Search results for: healthy%20body

Authors: Natida Thongsima, Patompong Satapornpong

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Introduction: Lamotrigine is widely used in the treatment of epilepsy and bipolar disorder. However, lamotrigine leads to adverse drug reactions (ADRs) consist of severe cutaneous adverse reactions (SCARs) include Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug rash with eosinophilia and systemic symptoms (DRESS). Moreover, lamotrigine-induced SCARs are usually manifested between 2 and 8 weeks after treatment initiation. According to a previous study, the association between HLA-B*15:02 and lamotrigine-induced cutaneous adverse drug reactions in the Thai population (odds ratio 4.89; 95% CI 1.28–18.66; p-value = 0.014) was found. Therefore, the distribution of pharmacogenetics markers a major role in predicting the culprit drugs for SCARs in many populations. Objective: In this study, we want to investigate the prevalence of HLA-B allele, which correlates with lamotrigine-induced SCARs in the healthy Thai population. Materials and Methods: We enrolled 350 healthy Thai individuals and were approved by the ethics committee of Rangsit University. HLA-B alleles were genotyped by the Lifecodes HLA SSO typing kits (Immucor, West Avenue, Stamford, USA). Results: The results presented HLA-B allele frequency in healthy Thai population were 14.71% (HLA-B*46:01), 8.57% (HLA-B*15:02), 6.71% (HLA-B*40:01), 5.86% (HLA-B*13:01), 5.71% (HLA-B*58:01), 5.14% (HLA-B*38:02), 4.86% (HLA-B*18:01), 4.86% (HLA-B*51:01), 3.86% (HLA-B*44:03) and 2.71% (HLA-B*07:05). Especially, HLA-B*15:02 allele was the high frequency in the Thais (8.57%), Han Chinese (7.30%), Vietnamese (13.50%), Malaysian (6.06%) and Indonesian (11.60%). Nevertheless, this allele was much lower in other populations, namely, Africans, Caucasians, and Japanese. Conclusions: Although the sample size of the healthy Thai population in this research was limited, there were found the frequency of the HLA-B*15:02 allele could predispose them toward to lamotrigine-induced SCARs in Thailand.

Keywords: lamotrigine, cutaneous adverse drug reactions, HLA-B, Thai population

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Authors: Ambrish Tiwari, Sudhasini Panda, Archana Singh, Kalpana Luthra, S. K. Sharma

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Introduction: On the basis of available literature we know that various host factors play a role in outcome of Tuberculosis (TB) infection by modulating innate immunity. One such factor is Inducible Nitric Oxide Synthase enzyme (iNOS) which help in the production of Nitric Oxide (NO), an antimicrobial agent. Expression of iNOS is in control of various host factors in which Vitamin D along with its nuclear receptor Vitamin D receptor (VDR) is one of them. Vitamin D along with its receptor also produces cathelicidin (antimicrobicidal agent). With this background, we attempted to investigate the levels of Vitamin D and NO along with their associated molecules in tuberculosis patients and household contacts as compared to healthy controls and assess the implication of these findings in susceptibility to tuberculosis (TB). Study subjects and methods: 100 active TB patients, 75 household contacts, and 70 healthy controls were taken. VDR and iNOS mRNA levels were studied using real-time PCR. Serum VDR, cathelicidin, iNOS levels were measured using ELISA. Serum Vitamin D levels were measured in serum samples using chemiluminescence based immunoassay. NO was measured using colorimetry based kit. Results: VDR and iNOS mRNA levels were found to be lower in active TB group compared to household contacts and healthy controls (P=0.0001 and 0.005 respectively). The serum levels of Vitamin D were also found to be lower in active TB group as compared to healthy controls (P =0.001). Levels of cathelicidin and NO was higher in patient group as compared to other groups (p=0.01 and 0.5 respectively). However, the expression of VDR and iNOS and levels of vitamin D was significantly (P < 0.05) higher in household contacts compared to both active TB and healthy control groups. Inference: Higher levels of Vitamin D along with VDR and iNOS expression in household contacts as compared to patients suggest that vitamin D might have a protective role against TB which prevents activation of the disease. From our data, we can conclude that decreased vitamin D levels could be implicated in disease progression and we can use cathelicidin and NO as a biomarker for early diagnosis of pulmonary tuberculosis.

Keywords: vitamin D, VDR, iNOS, tuberculosis

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Authors: Man-Yun Liu, Emily Chia-Yu Su

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Alzheimer's disease (AD) is the public health crisis of the 21st century. AD is a degenerative brain disease and the most common cause of dementia, a costly disease on the healthcare system. Unfortunately, the cause of AD is poorly understood, furthermore; the treatments of AD so far can only alleviate symptoms rather cure or stop the progress of the disease. Currently, there are several ways to diagnose AD; medical imaging can be used to distinguish between AD, other dementias, and early onset AD, and cerebrospinal fluid (CSF). Compared with other diagnostic tools, blood (plasma) test has advantages as an approach to population-based disease screening because it is simpler, less invasive also cost effective. In our study, we used blood biomarkers dataset of The Alzheimer’s disease Neuroimaging Initiative (ADNI) which was funded by National Institutes of Health (NIH) to do data analysis and develop a prediction model. We used independent analysis of datasets to identify plasma protein biomarkers predicting early onset AD. Firstly, to compare the basic demographic statistics between the cohorts, we used SAS Enterprise Guide to do data preprocessing and statistical analysis. Secondly, we used logistic regression, neural network, decision tree to validate biomarkers by SAS Enterprise Miner. This study generated data from ADNI, contained 146 blood biomarkers from 566 participants. Participants include cognitive normal (healthy), mild cognitive impairment (MCI), and patient suffered Alzheimer’s disease (AD). Participants’ samples were separated into two groups, healthy and MCI, healthy and AD, respectively. We used the two groups to compare important biomarkers of AD and MCI. In preprocessing, we used a t-test to filter 41/47 features between the two groups (healthy and AD, healthy and MCI) before using machine learning algorithms. Then we have built model with 4 machine learning methods, the best AUC of two groups separately are 0.991/0.709. We want to stress the importance that the simple, less invasive, common blood (plasma) test may also early diagnose AD. As our opinion, the result will provide evidence that blood-based biomarkers might be an alternative diagnostics tool before further examination with CSF and medical imaging. A comprehensive study on the differences in blood-based biomarkers between AD patients and healthy subjects is warranted. Early detection of AD progression will allow physicians the opportunity for early intervention and treatment.

