol and Pols' insights, the study offers a focused exploration of the ethical and existential dimensions of AI-mediated emotional caregiving. Anchored in ethnographic research within a pioneering private healthcare company in the Netherlands, this critical philosophical inquiry provides a unique lens into the dynamics of AI-mediated emotional practices. The study employs in-depth, semi-structured interviews with virtual caregivers and care receivers alongside ongoing ethnographic observations spanning approximately two and a half months. Delving into the lived experiences of those at the forefront of this technological evolution, the research aims to unravel subtle shifts in the emotional and moral landscape of healthcare, critically examining the implications of AI in reshaping the philosophy of care and human connection in virtual healthcare. Inspired by Mol and Pols' relational approach, the study prioritizes the lived experiences of individuals within the virtual healthcare landscape, offering a deeper understanding of the intertwining of technology, emotions, and the philosophy of care. In the realm of philosophy of care, the research elucidates how virtual tools, particularly those driven by AI, mediate emotions such as empathy, sympathy, and compassion—the bedrock of caregiving. Focusing on emotional nuances, the study contributes to the broader discourse on the ethics of care in the context of technological mediation. In the philosophy of emotions, the investigation examines how the introduction of AI alters the phenomenology of emotional experiences in caregiving. Exploring the interplay between human emotions and machine-mediated interactions, the nuanced analysis discerns implications for both caregivers and caretakers, contributing to the evolving understanding of emotional practices in a technologically mediated healthcare environment. Within applied philosophy, the study transcends empirical observations, positioning itself as a reflective exploration of the moral implications of AI in healthcare. The findings are intended to inform ethical considerations and policy formulations, bridging the gap between technological advancements and the enduring values of caregiving. In conclusion, this focused philosophical inquiry aims to provide a foundational understanding of the evolving landscape of virtual healthcare, drawing on the works of Mol and Pols to illuminate the essence of human connection, care, and empathy amid technological advancements.

Keywords: applied philosophy, artificial intelligence, healthcare, philosophy of care, philosophy of emotions

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Authors: Natalia C. E. S. Nascimento, Mercia L. Oliveira, Fernando R. A. Lima, Leonardo T. C. do Nascimento, Marina B. Silveira, Brigida G. A. Schirmer, Andrea V. Ferreira, Carlos Malamut, Juliana B. da Silva

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Tissue hypoxia is a common characteristic of solid tumors leading to decreased sensitivity to radiotherapy and chemotherapy. In the clinical context, tumor hypoxia assessment employing the positron emission tomography (PET) tracer ¹⁸F-fluoromisonidazole ([¹⁸F]FMISO) is helpful for physicians for planning and therapy adjusting. The aim of this work was to implement the synthesis of 18F-FMISO in a TRACERlab® MXFDG module and also to establish the quality control procedure. [¹⁸F]FMISO was synthesized at Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN/Brazil) using an automated synthesizer (TRACERlab® MXFDG, GE) adapted for the production of [¹⁸F]FMISO. The FMISO chemical standard was purchased from ABX. 18O- enriched water was acquired from Center of Molecular Research. Reagent kits containing eluent solution, acetonitrile, ethanol, 2.0 M HCl solution, buffer solution, water for injections and [¹⁸F]FMISO precursor (dissolved in 2 ml acetonitrile) were purchased from ABX. The [¹⁸F]FMISO samples were purified by Solid Phase Extraction method. The quality requirements of [¹⁸F]FMISO are established in the European Pharmacopeia. According to that reference, quality control of [¹⁸F]FMISO should include appearance, pH, radionuclidic identity and purity, radiochemical identity and purity, chemical purity, residual solvents, bacterial endotoxins, and sterility. The duration of the synthesis process was 53 min, with radiochemical yield of (37.00 ± 0.01) % and the specific activity was more than 70 GBq/µmol. The syntheses were reproducible and showed satisfactory results. In relation to the quality control analysis, the samples were clear and colorless at pH 6.0. The spectrum emission, measured by using a High-Purity Germanium Detector (HPGe), presented a single peak at 511 keV and the half-life, determined by the decay method in an activimeter, was (111.0 ± 0.5) min, indicating no presence of radioactive contaminants, besides the desirable radionuclide (¹⁸F). The samples showed concentration of tetrabutylammonium (TBA) < 50μg/mL, assessed by visual comparison to TBA standard applied in the same thin layer chromatographic plate. Radiochemical purity was determined by high performance liquid chromatography (HPLC) and the results were 100%. Regarding the residual solvents tested, ethanol and acetonitrile presented concentration lower than 10% and 0.04%, respectively. Healthy female mice were injected via lateral tail vein with [¹⁸F]FMISO, microPET imaging studies (15 min) were performed after 2 h post injection (p.i), and the biodistribution was analyzed in five-time points (30, 60, 90, 120 and 180 min) after injection. Subsequently, organs/tissues were assayed for radioactivity with a gamma counter. All parameters of quality control test were in agreement to quality criteria confirming that [¹⁸F]FMISO was suitable for use in non-clinical and clinical trials, following the legal requirements for the production of new radiopharmaceuticals in Brazil.

