Search results for: the self and the brain

Authors: Ayse Gul Bilen

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Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants that are used clinically for the treatment of anxiety disorders, obsessive-compulsive disorder (OCD), panic disorders and eating disorders. The first SSRI, fluoxetine (sold under the brand names Prozac and Sarafem among others), had an adverse effect profile better than any other available antidepressant when it was introduced because of its selectivity for serotonin receptors. They have been considered almost free of side effects and have become widely prescribed, however questions about the safety and tolerability of SSRIs have emerged with their continued use. Most SSRI side effects are dose-related and can be attributed to serotonergic effects such as nausea. Continuous use might trigger adverse effects such as hyponatremia, tremor, nausea, weight gain, sleep disturbance and sexual dysfunction. Moderate toxicity can be safely observed in the hospital for 24 hours, and mild cases can be safely discharged (if asymptomatic) from the emergency department once cleared by Psychiatry in cases of intentional overdose and after 6 to 8 hours of observation. Although fluoxetine is relatively safe in terms of overdose, it might still be cardiotoxic and inhibit platelet secretion, aggregation, and plug formation. There have been reported clinical cases of seizures, cardiac conduction abnormalities, and even fatalities associated with fluoxetine ingestions. While the medical literature strongly suggests that most fluoxetine overdoses are benign, emergency physicians need to remain cognizant that intentional, high-dose fluoxetine ingestions may induce seizures and can even be fatal due to cardiac arrhythmia. Our case is a 35-year old female patient who was sent to ER with symptoms of confusion, amnesia and loss of orientation for time and location after being found wandering in the streets unconsciously by police forces that informed 112. Upon laboratory examination, no pathological symptom was found except sinus tachycardia in the EKG and high levels of aspartate transaminase (AST) and alanine transaminase (ALT). Diffusion MRI and computed tomography (CT) of the brain all looked normal. Upon physical and sexual examination, no signs of abuse or trauma were found. Test results for narcotics, stimulants and alcohol were negative as well. There was a presence of dysrhythmia which required admission to the intensive care unit (ICU). The patient gained back her conscience after 24 hours. It was discovered from her story afterward that she had been using fluoxetine due to post-traumatic stress disorder (PTSD) for 6 months and that she had attempted suicide after taking 3 boxes of fluoxetine due to the loss of a parent. She was then transferred to the psychiatric clinic. Our study aims to highlight the need to consider toxicologic drug use, in particular, the abuse of selective serotonin reuptake inhibitors (SSRIs), which have been widely prescribed due to presumed safety and tolerability, for diagnosis of patients applying to the emergency room (ER).

Keywords: abuse, amnesia, fluoxetine, intoxication, SSRI

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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

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Authors: Anna Demian, Levi Howard, L. Ng, Leslie Simon, Mark Dragon, A. Desai, Timothy Devlantes, W. David Freeman

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Introduction: Out-of-hospital cardiac arrest (OHCA) can carry a high mortality. For survivors, the most common complication is hypoxic-ischemic brain injury (HIBI). Rarely, lumbosacral spinal cord and/or other spinal cord artery ischemia can occur due to anatomic variation and variable mean arterial pressure after the return of spontaneous circulation. We present a case of an OHCA survivor who later woke up with bilateral leg weakness with preserved sensation (ASIA grade B, L2 level). Methods: We describe a clinical, radiographic, and laboratory presentation, as well as a National Library of Medicine (NLM) search engine methodology, characterizing incidence/prevalence of this entity is discussed. A 70-year-old male, a longtime smoker, and alcohol user, suddenly collapsed at a bar surrounded by friends. He had complained of chest pain before collapsing. 911 was called. EMS arrived, and the patient was in pulseless electrical activity (PEA), cardiopulmonary resuscitation (CPR) was initiated, and the patient was intubated, and a LUCAS device was applied for continuous, high-quality CPR in the field by EMS. In the ED, central lines were placed, and thrombolysis was administered for a suspected Pulmonary Embolism (PE). It was a prolonged code that lasted 90 minutes. The code continued with the eventual return of spontaneous circulation. The patient was placed on an epinephrine and norepinephrine drip to maintain blood pressure. ECHO was performed and showed a “D-shaped” ventricle worrisome for PE as well as an ejection fraction around 30%. A CT with PE protocol was performed and confirmed bilateral PE. Results: The patient woke up 24 hours later, following commands, and was extubated. He was found paraplegic below L2 with preserved sensation, with hypotonia and areflexia consistent with “spinal shock” or anterior spinal cord syndrome. MRI thoracic and lumbar spine showed a conus medullaris level spinal cord infarction. The patient was given IV steroids upon initial discovery of cord infarct. NLM search using “cardiac arrest” and “spinal cord infarction” revealed 57 results, with only 8 review articles. Risk factors include age, atherosclerotic disease, and intraaortic balloon pump placement. AoA (Artery of Adamkiewicz) anatomic variation along with existing atherosclerotic factors and low perfusion were also known risk factors. Conclusion: Acute paraplegia from anterior spinal cord infarction of the AoA territory after cardiac arrest is rare. Larger prospective, multicenter trials are needed to examine potential interventions of hypothermia, lumbar drains, which are sometimes used in aortic surgery to reduce ischemia and/or other neuroprotectants.

Keywords: cardiac arrest, spinal cord infarction, artery of Adamkiewicz, paraplegia

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Authors: L. Bidyalakshmi, R. Ananthan, T. Longvah

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Antioxidants are substances that can prevent or delay oxidative damage of lipids, proteins and nucleic acids by reactive oxygen species. These help in lowering incidence of degenerative diseases such as cancer, arthritis, atherosclerosis, heart disease, inflammation, brain dysfunction and acceleration of the ageing process. The north eastern part of India falls among the global hotspots of biodiversity. Over the years, the local communities in the region have developed ingenious uses of many wild plants within their environment as food sources. Many of these less familiar foods form an integral part of the diet of these communities, and some are traditionally valued for its therapeutic effects. So the study was carried to estimate the antioxidant activity of some of these indigenous foods. Twenty-eight indigenous plant foods were studied for their antioxidant activity. Antioxidant activities were determined by using DPPH (2, 2-diphenyl-1-picrylhydrazyl) assay, FRAP (Ferric Reducing Antioxidant Power) assay and SOSA (Super Oxide Scavenging Assay). Out of the twenty-eight plant foods, there were thirteen leafy vegetables, four fruits, five roots and tubers, four spices and two mushrooms. Water extract and methanol extract of the samples were used for the analysis. The leafy vegetable samples exhibited antioxidant capacity with IC50 ranging from 8-1414 mg/ml for lipid extract and 34-37878 mg/ml for aqueous extract in DPPH assay. Total FRAP value ranging from 58-1005 mmol FeSO4 Eq/100g of the sample, which is comparatively higher than the antioxidant capacity of some commonly consumed leafy vegetables. In SOSA, water extract of leafy vegetables show a range of 0.05-193.68 µmol ascorbic acid equivalent/g of the samples. While the methanol extract of the samples show 0.20-21.94 µmol Trolox equivalent/g of the samples. Polygonum barbatum, Wendlandia glabrata and Polygonum posumbu have higher antioxidant activity among the leafy vegetables analysed. Among the fruits, Rhus hookerii showed the highest antioxidant activities in both FRAP and SOSA methods while Spondias magnifera exhibited higher antioxidant activity in DPPH method. Alocasia cucullata exhibited higher antioxidant activity in DPPH and FRAP assays while Alpinia galanga showed higher antioxidant activity in SOSA assay when compared to the other samples of roots and tubers. Elsholtzia communis showed high antioxidant activity in all the three parameters among the spices. For the mushrooms, Pleurotus ostreatus exhibited higher antioxidant activity than Auricularia delicate in DPPH and SOSA. The samples analysed exhibited antioxidant activity at varying levels and some exhibited higher antioxidant activity than the commonly consumed foods. So consumption of these less familiar foods may play a role in preventing human disease in which free radicals are involved. Further studies on these food samples on phytonutrients and its contribution to the antioxidant activities are required.