Keywords: Alzheimer's disease, blood-based biomarkers, diagnostics, early detection, machine learning

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Authors: Sitaram Dahal

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Among many strategic and practical needs in overcoming the threats and challenges being experienced in the global environment, constitutional provision for Rights to live in clean and healthy environment is one and so is the school curriculum incorporating information on such rights. Government of Nepal has also introduced information on rights to live in clean and healthy environment, as provisioned in its interim constitution of 2007, in the secondary level curriculum of formal education. As the predetermined specific objective of such curriculum is to prepare students who are conscious of citizens’ rights and responsibilities and are able to adopt functions, duties and rights of the rights holders and duty bearers; the study was designed to assess the effectiveness of such curriculum. The study was conducted in one private school and a community school to assess the effectiveness of such curriculum. The study shows that such curriculum has been able to make students responsible duty bearers as they were aware of their habits towards environment. Whereas only very few students are aware enough as being rights holders. Students of community schools were aware rights holders as they complain if they are not satisfied with the environment of the school itself. But private school is far behind in this case. It can be said that only curriculum with very few portion of information on such rights might not be capable enough to meet its objective.

Keywords: curriculum, environmental rights, constitution, effectiveness

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Authors: Rona Hanani Simamora, Bahagia Loebis, M. Surya Husada

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Background: The exact cause of schizophrenia is not known, although several etiology theories have been proposed for the disease, including immune dysfunction or autoimmune mechanisms. Cytokines including Tnf-α has an important role in the pathophysiology of schizophrenia and the effects of pharmacological treatment with antipsychotics. Nicotine is widespread effects on the brain, immune system and cytokine levels. Smoking among schizophrenic patients could play a role in the altered cytokine profiles of schizophrenia such as Tnf-α. Aims: To determine differences of serum Tnf-α levels between schizophrenic patients with smoking in male and healthy control. Methods: This study was a comparative analytic study, divided into two groups: 1) group of male schizophrenic patients with smoking (n1=30) with inclusion criteria were patients who have been diagnosed schizophrenic based PPDGJ-III, 20-60 years old, male, smoking, chronic schizophrenic patients in the stable phase and willing to participate this study. Exclusion criteria were having other mental disorders and comorbidity with other medical illnesses. 2) healthy control group (n2=30) with inclusion criteria were 20-60 years old, male, smoking, willing to participate this study. Exclusion criteria were having mental disorder, a family history of psychiatric disorders, the other medical illnesses, a history of alcohol and other substances abuse (except caffeine and nicotine). Serum Tnf-α were analyzed using the Quantikine HS Human Tnf –α Immunoassay. Results: Serum Tnf-α level measure in patient schizophrenia male with smoking and compared with the healthy control subjects. Tnf-α levels were significantly higher in patients schizophrenic male with smoking (25,79±27,96) to healthy control subjects (2,74±2,19), by using the Mann Whitney U test showed a statistically significant difference was observed for serum Tnf-α level (p < 0,001). Conclusions: Schizophrenia is a highly heterogeneous disorder, and this study shows an increase Tnf-α as pro-inflammation cytokines in schizophrenics. These results suggest an immune abnormalities may be involved in the etiology and pathophysiology of schizophrenia.

Keywords: male, schizophrenic, smoking, Tnf Alpha

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Authors: Ana M. G. Sperandio, Adriana A. C. Rosa, Jussara C. Guarnieri

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This study consists of a research of the Post Occupancy Assessment (POA) of Medicinal Gardens' project of Urban Social Center’s square, in the city of 'Santa Barbara d'Oeste', located in the interior of Sao Paulo, Brazil. In view of the fact that community gardens, as well as medicinal gardens, are based on innumerable functions. The addition to the pedagogical function rescues people from their origins through (re)contact with the land, as a vehicle for social integration. Bearing in mind the project has the potential to fight hunger among the low-income population, to treat some diseases, also works as a strategy of environmental recovery especially of idle land. Such as very often only accumulate weeds and garbage, and therefore, must be considered in the Municipal Master Plan for the activity to be regulated. Objective: Identify on implantation the medicinal plants' value and principles for the promotion of a healthy city. Methodology: Application of the walkthrough, where it is possible to affirm that this instrument has three routes: one officer applied within the urban social center and two complementary ones, one being about 3 miles and the other being almost 5,5 miles. Results: Through a dialogical course, one can observe the benefits that the community medicinal gardens bring to the local population. In addition, it is consistent with the proposal for the community to be enabled to access collective care with home orientations that rescue the local and regional culture making the physical environment. This project aims at promoting more pleasant and inclusive through the actions of the caregiver, local leadership and the co-participation of local government. Although with the aim of increasing the supply value and improving the living conditions of social groups and interrelationship. Conclusion: This type of urban intervention, which articulates social participation, rescue of medicinal cultures and local knowledge, intersectoriality, social inclusion, among other premises connected with health promotion, and the city presents a potential for reverberation of practices in social networks with the objective of meeting the healthy city strategies.

Keywords: healthy city, healthy urban planning, medicinal gardens, social participation

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Authors: Jodie Hughes

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Endometriosis affects 1 in 10 individuals that were born female globally. Endometriosis incidence rates peak between 30-40 year of age, in young women and adolescents it is a rarely suspected and often ill-diagnosed. The average cost of endometriosis is €9,579 per woman. More than 75% of women have reported being absent from work due to endometriosis, with 40% of women becoming unemployed due to the disease. 46% of patients with endometriosis need to have appointments with upward of five doctors to gain a correct diagnosis. Quantitative data were collected by way of an online PSS-10 survey that included demographic questions from two sample groups of females, group 1 was females with endometriosis, group 2 were healthy women. The data were scored using Cohens scoring system, overall scores were input to SPSS. A non-parametric Mann-Whitney U test and ANOVA was used to ascertain any differences between the PSS-10 scores of the two groups. A significance level of P<0.05 was adopted. Four women were invited to take part in a semi structured interview that was recorded, transcribed and coded using interpretive phenomenological analysis (IPA) using NVivo 12. Results showed that the PSS-10 scores were significantly higher in women with endometriosis compared to healthy women with a p=<0.005. Endometriosis affects all aspects of a patient’s life, to adequately diagnose and treat the condition and improve HRQoL there needs to be better understanding of the clinical symptoms and how they impact the lives of patients.