Keywords: automatic radiosynthesis, hypoxic tumors, pharmacopeia, positron emitters, quality requirements

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Authors: Sonia Boscenco, Zihan Wang, Euclides José de Mendoça Filho, João Paulo Hoppe, Irina Pokhvisneva, Geoffrey B.C. Hall, Michael J. Meaney, Patricia Pelufo Silveira

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Entropy can be described as a measure of the number of states of a system, and when used in the context of physiological time-based signals, it serves as a measure of complexity. In functional connectivity data, entropy can account for the moment-to-moment variability that is neglected in traditional functional magnetic resonance imaging (fMRI) analyses. While brain fMRI resting state entropy has been associated with some pathological conditions like schizophrenia, no investigations have explored the association between brain entropy measures and individual differences in child behavior in healthy children. We describe a novel exploratory approach to evaluate brain fMRI resting state data in two child cohorts, and MAVAN (N=54, 4.5 years, 48% males) and GUSTO (N = 206, 4.5 years, 48% males) and its associations to child behavior, that can be used in future research in the context of child exposures and long-term health. Following rs-fMRI data pre-processing and Shannon entropy calculation across 32 network regions of interest to acquire 496 unique functional connections, partial correlation coefficient analysis adjusted for sex was performed to identify associations between entropy data and Strengths and Difficulties questionnaire in MAVAN and Child Behavior Checklist domains in GUSTO. Significance was set at p < 0.01, and we found eight significant associations in GUSTO. Negative associations were found between two frontoparietal regions and cerebellar posterior and oppositional defiant problems, (r = -0.212, p = 0.006) and (r = -0.200, p = 0.009). Positive associations were identified between somatic complaints and four default mode connections: salience insula (r = 0.202, p < 0.01), dorsal attention intraparietal sulcus (r = 0.231, p = 0.003), language inferior frontal gyrus (r = 0.207, p = 0.008) and language posterior superior temporal gyrus (r = 0.210, p = 0.008). Positive associations were also found between insula and frontoparietal connection and attention deficit / hyperactivity problems (r = 0.200, p < 0.01), and insula – default mode connection and pervasive developmental problems (r = 0.210, p = 0.007). In MAVAN, ten significant associations were identified. Two positive associations were found = with prosocial scores: the salience prefrontal cortex and dorsal attention connection (r = 0.474, p = 0.005) and the salience supramarginal gyrus and dorsal attention intraparietal sulcus (r = 0.447, p = 0.008). The insula and prefrontal connection were negatively associated with peer problems (r = -0.437, p < 0.01). Conduct problems were negatively associated with six separate connections, the left salience insula and right salience insula (r = -0.449, p = 0.008), left salience insula and right salience supramarginal gyrus (r = -0.512, p = 0.002), the default mode and visual network (r = -0.444, p = 0.009), dorsal attention and language network (r = -0.490, p = 0.003), and default mode and posterior parietal cortex (r = -0.546, p = 0.001). Entropy measures of resting state functional connectivity can be used to identify individual differences in brain function that are correlated with variation in behavioral problems in healthy children. Further studies applying this marker into the context of environmental exposures are warranted.

Keywords: child behaviour, functional connectivity, imaging, Shannon entropy

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Authors: Elina Vroblevska, Toms Ratfelders

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This paper examines the impact of international status-seeking aspirations on great power behavior within the international system. In particular, we seek to test the assumption advanced by the proponents of the Social Identity Theory (SIT) that the inability to achieve social mobilization through joining perceived higher-status social groups (of states) leads great powers to adopt the approach of social competition in which they aim to equal or outdo the dominant group in the area on which its claim to superior status rests. Since the dissolution of the Soviet Union, Russia has struggled to be accepted as a great power by the group of Western states that had created the dominant international system order, while the Soviet states were isolated. While the 1990s and the beginning of the 21st century can be characterized by striving to integrate into the existing order, the second decade has seen a rather sharp turn towards creating a new power center for Russia through the realization of ideas of multipolarity rivalry and uniqueness of the state itself. Increasingly, we have seen the Kremlin striving to collaborate and mobilize groups of states that fall outside of the categories of democracy, multiculturalism, and international order, the way that is perceived by the dominant group, which can be described as the West. Instead, Russia builds its own narrative where it creates an alternative understanding of these values, differentiating from the higher-status social group. The Global South, from a Russian perspective, is the group of states that can still be swayed to create an alternative power center in the international system - one where Russia can assert its status as a great power. This is based on a number of reasons, the most important being that the global north is already highly institutionalized in terms of economy (the EU) and defense (NATO), leaving no room for Russia but to integrate within the existing framework. Second, the difference in values and their interpretation - Russia has been adamant, for the last twenty years, on basing its moral code on traditional values like religion, the heterosexual family model, and moral superiority, which contradict the overall secularism of the Global North. And last, the striking difference in understanding of state governance models - with Russia becoming more autocratic over the course of the last 20 years, it has deliberately created distance between itself and democratic states, entering a “gray area” of alternative understanding of democracy which is more relatable to the global South countries. Using computational text analysis of the excerpts of Vladimir Putin’s speeches delivered from 2000-2022 regarding the areas that fall outside the immediate area of interest of Russia (the Global South), we identify 80 topics that relate to the particular component of the great power status - interest to use force globally. These topics are compared across four temporal frames that capture the periods of more and less permissible Western social boundaries. We find that there exists a negative association between such permissiveness and Putin’s emphasis on the “use of force” topics. This lends further support to the Social Identity Theory and contributes to broadening its applicability to explaining the questions related to great power assertiveness in areas outside of their primary focus regions.

