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Search results for: eating disorders binge eating disorder

152 Investigating the Neural Heterogeneity of Developmental Dyscalculia

Authors: Fengjuan Wang, Azilawati Jamaludin

Abstract:

Developmental Dyscalculia (DD) is defined as a particular learning difficulty with continuous challenges in learning requisite math skills that cannot be explained by intellectual disability or educational deprivation. Recent studies have increasingly recognized that DD is a heterogeneous, instead of monolithic, learning disorder with not only cognitive and behavioral deficits but so too neural dysfunction. In recent years, neuroimaging studies employed group comparison to explore the neural underpinnings of DD, which contradicted the heterogenous nature of DD and may obfuscate critical individual differences. This research aimed to investigate the neural heterogeneity of DD using case studies with functional near-infrared spectroscopy (fNIRS). A total of 54 aged 6-7 years old of children participated in this study, comprising two comprehensive cognitive assessments, an 8-minute resting state, and an 8-minute one-digit addition task. Nine children met the criteria of DD and scored at or below 85 (i.e., the 16th percentile) on the Mathematics or Math Fluency subtest of the Wechsler Individual Achievement Test, Third Edition (WIAT-III) (both subtest scores were 90 and below). The remaining 45 children formed the typically developing (TD) group. Resting-state data and brain activation in the inferior frontal gyrus (IFG), superior frontal gyrus (SFG), and intraparietal sulcus (IPS) were collected for comparison between each case and the TD group. Graph theory was used to analyze the brain network under the resting state. This theory represents the brain network as a set of nodes--brain regions—and edges—pairwise interactions across areas to reveal the architectural organizations of the nervous network. Next, a single-case methodology developed by Crawford et al. in 2010 was used to compare each case’s brain network indicators and brain activation against 45 TD children’s average data. Results showed that three out of the nine DD children displayed significant deviation from TD children’s brain indicators. Case 1 had inefficient nodal network properties. Case 2 showed inefficient brain network properties and weaker activation in the IFG and IPS areas. Case 3 displayed inefficient brain network properties with no differences in activation patterns. As a rise above, the present study was able to distill differences in architectural organizations and brain activation of DD vis-à-vis TD children using fNIRS and single-case methodology. Although DD is regarded as a heterogeneous learning difficulty, it is noted that all three cases showed lower nodal efficiency in the brain network, which may be one of the neural sources of DD. Importantly, although the current “brain norm” established for the 45 children is tentative, the results from this study provide insights not only for future work in “developmental brain norm” with reliable brain indicators but so too the viability of single-case methodology, which could be used to detect differential brain indicators of DD children for early detection and interventions.

Keywords: brain activation, brain network, case study, developmental dyscalculia, functional near-infrared spectroscopy, graph theory, neural heterogeneity

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151 Restless Leg Syndrome as the Presenting Symptom of Neuroendocrine Tumor

Authors: Mustafa Cam, Nedim Ongun, Ufuk Kutluana

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Introduction: Restless LegsSyndrome (RLS) is a common, under-recognized disorder disrupts sleep and diminishes quality of life (1). The most common conditions highly associated with RLS include renalfailure, iron and folic acid deficiency, peripheral neuropathy, pregnancy, celiacdisease, Crohn’sdiseaseandrarelymalignancy (2).Despite a clear relation between low peripheral iron and increased prevalence and severity of RLS, the prevalence and clinical significance of RLS in iron-deficientanemic populations is unknown (2). We report here a case of RLS due to iron deficiency in the setting of neuroendocrinetumor. Report of Case: A 35 year-old man was referred to our clinic with general weakness, weight loss (10 kg in 2 months)and 2-month history of uncomfortable sensations in his legs with urge to move, partially relieved by movement. The symptoms were presented very day, worsening in the evening; the discomfort forced the patient to getup and walk around at night. RLS was severe, with a score of 22 at the International RLS ratingscale. The patient had no past medical history. The patient underwent a complete set of blood analyses and the following ab normal values were found (normal limitswithinbrackets): hemoglobin 9.9 g/dl (14-18), MCV 70 fL (80-94), ferritin 3,5 ng/mL (13-150). Brain and spinemagnetic resonance imaging was normal. The patient consultated with gastroenterology clinic and gastointestinal systemendoscopy was performed for theetiology of the iron deficiency anemia. After the gastricbiopsy, results allowed us to reach the diagnosis of neuroen docrine tumor and the patient referred to oncology clinic. Discussion: The first important consideration from this case report is that the patient was referred to our clinic because of his severe RLS symptoms dramatically reducing his quality of life. However, our clinical study clearly demonstrated that RLS was not the primary disease. Considering the information available for this patient, we believe that the most likely possibility is that RLS was secondary to iron deficiency, a very well-known and established cause of RLS in theliterature (3,4). Neuroendocrine tumors (NETs) are rare epithelial neoplasms with neuroendocrine differentiation that most commonly originate in the lungs and gastrointestinal tract (5). NETs vary widely in their clinical presentation; symptoms are often nonspecific and can be mistaken for those of other more common conditions (6). 50% of patients with reported disease stage have either regional or distant metastases at diagnosis (7). Accurate and earlier NET diagnosis is the first step in shortening the time to optimal care and improved outcomes for patients (8). The most important message from this case report is that RLS symptoms can sometimes be thesign of a life-threatening condition. Conclusion: Careful and complete collection of clinical and laboratory data should be carried out in RLS patients. Inparticular, if RLS onset coincides with weight loss and iron deficieny anemia, gastricendos copy should be performed. It is known about that malignancy is a rare etiology in RLS patients and to our knowledge; it is the first case with neuro endocrine tumor presenting with RLS.

Keywords: neurology, neuroendocrine tumor, restless legs syndrome, sleep

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150 Effect of Plant Growth Regulators on in vitro Biosynthesis of Antioxidative Compounds in Callus Culture and Regenerated Plantlets Derived from Taraxacum officinale

Authors: Neha Sahu, Awantika Singh, Brijesh Kumar, K. R. Arya

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Taraxacum officinale Weber or dandelion (Asteraceae) is an important Indian traditional herb used to treat liver detoxification, digestive problems, spleen, hepatic and kidney disorders, etc. The plant is well known to possess important phenolic and flavonoids to serve as a potential source of antioxidative and chemoprotective agents. Biosynthesis of bioactive compounds through in vitro cultures is a requisite for natural resource conservation and to provide an alternative source for pharmaceutical applications. Thus an efficient and reproducible protocol was developed for in vitro biosynthesis of bioactive antioxidative compounds from leaf derived callus and in vitro regenerated cultures of Taraxacum officinale using MS media fortified with various combinations of auxins and cytokinins. MS media containing 0.25 mg/l 2, 4-D (2, 4-Dichloro phenoxyacetic acid) with 0.05 mg/l 2-iP [N6-(2-Isopentenyl adenine)] was found as an effective combination for the establishment of callus with 92 % callus induction frequency. Moreover, 2.5 mg/l NAA (α-Naphthalene acetic acid) with 0.5 mg/l BAP (6-Benzyl aminopurine) and 1.5 mg/l NAA showed the optimal response for in vitro plant regeneration with 80 % regeneration frequency and rooting respectively. In vitro regenerated plantlets were further transferred to soil and acclimatized. Quantitative variability of accumulated bioactive compounds in cultures (in vitro callus, plantlets and acclimatized) were determined through UPLC-MS/MS (ultra-performance liquid chromatography-triple quadrupole-linear ion trap mass spectrometry) and compared with wild plants. The phytochemical determination of in vitro and wild grown samples showed the accumulation of 6 compounds. In in vitro callus cultures and regenerated plantlets, two major antioxidative compounds i.e. chlorogenic acid (14950.0 µg/g and 4086.67 µg/g) and umbelliferone (10400.00 µg/g and 2541.67 µg/g) were found respectively. Scopoletin was found to be highest in vitro regenerated plants (83.11 µg/g) as compared to wild plants (52.75 µg/g). Notably, scopoletin is not detected in callus and acclimatized plants, but quinic acid (6433.33 µg/g) and protocatechuic acid (92.33 µg/g) were accumulated at the highest level in acclimatized plants as compared to other samples. Wild grown plants contained highest content (948.33 µg/g) of flavonoid glycoside i.e. luteolin-7-O-glucoside. Our data suggests that in vitro callus and regenerated plants biosynthesized higher content of antioxidative compounds in controlled conditions when compared to wild grown plants. These standardized cultural conditions may be explored as a sustainable source of plant materials for enhanced production and adequate supply of oxidative polyphenols.

Keywords: anti-oxidative compounds, in vitro cultures, Taraxacum officinale, UPLC-MS/MS

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149 Severe Infestation of Laspeyresia Koenigana Fab. and Alternaria Leaf Spot on Azadirachta Indica (Neem)

Authors: Shiwani Bhatnagar, K. K. Srivastava, Sangeeta Singh, Ameen Ullah Khan, Bundesh Kumar, Lokendra Singh Rathore

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From the instigation of the world medicinal plants are treated as part and parcel of human society to fight against diseases. Azadirachta indica (Neem) a herbal plant has been used as an Indian traditional medicine since ages and its products are acknowledged to solve agricultural, forestry and public health related problems, owing to its beneficial medicinal properties. Each part of the neem tree is known for its medicinal property. Bark & leaf extracts of neem have been used to control leprosy, respiratory disorders, constipation and also as blood purifier and a general health tonic. Neem is still regarded as ' rural community dispensary' in India or a tree for solving medical problems. Use of Neem as pesticides for the management of insect pest of agriculture crops and forestry has been seen as a shift in the use of synthetic pesticides to ecofriendly botanicals. Neem oil and seed extracts possess germicidal and anti-bacterial properties which when sprayed on the plant helps in protecting them from foliage pests. Azadirachtin, the main active ingredient found in neem tree, acts as an insect repellent and antifeedant. However the young plants are susceptible to many insect pest and foliar diseases. Recently, in the avenue plantation, planted by Arid Forest Research Institute, Jodhpur, around the premises of IIT Jodhpur, two years old neem plants were found to be severely infested with tip borer Laspeyresia koenigana (Family: Eucosmidae). The adult moth of L. koenigana lays eggs on the tender shoots and the young larvae tunnel into the shoot and feed inside. A small pinhole can be seen at the entrance point, from where the larva enters in to the stem. The severely attached apical shoots exhibit profuse gum exudation resulting in development of a callus structure. The internal feeding causes the stem to wilt and the leaves to dry up from the tips resulting in growth retardation. Alternaria Leaf spot and blight symptoms were also recorded on these neem plants. For the management of tip borer and Alternaria Leaf spot, foliar spray of monocrotophos @0.05% and Dithane M-45 @ 0.15% and powermin @ 2ml/lit were found efficient in managing the insect pest and foliar disease problem. No Further incidence of pest/diseases was noticed.