Keywords: endometriosis, HRQoL, perceived stress, women

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Authors: F. Berahmandpour, K. Bagheri

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Introduction: Spirulina is nutritious blue - green algae which are used as supplement or a preservative in many foods. The studies about the algae argue that the Spirulina can improve immune system, increase fat utilization, reduce oxidative stress and promote endurance at high-intensity exercise. The purpose of study is to assess the effects of Spirulina supplement on healthy weight control. Method: the study is a cross-sectional study which had 30 participants. The participants were men and women who referred to the nutrition and diet therapy clinic (in west of Tehran / Iran) for control weight. The sampling was a purposeful sampling. The participants were divided into three groups, and they were surveyed for 4 weeks. In the first group, 10 participants were used Spirulia supplement (dose: 500mg of Spiruvit Supplement as tablet / 3 times per day) without any special diet. The second group was 10 participants who received Spirulia supplement (dose 500mg of Spiruvit Supplement as tablet / 3 times per day) with a weight loss exercise program and without any special diet. The third group was 10 participants who used Spirulia supplement (dose 500mg of Spiruvit Supplement as tablet / 3 times per day) with an optimum weight loss diet. Results and Discussion: The results show that there were not any significant loss weights in first group. In while, the participants of second group argued that the Spirulina supplement had positive effects on their mud and physical body; however the clinical results showed that the loss weight had fixed tilt in this group. The significant results of study were related to the third group, because the participations could continuous loss weight during 4 weeks. However, the optimum weight loss diets were effective effects on weight loss in this group, but the researchers found that Spirulina supplement could improve loss weight with set of hormonal system (especially in women with menopause). Conclusion: The study is concluded that the Spirulina as a supplement (Spiruvit Supplement) can be an effective effect on healthy weight control, if it is used with a nutritious healthy weight loss diet. In fact, the effect of Spirulina can be related to powerful antioxidant effects and improvable hormonal system in the body.

Keywords: diet, healthy weight control, spirulina, spiruvit supplement

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Authors: Manee Arpanantikul, Pennapa Unsanit, Dolrat Rujiwatthanakorn, Aporacha Lumdubwong

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In order to continuously perform self-care based on the sufficiency economy philosophy for the length of women’s lives is not easy. However, there are different ways that women can use to carry out self-care activities regularly. Some women individually perform self-care while others perform self-care in groups. Little is known about ways to sustaining self-care of women based on the fundamental principle of Thai culture. The purpose of this study was to investigate ways to sustaining self-care based on the sufficiency economy philosophy of Thai middle-aged women living in the community in order to achieve future healthy aging. This study employed a qualitative research design. Twenty women who were willing to participate in this study were recruited. Data collection were conducted through in-depth interviews with tape recording, doing field notes, and observation. All interviews were transcribed verbatim, and data were analyzed by using content analysis. The findings showed ways to sustaining self-care of Thai community women to achieve future healthy aging consisting of 7 themes: 1) having determination, 2) having a model, 3) developing a leader, 4) carrying on performing activities, 5) setting up rules, 6) building self-care culture, and 7) developing a self-care group/network. The findings of this study suggested that in order to achieve self-care sustainability women should get to know themselves, have intention and belief, together with having the power of community and support. Therefore, having self-care constantly will prevent disease and promote healthy in women’s lives.

Keywords: qualitative research, sufficiency economy philosophy, Thai middle-aged women, ways to sustaining self-care

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Authors: Ahmed M. Hjazi, Bader M. Hjazi

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Protein 4.1 is a crucial component of complex interactions between the cytoskeleton and other junctional complex proteins. When the gene encoding this protein is altered, resulting in reduced expression, or when the protein is absent, the red cell undergoes a significant structural change. This research aims to achieve a deeper comprehension of the biochemical effects of red cell protein deficiency. A Tandem Mass Spectrometry Analysis (TMT-MS/MS) of patient cells lacking protein 4.1 compared to three healthy controls was achieved by the Proteomics Institute of the University of Bristol. The SDS-PAGE and Western blotting were utilized on the original patient sample and controls to partially confirm TMT MS/MS data analysis of the protein-4.1-deficient cells. Compared to healthy controls, protein levels in samples lacking protein 4.1 had a significantly higher concentration of proteins that probably originated from reticulocytes. This could occur if the patient has an elevated reticulocyte count. The increase in chaperone and reticulocyte-associated proteins was most notable in this study. This may result from elevated quantities of reticulocytes in patients with hereditary elliptocytosis.

Keywords: hereditary elliptocytosis, protein 4.1, red cells, tandem mass spectrometry data.

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Authors: P. Gil Del Álamo, J. García Pereda, A. Castañeda De La Paz, D. Arazola Lopez, M. D. Cubiles De La Vega, A. Enguíx González, J. M. Muñoz Pichardo

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In the last decades, obesity has more than doubled and is, with overweight, the second leading cause of preventable death. Despite multiple strategies against obesity, no country to date has reduced the number of obese people. To achieve World Health Organization’s target to reverse this tendency we need dramatic and different actions to engage the civil society in creating demand for a healthy style of life. The objective of this study is to demonstrate that a social media as the television can be used to convince the civil society that a healthy nutrition and physical activity are affordable, effective and necessary to prevent and to treat the obesity. Methodology: 61 individuals (34 women and 27 men) with obesity (mean BMI 45,51) were recruited to follow during 22 weeks an intensive lifestyle intervention in order to lose weight in a healthy manner. They were not isolated or moved from their usual environment. This program included endocrinological and nutritional assessment, promotion of physical activity and psychological support. BMI was measured every week. Time to leave obesity between men and women was analyzed with a survival analysis. Results: BMI decreased in all the cases. Analysing Time to leave obesity, around the week 30, 25% of men leave the obesity and around the week 39, 25% of women leave the obesity too. Conclusion: We demonstrate the audience that improving the quality of the diet and increasing the physical activity is a realistic way to lose weight. This evidence can encourage the people to act in their own self-interest changing their style of life in order to prevent or to reduce their overweight.