Keywords: Russia, Global South, great power, identity

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Authors: Nishimwe Clemence, Mchunu Gugu, Mukamusoni Dariya

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Background: Community health workers and extension workers can play an important role in supporting families to adopt health practices, encourage delivery in a health care facility, and ensure time referral of mothers and newborns if needed. Saving the lives of neonates should, therefore, be a significant health outcome in any maternal and newborn health program that is being implemented. Furthermore, about half of a million mothers die from pregnancy-related causes. Maternal and newborn deaths related to the period of postnatal care are neglected. Some authors emphasized that in developing countries, newborn mortality rates have been reduced much more slowly because of the lack of many necessary facility-based and outreach service. The aim of this review was to critically analyze the implementation and integration process of the maternal and newborn health care program by maternal community health workers, into the health care system, in Africa. Furthermore, it aims to reduce maternal and newborn mortality. We addressed the following review question: (1) what process is involved in the implementation and integration of the maternal and newborn health care program by maternal community health workers during antenatal, delivery and postnatal care into health system care in Africa? Methods: The database searched was from Health Source: Nursing/Academic Edition through academic search complete via EBSCO Host. An iterative approach was used to go through Google scholarly papers. The reviewers considered adapted Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidance, and the Mixed Methods Appraisal Tool (MMAT) was used. Synthesis method in integrative review following elements of noting patterns and themes, seeing plausibility, clustering, counting, making contrasts and comparisons, discerning commons and unusual patterns, subsuming particulars into general, noting relations between variability, finding intervening factors and building a logical chain of evidence, using data–based convergent synthesis design. Results: From the seventeen of studies included, results focused on three dimensions inspired by the literature on antenatal, delivery, and postnatal interventions. From this, further conceptual framework was elaborated. The conceptual framework process of implementation and integration of maternal and newborn health care program by maternal community health workers was elaborated in order to ensure the sustainability of community based intervention. Conclusions: the review revealed that the implementation and integration of maternal and newborn health care program require planning. We call upon governments, non-government organizations, the global health community, all stakeholders including policy makers, program managers, evaluators, educators, and providers to be involved in implementation and integration of maternal and newborn health program in updated policy and community-based intervention. Furthermore, emphasis should be placed on competence, responsibility, and accountability of maternal community health workers, their training and payment, collaboration with health professionals in health facilities, and reinforcement of outreach service. However, the review was limited in focus to the African context, where the process of maternal and newborn health care program has been poorly implemented.

Keywords: Africa, implementation of integration, maternal, newborn

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Authors: Marina Gold, Yves Jackson, David Parrat

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The high predominance of Latin American migrants in Geneva from countries where Chagas disease is endemic (Bolivia, Brazil, Argentina, Colombia) is increasing the incidence of chronic Chagas-related problems, especially cardiovascular complications. The precarious migratory status of what are mostly undocumented migrants complicates access to health and affects patients’ and doctors’ health perceptions regarding screening, treatment and monitoring of Chagas-related health concerns. This project results from a 3 year collaboration between the Geneva University Hospital and the NGO Mundo Sano to understand the following questions: 1) how do Latin American migrants perceive their health? 2) What do they understand from Chagas disease? 3) Are patients’ and doctors’ health perceptions similar or do they have competing agendas? This paper aims to present the results of a long-term study that interrogates health perceptions among Latin American migrants in Geneva. The first phase consisted in completing surveys at three community screening events (2016, 2017. 2018), and the results of these surveys reveal the subordination of the importance of health to that of having met economic family obligation. That is, health is important only when it becomes an impediment to economic gain. The contradictory result emerged that people are aware of the importance of health prevention in order to ensure long-term health, but they do not always have agency over their life-style habits (healthy food, regular exercise, emotional stability). The second phase of the research collected open-ended interviews with selected participants, in order to explore in more detail how Latin American migrants deal with Chagas in a different socio-political and economic context to that of endemic countries. These interviews (5 in total) reveal mixed methods of managing health: social networks, access to health care transnationally (in Geneva, Spain and back in their home country), and different valuations of health problems in each situation. The third phase consisted in observations of doctor-patient consultations and further extended interviews with patients to determine doctor/patient health perceptions around Chagas disease. This phase is ongoing, but it has yielded preliminarily observations regarding the expectations that patients’ have of doctors, and the understanding of doctors’ to patients’ complex situations. Positive and complementary health perceptions include patients’ feeling that doctors in Geneva are more understanding, more knowledgeable and less racist than those in their home country, who do not provide detailed information about Chagas or its treatment and discriminate against them for being indigenous or from poor rural areas, enabling a better communication between doctors and patients. Possible conflicting health perceptions include patients addressing their health concerns more holistically and encountering the specialist’s limitations to only treating one health concern, given time limitations and lack of competition with their colleagues (the general practitioner that referred the patient, for example). The implications of this study extend the case of Chagas disease in Geneva and is relevant for all chronic concerns and migratory contexts of precarity.

Keywords: chagas disease, health perceptions, Latin American Migrants, non-endemic countries

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Authors: Emma Pope, Demos Parapanos

