Search results for: hereditary spastic paraparesis
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 64

Search results for: hereditary spastic paraparesis

34 Parental Perceptions and Practices toward Childhood Asthma

Authors: Amani K. Abu-Shaheen, Abdullah Nofal, Humariya Heena

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Introduction: Parental perceptions and practices are important for improving the asthma outcomes in children; indeed, evidence shows that parents of asthmatic children harbor considerable misperceptions of the disease. Objective: To identify the prevalence of asthma and to investigate the perceptions and practices of parents toward asthma and its management in Saudi children. Methods: A two-stage cross-sectional survey of 2000 parents of children aged 3–15 years from schools located in all five districts of Riyadh province located in central Saudi Arabia, was conducted. Data collection was accomplished using a self-administered questionnaire based on information obtained from the literature. Results: Of 1450 children whose parents participated in the study, 600 had asthma, dyspnea, or chest allergy. The overall number of children with parental reports of ever having been diagnosed with asthma was 478 (32.9%). The majority of parents (321, 53.5%) believed that asthma was a hereditary disease. Of these parents, 361 (60.3%) were concerned about side effects of inhaled steroids, and 192 (32%) about development of dependency on asthma medications. Three hundred sixty seven (61.2%) parents reported that they could treat the asthma attack at home and almost 76% of parents went to pediatric emergency department during asthma attack. Conclusions: In this study, the overall prevalence of children whose parents reported that they were diagnosed with asthma was high (32.9%). Furthermore, parents of children with asthma had misperceptions regarding asthma and exhibited ineffective practices in its management. To improve asthma care and compliance, adequate education should be provided to parents.

Keywords: asthma, management, parents, quality of life

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33 Extracorporeal Shock Wave Therapy versus Functional Electrical Stimulation on Spasticity, Function and Gait Parameters in Hemiplegic Cerebral Palsy

Authors: Mohamed A. Eid, Sobhy M. Aly

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Background: About 75% of children with spastic hemiplegic cerebral palsy walk independently, but most still show abnormal gait patterns because of contractures across the joints and muscle spasticity. Objective: The purpose of this study was to investigate and compare the effects of extracorporeal shock wave therapy (ESWT) versus functional electrical stimulation (FES) on spasticity, function, and gait parameters in children with hemiplegic cerebral palsy (CP). Methods: A randomized controlled trail was conducted for 45 children with hemiplegic CP ranging in age from 6 to 9 years. They were assigned randomly using opaque envelopes into three groups. Physical Therapy (PT) group consisted of 15 children and received the conventional physical therapy program (CPTP) in addition to ankle foot orthosis (AFO). ESWT group consisted of 15 children and received the CPTP, AFO in addition to ESWT. FES group also consisted of 15 children and received the CPTP, AFO in addition to FES. All groups received the program of treatment 3 days/week for 12 weeks. Evaluation of spasticity by using the Modified Ashworth Scale (MAS), function by using the Pediatric Evaluation Disability Inventory (PEDI) and gait parameters by using the 3-D gait analysis was conducted at baseline and after 12 weeks of the treatment program. Results: Within groups, significant improvements in spasticity, function, and gait (P = 0.05) were observed in both ESWT and FES groups after treatment. While between groups, ESWT group showed significant improvements in all measured variables compared with FES and PT groups (P ˂ 0.05) after treatment. Conclusion: ESWT induced significant improvement than FES in decreasing spasticity and improving function and gait in children with hemiplegic CP. Therefore, ESWT should be included as an adjunctive therapy in the rehabilitation program of these children.

Keywords: cerebral palsy, extracorporeal shock wave therapy, functional electrical stimulation, function, gait, spasticity

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32 The Use of Geographic Information System and Spatial Statistic for Analyzing Leukemia in Kuwait for the Period of 2006-2012

Authors: Muhammad G. Almatar, Mohammad A. Alnasrallah

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This research focuses on the study of three main issues: 1) The temporal analysis of leukemia for a period of six years (2006-2012), 2) spatial analysis by investigating this phenomenon in the Kuwaiti society spatially in the residential areas within the six governorates, 3) the use of Geographic Information System technology in investigating the hypothesis of the research and its variables using the linear regression, to show the pattern of linear relationship. The study depends on utilizing the map to understand the distribution of blood cancer in Kuwait. Several geodatabases were created for the number of patients and air pollution. Spatial interpolation models were used to generate layers of air pollution in the study area. These geodatabases were tested over the past six years to reach the conclusion: Is there a relationship with significant significance between the two main variables of the study: blood cancer and air pollution? This study is the first to our best knowledge. As far as the researchers know, the distribution of this disease has not been studied geographically at the level of regions in Kuwait within six years and in specific areas as described above. This study investigates the concentration of this type of disease. The study found that there is no relationship of significant value between the two variables studied, and this may be due to the nature of the disease, which are often hereditary. On the other hand, this study has reached a number of suggestions and recommendations that may be useful to decision-makers and interested in the study of leukemia in Kuwait by focusing on the study of genetic diseases, which may be a cause of leukemia rather than air pollution.

Keywords: Kuwait, GIS, cancer, geography

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31 Exploring Factors That May Contribute to the Underdiagnosis of Hereditary Transthyretin Amyloidosis in African American Patients

Authors: Kelsi Hagerty, Ami Rosen, Aaliyah Heyward, Nadia Ali, Emily Brown, Erin Demo, Yue Guan, Modele Ogunniyi, Brianna McDaniels, Alanna Morris, Kunal Bhatt

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Hereditary transthyretin amyloidosis (hATTR) is a progressive, multi-systemic, and life-threatening disease caused by a disruption in the TTR protein that delivers thyroxine and retinol to the liver. This disruption causes the protein to misfold into amyloid fibrils, leading to the accumulation of the amyloid fibrils in the heart, nerves, and GI tract. Over 130 variants in the TTR gene are known to cause hATTR. The Val122Ile variant is the most common in the United States and is seen almost exclusively in people of African descent. TTR variants are inherited in an autosomal dominant fashion and have incomplete penetrance and variable expressivity. Individuals with hATTR may exhibit symptoms from as early as 30 years to as late as 80 years of age. hATTR is characterized by a wide range of clinical symptoms such as cardiomyopathy, neuropathy, carpal tunnel syndrome, and GI complications. Without treatment, hATTR leads to progressive disease and can ultimately lead to heart failure. hATTR disproportionately affects individuals of African descent; the estimated prevalence of hATTR among Black individuals in the US is 3.4%. Unfortunately, hATTR is often underdiagnosed and misdiagnosed because many symptoms of the disease overlap with other cardiac conditions. Due to the progressive nature of the disease, multi-systemic manifestations that can lead to a shortened lifespan, and the availability of free genetic testing and promising FDA-approved therapies that enhance treatability, early identification of individuals with a pathogenic hATTR variant is important, as this can significantly impact medical management for patients and their relatives. Furthermore, recent literature suggests that TTR genetic testing should be performed in all patients with suspicion of TTR-related cardiomyopathy, regardless of age, and that follow-up with genetic counseling services is recommended. Relatives of patients with hATTR benefit from genetic testing because testing can identify carriers early and allow relatives to receive regular screening and management. Despite the striking prevalence of hATTR among Black individuals, hATTR remains underdiagnosed in this patient population, and germline genetic testing for hATTR in Black individuals seems to be underrepresented, though the reasons for this have not yet been brought to light. Historically, Black patients experience a number of barriers to seeking healthcare that has been hypothesized to perpetuate the underdiagnosis of hATTR, such as lack of access and mistrust of healthcare professionals. Prior research has described a myriad of factors that shape an individual’s decision about whether to pursue presymptomatic genetic testing for a familial pathogenic variant, such as family closeness and communication, family dynamics, and a desire to inform other family members about potential health risks. This study explores these factors through 10 in-depth interviews with patients with hATTR about what factors may be contributing to the underdiagnosis of hATTR in the Black population. Participants were selected from the Emory University Amyloidosis clinic based on having a molecular diagnosis of hATTR. Interviews were recorded and transcribed verbatim, then coded using MAXQDA software. Thematic analysis was completed to draw commonalities between participants. Upon preliminary analysis, several themes have emerged. Barriers identified include i) Misdiagnosis and a prolonged diagnostic odyssey, ii) Family communication and dynamics surrounding health issues, iii) Perceptions of healthcare and one’s own health risks, and iv) The need for more intimate provider-patient relationships and communication. Overall, this study gleaned valuable insight from members of the Black community about possible factors contributing to the underdiagnosis of hATTR, as well as potential solutions to go about resolving this issue.