Keywords: azadirachta indica, alternaria leaf spot, laspeyresia koenigana, management

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148 Head and Neck Extranodal Rosai-Dorfman Disease- Utility of immunohistochemistry

Authors: Beverly Wang

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Background: Rosai-Dorfman disease (RDD), aka sinus histiocytosis with massive lymphadenopathy, is a rare, idiopathic histiocytic proliferative disorder. Although RDD can be seen involving the head and neck lymph nodes, rarely it can affect other extranodal sites. It present 3 unique cases of RDD affecting the nasal cavity, paranasal sinuses, and ear canal. The initial clinical presentation on two cases mimicked a malignant neoplasm. The 3rd case of RDD co-existed with a cholesteatoma of the ear canal. The clinical presentation, histology and immunohistochemical stains, and radiographic findings are discussed. Design: An overview of 3 cases of RDD affected sinonasal cavity and ear canal from UCI Medical Center was conducted. Case 1: A 61 year old male complaining of breathing difficulty presented with bilateral polypoid sinonasal masses and severe nasal obstruction. The masses elevated the nasal floor, and involved the anterior nasal septum to lateral wall. It was endoscopically excised. At intraoperative consultation, frozen section reported a pleomorphic spindle cell neoplasm with scattered large atypical spindle cells, resembling a high grade sarcoma. Case 2: A 46 year old male presented with recurrent bilateral maxillary chronic sinusitis with mass formation, clinically suspicious for malignant lymphoma. Excisional tissue sample showed large irregular spindled histiocytes with abundant granular and vacuolated cytoplasm. Case 3: A 36 year old female with a history of asthma initially presented with left-sided chronic otalgia, occasional nausea, vertigo, and fluctuating pain exacerbated by head movement and temperature changes. CT scan revealed an external auditory canal mass extending to the middle ear, coexisting with a small cholesteatoma. Results: The morphology of all cases revealed large atypical spindled histiocytes resembling fibrohistiocytic or myofibroblastic proliferative neoplasms. Scattered emperipolesis was seen. All 3 cases were confirmed as extranodal sinus RDD, confirmed by immunohistochemistry. The large atypical cells were positive for S100, CD68, and CD163. No evidence for malignancy was identified. Case 3 showed concurrent RDD co-existing with a cholesteatoma. Conclusion: Due to its rarity and variable clinical presentations, the diagnosis of RDD is seldom clinically considered. Extranodal sinus RDD morphologically can be pitfall as mimicker of spindly neoplasm, especially at intraoperative consultation. It can create diagnostic and therapeutic challenges. Correlation of radiological findings with histologic features will help to reach the diagnosis.

Keywords: head and neck, extranodal, rosai-dorfman disease, mimicker, immunohistochemistry

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147 Poly(Acrylamide-Co-Itaconic Acid) Nanocomposite Hydrogels and Its Use in the Removal of Lead in Aqueous Solution

Authors: Majid Farsadrouh Rashti, Alireza Mohammadinejad, Amir Shafiee Kisomi

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Lead (Pb²⁺), a cation, is a prime constituent of the majority of the industrial effluents such as mining, smelting and coal combustion, Pb-based painting and Pb containing pipes in water supply systems, paper and pulp refineries, printing, paints and pigments, explosive manufacturing, storage batteries, alloy and steel industries. The maximum permissible limit of lead in the water used for drinking and domesticating purpose is 0.01 mg/L as advised by Bureau of Indian Standards, BIS. This becomes the acceptable 'safe' level of lead(II) ions in water beyond which, the water becomes unfit for human use and consumption, and is potential enough to lead health problems and epidemics leading to kidney failure, neuronal disorders, and reproductive infertility. Superabsorbent hydrogels are loosely crosslinked hydrophilic polymers that in contact with aqueous solution can easily water and swell to several times to their initial volume without dissolving in aqueous medium. Superabsorbents are kind of hydrogels capable to swell and absorb a large amount of water in their three-dimensional networks. While the shapes of hydrogels do not change extensively during swelling, because of tremendously swelling capacity of superabsorbent, their shape will broadly change.Because of their superb response to changing environmental conditions including temperature pH, and solvent composition, superabsorbents have been attracting in numerous industrial applications. For instance, water retention property and subsequently. Natural-based superabsorbent hydrogels have attracted much attention in medical pharmaceutical, baby diapers, agriculture, and horticulture because of their non-toxicity, biocompatibility, and biodegradability. Novel superabsorbent hydrogel nanocomposites were prepared by graft copolymerization of acrylamide and itaconic acid in the presence of nanoclay (laponite), using methylene bisacrylamide (MBA) and potassium persulfate, former as a crosslinking agent and the second as an initiator. The superabsorbent hydrogel nanocomposites structure was characterized by FTIR spectroscopy, SEM and TGA Spectroscopy adsorption of metal ions on poly (AAm-co-IA). The equilibrium swelling values of copolymer was determined by gravimetric method. During the adsorption of metal ions on polymer, residual metal ion concentration in the solution and the solution pH were measured. The effects of the clay content of the hydrogel on its metal ions uptake behavior were studied. The NC hydrogels may be considered as a good candidate for environmental applications to retain more water and to remove heavy metals.

Keywords: adsorption, hydrogel, nanocomposite, super adsorbent

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146 Evidence-Triggers for Care of Patients with Cleft Lip and Palate in Srinagarind Hospital: The Tawanchai Center and Out-Patients Surgical Room

Authors: Suteera Pradubwong, Pattama Surit, Sumalee Pongpagatip, Tharinee Pethchara, Bowornsilp Chowchuen

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Background: Cleft lip and palate (CLP) is a congenital anomaly of the lip and palate that is caused by several factors. It was found in approximately one per 500 to 550 live births depending on nationality and socioeconomic status. The Tawanchai Center and out-patients surgical room of Srinagarind Hospital are responsible for providing care to patients with CLP (starting from birth to adolescent) and their caregivers. From the observations and interviews with nurses working in these units, they reported that both patients and their caregivers confronted many problems which affected their physical and mental health. Based on the Soukup’s model (2000), the researchers used evidence triggers from clinical practice (practice triggers) and related literature (knowledge triggers) to investigate the problems. Objective: The purpose of this study was to investigate the problems of care for patients with CLP in the Tawanchai Center and out-patient surgical room of Srinagarind Hospital. Material and Method: The descriptive method was used in this study. For practice triggers, the researchers obtained the data from medical records of ten patients with CLP and from interviewing two patients with CLP, eight caregivers, two nurses, and two assistant workers. Instruments for the interview consisted of a demographic data form and a semi-structured questionnaire. For knowledge triggers, the researchers used a literature search. The data from both practice and knowledge triggers were collected between February and May 2016. The quantitative data were analyzed through frequency and percentage distributions, and the qualitative data were analyzed through a content analysis. Results: The problems of care gained from practice and knowledge triggers were consistent and were identified as holistic issues, including 1) insufficient feeding, 2) risks of respiratory tract infections and physical disorders, 3) psychological problems, such as anxiety, stress, and distress, 4) socioeconomic problems, such as stigmatization, isolation, and loss of income, 5)spiritual problems, such as low self-esteem and low quality of life, 6) school absence and learning limitation, 7) lack of knowledge about CLP and its treatments, 8) misunderstanding towards roles among the multidisciplinary team, 9) no available services, and 10) shortage of healthcare professionals, especially speech-language pathologists (SLPs). Conclusion: From evidence-triggers, the problems of care affect the patients and their caregivers holistically. Integrated long-term care by the multidisciplinary team is needed for children with CLP starting from birth to adolescent. Nurses should provide effective care to these patients and their caregivers by using a holistic approach and working collaboratively with other healthcare providers in the multidisciplinary team.

Keywords: evidence-triggers, cleft lip, cleft palate, problems of care

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145 Relationship between Glycated Hemoglobin in Adolescents with Type 1 Diabetes Mellitus and Parental Anxiety and Depression