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Rural tourism has become more obvious and prevalent, with tourists’ increasingly seeking authentic experiences. This movement accelerated post-Covid, putting destinations in danger of reaching levels of saturation called ‘overtourism’. Whereas the phenomenon of overtourism has been frequently discussed in the urban context by academics and practitioners over recent years, it has hardly been referred to in the context of rural tourism, where perhaps it is even more difficult to manage. Rural tourism was historically considered small-scale, marked by its traditional character and by having little impact on nature and rural society. The increasing number of rural areas experiencing overtourism, however, demonstrates the need for new approaches, especially as the impacts and enablers of overtourism are context specific. Cumbria, with approximately 47 million visitors each year, and 23,000 operational enterprises, is one of these rural areas experiencing overtourism in the UK. Using the county of Cumbria as an example, this paper aims to explore better planning and management in rural destinations by clustering the area into rural and ‘urban-rural’ tourism zones. To achieve the aim, this study uses secondary data from a variety of sources to identify variables relating to visitor economy development and demand. These data include census data relating to population and employment, tourism industry-specific data including tourism revenue, visitor activities, and accommodation stock, and big data sources such as Trip Advisor and All Trails. The combination of these data sources provides a breadth of tourism-related variables. The subsequent analysis of this data draws upon various validated models. For example, tourism and hospitality employment density, territorial tourism pressure, and accommodation density. In addition to these statistical calculations, other data are utilized to further understand the context of these zones, for example, tourist services, attractions, and activities. The data was imported into ARCGIS where the density of the different variables is visualized on maps. This study aims to provide an understanding of the geographical context of visitor economy development and tourist behavior in rural areas. The findings contribute to an understanding of the spatial dynamics of tourism within the region of Cumbria through the creation of thematized maps. Different zones of tourism industry clusters are identified, which include elements relating to attractions, enterprises, infrastructure, tourism employment and economic impact. These maps visualize hot and cold spots relating to a variety of tourism contexts. It is believed that the strategy used to provide a visual overview of tourism development and demand in Cumbria could provide a strategic tool for rural areas to better plan marketing opportunities and avoid overtourism. These findings can inform future sustainability policy and destination management strategies within the areas through an understanding of the processes behind the emergence of both hot and cold spots. It may mean that attract and disperse needs to be reviewed in terms of a strategic option. In other words, to use sector or zonal policies for the individual hot or cold areas with transitional zones dependent upon local economic, social and environmental factors.

Keywords: overtourism, rural tourism, sustainable tourism, tourism planning, tourism zones

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Authors: Fstemeh Rais Esmaili, Ehsan Ranjbar

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Pedestrian streets as one type of urban public spaces have an important role in improving the quality of urban life. In Iran, planning and designing of pedestrian streets is in its primary steps. In spite of starting this approach in Iran, and designing several pedestrian streets, there are still not organized studies about quality assessment of pedestrian streets. As a result, the strength and weakness points of the initial experiences have not been utilized. This inattention to quality assessment have caused designing pedestrian streets to be limited to just vehicles traffic control and preliminary actions like paving; so that, special potentials of pedestrian streets for creating social, livable and dynamic public spaces have not been used. This article, as an organized study about quality assessment of pedestrian streets in Iran, tries to reach two main goals: first, introducing a framework for quality assessment of pedestrian streets in Iran, and second, creating a context for improving the quality of pedestrian streets especially for further experiences. The main research methods are description and context analyzing. With respect to comparative analysis of ideas about quality, considering international and local case studies and analyzing existing condition of Saf Pedestrian Street, a particular model for quality assessment has been introduced. In this model, main components and assessment criteria have been presented. On the basis of this model, questionnaire and checklist for assessment have been prepared. The questionnaire and interview have been used to assess qualities which are in direct contact with people and the checklist has been used for analyzing visual qualities by authors through observation. Some results of questionnaire and checklist show that 7 of 11 primary components, diversity, flexibility, cleanness, legibility and imaginably, identity, livability, form and physical setting are rated low and very low in quality degree. Three components, efficiency, comfort and distinctiveness, have medium and low quality degree and one component, access, linkage and permeability has high quality degree. Therefore, based on implemented analyzing process, Saf Pedestrian Street needs to be improved and these quality improvement priorities are determined based on presented criteria. Adaption of final results with existing condition illustrates the shortage of services for satisfying user’s needs, inflexibility and impossibility of using spaces in various times, lack of facilities for different climatic conditions, lack of facilities such as drinking fountain, inappropriate designing of existing urban furniture like garbage cans, and creating pollution and unsuitable view, lack of visual attractions, neglecting disabled persons in designing entrances, shortage of benches and their undesirable designing, lack of vegetation, absence of special characters making it different from other streets, preventing people taking part in the space causing lack of affiliation, lack of appropriate elements for leisure time and lack of exhilaration in the space. On the other hand, these results present high access and permeability, high safety, less sound pollution and more relief, comfortable movement along the way due to suitable pavement and economic efficiency, as the strength points of Saf pedestrian street.

Keywords: pedestrian streets, quality assessment, quality criteria, Saf Pedestrian Street