Keywords: cardiac amyloidosis, heart failure, TTR, genetic testing

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30 Comparative Study of Amyloidogenic Potential of AgNO3 and Freund's Adjuvant (AF) with That of Vitamin Free Casein, on Spatio-Temporal Pattern of Experimental Amyloidosis in Mice

Authors: Alireza Javed, Keivan Jamshidi

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Reactive amyloidosis is a condition that complicates a long list of chronic inflammation, chronic infectious, malignant, and hereditary disorders. In the present study the potential effects of two amyloidogenic substances: ie. AgNO3 and Freund's Adjuvant (AF) with that of vitamin free casein, on spatio-temporal pattern of experimental amyloidosis in mice, were compared. For this purpose, a total of 40 male Swees mice, obtained from Pasteur Institute Tehran, after being weighted were randomly divided into 4 groups including 2 treatments, 1 control (vitamin free casein) and 1 positive control (normal saline). At the end of 3rd, 5th and 7th weeks of experiment 3 mice were randomly selected and euthnised. Spleen sample of each animal obtained and preserved in 10% neutral buffer formalin. Sample were then processed through different stages of dehydration, clearing and impregnation and finally embedded in paraffin blocks. Sections of 5µm thickness then cut and stained by alkaline Congo red techniques. Spleen weights and the data obtained from the microscopic quantitative analysis did show no significant differences between groups A and B, A and C, and B and C. However, significant differences were observed between groups A and D, B and D, and C and D respectively. It is concluded that two compounds ie; AgNO3 and Freund's Adjuvant have the same potential, as does vitamin free casein have, in spatio – temporal pattern of experimental amyloidosis in mice.

Keywords: amyloidosis, mice, AgNO3, Freund's Adjuvant

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29 High-Dimensional Single-Cell Imaging Maps Inflammatory Cell Types in Pulmonary Arterial Hypertension

Authors: Selena Ferrian, Erin Mccaffrey, Toshie Saito, Aiqin Cao, Noah Greenwald, Mark Robert Nicolls, Trevor Bruce, Roham T. Zamanian, Patricia Del Rosario, Marlene Rabinovitch, Michael Angelo

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Recent experimental and clinical observations are advancing immunotherapies to clinical trials in pulmonary arterial hypertension (PAH). However, comprehensive mapping of the immune landscape in pulmonary arteries (PAs) is necessary to understand how immune cell subsets interact to induce pulmonary vascular pathology. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to interrogate the immune landscape in PAs from idiopathic (IPAH) and hereditary (HPAH) PAH patients. Massive immune infiltration in I/HPAH was observed with intramural infiltration linked to PA occlusive changes. The spatial context of CD11c+DCs expressing SAMHD1, TIM-3 and IDO-1 within immune-enriched microenvironments and neutrophils were associated with greater immune activation in HPAH. Furthermore, CD11c-DC3s (mo-DC-like cells) within a smooth muscle cell (SMC) enriched microenvironment were linked to vessel score, proliferating SMCs, and inflamed endothelial cells. Experimental data in cultured cells reinforced a causal relationship between neutrophils and mo-DCs in mediating pulmonary arterial SMC proliferation. These findings merit consideration in developing effective immunotherapies for PAH.

Keywords: pulmonary arterial hypertension, vascular remodeling, indoleamine 2-3-dioxygenase 1 (IDO-1), neutrophils, monocyte-derived dendritic cells, BMPR2 mutation, interferon gamma (IFN-γ)

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28 Evaluation of Brca1/2 Mutational Status among Algerian Familial Breast Cancer

Authors: Arab M., Ait Abdallah M., Zeraoulia N., Boumaza H., Aoutia M., Griene L., Ait Abdelkader B.,

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breast and ovarian cancer are respectively the first and fourth leading causes of cancer among women in Algeria. A family story of cancer in the most important risk factor, and in most cases of families with breast and /or ovarian cancer, the pattern of cancer family can be attributed to mutation in BRCA1/2genes. objectibes: the aim of our study in to investigate the spectrum of BRCA1/2 germiline mutation in familial breast and /or ovarian cancer and to determine the prevalence and the nature of BRCA1/2mutation in Algeria methods: we deremined the prevalence of BRCA1/2 mutation within a cohort of 161 probands selected according the eisinger score double stranded sanger sequencing of all coding exons of BRCA1/2including flanking intronic region were performed results: we identified a total of 23 distinct deleterious mutations (class5) 12 differents mutations in BRCA1(52%) and 11 in BRCA2(48%). 78% (18/23) were protein truncating and 22%(5/23) missens mutations.3 novel deleterious mutations have been identified, which have not been described in public mutation database. one new mutation were found in two unrelated patients. the overall mutation detection rate in our study is 28,5%(46/161).more over, an UVS c7783 located in BRCA2 is found in two unrelated probands and segregate in the 02 families/ conclusion: our results sugget of large spectrum of BRCA1/2 mutation in Algerian breast/ovarian cancer family. The nature and prevalence of BRCA1/2mutation in algerian families are ongoing in a larger study, 80 probands are to day under investigation. This study which may therefore identify the genetic particularity of Algerian breast /ovarian cancer.

Keywords: BRCA1/2 mutations, hereditary breast cancer, algerian women, prvalence

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27 Prevalence of Lupus Glomerulonephritis in Renal Biopsies in an Eastern Region of the Arab World

Authors: M. Fayez Al Homsi, Reem Al Homsi

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Renal disease is a major cause of morbidity and mortality. Glomerular diseases make a small portion of the renal disease. Lupus glomerulonephritis (GN) is the commonest among the GN of systemic diseases. More than a hundred and eighty-eight consecutive renal biopsies are performed and evaluated for clinically suspected glomerular diseases over a period of two years. As in a standard practice after receiving the ultrasound-guided renal biopsies, the fresh biopsy is divided to three parts, one part is frozen for immunofluorescence evaluation, the second part is placed in 4% glutaraldehyde for electron microscopic evaluation, and the third part is placed in 10% buffered formalin for light microscopic evaluation. Primary glomerular diseases are detected in 83 biopsies; glomerulonephritis (GN) of systemic diseases are identified in 88, glomerular lesions in vascular diseases in 3, glomerular lesions in metabolic diseases in 7, hereditary nephropathies in 2, end-stage kidney in 2, and glomerular lesions in transplantation in 3 biopsies. Among the primary lesions, focal segmental glomerulosclerosis (28) and mesangial proliferative GN (26) were the most common. Lupus GN (67) and Ig A nephropathy (20) were the most common of the GN of systemic diseases. Lupus nephritis biopsies included one biopsy diagnosed as class 1 (normal), 17 biopsies class 2 (mesangial proliferation), 5 biopsies class 3 (focal proliferative GN), 39 biopsies class 4 diffuse proliferative GN), 3 biopsies class 5 (membranous GN), and 2 biopsies class 6 (crescentic GN). Lupus GN is the most common among GN of systemic diseases. While diabetes is very common here, diabetic GN (3 biopsies) is not as common as might one expects. Most likely this is due to sampling and reluctance on part of nephrologists and patients in sampling the kidney in diabetes mellitus.