Keywords: antioxidant activity, DPPH, FRAP, SOSA

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Authors: Anthony S. Machi, Joseph Minardi

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We present a case report of left atrial myxoma diagnosed by bedside transesophageal (TEE) ultrasound. Left atrial myxoma is the most common benign cardiac tumor and can obstruct blood flow and cause valvular insufficiency. Common symptoms consist of dyspnea, pulmonary edema and other features of left heart failure in addition to thrombus release in the form of tumor fragments. The availability of bedside ultrasound equipment is essential for the quick diagnosis and treatment of various emergency conditions including cardiac neoplasms. A 48-year-old Caucasian female with a four-year history of an untreated renal mass and anemia presented to the ED with two months of sharp, intermittent, bilateral flank pain radiating into the abdomen. She also reported intermittent vomiting and constipation along with generalized body aches, night sweats, and 100-pound weight loss over last year. She had a CT in 2013 showing a 3 cm left renal mass and a second CT in April 2016 showing a 3.8 cm left renal mass along with a past medical history of diverticulosis, chronic bronchitis, dyspnea on exertion, uncontrolled hypertension, and hyperlipidemia. Her maternal family history is positive for breast cancer, hypertension, and Type II Diabetes. Her paternal family history is positive for stroke. She was a current everyday smoker with an 11 pack/year history. Alcohol and drug use were denied. Physical exam was notable for a Grade II/IV systolic murmur at the right upper sternal border, dyspnea on exertion without angina, and a tender left lower quadrant. Her vitals and labs were notable for a blood pressure of 144/96, heart rate of 96 beats per minute, pulse oximetry of 96%, hemoglobin of 7.6 g/dL, hypokalemia, hypochloremia, and multiple other abnormalities. Physicians ordered a CT to evaluate her flank pain which revealed a 7.2 x 8.9 x 10.5 cm mixed cystic/solid mass in the lower pole of the left kidney and a filling defect in the left atrium. Bedside TEE was ordered to follow up on the filling defect. TEE reported an ejection fraction of 60-65% and visualized a mobile 6 x 3 cm mass in the left atrium attached to the interatrial septum extending into the mitral valve. Cardiothoracic Surgery and Urology were consulted and confirmed a diagnosis of left atrial myxoma and clear cell renal cell carcinoma. The patient returned a week later due to worsening nausea and vomiting and underwent emergent nephrectomy, lymph node dissection, and colostomy due to a necrotic colon. Her condition declined over the next four months due to lung and brain metastases, infections, and other complications until she passed away.

Keywords: bedside ultrasound, echocardiography, emergency medicine, left atrial myxoma

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Authors: Cameron Wilson, Megan Hanrahan, Katie Brittain, Riona McArdle, Alison Keogh, Lynn Rochester

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Background: The loss of mobility and functional dependence is a significant marker in the progression of neurodegenerative diseases such as Parkinson’s Disease (PD). Pharmacological, surgical, and therapeutic treatments are available that can help in the management and amelioration of PD symptoms; however, these only prolong more severe symptoms. Accordingly, ensuring people with PD can maintain independence and a healthy wellbeing are essential in establishing an effective treatment option for those afflicted. Existing literature reviews have examined experiences in engaging with PD treatment options and the impact of PD on independence and wellbeing. Although, the literature fails to explore the influence of treatment options on independence and wellbeing and therefore misses what people value in their treatment. This review is the first that synthesises the impact of mobility-related treatments on independence and wellbeing in people with PD and their carers, offering recommendations to clinical practice and provides a conceptual framework (in development) for future research and practice. Objectives: To explore the impact of mobility-related treatment (both pharmacological and non-pharmacological) on the independence and wellbeing of people with PD and their carers. To propose a conceptual framework to patients, carers and clinicians which captures the qualities people with PD value as part of their treatment. Methods: We performed a critical interpretive synthesis of qualitative evidence, searching six databases for reports that explored the impact of mobility-related treatments (both drug and non-pharmacological) on independence and wellbeing in Parkinson’s Disease. The types of treatments included medication (Levodopa and Amantadine), dance classes, Deep-Brain Stimulation, aquatic therapies, physical rehabilitation, balance training and foetal transplantation. Data was extracted, and quality was assessed using an adapted version of the NICE Quality Appraisal Tool Appendix H before being synthesised according to the critical interpretive synthesis framework and meta-ethnography process. Results: From 2301 records, 28 were eligible. Experiences and impact of treatment pathway on independence and wellbeing was similar across all types of treatments and are described by five inter-related themes: (i) desire to maintain independence, (ii) treatment as a social experience during and after, (iii) medication to strengthen emotional health, (iv) recognising physical capacity and (v) emphasising the personal journey of Parkinson’s treatments. Conclusion: There is a complex and inter-related experience and effect of PD treatments common across all types of treatment. The proposed conceptual framework (in development) provides patients, carers, and clinicians recommendations to personalise the delivery of PD treatment, thereby potentially improving adherence and effectiveness. This work is vital to disseminate as PD treatment transitions from subjective and clinically captured assessments to a more personalised process supplemented using wearable technology.

Keywords: parkinson's disease, medication, treatment, dance, review, healthcare, delivery, levodopa, social, emotional, psychological, personalised healthcare

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Authors: Jolanta Jonak, Sylvia Tolczyk

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Educational systems are tasked with preparing students for future success in academic or work environments. Schools strive to achieve this goal, but often it is challenging as conventional teaching approaches are often ineffective in increasingly diverse educational systems. In today’s ever-increasing global society, educational systems become increasingly diverse in terms of cultural and linguistic differences, learning preferences and styles, ability and disability. Through increased understanding of disabilities and improved identification processes, students having some form of disabilities tend to be identified earlier than in the past, meaning that more students with identified disabilities are being supported in our classrooms. Also, a large majority of students with disabilities are educated in general education environments. Due to cognitive makeup and life experiences, students have varying learning styles and preferences impacting how they receive and express what they are learning. Many students come from bi or multilingual households and with varying proficiencies in the English language, further impacting their learning. All these factors need to be seriously considered when developing learning opportunities for student's. Educators try to adjust their teaching practices as they discover that conventional methods are often ineffective in reaching each student’s potential. Many teachers do not have the necessary educational background or training to know how to teach students whose learning needs are more unique and may vary from the norm. This is further complicated by the fact that many classrooms lack consistent access to interventionists/coaches that are adequately trained in evidence-based approaches to meet the needs of all students, regardless of what their academic needs may be. One evidence-based way for providing successful education for all students is by incorporating cognitive approaches and strategies that tap into affective, recognition, and strategic networks in the student's brain. This can be done through Differentiated Instruction (DI). Differentiated Instruction is increasingly recognized model that is established on the basic principles of Universal Design for Learning. This form of support ensures that regardless of the students’ learning preferences and cognitive learning profiles, they have opportunities to learn through approaches that are suitable to their needs. This approach improves the educational outcomes of students with special needs and it benefits other students as it accommodates learning styles as well as the scope of unique learning needs that are evident in the typical classroom setting. Differentiated Instruction also is recognized as an evidence-based best practice in education and is highly effective when it is implemented within the tiered system of the Response to Intervention (RTI) model. Recognition of DI becomes more common; however, there is still limited understanding of the effective implementation and use of strategies that can create unique learning environments for each student within the same setting. Through employing knowledge of a variety of instructional strategies, general and special education teachers can facilitate optimal learning for all students, with and without a disability. A desired byproduct of DI is that it can eliminate inaccurate perceptions about the students’ learning abilities, unnecessary referrals for special education evaluations, and inaccurate decisions about the presence of a disability.

Keywords: differentiated instruction, universal design for learning, special education, diversity

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Authors: Mbonigaba Swale

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Malaria is an infection or disease caused by parasites (Plasmodium Falciparum — causes severe Malaria, plasmodium Vivax, Plasmodium Ovale, and Plasmodium Malariae), transmitted by bites of infected anopheles (female) mosquitoes to humans. These vectors comprise of two types in Africa, particularly in Uganda, i.e. anopheles fenestus and Anopheles gambaie (‘example Anopheles arabiensis,,); feeds on man inside the house mainly at dusk, mid-night and dawn and rests indoors and makes them effective transmitters (vectors) of the disease. People in both urban and rural areas have consistently become prone to repetitive attacks of malaria, causing a lot of deaths and significantly increasing the poverty levels of the rural poor. Malaria is a national problem; it causes a lot of maternal pre-natal and antenatal disorders, anemia in pregnant mothers, low birth weights for the newly born, convulsions and epilepsy among the infants. Cumulatively, it kills about one million children every year in sub-Saharan Africa. It has been estimated to account for 25-35% of all outpatient visits, 20-45% of acute hospital admissions and 15-35% of hospital deaths. Uganda is the leading victim country, for which Rakai and Masaka districts are the most affected. So, it is not clear whether these abhorrent situations and episodes of recurrences and failure to cure from the disease are a result of poor diagnosis, prescription and dosing, treatment habits and compliance of the patients to the drugs or the ethical domain of the stake holders in relation to the main stream methodology of malaria management. The research is aimed at offering an alternative approach to manage and deal absolutely with problem by using a knowledge based software model of Artificial Intelligence (Al) that is capable of performing common-sense and cognitive reasoning so as to take decisions like the human brain would do to provide instantaneous expert solutions so as to avoid speculative simulation of the problem during differential diagnosis in the most accurate and literal inferential aspect. This system will assist physicians in many kinds of medical diagnosis, prescribing treatments and doses, and in monitoring patient responses, basing on the body weight and age group of the patient, it will be able to provide instantaneous and timely information options, alternative ways and approaches to influence decision making during case analysis. The computerized system approach, a new model in Uganda termed as “Software Aided Treatment” (SAT) will try to change the moral and ethical approach and influence conduct so as to improve the skills, experience and values (social and ethical) in the administration and management of the disease and drugs (combination therapy and generics) by both the patient and the health worker.