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Authors: Judith Sue Hwa Joo

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Guanyin (Avalokiteśvara in Sanskrit), the Bodhisattva of Mercy and Compassion, is the most widely worshipped Buddhist Divinity in Chinese societies and is also believed by more than half of Asian populations across various countries. The most overwhelming reason for the popularity of Guanyin in Chinese societies is, according to the Lotus Sutra, that Guanyin would apperceive voices of those suffering from immense afflictions and troubles, and liberate them upon crying for his/her holy name with wholeheartedness. Its pervasive social influence has spanned more than two thousand years and is still deeply affecting the lives of most Chinese people. This study aimed to investigate whether Guanyin Worship has evolved and changed in modern Chinese societies across the Taiwan Strait. Taiwan and China, albeit having the same language and culture, have been territorially divided and governed by two different political regimes for over 70 years. It would be scientifically intriguing to unveil any substantial changes in religious behaviors in the context of Guanyin Worship. A comprehensive anonymous questionnaire survey in Chinese communities was conducted from October 2017 to May 2019 across various countries, mostly in China, Taiwan, and Hong Kong areas. Since the religious survey is officially prohibited in China, the study was difficult and could only be exercised by means of snowball sampling. Demographic data (age, sex, education, religious belief) were registered and Guanyin’s salvation functions under various confronting situations were investigated. Psychological dimensions of religious belief in Guanyin were probed in terms of the worship experience, the willingness of veneration, and egoistic or altruistic ideations. A literature review on documented functional attributes was carried out in parallel for comparison analyses with traditional roles. Effective 1123 out of 1139 samples were obtained. Statistical analysis revealed that Guanyin Worship is still commonly practiced and deeply rooted in the hearts of all Chinese people regardless of gender, age, education, and residential area, even though they may not enshrine Guanyin at home nowadays. The conventional roles of Guanyin Bodhisattva are still valid and best satisfy the real interests of lifestyles in modern times. When comparing the traditional Buddhist Sutra and the documented literature, the divine power of modern Guanyin has notably empowered to recover, protect and transform fetal and infant spirits due to the sexual liberation, increased abortion rate, gender awakening and enhanced female autonomy in the reproductive decision. However, the One-Child policy may have critically impacted the trajectory of Guanyin Worship so that people in China prevail over those in Taiwan praying for aborted lives or premature deaths. Furthermore, particularly in Hong Kong and Macao, Guanyin not only serves as the sea guardian for the fishermen but also additional services a new function as the God of Wealth. The divine powers and salvation functions of Guanyin are indeed evolving and expanding to comply with the modern psychosocial, cultural and societal needs. This study sheds light on the modernization process of the two-thousand-year-old Guanyin Worship of contemporary Chinese societies.

Keywords: Buddhism, Guanyin, religious behavior, salvation function

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Authors: Vasundhara Arora, Anupam Jhobta, Suresh Thakur, Sanjiv Sharma

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Aims and Objectives: Intracranial tuberculosis (TB) is one of the most devastating manifestations of TB and a challenging public health issue of considerable importance and magnitude world over. This study elaborates on the imaging spectrum of neurotuberculosis on magnetic resonance imaging (MRI) in 29 clinically suspected cases from a tertiary care hospital. Materials and Methods: The prospective hospital based evaluation of MR imaging features of neuro-tuberculosis in 29 clinically suspected cases was carried out in Department of Radio-diagnosis, Indira Gandhi Medical Hospital from July 2017 to August 2018. MR Images were obtained on a 1.5 T Magnetom Avanto machine and were analyzed to identify any abnormal meningeal enhancement or parenchymal lesions. Microbiological and Biochemical CSF analysis was performed in radio-logically suspected cases and the results were compared with the imaging data. Clinical follow up of the patients started on anti-tuberculous treatment was done to evaluate the response to treatment and clinical outcome. Results: Age range of patients in the study was between 1 year to 73 years. The mean age of presentation was 11.5 years. No significant difference in the distribution of cerebral tuberculosis was noted among the two genders. Imaging findings of neuro-tuberculosis obtained were varied and non specific ranging from lepto-meningeal enhancement, cerebritis to space occupying lesions such as tuberculomas and tubercular abscesses. Complications presenting as hydrocephalus (n= 7) and infarcts (n=9) was noted in few of these patients. 29 patients showed radiological suspicion of CNS tuberculosis with meningitis alone observed in 11 cases, tuberculomas alone were observed in 4 cases, meningitis with parenchymal tuberculomas in 11 cases. Tubercular abscess and cerebritis were observed in one case each. Tuberculous arachnoiditis was noted in one patient. Gene expert positivity was obtained in 11 out of 29 radiologically suspected patients; none of the patients showed culture positivity. Meningeal form of the disease alone showed higher positivity rate of gene Xpert (n=5) followed by combination of meningeal and parenchymal forms of disease (n=4). The parenchymal manifestation of disease alone showed least positivity rates (n= 3) with gene xpert testing. All 29 patients were started on anti tubercular treatment based on radiological suspicion of the disease with clinical improvement observed in 27 treated patients. Conclusions: In our study, higher incidence of neuro- tuberculosis was noted in paediatric population with predominance of the meningeal form of the disease. Gene Xpert positivity obtained was low due to paucibacillary nature of cerebrospinal fluid (CSF) with even lower positivity of CSF samples in parenchymal form of the manifestation. MRI showed high accuracy in detecting CNS lesions in neuro-tuberculosis. Hence, it can be concluded that MRI plays a crucial role in the diagnosis because of its inherent sensitivity and specificity and is an indispensible imaging modality. It caters to the need of early diagnosis owing to poor sensitivity of microbiological tests more so in the parenchymal manifestation of the disease.

Keywords: neurotuberculosis, tubercular abscess, tuberculoma, tuberculous meningitis

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Authors: Masood Otarod, Ronald M. Supkowski