Keywords: obesity epidemic, obesity prevention, obesity strategies, social media

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Authors: D. Hammad, D. P. Tonge

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Rheumatoid arthritis (RA) is a disabling and common autoimmune disease during which the body's immune system attacks healthy tissues. This results in complicated and long-lasting actions being carried out by the immune system, which typically only occurs when the immune system encounters a foreign object. In the case of RA, the disease affects millions of people and causes joint inflammation, ultimately leading to the destruction of cartilage and bone. Interestingly, the disease mechanism still remains unclear. It is likely that RA occurs as a result of a complex interplay of genetic and environmental factors including an imbalance in the microorganism population inside our body. The human microbiome or microbiota is an extensive community of microorganisms in and on the bodies of animals, which comprises bacteria, fungi, viruses, and protozoa. Recently, the development of molecular techniques to characterize entire bacterial communities has renewed interest in the involvement of the microbiome in the development and progression of RA. We believe that an imbalance in some of the specific bacterial species in the gut, mouth and other sites may lead to atopobiosis; the translocation of these organisms into the blood, and that this may lead to changes in immune system status. The aim of this study was, therefore, to characterize the microbiome of RA serum samples in comparison to healthy control subjects using 16S rRNA gene amplification and sequencing. Serum samples were obtained from healthy control volunteers and from patients with RA both prior to, and following treatment. The bacterial community present in each sample was identified utilizing V4 region 16S rRNA amplification and sequencing. Bacterial identification, to the lowest taxonomic rank, was performed using a range of bioinformatics tools. Significantly, the proportions of the Lachnospiraceae, Ruminococcaceae, and Halmonadaceae families were significantly increased in the serum of RA patients compared with healthy control serum. Furthermore, the abundance of Bacteroides and Lachnospiraceae nk4a136_group, Lachnospiraceae_UGC-001, RuminococcaceaeUCG-014, Rumnococcus-1, and Shewanella was also raised in the serum of RA patients relative to healthy control serum. These data support the notion of a blood microbiome and reveal RA-associated changes that may have significant implications for biomarker development and may present much-needed opportunities for novel therapeutic development.

Keywords: blood microbiome, gut and oral bacteria, Rheumatoid arthritis, 16S rRNA gene sequencing

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Authors: H. Feza Carlak, N. G. Gencer

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To increase the temperature contrast in thermal images, the characteristics of the electrical conductivity and thermal imaging modalities can be combined. In this experimental study, it is objected to observe whether the temperature contrast created by the tumor tissue can be improved just due to the current application within medical safety limits. Various thermal breast phantoms are developed to simulate the female breast tissue. In vitro experiments are implemented using a thermal infrared camera in a controlled manner. Since experiments are implemented in vitro, there is no metabolic heat generation and blood perfusion. Only the effects and results of the electrical stimulation are investigated. Experimental study is implemented with two-dimensional models. Temperature contrasts due to the tumor tissues are obtained. Cancerous tissue is determined using the difference and ratio of healthy and tumor images. 1 cm diameter single tumor tissue causes almost 40 °mC temperature contrast on the thermal-breast phantom. Electrode artifacts are reduced by taking the difference and ratio of background (healthy) and tumor images. Ratio of healthy and tumor images show that temperature contrast is increased by the current application.

Keywords: medical diagnostic imaging, breast phantom, active thermography, breast cancer detection

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Authors: Fu-Chien Hung, Chi‐Wen Liang

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Background: People who suffer from chronic fatigue syndrome (CFS) frequently complain about continuous tiredness, weakness or lack of strength, but without apparent organic etiology. The prevalence rate of the CFS is nearly from 3% to 20%, yet more than 80% go undiagnosed or misdiagnosed as depression. The biopsychosocial model has suggested the associations among the CFS, depressive syndrome, and stress. This study aimed to investigate the difference between individuals with the CFS and with the depressive syndrome on psychophysiological responses under stress. Method: There were 23 participants in the CFS group, 14 participants in the depression group, and 23 participants in the healthy control group. All of the participants first completed the measures of demographic data, CFS-related symptoms, daily life functioning, and depressive symptoms. The participants were then asked to perform a stressful cognitive task. The participants’ psychophysiological responses including the HR, BVP and SC were measured during the task. These indexes were used to assess the reactivity and recovery rates of the automatic nervous system. Results: The stress reactivity of the CFS and depression groups was not different from that of the healthy control group. However, the stress recovery rate of the CFS group was worse than that of the healthy control group. Conclusion: The results from this study suggest that the CFS is a syndrome which can be independent from the depressive syndrome, although the depressive syndrome may include fatigue syndrome.

Keywords: chronic fatigue syndrome, depression, stress response, misdiagnosis

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Authors: Abeer Mohammed, Nevein Mustafa Elashery, Mona Hassan Abdel Aal, Ereny Wilson Nagib

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The Aim of the current study is to investigate nutrition role in the management of psychiatric disorders. Research Design: A quasi- experimental research design was utilized for this study. Setting The study was conducted at outpatient clinic at Institute of Psychiatry affiliated to Ain Shams University hospitals, using a convenient sample of 50 psychiatric patients with depression, schizophrenia, bipolar disorders, and obsessive compulsive disorders. Tools: data were collected through; first, an interview questionnaire covering socio-demographic characteristics, second, nutrition assessment tools Third, nutrition risk assessment. Fourth, nutrition management program Results showed that there were highly statistically significant improvements in modified nutritional supplements for patients with depression, schizophrenia, bipolar disorders, and obsessive compulsive disorders' patients after conducting the nutrition management program. Regarding psychiatric patients’ knowledge about healthy food, healthy nutritional habits, and patients’ awareness & readiness for change, there were highly statistically significant improvements. Concerning signs and symptoms of psychiatric disorders, there were highly statistically significant improvements for depression, schizophrenia, bipolar disorders, and obsessive-compulsive patients after conducting the management program. In conclusion, the nutrition management program was effective in improving symptoms associated with, depression, schizophrenia, bipolar disorders, and obsessive compulsive disorders. The study recommended that nurses should have more contribution in counseling psychiatric patients, and their families about healthy diet and healthy habits. Further research should recommend studying the effectiveness of herbs on enhancing mental health for psychiatric patients.