Keywords: knowledge based software, management, treatment, diagnosis

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Authors: Ippei Torii, Kaoruko Ohtani, Takahito Niwa, Naohiro Ishii

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This paper shows developing an objectivity index using the measurement of subtle eyeball movement to diagnose autism. The developmentally disabled assessment varies, and the diagnosis depends on the subjective judgment of professionals. Therefore, a supplementary inspection method that will enable anyone to obtain the same quantitative judgment is needed. The diagnosis are made based on a comparison of the time of gazing an object in the conventional autistic study, but the results do not match. First, we divided the pupil into four parts from the center using measurements of subtle eyeball movement and comparing the number of pixels in the overlapping parts based on an afterimage. Then we developed the objective evaluation indicator to judge non-autistic and autistic people more clearly than conventional methods by analyzing the differences of subtle eyeball movements between the right and left eyes. Even when a person gazes at one point and his/her eyeballs always stay fixed at that point, their eyes perform subtle fixating movements (ie. tremors, drifting, microsaccades) to keep the retinal image clear. Particularly, the microsaccades link with nerves and reflect the mechanism that process the sight in a brain. We converted the differences between these movements into numbers. The process of the conversion is as followed: 1) Select the pixel indicating the subject's pupil from images of captured frames. 2) Set up a reference image, known as an afterimage, from the pixel indicating the subject's pupil. 3) Divide the pupil of the subject into four from the center in the acquired frame image. 4) Select the pixel in each divided part and count the number of the pixels of the overlapping part with the present pixel based on the afterimage. 5) Process the images with precision in 24 - 30fps from a camera and convert the amount of change in the pixels of the subtle movements of the right and left eyeballs in to numbers. The difference in the area of the amount of change occurs by measuring the difference between the afterimage in consecutive frames and the present frame. We set the amount of change to the quantity of the subtle eyeball movements. This method made it possible to detect a change of the eyeball vibration in numerical value. By comparing the numerical value between the right and left eyes, we found that there is a difference in how much they move. We compared the difference in these movements between non-autistc and autistic people and analyzed the result. Our research subjects consists of 8 children and 10 adults with autism, and 6 children and 18 adults with no disability. We measured the values through pasuit movements and fixations. We converted the difference in subtle movements between the right and left eyes into a graph and define it in multidimensional measure. Then we set the identification border with density function of the distribution, cumulative frequency function, and ROC curve. With this, we established an objective index to determine autism, normal, false positive, and false negative.

Keywords: subtle eyeball movement, autism, microsaccade, pursuit eye movements, ROC curve

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Authors: Lucia Liu, Matthew Koziol

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Obsessive-compulsive disorder (OCD), a long-lasting anxiety disorder involving recurrent, intrusive thoughts, affects over 2 million adults in the United States. Transcranial magnetic stimulation (TMS) stands out as a noninvasive, cutting-edge therapy that has been shown to reduce symptoms in patients with treatment-resistant OCD. The Food and Drug Administration (FDA) approved protocol pairs TMS sessions with individualized symptom provocation, aiming to improve the susceptibility of brain circuits to stimulation. However, limited standardization or guidance exists on how to conduct symptom provocation and which methods are most effective. This study aims to compare the effect of internal versus external techniques to induce obsessional stress in a clinical setting during TMS therapy. Two symptom provocation methods, (i) Asking patients thought-provoking questions about their obsessions (internal) and (ii) Requesting patients to perform obsession-related tasks (external), were employed in a crossover design with repeated measurement. Thirty-six treatments of NeuroStar TMS were administered to each of two patients over 8 weeks in an outpatient clinic. Patient One received 18 sessions of internal provocation followed by 18 sessions of external provocation, while Patient Two received 18 sessions of external provocation followed by 18 sessions of internal provocation. The primary outcome was the level of self-reported obsessional stress on a visual analog scale from 1 to 10. The secondary outcome was self-reported OCD severity, collected biweekly in a four-level Likert-scale (1 to 4) of bad, fair, good and excellent. Outcomes were compared and tested between provocation arms through repeated measures ANOVA, accounting for intra-patient correlations. Ages were 42 for Patient One (male, White) and 57 for Patient Two (male, White). Both patients had similar moderate symptoms at baseline, as determined through the Yale-Brown Obsessive Compulsive Scale (YBOCS). When comparing obsessional stress induced across the two arms of internal and external provocation methods, the mean (SD) was 6.03 (1.18) for internal and 4.01 (1.28) for external strategies (P=0.0019); ranges were 3 to 8 for internal and 2 to 8 for external strategies. Internal provocation yielded 5 (31.25%) bad, 6 (33.33%) fair, 3 (18.75%) good, and 2 (12.5%) excellent responses for OCD status, while external provocation yielded 5 (31.25%) bad, 9 (56.25%) fair, 1 (6.25%) good, and 1 (6.25%) excellent responses (P=0.58). Internal symptom provocation tactics had a significantly stronger impact on inducing obsessional stress and led to better OCD status (non-significant). This could be attributed to the fact that answering questions may prompt patients to reflect more on their lived experiences and struggles with OCD. In the future, clinical trials with larger sample sizes are warranted to validate this finding. Results support the increased integration of internal methods into structured provocation protocols, potentially reducing the time required for provocation and achieving greater treatment response to TMS.

Keywords: obsessive-compulsive disorder, transcranial magnetic stimulation, mental health, symptom provocation

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Authors: Suhrita Saha

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Barbie is a fashion doll manufactured by the American toy company Mattel Inc and it made debut at the American International Toy Fair in New York in 9 March 1959. From being a fashion doll to a symbol of fetishistic commodification, Barbie has come a long way. A Barbie doll is sold every three seconds across the world, which makes the billion dollar brand the world’s most popular doll for the girls. The 11.5 inch moulded plastic doll has a height of 5 feet 9 inches at 1/6 scale. Her vital statistics have been estimated at 36 inches (chest), 18 inches (waist) and 33 inches (hips). Her weight is permanently set at 110 pounds which would be 35 pounds underweight. Ruth Handler, the creator of Barbie wanted a doll that represented adulthood and allowed children to imagine themselves as teenagers or adults. While Barbie might have been intended to be independent, imaginative and innovative, the physical uniqueness does not confine the doll to the status of a play thing. It is a cultural icon but with far reaching critical implications. The doll is a commodity bearing more social value than practical use value. The way Barbie is produced represents industrialization and commodification of the process of symbolic production. And this symbolic production and consumption is a standardized planned one that produce stereotypical ‘pseudo-individuality’ and suppresses cultural alternatives. Children are being subject to and also arise as subjects in this consumer context. A very gendered, physiologically dissected sexually charged symbolism is imposed upon children (both male and female), childhood, their social worlds, identity, and relationship formation. Barbie is also very popular among Indian children. While the doll is essentially an imaginative representation of the West, it is internalized by the Indian sensibilities. Through observation and questionnaire-based interview within a sample population of adolescent children (primarily female, a few male) and parents (primarily mothers) in Kolkata, an Indian metropolis, the paper puts forth findings of sociological relevance. 1. Barbie creates, recreates, and accentuates already existing divides between the binaries like male- female, fat- thin, sexy- nonsexy, beauty- brain and more. 2. The Indian girl child in her associative process with Barbie wants to be like her and commodifies her own self. The male child also readily accepts this standardized commodification. Definition of beauty is thus based on prejudice and stereotype. 3. Not being able to become Barbie creates health issues both psychological and physiological varying from anorexia to obesity as well as personality disorder. 4. From being a plaything Barbie becomes the game maker. Barbie along with many other forms of simulation further creates a consumer culture and market for all kind of fitness related hyper enchantment and subsequent disillusionment. The construct becomes the reality and the real gets lost in the play world. The paper would thus argue that Barbie from being an innocuous doll transports itself into becoming social construct with long term and irreversible adverse impact.

Keywords: barbie, commodification, personality disorder, sterotype

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Authors: Megan L. Srinivas

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Individuals with underlying rheumatologic diseases such as dermatomyositis may not adequately respond to tuberculin (PPD) skin tests, creating false negative results. These illnesses are frequently treated with immunosuppressive therapy making proper identification of TB infection imperative. A 59-year-old Filipino man was diagnosed with dermatomyositis on the basis of rash, electromyography, and muscle biopsy. He was initially treated with IVIG infusions and transitioned to oral prednisone and mycophenolate. The patient’s symptoms improved on this regimen. Six months after starting mycophenolate, the patient began having fevers, night sweats, and productive cough without hemoptysis. He moved from the Philippines 5 years prior to dermatomyositis diagnosis, denied sick contacts, and was PPD negative both at immigration and immediately prior to starting mycophenolate treatment. A third PPD was negative following the onset of these new symptoms. He was treated for community-acquired pneumonia, but symptoms worsened over 10 days and he developed watery diarrhea and a growing non-tender, non-mobile mass on the left side of his neck. A chest x-ray demonstrated a cavitary lesion in right upper lobe suspicious for TB that had not been present one month earlier. Chest CT corroborated this finding also exhibiting necrotic hilar and paratracheal lymphadenopathy. Neck CT demonstrated the left-sided mass as cervical chain lymphadenopathy. Expectorated sputum and stool samples contained acid-fast bacilli (AFB), cultures showing TB bacteria. Fine-needle biopsy of the neck mass (scrofula) also exhibited AFB. An MRI brain showed nodular enhancement suspected to be a tuberculoma. Mycophenolate was discontinued and dermatomyositis treatment was switched to oral prednisone with a 3-day course of IVIG. The patient’s infection showed sensitivity to standard RIPE (rifampin, isoniazid, pyrazinamide, and ethambutol) treatment. Within a week of starting RIPE, the patient’s diarrhea subsided, scrofula diminished, and symptoms significantly improved. By the end of treatment week 3, the patient’s sputum no longer contained AFB; he was removed from isolation, and was discharged to continue RIPE at home. He was discharged on oral prednisone, which effectively addressed his dermatomyositis. This case illustrates the unreliability of PPD tests in patients with long-term inflammatory diseases such as dermatomyositis. Other immunosuppressive therapies (adalimumab, etanercept, and infliximab) have been affiliated with conversion of latent TB to disseminated TB. Mycophenolate is another immunosuppressive agent with similar mechanistic properties. Thus, it is imperative that patients with long-term inflammatory diseases and high-risk TB factors initiating immunosuppressive therapy receive a TB blood test (such as a quantiferon gold assay) prior to the initiation of therapy to ensure that latent TB is unmasked before it can evolve into a disseminated form of the disease.