Keywords: diabetes, glomerulonephritis, lupus, mesangial proliferation, nephropathy

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26 In silico Analysis of a Causative Mutation in Cadherin-23 Gene Identified in an Omani Family with Hearing Loss

Authors: Mohammed N. Al Kindi, Mazin Al Khabouri, Khalsa Al Lamki, Tommasso Pappuci, Giovani Romeo, Nadia Al Wardy

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Hereditary hearing loss is a heterogeneous group of complex disorders with an overall incidence of one in every five hundred newborns presented as syndromic and non-syndromic forms. Cadherin-related 23 (CDH23) is one of the listed deafness causative genes. CDH23 is found to be expressed in the stereocilia of hair cells and the retina photoreceptor cells. Defective CDH23 has been associated mostly with prelingual severe-to-profound sensorineural hearing loss (SNHL) in either syndromic (USH1D) or non-syndromic SNHL (DFNB12). An Omani family diagnosed clinically with severe-profound sensorineural hearing loss was genetically analysed by whole exome sequencing technique. A novel homozygous missense variant, c.A7451C (p.D2484A), in exon 53 of CDH23 was detected. One hundred and thirty control samples were analysed where all were negative for the detected variant. The variant was analysed in silico for pathogenicity verification using several mutation prediction software. The variant proved to be a pathogenic mutation and is reported for the first time in Oman and worldwide. It is concluded that in silico mutation prediction analysis might be used as a useful molecular diagnostics tool benefiting both genetic counseling and mutation verification. The aspartic acid 2484 alanine missense substitution might be the main disease-causing mutation that damages CDH23 function and could be used as a genetic hearing loss marker for this particular Omani family.

Keywords: Cdh23, d2484a, in silico, Oman

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25 Egalitarianism and Social Stratification: An Overview of the Caste System among the Southern Muslims of Sri Lanka

Authors: Mohamed Faslan

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This paper describes how caste-based differentiation functions among the Southern Muslims of Sri Lanka despite Islamic egalitarian principles. Such differences are not promoted by religious teachings, mosques, or the various Islamic religious denominations. Instead, it underpins a hereditary, hierarchical stratification in social structure. Since Islam is against social stratification and promotes egalitarianism, what are the persuasive social structures that organize the existing caste system among Southern Muslims? To answer this puzzle, this paper discusses and analyses the caste system under these five subsections: ancestry; marriage; geography; mosque ownership or trustees; and occupation. The study of caste in Sri Lanka is generally compartmentalized into separate Sinhala and Tamil systems. Most caste studies have focused on the characteristics, upward mobility, or discrimination of specific castes in relation to other castes within ethnic systems. As an operational definition, in this paper, by “southern” or the south of Sri Lanka, I refer to the Kalutara, Galle and Matara Districts. This research was conducted in these three districts, and the respondents were selected purposively. Community history interviews were used as a tool for collecting information, and grounded theory used for analysis. Caste stratification among the Southern Muslims of Sri Lanka is directly connected to whether they are descended from Arab or South Indian ancestors. Arab ancestors are considered upper caste and South Indian ancestors are considered lower caste. Endogamy is the most serious driving factor keeping caste system functioning among Muslims while the other factors—geography, mosques, and occupations—work as supporting factors.

Keywords: caste, social stratification, Sri Lanka Muslims, endogamy

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24 Sustainable Development: Soil Conservation with Cultivation of Cassava (Manihot esculenta) Based on Local Wisdom

Authors: Adiyasa Muda Zannatan

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Cassava (Manihot esculenta) is a plant originating from Brazil. Cassava plants categorized as sixth major food in the world after wheat, rice, corn and potatoes. It has been cultivated on hilly land for 97 years since 1918 at Cireundeu village, West Java Province, Indonesia. Cireundeu traditional village located in the mountain valleys and has a hilly slope up to 38%. Cassava is used as the primary food in that area. Uniquely, Cassava productivity is stable and continues until now. The assessment of soil quality is taking soil samples in the area and analysis the soil in laboratory. The result of analysis that soil in the area is not degraded because it has optimum nutrient, organic matter, and high value of cation exchange capacity in soil even though it has been cultivated in scarp with high slope. Commonly, soil on scarp with high slope has a high rate erosion and poor nutrient. It proved that cassava is able to be an alternative technique of soil conservation in the areas that have a high slope. Beside that, cassava can be utilized as a plant food, feed, fertilizer, and energy. With the utilization of Cassava, the target of Sustainable Development Goals (SDG's) will be achieved with consideration three important components include economy, social, and environment. In economy, Cassava can to be the commercial product like processed food, feed, and alternative energy. In social, it will increase social welfare and will be hereditary. And for environment, Cassava prevents soil from erosion and keeps soil quality.

Keywords: Cassava, local wisdom, conservation, soil quality, sustainable

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23 Mutation Profiling of Paediatric Solid Tumours in a Cohort of South African Patients

Authors: L. Lamola, E. Manolas, A. Krause

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Background: The incidence of childhood cancer incidence is increasing gradually in low-middle income countries, such as South Africa. Globally, there is an extensive range of familial- and hereditary-cancer syndromes, where underlying germline variants increase the likelihood of developing cancer in childhood. Next-Generation Sequencing (NGS) technologies have been key in determining the occurrence and genetic contribution of germline variants to paediatric cancer development. We aimed to design and evaluate a candidate gene panel specific to inherited cancer-predisposing genes to provide a comprehensive insight into the contribution of germline variants to childhood cancer. Methods: 32 paediatric patients (aged 0-18 years) diagnosed with a malignant tumour were recruited, and biological samples were obtained. After quality control, DNA was sequenced using an ion Ampliseq 50 candidate gene panel design and Ion Torrent S5 technologies. Sequencing variants were called using Ion Torrent Suite software and were subsequently annotated using Ion Reporter and Ensembl's VEP. High priority variants were manually analysed using tools such as MutationTaster, SIFT-INDEL and VarSome. Putative identified candidates were validated via Sanger Sequencing. Results: The patients studied had a variety of cancers, the most common being nephroblastoma (13), followed by osteosarcoma (4) and astrocytoma (3). We identified 10 pathogenic / likely pathogenic variants in 10 patients, most of which were novel. Conclusions: According to the literature, we expected ~10% of our patient population to harbour pathogenic or likely pathogenic germline variants, however, we reported about 3 times (~30%) more than we expected. Majority of the identified variants are novel; this may be because this is the first study of its kind in an understudied South African population.

Keywords: Africa, genetics, germline-variants, paediatric-cancer

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22 Influence of Genetic Counseling in Family Dynamics in Patients with Deafness in Merida, Yucatán, Mexico

Authors: Damaris Estrella Castillo, Zacil ha Vilchis Zapata, Leydi Peraza Gómez

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Hearing loss is an etiologically heterogeneous condition, where almost 60% is genetic in origin, 20% is due to environmental factors, and 20% have unknown causes. However, it is now known that the gene, GJB2, which encodes the connexin 26 protein, accounts for a large percentage of non-syndromic genetic hearing loss, and variants in this gene have been identified to be a common cause of hereditary hearing loss in many populations. The literature reports that the etiology in deafness helps improve family functioning but low-income countries this is difficult. Therefore, it is difficult to contribute the right of families to know about the genetic risk in future pregnancies as well as determining the certainty of being a carrier or affected. In order to assess the impact of genetic counseling and the functionality, 100 families with at least one child with profound hearing loss, were evaluated by specialists in audiology, clinical genetics and psychology. Targeted mutation analysis for one of the two known large deletions of upstream of GJB2/GJB6 gene (35delG; and including GJB2 regulatory sequences and GJB6) were performed in patients with diagnosis of non-syndromic hearing loss. Genetic counseling was given to all parents and primary caregivers, and APGAR family test was applied before and after the counseling. We analyzed a total of 300 members (children, parents) to determine the presence of the GJB2 gene mutation. Twelve patients (carriers and affected) were positive for the mutation, from 5 different families. The subsequent family APGAR testing and genetic counseling, showed that 14% perceived their families as functional, 62 % and 24 % moderately functional dysfunctional. This shows the importance of genetic counseling in the perception of family function that can directly impact the quality of life of these families.