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This abstract discusses a method that reduces the general dispersion model in cylindrical coordinates to a second order linear ordinary differential equation with constant coefficients so that it can be utilized to conduct kinetic studies in packed bed tubular catalytic reactors at a broad range of Reynolds numbers. The model was tested by 13CO isotope transient tracing of the CO adsorption of Boudouard reaction in a differential reactor at an average Reynolds number of 0.2 over Pd-Al2O3 catalyst. Detailed experimental results have provided evidence for the validity of the theoretical framing of the model and the estimated parameters are consistent with the literature. The solution of the general dispersion model requires the knowledge of the radial distribution of axial velocity. This is not always known. Hence, up until now, the implementation of the dispersion model has been largely restricted to the plug-flow regime. But, ideal plug-flow is impossible to achieve and flow regimes approximating plug-flow leave much room for debate as to the validity of the results. The reduction of the general dispersion model transpires as a result of the application of a factorization theorem. Factorization theorem is derived from the observation that a cross section of a catalytic bed consists of a solid phase across which the reaction takes place and a void or porous phase across which no significant measure of reaction occurs. The disparity in flow and the heterogeneity of the catalytic bed cause the concentration of reacting compounds to fluctuate radially. These variabilities signify the existence of radial positions at which the radial gradient of concentration is zero. Succinctly, factorization theorem states that a concentration function of axial and radial coordinates in a catalytic bed is factorable as the product of the mean radial cup-mixing function and a contingent dimensionless function. The concentration of adsorbed compounds are also factorable since they are piecewise continuous functions and suffer the same variability but in the reverse order of the concentration of mobile phase compounds. Factorability is a property of packed beds which transforms the general dispersion model to an equation in terms of the measurable mean radial cup-mixing concentration of the mobile phase compounds and mean cross-sectional concentration of adsorbed species. The reduced model does not require the knowledge of the radial distribution of the axial velocity. Instead, it is characterized by new transport parameters so denoted by Ωc, Ωa, Ωc, and which are respectively denominated convection coefficient cofactor, axial dispersion coefficient cofactor, and radial dispersion coefficient cofactor. These cofactors adjust the dispersion equation as compensation for the unavailability of the radial distribution of the axial velocity. Together with the rest of the kinetic parameters they can be determined from experimental data via an optimization procedure. Our data showed that the estimated parameters Ωc, Ωa Ωr, are monotonically correlated with the Reynolds number. This is expected to be the case based on the theoretical construct of the model. Computer generated simulations of methanation reaction on nickel provide additional support for the utility of the newly conceptualized dispersion model.

Keywords: factorization, general dispersion model, isotope transient kinetic, partial differential equations

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Authors: Priyanka Jain, Ashish K. Sharma, Esha Shukla, K. J. Mukherjee

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We propose a paradigm shift in our approach to design improved platforms for recombinant protein production, by addressing system level issues rather than the individual steps associated with recombinant protein synthesis like transcription, translation, etc. We demonstrate that by controlling and modulating the cellular stress response (CSR), which is responsible for feedback control of protein synthesis, we can generate hyper-producing strains. We did transcriptomic profiling of post-induction cultures, expressing different types of protein, to analyze the nature of this cellular stress response. We found significant down-regulation of substrate utilization, translation, and energy metabolism genes due to generation CSR inside the host cell. However, transcription profiling has also shown that many genes are up-regulated post induction and their role in modulating the CSR is unclear. We hypothesized that these up-regulated genes trigger signaling pathways, generating the CSR and concomitantly reduce the recombinant protein yield. To test this hypothesis, we knocked out the up-regulated genes, which did not have any downstream regulatees, and analyzed their impact on cellular health and recombinant protein expression. Two model proteins i.e., GFP and L-Asparaginase were chosen for this analysis. We observed a significant improvement in expression levels, with some knock-outs showing more than 7-fold higher expression compared to control. The 10 best single knock-outs were chosen to make 45 combinations of all possible double knock-outs. A further increase in expression was observed in some of these double knock- outs with GFP levels being highest in a double knock-out ΔyhbC + ΔelaA. However, for L-Asparaginase which is a secretory protein, the best results were obtained using a combination of ΔelaA+ΔcysW knock-outs. We then tested all the knock outs for their ability to enhance the expression of a 'difficult-to-express' protein. The Rubella virus E1 protein was chosen and tagged with sfGFP at the C-terminal using a linker peptide for easy online monitoring of expression of this fusion protein. Interestingly, the highest increase in Rubella-sGFP levels was obtained in the same double knock-out ΔelaA + ΔcysW (5.6 fold increase in expression yield compared to the control) which gave the highest expression for L-Asparaginase. However, for sfGFP alone, the ΔyhbC+ΔmarR knock-out gave the highest level of expression. These results indicate that there is a fair degree of commonality in the nature of the CSR generated by the induction of different proteins. Transcriptomic profiling of the double knock out showed that many genes associated with the translational machinery and energy biosynthesis did not get down-regulated post induction, unlike the control where these genes were significantly down-regulated. This confirmed our hypothesis of these genes playing an important role in the generation of the CSR and allowed us to design a strategy for making better expression hosts by simply knocking out key genes. This strategy is radically superior to the previous approach of individually up-regulating critical genes since it blocks the mounting of the CSR thus preventing the down-regulation of a very large number of genes responsible for sustaining the flux through the recombinant protein production pathway.

Keywords: cellular stress response, GFP, knock-outs, up-regulated genes

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Authors: Oyedele Ogundana, Amon Simba, Kostas Galanakis, Lynn Oxborrow