Keywords: dermatomyositis, immunosuppressant medications, mycophenolate, disseminated tuberculosis

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Authors: Rajkumar Ghosh, Bhabani Prasad Mukhopadhay

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Rice milling is an important activity in agricultural economy of India, particularly the Burdwan district. However, the environmental impact of rice mills is frequently underestimated. The environmental impact of rice mills in the Burdwan district is a major source of concern, given the importance of rice milling in the local economy and food supply. In the Burdwan district, more than fifty (50) rice mills are in operation. The goal of this study is to investigate the effects of rice mills on several environmental components, with a particular emphasis on groundwater, surface water, soil, and vegetation. The research comprises a thorough review of numerous rice mills located around the district, utilising both qualitative and quantitative approaches. Water samples taken from wells near rice mills will be tested for groundwater quality, with an emphasis on factors such as heavy metal pollution and pollutant concentrations. Monitoring rice mill discharge into neighbouring bodies of water and studying the potential impact on aquatic ecosystems will be part of surface water evaluations. Furthermore, soil samples from the surrounding areas will be taken to examine changes in soil characteristics, nutrient content, and potential contamination from milling waste disposal. Vegetation studies will be conducted to investigate the effects of emissions and effluents on plant health and biodiversity in the region. The findings will provide light on the extent of environmental degradation caused by rice mills in the Burdwan district, as well as valuable insight into the effects of such operations on water, soil, and vegetation. The findings will aid in the development of appropriate legislation and regulations to reduce negative environmental repercussions and promote sustainable practises in the rice milling business. In some cases, heavy metals have been related to health problems. Heavy metals (As, Cd, Cu, Pb, Cr, Hg) are linked to skin, lung, brain, kidney, liver, metabolic, spleen, cardiovascular, haematological, immunological, gastrointestinal, testes, pancreatic, metabolic, and bone problems. As a result, this study contributes to a better knowledge of industrial environmental impacts and establishes the framework for future studies aimed at developing a more ecologically balanced and resilient Burdwan district. The following recommendations are offered for reducing the rice mill's environmental impact: To keep untreated effluents out of bodies of water, adequate waste management systems must be established. Use environmentally friendly rice milling processes to reduce pollution. To avoid soil pollution, rice mill by-products should be used as fertiliser in a controlled and appropriate manner. Groundwater, surface water, soil, and vegetation are all regularly monitored in order to study and adapt to environmental changes. By adhering to these principles, the rice milling industry of Burdwan district may achieve long-term growth while lowering its environmental effect and safeguarding the environment for future generations.

Keywords: groundwater, environmental analysis, biodiversity, rice mill, waste management, diseases, industrial impact

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Authors: Sandhya Parameswaran, Prajakta Dhuri

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Despite great improvements in health care, the world oral health report states that dental problems still persist, particularly among underprivileged groups in both developing and developed countries. Dental caries and periodontal diseases are identified as the most important oral health problems globally. Acidic foods and beverages can affect natural teeth, and chronic exposure often leads to the development of dental erosion, abrasion, and decay. In recent years, there has been an increased interest toward essential oils. These are secondary metabolites and possess antibacterial, antifungal and antioxidant properties. Essential oils are volatile and chemically unstable in the presence of air, light, moisture and high temperature. Hence many novel methods like a liposomal encapsulation of oils have been introduced to enhance the stability and bioavailability. This research paper focuses on two essential oils, clove and cinnamon oil. Clove oil was obtained from Syzygium aromaticum Linn using clavengers apparatus. It contains eugenol and β caryophyllene. Cinnamon oil, from the barks of Cinnamomum cassia, contains cinnamaldehyde, The objective of the current research was to develop a liposomal carrier system containing clove and cinnamon oil and study their synergistic activity against dental pathogens when formulated as a gel. Methodology: The essential oil were first tested for their antimicrobial activity against dental pathogens, Lactobacillus acidophillus (MTCC No. 10307, MRS broth) and Streptococcus Mutans (MTCC No .890, Brain Heart Infusion agar). The oils were analysed by UV spectroscopy for eugenol and cinnamaldehyde content. Standard eugenol was linear between 5ppm to 25ppm at 282nm and standard cinnamaldehde from 1ppm to 5pmm at 284nm. The concentration of eugenol in clove oil was found to be 62.65 % w/w, and that of cinnamaldehyde was found to be 5.15%s w/w. The oils were then formulated into liposomes. Liposomes were prepared by thin film hydration method using Phospholipid, Cholesterol, and other oils dissolved in a chloroform methanol (3:1) mixture. The organic solvent was evaporated in a rotary evaporator above lipid transition temperature. The film was hydrated with phosphate buffer (pH 5.5).The various batches of liposomes were characterized and compared for their size, loading rate, encapsulation efficiency and morphology. The prepared liposomes when evaluated for entrapment efficiency showed 65% entrapment for clove and 85% for cinnamon oil. They were also tested for their antimicrobial activity against dental pathogens and their synergistic activity studied. Based on the activity and the entrapment efficiency the amount of liposomes required to prepare 1gm of the gel was calculated. The gel was prepared using a simple ointment base and contained 0.56% of cinnamon and clove liposomes. A simultaneous method of analysis for eugenol and cinnamaldehyde.was then developed using HPLC. The prepared gels were then studied for their stability as per ICH guidelines. Conclusion: It was found that liposomes exhibited spherical shaped vesicles and protected the essential oil from degradation. Liposomes, therefore, constitute a suitable system for encapsulation of volatile, unstable essential oil constituents.

Keywords: cinnamon oil, clove oil, dental caries, liposomes

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Authors: Catia Correia Caeiro, Kun Guo, Daniel Mills

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Despite its growing interest, emotions are still an understudied cognitive process and their origins are currently the focus of much debate among the scientific community. The use of facial expressions as traditional hallmarks of discrete and holistic emotions created a circular reasoning due to a priori assumptions of meaning and its associated appearance-biases. Ekman and colleagues solved this problem and laid the foundations for the quantitative and systematic study of facial expressions in humans by developing an anatomically-based system (independent from meaning) to measure facial behaviour, the Facial Action Coding System (FACS). One way of investigating emotion cognition processes is by applying comparative psychology methodologies and looking at either closely-related species (e.g. chimpanzees) or phylogenetically distant species sharing similar present adaptation problems (analogy). In this study, the domestic dog was used as a comparative animal model to look at facial expressions in social interactions in parallel with human facial expressions. The orofacial musculature seems to be relatively well conserved across mammal species and the same holds true for the domestic dog. Furthermore, the dog is unique in having shared the same social environment as humans for more than 10,000 years, facing similar challenges and acquiring a unique set of socio-cognitive skills in the process. In this study, the spontaneous facial movements of humans and dogs were compared when interacting with hetero- and conspecifics as well as in solitary contexts. In total, 200 participants were examined with FACS and DogFACS (The Dog Facial Action Coding System): coding tools across four different emotionally-driven contexts: a) Happiness (play and reunion), b) anticipation (of positive reward), c) fear (object or situation triggered), and d) frustration (negation of a resource). A neutral control was added for both species. All four contexts are commonly encountered by humans and dogs, are comparable between species and seem to give rise to emotions from homologous brain systems. The videos used in the study were extracted from public databases (e.g. Youtube) or published scientific databases (e.g. AM-FED). The results obtained allowed us to delineate clear similarities and differences on the flexibility of the facial musculature in the two species. More importantly, they shed light on what common facial movements are a product of the emotion linked contexts (the ones appearing in both species) and which are characteristic of the species, revealing an important clue for the debate on the origin of emotions. Additionally, we were able to examine movements that might have emerged for interspecific communication. Finally, our results are discussed from an evolutionary perspective adding to the recent line of work that supports an ancient shared origin of emotions in a mammal ancestor and defining emotions as mechanisms with a clear adaptive purpose essential on numerous situations, ranging from maintenance of social bonds to fitness and survival modulators.