Keywords: family dynamics, deafness, APGAR, counseling

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21 Long-Term Cohort of Patients with Beta Thalassemia; Prevailing Role of Serum Ferritin Levels in Hypocalcemia and Growth Retardation

Authors: Shervin Rashidinia, Sara Shahmoradi, Seyyed Shahin Eftekhari, Mohsen Talebizadeh, Mohammad Saleh Sadeghi

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Background: Beta-thalassemia Major (BTM) is a kind of hereditary hemolytic anemia which depended on regular monthly blood transfusion. However, iron deposition into the organs leads to multi-organ damage. The present study is the first study which aimed to evaluate the average of five-years serum ferritin level and compared by the prevalence of short stature and hypocalcemia. Materials/Methods: A cross-sectional retrospective study which a total of 140 patients with beta-thalassemia who were referred to Qom Thalassemia Clinic between February 2011 and July 2016 were enrolled to be reviewed. The exclusion criteria were consisting of incomplete medical records, diagnosis less than 2-years-ago and the blood transfusion less than every 4 weeks. The data including age, gender, weight, height, age of initial blood transfusion, age of initial chelation therapy, ferritin, and calcium were collected and analysis by SPSS version 24. Results: A total of 140 patients were enrolled. Of them, 75 (53.4%) were female. The mean age of the patients was 13.4±4.6 years.The mean age of initial diagnosis was 20.2±7.4 months. Hypocalcemia and short stature were occurred in 41 (29.3%) and 37 (26.4%) patients, respectively. The mean five-years serum ferritin level was significantly higher in the patients with short stature and hypocalcemia (P<0.0001). However, rise in serum ferritin level significantly increases the risk of short-stature and hypocalcemia (1.0004- and 1.0029 fold, respectively). Conclusion: We demonstrated that prevalence of short stature and hypocalcemia were significantly higher in the BTM.However, ferritin significantly increases the risk of short stature and hypocalcemia.

Keywords: beta-thalassemia, ferritin, growth retardation, hypocalcemia

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20 The Nexus of Federalism and Economic Development: A Politico-Economic Analysis of Balochistan, Pakistan

Authors: Rameesha Javaid

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Balochistan, the largest landmass named after and dominated by the 55% Baloch population, which has had a difficult anti-center history like their brothers the Kurds of Middle East, reluctantly acceded to Pakistan in 1947. The region, which attained the status of a province after two decades of accession, has lagged behind in social development and economic growth as compared to the other three federating units. The province has seen the least financial autonomy and administrative decentralization both in autocratic and democratic dispensations under geostrategic and security considerations. Significant corrections have been recently made in the policy framework through changing the formula for intra-provincial National Finance Award, curtailing the number of subjects under federal control, and reactivating the Council of Common Interests. Yet policymaking remains overwhelmingly bureaucratic under a weak parliamentary oversight. The provincial coalition governments are unwieldy and directionless. The government machinery has much less than the optimal capability, character, integrity, will, and opportunity to perform. Decentralization further loses its semblance in the absence of local governments for long intervals and with the hold of hereditary tribal chiefs. Increased allocations failed to make an impact in the highest per capita cost environment due to long distances and scattered settlements. Decentralization, the basic ingredient of federalism has remained mortgaged to geo-strategic factors, internal security perceptions, autocratic and individualistic styles of governments, bureaucratic policymaking structures, bad governance, non-existent local governments, and feudalistic tribal lords. This suboptimal federalism speaks for the present underdevelopment in Balochistan and will earmark the milestones in the future.

Keywords: Balochistan, economic development, federalism, political economy

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19 The Effect of Physical Guidance on Learning a Tracking Task in Children with Cerebral Palsy

Authors: Elham Azimzadeh, Hamidollah Hassanlouei, Hadi Nobari, Georgian Badicu, Jorge Pérez-Gómez, Luca Paolo Ardigò

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Children with cerebral palsy (CP) have weak physical abilities and their limitations may have an effect on performing everyday motor activities. One of the most important and common debilitating factors in CP is the malfunction in the upper extremities to perform motor skills and there is strong evidence that task-specific training may lead to improve general upper limb function among this population. However, augmented feedback enhances the acquisition and learning of a motor task. Practice conditions may alter the difficulty, e.g., the reduced frequency of PG could be more challenging for this population to learn a motor task. So, the purpose of this study was to investigate the effect of physical guidance (PG) on learning a tracking task in children with cerebral palsy (CP). Twenty-five independently ambulant children with spastic hemiplegic CP aged 7-15 years were assigned randomly to five groups. After the pre-test, experimental groups participated in an intervention for eight sessions, 12 trials during each session. The 0% PG group received no PG; the 25% PG group received PG for three trials; the 50% PG group received PG for six trials; the 75% PG group received PG for nine trials; and the 100% PG group, received PG for all 12 trials. PG consisted of placing the experimenter's hand around the children's hand, guiding them to stay on track and complete the task. Learning was inferred by acquisition and delayed retention tests. The tests involved two blocks of 12 trials of the tracking task without any PG being performed by all participants. They were asked to make the movement as accurate as possible (i.e., fewer errors) and the number of total touches (errors) in 24 trials was calculated as the scores of the tests. The results showed that the higher frequency of PG led to more accurate performance during the practice phase. However, the group that received 75% PG had significantly better performance compared to the other groups in the retention phase. It is concluded that the optimal frequency of PG played a critical role in learning a tracking task in children with CP and likely this population may benefit from an optimal level of PG to get the appropriate amount of information confirming the challenge point framework (CPF), which state that too much or too little information will retard learning a motor skill. Therefore, an optimum level of PG may help these children to identify appropriate patterns of motor skill using extrinsic information they receive through PG and improve learning by activating the intrinsic feedback mechanisms.

Keywords: cerebral palsy, challenge point framework, motor learning, physical guidance, tracking task

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18 Communicating Through Symbolisms in Anthropoligical Medicine with Reference to Traditional Performances of Wayang Kulit, Main Puteri and Kuda Kepang

Authors: M. G. Nasuruddin, S. Ishak

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In anthropological medicine (traditional therapeutic healing) symbolic interface are used to connect with the cognitive and metacognitive mechanisms to activate conscious and unconscious response of patients or other recipients. At the same time they are used to communicate with the inhabitants of the nether world to whom are ascribed almost all cases of psychosomatic illness. The symbols, which are cultural specific, are divided into verbal and non-verbal forms of communication. The verbal forms are chanting of mantra and doa and the invocation to invoke the spirits while the non-verbal ones are the physical materials such as the offerings, props and decorative elements, music, movements, olfactory sensation and the performance space. The process of communication through these symbols is affected by the Shaman who is a link or intermediary between the healer (Shaman) and the patients and between the healer and the spirits of the nether world. The paper also examines the scientific perspective of the traditional healing through the use of these symbols. The response to these symbols as external stimuli is embedded in the genes that are linked to the hereditary factor in the person’s DNA. When the patients are tuned in to external stimuli such as music, chanting and singing (sonic orders), it can triggers a response from the brain, which may activate its inner pharmacy by releasing drugs such as dopamine and/or opiodsto ameliorate pain and counter depression, anxiety and create a feel good feeling. These symbols act like placebo, evoking the power of the mind over the body and triggering the innate self-healing energy. At the same time they could also be used as nocebo, for example black magic, which has the opposite effect of placebo. In whatever capacity they operate these symbols, which are either visual or auditory, is an integral part of anthropological medicine. For they communicate and conjure emotional responses that are conducive to healing by activating the internal brain pharmacy.