Keywords: nutrition, role, management, psychiatric disorders

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Authors: Watchawin Ekphinitphithaya, Patompong Satapornpong

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Introduction: Carbamazepine (CBZ) is one of the most prescribed antiepileptic drugs (AEDs) by neurologists and non-neurologist worldwide. CBZ is usually prescribed along with other drugs, leading to the possibility of severe cutaneous adverse drug reactions (SCARs). The HLA-B*15:02 is strongly associated with CBZ-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS–TEN) in the Han Chinese and other Asian populations but not in European populations, while HLA-A*31:01 allele has been reported to be associated with CBZ-induced SCARs in European population and Japanese. Objective: The aim of this study is to investigate the distribution of pharmacogenetics HLA-A*31:01 marker in a healthy Thai population associated with Carbamazepine-induced SCARs. Materials and Methods: Prospective study, 350 unrelated healthy Thais were recruited in this study. Human leukocyte antigen-A alleles were genotyped using PCR-sequence specific oligonucleotides (PCR-SSOs). Results: The frequency of HLA-A alleles were HLA-A*11:01 (190 alleles, 27.14%), HLA-A*24:02 (82 alleles, 11.71%), HLA-A*02:03 (80 alleles, 11.43%), HLA-A*33:03 (76 alleles, 10.86%), HLA-A*02:07 (58 alleles, 8.29%), HLA-A*02:01 (35 alleles, 5.00%), HLA-A*24:07 (29 alleles, 4.14%), HLA-A*02:06 – HLA-A*30:01 (15 alleles, 2.14%), and HLA-A*01:01 (14 alleles, 2.00%). Particularly, the number of HLA-A*31:01 alleles was 6 of 700 (0.86%) in the healthy Thai population. Many research presented varying distributions of HLA-A*31:01 in Asians, including 2% of Han Chinese, 9% of Japanese and 5% of Koreans. In addition, this allele was found approximately 2-5% in the Caucasian population. Conclusions: Thus, the pharmacogenetics database is vital to support in many populations, especially in Thais, for screening HLA-A*31:01 allele to avoid CBZ-induced SCARs before initiating treatments in each population.

Keywords: Carbamazepine, HLA-A*31:01, Thai population, pharmacogenetics

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Authors: Tertia Delia Nova, Masaji Watanabge

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Infection of bird flu within a poultry farm involves hosts, virus, and medium. Intrusion of bird flu into a poultry farm divides the population into two groups; healthy and susceptible chickens and infected chickens. A healthy and susceptible bird is infected to become an infected bird. Bird flu viruses spread among chickens through medium such as air and droppings, and increase in hosts. A model for an infection process of bird flu within a poultry farm is described, numerical techniques are illustrated, and numerical results are introduced.

Keywords: bird flu, poultry farm, model for an infection process, flu viruses

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Authors: Christiena Van Der Bank, Marjone Van Der Bank, Ronelle Prinsloo

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The constitutional right to a healthy environment and the constitutional duty imposed on the state actively to protect the environment fulfill the specific duties to prevent pollution and ecological degradation and to promote conservation. The aim of this paper is to draw attention to the relationship between child rights and the environment. The focus is to analyse government’s responses as mandated with section 24 of the Bill of Rights for ensuring the right to a clean and healthy environment. The principle of sustainability of the environment encompasses the notion of equity and the harm to the environment affects the present as well as future generations. Section 24 obliges the state to ensure that the legacy of future generations is protected, an obligation that has been said to be part of the common law. The environment is an elusive and wide concept that can mean different things to different people depending on the context in which it is used for example clean drinking water or safe food. An extensive interpretation of the term environment would include almost everything that may positively or negatively influence the quality of human life. The analysis will include assessing policy measures, legislation, budgetary measures and other measures taken by the government in order to progressively meet its constitutional obligation. The opportunity of the child to grow up in a healthy and safe environment is extremely unjustly distributed. Without a realignment of political, legal and economic conditions this situation will not fundamentally change. South Africa as a developing country that needs to meet the demand of social transformation and economic growth whilst at the same time expediting its ability to compete in global markets, the country will inevitably embark on developmental programmes as a measure for sustainable development. The courts would have to inquire into the reasonableness of those measures. Environmental threats to children’s rights must be identified, taking into account children’s specific needs and vulnerabilities, their dependence and marginalisation. Obligations of states and violations of rights must be made more visible to the general public.

Keywords: environment, children rights, pollution, healthy, violation

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Authors: Michelle Eichinger, Upali Nanda

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Behavior choices during college years can establish the pattern of lifelong healthy living. Nearly 1/3rd of American college students are either overweight (25 < BMI < 30) or obese (BMI > 30). In addition, overweight/obesity contributes to depression, which is a rising epidemic among college students, affecting academic performance and college drop-out rates. Overweight and obesity result in an imbalance of energy consumption (diet) and energy expenditure (physical activity). Overweight/obesity is a significant contributor to heart disease, diabetes, stroke, physical disabilities and some cancers, which are the leading causes of death and disease in the US. There has been a significant increase in obesity and obesity-related disorders such as type 2 diabetes, hypertension, and dyslipidemia among people in their teens and 20s. Historically, the evidence-based interventions for obesity prevention focused on changing the health behavior at the individual level and aimed at increasing awareness and educating people about nutrition and physical activity. However, it became evident that the environmental context of where people live, work and learn was interdependent to healthy behavior change. As a result, a comprehensive approach was required to include altering the social and built environment to support healthy living. College campus provides opportunities to support lifestyle behavior and form a health-promoting culture based on some key point of decisions such as stairs/ elevator, walk/ bike/ car, high-caloric and fast foods/balanced and nutrient-rich foods etc. At each point of decision, design, can help/hinder the healthier choice. For example, stair well design and motivational signage support physical activity; grocery store/market proximity influence healthy eating etc. There is a need to collate the vast information that is in planning and public health domains on a range of successful point of decision prompts, and translate it into architectural guidelines that help define the edge condition for critical point of decision prompts. This research study aims to address healthy behaviors through the built environment with the questions, how can we make the healthy choice an easy choice through the design of critical point of decision prompts? Our hypothesis is that well-designed point of decision prompts in the built environment of college campuses can promote healthier choices by students, which can directly impact mental and physical health related to obesity. This presentation will introduce a combined health and architectural framework aimed to influence healthy behaviors through design applied for college campuses. The premise behind developing our concept, point-of-decision design (PODD), is healthy decision-making can be built into, or afforded by our physical environments. Using effective design intervention strategies at these 'points-of-decision' on college campuses to make the healthy decision the default decision can be instrumental in positively impacting health at the population level. With our model, we aim to advance health research by utilizing point-of-decision design to impact student health via core sectors of influences within college settings, such as campus facilities and transportation. We will demonstrate how these domains influence patterns/trends in healthy eating and active living behaviors among students. how these domains influence patterns/trends in healthy eating and active living behaviors among students.