Keywords: comparative and evolutionary psychology, emotion, facial expressions, FACS

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Authors: Saman Kumara, Duminda Guruge, Krishani Jayasinghe

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Introduction: Nutrition strongly influences good health and development in early life. This study, based on a health promotion approach, used a community-based intervention to improve child nutrition. The approach provides the community with control of interventions, thereby building its capacity and empowering individuals and communities. The aim of this research was to reduce stunting, low birth weight and underweight in communities from Anuradhapura District in Sri Lanka, by identifying and addressing the underlying determinants of under-nutrition and strengthening families and communities to address them. Methods: A health promotion intervention was designed and implemented-based on a logical framework developed in collaboration with members of targeted community. Community members’ implements action, so they fully own the process. Members of the community identify and address the most crucial determinants of health including child health and development and monitor the initial results of their action and modify action to optimize outcomes as well as future goals. Group Discussion, group activities, awareness programs, cluster meetings, community tools and sharing success stories were major activities to address determinants. Continuous data collection was planned at different levels. Priority was given to strengthening the ability of families and groups or communities to collect meaningful data and analyze these themselves. Results: Enthusiasm and interest of the mother, happiness of the child/ family, dietary habits, money management, tobacco and alcohol use of fathers, media influences, illnesses in the child or others, hygiene and sanitary practices, community sensitiveness and domestic violence were the major perceived determinants elicited from the study. There were around 1000 well-functioning mothers groups in this district. ‘Happiness calendar’, ‘brain calendar’, ‘money tool’ and ‘stimulation books’ were created by the community members, to address determinants and measure the process. Evaluation of the process has shown positive early results, such as improvement of feeding habits among mothers, innovative ways of providing early stimulation and responsive care, greater involvement of fathers in childcare and responsive feeding. There is a positive movement of communities around child well-being through interactive play areas. Family functioning and community functioning improved. Use of alcohol and tobacco declined. Community money management improved. Underweight was reduced by 40%. Stunting and low birth weight among under-fives also declined within one year. Conclusion: The health promotion intervention was effective in changing the determinants of under-nutrition in early childhood. Addressing the underlying determinants of under-nutrition in early childhood can be recommended for similar contexts.

Keywords: birth-weight, community, determinants, stunting, underweight

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Authors: Vanessa Do, Lauren Smith, Leslie Carver

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It is widely known that individuals with autism spectrum disorder (ASD) may exhibit sensitivity to stimuli. Even at a young age, they tend to display stimuli-related discomfort in their behavior during play. Play serves a crucial role in a child’s early years as it helps support healthy brain development, socio-emotional skills, and adaptation to their environment There is research dedicated to studying infant preferences for toys, especially in regard to: gender preferences, the advantages of promoting play, and the caregiver’s role in their child’s play routines. However, there is a disproportionate amount of literature examining how play patterns may differ in children with sensory sensitivity, such as children diagnosed with ASD. Prior literature has studied and found supporting evidence that individuals with ASD have deficits in social communication and have increased presence of repetitive behaviors and/or restricted interests, which also display in early childhood play patterns. This study aims to examine potential differences in toy preference between infants with (FH+) and without (FH-) a familial history of ASD ages 6. 9, and 12 months old. More specifically, this study will address the question, “do FH+ infants tend to play more with toys that require less social engagement compared to FH- infants?” Infants and their caregivers were recruited and asked to engage in a free-play session in their homes that lasted approximately 5 minutes. The sessions were recorded and later coded offline for engagement behaviors categorized by toy; each toy that the infants interacted with was coded as belonging to one of 6 categories: sensory (designed to stimulate one or more senses such as light-up toys or musical toys) , construction (e.g., building blocks, rubber suction cups), vehicles (e.g., toy cars), instructional (require steps to accomplish a goal such as flip phones or books), imaginative (e.g., dolls, stuffed animals), and miscellaneous (toys that do not fit into these categories). Toy engagement was defined as the infant looking and touching the toy (ILT) or looking at the toy while their caregiver was holding it (IL-CT). Results reported include/will include the proportion of time the infant was actively engaged with the toy out of the total usable video time per subject — distractions observed during the session were excluded from analysis. Data collection is still ongoing; however, the prediction is that FH+ infants will have higher engagement with sensory and construction toys as they require the least amount of social effort. Furthermore, FH+ infants will have the least engagement with the imaginative toys as prior literature has supported the claim that individuals with ASD have a decreased likelihood to engage in play that requires pretend play and other social skills. Looking at what toys are more or less engaging to FH+ infants is important as it provides significant contributions to their healthy cognitive, social, and emotional development. As play is one of the first ways for a child to understand the complexities of the larger world, the findings of this study may help guide further research into encouraging play with toys that are more engaging and sensory-sensitive for children with ASD.

Keywords: autism engagement, children’s play, early development, free-play, infants, toy

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Authors: Amelia J. McFarland, Andrew K. Davey, Shailendra Anoopkumar-Dukie

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Microglia are the resident macrophage population of the central nervous system (CNS), contributing to both innate and adaptive immune response, and brain homeostasis. Activation of microglia occurs in response to a multitude of pathogenic stimuli in their microenvironment; this induces morphological and functional changes, resulting in a state of acute neuroinflammation which facilitates injury resolution. Adequate microglial function is essential for the health of the neuroparenchyma, with microglial dysfunction implicated in numerous CNS pathologies. Given the critical role that these macrophage-derived cells play in CNS homeostasis, there is a high demand for microglial models suitable for use in neuroscience research. The isolation of primary human microglia, however, is both difficult and costly, with microglial activation an unwanted but inevitable result of the extraction process. Consequently, there is a need for the development of alternative experimental models which exhibit morphological, biochemical and functional characteristics of human microglia without the difficulties associated with primary cell lines. In this study, our aim was to evaluate whether THP-1 human peripheral blood monocytes would display microglial-like qualities following an induced differentiation, and, therefore, be suitable for use as surrogate microglia. To achieve this aim, THP-1 human peripheral blood monocytes from acute monocytic leukaemia were differentiated with a range of phorbol 12-myristate 13-acetate (PMA) concentrations (50-200 nM) using two different protocols: a 5-day continuous PMA exposure or a 3-day continuous PMA exposure followed by a 5-day rest in normal media. In each protocol and at each PMA concentration, microglial-like cell morphology was assessed through crystal violet staining and the presence of CD-14 microglial / macrophage cell surface marker. Lipopolysaccharide (LPS) from Escherichia coli (055: B5) was then added at a range of concentrations from 0-10 mcg/mL to activate the PMA-differentiated THP-1 cells. Functional microglial-like behavior was evaluated by quantifying the release of prostaglandin (PG)-E2 and pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α using mediator-specific ELISAs. Furthermore, production of global reactive oxygen species (ROS) and nitric oxide (NO) were determined fluorometrically using dichlorodihydrofluorescein diacetate (DCFH-DA) and diaminofluorescein diacetate (DAF-2-DA) respectively. Following PMA-treatment, it was observed both differentiation protocols resulted in cells displaying distinct microglial morphology from 10 nM PMA. Activation of differentiated cells using LPS significantly augmented IL-1β, TNF-α and PGE2 release at all LPS concentrations under both differentiation protocols. Similarly, a significant increase in DCFH-DA and DAF-2-DA fluorescence was observed, indicative of increases in ROS and NO production. For all endpoints, the 5-day continuous PMA treatment protocol yielded significantly higher mediator levels than the 3-day treatment and 5-day rest protocol. Our data, therefore, suggests that the differentiation of THP-1 human monocyte cells with PMA yields a homogenous microglial-like population which, following stimulation with LPS, undergo activation to release a range of pro-inflammatory mediators associated with microglial activation. Thus, the use of PMA-differentiated THP-1 cells represents a suitable microglial model for in vitro research.

Keywords: differentiation, lipopolysaccharide, microglia, monocyte, neuroscience, THP-1

Procedia PDF Downloads 388

Authors: Lilah Inzelberg, David Rand, Stanislav Steinberg, Moshe David Pur, Yael Hanein

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Human facial expressions carry important psychological and neurological information. Facial expressions involve the co-activation of diverse muscles. They depend strongly on personal affective interpretation and on social context and vary between spontaneous and voluntary activations. Smiling, as a special case, is among the most complex facial emotional expressions, involving no fewer than 7 different unilateral muscles. Despite their ubiquitous nature, smiles remain an elusive and debated topic. Smiles are associated with happiness and greeting on one hand and anger or disgust-masking on the other. Accordingly, while high-resolution recording of muscle activation patterns, in a non-interfering setting, offers exciting opportunities, it remains an unmet challenge, as contemporary surface facial electromyography (EMG) methodologies are cumbersome, restricted to the laboratory settings, and are limited in time and resolution. Here we present a wearable and non-invasive method for objective mapping of facial muscle activation and demonstrate its application in a natural setting. The technology is based on a recently developed dry and soft electrode array, specially designed for surface facial EMG technique. Eighteen healthy volunteers (31.58 ± 3.41 years, 13 females), participated in the study. Surface EMG arrays were adhered to participant left and right cheeks. Participants were instructed to imitate three facial expressions: closing the eyes, wrinkling the nose and smiling voluntary and to watch a funny video while their EMG signal is recorded. We focused on muscles associated with 'enjoyment', 'social' and 'masked' smiles; three categories with distinct social meanings. We developed a customized independent component analysis algorithm to construct the desired facial musculature mapping. First, identification of the Orbicularis oculi and the Levator labii superioris muscles was demonstrated from voluntary expressions. Second, recordings of voluntary and spontaneous smiles were used to locate the Zygomaticus major muscle activated in Duchenne and non-Duchenne smiles. Finally, recording with a wireless device in an unmodified natural work setting revealed expressions of neutral, positive and negative emotions in face-to-face interaction. The algorithm outlined here identifies the activation sources in a subject-specific manner, insensitive to electrode placement and anatomical diversity. Our high-resolution and cross-talk free mapping performances, along with excellent user convenience, open new opportunities for affective processing and objective evaluation of facial expressivity, objective psychological and neurological assessment as well as gaming, virtual reality, bio-feedback and brain-machine interface applications.