Keywords: communication, healing, placebo, nacebo, symbol

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17 Post-Operative Pain Management in Ehlers-Danlos Hypermobile-Type Syndrome Following Wisdom Teeth Extraction: A Case Report and Literature Review

Authors: Aikaterini Amanatidou

Abstract:

We describe the case of a 20-year-old female patient diagnosed with Ehlers-Danlos Syndrome (EDS) who was scheduled to undergo a wisdom teeth extraction in outpatient surgery. EDS is a hereditary connective tissue disorder characterized by joint hypermobility, skin hyper-extensibility, and vascular and soft tissue fragility. There are six subtypes of Ehlers-Danlos, and in our case, the patient had EDS hyper-mobility (HT) type disorder. One important clinical feature of this syndrome is chronic pain, which is often poorly understood and treated. Our patient had a long history of articular and lumbar pain when she was diagnosed. She was prescribed analgesic treatment for acute and neuropathic pain and had multiple sessions of psychotherapy and physiotherapy to ease the pain. Unfortunately, her extensive medical history was underrated by our anesthetic team, and no further measures were taken for the operation. Despite an uneventful intra-operative phase, the patient experienced several episodes of hyperalgesia during the immediate post-operative care. Management of pain was challenging for the anesthetic team: initial opioid treatment had only a temporary effect and a paradoxical reaction after a while. Final pain relief was eventually obtained with psycho-physiologic treatment, high doses of ketamine, and patient-controlled analgesia infusion of morphine-ketamine-dehydrobenzperidol. We suspected an episode of Opioid-Induced hyperalgesia. This case report supports the hypothesis that anti-hyperalgesics such as ketamine as well as lidocaine, and dexmedetomidine should be considered intra-operatively to avoid opioid-induced hyperalgesia and may be an alternative solution to manage complex chronic pain like others in neuropathic pain syndromes.

Keywords: Ehlers-Danlos, post-operative management, hyperalgesia, opioid-induced hyperalgesia, rare disease

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16 Characterization of Bovine SERPIN- Alpha-1 Antitrypsin (AAT)

Authors: Sharique Ahmed, Khushtar Anwar Salman

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Alpha-1-antitrypsin (AAT) is a major plasma serine protease inhibitor (SERPIN). Hereditary AAT deficiency is one of the common diseases in some part of the world. AAT is mainly produced in the liver and functions to protect the lung against proteolytic damage (e.g., from neutrophil elastase) acting as the major inhibitor for neutrophil elastase. α (1)-Antitrypsin (AAT) deficiency is an under recognized genetic condition that affects approximately 1 in 2,000 to 1 in 5,000 individuals and predisposes to liver disease and early-onset emphysema. Not only does α-1-antitrypsin deficiency lead to disabling syndrome of pulmonary emphysema, there are other disorders too which include ANCA (antineutrophilic cytoplasmic antibody) positive Wegener's granulomatosis, diffuse bronchiectasis, necrotizing panniculitis in α-1-antitrypsin phenotype (S), idiopathic pulmonary fibrosis and steroid dependent asthma. Augmentation therapy with alpha-1 antitrypsin (AAT) from human plasma has been available for specific treatment of emphysema due to AAT deficiency. Apart from this several observations have also suggested a role for endogenous suppressors of HIV-1, alpha-1 antitrypsin (AAT) has been identified to be one of those. In view of its varied important role in humans, serum from a mammalian source was chosen for the isolation and purification. Studies were performed on the homogeneous fraction. This study suggests that the buffalo serum α-1-antritrypsin has characteristics close to ovine, dog, horse and more importantly to human α-1-antritrypsin in terms of its hydrodynamic properties such as molecular weight, carbohydrate content, etc. The similarities in the hydrodynamic properties of buffalo serum α-1-antitrypsin with other sources of mammalian α-1-antitrypsin mean that it can be further studied and be a potential source for "augmentation therapy", as well as a source of AAT replacement therapy to raise serum levels above the protective threshold. Other parameters like the amino acid sequence, the effect of denaturants, and the thermolability or thermostability of the inhibitor will be the interesting basis of future studies on buffalo serum alpha-1 antitrypsin (AAT).

Keywords: α-1-antitrypsin, augmentation therapy , hydrodynamic properties, serine protease inhibitor

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15 New Experiences into Pancreatic Disease Science

Authors: Nadia Akbarpour

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Pancreatic ductal adenocarcinoma is a forceful and obliterating illness, which is portrayed by intrusiveness, fast movement, and significant protection from treatment. Advances in neurotic arrangement and malignant growth hereditary qualities have worked on our illustrative comprehension of this infection; be that as it may, significant parts of pancreatic disease science remain ineffectively comprehended. A superior comprehension of pancreatic disease science should lead the way to more viable medicines. In the course of the most recent couple of years, there have been significant advances in the sub-atomic and organic comprehension of pancreatic malignancy. This included comprehension of the genomic intricacy of the illness, the job of pancreatic malignant growth undifferentiated organisms, the importance of the growth microenvironment, and the one-of-a-kind metabolic transformation of pancreas disease cells to acquire supplements under hypoxic climate. Endeavors have been made towards the advancement of the practical answer for its treatment with compelled achievement due to its complicated science. It is grounded that pancreatic malignancy undifferentiated cells (CSCs), yet present in a little count, contribute extraordinarily to PC inception, movement, and metastasis. Standard chemo and radiotherapeutic choices, notwithstanding, grow general endurance, the connected aftereffects are a huge concern. In the midst of the latest decade, our understanding with regards to atomic and cell pathways engaged with PC and the job of CSCs in its movement has expanded massively. By and by, the center is to target CSCs. The natural items have acquired a lot of thought as of late as they, generally, sharpen CSCs to chemotherapy and target atomic flagging engaged with different cancers, including PC. Some arranged investigations have demonstrated promising outcomes recommending that assessments in this course bring a ton to the table for the treatment of PC. Albeit preclinical investigations uncovered the significance of natural items in lessening pancreatic carcinoma, restricted examinations have been led to assess their part in centers. The current survey gives another knowledge to late advances in pancreatic malignancy science, treatment, and the current status of natural items in its expectation.