Authors: Evija Silina, Maris Taube, Maksims Zolovs

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Background: Type 1 diabetes mellitus (T1D) is the most common chronic endocrine pathology in children. The management of type 1 diabetes requires a strong diet, physical activity, lifelong insulin therapy, and proper self-monitoring of blood glucose and is usually complicated and, therefore, may result in a variety of psychosocial problems for children, adolescents, and their families. Metabolic control of the disease is determined by glycated haemoglobin (HbA1c), the main criterion for diabetes compensation. A correlation was observed between anxiety and depression levels and glycaemic control in many previous studies. It is assumed that anxiety and depression symptoms negatively affect glycaemic control. Parental psychological distress was associated with higher child self-report of stress and depressive symptoms, and it had negative effects on diabetes management. Objective: The main objective of this paper is to evaluate the relationship between parental mental health conditions (depression and anxiety) and metabolic control of their adolescents with T1DM. Methods: This cross-sectional study recruited adolescents with T1D (N=251) and their parents (N=251). The respondents completed questionnaires. The 7-item Generalized Anxiety Disorder (GAD-7) scale measured anxiety level; The Patient Health Questionnaire – 9 (PHQ-9) measured depressive symptoms. Glycaemic control of patients was assessed using the last glycated haemoglobin (HbA1c) values. GLM mediation analysis was performed to determine the potential mediating effect of the parent’s mental health conditions (depression and anxiety) on the relationship between the mental health conditions (depression and anxiety) of a child on the level of glycated hemoglobin (HbA1c). To test the significance of the mediated effect (ME) for non-normally distributed data, bootstrapping procedures (10,000 bootstrapped samples) were used. Results: 502 respondents were eligible for screening to detect anxiety and depression symptoms. Mediation analysis was performed to assess the mediating role of parent GAD-7 on the linkage between a dependent variable (HbA1c) and independent variables (child GAD-7 un child PHQ-9). The results revealed that the total effect of child GAD-7 (B = 0.479, z = 4.30, p < 0.001) on HbA1c was significant but the total effect of child PHQ-9 (B = 0.166, z = 1.49, p = 0.135) was not significant. With the inclusion of the mediating variable (parent GAD-7), the impact of child GAD-7 on HbA1c was found insignificant (B = 0.113, z=0.98, p = 0.326), the impact of child PHQ-9 on HbA1c was found also insignificant (B = 0.068, z=0.74, p = 0.458). The indirect effect of child GAD-7 on HbA1c through parent GAD-7 was found significant (B = 0.366, z = 4.31, p < 0.001) and the indirect effect of child PHQ-9 on HbA1c through parent GAD-7 was found also significant (B = 0.098, z = 2.56, p = 0.010). This indicates that the relationship between a dependent variable (HbA1c) and independent variables (child GAD-7 un child PHQ-9) is fully mediated by parent GAD-7. Conclusion: The main result suggests that glycated haemoglobin in adolescents with Type 1 diabetes is related to adolescents’ mental health via parents’ anxiety. It means that parents’ anxiety plays a more significant role in the level of glycated haemoglobin in adolescents than depression and anxiety in the adolescent.

Keywords: type 1 diabetes, adolescents, parental diabetes-specific mental health conditions, glycated haemoglobin, anxiety, depression

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144 Association of Brain Derived Neurotrophic Factor with Iron as well as Vitamin D, Folate and Cobalamin in Pediatric Metabolic Syndrome

Authors: Mustafa M. Donma, Orkide Donma

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The impact of metabolic syndrome (MetS) on cognition and functions of the brain is being investigated. Iron deficiency and deficiencies of B9 (folate) as well as B12 (cobalamin) vitamins are best-known nutritional anemias. They are associated with cognitive disorders and learning difficulties. The antidepressant effects of vitamin D are known and the deficiency state affects mental functions negatively. The aim of this study is to investigate possible correlations of MetS with serum brain-derived neurotrophic factor (BDNF), iron, folate, cobalamin and vitamin D in pediatric patients. 30 children, whose age- and sex-dependent body mass index (BMI) percentiles vary between 85 and 15, 60 morbid obese children with above 99th percentiles constituted the study population. Anthropometric measurements were taken. BMI values were calculated. Age- and sex-dependent BMI percentile values were obtained using the appropriate tables prepared by the World Health Organization (WHO). Obesity classification was performed according to WHO criteria. Those with MetS were evaluated according to MetS criteria. Serum BDNF was determined by enzyme-linked immunosorbent assay. Serum folate was analyzed by an immunoassay analyzer. Serum cobalamin concentrations were measured using electrochemiluminescence immunoassay. Vitamin D status was determined by the measurement of 25-hydroxycholecalciferol [25-hydroxy vitamin D3, 25(OH)D] using high performance liquid chromatography. Statistical evaluations were performed using SPSS for Windows, version 16. The p values less than 0.05 were accepted as statistically significant. Although statistically insignificant, lower folate and cobalamin values were found in MO children compared to those observed for children with normal BMI. For iron and BDNF values, no alterations were detected among the groups. Significantly decreased vitamin D concentrations were noted in MO children with MetS in comparison with those in children with normal BMI (p ≤ 0.05). The positive correlation observed between iron and BDNF in normal-BMI group was not found in two MO groups. In THE MetS group, the partial correlation among iron, BDNF, folate, cobalamin, vitamin D controlling for waist circumference and BMI was r = -0.501; p ≤ 0.05. None was calculated in MO and normal BMI groups. In conclusion, vitamin D should also be considered during the assessment of pediatric MetS. Waist circumference and BMI should collectively be evaluated during the evaluation of MetS in children. Within this context, BDNF appears to be a key biochemical parameter during the examination of obesity degree in terms of mental functions, cognition and learning capacity. The association observed between iron and BDNF in children with normal BMI was not detected in MO groups possibly due to development of inflammation and other obesity-related pathologies. It was suggested that this finding may contribute to mental function impairments commonly observed among obese children.

Keywords: brain-derived neurotrophic factor, iron, vitamin B9, vitamin B12, vitamin D

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143 Sleep Quality as Perceived by Critically Ill Patients at El Manial University Hospitals

Authors: Mohamed Adel Ahmed, Warda Youssef Morsy , Hanaa Ali El Feky

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Background: Literature review cited that sleep is absolutely essential for surviving and reclamation of the quality of life. Critically ill patients often have poor sleep quality with prolonged sleep latency, sleep fragmentation, decreased sleep efficiency and frequent arousals. Nurses have a unique role for the early diagnosis of sleep disorders, decreasing stressors levels and providing the necessary environmental regulations to create a therapeutic ambiance. The aim of the study: to assess perceived sleep quality and identify factors affecting sleep quality among adult critically ill patients At El Manial University Hospital. Research Design: A descriptive exploratory design was utilized. Research questions: a) how do adult critically ill patients perceive sleep quality in the Critical Care Department of El Manial University Hospital? b) What are the factors affecting sleep quality among adult critically ill patients at El Manial University Hospital? Setting: selected critical and cardiac care units at El Manial University Hospital. Sample: A samples of convenience consisting of 100 adult male and female patients were included in the study. Tools of data collection: tool 1: Socio-demographic and Medical Data Sheet, tool 2: Modified St Mary's Hospital Sleep Questionnaire tool 3: Factors Affecting Sleep Quality Questionnaire among ICU Patients Results: The current study revealed that 76.0% of the studied sample had lack of sleep disturbance before hospitalization. However, 84 % had sleep disturbances during ICU stay, of these more than two-thirds (67 %) had moderate sleep disturbance. Presence of strange and bad odors, noise, having pain, fear of death and a loud voice produced by the ICU personnel had the most significant negative impact on patients’ sleep in percentage of 52.4, 50, 61.9, 45.2, 52.4, respectively. Conclusion: Sleep disturbances in the ICU are multifactorial, and ICU patients’ perceived degrees of sleep disturbance as a moderate. Recommendations: Based on findings of the present study, the following are recommended to be done by ICU nurses; create a healing ICU environment that should incorporate noise, light and temperature controls; decrease stimuli during night time hours to promote regulation of the circadian rhythm, allow usage of sleeping aids such as relaxing music, eye patches and earplugs into their daily nursing practice; cluster nursing activities and eliminate non-essential treatments during night time hours to allow uninterrupted sleep periods of at least 90 minutes to complete one sleep cycle , and minimize staff conversation, alarm noise and light during the quiet night time hours.

Keywords: sleep quality, critically ill, patients, perception

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142 Risk Factors Associated with Increased Emergency Department Visits and Hospital Admissions Among Child and Adolescent Patients

Authors: Lalanthica Yogendran, Manassa Hany, Saira Pasha, Benjamin Chaucer, Simarpreet Kaur, Christopher Janusz

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Children and adolescent patients visit the Psychiatric Emergency Department (ED) for multiple reasons. Visiting the Psychiatric ED itself can be a traumatic experience that can affect an adolescents mental well-being, regardless of a history of mental illness. Despite this, limited research exists in this domain. Prospective studies have correlated adverse psychosocial determinants among adolescents to risk factors for poor well-being and unfavorable behavior outcomes. Studies have also shown that physiological stress is a contributor in the development of health problems and an increase in substance abuse in adolescents. This study aimed to retrospectively determine which psychosocial factors are associated with an increase in psychiatric ED visits. 600 charts of patients who had a psychiatric ED and inpatient admission visit from January 2014 through December 2014 were reviewed. Sociodemographics, diagnoses, ED visits and inpatient admissions were collected. Descriptive statistics, chi-square tests and independent t-test analyses were utilized to examine differences in the sample to determine which factors affected ED visits and admissions. The sample was 50% female, 35.2% self-identified black, and had a mean age of 13 years. The majority, 85%, went to public school and 17% were in special education. Attention Deficit Hyperactivity Disorder was the most common admitting diagnosis, found in 132(23%) responders. Most patients came from single parent household 305 (53%). The mean ages of patients that were sexually active, with legal issues, and reporting marijuana substance abuse were 15, 14.35, and 15 years respectively. Patients from two biological parent households had significantly fewer ED visits (1.2 vs. 1.7, p < 0.01) and admissions (0.09 vs. 0.26, p < 0.01). Among social factors, those who reported sexual, physical or emotional abuse had a significantly greater number of ED visits (2.1 vs. 1.5, p < 0.01) and admissions (0.61 vs. 0.14, p < 0.01) than those who did not. Patients that were sexually active or had legal issues or substance abuse with marijuana had a significantly greater number of admissions (0.43 vs. 0.17, p < 0.01), (0.54 vs. .18, p < 0.01) and (0.46 vs. 0.18, p < 0.01) respectively. This data supports the theory of the stability of a two parent home. Dual parenting plays a role in creating a safe space where a child can develop; this is shown by subsequent decreases in psychiatric ED visits and admissions. This may highlight the psychological protective role of a two parent household. Abuse can exacerbate existing psychiatric illness or initiate the onset of new disease. Substance abuse and legal issues result in early induction to the criminal system. Results show that this causes an increase in frequency of visits and severity of symptoms. Only marijuana, but not other illicit substances, correlated with higher incidence of psychiatric ED visits. This may speak to the psychotropic nature of tetrahydrocannabinols and their role in mental illness. This study demonstrates the array of psychosocial factors that lead to increased ED visits and admissions in children and adolescents.