Keywords: affective expressions, affective processing, facial EMG, high-resolution electromyography, independent component analysis, wireless electrodes

Procedia PDF Downloads 246

Authors: Ho Yin Wickson Cheung, Liora Malki-Epshtein

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Outdoor air pollution presents a significant challenge for public health globally, especially in urban areas, with road traffic acting as the primary contributor to air pollution. Several studies have documented the antagonistic relation between traffic-related air pollution (TRAP) and the impact on health, especially to the vulnerable group of population, particularly young pupils. Generally, TRAP could cause damage to their brain, restricting the ability of children to learn and, more importantly, causing detrimental respiratory issues in later life. Butlittle is known about the specific exposure of children at school during the school day and the impact this may have on their overall exposure to pollution at a crucial time in their development. This project has set out to examine the air quality across primary schools in South-East London and assesses the variability of data found based on their geographic location and surroundings. Nitrogen dioxide, PM contaminants, and carbon dioxide were collected with diffusion tubes and portable monitoring equipment for eight schools across three local areas, that are Greenwich, Lewisham, and Tower Hamlets. This study first examines the geographical features of the schools surrounding (E.g., coverage of urban road structure and green infrastructure), then utilize three different methods to capture pollutants data. Moreover, comparing the obtained results with existing data from monitoring stations to understand the differences in air quality before and during the pandemic. Furthermore, most studies in this field have unfortunately neglected human exposure to pollutants and calculated based on values from fixed monitoring stations. Therefore, this paper introduces an alternative approach by calculating human exposure to air pollution from real-time data obtained when commuting within related areas (Driving routes and field walking). It is found that schools located highly close to motorways are generally not suffering from the most air pollution contaminants. Instead, one with the worst traffic congested routes nearby might also result in poor air quality. Monitored results also indicate that the annual air pollution values have slightly decreased during the pandemic. However, the majority of the data is currently still exceeding the WHO guidelines. Finally, the total human exposures for NO2 during commuting in the two selected routes were calculated. Results illustrated the total exposure for route 1 were 21,730 μm/m3 and 28,378.32 μm/m3, and for route 2 were 30,672 μm/m3 and 16,473 μm/m3. The variance that occurred might be due to the difference in traffic volume that requires further research. Exposure for NO2 during commuting was plotted with detailed timesteps that have shown their peak usually occurred while commuting. These have consolidated the initial assumption to the extremeness of TRAP. To conclude, this paper has yielded significant benefits to understanding air quality across schools in London with the new approach of capturing human exposure (Driving routes). Confirming the severity of air pollution and promoting the necessity of considering environmental sustainability for policymakers during decision making to protect society's future pillars.

Keywords: air pollution, schools, pupils, congestion

Procedia PDF Downloads 117

Authors: Bruno Biagianti, Angela Tseng, Kathy Wannaviroj, Allison Corlett, Megan DuBois, Kyu Lee, Suma Jacob

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Background: ASD is characterized by pervasive Sensory Processing Abnormalities (SPA) and social cognitive deficits that persist throughout the course of the illness and have been linked to functional abnormalities in specific neural systems that underlie the perception, processing, and representation of sensory information. SPA and social cognitive deficits are associated with difficulties in interpersonal relationships, poor development of social skills, reduced social interactions and lower academic performance. Importantly, they can hamper the effects of established evidence-based psychological treatments—including PEERS (Program for the Education and Enrichment of Relationship Skills), a parent/caregiver-assisted, 16-weeks social skills intervention—which nonetheless requires a functional brain capable of assimilating and retaining information and skills. As a matter of fact, some adolescents benefit from PEERS more than others, calling for strategies to increase treatment response rates. Objective: We will present interim data on CICADAS (Care Improving Cognition for ADolescents on the Autism Spectrum)—a clinician-assisted, closed-loop technology mobile application for adolescents with ASD. Via ten mobile assessments, CICADAS captures data on sensory processing abnormalities and associated cognitive deficits. These data populate a machine learning algorithm that tailors the delivery of ten neuroplasticity-based social cognitive training (NB-SCT) exercises targeting sensory processing abnormalities. Methods: In collaboration with the Autism Spectrum and Neurodevelopmental Disorders Clinic at the University of Minnesota, we conducted a fully remote, three-arm, randomized crossover trial with adolescents with ASD to document the acceptability of CICADAS and evaluate its potential as a stand-alone treatment or as a treatment enhancer of PEERS. Twenty-four adolescents with ASD (ages 11-18) have been initially randomized to 16 weeks of PEERS + CICADAS (Arm A) vs. 16 weeks of PEERS + computer games vs. 16 weeks of CICADAS alone (Arm C). After 16 weeks, the full battery of assessments has been remotely administered. Results: We have evaluated the acceptability of CICADAS by examining adherence rates, engagement patterns, and exit survey data. We found that: 1) CICADAS is able to serve as a treatment enhancer for PEERS, inducing greater improvements in sensory processing, cognition, symptom reduction, social skills and behaviors, as well as the quality of life compared to computer games; 2) the concurrent delivery of PEERS and CICADAS induces greater improvements in study outcomes compared to CICADAS only. Conclusion: While preliminary, our results indicate that the individualized assessment and treatment approach designed in CICADAS seems effective in inducing adaptive long-term learning about social-emotional events. CICADAS-induced enhancement of processing and cognition facilitates the application of PEERS skills in the environment of adolescents with ASD, thus improving their real-world functioning.

Keywords: ASD, social skills, cognitive training, mobile app

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Authors: Berengere Vire, Nicolas Salvetat, Yoann Lannay, Guillaume Marcellin, Siem Van Der Laan, Franck Molina, Dinah Weissmann

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Predicting suicidal behaviors is one of the most complex challenges of daily psychiatric practices. Today, suicide risk prediction using biological tools is not validated and is only based on subjective clinical reports of the at-risk individual. Therefore, there is a great need to identify biomarkers that would allow early identification of individuals at risk of suicide. Alterations of adenosine-to-inosine (A-to-I) RNA editing of neurotransmitter receptors and other proteins have been shown to be involved in etiology of different psychiatric disorders and linked to suicidal behavior. RNA editing is a co- or post-transcriptional process leading to a site-specific alteration in RNA sequences. It plays an important role in the epi transcriptomic regulation of RNA metabolism. On postmortem human brain tissue (prefrontal cortex) of depressed suicide victims, Alcediag found specific alterations of RNA editing activity on the mRNA coding for the serotonin 2C receptor (5-HT2cR). Additionally, an increase in expression levels of ADARs, the RNA editing enzymes, and modifications of RNA editing profiles of prime targets, such as phosphodiesterase 8A (PDE8A) mRNA, have also been observed. Interestingly, the PDE8A gene is located on chromosome 15q25.3, a genomic region that has recurrently been associated with the early-onset major depressive disorder (MDD). In the current study, we examined whether modifications in RNA editing profile of prime targets allow identifying disease-relevant blood biomarkers and evaluating suicide risk in patients. To address this question, we performed a clinical study to identify an RNA editing signature in blood of depressed patients with and without the history of suicide attempts. Patient’s samples were drawn in PAXgene tubes and analyzed on Alcediag’s proprietary RNA editing platform using next generation sequencing technology. In addition, gene expression analysis by quantitative PCR was performed. We generated a multivariate algorithm comprising various selected biomarkers to detect patients with a high risk to attempt suicide. We evaluated the diagnostic performance using the relative proportion of PDE8A mRNA editing at different sites and/or isoforms as well as the expression of PDE8A and the ADARs. The significance of these biomarkers for suicidality was evaluated using the area under the receiver-operating characteristic curve (AUC). The generated algorithm comprising the biomarkers was found to have strong diagnostic performances with high specificity and sensitivity. In conclusion, we developed tools to measure disease-specific biomarkers in blood samples of patients for identifying individuals at the greatest risk for future suicide attempts. This technology not only fosters patient management but is also suitable to predict the risk of drug-induced psychiatric side effects such as iatrogenic increase of suicidal ideas/behaviors.