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The debate about factors influencing the business growth of women-owned businesses has been a topical issue in business management. Currently, scholars have identified the issues of access to money, market, and management as canvasing factors influencing the business growth of women-owned businesses. However, the influence of motherhood (household/family context) on business growth is inconclusive in the literature; despite that women are more family-oriented than their male counterparts. Therefore, this research study considers the influence of motherhood factor (household/family context) on the business growth of women-owned sewing businesses (WOSBs) in Lagos, Nigeria. The sewing business sector is chosen as the fashion industry (which includes sewing businesses) currently accounts for the second largest number of jobs in Sub-Saharan Africa, following agriculture. Thus, sewing businesses provide a rich ground for contributing to existing scholarly work. Research questions; (1) In what way does the motherhood factor influence the business growth of WOSBs in Lagos? (2) To what extent does the motherhood factor influence the business growth of WOSBs in Lagos? For the method design, a pragmatic approach, a mixed-methods technique and an abductive form of reasoning are adopted. The method design is chosen because it fits, better than other research perspectives, with the research questions posed in this study. For instance, using a positivist approach will not sufficiently answer research question 1, neither will an interpretive approach sufficiently answer research question 2. Therefore, the research method design is divided into 2 phases, and the results from one phase are used to inform the development of the subsequent phases (only phase 1 has been completed at the moment). The first phase uses qualitative data and analytical method to answer research question 1. While the second phase of the research uses quantitative data and analytical method to answer research question 2. For the qualitative phase, 5 WOSBs were purposefully selected and interviewed. The sampling technique is selected as it was not the intention of the researcher to make any statistical inferences, at this phase, rather the purpose was just exploratory. Therefore, the 5 sampled women comprised of 2 unmarried women, 1 married woman with no child, and 2 married women with children. A 40-60 minutes interview was conducted per participants. The interviews were audio-recorded and transcribed. Thereafter, the data were analysed using thematic analysis in order to unearth patterns and relationships. Findings for the first phase of this research reveals that motherhood (household/family context) directly influences (positively/negatively) the performance of WOSBs in Lagos. Apart from a direct influence on WOSBs, motherhood also moderates (positively/negatively) other factors–e.g., access to money, management/human resources and market/opportunities– influencing WOSBs in Lagos. To further strengthen this conclusion, a word frequency query result shows that ‘family,’ ‘husband’ and ‘children’ are among the 10 words used frequently in all the interview transcripts. This first phase contributes to existing studies by showing the various forms by which motherhood influences WOSBs. The second phase (which data are yet to be collected) would reveal the extent to which motherhood influence the business growth of WOSBs in Lagos.

Keywords: women-owned sewing businesses, business growth, motherhood, Lagos

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Authors: Tatjana Kadifkova Panovska, Svetlana Kulevanova, Blagica Jovanova

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Biological systems possess the ability to neutralize the excess of reactive oxygen species (ROS) and to protect cells from destructive alterations. However, many pathological conditions (cardiovascular diseases, autoimmune disorders, cancer) are associated with inflammatory processes that generate an excessive amount of reactive oxygen species (ROS) that shift the balance between endogenous antioxidant systems and free oxygen radicals in favor of the latter, leading to oxidative stress. Therefore, an additional source of natural compounds with antioxidant properties that will reduce the amount of ROS in cells is much needed despite their broad utilization; many plant species remain largely unexplored. Therefore, the purpose of the present study is to investigate the antioxidant activity of twenty-five selected medicinal and aromatic plant species. The antioxidant activity of the ethanol extracts was evaluated with in vitro assays: 2,2’-diphenyl-1-pycryl-hydrazyl (DPPH), ferric reducing antioxidant power (FRAP), non-site-specific- (NSSOH) and site-specific hydroxyl radical-2-deoxy-D-ribose degradation (SSOH) assays. The Folin-Ciocalteu method and AlCl3 method were performed to determine total phenolic content (TPC) and total flavonoid content (TFC). All examined plant extracts manifested antioxidant activity to a different extent. Cinnamomum verum J.Presl bark and Ocimum basilicum L. Herba demonstrated strong radical scavenging activity and reducing power with the DPPH and FRAP assay, respectively. Additionally, significant hydroxyl scavenging potential and metal chelating properties were observed using the NSSOH and SSOH assays. Furthermore, significant variations were determined in the total polyphenolic content (TPC) and total flavonoid content (TFC), with Cinnamomum verum and Ocimum basilicum showing the highest amount of total polyphenols. The considerably strong radical scavenging activity, hydroxyl scavenging potential and reducing power for the species mentioned above suggest of a presence of highly bioactive phytochemical compounds, predominantly polyphenols. Since flavonoids are the most abundant group of polyphenols that possess a large number of available reactive OH groups in their structure, it is considered that they are the main contributors to the radical scavenging properties of the examined plant extracts. This observation is supported by the positive correlation between the radical scavenging activity and the total polyphenolic and flavonoid content obtained in the current research. The observations from the current research nominate Cinnamomum verum bark and Ocimum basilicum herba as potential sources of bioactive compounds that could be utilized as antioxidative additives in the food and pharmaceutical industries. Moreover, the present study will help the researchers as basic data for future research in exploiting the hidden potential of these important plants that have not been explored so far.

Keywords: ethanol extracts, radical scavenging activity, reducing power, total polyphenols.

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Authors: Rauan Sakenov, Peter Bukovics, Peter Gaszler, Veronika Tokacs-Kollar, Beata Bugyi