Keywords: pancreatic, genomic, organic, cancer

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14 The Effects of a Hippotherapy Simulator in Children with Cerebral Palsy: A Pilot Study

Authors: Canan Gunay Yazici, Zubeyir Sarı, Devrim Tarakci

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Background: Hippotherapy considered as global techniques used in rehabilitation of children with cerebral palsy as it improved gait pattern, balance, postural control, balance and gross motor skills development but it encounters some problems (such as the excess of the cost of horses' care, nutrition, housing). Hippotherapy simulator is being developed in recent years to overcome these problems. These devices aim to create the effects of hippotherapy made with a real horse on patients by simulating the movements of a real horse. Objectives: To evaluate the efficacy of hippotherapy simulator on gross motor functions, sitting postural control and dynamic balance of children with cerebral palsy (CP). Methods: Fourteen children with CP, aged 6–15 years, seven with a diagnosis of spastic hemiplegia, five of diplegia, two of triplegia, Gross Motor Function Classification System level I-III. The Horse Riding Simulator (HRS), including four-speed program (warm-up, level 1-2-3), was used for hippotherapy simulator. Firstly, each child received Neurodevelopmental Therapy (NDT; 45min twice weekly eight weeks). Subsequently, the same children completed HRS+NDT (30min and 15min respectively, twice weekly eight weeks). Children were assessed pre-treatment, at the end of 8th and 16th week. Gross motor function, sitting postural control, dynamic sitting and standing balance were evaluated by Gross Motor Function Measure-88 (GMFM-88, Dimension B, D, E and Total Score), Trunk Impairment Scale (TIS), Pedalo® Sensamove Balance Test and Pediatric Balance Scale (PBS) respectively. Unit of Scientific Research Project of Marmara University supported our study. Results: All measured variables were a significant increase compared to baseline values after both intervention (NDT and HRS+NDT), except for dynamic sitting balance evaluated by Pedalo®. Especially HRS+NDT, increase in the measured variables was considerably higher than NDT. After NDT, the Total scores of GMFM-88 (mean baseline 62,2 ± 23,5; mean NDT: 66,6 ± 22,2; p < 0,05), TIS (10,4 ± 3,4; 12,1 ± 3; p < 0,05), PBS (37,4 ± 14,6; 39,6 ± 12,9; p < 0,05), Pedalo® sitting (91,2 ± 6,7; 92,3 ± 5,2; p > 0,05) and Pedalo® standing balance points (80,2 ± 10,8; 82,5 ± 11,5; p < 0,05) increased by 7,1%, 2%, 3,9%, 5,2% and 6 % respectively. After HRS+NDT treatment, the total scores of GMFM-88 (mean baseline: 62,2 ± 23,5; mean HRS+NDT: 71,6 ± 21,4; p < 0,05), TIS (10,4 ± 3,4; 15,6 ± 2,9; p < 0,05), PBS (37,4 ± 14,6; 42,5 ± 12; p < 0,05), Pedalo® sitting (91,2 ± 6,7; 93,8 ± 3,7; p > 0,05) and standing balance points (80,2 ± 10,8; 86,2 ± 5,6; p < 0,05) increased by 15,2%, 6%, 7,3%, 6,4%, and 11,9%, respectively, compared to the initial values. Conclusion: Neurodevelopmental therapy provided significant improvements in gross motor functions, sitting postural control, sitting and standing balance of children with CP. When the hippotherapy simulator added to the treatment program, it was observed that these functions were further developed (especially with gross motor functions and dynamic balance). As a result, this pilot study showed that the hippotherapy simulator could be a useful alternative to neurodevelopmental therapy for the improvement of gross motor function, sitting postural control and dynamic balance of children with CP.

Keywords: balance, cerebral palsy, hippotherapy, rehabilitation

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13 Prevalence of Seropositivity for Cytomegalovirus in Patients with Hereditary Bleeding Diseases in West Azerbaijan of Iran

Authors: Zakieh Rostamzadeh, Zahra Shirmohammadi

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Human cytomegalovirus is a species of the cytomegalovirus family of viruses, which in turn is a member of the viral family known as herpesviridae or herpesviruses. Although they may be found throughout the body, HCMV infections are frequently associated with the salivary glands. HCMV infection is typically unnoticed in healthy people, but can be life-threatening for the immunocompromised such as HIV-infected persons, organ transplant recipients, or newborn infants. After infection, HCMV has an ability to remain latent within the body over long periods. Cytomegalovirus (CMV) causes infection in immunocompromised, hemophilia patients and those who received blood transfusion frequently. This study aimed at determining the prevalence of cytomegalovirus (CMV) antibodies in hemophilia patients. Materials and Methods: A retrospective observational study was carried out in Urmia, North West of Iran. The study population comprised a sample of 50 hemophilic patients born after 1985 and have received blood factors in West Azerbaijan. The exclusion criteria include: drug abusing, high risk sexual contacts, vertical transmission of mother to fetus and suspicious needling. All samples were evaluated with the method of ELISA, with a certain kind of kit and by a certain laboratory. Results: Fifty hemophiliacs from 250 patients registered with Urmia Hemophilia Society were enrolled in the study including 43 (86%) male, and 7 (14%) female. The mean age of patients was 10.3 years, range 3 to 25 years. None of patients had risk factors mentioned above. Among our studied population, 34(68%) had hemophilia A, 1 (2%) hemophilia B, 8 (16%) VWF, 3(6%) factor VII deficiency, 1 (2%) factor V deficiency, 1 (2%) factor X deficiency, 1 (2%). Sera of 50 Hemodialysis patients were investigated for CMV-specific immunoglobulin G (IgG) and IgM. % 91.89 patients were anti-CMV IgG positive and %40.54 was seropositive for anti-CMV IgM. 37.8% patient had serological evidence of reactivation and 2.7% of patients had the primary infection. Discussion: There was no relationship between the antibody titer and: drug abusing, high risk sexual contacts, vertical transmission of mother to fetus and suspicious needling.

Keywords: bioinformatics, biomedicine, cytomegalovirus, immunocompromise

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12 Whole Exome Sequencing in Characterizing Mysterious Crippling Disorder in India

Authors: Swarkar Sharma, Ekta Rai, Ankit Mahajan, Parvinder Kumar, Manoj K Dhar, Sushil Razdan, Kumarasamy Thangaraj, Carol Wise, Shiro Ikegawa M.D., K.K. Pandita M.D.

Abstract:

Rare disorders are poorly understood hence, remain uncharacterized or patients are misdiagnosed and get poor medical attention. A rare mysterious skeletal disorder that remained unidentified for decades and rendered many people physically challenged and disabled for life has been reported in an isolated remote village ‘Arai’ of Poonch district of Jammu and Kashmir. This village is located deep in mountains and the population residing in the region is highly consanguineous. In our survey of the region, 70 affected people were reported, showing similar phenotype, in the village with a population of approximately 5000 individuals. We were able to collect samples from two multi generational extended families from the village. Through Whole Exome sequencing (WES), we identified a rare variation NM_003880.3:c.156C>A NP_003871.1:p.Cys52Ter, which results in introduction of premature stop codon in WISP3 gene. We found this variation perfectly segregating with the disease in one of the family. However, this variation was absent in other family. Interestingly, a novel splice site mutation at position c.643+1G>A of WISP3 gene, perfectly segregating with the disease was observed in the second family. Thus, exploiting WES and putting different evidences together (familial histories and genetic data, clinical features, radiological and biochemical tests and findings), the disease has finally been diagnosed as a very rare recessive hereditary skeletal disease “Progressive Pseudorheumatoid Arthropathy of Childhood” (PPAC) also known as “Spondyloepiphyseal Dysplasia Tarda with Progressive Arthropathy” (SEDT-PA). This genetic characterization and identification of the disease causing mutations will aid in genetic counseling, critically required to curb this rare disorder and to prevent its appearance in future generations in the population. Further, understanding of the role of WISP3 gene the biological pathways should help in developing treatment for the disorder.