Keywords: adolescent, child psychiatry, emergency department, substance abuse

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141 Comparison of Incidence and Risk Factors of Early Onset and Late Onset Preeclampsia: A Population Based Cohort Study

Authors: Sadia Munir, Diana White, Aya Albahri, Pratiwi Hastania, Eltahir Mohamed, Mahmood Khan, Fathima Mohamed, Ayat Kadhi, Haila Saleem

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Preeclampsia is a major complication of pregnancy. Prediction and management of preeclampsia is a challenge for obstetricians. To our knowledge, no major progress has been achieved in the prevention and early detection of preeclampsia. There is very little known about the clear treatment path of this disorder. Preeclampsia puts both mother and baby at risk of several short term- and long term-health problems later in life. There is huge health service cost burden in the health care system associated with preeclampsia and its complications. Preeclampsia is divided into two different types. Early onset preeclampsia develops before 34 weeks of gestation, and late onset develops at or after 34 weeks of gestation. Different genetic and environmental factors, prognosis, heritability, biochemical and clinical features are associated with early and late onset preeclampsia. Prevalence of preeclampsia greatly varies all over the world and is dependent on ethnicity of the population and geographic region. To authors best knowledge, no published data on preeclampsia exist in Qatar. In this study, we are reporting the incidence of preeclampsia in Qatar. The purpose of this study is to compare the incidence and risk factors of both early onset and late onset preeclampsia in Qatar. This retrospective longitudinal cohort study was conducted using data from the hospital record of Women’s Hospital, Hamad Medical Corporation (HMC), from May 2014-May 2016. Data collection tool, which was approved by HMC, was a researcher made extraction sheet that included information such as blood pressure during admission, socio demographic characteristics, delivery mode, and new born details. A total of 1929 patients’ files were identified by the hospital information management when they apply codes of preeclampsia. Out of 1929 files, 878 had significant gestational hypertension without proteinuria, 365 had preeclampsia, 364 had severe preeclampsia, and 188 had preexisting hypertension with superimposed proteinuria. In this study, 78% of the data was obtained by hospital electronic system (Cerner) and the remaining 22% was from patient’s paper records. We have gone through detail data extraction from 560 files. Initial data analysis has revealed that 15.02% of pregnancies were complicated with preeclampsia from May 2014-May 2016. We have analyzed difference in the two different disease entities in the ethnicity, maternal age, severity of hypertension, mode of delivery and infant birth weight. We have identified promising differences in the risk factors of early onset and late onset preeclampsia. The data from clinical findings of preeclampsia will contribute to increased knowledge about two different disease entities, their etiology, and similarities/differences. The findings of this study can also be used in predicting health challenges, improving health care system, setting up guidelines, and providing the best care for women suffering from preeclampsia.

Keywords: preeclampsia, incidence, risk factors, maternal

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140 Tip60 Histone Acetyltransferase Activators as Neuroepigenetic Therapeutic Modulators for Alzheimer’s Disease

Authors: Akanksha Bhatnagar, Sandhya Kortegare, Felice Elefant

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Context: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive cognitive decline and memory loss. The cause of AD is not fully understood, but it is thought to be caused by a combination of genetic, environmental, and lifestyle factors. One of the hallmarks of AD is the loss of neurons in the hippocampus, a brain region that is important for memory and learning. This loss of neurons is thought to be caused by a decrease in histone acetylation, which is a process that regulates gene expression. Research Aim: The research aim of the study was to develop mall molecule compounds that can enhance the activity of Tip60, a histone acetyltransferase that is important for memory and learning. Methodology/Analysis: The researchers used in silico structural modeling and a pharmacophore-based virtual screening approach to design and synthesize small molecule compounds strongly predicted to target and enhance Tip60’s HAT activity. The compounds were then tested in vitro and in vivo to assess their ability to enhance Tip60 activity and rescue cognitive deficits in AD models. Findings: The researchers found that several of the compounds were able to enhance Tip60 activity and rescue cognitive deficits in AD models. The compounds were also developed to cross the blood-brain barrier, which is an important factor for the development of potential AD therapeutics. Theoretical Importance: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Data Collection: The study collected data from a variety of sources, including in vitro assays and animal models. The in vitro assays assessed the ability of compounds to enhance Tip60 activity using histone acetyltransferase (HAT) enzyme assays and chromatin immunoprecipitation assays. Animal models were used to assess the ability of the compounds to rescue cognitive deficits in AD models using a variety of behavioral tests, including locomotor ability, sensory learning, and recognition tasks. The human clinical trials will be used to assess the safety and efficacy of the compounds in humans. Questions: The question addressed by this study was whether Tip60 HAT activators could be developed as therapeutic agents for AD. Conclusions: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Further research is needed to confirm the safety and efficacy of these compounds in humans.

Keywords: Alzheimer's disease, cognition, neuroepigenetics, drug discovery

Procedia PDF Downloads 45
139 In vivo Wound Healing Activity and Phytochemical Screening of the Crude Extract and Various Fractions of Kalanchoe petitiana A. Rich (Crassulaceae) Leaves in Mice

Authors: Awol Mekonnen, Temesgen Sidamo, Epherm Engdawork, Kaleab Asresb

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Ethnopharmacological Relevance: The leaves of Kalanchoe petitiana A. Rich (Crassulaceae) are used in Ethiopian folk medicine for treatment of evil eye, fractured surface for bone setting and several skin disorders including for the treatment of sores, boils, and malignant wounds. Aim of the Study: In order to scientifically prove the claimed utilization of the plant, the effects of the extracts and the fractions were investigated using in vivo excision, incision and dead space wound models. Materials and Method: Mice were used for wound healing study, while rats and rabbit were used for skin irritation test. For studying healing activity, 80% methanolic extract and the fractions were formulated in strength of 5% and 10%, either as ointment (hydroalcoholic extract, aqueous and methanol fractions) or gel (chloroform fraction). Oral administration of the crude extract was used for dead space model. Negative controls were treated either with simple ointment or sodium carboxyl methyl cellulose xerogel, while positive controls were treated with nitrofurazone (0.2 w/v) skin ointment. Negative controls for dead space model were treated with 1% carboxy methyl cellulose. Parameters, including rate of wound contraction, period of complete epithelializtion, hydroxyproline contents and skin breaking strength were evaluated. Results: Significant wound healing activity was observed with ointment formulated from the crude extract at both 5% and 10% concentration (p<0.01) compared to controls in both excision and incision models. In dead space model, 600 mg/kg (p<0.01), but not 300 mg/kg, significantly increased hydroxyproline content. Fractions showed variable effect, with the chloroform fraction lacking any significant effect. Both 5% and 10% formulations of the aqueous and methanolic fractions significantly increased wound contraction, decreased epithelializtion time and increased hydroxyproline content in excision wound model (p<0.05) as compared to controls. These fractions were also endowed with higher skin breaking strength in incision wound model (p<0.01). Conclusions: The present study provided evidence that the leaves of Kalanchoe petitiana A. Rich possess remarkable wound healing activities supporting the folkloric assertion of the plant. Fractionation revealed that polar or semi-polar compound may play vital role, as both aqueous and methanolic fractions were endowed with wound healing activity.

Keywords: wound healing, Kalanchoae petitiana, excision wound, incision wound, dead space model

Procedia PDF Downloads 282
138 Phenotypic and Molecular Heterogeneity Linked to the Magnesium Transporter CNNM2

Authors: Reham Khalaf-Nazzal, Imad Dweikat, Paula Gimenez, Iker Oyenarte, Alfonso Martinez-Cruz, Domonik Muller

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Metal cation transport mediator (CNNM) gene family comprises 4 isoforms that are expressed in various human tissues. Structurally, CNNMs are complex proteins that contain an extracellular N-terminal domain preceding a DUF21 transmembrane domain, a ‘Bateman module’ and a C-terminal cNMP-binding domain. Mutations in CNNM2 cause familial dominant hypomagnesaemia. Growing evidence highlights the role of CNNM2 in neurodevelopment. Mutations in CNNM2 have been implicated in epilepsy, intellectual disability, schizophrenia, and others. In the present study, we aim to elucidate the function of CNNM2 in the developing brain. Thus, we present the genetic origin of symptoms in two family cohorts. In the first family, three siblings of a consanguineous Palestinian family in which parents are first cousins, and consanguinity ran over several generations, presented a varying degree of intellectual disability, cone-rod dystrophy, and autism spectrum disorder. Exome sequencing and segregation analysis revealed the presence of homozygous pathogenic mutation in the CNNM2 gene, the parents were heterozygous for that gene mutation. Magnesium blood levels were normal in the three children and their parents in several measurements. They had no symptoms of hypomagnesemia. The CNNM2 mutation in this family was found to locate in the CBS1 domain of the CNNM2 protein. The crystal structure of the mutated CNNM2 protein was not significantly different from the wild-type protein, and the binding of AMP or MgATP was not dramatically affected. This suggests that the CBS1 domain could be involved in pure neurodevelopmental functions independent of its magnesium-handling role, and this mutation could have affected a protein partner binding or other functions in this protein. In the second family, another autosomal dominant CNNM2 mutation was found to run in a large family with multiple individuals over three generations. All affected family members had hypomagnesemia and hypermagnesuria. Oral supplementation of magnesium did not increase the levels of magnesium in serum significantly. Some affected members of this family have defects in fine motor skills such as dyslexia and dyslalia. The detected mutation is located in the N-terminal part, which contains a signal peptide thought to be involved in the sorting and routing of the protein. In this project, we describe heterogenous clinical phenotypes related to CNNM2 mutations and protein functions. In the first family, and up to the authors’ knowledge, we report for the first time the involvement of CNNM2 in retinal photoreceptor development and function. In addition, we report the presence of a neurophenotype independent of magnesium status related to the CNNM2 protein mutation. Taking into account the different modes of inheritance and the different positions of the mutations within CNNM2 and its different structural and functional domains, it is likely that CNNM2 might be involved in a wide spectrum of neuropsychiatric comorbidities with considerable varying phenotypes.