Keywords: architecture and health promotion, college campus, design strategies, health in built environment

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Authors: Rock-Hyun Choi, Won-Seok Kang, Chang-Sik Son

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Physical activity is important for healthy living. Recently wearable devices which motivate physical activity are quickly developing, and become cheaper and more comfortable. In particular, fitness trackers provide a variety of information and need to provide well-analyzed, and user-friendly results. In this study, frequency analysis was performed to classify various data sets of Fitbit into simple activity status. The data from Fitbit cloud server consists of 263 subjects who were healthy factory and office workers in Korea from March 7th to April 30th, 2016. In the results, we found assumptions of activity state classification seem to be sufficient and reasonable.

Keywords: activity status, fitness tracker, heart rate, steps

Procedia PDF Downloads 353

Authors: Svetlana Zhikrivetskaya, Nataliya Shirokova, Roman Bikanov, Elizaveta Musatova, Yana Kovaleva, Nataliya Vetrova, Ekaterina Pomerantseva

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Nowadays there is a growing number of couples with conceiving problems due to male or female infertility. Genetic abnormalities are responsible for about 31% of all cases of male infertility. These abnormalities include both chromosomal aberrations or aneuploidies and mutations in certain genes. Chromosomal abnormalities can be easily identified, thus the development of screening panels able to reveal genetic reasons of male infertility on gene level is of current interest. There are approximately 2,000 genes involved in male fertility that is the reason why it is very important to determine the most clinically relevant in certain population and ethnic conditions. An infertility screening panel containing 48 mutations in genes AMHR2, CFTR, DNAI1, HFE, KAL1, TSSK2 and AZF locus which are the most clinically relevant for the European population according to databases NCBI and ClinVar was designed. The aim of this research was to confirm clinic relevance of these mutations in the Russian population. Genotyping was performed in 220 patients with different types of male infertility and in 57 healthy males with normozoospermia. Mutations were identified by end-point PCR with TaqMan probes in microfluidic plates. The frequency of 5 mutations in healthy males and 13 mutations in patients with infertility was revealed and estimated. The frequency of mutation c.187C>G in HFE gene was significantly lower for healthy males (8.8%) compared with patients (17.7%) and the values for the European population according to ExAc database (13.7%) and dbSNP (17.2%). Analysis of c.3454G>C, and c.1545_1546delTA mutations in the CFTR gene revealed increased frequency (0.9 and 0.2%, respectively) in patients with infertility compared with data for the European population (0.04%, respectively (ExAc, European (Non-Finnish) and for the Aggregated Populations (0.002% (ExAc), because there is no data for European population for c.1545_1546delTA mutation. The frequency of del508 mutation (CFTR) in patients (1.59%) were lower comparing with male infertility Europeans (3.34-6.25% depending on nationality) and at the same level with healthy Europeans (1.06%, ExAc, European (Non-Finnish). Analysis of c.845G>A (HFE) mutation resulted in decreased frequency in patients (1.8%) in contrast with the European population data (5.1%, respectively, ExAc, European (Non-Finnish). Moreover, obtained data revealed no statistically significant frequency difference for c.845G>A mutation (HFE) between healthy males in the Russian and the European populations. Allele frequencies of mutations c.350G>A (CFTR), c.193A>T (HFE), c.774C>T, and c.80A>G (gene TSSK2) showed no significantly difference among patients with infertility, healthy males and Europeans. Analysis of AZF locus revealed increased frequency for AZFc microdeletion in patients with male infertility. Thereby, the new data of the allele frequencies in infertility patients in the Russian population was obtained. As well as the frequency differences of mutations associated with male infertility among patients, healthy males in the Russian population and the European one were estimated. The revealed differences showed that for high effectiveness of screening panel detecting genetically caused male infertility it is very important to consider ethnic and population characteristics of patients which will be screened.

Keywords: allele frequency, azoospermia, male infertility, mutation, population

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Authors: David Karasek, Veronika Kubickova, Ondrej Krystynik, Dominika Goldmannova, Lubica Cibickova, Jan Schovanek

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Introduction: Adiponectin, adipocyte-fatty acid-binding protein (A-FABP), and Wnt1 inducible signaling pathway protein-1 (WISP-1) are adipokines particularly associated with insulin resistance. The aim of the study was to compare their levels in women with gestational diabetes (GDM), type 2 diabetes mellitus (T2DM) and healthy controls and determine their relation with metabolic parameters. Methods: Fifty women with GDM, 50 women with T2DM, and 35 healthy women were included in the study. In addition to adipokines, anthropometric, lipid parameters, and markers, insulin resistance, and glucose control were assessed in all participants. Results: Compared to healthy controls only significantly lower levels of adiponectin were detected in women with GDM, whereas lower levels of adiponectin, higher levels of A-FABP and of WISP-1 were present in women with T2DM. Women with T2DM had also lower levels of adiponectin and higher levels of A-FABP compared to women with GDM. In women with GDM or T2DM adiponectin correlated negatively with body mass index (BMI), triglycerides (TG), C-peptide and positively with HDL-cholesterol; A-FABP positively correlated with BMI, TG, waist, and C-peptide. Moreover, there was a positive correlation between WISP-1 and C-peptide in women with T2DM. Conclusion: Adverse adipokines production detecting dysfunctional fat tissue is in women with GDM less presented than in women with T2DM, but more expressed compared to healthy women. Acknowledgment: Supported by AZV NV18-01-00139 and MH CZ DRO (FNOl, 00098892).