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FH2 (formin homology-2) domains of several proteins, collectively known as formins, including DAAM, DAAM1 and mDia1, promote G-actin nucleation and elongation. FH2 domains of these formins exist as oligomers. Chain dimerization by ring structure formation serves as a structural basis for actin polymerization function of FH2 domain. Proper single chain configuration and specific interactions between its various regions are necessary for individual chains to form a dimer functional in G-actin nucleation and elongation. FH1 and WH2 domain-containing formins were shown to behave as intrinsically disordered proteins. Thus, the aim of this research was to study structural dynamics of FH2 domain of DAAM. To investigate structural features of FH2 domain of DAAM, molecular dynamics simulation of chain A of FH2 domain of DAAM solvated in water box in 50 mM NaCl was conducted at temperatures from 293.15 to 353.15K, with VMD 1.9.2, NAMD 2.14 and Amber Tools 21 using 2z6e and 1v9d PDB structures of DAAM was obtained on I-TASSER webserver. Calcium and ATP bound G-actin 3hbt PDB structure was used as a reference protein with well-described structural dynamics of denaturation. Topology and parameter information of CHARMM 2012 additive all-atom force fields for proteins, carbohydrate derivatives, water and ions were used in NAMD 2.14 and ff19SB force field for proteins in Amber Tools 21. The systems were energy minimized for the first 1000 steps, equilibrated and produced in NPT ensemble for 1ns using stochastic Langevin dynamics and the particle mesh Ewald method. Our root-mean square deviation (RMSD) analysis of molecular dynamics of chain A of FH2 domains of DAAM revealed similar insignificant changes of total molecular average RMSD values of FH2 domain of these formins at temperatures from 293.15 to 353.15K. In contrast, total molecular average RMSD values of G-actin showed considerable increase at 328K, which corresponds to the denaturation of G-actin molecule at this temperature and its transition from native, ordered, to denatured, disordered, state which is well-described in the literature. RMSD values of lasso and tail regions of chain A of FH2 domain of DAAM exhibited higher than total molecular average RMSD at temperatures from 293.15 to 353.15K. These regions are functional in intra- and interchain interactions and contain highly conserved tryptophan residues of lasso region, highly conserved GNYMN sequence of post region and amino acids of the shell of hydrophobic pocket of the salt bridge between Arg171 and Asp321, which are important for structural stability and ordered state of FH2 domain of DAAM and its functions in FH2 domain dimerization. In conclusion, higher than total molecular average RMSD values of lasso and post regions of chain A of FH2 domain of DAAM may explain disordered state of FH2 domain of DAAM at temperatures from 293.15 to 353.15K. Finally, absence of marked transition, in terms of significant changes in average molecular RMSD values between native and denatured states of FH2 domain of DAAM at temperatures from 293.15 to 353.15K, can make it possible to attribute these formins to the group of intrinsically disordered proteins rather than to the group of intrinsically ordered proteins such as G-actin.

Keywords: FH2 domain, DAAM, formins, molecular modelling, computational biophysics

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Authors: Saule Balmagambetova, Zhenisgul Tlegenova, Saule Madinova

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Cardiotoxicity associated with anticancer treatment, now defined as cancer therapy-related cardiac dysfunction (CTRCD), accompanies cancer patients and negatively impacts their survivorship. Currently, a cardio-oncological service is being created in Kazakhstan based on the provisions of the European Society of Cardio-oncology (ESC) Guidelines. In the frames of a pilot project, a cohort study on CTRCD conditions was initiated at the Aktobe Cancer center. One hundred twenty-eight newly diagnosed breast cancer patients started on doxorubicin and/or trastuzumab were recruited. Echocardiography with global longitudinal strain (GLS) assessment, biomarkers panel (cardiac troponin (cTnI), brain natriuretic peptide (BNP), myeloperoxidase (MPO), galectin-3 (Gal-3), D-dimers, C-reactive protein (CRP)), and other tests were performed at baseline and every three months. Patients were stratified by the cardiovascular risks according to the ESC recommendations and allocated into the risk groups during the pre-treatment visit. Of them, 10 (7.8%) patients were assigned to the high-risk group, 48 (37.5%) to the medium-risk group, and 70 (54.7%) to the low-risk group, respectively. High-risk patients have been receiving their cardioprotective treatment from the outset. Patients were also divided by treatment - in the anthracycline-based 83 (64.8%), in trastuzumab- only 13 (10.2%), and in the mixed anthracycline/trastuzumab group 32 individuals (25%), respectively. Mild symptomatic CTRCD was revealed and treated in 2 (1.6%) participants, and a mild asymptomatic variant in 26 (20.5%). Mild asymptomatic conditions are defined as left ventricular ejection fraction (LVEF) ≥50% and further relative reduction in GLS by >15% from baseline and/or a further rise in cardiac biomarkers. The listed biomarkers were assessed longitudinally in repeated-measures linear regression models during 12 months of observation. The associations between changes in biomarkers and CTRCD and between changes in biomarkers and LVEF were evaluated. Analysis by risk groups revealed statistically significant differences in baseline LVEF scores (p 0.001), BNP (p 0.0075), and Gal-3 (p 0.0073). Treatment groups found no statistically significant differences at baseline. After 12 months of follow-up, only LVEF values showed a statistically significant difference by risk groups (p 0.0011). When assessing the temporal changes in the studied parameters for all treatment groups, there were statistically significant changes from visit to visit for LVEF (p 0.003); GLS (p 0.0001); BNP (p<0.00001); MPO (p<0.0001); and Gal-3 (p<0.0001). No moderate or strong correlations were found between the biomarkers values and LVEF, between biomarkers and GLS. Between the biomarkers themselves, a moderate, close to strong correlation was established between cTnI and D-dimer (r 0.65, p<0.05). The dose-dependent effect of anthracyclines has been confirmed: the summary dose has a moderate negative impact on GLS values: -r 0.31 for all treatment groups (p<0.05). The present study found myeloperoxidase as a promising biomarker of cardiac dysfunction in the mixed anthracycline/trastuzumab treatment group. The hazard of CTRCD increased by 24% (HR 1.21; 95% CI 1.01;1.73) per doubling in baseline MPO value (p 0.041). Increases in BNP were also associated with CTRCD (HR per doubling, 1.22; 95% CI 1.12;1.69). No cases of chemotherapy discontinuation due to cardiotoxic complications have been recorded. Further observations are needed to gain insight into the ability of biomarkers to predict CTRCD onset.

Keywords: breast cancer, chemotherapy, cardiotoxicity, Kazakhstan

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