Keywords: whole exome sequencing, Next Generation Sequencing, rare disorders

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11 Meniere's Disease and its Prevalence, Symptoms, Risk Factors and Associated Treatment Solutions for this Disease

Authors: Amirreza Razzaghipour Sorkhab

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One of the most common disorders among humans is hearing impairment. This paper provides an evidence base that recovers understanding of Meniere’s disease and highlights the physical and mental health correlates of the disorder. Meniere's disease is more common in the elderly. The term idiopathic endolymphatic hydrops has been attributed to this disease by some in the previous. Meniere’s disease demonstrations a genetic tendency, and a family history is found in 10% of cases, with an autosomal dominant inheritance pattern. The COCH gene may be one of the hereditary factors contributing to Meniere’s disease, and the possibility of a COCH mutation should be considered in patients with Meniere’s disease symptoms. Should be considered Missense mutations in the COCH gene cause the autosomal dominant sensorineural hearing loss and vestibular disorder. Meniere’s disease is a complex, heterogeneous disorder of the inner ear and that is characterized by episodes of vertigo lasting from minutes to hours, fluctuating sensorineural hearing loss, tinnitus, and aural fullness. The existing evidence supports the suggestion that age and sleep disorder are risk factors for Meniere's disease. Many factors have been reported to precipitate the progress of Menier, including endolymphatic hydrops, immunology, viral infection, inheritance, vestibular migraine, and altered intra-labyrinthine fluid dynamics. Although there is currently no treatment that has a proven helpful effect on hearing levels or on the long-term evolution of the disease, however, in the primary stages, the hearing may improve among attacks, but a permanent hearing loss occurs in the majority of cases. Current publications have proposed a role for the intratympanic use of medicine, mostly aminoglycosides, for the control of vertigo. more than 85% of patients with Meniere's disease are helped by either changes in lifestyle and medical treatment or minimally aggressive surgical procedures such as intratympanic steroid therapy, intratympanic gentamicin therapy, and endolymphatic sac surgery. However, unilateral vestibular extirpation methods (intratympanic gentamicin, vestibular nerve section, or labyrinthectomy) are more predictable but invasive approaches to control the vertigo attacks. Medical therapy aimed at reducing endolymph volume, such as low-sodium diet, diuretic use, is the typical initial treatment.

Keywords: meniere's disease, endolymphatic hydrops, hearing loss, vertigo, tinnitus, COCH gene

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10 Congenital Malformations in Neonate Dogs in the Sao Paulo State University Veterinary Hospital, Botucatu, Sao Paulo, Brazil

Authors: Maria Lucia G. Lourenco, Keylla H. N. P. Pereira, Viviane Y. Hibaru, Fabiana F. Souza, Joao C. P. Ferreira, Simone B. Chiacchio, Luiz H. A. Machado

Abstract:

Congenital malformations are organ defects due to genetic or teratogenic causes, which can lead to high mortality in dog litters. This study assessed and described the congenital malformations in newborn dogs. The study included litters attend in the São Paulo State University (UNESP) Veterinary Hospital, Botucatu, Sao Paulo, Brazil. One hundred seventy-eight litters and 803 newborns were evaluated. The occurrence of litters with malformations was 24.7%, and of newborns was 6.7%. Twenty-seven different malformations were registered: anasarca, anal atresia, cleft lip, cleft palate, duplicated right ribcage, equinovarus, exencephaly, gastroschisis, hydrocephaly, lissencephaly, macroglossia, microphthalmia, mitral valve dysplasia, omphalocele, eyelid agenesis, persistent urachus, polydactyly, pulmonary hypoplasia, pulmonary valve stenosis, rectovaginal fistula, agenesis of abdominal muscles, rib hypoplasia, scoliosis, segmental aplasia of the intestines, tricuspid valve dysplasia, unilateral kidney agenesis, and vaginal atresia. 68.7% of newborns died as a result of malformations. The pure breeds with the highest chances of manifesting malformations in contrast with mixed breeds were French Bulldog, Pug, English Bulldog, Rottweiler, German Spitz, Pinscher, Pitbull, Yorkshire Terrier, and Shih-Tzu. Significant values (P<0.05) occurred in races French Bulldogs and Pugs. The causes of congenital disabilities are possibly related to hereditary genetic factors considering that the highest incidence of malformations was observed among purebreds. There as one case of exposure to a teratogenic agent, but no other mothers were exposed to such agents during pregnancy. Two cases of consanguineal breeding between siblings were reported. The mortality rate was high. Genetic breeding programs for reproduction, avoiding consanguineous mating, care in choosing parents, and avoiding maternal exposure to teratogenic agents are of utmost importance in reducing dog malformations and consequent mortality.

Keywords: congenital defects, teratogenesis, canine neonatology, newborn puppy

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9 Postmortem Genetic Testing to Sudden and Unexpected Deaths Using the Next Generation Sequencing

Authors: Eriko Ochiai, Fumiko Satoh, Keiko Miyashita, Yu Kakimoto, Motoki Osawa

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Sudden and unexpected deaths from unknown causes occur in infants and youths. Recently, molecular links between a part of these deaths and several genetic diseases are examined in the postmortem. For instance, hereditary long QT syndrome and Burgada syndrome are occasionally fatal through critical ventricular tachyarrhythmia. There are a large number of target genes responsible for such diseases, the conventional analysis using the Sanger’s method has been laborious. In this report, we attempted to analyze sudden deaths comprehensively using the next generation sequencing (NGS) technique. Multiplex PCR to subject’s DNA was performed using Ion AmpliSeq Library Kits 2.0 and Ion AmpliSeq Inherited Disease Panel (Life Technologies). After the library was constructed by emulsion PCR, the amplicons were sequenced 500 flows on Ion Personal Genome Machine System (Life Technologies) according to the manufacture instruction. SNPs and indels were analyzed to the sequence reads that were mapped on hg19 of reference sequences. This project has been approved by the ethical committee of Tokai University School of Medicine. As a representative case, the molecular analysis to a 40 years old male who received a diagnosis of Brugada syndrome demonstrated a total of 584 SNPs or indels. Non-synonymous and frameshift nucleotide substitutions were selected in the coding region of heart disease related genes of ANK2, AKAP9, CACNA1C, DSC2, KCNQ1, MYLK, SCN1B, and STARD3. In particular, c.629T-C transition in exon 3 of the SCN1B gene, resulting in a leu210-to-pro (L210P) substitution is predicted “damaging” by the SIFT program. Because the mutation has not been reported, it was unclear if the substitution was pathogenic. Sudden death that failed in determining the cause of death constitutes one of the most important unsolved subjects in forensic pathology. The Ion AmpliSeq Inherited Disease Panel can amplify the exons of 328 genes at one time. We realized the difficulty in selection of the true source from a number of candidates, but postmortem genetic testing using NGS analysis deserves of a diagnostic to date. We now extend this analysis to SIDS suspected subjects and young sudden death victims.

Keywords: postmortem genetic testing, sudden death, SIDS, next generation sequencing

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8 Genome Sequencing, Assembly and Annotation of Gelidium Pristoides from Kenton-on-Sea, South Africa

Authors: Sandisiwe Mangali, Graeme Bradley

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Genome is complete set of the organism's hereditary information encoded as either deoxyribonucleic acid or ribonucleic acid in most viruses. The three different types of genomes are nuclear, mitochondrial and the plastid genome and their sequences which are uncovered by genome sequencing are known as an archive for all genetic information and enable researchers to understand the composition of a genome, regulation of gene expression and also provide information on how the whole genome works. These sequences enable researchers to explore the population structure, genetic variations, and recent demographic events in threatened species. Particularly, genome sequencing refers to a process of figuring out the exact arrangement of the basic nucleotide bases of a genome and the process through which all the afore-mentioned genomes are sequenced is referred to as whole or complete genome sequencing. Gelidium pristoides is South African endemic Rhodophyta species which has been harvested in the Eastern Cape since the 1950s for its high economic value which is one motivation for its sequencing. Its endemism further motivates its sequencing for conservation biology as endemic species are more vulnerable to anthropogenic activities endangering a species. As sequencing, mapping and annotating the Gelidium pristoides genome is the aim of this study. To accomplish this aim, the genomic DNA was extracted and quantified using the Nucleospin Plank Kit, Qubit 2.0 and Nanodrop. Thereafter, the Ion Plus Fragment Library was used for preparation of a 600bp library which was then sequenced through the Ion S5 sequencing platform for two runs. The produced reads were then quality-controlled and assembled through the SPAdes assembler with default parameters and the genome assembly was quality assessed through the QUAST software. From this assembly, the plastid and the mitochondrial genomes were then sampled out using Gelidiales organellar genomes as search queries and ordered according to them using the Geneious software. The Qubit and the Nanodrop instruments revealed an A260/A280 and A230/A260 values of 1.81 and 1.52 respectively. A total of 30792074 reads were obtained and produced a total of 94140 contigs with resulted into a sequence length of 217.06 Mbp with N50 value of 3072 bp and GC content of 41.72%. A total length of 179281bp and 25734 bp was obtained for plastid and mitochondrial respectively. Genomic data allows a clear understanding of the genomic constituent of an organism and is valuable as foundation information for studies of individual genes and resolving the evolutionary relationships between organisms including Rhodophytes and other seaweeds.