Keywords: adiponectin, adipocyte-fatty acid binding protein, wnt1 inducible signaling pathway protein-1, gestational diabetes, type 2 diabetes mellitus

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Authors: Somaiya Mateen, Shagufta Moin, Mohammad Owais, Abdul Khan, Atif Zafar

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In rheumatoid arthritis (RA), impaired oxidative metabolism and imbalance between pro-and anti-inflammatory cytokines are responsible for causing inflammation and the degradation of cartilage and bone. The present study was done to evaluate the level and hence the role of reactive oxygen species (ROS) and inflammatory cytokines in the pathogenesis of RA. The present study was performed in the blood of 80 RA patients and 55 age and sex-matched healthy controls. The level of ROS (in 5% hematocrit) and the plasma level of pro-inflammatory cytokines [TNF-α, interleukin-6 (IL-6), IL-22] and anti-inflammatory cytokines (IL-4 and IL-5) were monitored in healthy subjects and RA patients. For evaluating the role of rheumatoid factor (RF) in the pathogenesis of RA, patients were sub-divided on the basis of presence or absence of RF. Reactive species and inflammatory cytokines were correlated with disease activity measure-Disease Activity Score for 28 joints (DAS28). The level of ROS, TNF-α, IL-6 and IL-22 were found to be significantly higher in RA patients as compared to the healthy controls, with the increase being more significant in patients positive for rheumatoid factor and those having high disease severity. On the other hand, a significant decrease in the level of IL-4 and IL-10 were observed in RA patients compared with healthy controls, with the decrease being more prominent in severe cases of RA. Higher ROS (indicative of impaired anti-oxidant defence system) and pro-inflammatory cytokines level in RA patients may lead to the damage of biomolecules which in turn contributes to tissue damage and hence to the development of more severe RA. The imbalance between pro-and anti-inflammatory cytokines may lead to the development of multi-system immune complications. ROS and inflammatory cytokines may also serve as a potential biomarker for assessing the disease severity.

Keywords: rheumatoid arthritis, reactive oxygen species, pro-inflammatory cytokines, anti-inflammatory cytokines

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Authors: Ana Maria G. Sperandio, Murilo U. Malek-Zadeh, João Luiz de S. Areas, Jussara C. Guarnieri

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Intersectoral governance is a requirement for developing healthy cities. However, this achievement is difficult to be succeeded, especially in regions at low resources condition. Therefore, it was developed a cheap investigative procedure to diagnose sectoral wishes related to urban planning and health promotion. This procedure is composed of two phases, which can be applied to different groups in order to compare the results. The first phase is a conversation guided by a list of questions. Some of those questions aim to gather information about how individuals understand concepts such as healthy city or a health promotion and what they believe that constitutes the relation between urban planning and urban health. Other questions investigate local issues, and how citizens would like to promote dialogue between sectors. At second phase individuals stand around the investigated city (or city region) map and are asked to represent their wishes on it. They can represent it by writing text notations or inserting icons on it, with the latter representing a city element, for example, some trees, a square, a playground, a hospital, a cycle track. After groups had represented their wishes, the map can be photographed, and then the results from distinct groups can be compared. This procedure was conducted at a small city in Brazil (Holambra), in 2017 which is the first out of four years of the mayor’s term. The prefecture asked for this tool in order to make Holambra become a city of Potential Healthy Municipalities Network in Brazil. Two sectors were investigated: the government and the urban population. By the end of our investigation, the intersection from the group (i.e., population and government) maps was accounted for creating a map of common wishes. Therefore, the material produced can be used as a guide for promoting dialogue between sectors and as a tool of monitoring politics progress. The report of this procedure was directed to public managers, so they could see the common wishes between themselves and local populations, and use this tool as a guide for creating urban politics which intends to enhance health promotion and to develop a healthy city, even at low resources condition.

Keywords: governance, health promotion, intersectorality, urban planning

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Authors: Panagiotis T. Kanellos, Vaios T. Karathanos, Andriana C. Kaliora

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Introduction: The role of ghrelin and obestatin in appetite regulation has been investigated. However, data on ghrelin and obestatin changes after food ingestion are negligible. Objective: We aimed at assessing the appetite-regulating hormones, ghrelin, and obestatin, and furthermore calculate ghrelin/obestatin ratio in healthy normal-weight subjects after consumption of raisins. This survey is a comparative study of a glucose control with raisins containing fructose and glucose in similar concentrations as well as fibers. Methodology: Ten apparently healthy subjects who reported no history of glucose intolerance, diabetes, gastrointestinal disorders, or recent use of any antibiotics were enrolled in the study. The raisins used (Vitis vinifera) originate in Greece and are distributed worldwide as Corinthian raisins. In a randomized crossover design, all subjects after an overnight fast consumed, either 50g of glucose diluted in 240 mL of water (control) or 74 g of raisins (sugar content 50 g) with a 5-day interval between individual trials. Vein blood samples were collected at baseline and at 60, 120 and 180 min postprandially. In blood samples ghrelin and obestatin were measured applying specific enzyme linked immuno absorbent assays. Results: The subjects were of mean age 26.3 years, with BMI of 21.6 kg/m2, waist circumference of 77.7 cm, normal serum lipidemic parameters and normal HbA1c levels. Ghrelin levels were significantly lower after raisin consumption compared to glucose at 120 and at 180 min post-ingestion (p= 0.011 and p= 0.035, respectively). However, obestatin did not reach statistical significance between the two interventions. The ghrelin/obestatin ratio was found significantly lower (p=0.020) at 120 min after raisin ingestion compared to control. Conclusion: Two isocaloric foods containing equal amounts of sugars, however with a different composition, have different effects on appetite hormones ghrelin and obestatin in normal-weight healthy subjects.