Keywords: magnesium transport, autosomal recessive, autism, neurodevelopment, CBS domain

Procedia PDF Downloads 124
137 Development and Preliminary Testing of the Dutch Version of the Program for the Education and Enrichment of Relational Skills

Authors: Sakinah Idris, Gabrine Jagersma, Bjorn Jaime Van Pelt, Kirstin Greaves-Lord

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Background: The PEERS (Program for the Education and Enrichment of Relational Skills) intervention can be considered a well-established, evidence-based intervention in the USA. However, testing the efficacy of cultural adaptations of PEERS is still ongoing. More and more, the involvement of all stakeholders in the development and evaluation of interventions is acknowledged as crucial for the longer term implementation of interventions across settings. Therefore, in the current project, teens with ASD (Autism Spectrum Disorder), their neurotypical peers, parents, teachers, as well as clinicians were involved in the development and evaluation of the Dutch version of PEERS. Objectives: The current presentation covers (1) the formative phase and (2) the preliminary adaptation test phase of the cultural adaptation of evidence-based interventions. In the formative phase, we aim to describe the process of adaptation of the PEERS program to the Dutch culture and care system. In the preliminary adaptation phase, we will present results from the preliminary adaptation test among 32 adolescents with ASD. Methods: In phase 1, a group discussion on common vocabulary was conducted among 70 teenagers (and their teachers) from special and regular education aged 12-18 years old. This inventory concerned 14 key constructs from PEERS, e.g., areas of interests, locations for making friends, common peer groups and crowds inside and outside of school, activities with friends, commonly used ways for electronic communication, ways for handling disagreements, and common teasing comebacks. Also, 15 clinicians were involved in the translation and cultural adaptation process. The translation and cultural adaptation process were guided by the research team, and who included input and feedback from all stakeholders through an iterative feedback incorporation procedure. In phase 2, The parent-reported Social Responsiveness Scale (SRS), the Test of Adolescent Social Skills Knowledge (TASSK), and the Quality of Socialization Questionnaire (QSQ) were assessed pre- and post-intervention to evaluate potential treatment outcome. Results: The most striking cultural adaptation - reflecting the standpoints of all stakeholders - concerned the strategies for handling rumors and gossip, which were suggested to be taught using a similar approach as the teasing comebacks, more in line with ‘down-to-earth’ Dutch standards. The preliminary testing of this adapted version indicated that the adolescents with ASD significantly improved their social knowledge (TASSK; t₃₁ = -10.9, p < .01), social experience (QSQ-Parent; t₃₁ = -4.2, p < .01 and QSQ-Adolescent; t₃₂ = -3.8, p < .01), and in parent-reported social responsiveness (SRS; t₃₃ = 3.9, p < .01). In addition, subjective evaluations of teens with ASD, their parents and clinicians were positive. Conclusions: In order to further scrutinize the effectiveness of the Dutch version of the PEERS intervention, we recommended performing a larger scale randomized control trial (RCT) design, for which we provide several methodological considerations.

Keywords: cultural adaptation, PEERS, preliminary testing, translation

Procedia PDF Downloads 135
136 The Invaluable Contributions of Radiography and Radiotherapy in Modern Medicine

Authors: Sahar Heidary

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Radiography and radiotherapy have emerged as crucial pillars of modern medical practice, revolutionizing diagnostics and treatment for a myriad of health conditions. This abstract highlights the pivotal role of radiography and radiotherapy in favor of healthcare and society. Radiography, a non-invasive imaging technique, has significantly advanced medical diagnostics by enabling the visualization of internal structures and abnormalities within the human body. With the advent of digital radiography, clinicians can obtain high-resolution images promptly, leading to faster diagnoses and informed treatment decisions. Radiography plays a pivotal role in detecting fractures, tumors, infections, and various other conditions, allowing for timely interventions and improved patient outcomes. Moreover, its widespread accessibility and cost-effectiveness make it an indispensable tool in healthcare settings worldwide. On the other hand, radiotherapy, a branch of medical science that utilizes high-energy radiation, has become an integral component of cancer treatment and management. By precisely targeting and damaging cancerous cells, radiotherapy offers a potent strategy to control tumor growth and, in many cases, leads to cancer eradication. Additionally, radiotherapy is often used in combination with surgery and chemotherapy, providing a multifaceted approach to combat cancer comprehensively. The continuous advancements in radiotherapy techniques, such as intensity-modulated radiotherapy and stereotactic radiosurgery, have further improved treatment precision while minimizing damage to surrounding healthy tissues. Furthermore, radiography and radiotherapy have demonstrated their worth beyond oncology. Radiography is instrumental in guiding various medical procedures, including catheter placement, joint injections, and dental evaluations, reducing complications and enhancing procedural accuracy. On the other hand, radiotherapy finds applications in non-cancerous conditions like benign tumors, vascular malformations, and certain neurological disorders, offering therapeutic options for patients who may not benefit from traditional surgical interventions. In conclusion, radiography and radiotherapy stand as indispensable tools in modern medicine, driving transformative improvements in patient care and treatment outcomes. Their ability to diagnose, treat, and manage a wide array of medical conditions underscores their favor in medical practice. As technology continues to advance, radiography and radiotherapy will undoubtedly play an ever more significant role in shaping the future of healthcare, ultimately saving lives and enhancing the quality of life for countless individuals worldwide.

Keywords: radiology, radiotherapy, medical imaging, cancer treatment

Procedia PDF Downloads 41
135 Giving Children with Osteogenesis Imperfecta a Voice: Overview of a Participatory Approach for the Development of an Interactive Communication Tool

Authors: M. Siedlikowski, F. Rauch, A. Tsimicalis

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Osteogenesis Imperfecta (OI) is a genetic disorder of childhood onset that causes frequent fractures after minimal physical stress. To date, OI research has focused on medically- and surgically-oriented outcomes with little attention on the perspective of the affected child. It is a challenge to elicit the child’s voice in health care, in other words, their own perspective on their symptoms, but software development offers a way forward. Sisom (Norwegian acronym derived from ‘Si det som det er’ meaning ‘Tell it as it is’) is an award-winning, rigorously tested, interactive, computerized tool that helps children with chronic illnesses express their symptoms to their clinicians. The successful Sisom software tool, that addresses the child directly, has not yet been adapted to attend to symptoms unique to children with OI. The purpose of this study was to develop a Sisom paper prototype for children with OI by seeking the perspectives of end users, particularly, children with OI and clinicians. Our descriptive qualitative study was conducted at Shriners Hospitals for Children® – Canada, which follows the largest cohort of children with OI in North America. Purposive sampling was used to recruit 12 children with OI over three cycles. Nine clinicians oversaw the development process, which involved determining the relevance of current Sisom symptoms, vignettes, and avatars, as well as generating new Sisom OI components. Data, including field notes, transcribed audio-recordings, and drawings, were deductively analyzed using content analysis techniques. Guided by the following framework, data pertaining to symptoms, vignettes, and avatars were coded into five categories: a) Relevant; b) Irrelevant; c) To modify; d) To add; e) Unsure. Overall, 70.8% of Sisom symptoms were deemed relevant for inclusion, with 49.4% directly incorporated, and 21.3% incorporated with changes to syntax, and/or vignette, and/or location. Three additions were made to the ‘Avatar’ island. This allowed children to celebrate their uniqueness: ‘Makes you feel like you’re not like everybody else.’ One new island, ‘About Me’, was added to capture children’s worldviews. One new sub-island, ‘Getting Around’, was added to reflect accessibility issues. These issues were related to the children’s independence, their social lives, as well as the perceptions of others. In being consulted as experts throughout the co-creation of the Sisom OI paper prototype, children coded the Sisom symptoms and provided sound rationales for their chosen codes. In rationalizing their codes, all children shared personal stories about themselves and their relationships, insights about their OI, and an understanding of the strengths and challenges they experience on a day-to-day basis. The child’s perspective on their health is a basic right, and allowing it to be heard is the next frontier in the care of children with genetic diseases. Sisom OI, a methodological breakthrough within OI research, will offer clinicians an innovative and child-centered approach to capture this neglected perspective. It will provide a tool for the delivery of health care in the center that established the worldwide standard of care for children with OI.

Keywords: child health, interactive computerized communication tool, participatory approach, symptom management

Procedia PDF Downloads 136
134 Neuropsychiatric Outcomes of Intensive Music Therapy in Stroke Rehabilitation A Premilitary Investigation

Authors: Honey Bryant, Elvina Chu

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Stroke is the leading cause of disability in adults in Canada and directly related to depression, anxiety, and sleep disorders; with an estimated annual cost of $50 billion in health care. Strokes not only impact the individual but society as a whole. Current stroke rehabilitation does not include Music Therapy, although it has success in clinical research in the use of stroke rehabilitation. This study examines the use of neurologic music therapy (NMT) in conjunction with stroke rehabilitation to improve sleep quality, reduce stress levels, and promote neurogenesis. Existing research on NMT in stroke is limited, which means any conclusive information gathered during this study will be significant. My novel hypotheses are a.) stroke patients will become less depressed and less anxious with improved sleep following NMT. b.) NMT will reduce stress levels and promote neurogenesis in stroke patients admitted for rehabilitation. c.) Beneficial effects of NMT will be sustained at least short-term following treatment. Participants were recruited from the in-patient stroke rehabilitation program at Providence Care Hospital in Kingston, Ontario, Canada. All participants-maintained stroke rehabilitation treatment as normal. The study was spilt into two groups, the first being Passive Music Listening (PML) and the second Neurologic Music Therapy (NMT). Each group underwent 10 sessions of intensive music therapy lasting 45 minutes for 10 consecutive days, excluding weekends. Psychiatric Assessments, Epworth Sleepiness Scale (ESS), Hospital Anxiety & Depression Rating Scale (HADS), and Music Engagement Questionnaire (MusEQ), were completed, followed by a general feedback interview. Physiological markers of stress were measured through blood pressure measurements and heart rate variability. Serum collections reviewed neurogenesis via Brain-derived neurotrophic factor (BDNF) and stress markers of cortisol levels. As this study is still on-going, a formal analysis of data has not been fully completed, although trends are following our hypotheses. A decrease in sleepiness and anxiety is seen upon the first cohort of PML. Feedback interviews have indicated most participants subjectively felt more relaxed and thought PML was useful in their recovery. If the hypothesis is supported, larger external funding which will allow for greater investigation of the use of NMT in stroke rehabilitation. As we know, NMT is not covered under Ontario Health Insurance Plan (OHIP), so there is limited scientific data surrounding its uses as a clinical tool. This research will provide detailed findings of the treatment of neuropsychiatric aspects of stroke. Concurrently, a passive music listening study is being designed to further review the use of PML in rehabilitation as well.