Keywords: Gelidium pristoides, genome, genome sequencing and assembly, Ion S5 sequencing platform

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7 One Year Follow up of Head and Neck Paragangliomas: A Single Center Experience

Authors: Cecilia Moreira, Rita Paiva, Daniela Macedo, Leonor Ribeiro, Isabel Fernandes, Luis Costa

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Background: Head and neck paragangliomas are a rare group of tumors with a large spectrum of clinical manifestations. The approach to evaluate and treat these lesions has evolved over the last years. Surgery was the standard for the approach of these patients, but nowadays new techniques of imaging and radiation therapy changed that paradigm. Despite advances in treating, the growth potential and clinical outcome of individual cases remain largely unpredictable. Objectives: Characterization of our institutional experience with clinical management of these tumors. Methods: This was a cross-sectional study of patients followed in our institution between 01 January and 31 December 2017 with paragangliomas of the head and neck and cranial base. Data on tumor location, catecholamine levels, and specific imaging modalities employed in diagnostic workup, treatment modality, tumor control and recurrence, complications of treatment and hereditary status were collected and summarized. Results: A total of four female patients were followed between 01 January and 31 December 2017 in our institution. The mean age of our cohort was 53 (± 16.1) years. The primary locations were at the level of the tympanic jug (n=2, 50%) and carotid body (n=2, 50%), and only one of the tumors of the carotid body presented pulmonary metastasis at the time of diagnosis. None of the lesions were catecholamine-secreting. Two patients underwent genetic testing, with no mutations identified. The initial clinical presentation was variable highlighting the decrease of visual acuity and headache as symptoms present in all patients. In one of the cases, loss of all teeth of the lower jaw was the presenting symptomatology. Observation with serial imaging, surgical extirpation, radiation, and stereotactic radiosurgery were employed as treatment approaches according to anatomical location and resectability of lesions. As post-therapeutic sequels the persistence of tinnitus and disabling pain stands out, presenting one of the patients neuralgia of the glossopharyngeal. Currently, all patients are under regular surveillance with a median follow up of 10 months. Conclusion: Ultimately, clinical management of these tumors remains challenging owing to heterogeneity in clinical presentation, the existence of multiple treatment alternatives, and potential to cause serious detriment to critical functions and consequently interference with the quality of life of the patients.

Keywords: clinical outcomes, head and neck, management, paragangliomas

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6 Endocrine Therapy Resistance and Epithelial to Mesenchymal Transition Inhibits by INT3 & Quercetin in MCF7 Cell Lines

Authors: D. Pradhan, G. Tripathy, S. Pradhan

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Objectives: Imperviousness gainst estrogen treatments is a noteworthy reason for infection backslide and mortality in estrogen receptor alpha (ERα)- positive breast diseases. Tamoxifen or estrogen withdrawal builds the reliance of breast malignancy cells on INT3 flagging. Here, we researched the commitment of Quercetin and INT3 motioning in endocrine-safe breast tumor cells. Methods: We utilized two models of endocrine treatments safe (ETR) breast tumor: Tamoxifen-safe (TamR) and long haul estrogen-denied (LTED) MCF7 cells. We assessed the transitory and intrusive limit of these cells by Transwell cells. Articulation of epithelial to mesenchymal move (EMT) controllers and in addition INT3 receptors and targets were assessed by constant PCR and western smudge investigation. Besides, we tried in-vitro hostile to Quercetin monoclonal Antibodies (mAbs) and Gamma Secretase Inhibitors (GSIs) as potential EMT inversion remedial specialists. At last, we created stable Quercetin overexpressing MCF7 cells and assessed their EMT components and reaction to Tamoxifen. Results: We found that ETR cells procured an Epithelial to Mesenchymal move (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we distinguished more elevated amount of INT3 however lower levels of INT1 and INT3 proposing a change to motioning through distinctive INT3 receptors after obtaining of resistance. Against Quercetin monoclonal antibodies and the GSI PF03084014 were powerful in obstructing the Quercetin/INT3 pivot and in part repressing the EMT process. As a consequence of this, cell relocation and attack were weakened and the immature microorganism like populace was essentially decreased. Hereditary hushing of Quercetin and INT3 prompted proportionate impacts. At long last, stable overexpression of Quercetin was adequate to make MCF7 lethargic to Tamoxifen by INT3 initiation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives intrusive conduct. Hostile to Quercetin mAbs and GSI PF03084014 lessen articulation of EMT particles decreasing cell obtrusiveness. Quercetin overexpression instigates Tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and INT3 warrants further clinical Correlation as substantial restorative methodologies in endocrine-safe breast.

Keywords: endocrine, epithelial, mesenchymal, INT3, quercetin, MCF7

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5 Analytical Validity Of A Tech Transfer Solution To Internalize Genetic Testing

Authors: Lesley Northrop, Justin DeGrazia, Jessica Greenwood

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ASPIRA Labs now offers an en-suit and ready-to-implement technology transfer solution to enable labs and hospitals that lack the resources to build it themselves to offer in-house genetic testing. This unique platform employs a patented Molecular Inversion Probe (MIP) technology that combines the specificity of a hybrid capture protocol with the ease of an amplicon-based protocol and utilizes an advanced bioinformatics analysis pipeline based on machine learning. To demonstrate its efficacy, two independent genetic tests were validated on this technology transfer platform: expanded carrier screening (ECS) and hereditary cancer testing (HC). The analytical performance of ECS and HC was validated separately in a blinded manner for calling three different types of variants: SNVs, short indels (typically, <50 bp), and large indels/CNVs defined as multi-exonic del/dup events. The reference set was constructed using samples from Coriell Institute, an external clinical genetic testing laboratory, Maine Molecular Quality Controls Inc. (MMQCI), SeraCare and GIAB Consortium. Overall, the analytical performance showed a sensitivity and specificity of >99.4% for both ECS and HC in detecting SNVs. For indels, both tests reported specificity of 100%, and ECS demonstrated a sensitivity of 100%, whereas HC exhibited a sensitivity of 96.5%. The bioinformatics pipeline also correctly called all reference CNV events resulting in a sensitivity of 100% for both tests. No additional calls were made in the HC panel, leading to a perfect performance (specificity and F-measure of 100%). In the carrier panel, however, three additional positive calls were made outside the reference set. Two of these calls were confirmed using an orthogonal method and were re-classified as true positives leaving only one false positive. The pipeline also correctly identified all challenging carrier statuses, such as positive cases for spinal muscular atrophy and alpha-thalassemia, resulting in 100% sensitivity. After confirmation of additional positive calls via long-range PCR and MLPA, specificity for such cases was estimated at 99%. These performance metrics demonstrate that this tech-transfer solution can be confidently internalized by clinical labs and hospitals to offer mainstream ECS and HC as part of their test catalog, substantially increasing access to quality germline genetic testing for labs of all sizes and resources levels.

Keywords: clinical genetics, genetic testing, molecular genetics, technology transfer

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