Keywords: appetite, ghrelin, obestatin, raisins

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Authors: Sarah Sayed El- Tawab, Emmanuel Kamal Azix Saba

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Objectives: Somatosensory blink reflex (SBR) is an eye blink response obtained from electrical stimulation of peripheral nerves or skin area of the body. It has been studied in various neurological diseases as well as among healthy subjects in different population. We designed this study to detect SBR positivity in patients with facial palsy and patients with post facial syndrome, to relate the facial palsy severity and the presence of SBR, and to associate between trigeminal BR changes and SBR positivity in peripheral facial palsy patients. Methods: 50 patients with peripheral facial palsy and post-facial syndrome 31 age and gender matched healthy volunteers were enrolled to this study. Facial motor conduction studies, trigeminal BR, and SBR were studied in all. Results: SBR was elicited in 67.7% of normal subjects, in 68% of PFS group, and in 32% of PFP group. On the non-paralytic side SBR was found in 28% by paralyzed side stimulation and in 24% by healthy side stimulation among PFP patients. For PFS group SBR was found on the non- paralytic side in 48%. Bilateral SBR elicitability was higher than its unilateral elicitability. Conclusion: Increased brainstem interneurons excitability is not essential to generate SBR. The hypothetical sensory-motor gating mechanism is responsible for SBR generation.

Keywords: somatosensory evoked blink reflex, post facial syndrome, blink reflex, enchanced gain

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Authors: Maretha Le Roux, Corinna Walsh, Mariette M. Nel

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Introduction: The first 1000 days from conception to 24 months, is a critical period for healthy growth and development. In South Africa, stunting is a major public health issue with significant health consequences. We determined associations between demographic, health and anthropometric indicators of mothers and their infants. Methods: A cross-sectional study was conducted in all districts in the Northern Cape. All mothers with 5-7 week old babies visiting PHC facilities could participate. A questionnaire was completed in a structured interview with each mother. Weight and length of the baby at birth and at 6 weeks were used to determine stunting, while weight and height of the mother were measured for body mass index (BMI). Results: Eight hundred questionnaires were completed in 92 facilities. The median age of mothers was 26 years (range 10-46 years), and 44,9% were married. Almost 40% relied on a government grant as main source of income. Two-thirds (64,9%) had not planned the pregnancy, and 19.4% had a Caesarian section. Although 79% breastfed exclusively, more than a quarter (26,1%) smoked cigarettes or used snuff during pregnancy, while 9,4% drank alcohol. At birth, 17.7% of boys and 13.0% of girls were stunted (height-for-age below -2SD from the WHO reference values), while at 6 weeks this had increased to 30.8% of boys and 14.1% of girls. In terms of mothers, 25,4% were classified as obese and 24,6% as overweight at 6 weeks. Compared to babies that were not stunted, significantly more babies of mothers that were older, overweight, used ART, relied on a grant and smoked/snuffed during pregnancy were stunted. Conclusion: To address stunting, interventions aimed at encouraging healthy lifestyles with the emphasis on maintaining a healthy weight, healthy eating and smoking cessation before pregnancy are urgently required.

Keywords: growth, health, South Africa, stunting

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Authors: O. Katz-Shufan, T. Simon-Tuval, L. Sabag, L. Granek, D. R. Shahar

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Meals provided at catering systems are a common source of workers' nutrition and were found as contributing high amounts calories and fat. Thus, eating daily catering food can lead to overweight and chronic diseases. On the other hand, the institutional dining room may be an ideal environment for implementation of intervention programs that promote healthy eating. This may improve diners' lifestyle and reduce their prevalence of overweight, obesity and chronic diseases. The significance of this study is in developing an intervention program based on the diners’ dietary habits, preferences and their attitudes towards various intervention programs. In addition, a successful catering-based intervention program may have a significant effect simultaneously on a large group of diners, leading to improved nutrition, healthier lifestyle, and disease-prevention on a large scale. In order to develop the intervention program, we conducted a qualitative study. We interviewed 13 diners who eat regularly at catering systems, using a semi-structured interview. The interviews were recorded, transcribed and then analyzed by the thematic method, which identifies, analyzes and reports themes within the data. The interviews revealed several major themes, including expectation of diners to be provided with healthy food choices; their request for nutrition-expert involvement in planning the meals; the diners' feel that there is a conflict between sensory attractiveness of the food and its' nutritional quality. In the context of the catering-based intervention programs, the diners prefer scientific and clear messages focusing on labeling healthy dishes only, as opposed to the labeling of unhealthy dishes; they were interested in a nutritional education program to accompany the intervention program. Based on these findings, we have developed an intervention program that includes: changes in food served such as replacing several menu items and nutritional improvement of some of the recipes; as well as, environmental changes such as changing the location of some food items presented on the buffet, placing positive nutritional labels on healthy dishes and an ongoing healthy nutrition campaign, all accompanied by a nutrition education program. The intervention program is currently being tested for its impact on health outcomes and its cost-effectiveness.

Keywords: catering system, food services, intervention, nutrition policy, public health, qualitative research

Procedia PDF Downloads 161

Authors: Faisal O. Al-Otaibi, Arthur T. Tucker, Richard M. Langford, Stuart Ratcliffe, Atholl Johnston, Terry D. Lee, Kenneth B. Kirby, Chandan A. Alam

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The Transdermal Delivery System (TDS®) is a proprietary liquid formulation that can be applied to intact skin via a metered pump spray to facilitate drug delivery to the circulation. The aim of this study was to assess the ability of the TDS preparation to deliver diazepam systemically, and to characterize the pharmacokinetic profile of the drug in healthy adult subjects. We conducted a randomized, single-dose, two-period, crossover phase I (pharmacokinetic) comparative study in twelve healthy volunteers. All volunteers received both 10 mg TDS-diazepam topically to the upper chest and 10 mg of the rectal diazepam preparation (Diastat®, 10 mg diazepam gel), with a minimum washout of 14 days between dosing episodes. Both formulations were well tolerated in all volunteers. Following topical application of TDS-diazepam, the mean AUC0-72h was 1241 ng/mL.h and the Cmax 34 ng/mL. The values for rectal Diastat were 4109 ng/mL.h and 300 ng/mL respectively. This proof of concept study demonstrates that the TDS preparation successfully delivered diazepam systemically to adults. As expected, the concentration of diazepam following the TDS application was lower and not bioequivalent to rectal gel. Future development of this unique system is required.

Keywords: transdermal delivery system, diazepam, seizure, bioequivalence, pharmacokinetic

Procedia PDF Downloads 398

Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean

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Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.

Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics

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