Keywords: music therapy, psychotherapy, neurologic music therapy, passive music listening, neuropsychiatry, counselling, behavioural, stroke, stroke rehabilitation, rehabilitation, neuroscience

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133 Poly(propylene fumarate) Copolymers with Phosphonic Acid-based Monomers Designed as Bone Tissue Engineering Scaffolds

Authors: Görkem Cemali̇, Avram Aruh, Gamze Torun Köse, Erde Can ŞAfak

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In order to heal bone disorders, the conventional methods which involve the use of autologous and allogenous bone grafts or permanent implants have certain disadvantages such as limited supply, disease transmission, or adverse immune response. A biodegradable material that acts as structural support to the damaged bone area and serves as a scaffold that enhances bone regeneration and guides bone formation is one desirable solution. Poly(propylene fumarate) (PPF) which is an unsaturated polyester that can be copolymerized with appropriate vinyl monomers to give biodegradable network structures, is a promising candidate polymer to prepare bone tissue engineering scaffolds. In this study, hydroxyl-terminated PPF was synthesized and thermally cured with vinyl phosphonic acid (VPA) and diethyl vinyl phosphonate (VPES) in the presence of radical initiator benzoyl peroxide (BP), with changing co-monomer weight ratios (10-40wt%). In addition, the synthesized PPF was cured with VPES comonomer at body temperature (37oC) in the presence of BP initiator, N, N-Dimethyl para-toluidine catalyst and varying amounts of Beta-tricalcium phosphate (0-20 wt% ß-TCP) as filler via radical polymerization to prepare composite materials that can be used in injectable forms. Thermomechanical properties, compressive properties, hydrophilicity and biodegradability of the PPF/VPA and PPF/VPES copolymers were determined and analyzed with respect to the copolymer composition. Biocompatibility of the resulting polymers and their composites was determined by the MTS assay and osteoblast activity was explored with von kossa, alkaline phosphatase and osteocalcin activity analysis and the effects of VPA and VPES comonomer composition on these properties were investigated. Thermally cured PPF/VPA and PPF/VPES copolymers with different compositions exhibited compressive modulus and strength values in the wide range of 10–836 MPa and 14–119 MPa, respectively. MTS assay studies showed that the majority of the tested compositions were biocompatible and the overall results indicated that PPF/VPA and PPF/VPES network polymers show significant potential for applications as bone tissue engineering scaffolds where varying PPF and co-monomer ratio provides adjustable and controllable properties of the end product. The body temperature cured PPF/VPES/ß-TCP composites exhibited significantly lower compressive modulus and strength values than the thermal cured PPF/VPES copolymers and were therefore found to be useful as scaffolds for cartilage tissue engineering applications.

Keywords: biodegradable, bone tissue, copolymer, poly(propylene fumarate), scaffold

Procedia PDF Downloads 145
132 Ahmad Sabzi Balkhkanloo, Motahareh Sadat Hashemi, Seyede Marzieh Hosseini, Saeedeh Shojaee-Aliabadi, Leila Mirmoghtadaie

Authors: Elyria Kemp, Kelly Cowart, My Bui

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According to the National Institute of Mental Health, an estimated 31.9% of adolescents have had an anxiety disorder. Several environmental factors may help to contribute to high levels of anxiety and depression in young people (i.e., Generation Z, Millennials). However, as young people negotiate life on social media, they may begin to evaluate themselves using excessively high standards and adopt self-perfectionism tendencies. Broadly defined, self-perfectionism involves very critical evaluations of the self. Perfectionism may also come from others and may manifest as socially prescribed perfectionism, and young adults are reporting higher levels of socially prescribed perfectionism than previous generations. This rising perfectionism is also associated with anxiety, greater physiological reactivity, and a sense of social disconnection. However, theories from psychology suggest that improvement in emotion regulation can contribute to enhanced psychological and emotional well-being. Emotion regulation refers to the ways people manage how and when they experience and express their emotions. Cognitive reappraisal and expressive suppression are common emotion regulation strategies. Cognitive reappraisal involves changing the meaning of a stimulus that involves construing a potentially emotion-eliciting situation in a way that changes its emotional impact. By contrast, expressive suppression involves inhibiting the behavioral expression of emotion. The purpose of this research is to examine the efficacy of social marketing initiatives which promote emotion regulation strategies to help young adults regulate their emotions. In Study 1 a single factor (emotional regulation strategy: a cognitive reappraisal, expressive, control) between-subjects design was conducted using an online, non-student consumer panel (n=96). Sixty-eight percent of participants were male, and 32% were female. Study participants belonged to the Millennial and Gen Z cohort, ranging in age from 22 to 35 (M=27). Participants were first told to spend at least three minutes writing about a public speaking appearance which made them anxious. The purpose of this exercise was to induce anxiety. Next, participants viewed one of three advertisements (randomly assigned) which promoted an emotion regulation strategy—cognitive reappraisal, expressive suppression, or an advertisement non-emotional in nature. After being exposed to one of the ads, participants responded to a measure composed of two items to access their emotional state and the efficacy of the messages in fostering emotion management. Findings indicated that individuals in the cognitive reappraisal condition (M=3.91) exhibited the most positive feelings and more effective emotion regulation than the expressive suppression (M=3.39) and control conditions (M=3.72, F(1,92) = 3.3, p<.05). Results from this research can be used by institutions (e.g., schools) in taking a leadership role in attacking anxiety and other mental health issues. Social stigmas regarding mental health can be removed and a more proactive stance can be taken in promoting healthy coping behaviors and strategies to manage negative emotions.

Keywords: emotion regulation, anxiety, social marketing, generation z

Procedia PDF Downloads 180
131 Correlation Analysis between Sensory Processing Sensitivity (SPS), Meares-Irlen Syndrome (MIS) and Dyslexia

Authors: Kaaryn M. Cater

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Students with sensory processing sensitivity (SPS), Meares-Irlen Syndrome (MIS) and dyslexia can become overwhelmed and struggle to thrive in traditional tertiary learning environments. An estimated 50% of tertiary students who disclose learning related issues are dyslexic. This study explores the relationship between SPS, MIS and dyslexia. Baseline measures will be analysed to establish any correlation between these three minority methods of information processing. SPS is an innate sensitivity trait found in 15-20% of the population and has been identified in over 100 species of animals. Humans with SPS are referred to as Highly Sensitive People (HSP) and the measure of HSP is a 27 point self-test known as the Highly Sensitive Person Scale (HSPS). A 2016 study conducted by the author established base-line data for HSP students in a tertiary institution in New Zealand. The results of the study showed that all participating HSP students believed the knowledge of SPS to be life-changing and useful in managing life and study, in addition, they believed that all tutors and in-coming students should be given information on SPS. MIS is a visual processing and perception disorder that is found in approximately 10% of the population and has a variety of symptoms including visual fatigue, headaches and nausea. One way to ease some of these symptoms is through the use of colored lenses or overlays. Dyslexia is a complex phonological based information processing variation present in approximately 10% of the population. An estimated 50% of dyslexics are thought to have MIS. The study exploring possible correlations between these minority forms of information processing is due to begin in February 2017. An invitation will be extended to all first year students enrolled in degree programmes across all faculties and schools within the institution. An estimated 900 students will be eligible to participate in the study. Participants will be asked to complete a battery of on-line questionnaires including the Highly Sensitive Person Scale, the International Dyslexia Association adult self-assessment and the adapted Irlen indicator. All three scales have been used extensively in literature and have been validated among many populations. All participants whose score on any (or some) of the three questionnaires suggest a minority method of information processing will receive an invitation to meet with a learning advisor, and given access to counselling services if they choose. Meeting with a learning advisor is not mandatory, and some participants may choose not to receive help. Data will be collected using the Question Pro platform and base-line data will be analysed using correlation and regression analysis to identify relationships and predictors between SPS, MIS and dyslexia. This study forms part of a larger three year longitudinal study and participants will be required to complete questionnaires at annual intervals in subsequent years of the study until completion of (or withdrawal from) their degree. At these data collection points, participants will be questioned on any additional support received relating to their minority method(s) of information processing. Data from this study will be available by April 2017.

Keywords: dyslexia, highly sensitive person (HSP), Meares-Irlen Syndrome (MIS), minority forms of information processing, sensory processing sensitivity (SPS)

Procedia PDF Downloads 205
130 A Clinical Cutoff to Identify Metabolically Unhealthy Obese and Normal-Weight Phenotype in Young Adults

Authors: Lívia Pinheiro Carvalho, Luciana Di Thommazo-Luporini, Rafael Luís Luporini, José Carlos Bonjorno Junior, Renata Pedrolongo Basso Vanelli, Manoel Carneiro de Oliveira Junior, Rodolfo de Paula Vieira, Renata Trimer, Renata G. Mendes, Mylène Aubertin-Leheudre, Audrey Borghi-Silva

Abstract:

Rationale: Cardiorespiratory fitness (CRF) and functional capacity in young obese and normal-weight people are associated with metabolic and cardiovascular diseases and mortality. However, it remains unclear whether their metabolically healthy (MH) or at risk (AR) phenotype influences cardiorespiratory fitness in this vulnerable population such as obese adults but also in normal-weight people. HOMA insulin resistance index (HI) and leptin-adiponectin ratio (LA) are strong markers for characterizing those phenotypes that we hypothesized to be associated with physical fitness. We also hypothesized that an easy and feasible exercise test could identify a subpopulation at risk to develop metabolic and related disorders. Methods: Thirty-nine sedentary men and women (20-45y; 18.530 kg.m-2) underwent a clinical evaluation, including the six-minute step test (ST), a well-validated and reliable test for young people. Body composition assessment was done by a tetrapolar bioimpedance in a fasting state and in the folicular phase for women. A maximal cardiopulmonary exercise testing, as well as the ST, evaluated the oxygen uptake at the peak of the test (VO2peak) by an ergospirometer Oxycon Mobile. Lipids, glucose, insulin were analysed and the ELISA method quantified the serum leptin and adiponectin from blood samples. Volunteers were divided in two groups: AR or MH according to a HI cutoff of 1.95, which was previously determined in the literature. T-test for comparison between groups, Pearson´s test to correlate main variables and ROC analysis for discriminating AR from up-and-down cycles in ST (SC) were applied (p<0.05). Results: Higher LA, fat mass (FM) and lower HDL, SC, leg lean mass (LM) and VO2peak were found in AR than in MH. Significant correlations were found between VO2peak and SC (r= 0.80) as well as between LA and FM (r=0.87), VO2peak (r=-0.73), and SC (r=-0.65). Area under de curve showed moderate accuracy (0.75) of SC <173 to discriminate AR phenotype. Conclusion: Our study found that at risk obese and normal-weight subjects showed an unhealthy metabolism as well as a poor CRF and functional daily activity capacity. Additionally, a simple and less costly functional test associated with above-mentioned aspects is able to identify ‘at risk’ subjects for primary intervention with important clinical and health implications.