Keywords: blood biomarker, next-generation-sequencing, RNA editing, suicide

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Authors: Jessica M. Black

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Although much of natural and social science research aims to enhance human flourishing and address social problems, the training within the two fields is significantly different across theory, methodology, and implementation of results. Social scientists are trained in social, psychological, and to the extent that it is relevant to their discipline, spiritual development, theory, and accompanying methodologies. They tend not to receive training or learn about accompanying methodology related to interrogating human development and social problems from a biological perspective. On the other hand, those in the natural sciences, and for the purpose of this work, human biological sciences specifically – biology, neuroscience, genetics, epigenetics, and physiology – are often trained first to consider cellular development and related methodologies, and may not have opportunity to receive formal training in many of the foundational principles that guide human development, such as systems theory or person-in-environment framework, methodology related to tapping both proximal and distal psycho-social-spiritual influences on human development, and foundational principles of equity, justice and inclusion in research design. There is a need for disciplines heretofore siloed to know one another, to receive streamlined, easy to access training in theory and methods from one another and to learn how to build interdisciplinary teams that can speak and act upon a shared research language. Team science is more essential than ever, as are transdisciplinary approaches to training and research design. This study explores the use of a methodological toolbox that natural and social scientists can use by employing a decision-making tree regarding project aims, costs, and participants, among other important study variables. The decision tree begins with a decision about whether the researcher wants to learn more about social sciences approaches or biological approaches to study design. The toolbox and platform are flexible, such that users could also choose among modules, for instance, reviewing epigenetics or community-based participatory research even if those are aspects already a part of their home field. To start, both natural and social scientists would receive training on systems science, team science, transdisciplinary approaches, and translational science. Next, social scientists would receive training on grounding biological theory and the following methodological approaches and tools: physiology, (epi)genetics, non-invasive neuroimaging, invasive neuroimaging, endocrinology, and the gut-brain connection. Natural scientists would receive training on grounding social science theory, and measurement including variables, assessment and surveys on human development as related to the developing person (e.g., temperament and identity), microsystems (e.g., systems that directly interact with the person such as family and peers), mesosystems (e.g., systems that interact with one another but do not directly interact with the individual person, such as parent and teacher relationships with one another), exosystems (e.g., spaces and settings that may come back to affect the individual person, such as a parent’s work environment, but within which the individual does not directly interact, macrosystems (e.g., wider culture and policy), and the chronosystem (e.g., historical time, such as the generational impact of trauma). Participants will be able to engage with the toolbox and one another to foster increased transdisciplinary work

Keywords: methodology, natural science, social science, transdisciplinary

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Authors: Nilam Bano, Uzma Iram

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Globally, the dilemma of undernutrition has become a notable concern for the researchers, academicians, and policymakers because of its severe consequences for many centuries. The nutritional deficiencies create hurdles for the people to achieve goals related to live a better lifestyle. Not only at micro level but also at the macro level, the consequences of undernutrition affect the economic progress of the country. The initial five years of a child’s life are considered critical for the physical growth and brain development. In this regard, children require special care and good quality food (nutrient intake) to fulfill their nutritional demand of the growing body. Having the sensitive stature and health, children specially under the age of 5 years are more vulnerable to the poor economic, housing, environmental and other social conditions. Beside confronting economic challenges and political upheavals, Pakistan is also going through from a rough patch in the context of social development. Majority of the children are facing serious health problems in the absence of required nutrition. The complexity of this issue is getting severe day by day and specially children are left behind with different type of immune problems and vitamins and mineral deficiencies. It is noted that children from the well-off background are less likely affected by the undernutrition. In order to underline this issue, the present study aims to highlight the existing nutritional inequalities among the children of under five years in Pakistan. Moreover, this study strives to decompose those factors that severely affect the existing nutritional inequality and standing in the queue to capture the consideration of concerned authorities. Pakistan Demographic and Health Survey 2012-13 was employed to assess the relevant indicators of undernutrition such as stunting, wasting, underweight and associated socioeconomic factors. The objectives were executed through the utilization of the relevant empirical techniques. Concentration indices were constructed to measure the nutritional inequalities by utilizing three measures of undernutrition; stunting, wasting and underweight. In addition to it, the decomposition analysis following the logistic regression was made to unfold the determinants that severely affect the nutritional inequalities. The negative values of concentration indices illustrate that children from the marginalized background are affected by the undernutrition more than their counterparts who belong from rich households. Furthermore, the result of decomposition analysis indicates that child age, size of a child at birth, wealth index, household size, parents’ education, mother’s health and place of residence are the most contributing factors in the prevalence of existing nutritional inequalities. Considering the result of the study, it is suggested to the policymakers to design policies in a way so that the health sector of Pakistan can stimulate in a productive manner. Increasing the number of effective health awareness programs for mothers would create a notable difference. Moreover, the education of the parents must be concerned by the policymakers as it has a significant association with the present research in terms of eradicating the nutritional inequalities among children.

Keywords: concentration index, decomposition analysis, inequalities, undernutrition, Pakistan

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Authors: Reggie Chandra

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Trafficaccidents and traffic signal optimization are correlated. However, 70-90% of the traffic signals across the USA are not synchronized. The reason behind that is insufficient resources to create and implement timing plans. In this work, we will discuss the use of a breakthrough Artificial Intelligence (AI) technology to optimize traffic flow and collect 24/7/365 accurate traffic data using a vehicle detection system. We will discuss what are recent advances in Artificial Intelligence technology, how does AI work in vehicles, pedestrians, and bike data collection, creating timing plans, and what is the best workflow for that. Apart from that, this paper will showcase how Artificial Intelligence makes signal timing affordable. We will introduce a technology that uses Convolutional Neural Networks (CNN) and deep learning algorithms to detect, collect data, develop timing plans and deploy them in the field. Convolutional Neural Networks are a class of deep learning networks inspired by the biological processes in the visual cortex. A neural net is modeled after the human brain. It consists of millions of densely connected processing nodes. It is a form of machine learning where the neural net learns to recognize vehicles through training - which is called Deep Learning. The well-trained algorithm overcomes most of the issues faced by other detection methods and provides nearly 100% traffic data accuracy. Through this continuous learning-based method, we can constantly update traffic patterns, generate an unlimited number of timing plans and thus improve vehicle flow. Convolutional Neural Networks not only outperform other detection algorithms but also, in cases such as classifying objects into fine-grained categories, outperform humans. Safety is of primary importance to traffic professionals, but they don't have the studies or data to support their decisions. Currently, one-third of transportation agencies do not collect pedestrian and bike data. We will discuss how the use of Artificial Intelligence for data collection can help reduce pedestrian fatalities and enhance the safety of all vulnerable road users. Moreover, it provides traffic engineers with tools that allow them to unleash their potential, instead of dealing with constant complaints, a snapshot of limited handpicked data, dealing with multiple systems requiring additional work for adaptation. The methodologies used and proposed in the research contain a camera model identification method based on deep Convolutional Neural Networks. The proposed application was evaluated on our data sets acquired through a variety of daily real-world road conditions and compared with the performance of the commonly used methods requiring data collection by counting, evaluating, and adapting it, and running it through well-established algorithms, and then deploying it to the field. This work explores themes such as how technologies powered by Artificial Intelligence can benefit your community and how to translate the complex and often overwhelming benefits into a language accessible to elected officials, community leaders, and the public. Exploring such topics empowers citizens with insider knowledge about the potential of better traffic technology to save lives and improve communities. The synergies that Artificial Intelligence brings to traffic signal control and data collection are unsurpassed.

Keywords: artificial intelligence, convolutional neural networks, data collection, signal control, traffic signal

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Authors: Saule Balmagambetova, Zhenisgul Tlegenova, Saule Madinova

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

Keywords: breast cancer, chemotherapy, cardiotoxicity, Kazakhstan

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Authors: Soumia Hammadi, Imane Nouacer, Lamine Hamida, Younes A. Hammadi, Rachid Chaibi

Abstract:

Aims and objective: In the present work, we investigate the impact of both acute and chronic diabetes mellitus induced by streptozotocin (STZ) on the hypothalamus of the small gerbil (Gerbillus gerbillus). In this purpose, we aimed to study the histologic structure of the gerbil’s hypothalamic supraoptic (NSO) and paraventricular nucleus (NPV) at two distinct time points: two days and 30 days after diabetes onset. Methods: We conducted our investigation using 19 adult male gerbils weighing 25 to 28 g, divided into three groups as follow: Group I: Control gerbils (n=6) received an intraperitoneal injection of citrate buffer. Group II: STZ-diabetic gerbils (n=8) received a single intraperitoneal injection of STZ at a dose of 165 mg/kg of body weight. Diabetes onset (D0) is considered with the first hyperglycemia level exceeding 2,5 g/L. This group was further divided into two subgroups: Group II-1: Experimental Gerbils, at acute state of diabetes (n=8) sacrificed after 02 days of diabetes onset, Group II-2: Experimental Gerbils at chronic state of diabetes (n=7) sacrificed after 30 days of diabetes onset. Two and 30 days after diabetes onset, gerbils had blood drawn from the retro-orbital sinus into EDTA tubes. After centrifugation at -4°C, plasma was frozen at -80°C for later measurement of Cortisol, ACTH, and insulin. Afterward, animals were decapitated; their brain was removed, weighed, fixed in aqueous bouin, and processed and stained with Toluidine Bleu stain for histo-stereological analysis. A comparison was done with control gerbils treated with citrate buffer. Results: Compared to control gerbils, at 02 Days post diabetes onset, the neuronal somata of the paraventricular (NPV) and supraoptic nuclei (NSO) expressed numerous vacuoles of various sizes, we distinct also a neuronal juxtaposition and several unidentifiable vacuolated profiles were also seen in the neuropile. At the same time, we revealed the presence of à shrunken and condensed nuclei, which seem to touch the parvocellular neurons ( NPV); this leads us to suggest the presence of an apoptotic process in the early stage of diabetes. At 30 days of diabetes mellitus, the NPV manifests a few neurons with a distant appearance, in addition the magnocellular neurons in both NPV and NSO were hypertrophied with a rich euchromatin nucleus, a well-defined nucleolus, and a granular cytoplasm. Despite the neuronal degeneration at this stage, unexpectedly, ACTH registers a continuous significant high level compared to the early stage of diabetes mellitus and to control gerbils. Conclusion: The results suggest that the induction of diabetes mellitus using STZ in the small gerbils lead to alterations in the structure and morphology of the hypothalamus and hyper-secretion of ACTH and cortisol, possibly indicating hyperactivity of the hypothalamo-pituitary adrenal axis (HPA) during both the early and later stages of the disease. The subsequent quantitative evaluation of CRH, immunehistochemical evaluation of apoptosis, and oxidative stress assessment could corroborate our results.

Keywords: diabetes type 1., streptozotocin., small gerbil., hypothalamus., paraventricular nucleus., supraoptic nucleus.

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Authors: Michael Brave, Mark Kroll, Steven Karch, Charles Wetli, Michael Graham, Sebastian Kunz, Dorin Panescu

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Background: Conducted electrical weapons (CEW) are now used in 107 countries and are a common law enforcement less-lethal force practice in the United Kingdom (UK), United States of America (USA), Canada, Australia, New Zealand, and others. Use of these devices is rarely temporally associated with the occurrence of sudden arrest-related deaths (ARD). Because such deaths are uncommon, few Medical Examiners (MEs) ever encounter one, and even fewer offices have established comprehensive investigative protocols. Without sufficient scientific data, the role, if any, played by a CEW in a given case is largely supplanted by conjecture often defaulting to a CEW-induced fatal cardiac arrhythmia. In addition to the difficulty in investigating individual deaths, the lack of information also detrimentally affects being able to define and evaluate the ARD cohort generally. More comprehensive, better information leads to better interpretation in individual cases and also to better research. The purpose of this presentation is to provide MEs with a comprehensive evidence-based checklist to assist in the assessment of CEW-ARD cases. Methods: PUBMED and Sociology/Criminology data bases were queried to find all medical, scientific, electrical, modeling, engineering, and sociology/criminology peer-reviewed literature for mentions of CEW or synonymous terms. Each paper was then individually reviewed to identify those that discussed possible bioelectrical mechanisms relating CEW to ARD. A Naranjo-type pharmacovigilance algorithm was also employed, when relevant, to identify and quantify possible direct CEW electrical myocardial stimulation. Additionally, CEW operational manuals and training materials were reviewed to allow incorporation of CEW-specific technical parameters. Results: Total relevant PUBMED citations of CEWs were less than 250, and reports of death extremely rare. Much relevant information was available from Sociology/Criminology data bases. Once the relevant published papers were identified, and reviewed, we compiled an annotated checklist of data that we consider critical to a thorough CEW-involved ARD investigation. Conclusion: We have developed an evidenced-based checklist that can be used by MEs and their staffs to assist them in identifying, collecting, documenting, maintaining, and objectively analyzing the role, if any, played by a CEW in any specific case of sudden death temporally associated with the use of a CEW. Even in cases where the collected information is deemed by the ME as insufficient for formulating an opinion or diagnosis to a reasonable degree of medical certainty, information collected as per the checklist will often be adequate for other stakeholders to use as a basis for informed decisions. Having reviewed the appropriate materials in a significant number of cases careful examination of the heart and brain is likely adequate. Channelopathy testing should be considered in some cases, however it may be considered cost prohibitive (aprox $3000). Law enforcement agencies may want to consider establishing a reserve fund to help manage such rare cases. The expense may stay the enormous costs associated with incident-precipitated litigation.

Keywords: ARD, CEW, police, TASER

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Authors: Asma Ben Hmidene, Mizuho Hanaki, Kazuma Murakami, Kazuhiro Irie, Hiroko Isoda, Hideyuki Shigemori

Abstract:

Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are characterized as a peripheral metabolic disorder and a degenerative disease of the central nervous system, respectively. It is now widely recognized that T2DM and AD share many pathophysiological features including glucose metabolism, increased oxidative stress and amyloid aggregation. Amyloid beta (Aβ) is the components of the amyloid deposits in the AD brain and while the component of the amyloidogenic peptide deposit in the pancreatic islets of Langerhans is identified as human islet amyloid polypeptide (hIAPP). These two proteins are originated from the amyloid precursor protein and have a high sequence similarity. Although the amino acid sequences of amyloidogenic proteins are diverse, they all adopt a similar structure in aggregates called cross-beta-spine. Add at that, extensive studies in the past years have found that like Aβ1-42, IAPP forms early intermediate assemblies as spherical oligomers, implicating that these oligomers possess a common folding pattern or conformation. These similarities can be used in the search for effective pharmacotherapy for DM, since potent therapeutic agents such as antioxidants with a catechol moiety, proved to inhibit Aβ aggregation, may play a key role in the inhibit the aggregation of hIAPP treatment of patients with DM. Tamarix gallica is one of the halophyte species having a powerful antioxidant system. Although it was traditionally used for the treatment of various liver metabolic disorders, there is no report about the use of this plant for the treatment or prevention of T2DM and AD. Therefore, the aim of this work is to investigate their protective effect towards T2DM and AD by isolation and identification of α-glucosidase inhibitors, with antioxidant potential, that play an important role in the glucose metabolism in diabetic patient, as well as, the polymerization of hIAPP and Aβ aggregation inhibitors. Structure-activity relationship study was conducted for both assays. And as for α-glucosidase inhibitors, their mechanism of action and their synergistic potential when applied with a very low concentration of acarbose were also suggesting that they can be used not only as α-glucosidase inhibitors but also be combined with established α-glucosidase inhibitors to reduce their adverse effect. The antioxidant potential of the purified substances was evaluated by DPPH and SOD assays. Th-T assay using 42-mer amyloid β-protein (Aβ42) for AD and hIAPP which is a 37-residue peptide secreted by the pancreatic β –cells for T2DM and Transmission electronic microscopy (TEM) were conducted to evaluate the amyloid aggragation of the actives substances. For α-glucosidase, p-NPG and glucose oxidase assays were performed for determining the inhibition potential and structure-activity relationship study. The Enzyme kinetic protocol was used to study the mechanism of action. From this research, it was concluded that polyphenols playing a role in the glucose metabolism and oxidative stress can also inhibit the amyloid aggregation, and that substances with a catechol and glucuronide moieties inhibiting amyloid-β aggregation, might be used to inhibit the aggregation of hIAPP.

Keywords: α-glucosidase inhibitors, amyloid aggregation inhibition, mechanism of action, polyphenols, structure activity relationship, synergistic potential, tamarix gallica

Procedia PDF Downloads 279

Authors: V. K. Tewari, M. Hussain, H. K. D. Gupta

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Background: Nitric Oxide Donars (NODs) (intrathecal sodium nitroprusside (ITSNP) and oral tadalafil 20mg post ITSNP) has been studied in this context in cerebral palsy patients for fast recovery. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a) Retrograde Neurotransmission (acute cases): 1) Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2) Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b) Vasopasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c) Long-Term Potentiation (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Design: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat cerebral palsy cases. Case-control prospective study. Materials and Methods: The experimental population included 82 cerebral palsy patients (10 patients were given control treatments without NOD or with 5% dextrose superfusion, and 72 patients comprised the NOD group). The mean time for superfusion was 5 months post-cerebral palsy. Pre- and post-NOD status was monitored by Gross Motor Function Classification System for Cerebral Palsy (GMFCS), MRI, and TCD studies. Results: After 7 days in the NOD group, the mean change in the GMFCS score was an increase of 1.2 points mean; after 3 months, there was an increase of 3.4 points mean, compared to the control-group increase of 0.1 points at 3 months. MRI and TCD documented the improvements. Conclusions: NOD (ITSNP boosts up the recovery and oral tadalafil maintains the recovery to a well-desired level) acts swiftly in the treatment of CP, acting within 7 days on 5 months post-cerebral palsy either of the three mechanisms.

Keywords: cerebral palsy, intrathecal sodium nitroprusside, oral tadalafil, perforators, vasodilations, retrograde transmission, the 10, 000-fold effect, long-term potantiation

Procedia PDF Downloads 362