Keywords: aerobic capacity, exercise, fitness, metabolism, obesity, 6MST

Procedia PDF Downloads 326
129 Innovative Technologies Functional Methods of Dental Research

Authors: Sergey N. Ermoliev, Margarita A. Belousova, Aida D. Goncharenko

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Application of the diagnostic complex of highly informative functional methods (electromyography, reodentography, laser Doppler flowmetry, reoperiodontography, vital computer capillaroscopy, optical tissue oximetry, laser fluorescence diagnosis) allows to perform a multifactorial analysis of the dental status and to prescribe complex etiopathogenetic treatment. Introduction. It is necessary to create a complex of innovative highly informative and safe functional diagnostic methods for improvement of the quality of patient treatment by the early detection of stomatologic diseases. The purpose of the present study was to investigate the etiology and pathogenesis of functional disorders identified in the pathology of hard tissue, dental pulp, periodontal, oral mucosa and chewing function, and the creation of new approaches to the diagnosis of dental diseases. Material and methods. 172 patients were examined. Density of hard tissues of the teeth and jaw bone was studied by intraoral ultrasonic densitometry (USD). Electromyographic activity of masticatory muscles was assessed by electromyography (EMG). Functional state of dental pulp vessels assessed by reodentography (RDG) and laser Doppler flowmetry (LDF). Reoperiodontography method (RPG) studied regional blood flow in the periodontal tissues. Microcirculatory vascular periodontal studied by vital computer capillaroscopy (VCC) and laser Doppler flowmetry (LDF). The metabolic level of the mucous membrane was determined by optical tissue oximetry (OTO) and laser fluorescence diagnosis (LFD). Results and discussion. The results obtained revealed changes in mineral density of hard tissues of the teeth and jaw bone, the bioelectric activity of masticatory muscles, regional blood flow and microcirculation in the dental pulp and periodontal tissues. LDF and OTO methods estimated fluctuations of saturation level and oxygen transport in microvasculature of periodontal tissues. With LFD identified changes in the concentration of enzymes (nicotinamide, flavins, lipofuscin, porphyrins) involved in metabolic processes Conclusion. Our preliminary results confirmed feasibility and safety the of intraoral ultrasound densitometry technique in the density of bone tissue of periodontium. Conclusion. Application of the diagnostic complex of above mentioned highly informative functional methods allows to perform a multifactorial analysis of the dental status and to prescribe complex etiopathogenetic treatment.

Keywords: electromyography (EMG), reodentography (RDG), laser Doppler flowmetry (LDF), reoperiodontography method (RPG), vital computer capillaroscopy (VCC), optical tissue oximetry (OTO), laser fluorescence diagnosis (LFD)

Procedia PDF Downloads 248
128 Effects of Long-Term Exposure of Cadmium to the Ovary of Lithobius forficatus (Myriapoda, Chilopoda)

Authors: Izabela Poprawa, Alina Chachulska-Zymelka, Lukasz Chajec, Grazyna Wilczek, Piotr Wilczek, Sebastian Student, Magdalena Rost-Roszkowska

Abstract:

Heavy metals polluting the environment, especially soil, have a harmful effect on organisms, because they can damage the organ structure, disturb their function and cause developmental disorders. They can affect not only the somatic tissues but also the germinal tissues. In the natural environment, plants and animals are exposed to short- and long-term exposure to these stressors, which have a major influence on the functioning of these organisms. Numerous animals have been treated as the bioindicators of the environment. Therefore, studies on any alterations caused by, e.g., heavy metals are in the center of interests of not only environmental but also medical and biological science. Myriapods are invertebrates which are bioindicators of the environment. One of the species which lives in the upper layers of soil, particularly under stones and rocks is Lithobius forficatus (Chilopoda), commonly known as the brown centipede or stone centipede. It is a European species of the family Lithobiidae. This centipede living in the soil is exposed to, e.g., heavy metals such as cadmium, lead, arsenic. The main goal of our project was to analyze the impact of long-term exposure to cadmium on the structure of ovary with the emphasis on the course of oogenesis. As the material for analysis of cadmium exposure to ovaries, we chose the centipede species, L. forficatus. Animals were divided into two experimental groups: C – the control group, the animals cultured in laboratory conditions in a horticultural soil; Cd2 – the animals cultured in a horticultural soil supplemented with 80 mg/kg (dry weight) of CdCl2 for 45 days – long-term exposure. Animals were fed with Acheta and Chironomus larvae maintained in tap water. The analyzes were carried out using transmission electron microscopy (TEM), flow cytometry and laser scanning (confocal) microscopy. Here we present the results of long-term exposure to cadmium concentration in soil on the organ responsible for female germ cell formation. Analysis with the use of the transmission electron microscope showed changes in the ultrastructure of both somatic and germ cells in the ovary. Moreover, quantitative analysis revealed the decrease in the percentage of cells viability, the increase in the percentage of cells with depolarized mitochondria and increasing the number of early apoptotic cells. All these changes were statistically significant compared to the control. Additionally, an increase in the ADP/ATP index was recorded. However, changes were not statistically significant to the control. Acknowledgment: The study has been financed by the National Science Centre, Poland, grant no 2017/25/B/NZ4/00420.

Keywords: cadmium, centipede, ovary, ultrastructure

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127 Prevalence of Behavioral and Emotional Problems in School Going Adolescents in India

Authors: Anshu Gupta, Charu Gupta

Abstract:

Background: Adolescence is the transitional period between puberty and adulthood. It is marked by immense turmoil in emotional and behavioral spheres. Adolescents are at risk of an array of behavioral and emotional problems, resulting in social, academic and vocational function impairments. Conflicts in the family and inability of the parents to cope with the changing demands of an adolescent have a negative impact on the overall development of the child. This augers ill for the individual’s future, resulting in depression, delinquency and suicides among other problems. Aim: The aim of the study was to compare the prevalence of behavioral and emotional problems in school going adolescents aged 13 to 15 years residing in Ludhiana city. Method: A total of 1380 school children in the age group of 13 to 15 years were assessed by the adolescent health screening questionnaire (FAPS) and Youth Self-Report (2001) questionnaire. Statistical significance was ascertained by t-test, chi-square test (x²) and ANOVA, as appropriate. Results: A considerably high prevalence of behavioral and emotional problems was found in school going adolescents (26.5%), more in girls (31.7%) than in boys (24.4%). In case of boys, the maximum problem was in the 13 year age group, i.e., 28.2%, followed by a significant decline by the age of 14 years, i.e., 24.2% and 15 years, i.e., 19.6%. In case of girls also, the maximum problem was in the 13 year age group, i.e., 32.4% followed by a marginal decline in the 14 years i.e., 31.8% and 15 year age group, i.e., 30.2%. Demographic factors were non contributory. Internalizing syndrome (22.4%) was the most common problem followed by the neither internalizing nor externalizing (17.6%) group. In internalizing group, most (26.5%) of the students were observed to be anxious/ depressed. Social problem was observed to be the most frequent (10.6%) among neither internalizing nor externalizing group. Aggressive behavior was the commonest (8.4%) among externalizing group. Internalizing problems, mainly anxiety and depression, were commoner in females (30.6%) than males (24.6%). More boys (16%) than girls (13.4%) were reported to suffer from externalizing disorders. A critical review of the data showed that most of the adolescents had poor knowledge about reproductive health. Almost 36% reported that the source of their information on sexual and reproductive health being friends and the electronic media. There was a high percentage of adolescents who reported being worried about sexual abuse (20.2%) with majority of them being girls (93.6%) reflecting poorly on the social setup in the country. About 41% of adolescents reported being concerned about body weight and most of them being girls (92.4%). Up to 14.5% reported having thoughts of using alcohol or drugs perhaps due to the easy availability of substances of abuse in this part of the country. 12.8% (mostly girls) reported suicidal thoughts. Summary/conclusion: There is a high prevalence of emotional and behavioral problems among school-going adolescents. Resolution of these problems during adolescence is essential for attaining a healthy adulthood. The need of the hour is to spread awareness among caregivers and formulation of effective management strategies including school mental health programme.

Keywords: adolescence, behavioral, emotional, internalizing problem

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126 Encapsulation of Venlafaxine-Dowex® Resinate: A Once Daily Multiple Unit Formulation

Authors: Salwa Mohamed Salah Eldin, Howida Kamal Ibrahim

Abstract:

Introduction: Major depressive disorder affects high proportion of the world’s population presenting cost load in health care. Extended release venlafaxine is more convenient and could reduce discontinuation syndrome. The once daily dosing also reduces the potential for adverse events such as nausea due to reduced Cmax. Venlafaxine is an effective first-line agent in the treatment of depression. A once daily formulation was designed to enhance patient compliance. Complexing with a resin was suggested to improve loading of the water soluble drug. The formulated systems were thoroughly evaluated in vitro to prove superiority to previous trials and were compared to the commercial extended release product in experimental animals. Materials and Methods: Venlafaxine-resinates were prepared using Dowex®50WX4-400 and Dowex®50WX8-100 at drug to resin weight ratio of 1: 1. The prepared resinates were evaluated for their drug content, particle shape and surface properties and in vitro release profile in gradient pH. The release kinetics and mechanism were evaluated. Venlafaxine-Dowex® resinates were encapsulated using O/W solvent evaporation technique. Poly-ε-caprolactone, Poly(D, L-lactide-co-glycolide) ester, Poly(D, L-lactide) ester and Eudragit®RS100 were used as coating polymers alone and in combination. Drug-resinate microcapsules were evaluated for morphology, entrapment efficiency and in-vitro release profile. The selected formula was tested in rabbits using a randomized, single-dose, 2-way crossover study against Effexor-XR tablets under fasting condition. Results and Discussion: The equilibrium time was 30 min for Dowex®50WX4-400 and 90 min for Dowex®50WX8-100. The percentage drug loaded was 93.96 and 83.56% for both resins, respectively. Both drug-Dowex® resintes were efficient in sustaining venlafaxine release in comparison to the free drug (up to 8h.). Dowex®50WX4-400 based venlafaxine-resinate was selected for further encapsulation to optimize the release profile for once daily dosing and to lower the burst effect. The selected formula (coated with a mixture of Eudragit RS and PLGA in a ratio of 50/50) was chosen by applying a group of mathematical equations according to targeted values. It recorded the minimum burst effect, the maximum MDT (Mean dissolution time) and a Q24h (percentage drug released after 24 hours) between 95 and 100%. The 90% confidence intervals for the test/reference mean ratio of the log-transformed data of AUC0–24 and AUC0−∞ are within (0.8–1.25), which satisfies the bioequivalence criteria. Conclusion: The optimized formula could be a promising extended release form of the water soluble, short half lived venlafaxine. Being a multiple unit formulation, it lowers the probability of dose dumping and reduces the inter-subject variability in absorption.

Keywords: biodegradable polymers, cation-exchange resin, microencapsulation, venlafaxine hcl

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125 Excess Body Fat as a Store Toxin Affecting the Glomerular Filtration and Excretory Function of the Liver in Patients after Renal Transplantation

Authors: Magdalena B. Kaziuk, Waldemar Kosiba, Marek J. Kuzniewski

Abstract:

Introduction: Adipose tissue is a typical place for storage water-insoluble toxins in the body. It's connective tissue, where the intercellular substance consist of fat, which level in people with low physical activity should be 18-25% for women and 13-18% for men. Due to the fat distribution in the body we distinquish two types of obesity: android (visceral, abdominal) and gynoidal (gluteal-femoral, peripheral). Abdominal obesity increases the risk of complications of the cardiovascular system diseases, and impaired renal and liver function. Through the influence on disorders of metabolism, lipid metabolism, diabetes and hypertension, leading to emergence of the metabolic syndrome. So thus, obesity will especially overload kidney function in patients after transplantation. Aim: An attempt was made to estimate the impact of amount fat tissue on transplanted kidney function and excretory function of the liver in patients after Ktx. Material and Methods: The study included 108 patients (50 females, 58 male, age 46.5 +/- 12.9 years) with active kidney transplant after more than 3 months from the transplantation. An analysis of body composition was done by using electrical bioimpedance (BIA) and anthropometric measurements. Estimated basal metabolic rate (BMR), muscle mass, total body water content and the amount of body fat. Information about physical activity were obtained during clinical examination. Nutritional status, and type of obesity were determined by using indicators: Waist to Height Ratio (WHR) and Waist to Hip Ratio (WHR). Excretory functions of the transplanted kidney was rated by calculating the estimated renal glomerular filtration rate (eGFR) using the MDRD formula. Liver function was rated by total bilirubin and alanine aminotransferase levels ALT concentration in serum. In our patients haemolitic uremic syndrome (HUS) was excluded. Results: In 19.44% of patients had underweight, 22.37% of the respondents were with normal weight, 11.11% had overweight, and the rest were with obese (49.08%). People with android stature have a lower eGFR compared with those with the gynoidal stature (p = 0.004). All patients with obesity had higher amount of body fat from a few to several percent. The higher amount of body fat percentage, the lower eGFR had patients (p <0.001). Elevated ALT levels significantly correlated with a high fat content (p <0.02). Conclusion: Increased amount of body fat, particularly in the case of android obesity can be a predictor of kidney and liver damage. Due to that obese patients should have more frequent control of diagnostic functions of these organs and the intensive dietary proceedings, pharmacological and regular physical activity adapted to the current physical condition of patients after transplantation.

Keywords: obesity, body fat, kidney transplantation, glomerular filtration rate, liver function

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124 Assessment of Neurodevelopmental Needs in Duchenne Muscular Dystrophy

Authors: Mathula Thangarajh

Abstract:

Duchenne muscular dystrophy (DMD) is a severe form of X-linked muscular dystrophy caused by mutations in the dystrophin gene resulting in progressive skeletal muscle weakness. Boys with DMD also have significant cognitive disabilities. The intelligence quotient of boys with DMD, compared to peers, is approximately one standard deviation below average. Detailed neuropsychological testing has demonstrated that boys with DMD have a global developmental impairment, with verbal memory and visuospatial skills most significantly affected. Furthermore, the total brain volume and gray matter volume are lower in children with DMD compared to age-matched controls. These results are suggestive of a significant structural and functional compromise to the developing brain as a result of absent dystrophin protein expression. There is also some genetic evidence to suggest that mutations in the 3’ end of the DMD gene are associated with more severe neurocognitive problems. Our working hypothesis is that (i) boys with DMD do not make gains in neurodevelopmental skills compared to typically developing children and (ii) women carriers of DMD mutations may have subclinical cognitive deficits. We also hypothesize that there may be an intergenerational vulnerability of cognition, with boys of DMD-carrier mothers being more affected cognitively than boys of non-DMD-carrier mothers. The objectives of this study are: 1. Assess the neurodevelopment in boys with DMD at 4-time points and perform baseline neuroradiological assessment, 2. Assess cognition in biological mothers of DMD participants at baseline, 3. Assess possible correlation between DMD mutation and cognitive measures. This study also explores functional brain abnormalities in people with DMD by exploring how regional and global connectivity of the brain underlies executive function deficits in DMD. Such research can contribute to a better holistic understanding of the cognition alterations due to DMD and could potentially allow clinicians to create better-tailored treatment plans for the DMD population. There are four study visits for each participant (baseline, 2-4 weeks, 1 year, 18 months). At each visit, the participant completes the NIH Toolbox Cognition Battery, a validated psychometric measure that is recommended by NIH Common Data Elements for use in DMD. Visits 1, 3, and 4 also involve the administration of the BRIEF-2, ABAS-3, PROMIS/NeuroQoL, PedsQL Neuromuscular module 3.0, Draw a Clock Test, and an optional fMRI scan with the N-back matching task. We expect to enroll 52 children with DMD, 52 mothers of children with DMD, and 30 healthy control boys. This study began in 2020 during the height of the COVID-19 pandemic. Due to this, there were subsequent delays in recruitment because of travel restrictions. However, we have persevered and continued to recruit new participants for the study. We partnered with the Muscular Dystrophy Association (MDA) and helped advertise the study to interested families. Since then, we have had families from across the country contact us about their interest in the study. We plan to continue to enroll a diverse population of DMD participants to contribute toward a better understanding of Duchenne Muscular Dystrophy.

Keywords: neurology, Duchenne muscular dystrophy, muscular dystrophy, cognition, neurodevelopment, x-linked disorder, DMD, DMD gene

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123 Synthesis of Functionalized-2-Aryl-2, 3-Dihydroquinoline-4(1H)-Ones via Fries Rearrangement of Azetidin-2-Ones

Authors: Parvesh Singh, Vipan Kumar, Vishu Mehra

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Quinoline-4-ones represent an important class of heterocyclic scaffolds that have attracted significant interest due to their various biological and pharmacological activities. This heterocyclic unit also constitutes an integral component in drugs used for the treatment of neurodegenerative diseases, sleep disorders and in antibiotics viz. norfloxacin and ciprofloxacin. The synthetic accessibility and possibility of fictionalization at varied positions in quinoline-4-ones exemplifies an elegant platform for the designing of combinatorial libraries of functionally enriched scaffolds with a range of pharmacological profles. They are also considered to be attractive precursors for the synthesis of medicinally imperative molecules such as non-steroidal androgen receptor antagonists, antimalarial drug Chloroquine and martinellines with antibacterial activity. 2-Aryl-2,3-dihydroquinolin-4(1H)-ones are present in many natural and non-natural compounds and are considered to be the aza-analogs of favanones. The β-lactam class of antibiotics is generally recognized to be a cornerstone of human health care due to the unparalleled clinical efficacy and safety of this type of antibacterial compound. In addition to their biological relevance as potential antibiotics, β-lactams have also acquired a prominent place in organic chemistry as synthons and provide highly efficient routes to a variety of non-protein amino acids, such as oligopeptides, peptidomimetics, nitrogen-heterocycles, as well as biologically active natural and unnatural products of medicinal interest such as indolizidine alkaloids, paclitaxel, docetaxel, taxoids, cyptophycins, lankacidins, etc. A straight forward route toward the synthesis of quinoline-4-ones via the triflic acid assisted Fries rearrangement of N-aryl-βlactams has been reported by Tepe and co-workers. The ring expansion observed in this case was solely attributed to the inherent ring strain in β-lactam ring because -lactam failed to undergo rearrangement under reaction conditions. Theabovementioned protocol has been recently extended by our group for the synthesis of benzo[b]-azocinon-6-ones via a tandem Michael addition–Fries rearrangement of sorbyl anilides as well as for the single-pot synthesis of 2-aryl-quinolin-4(3H)-ones through the Fries rearrangement of 3-dienyl-βlactams. In continuation with our synthetic endeavours with the β-lactam ring and in view of the lack of convenient approaches for the synthesis of C-3 functionalized quinolin-4(1H)-ones, the present work describes the single-pot synthesis of C-3 functionalized quinolin-4(1H)-ones via the trific acid promoted Fries rearrangement of C-3 vinyl/isopropenyl substituted β-lactams. In addition, DFT calculations and MD simulations were performed to investigate the stability profles of synthetic compounds.

Keywords: dihydroquinoline, fries rearrangement, azetidin-2-ones, quinoline-4-ones

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